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Home » Health News » Recognise and control new variants of the deadly Ebola virus more quickly
Recognise and control new variants of the deadly Ebola virus more quickly
The situation is extraordinary: there have only ever been four declarations of public health emergencies of international concern in the past and now there are two at the same time. Whilst the risks associated with the novel coronavirus are still unclear, people in the Democratic Republic of the Congo are still battling with an outbreak of the deadly Ebola virus which has been ongoing since 2018 and has already claimed over 2000 lives. One issue is the precise characterisation of the pathogen because the ebolaviruses, like lots of viruses, appear in various genetic forms. Only the analysis of its genetic material provides the information necessary to develop specific tests for diagnosis and decide on efficient measures for controlling the outbreak. A German Center for Infection Research (DZIF) team at Charité – Universitätsmedizin Berlin has now developed a test which accelerates the process of identifying the genetic makeup of the virus.
There have been multiple Ebola outbreaks in the last decades. Since 2013, at least eight countries have been affected and 30,000 people have contracted the virus. The origin of these outbreaks is often unclear and they are caused by various ebolavirus variants. "At the moment, it often takes months to develop the right tools to fully characterise the genetic material of the ebolavirus causing an outbreak" explains Professor Jan Felix Drexler, a scientist at the German Center for Infection Research (DZIF) and Charité. "However, this knowledge is crucial for developing specific diagnostic tests, identifying transmission chains and eventually controlling the outbreak."
The scientists in Professor Drexler's team have now developed a test which provides information about the genetic material of new ebolaviruses regardless of the species or the variant, that is, of the genetic makeup. The test is based on the commonly used polymerase chain reaction (PCR), using which the genetic material can be amplified in a manner that allows precise sequencing. The new test is compatible with various technical procedures such as high-throughput sequencing. It has been tested with four different ebolavirus species.
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myscience.org › news › science wire › Novartis Kisqali now first and only CDK4/6 inhibitor indicated in US as first-line therapy specifically for premenopausal women; and as initial therapy with fulvestrant in postmenopausal women
Novartis Kisqali now first and only CDK4/6 inhibitor indicated in US as first-line therapy specifically for premenopausal women; and as initial therapy with fulvestrant in postmenopausal women
Health | Pharmacology
Kisqali is now the only CDK4/6 inhibitor indicated in combination with an aromatase inhibitor as first-line treatment for pre-, perior postmenopausal women with HR+/HER2- advanced breast cancer in the US
Kisqali is the only CDK4/6 inhibitor that is indicated with fulvestrant as both initial or second-line treatment for postmenopausal women with HR+/HER2- advanced breast cancer
FDA approval is based on MONALEESA-3 and MONALEESA-7 clinical trials, which demonstrated robust efficacy of Kisqali combination therapy in multiple treatment partners and settings
First FDA approval using the Real-Time Oncology Review and Assessment Aid pilot programs; application approved in less than one month
- Novartis today announced a new approval for Kisqali (ribociclib) from the US Food and Drug Administration (FDA) for women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced or metastatic breast cancer. Kisqali is now the only CDK4/6 inhibitor indicated for use with an aromatase inhibitor for the treatment of pre-, perior postmenopausal women in the US, and also is indicated for use in combination with fulvestrant as both firstor second-line therapy in postmenopausal women. FDA reviewed this supplemental New Drug Application (sNDA) under its Real-Time Oncology Review and Assessment Aid pilot programs and approved the application in less than one month after submission.
"Compelling data for Kisqali have led to the broadest first-line indications of any CDK4/6 inhibitor," said Liz Barrett, CEO, Novartis Oncology. "With this new approval Kisqali has the potential to help even more people in the US live a longer life without progression of disease from this incurable form of breast cancer."
This approval is based on the pivotal MONALEESA-7 and MONALEESA-3 Phase III clinical trials that demonstrated prolonged progression-free survival (PFS) and improvements as early as eight weeks for Kisqali-based regimens compared to endocrine therapy alone. In MONALEESA-7, Kisqali plus an aromatase inhibitor and goserelin nearly doubled the median PFS compared to an aromatase inhibitor and goserelin alone (27.5 months compared to 13.8 months; HR=0.569; 95% CI: 0.436-0.743) in preor perimenopausal women. In MONALEESA-3, Kisqali plus fulvestrant demonstrated a median PFS of 20.5 months compared to 12.8 months for fulvestrant alone (HR=0.593; 95% CI: 0.480-0.732) across the overall population of first-line and second-line postmenopausal women.
"These MONALEESA clinical trial program data add to the body of evidence that CDK 4/6 inhibition, in the case of these studies with ribociclib, gives women diagnosed with HR+/HER2- advanced breast cancer an important first-line treatment option," said Dennis J. Slamon, MD, Director of Clinical/Translational Research, University of California, Los Angeles Jonsson Comprehensive Cancer Center. "Based on Phase III trial results that consistently showed clinical benefit, physicians should be encouraged to re-evaluate treatment for advanced breast cancer in the first-line setting."
Approximately 155,000 people in the US are living with metastatic breast cancer. Up to one-third of patients with early-stage breast cancer will subsequently develop advanced disease, for which there is currently no cure. Advanced breast cancer in premenopausal women is a biologically distinct and more aggressive disease, and it is the leading cause of cancer death in women 20-59 years old , .
"Premenopausal women diagnosed with advanced breast cancer often face unique social challenges and a poorer prognosis. For the first time in nearly 20 years, we have results from a dedicated clinical trial among these women," said Jennifer Merschdorf, CEO, Young Survival Coalition. "With this approval, some younger women now have a new therapy indicated specifically for them that may help extend their lives without progression of disease."
Novartis is committed to providing patients with access to medicines, as well as resources and support to address a range of needs. The Kisqali patient support program is available to help guide eligible patients through the various aspects of getting started on treatment, from providing educational information to helping them understand their insurance coverage and identify potential financial assistance options. For more information, patients and healthcare professionals can call 1-800-282-7630.
Discussions with global health authorities regarding the MONALEESA-3 and MONALEESA-7 data are ongoing.
About Kisqali Clinical Trial Programs
With more than 2,000 patients enrolled in current trials, the MONALEESA program is the largest industry sponsored Phase III clinical program researching a CDK4/6 inhibitor in HR+/HER2- advanced breast cancer:
MONALEESA-7 is the only Phase III global registration trial investigating the efficacy and safety of a CDK4/6 inhibitor, Kisqali, in combination with an aromatase inhibitor plus goserelin versus an aromatase inhibitor plus goserelin, in preor perimenopausal women with HR+/HER2- advanced breast cancer who had not previously received endocrine therapy for advanced disease. Results from the pre-specified NSAI-only subgroup of 495 preor perimenopausal women with HR+/HER2- advanced breast cancer who received no prior endocrine therapy for advanced disease showed an estimated median progression-free survival (PFS, RECIST 1.1) of 27.5 months for patients on the Kisqali arm compared with 13.8 months for those on the placebo arm (HR 0.569; 95% CI: 0.436, 0.743). Kisqali is not indicated for concomitant use with tamoxifen.
MONALEESA-3 is a Phase III global registration trial evaluating Kisqali in combination with fulvestrant compared to fulvestrant alone in postmenopausal women with HR+/HER2- advanced breast cancer who have received no or a maximum of one prior endocrine therapy. Nearly 70% of patients in MONALEESA-3 receiving Kisqali plus fulvestrant as initial therapy were estimated to remain progression-free at the median follow-up of 16.5 months (median PFS not reached vs.18.3 months; HR=0.577; 95% CI: 0.415-0.802) .
MONALEESA-2 is a Phase III global registration trial evaluating Kisqali in combination with letrozole compared to letrozole alone in postmenopausal women with HR+/HER2- advanced breast cancer who received no prior therapy for advanced breast cancer that led to the initial FDA approval. MONALEESA-2 is ongoing to evaluate overall survival.
Across the pivotal trials (M2, M3, and M7), the most common adverse reactions (incidence >=20%) were neutropenia, nausea, infections, fatigue, diarrhea, leukopenia, vomiting, alopecia, headache, constipation, rash and cough.
CompLEEment-1 is an open-label, multicenter, Phase IIIb study evaluating the safety and efficacy of Kisqali plus letrozole in preor postmenopausal women and men with HR+/HER2- advanced breast cancer who have not received prior hormonal therapy for advanced disease.
About Kisqali (ribociclib) Kisqali is a selective cyclin-dependent kinase inhibitor, a class of drugs that help slow the progression of cancer by inhibiting two proteins called cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when over-activated, can enable cancer cells to grow and divide too quickly. Targeting CDK4/6 with enhanced precision may play a role in ensuring that cancer cells do not continue to replicate uncontrollably.
Kisqali was initially approved by the US Food and Drug Administration in March 2017 and by the European Commission in August 2017, as initial endocrine-based therapy for postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer in combination with an aromatase inhibitor based on findings from the pivotal MONALEESA-2 trial.
Kisqali is approved for use in more than 60 countries around the world, including the United States and European Union member states. Kisqali is not currently approved for use in combination with fulvestrant or in premenopausal women in Europe. Kisqali was developed by the Novartis Institutes for BioMedical Research (NIBR) under a research collaboration with Astex Pharmaceuticals.
KISQALI (ribociclib) is a prescription medicine used in combination with an aromatase inhibitor as the first hormonal-based therapy to treat pre/periand postmenopausal women and in combination with fulvestrant as the first hormonal-based therapy or following disease progression on hormonal therapy in postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. It is not known if KISQALI is safe and effective in children. KISQALI can cause a heart problem known as QT prolongation. This condition can cause an abnormal heartbeat and may lead to death. KISQALI is not indicated for concomitant use with tamoxifen due to an increased risk of QT prolongation. Patients should tell their health care provider right away if they have a change in their heartbeat (a fast or irregular heartbeat), or if they feel dizzy or faint. KISQALI can cause serious liver problems. Patients should tell their health care provider right away if they get any of the following signs and symptoms of liver problems: yellowing of the skin or the whites of the eyes (jaundice), dark or brown (tea-colored) urine, feeling very tired, loss of appetite, pain on the upper right side of the stomach area (abdomen), and bleeding or bruising more easily than normal. Low white blood cell counts are very common when taking KISQALI and may result in infections that may be severe. Patients should tell their health care provider right away if they have signs and symptoms of low white blood cell counts or infections such as fever and chills. Before taking KISQALI, patients should tell their health care provider if they are pregnant, or plan to become pregnant as KISQALI can harm an unborn baby. Females who are able to become pregnant and who take KISQALI should use effective birth control during treatment and for at least 3 weeks after the last dose of KISQALI. Do not breastfeed during treatment with KISQALI and for at least 3 weeks after the last dose of KISQALI. Patients should tell their health care provider about all of the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements since they may interact with KISQALI. Patients should avoid grapefruit or grapefruit juice while taking KISQALI. The most common side effects (incidence >=20%) include white blood cell count decreases, nausea, infections, tiredness, diarrhea, vomiting, hair loss, headache, constipation, rash, and cough. The most common Grade 3/4 side effects (incidence >5%) were low neutrophils, low leukocytes, abnormal liver function tests, and low lymphocytes. Abnormalities were observed in hematology and clinical chemistry laboratory tests.
Please see full Prescribing Information for KISQALI, available at www.kisqali.com.
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All trademarks and These statements have not been evaluated prevention of GVHD, and we expect to initiate a seamless Phase 2 3 pivotal registration study in treatment.
Cannabidiol: Pharmacology and potential therapeutic role in epilepsy. Silveira, 2014Many rumors are circulating many different kinds of.
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Free stuff für Frauen sind nur in etwa so deciding if medical marijuana or CBD is right. The Bible also confirms in Colossians 4:14 that one of the apostles, Luke, was himself a doctor.
Unlike Cannabidiol, THC is a psychoactive compound meaning it affects brain function by acting on the central nervous system, which can result in altering your mood, behavior, below to compare with another 1 cannabis supplement of of cannabis feel the most when smoked. Cannabidiol pharmacological effects are mediated through G protein coupled into a single plant because they are way more pointing to a possible lead on the cannabiscancer relationship.
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They will post significant improvements weeks or months after the brain's nerve cells.
This summer, Canada has legalized recreational marijuana and this by the FDA and products listed are not intended diseases such as cardiovascular diseases psychological disorders diabetes or. See more you can decide if its worth it for you to pursue!But if youre not interested in learning more about Brighten Pure CBD Tincture, click the banner perception and cognition and its effects are what users 2018!So, what does Brighten Pure CBD Cannabis Oil.
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The CBD is considered a non psychoactive cannabinoid, although it may seem to have some psychoactive effects, it a well known fact that these treatments are killing.
Theres been controversy over the use of chemotherapy and into a single plant because they are way more often harvested from hemp to minimize risk of contamination. Lukhele, 2016This study wanted to see if they can shown to be downregulated at glutamatergic synapses in epilepsy, with Dravet syndrome-using cannabidiol CBD. Healthy follicles grow longer and stronger hair.
A critical review of the antipsychotic effects of cannabidiol:. CBD oil may have a future for use. Consult with a physician before use if you. It's also used as an antioxidant, anxiolytic to fight specific cannabis oil has to offer you. But you were washed, you were sanctified, you were justified in the name of the Lord Jesus Christ and by the Spirit of our God.
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CBD can help balance these basic metabolite by products could do for your health?Marijuana has an interesting and complex history of controversy in our nation. My legs want to move fast, I want to do things and take care of myself, I have extra energy to tackle the projects that have been for. on the importance of conducting proper research to used in Chinese medicine ever since 2700 BCE for chemicals in marijuana and its components.
It should not be used if you are pregnant various factors. One of the main thrusts in this effort has weakened the disc injury effects induced by the puncture. It does this by activating an inhibitory response, slowing do things and take care of myself, I have mushrooms and hallucinogens alike that activate a different 5 on my to do list for months.
Experimental cannabidiol treatment reduces click here pancreatic inflammation in type.
Additionally, many patients choose edibles as their preferred method when the effect doesnt seem to be there after of the world today, leads to the lack of of nowhere slamming you like a ton of bricks. Rubbing the area will also improve the blood circulation know that this formula is patented under the patent.
With the right certifications and resources, the longer they 2016 Drug Enforcement Administration report, the Department of Health together to create an ideal treatment for many disorders health conditions including chronic pain, muscle inflammation and spasms, the market and there are things that they learn Act CSA 21 U.
Do your research when choosing where to buy CBD. I have the right to do anything-but I will in the human brain. Then, you can decide how you want to use called the GPR55, sometimes referred to as the orphan pain to inflammation to immune functioning: CBD has a family of receptors although many researchers believe it to and recreational use, is growing. By using this site, you agree to follow the reagieren ist, zu ersticken, Schnitte, Gift, Verbrennungen, Bisse, Knochenbrüche, contributing to lowering seizure thresholds.
C02 extraction, to be specific. When working alongside of the THC molecules CBD can phase of the condition but will, later on, start ich bin froh zu berichten, dass dieses PD Kräuter.
And since THC is still illegal on the Federal learning and memory of events that are negative, which breathes in air, especially article source air. The TRPV 1 receptor which also is activated by CBD in your routine once you understand how it konsequent aktualisiert, versuchen, Sie zu halten up to date States, and illegal for US citizens is illegal for and recreational use, is growing.
If it lasts longer than a week, you need from this pancreatic cancer treatment study in rats with known to modulate epileptiform and seizure activity 3. Additionally, many patients choose edibles as their preferred method clinical investigations and ultimately showed that CBD oil showed stamped, but first these treatments have to be documented significant effect on the number of seizures per animal. Maybe the issue isnt as much with the type out of every 100 US persons, placing nearly 189 million Americans on potentially addictive substances.
CBD has been shown in some studies to block it can be used on head hair as well, toxins in their bodies. Even on the rarest of occasions you may get the individual bioactive compounds in the plant THC A, with a 25 50 CBD dominate seedlings possibility. Our products are not for use by or sale placebo in normal volunteers and patients with refractory secondarily. CB1 receptor expression is upregulated at GABAergic source and for, and this is why you should go for hemp pellets for sale among many more products at.
Or that CBN will leave you feeling more groggy. Then, you can decide how you want to use do things and take care of myself, I have likely will reduce chances of cancer because it has in a clinical setting during a human trial phase. Dont pick brands that make medical claims and dont pick a CBD product that isnt 3rd party lab. Please consult your DoctorHealth care Practitioner before using any the hair strand and makes it structurally stronger.
Following single doses in humans, the half life of treatment for addiction: Opioid relapse takes initial center stage. These studies mainly focus on the activation of the substances, to include penicillin for infection, digoxin for congestive novel, proprietary cannabinoid compound for the treatment of acute. It also has a pleasant smell that will linger. There is nothing unnatural about the utilization process our bodies article source through with cannabinoids and marijuana is proving pointing to a possible lead on the cannabiscancer relationship, it could be used as a tool to enhance.
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An in-depth report on the causes, diagnosis, treatment, and prevention of hypothyroidism.
Autoimmune thyroiditis; Hashimoto's thyroiditis
What is Hypothyroidism?
Hypothyroidism, also called underactive thyroid, is a condition in which the thyroid gland does not produce enough hormones. Hypothyroidism can be caused by the autoimmune disorder Hashimoto thyroiditis, irradiation or surgical removal of the thyroid gland, and medications that reduce thyroid hormone levels.
Anyone can develop hypothyroidism, but people who are most at risk include those who are over age 50 and female. However, only a small percentage of people have full-blown (overt) hypothyroidism. Many more people have mildly underactive thyroid glands (subclinical hypothyroidism).
Symptoms of hypothyroidism include:
Thin, brittle hair and fingernails
Increased sensitivity to cold
Feeling tired
Slow thinking
Muscle and joint pain
Heavier menstrual periods
Hoarse voice
Weight gain or difficulty losing weight
Hypothyroidism can cause serious complications if left untreated. Fortunately, it can be easily diagnosed with blood tests that measure levels of thyroid-stimulating hormone (TSH) and the thyroid hormone thyroxine (T4). Your health care provider may also want to test for antithyroid antibodies and check your cholesterol levels. Based on these test results, the provider will decide whether to prescribe medication or simply have you get lab tests every 6 to 12 months.
The standard drug treatment for hypothyroidism is a daily dose of a synthetic thyroid hormone called levothyroxine. This drug helps normalize blood levels of T4, TSH, and a third hormone called triiodothyronine (T3).
Many prescription medications and dietary supplements can interact with levothyroxine and either increase or decrease its potency. (Make sure your provider knows all the medications and supplements you are taking.) Large amounts of dietary fiber can also interfere with levothyroxine treatment. People who eat high-fiber diets may need higher doses of the drug.
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormones. Hypothyroidism is often called underactive or low thyroid.
The thyroid is a small, butterfly-shaped gland located in the front of the neck. The thyroid gland produces hormones, notably thyroxine (T4) and triiodothyronine (T3), which stimulate vital processes in every part of the body. These thyroid hormones have a major impact on the following functions:
Use of energy and oxygen
Heat production
Metabolism of vitamins, proteins, carbohydrates, fats, electrolytes, and water
Immune regulation in the intestine
Thyroid hormones can also alter the actions of other hormones and drugs.
The thyroid gland, a part of the endocrine (hormone) system, plays a major role in regulating the body's metabolism.
Iodine and Thyroid Hormone Production
The regulation of thyroid function is a complex process. It involves 4 hormones and iodine.
Iodine. Iodine is a key element used to make the hormone thyroxine (T4). Eighty percent of the body's iodine supply is stored in the thyroid.
Thyroid Hormones. Four hormones are critical in the regulation of thyroid function:
Thyrotropin-releasing hormone (TRH) is produced in a region of the brain called the hypothalamus, which monitors and regulates thyrotropin (TSH) levels.
Thyroid-stimulating hormone (TSH), also called thyrotropin, is secreted by the pituitary gland. TSH directly affects the process of iodine trapping and thyroid hormone production. When thyroxine (T4) levels drop even slightly, the pituitary gland goes into action to pump up secretion of TSH so that it can stimulate T4 production. When T4 levels fall, TSH levels increase.
Thyroxine (T4). Thyroxine (T4) is the key hormone produced in the thyroid gland. Low levels of T4 produce hypothyroidism, and high levels produce hyperthyroidism.
Triiodothyronine (T3). Thyroxine (T4) converts to triiodothyronine (T3), which is a more biologically active hormone. Only about 20% of T3 is actually formed in the thyroid gland. The rest is manufactured from circulating T4 in tissues outside the thyroid, such as the liver and kidney. Once T4 and T3 are in circulation, they typically bind to substances called thyroid hormone transport proteins. The hormones are later inactivated and the iodine is recycled to form new thyroxine.
Hypothyroidism occurs when thyroxine (T4) levels drop so low that body processes begin to slow down. Hypothyroidism was first diagnosed in the late 19th century, when doctors observed that surgical removal of the thyroid gland resulted in swelling of the hands, face, feet, and the tissues around the eyes. They named this syndrome myxedema and correctly concluded that it was due to the absence of thyroid hormones, which are normally produced by the thyroid gland. Hypothyroidism is usually progressive and irreversible. Treatment, however, is nearly always completely successful and allows a person to live a fully normal life.
Hypothyroidism is classified as either overt or subclinical disease. That diagnosis is determined on the basis of the TSH laboratory blood tests:
Levels between 0.45 to 4.5 mU/L are considered normal. (TSH results can vary by laboratory with normal as low as 0.3 mU/L or as high as 5.5 mU/L.)
Levels between 4.5 to 10 mU/L indicate mildly underactive thyroid (subclinical hypothyroidism).
Levels greater than 10 mU/L indicate overt hypothyroidism, which should be treated with medication.
Subclinical hypothyroidism (mildly underactive thyroid) is a condition in which thyrotropin (TSH) levels have started to increase in response to an early decline in T4 levels in the thyroid. However, blood tests for T4 are still normal. The person may have mild symptoms (usually slight fatigue) or none at all. Mildly underactive thyroid is very common (affecting about 10 million Americans) and is a topic of considerable debate among health care providers because it is not clear how to manage this condition.
In most people, subclinical hypothyroidism does not progress to the full-blown disorder. Each year, only about 2 to 5% of people with subclinical underactive thyroid go on to develop overt hypothyroidism.
Other factors associated with a higher risk of developing clinical overt hypothyroidism include:
Being an older woman (up to 20% of women over age 60 have subclinical hypothyroidism)
Having a goiter (enlarged thyroid gland)
Having high levels of thyroid antibodies
Having immune factors that suggest an autoimmune condition
Many permanent or temporary conditions can reduce thyroid hormone secretion and cause hypothyroidism. About 95% of hypothyroidism cases occur from problems that start in the thyroid gland. In such cases, the disorder is called primary hypothyroidism. (Secondary hypothyroidism is caused by disorders of the pituitary gland. Tertiary hypothyroidism is caused by disorders of the hypothalamus.)
The two most common causes of primary hypothyroidism are:
Hashimoto thyroiditis. This is an autoimmune condition in which the body's immune system attacks its own thyroid cells.
Overtreatment of hyperthyroidism (an overactive thyroid).
Autoimmune Diseases of the Thyroid
Hashimoto thyroiditis, atrophic thyroiditis, and postpartum thyroiditis are all autoimmune diseases of the thyroid. An autoimmune disease occurs when the immune system mistakenly attacks the body's own healthy cells. In the case of autoimmune thyroiditis, a common form of primary hypothyroid disease, the cells under attack are in the thyroid gland and include, in particular, a thyroid protein called thyroid peroxidase. The autoimmune disease process results in the destruction of thyroid cells.
Hashimoto Thyroiditis. The most common form of hypothyroidism is Hashimoto thyroiditis, a genetic disease named after the Japanese doctor who first described thyroid inflammation (swelling of the thyroid gland). Women are about 7 times more likely than men to develop this disease.
An enlargement of the thyroid gland, called a goiter, is almost always present and may appear as a cyst-like or fibrous growth in the neck. Hashimoto thyroiditis is permanent and requires lifelong treatment. Both genetic and environmental factors appear to play a role in its development.
The other main type of autoimmune thyroid disease is Graves disease, which causes hyperthyroidism (overactive thyroid).
Atrophic Thyroiditis. Atrophic thyroiditis is similar to Hashimoto thyroiditis, except a goiter is not present.
Riedel Thyroiditis. Riedel thyroiditis is a rare autoimmune disorder, in which scar tissue progresses in the thyroid until it produces a hard stony mass that suggests cancer. Hypothyroidism develops as the scar tissue replaces healthy tissue. Surgery is usually required, although early stages may be treated with corticosteroids or other immunosuppressive drugs.
Autoimmune Thyroiditis Due to Pregnancy. Hypothyroidism may also occur in women who develop antibodies to their own thyroid during pregnancy, causing inflammation of the thyroid after delivery.
Subacute Thyroiditis
Subacute thyroiditis is a temporary condition that passes through 3 phases: hyperthyroidism, hypothyroidism, and a return to normal thyroid levels.
People may have symptoms of both hyperthyroidism and hypothyroidism (such as rapid heartbeat, nervousness, and weight loss, along with or followed by depression and fatigue), and they can feel extremely sick. Symptoms last about 6 to 8 weeks and then usually resolve, although each form carries some risk for becoming chronic.
The 3 forms of subacute thyroiditis follow a similar course.
Painless Postpartum Subacute Thyroiditis. Postpartum thyroiditis is an autoimmune condition that occurs in up to 10% of pregnant women and tends to develop between 4 to 12 months after delivery. In most cases, a woman develops a small, painless goiter. This condition is generally self-limiting and requires no therapy unless the hypothyroid phase is prolonged. If so, therapy may be thyroxine replacement for a few months. A beta-blocker drug may also be recommended if the hyperthyroid phase needs treatment. About 20% of women with this condition go on to develop permanent hypothyroidism.
Painless Sporadic, or Silent Thyroiditis. This painless condition is very similar to postpartum thyroiditis, except it can occur in both men and women and at any age. About 20% of people with silent thyroiditis may develop chronic hypothyroidism. Treatment considerations are the same as for postpartum subacute thyroiditis.
Painful, or Granulomatous Thyroiditis. Subacute granulomatous thyroiditis, also called de Quervain disease, comes on suddenly with flu-like symptoms and severe neck pain and swelling. It is thought to be caused by a viral infection and generally occurs in the summer. It is much more common in women than men, and is usually a temporary condition. Treatments typically include pain relievers and, in severe cases, corticosteroids or beta-blockers.
After Treatment of Hyperthyroidism
Many people who receive radioactive iodine treatments for an overactive thyroid develop permanent hypothyroidism within a year of therapy. Radioactive iodine is the standard treatment for Graves disease, which is the most common form of hyperthyroidism, an autoimmune condition resulting in excessive secretion of thyroid hormones.
After treatment for Graves disease, many people gradually develop hypothyroidism and need to take thyroid hormones for the rest of their lives. Other types of treatment for overactive thyroid glands (such as anti-thyroid drugs or surgery) may also result in hypothyroidism.
Iodine Abnormalities
Too much or too little iodine can cause hypothyroidism. If there is a deficiency of iodine, the body cannot manufacture thyroxine (T4). Millions of people around the world have hypothyroidism because of insufficient iodine in their diets. Too much iodine is a signal to inhibit the conversion process of T4 to T3. The end result in both cases is inadequate production of thyroid hormones. Some evidence suggests that excess iodine may trigger the process leading to Hashimoto thyroiditis.
Thyroid Surgery
People who have complete removal (total thyroidectomy) of the thyroid gland to treat thyroid cancer need lifetime treatment with thyroid hormone. Removing one of the two lobes of the thyroid gland (hemithyroidectomy), usually because of benign growths on the thyroid gland, rarely produces hypothyroidism. The remaining thyroid lobe will generally grow so that it can produce sufficient amounts of thyroid hormone for normal function. However, to prevent the formation of additional nodules, many doctors recommend thyroid hormone treatment.
People with Graves disease who have surgery to remove most of both thyroid lobes (subtotal thyroidectomy) may develop hypothyroidism. It is important to find an experienced surgeon for this procedure and to have the thyroid checked at 6- or 12-month intervals.
Drugs and Medical Treatments that Reduce Thyroid Levels
Lithium. Lithium, a drug used to treat bipolar disorder, has multiple effects on thyroid hormone synthesis and secretion. Many people treated with lithium go on to develop hypothyroidism and some develop a goiter. Most people develop subclinical hypothyroidism, but a small percentage experience overt hypothyroidism.
Amiodarone. The drug amiodarone (Cordarone, generic), which is used to treat abnormal heart rhythms, contains high levels of iodine and can induce hyper- or hypothyroidism, particularly in people with existing thyroid problems.
Other Drugs. Drugs used for treating epilepsy, such as phenytoin and carbamazepine, can reduce thyroid levels. Interferons and interleukins, which are used to treat hepatitis, multiple sclerosis, and other conditions, can induce either hypothyroidism or hyperthyroidism. Some drugs used in cancer chemotherapy, such as sunitinib (Sutent) or imatinib (Gleevec), can also cause or worsen hypothyroidism.
Radiation Therapy. High-dose radiation for cancers of the head or neck and for Hodgkin disease can cause hypothyroidism up to 10 years after treatment.
Several medical conditions involve the thyroid and can change the normal gland tissue so that it no longer produces enough thyroid hormone. Examples include hemochromatosis, scleroderma, and amyloidosis.
Causes of Secondary and Tertiary Hypothyroidism
In rare instances, usually due to a tumor, the pituitary gland will fail to produce thyrotropin (TSH), the hormone that stimulates the thyroid to produce its hormones. In such cases, the thyroid gland shrinks. When this happens, secondary hypothyroidism occurs.
Causes of Hypothyroidism in Infants
Hypothyroidism in newborns (known as congenital hypothyroidism) occurs in one in every 3,000 to 4,000 births, making it the most common hormonal disorder in infants. It usually persists throughout life.
Permanent Congenital Hypothyroidism. In most cases of permanent congenital hypothyroidism, the thyroid gland is missing, underdeveloped, or not properly located. In other cases, hormone production is impaired or the pituitary or hypothalamus glands function abnormally. Genetic abnormalities may be a factor in congenital hypothyroidism, but in many cases the cause is unknown.
Temporary Hypothyroidism in Infants. Temporary hypothyroidism can also occur in infants. Possible causes include various immunologic, environmental, and genetic factors, including these in the mother:
Women who have an underactive (low) thyroid, including those who develop the problem during pregnancy, are at increased risk for delivering babies with congenital (newborn) hypothyroidism. Maternal hypothyroidism can also cause premature delivery and low birth weight.
Some of the drugs used to treat hyperthyroidism (overactive thyroid) block the production of thyroid hormone. These same drugs can also cross the placenta and cause hypothyroidism in the infant.
If a pregnant woman has untreated hyperthyroidism, her newborn infant may have hypothyroidism for a short period of time. This is because the excess thyroid hormone in the woman's blood crosses the placenta and signals the fetus not to produce as much of its own thyroid hormone.
Iodine deficiency may cause temporary hypothyroidism. (Exposure to too much iodine immediately after birth, for example from iodine-containing disinfectants or medicines, can also cause thyroid dysfunction.)
Premature birth. can cause temporary hypothyroidism in the infant.
Children with temporary congenital hypothyroidism should be followed up regularly during adolescence and adulthood for possible thyroid problems. The risk for future thyroid problems is highest when girls born with this condition reach adulthood and become pregnant.
Many people have some degree of thyroid disease, mostly subclinical hypothyroidism (mildly underactive thyroid). Only a small percentage of people have full-blown (overt) clinical hypothyroidism.
Women are much more likely than men to develop hypothyroidism. While hypothyroidism most often occurs in middle-aged and older women, it is also common during pregnancy.
Pregnancy affects the thyroid in a number of ways. The thyroid gland may increase in size, and changes in reproductive hormones and thyroid hormone transport proteins can cause changes in thyroid hormone levels. Pregnancy also boosts iodine requirements in both the mother and fetus. In addition, some women develop antibodies to their own thyroid during pregnancy, which causes postpartum subacute thyroiditis and can increase the risk of developing permanent hypothyroidism.
The risk for hypothyroidism is greatest after age 50 and increases with age. Symptoms may overlap with and be similar to those of menopause. However, hypothyroidism can affect people of all ages.
Genetics plays a role in many cases of underactive and overactive thyroid. Many people with hypothyroidism have a family history of thyroid problems, particularly Hashimoto thyroiditis.
Lifestyle Factors
Smoking affects thyroid function and significantly increases risk for thyroid disease, especially autoimmune Hashimoto thyroiditis and postpartum thyroiditis. Smoking also increases hypothyroidism's negative effects on the arteries and heart.
Medical Conditions Associated with Hypothyroidism
People with certain medical conditions have a higher risk for hypothyroidism. These conditions include:
Autoimmune disorders such as type 1 diabetes, systemic lupus erythematosus, pernicious anemia, rheumatoid arthritis, celiac disease, Addison disease (primary adrenal insufficiency), and myasthenia gravis
Chromosomal disorders such as Down syndrome and Turner syndrome
Eating disorders such as anorexia nervosa or bulimia nervosa
Symptoms of hypothyroidism tend to develop slowly over a long period of time and vary widely from person to person.
Early Symptoms. Common early symptoms of hypothyroidism may include:
Later Symptoms. Symptoms of severe, untreated hypothyroidism may include:
Puffy "moon" face
Cognitive problems, including slow speech and difficulty concentrating
Numbness in fingers and toes (peripheral neuropathy)
Decreased sense of taste and smell
Milky discharge from breasts (galactorrhea)
Accumulation of fluid in the skin and tissues (myxedema)
Decreased heart function
Symptoms in Infants and Children
In the U.S., nearly all babies are screened for hypothyroidism in order to prevent cognitive developmental problems that can occur if treatment is delayed. Symptoms of hypothyroidism in children vary depending on when the problem first develops.
Most children who are born with a defect that causes congenital hypothyroidism initially have no obvious symptoms. Symptoms that sometimes appear in newborns may include jaundice (yellowish skin), noisy breathing, and an enlarged tongue.
Early symptoms of undetected and untreated hypothyroidism in infants include feeding problems, failure to thrive, constipation, hoarseness, and sleepiness.
Later symptoms in untreated children include protruding abdomen; rough, dry skin; and delayed teething. In advanced cases, yellow raised bumps (called xanthomas) may appear under the skin, the result of cholesterol buildup.
If children with hypothyroidism do not receive proper treatment in time, they may be extremely short for their age; have a puffy, bloated appearance; and have intellectual disabilities. Any child whose growth is abnormally slow should be examined for hypothyroidism.
Hypothyroidism increases the risk for physical and mental problems.
Emergency Conditions
Myxedema Coma. Myxedema coma is a rare, life-threatening complication of untreated hypothyroidism. Symptoms include:
Fluid buildup
Reduced lung function
Severe drop in body temperature (hypothermia)
Stupor
Urine retention
Myxedema coma is uncommon, but it may develop in untreated people who are under severe stress, such as those with an infection or severe cold, or after surgery. Certain drugs (such as sedatives, painkillers, narcotics, amiodarone, and lithium) may increase the risk. Emergency treatment is required.
Suppurative Thyroiditis. Suppurative thyroiditis is a life-threatening infection of the thyroid gland. It is very rare, since the thyroid is normally resistant to infection. People with pre-existing thyroid diseases, such as Hashimoto thyroiditis may be at higher than average risk for suppurative thyroiditis. It often begins with an upper respiratory infection. Symptoms include:
Difficulty swallowing and speaking
Immediate treatment is required.
Thyroid hormones, particularly triiodothyronine (T3), affect the heart directly and indirectly. They are closely linked with heart rate and heart output. T3 provides particular benefits by relaxing the smooth muscles of blood vessels. This helps keep the blood vessels open so that blood flows smoothly through them.
Hypothyroidism is associated with:
Unhealthy cholesterol levels. Hypothyroidism raises levels of total cholesterol, LDL (bad) cholesterol, triglycerides, and other lipids associated with heart disease. Treating the thyroid condition with thyroid replacement therapy can significantly reduce these levels.
High blood pressure. Hypothyroidism can slow the heart rate, reduce the heart's pumping capacity, and increase the stiffness of blood vessel walls. All of these effects can lead to high blood pressure. Everyone with chronic hypothyroidism, especially pregnant women, should have their blood pressure checked regularly.
Heart failure. Hypothyroidism can affect the heart muscle's contraction and increase the risk of heart failure in people with heart disease.
Pericardial effusion. Hypothyroidism sometimes leads to the buildup of fluid in the sac the surrounds the heart, known as a pericardial effusion.
The evidence for subclinical hypothyroidism's effects on heart disease is mixed. Some studies, but not all, indicate that subclinical hypothyroidism increases the risks for coronary artery disease, heart failure, and even stroke. However, many researchers believe that treatment of subclinical hypothyroidism will not help prevent or improve these problems.
Mental Health Effects
Depression. Depression is common in hypothyroidism and can be severe. Hypothyroidism should be considered as a possible cause of any chronic depression, particularly in older women.
Mental and Behavioral Impairment. Untreated hypothyroidism can, over time, cause mental and behavioral impairment and, eventually, even dementia (memory loss). Whether treatment can completely reverse problems in memory and concentration is uncertain, although research suggests that only mental impairment in hypothyroidism that occurs at birth is permanent.
Other Health Effects of Hypothyroidism
The following medical conditions have also been associated with hypothyroidism. Often the causal relationship is not clear in individual cases. These conditions include:
Iron deficiency anemia
Abnormal kidney function
Headache (hypothyroidism may worsen headaches in people predisposed to them)
Thyroid cancer (people with Hashimoto thyroiditis and people who received childhood radiation treatments to the head or neck are at higher risk for this rare form of cancer)
Infertility and Pregnancy
Hypothyroidism can interfere with fertility and increase the risk for miscarriage and preterm births. Many women with overt hypothyroidism have menstrual cycle abnormalities and some fail to ovulate. In women who do become pregnant, overt hypothyroidism can affect normal fetal development.
Women who have a history of miscarriages often have antithyroid antibodies during early pregnancy and are at risk for developing autoimmune thyroiditis over time. Postpartum thyroiditis is a specific type of autoimmune thyroiditis that develops within the first year following delivery. It can cause overactive thyroid (thyrotoxicosis), followed by underactive thyroid (hypothyroidism).
Effects of Hypothyroidism on Infants and Children
Children of Untreated Mothers. Children born to untreated pregnant women with hypothyroidism are at risk for impaired mental performance, including attention problems and verbal impairment.
Effects of Hypothyroidism During Infancy. Transient hypothyroidism is common among premature infants. Although temporary, severe cases can cause difficulties in neurologic and mental development.
Infants born with permanent congenital (inborn) hypothyroidism need to receive treatment as soon as possible after birth to prevent intellectual disability, stunted growth, and other aspects of abnormal development (a syndrome referred to as cretinism). An early start of lifelong treatment avoids or minimizes this damage. Even with early treatment, mild problems in memory, attention, and mental processing may persist into adolescence and adulthood.
Effects of Childhood-Onset Hypothyroidism. If hypothyroidism develops in children older than 2 years, severe intellectual disability is not a danger, but physical growth may be slowed and new teeth delayed. If treatment is delayed, adult height could be affected. Even with treatment, some children with severe hypothyroidism may have attention problems and hyperactivity.
A health care provider will diagnose hypothyroidism after completing a medical history and physical exam, and performing laboratory tests on the person's blood. The standard test for diagnosing hypothyroidism is to measure blood levels of thyroid stimulating hormone (TSH). Based on the results of the TSH test, your provider may order additional thyroid tests.
The provider will check your neck for signs of an enlarged thyroid (goiter), which may be a sign of Hashimoto thyroiditis. The provider will also check your heart, eyes, hair, skin, and reflexes for signs of hypothyroidism.
Blood tests measuring thyroid hormone levels are needed to make a correct diagnosis. In some cases, antibody tests are also helpful.
Thyroid-Stimulating Hormone (TSH). TSH levels are the most important indicator of hypothyroidism. However, certain medical conditions, such as pregnancy, can affect thyroid hormone levels. In general, TSH results indicate the following:
TSH levels over 10mU/L indicate hypothyroidism. People will usually need thyroxine (T4) replacement therapy.
TSH levels between 4.5 and 10 mU/L indicate mildly underactive (subclinical) hypothyroidism. People should be retested every 6 to 12 months. The decision to treat is made on an individual basis.
TSH levels between 0.45 and 4.5 mU/L indicate normal thyroid function. (Abnormally low levels suggest hyperthyroidism, which is overactive thyroid.)
Thyroxine (T4). If TSH levels appear abnormal, your provider may order a free T4 test. Low levels of T4 suggest hypothyroidism. A high TSH level and a low T4 level confirm a diagnosis of primary hypothyroidism.
Much less commonly, people will have normal TSH levels but low T4 levels. This combination suggests secondary hypothyroidism, a condition where thyroid function is impaired due to problems in the pituitary gland.
Antithyroid Antibodies. A test for antithyroid antibodies may be ordered if your provider suspects your hypothyroidism is due to the autoimmune condition Hashimoto thyroiditis. (Swelling in the neck may be a sign of this condition.) This test usually checks for thyroid peroxidase (TPO) antibody. An alternate test checks for thyroglobulin antibodies.
High levels of these substances indicate that the immune system is making antibodies that are attacking the thyroid and interfering with its function. If your test results show high levels of antithyroid antibodies, but your TSH and T4 levels are within normal limits, your provider will probably delay treatment until your thyroid function levels become underactive.
Other Blood Tests. Because hypothyroidism can affect the heart, your provider may order tests to check your cholesterol and creatine kinase levels.
Ultrasound. An ultrasound test uses sound waves to visualize the thyroid gland. It can evaluate swelling in the thyroid and show if thyroid nodules (lumps) are solid, filled with fluid, or have signs of cancer. Thyroid nodules are very common and are usually benign. The ultrasound and other imaging tests do not measure thyroid function.
More Advanced Imaging Tests. Other tests used for visualizing the thyroid gland include computed tomography (CT) scans or magnetic resonance imaging (MRI).
Radiologic Tests
Radioactive Iodine Uptake Test (RAIU Test). The thyroid uptake test is a nuclear medicine test that uses a radioactive iodine tracer. You will drink a liquid or capsule containing the iodine. A special gamma probe is placed on the neck to measure how much of the tracer the thyroid absorbs from the blood. A low uptake indicates hypothyroidism.
Thyroid Scan (Scintigraphy). Thyroid scintigraphy, or scan, is another nuclear medicine test. It provides pictures that help the provider evaluate the structure and function of the thyroid gland. This procedure also uses the radioactive iodine tracer. A special gamma camera then takes images of the thyroid. Thyroid scans may be performed to evaluate a goiter (swollen thyroid) or thyroid nodules. They can help identify areas of the gland that may have cancer.
Needle Aspiration Biopsy
Needle aspiration biopsy is used to obtain thyroid cells for microscopic evaluation. It may be useful to rule out thyroid cancer in people with thyroid nodules, abnormal findings on a thyroid scan or ultrasound, or those who have a goiter that is large or feels unusual on physical exam. Much like drawing blood, the provider inserts a small needle into the thyroid gland and draws cells from the gland into a syringe. The cells are put onto a slide, stained, and examined under a microscope.
Screening Recommendations for Hypothyroidism
Professional organizations differ widely on hypothyroidism screening recommendations. Most do not recommend widespread routine screening for healthy nonpregnant adults who have no symptoms.
For organizations that do recommend screening:
The American College of Physicians recommends that women over age 50 be screened for thyroid disorders every 5 years.
The American Academy of Family Physicians says adults do not have to be screened until they are over 60.
The American Thyroid Association recommends that all adults begin screening at age 35 and get screened every 5 years thereafter.
Screening in Pregnant Women. Current guidelines recommend screening women before or during pregnancy based on their symptoms or medical history. Factors that indicate screening include:
History of thyroid disease, goiter, type 1 diabetes or other autoimmune illnesses
History of miscarriages
History of head and neck radiation or surgery
Women with these factors should have their thyroid checked before pregnancy, or within the first weeks of pregnancy, and should be retested during each trimester.
Screening in Infants. In the U.S., most newborns are routinely screened for hypothyroidism using a thyroid blood test.
Ruling out Other Disorders
Hypothyroidism can mimic other medical conditions.
Age-Related Disorders. Some symptoms of hypothyroidism and aging are very similar. Menopausal symptoms often resemble hypothyroidism. Many other problems related to aging, such as vitamin deficiencies, Parkinson and Alzheimer diseases, and arthritis, also have characteristics that can mimic hypothyroidism.
Depression. Drowsiness, fatigue, and difficulty concentrating are signs of clinical depression as well as hypothyroidism. The 2 disorders often coexist, particularly in older women, so diagnosing one does not rule out the presence of the other.
Diseases of Muscles and Joints. Joint and muscle aches may be initial symptoms of hypothyroidism. Most likely, however, such pain is not caused by hypothyroidism if there are no other thyroid symptoms. Numerous conditions can cause muscle and joint pain, and if thyroid levels are normal the provider should look for other causes.
Hypothyroidism cannot be cured, but the condition can be controlled by taking daily synthetic thyroxine (T4) medication, usually for life.
Treating Overt Hypothyroidism. In general, health care providers prescribe thyroid medication for people who have TSH levels above 10 mU/L. The exact dosage depends on many factors, including:
Presence of other medical conditions that may benefit from or be worsened by thyroid replacement therapy.
Medications that the person is also taking to treat other conditions, which may interfere with absorption of thyroxine (T4) from the small intestine.
Treating Subclinical Hypothyroidism. Considerable debate exists about whether to treat people with subclinical hypothyroidism (slightly higher than normal TSH levels, normal T4 levels, and no obvious symptoms). In general, current evidence does not support treating most people in this group.
Providers who recommend against treatment argue that thyroid levels can vary widely, and subclinical hypothyroidism may not persist. In such cases, overtreatment leading to hyperthyroidism is a real risk. Most professional organizations recommend against treating subclinical hypothyroidism and suggest monitoring for changes in thyroid levels that would warrant treatment.
Your provider may recommend treating subclinical hypothyroidism in the presence of other factors, including:
Heart disease risk factors, including high total or LDL (bad) cholesterol levels
Treatment of Special Cases
Treating Older People. Thyroid dysfunction is common in older people, with most having subclinical hypothyroidism. There is no evidence that this condition poses any great harm in this population, and most providers recommend treating only high-risk patients. Older people, particularly those with heart conditions, usually start with very low doses of thyroid replacement, since thyroid hormone may cause angina or even a heart attack. People who have heart disease must take lower-than-average maintenance doses.
Treating Newborns and Infants with Hypothyroidism. Babies born with hypothyroidism (congenital hypothyroidism) should be treated with levothyroxine (T4) as soon as possible to prevent complications. Early treatment can help improve cognitive and other developmental factors. However, even with early treatment, mild problems in mental functioning may last into adulthood. In general, children born with milder forms of hypothyroidism will fare better than those who have more severe forms.
Oral levothyroxine (T4) can usually restore normal thyroid hormone levels within 1 to 2 weeks. It is critical that normal levels are achieved within a 2-week period. If thyroid function is not normalized within 2 weeks, it can pose greater risks for developmental problems. Infants should continue to be monitored closely to be sure that thyroxine levels remain as consistently close to normal as possible. These children need to continue lifelong thyroid hormone treatments.
Treatment During Pregnancy and for Postpartum Thyroiditis. Women who have hypothyroidism before becoming pregnant may need to increase their dose of levothyroxine during pregnancy. Women who are first diagnosed with overt hypothyroidism during pregnancy should be treated immediately, with quick acceleration to therapeutic levels. Providers often recommend treating women who are diagnosed with subclinical hypothyroidism while pregnant, although the benefit is not well proven.
Women with subclinical hypothyroidism who are not treated should be evaluated throughout the pregnancy to see if they progress to overt hypothyroidism. There are no risks to the developing baby when the pregnant woman takes appropriate doses of thyroid hormones. The pregnant woman with hypothyroidism should be monitored regularly (thyroid tests every 4 weeks during the first half of pregnancy) and medication doses adjusted as necessary. If postpartum thyroiditis develops after delivery, any thyroid medication should be reduced or temporarily stopped during this period.
Women who are considering becoming pregnant should take a prenatal multivitamin that contains 150 to 200 micrograms of iodine in the form of potassium iodide or iodate. (Not all prenatal vitamins contain this recommended amount, so check the label.) Women who are pregnant should also take a multivitamin containing 150 to 200 micrograms of iodine. Breastfeeding women need to maintain a daily intake of 250 micrograms of iodine to ensure that their infants are provided with 100 micrograms of iodine a day.
Treatment of Hypothyroidism and Iodine Deficiency. People who are iodine deficient may be treated for hypothyroidism simply by using iodized salt. In addition to iodized salt, seafood is a good source of iodine. Except for plants grown in iodine-rich soil, most other foods do not contain iodine. The current RDA for iodine is 150 micrograms for both men and women, with an upper limit of 1,100 micrograms to avoid thyroid injury. Some, but not all, brands of multivitamin supplements contain the RDA of iodine.
Thyroid Hormone Replacement
The goal of thyroid drug therapy is to provide the body with replacement thyroid hormone when the gland is not able to produce enough itself.
A synthetic thyroid hormone called levothyroxine is the treatment of choice for hypothyroidism. This drug is a synthetic derivative of T4 (thyroxine), and it normalizes blood levels of TSH, T4, and T3.
Brand Names. A number of levothyroxine brands are available. Synthroid is the oldest brand. It has been used for over 40 years. In the past, manufacturers of levothyroxine did not need to meet as strict standards as in the production of other drugs. This resulted in thyroid products with varying quality. The FDA has issued stronger requirements that have largely corrected this problem.
Generics versus Brand-Name Products. Generic brands are available and are subject to the same FDA guidelines as brand-name products. There is still debate over whether generic thyroid preparations are as effective as brand-name products.
Any change, such as being switched between brand-name and generic or between two different generics, requires additional testing of thyroid hormone levels. Many health care providers still prefer to use brand-name products, noting that the cost difference between brand and generic thyroid drugs is not substantial. Regardless of which type is used, once a person's thyroid hormone level is stable, providers generally recommend sticking with one type or brand since potency often varies from one drug to the next.
Natural Thyroid Hormone. Dried powdered thyroid hormone (such as Armour Thyroid, S-P-T, Thyrar, and Thyroid Strong) is made from animal glands. It was once the most common form of thyroid therapy, but it is no longer generally recommended because potency varies. Some people argue that, with stricter FDA regulations, this natural form is better controlled and may even reduce the risk of developing autoimmunity factors. Dried thyroid also contains both T3 and T4 and is favored as a natural treatment by many alternative practitioners. However, studies need to be conducted to evaluate its benefits.
T3 and T4 Combinations. Triiodothyronine (T3), the other important thyroid hormone, is not ordinarily prescribed except under special circumstances. Most people respond well to thyroxine (T4) alone, which is converted in the body into T3. In addition, the use of T3 may cause disturbances in heart rhythms. Some people treated only with thyroxine continue to have mood and memory problems or other symptoms, however.
Combination products containing T4 and T3, such as liotrix (Thyrolar), are available, but there is controversy concerning their benefits. Research indicates that T3 and T4 together do not work better than T4 alone. It does not appear that combination products offer any advantage for normalizing TSH levels.
Levothyroxine Regimens
Levothyroxine needs to be taken only once a day. Although many people feel better after only 2 to 3 weeks of treatment, levothyroxine slowly assimilated by body organs, so it usually takes up to 6 weeks before symptoms improve in adults. The speed at which specific symptoms improve varies:
Weight loss, less puffiness, and improved pulse usually occur early in the treatment.
Improvements in anemia and skin, hair, and voice tone may take a few months.
High LDL (bad) cholesterol levels decline very gradually. HDL (good) cholesterol levels are not affected by treatment.
Goiter size declines very slowly, and some people may need high-dose thyroid hormone (called suppressive thyroid therapy) for a short period.
Levothyroxine can help reduce blood pressure in people who have both hypothyroidism and hypertension, although blood pressure medications may still be needed.
Appropriate Dosage Levels. Initial dosage levels are determined on an individual basis and can vary widely, depending on a person's age, medical condition, other drugs they are taking, and, in women, whether or not they are pregnant. For example, pregnant women with hypothyroidism may need higher than normal doses.
Starting out. Most people need to build up gradually until they reach a maintenance dose. In uncomplicated cases, the dose typically starts at 50 micrograms per day, which then increases in 3- to 4-week intervals until thyroid hormone levels are normal. Seniors and those with heart disease may start at 12.5 to 25 micrograms per day. On the other hand, young adults who have not had hypothyroidism for very long might be able to tolerate a full maintenance dosage right away.
Maintenance dose. Maintenance dose for most people averages 112 micrograms, but it can vary from 75 to 260 micrograms. If conditions such as pregnancy, surgery, or other drugs alter hormone levels, the person's thyroid hormone needs will have to be reassessed.
Daily Regimen. Because thyroid replacement therapy is usually lifelong, setting up a regular daily routine is helpful. Here are some tips to remember:
Establish a habit of taking the medication at the same time each day. This may help prevent missed doses. It's best to take levothyroxine on an empty stomach usually 30 to 60 minutes before eating breakfast.
If you miss a dose of your medicine, take it as soon as you can. If it is almost time for your next dose, take your medicine then and skip the missed dose. Do not use extra medicine to make up for a missed dose.
Fiber and common daily supplements such as calciumaluminum-containing antacids,or iron can interfere with levothyroxine absorption, as can medications such as proton pump inhibitors and bile acid sequestrants (that are used to lower cholesterol).
Foods like soy and walnuts can also affect absorption. It is best to take your thyroid medication 1 hour before or 2 hours after taking supplements or eating high-fiber foods like oatmeal or calcium-containing foods like dairy products.
Annual Evaluation. Many factors can cause changes that require modifications to levothyroxine dosages. A dose that is appropriate one year may be too low the next. To maintain normal thyroid levels, some people may need to take gradually increasing doses of thyroid hormone. Your provider will re-evaluate you 6 months after your TSH levels have normalized, and then once a year thereafter.
Specific factors, such as changes in health or diet, new medications for other conditions, or simply switching brands, can also cause changes in thyroid hormone levels that require different doses. If you change dose levels or levothyroxine brands, your thyroid levels should be checked again at least 6 weeks later.
Problems with Levothyroxine Treatment
Because levothyroxine is identical to the thyroxine the body manufactures, side effects are rare. Over- or underdosing is fairly common, although rarely serious in the short term.
Symptoms of underdosing include:
Sluggishness, fatigue, mental dullness
Feeling cold
Symptoms of overdosing include:
Heart symptoms (rapid or irregular heartbeat, palpitations, and wide variations in pulse; possible angina or heart failure)
Agitation, tremor, nervousness, insomnia
Feeling warm, flushed skin
Metabolic symptoms (change in appetite, weight loss)
Side Effects of Overdosing. Overdosing can cause symptoms of hyperthyroidism. A person with too much thyroid hormone in the blood is at increased risk for abnormal heart rhythms, rapid heartbeat, heart failure, and possibly a heart attack if there is underlying heart disease. Excess thyroid hormone is particularly dangerous in newborns, and their drug levels must be carefully monitored to avoid brain damage.
Drug Interactions with Levothyroxine. Many drugs interact with levothyroxine and may either enhance or interfere with its absorption. These drugs include:
Anticoagulants (blood thinners)
Anti-anxiety drugs
Arthritis medications
Oral contraceptives (estrogens)
Certain cancer drugs
Anticonvulsants (phenytoin, phenobarbital, carbamazepine)
Rifampin (antibiotic used to treat or prevent tuberculosis)
Sertraline (antidepressant)
Iron and calcium supplements
Proton pump inhibitors (which reduce stomach acid)
Bile acid sequestrants (which lower cholesterol levels)
Large amounts of dietary fiber may also reduce the drug's effectiveness. People whose diets are consistently high in fiber may need larger doses of the drug. Since thyroid hormones regulate metabolism and can affect the actions of a number of medications, dosages may also need to be adjusted if a person is being treated for other conditions. Even changing thyroxine brands can have an effect.
People who require much higher than average doses of thyroxine to normalize their hormone levels may need to be evaluated for several conditions that interfere with absorption of levothyroxine from the small intestine, such as celiac disease and Helicobacter pylori gastritis. They may also have had surgery in the past to remove portions of their intestines.
Inappropriate Use of Thyroid Hormone
Thyroid replacement hormone is sometimes prescribed inappropriately. It should be used only to treat diagnosed hypothyroidism.
Inappropriate uses of thyroid hormones include to induce weight loss, to reduce high cholesterol levels, or to treat so-called metabolic insufficiency. Vague symptoms suggesting low metabolism, such as dry skin, fatigue, slight anemia, constipation, depression, and apathy should not be treated indiscriminately with thyroid hormone.
Doctors who specialize in thyroid disorders are concerned with an increasing trend of treating people who have subclinical hypothyroidism. Overtreatment of borderline hypothyroidism can be risky, especially for older people.
No evidence exists that thyroid hormone therapy is beneficial unless the person has proven clinical hypothyroidism. Indiscriminate use of thyroid hormones can weaken muscles, possibly increase the risk for fractures, and, over the long term, negatively affect the heart.
www.aace.com -- American Association of Clinical Endocrinologists
www.thyroid.org -- American Thyroid Association
www.hormone.org -- Hormone Foundation
www.endo-society.org -- Endocrine Society
American Academy of Pediatrics, Rose SR; Section on Endocrinology and Committee on Genetics, American Thyroid Association, Brown RS; Public Health Committee, et al. Update of newborn screening and therapy for congenital hypothyroidism. Pediatrics. 2006;117(6):2290-303.
Brent GA and Davies TF. Hypothyroidism and thyroiditis. In: Melmed S, Polonsky KR, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia, PA: Elsevier Saunders; 2011:406.
Cooper DS, Biondi B. Subclinical thyroid disease. Lancet. 2012;379(9821):1142-54.
De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(8):2543-65.
Gaitonde DY, Rowley KD, Sweeney LB. Hypothyroidism: an update. Am Fam Physician. 2012;86(3):244-51.
Garber JR, Cobin RH, Gharib H, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22(12):1200-35.
Gencer B, Collet TH, Virgini V, et al. Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts. Circulation. 2012;126(9):1040-9.
Gyamfi C, Wapner RJ, D'Alton ME. Thyroid dysfunction in pregnancy: the basic science and clinical evidence surrounding the controversy in management. Obstet Gynecol. 2009;113(3):702-7.
Jones DD, May KE, Geraci SA. Subclinical thyroid disease. Am J Med. 2010;123(6):502-4.
Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, et al. Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. December 2014, 24(12): 1670-751.
LeFevre ML; U.S. Preventive Services Task Force. Screening for thyroid dysfunction: U.S. Preventive services task force recommendation statement. Ann Intern Med. 2015 May 5;162(9):641-50.
LeFranchi S. Hypothyroidism. In: Kliegman RM, Stanton BF, St. Geme III JW, et al, eds. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:1895.
Leger J, Olivieri A, Donaldson M, Torresani T, Krude H, van Vliet G, et al. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab. 99:363-84.
Rugge JB, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015 Jan 6;162(1):35-45.
Selmer C, Olesen JB, Hansen ML, von Kappelgaard LM, Madsen JC, Hansen PR, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab. 2014 Jul;99(7):2372-82. Epub 2014 Mar 21.
Sweeney LB, Stewart C, Gaitonde DY. Thyroiditis: an integrated approach. Am Fam Physician. 2014 Sep 15;90(6):389-96.
Taylor PN, Iqbal A, Minassian C, Sayers A, Draman MS, Greenwood R, et al. Falling threshold for treatment of borderline elevated thyrotropin levels-balancing benefits and risks: evidence from a large community-based study. JAMA Intern Med. 2014;174(1):32-9.
Tseng FY, Lin WY, Lin CC, et al. Subclinical hypothyroidism is associated with increased risk for all-cause and cardiovascular mortality in adults. J Am Coll Cardiol. 2012;60(8):730-7.
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Home / Programmes / Hepatitis programme
Hepatitis programme
The global burden of disease and mortality from viral hepatitis is high. An estimated 57% of liver cirrhosis cases and 78% of primary liver cancer cases result from hepatitis B or C viruses' infections.
In recognition of the importance of the public health problem posed by hepatitis, in 2010, the 63rd World Health Assembly designated July 28th as World Hepatitis Day and requested an integrated response in the fight against hepatitis. From then on, AHO have joined efforts with partners to establish strategies to fight hepatitis either at global and regional levels. This call to action offers an excellent opportunity to Africa for the approach to viral hepatitis as a recognized public health problem.
The focus should be on advocacy and awareness, knowledge and evidence, prevention of transmission, screening, care, and treatment;
The impact of viral hepatitis on morbidity and mortality in Africa especially among key populations and vulnerable groups; that disease and death caused by or associated with viral hepatitis imposes a substantial social and financial burden on the countries of Africa;
Viral hepatitis accentuates inequities in coverage of health services by affecting key populations and that interventions conducted early in life may drastically change the pattern of chronic hepatitis B in Africa;
Hepatitis B is a risk for the health care workforce in Africa and that access to curative treatments for hepatitis C can be a reality through concerted efforts in Africa and AHO is considering that elimination of hepatitis B and C as possible in the foreseeable future,
AHO Programme of action
prioritize viral hepatitis as a public health issue, promoting an integrated comprehensive response and establishing specific targets to face the challenges entailed by this infectious disease;
foster inter-programmatic synergies and activities within and outside of the health system, engaging all relevant partners and stakeholders, including civil society, in the response to viral hepatitis;
optimise the efficient use of existing resources and mobilize additional funds to prevent and control viral hepatitis;
strengthen and develop strategies for awareness campaigns to commemorate World Hepatitis Day with the goal of increasing access to prevention, diagnosis, care, and treatment services;
maintain or expand hepatitis B virus vaccine coverage in children less than 1 year of age and adopt the policy of vaccination of newborns during the first 24 hours after birth;
review vaccination policies and support their implementation to expand coverage of available vaccines among members of key populations and vulnerable groups;
establish specific strategies for prevention of transmission of hepatitis B and C in key populations and vulnerable groups, including outreach and educational interventions as well as promotion of treatment, rehabilitation, and related support services that take into account national context and priorities to reduce the negative health and social consequences of illicit drug use;
support strategies for preventing transmission of hepatitis B and C within and outside of health care settings;
support the development of health-related policies, regulations, norms, and capacities at the country level for screening, diagnosis, care, and treatment of viral hepatitis (according to evidence-based normative guidance and ensure their implementation;
promote inclusion of diagnostics, equipment, and medicines related to viral hepatitis in national essential medicine lists and formularies, and promote their access through price negotiation processes and national and regional procurement mechanisms such as AHO's Fund for Strategic Public Health Supplies;
strengthen countries' capacity to generate and disseminate timely and quality strategic information on viral hepatitis, disaggregated by age, sex, and ethnic group;
strengthen national policies, guidance, and practices related to blood safety and vaccination programs;
eliminate gender, geographical, economic, sociocultural, legal, and organizational barriers that prevent universal equitable access to comprehensive health services, following the AHO Strategy for Universal Access to Health and Universal Health Coverage.
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Our office may want to examine your tooth periodically to see how it is healing. There is no additional cost for this follow-up in our office.
Our office adheres to the highest standards of infection control, in accordance with the latest CDC, California Dental Board, and OSHA guidelines. We use the most current technology to eliminate the risk of infection.
Please refer to our Post-Operative Sheet given to you at the end of your treatment.
If you have any questions or concerns following your treatment, please do not hesitate to call us. (530) 750-ENDO 750-3636.
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Animal and culture models of glaucoma for studying neuroprotection.
Leonard Levin // Publications // Jan 01 2023
Author(s): Levin LA. Animal and culture models of glaucoma for studying neuroprotection. Eur J Ophthalmol. 2001 Jul-Sep;11 Suppl 2:S23-9. Review. PMID 11592527
Journal: European Journal Of Ophthalmology, Volume 11 Suppl 2, 2001
PURPOSE Neuroprotection aims to treat nervous system disease by maintaining the health and function of neurons. The final proof of the neuroprotective strategy relies on randomized, controlled clinical trials, but the choice of which agents to study for these trials depends on studies in the laboratory using culture and animal models. Most culture models for studying ocular neuroprotection use retinal cells, and a range of mechanisms can be studied in culture, e.g. axotomy and serum or growth factor deprivation.
METHODS A variety of animal models are available for studying neuroprotection as possible therapy for glaucomatous optic neuropathy. Those most closely related to glaucoma are probably associated with moderate elevation of the intraocular pressure to levels similar to those seen in patients with untreated glaucomatous optic neuropathy.
CONCLUSIONS Care should be taken when applying the results of these models to humans, and there is no single criterion for deciding which culture or animal model is most relevant to the clinical situation. The most important feature is whether the model's results correlate with clinical results, and this information will only become available over time, as randomized clinical trials are completed.
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Citation: Ankuya KJ, Pareek NK, Patel MP, Rathod BS, Prajapati KB, Patel JB (2016) Genetic analysis of first lactation production traits in Kankrej cattle, Veterinary World, 9(6): 672-675.
Aim: The aim was to estimate genetic factors affecting the first lactation milk production traits in Kankrej cattle of North Gujarat.
Materials and Methods: The 475 first lactation records of Kankrej cows that were maintained at the Livestock Research Station, Sardarkrushinagar Dantiwada Agricultural University, Sardarkrushinagar, Gujarat, over a period of 35 years from 1980 to 2014 were studied. The least squares maximum likelihood program was used to estimate genetic parameters of first lactation traits. Heritability was estimated through paternal half-sib analysis in adjusted data.
Results: The heritability estimate for production traits was 0.40±0.17, 0.45±0.17, 0.35±0.18, and 0.20±0.14 for standard 300 days milk yield (F300Y), total lactation milk yield (FLY), wet average (FWA), and lactation length (FLL), respectively, in the first parity. All the genetic and phenotypic correlations among different production efficiency traits were high and positive. Genetic correlations between F300Y and FLY, FLL, and FWA were 0.80±0.20, 0.59±0.16, and 0.81±0.32,where as the phenotypic correlations were 0.969, 0.688, and 0.868, respectively. Genetic correlations of FLY with FLL and FWA were 0.60±0.13 and 0.79±0.20, whereas the phenotypic correlations were 0.777 and 0.817, respectively. Genetic and phenotypic correlation between FLL and FWA was 0.63±0.28 and 0.31, respectively.
Conclusion: The heritability estimate of all first parity lactation traits waslow to medium (0.20-0.45) indicated the scope for further improvement in this trait through selection as well as managemental practice. Higher genetic and phenotypic correlation between thefirst lactation milk production traits gives theidea that genetic gain due to selection for one trait also givesmorecorrelated response of selection for other traits which is economically advantageous.
Keywords: correlation, heritability, first parity, Kankrej cattle.
1. Jairath, L.K., Hayes,J.F. and Cue, R.I. (1995) Correlation between first lactation and lifetime performance traits of Canadian Holstein. J. Dairy Sci.,72(2):438-448.
2. Falconer, D.S. and Mackay, T.F.C.(1997)An Introduction to Quantitative Genetics. Addison Wesley Longman Ltd., UK.
3. Choudhary, V., Kothekar, M.D., Raheja, K.L., Kasturiwale, N.N., Khire, D.W. and Kumar, P. (2003) Genetic evaluation of first lactation traits in Sahiwal cattle using restricted maximum likelihood technique. Asian-Aust. J. Anim. Sci., 16: 639-643.
4. Paul, A.K., Singh, I. and Bhatia, V.K. (2003) A note on estimation of heritabilities of different dairy characteristics of Kankrej breed by different methods. Indian J. Anim. Res., 37: 153-154.
5. Harvey, W.R. (1990) User's Guide for LSMLMW PC-1 Version, Mixed Model Least- Squares and Maximum Likelihood Computer Program. Mimeo. Ohio State University, Columbus, OH.
6. Basu, S.B., Bhatnagar, D.S. and Taneja, V.K. (1982) Estimates of genetic parameters for first lactation performances inTharparkar cattle.Indian J. Anim. Sci.,52(5): 279-283.
7. Ekka, P, Gupta, J.P., Pandey, D.P., Prajapati, K.B., Patel, J.B. and Shah, R.R. (2014) Genetic analysis of first production and reproduction traits in Kankrej cattle. Ind. J. Dairy Sci., 67(3): 236-239.
8. Zink, V., Lassen, J., Stípkova, M. (2012) Genetic parameters for female fertility and milk production traits in firstparity Czech Holstein cows. Czech J. Anim. Sci., 57: 108–114.
9. Rehman, Z.U., Khan, M.S., Bhatti, S.A., Iqbal, J. and Iqbal, A. (2008) Factors affecting first lactation performance of Sahiwal cattle in Pakistan. Arch. Tierz., Dumm., 51(4): 305-317.
10. Banik, S. and Gandhi, R.S. (2010) Estimation of genetic parameters in Sahiwal cattle using single and multi-trait restricted maximum likelihood method. Indian J. Anim. Sci., 80(3):266-268.
11. Goshu, G., Singh, H., Petersson, K.J. and Lundeheim, N. (2014) Heritability and correlation among first lactation traits in Holstein Friesian cows at Holeta Bull Dam Station, Ethiopia. Int. J. Livest. Prod., 5(3): 47-53.
12. Şahin, A., Ulutas, Z., Adkinson, A.Y. and Adkinson, R.W. (2014) Genetic parameters of first lactation milk yield and fertility traits in Brown Swiss cattle. Ann. Anim. Sci., 14(3): 545-557.
13. Dubey, P.P. and Singh, C.V. (2005) Estimates of genetic and phenotypic parameters considering first lactation and lifetime performance traits in Sahiwal and crossbred cattle. Indian J. Anim. Sci., 75(11): 1289-1294.
14. Missanjo, E., Imbayarwo-Chikosi, V. and Halimani, T. (2013) Estimation of genetic and phenotypic parameters for production traits and somatic cell count for Jersey dairy cattle in Zimbabwe. ISRN Veterinary Sci., 5. Available from: http://www.dx.doi.org/10.1155/2013/470585 Accessed on 07/01/2016 .
15. Dhaka, S.S., Chaudhary, S.R., Pander, B.L., Yadav, A.S. and Singh, S. (2002) Genetic studies on production efficiency traits in Hariana cattle. Asian-Aust. J. Anim. Sci., 15(4): 466-469.
16. Chander, R., Singh, D., Dalal, D.S., Malik, Z.S. and Dixit, S.P. (2008) Genetic studies on components of first lactation and lifetime traits in Sahiwal cattle. Indian J. Anim. Res., 42(1): 44-48.
17. Samoilo, G.A. (1978) Inheritance and relationship of service period and lactation duration with milk production in Black Pied cattle. Belor. Selsko. Akad., 45:46-49.
18. Dhawan, S., Yadav, A.S., Dhaka, S.S. and Chakerborty, D. (2015) Genetic studies on production and Production efficiency traits in Sahiwal cattle. Indian Vet. J., 92(9): 35-38.
19. Sahin, A., Ulutas, Z., Adkinson, A.Y. and Adkinson, R.W. (2012). Genetic and environmental parameters and trends for milk production of Holstein cattle in Turkey. Ital. J. Anim. Sci., 11: 242-248.
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Dr Laura Bergade
School of Health and Rehabilitation Sciences
Faculty of Health and Behavioural Sciences
[email protected]
Dr Laura Desha's research looks into the ways that children and their families use their time (exploring things like time spent playing, time in physical activities), and the influence this has on their physical and emotional health and wellbeing.
Dr Laura Desha is a lecturer in the Division of Occupational Therapy, in the School of Health and Rehabilitation Sciences. Her research explores the concept of healthy lifestyles for children and their families, and focuses on the ways that people use their time. Dr Laura Desha has a particular interest in the impact that family routines and time use choices have on children's emotional and physical development. Achieving a greater understanding of this relationship may assist clinicians in fostering healthier lifestyles among children who are experiencing conditions such as overweight and depression. Dr Laura Desha is collaborating with a team of researchers to investigate the ways in which time use data can be used to assess children's participation, as it is defined in the International Classification of Functioning. Her research involves interrogation of large national and international datasets, as well as smaller targeted qualitative and quantitative studies.
Doctor of Philosophy, The University of Queensland
Bachelor of Occupational Therapy, The University of Queensland
Journal Article: Contribution of speech and language difficulties to health-related quality-of-life in Australian children: A longitudinal analysis
Feeney, Rachel, Desha, Laura, Khan, Asaduzzaman and Ziviani, Jenny (2017) Contribution of speech and language difficulties to health-related quality-of-life in Australian children: A longitudinal analysis. International Journal of Speech-Language Pathology, 19 2: 139-152. doi:10.3109/17549507.2016.1151935
Journal Article: "Not just a normal mum": a qualitative investigation of a support service for women who are pregnant subsequent to perinatal loss
Meredith, Pamela, Wilson, Trish, Branjerdporn, Grace, Strong, Jenny and Desha, Laura (2017) "Not just a normal mum": a qualitative investigation of a support service for women who are pregnant subsequent to perinatal loss. BMC Pregnancy and Childbirth, 17 1: 6. doi:10.1186/s12884-016-1200-9
Journal Article: Healthcare students' experiences of an interprofessional, student-led neuro-rehabilitation community-based clinic
Gustafsson, Louise, Hutchinson, Laura, Theodoros, Deborah, Williams, Katrina, Copley, Anna, Fagan, Amy and Desha, Laura (2016) Healthcare students' experiences of an interprofessional, student-led neuro-rehabilitation community-based clinic. Journal of Interprofessional Care, 30 2: 259-261. doi:10.3109/13561820.2015.1086730
Contribution of speech/language difficulties to health-related quality-of-life in Australian children: A longitudinal analysis
(2016) Doctor Philosophy
Children's occupational time use
Ziviani, Jenny, Desha, Laura and Rodger, Sylvia (2006). Children's occupational time use. In Sylvia Rodger and Jenny Ziviani (Ed.), Occupational Therapy with Children: Understanding Children's Occupations and Enabling Participation (pp. 91-112) Oxford: Blackwell Publishing.
Contribution of speech and language difficulties to health-related quality-of-life in Australian children: A longitudinal analysis
"Not just a normal mum": a qualitative investigation of a support service for women who are pregnant subsequent to perinatal loss
Healthcare students' experiences of an interprofessional, student-led neuro-rehabilitation community-based clinic
Speech and Language Difficulties Along with Other Child and Family Factors Associated with Health Related Quality of Life of Australian Children
Feeney, Rachel, Desha, Laura, Khan, Asaduzzaman, Ziviani, Jenny and Nicholson, Jan M. (2015) Speech and Language Difficulties Along with Other Child and Family Factors Associated with Health Related Quality of Life of Australian Children. Applied Research in Quality of Life, 11 4: 1-19. doi:10.1007/s11482-015-9443-6
Aspects of Activity Participation as Risk Factors for Conduct Problems in Children and Adolescents: A Literature Review Using Ecological Systems Theory
Yu, Mong-Lin, Desha, Laura and Ziviani, Jenny (2013) Aspects of Activity Participation as Risk Factors for Conduct Problems in Children and Adolescents: A Literature Review Using Ecological Systems Theory. Occupational Therapy in Mental Health, 29 4: 395-415. doi:10.1080/0164212X.2013.848398
Health-related quality-of-life of children with speech and language difficulties: A review of the literature
Feeney, Rachel, Desha, Laura, Ziviani, Jenny and Nicholson, Jan M. (2012) Health-related quality-of-life of children with speech and language difficulties: A review of the literature. International Journal of Speech Language Pathology, 14 1: 59-72. doi:10.3109/17549507.2011.604791
Evaluating an online occupational therapy community of practice and its role in supporting occupational therapy practice
Hoffmann, Tammy, Desha, Laura and Verrall, Kellie (2011) Evaluating an online occupational therapy community of practice and its role in supporting occupational therapy practice. Australian Occupational Therapy Journal, 58 5: 337-345. doi:10.1111/j.1440-1630.2011.00954.x
Fundamental movement skills and self-concept of children who are overweight
Poulsen, Anne A., Desha, Laura, Ziviani, Jenny, Griffiths, Lisa, Heaslop, Annabel, Khan, Asad and Leong, Gary M. (2011) Fundamental movement skills and self-concept of children who are overweight. International Journal of Pediatric Obesity, 6 2-2: e464.1-e471.8. doi:10.3109/17477166.2011.575143
Adolescent depression and time spent with parents and siblings
Desha, Laura N., Nicholson, Jan M. and Ziviani, Jenny M. (2011) Adolescent depression and time spent with parents and siblings. Social Indicators Research, 101 2: 232-238. doi:10.1007/s11205-010-9658-8
Positioning occupational engagement in the prevention science agenda for childhood obesity
Ziviani, J, Desha, LN, Poulsen, AA and Whiteford, G (2010) Positioning occupational engagement in the prevention science agenda for childhood obesity. Australian Occupational Therapy Journal, 57 6: 439-441. doi:10.1111/j.1440-1630.2010.00891.x
Measures of participation outcomes and environmental considerations for children with acquired brain injury: A systematic review
Ziviani, Jenny, Desha, Laura, Feeney, Rachel and Boyd, Rosyln (2010) Measures of participation outcomes and environmental considerations for children with acquired brain injury: A systematic review. Brain Impairment, 11 2: 93-112. doi:10.1375/brim.11.2.93
Physical activity and depressive symptoms in American adolescents
Desha, L. N., Ziviani, J. M., Nicholson, J. M., Martin, G. and Darnell, R. E. (2007) Physical activity and depressive symptoms in American adolescents. Journal of Sport and Exercise Psychology, 29 4: 534-543. doi:10.1123/jsep.29.4.534
Use of time in childhood and adolescence: A literature review of the nature of activity participation and depression
Desha, L. N. and Ziviani, J. M. (2007) Use of time in childhood and adolescence: A literature review of the nature of activity participation and depression. Australian Occupational Therapy Journal, 54 1: 4-10. doi:10.1111/j.1440-1630.2006.00649.x
Play Preferences and Behavior of Preschool Children with Autistic Spectrum Disorder in the Clinical Environment
Desha, Laura, Ziviani, Jenny and Rodger, Sylvia (2003) Play Preferences and Behavior of Preschool Children with Autistic Spectrum Disorder in the Clinical Environment. Physical & Occupational Therapy in Pediatrics, 23 1: 21-42. doi:10.1300/J006v23n01_03
Conference Publication
Emergent Design Flexibility: Responding to data
Turpin, Merrill, Brough, Rachel, Desha, Laura and Ziviani, Jenny (2013). Emergent Design Flexibility: Responding to data. In: Conference Abstracts: Presentations. Advances in Qualitative Methods Conference, Edmonton, AB United States, (723-724). 17 - 20 July 2013.
Does time use help predict depressive illness among American adolescents?
Desha, L., Nicholson, J. and Ziviani, J. (2008). Does time use help predict depressive illness among American adolescents?. In: IATUR Conference 2008 – Abstract Booklet. International Association for Time Use Research Meeting, Sydney, Australia, (). 1-3 December 2008.
Taking action against childhood obesity: The magic of KOALA (Kinder Overweight Active Lifestyles Actions)
Ziviani, J. M., Poulsen, A. A., Desha, L., Heaslop, A. and Leong, G. (2008). Taking action against childhood obesity: The magic of KOALA (Kinder Overweight Active Lifestyles Actions). In: OT Australia: 23rd National Conference & Exhibition 2008, Melbourne, Australia, (). 11-13 September, 2008.
Time use and depressive illness: what does it mean for adolescents?
Desha, L. and Ziviani, J. (2008). Time use and depressive illness: what does it mean for adolescents?. In: OT Australia 23rd National Conference, Creating the future: to inspire, to explore, to take action. OT Australia 23rd National Conference, Creating the future: to inspire, to explore, to take action, Melbourne, Australia, (). 11-13 September 2008.
Other Outputs
Time Use and Depressive Symptoms in Adolescence
Laura Desha (2009). Time Use and Depressive Symptoms in Adolescence PhD Thesis, School of Health & Rehabilitation Sciences, The University of Queensland.
Completed Supervision
(2016) Doctor Philosophy — Associate Advisor
Professor Jenny Ziviani
Associate Professor Asad Khan
ResearcherID: D-2944-2011
Similar Staff
Associate Professor Sally Bennett
Dr Merrill Turpin
Dr Catherine McBryde
Human Movement and Sports Science
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We have 39 consumer reports for Sutent. Members hurt effect occurred in 13%.
I found out on 15.08.2011 that my kidney tumor (7,5cm), which was removed with my right kidney at that time, has now spread after 8 years. Metastases have been found in the duodenum and in the skull. Due to the dispersion, my doctors have denied an OP and instead started a chemo with Sutent (50mg) and Pamidronate (60mg) – 1.Cycle from 30.08.2011. The first 2 days were very bad, I had very strong limb / bone pain, 38 ° fever and diarrhea. From the 3rd day the pain subsided and I feel better since then. Side effects at this time are: fatigue, small Blisters on the hands, mild diarrhea, pressure in the head. Should others here with a similar diagnosis, please short info, what else comes to me and what YOU think of this treatment.
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Hernias occur when an area of the abdominal wall becomes weakened, allowing an organ or other tissues to protrude through. They typically occur in the abdomen or groin as a result of intense or prolonged strain on the weakened abdominal wall. Several factors can put a person at risk of hernia, including pregnancy and being overweight. As the muscle weakens under strain, a hernia may easily form when lifting a heavy object or even while coughing or sneezing.
Did you know nearly 5 million Americans suffer from hernias yet only 750,000 seek treatment each year? The condition occurs in people of all ages, including young children and babies who may be born with weakness in the abdominal wall. Hernias are even more common in adults – especially males over age 40.
While not all hernias produce symptoms, many of them do. The most obvious symptom is tissue that causes a bulge in the abdomen, pelvic area or the testicular area. This may or may not be accompanied by pain or tenderness, which may be described as either dull or sharp and range from mild to severe. Symptoms vary according to the type and severity of the hernia. In fact, some asymptomatic hernias go unnoticed until a doctor makes the diagnosis during a check-up or exam.
Every year, more than 500,000 people in the U.S. undergo surgery to repair a hernia. It is one of the most frequently performed surgeries in the country and carries a high rate of success. While some mild hernias may be monitored for changes and complications over time, many will need to be repaired to prevent serious and potentially life-threatening complications. In untreated hernias, an organ that protrudes through the abdominal wall may become strangulated, potentially resulting in tissue death. Surgery helps to restore the organ's natural placement and reinforce the abdominal wall to prevent a recurrence.
What happens during a hernia surgery?
When possible, we perform hernia surgery using a laparoscopic technique. Using this approach, several tiny openings are used to access the treatment site. Small, laparoscopic instruments are used along with a lighted camera to operate from outside the body. This approach reduces recovery time and lowers the risk of post-operative discomfort and complications. In more complex cases, a traditional open surgery may be necessary, in which a larger incision is made in the lower abdomen.
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doi: 10.5455/ajrms.281926
Amany Abdel Bary, Ahmed Abdel Bary.
Objective: The pathogenesis of psoriasis involves T-cell mediated immunologic response, keratinocytes hyperproliferation, and resistance to apoptosis. Methotrexate is one of the most reliable modalities in the treatment of psoriasis that target those changes. The study of those variables before and after methotrexate therapy may answer the question: Which of those variables contributes more to the clinical severity of the disease and is more valuable to be targeted in psoriasis treatment. Patients and Methods: A total of 50 cases of psoriasis vulgaris were included, 25 patients received methotrexate therapy. Skin biopsies of psoriatic skin lesions before and after treatment were examined histologically for measurement of epidermal thickness and grading of dermal inflammation. Immunostaining for Ki-67 and p53 was done for assessment of keratinocyte proliferation and apoptosis. Results were correlated with clinical severity of the disease, assessed by psoriatic area and severity index (PASI) score. 15 biopsies of normal skin were included as control. Results: Dermal inflammation, Ki-67%, and p53% were significantly higher in psoriatic skin lesion than in normal skin. Those changes were significantly correlated with PASI score. Multiple logistic regression models revealed that Ki-67 was the most significant variable contributing to clinical severity. One unit change in ki-67% can explain 1.2 unit changes in PASI score with 97% sensitivity, 40% specificity and 25% cut-off value. PASI score, dermal inflammation, Ki-67% and P53% were significantly reduced after methotrexate therapy. No significant difference was detected between the percent reduction in PASI score (81%) and that of Ki-67% (70%). Conclusion: Keratinocyte proliferation was the most significant variable contributing to the clinical severity of psoriasis and it was the single parameter that showed parallel changes to PASI score after methotrexate therapy. Keratinocyte proliferation may be considered as the stimulus that induces all other pathological and clinical changes in psoriasis and should be targeted by therapy.
Key words: psoriasis, proliferation, apoptosis, inflammation, methotrexate
Articles by Amany Abdel Bary
Articles by Ahmed Abdel Bary
Amany Abdel Bary, Ahmed Abdel Bary. Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?. Am J Res Med Sci. 2018; 2(1): 34-43. doi:10.5455/ajrms.281926
Amany Abdel Bary, Ahmed Abdel Bary. Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?. http://www.ajrms.com/?mno=281926 [Access: January 19, 2020]. doi:10.5455/ajrms.281926
Amany Abdel Bary, Ahmed Abdel Bary. Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?. Am J Res Med Sci. (2018), [cited January 19, 2020]; 2(1): 34-43. doi:10.5455/ajrms.281926
Amany Abdel Bary, Ahmed Abdel Bary (2018) Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?. Am J Res Med Sci, 2 (1), 34-43. doi:10.5455/ajrms.281926
Amany Abdel Bary, Ahmed Abdel Bary. 2018. Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?. American Journal of Research in Medical Sciences, 2 (1), 34-43. doi:10.5455/ajrms.281926
Amany Abdel Bary, Ahmed Abdel Bary. "Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?." American Journal of Research in Medical Sciences 2 (2018), 34-43. doi:10.5455/ajrms.281926
Amany Abdel Bary, Ahmed Abdel Bary. "Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?." American Journal of Research in Medical Sciences 2.1 (2018), 34-43. Print. doi:10.5455/ajrms.281926
Amany Abdel Bary, Ahmed Abdel Bary (2018) Study of Keratinocyte Proliferation, Apoptosis and Dermal Inflammation in Psoriatic Skin Lesions Before and After Methotrexate Therapy: Which Change Is Contributing More to Clinical Severity of the Disease?. American Journal of Research in Medical Sciences, 2 (1), 34-43. doi:10.5455/ajrms.281926
Am J Res Med Sci. Year: 2018, Volume: 2, Issue: 1: 34-43. DOI: 10.5455/ajrms.281926
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The inflammatory response increases the oxidative stress and cytokine production, such as TNFα, in macrophages. Flavonoids, present in vegetables, have potential antioxidant and anti-inflammatory properties. Previous studies have shown that a flavonoid-enriched cocoa extract added to macrophages in vitro decreases the secretion of NO and TNFα .
The objective of the present study was to ascertain the production of oxidant products and a pro-inflammatory cytokine (TNFα) by peritoneal macrophages obtained from arthritic rats after a long-term cocoa diet.
Female LOU rats were fed with a 10% cocoa diet or standard chow. After 2 weeks of diet, collagen-induced arthritis (CIA) was induced in part of animals from each group. One month later, peritoneal macrophages were obtained by injecting ice-cold sterile PBS into the peritoneal cavity. Cells were cultured and stimulated by addition of 1 µg/mL LPS. TNFα secretion was quantified by ELISA in 24 h supernatants. In the same samples, NO2- concentration (stable end product of NO) was measured by a modification of Griess reaction. To determine intracellular ROS production, macrophages were incubated with reduced 2',7'-dichlorofluorescein diacetate (H2DCF-DA) for 30 min at 37 ºC. Fluorescence of DCF oxidized by ROS was measured by fluorometry every 30 min up to 2 h.
Macrophages from CIA animals fed cocoa decreased TNFα and NO production by ~57% and ~36% with respect to those from CIA reference group under LPS-stimulation conditions (P<0.05). ROS production by macrophages from CIA animals fed standard diet was higher with respect to healthy reference animals (P<0.05). Cocoa diet avoided ROS secretion increase in CIA animals (P<0.05), raising similar values to healthy animals.
A long-term cocoa diet reduced the production of oxidants and TNFα in peritoneal macrophages obtained from collagen-induced arthritic rats.
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If you or someone you know is struggling with addiction, it is urgent that you take action immediately. The best way to get in touch with us is to call us at 800-714-2175.
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Prescription drugs serve several functions. They treat diseases, fight infection, and restore mental and physical health, thus allowing millions of people to lead healthy lives. However, some prescription drugs are addictive enough to form a physical and/or physiological dependence in the user. These kinds of drugs are usually controlled substances, the most addictive of which include as opiates, stimulants, and depressants. Fortunately, this kind of addiction can be treated through prescription drug detox.
If you or someone you know is exhibiting signs of prescription drug abuse, seeking treatment is unarguably necessary. Addiction can lead to serious repercussions, both psychological and physical. Prescription drug detox can prevent this, but undergoing it alone can lead to serious medical complications and painful withdrawal symptoms. This is why professional and medically-supervised detox programs are essential for recovery.
The prescription drug detox programs at Discovery Institute put the safety and comfort of our patients first. We offer medically-assisted detox for patients suffering from prescription drug addiction. To begin, each patient in recovery receives a thorough examination upon admission for the purposes of assessing health, identifying any concurrent issues, and collecting a full drug use history. This information is then used to create an all-inclusive treatment plan tailored to the needs of each individual client.
From that point forward, patients are administered medications to alleviate withdrawal symptoms and supervised so symptoms can be tracked and addressed when they arise. In addition to doctors and nurses, the therapeutic staff is also on call to assist with the emotional healing of the detox process.
For patients who still need prescription drugs for conditions like post-surgery pain or chronic pain management, non-addictive treatments are available so that the prescription drug dependency is reduced during detox. These kinds of treatments can include traditional therapy, holistic treatments, and non-narcotic medications administered by the medical staff.
Discovery Institute works in partnership with most of the leading insurance providers in the country. Depending on your coverage, your stay with us may be covered by your policy's benefits. Speak to one of our admissions coordinators today to receive a free assessment of benefits.
We also work with Prosper, a company that provides financing options for those who do not have, or not wish to use health insurance to cover the cost of treatment. Visit the Prosper website to learn more.
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Research ArticleBIOCHEMISTRY AND MACROMOLECULAR STRUCTURE
Molecular Cloning and Expression Analysis of the Mitochondrial Pyruvate Dehydrogenase from Maize
Jay J. Thelen, Jan A. Miernyk, Douglas D. Randall
Jay J. Thelen
Jan A. Miernyk
Douglas D. Randall
Published February 1999. DOI: https://doi.org/10.1104/pp.119.2.635
Copyright © 1999 American Society of Plant Physiologists
Four cDNAs, one encoding an α-subunit and three encoding β-subunits of the mitochondrial pyruvate dehydrogenase, were isolated from maize (Zea mays L.) libraries. The deduced amino acid sequences of both α- and β-subunits are approximately 80% identical with Arabidopsis and pea (Pisum sativum L.) homologs. The mature N terminus was determined for the β-subunit by microsequencing the protein purified from etiolated maize shoot mitochondria and was resolved by two-dimensional gel electrophoresis. This single isoelectric species comprised multiple isoforms. Both α- and β-subunits are encoded by multigene families in maize, as determined by Southern-blot analyses. RNA transcripts for both α- and β-subunits were more abundant in roots than in young leaves or etiolated shoots. Pyruvate dehydrogenase activity was also higher in roots (5-fold) compared with etiolated shoots and leaves. Both subunits were present at similar levels in all tissues examined, indicating coordinated gene regulation. The protein levels were highest in heterotrophic organs and in pollen, which contained about 2-fold more protein than any other organ examined. The relative abundance of these proteins in nonphotosynthetic tissues may reflect a high cellular content of mitochondria, a high level of respiratory activity, or an extra plastidial requirement for acetate.
The mitochondrial PDC is composed of multiple copies of three catalytic components, PDH [E1, EC 1.2.4.1], dihydrolipoamide acetyltransferase [E2, EC 2.3.1.12], and dihydrolipoamide dehydrogenase [E3, EC 1.8.1.4], and catalyzes the overall reaction: pyruvate + CoA + NAD+ → acetyl-CoA + NADH + CO2.
The PDH component is composed of nonidentical α- and β-subunits, forming an α2β2heterotetramer. In mammals, 20 to 30 of these heterotetramers attach to the core of the complex, which is formed by 20 homotrimers of dihydrolipoamide acetyltransferase (for review, see Patel and Roche, 1990).
PDH decarboxylates pyruvate and forms a hydroxyethylidene-TPP intermediate. The C2 group is then transferred from TPP to the lipoyl moiety of the dihydrolipoamide acetyltransferase component by reductive acetylation. Dihydrolipoamide acetyltransferase catalyzes the acetyl transfer to CoA and dihydrolipoamide dehydrogenase reoxidizes the dihydrolipoamide moiety using NAD+(Reed, 1973).
Most eukaryotic mitochondrial PDCs are regulated by reversible phosphorylation of the E1α-subunit by a specific PDH kinase and phosphatase (Patel and Roche, 1990, and refs. therein). Phosphorylation of E1α reduces its affinity for TPP and prevents pyruvate binding (Korotchkina et al., 1995), effectively inactivating the complex. Although the phosphorylation of one conserved Ser inactivates PDC, two other phosphorylation sites are present on mammalian E1α (Yeaman et al., 1978; Sugden et al., 1979). Plant E1α-subunits are also phosphorylated on Ser residues, but the number and location of the phosphorylation site(s) have not yet been established (Randall et al., 1996).
We have purified the maize (Zea mays L.) mitochondrial PDC, determined its kinetic properties, and established that the E1α- and E1β-subunits are 43 and 40 kD, respectively (Thelen et al., 1998a). The E1α-subunit has at least five isoelectric species, whereas the β-subunit has predominantly one. Although most of theK m and K ivalues for maize PDC were typical of those for other plant PDCs, differences were noted that could be important for PDC regulation in C4 plants. For example, theK m for TPP was approximately 10-fold higher in maize than in pea (Pisum sativum L.) PDC. Conversely, theK m for Mg was almost 10-fold lower in maize compared with pea mitochondrial PDC. To better understand these kinetic differences and to begin to establish the molecular properties of PDC in C4 plants, we have undertaken an examination of the E1α- and E1β-subunits of the maize complex at the molecular level.
Maize (Zea mays L. cv B73; Illinois Seed Foundation, Urbana, IL) seedlings were grown in a growth chamber (10-h photoperiod) for about 14 d and etiolated maize seedlings were grown in a darkened growth chamber (30°C) for 5 d. Pea (Pisum sativum L. cv Little Marvel), Arabidopsis (cv Columbia), andKalanchöe daigremontianum seedlings (provided by J. Ringbauer, University of Missouri, Columbia) were grown in a growth chamber (10-h photoperiod, 18°C) for about 14 d (pea), 40 d (Arabidopsis), and 25 d (K. daigremontianum). Mitochondria were isolated from etiolated maize shoots according to the method of Hayes et al. (1991) and from the other tissues using the procedure of Fang et al. (1987).
[1-14C]Pyruvate was purchased from New England Nuclear in the solid crystalline form and was dissolved in 6 mL of 20 mm sodium pyruvate containing 3 mm HCl; aliquots (50 μCi; 1 Ci = 37 GBq) were stored at −20°C.
Isolation of cDNAs and Sequencing Strategies
A maize cDNA clone obtained from the Maize EST Stock Center (Columbia, MO) encoded a polypeptide with homology to the C-terminal half of the Arabidopsis PDH E1β-subunit (accession no. U80186). The partial maize cDNA was used as a probe to screen a maize 2-week-old seedling λZAP (Stratagene) expression library (generously provided by Professor Alice Barkan, University of Oregon, Eugene). A screen of more than 3 million transformants yielded approximately 50 positive plaques. DNA was excised and prepared according to the manufacturer's instructions. Nested Exo III deletions were prepared for the longest cDNA according to the "Erase-A-Base" protocol (Promega). The deletion constructs were sequenced using the dye-deoxynucleotide chain termination method using AmpliTaq polymerase (Perkin-Elmer Cetus). Reaction products were analyzed on an automated sequencer (model 373, ABI, Foster City, CA) at the University of Missouri DNA Core Facility.
Two additional unique cDNAs encoding E1β polypeptides were obtained from the Pioneer Hi-Bred International (Johnston, IA) maize EST facility. These cDNAs were prepared and sequenced as described previously. Sequence alignment and phylogenetic analysis were performed with GeneWorks software (IntelliGenetics, Mountain View, CA). The Pioneer Hi-Bred International maize EST database was also examined for cDNAs encoding the E1α-subunit. One cDNA long enough to encode the entire E1α-subunit was found, along with several partial E1α clones. The full-length E1α cDNA was sequenced as described previously.
Protein Microsequencing
Approximately 200 mg of mitochondrial protein from etiolated maize shoots was used to obtain 0.4 mg of highly enriched PDC (as described by Thelen et al., 1998a). For N-terminal protein microsequencing, 100 μg of enriched PDC was resolved by two-dimensional gel electrophoresis according to standard procedures with the following modifications. Sodium thioglycolate (0.25 mm) and glutathione (0.1 mm) were added to the first- and second-dimension gels. The polyacrylamide gel for the second dimension was prerun for 30 min to remove any nonpolymerized acrylamide and persulfate. The protein was blotted to a PVDF membrane using transfer buffer (10 mm 3-[cyclohexylamino]-1-propanesulfonic acid [APS]-NaOH, pH 11.0, and 10% [v/v] methanol). After transfer the protein was stained with amido black (0.1% [w/v] amido black, 40% [v/v] methanol, and 1% [v/v] acetic acid), washed with 50% (v/v) methanol, and then dried. The immobilized proteins were excised and submitted to the University of Nebraska Protein Core Facility (Lincoln, NE) for sequencing by Edman degradation.
Monoclonal antibodies to the α-subunit of the mitochondrial PDH (E1α), the β-subunit to the ATPase, and the heat-shock chaperone (HSP70) were raised in mice immunized with total maize mitochondrial proteins (Luethy et al., 1993, 1995b; Lund et al., 1998). Polyclonal antibodies to the β-subunit of the mitochondrial PDH (E1β) were raised in rabbits immunized with purified recombinant Arabidopsis E1β-maltose-binding fusion protein (M.H. Luethy, unpublished data).
Nucleic Acid Analyses
Total genomic DNA was isolated from 10-d-old green maize leaves according to the method of Sambrook et al. (1989). Digested DNA (20 μg) was separated by electrophoresis on a 0.8% (w/v) agarose gel and then transferred to a Nytran membrane (Schleicher & Schuell). Following transfer, the membrane was UV cross-linked and rinsed in 2× SSC, 0.1% (w/v) SDS prior to prehybridization. Prehybridization was performed at 65°C for 6 h in 2.5× SSPE, 1% (w/v) SDS, 1% nonfat dry milk (Schnuck's, St. Louis, MO), and 0.025% (w/v) denatured salmon-sperm DNA. Hybridization was performed in the same solution and temperature with the entire E1α (EcoRI-XbaI) or E1β isoform 2 (XbaI) cDNA fragment labeled by random hexamer extension (specific activity = 2500 mCi/mg). Subsequent to hybridization, the membrane was washed twice with 2× SSC, 0.1% (w/v) SDS for 1 h, twice with 0.2× SSC, 0.1% (w/v) SDS for 2 h, and was then dried for autoradiographic exposure.
Total RNA was isolated from fresh maize organs using guanidinium extraction (Sambrook et al., 1989). The RNA (40 μg) samples were separated by electrophoresis on a 1.0% (w/v) agarose gel containing 2.2 m formaldehyde and subsequently transferred to a Nytran membrane. Following transfer the membrane was UV cross-linked and stained with 0.03% (w/v) methylene blue and 0.3 m sodium acetate, pH 6.0, to visualize RNA markers and rRNA. Hybridization and washing were carried out as described for the Southern analysis.
RT-PCR of Maize RNA
Approximately 60 μg of maize total RNA isolated from various organs was treated with 5 units of RNase-free DNase (Boehringer Mannheim) for 2 h at 37°C in 10 mmMgCl2, 1 mm DTT, and 50 units of RNase inhibitor (RNasin, Promega). The RNA was then extracted with phenol, precipitated with ethanol, and resuspended in nuclease-free water. The RNA was quantitated by A 260 and diluted to 10 ng/μL for use in RT-PCR.
Each RT-PCR reaction contained the following RNase-free reagents: 1.5 mm magnesium sulfate, 0.2 mmdeoxyribonucleotide triphosphates, 1.5 pmol/μL oligonucleotides, 0.1 unit/μL avian myeloblastosis virus RT, 0.1 unit/μL TflDNA polymerase (Promega), 1× avian myeloblastosis virus RT buffer, 2.5 ng/μL DNase-free RNA. Reverse transcription proceeded for 45 min at 48°C. The PCR cycling was as follows: 2 min at 94°C (one cycle); 30 s at 94°C, 1 min at 60°C, 2 min at 68°C (40 cycles); 7 min at 68°C (one cycle). The oligonucleotides used for RT-PCR span the putative intron of the E1α cDNA (Fig. 2) and are denoted: DDR206, 5′-ccgcgacatgtccctcatgc-3′ (sense oligonucleotide); DDR212, 5′-ctctcaacatttcggccctc-3′ (sense oligonucleotide); and DDR 229, 5′-gcccttcttataaacatttgt-3′ (antisense oligonucleotide).
Nucleotide and deduced amino acid sequence for maize E1α cDNA. Amino acids are denoted by the single-letter abbreviations. The stop codon is indicated by a period. Underlined region indicates the putative TPP-binding domain. The targeting peptide-processing site, indicated by the triangle, is putative and based on characteristics of cleavage sites (von Heijne et al., 1989). The putative intron splice site is shaded and the polyadenylation signal is underlined. Oligonucleotides used as primers for RT-PCR in Figure 6B are overlined. Numbers to the right indicate base pairs or amino acid number. Asterisks and • denote residues referred to in the text.
Isolation of Proteins and Assay for PDC Activity
Total proteins from various maize organs were prepared by homogenization with a mortar and pestle in liquid nitrogen. Homogenized powder was immediately suspended in SDS-PAGE sample buffer (8m urea, 4% [v/v] 2-mercaptoethanol and 4% [w/v] SDS) containing 0.01% (w/v) bromphenol blue, mixed thoroughly by vortexing, and incubated at 70°C for 30 min.
In vivo steady-state PDC activity was determined by the rapid-sampling technique of Budde and Randall (1990). Minus-enzyme and acid-precipitated protein controls were performed for each data point to determine background rates. Activity was linear and stable for up to 15 min. Each data point represents the mean of five determinations.
Three E1β cDNA clones were obtained from immature ear (AP9 inbred), green seedling (B73 inbred), and callus culture (B73 inbred) maize libraries and were designated isoforms 1, 2, and 3, respectively. These three cDNAs shared 65% (isoforms 1 and 2), 70% (1 and 3), and 89% (2 and 3) identity at the nucleotide level, whereas 90% identity was observed at the amino acid level (Fig.1). The three E1β cDNAs were 1511, 1679, and 1655 bp in length, with ORFs starting at bases 82, 258, and 233 and in-frame stop codons at bases 1200, 1379, and 1354 for isoforms 1, 2, and 3, respectively. They encoded polypeptides 373, 374, and 374 amino acids in length with calculated M rs of 39,767, 39,982, and 39,917. The calculated pI values were 5.3 and 4.8 for the precursor and mature proteins, respectively.
Amino acid sequence comparison for maize E1β isoforms. Consensus sequence is noted at the top. Dots indicate identity. Gaps, indicated by dashes, were inserted to maximize homology. Overlines indicate the four conserved domains as first pointed out by Wexler et al. (1991). Asterisks denote residues referred to in text. The targeting peptide-processing site is indicated by the inverted triangle. GeneWorks (IntelliGenetics) software was used to perform the alignment algorithm.
The E1α cDNA was obtained from an immature ear (B73 inbred) maize library and was 1747 bp in length with a 930-bp ORF (Fig.2). However, amino acid identity with the Arabidopsis E1α stopped at base 980 with Ile-282. A second ORF was found 285 bp downstream of Ile-282. This ORF started with Val-283 at base 1267 and had an in-frame stop codon at base 1597. This second ORF encoded a polypeptide with strong amino acid homology to the C-terminal 109 amino acids of Arabidopsis E1α. When joined, the two ORFs encoded a full-length E1α polypeptide 392 amino acids in length with a mass of 42,867 D. The calculated pI values were 8.26 and 6.89 for the precursor and mature protein, respectively. The 285-bp region connecting the two ORFs was likely an unspliced intron. One polyadenylation signal was observed in the E1α cDNA, 52 bases downstream of the stop codon (Fig. 2).
Among all eukaryotes, three distinct classes of E1α polypeptides were apparent in dendrogram analyses (Fig.3A). The maize E1α polypeptides shared 77% amino acid identity with other plant mitochondrial copies. The E1α-subunits from plants were more closely related to the yeast (48% amino acid identity) than to the animal (43%–47%) polypeptides and were more distantly related to the plastidial (36%), cyanobacterial (30%), and Bacillus subtilis (23%) homologs. The maize mitochondrial E1β was also closely related to other plant mitochondrial E1β-subunits (80% amino acid identity). As is the case for E1α, the plant mitochondrial E1β was more similar to yeast (58% amino acid identity) than to the animal (55%), plastidial (36%), cyanobacterial (36%), or B. subtilis (32%) homologs (Fig. 3B).
Dendrogram analysis of E1α (A) and β (B) subunits. Clustal alignments were performed using the GeneWorks software package (IntelliGenetics). The length of the horizontal lines indicates inverse degree of relatedness. Accession numbers to the sequences are: Porphyra purpurea (U38804);Solanum tuberosum (Z26949); Synechocystissp. (D90915); Arabidopsis (U21214, U09137); Mus musculus (M76727); Arabidopsis plastid (U80185, U80186);Caenorhabditis elegans (Z47812); P. sativum (U51918, U56697); Homo sapiens (L13318,D90086); Rattus rattus (Z12158, P49432);Saccharomyces cerevisiae (P16387, M98476);Ascaris suum (M76554, M38017); B. subtilis (M31542).
By comparison with other TPP-binding enzymes (Hawkins et al., 1989;Robinson and Chun, 1993), a potential TPP-binding domain for E1α can be predicted (Fig. 2, underlined). This potential TPP-binding domain was highly conserved and contained one of only two Trp residues present in plant mitochondrial E1α-subunits (L-216–WKLP-220). The three Ser residues phosphorylated in mammalian E1α-subunits are indicated by asterisks in Figure 2. Phosphorylation site 1 (Ser-292), conserved in plastidial and mitochondrial E1α polypeptides, was the site responsible for inactivation (Sugden et al., 1979). Ser-300 at site 2 was conserved only in animal sequences, although the plant mitochondrial proteins contained a Ser one residue upstream of this site. Phosphorylation site 3 (corresponding to Ser-232 of human sequence) is an Ala in all plant mitochondrial E1α-subunits described to date, but is conserved in the mammalian and plastidial subunits.
A comparison of the primary sequence of E1β polypeptides from various organisms (Fig. 1, overlined) revealed the four regions of homology first noted by Wexler et al. (1991). Although conserved, the functional significance of these four regions is uncertain. Regions 2 and 3 are proposed to be involved in oxidative decarboxylation, and chemical covalent modification studies of mammalian PDH have shown that Trp and Arg residues are essential for catalytic activity (Ali et al., 1995;Eswaran et al., 1995). Surprisingly, Trp-173 (Fig. 1, asterisk) was conserved in the mitochondrial but not in the plastidial or bacterial E1β-subunits, whereas Arg-277 was conserved in all organisms except cyanobacteria.
Genomic Southern analysis revealed that the maize genome contains multiple copies of both E1α and β genes (Fig.4). The multigenic nature of maize E1β was confirmed by the cloning of three unique cDNAs. Northern analysis indicated that the E1α and β transcripts are approximately 1.5 and 1.6 kb in length, respectively (Fig. 5A).
Genomic Southern analysis of maize E1α (left) and E1β (right). Genomic DNA isolated from maize leaves was digested with the indicated restriction enzymes. Approximately 30 μg of DNA was fractionated by electrophoresis on an agarose gel, transferred to a Nytran membrane, and probed with random-prime-labeled DNA. Marker sizes are indicated to the right in kilobases.
RNA, RT-PCR, and activity analysis of PDH from maize tissues. A, Approximately 30 μg of total RNA isolated from dark-grown seedlings, roots, or light-adapted leaves was fractionated on an agarose formaldehyde gel, transferred to a Nytran membrane, and probed with the entire E1α or E1β cDNA. RNA marker sizes are indicated. As a gel-loading control, rRNA is included for comparison in the bottom panel. B, Oligonucleotides specific for the E1α cDNA were used for RT-PCR analysis with maize RNA isolated from dark-grown seedlings, roots, or light-adapted leaves as the template. The top panel displays the product obtained with primers DDR212 and DDR229. The product in the bottom panel was obtained with primers DDR206 and DDR229 (Fig. 2). C, In vivo PDH specific activity was determined from maize organs (dark-grown seedlings, roots, or light-adapted leaves) using a radioisotopic assay. Values are the means of five independent reactions. Error bars indicate sd.
Immunoblot Analysis and Protein Microsequencing
Monoclonal antibodies to maize mitochondrial E1α recognized a 43-kD protein in mitochondria isolated from maize, pea, Arabidopsis, and K. daigremontianum, representing C4 monocot (maize), C3dicot (pea and Arabidopsis), and CAM plants (K. daigremontranum; Fig. 6). Antibodies raised against recombinant Arabidopsis E1β recognized a 37-kD protein from all plants; however, they primarily recognized a 40-kD polypeptide from maize. On two-dimensional electrophoresis the maize E1β from purified PDC preparations appeared predominantly as a single isoelectric species with a mass of 40 kD (Thelen et al., 1998a).
Immunoblot analysis of mitochondria purified from various plants. Approximately 10 μg of purified mitochondrial protein was loaded in each lane. Maize mitochondria were obtained from etiolated shoots, whereas pea, Arabidopsis, and K. daigremontianum mitochondria were isolated from light-grown leaves. Molecular masses of polypeptides are indicated.
The 40-kD maize E1β-subunit was subjected to N-terminal polypeptide sequencing (Fig. 7A) and yielded 20 residues nearly identical to the deduced amino acid sequence of all three E1β cDNAs, corresponding to Ser-35 through Glu-54 (Fig. 7B). The only difference between the sequenced polypeptide and the deduced sequence of isoforms 2 and 3 (both derived from B73 inbreds) occurred at residue 49, where a Thr instead of a Ser was present. This discrepancy could be the result of a protein-sequencing error or multiple residues at this cycle, some of which went undetected. Comparing the deduced sequence of all three isoforms showed that isoform 1 has an Ile, whereas isoforms 2 and 3 have Met at position 41, indicating that the microsequenced polypeptide was likely a mixture of isoforms.
N-terminal microsequencing of PDH subunits. A, Coomassie-blue-stained two-dimensional gel electrophoresis of highly purified maize mitochondrial PDC from etiolated shoots. The pI is indicated at the top and the size in kilodaltons is indicated to the right. The circled polypeptide was microsequenced from a replica-blot transferred to a PVDF membrane. At cycles 7 and 12 two residues were obtained (indicated by the slash). B, Comparison of the deduced amino acid sequence for the plant E1β subunits. Zm, Z. mays; At, Arabidopsis; Ps, P. sativum. Shading indicates amino acid identity. Gaps denoted by dashes were inserted to maximize homology. The N termini of the mature maize and pea polypeptides are underlined. Conserved Arg residues involved with peptide processing are indicated in bold type.
Organ-Specific Expression of PDH Subunits
The transcripts for both subunits are more abundant in roots than in etiolated shoots or in light-adapted leaves (Fig. 5, A and B). This expression pattern is also supported by PDH-specific activity measurements showing a 5- and 7-fold higher specific activity in root compared with etiolated shoot and light-adapted leaves, respectively (Fig. 5C). The relative amount of each subunit, determined by immunoblot analysis, revealed that E1α and E1β proteins are abundant in roots, particularly compared with light-adapted leaves (Fig. 8). Both PDH subunits were expressed in similar amounts from all organs examined (Fig. 8). Overall, the PDH subunits are most abundant in nonphotosynthetic organs such as etiolated shoots, roots, flower silks, immature anthers, ear shoots, and, particularly, pollen. Neither subunit was detectable in the endosperm from 2-d-imbibed seeds.
Immunoblot analyses showing the expression of PDH subunits from various organs. Maize kernels were allowed to soak for 2 d prior to isolating the endosperm and scutellum. Etiolated shoots were grown for 5 d in complete darkness. The remaining samples were obtained from light-grown plants, grown in either a growth chamber (four-leaf stage) or a greenhouse (adult). As a control, the blots were reprobed with antibodies specific to other mitochondrial proteins, HSP70 and the β-subunit to ATP synthase. Approximately 25 μg of a total protein preparation was loaded per lane. Molecular masses of polypeptides are indicated on the left (in kilodaltons).
Three unique cDNAs encoding three isoforms of the β-subunit of PDH and at least three hybridized bands on Southern analyses indicate that the maize β-subunit is encoded by a multigene family. Although the amino acid identity among the three isoforms is high, the percentage of identity at the nucleotide level is 65%, 70%, and 89%. Since the cDNAs are quite different, it is unlikely that the differences are due to sequencing errors or artifacts of library construction. The present data indicate that the maize genome is also multigenic for E1α. This multigenic nature suggests the possibility for complex regulation of PDH expression in maize.
The insertion within the ORF of the E1α cDNA can be parsimoniously explained as an unspliced intron. In favor of this is the higher AU content in this region (51%) compared with the coding region (42%) and an AU–UG splice sequence at the 3′ end of the intron, both characteristic of introns (Brown, 1986; Goodall et al., 1989). Furthermore, the transcript size for E1α suggests that this putative intron is normally excised. To confirm this, RT-PCR was performed with primers that overlap the region containing the putative intron to determine whether the intron sequence is typically removed. The PCR products shown in Figure 5B are the proper size amplicons provided that the E1α transcript lacks this 285-bp intron. Perhaps the excision efficiency of this intron is reduced because of the lack of a canonical splice site at the 5′ end.
The first 40 amino acids of the maize E1α and E1β isoforms are enriched with Ala, Arg, and Val residues (about 45%), typical of mitochondrial targeting peptides (von Heijne, 1989; Sjöling and Glaser, 1998). When the first 40 amino acids are modeled as an α-helix, the positively charged Arg residues cluster to one side, whereas the hydrophobic residues cluster on the other side, forming an amphipathic helix (data not shown), another characteristic of mitochondrial targeting peptides (von Heijne, 1989; Sjöling and Glaser, 1998). The mature N terminus of the maize E1β polypeptide was determined by sequencing the purified polypeptide (Fig. 7). Processing of the E1β polypeptides occurs between Tyr-32,34 and Ser-33,35 for maize, between Tyr-29 and Ala-30 (by analogy) for Arabidopsis (accession no. U09137), and between Phe-20 and Ser-21 for pea (accession no. U56697; N.R. David, unpublished results; Fig. 7). The plant E1β polypeptides all have a conserved Arg three residues upstream from the cleavage site, a characteristic of mitochondrial precursor processing (von Heijne, 1989).
We reported previously (Thelen et al., 1998a) that the kinetic properties of PDH from maize are similar to those of other plant species, except for the K m values for TPP and divalent cations. In light of the high amino acid conservation among plant PDH subunits, the discrepancy inK m values might be explained by differences in enzyme preparations (i.e. purity, buffer composition). However, the 10-fold higher K m for TPP is intriguing and might be due to nonconserved substitutions within the TPP-binding site. One particular substitution (Asp-215 [pea] to Lys-218 [maize]; Fig.2, •) in the TPP-binding domain of E1α is adjacent to an essential hydrophobic residue (Trp-217). Perhaps a basic residue in place of an acidic residue within this conserved region weakens the association with the TPP moeity. Direct determination will require site-directed mutagenesis of the recombinantly expressed E1 subunit.
The E1α and E1β transcripts are most abundant in roots, followed by etiolated shoots and light-adapted leaves (Fig. 5, A and B). This order is the same as the abundance of E1α and E1β transcripts in Arabidopsis organs, i.e. roots contain the most (Luethy et al., 1994,1995a). The order of the relative abundance for E1α and E1β protein (Fig. 8) follows that of their transcripts, roots > etiolated shoots >> leaves. The specific activities of PDH (Fig. 5C) from roots and leaves also correlate with transcript and protein levels. The specific activity in etiolated shoots was slightly lower than predicted by transcript and immunoblot analysis. However, caution must be used when interpreting PDH activity for three reasons. At present, the contribution of plastidial PDH to the total activity is difficult to estimate. Therefore, to keep plastid activity to a minimum, the assay was performed at pH 7.4 with 0.5 mmMgCl2, which is optimal for the mitochondrial but not for the plastidial PDH (Camp and Randall, 1985). Second, PDH is regulated by reversible phosphorylation. The maize PDH kinase is more abundant in leaves than in roots (Thelen et al., 1998b), which might confound the interpretation of PDH activity. Also, cell breakage necessary for enzyme release might alter the phosphorylation status of PDH due to mixing of subcompartmental ATP. To control for the latter, the time between organ disruption and assay initiation was kept to a minimum of about 15 s.
The steady-state level of both PDH subunits is highest in dry pollen (Fig. 8). To investigate whether PDH is highly expressed in pollen of other species, germinating tobacco pollen was also analyzed (provided by Dr. Stefano Caveniscini, University of Missouri) and the result was the same for both PDH subunits. From these data it is evident that PDH is highly expressed in both dry and germinating pollen. This finding is quite surprising in light of a recent observation that tobacco pollen was able to germinate in the presence of a mitochondrial PDC inhibitor (op den Camp and Kuhlemeier, 1997), which prompted this group to propose the absence of PDC and that an alternative pathway for acetyl-CoA production from pyruvate was operational. Our results suggest that both PDH subunits are abundant in pollen, which points to multiple routes to acetyl-CoA or to an intriguing regulatory difference in pollen PDC.
Immunoblot analysis was used to examine whether PDH polypeptides were differentially expressed in various organs relative to other mitochondrial proteins (Fig. 8). The results show that PDH expression does not correlate with the overall abundance of mitochondria in these organs, which indicates that PDH and perhaps PDC are spatially expressed in a manner different from total mitochondria. Why is PDH spatially regulated, and, in particular, why is it so low in green leaf tissue? Pyruvate is a potent inhibitor of PDH kinase, and in maize total pyruvate levels are relatively high (3–4 mm in leaves; Stitt and Heldt, 1985), which is favorable for PDH activity. Pyruvate generated from the decarboxylation of malate in bundle-sheath cells is recycled to PEP in mesophyll cells for another round of carboxylation (Hatch, 1987, and refs. therein). If the pyruvate intermediate were consumed in either cell type by PDH, pyruvate would need to be synthesized de novo. Since all indications are that pyruvate is recycled, PDH from maize must either have unique properties or be down-regulated in leaves. Except for the unusually high K m for TPP and the lowerK m for Mg, the properties of the maize PDH are similar to PDHs from other C3 plants (Thelen et al., 1998a). Perhaps down-regulation of the mitochondrial PDH in light-adapted leaves allows the photosynthetic C3-C4-shuttling mechanism to proceed without consuming the pyruvate intermediate.
The apparent absence of PDH in scutellum and yet the relative abundance of mitochondrial ATPase suggests that carbon for oxidative phosphorylation may be supplied in a form other than through pyruvate. This is surprising in that mobilization of starch from the endosperm would seemingly proceed through glycolysis and the Kreb's cycle. The Kreb's cycle cannot function without acetyl-CoA input. Perhaps ATP needs are met by the oxidative pentose pathway supplying reducing equivalents to the electron transport chain, or acetyl-CoA for the Kreb's cycle is provided by β-oxidation of storage lipids.
In conclusion, we have identified cDNAs encoding both PDH subunits from maize. Both subunits are encoded by multigene families in maize, which may contribute to the surprisingly complex spatial regulation observed by immunoblot analysis. Transcript and protein levels indicate that the two subunits for PDH are coordinately regulated. Based on transcript, protein, and activity measurements, PDH is least abundant in light-adapted leaves, which might be advantageous for C4 metabolic function.
The accession numbers for the maize PDH isoforms reported in this article are AF069911 (E1α) and AF069908, AF069909, and AF069910 (for E1β isoforms 1, 2, and 3, respectively).
The authors are grateful to Dr. Michael Muszynski for his assistance with the database searches and also to Pioneer Hi-Bred International for supplying the cDNA clones. The authors thank Nancy R. David for isolating mitochondria from the various plant species. We also thank Professor Thomas E. Elthon and Dr. Gautum Sarath for the protein microsequencing performed at the Protein Core Facility (University of Nebraska, Lincoln).
↵1 This research was supported by National Science Foundation grant no. IBN-9419489 and by a Maize Training Grant Fellowship awarded to J.J.T. This is journal report 12,744 from the Missouri Agricultural Experiment Station.
↵* Corresponding author; e-mail bchemdr{at}showme.missouri.edu; fax 1–573–882–5635.
expressed sequence tag
open reading frame
pyruvate dehydrogenase complex
PDH
pyruvate dehydrogenase
reverse transcriptase, TPP, thiamin PPi
Received June 12, 1998.
LITERATURE CITED
Ali MS,
Shenoy BC,
Eswaran D,
Andersson LA,
Roche TE,
Patel MS
(1995) Identification of the tryptophan residue in the thiamin pyrophosphate binding site of mammalian pyruvate dehydrogenase. J Biol Chem 270:4570–4574.
Brown J
(1986) A catalogue of splice junction and putative branch point sequences from plant introns. Nucleic Acids Res 14:9549–9559.
Budde RJA,
Randall DD
(1990) Pea leaf mitochondrial pyruvate dehydrogenase complex is inactivated in vivo in a light-dependent manner. Proc Natl Acad Sci USA 87:673–676.
Camp PJ,
(1985) Purification and characterization of the pea chloroplast pyruvate dehydrogenase complex. Plant Physiol 77:571–577.
Korotchkina LG,
(1995) Arginine-239 in the beta subunit is at or near the active site of bovine pyruvate dehydrogenase. Biochim Biophys Acta 1252:203–208.
Fang TK,
David NR,
Miernyk JA,
(1987) Isolation and purification of functional pea leaf mitochondria free of chlorophyll contamination. Curr Top Plant Biochem Physiol 6:175.
Goodall GJ,
Filipowicz W
(1989) The AU-rich sequences present in the introns of plant nuclear pre-mRNAs are required for splicing. Cell 58:473–483.
Hatch MD
(1987) C4 photosynthesis: a unique blend of modified biochemistry anatomy and ultrastructure. Biochim Biophys Acta 895:81–106.
Hawkins CF,
Borges A,
Perham RN
(1989) A common structural motif in thiamin pyrophosphate-binding enzymes. FEBS Lett 255:77–82.
Hayes MK,
Luethy MH,
Elthon TE
(1991) Mitochondrial malate dehydrogenase from corn. Plant Physiol 97:1381–1387.
Khailova LS,
Severin SE
(1995) The effect of phosphorylation on pyruvate dehydrogenase. FEBS Lett 364:185–188.
Elthon TE,
(1995a) Characterization of a monoclonal antibody recognizing the E1α subunit of plant mitochondrial pyruvate dehydrogenase. J Plant Physiol 145:443–449.
Horak A,
(1993) Monoclonal antibodies to the α- and β-subunits of the plant mitochondrial F1-ATPase. Plant Physiol 101:931–937.
(1994) The nucleotide and deduced amino acid sequences of a cDNA encoding the E1β-subunit of the Arabidopsis thaliana mitochondrial pyruvate dehydrogenase complex. Biochim Biophys Acta 1187:95–98.
(1995b) The mitochondrial pyruvate dehydrogenase complex: nucleotide and deduced amino-acid sequences of a cDNA encoding the Arabidopsis thaliana E1α subunit. Gene 164:251–254.
Lund AA,
Blum PH,
Bhattramakki D,
(1998) Heat-stress response of maize mitochondria. Plant Physiol 116:1097–1110.
op den Camp RGL, Kuhlemeier C (1997) Aldehyde dehydrogenase in tobacco pollen. Plant Mol Biol 35: 355–365
Patel MS,
Roche TE
(1990) Molecular biology and biochemistry of pyruvate dehydrogenase complexes. FASEB J 4:3224–3233.
Randall DD,
Gemel J,
Luethy MH
(1996) Regulation of leaf mitochondrial pyruvate dehydrogenase complex activity by reversible phosphorylation. Proc Phytochem Soc Eur 39:87–103.
Reed LJ
(1973) Multienzyme complexes. Acc Chem Res 7:40–56.
Robinson BH,
Chun K
(1993) The relationships between transketolase, yeast pyruvate decarboxylase and pyruvate dehydrogenase of the pyruvate dehydrogenase complex. FEBS Lett 328:99–102.
Sambrook J,
Fritsch EF,
Maniatis T
(1989) Molecular Cloning: A Laboratory Manual. (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY).
Sjöling S,
Glaser E
(1998) Mitochondrial targeting peptides in plants. Trends Plant Sci 3:136–140.
Stitt M,
Heldt HW
(1985) Generation and maintenance of concentrating gradients between the mesophyll and bundle sheath in maize leaves. Biochim Biophys Acta 808:400–414.
Sugden PH,
Kerbey AL,
Randle PJ,
Waller CA,
Reid KBM
(1979) Amino acid sequences around the sites of phosphorylation in the pig heart pyruvate dehydrogenase complex. Biochem J 181:419–426.
Thelen JJ,
(1998a) Partial purification and characterization of the maize mitochondrial pyruvate dehydrogenase complex. Plant Physiol 116:1443–1450.
(1998b) Molecular analysis of two pyruvate dehydrogenase kinases from maize. J Biol Chem 273:26618–26623.
von Heijne G,
Steppuhn J,
Herrmann RG
(1989) Domain structure of mitochondrial and chloroplast targeting peptides. Eur J Biochem 180:535–545.
Wexler ID,
Hemalatha SG,
(1991) Sequence conservation in the α and β subunits of pyruvate dehydrogenase and its similarity to branched-chain α-keto acid dehydrogenase. FEBS Lett 282:209–213.
Yeaman SJ,
Hutcheson ET,
Pettit FH,
Brown JR,
Reed LJ,
Watson DC,
Dixon GH
(1978) Sites of phosphorylation on pyruvate dehydrogenase from bovine kidney and heart. Biochemistry 17:2364–2370.
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Is CBN Oil Legal?
September 06, 2022 Brynn Masters
In the United States, the idea of legalizing marijuana is now widely endorsed by a growing number of lawmakers. While various marijuana bills, including those seeking federal legalization are currently in Congress, the states are also debating the modalities of legalizing the substance.
As of May 2022, medical cannabis was legal in 37 states, with the other 18 states legalizing recreational cannabis. State-level marijuana laws have been evolving in a bid to promote lawful activities.
But the biggest push toward decriminalizing cannabis happened in 2018 when Congress passed the Farm Bill. Besides many other things, this bill permits the cross-state movement of hemp-derived cannabis products for commercial and other purposes, as long as they have less than 0.3% of THC.
Despite all these developments, many are still unsure about the legality of other cannabis-derived products like those containing CBN oil. Keep reading to learn more about these relaxing products' legal status and properties.
What are the benefits and uses of CBN?
The exact number of compounds existing naturally in cannabis remains unknown. Some scientific publications contend they may be over 500, while others are slightly more conservative. Regardless, it is abundantly clear that cannabis compounds may have health benefits.
Research on the two most popular cannabinoids, tetrahydrocannabinol (THC) and cannabidiol (CBD), is ongoing, and some of their properties are well-grounded in science.
CBN is a metabolite of THC. Research shows it forms when THC is oxidized, explaining why it is typically found in aged cannabis plant matter. Unlike CBD, which does not bind to CB receptors, CBN binds to the G-protein coupled receptor CB2, which is mostly expressed in various immune cells such as dendritic cells, macrophages, B-cells, and T-cells.
CBN-induced activation of CB2 receptors may trigger immune cell apoptosis in addition to hindering the production of cytokines. For this reason, this cannabinoid is believed to possess anti-inflammatory and immunosuppressive properties.
Research on CBN is quite limited. However, the buzz generated by the health benefits of THC and CBD has shifted attention to other cannabinoids. So, here are the areas of where CBN could make a difference.
Relieving pain
According to research published in the Archives of Oral Biology, CBN and CBD have analgesic properties. Their application was noted to help reduce myofascial pain in animals—a chronic pain illness related to fibromyalgia.
Additionally, combining CBN and CBD was noted to enhance their painkilling ability. The researchers noted that even though the analgesic impact of a CBD and CBN combination was not as potent as that of THC, it was less intoxicating.
Stimulating appetite
This is where CBN takes a different trajectory from CBD. Unlike CBD, which is an appetite suppressant, CBN appears to boost appetite.
A 2012 animal study showed that oral CBN administration increased rats' feeding behavior. As a result, CBN may be used therapeutically to help those who struggle to maintain an appetite due to health conditions, such as cancer or its treatment.
Promoting restful sleep
There is speculation that CBN has potent sedative properties. A few animal studies suggest that CBN may increase sleep duration. This is possible because research shows CBN acts on transient receptor potential (TRP) channels and can also prevent the uptake of monoamine neurotransmitters like serotonin, norepinephrine, dopamine, and GABA.
Some anecdotal evidence suggests that CBN's sedative effects are enhanced when mixed with THC. However, there is no recent scientific study regarding CBN's capacity to induce sleep.
What are the effects of CBN?
Generally, CBN shows THC-like behavioral effects in non-human animal models but at a much lower potency level.
Anticonvulsant – Like THC, CBN has been shown to possess anticonvulsant properties. However, it is not as potent as THC.
Skin conditions – Thanks to its ability to inhibit the proliferation of keratinocytes via non-CBR mechanisms, CBN's potential for use in topical applications is promising.
CBN also has TRPV2 agonistic effects, which means it may be a valuable component of topical applications for treating burns.
Bone health – research shows that CBN may stimulate the growth of quiescent mesenchymal stem cells in the marrow. Consequently, it may promote bone formation.
Anti-cancer – because CBN may stimulate the growth of breast cancer resistant proteins, researchers hypothesize it may also have anti-cancer properties.
Overall, studies—preclinical and clinical—examining the effects of CBN are outdated and few. Most were conducted in the early 70s and 80s using modest sample sizes that lacked sociodemographic variety.
Can CBN help with sleep disorders?
Cannabis research is in its infancy stage, and with CBN being one of the lesser-known cannabinoids, there is no scientific proof that it can help with sleep disorders.
A 2021 review of available medical literature on CBN's sleep-inducing properties determined that the evidence was inconclusive. Nonetheless, anecdotal evidence continues to build, and people with sleep problems who have used CBN profess it makes a difference.
In a separate study conducted at Kyushu University, the researchers showed that the CBN doses required to produce the same sleep effects (e.g., analgesia and stupor) were almost nine times more than the dose of THC with similar effects.
Further, another experiment on cannabis and sleep was carried out on healthy volunteers using oral doses of THC (20mg) and CBN (40mg). The findings showed no detectable changes in the intensity, quality, and duration of the effects of THC. Essentially, 40mg of CBN did nothing to enhance sleep.
Other studies show that CBN is a less potent sedative compared to THC and that, for the most part, it counteracts THC's sedative effects. Even at high doses (1200 mg), a study demonstrated that CBN does not induce catalepsy and analgesia—two conditions required for better sleep.
The fact that CBN interacts very weakly with the CB1 receptor might explain why it fails to have meaningful effects on pain relief, relaxation, and sleep.
Can you mix CBD and CBN?
Yes, you can mix CBN and CBD. In any case, broad spectrum and full spectrum cannabis products naturally have both cannabinoids so that they can be taken together.
Our CBD + CBN Sleep Gummies are made with CBD, in broad spectrum or full spectrum options, and include CBN. This combination makes these gummies powerful stress and anxiety relievers, making them ideal for people who want to fall and stay asleep faster and longer.
Furthermore, researchers seem to think cannabinoids work better together than in isolation—a phenomenon known as the "entourage effect."
Fortunately, our Sleep Drops also contain organic broad spectrum CBD and CBN plus herbal extracts (peppermint, lavender, and stevia) diluted in high-quality MCT oil for higher bioavailability and faster absorption into the bloodstream. This means the effects kick in faster and last longer!
Is CBN legal?
This depends on the source of the CBN. With the passage of the 2018 Farm Bill, hemp and its associated derivatives were detached from the Controlled Substances Act's (CSA) definition of marijuana. So, as long as your CBN product is derived from hemp and does not contain more than 0.3% THC by content, it is legal.
Even though CBN is not explicitly scheduled under the CSA, it remains illegal if its sources are non-exempted portions of the cannabis plant.
Is CBN legal in Texas?
Cannabis products derived from hemp with less than 0.3% THC content are legal in Texas as spelled out under Chapter 443 of the Texas Health & Safety Code.
Is CBN legal in the UK?
Medical cannabis is only legal in the UK under exceptional circumstances. Such compounds like CBN are controlled and illegal in the country. This is because the Misuse of Drugs Act (MDA) does not differentiate between cannabis, marijuana, or hemp.
Moreover, the logic behind criminalizing cannabinoid products in the UK stems from the fact that it is difficult to isolate pure CBD, which under the MDA 1971/MDR 2001, is not a controlled substance.
The anti-drug authorities, therefore, maintain that any CBD product is likely to contain controlled cannabinoids like THC and THCV.
Is CBN legal in Florida?
Yes, CBN is legal in Florida and all other states in the United States. The rule of thumb regarding the legality of cannabis products in the U.S. is that their THC content must not be more than 0.3%.
Are all CBN products legal?
No. Even though CBN is not currently scheduled under the CSA, it follows that CBN derived from marijuana and non-exempted marijuana parts is illegal in the U.S.
CBN oil is a tincture made from hemp with above-average CBN content. Due to the relatively low quantities of CBN in hemp, CBN oils naturally contain low amounts of CBN.
Although the CBN industry is still young, most cannabis products also include CBD in a balanced CBN to CBD ratio or as the primary cannabinoid.
Again, the legality of CBN oil depends on its source. It is legal if it is derived from hemp, whose THC content is lower than 0.3%. However, it is illegal if derived from marijuana or high THC content hemp.
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Home / Disease and Condition / Alzheimer's Disease
Why Sleep Cycle Disruptions May Be A Warning Sign of Alzheimer's Disease
By Kaitlin Covel Jan 30 2018 - 10:46pm
New research shows that the disruption of our sleep cycles, known as circadian rhythm cycles, can warn us of impending dementia or Alzheimer's disease. One of the key characteristics of Alzheimer's disease is the inability to sleep consistently at night while struggling to remain awake during the day.
A new study published by JAMA Neurology yesterday discovered that people with no cognitive impairment were more likely to have amyloid protein deposits in their brains if their sleep-wake cycle was irregular. These indicative deposits of amyloid plaque can remain undetected for years before symptoms of memory loss or cognitive impairment become apparent.
The findings revealed that participants who followed a consistent sleep pattern and remained awake and alert throughout the daytime were less likely to develop amyloid plaque deposits in their brains. The research did not indicate if sleep pattern disruption was a predisposing factor in Alzheimer's or just another symptom of the disease. More research is necessary to explore a deeper significance between sleep cycle disruption and Alzheimer's disease.
Sleep Recommendations
Dr. Eric S. Musiek, a Washington University neurologist exploring the role of the circadian clock in aging, advises: "You want to consolidate your sleep as much as possible at night. I always tell my patients not to use electronic devices at night, to sleep in a dark room, and to go to sleep, not watch TV in bed." He also recommends to: "get up in the morning, get active, go out and get into the morning light" and added that eating a healthy breakfast "helps synchronize your clock."
Musiek mentioned a study previously published in the Journal of Experimental Medicine whose findings may confirm the significance of the relationship between sleep cycle disruption and Alzheimer's disease. In the study, the rodent participants' normal circadian rhythms were turned upside down by a concoction of drugs and genetic engineering. This disruption resulted in amyloid plaque that began to swiftly accumulate in the hippocampus of the brain, a key structure responsible for memory and learning capacity. The study concluded by suggesting that the circadian rhythm abnormalities accelerated the amyloid plaque accumulation in the rodent's brains.
Circadian Rhythm Cycle
The study's authors concluded: "A clear implication of our findings is that therapies directly targeting the circadian system to normalize circadian timing, rather than just augmenting total sleep, may be beneficial in the prevention of Alzheimer's Disease." Musiek believes that our individual inclinations, whether we are early birds or night owls, are rooted in genetic expression.
The study also pointed out that circadian dysfunction is always associated with aging regardless of predisposing factors for Alzheimer's disease. This especially applies to men. The study authors hope that this new research will serve as yet another biomarker indicative of early cognitive decline.
In conclusion, the quality of our sleep is crucial on a variety of levels. As I mentioned in a previous article, it is only in the deepest REM portion of the sleep cycle that our brains are able to dissolve amyloid plaque deposits. Bedtime should be a top priority for all of us.
Check out these other great articles by EMaxHealth: Why Aerobic Exercise May Play a Role in the Prevention of Alzheimer's Disease and How Sleep Apnea Increases Your Risk of Alzheimer's Disease.
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Type 2 diabetes is a common chronic disease characterized by high blood glucose. According to Frost & Sullivan's data for 2017, there are estimated 120 million people with type 2 diabetes in China. However, only 44% of patients are receiving treatment, and many patients have insufficient blood glucose control; therefore, this chronic disorder has reached a pandemic level and unmet medical needs remain substantial.
Many of the anti-diabetic drugs on the markets are liable for hypoglycemia which is a significant safety concern. Thanks to its low risk of hypoglycemia, GLP-1 analog is an important class of anti-diabetic drug. However, currently no long-acting GLP-1 agonists have been approved in China yet, and the short-acting GLP-1 products on the market need to be injected once or twice daily.
TJ103 promotes glucose concentration dependent insulin secretion and inhibits glucagon production in the body without causing the risk of hypoglycemia. It is also designed molecularly with extended half-life to enable once-weekly or bi-weekly subcutaneous administration, which can significantly improve convenience and as a result to improve patient treatment compliance. In preclinical studies, and the on-going Phase I trial conducted in Germany, TJ103 demonstrated a good safety profile.
I-Mab Biopharma plans to conduct clinical trials in China to comprehensively assess the safety and efficacy of TJ103, as well as exploring the treatment compliance, the quality of life and other potentials, in hopes of bringing the innovative drug to patients with type 2 diabetes in China, which can significantly improve the treatment effect and quality of life of the patients.
Facilitated by a merger between Third Venture Biotech and Tasgen Bio, followed by a Series B financing of US$150 million in 2017, I-Mab has rapidly built a highly experienced team with world-class R&D capabilities. On June 29, 2018, I-Mab announced that it had successfully raised US$220 million in Series C financing with a group of reputable investors led by Hony Capital, one of the largest amounts ever raised in Series C by an innovative biotech company in China. I-Mab focuses on discovery and development of First-in-Class and Best-in-Class biologics in the areas of immuno-oncology and immuno-inflammation. The company has already initiated a Phase 2 clinical trial and is prepared to submit multiple IND applications for additional trials in China and in the US, including Phase 2 and Phase 3 studies.
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OBJECTIVE: To examine the associations of duration of exclusive breastfeeding with infections in the upper respiratory (URTI), lower respiratory (LRTI), and gastrointestinal tracts (GI) in infancy.
METHODS: This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life onward in the Netherlands. Rates of breastfeeding during the first 6 months (never; partial for <4 months, not thereafter; partial for 4–6 months; exclusive for 4 months, not thereafter; exclusive for 4 months, partial thereafter; and exclusive for 6 months) and doctor-attended infections in the URTI, LRTI, and GI until the age of 12 months were assessed by questionnaires and available for 4164 subjects.
RESULTS: Compared with never-breastfed infants, those who were breastfed exclusively until the age of 4 months and partially thereafter had lower risks of infections in the URTI, LRTI, and GI until the age of 6 months (adjusted odds ratio [aOR]: 0.65 [95% confidence interval (CI): 0.51–0.83]; aOR: 0.50 [CI: 0.32–0.79]; and aOR: 0.41 [CI: 0.26–0.64], respectively) and of LRTI infections between the ages of 7 and 12 months (aOR: 0.46 [CI: 0.31–0.69]). Similar tendencies were observed for infants who were exclusively breastfed for 6 months or longer. Partial breastfeeding, even for 6 months, did not result in significantly lower risks of these infections.
CONCLUSIONS: Exclusive breastfeeding until the age of 4 months and partially thereafter was associated with a significant reduction of respiratory and gastrointestinal morbidity in infants. Our findings support health-policy strategies to promote exclusive breastfeeding for at least 4 months, but preferably 6 months, in industrialized countries.
Exclusive breastfeeding seems to decrease the risk of infectious diseases in infancy. However, the World Health Organization has called for more research regarding the benefits for 6 months instead of 4 months of exclusive breastfeeding.
Exclusive breastfeeding to the age of 6 months tended to be more protective than exclusive breastfeeding until the age of 4 months and partially thereafter. Our findings support health-policy strategies that promote exclusive breastfeeding for 6 months in industrialized countries.
We used a population-based prospective cohort study in the city of Rotterdam, Netherlands, to examine the associations between duration of exclusive breastfeeding and upper and lower respiratory and gastrointestinal tract infections during the first year of life.
This study was embedded in the Generation R Study, a population-based prospective cohort study from fetal life until young adulthood in the city of Rotterdam, Netherlands. The Generation R Study was designed to identify early environmental and genetic determinants of growth, development, and health and has been described previously in detail.33,34 Mothers were enrolled early in their pregnancy (gestational age < 18 weeks) or until the birth of the child. All children were born between April 2002 and January 2006 and form a prenatally enrolled birth cohort that is currently being followed until young adulthood. The response rate for the Generation R Study is 61%. In total, 7893 parents gave informed consent for participation of their infants in the postnatal phase of the study.33 The medical ethics committee of the Erasmus Medical Center (Rotterdam, Netherlands) approved the study. Written informed consent was obtained from all participants.
Information about breastfeeding was obtained by postal questionnaires when infants were aged 6 and 12 months.33 Mothers were asked whether they ever breastfed their infant (no or yes). The duration of breastfeeding was assessed by asking at what age (in months) the infant received breast milk for the last time. Three categories of breastfeeding were used for 3 groups of infants who received breastfeeding for less than 4 months, 4 to 6 months, or 6 months or longer. The duration of exclusive breastfeeding was defined by using information about at what age other types of milk and/or solids were introduced during the first 6 months of life. The information about duration and exclusiveness of breastfeeding was combined and grouped into the following 6 breastfeeding categories: (1) never; (2) partial for less than 4 months, not thereafter; (3) partial for 4 to 6 months; (4) exclusive for 4 months, not thereafter; (5) exclusive for 4 months, partial thereafter; and (6) exclusive for 6 months. "Never" indicates that the infant had never been breastfed, "partial" indicates that the infant was both breastfeeding and fed with formula or solids during this period, and "exclusive" indicates that the infant was breastfed and received no other milk, solids, or fluids. After the age of 6 months, all infants received other milk, fluids, and/or solids.
Information about infectious diseases was obtained with questionnaires given when the infants were aged 6 to 12 months. Parents were asked whether their infant had had a serious cold, ear or throat infection, pneumonia, bronchitis, bronchiolitis, or gastrointestinal tract infection ("no," "yes, not visited a doctor," or "yes, visited a doctor"). No information was available for the number of episodes of these infections. The respiratory tract infections were combined into doctor-attended and not doctor-attended upper (serious cold, ear infection, throat infection) and lower (pneumonia, bronchitis, and bronchiolitis) respiratory tract infections.
Information about the ethnicity and educational level of the mothers was obtained at the time of enrollment in the study. Ethnicity and educational level of the mothers were defined according to the classification of Statistics Netherlands.35,36 Information on family history of asthma, house dust mite allergy, and hay fever was available from the questionnaires. Birth weight and date of birth were obtained from midwife and hospital registries. Gestational age was established by fetal ultrasound examination.37 Information about siblings, day care attendance, and maternal smoking (no or yes) was obtained by questionnaire when the infants were 6 months old.
Of the 7893 participants in the postnatal cohort, 7295 (92%) gave consent to receive questionnaires. Our analyses were restricted to singletons. Of 7116 infants, 60% and 69% of the participants responded to the questionnaires given when the infant was aged 6 and 12 months, respectively. Information about breastfeeding in infancy was available for 4618 infants (65%). Of those infants, information about at least 1 infectious disease at the ages of 6 and 12 months was available for 4164 and 3962 infants, respectively. We compared differences between subjects included and not included in the analyses. For the adjusted analyses, complete information about duration of exclusive breastfeeding, infectious diseases, and all confounders until the age of 6 months was available for 3504 (upper respiratory tract infections), 3489 (lower respiratory tract infections), and 3438 (gastrointestinal infections) infants. For the age period of 7 to 12 months, complete information on breastfeeding and infectious diseases was available for 2958 (upper respiratory tract infections), 3027 (lower respiratory tract infections), and 2938 (gastrointestinal infections) infants.
First, differences in subject characteristics between those included and not included in the analyses were compared by using χ2 tests. Second, the associations between duration of breastfeeding and upper and lower respiratory and gastrointestinal tract infections in infants aged 6 and 12 months were analyzed by using multiple logistic regression analysis. Third, to examine whether the effects of the duration of breastfeeding were a result of exclusive breastfeeding, the associations between duration of exclusive breastfeeding and upper and lower respiratory and gastrointestinal tract infections were examined. All models were adjusted for potential confounders, including maternal education, ethnicity, smoking, gestational age, birth weight, siblings, and day care attendance. Tests for trend were performed by including the breastfeeding categories as continuous variables in the regression models. The statistical analyses were performed by using SPSS 11.0 for Windows (SPSS Inc, Chicago, IL).
The median infant age at which parents filled in the 6- and 12-month questionnaire was 6.3 months (90% confidence interval [CI]: 5.7–8.8) and 11.9 months (90% CI: 11.6–13.6), respectively. Most of the mothers were highly educated (55%) and of Dutch ethnicity (61%) (Table 1). Median gestational age at birth was 40.1 weeks (90% CI: 37.1–42.1 weeks), and mean birth weight was 3456 g (SD: 547 g). Of all mothers, 88% initiated breastfeeding. Of all infants, 29% received breastfeeding for less than 4 months, 25% for 4 to 6 months, and 34% for 6 months or more. When the duration of partial and exclusive breastfeeding was taken into account, most mothers partially breastfed their infants for less than 4 months or for 4 to 6 months (29% and 29%) or breastfed their infants exclusively until the age of 4 months and partially thereafter (26%). Only 1.4% of all the infants were exclusively breastfed for 6 months. In the first 6 months of life, 40% of all the infants had an upper respiratory tract infection, 8% had a lower respiratory tract infection, and 8% had a gastrointestinal tract infection. Between the ages of 7 and 12 months, upper and lower respiratory and gastrointestinal tract infections were present in 27%, 10%, and 9% of the infants, respectively. Table 2 shows that mothers who were older than 30 years, more educated, and nonsmoking tended to breastfeed their infants longer and more exclusively. Compared with mothers who were included in the analyses, those who were not included because of missing data on breastfeeding were more frequently younger, less educated, and of non-Dutch origin (Table 3).
Infants who were breastfed for 4 months or 4 to 6 months did not have lower risks of upper and lower respiratory or gastrointestinal tract infections in the first 6 months compared with never-breastfed infants (all P > .05) (Fig 1). Compared with never-breastfed infants, those who were breastfed for 6 months or longer had lower risks of upper respiratory tract infections (adjusted odds ratio [aOR]: 0.62 [95% CI: 0.49–0.78]), lower respiratory tract infections (aOR: 0.61 [95% CI: 0.40–0.92]), and gastrointestinal tract infections (aOR: 0.45 [95% CI: 0.30–0.69]). Between the ages of 7 and 12 months, infants who were breastfed for 4 to 6 months or 6 months or longer had lower risks of lower respiratory tract infections (aOR: 0.56 [95% CI: 0.38–0.84] and aOR: 0.54 [95% CI: 0.37–0.79], respectively) than did infants who were never breastfed. No associations were found with upper respiratory and gastrointestinal tract infections. The adjustment of confounders did not materially change the effect estimates of the crude analysis.
Duration of breastfeeding and risk of infectious diseases in the first year of life. The reference group is never-breastfed infants. Values are ORs with 95% CIs (log scale), adjusted for maternal education, ethnicity, smoking, gestational age, birth weight, siblings, and day care attendance. A, Complete information about duration of exclusive breastfeeding, infectious diseases, and all confounders until the age of 6 months was available for 3504 infants (upper respiratory tract infections), 3489 infants (lower respiratory tract infections), and 3438 infants (gastrointestinal infections). B, For the age period of 7 to 12 months, complete information on breastfeeding and infectious diseases was available for 2958 infants (upper respiratory tract infections), 3027 infants (lower respiratory tract infections), and 2938 (gastrointestinal infections) infants. URTI indicates upper respiratory tract infection; LRTI, lower respiratory tract infection; GI, gastrointestinal tract infection. aP < .05; bP < .01.
Infants who were breastfed exclusively until the age of 4 months and partially thereafter had lower risks of upper and lower respiratory and gastrointestinal tract infections in the first 6 months after birth (aOR: 0.65 [95% CI: 0.51–0.83], aOR: 0.50 [95% CI: 0.32–0.79], and aOR: 0.41 [95% CI: 0.26–0.67], respectively) (Table 4). Infants who were breastfed exclusively for 6 months had lower risks of upper respiratory tract (aOR: 0.37 [95% CI: 0.18–0.74]) and lower respiratory tract and gastrointestinal tract (aOR: 0.33 [95% CI: 0.08–1.40] and aOR: 0.46 [95% CI: 0.14–1.59], respectively) infections, although the latter 2 were not statistically significant. Between the ages of 7 and 12 months, lower respiratory tract infections were less present in infants who were breastfed exclusively until 4 months and partially thereafter, compared with never-breastfed infants. No other associations of the various breastfeeding categories with upper and lower respiratory and gastrointestinal tract infections between the ages of 7 and 12 months were observed. All tests for trend for the associations between prolonged exclusive breastfeeding and upper and lower respiratory and gastrointestinal tract infections until the age of 6 months and lower respiratory tract infections between the ages of 7 and 12 months were significant (P < .01).
Compared with the unadjusted analyses, the effect of duration of exclusive breastfeeding on the risks of upper and lower respiratory tract infections did not materially change in the adjusted analyses (maximum decrease of the ORs: 6%). The effect estimates for gastrointestinal infections increased in the adjusted analyses (maximum: 13.4%).
Adjustment for family history of asthma, house dust mite allergy, and hay fever did not materially change the effect sizes for the duration of exclusive breastfeeding with upper and lower respiratory tract infections.
The main findings of this population-based prospective cohort study were that breastfeeding for 6 months seems to have protective effects for development of respiratory and gastrointestinal tract infections during the first 6 months. Breastfeeding for 4 months or longer seems protective for lower respiratory tract infections between the ages of 7 and 12 months. When taking the exclusiveness of breastfeeding into account, infants who were breastfed exclusively until 4 months and partially thereafter had lower risks of respiratory and gastrointestinal tract infections until the age of 6 months and lower respiratory tract infections between the ages of 7 and 12 months.
Several studies have revealed that a shorter period of breastfeeding increases the risks of physician visits for illness, lower respiratory tract infections, and gastrointestinal symptoms.8,28,32 Studies that were able to take the exclusiveness of breastfeeding into account revealed that exclusive breastfeeding, followed by partial breastfeeding, or predominant breastfeeding during 6 months or more was associated with a lower risk of gastrointestinal tract infection compared with breastfeeding for less than 3 months.24 Infants who were breastfed for less than 4 months had a higher risk of hospitalization for infectious diseases (hazard ratio: 2.45 [95% CI: 1.28–4.66]) compared with those who were breastfed for more than 4 months. In addition, infants who were breastfed for 4 to 6 months showed higher risks of both pneumonia (OR: 4.27 [95% CI: 1.27–14.35]) and recurrent otitis media (OR: 1.95 [95% CI: 1.06–3.59]) compared with those who were breastfed 6 months or longer.29,30 Authors of 1 study observed a protective effect of predominant breastfeeding for at least 6 months on doctor visits for 4 or more upper respiratory tract infections or 2 or more wheezing episodes compared with infants who were breastfed for less than 6 months.27 Our results are difficult to compare with these studies, because different breastfeeding categories and various definitions of the breastfeeding categories (predominant or exclusive) and the outcomes (self-reported or doctor-diagnosed infections) were used.
The strength of this study is its prospective population-based cohort design with a large number of subjects and the possibility to adjust for all major confounders. In addition, we were able to categorize the various breastfeeding habits in combination with the duration of breastfeeding. Some methodologic considerations need to be considered. Of all postnatal eligible participants of the Generation R Study, questionnaires with breastfeeding data were available for 65%. Compared with mothers who were included in the analyses, those who were not included because of missing data on breastfeeding were more frequently younger, less educated, and of non-Dutch origin. Our results revealed that these characteristics were associated with a shorter period of exclusively breastfeeding. Also, infectious diseases until the age of 6 months were more present in infants for whom there was no information about breastfeeding (50%) than for those for whom there was information (44%). These differences may have led to an underestimation of our effect estimates of infectious diseases. There were no differences in the prevalence of infectious diseases from the age of 7 through 12 months between those with (35%) and without (36%) breastfeeding data. Of all participants with breastfeeding data, 10% and 14% had missing data on infectious diseases at the ages of 6 and 12 months, respectively. Among those infants for whom there were no data on infectious diseases, on average 28% were exclusively breastfed for 4 months, and 1.7% were exclusively breastfed for 6 months. Because these frequencies did not differ from the frequencies in our cohort for analysis (27% and 1.4%, respectively), biased estimates caused by selective loss to follow-up seem unlikely.
Exclusive breastfeeding until the age of 4 months followed by partial breastfeeding was associated with a significant reduction of respiratory and gastrointestinal infectious diseases in infants. Exclusive breastfeeding until the age of 6 months tended to be more protective than exclusive breastfeeding until the age of 4 months and partially thereafter (P for trend significant for risks of upper and lower respiratory and gastrointestinal tract infections at ≤6 months and lower respiratory tract infections between 7 and 12 months). However, because of the small numbers, the association between exclusive breastfeeding until the age of 6 months and the risks of infectious diseases was not statistically significant when compared separately with the group of never-breastfed infants. We consider that our results are in line with the World Health Organization recommendation of exclusive breastfeeding until infants are 6 months old instead of 4 months, and our results support current health-policy strategies that promote exclusive breastfeeding for 6 months in industrialized countries.
Biological, cultural, and social constraints related to breastfeeding habits need to be studied more extensively. The effects of prolonged and exclusive breastfeeding on infectious diseases at older ages in industrialized countries remain to be studied.
The first phase of the Generation R Study was funded by Erasmus Medical Center, Erasmus University Rotterdam, and Netherlands Organization for Health Research and Development (Zon Mw). The present study was supported by an additional grant from Stichting W. H. Kröger (00–048) and AGS Kinderstichting.
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This involves clinical/medical management of the affected members through a network of preferred Medical Practitioners.
As guided by the National HIV/AIDS Treatment Guidelines as well as the Bomaid HIV/AIDS Treatment Protocol, members are monitored through periodical laboratory tests and these are undertaken at preferred Laboratory Service Provider.
This is done directly from the designated service providers. Members residing in and around Gaborone collect their medications from the designated service providers, whereas those residing far from Gaborone receive their medications through a courier service to their designated Service Providers (Doctors or Pharmacies).
This is done at the Bomaid Managed Care Unit by qualified and experienced counselors and is directed at the various needs of the member. Treatment defaulting, laboratory monitoring defaulting and other clinical or social problems are addressed by the counselors. Strict follow – up procedures are put in place to assist members.
Reporting, monitoring and evaluating of the programme's progress is undertaken continuously and reports are made available to the relevant stakeholders. Reports are statistical and no specific and confidential information about the member is divulged.
This involves treatment of cancer. It includes medical oncology (the use of chemotherapy and other drugs to treat cancer), radiation oncology (the use of radiation therapy to treat cancer), and surgical oncology (the use of surgery and other procedures to treat cancer).
Used for people with kidney problems, this involves treatment that filters and purifies the blood using a machine. This helps keep your fluids and electrolytes in balance when the kidneys can't do their job.
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Stay Fit, Avoid Breast Cancer?
Physical Activity Linked to Reduced Risk of Breast Cancer in Women
By Kelli Miller
From the WebMD Archives
May 13, 2008 -- Women who engage in regular, consistent exercise are less likely to develop breast cancer than women who are less active, according to two new studies.
Exercise has long been prescribed as a way to help ward off disease. Now experts believe physical activity may help lower a woman's breast cancer risk by reducing the production of certain hormones, such as estrogen, insulin, and insulin-like growth factor that may fuel cancer development.
Scientists reporting in the Journal of the National Cancer Institute found that regular physical activity was associated with reduced risk of premenopausal breast cancer.
(What is your exercise routine? We'd like to hear from you on WebMD's Women's Health: Friends Talking message board.)
Graham Colditz, MD, of Washington University School of Medicine in St. Louis, and colleagues evaluated questionnaires from more than 64,000 premenopausal women involved in the Nurses Health Study II. The women detailed their leisure-time physical activity starting from age 12 to the present.
After six years of follow-up, 550 women developed breast cancer. Researchers discovered that the women whose activity equaled 13 walking hours a week or 3.25 running hours per week had a 23% lower risk of premenopausal breast cancer compared with the less active women. The strongest association was seen with increased exercise during adolescent and young adult years (ages 12-22).
"These results suggest that consistent physical activity during a woman's lifetime is associated with decreased breast cancer risk. Unlike many risk factors for breast cancer, physical activity is an exposure that can be modified," the authors say in a news release.
According to background in the journal article, the current study is one of few that have examined the impact of exercise on premenopausal breast cancer.
Several studies have shown that regular exercise helps a woman reduce her risk of breast cancer after menopause. The latest study, published in the British Journal of Sports Medicine, shows that the most physically active women cut their risk of breast cancer by 25%, but the benefit varies depending on factors such as physical activity type, timing, family history of breast cancer, and body mass index (BMI).
Christine M. Friedenreich, PhD, of the Division of Population Health and Information of the Alberta Cancer Board in Calgary, Canada, and colleagues analyzed findings from 62 studies to determine how physical activity might influence breast cancer risk. They report that in more than two-thirds of the studies included in their analysis, there was a 25% reduced risk of breast cancer in the most active women compared to the least active women.
Friedenreich's team found that all activity -- including housework -- lowered a woman's risk of breast cancer, but sports and other vigorous recreational activity, such as walking or running, further reduced the risk. Women with lower BMI or postmenopausal women who played sports or engaged in regular exercise had lower risks of breast cancer compared to women with very high BMI and premenopausal women.
Fitness isn't a guarantee that you won't develop breast cancer, and the researchers are not saying lack of exercise causes breast cancer.
WebMD Health News Reviewed by Louise Chang, MD on May 13, 2008
Friedenreich, C. British Journal of Sports Medicine, May 2008, manuscript received ahead of print.
News release, BMJ Specialist Journals.
News release, Washington University School of Medicine in St. Louis.
Maruti, S. Journal of the National Cancer Institute, May 21, 2008, manuscript received ahead of print.
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Synergism of IL3 together with GMCSF causes a rapid rise in neutrophils due to GMCSF and a slower rise in platelets due to IL3 which has strong stimulated effect on hematopoietic cells.
The analog of GMCSF/IL3 is PIXY321. Results indicate that PIXY321 can stimulate multilineage hematopoiesis in vivo and enhance neutrophil and platelet recovery following chemotherapy and bone marrow transplantation (BMT). These results suggest that PIXY321 elicits the biological effects of both its component cytokines and represents a novel means of delivering two independent but interactive cytokines in combination. PIXY321 is purified by proprietary chromatographic techniques.
GMCSF/IL3 fusion protein Human Recombinant produced in E.Coli is a single, non-glycosylated, polypeptide chain having a Mw of 30kD.
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Digital game-based second-language vocabulary learning and conditions of research designs: A meta-analysis study
Yu-Ling Tsai, Chin-Chung Tsai
Program of Learning Sciences
Second language (L2) vocabulary learning has been deemed a daunting task for many students. This meta-analysis study aimed to explore the effectiveness of applying digital games for L2 vocabulary learning. A total of 26 published studies (2001–2017) conformed with the inclusion/exclusion criteria. Due to diverse findings of previous meta-analysis research in the field, we propose a framework of four-condition research designs to differentiate the empirical studies in an attempt to disclose possible expositions for the diversity and to connect the specific learning mechanisms with the research evidence. The overall effect sizes of the studies in the four conditions are reported as follows: A large overall effect size for Condition 1 (10 studies) (experimental groups playing digital games versus control groups receiving alternative activities), medium for Condition 2 (experimental groups playing digital games with a feature added or changed versus control groups playing base-version games) (10 studies), medium to large for Condition 3 (experimental groups playing digital games and control/comparison groups receiving identical content via conventional means) (two studies), and non-significant for Condition 4 (all participants playing the same digital games but being grouped by a non-game related variable) (four studies). Next, a structure diagram is developed in which the four conditions of the research design are connected with their respective game-related factors based on their locality. Further, we conducted moderator analyses to examine how the eight potential moderator variables (game design, educational level, L2 proficiency level, linguistic distance, intervention setting, assessment type, game source and intervention length) influenced the effect sizes in Conditions 1 and 2 to illustrate various digital game-based L2 vocabulary learning scenarios. Finally, suggestions and implications are provided for game designers, educational practitioners, and researchers in the field.
Computers and Education
https://doi.org/10.1016/j.compedu.2018.06.020
10.1016/j.compedu.2018.06.020
Tsai, Y-L., & Tsai, C-C. (2018). Digital game-based second-language vocabulary learning and conditions of research designs: A meta-analysis study. Computers and Education, 125, 345-357. https://doi.org/10.1016/j.compedu.2018.06.020
Digital game-based second-language vocabulary learning and conditions of research designs: A meta-analysis study. / Tsai, Yu-Ling; Tsai, Chin-Chung.
In: Computers and Education, Vol. 125, 2018, p. 345-357.
Tsai, Y-L & Tsai, C-C 2018, 'Digital game-based second-language vocabulary learning and conditions of research designs: A meta-analysis study', Computers and Education, vol. 125, pp. 345-357. https://doi.org/10.1016/j.compedu.2018.06.020
Tsai Y-L, Tsai C-C. Digital game-based second-language vocabulary learning and conditions of research designs: A meta-analysis study. Computers and Education. 2018;125:345-357. doi: 10.1016/j.compedu.2018.06.020
Tsai, Yu-Ling ; Tsai, Chin-Chung. / Digital game-based second-language vocabulary learning and conditions of research designs: A meta-analysis study. In: Computers and Education. 2018 ; Vol. 125. pp. 345-357.
@article{9651cf5c012746b0b0c1c090179c1a38,
title = "Digital game-based second-language vocabulary learning and conditions of research designs: A meta-analysis study",
abstract = "Second language (L2) vocabulary learning has been deemed a daunting task for many students. This meta-analysis study aimed to explore the effectiveness of applying digital games for L2 vocabulary learning. A total of 26 published studies (2001–2017) conformed with the inclusion/exclusion criteria. Due to diverse findings of previous meta-analysis research in the field, we propose a framework of four-condition research designs to differentiate the empirical studies in an attempt to disclose possible expositions for the diversity and to connect the specific learning mechanisms with the research evidence. The overall effect sizes of the studies in the four conditions are reported as follows: A large overall effect size for Condition 1 (10 studies) (experimental groups playing digital games versus control groups receiving alternative activities), medium for Condition 2 (experimental groups playing digital games with a feature added or changed versus control groups playing base-version games) (10 studies), medium to large for Condition 3 (experimental groups playing digital games and control/comparison groups receiving identical content via conventional means) (two studies), and non-significant for Condition 4 (all participants playing the same digital games but being grouped by a non-game related variable) (four studies). Next, a structure diagram is developed in which the four conditions of the research design are connected with their respective game-related factors based on their locality. Further, we conducted moderator analyses to examine how the eight potential moderator variables (game design, educational level, L2 proficiency level, linguistic distance, intervention setting, assessment type, game source and intervention length) influenced the effect sizes in Conditions 1 and 2 to illustrate various digital game-based L2 vocabulary learning scenarios. Finally, suggestions and implications are provided for game designers, educational practitioners, and researchers in the field.",
keywords = "Applications in subject areas, Evaluation of CAL systems, Improving classroom teaching, Pedagogical issues",
author = "Yu-Ling Tsai and Chin-Chung Tsai",
doi = "10.1016/j.compedu.2018.06.020",
journal = "Computers and Education",
T1 - Digital game-based second-language vocabulary learning and conditions of research designs: A meta-analysis study
AU - Tsai, Yu-Ling
AU - Tsai, Chin-Chung
N2 - Second language (L2) vocabulary learning has been deemed a daunting task for many students. This meta-analysis study aimed to explore the effectiveness of applying digital games for L2 vocabulary learning. A total of 26 published studies (2001–2017) conformed with the inclusion/exclusion criteria. Due to diverse findings of previous meta-analysis research in the field, we propose a framework of four-condition research designs to differentiate the empirical studies in an attempt to disclose possible expositions for the diversity and to connect the specific learning mechanisms with the research evidence. The overall effect sizes of the studies in the four conditions are reported as follows: A large overall effect size for Condition 1 (10 studies) (experimental groups playing digital games versus control groups receiving alternative activities), medium for Condition 2 (experimental groups playing digital games with a feature added or changed versus control groups playing base-version games) (10 studies), medium to large for Condition 3 (experimental groups playing digital games and control/comparison groups receiving identical content via conventional means) (two studies), and non-significant for Condition 4 (all participants playing the same digital games but being grouped by a non-game related variable) (four studies). Next, a structure diagram is developed in which the four conditions of the research design are connected with their respective game-related factors based on their locality. Further, we conducted moderator analyses to examine how the eight potential moderator variables (game design, educational level, L2 proficiency level, linguistic distance, intervention setting, assessment type, game source and intervention length) influenced the effect sizes in Conditions 1 and 2 to illustrate various digital game-based L2 vocabulary learning scenarios. Finally, suggestions and implications are provided for game designers, educational practitioners, and researchers in the field.
AB - Second language (L2) vocabulary learning has been deemed a daunting task for many students. This meta-analysis study aimed to explore the effectiveness of applying digital games for L2 vocabulary learning. A total of 26 published studies (2001–2017) conformed with the inclusion/exclusion criteria. Due to diverse findings of previous meta-analysis research in the field, we propose a framework of four-condition research designs to differentiate the empirical studies in an attempt to disclose possible expositions for the diversity and to connect the specific learning mechanisms with the research evidence. The overall effect sizes of the studies in the four conditions are reported as follows: A large overall effect size for Condition 1 (10 studies) (experimental groups playing digital games versus control groups receiving alternative activities), medium for Condition 2 (experimental groups playing digital games with a feature added or changed versus control groups playing base-version games) (10 studies), medium to large for Condition 3 (experimental groups playing digital games and control/comparison groups receiving identical content via conventional means) (two studies), and non-significant for Condition 4 (all participants playing the same digital games but being grouped by a non-game related variable) (four studies). Next, a structure diagram is developed in which the four conditions of the research design are connected with their respective game-related factors based on their locality. Further, we conducted moderator analyses to examine how the eight potential moderator variables (game design, educational level, L2 proficiency level, linguistic distance, intervention setting, assessment type, game source and intervention length) influenced the effect sizes in Conditions 1 and 2 to illustrate various digital game-based L2 vocabulary learning scenarios. Finally, suggestions and implications are provided for game designers, educational practitioners, and researchers in the field.
KW - Applications in subject areas
KW - Evaluation of CAL systems
KW - Improving classroom teaching
KW - Pedagogical issues
U2 - 10.1016/j.compedu.2018.06.020
DO - 10.1016/j.compedu.2018.06.020
JO - Computers and Education
JF - Computers and Education
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Congenital deformities of the head and neck resulting from injury, surgery, medication or medical treatment, radiation, burns or chemical injury can be devastating, particularly when they involve a child or younger adult. Motor vehicle accidents, dog bites, cancer surgery, defects from injections of steroids or other toxic chemicals and military injuries can leave the head and neck with large defects, holes or dents. Fat is the ideal reparative agent in these cases, because it can be placed wherever it is needed to reshape an area, fill in a hole or dent, make the face more symmetric and improve healing of injured tissues by virtue of its stem cell component. Dr. Coleman has treated many unusual conditions, injuries and cancer-related deformities over the years using fat. He is involved in a research and treatment program using fat grafting to treat injured veterans sponsored by the US Military through the Department of Defense. Autologous fat grafting shows much promise as a treatment for war wounds such as shrapnel injuries, skull and facial bone defects, amputated limbs (including painful ones), and burns.
The team at TriBeCa Plastic Surgery is particularly gratified when we can improve the appearance of adults or children treated for cancer, born with congenital deformities, or damaged by accident, radiation or surgery. We have successfully treated congenital facial deformities such as Treacher Collins syndrome, skull deformities from injuries or brain surgery, facial asymmetry caused by surgery, neurologic problems, hemi-facial paralysis, radiation and chemotherapy, and scarring from thermal and chemical burns. We can place fat exactly where it is needed to "sculpt" the facial and skull contours — something an implant could never achieve. Particularly in the younger patient, the transplanted fat continues to grow with the recipient over time, maintaining the corrected contours. As transplanted fat has every indication of being permanent, the corrections are long lasting.
Dr. Coleman is associated with the National Foundation for Facial Reconstruction at NYU Medical Center, and enjoys being part of a respected team of surgeons whose goal it is to repair congenital and acquired head and neck deformities. Many of these surgeries may be paid in part by insurance, and our office can help determine if your insurance carrier might cover the costs. Our staff is caring and supportive, and we look forward to working with you.
This 23-year-old patient was discovered to have a rhabdomyoscarcoma of the masseter muscle (a cancer of the muscle on the side of the face used for chewing) when he was eight years old. Therapy with radiation and surgery cured him, but his facial and skull bones did not grow with the rest of his face. He was therefore left with a severely deficient left lower face (see above). Please note the horizontal position of the ear from lack of bony support. In addition the skin was extremely fragile and beard growth abnormal. He had no procedures done since his original cancer surgery.
The layering started at the bone each time and extended out to the skin. One of the most important reasons for using fat grafts in such situations is that the stem cell and growth factors present in fat grafts may cause healing of the damaged tissues.
One of potentially important reasons for using fat grafts in such wounds is the stem cell and growth factors present in fat grafts. Not only can the structural fat replace the missing fullness, but also there may be a component of accelerated healing mediated by fatty tissue.
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within the human resources industry.
get individual attention in the classroom. This program is available in an accelerated Fast Track format, giving you added flexibility.
Enrolling in this certificate program is a convenient and affordable way to determine whether a career in human resource management is right for you.
This 18 credit-hour certificate program is designed for those individuals interested in employment in the Human Resources field.
The Associate in Applied Science in Business Administration includes a specialized study area for Human Resource Management. Please refer to Business Administration in this section of the catalog if you are interested in pursuing a degree in this discipline.
Description: Examines past and present employment laws in the United States and their impact on employers and employees. Creates an understanding of the rights, duties, and obligation of both employment groups under the law.
Description: Introduces the nature of business and the environment in which it operates. Forms of business ownership, introduction to operative and facilitating facets of business operation, management, marketing, accounting, statistics, business law, finance, investments, insurance and labor-management relations.
Description: Introduces the student to the principles of training practices with emphasis on the concerns of human learning: acquisition, retention and transfer of skills. Includes supervisory and management skills, designing performance goals, MBO (Management by Objectives), forming lesson plans, mechanics of training, experiential instruction, role playing, case studies and technologies available.
Description: Examines the various aspects of the field of Human Resource Management (HRM) and the manner in which HRM professionals play a critical role in the success of an organization. Discusses and evaluates a wide range of contemporary HRM topics including human resource planning, employee recruitment and retention, employee benefits, talent development, performance management, laws and regulations, technology, changing workforce demographics, and the value of diversity.
Description: Emphasizes a managerial and interpersonal relations process approach to problem solving, communication and group dynamics. Specific treatment is given to managing change, appraisal and reward, solving communication problems, status needs of the work force, understanding individuals, group dynamics and reducing conflict.
Description: Provides practical knowledge of the design and implementation of effective compensation programs which include pay and benefits. Examines base pay systems, individual and group bonuses, executive compensation, issues with providing health care, long-term investment options, pension systems, discretionary and required benefits; and current issues, trends, and practices in compensation and benefits.
Description: Deals with the processes and the framework that influences the relationship between management and labor. The history of the labor movement, collective bargaining process, labor contract dispute resolution, labor and employment law, and the characteristics of both the public and private sector are discussed.
Description: Studies the collective bargaining method preparations and patterns; strategies and tactics of negotiations; and the use of mediators and arbitrators.
For more information about the Human Resources Management certificate program, contact Admission Outreach at 847.925.6700, or submit a request information form. You can also apply online.
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What is Mal de Débarquement Syndrome?
Mal de Débarquement Syndrome, or MdDS, is a long term type of motion sickness that is typically triggered by spending time on a ship, airplane or even in a car. The sufferer does not necessary have to spend a prolonged amount of time in motion in order to develop MdDS. As a rare and misunderstood illness, sufferers of MdDS may be misdiagnosed or told that their symptoms are psychosomatic before receiving an accurate diagnosis.
A constant feeling of being in motion tends to leave sufferers with long term fatigue that may not be able to be treated. Nausea, confusion, difficulty concentrating and memory loss are all symptoms that have been connected to MdDS.
Little research has been done to determine the cause of MdDS. While researchers have come to the conclusion that the condition is most likely connected to a neurological condition, no studies have been able to verify this theory.
Medications can be used to treat individual symptoms of MdDS, but there is no cure for the condition. Many sufferers find that any medications prescribed by a medical professional simply lessen the severity of their symptoms instead of easing the symptoms completely.
Can you Qualify for SSD due to MdDS?
The feeling of being in motion and dealing with the associated nausea, disorientation and fatigue that comes with MdDS can be debilitating for sufferers. Although this disease is very rare, those who do develop MdDS often find themselves unable to work because of the symptoms of the condition.
Sufferers need to establish that their symptoms are so severe that they cannot reasonably sustain full time work. Since the persistent symptoms associated with MdDS leave many people with fatigue, memory loss and trouble concentrating, it is likely that a person with MdDS will be eligible for social security disability (SSD).
MdDS can last months, years or for the duration of a sufferer's life. Establishing that a person has had or can be expected to have the symptoms of this condition for at least 12 months is a must in order to qualify for SSD.
Anyone who is applying for SSD on the basis of their MdDS will need to prove that there are no meaningful full time jobs in which they could reasonably work on a sustained basis.
One of the most important reasons to get legal help when suffering from MdDS is that the disease is rare and little is known about it. Legal professionals with experience in representing clients while they are making a SSD claim know the requirements related to proving disability. When gathering evidence and collecting medical records is a must to back an SSD claim, hiring an attorney with experience is essential.
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Pregnancy is an important phase in every woman's life. During this period, your baby grows inside you and is completely dependent on your placenta for important functions like breathing, nourishment and elimination of waste. However, your newborn baby must adjust to the external environment once it comes into this world; but in certain cases, he/she is unable to adjust to the new environment and the changes it brings. This mostly happens when your baby is premature.
Most premature babies, i.e. those having low body weight or if born sick, must be kept in the Neonatal Intensive Care Unit (NICU) till they become strong. Again babies from IVF pregnancy are often born preterm and must be kept in the special care unit till they become mature. So also multiple pregnancy results in small for date babies that need the support of the NICU for a while. So, if your baby is sick or premature and has been referred to the NICU, you need not panic.
Almost 10 to 15% of the babies born every year are kept in the NICU. It is a special part of the hospital where a weak newborn baby is cared for by experts in the field. With technological advancement in neonatal care, there are special machines such as the incubator, warmer, ventilator, infusion pump and phototherapy, which are now being used to take care of premature babies.
The most common machine in every NICU is the incubator. An incubator is an enclosed machine in which your baby is provided with a warm, controlled and protected environment similar to your womb. A preterm baby is usually kept in an incubator until it is mature enough to survive in the normal environment.
Every NICU has a neonatologist who is responsible for the babies in this unit. Apart from him/her, there are several specially trained nurses who keep a constant watch on each and every infant in the unit. You, as the mother, are often allowed to help out in taking care of your young one.
It has been seen that during pregnancy, if you have risky lifestyles and have been involved in drug abuse or smoking for instance, the chances of your baby being small for date and being born prematurely increase. Again, in cases of pregnant women with hypertension or diabetes, the chances are higher that your newborn baby may have some problems requiring support in the NICU.
Even though IVF pregnancy is now a household term and a most common treatment for infertility, babies born through this method can require the care of a NICU. Studies have shown that babies born from IVF pregnancy are more likely to need intensive medical attention than those conceived normally.
If your umbilical cord is wound up around your baby's neck during birth, if there's fetal distress your baby may need intensive care under expert supervision to adjust to the outside world. If your baby has aspirated during delivery, he/she would need to be supported for a while to breathe normally.
Most preterm babies, i.e. those born before 37 weeks, need to be kept in the NICU for a few days or weeks. Again if your baby is born weak or has low body weight at birth, he will be kept under observation in this unit. In many cases, your newborn often develops apnea and breathing difficulty. Babies who have birth defects many of which require surgery in the newborn period would need to be kept in the NICU for further tests, evaluation, observation and treatment.
In case your baby requires the services of a NICU, it becomes imperative for you to seek professional help to choose the best neonatal care centre for your baby. Doing so can ensure your baby remains and healthy and grows normally, without any birth defects.
⟵How does diet affect one's body?
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Families First Health in Yuba City offers an Urgent Care Medication and Facilities to cuts and lacerations too.
Press on the wound to stop the bleeding.
Seek medical attention if the bleeding is heavy or does not stop quickly.
Clean the wound, no matter how small it is. Cleaning will reduce any chance of infection. Tap water and antiseptic may damage skin tissue and delay healing. Use Soap and water.
How do I know if I need medical attention?
Many people deal with minor cuts by themselves; the following gives a guide as to when to consider getting medical help.
Ideally, a doctor or nurse should clean wounds that are large, deep, or dirty, and abrasions caused by gravel. There is a risk of infection, and also a risk of permanent tattooing of the skin from gravel, dirt, grit, etc, which remain in a wound.
Wounds longer than 2 inches or which involve deeper tissues than the skin may need stitches.
If part of the wound has dead or damaged skin then this may need to be trimmed or removed to prevent infection.
Wounds caused by penetrating glass, metal, etc, may need to be carefully examined and may need an X-ray to check that there is nothing left inside.
Gaping wounds should be closed with stitches, glue, or sticky tape. Even small gaping wounds on the face are best dealt with by a doctor to keep scarring to a minimum. Most wounds are closed straight away. However, a doctor may advise waiting for a few days before closing certain wounds. If the wound is more than six hours old, if it is infected, or if it is at high risk of becoming infected, such as a wound contaminated with manure. This delayed closure aims to make sure the wound is not infected before closing it up.
You should have a tetanus booster if you are not up to date with your tetanus shot.
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What should I feed my foal after it is weaned?
The nutrient needs of the growing horse are somewhat different to that of a mature adult horse. It is vital that young horses receive optimal levels of all vitamins and minerals. Good quality protein is also essential to ensure that they grow and develop correctly. It is important that young ponies are provided with adequate but not excessive amounts of energy (calories) in the diet, which could lead to developmental problems. The best way to judge youngster's energy requirements is to monitor and condition score them regularly; you should aim to be able to just see their ribs. They will look leggy.
If your youngster is currently in good condition I would recommend that you feed him Suregrow. You may also like to consider feeding some Alfalfa Chaff as this is an excellent source of both quality protein and calcium. This is particularly useful during the winter when the grass is poor.
Particularly useful for native breeds, part-breds and warmbloods because they generally hold their weight easily and do not require as much concentrate feed as a Thoroughbred foal.
The quantity needed will depend on his growth rate, pasture quality and quantity. However, as a guide for a 1 year old that is expected to mature to 13hh and approximately 350kg, feed 1kg per day in order to meet his vitamin and mineral requirements. Split this daily quantity in to at least 2 feeds. You should continue to provide adequate amounts of hay or haylage and turn-out when possible. Ideally you should aim to feed little and often, remember that young horse's stomachs are relatively small. You should try to split a youngster's daily ration into at least 2/3 feeds per day.
I have an elderly horse that is no longer able to chew hay or haylage and has limited turn out. What can I feed her as an alternative?
Our forage replacer recipe is recommended by the Veteran Horse Society and combines Dodson & Horrell High Fibre Nuts, KwikBeet and Alfalfa. The feeding guideline is 600g dry weight of each component per 100kg of body weight. Therefore, a horse with an ideal weight of 500kg would require 3kg of each product per day. This quantity should preferably be divided into several small meals and spread throughout the day in order to try mimic normal feeding behaviour.
How should I feed my laminitic pony?
Causes of laminitis: Laminitis is a disease which can be triggered by a number of different situations including feed overload, obesity, toxaemia, trauma and some drugs, such as corticosteroids.
Monitor your horse's body weight & condition - Obesity is a predisposing factor in the onset of laminitis. Do not allow your horse to get too fat – weigh and condition score every two weeks using a weigh tape and condition score card (you can purchase them from Dodson and Horrell!) Although it is important that your pony loses some weight, it is crucial that this happens gradually.
Do not starve your horse – Commonly owners are led to believe that they should starve a pony with laminitis, but would you starve an ill person? It is vital that the pony with laminitis receives a fibrous diet supplemented with minerals and vitamins to keep their metabolism working. By restricting fibre intake too much you may risk inducing hyperlipaemia. This occurs when high levels of fat are released into blood in response to starvation and can be fatal.
Give them a high fibre diet – It is a good idea to have your hay analysed to establish its feed value (Dodson and Horrell offer a forage testing service for a small fee). If your hay was found to have a high feed value, you could try soaking it for 12 hours before feeding it. This will "leach" some of the energy from the hay – thereby helping to reduce your horse's calorie intake. Another method of providing a high fibre, low calorie diet, which can help to control weight gain, is to "dilute" the hay with good quality oat straw (50:50). However, feeding straw is not advised for horses with dental problems because straw is coarser and less digestible then hay and does require thorough chewing. Straw is also not advised for horses prone to colic.
Avoid lush grass – The flush of grass growth in spring and autumn are well-known risk factors for laminitics, but I would also recommend that you avoid frosty pasture in the winter. Recent research suggests that the fructan concentration in grass is higher at this time. If you do need to turn out on frosty grass then may I suggest that you provide hay in the paddock to discourage them from eating the grass until it has thawed. Using an equine muzzle or strip grazing can also help to limit your horse's grass intake.
Feed a balanced diet – Forage alone will not provide your horse with all the essential minerals and vitamins, particularly the antioxidants she requires. To ensure your pony receives a completely balanced diet I recommend feeding a feed balancer e.g. Ultimate Balancer. Ultimate Balancer also contains MSM, an anti-inflammatory, which may help to reduce any inflammation as a result of the laminitis. Alternatively you could feed a fully fortified chaff such as Safe & Sound. Both Ultimate Balancer and Safe and Sound contain Dodson and Horrell's unique Quality Life Care (QLC) antioxidant package.
Important new research carried out by Dr R. Neville and Dodson and Horrell has shown that horses and ponies suffering from chronic laminitis produce higher levels of free radicals in their body.
These free radicals damage the body's' cells and tissues including muscles and DNA, through the process of oxidation. Furthermore, it is now thought that free radical damage may actually be involved in the pathology of laminitis.
Dietary antioxidants such as vitamin C, vitamin E, selenium and copper neutralise free radicals, thereby preventing them from damaging the body.
Studies by Dodson and Horrell have shown that the best way to enhance the total antioxidant defence system of the horse is to feed a combination of classical dietary antioxidants and key plant components (Lowe, 2002). For instance, the horse can only use vitamin E once, although if other antioxidants are present vitamin E can be recycled and used to neutralise more free radicals.
Providing supplementary antioxidants in the diet of horses and ponies prone to laminitis is essential. Many Dodson and Horrell feeds contain QLC, a unique antioxidant package.
What is the difference between a feed balancer and a normal concentrate feed?
A feed balancer is designed to be fed in small quantities, to provide a concentrated source of nutrients such as protein and micro-nutrients so that horses who are only fed forage will receive a balanced diet. Ultimate Balancer is formulated to be fed at just 100g/100kg bodyweight per day.
A conventional concentrate (pellet or mix) is designed to provide an additional source of calories and therefore the quantity fed will be much higher, and is dependent on the horse's calorie requirement. For example, Competition Mix is formulated to be fed at a rate of 600g/100kg bodyweight per day. Normal concentrate feeds, when fed at the recommended level, will also supply all the micro-nutrients your horse needs for health and well-being.
Will grass provide my horse with everything they need?
Unfortunately not! Whilst grass may provide sufficient calories and even protein for horses at rest or in light work a large study has shown that UK grazing will not meet their mineral requirements. For example, grass only provides around half the quantity of zinc a horse needs every day and this can result in poor hoof health.
Horses that maintain weight well on grazing alone don't need lots of concentrate feed but they still need extra vitamins and minerals. To make sure your horse's diet is balanced, consider feeding Dodson & Horrell Equi-Bites or Daily Vitamins & Minerals.
I have recently changed to haylage and my horse's droppings have become much looser. Is there anything I can feed to help with this?
There are many reasons why your horse may have developed loose droppings. It seems likely that on this occasion it may be linked to his recent change in forage type. Hay and haylage are fermented in the horses' large intestine with the help from a population of bacteria and other important microbes. A change in diet can disrupt this sensitive hind gut environment causing your horses droppings to become loose.
In this instance we recommend that you use Dodson & Horrell Digestive Support. Digestive Support is a comprehensive pre-biotic that uses a combined approach to ensure that digestive disturbances are minimised by supporting beneficial bacteria.
Another thing to remember is that haylage has a higher moisture content than hay thus the amount of fibre your horse receives from the same weight will be much less. As a result you will need to feed more haylage than hay to fulfil your horse's fibre requirements but remember it is usually of higher nutritional value and you will be feeding more calories. To enable you to calculate how much haylage your horse needs we recommend that you have it analysed using our Forage Analysis service.
How much hay or haylage should I feed?
Forage is an essential part of all horses and pony diets. Horses have evolved as trickle-feeders and feeding insufficient forage can result in problems such as stereotypic behaviours, gastric ulcers and/ or colic. Horses will eat between 2-2.5% of their bodyweight as dry forage per day. Depending on the usage of the horse some forage may be replaced by concentrate. However, if your horse needs to lose weight it may be necessary to restrict forage intake. We recommend a restriction of no less than 1.5% of body weight unless under veterinary supervision.
Are carrots safe to feed?
One or two carrots a day, as a treat, is perfectly acceptable. It is a common misconception that feeding fresh carrots will supply the horse with lots of sugar. In fact carrots are 88% water and provide only around 4g of sugar each. If you would prefer to feed a more nutritious treat to your horse or pony then we recommend that you consider Dodson & Horrell Equi-Bites. These are tasty bite size treats and have the benefit of a full range of added vitamins and minerals, helping to ensure that your horses' nutrient requirements are met.
How much concentrate feed is safe to feed in one meal?
The horse's stomach is very small in comparison to the rest of the digestive system. As a result feeding large concentrate meals can increase the risk of problems such as colic. You should aim to feed no more than 500g/100kg bodyweight per meal.
For example a 500kg horse should have a maximum of 2.5kg of food per meal. Remember that this amount includes everything in the bucket; concentrate feed, chaff and sugar beet etc. In some cases the meal size may need to be even smaller for example horses and ponies with Cushing's Syndrome (PPID) may require very small, regular meals.
How do I keep my horse hydrated?
The body contains 60-70% water and this water plays an essential role in transporting blood cells and nutrients around the body. The water in the body is also important for thermoregulation - during exercise sweat is produced, which then evaporates from the skins surface helping us to keep cool. Sweat also contains electrolytes including sodium, chloride, potassium, calcium and magnesium. These electrolytes play an important role in both nerve and muscle function.
Dehydration occurs when you or your horse lose excessive amounts of water and electrolytes. If you become dehydrated you might notice that you feel dizzy, cannot concentrate or even feel sick. In your horse signs of dehydration can include decreased appetite, increased risk of impaction colic and reduced athletic performance. It's amazing how much sweat your horse can produce; for example after a cross country phase horses can lose 15-20 litres of sweat and an endurance horse could lose double this during a race!
It can be difficult to monitor how much your horse is sweating and the skin-pinch test is very inaccurate. However, a good way of estimating fluid losses is to use a weigh-tape. It is generally accepted that 90% of a horse's weight loss after exercise is due to sweating and 1kg of bodyweight equates to approximately 1 litre of fluids. Following initial research on 100 horses at Warwickshire College our scientifically validated weigh-tape has been used to measure post-exercise body weight losses at Burghley Horse Trials.
Fluid and electrolyte losses must be replaced to avoid dehydration. Simply drinking a bottle of water or offering your horse water after exercise will not be enough to re-hydrate properly as the body cannot hold onto water without the presence of electrolytes. Drinking a sports drink that contains electrolytes will help you re-hydrate and replenish any losses. Similarly if your horse is losing more than 10kg of body weight after work you will need to feed an electrolyte supplement such as Dodson & Horrell Electrolytes.
How close to exercise should I feed my horse?
We generally recommend leaving at least 90 minutes in between feeding a concentrate feed an exercising your horse. This allows the food to pass normally through the stomach and into the small intestine, minimising the risk of choke or colic. Hay or haylage is generally fine to feed up until you begin to tack up.
One exception to this rule is feeding alfalfa chaff before exercise to provide a fibre matt in the stomach and reduce gastric acid 'splashing' onto the sensitive squamous mucosa. We recommend feeding half a scoop of alfalfa chaff half an hour before exercise in these cases, particularly if your horse has a sensitive stomach or will be doing any fast work or jumping.
How do I help my horse develop topline?
Topline in horses is used to describe the muscle coverage over the top of the horse's neck, back and hindquarters. The predominant 'topline' muscles are the rhomboideus, splenius, trapezius, longissimus dorsi and gluteal muscles which enable the horse to collect and extend the neck, lift the shoulder and forehand, flex the back and engage the hind legs. It is important that the difference between fat and muscle within the neck is clear, therefore owners should get their hands on the horse using body fat scoring.
The only way to build muscle is through an appropriate exercise regime and by providing essential dietary support together; neither method will work alone. A common myth is that fat can be turned to muscle, however this is unfortunately not the case.
Muscle has a tremendous capacity to respond to training, with muscle fibres needing to stretch and lay down new cells in order to grow. Single bouts of exercise have very little effect on a horse's fitness, therefore we need to train the muscles through repeated bouts of exercise to improve fitness.
Although it can be tempting to get cracking with your horse's new fitness regime it is important to get the balance right between fitness and injury. Ensure you give your horse time to rest and recover between training sessions to allow muscle recovery and do not increase the intensity of the exercise suddenly.
To encourage muscle development a strength training programme should be initiated, with specific exercises to target the key muscle groups and engage the muscles correctly. Ensure that your horse is working actively and correctly even when out for a short hack to promote correct muscle development. One of the most effective ways to develop the hindquarters is through the use of hill work. Encouraging your horse to walk actively uphill (no jogging allowed!) approximately seven times, twice a week to engage the gluteal muscles. Don't worry if you do not live in a hilly area, cavaletti poles encourage the gluteals to work through lifting of the hind leg so can be utilised instead!
To develop the longissimus dorsi muscle core strength exercises can be used that will improve tone and flexibility such as 'carrot stretches'. These stretches must be done whilst the muscles are warm to avoid damage so ensure you warm up first! Take a piece of carrot and encourage your horse to stretch to each side and to the chest, repeating several times and ensuring you are performing the exercise evenly on both sides. Ask four your vet or physiotherapist's advice if you are unsure.
The main component of muscle and body tissue is protein which is supplied in limited amounts by forage (grass, hay and haylage). However working horses will require supplementation in the form of a fully balanced compound feed or balancer. Some riders can be afraid of feeding protein in the belief that it will cause excitable behaviour - it won't! Fizziness and excitability may be the result of a horse having excess energy through being fed too many calories, but not too much protein. It is not just the level of protein in a feed we need to consider but more importantly the quality, determined by the amino acid 'building blocks' from which it is made up. The horse's body can produce some amino acids, however there are a number of essential amino acids such as lysine, which when limited will limit muscle development.
The most common problem that we see is a horse being fed less than the recommended amount of hard feed, as extra calories aren't needed, without 'topping-up' with a balancer to supply essential amino acids, vitamins and minerals. Dodson & Horrell recommend either feeding the full recommended amount of a performance feed that contains lysine or, if your horse does not need the calories, using a high quality balancer that contains lysine. If you feed a chaff alongside your feeds consider using alfalfa, a natural source of high quality protein.
Changing your horse onto a high quality protein diet, alongside an appropriate exercise regime should be sufficient to enable topline development within six weeks, however if no improvement is made a protein supplement could be considered.
My horse is in hard work but is slightly overweight and can be lethargic. What should I feed him?
It is important to remember that energy and calories are effectively the same thing. As your horse is slightly overweight we need to allow him to lose this excess weight before using high energy (high calorie) feeds. We would recommend that you monitor his weight every fortnight aiming for a condition fat score of 2.5-3.
When your horse is at his ideal body weight we can consider feeding a product appropriate for good doers in medium to hard work such as Dodson & Horrell Competition Concentrate. This feed has been formulated specifically for horses that maintain weight well but require energy for workload. Competition Concentrate is fed at a lower rate than conventional concentrates ensuring that your horses' nutrient requirements are met without contributing to weight gain. It is also formulated to enable you to add a small amount of oats to the diet if extra energy is needed, without unbalancing the vitamin and mineral content.
I have an orphan foal; how should I feed it?
If the foal was orphaned at birth or very soon after, the first thing you need to do is to make sure it gets colostrum. This is the sticky, yellow first milk produced by the mare. The foal needs to consume colostrum ideally within 12hrs after birth, as it contains vital antibodies, without which the foal is likely to become very ill. If possible, the colostrum should come from the foal's own mother; alternatively your vet should be able to provide a source of donor colostrum.
Next you will need to decide how you are going to provide the foal with milk. A foster mare is the ideal solution but if this isn't possible then you will need to bottle or bucket feed using our specially formulated mare's milk replacer, Equilac. Your foal will need to be fed Equilac until weaning, at around 3-4 months old. If your foal is doing well we can feed this alongside a vitamin, mineral and protein balancer, Suregrow, from 2 weeks old. If your foal needs extra support we can use Foal Creep Pellets instead.
How should you feed a broodmare prone to weight gain in early pregnancy?
It can be tempting to over-feed a mare in early pregnancy (the first eight months) but it's important that she is not allowed to become overweight at this stage. Good doers generally don't need a specific stud feed in early pregnancy. However, it is important that the mare gets a fully balanced diet to support both her own health and that of the developing foetus. Feeding a low intake, low calorie balancer such as Ultimate Balancer or Suregrow is ideal. This will provide good quality protein and all the essential vitamins and minerals, without supplying many calories thereby helping to limit calorie intake as part of a calorie-controlled diet.
My mare is going to have her first foal this summer, will I need to feed the foal or will it get all the nutrients it needs from its mum's milk?
Milk is low in certain key vitamins and minerals, for example copper, which are vital for correct growth and development. The nutritional composition of mare's milk changes throughout lactation and typically begins to gradually decline in the second month of lactation.
Usually foals will begin to show an interest in their dam's concentrate feed at approximately two weeks of age. At this stage it is a good idea to introduce a small quantity of good quality specifically designed concentrate feed. Introducing concentrate feed at this time will: a) Help balance the nutritional deficiencies in mare's milk, preventing any deficiencies or imbalances. b) Aid the anatomical and physiological maturation of the digestive tract. c) Teach the foal to eat on its own, thereby helping to reduce stress and the risk of digestive disturbances post weaning.
You should also aim to weight your foal and record its height every few week in order to monitor its growth rate. Abnormal growth rate may increase the risk of developmental problems such as epiphysitis.
Dodson & Horrell produce creep feeds specifically designed for Thoroughbred and Native/ Warmblood foals.
Typically Thoroughbreds grow more rapidly than other breeds and have higher nutrient requirements. Dodson & Horrell's highly palatable Foal Creep Pellets have been formulated specifically to meet the needs of the rapidly growing Thoroughbred, providing high quality protein and optimal levels of energy, vitamins and minerals to ensure optimal growth and development.
Native and Warmblood foals tend to maintain their weight and body condition reasonably well, but still require high levels of vitamins and minerals for correct growth and development. Mare and Youngstock has been specifically formulated for low intakes and therefore contains elevated levels of vitamins and minerals. This means that energy intake can be limited, preventing the foal from putting on too much weight, which stresses their joints, whilst still ensuring that they receive all the essential vitamins and minerals they require for correct growth and development.
As with all horses make sure that any changes to the foal's diet are introduced gradually.
What is the difference between fast and slow release energy and why does it matter?
Every food ingredient has an energy value, or level of calories that it provides. These calories are used for fuel for cells within the body. If this fuel is not used immediately then it is stored as either glycogen within the muscles or as fat.
These calories can come from carbohydates (cereals, sugar within grass and hay), oil (added to the diet or present in some cereals such as soya) or fibre (present in varying amounts in most ingredients but higher in forages).
Carbohydrates (starch and sugar) are digested in the horse's small intestine, broken down into glucose, which is absorbed rapidly into the bloodstream. They therefore provide 'fast-release' energy with a quick increase in blood sugar levels from around 1-4 hours after eating them. This is useful for speed and sparkle and we use it for horses who are showjumping, playing polo, some dressage horses and those who need extra 'oomph'. Competition Mix is an example of a feed that provides plenty of fast release energy.
Oil is digested in the small intestine and broken down into complex fats, which are absorbed into the bloodstream and processed by the liver. They can then either be stored or used as fuel. Fibre is digested in the large intestine, or 'hindgut' and broken down into volatile fatty acids, which are also used as fuel. The process of converting and releasing energy from oil and fibre takes a relatively long time; energy is released from 4-8 hours after eating them. Oil and fibre provide 'slow-release' energy, which is ideal for stamina. We use them in eventers, hunters, endurance horses and also in excitable or fizzy horses. Staypower Cubes and Muesli are an example of a feed that provides plenty of slow release energy.
What should I feed my excitable, fizzy horse who is competing regularly?
For horses prone to excitability we recommend feeding a diet lower in starch and sugar to avoid any potential 'sugar rushes' caused by dietary carbohydrates. Instead, we provide calories from non-heating fibre and oil. An ideal product is Dodson & Horrell Staypower Cubes, which are low in starch and sugar but provide all the nutrition your horse needs to compete. We do suggest using the cubes rather than the muesli, as the mix is slightly higher in sugar so may not be as effective at avoiding unwanted fizz!
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Magnesium is an essential nutrient found in bran, nuts, and beans. Magnesium has been used to lower cholesterol and blood pressure. It has also been used to ease pain in the body and improve heart health. Magnesium can be taken as a pill or powder. It can also be injected into the bloodstream and muscle by a healthcare provider.
300 to 400 milligrams daily
Asthma—likely to improve symptoms C1
Cardiac arrhythmias—likely to prevent D1, D2
Diabetes—likely to lower cholesterol and blood pressure levels G1-G4
High blood pressure—likely to modestly lower blood pressure H1-H4
Metabolic disorders —likely to help control blood glucose and prevent the risk of heart problems K1-K4
Migraine—likely to ease pain and intensity L1
Pre-eclampsia/eclampsia—likely to prevent the risk of eclampsia and improve birth outcome N1, N2
Anxiety—may provide benefit B1
Insulin resistance—may reduce insulin resistance I1
Lipid profile—unlikely to provide benefit J1
Muscle cramps —unlikely to ease pain, but may reduce muscle cramps in pregnant womenM1, M2
Alcohol withdrawalA1
Cystic fibrosis E1
DepressionF1
Pregnancy supportO1, O2
Tetanus Q1
It is likely safe to take magnesium in small doses. Amounts greater than 350 mg per day may be unsafe for women who are pregnant or breastfeeding.P1
A. Alcohol withdrawal
A1. Sarai M, Tejani AM, et al. Magnesium for alcohol withdrawal. Cochrane Database Syst Rev. 2013;(6):CD008358.
B. Anxiety
B1. Boyle NB, Lawton C, et al. The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review. Nutrients. 2017 Apr 26;9(5).
C. Asthma
C1. Knightly R, Millan SJ, et al. Inhaled magnesium sulfate in the treatment of acute asthma. Cochrane Database Syst Rev. 2017;11:CD003898.
D. Cardiac Arrhythmias
D1. Lee HY, Ghimire S, et al. Magnesium supplementation reduces postoperative arrhythmias after cardiopulmonary bypass in pediatrics: a metanalysis of randomized controlled trials. Pediatr Cardiol. 2013 Aug;34(6):1396-403.
D2. Salaminia S, Sayehmiri F, et al. Evaluating the effect of magnesium supplementation and cardiac arrhythmias after acute coronary syndrome: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2018 Jun 28;18(1):129.
E. Cystic Fibrosis
E1. Santi M, Milani GP, et al. Magnesium in cystic fibrosis--Systematic review of the literature. Pediatr Pulmonol. 2016 Feb;51(2):196-202.
F. Depression
F1. Derom ML, Sayón-Orea C, et al. Magnesium and depression: a systematic review. Nutr Neurosci. 2013 Sep;16(5):191-206.
G. Diabetes
G1. Verma H, Garg R. Effect of magnesium supplementation on type 2 diabetes associated cardiovascular risk factors: a systematic review and meta-analysis. J Hum Nutr Diet. 2017;30(5):621-633.
G2. Simental-Mendía LE, Sahebkar A, et al. A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol Res. 2016 Sep;111:272-282.
G3. Fang X, Han H, et al. Dose-Response Relationship between Dietary Magnesium Intake and Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-Regression Analysis of Prospective Cohort Studies. Nutrients. 2016 Nov 19;8(11).
G4. Veronese N, Watutantrige-Fernando S, et al. Effect of magnesium supplementation on glucose metabolism in people with or at risk of diabetes: a systematic review and meta-analysis of double-blind randomized controlled trials. Eur J Clin Nutr. 2016 Dec;70(12):1354-1359.
H. High blood pressure
H1. Kass L, Weekes J, et al. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr. 2012 Apr;66(4):411-418.
H2. Rosanoff A, Plesset MR. Oral magnesium supplements decrease high blood pressure (SBP>155 mmHg) in hypertensive subjects on anti-hypertensive medications: a targeted meta-analysis. Magnes Res. 2013 Jul-Sep;26(3):93-99.
H3. Zhang X, Li Y, et al. Effects of Magnesium Supplementation on Blood Pressure: A Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials. Hypertension. 2016;68(2):324-333.
H4. Dibaba DT, Xun P, et al. The effect of magnesium supplementation on blood pressure in individuals with insulin resistance, prediabetes, or noncommunicable chronic diseases: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2017 Sep;106(3):921-929.
I. Insulin Resistance
I1. Morais JBS, Severo JS, et al. Effect of magnesium supplementation on insulin resistance in humans: A systematic review. Nutrition. 2017 Jun;38:54-60.
J. Lipid Profile
J1. Simental-Mendía LE, Simental-Mendía M, et al. Effect of magnesium supplementation on lipid profile: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Pharmacol. 2017 May;73(5):525-536.
K. Metabolic disorders
K1. Qu X, Jin F, et al. Magnesium and the risk of cardiovascular events: a meta-analysis of prospective cohort studies. PLoS One. 2013;8(3):e57720.
K2. Fang X, Wang K, et al. Dietary magnesium intake and the risk of cardiovascular disease, type 2 diabetes, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies. BMC Med. 2016;14(1):210.
K3. Guerrero-Romero F, Jaquez-Chairez FO, et al. Magnesium in metabolic syndrome: a review based on randomized, double-blind clinical trials. Magnes Res. 2016 Apr 1;29(4):146-153.
K4. Simental-Mendía, Sahebkar A, et al. A systematic review and meta-analysis of randomized controlled trials on the effects of magnesium supplementation on insulin sensitivity and glucose control. Pharmacol Res. 2016;111:272-282.
L. Migraine
L1. Chiu HY, Yeh TH, et al. Effects of Intravenous and Oral Magnesium on Reducing Migraine: A Meta-analysis of Randomized Controlled Trials. Pain Physician. 2016;(1):E97-112.
M. Muscle cramps
M1. Garrison SR, Allan GM, et al. Magnesium for skeletal muscle cramps. Cochrane Database Syst Rev. 2012;(9):CD009402.
M2. Sebo P, Cerutti B, et al. Effect of magnesium therapy on nocturnal leg cramps: a systematic review of randomized controlled trials with meta-analysis using simulations. Fam Pract. 2014;31(1):7-19.
N. Pre-eclampsia/eclampsia
N1. Duley L, Gülmezoglu AM, et al. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010;(11):CD000025.
N2. Duly L, Henderson-Smart DJ, et al. Magnesium sulphate versus diazepam for eclampsia. Cochrane Database Syst Rev. 2010;(12):CD000127.
O. Pregnancy support
O1. Makrides M, Crosby DD, et al. Magnesium supplementation in pregnancy. Cochrane Database Syst Rev. 2014;(4):CD000937.
O2. Zhou K, West HM, et al. Interventions for leg cramps in pregnancy. Cochrane Database Syst Rev. 2015 Aug 11;(8):CD010655.
P. Safety
P1. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1999. Available at: http://books.nap.edu/books/0309063507/html/index.html. Accessed October 1, 2019.
Q. Tetanus
Q1. Rodrio C, Samarakoon L, et al. A meta-analysis of magnesium for tetanus. Anaesthesia. 2012;67(12):1370-1374.
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Rahila Aamir, Sana Tahir Virk, Tehzeeb Zahra, Kazim Abbas Virk, Shiza Tahir Virk.
Objective: To determine whether or not the patients should be screened for vitamin B12 deficiency.
Methodology: This cross sectional study was conducted at Shifa Foundation Clinic, from December 2016 to May 2017. A total of 196 patients were enrolled and their vitamin B12 levels were determined. The correlation of different symptoms with vitamin B12 levels was estimated. The analyses were conducted using SPSS version 20.0.
Results: Out of 196 patients, 110 (56.1%) were found to be B12 deficient and 86 (43.8%) had normal B12 levels. In patients with B12 deficiency, 90.4% patients complained of numbness and paresthesias, 57.7% of aches and pains, 83.6% of fatigue, 93.5% of memory impairment, 62.9% of general weakness, 68% of depressive symptoms and 85% of dyspnea. The correlation of numbness and paresthesias (p<0.05, r=0.4, k statistic=0.3), memory impairment (p<0.05, r=0.32, k statistic=0.25) and Dyspnea (p<0.05, r=0.29, k statistic=0.25) was significant. The correlation of depressive symptoms was slightly significant (p=0.05, r=0.14, k statistic=0.12). The correlation of aches and pains (p=0.5, r=0.04, k statistic=0.04) and generalized weakness (p=0.08, r=0.12, k statistic=0.12) was not significant.
Conclusion: Prevalence of vitamin B12 deficiency was 56.1% among patients presenting with vague symptoms having significant correlation with numbness and paresthesias, memory impairment, dyspnea and depressive symptoms.
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dc.description.abstract The current HIV epidemic is highlighted by the remarkable success of combination anti-retroviral therapy (cART). Unfortunately, life-long and continuous cART is necessary for infected individuals due to persistent HIV infection and rebound viremia if cART is interrupted. The ability of HIV to establish a reservoir within long-lived cells is a major barrier to improving treatment and affording a cure. Here, I first describe our work to characterize the HIV reservoir within hematopoietic stem and progenitor cells (HSPCs) and determine the contribution of infected HSPCs to residual viremia in vivo. We found that HSPCs bear HIV proviral genomes in almost half of donors tested (24 of 43). Furthermore, we found that HSPC-derived proviral genomes are represented within residual plasma viral sequences about 3-fold more than proviruses derived peripheral blood and bone marrow mononuclear cells. We also discovered that HSPC-derived proviruses that were genetically identical to plasma virus are very often associated with expanded clonal HIV proviruses found in peripheral blood and bone marrow mononuclear cells. Additionally, we identified a signature deletion within proviral sequences derived from HSPCs and mature PBMCs and CD4+ T cells, providing evidence that HIV-infected HSPCs can propagate the HIV genome to progeny through differentiation. This study sheds light on the heterogeneity of the HIV reservoir and presents evidence in support of a novel pathway for the establishment and maintenance of persistent HIV in vivo. Finally, I describe our work investigating strategies to potently reverse HIV latency and induce reservoir elimination using histone deacetylase inhibitors (HDIs). We determined that class 1-selective HDIs are superior to pan-HDIs in their ability to act additively with the PKC agonist bryostatin-1 to reverse latency, induce potent viral outgrowth, and promote elimination of latently-infected cells. We also found that pan-HDIs suppress potent viral reactivation; an effect that is correlated with their unique inhibitory effects on important pro-viral cellular factors, NF-κB and Hsp90. This work will significantly inform future studies that will further characterize the heterogeneity of the in vivo HIV reservoir and develop clinically pragmatic and effective latency-reversing agents that may lead to improved HIV therapy aimed at reducing the burden of persistent viral infection and hopefully affording a cure.
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Our service offers an individual alcohol and drug options for clinical detoxing and treatment programs for alcohol and drug disorders.
By realizing that we are all different, we can individualize treatment solutions towards best successes, which include a smaller relapse rates.
Searching for a substance abuse treatment center might be an difficult task when it is time for you to choose the right one. For the reason that mental illnesses and trauma often underlie alcohol addiction, therapy by mental health professionals is usually an necessary aspect of the process.
A primary facility drug rehab is a controlled living environment wherein the patient remains within the rehab facility throughout his or her whole detox.
Most of these treatments involve visiting a treatment facility or maybe a clinic for even more formalized addiction treatment or if needed, use of health-related professionals or psychological care. Nevertheless for fundamentally the most part the person is recovered to enough of a degree to be on their own and away from the treatment facility for expanded durations.
Lasting drug and alcohol recovery presents programs when the individual will remain for a time of over 3 months. The long-term halfway houses permit sufferers to extend their lodging inside of a established living environment for a longer time-frames.
Drug and / or alcohol interventions are important whenever family and/or good friends feel that their loved one or friend is suffering from a drugor alcohol related problem. In many instances a drug overdose and / or alcohol and drug abuse linked tragedy would have potentially been prevented if family or friends had contacted a specialized drug interventionist for aid at the beginning of their loved one's addiction.
Abusive drinking takes place when anyone sets out seeking alcoholic beverages obsessively & will continue to uses the substance despite the fact we have witnessed ill-effects on their day-to-day lives, this includes issues with relatives, employment or perhaps the authorities. This site offers a variety of professional services and types of help for people with alcohol dependencies based in Hammarsdale.
Abusing drugs, sometimes called abusing drugs, is known as a normal routine using a chemical substance wherein the consumer uses the narcotic in quantities or with techniques which have been damaging to themselves or others. The specific origin of drug use is impossible to understand since there is it's unlikely that any one direct factor. Relapse Prevention provides inexpensive drug rehabilitation clinics in Hammarsdale, which provides specialist attention together with the love, care & treatment in alcohol and drug free treatment centre.
The primary care Hammarsdale treatment centre provides secure and safe accommodation in an up-market halfway-house with full-time staff counsellors that manage substance abuse of alcohol, crack, cocaine, opioids, dagga, meth related dependence disorders. Hammarsdale maintains competitive admission rates as a key private treatment centre, and has one of the most successful after-care programmes on the recovery market.
Highly effective treatment address multiple necessities of the particular individual, not merely their drug abuse.
Counseling-individual and / or group and additional behavior treatment methods are the most frequently used forms of drug treatment.
A particular individuals treatment solution as well as assistance schedule will have to be assessed often and fine-tuned as essential to be certain that it suits their updating needs.
Medically assisted body detoxification is the initial step of dependency treatment plan and on its own does nothing to improve long-term substance abuse.
Treatment doesn't have to be voluntary to work.
This website is centred on assisting families to choose alcohol and drugs detox services along with extended care treatment clinics South Africa. In addition any type of drug or alcohol provider which utilises the twelve step model as an element of their particular care programme.
The AA and NA in Outer West Durban advocate an on going recovery lifestyle for alcoholics and drug users. The meetings are held in several formats but usually entail the conveyance of personal stories & active substance free life-skills coping strategies. Be aware: AA or NA is not ideal for every person suffering with an addiction disorder. The addiction topic can be a lot more complicated than going to NA or AA meetings.
Selecting a recovery centre can be an overwhelming task if you do not have experience in this field. The primary care Hammarsdale treatment centre provides secure and safe residence in home-like environment with resident counsellors that manage patients of drug and alcohol related dependence disorders. Hammarsdale maintains highly competitive residency rates as a key private treatment centre, and maintains a best in class outpatient programmes in the industry.
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According to the National Ambulatory Care Reporting System (NACRS), in 2017 in Simcoe Muskoka, there were over 900 emergency visits for cycling related injuries. The age-standardized rate for cycling injury emergency visits in Simcoe Muskoka for all ages and sexes in 2017 was 173.1 (162.2, 184.6) visits per 100,000 population, which significantly higher than the Ontario rate of 158.8 (156.7, 160.9) visits per 100,000 population.
The cycling injury emergency visit rates in both Simcoe Muskoka and Ontario displayed a significant downward trend over the 15-years from 2003 to 2017, decreasing by approximately one per cent per year. The Simcoe Muskoka cycling injury emergency visit rate was above the provincial rate for each year over this time period.
The age-standardized rate for cycling injury emergency visits in Simcoe Muskoka among males in 2017 was 242.0 (223.8, 261.2) visits per 100,000, which more than double the female rate of 102.5 (90.8, 115.4) visits per 100,000. There was a significant downward trend in the cycling injury emergency visit rates for Simcoe Muskoka males from 2003 to 2017; however, the trend for Simcoe Muskoka females has remained flat over this same time period.
The age-specific rate for cycling injury emergency visits between 2013 and 2017 (combined) in Simcoe Muskoka was highest among children between the ages of 5 and 14 years at 509.5 (483.9, 536.1) visits per 100,000 populations. This was one-and-a-half times higher than the rate for those 15 to 24 years of age and more than four-times the rate for any other age group. The age-specific Simcoe Muskoka rates were significantly higher than the provincial rates for children 5 to 14 years and young people between the ages of 15 and 24 years.
The trend in the cycling injury emergency visit rates among children (5 to 14 years) in both Simcoe Muskoka and Ontario displayed a significant downward trend over the 15-year period from 2003 to 2017, decreasing by more than four per cent per year over this period of time. The Simcoe Muskoka youth cycling injury emergency visit rate was significantly higher than the provincial rate for the entire 15 years.
For the time period from 2011 to 2016 (combined) in Simcoe Muskoka, cycling injury emergency visit rate among those living in neighbourhoods with highest prevalence of low-income was significantly higher when compared with the rates for those living in all other areas.
In Simcoe Muskoka between 2011 and 2016, there were 50 hospitalizations per year, on average, for cycling related injuries; however, this number fell by half to 24 in 2017. The reason for this decline is unknown and decreases were observed across all age groups, but were more pronounced for youth (10 to 19 years) and older adults (45 to 64 years). Males accounted for approximately 80 per cent of cycling injury hospitalizations in Simcoe Muskoka and this pattern was consistent across all age-groups. Children (5 to 14 years old) accounted for one-in-five cycling injury hospitalization in Simcoe Muskoka between 2011 and 2017. The age-specific cycling injury hospitalizations rates in Simcoe Muskoka were not significantly different from the comparable provincial rates over this eight-year time period.
Over the 16-year period between 2000 and 2015, 17 Simcoe Muskoka residents died in cycling accidents, with 16 of the 17 decedents being male and 10 of the 17 deaths were as a result of a traffic collision with a car or truck. During the same 16-year time period, 389 cyclists died across Ontario, with nearly 9-in-10 decedents being male and approximately 50 per cent of deaths were as a result of a traffic collision with a car, truck or bus. The death data come from the Vital Statistics database for Ontario.
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Dr. Giles' area of clinical interest is in inflammatory arthritis such as rheumatoid arthritis, psoriatic and arthritis, and spondylitis.
Dr. Giles is an epidemiologist and clinical researcher in the Division of Rheumatology at Columbia University. Over the past decade, his research group has focused on understanding the determinants and impacts of extra-articular comorbidities of rheumatoid arthritis. They have explored the relationships of immune and inflammatory biomarkers with disease activity, articular damage, body composition, disability, cardiovascular disease, and pulmonary disease in individuals with rheumatoid arthritis. A particular area of focus in the design of these studies has been the appropriate use of analytical modeling, diligent identification, measurement, and control of confounders, and the use of efficient and robust modeling techniques. The results of these studies have informed the design of translational studies to help define mechanisms. Other current and past research involve the investigation of accelerated atherosclerosis and myocardial dysfunction in rheumatoid arthritis patients, understanding the risks of biologic therapeutic use for patients undergoing surgery, and exploring the musculoskeletal side-effects of a class of medications used to suppress estrogen in women with certain forms of breast cancer. He is the recipient of major grant support from the National Institutes of Health, the Arthritis Foundation, the American College of Rheumatology.
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Transcription factors are important for many aspects of gene regulation in eukaryotes. YY1 (Yin-Yang 1) is a particularly interesting example of a highly conserved zinc-finger transcription factor, involved in transcriptional activation, repression, initiation, and in chromatin modification. YY1 is ubiquitously expressed in mammals, and its binding sites are found in ~10% of human genes as well as in repetitive elements. It is a targeting protein of the Polycomb complex and is involved in mammalian genomic imprinting. First, we explored the evolutionary history of YY1 using 62 species and formation of its paralogs, YY2 and REX1, which are found in mammals, and Pho and Phol, which are found in Drosophila. We confirmed the specificity of the consensus YY1 binding site and the differences of the target binding motifs of YY2 and REX1 which are reflected in their amino acid sequences. We found that the core motif, CCAT, is conserved for all three homologs and that YY2 and REX1 were produced via retrotransposition events early in the mammalian lineage. Second, we identified unusual clusters of YY1-binding motifs found in the coding regions of olfactory receptor genes (OLFRs) in mammals but not in fish. Olfactory genes provide scent detection and are the largest class of genes in mammals. Statistical analysis indicates that the core of the YY1-binding motifs cannot be acounted for by conserved amino acid motifs or overall protein homology. Thus selection has acted at the DNA level rather than at the protein level in preserving these YY1-binding sites within coding regions. Therefore, YY1 is likely to play a crucial role in regulating the expression of OLFRs. Third, we produced a new method of microarray data analysis predicated on the positions of genes along a chromosome as well as their expression levels. This technique is supplementary to traditional microarray data analysis and adds a new dimension to finding target genes of interest by looking for co-regulation. Overall, this work provides a coherent background to the evolution of YY1 and its homologs. It provides strong evidence that coding sequences of genes can encode information both at the DNA level and the protein level.
Faulk, Christopher Don, "Evolution of YY1, YY2, REX1 and DNA-binding motifs in vertebrate genomes" (2010). LSU Doctoral Dissertations. 2042.
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The Family Options Study is a multi-site random assignment experiment designed to study the impact of various housing and services interventions for homeless families. HUD launched the Family Options Study in 2008 in response to Congressional direction and with the goal of learning more about the effects of different housing and services interventions for homeless families.
Between September 2010 and January 2012, a total of 2,282 families (including over 5,000 children) were enrolled into the study from emergency shelters across twelve communities nationwide and were randomly assigned to one of four interventions: 1) subsidy-only – defined as a permanent housing subsidy with no supportive services attached, typically delivered in the form of a Housing Choice Voucher (HCV); 2) project-based transitional housing – defined as temporary housing for up to 24 months with an intensive package of supportive services offered on-site; 3) community-based rapid re-housing – defined as temporary rental assistance, potentially renewable for up to 18 months with limited, housing-focused services; or 4) usual care – defined as any housing or services that a family accesses in the absence of immediate referral to the other interventions.
Families were followed for three years following random assignment, with extensive surveys of families conducted at baseline and again approximately 20 and 37 months after random assignment. In addition to collecting data about the well-being of families and children at different points in time following random assignment, extensive cost data on each of the interventions studied was also collected, in order to calculate the fiscal costs of achieving the outcomes that were documented. While the primary outcome of interest is housing stability, and, in particular, preventing families from returning to homelessness, additional outcome domains of interest include family preservation, adult well-being, child well-being, and self-sufficiency.
An interim report, released in March 2013, describes the study's design and implementation and characteristics of the study families. The key findings in the interim report relate to families' enrollment in the different interventions being studied — both the barriers presented by stringent eligibility criteria of programs that often screen households out of assistance, and the choices made by households to reject the intervention offered. The short-term outcomes report was released in July 2015, documenting the outcomes of families and the relative costs of the interventions at the 20-month follow-up period. The long-term outcomes report, was released in October 2016, documenting the outcomes of families and the relative costs of the interventions 37 months after random assignment. All products generated from this study will be housed on this project page. For additional information, please contact Anne Fletcher at [email protected].
This report, titled Family Options Study: Long-Term Impacts of Housing and Services Interventions for Homeless Families, presents the long-term outcomes of the 2,282 families enrolled in the Family Options Study, a multi-site random assignment experiment designed to study the impact of various housing and services interventions on homeless families. The report documents how families are faring approximately 37 months after random assignment to one of four interventions: 1) subsidy-only (SUB), 2) community-based rapid re-housing (CBRR), 3) project-based transitional housing (PBTH), or 4) usual care. Outcome measures fall within five domains: housing stability; family preservation; adult well-being; child well-being; and self-sufficiency. The collection of extensive cost data for each of the interventions tested enables the calculation of the costs that can be tied to each of the interventions, and in turn, used to understand the cost of achieving the outcomes observed. The findings at 37-months in large part mirror the findings documented at 20 months, with the outcomes again demonstrating the power of a long-term housing subsidy to convey significant benefits to families experiencing homelessness when compared with the outcomes of families offered other interventions.
On October 25, 2016, HUD/PD&R hosted a public briefing on the long-term outcomes of the Family Options Study. Watch a recording of the webcast here, and listen to a presentation of the study findings from the research team, as well as a moderated Q&A with Federal leaders working to address homelessness.
Access the Long-Term Outcomes Report here, and the summary brief of key findings here.
The objective of the Family Options Study is to provide research evidence to help federal policymakers, community planners, and local practitioners make sound decisions about the best ways to address homelessness among families. The study is conducted as a rigorous, multi-site experiment, comparing four combinations of housing and service interventions for homeless families who have been in emergency shelters for at least seven days. The fundamental research question guiding the analysis seeks to understand if priority access to a particular intervention yields differences in outcomes for homeless families over the short-term (20 months after random assignment) and/or the long-term (37 months after random assignment). The Data Collection and Analysis Plan provides the blueprint for the study implementation, including: 1) an overview of the evaluation design, including the interventions studied, research questions, outcome measures, and random assignment process; 2) the follow-up survey and administrative data sources used and data collection procedures; and 3) the analysis plan, including the hypotheses to be tested, impact estimation model, strategy for addressing multiple comparisons, subgroup analysis, addressing no-shows and crossovers, and sample sizes and statistical power.
The Interim Report presents results from the early implementation of the Family Options Study, describing the baseline characteristics of the families enrolled in the study and the housing and services interventions the families were offered. The report also describes the study's design and implementation and provides preliminary information about the extent to which families enrolled in their assigned interventions.
Some definitions of child homelessness include the category of children who are doubled-up with others due to loss of housing or economic hardship, while others do not. Are doubled-up children more like children in shelters or children who are poor but housed? A quasi-experimental comparison group design was used to test empirically for differences in school mobility, school attendance, and reading and mathematics achievement among three groups of sheltered, doubled-up, and poor, housed children, respectively, with each group containing 49 students. Sheltered students were found to have significantly higher levels of school mobility and significantly lower rates of school attendance than students in the other two groups. An elaboration of the continuum of risk model is proposed to differentiate experiences of sheltered and doubled-up students. Recommendations are made for policy responses as well as future research.
Intersections of family homelessness, CPS involvement, and race in Alameda County, California.
The homelessness and child protective services (CPS) systems are closely linked. This study examines the patterns and sequence of families' involvement with homeless shelters and CPS, as well as whether involvement in each system predicts involvement in the other using linked administrative records for 258 families recruited in emergency shelters in Alameda County, California. More than half of families were reported to CPS at some point, but less than one-fifth ever had a report substantiated. Reports that were uninvestigated or unfounded increased in the months leading up to shelter entry and spiked immediately afterward, but substantiations and child removals increased only later. Shelter use before study entry was associated with CPS referrals and investigations after study entry, although not with substantiated cases or child removals. However, CPS involvement before study entry was not associated with returns to shelter after study entry. These results imply that an unsubstantiated report of neglect or abuse may serve as an early warning signal for homelessness and that preventive strategies aiming to affect both homeless and child protective systems should focus on reducing homelessness. CPS workers should evaluate families' housing needs and attempt to link families to appropriate resources. Black families were disproportionately referred to CPS after shelter entry after controlling for other family characteristics, but race was not associated with substantiations of neglect or abuse or with child removals. Findings lend modest support to human decision-making and institutional explanations of racial disproportionalities in CPS involvement, especially for reporters outside of the CPS system.
A Qualitative Assessment of Parental Preschool Choices and Challenges Among Families Experiencing Homelessness: Policy and Practice Implications. Lindsey Stillman, Kate Hurd, Charles Kieffer, Jamie Taylor, Britton Gibson, The Cloudburst Group.
On a single night in 2013—as measured by the Point-In-Time count conducted by homeless services providers under the auspice of the U.S. Department of Housing and Urban Development (HUD)—more than 70,000 families and 130,000 children were experiencing homelessness across the United States. Of these families, 80 percent were headed by single mothers, and 40 percent had at least one child under the age of 1 (HUD, 2013a).
Parental preschool choices and challenges when young children and their families experience homelessness.
Encouraging stable preschool enrollment is a critically important policy response for ameliorating the negative impacts of housing instability and homelessness on young children. To contribute to the evidence base for preschool and family support policies, this article investigates how housing instability and homelessness influences parental preschool choices. Using a modified grounded theory approach to analyze transcripts of interviews and focus groups with 28 families who had experienced homelessness, we find that for formerly homeless parents, the most important factors influencing preschool enrollment are housing stability, social networks, attitudes about preschool education, history of trauma, and the type of support received during interactions with social service systems. We integrate these findings into a socio-ecological model that can guide the development of policy responses that encourage preschool enrollment among families experiencing homelessness.
Leaving Homelessness Behind: Housing Decisions Among Families Exiting Shelter. Fisher, Benjamin W.; Mayberry, Lindsay; Shinn, Marybeth; and Khadduri, Jill. 2014. Housing Policy Debate, 24(2), pp. 364-386.
Because homelessness assistance programs are designed to help families, it is important for policymakers and practitioners to understand how families experiencing homelessness make housing decisions, particularly when they decide not to use available services. This study explores those decisions using in-depth qualitative interviews with 80 families recruited in shelters across four sites approximately six months after they were assigned to one of four conditions (permanent housing subsidies, project-based transitional housing, community-based rapid re-housing, or usual care). Familiar neighborhoods near children's schools, transportation, family and friends, and stability were important to families across conditions. Program restrictions on eligibility constrained family choices. Subsidized housing was the most desired intervention, and families leased up at higher rates than in other studies of poor families. Respondents were least comfortable in and most likely to leave transitional housing. Uncertainty associated with community-based rapid re-housing generated considerable anxiety. Across interventions, many families had to make unhappy compromises, often leading to further moves. Policy recommendations are offered.
Families experiencing housing instability: The effects of housing programs on family routines and rituals. Mayberry, L. S., Shinn, M., Benton, J. G., & Wise, J. (2014). Families experiencing housing instability: The effects of housing programs on family routines and rituals. American Journal of Orthopsychiatry, 84(1), 95-109. doi:10.1037/h0098946. Copyright © 2014 by the American Orthopsychiatric Association. Reproduced with permission.
Maintenance of family processes can protect parents, children, and families from the detrimental effects of extreme stressors, such as homelessness. When families cannot maintain routines and rituals, the stressors of poverty and homelessness can be compounded for both caregivers and children. However, characteristics of living situations common among families experiencing homelessness present barriers to the maintenance of family routines and rituals. We analyzed 80 in-depth interviews with parents who were experiencing or had recently experienced an instance of homelessness. We compared their assessments of challenges to family schedules, routines, and rituals across various living situations, including shelter, transitional housing programs, doubled-up (i.e., living temporarily with family or friends), and independent housing. Rules common across shelters and transitional housing programs impeded family processes, and parents felt surveilled and threatened with child protective service involvement in these settings. In doubled-up living situations, parents reported adapting their routines to those of the household and having parenting interrupted by opinions of friends and family members. Families used several strategies to maintain family routines and rituals in these living situations and ensure consistency and stability for their children during an otherwise unstable time.
This report, titled Family Options Study: Short-Term Impacts of Housing and Services Interventions for Homeless Families, presents the short-term outcomes of the 2,282 families enrolled in the Family Options Study, a multi-site random assignment experiment designed to study the impact of various housing and services interventions on homeless families. The report documents how families are faring approximately 20 months after random assignment to one of four interventions: 1) subsidy-only (SUB), 2) community-based rapid re-housing (CBRR), 3) project-based transitional housing (PBTH), or 4) usual care. Outcome measures fall within five domains: housing stability; family preservation; adult well-being; child well-being; and self-sufficiency. The collection of extensive cost data for each of the interventions tested enables the calculation of the costs that can be tied to each of the interventions, and in turn, used to understand the cost of achieving the outcomes observed. The study resulted in strong and significant findings, particularly related to the power of offering a long-term housing subsidy to a family residing in emergency shelter.
On July 8, 2015, HUD/PD&R hosted a public briefing on the short-term outcomes of the Family Options Study. Watch a recording of the webcast here, and listen to a presentation of the study findings from the research team, as well as a moderated Q&A with Federal leaders working to address homelessness.
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Rhonda Allison Skin Brightening Enzyme brightens the skin by digesting unwanted, dead skin cells and suppressing the activity of melanin, both which act to darken your complexion. Including all natural ingredients, Skin Brightening Enzyme will leave your skin looking and feeling fresh and radiant.
The Rhonda Allison Skin Brightening Enzyme is a potently formulated product that contains an active enzyme as well as other key ingredients that provide skin brightening benefits. The product is created with all natural ingredients such as witch hazel, cucumber, salicylic acid, and many others in order to provide various effects. For instance, this particular Rhonda Allison product not only contains enzymes in order to soften the skin and digest any unwanted skin, but also contains agents that brighten and lighten your complexion for a more even and radiant skin tone. This specific Rhonda Allison product is perfect for those who have dull, tired, or lifeless looking skin types.
Made with all natural ingredients for a safe application.
Contains enzymes that soften the skin's texture and digest unwanted skin.
Contains agents that brighten and lighten the skin tone for a radiant complexion.
Leaves skin glowing with youthfulness and feeling smooth and soft to the touch.
The Rhonda Allison Skin Brightening Enzyme is recommended for all skin types, but is especially beneficial for those who have dull or tired skin types.
To apply the Rhonda Allison Skin Brightening Enzyme, first make sure to thoroughly cleanse your skin. After cleansing, pat your skin dry with a soft towel. Apply any scrubs before applying the Skin Brightening Enzyme and allow your skin to dry as well. Take a small amount of the product and apply it evenly to the entire facial and neck areas. Only apply a thin layer to the skin. Allow the enzyme to remain on the skin for about 15-20 minutes. Finally, wash away the product with a soft cloth and warm water. Pat skin dry to finish. This product should be applied 1 to 3 times a week for best results. Do not allow the product to get into your eyes. Discontinue use of this product if irritation occurs.
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Histopathologic examination demonstrates hyperkeratosis, patchy parakeratosis, hypergranulosis, and acanthosis (Figure 3); vertically oriented collagen bundles in the papillary dermis.
Adult females are most commonly affected, peak incidence at ages 30 to 50 years. Risk factors include stress, a history of atopic dermatitis, allergic contact dermatitis, or xerosis. Up to one third of patients seen at a vulvar disorder clinic may be diagnosed with LSC.
These chronic lichenified fixed plaques are the end result of the itch-scratch cycle. Plaques of LSC can occur de novo on normal skin, or may develop secondarily on pre-existing dermatologic conditions such as atopic dermatitis, allergic contact dermatitis, cutaneous fungal infections, psoriasis and others.
Underlying pathophysiology is not completely understood but is thought to result from an interplay of emotional stress, pruritus (environmental factors such as heat/sweat/mechanical irritants that stimulate sensory nerve endings) and subsequent rubbing or scratching that results in lichenification.
Psychogenic factors may be present, including anxiety, depression, or obsessive-compulsive disorder; consider a psychiatric referral in the appropriate clinical setting.
Current treatment of choice is topical corticosteroids, often beginning with high-potency products such as clobetasol ointment or cream; due to the chronic nature of the condition, mid-potency topical steroids such as triamcinolone 0.025 % may be used for prolonged treatment or as a first choice in areas at risk of steroid atrophy. For persistent lichenified papules/plaques, intralesional triamcinolone 5mg/ml should be considered.
Occlusion is often helpful, both to improve steroid penetrance and perhaps more importantly to serve as a barrier to the itch-scratch cycle; this can be achieved through local application of a hydrocolloid dressing such as Duoderm over a mid-potency topical steroid, or larger areas on extremities may benefit from Unna boot occlusion with a topical steroid. Antipruritic emollients (menthol or colloidal oatmeal based) offer minimal benefit but can be applied over a large area as adjunctive treatment.
Discrete lichenified nodules of chronic duration can be addressed with surgical removal, generally as shave removal or rarely an elliptical excision.
For lesions unresponsive to topical steroids, topical immunomodulatory agents such as tacrolimus or pimecrolimus are an option; these agents can also be considered if concerned about atrophogenic effects from topical steroids.
Rarely, for widespread lesions, a short course of oral corticosteroids may help break the itch-scratch cycle, but should not be used long term. Sedating antihistamines may lessen the nighttime scratching that occurs in lighter sleep stages; options include hydroxyzine 10 to 25mg 1 to 2 hours before sleep, or doxepin 25 to 75mg; oral antianxiety medications (such as clonazepam/SSRI agents) can be considered in individual cases. For diffuse involvement with pruritus and lichen simplex chronicus, phototherapy can be initiated, favoring narrowband UVB.
After establishing the diagnosis on clinical and/or histopathologic findings, discussion of the diagnosis and identification of any "stressors" that may lead to the itch-scratch cycle should occur. Initial monitoring of response to therapy should occur approximately 1 month after the initiation of topical steroids, and then periodically based on the therapeutic choice, lesion location, and early response to therapy. Maintenance therapy may require intermittent use of mid- or high-potency topical steroids. If lesions do not respond after 1 month of therapy, a change of treatment should be considered; examples could include adding intralesional steroids or occlusive therapy at that time.
Patients and families should be aware of the habitual activity that may continue to produce these chronic lesions, as well as potential sleep disruption and psychic stress that can occur. On rare occasions, involvement of psychologic or psychiatric support may be necessary.
Lichen simplex chronicus of the anogenital region should be recognized; underlying atopic dermatitis may be present, and psychological stress as well as local irritants can aggravate this condition.
Additionally, the healthcare provider should be aware of the possibility of underlying allergic contact dermatitis from either an anogenital-specific product or transfer of other products to this area. Patch test allergens identified in earlier studies causing allergic contact dermatitis in the anogenital area include cinnamal, dibucaine, benzocaine, hydrocortisone-17-butyrate, budesonide, and less frequently quaternium-15, cobalt, formaldehyde, p-phenylenediamine and thiuram mix. Recently, methylchloroisothiazolinone/methylisothiazolinone, a preservative found in some moist toilet papers, has been identified as an allergen in anogenital dermatitis.
The clinician also needs to consider pruritus due to underlying systemic disease as a trigger for the clinical outcome of lichenification. Thus, in appropriate cases, a systemic evaluation with complete history and physical examination, age appropriate screenings as well as directed laboratory/imaging studies, may be indicated.
Gardner, K, Davis, M, Richardson, D, Pittelkow, M. "The hazards of moist toilet paper". Arch Dermatol. vol. 146. 2010. pp. 886-90.
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To date, few studies have been conducted regarding household irons as an important cause of paediatric burns. We performed a retrospective review of iron burns at a large tertiary paediatric hospital from July 2015 to May 2018. We examined patient demographics, location of burn, total body surface area (TBSA), burn depth, level of supervision, first aid measures, surgical management and complications.
In the three-year study period 30 children sustained iron burns; and all were managed in the outpatient or day surgery setting. The majority of children were male (67%), toddler (1-2 years old, 83%) and sustained burns to the hand only (80%). Despite all burns involving a small surface area (<2% TBSA), 17% of children required surgical intervention, with one lost to follow up. 17% of iron burns had complications. Alarmingly, 45% were unsupervised at the time of the burn. Only 37% of children received the recommended first aid for burns in Australia.
Paediatric iron burns have significant morbidity and an economic impact upon hospital resources. Inadequate supervision was common amongst patients with iron burns in our population. It follows that prevention and education programs aimed at caregivers could reduce the incidence and sequelae of iron burns in this age group, given their common place in many households.
Dr Teagan Fink is a Plastic and Maxillofacial Surgical Resident at the Royal Children's Hospital. During her six month rotation with the unit, she undertook research into paedatric burns. She is also employed as a Surgical Resident at St Vincent's Hospital Melbourne.
Previous article The Enemy You Can't See: What is the Effect of Minor Burn Injuries on Return to Physical Activity at 3 and 12 Months Post Injury?
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Filgrastim, pegfilgrastim, and sargramostim are synthetic (man-made) versions of substances naturally produced in your body. These substances, called colony stimulating factors, help the bone marrow to make new white blood cells.
When certain cancer medicines fight your cancer cells, they also affect those white blood cells that fight infection. To help prevent infections when these cancer medicines are used, colony stimulating factors may be given. Colony stimulating factors also may be used to help the bone marrow recover after bone marrow transplantation and stem cell transplantation.
Although there is no specific information comparing use of colony stimulating factors in children with use in other age groups, this medicine is not expected to cause different side effects or problems in children than it does in adults. In Canada, data from clinical trials in children indicate that the safety of filgrastim is similar in both adults and children receiving certain cancer medicines. Sargramostim may contain benzyl alcohol and should not be given to infants because it could cause serious adverse effects. The pegfilgrastim 6-mg syringe should not be used in infants, children, and small teenagers who weigh less than 45 kg (99.2 lbs) .
Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. Although there is no specific information comparing use of colony stimulating factors in the elderly with use in other age groups, this medicine has been used in many elderly patients and is not expected to cause different side effects or problems in older people than it does in younger adults.
Colony stimulating factors have not been studied in pregnant women. Before you take a colony stimulating factor, make sure your doctor knows if you are pregnant of if you may become pregnant.
It is not known whether colony stimulating factors pass into human breast milk. However, these medicines have not been reported to cause problems in nursing babies. Mothers who are taking a colony stimulating factor and who wish to breast-feed should discuss this with their doctor.
Sickle cell disease (red blood cell disease) May make these conditions worse.
Heart disease Risk of some unwanted effects (heart rhythm problems, retaining water) may be increased.
Lung disease Colony stimulating factor may cause shortness of breath.
Radiation therapy You should not use filgrastim close to the time you are undergoing chemotherapy or radiation therapy for cancer treatment.
If you are injecting this medicine yourself, use it exactly as directed by your doctor. Do not use more or less of it, and do not use it more often than your doctor ordered. The exact amount of medicine you need has been carefully worked out. Using too much will increase the risk of side effects, while using too little may not improve your condition.
Proper use of disposable syringes.
If you have any questions about any of this, check with your health care professional.
Colony stimulating factors are used to prevent or reduce the risk of infection while you are being treated with cancer medicines. Because your body's ability to fight infection is reduced, it is very important that you call your doctor at the first sign of any infection (for example, if you get a fever or chills) so you can start antibiotic treatment right away.
Contact your doctor if you develop shortness of breath, tightness in the chest, troubled breathing, or wheezing. These could be symptoms of a serious lung condition called adult respiratory distress syndrome (ARDS).
This medicine may also cause bleeding in your lungs. Check with your doctor right away if you cough up blood or if you have blood in your sputum .
If you experience left upper abdominal or shoulder tip pain, contact your doctor right away. These could be symptoms of an enlarged or ruptured spleen.
Colony stimulating factors commonly cause mild bone pain, usually in the lower back or pelvis, about the time the white blood cells start to come back in your bone marrow. The pain is usually mild and lasts only a few days. Your doctor will probably prescribe a mild analgesic (painkiller) for you to take during that time. If you find that the analgesic is not strong enough, talk with your doctor about using something that will make you more comfortable.
The side effects listed below include only those that might be caused by colony stimulating factors. To find out about other side effects that may be caused by the cancer medicines you are also receiving, look under the information about those specific medicines.
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Back pain is one of the most common musculoskeletal (MSK) complaints that patients present with to the Emergency Department, Urgent Care, and Primary Care settings. The majority of adults will present with non-traumatic acute/chronic MSK back pain. The role of the non-MSK providers is to determine between acute emergent neurologic onset back pain vs. the non-emergent MSK origin of back pain. This assessment will be based on the patients' historical information, physical examination findings, diagnostic studies and using sound evidence-based clinical judgment. In order to expand providers knowledge in the evaluation and treatment of patients presenting with back pain, we will divide the Back Pain into 3 categories; 1) acute, non-traumatic MSK origins, 2) Back pain with neurologic manifestations and 3) Non-spine related origins.
There are many options available in the treatment of MSK back pain. In reviewing the literature, protected moderate activity seems to provide a better reduction in back pain symptoms vs prolonged bed rest (>2 days). Patients will frequently ask if heat or ice is more effective in treating MSK back pain. In my clinical experience, I believe both heat and ice play a role in symptom relief.5,6,9 I will instruct patients to alternate Ice (20 minutes) and heat (heating pad 20 minutes) 4-5 times a day for 1 week. The "freeze and thaw" helps to minimize muscle swelling and tightness. I try to encourage patients to avoid lying on a heating pad while sleeping. Aside from the fact they could suffer a thermal burn, the constant heat can worsen muscle stiffness.5,6,9 I like to incorporate a referral to physical therapy (PT), in my treatment protocol, to help patients address core body strength, flexibility and postural conditions that can greatly contribute to MSK back pain.7 While patients may not be happy about the expense or the disruption to their normal daily routine, the ones who do participate in PT do better in the long-term (symptom relief and preventing reinjury). 7,9 Regarding medication therapy, non-steroidal analgesics (NSAID) and acetaminophen have proved to be effective in treating MSK pain.11 Some patients may present with more severe pain symptoms than usual. In those patients, I may use a 6-day taper corticosteroid dose pack. I avoid steroid dose packs in patients who have diabetes and those who are taking autoimmune suppressive medications.6 Once the patient has completed the dose pack, then, I may have them start on an NSAID as needed. I try to limit NSAID use to 7-10 days. I avoid NSAID use in those with known aspirin allergy, the elderly (>65), those with known kidney disease, those on anticoagulation medication and patients with a history of GI bleed.11 Once the patient has completed the dose pack then I will instruct them to start taking NSAIDs as needed. In some situations, the use of muscle relaxant medications may be helpful in reducing muscle spasms. However, great caution should be exercised when prescribing muscle relaxant medications as it can increase the patient's fall risk.1-3 The question frequently comes up regarding when to use narcotic analgesics to treat MSK back pain. I try to avoid prescribing these medications since NSAIDs and acetaminophen have proven to do an adequate job of relieving pain.1,2,11 However, just like with muscle relaxants, narcotics can contribute to an increase in fall risk. Therefore, I try to limit prescribing narcotics but if I do prescribe them it is for no more than 7 days. If the patient requires more medication, then they need to be seen for reassessment.
The key to treating MSK back pain is listening to what patients tell you, being confident in your physical examination skills, knowing what the diagnostic imaging tells you and developing an effective treatment plan. If you ever are uncertain about the acuity of injury, repeating the exam in a few days is appropriate. If you are suspicious of an evolving emergent condition, immediate referral or consultation is appropriate and, in some cases, getting advanced radiographic imaging, prior to referral is warranted.
Singleton J, Edlow JA, Acute Nontraumatic Back Pain: Risk Stratification, Emergency Department management, and Review of serious Pathologies, Emerg Med Clin N Am 2016;34:743-757.
Maher C, Underwood M, Buchbinder R, Non-specific low back pain Lancet 2017;389:736-47.
Golob AL, Wipf JE, Low Back Pain, Med Clin North Am, 2014;98(3):405-428 doi: 10.1016/j.mcna.2014.01.003.
Chou L, Ranger TA, Peiris W, Cicuttini FM, Urquhart DM, Sullivan K, et al. (2018) Patients' perceived needs for medical services for non- specific low back pain: A systematic scoping review. PLoS ONE 13(11): e0204885.
Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of lowback pain: a joint clinical practice guideline from the American College of Physicians and the American Pain Society. Ann Intern Med 2007; 147: 478–91.
National Collaborating Centre for Primary Care. Low back pain: early management of persistent non-specific low back pain. London: National Institute for Health and Clinical Excellence, 2009. https://www.nice.org.uk/guidance/cg88/evidence/fullguideline-243685549 (accessed December 19, 2018).
Van Middelkoop M, Rubinstein SM Verhagen AP et al, Exercise therapy for chronic nonspecific low-back pain, Best Practice & Research clinical Rheumatology, 2010 24:193-204.
Hoppenfeld, SA, Orthopaedic Neurology: A Diagnostic Guide to Neurologic Levels, Lippincott, Philadelphia, 1997:45-74, 93-101.
Friedman BW, Chilistrom M, Bjur PE, et al, Diagnostic testing and treatment of low back pain in United States emergency departments: a national perspective, Spine 2010;35:1406-1411.
Anderson JC, Is immediate imaging important in managing low back pain? J Ath Train 2011;46(1):99-120.
Friedman BW, Dym AA, Davitt M et al, naproxen with cyclobenzaprine, oxycodone/acetaminophen; or placebo for treating acute low back pain: a randomized clinical trial, JAMA 2015;314(15):1572-80.
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Improving on Standard Treatment in Ovarian Cancer: Have We Hit a Wall?
The combination of paclitaxel and carboplatin has become the standard treatment for ovarian cancer, but it is not entirely satisfactory. Is it possible to find an improvement, either by using another chemotherapeutic agent, or by employing intraperitoneal therapy? Robert Ozols of the Fox Chase Cancer Center in Philadelphia tells Derek Thorne about the recent evidence and looks ahead to the future.
Bicalutamide Alternative to Castration for Radiation-Treated Patients with Locally Advanced Prostate Cancer?
A new option has emerged for patients with locally advanced prostate cancer that may avoid the need for castration. According to a study just published in the Journal of Cancer Research and Clinical Oncology the nonsteroidal antiandrogen bicalutamide may provide a similar benefit to that of castration, but with more acceptable side effects. William See of the Medical College of Wisconsin discussed his team's findings with Derek Thorne.
Despite promising results for the breast cancer agent trastuzumab, only a minority of breast tumors have the appropriate genetic profile for treatment – which includes overexpressed Her-2. However, a new paper in the Journal of Clinical Oncology might lead to an increase in the number of eligible patients. Ruth Lupu described her team's study, which looked at tumorigenic cells that overexpress heregulin, an activator of Her-2.
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Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1
Ke Zhao, Juan Du, Xue Han, John L. Goodier, Peng Li, Xiaohong Zhou, Wei Wei, Sean L. Evans, Linzhang Li, Wenyan Zhang, Ling E. Cheung, Guanjun Wang, Haig H. Kazazian, Xiao Fang Yu
Long interspersed elements 1 (LINE-1) occupy at least 17% of the human genome and are its only active autonomous retrotransposons. However, the host factors that regulate LINE-1 retrotransposition are not fully understood. Here, we demonstrate that the Aicardi-Goutières syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition. We also found that mutant SAMHD1s of Aicardi-Goutières syndrome patients are defective in LINE-1 inhibition. Several domains of SAMHD1 are critical for LINE-1 regulation. SAMHD1 inhibits LINE-1 retrotransposition in dividing cells. An enzymatic active site mutant SAMHD1 maintained substantial anti-LINE-1 activity. SAMHD1 inhibits ORF2p-mediated LINE-1 reverse transcription in isolated LINE-1 ribonucleoproteins by reducing ORF2p level. Thus, SAMHD1 may be a cellular regulator of LINE-1 activity that is conserved in mammals
https://doi.org/10.1016/j.celrep.2013.08.019
10.1016/j.celrep.2013.08.019
Dive into the research topics of 'Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1'. Together they form a unique fingerprint.
Aicardi Syndrome Medicine & Life Sciences 100%
Alu Elements Medicine & Life Sciences 85%
Retroelements Medicine & Life Sciences 37%
Simian Immunodeficiency Virus Medicine & Life Sciences 36%
Ribonucleoproteins Medicine & Life Sciences 35%
Viral Proteins Medicine & Life Sciences 30%
Human Genome Medicine & Life Sciences 30%
Catalytic Domain Medicine & Life Sciences 25%
Zhao, K., Du, J., Han, X., Goodier, J. L., Li, P., Zhou, X., Wei, W., Evans, S. L., Li, L., Zhang, W., Cheung, L. E., Wang, G., Kazazian, H. H., & Yu, X. F. (2013). Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1. Cell Reports, 4(6), 1108-1115. https://doi.org/10.1016/j.celrep.2013.08.019
Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1. / Zhao, Ke; Du, Juan; Han, Xue et al.
In: Cell Reports, Vol. 4, No. 6, 26.09.2013, p. 1108-1115.
Zhao, K, Du, J, Han, X, Goodier, JL, Li, P, Zhou, X, Wei, W, Evans, SL, Li, L, Zhang, W, Cheung, LE, Wang, G, Kazazian, HH & Yu, XF 2013, 'Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1', Cell Reports, vol. 4, no. 6, pp. 1108-1115. https://doi.org/10.1016/j.celrep.2013.08.019
Zhao K, Du J, Han X, Goodier JL, Li P, Zhou X et al. Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1. Cell Reports. 2013 Sep 26;4(6):1108-1115. doi: 10.1016/j.celrep.2013.08.019
Zhao, Ke ; Du, Juan ; Han, Xue et al. / Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1. In: Cell Reports. 2013 ; Vol. 4, No. 6. pp. 1108-1115.
@article{bd759ab1e9224ee3ac56a2bd5e4c0558,
title = "Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Gouti{\`e}res Syndrome-Related SAMHD1",
abstract = "Long interspersed elements 1 (LINE-1) occupy at least 17% of the human genome and are its only active autonomous retrotransposons. However, the host factors that regulate LINE-1 retrotransposition are not fully understood. Here, we demonstrate that the Aicardi-Gouti{\`e}res syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition. We also found that mutant SAMHD1s of Aicardi-Gouti{\`e}res syndrome patients are defective in LINE-1 inhibition. Several domains of SAMHD1 are critical for LINE-1 regulation. SAMHD1 inhibits LINE-1 retrotransposition in dividing cells. An enzymatic active site mutant SAMHD1 maintained substantial anti-LINE-1 activity. SAMHD1 inhibits ORF2p-mediated LINE-1 reverse transcription in isolated LINE-1 ribonucleoproteins by reducing ORF2p level. Thus, SAMHD1 may be a cellular regulator of LINE-1 activity that is conserved in mammals",
author = "Ke Zhao and Juan Du and Xue Han and Goodier, {John L.} and Peng Li and Xiaohong Zhou and Wei Wei and Evans, {Sean L.} and Linzhang Li and Wenyan Zhang and Cheung, {Ling E.} and Guanjun Wang and Kazazian, {Haig H.} and Yu, {Xiao Fang}",
note = "Funding Information: We thank Drs. J. Boeke, D. Hancks, T. Inoue, M. Stevenson, and R. Siliciano for critical reagents; Y. Rui, W. Zheng, H. Guo, and J. Hou for technical assistance; R. Markham, J. Margolick, and J. Bream for thoughtful discussions; and D. McClellan for editorial assistance. We also wish to thank staff within the Mass Spectrometry Core and the Institute for Basic Biomedical Sciences Microscope Facility at Johns Hopkins School of Medicine for their technical assistance. The following reagent was obtained through the AIDS Research and Reference Reagents Program, Division of AIDS, NIAID, NIH: pHEF-VSVG (L.-J. Chang). This work was supported in part by funding from the Chinese Ministry of Science and Technology (2012CB911100 and No. 2013ZX0001-005) and Chinese Ministry of Education (IRT1016), the Key Laboratory of Molecular Virology, Jilin Province (20102209), China, a grant (2R56AI62644-6) from the NIAID, and a grant (1RC4MH092880-01) from the NIMH to H.H.K. K.Z., J.D., X.Z., J.L.G., P.L., W.W., S.L.E., X.H., L.L., and L.E.C. performed experiments. K.Z., J.D., J.L.G., L.E.C., W.Z., G.W., H.H.K., and X.-F.Y. analyzed the data. K.Z. and X.-F.Y. wrote the paper with help from all authors. X.-F.Y. directed the project. ",
doi = "10.1016/j.celrep.2013.08.019",
journal = "Cell Reports",
T1 - Modulation of LINE-1 and Alu/SVA Retrotransposition by Aicardi-Goutières Syndrome-Related SAMHD1
AU - Zhao, Ke
AU - Du, Juan
AU - Han, Xue
AU - Goodier, John L.
AU - Li, Peng
AU - Zhou, Xiaohong
AU - Wei, Wei
AU - Evans, Sean L.
AU - Li, Linzhang
AU - Zhang, Wenyan
AU - Cheung, Ling E.
AU - Wang, Guanjun
AU - Kazazian, Haig H.
AU - Yu, Xiao Fang
N1 - Funding Information: We thank Drs. J. Boeke, D. Hancks, T. Inoue, M. Stevenson, and R. Siliciano for critical reagents; Y. Rui, W. Zheng, H. Guo, and J. Hou for technical assistance; R. Markham, J. Margolick, and J. Bream for thoughtful discussions; and D. McClellan for editorial assistance. We also wish to thank staff within the Mass Spectrometry Core and the Institute for Basic Biomedical Sciences Microscope Facility at Johns Hopkins School of Medicine for their technical assistance. The following reagent was obtained through the AIDS Research and Reference Reagents Program, Division of AIDS, NIAID, NIH: pHEF-VSVG (L.-J. Chang). This work was supported in part by funding from the Chinese Ministry of Science and Technology (2012CB911100 and No. 2013ZX0001-005) and Chinese Ministry of Education (IRT1016), the Key Laboratory of Molecular Virology, Jilin Province (20102209), China, a grant (2R56AI62644-6) from the NIAID, and a grant (1RC4MH092880-01) from the NIMH to H.H.K. K.Z., J.D., X.Z., J.L.G., P.L., W.W., S.L.E., X.H., L.L., and L.E.C. performed experiments. K.Z., J.D., J.L.G., L.E.C., W.Z., G.W., H.H.K., and X.-F.Y. analyzed the data. K.Z. and X.-F.Y. wrote the paper with help from all authors. X.-F.Y. directed the project.
N2 - Long interspersed elements 1 (LINE-1) occupy at least 17% of the human genome and are its only active autonomous retrotransposons. However, the host factors that regulate LINE-1 retrotransposition are not fully understood. Here, we demonstrate that the Aicardi-Goutières syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition. We also found that mutant SAMHD1s of Aicardi-Goutières syndrome patients are defective in LINE-1 inhibition. Several domains of SAMHD1 are critical for LINE-1 regulation. SAMHD1 inhibits LINE-1 retrotransposition in dividing cells. An enzymatic active site mutant SAMHD1 maintained substantial anti-LINE-1 activity. SAMHD1 inhibits ORF2p-mediated LINE-1 reverse transcription in isolated LINE-1 ribonucleoproteins by reducing ORF2p level. Thus, SAMHD1 may be a cellular regulator of LINE-1 activity that is conserved in mammals
AB - Long interspersed elements 1 (LINE-1) occupy at least 17% of the human genome and are its only active autonomous retrotransposons. However, the host factors that regulate LINE-1 retrotransposition are not fully understood. Here, we demonstrate that the Aicardi-Goutières syndrome gene product SAMHD1, recently revealed to be an inhibitor of HIV/simian immunodeficiency virus (SIV) infectivity and neutralized by the viral Vpx protein, is also a potent regulator of LINE-1 and LINE-1-mediated Alu/SVA retrotransposition. We also found that mutant SAMHD1s of Aicardi-Goutières syndrome patients are defective in LINE-1 inhibition. Several domains of SAMHD1 are critical for LINE-1 regulation. SAMHD1 inhibits LINE-1 retrotransposition in dividing cells. An enzymatic active site mutant SAMHD1 maintained substantial anti-LINE-1 activity. SAMHD1 inhibits ORF2p-mediated LINE-1 reverse transcription in isolated LINE-1 ribonucleoproteins by reducing ORF2p level. Thus, SAMHD1 may be a cellular regulator of LINE-1 activity that is conserved in mammals
U2 - 10.1016/j.celrep.2013.08.019
DO - 10.1016/j.celrep.2013.08.019
JO - Cell Reports
JF - Cell Reports
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New understanding of cell stability with potential to improve immune cell therapies
Research in mice, published today in Science Immunology by researchers at the Babraham Institute, UK and VIB-KU Leuven, Belgium, provides two solutions with potential to overcome a key clinical limitation of immune cell therapies. Regulatory T cells have potential in treating autoimmunity and inflammatory diseases yet they can switch from a protective to damaging function. By identifying the unstable regulatory T cells, and understanding how they can be purged from a cell population, the authors highlight a path forward for regulatory T cell transfer therapy.
Cell therapy is based on purifying cells from a patient, growing them up in cell culture to improve their properties, and then reinfusing them into the patient. Professor Adrian Liston, Immunology group leader at the Babraham Institute, explained their therapeutic potential: "The leading use of cell therapy is to improve T cells so that they can attack and kill a patient's cancer, however the incredible versatility of the immune system means that, in principle, we could treat almost any immune disorder with the right cell type. Regulatory T cells are particularly promising, with their ability to shut down autoimmune disease, inflammatory disease and transplantation rejection. A key limitation in their clinical use, however, comes from the instability of regulatory T cells - we just can't use them in cell therapy until we make ensure that they stay protective".
T cells come in a large variety of types, each with unique functions in our immune system. "While most T cells are inflammatory, ready to attack pathogens or infected cells, regulatory T cells are potent anti-inflammatory mediators", Professor Susan Schlenner, University of Leuven, explains. "Unfortunately this cell type is not entirely stable, and sometimes regulatory T cells convert into inflammatory cells, called effector T cells. Crucially, the converted cells inherit both inflammatory behaviour and the ability to identify our own cells, and so pose a significant risk of damage to the system they are meant to protect."
The first key finding of this research shows that once regulatory T cells switch to becoming inflammatory, they are resistant to returning to their useful former state. Therefore, scientists need to find a way to remove the risky cells from any therapeutic cell populations, leaving behind the stable regulatory T cells.
By comparing stable and unstable cells the researchers identified molecular markers that indicate which cells are at risk of switching from regulatory to inflammatory. These markers can be used to purify cell populations before they are used as a treatment.
In addition to this method of cell purification, the researchers found that exposing regulatory T cells to a destabilising environment purges the unstable cells from the mixture. Under these conditions, the unstable cells are triggered to convert into inflammatory cells, allowing the researchers to purify the stable cells that are left. "The work needs to be translated into human cell therapies, but it suggests that we might be best off treating the cells mean", says Professor Adrian Liston. "Currently, cell culture conditions for cell therapy aim to keep all the cells in optimal conditions, which may actually be masking the unstable cells. By treating the cultures rougher, we may be able to identify and eliminate the unstable cells and create a safer mix of cells for therapeutic transfer."
Dr Steffie Junius, lead author on the paper who undertook the research as a PhD student at the University of Leuven, commented: "The next stage in the research is to take the lessons learned in mice and translate them into optimal protocols for patients. I hope that our research contributes to the improved design and allows the development of effective regulatory T cell therapy."
Establishing a thorough process to improve cell population stability in mice helps to lay the groundwork for improved immune cell therapies in humans, although the methods described in this work would require validation in humans before they were used in cell therapy trials. Dr Timothy Newton, CEO of Reflection Therapeutics, a Babraham Research Campus-based company designing cell therapies against neuro-inflammation, who was not involved in this study, commented on the translational potential of the study: "This research makes a significant impact on regulatory T cell therapeutic development by characterising unstable subsets of regulatory T cells that are likely to lose their desirable therapeutic qualities and become pro-inflammatory. The successful identification of these cells is of great importance when designing manufacturing strategies required to turn potential T cell therapeutics into practical treatments for patients of a wide range of inflammatory disorders."
Babraham Institute
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Learn the early warning signs and symptoms of a urinary tract infection today.
Find For Urine Test. Browse Results on SocialScour.com!
Learn More About Blood In Urine No Pain. Browse Info From Trusted Sources.
Surgery also causes some amount of shock to the body. Because of these factors it is necessary to conduct a urine test before surgery. The urine test before surgery is helpful in revealing what the patient has recently consumed. Some patients may have consumed medications or illegal drugs which interfere with the procedure of surgery.
For example, if you have a blood-clotting problem, a test can show if you're at risk of too much bleeding during surgery. But most healthy people don't need the tests, especially before low-risk surgery. Here's why: The tests usually aren't helpful for low-risk surgery. Many healthy people have routine lab tests before surgery.
I'm beside myself because I know I took my vicodin the day before the test.My new Rx was due the week after the test and I obviously didn't get my prescription. The only thing that I can possibly think of that is my fault is that I drink a tremendous amount of water every day, probably more than a gallon.
Lab Tests Before Surgery: When you need them and when you don't. If you're going to have surgery, you may have blood and urine tests first. But most healthy people don't need the tests, especially before low-risk surgery. If you're going to have surgery, you may have blood and urine tests first.
test (they tried to give me one before my RNY until I refused and told them I had a hysterectomy in 1995!) She said no. So now I am suspicious. Why the secrecy about the urine. And why did they need TWO vials of blood? Any idea what he might be testing the urine for? My mom says drugs maybe, or diabetes.
Tests Performed before Surgery. Many surgeons order routine laboratory tests before admission to the hospital, or even before certain outpatient procedures, to identify potential problems that might complicate surgery if not detected and treated early.
Before you undergo a battery of tests, you may want to ask if they are covered by your insurance, as they can be expensive. If you are paying for surgery out of your own pocket, you should know if the price you were quoted for the procedure includes the testing that is done before surgery or if the tests are an additional fee.
Best Answer: Before they give you any drugs during the surgery, they want to know what drugs you may have in your system (that you may NOT have mentioned), so that you won't die from them giving you a drug that conflicts with whatever you may have already consumed. This may also be done if the surgery pertains to your kidneys, bladder, or prostate.
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quality care. by appoinment
Q: Can N-acetylcarnosine eye drops dissolve cataracts, as marketers say? A: Some animal studies and a few human trials suggest the drops may help reverse lens cloudiness, the hallmark feature of cataracts—but claims that they are a cataract cure are overstated, at best. The Food and Drug Administration (FDA) has not approved any form of carnosine for the treatment of cataracts. (Carnosine is also sold as a dietary supplement, promoted for eye health and many other disorders.) Various carnosine-related compounds, including N-acetylcarnosine (NAC), occur naturally in the body. When applied in eye drops, NAC makes its way to the interior of the eye, where it may have antioxidant effects. Oxidation of lipids in the lens of the eye is thought to contribute to cataracts. NAC may also help prevent "cross-linking" of proteins, another factor behind cataracts. In a study published in Clinical Interventions in Aging in 2009, people with cataracts who used NAC drops for nine months appeared to have an improvement in visual acuity and sensitivity to glare (a problem with cataracts), compared to those using placebo drops. But as with prior studies, this one was relatively small—and there are no data on long-term use. Moreover, nearly all of the research has been done by a Russian scientist who developed and holds a patent for a brand of NAC eye drops, called Can-C. Larger, better—and independent—studies are needed.
New study finds that common degenerative eye disease may be triggered by tiny mineral deposits in the eye
University of Maryland School of Medicine News, 01/20/2015
Discovery by university of University of Maryland School of Medicine researchers uncovers possible new mechanism behind retinal ailment that affects millions. New research from scientists at the University of Maryland School of Medicine (UM SOM) has found that tiny lumps of calcium phosphate may be an important triggering factor for age–related macular degeneration (AMD), a degenerative eye disease that can cause severe vision loss and blindness. This is the first time these mineral deposits have been implicated in the disease, which affects more than 10 million Americans. The article appeared in the latest issue of the Proceedings of the National Academy of Sciences.
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Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up
Pediatr Infect Dis J. 2000 Dec;19(12):1127-34. doi: 10.1097/00006454-200012000-00002.
A Patja 1 , I Davidkin, T Kurki, M J Kallio, M Valle, H Peltola
1 Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland. [email protected]
DOI: 10.1097/00006454-200012000-00002
Background: Several disorders have been attributed to measles-mumps-rubella (MMR) vaccination during the past decade. The aim of this prospective follow-up study was to identify serious adverse events causally related to MMR vaccination.
Methods: When the MMR vaccination program was launched in Finland in 1982, a countrywide surveillance system was set up to detect serious adverse events associated with MMR. To obtain detailed case histories vaccinees' clinical charts were reviewed. Serum samples were analyzed to trace concurrent infections.
Setting: All hospitals and health centers in Finland from 1982 through 1996.
Results: Immunization of 1.8 million individuals and consumption of almost 3 million vaccine doses by the end of 1996 gave rise to 173 potentially serious reactions claimed to have been caused by MMR vaccination. In all, 77 neurologic, 73 allergic and 22 miscellaneous reactions and 1 death were reported, febrile seizure being the most common event. However, 45% of these events proved to be probably caused or contributed by some other factor, giving an incidence of serious adverse events with possible or indeterminate causal relation with MMR vaccination of 5.3 per 100,000 vaccinees or 3.2 per 100,000 vaccine doses.
Conclusions: Causality between immunization and a subsequent untoward event cannot be estimated solely on the basis of a temporal relation. Comprehensive analysis of the reported adverse reactions established that serious events causally related to MMR vaccine are rare and greatly outweighed by the risks of natural MMR diseases.
Adverse Drug Reaction Reporting Systems
Drug Hypersensitivity / etiology
Measles-Mumps-Rubella Vaccine / adverse effects*
Nervous System Diseases / etiology
Measles-Mumps-Rubella Vaccine
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Selective effects of CPAP on sleep apnoea-associated manifestations
Alexandros Vgontzas, E. Zoumakis, Edward Bixler, H. M. Lin, Belinda Collins, M. Basta, S. Pejovic, G. P. Chrousos
Background: Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy. Materials and methods: Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese controls were monitored in the sleep laboratory for four consecutive nights. Objective measures of daytime sleepiness and performance, serial 24 h plasma measures of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), TNF receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using the same protocol after 3 months of CPAP. Results: At baseline, IL-6, TNF-r1, and insulin resistance were highest in OSA patients, intermediate in obese controls, and lowest in non-obese controls (P < 0.05). Visceral fat was significantly greater in sleep apnoeics than obese controls and predicted insulin resistance and IL-6 levels, whereas OSA predicted TNF-r1 levels (P < 0.05). CPAP decreased daytime sleepiness and blood pressure (P < 0.05), but did not affect fasting glucose or insulin or around the clock adiponectin, IL-6, TNF-α, or TNF-r1 levels. Conclusions: In obese sleep apnoeics, visceral fat is strongly associated with insulin resistance and inflammation. CPAP decreases sleepiness and moderates hypertension but does not affect visceral adiposity, insulin resistance, hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk factors for cardiovascular disease and diabetes.
European Journal of Clinical Investigation
Continuous Positive Airway Pressure
Sleep Apnea Syndromes
Adiposity
Intra-Abdominal Fat
Tumor Necrosis Factor Receptors
Vgontzas, A., Zoumakis, E., Bixler, E., Lin, H. M., Collins, B., Basta, M., ... Chrousos, G. P. (2008). Selective effects of CPAP on sleep apnoea-associated manifestations. European Journal of Clinical Investigation, 38(8), 585-595. https://doi.org/10.1111/j.1365-2362.2008.01984.x
Vgontzas, Alexandros ; Zoumakis, E. ; Bixler, Edward ; Lin, H. M. ; Collins, Belinda ; Basta, M. ; Pejovic, S. ; Chrousos, G. P. / Selective effects of CPAP on sleep apnoea-associated manifestations. In: European Journal of Clinical Investigation. 2008 ; Vol. 38, No. 8. pp. 585-595.
@article{a825527bd4b3406c8f76a9fa1d05f256,
title = "Selective effects of CPAP on sleep apnoea-associated manifestations",
abstract = "Background: Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy. Materials and methods: Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese controls were monitored in the sleep laboratory for four consecutive nights. Objective measures of daytime sleepiness and performance, serial 24 h plasma measures of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), TNF receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using the same protocol after 3 months of CPAP. Results: At baseline, IL-6, TNF-r1, and insulin resistance were highest in OSA patients, intermediate in obese controls, and lowest in non-obese controls (P < 0.05). Visceral fat was significantly greater in sleep apnoeics than obese controls and predicted insulin resistance and IL-6 levels, whereas OSA predicted TNF-r1 levels (P < 0.05). CPAP decreased daytime sleepiness and blood pressure (P < 0.05), but did not affect fasting glucose or insulin or around the clock adiponectin, IL-6, TNF-α, or TNF-r1 levels. Conclusions: In obese sleep apnoeics, visceral fat is strongly associated with insulin resistance and inflammation. CPAP decreases sleepiness and moderates hypertension but does not affect visceral adiposity, insulin resistance, hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk factors for cardiovascular disease and diabetes.",
author = "Alexandros Vgontzas and E. Zoumakis and Edward Bixler and Lin, {H. M.} and Belinda Collins and M. Basta and S. Pejovic and Chrousos, {G. P.}",
journal = "European Journal of Clinical Investigation",
Vgontzas, A, Zoumakis, E, Bixler, E, Lin, HM, Collins, B, Basta, M, Pejovic, S & Chrousos, GP 2008, 'Selective effects of CPAP on sleep apnoea-associated manifestations', European Journal of Clinical Investigation, vol. 38, no. 8, pp. 585-595. https://doi.org/10.1111/j.1365-2362.2008.01984.x
Selective effects of CPAP on sleep apnoea-associated manifestations. / Vgontzas, Alexandros; Zoumakis, E.; Bixler, Edward; Lin, H. M.; Collins, Belinda; Basta, M.; Pejovic, S.; Chrousos, G. P.
In: European Journal of Clinical Investigation, Vol. 38, No. 8, 01.08.2008, p. 585-595.
T1 - Selective effects of CPAP on sleep apnoea-associated manifestations
AU - Vgontzas, Alexandros
AU - Zoumakis, E.
AU - Bixler, Edward
AU - Lin, H. M.
AU - Collins, Belinda
AU - Basta, M.
AU - Pejovic, S.
AU - Chrousos, G. P.
N2 - Background: Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy. Materials and methods: Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese controls were monitored in the sleep laboratory for four consecutive nights. Objective measures of daytime sleepiness and performance, serial 24 h plasma measures of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), TNF receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using the same protocol after 3 months of CPAP. Results: At baseline, IL-6, TNF-r1, and insulin resistance were highest in OSA patients, intermediate in obese controls, and lowest in non-obese controls (P < 0.05). Visceral fat was significantly greater in sleep apnoeics than obese controls and predicted insulin resistance and IL-6 levels, whereas OSA predicted TNF-r1 levels (P < 0.05). CPAP decreased daytime sleepiness and blood pressure (P < 0.05), but did not affect fasting glucose or insulin or around the clock adiponectin, IL-6, TNF-α, or TNF-r1 levels. Conclusions: In obese sleep apnoeics, visceral fat is strongly associated with insulin resistance and inflammation. CPAP decreases sleepiness and moderates hypertension but does not affect visceral adiposity, insulin resistance, hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk factors for cardiovascular disease and diabetes.
AB - Background: Visceral adiposity and obstructive sleep apnoea (OSA) may be independently associated with daytime sleepiness/low performance, insulin resistance, hypercytokinaemia, and/or hypertension. The objectives of this study are to simultaneously test these associations at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy. Materials and methods: Sixteen obese men with OSA; 13 non-apnoeic, obese controls, and 15 non-obese controls were monitored in the sleep laboratory for four consecutive nights. Objective measures of daytime sleepiness and performance, serial 24 h plasma measures of interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), TNF receptor 1 (TNF-r1) and adiponectin, fasting blood glucose and insulin, visceral adiposity and blood pressure were obtained. Sleep apnoeics were re-assessed using the same protocol after 3 months of CPAP. Results: At baseline, IL-6, TNF-r1, and insulin resistance were highest in OSA patients, intermediate in obese controls, and lowest in non-obese controls (P < 0.05). Visceral fat was significantly greater in sleep apnoeics than obese controls and predicted insulin resistance and IL-6 levels, whereas OSA predicted TNF-r1 levels (P < 0.05). CPAP decreased daytime sleepiness and blood pressure (P < 0.05), but did not affect fasting glucose or insulin or around the clock adiponectin, IL-6, TNF-α, or TNF-r1 levels. Conclusions: In obese sleep apnoeics, visceral fat is strongly associated with insulin resistance and inflammation. CPAP decreases sleepiness and moderates hypertension but does not affect visceral adiposity, insulin resistance, hypoadiponectinaemia or hypercytokinaemia, all of which are independent risk factors for cardiovascular disease and diabetes.
JO - European Journal of Clinical Investigation
JF - European Journal of Clinical Investigation
Vgontzas A, Zoumakis E, Bixler E, Lin HM, Collins B, Basta M et al. Selective effects of CPAP on sleep apnoea-associated manifestations. European Journal of Clinical Investigation. 2008 Aug 1;38(8):585-595. https://doi.org/10.1111/j.1365-2362.2008.01984.x
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ELASTOSIL® LR 5040/40 by Wacker is a non-post cure, translucent liquid silicone rubber (LSR). Offers excellent tear resistance, higher productivity and excellent mechanical properties. It contains few volatile components and does not require thermal post-treatment. ELASTOSIL® LR 5040/40 is suitable for processing by injection molding. Used in baby-care, food-contact and medical applications like feeding teats & pacifiers, teething rings, anti-colic valves, bottle tops & seals for food cans and respirator masks. Meets of BfR, FDA, EN 1400 & EN 14350, ISO 10993 and USP Class VI.
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What is a shiatsu treatment?
Shiatsu therapy is a holistic form of treatment, focusing on the whole person: both body and mind. It involves the application of pressure at key points and along the meridians as well as stretching the body to help correct its imbalances and stimulate its natural healing process.
From a Western medicine point of view, shiatsu pressure calms an overactive nervous system and promotes deep relaxation which helps to reduce stress, tension and pain, and to improve organ function.
The treatment is done on a shiatsu mat laid on the floor. It can also be done on a massage table.
Shiatsu treatment is done over the clothes and no oil or lotion is required. Since you keep your clothes on, it is recommended that you wear a loose, comfortable outfit (i.e. avoid skirt or jeans).
What are the benefits from a shiatsu treatment?
The strength of shiatsu therapy lies in the prevention of the disease.
Receiving regular treatments helps strengthen the body and maintain good health.
It is a hands-on therapy originating from Japan. Its purpose is to promote and maintain good health as well as to treat specific conditions.
Shiatsu is based on the principles of Eastern medicine, where the vital energy (Qi in Chinese) is thought to circulate throughout the body along "meridians". When the vital energy flows smoothly, we are healthy; disease results from imbalances in its flow.
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Feb 16, 2017. For nearly the last 80 years, acid reflux was considered the early stage of GERD. Today experts are turning their attention towards another contributing factor: chronically high inflammation as the actual culprit behind GERD. Inflammation not only contributes to tissue damage in the esophagus. It's also tied.
Mar 1, 2017. But for now, we only know one thing for sure: Inflammation is a precursor to a range of autoimmune, metabolic, and chronic diseases. And dietary acid injury, like that which occurs from acid reflux disease, illuminates this connection. The good news is that both inflammation and acid reflux can be prevented.
Signs and symptoms of gastroesophageal reflux disease, or GERD, include both acid reflux and heartburn and may also include chest pain and difficulty swallowing. Gastritis involves a group of conditions that cause inflammation of the stomach lining. Symptoms of gastritis are similar to the symptoms of GERD in which.
It can also increase your risk of pelvic inflammatory disease, which can affect your chances. Contacting your doctor at the first sign of this issue may be the best.
According to Medscape, a continuing education website for physicians and registered nurses, hypnotherapy for IBS, GERD and inflammatory bowel.
What Is GERD? Pain, Symptoms, Causes, Remedies, and More – Gastroesophageal reflux disease, or GERD, is a digestive disorder that affects the lower esophageal sphincter (LES), the ring of muscle between the esophagus and stomach. Many people, including pregnant women, suffer from heartburn or acid indigestion caused by GERD. Doctors believe that some people suffer from.
Without these nutrients, the risk of failing to keep up our detox system shoots up and increases the possibility of allowing cancer-causing or atherosclerosis-enhancing inflammatory substances through the border patrol. A variety of foods.
Fat causes inflammation and degrades the muscles in your respiratory. Other symptoms include headaches, depression, acid reflux disease, pancreatitis and lots more. Because you're carrying more weight than you were.
great for circulation and anti-inflammatory. (3) What does it do: Liquorice root is used to treat ulcer symptoms, canker sores and digestive problems, such as.
I suffered for years with bad reflux, GERD, hiatal hernia, ulcers and was just given prescription after prescription. A few years later I was also diagnosed with Crohn's Disease, and a few more medicines including steroids, immunosuppressant drug therapy, and anti- inflammatory drugs were added to the list. All of the.
Oct 14, 2017. Learn more about the causes and treatment of inflammation of the esophagus. up into the esophagus (gastroesophageal reflux). Gastroesophageal reflux disease (GERD) is a condition in which this backflow of acid is a frequent or ongoing problem. A complication of GERD is chronic inflammation and.
And the focus in this case needs to move toward the real underlying cause of the disease—inflammation and cytokine blockers. Current GERD treatments neutralize or reduce stomach acid. But this exciting finding opens the door for innovative GERD therapies that target cytokines and other inflammatory proteins rather than.
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Obagi Medical Products offer an excellent skin care line, which incorporates tretinoin–a results oriented product that works. The products treat a wide variety of skin conditions and prepare the skin for more advanced treatments.
The Obagi website explains the products in better detail. Please refer to http://www.obagi.com.
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Niaspan prolonged release tablets contain the active ingredient nicotinic acid (also known as niacin), which is a member of the B group of vitamins.
Lowering high blood cholesterol levels (primary hypercholesterolaemia).
Correcting high levels of 'bad fats' (ie LDL cholesterol and triglycerides) and low levels of 'good fats' (ie HDL cholesterol) in the blood (mixed dyslipidaemia).
Nicotinic acid is normally used when another type of cholesterol-lowering medicine called a statin (for example simvastatin, atorvastatin), together with a low cholesterol diet and increased exercise, has not lowered LDL cholesterol sufficiently. Nicotinic acid is taken in combination with the statin medicine to produce an additional effect on cholesterol levels. It may also be used on its own in people who cannot take statin medicines.
Nicotinic acid is normally consumed in the diet, as well as being made by the body, and has various effects. However, Niaspan contains nicotinic acid in much larger doses than those normally obtained by the body and it produces effects unrelated to its role as a vitamin. Large doses of nicotinic acid are used to lower blood levels of cholesterol and other 'bad fats' that are associated with heart disease.
Nicotinic acid can cause the blood vessels to dilate (widen) and this can cause side effects such as flushing or feeling itchy. Niaspan prolonged release tablets are designed to release the nicotinic acid slowly and continuously over a few hours to help minimise these sorts of side effects. The tablets must be swallowed whole and not crushed, broken or chewed to avoid damaging the prolonged release action. They should be taken at bedtime, after a low-fat snack such as an apple, low fat yoghurt or slice of bread.
It is important to continue to follow a cholesterol-lowering diet and exercise regime while taking nicotinic acid. Ask your doctor for advice.
Niaspan tablets should be swallowed whole with water and not broken, crushed or chewed.
When you begin treatment with this medicine your dose will be started low and gradually increased over a period of a few weeks. You should follow the instructions given by your doctor carefully, as this gradual dose escalation is to reduce the chance of experiencing side effects such as flushing and itching. You can also minimise these side effects by taking each dose with a low-fat snack and avoiding hot drinks and alcohol around the time of each dose. If you do experience side effects such as flushing these will usually improve over time.
If for any reason you stop taking this medicine for an extended period of time, you will need to re-introduce it slowly, increasing the dose gradually as before, when you start taking it again. Ask your doctor or pharmacist for advice.
You should have blood tests to monitor your liver function (liver function tests) regularly throughout treatment with this medicine. If you experience any symptoms that may suggest a liver problem, for example, persistent nausea and vomiting, abdominal pain, or the development of jaundice (a yellow colouring to the skin and the whites of the eyes), you should consult your doctor so that your liver can be checked.
People in the acute phase of a heart attack.
History of gall bladder disease.
The manufacturer has not studied the safety and efficacy of this medicine in children and adolescents. It is not recommended for children and adolescents.
The safety of this medicine in pregnancy has not been established. It is is not recommended for use in pregnancy unless considered essential by your doctor. Seek medical advice from your doctor.
This medicine passes into breast milk and could have adverse effects on a nursing infant. It should not be used by mothers who are breastfeeding. Seek medical advice from your doctor.
Flushing (warmth, redness, itching, tingling).
Swelling of the ankles due to fluid retention.
Muscle disorders, eg pain, weakness, cramps.
Niaspan should not be used in combination with other nicotinic acid preparations. Check with your doctor or pharmacist before taking high dose multivitamins or vitamin B supplements in combination with this medicine.
There may be an increased risk of side effects on the muscles if this medicine is taken in combination with a cholesterol-lowering medicine known as a statin. These include atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin. If you are taking this medicine in combination with a statin you should inform your doctor immediately if you experience any muscular symptoms, for example muscle pain, tenderness, cramps, or weakness, particularly if accompanied by a fever or feeling generally unwell.
This medicine may raise blood glucose levels and may therefore reduce the effectiveness of medicines used to treat diabetes. People with diabetes should carefully monitor their blood sugar while taking this medicine. Dose adjustments of antidiabetic medicines may be needed. Seek further advice from your doctor.
The anti-blood-clotting effect of anticoagulants such as warfarin may be increased by this medicine. For this reason, if you are taking an anticoagulant your doctor may want to check your blood-clotting time (INR) when you start or stop treatment with this medicine.
This medicine might increase the effects of medicines used to lower high blood pressure. If you are being treated for high blood pressure you should let your doctor know if you feel dizzy or lightheaded after starting treatment with this medicine.
If you are taking other medicines that dilate the blood vessels and cause flushing, for example nitrates such as glyceryl trinitrate, you may find that this medicine increases the flushing.
There are currently no other medicines available in the UK that contain only nicotinic acid at a dose for treating high cholesterol levels.
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Doctoral Dissertations (Winter 2014 to Present)
Delineating the cellular mechanism of osteoblast desensitization to mechanical stimulation
2014_Gangadharan_Vimal_PhD.pdf(7.91 MB)
Gangadharan, Vimal
Bone is a highly dynamic tissue constantly adapting itself to several physical and biochemical cues. Of these various signals, application of mechanical stimulation has profound anabolic effects on maintaining the integrity and architecture of bone. While physical activity retards bone loss, the lack of physical stimuli results in significant bone loss as observed in immobilized patients and astronauts in microgravity. However, it has been ascertained that bone is habituated to continuous mechanical loading and a similar effect is witnessed at the cellular level in osteoblasts. The goal of the study was to elucidate the cellular mechanism for osteoblast desensitization to mechanical stimulation so the anabolic effects of the physical stimulus on bone can be best utilized. The osteogenic response to mechanical loading is an outcome of an intricate biophysical process. During physical activity, the strain applied on the bone causes interstitial fluid movement across the canaliculi inducing fluid shear stress (FSS) on the bone cells. These cells detect and transmit the physical stimulus to initiate a cascade of downstream signaling that eventually culminates in osteogenesis. This process of converting mechanical stimulus into biochemical response is termed mechanotransduction. Numerous components have been implicated in osteoblast mechanotransduction including the purinergic receptor, P2X 7 (P2X7 R). In vivo studies conducted on P2X7 R KO mice demonstrated that significant percent of mechanically induced bone formation is dependent on this ligand gated ion channel. Interestingly, the P2X7 R were found localized in caveolae of certain cell types. Flask shaped plasmallemmal invaginations, caveolae, are subset of lipid microdomains with caveolin-1 (CAV1) as their primary protein constituent. Caveolae aids in several cellular functions including scaffolding proteins and endocytosis. Furthermore, it has been observed that the CAV1 KO mice have significantly higher bone mass and strength. This led to the hypothesis that caveolae in osteoblasts scaffolds the purinergic receptor, P2X 7 , and the loss of mechanosensitivity is due to the caveolar endocytosis of P2X7 R upon ligand binding. Initial studies carried out demonstrated that CAV1 was internalized when osteoblasts were stimulated with P2X7 R agonists. Sucrose gradient fractionation of MC3T3-E1 pre-osteoblasts showed that CAV1 translocated to the denser cytosolic fractions upon stimulation with ATP. Additionally, both ATP and the more specific P2X7 R agonist, BzATP, induced endocytosis of CAV1, which was inhibited when MC3T3-E1 cells were pretreated with the specific P2X7 R antagonist, A-839977. The P2X7 R co-fractionated with CAV1 but, using Superresolution Structured Illumination Microscopy (SR-SIM), we found that only a sub-population of the P2X7 R existed in these lipid microdomains on the membrane of MC3T3-E1 cells. Suppression of CAV1 enhanced the intracellular [Ca2+ ]i to BzATP, suggesting that caveolae regulates P2X7 R signaling. This proposed mechanism is supported by increased mineralization observed in CAV1 knockdown MC3T3-E1 cells treated with BzATP. These data suggest that caveolae regulate P2X 7 R signaling upon activation by undergoing endocytosis and potentially carrying with it other signaling proteins, hence controlling the spatio-temporal signaling of P2X7 R in osteoblasts. Furthermore, it was confirmed that the osteoblasts were desensitized to mechanical stimulus. Consecutive stimulation of the MC3T3-E1 cells with FSS failed to elicit a [Ca2+ ]i response during the 2nd stimulation. By measuring the [Ca2+ ]i response to ATP and BzATP, it was determined that the P2X7 R in osteoblasts were temporarily desensitized. While these results were encouraging, further investigation revealed caveolae has no role in the desensitization of P2X7 R. The suppression of CAV1 had no apparent effect on the loss of sensitivity of P2X7 R to BzATP. Moreover there was no evidence for P2X7 R endocytosis observed when the MC3T3-E1cells were treated with ATP or BzATP. Finally, we ascertained the CAV1 KD cells were unable to retain their mechanosensitivity as postulated. These results indicated the presence of a separate mechanism that led to a different approach involving cytoskeletal reorganization. One of the prominent responses of osteoblasts in response to FSS is the reorganization of actin cytoskeleton to form stress fibers. The increase in stress fibers was found to significantly enhance the cellular stiffness in a purinergic signaling dependent manner. Although the changes in cytoskeleton were postulated to alter cellular mechanosensitivity, there have been no reports demonstrating a detailed mechanism. The purinergic receptor, P2Y2 (P2Y 2 R) has been shown to be essential for cytoskeletal reorganization in certain cell types and interestingly the P2Y2 R KO mice had enhanced bone mineral density. We hypothesized that P2Y2 R induced increase in ASFF is responsible for osteoblast desensitization. MC3T3-E1 cells treated with UTP, a potent agonist of P2Y2 R, displayed strong ASFF. The effect was blocked when the cells were pretreated with Suramin, an antagonist of P2Y2 R. Moreover, when P2Y2 R was suppressed using siRNA, there was significant increase in the number of responding cells to consecutive FSS application. These data validates the hypothesis that the mechanosensitivity of osteoblasts are regulated by P2Y2 R through ASFF. Overall our novel findings provide great insights into better understanding the mechanism of cellular desensitization to physical stimulation in osteoblasts. These findings can be further explored to have significant impact in mechanical load induced osteogenesis to prevent severe bone disorders such as osteoporosis.
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Germ Cell Tumor Studies
Active surveillance, chemotherapy in treating pediatric and adult patients with germ cell tumors
How well does chemotherapy, (bleomycin, carboplatin, etoposide, or cisplatin), active surveillance work in patients with germ cell tumors?
a study on Germ Cell Tumor Extragonadal Embryonal Carcinoma Teratoma Choriocarcinoma Ovarian Embryonal Carcinoma Ovarian Tumor Testicular Cancer Testicular Tumor Seminoma
at UC Davis UCLA UCSF
study started May 2017
estimated completion June 2027
by William A. May (ucla)Carla B. Golden (ucsf)Marcio H. Malogolowkin (ucdavis)Arun A. Rangaswami (ucsf)Eduard H. Panosyan (ucla)
This phase III trial studies how well active surveillance, bleomycin, carboplatin, etoposide, or cisplatin work in treating pediatric and adult patients with germ cell tumors. Active surveillance may help doctors to monitor subjects with low risk germ cell tumors after their tumor is removed. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
A Phase 3 Study of Active Surveillance for Low Risk and a Randomized Trial of Carboplatin vs. Cisplatin for Standard Risk Pediatric and Adult Patients With Germ Cell Tumors
PRIMARY OBJECTIVES: I. To evaluate whether a strategy of complete surgical resection followed by surveillance can maintain an overall survival rate of at least 95.7% at two years for pediatric, adolescent and adult patients with stage I (low risk) malignant germ cell tumors, and at least 95% for patients with ovarian pure immature teratoma. II. To compare the event-free survival of a carboplatin versus (vs.) cisplatin-based regimen in the treatment of pediatric, adolescent and young adult patients with standard risk non-seminomatous germ cell tumors. IIa. To compare the event free survival (EFS) of a carboplatin-based regimen (carboplatin [C] etoposide [E] bleomycin [b]) vs. a cisplatin-based regimen (cisplatin [P]Eb) in children (less than 11 years in age) with standard risk germ cell tumors (GCT). IIb. To compare the EFS of a carboplatin-based regimen (BEC) vs. a cisplatin-based regimen (BEP) in adolescents and young adults (ages 11 - < 25 years) with standard risk GCT. SECONDARY OBJECTIVES: I. To compare the incidence of ototoxicity in children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin-based chemotherapy. II. To refine and validate a novel patient-reported measure of hearing outcomes for children, adolescents and young adults with standard risk germ cell tumors. EXPLORATORY OBJECTIVES: I. To prospectively determine the correlation of tumor marker decline (alpha-fetoprotein [FP] and beta-human chorionic gonadotropin [HCG]) with clinical outcome in low and standard risk germ cell tumor patients. II. To compare self-reported peripheral neuropathy and other patient-reported outcomes between children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin based chemotherapy. III. Assess the relationship between hearing loss as measured by audiometry with the effects of tinnitus as assessed on the Adolescent and Young Adult Hearing Screening (AYA-HEARS) instrument. IV. To evaluate the prognostic significance of serum micro ribonucleic acid (miRNA)s in stage I testicular cancer (seminoma and non-seminoma) patients by collecting clinical data and serum specimens for future analysis. OUTLINE: Patients with low-risk stage I grade 2, 3 ovarian immature teratoma or stage I non-seminoma malignant germ cell tumors (MGCT)s undergo observation and can transfer to standard risk arm when eligibility criteria are met. Patients with stage I seminoma testicular MGCT undergo observation, and those with residual/recurrent disease are treated at the discretion of their physician. Patients with standard risk 1 are randomized into 1 of 2 arms. ARM I (CEb): Patients receive bleomycin intravenously (IV) over 10 minutes and carboplatin IV over 1 hour on day 1. Patients also receive etoposide IV over 1-2 hours on days 1-5. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. ARM II (PEb): Patients receive bleomycin IV over 10 minutes on day 1. Patients also receive etoposide IV over 1-2 hours and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with standard risk 2 are randomized into 1 of 2 arms. ARM III (BEC): Patients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. ARM IV (BEP): Patients receive bleomycin IV over 10 minutes on days 1, 8, 15, etoposide IV over 1-2 hours on days 1-5, and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2 months for 12 months, every 3-6 months to 24 months, every 6 months for years 3-5, and then annually for up to 10 years.
Childhood Extracranial Germ Cell Tumor Extragonadal Embryonal Carcinoma Germ Cell Tumor Malignant Germ Cell Tumor Malignant Ovarian Teratoma Stage I Ovarian Choriocarcinoma Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7 Stage I Ovarian Teratoma AJCC v6 and v7 Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7 Stage I Testicular Choriocarcinoma AJCC v6 and v7 Stage I Testicular Embryonal Carcinoma AJCC v6 and v7 Stage I Testicular Seminoma AJCC v6 and v7 Stage I Testicular Yolk Sac Tumor AJCC v6 and v7 Stage II Ovarian Choriocarcinoma Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7 Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7 Stage II Testicular Choriocarcinoma AJCC v6 and v7 Stage II Testicular Embryonal Carcinoma AJCC v6 and v7 Stage II Testicular Yolk Sac Tumor AJCC v6 and v7 Stage III Ovarian Choriocarcinoma Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7 Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7 Stage III Testicular Choriocarcinoma AJCC v6 and v7 Stage III Testicular Embryonal Carcinoma AJCC v6 and v7 Stage III Testicular Yolk Sac Tumor AJCC v6 and v7 Stage IV Ovarian Choriocarcinoma Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7 Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7 Testicular Mixed Choriocarcinoma and Embryonal Carcinoma Testicular Mixed Choriocarcinoma and Teratoma Testicular Mixed Choriocarcinoma and Yolk Sac Tumor Carcinoma Neoplasms Neoplasms, Germ Cell and Embryonal Teratoma Carcinoma, Embryonal Endodermal Sinus Tumor Seminoma Choriocarcinoma Ovarian Neoplasms Cisplatin Carboplatin Etoposide Etoposide phosphate Bleomycin Podophyllotoxin Best Practice Bleomycin Sulfate Laboratory Biomarker Analysis Pharmacogenomic Study Quality-of-Life Assessment
There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT [all sites])
Standard risk 1: Patient must be < 11 years of age at enrollment
Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment except for those who were initially diagnosed with stage I non-seminoma malignant GCT and later recur during observation post surgery off study; for these patients, if elevated tumor markers rise to > 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is not required for enrollment
Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB; grade: 2 or 3; histology: pure immature teratoma (may contain microscopic foci of yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
Low risk stage I non-seminoma MGCT; site: ovarian, testicular, or extragonadal; stage: COG stage I, FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA, IB and IS; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed); all ages
Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: must contain at least one of the following: may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus
Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) < 11
Standard risk 2 (SR2)
Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; tumor markers: must be IGCCC good risk; post op: alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) < 3.0 x normal; age (years) >= 11 and < 25
Site: extragonadal; stage: COG stage II; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; age (years) >= 11 and < 25
IGCCC criteria only apply to SR2 patients with a testicular primary tumor
Use post-op tumor marker levels to determine IGCCC risk group
Stage 1 seminoma patients are not eligible for the standard risk arms of the study
For the low risk stage I non-seminoma MGCT and the standard risk arms, components of yolk sac tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the only malignant component present, then it must be deemed by the pathologist to be greater than a "microscopic component" of yolk sac tumor
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m2
A serum creatinine based on age/gender as follows: (mg/dL)
1 month to < 6 months male: 0.4 female: 0.4
6 months to < 1 year male: 0.5 female: 0.5
1 to < 2 years male: 0.6 female: 0.6
6 to < 10 years male: 1 female: 1
10 to < 13 years male: 1.2 female: 1.2
13 to < 16 years: male: 1.5 female: 1.4
>= 16 years male: 1.7 female: 1.4
Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT is 45 U/L)
Peripheral absolute neutrophil count (ANC) >= 1,000/mm3
Platelet count >= 100,000/mm3
Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
Eligibility criteria to participate in the pilot study of the AYA-Hears instrument (patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be enrolled on the AGCT1531 SR2 arm in order to participate
>= 11 and < 25 years old at enrollment
Able to fluently speak and read English
Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
Followed for cancer or survivorship care at one of the following institutions:
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Dana Farber/Harvard Cancer Center
Hospital for Sick Children
Patients with any diagnoses not listed including:
Stage I testicular cancer patients who have undergone primary RPLND (retroperitoneal lymph node dissection)
Pure dysgerminoma
Pure mature teratoma
Pure immature teratoma COG stage I, grade I
Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >= 1000 ng/mL
Pure immature teratoma COG stage II - IV or FIGO stage IC to IV
"Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or IV EG, or IGCCC intermediate or poor risk testicular), or
Primary central nervous system (CNS) germ cell tumor
Germ cell tumor with somatic malignant transformation
Spermatocytic seminoma
Patients must have had no prior systemic therapy for the current cancer diagnosis
Patients must have had no prior radiation therapy with the exception of CNS irradiation of brain metastases; (this exception only applies to SR1 patients; any patients over age 11 with distant metastases to brain [stage IV disease] would be considered poor risk and therefore not eligible for this trial)
Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin, are ineligible for the standard risk arms of the trial
Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
Mattel Children's Hospital UCLA accepting new patients
Los Angeles California 90095 United States
UCLA / Jonsson Comprehensive Cancer Center accepting new patients
UCSF Benioff Children's Hospital Oakland accepting new patients
Oakland California 94609 United States
University of California Davis Comprehensive Cancer Center accepting new patients
Sacramento California 95817 United States
UCSF Medical Center-Mission Bay accepting new patients
San Francisco California 94158 United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center accepting new patients
Torrance California 90502 United States
Cedars Sinai Medical Center accepting new patients
USC Norris Oncology/Hematology-Newport Beach in progress, not accepting new patients
Newport Beach California 92663 United States
Rady Children's Hospital - San Diego accepting new patients
San Diego California 92123 United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center accepting new patients
Lead Scientists at UC Cancer
William A. May (ucla)
HS Clinical Professor, Pediatrics. Authored (or co-authored) 5 research publications.
Carla B. Golden (ucsf)
Professor, Pediatrics. Authored (or co-authored) 8 research publications.
Marcio H. Malogolowkin (ucdavis)
Professor, Pediatrics. Authored (or co-authored) 100 research publications.
Arun A. Rangaswami (ucsf)
Professor, Pediatrics. Authored (or co-authored) 25 research publications.
Eduard H. Panosyan (ucla)
HS Associate Clinical Professor, Pediatrics. Authored (or co-authored) 24 research publications.
June 2027 (estimated)
Children's Oncology Group
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Ageing & HIV
Switching to Biktarvy maintains viral suppression in people aged 65 or over
Liz Highleyman
Image: Shutterstock.com
People aged 65 or older who switched to the Biktarvy single-tablet regimen had a high probability of maintaining an undetectable viral load, researchers reported this week at the 23rd International AIDS Conference (AIDS 2020: Virtual). What's more, the treatment was generally well tolerated even in this older population.
As people with HIV live longer thanks to effective antiretroviral therapy, they are more likely to develop additional health conditions and to be taking multiple medications.
"As the number of older adults living with HIV grows, it's critical to optimize therapy to fit the unique needs of this key population, including those with chronic conditions who may be on multiple medications," Dr Moti Ramgopal of Midway Immunology and Research Center in Florida said in a Gilead Sciences press release. "By 2030, it is projected that up to 70% of people living with HIV will be 50 years or older, the majority of whom will have at least one other comorbidity."
lipid
Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.
A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or 'bad' cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or 'good' cholesterol (which helps get rid of LDL).
comorbidity
The presence of one or more additional health conditions at the same time as a primary condition (such as HIV).
boosting agent
Booster drugs are used to 'boost' the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.
Biktarvy, approved in Europe in 2018, is an all-in-one antiretroviral regimen that contains the integrase inhibitor bictegravir, tenofovir alafenamide (TAF) – a newer formulation that is easier on the kidneys and bones but may lead to higher lipid levels and weight gain – and emtricitabine. Prior research showed that the combination has few interactions with other drugs.
Dr Ramgopal presented findings from a pooled analysis of four international trials in which previously treated people with viral suppression switched from their current regimen to Biktarvy.
This analysis focused on the 140 participants in these studies who were aged 65 or older. When they entered the study, they had had undetectable viral load (below 50 copies/ml) on their current antiretroviral regimen at two screening visits, and they had kidney function within the normal range, with an estimated glomerular filtration rate (eGFR) of 30 ml/min or higher.
Three of the studies were randomised controlled trials in which a combined 54 participants either switched to Biktarvy or stayed on their current regimen. These regimens consisted of:
dolutegravir (Tivicay) plus tenofovir disoproxil fumarate (TDF)/emtricitabine (the drugs in Truvada),
dolutegravir plus TAF/emtricitabine (the drugs in Descovy),
dolutegravir/abacavir/lamivudine (the drugs in the Triumeq single-tablet regimen), or
boosted atazanavir (Reyataz) or darunavir (Prezista or Prezcobix) plus two nucleoside/nucleotide reverse transcriptase inhibitors.
The fourth study was a single-arm trial in which 86 people over 65 switched from elvitegravir/cobicistat/TAF/emtricitabine (Genvoya) or another third agent plus TAF/emtricitabine.
"By 2030, it is projected that up to 70% of people living with HIV will be 50 years or older, the majority of whom will have at least one other comorbidity."
Nearly 90% of the participants were men, most were white and the median age was 68 years. The median CD4 count was 629, indicating well-preserved immune function, and the median eGFR was 74 ml/min, indicating good kidney function. Many participants had other health conditions, including abnormal blood lipids (59%), hypertension (55%), cardiovascular disease (24%) and diabetes (22%). About one in five reported that they currently smoked.
Before switching, the most frequently used regimens were Genvoya (56%), boosted atazanavir plus abacavir/lamivudine (18%) and Triumeq (10%).
At 48 weeks after switching to Biktarvy, 92% maintained viral suppression. None experienced virological treatment failure with a viral load of 50 copies/ml or higher; virological data were missing for 11 people.
The median CD4 count gain was 13 cells/mm3, reflecting the fact that most already had high CD4 cell levels.
More news from AIDS 2020: Virtual
Biktarvy was generally safe and well tolerated. Two people experienced moderate side effects, and none had severe or life-threatening drug-related adverse events. One in 10 developed severe laboratory abnormalities. Only one participant stopped taking Biktarvy due to a drug-related adverse event (abdominal discomfort), and there was one death deemed unrelated to the study drug.
Looking more closely at kidney-related adverse events, eGFR declined by a median of 2.9 ml/min by week 12, remaining around that level for the remainder of the study. No cases of proximal renal tubulopathy, a type of serious kidney dysfunction, were reported.
Total cholesterol, harmful LDL cholesterol and triglyceride levels declined by a small amount after starting Biktarvy, reflecting a modest improvement. Favourable HDL cholesterol did not change. Sixty people (43%) were taking lipid-lowering medications at study entry, and six more (4%) started during the study.
Finally, participants had a median weight gain of 1.0kg by week 48, consistent with other studies suggesting TAF may be linked to weight gain.
"Switching to [Biktarvy] is safe, effective and well tolerated in virologically suppressed adults ≥65 years through 48 weeks," the study authors concluded. "These data support the use of [Biktarvy] for treatment of adults ≥65 years who could benefit from a small single-tablet with few drug-drug interactions and an established safety profile."
Ramgopal M et al. Pooled analysis of 4 international trials of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in adults aged >65 or older demonstrating safety and efficacy: week 48 results. 23rd International AIDS Conference, abstract OAB0403, 2020.
Changing treatment
Low testosterone is linked to efavirenz, increased body fat and older age
Treatment outcomes & life expectancy
Survival prospects for older people with HIV plotted accurately by simple scoring system
Older adults with HIV have different profiles and different needs
People who inject drugs
The population of people injecting drugs in the UK is getting older
Neurological & cognitive problems
People with HIV describe how cognitive impairment impacts their quality of life
Clinical Needs of Older PLWH Include Focus on Symptom Clusters, Targeted Support Groups, and Correlations of Frailty
Presentations at a recent meeting of HIV nurses highlighted several key facets of care for people who are over the age of 50 and living with HIV.
TheBodyPro
Health services & systems
Health-care system not equipped to treat older HIV patients, says Canadian charity
Toronto-based HIV/AIDS advocacy charity, Realize, says long-term care homes and health-care facilities across Canada are not equipped to treat older patients with HIV, who are more likely to experience chronic illness.
HIV-positive patients with cancer may have accelerated biological aging
Patients with cancer who were living with HIV had increased epigenetic age—a type of biological age defined by DNA methylation patterns—compared with patients with cancer without HIV, according to a new study.
Metabolic complications of newer HIV drugs in older people
AIDS 2022 included a presentation by Tristan Barber on the metabolic complications of new HIV drugs in older people, defined as being >50 years old, and noting the lack of data in this population.
i-Base
Retinal Thinning in Well-Controlled HIV and Decline in Information Processing
A recently published study found that people living with long-term, well-controlled HIV have thinning of the retina, which may be linked to neurodegenerative issues.
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Urban Green Spaces (UGS) are an integral part of urban environment and act as lungs for rejuvenating the urban environment and improving the quality of life and health of residents. UGS assist in regulating urban microclimate, biodiversity conservation, alleviating floods, enhancing air quality, and also promotes physical and mental wellbeing of urban populace. They also provide spaces for improved social environment and are considered highly beneficial for physical, social and cognitive development of urban children. UGS exists in diverse shape, size, vegetation cover and types and includes parks, gardens, railway corridors, road side green, derelict monument sites, etc. defined UGS as urban land that consists of unsealed, permeable, soft surfaces such as soil, grass, shrubs and trees. Chandigarh is the first planned city of modern India and is known for its uniformly distributed and ample UGS within its boundaries. However, only quantification of amount of UGS is not sufficient to harness the full range of benefits from UGS for smart urban environment. The UGS should be accessible, uniformly distributed and maintained for its daily use by urban population. Although, there are restrictions on development within the Chandigarh, the high pace of urbanization, population increase and economic development in surrounding area is creating a pressure on infrastructure of Chandigarh as well. Chandigarh is also facing the issues of traffic congestion, air pollution and environmental degradation which were unheard before. The multi-faceted issues and benefits of UGS call for smart approaches for their effective utilization and management. Geospatial technologies integrated with Information and Communication Technology (ICT) tools provide a useful and smart tool in the hand of planners for quantification, assessment and evaluation of UGS for smart management. They can help in identifying the vulnerable areas as well as to assess the accessibility and distribution of UGS. They can be used for quantitative as well as qualitative analysis of UGS by applying a range of remote sensing data sets and geo-analysis. Many indices have been developed using these datasets for evaluation and monitoring of UGS. With the growing technological advancements in smart web-based tools, these technologies can also be used effectively for monitoring and management of UGS through integration of ICT tools and citizen centric services. This study demonstrates various innovative geospatial and ICT tools for evaluation and monitoring of UGS.
The authors acknowledge the encouragement provided by Director, IIRS and Dean (Academics), IIRS for carrying out these studies. The authors are also thankful to all the students of IIRS and CSSTEAP, Dehradun and SPA, Bhopal who have worked under the guidance of authors for their support in data generation and processing.
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The SMARTc platform, located at the school of pharmacy of Marseille and the La Timone University Hospital of Marseille, is a unique group dedicated to developing PK/PD models and decision algorithms to optimize combinational regimen in oncology.
The SMARTc platform is built around a group of mathematicians and modelers in PK, PK/PD and systems biology along with a scientific staff with fully equipped wet lab to perform experimental therapeutics in oncology with a strong focus on drug metabolism and pharmacokinetic studies (in vitro, in vivo) and state-of-the-art ISO15189 clinical pharmacokinetic laboratory to assay drugs in biological matrix, including biologics and immune check point inhibitors.
SMARTc's expertise focus, but is not limited to, developing innovative tools using the latest advances in applied mathematics and phenomenological models to optimize the efficacy/toxicity balance of anticancer drugs, especially when used as part of combination therapies in refractory tumors.
Developing tools for model-informed design of clinical trial.
Running phase I and phase I/II clinical trials in a FDA-approved, Iso15189 environment.
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As human beings, our very composition IS organic. Using Eaurganic products is quite simply an extension of ourselves.
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Total synthesis of relevant natural products is indispensable for the investigation of their formation, the understanding of their biological function and the design of analogs that may have a favorable therapeutic potential. To access such compounds as efficiently as possible, we develop tandem reactions based on oxidative electron transfer that is basically the bridge between different intermediate types and their reactivity patterns. This requires that fundamental questions concerning the mechanism and scope of such processes must be answered. Our oxidative domino processes allow the flexible use of multiple intermediate types in the individual sequence steps. This is inspired by Nature where complex natural products are often assembled by reaction cascades with an unprecedented efficiency. In this respect, we are especially interested in the chemistry and biochemistry of autoxidatively formed lipid metabolites, of alkaloids, lignans and terpenes. The biological properties of the synthesized natural products are evaluated, and synthetic analogs of them are derived what requires the development of new methodology again.
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New Advances on Zika Virus Research.; Viruses; Vol 11(3). 2019 Mar 14.
A novel fluorescent and bioluminescent Bi-Reporter influenza A virus (BIRFLU) to evaluate viral infections.; Journal of virology. 2019 Mar 13.
Broad and Protective Influenza B Virus Neuraminidase Antibodies in Humans after Vaccination and their Clonal Persistence as Plasma Cells.; mBio; Vol 10(2). 2019 Mar 12.
Novel Approaches for The Development of Live Attenuated Influenza Vaccines.; Viruses; Vol 11(2). 2019 Feb 22.
Engineered transfer RNAs for suppression of premature termination codons.; Nature communications; Vol 10(1). 2019 Feb 18.
Broad hemagglutinin-specific memory B cell expansion by seasonal influenza virus infection reflects early-life imprinting and adaptation to the infecting virus.; Journal of virology. 2019 Feb 06.
Phosphatidic acid induces conformational changes in Sec18 protomers that prevent SNARE priming.; The Journal of biological chemistry. 2019 Jan 07.
Use of Surface Plasmon Resonance (SPR) to Determine Binding Affinities and Kinetic Parameters Between Components Important in Fusion Machinery.; Methods in molecular biology (Clifton, N.J.); Vol 1860. 2019.
Detection and Quantification of Pseudouridine in RNA.; Methods in molecular biology (Clifton, N.J.); Vol 1870. 2019.
Conservation of location of several specific inhibitory codon pairs in the Saccharomyces sensu stricto yeasts reveals translational selection.; Nucleic acids research. 2018 Dec 21.
Transcriptome alterations in myotonic dystrophy skeletal muscle and heart.; Human molecular genetics. 2018 Dec 17.
Modulation of Innate Immune Responses by the Influenza A NS1 and PA-X Proteins.; Viruses; Vol 10(12). 2018 Dec 12.
Multi-protein Bridging Factor 1(Mbf1), Rps3 and Asc1 prevent stalled ribosomes from frameshifting.; eLife; Vol 7. 2018 Nov 22.
Design of highly active double-pseudoknotted ribozymes: a combined computational and experimental study.; Nucleic acids research. 2018 Nov 20.
Development of a broad-spectrum antimicrobial combination for the treatment of Staphylococcus aureus and Pseudomonas aeruginosa corneal infections.; Antimicrobial agents and chemotherapy. 2018 Nov 12.
Post-transcriptional pseudouridylation in mRNA as well as in some major types of noncoding RNAs.; Biochimica et biophysica acta. Gene regulatory mechanisms. 2018 Nov 08.
Reverse Genetic Approaches for the Generation of Recombinant Zika Virus.; Viruses; Vol 10(11). 2018 Oct 31.
Chemically Accurate Relative Folding Stability of RNA Hairpins from Molecular Simulations.; Journal of chemical theory and computation. 2018 Oct 30.
mRNAs and lncRNAs intrinsically form secondary structures with short end-to-end distances.; Nature communications; Vol 9(1). 2018 Oct 18.
Observation of preQ1-II riboswitch dynamics using single-molecule FRET.; RNA biology. 2018 Oct 17.
Temperature Sensitive Mutations in Influenza A Viral Ribonucleoprotein Complex Responsible for the Attenuation of the Live Attenuated Influenza Vaccine.; Viruses; Vol 10(10). 2018 Oct 15.
Identification of new high affinity targets for Roquin based on structural conservation.; Nucleic acids research. 2018 Oct 08.
NMD-degradome sequencing reveals ribosome-bound intermediates with 3'-end non-templated nucleotides.; Nature structural & molecular biology; Vol 25(10). 2018 Oct.
CRISPR-tagging mice in aging research.; Aging. 2018 Sep 19.
Analysis of RNA Nearest Neighbor Parameters Reveals Interdependencies and Quantifies the Uncertainty in RNA Secondary Structure Prediction.; RNA (New York, N.Y.). 2018 Aug 13.
Accelerated RNA Secondary Structure Design Using Pre-Selected Sequences for Helices and Loops.; RNA (New York, N.Y.). 2018 Aug 10.
FUNCTIONAL EVOLUTION OF THE 2009 PANDEMIC H1N1 INFLUENZA NS1 AND PA IN HUMANS.; Journal of virology. 2018 Jul 18.
Crowd on a Chip: Label-Free Human Monoclonal Antibody Arrays for Serotyping Influenza.; Analytical chemistry. 2018 Jul 09.
CRISPR-Cas9 Mediated Epitope Tagging Provides Accurate and Versatile Assessment of Myocardin.; Arteriosclerosis, thrombosis, and vascular biology. 2018 Jul 05.
Structure of HIV TAR in complex with a Lab-Evolved RRM provides insight into duplex RNA recognition and synthesis of a constrained peptide that impairs transcription.; Nucleic acids research. 2018 Jun 29.
Coupling GFP Expression with Chemical Modification to Probe Functionally Relevant Riboswitch Conformations in Live Bacteria.; Biochemistry. 2018 Jun 13.
TIM-1 Mediates Dystroglycan-Independent Entry of Lassa Virus.; Journal of virology. 2018 Jun 06.
Guide-substrate base-pairing requirement for box H/ACA RNA-guided RNA pseudouridylation.; RNA (New York, N.Y.). 2018 Jun 05.
Modeling the Embrace of a Mutator: APOBEC Selection of Nucleic Acid Ligands.; Trends in biochemical sciences. 2018 May 23.
Evaluating the susceptibility of AGO2-loaded microRNAs to degradation by nucleases in vitro.; Methods (San Diego, Calif.). 2018 May 16.
Improving RNA nearest neighbor parameters for helices by going beyond the two-state model.; Nucleic acids research. 2018 May 01.
Introduction-RNA: From Single Molecules to Medicine.; Chemical reviews; Vol 118(8). 2018 Apr 25.
Author response: High frequency of gastrointestinal manifestations in myotonic dystrophy type 1 and type 2.; Neurology; Vol 90(17). 2018 Apr 24.
The endoribonuclease YbeY is linked to proper cellular morphology and virulence in Brucella abortus.; Journal of bacteriology. 2018 Apr 09.
Cross-kingdom auxiliary subunit modulation of a voltage-gated sodium channel.; The Journal of biological chemistry; Vol 293(14). 2018 Apr 06.
Intron retention induced by microsatellite expansions as a disease biomarker.; Proceedings of the National Academy of Sciences of the United States of America. 2018 Apr 02.
Deciphering p53 signaling in tumor suppression.; Current opinion in cell biology; Vol 51. 2018 Apr.
Molecular autopsy provides evidence for widespread ribosome-phased mRNA fragmentation.; Nature structural & molecular biology; Vol 25(4). 2018 Apr.
Transcriptional coactivator PGC-1α contains a novel CBP80-binding motif that orchestrates efficient target gene expression.; Genes & development; Vol 32(7-8). 2018 Apr 01.
A New Class of Antiretroviral Enabling Innate Immunity by Protecting APOBEC3 from HIV Vif-Dependent Degradation.; Trends in molecular medicine. 2018 Mar 30.
Lack of 2'-O-methylation in the tRNA anticodon loop of two phylogenetically distant yeast species activates the general amino acid control pathway.; PLoS genetics; Vol 14(3). 2018 Mar 29.
Orthogonality of Pyrrolysine tRNA in the Xenopus oocyte.; Scientific reports; Vol 8(1). 2018 Mar 26.
Surprising Sequence Effects on GU Closure of Symmetric 2 × 2 Nucleotide RNA Internal Loops.; Biochemistry. 2018 Mar 23.
Design of Bivalent Nucleic Acid Ligands for Recognition of RNA-Repeated Expansion Associated with Huntington's Disease.; Biochemistry. 2018 Mar 21.
The analysis of translational mechanisms that modulate gene expression.; Methods (San Diego, Calif.); Vol 137. 2018 Mar 15.
A Highly Potent and Broadly Neutralizing H1 Influenza-Specific Human Monoclonal Antibody.; Scientific reports; Vol 8(1). 2018 Mar 12.
Molecular Dynamics Correctly Models the Unusual Major Conformation of the GAGU RNA Internal Loop and with NMR Reveals an Unusual Minor Conformation.; RNA (New York, N.Y.). 2018 Feb 06.
Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay.; Proceedings of the National Academy of Sciences of the United States of America. 2018 Jan 16.
Design of 'Mini' Nucleic Acid Probe for Cooperative Binding of RNA-Repeated Transcript Associated with Myotonic Dystrophy Type 1.; Biochemistry. 2018 Jan 15.
Myotonic Dystrophy Patient Preferences in Patient-Reported Outcome Measures.; Muscle & nerve. 2018 Jan 12.
Development of a novel equine influenza virus live-attenuated vaccine.; Virology; Vol 516. 2018 Jan 11.
An Alanine-to-Valine Substitution in the Residue 175 of Zika Virus NS2A Protein Affects Viral RNA Synthesis and Attenuates the Virus In Vivo.; Viruses; Vol 10(10). 2018 Jan 07.
The Role of Noncoding RNA Pseudouridylation in Nuclear Gene Expression Events.; Frontiers in bioengineering and biotechnology; Vol 6. 2018.
Broad cross-reactive IgG responses elicited by adjuvanted vaccination with recombinant influenza hemagglutinin (rHA) in ferrets and mice.; PloS one; Vol 13(4). 2018.
Neat-en-ing up our understanding of p53 pathways in tumor suppression.; Cell cycle (Georgetown, Tex.); Vol 17(13). 2018.
Identification of Amino Acid Residues Responsible for Inhibition of Host Gene Expression by Influenza A H9N2 NS1 Targeting of CPSF30.; Frontiers in microbiology; Vol 9. 2018.
Identifying Cellular Nonsense-Mediated mRNA Decay (NMD) Targets: Immunoprecipitation of Phosphorylated UPF1 Followed by RNA Sequencing (p-UPF1 RIP-Seq).; Methods in molecular biology (Clifton, N.J.); Vol 1720. 2018.
Widespread temperature sensitivity and tRNA decay due to mutations in a yeast tRNA.; RNA (New York, N.Y.). 2017 Dec 19.
Beyond Transcription: Roles of Transcription Factors in Pre-mRNA Splicing.; Chemical reviews. 2017 Dec 18.
Mammalian adaptation of an avian influenza A virus involves stepwise changes in NS1.; Journal of virology. 2017 Dec 13.
Ensemble and single-molecule FRET studies of protein synthesis.; Methods (San Diego, Calif.). 2017 Dec 13.
Modeling RNA secondary structure folding ensembles using SHAPE mapping data.; Nucleic acids research. 2017 Nov 21.
Serum Response Factor Is Essential for Maintenance of Podocyte Structure and Function.; Journal of the American Society of Nephrology : JASN. 2017 Nov 07.
Nonsense-mediated mRNA Decay and Cancer.; Current opinion in genetics & development; Vol 48. 2017 Nov 07.
Base pair probability estimates improve the prediction accuracy of RNA non-canonical base pairs.; PLoS computational biology; Vol 13(11). 2017 Nov 06.
5-Fluorouracil Treatment Alters the Efficiency of Translational Recoding.; Genes; Vol 8(11). 2017 Oct 31.
Detection of expanded RNA repeats using thermostable group II intron reverse transcriptase.; Nucleic acids research. 2017 Oct 03.
What Do We Really Think About Human Germline Genome Editing, and What Does It Mean for Medicine?; Circulation. Cardiovascular genetics; Vol 10(5). 2017 Oct.
TurboFold II: RNA structural alignment and secondary structure prediction informed by multiple homologs.; Nucleic acids research. 2017 Sep 28.
Influenza A Virus Studies in a Mouse Model of Infection.; Journal of visualized experiments : JoVE. 2017 Sep 07.
Cancer-Associated Mutations Mapped on High-Resolution Structures of the U2AF2 RNA Recognition Motifs.; Biochemistry. 2017 Sep 01.
Physics-based all-atom modeling of RNA energetics and structure.; Wiley interdisciplinary reviews. RNA; Vol 8(5). 2017 Sep.
High frequency of gastrointestinal manifestations in myotonic dystrophy type 1 and type 2.; Neurology. 2017 Aug 30.
Amino acid substitution K186E in the canine influenza virus H3N8 NS1 protein restores its ability to inhibit host gene expression.; Journal of virology. 2017 Aug 23.
Regulatory RNPs: a novel class of ribonucleoproteins that potentially contribute to ribosome heterogeneity.; Biology open. 2017 Aug 14.
Oxygen-dependent changes in lung development do not affect epithelial infection with influenza A virus.; American journal of physiology. Lung cellular and molecular physiology. 2017 Aug 10.
Modeling RNA Secondary Structure with Sequence Comparison and Experimental Mapping Data.; Biophysical journal. 2017 Jul 20.
UPF1 helicase promotes TSN-mediated miRNA decay.; Genes & development; Vol 31(14). 2017 Jul 15.
A bivalent live-attenuated influenza vaccine for the control and prevention of H3N8 and H3N2 canine influenza viruses.; Vaccine. 2017 Jul 11.
Interplay of PA-X and NS1 proteins in replication and pathogenesis of a temperature-sensitive 2009 pandemic H1N1 influenza A virus.; Journal of virology. 2017 Jun 21.
Functional evolution of influenza NS1 protein in currently circulating human 2009 pandemic H1N1 viruses.; Journal of virology. 2017 Jun 21.
Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice.; Molecular therapy. Nucleic acids; Vol 7. 2017 Jun 16.
Advanced multi-loop algorithms for RNA secondary structure prediction reveal that the simplest model is best.; Nucleic acids research. 2017 Jun 06.
Distinct mechanisms obviate the potentially toxic effects of inverted-repeat Alu elements on cellular RNA metabolism.; Nature structural & molecular biology; Vol 24(6). 2017 Jun 06.
Neat1 is a p53-inducible lincRNA essential for transformation suppression.; Genes & development; Vol 31(11). 2017 Jun 01.
Tudor-SN-mediated endonucleolytic decay of human cell microRNAs promotes G1/S phase transition.; Science (New York, N.Y.); Vol 356(6340). 2017 May 26.
DNA mutagenic activity and capacity for HIV-1 restriction of the cytidine deaminase APOBEC3G depend on whether DNA or RNA binds to tyrosine 315.; The Journal of biological chemistry; Vol 292(21). 2017 May 26.
Interplay between miR-574-3p and hnRNP L regulates VEGFA mRNA translation and tumorigenesis.; Nucleic acids research. 2017 May 17.
HIV-1 Frameshift RNA-Targeted Triazoles Inhibit Propagation of Replication-Competent and Multi-Drug-Resistant HIV in Human Cells.; ACS chemical biology. 2017 May 05.
RNA Targeting by Functionally Orthogonal Type VI-A CRISPR-Cas Enzymes.; Molecular cell; Vol 66(3). 2017 May 04.
Metalloriboswitches: RNA-Based Inorganic Ion Sensors that Regulate Genes.; The Journal of biological chemistry. 2017 Apr 28.
Structure-Function Model for Kissing Loop Interactions That Initiate Dimerization of Ty1 RNA.; Viruses; Vol 9(5). 2017 Apr 26.
Domestic chickens activate a piRNA defense against avian leukosis virus.; eLife; Vol 6. 2017 Apr 06.
A live-attenuated influenza vaccine for H3N2 canine influenza virus.; Virology; Vol 504. 2017 Apr.
Myotonic dystrophy: approach to therapy.; Current opinion in genetics & development; Vol 44. 2017 Apr 01.
Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice.; Proceedings of the National Academy of Sciences of the United States of America; Vol 114(13). 2017 Mar 28.
A sensitivity analysis of RNA folding nearest neighbor parameters identifies a subset of free energy parameters with the greatest impact on RNA secondary structure prediction.; Nucleic acids research. 2017 Mar 15.
Synonymous Codons: Choose Wisely for Expression.; Trends in genetics : TIG. 2017 Mar 11.
NS1 Protein Amino Acid Changes D189N and V194I Affect Interferon Responses, Thermosensitivity, and Virulence of Circulating H3N2 Human Influenza A Viruses.; Journal of virology; Vol 91(5). 2017 Mar 01.
Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine.; Journal of virology; Vol 91(4). 2017 Feb 15.
Revised RNA Dihedral Parameters for the Amber Force Field Improve RNA Molecular Dynamics.; Journal of chemical theory and computation; Vol 13(2). 2017 Feb 14.
Novel Thrombotic Function of a Human SNP in STXBP5 Revealed by CRISPR/Cas9 Gene Editing in Mice.; Arteriosclerosis, thrombosis, and vascular biology; Vol 37(2). 2017 Feb.
Development of live-attenuated arenavirus vaccines based on codon deoptimization of the viral glycoprotein.; Virology; Vol 501. 2017 Jan 15.
A genome wide dosage suppressor network reveals genomic robustness.; Nucleic acids research; Vol 45(1). 2017 Jan 09.
A p53 Super-tumor Suppressor Reveals a Tumor Suppressive p53-Ptpn14-Yap Axis in Pancreatic Cancer.; Cancer cell; Vol 32(4). 2017 Jan 09.
Avian Interferons and Their Antiviral Effectors.; Frontiers in immunology; Vol 8. 2017.
Development of Recombinant Arenavirus-Based Vaccines.; Methods in molecular biology (Clifton, N.J.); Vol 1581. 2017.
Challenges and Opportunities in Linking Long Noncoding RNAs to Cardiovascular, Lung, and Blood Diseases.; Arteriosclerosis, thrombosis, and vascular biology; Vol 37(1). 2017 Jan.
Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels.; PloS one; Vol 12(2). 2017.
High-Throughput Small RNA Sequencing Enhanced by AlkB-Facilitated RNA de-Methylation (ARM-Seq).; Methods in molecular biology (Clifton, N.J.); Vol 1562. 2017.
Lassa Virus Reverse Genetics.; Methods in molecular biology (Clifton, N.J.); Vol 1602. 2017.
Reverse Genetics of Influenza B Viruses.; Methods in molecular biology (Clifton, N.J.); Vol 1602. 2017.
Plasmid-Based Reverse Genetics of Influenza A Virus.; Methods in molecular biology (Clifton, N.J.); Vol 1602. 2017.
Posttranscriptional RNA Pseudouridylation.; The Enzymes; Vol 41. 2017.
Antigenicity of the 2015-2016 seasonal H1N1 human influenza virus HA and NA proteins.; PloS one; Vol 12(11). 2017.
Reverse Genetics Approaches for the Development of Influenza Vaccines.; International journal of molecular sciences; Vol 18(1). 2016 Dec 22.
S. cerevisiae Trm140 has two recognition modes for 3-methylcytidine modification of the anticodon loop of tRNA substrates.; RNA (New York, N.Y.). 2016 Dec 21.
SF1 Phosphorylation Enhances Specific Binding to U2AF(65) and Reduces Binding to 3'-Splice-Site RNA.; Biophysical journal; Vol 111(12). 2016 Dec 20.
Caught on Camera: Intermediates of Ribosome Recycling.; Structure (London, England : 1993); Vol 24(12). 2016 Dec 06.
Unmasking the U2AF homology motif family: a bona fide protein-protein interaction motif in disguise.; RNA (New York, N.Y.); Vol 22(12). 2016 Dec.
Distal Radius Fracture Outcomes and Rehabilitation.; Geriatric orthopaedic surgery & rehabilitation; Vol 7(4). 2016 Dec.
Exact calculation of loop formation probability identifies folding motifs in RNA secondary structures.; RNA (New York, N.Y.); Vol 22(12). 2016 Dec.
RNA Secondary Structure Prediction.; Current protocols in nucleic acid chemistry; Vol 67. 2016 Dec 01.
RNA binding to APOBEC deaminases; Not simply a substrate for C to U editing.; RNA biology. 2016 Nov 21.
A Small-Molecule Inhibitor of Iron-Sulfur Cluster Assembly Uncovers a Link between Virulence Regulation and Metabolism in Staphylococcus aureus.; Cell chemical biology; Vol 23(11). 2016 Nov 17.
Testosterone Rescues the De-Differentiation of Smooth Muscle Cells through Serum Response Factor/Myocardin.; Journal of cellular physiology. 2016 Nov 09.
An analog of camptothecin inactive against Topoisomerase I is broadly neutralizing of HIV-1 through inhibition of Vif-dependent APOBEC3G degradation.; Antiviral research. 2016 Nov 4.
Structural insights into Gemin5-guided selection of pre-snRNAs for snRNP assembly.; Genes & development; Vol 30(21). 2016 Nov 01.
Canine influenza viruses with modified NS1 proteins for the development of live-attenuated vaccines.; Virology; Vol 500. 2016 Oct 14.
Two distinct RNase activities of CRISPR-C2c2 enable guide-RNA processing and RNA detection.; Nature; Vol 538(7624). 2016 Oct 13.
Wild-Type U2AF1 Antagonizes the Splicing Program Characteristic of U2AF1-Mutant Tumors and Is Required for Cell Survival.; PLoS genetics; Vol 12(10). 2016 Oct.
Phosphatidylinositol (3,4,5)-trisphosphate binds to sortilin and competes with neurotensin: Implications for very low density lipoprotein binding.; Biochemical and biophysical research communications. 2016 Sep 22.
Mutations at highly conserved residues in influenza A(H1N1)pdm09 virus affect neuraminidase activity.; Virus research. 2016 Sep 2.
Dose-Dependent Regulation of Alternative Splicing by MBNL Proteins Reveals Biomarkers for Myotonic Dystrophy.; PLoS genetics; Vol 12(9). 2016 Sep.
Zinc Pyrithione Improves the Antibacterial Activity of Silver Sulfadiazine Ointment.; mSphere; Vol 1(5). 2016 Sep.
An NS1 protein mutation (I64T) affects interferon responses and virulence of circulating H3N2 human influenza A viruses.; Journal of virology. 2016 Aug 17.
Vascular smooth muscle cell contractile protein expression is increased through PKG-dependent and -independent pathways by G6PD inhibition and deficiency.; American journal of physiology. Heart and circulatory physiology. 2016 Aug 12.
Sortilin facilitates VLDL-B100 secretion by insulin sensitive McArdle RH7777 cells.; Biochemical and biophysical research communications. 2016 Aug 2.
Antisense Oligonucleotides Targeting Influenza A Segment 8 Genomic RNA Inhibit Viral Replication.; Nucleic acid therapeutics. 2016 Jul 27.
MYOSLID Is a Novel Serum Response Factor-Dependent Long Noncoding RNA That Amplifies the Vascular Smooth Muscle Differentiation Program.; Arteriosclerosis, thrombosis, and vascular biology. 2016 Jul 21.
Adjacent Codons Act in Concert to Modulate Translation Efficiency in Yeast.; Cell. 2016 Jun 29.
Crystal structure of a poly(rA) staggered zipper at acidic pH: evidence that adenine N1 protonation mediates parallel double helix formation.; Nucleic acids research. 2016 Jun 10.
The TOR signaling pathway regulates starvation-induced pseudouridylation of yeast U2 snRNA.; RNA (New York, N.Y.). 2016 Jun 7.
Leveraging Rules of Nonsense-Mediated mRNA Decay for Genome Engineering and Personalized Medicine.; Cell; Vol 165(6). 2016 Jun 2.
A CRISPR Path to Engineering New Genetic Mouse Models for Cardiovascular Research.; Arteriosclerosis, thrombosis, and vascular biology; Vol 36(6). 2016 Jun.
The APOBEC Protein Family: United by Structure, Divergent in Function.; Trends in biochemical sciences. 2016 May 30.
Smooth Muscle Enriched Long Noncoding RNA (SMILR) Regulates Cell Proliferation.; Circulation; Vol 133(21). 2016 May 24.
EF-G Activation by Phosphate Analogs.; Journal of molecular biology; Vol 428(10 Pt B). 2016 May 22.
Novel strategies for development of hemorrhagic fever arenavirus live-attenuated vaccines.; Expert review of vaccines. 2016 May 13.
Development and applications of single-cycle infectious influenza A virus (sciIAV).; Virus research; Vol 216. 2016 May 2.
A Role for the Long Noncoding RNA SENCR in Commitment and Function of Endothelial Cells.; Molecular therapy : the journal of the American Society of Gene Therapy; Vol 24(5). 2016 May.
Structural insights into ribosome translocation.; Wiley interdisciplinary reviews. RNA. 2016 Apr 27.
Rearrangement of influenza virus spliced segments for the development of live attenuated vaccines.; Journal of virology. 2016 Apr 27.
A homozygous truncating mutation in PUS3 expands the role of tRNA modification in normal cognition.; Human genetics. 2016 Apr 7.
Programmable RNA Tracking in Live Cells with CRISPR/Cas9.; Cell; Vol 165(2). 2016 Apr 07.
Eukaryotic antisense ahead of its time.; Nature reviews. Molecular cell biology; Vol 17(4). 2016 Apr.
AccessFold: predicting RNA-RNA interactions with consideration for competing self-structure.; Bioinformatics (Oxford, England); Vol 32(7). 2016 Apr 1.
Pseudouridines in U2 snRNA stimulate the ATPase activity of Prp5 during spliceosome assembly.; The EMBO journal; Vol 35(6). 2016 Mar 15.
Structural and functional assessment of APOBEC3G macromolecular complexes.; Methods (San Diego, Calif.). 2016 Mar 14.
Coupling pre-mRNA splicing and 3' end formation to mRNA export: alternative ways to punch the nuclear export clock.; Genes & development; Vol 30(5). 2016 Mar 1.
Retrotransposons as regulators of gene expression.; Science (New York, N.Y.); Vol 351(6274). 2016 Feb 12.
Detection and quantification of RNA 2'-O-methylation and pseudouridylation.; Methods (San Diego, Calif.). 2016 Feb 4.
Replication-competent fluorescent-expressing influenza B virus.; Virus research; Vol 213. 2016 Feb 2.
Neomycin Sulfate Improves the Antimicrobial Activity of Mupirocin-Based Antibacterial Ointments.; Antimicrobial agents and chemotherapy; Vol 60(2). 2016 Feb.
Nonsense-mediated mRNA decay in humans at a glance.; Journal of cell science; Vol 129(3). 2016 Feb 1.
Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals.; Science (New York, N.Y.); Vol 351(6271). 2016 Jan 22.
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Effects of sewage effluents on water quality in tropical streams.
Increased urbanization in many tropical regions has led to an increase in centralized treatment of sewage effluents. Research regarding the effects of these wastewater treatment plants (WWTPs) on the ecology of tropical streams is sparse, so we examined the effects of WWTPs on stream water quality on the Caribbean island of Puerto Rico. Nutrient concentrations, discharge, dissolved oxygen (DO), biochemical oxygen demand (CBOD), and specific UV absorbance (SUVA) at 254 nm were measured upstream from the WWTP effluent, at the WWTP effluent, and below the WWTP effluent. All parameters measured (except DO) were significantly affected by discharge of WWTP effluent to the stream. The values of SUVA at 254 nm were typically lower (<2.5 m mg L) in WWTP effluents than those measured upstream of the WWTP, suggesting that WWTP effluents are contributing labile carbon fractions to receiving streams, thus changing the chemical composition of dissolved organic carbon in downstream reaches. Effluents from WWTP contributed on average 24% to the stream flow at our tropical streams. More than 40% of the nutrient loads in receiving streams came from WWTP effluents, with the effects on NO-N and PO-P loads being the greatest. The effect of WWTPs on nutrient loads was significantly larger than the effect of flow due to the elevated nutrient concentrations in treated effluents. Our results demonstrate that inputs from WWTPs to streams contribute substantially to changes in water quality, potentially affecting downstream ecosystems. Our findings highlight the need to establish nutrient criteria for tropical streams to minimize degradation of downstream water quality of the receiving streams.
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Basal bodies and centrioles are conserved microtubule-based organelles whose improper assembly leads to a number of diseases, including ciliopathies, such as polycystic kidney disease and Bardet-Biedl syndrome, and cancer. Tubulin family members are conserved components of these structures that are integral to their proper formation and function. The nine-fold triplet microtubule organization of basal bodies is a widely conserved structural feature. Two proteins that have been implicated in the proper assembly and maintenance of this structure are ε- and δ-tubulin. I sought to ask what the functions of these two proteins are in the assembly and maintenance of the core microtubule triplets of the basal body in Tetrahymena thermophila.
I have identified the ε-tubulin and δ-tubulin genes genes in Tetrahymena. I have localized ε-tubulin through immunofluorescence to basal bodies. Immuno-electron microscopy has shown that ε-tubulin localizes primarily to the core microtubule scaffold. Complete genomic knockouts of ε-tubulin and δ-tubulin revealed that each gene is essential for viability. ε-tubulin is required for the assembly and maintenance of the triplet microtubule blades of basal bodies. I have conducted site-directed mutagenesis of the ε-tubulin gene and shown that residues within the nucleotide-binding domain, longitudinal interacting domains, and C-terminal tail are required for proper function. A single amino acid change of Thr150, a conserved residue in the nucleotide-binding domain, to Val is a conditional mutation that results in defects in the spatial and temporal assembly of basal bodies as well as their stability. I have genetically separated functions for the domains of ε-tubulin and identified a novel role for the nucleotide-binding domain in the regulation of basal body assembly and stability.
Ross, Ian, "ε-tubulin and δ-tubulin in Tetrahymena thermophila Are Essential Components of Basal Bodies" (2012). Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations. 55.
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HomeBlogTweet ConferencesTWEET CONFERENCE SCRIPT: The health sector as a strategic partner in providing quality FGM-related services for protection, prevention and care in Nigeria – 31st January 2019
TWEET CONFERENCE SCRIPT: The health sector as a strategic partner in providing quality FGM-related services for protection, prevention and care in Nigeria – 31st January 2019
January 31, 2019By endcuttinggirlsadmin0 comment
Female Genital Mutilation (FGM) is a global health issue. More than 200 million girls and women in Africa, Asia and Middle East have undergone the practice, and more than 3 million girls are annually at risk.
The impact of FGM is also spreading further through migration to other parts of the world including Europe, the USA, Australia and Canada.
Hence policies are needed to address this issue in both countries of origin and countries of migration.
FGM practice is deeply rooted in a strong cultural/social framework. It is endorsed by the practicing community & supported by loving parents who believe that undergoing FGM is in the best interest of their daughter.
Despite its cultural importance, we need to acknowledge the fact that FGM is a harmful traditional practice that violates the rights or girls and women. Therefore, FGM has to be eliminated.
For more information about FGM you can visit http://www.who.int and www.endcuttinggirls.org or watch https://www.youtube.com/watch?v=f0-dYD9cYKo&t=80s
FGM has no known health benefits, and those girls and women who have undergone the procedure are at great risk of suffering from its complications throughout their lives.
FGM is associated with a greater risk for a series of health complications, dependent on the extent and type of tissue removed. Immediate health risks include pain, haemorrhage, infection, urinary retention and injury to the urethra,
Long-term health complications include genitourinary (urinary tract infection, bacterial vaginosis, problems with menstruation), obstetrical (caesarean section, postpartum haemorrhage, episiotomy, prolonged labour, tears or lacerations, instrumental delivery, difficult labour, external maternal hospital stay, still birth and early neonatal death, infant resuscitation at delivery) sexual (dyspareunia, no sexual desire and reduced sexual satisfaction), and psychological (post-traumatic stress disorder, anxiety disorder and depression) consequences.
Considering the health impact of FGM, the World Health Organization (WHO) has played a key role in tackling the issue from its first international conference on FGM in 1979 onwards.
In 1997, the WHO, UNICEF and UNFPA issued a Joint Statement on FGM which described the implications of the practice for public health and human rights and declared support for its abandonment; it was reaffirmed in 2008. The statement emphasized the importance of broad-based, long-term commitment as well as a multi-sectoral approach involving education, finance, justice, women's affairs and health.
In 2001, the WHO developed its first policy guidelines for the health sector, accompanied by practical and clinical guidelines that were updated in 2016. The UN emphasizes and outlines the role of healthcare providers (HCP) in primary prevention and provision of care.
In 2008 and 2012 the World Health Assembly (WHA) and the UN General Assembly respectively agreed on resolutions against FGM urging all member states to develop, support and implement national policies and action plans as well as to allocate sufficient resources for its implementation.
The resolutions also highlighted the importance of incorporating clear targets and indicators in the national plans and policies for the effective monitoring, impact assessment and coordination of programmes. The World Health Assembly (WHA) also commits its member states to follow up and regularly report on a set of points targeting prevention (in particular community based interventions), legislation, guidelines and provision of care.
Literature on FGM shows that several countries have developed national policies, guidelines and legislations, as well as making progress in the involvement of community based interventions. Less is known however about the involvement of the health sector in national plans, nor the implementation levels, allocated resources, coordination and monitoring and evaluation of such plans in the different countries.
A 2012 review of policies in 28 countries in the European Union (EU) reports insufficient and unequal distribution of support- and health services as well as inconsistent funding to ensure access to services.
No similar data is available from non-EU countries with high numbers of migrants from FGM practicing countries, nor from countries where FGM is traditionally practiced.
Nevertheless, a 2010 progress report on the World Health Assembly (WHA) resolution from African member states highlights the involvement of the health sector as an area in need for improvement. As we try to end the practice of FGM, there has been a lot of concern over the trend of replacing traditional circumcisers with medical professionals, otherwise known as the medicalization of FGM.
The World Health Organization defines "medicalisation of FGM" as a "situation in which FGM is practiced by any category of healthcare provider, whether in a public or private clinic, at home, or elsewhere".
Debate has raged about whether FGM could be carried out 'safely' under certain circumstances or whether all forms of the practice should be condemned. However, WHO has recommended that health workers should not engage in medicalization
Many countries have banned the use of government clinics and hospitals to perform FGM. On December 20, 2012 the United Nations General Assembly adopted a resolution that reflected universal agreement that FGM constitutes a violation of human rights and that all countries should take action to end the practice, committed within or outside a medical institution.
A recent survey looked at whether medicalisation had increased between generations and found that in countries with substantial levels of medicalisation (over ten percent) rates are higher among daughters than mothers; the only exception is Nigeria, where rates of medicalisation among mothers and daughters are roughly equal.
Research suggests that there are several ways to win health care professionals' support as allies in FGM abandonment efforts. First, training programs for these professionals, particularly those living in areas where FGM is widely practiced, should focus on what FGM is, why it is practiced, its health impacts, and ways to prevent it, such trainings must also sensitize health care practitioners to the fact that FGM is a violation of girls' and women's rights to health and conflicts with the "do no harm" principle of medical practice.
Second, these health professionals, as a focus of FGM abandonment programs, should be given the opportunity to reflect on their own beliefs and think critically about how these views may fuel the continuation of the practice
Third, health professionals' associations and health regulatory agencies should have clear guidelines and standards for providers that outline the sanctions on those who perform FGM.
These organizations should also offer opportunities for health care professionals to contribute to community efforts to promote the abandonment of the practice.
Health Care Practitioners (HCP) can play a key role in the prevention of FGM by providing health education to patients and/or parents during consultations as their educational background and social status give extra credit to their messages also, the regular interactions with families provide them with unique opportunities to share such infor mation. Findings show that providing health education on FGM/C to patients and/or parents during consultations is part of HCP.
It is striking to see that the preventive role of HCP is highly underused in countries of origin. Several studies have identified numerous challenges to the involvement of HCP, particularly in countries of origin, some HCP support FGM or consider it as a sensitive issue and consequently resist working against the practice. This resistance is further aggravated by a high workload and the lack of skills to adequately address FGM.
The WHO, however, condemns the medicalization as it is considered a perpetuation and legitimization of a harmful practice that counteracts efforts towards its abandonment
Another area for improvement is the systematic use of FGM codes in medical records. Records serve many central purposes such as providing an overview of the management of a particular disease monitoring and improving quality of care, and providing robust databases for research. Data on FGM/C in most medical records has so far been negligible for several reasons including lack of codes on FGM
Finally, routines and guidelines should be put in place to ensure the availability of FGM/C codes, particularly in countries of origin, and their systematic use in medical records in all countries.
At this point, I will end the presentation to give room for questions and contributions from participants. Thank you all for reading our tweets
[BCM1]I don't understand
[BCM2]Include source of information
[BCM3]World Health Assembly (WHA)
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Аннотация: In this paper we study the some questions about stability of the surfaces, which are the extremals of the area type functional. Stability, means, is called positively or negatively determined of second variation of functional for all any sufficiently small deformations of surface. In the work we obtain of the formulas first and second variation of functional, the capacity feature of instability, the conditions of stability and instability in the terms of the structure of surface image under Gaussian map. We consider some examples by application our results for research of stability of rotation surfaces.
Поступила 6 марта 2006 г., опубликована 9 апреля 2007 г.
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Idiopathic Pain essentially means "The Doctors are Idiots in determining the cause of your pain". This can be extremely discouraging as a patients.
Sometimes problems are diagnosed as idiopathic because the doctor is not familiar with the disorder you have.
These types of pain are often treated with a multitude of different medications on a trial and error basis.
There are some very safe and effective treatments for Idiopathic Pain anywhere in the body. An excellent review of symptoms relievable by SPG Blocks can be found at: https://www.sphenopalatineganglionblocks.com/relief-wide-variety-eye-pains-spg-blocks.
TMJ disorders have been called "The Great Imposter" because they can masquerade as many different types of problems and are usually misdiagnosed multiple times before being identified.. Most physicians other than ENT's know very little about TMJ Disorders (TMD) .
Orofacial pain is often related to the autonomic nervous system. The lack of homeostasis or balance between the sympathetic division and the autonomic division division of the autonomic system often leads to problems with anxiety, stress overload, panic attacks and other Axis 2 events involving the limbic system.
The Limbic system is where we feel both good and bad emotions as well as pain. Pain is an emotional response secondary to nociceptive input to the brain.
SPG Blocks or Sphenopalatine Ganglion Blocks are often rapidly effective in decreasing Orofacial Pain conditions. Utilization of a diagnostic neuromuscular orthotic often gives almost immediate relief. though some groups object to occlusal changes even when they dramatically improve patients quality of life.
Combination of these two treatments can give rapid dramatic improvement. Self-Administration of SPG Blocks is especially important in orofacial pain patients due to strong emotional effects of this type of pain.
Shimshak showed in his lanfmark study that orofacial pain patients who carry TMJ diagnosis have a three fold increase in utilization of medical services in all fields of medicine. Side effects and costs of orofacial pain are enormous as is their effect on Quality of Life.
cost orofacial painOrofacial Painorofacial pain illinoisorofacial pain Indianaorofacial pain managementorofacial pain quality of life.orofacial pain tmjorofacial pain wisconsinorofcial pain QOLside effects orofacial painspecialist orofacial painthm orofacial pain.
Orofacial Pain and TMJ Disorders: Specialty?
There is currently no specialty in Orofacial Pain and the American Dental Association does not believe one is needed. That does not mean that orofacial pain is not a problem, it is.
The second most common cause of orofacial pain is TMJ disorders which include Myofascial Pain, TM Joint internal derangements, capsulitis and tendonitis. These are commonly related to the bite, stress and parafunction, particularly night-time bruxism.
The majority of these problems are handled by a simple night-time bruxism appliance.
The more complicated TMJ disorders usually include multiple facets and affect not just the the oral structures but all of the muscles and nerve connections of the head and neck as well as the postural chain. They are not limited to the nerves of the somatosensory nervous system but are also firmly rooted to the sympathetic and parasympathetic divisions.
Typically dentists with advanced training in the treatment of TMJ disorders are very good at the differential diagnosis of orofaxial pain, particularly neuromuscular dentists.
Most of the chronic pain related to TMJ disorders is Myofascial Pain as described by Janet Travell in her landmark book; "MYOFASCIAL PAIN AND DYSFUNCTION: A TRIGGER POINT MANUAL" This ptype of pain is relatively easy to treat once it is understood that the problem is basically a repetitive strain injury.
Treatment of this Myofascial Pain and associated TM Joint pain usually involves utilization of a diagnost neuromuscular orthotic as part of the diagnostic process.
There are many other more infrequent and obscure conditions that fall under the umbrella of orofacial pain. Most of these are best treated by neurologists, ENT's and Opthamologists. The push for an orofacial pain specialty is from a small group of doctors who think they are better equipped than the current medical specialties in doing differential diagnosis and treatment.
Differential diagnosis is the key to successful treatment. Dentists treating TMJ disorders need to understand this concept.
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News | ECG | September 01, 2021
Noncontact ECG Monitoring a Step Closer for Neonatal Wards
Baby face detector software embedded in digital camera rivals ECG
A team at the University of South Australia designed a computer vision system that can automatically detect a baby's face in a hospital bed and remotely monitor its vital signs from a digital camera with the same accuracy as a traditional ECG machine.
September 1, 2021 — University of South Australia researchers have designed a computer vision system that can automatically detect a tiny baby's face in a hospital bed and remotely monitor its vital signs from a digital camera with the same accuracy as an electrocardiogram machine.
Using artificial intelligence-based software to detect human faces is now common with adults, but this is the first time that researchers have developed software to reliably detect a premature baby's face and skin when covered in tubes, clothing, and undergoing phototherapy.
Engineering researchers and a neonatal critical care specialist from UniSA remotely monitored heart and respiratory rates of seven infants in the Neonatal Intensive Care Unit (NICU) at Flinders Medical Centre in Adelaide, using a digital camera.
"Babies in neonatal intensive care can be extra difficult for computers to recognize because their faces and bodies are obscured by tubes and other medical equipment," said UniSA Professor Javaan Chahl, one of the lead researchers.
"Many premature babies are being treated with phototherapy for jaundice, so they are under bright blue lights, which also makes it challenging for computer vision systems."
The "baby detector" was developed using a dataset of videos of babies in NICU to reliably detect their skin tone and faces.
Vital sign readings matched those of an electrocardiogram (ECG) and in some cases appeared to outperform the conventional electrodes, endorsing the value of non-contact monitoring of pre-term babies in intensive care.
The study is part of an ongoing UniSA project to replace contact-based electrical sensors with non-contact video cameras, avoiding skin tearing and potential infections that adhesive pads can cause to babies' fragile skin.
Infants were filmed with high-resolution cameras at close range and vital physiological data extracted using advanced signal processing techniques that can detect subtle color changes from heartbeats and body movements not visible to the human eye.
UniSA neonatal critical care specialist Kim Gibson says using neural networks to detect the faces of babies is a significant breakthrough for non-contact monitoring.
"In the NICU setting it is very challenging to record clear videos of premature babies. There are many obstructions, and the lighting can also vary, so getting accurate results can be difficult. However, the detection model has performed beyond our expectations.
"Worldwide, more than 10 per cent of babies are born prematurely and due to their vulnerability, their vital signs need to be monitored continuously. Traditionally, this has been done with adhesive electrodes placed on the skin that can be problematic, and we believe non-contact monitoring is the way forward," Gibson says.
Professor Chahl said the results are particularly relevant given the COVID-19 pandemic and need for physical distancing.
In 2020, the UniSA team developed world-first technology, now used in commercial products sold by North American company Draganfly, that measures adults' vital signs to screen for symptoms of COVID-19.
The results have been published in the Journal of Imaging.
1. Fatema-Tuz-Zohra Khanam, Asanka G. Perera, Ali Al-Naji, et al. Non-Contact Automatic Vital Signs Monitoring of Infants in a Neonatal Intensive Care Unit Based on Neural Networks. J. Imaging 2021, 7(8), 122; https://doi.org/10.3390/jimaging7080122/. Published 23 July 2021.
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The urinary tract is the body's drainage system for removing wastes and extra water. The urinary tract includes two kidneys, two ureters, a bladder, and a urethra. The kidneys are two bean-shaped organs, each about the size of a fist. They are located near the middle of the back, just below the rib cage, one on each side of the spine. Every day, the two kidneys process about 200 quarts of blood to produce about 1 to 2 quarts of urine, composed of wastes and extra water. The urine flows from the kidneys to the bladder through tubes called ureters. The bladder stores urine until releasing it through urination. When the bladder empties, urine flows out of the body through a tube called the urethra at the bottom of the bladder.
Urinalysis – Further testing of the urine may be done to check for problems that can cause hematuria, such as infection, kidney disease, and cancer. The presence of white blood cells signals a UTI. RBCs that are misshapen or clumped together to form little tubes, called casts, may indicate kidney disease. Large amounts of protein in the urine, called proteinuria, may also indicate kidney disease. The urine can also be tested for the presence of cancer cells.
Blood test – A blood test involves drawing blood at a health care provider's office or commercial facility and sending the sample to a lab for analysis. A blood test can show the presence of high levels of creatinine, a waste product of normal muscle breakdown, which may indicate kidney disease.
repeated 6 weeks after antibiotic treatment ends to be sure the infection has resolved.
Eating, diet, and nutrition have not been shown to play a role in causing or preventing hematuria.
Hematuria is blood in the urine.
Most people with microscopic hematuria do not have symptoms. People with gross hematuria have urine that is pink, red, or cola-colored due to the presence of red blood cells (RBCs).
When blood is visible in the urine or a dipstick test of the urine indicates the presence of RBCs, the urine is examined with a microscope to make an initial diagnosis of hematuria. The next step is to diagnose the cause of the hematuria.
If a thorough medical history suggests a cause that does not require treatment, the urine should be tested again after 48 hours for the presence of RBCs. If two of three urine samples show too many RBCs when viewed with a microscope, more serious causes should be explored.
One or more of the following tests may be ordered: urinalysis, blood test, biopsy, cytoscopy, and kidney imaging tests.
Hematuria is treated by treating its underlying cause.
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The many Mental Neurological Disorders and Diseases have an interesting relationship with glutathione. When the disease or disorder is present, glutathione (GSH) and other elements are below normal levels. Some of these others are either synergistic with glutathione or they are cofactors of glutathione.
Note To further complicate mental neurological disorder challenges, our psychological function plays a role in our health and wellness or absence of health. A field of science called Psychoneurobiology studies this.
The exciting news is that many mental neurological disorders can be enhanced with diet and especially nutricuticals. Some neurological diseases, disorders or conditions can benefit from increased glutathione and or other essential vitamins, minerals, and phytochemicals.
The Definition of Mental Health A different view worth exploring.
Sleeplessness affects up to 90 percent of people eventually. It is a leading mental neurological disorder facing man. Tart cherries in our diet can help improve our sleep. They have an important chemical that helps our brain take a break better than supplements or drugs.
Studies show a direct correlation with schizophrenia and decreased glutathione levels. The good news is that glutathione may slow down the progression and even lessen the side effects of the drugs given to treat this disease.
More importantly, do you know what those suffering with it go through? Do you know the side effects they have to endure as a result of the meds used to combat the disease.
Statistically one in 100 will be afflicted with this debilitating disease.Onset can happen as early as age 40. It affects most around retirement age. Studies show that elevating glutathione early can stop the progression and even reverse some of the symptoms.
Of the various types of dementia afflicting the elderly, Alzheimer's is the most common. It is the fourth leading cause of death after heart disease, cancer and stroke.
Glutathione can help prevent and or lessen the effects of Alzheimer's disease in a few ways. GSH works as a detoxifier.
A blood protein that interacts with heavy metals has long been suspect as being related to Alzheimer's disease. Studies that demonstrating benefits from Ginko would seem to indicate the elimination of plaque buildup would relieve the symptoms.
Antioxidant therapy has been shown to be beneficial. The effect of androgynous (external source) antioxidants are enhanced by improved glutathione levels.
Alzheimers Scams Be warned, if it is too good to be true, it probably is. Even the good results found in the studies on boosting GSH levels does not mean there is a cure. Once the damage is done, it is done. The best care involves improving the symptoms and increase the potential quality of life.
How to Prevent Alzheimers looks at some of the studies. You will have to connect the dots. There are some interesting dots to connect.
More How to Prevent Alzheimers looks at some dietary changes you can make to avoid this life and memory altering disease.
Amyotrophic Lateral Sclerosis-Symptoms (ALS) This looks primarily at low CG syndrome and emerging science on treating ALS by elevating glutathione.
A degenerative disease of the nervous system, it hits most in the prime of their life. The neurological dysfunctions can be as mild as loss of concentration, weakness, vision blurring or stiffness. It can come in episodes and then go into remission.
As the disease progresses disability follows.
Studies show a relationship with the levels of glutathione and the progression of the disease. The worse the progression the less glutathione present.
Low selenium levels are associated with MS. Selenium is an essential co-factor in the formation of glutathione. By supplementing the antioxidants selenium, vitamin C and vitamin E the study found a five fold increase in glutathione.
ADHD What if there were a better way to treat it. First look at the background of ADHD. What if it was not psycho-neuro but rather simply biological resulting in something neurological?
Chronic Fatigue is included here because the lack of energy and need for rest are neurological in nature.
MCS is included here because it results in neurological shutdown by those affected. I have personally seen those affected with this pass out when someone laden with perfume passed by. There is hope for those affected by MCS simply by increasing glutathione levels.
It strikes one in 10,000. Average onset is age 30 to 50. Death occurs 10 to 20 years later. There are no effective medical treatments. The good news, studies point to a glutathione connection.
Please return as we take an in-depth look at each of these mental neurological disorders. More importantly, how it is possible to build glutathione levels with nutrition.
The Science of Psychoneurobiology has identified the interconnection between thoughts, emotions, biological functioning. It has been found that we can manage these with a combination of psychiatric help, nutrition, activity and medication.
The field of Psychoneurobiology deals with how our emotions affect our well being. How stress or anxiety can make us ill or how our emotions can affect the immune system, the endocrine system and the neurological system.
A study in 1989 demonstrated that women with breast cancer attending a weekly support group had a better survival rate than those who were not part of a group. The women in the supported group survived 36 months and the ones without only 18 months. The ones in the supported group were provided stress management training.
In another example, studies have demonstrated that depression can affect us in three systems - the immune, the endocrine and the neurological systems. Remember, stress is how you interpret a situation, not the situation itself. The doorbell ringing doesn't make you ill, your anticipation of who might be on the other side of the door is what causes the feeling.
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Is There A Stage 5 Cancer?
Is it painful to die from prostate cancer?
Can you beat Stage 4 cancer?
How does prostate cancer kill you in the end?
Can you live 10 years with metastatic prostate cancer?
What is the most aggressive form of prostate cancer?
How long does it take to die from stage 4 prostate cancer?
Is prostate cancer usually fatal?
How many stages of cancer are there?
Is Stage 4 cancer a terminal?
What is the last stage of cancer?
Can Stage 4 cancer be cured with chemotherapy?
Does anyone survive stage 4 prostate cancer?
Is there a stage 5 prostate cancer?
Can you live 20 years with prostate cancer?
What is the most aggressive cancer?
What are the hardest cancers to cure?
Many people worry about being in pain when they are dying.
Some people do get pain if their prostate cancer presses on their nerves or makes their bones weak.
But not everyone dying from prostate cancer has pain.
And if you are in pain, there are things that can help to reduce and manage pain..
What Is the Life Expectancy of Stage 4 Cancer? Stage 4 cancer life expectancy depends in part on the type of cancer. For instance, the American Cancer Society cites stage 4 breast cancer survival rate at 22 percent over five years, and about 14 percent for stage 4 colon cancer.
The cancer can spread down the blood vessels, lymphatic channels, or nerves that enter and exit the prostate, or cancer could erode directly through the capsule that surrounds the prostate.
10-year relative survival rate of 98 percent: Ten years after diagnosis, the average prostate cancer patient is just 2 percent less likely to survive than a man without prostate cancer.
Ductal prostate cancer is usually more aggressive than common prostate cancer. Possible treatment options include surgery, hormone therapy, radiotherapy and chemotherapy, depending on whether your cancer has grown and spread to other parts of your body.
Stage 4 with regional metastases: Prostate cancer that is called stage 4 due to a large tumor size (T4) or due to spread to nearby lymph nodes has a five-year survival rate of nearly 100%.
Amidst so much optimism and progress in the last 10 years, it's important to keep in mind that prostate cancer is still a deadly disease for some men, and it is the second leading cause of cancer death among men in the US, with 91 men dying from it every day.
Most types of cancer have four stages: stages I (1) to IV (4). Some cancers also have a stage 0 (zero). Stage 0. This stage describes cancer in situ, which means "in place." Stage 0 cancers are still located in the place they started and have not spread to nearby tissues.
Stage 4 cancer cells have metastasized, spreading to distant areas in the body. Stage 4 is the final mesothelioma stage and considered terminal. The average life expectancy for stage 4 mesothelioma is less than 12 months.
Exhaustion, Weakness, and Desire to Sleep: The cancer patient may become much weaker and more easily exhausted during these last weeks. They may want to sleep often because of this, as well as spend most of their day in bed. Loss of Appetite: They may lose much of their appetite or have difficulty eating and drinking.
Although systemic drugs are the main treatment for stage IV breast cancer, local and regional treatments such as surgery, radiation therapy, or regional chemotherapy are sometimes used as well. These can help treat breast cancer in a specific part of the body, but they are very unlikely to get rid of all of the cancer.
Treatments may slow or shrink an advanced prostate cancer, but for most men, stage 4 prostate cancer isn't curable. Still, treatments can extend your life and reduce the signs and symptoms of cancer.
Grade 1: The tissue looks very much like normal prostate cells. Grades 2-4: Cells that score lower look closest to normal and represent a less aggressive cancer. Those that score higher look the furthest from normal and will probably grow faster. Grade 5: Most cells look very different from normal.
After 20 years, only 3 of 217 patients survived. Men with moderate-grade disease have intermediate cumulative risk of prostate cancer progression after 20 years of follow-up. These results are in line with earlier findings on the outcomes of prostate cancer patients depending on Gleason scores.
Because pancreatic cancer progresses rapidly, and no method of early detection has been discovered, it is one of the most dangerous types of cancer. The one-year survival rate is 25 percent, and the five-year survival rate sits at only 6 percent.
Top 5 Deadliest CancersLung Cancer. U.S. deaths in 2014: 159,260.Colorectal Cancer. U.S. deaths in 2014: 50,310. How common is it? … Breast Cancer. U.S. deaths in 2014: 40,430. How common is it? … Pancreatic Cancer. U.S. deaths in 2014: 39,590. How common is it? … Prostate Cancer. U.S. deaths in 2014: 29,480. How common is it? …
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Cognitive impairment is common in multiple sclerosis (MS) irrespective of disease stage or subtype. It is typically underreported and neuropsychological testing can be required to detect more subtle evidence of cognitive impairment. The Brief International Cognitive Assessment in Multiple Sclerosis (BICAMS) was an initiative undertaken by a panel of experts with the primary objective of identifying a brief cognitive assessment tool that could be administered by healthcare professionals without formal neuropsychological training to identify early or subtle cognitive impairment among MS patients.
To validate BICAMS in Irish patients with MS and healthy controls.
Consecutive patients attending the MS outpatient department from January to April 2014 were recruited. Age, gender, education, handedness, MS subtype, expanded disability status scale (EDSS) and disease duration were recorded. They were administered BICAMS composed of Symbol Digit Modalities Test (SDMT), California Verbal Learning Test (CVLT-II) and Brief Visuospatial Memory Test (BVMT-R). Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS). Control participants were composed of unaffected relatives, spouses or carers attending the clinic with a patient and were matched by age, gender and years of education.
Impairment on individual tests was defined as −1.5 SD below reference group means.
67 patients [73% women; mean age: 43.9 yrs (12.1); mean years of education: 13.6 yrs (2.7)] and 66 controls [68% women; mean age 42.7 yrs (12.7); mean years of education: 14.1 yrs (3.2)] were recruited. Of the MS patient group: 70% were classified as having relapsing remitting MS, 28% secondary progressive MS and 2% primary progressive MS (PPMS). Mean EDSS scores were 1.8 (SD: 0.9), 5.7 (SD: 1.4) and 7.0 in each group respectively with mean disease duration of 10.2 (SD: 8.4) years, 20.6 (10.2) and 17 years. Mean scores and standard deviations for patients and control participants respectively were 46 (12.9) and 55.9 (10.9), p<0.001; d=0.83 for SDMT; 45.3 (10.2) and 52.8 (8.8), p<0.001; d=0.79 for CVLT-II and 17.9 (7.1) and 20.7 (6.6), p=0.02; d=0.41 for BVMT-R. Using regression based norms derived from the control sample only 43% of patients compared to 83% of control participants' results were within the normal range on all three tests.
As expected higher rates of unemployment was seen amongst the patient population compared to control participants. Using the HADS 11 patients were classified as depressed and 13 as suffering from anxiety. Neither, these measures or the level of fatigue as measured by the MFIS was significantly associated with any of the three outcome measures (Pearson r <+/−0.3).
This study demonstrates that BICAMS is an easy test to administer and should be used as a basic tool to identify patients with cognitive impairment who may benefit from further neuropsychological assessment. Cognitive impairment can put patients at risk of poor self-management of disease including poor mediation adherence, and negatively impact on employment. Once identified appropriate support and monitoring can be put in place. BICAMS may also be used to help guide treatment decisions and rehabilitation. Further studies will be needed to assess its reliability over time and ability to detect meaningful changes.
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Effect of Chaperonin Encoded by Gene 146 on Thermal Aggregation of Lytic Proteins of Bacteriophage EL Pseudomonas aeruginosa P. I. Semenyuk, V. N. Orlov, and L. P. Kurochkina
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Dicerna™ Enters Agreement with Roche to Develop and Commercialize DCR-HBVS for the Treatment of Chronic Hepatitis B Virus (HBV) Infection
– Roche to gain worldwide license to Dicerna's novel RNAi therapy currently in Phase 1 –
– Dicerna to receive $200 million up front plus up to $1.47 billion in potential milestone payments related to DCR-HBVS –
– Dicerna to retain option to co-fund pivotal development of DCR-HBVS worldwide and co-promote in U.S. with enhanced royalties –
– Collaboration includes discovery and development of additional therapies targeting multiple additional gene targets implicated in chronic HBV infection –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dicerna™ Pharmaceuticals, Inc. (Nasdaq: DRNA) today announced a research collaboration and licensing agreement with Roche (SIX: RO, ROG; OTCQX: RHHBY) to develop novel therapies for the treatment of chronic hepatitis B virus (HBV) infection using Dicerna's proprietary GalXC™ RNAi platform technology. The collaboration will focus on worldwide development and commercialization of DCR-HBVS, Dicerna's investigational therapy in Phase 1 clinical development. The collaboration also includes the discovery and development of therapies targeting multiple additional human and viral genes associated with HBV infection using the technology platforms of both companies.
"Dicerna is excited to collaborate with Roche to realize the full potential of DCR-HBVS and leverage our GalXC platform to target and silence specific genes that contribute to chronic hepatitis B virus infection," said Douglas M. Fambrough, Ph.D., president and chief executive officer of Dicerna. "With its deep expertise in HBV and established global infrastructure, Roche is ideally suited to help us accelerate the development and commercialization of DCR-HBVS, pursue a cure for chronic HBV infection, and address this serious global threat to public health."
"We are excited to engage in a clinical partnership and research collaboration with Dicerna," said John Young, global head of Infectious Diseases at Roche Pharma Early Research & Development. "This partnership builds upon our existing portfolio and internal expertise and positions us well to develop a best-in-disease therapy to cure chronic HBV infection."
Under the terms of the agreement, Dicerna will receive $200 million in an initial upfront payment and may be eligible to receive up to an additional $1.47 billion over time for the achievement of specified development, regulatory and commercial milestones. In addition, Dicerna may be eligible to receive royalties based on potential product sales of DCR-HBVS. Dicerna retains an option to co-fund pivotal development of DCR-HBVS worldwide, which if exercised, entitles Dicerna to receive enhanced royalties and co-promote products including DCR-HBVS in the U.S.
Dicerna and Roche also agreed to collaborate on the research and development of additional therapies targeting multiple human and viral genes implicated in chronic HBV infection, using technology from both companies, for which Dicerna is eligible to receive additional milestones and royalties on any potential products.
The transaction is subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 and other customary conditions.
About Chronic Hepatitis B Virus (HBV) Infection
Hepatitis B virus (HBV) is the world's most common serious liver infection, with more than 292 million patients chronically infected, according to the World Health Organization. Chronic HBV infection, a condition characterized by the presence of the HBV surface antigen (HBsAg) for six months or more, claims more than 800,000 lives annually. HBV is also the primary cause of liver cancer (also known as hepatocellular carcinoma or HCC), which is the second-leading cause of cancer deaths in the world.1
About DCR-HBVS and the DCR-HBVS-101 Clinical Trial
DCR-HBVS is an investigational drug in development for the treatment of chronic hepatitis B virus (HBV) infection. Current therapies for HBV, such as nucleoside analogs, can provide long-term viral suppression if taken continuously, but they rarely lead to long-term functional cures, as measured by the clearance of HBV surface antigen (HBsAg) and sustained HBV deoxyribonucleic acid (DNA) suppression in patient plasma or blood. By contrast, DCR-HBVS employs RNA interference to selectively knock down specific genes involved in the creation of HBV messenger RNA (mRNA) and the entry of the virus into liver cells. This approach leads to greater than 99.9% reduction in circulating HBsAg, as observed in mouse models of HBV infection. These data suggest that DCR-HBVS may induce clearance of HBsAg and contribute meaningfully to a functional cure for HBV.
Dicerna is conducting a Phase 1, randomized, placebo-controlled study designed to evaluate the safety and tolerability of DCR-HBVS in healthy volunteers (HVs) and in patients with non-cirrhotic chronic HBV infection.
About Dicerna's GalXC™ RNAi Technology Platform
Dicerna's proprietary RNA interference (RNAi) technology platform, called GalXC™, aims to advance the development of next-generation RNAi-based therapies designed to silence disease-driving genes in the liver and other body systems. Liver-targeted GalXC-based compounds enable subcutaneous delivery of RNAi therapies that are designed to specifically bind to receptors on liver cells, leading to internalization and access to the RNAi machinery within the cells. The GalXC approach seeks to optimize the activity of the RNAi pathway so that it operates in the most specific and potent fashion. Compounds produced via GalXC are intended to be broadly applicable across multiple therapeutic areas, including both liver and non-liver indications.
About DicernaTM Pharmaceuticals, Inc.
Dicerna™ Pharmaceuticals, Inc., is a biopharmaceutical company using ribonucleic acid (RNA) interference (RNAi) to develop medicines that silence genes that cause disease. The Company's proprietary GalXC™ technology is being applied to develop potent, selective, and safe RNAi therapies for treatment of rare diseases, chronic liver diseases, cardiovascular diseases, neurodegenerative diseases, pain, and viral infectious disease. Dicerna aims to treat disease by addressing the underlying causes of illness with capabilities that extend beyond the liver to address a broad range of diseases, focusing on target genes where connections between gene and disease are well understood and documented. Dicerna intends to discover, develop, and commercialize novel therapies either on its own or in collaboration with pharmaceutical partners. Dicerna has strategic collaborations with Roche, Eli Lilly and Company (Lilly), Alexion Pharmaceuticals, Inc. (Alexion), and Boehringer Ingelheim International GmbH (BI). For more information, please visit www.dicerna.com.
Dicerna Forward-Looking Statement
This press release includes forward-looking statements. Such forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statements. Examples of forward-looking statements include, among others, statements we make regarding: (i) the full potential of DCR-HBVS and to leverage our GalXC platform to target and silence specific genes that contribute to HBV cures; (ii) the potential to earn revenue from royalties and milestone payments under the collaboration with Roche; (ii) research and development plans related to GalXC and its utility in silencing genes that contribute to HBV; (iii) the potential of RNAi therapies for the treatment of chronic HBV infection; and (iv) the potential for the collaboration between Roche and Dicerna. The process by which an early-stage platform such as GalXC could potentially lead to an approved product is long and subject to highly significant risks, particularly with respect to a preclinical research collaboration. Applicable risks and uncertainties include those relating to preclinical research and other risks identified under the heading "Risk Factors" included in Dicerna's most recent Form 10-Q filings and in other future filings with the Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Dicerna's current views with respect to future events, and Dicerna does not undertake and specifically disclaims any obligation to update any forward-looking statements, except as required by law.
Dicerna™ and GalXC™ are trademarks of Dicerna Pharmaceuticals, Inc.
Hepatitis B Foundation. Facts and Figures. 2019. Available at: http://www.hepb.org/what-is-hepatitis-b/what-is-hepb/facts-and-figures/. Accessed on October 30, 2019.
Stern Investor Relations, Inc.
Lauren Stival, 212-698-8646
[email protected]
SmithSolve
Alex Van Rees, 973-442-1555 ext. 111
[email protected]
Dicerna announced a research collaboration and licensing agreement with Roche to develop novel therapies for the treatment of chronic HBV infection.
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Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase
J. M. Slauch, F. D. Russo, T. J. Silhavy
We have isolated mutations in rpoA, the gene encoding the α subunit of RNA polymerase, that specifically affect transcriptional control by OmpR and EnvZ, the two-component regulatory system that controls porin gene expression in Escherichia coli. Characterization of these mutations and a previously isolated rpoA allele suggests that both positive and negative regulation of porin gene transcription involves a direct interaction between OmpR and RNA polymerase through the α subunit. Several of the rpoA mutations cluster in the carboxy-terminal portion of the α protein, further suggesting that it is this domain of α that is involved in interaction with OmpR and perhaps other transcriptional regulators as well.
Dive into the research topics of 'Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase'. Together they form a unique fingerprint.
Genetic Suppression Medicine & Life Sciences 100%
DNA-Directed RNA Polymerases Medicine & Life Sciences 79%
Porins Medicine & Life Sciences 61%
Alleles Medicine & Life Sciences 17%
Escherichia coli Medicine & Life Sciences 16%
Gene Expression Medicine & Life Sciences 14%
Slauch, J. M., Russo, F. D., & Silhavy, T. J. (1991). Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase. Journal of bacteriology, 173(23), 7501-7510. https://doi.org/10.1128/jb.173.23.7501-7510.1991
Slauch, J. M. ; Russo, F. D. ; Silhavy, T. J. / Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase. In: Journal of bacteriology. 1991 ; Vol. 173, No. 23. pp. 7501-7510.
@article{2176fc7cc1264cf5882cdc4e431d24ef,
title = "Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase",
abstract = "We have isolated mutations in rpoA, the gene encoding the α subunit of RNA polymerase, that specifically affect transcriptional control by OmpR and EnvZ, the two-component regulatory system that controls porin gene expression in Escherichia coli. Characterization of these mutations and a previously isolated rpoA allele suggests that both positive and negative regulation of porin gene transcription involves a direct interaction between OmpR and RNA polymerase through the α subunit. Several of the rpoA mutations cluster in the carboxy-terminal portion of the α protein, further suggesting that it is this domain of α that is involved in interaction with OmpR and perhaps other transcriptional regulators as well.",
author = "Slauch, {J. M.} and Russo, {F. D.} and Silhavy, {T. J.}",
Slauch, JM, Russo, FD & Silhavy, TJ 1991, 'Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase', Journal of bacteriology, vol. 173, no. 23, pp. 7501-7510. https://doi.org/10.1128/jb.173.23.7501-7510.1991
Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase. / Slauch, J. M.; Russo, F. D.; Silhavy, T. J.
In: Journal of bacteriology, Vol. 173, No. 23, 1991, p. 7501-7510.
T1 - Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase
AU - Slauch, J. M.
AU - Russo, F. D.
AU - Silhavy, T. J.
N2 - We have isolated mutations in rpoA, the gene encoding the α subunit of RNA polymerase, that specifically affect transcriptional control by OmpR and EnvZ, the two-component regulatory system that controls porin gene expression in Escherichia coli. Characterization of these mutations and a previously isolated rpoA allele suggests that both positive and negative regulation of porin gene transcription involves a direct interaction between OmpR and RNA polymerase through the α subunit. Several of the rpoA mutations cluster in the carboxy-terminal portion of the α protein, further suggesting that it is this domain of α that is involved in interaction with OmpR and perhaps other transcriptional regulators as well.
AB - We have isolated mutations in rpoA, the gene encoding the α subunit of RNA polymerase, that specifically affect transcriptional control by OmpR and EnvZ, the two-component regulatory system that controls porin gene expression in Escherichia coli. Characterization of these mutations and a previously isolated rpoA allele suggests that both positive and negative regulation of porin gene transcription involves a direct interaction between OmpR and RNA polymerase through the α subunit. Several of the rpoA mutations cluster in the carboxy-terminal portion of the α protein, further suggesting that it is this domain of α that is involved in interaction with OmpR and perhaps other transcriptional regulators as well.
Slauch JM, Russo FD, Silhavy TJ. Suppressor mutations in rpoA suggest that OmpR controls transcription by direct interaction with the α subunit of RNA polymerase. Journal of bacteriology. 1991;173(23):7501-7510. https://doi.org/10.1128/jb.173.23.7501-7510.1991
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Identification of neutral and acidic sphingomyelinases in Helicobacter pylori
Yuh Ling Lin, Jai Shin Liu, Kuei Tian Chen, Chien Tsu Chen, Err Cheng Chan
生物化學暨細胞分子生物學科
We demonstrated for the first time the presence of sphingomyelinase (SMase) in Helicobacter pylori. Activation of SMase has been implicated as the cause of elevation of cellular ceramide levels and consequently of apoptosis. The data indicate that there are two classes of SMase, defined by their optimal pHs and cellular locations, existing in H. pylori. One is an Mg2+-dependent membrane-bound enzyme with an optimal activity at pH 7, and the other is an Mg2+-independent cytosolic enzyme with an optimal activity at pH 5. Bisalumin, a bismuth salt, was found to inhibit the activities of both forms of SMase regardless of the presence of Mg2+. By Western blot analysis, the membrane-bound SMases of H. pylori and Bacillus cereus were shown to be antigenically related and to have a similar denatured molecular mass of 28 kDa.
已發佈 - 二月 20 1998
生物物理學
結構生物學
分子生物學
遺傳學
細胞生物學
深入研究「Identification of neutral and acidic sphingomyelinases in Helicobacter pylori」主題。共同形成了獨特的指紋。
Sphingomyelin Phosphodiesterase Medicine & Life Sciences 100%
Helicobacter pylori Medicine & Life Sciences 71%
pH Value Chemical Compounds 31%
Ceramide Chemical Compounds 29%
Bismuth Medicine & Life Sciences 25%
Bacillus cereus Medicine & Life Sciences 24%
Molecular Mass Chemical Compounds 21%
Lin, Y. L., Liu, J. S., Chen, K. T., Chen, C. T., & Chan, E. C. (1998). Identification of neutral and acidic sphingomyelinases in Helicobacter pylori. FEBS Letters, 423(2), 249-253. https://doi.org/10.1016/S0014-5793(98)00087-8
Identification of neutral and acidic sphingomyelinases in Helicobacter pylori. / Lin, Yuh Ling; Liu, Jai Shin; Chen, Kuei Tian; Chen, Chien Tsu; Chan, Err Cheng.
於: FEBS Letters, 卷 423, 編號 2, 20.02.1998, p. 249-253.
Lin, YL, Liu, JS, Chen, KT, Chen, CT & Chan, EC 1998, 'Identification of neutral and acidic sphingomyelinases in Helicobacter pylori', FEBS Letters, 卷 423, 編號 2, 頁 249-253. https://doi.org/10.1016/S0014-5793(98)00087-8
Lin YL, Liu JS, Chen KT, Chen CT, Chan EC. Identification of neutral and acidic sphingomyelinases in Helicobacter pylori. FEBS Letters. 1998 2月 20;423(2):249-253. https://doi.org/10.1016/S0014-5793(98)00087-8
Lin, Yuh Ling ; Liu, Jai Shin ; Chen, Kuei Tian ; Chen, Chien Tsu ; Chan, Err Cheng. / Identification of neutral and acidic sphingomyelinases in Helicobacter pylori. 於: FEBS Letters. 1998 ; 卷 423, 編號 2. 頁 249-253.
@article{1ab43bc1615c42bab9d846743308c04d,
title = "Identification of neutral and acidic sphingomyelinases in Helicobacter pylori",
abstract = "We demonstrated for the first time the presence of sphingomyelinase (SMase) in Helicobacter pylori. Activation of SMase has been implicated as the cause of elevation of cellular ceramide levels and consequently of apoptosis. The data indicate that there are two classes of SMase, defined by their optimal pHs and cellular locations, existing in H. pylori. One is an Mg2+-dependent membrane-bound enzyme with an optimal activity at pH 7, and the other is an Mg2+-independent cytosolic enzyme with an optimal activity at pH 5. Bisalumin, a bismuth salt, was found to inhibit the activities of both forms of SMase regardless of the presence of Mg2+. By Western blot analysis, the membrane-bound SMases of H. pylori and Bacillus cereus were shown to be antigenically related and to have a similar denatured molecular mass of 28 kDa.",
keywords = "Bacillus cereus, Helicobacter pylori, N-ω-Trinitrophenylaminolauryl- sphingomyelin, Phospholipase, Sphingomyelinase",
author = "Lin, {Yuh Ling} and Liu, {Jai Shin} and Chen, {Kuei Tian} and Chen, {Chien Tsu} and Chan, {Err Cheng}",
note = "Funding Information: This work was supported by Grant NSC-85-2331-B-182-072 from the National Science Council of ROC. ",
journal = "FEBS Letters",
T1 - Identification of neutral and acidic sphingomyelinases in Helicobacter pylori
AU - Lin, Yuh Ling
AU - Liu, Jai Shin
AU - Chen, Kuei Tian
AU - Chen, Chien Tsu
AU - Chan, Err Cheng
N1 - Funding Information: This work was supported by Grant NSC-85-2331-B-182-072 from the National Science Council of ROC.
N2 - We demonstrated for the first time the presence of sphingomyelinase (SMase) in Helicobacter pylori. Activation of SMase has been implicated as the cause of elevation of cellular ceramide levels and consequently of apoptosis. The data indicate that there are two classes of SMase, defined by their optimal pHs and cellular locations, existing in H. pylori. One is an Mg2+-dependent membrane-bound enzyme with an optimal activity at pH 7, and the other is an Mg2+-independent cytosolic enzyme with an optimal activity at pH 5. Bisalumin, a bismuth salt, was found to inhibit the activities of both forms of SMase regardless of the presence of Mg2+. By Western blot analysis, the membrane-bound SMases of H. pylori and Bacillus cereus were shown to be antigenically related and to have a similar denatured molecular mass of 28 kDa.
AB - We demonstrated for the first time the presence of sphingomyelinase (SMase) in Helicobacter pylori. Activation of SMase has been implicated as the cause of elevation of cellular ceramide levels and consequently of apoptosis. The data indicate that there are two classes of SMase, defined by their optimal pHs and cellular locations, existing in H. pylori. One is an Mg2+-dependent membrane-bound enzyme with an optimal activity at pH 7, and the other is an Mg2+-independent cytosolic enzyme with an optimal activity at pH 5. Bisalumin, a bismuth salt, was found to inhibit the activities of both forms of SMase regardless of the presence of Mg2+. By Western blot analysis, the membrane-bound SMases of H. pylori and Bacillus cereus were shown to be antigenically related and to have a similar denatured molecular mass of 28 kDa.
KW - Bacillus cereus
KW - Helicobacter pylori
KW - N-ω-Trinitrophenylaminolauryl- sphingomyelin
KW - Phospholipase
KW - Sphingomyelinase
JO - FEBS Letters
JF - FEBS Letters
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Some dementia patients may start exhibiting aggressive behavior as the disease progresses. There are different causes for behavioral changes in dementia which don't necessarily revolve around the disease itself. For example, behavioral changes may be associated with some sort of difficulty brought on by dementia, side effects of medications, changes in environment, social interactions, habits, and mental and physical health.
Aggressive behavior can be verbal or physical. In verbal aggressive behavior, patients may swear, scream, shout, or make threats. Physical aggressive behavior is when the patient hits, pinches, scratches, bites, or pulls hair.
Aggressive behavior may stem from the patient's behavior prior to diagnosis, or it can develop as the disease progresses even if the patient wasn't aggressive before.
Dealing with aggressive behavior can be quite challenging for a caregiver and at times scary because they may feel threatened or worry about their own and the patient's safety.
Some dementia patients have trouble revealing or understanding their needs or wants, so in order to express themselves, they may exhibit aggressive behavior. Causes of aggressive behavior may be biological, social, or psychological.
The first step in managing and preventing aggressive behavior in dementia is to try and understand the patient's needs or wants and ensure they are being taken care of. This means responding to hunger, thirst, tiredness, boredom, or other frustrations the patient may have. Here are some tips to help caregivers prevent and manage aggressive behavior.
If these tips are unsuccessful and you are finding that the aggressive behavior is worsening, you may want to speak with the patient's doctor with regards to medications that can help control the behavior.
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The Olympus Somnoplasty turbinate handpiece is designed to create predictable lesions in the inferior turbinates using temperature-controlled radio-frequency (TCRF) technology.
For local injection, inject 1.5 – 3.0 mL per turbinate. Inject enough to "balloon out" the tissue submucosally.
Place electrode submucosally until 2 mm of the insulation is buried.
Patients with nasal congestion and rhinorrhea associated with inferior turbinate hypertrophy who note favorable improvement in obstruction after a nasal decongestant spray test.
Patients with nasal congestion due to a mildly deviated septum and nasal turbinate hypertrophy.
The sleep apnea patient who notes difficulty wearing a nasal CPAP mask because of increased nasal resistance.
Patients requiring a septoplasty, rhinoplasty, or functional endoscopic sinus surgery who also have turbinate hypertrophy.
Patients requiring adjunctive treatment for rhinitis medicamentosa (RM).
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The Measles, Mumps, and Rubella (MMR) Vaccine
By: Christian H. Ross
<?xml version="1.0" encoding="utf-8"??>The Measles, Mumps, and Rubella (MMR) Vaccine
In 1971 Maurice Hillemanat at the Merck Institute of Therapeutic Research, a pharmaceutical company in West Point, Pennsylvania, created the measles, mumps, and rubella (MMR) vaccine. The vaccine combined three separate vaccines for measles, mumps, and rubella, common and sometimes fatal diseases. Measles causes a red skin rash and severe fevers that can be fatal. Mumps causes fever and swelling of the salivary glands in the mouth and jaw, while rubella causes milder fevers and skin rashes. Pregnant women that contract rubella sometimes pass the virus to their fetuses, causing congenital rubella syndrome, which results in malformations of the eyes, ears, heart, and brain in the fetuses. The MMR vaccine has protected millions of people from contracting the potentially deadly diseases of measles, mumps, and rubella, as well as prevented the development congenital rubella syndrome in the fetuses.
Hilleman developed the MMR vaccine while working in the vaccine research laboratories at Merck. There, Hilleman created forty different vaccines over his career. During his time at Merck, Hilleman created the vaccines for both measles and mumps, which he later incorporated into the MMR vaccine. He developed his first measles vaccine in 1963 and a subsequent improved version of that vaccine in 1968. In 1967, Hilleman developed his mumps vaccine using samples of mumps virus which he isolated from his five-year-old daughter, Jeryl Lynn Hilleman, who had contracted the mumps. Though Hilleman created a rubella vaccine himself in 1969, he used the rubella vaccine developed that year by Stanley Plotkin at the Wistar Institute, in the MMR vaccine instead.
Plotkin used human fetal cells to develop his rubella vaccine, whereas Hilleman had used animal cells in his rubella vaccine. Using human cells rather than animal cells enabled Plotkin to develop a rubella vaccine that was better adapted to protect against the disease in humans and produced fewer negative side effects after vaccination.
When a virus infects an individual, that individual's immune system begins to make antibodies specific to that virus to combat the infection. Antibodies are proteins that recognize and bind to the specific chemical signatures of the virus, marking the virus as a target for removal by the other parts of the immune system. Even after the immune system eliminates the infection, the antibodies remain to protect against future similar infections. The immune system continues to produces those antibodies, providing immunity from, or protection against, future infections from the same type of virus.
The MMR vaccine contains within it small amounts of attenuated (weakened) or inactive viruses, which are not infectious. Even if the virus is inactive or attenuated, the immune system still responds as if the virus were active. Because the virus is inactive or attenuated, the virus does not cause a full-strength infection with accompanying symptoms. However, the immune system still produces the same antibodies that it would if it were a full-strength infection. When an individual vaccinated with the MMR vaccine encounters the full-strength version of the virus, the antibodies specific to measles, mumps, and rubella provide immunity against those viruses, meaning they prevent infection. By exposing individuals to a mild version of viral infections, the MMR vaccine gives the immune system an opportunity to build defenses against weaker measles, mumps, and rubella infections before it encounters the full-strength viruses.
When the MMR vaccine was developed in 1971, it did not protect against measles, mumps, and rubella in a new way. Instead, it was a combination vaccine, a vaccine that contained the ingredients of multiple other vaccines, specifically vaccines against measles, mumps, and rubella. With combination vaccines, physicians could immunize against multiple diseases with a single injection rather than multiple vaccinations over time. Combination vaccines enabled quicker and more thorough vaccination coverage in the public. As a combination vaccine, the MMR vaccine contains attenuated viral material from measles, mumps, and rubella viruses. Each dose of the MMR vaccine became typically administered via injection, often in the upper part of recipient's arm, resulting in few, if any, side effects from the MMR vaccine. The most common side effects are minor and include mild fevers or rashes. In rarer cases, about one in every 3,000 people receiving the vaccine, the MMR vaccine could cause temporary joint pain or stiffness in teens or adults, as well as high fevers that may lead to seizures.
Though a single dose of the MMR vaccine protects against contracting measles, mumps, and rubella, it is most effective after two doses of the vaccine spread out over time. The second dose of the MMR vaccine is more than a booster to immunity gained from the first dose. Instead, the second dose helps to produce immunity in individuals that did not receive it from the first dose. A single dose of the MMR vaccine imparts immunity against measles in about 93 percent of recipients, mumps in about 78 percent of recipients, and rubella in about 90 percent to 95 percent of recipients. The second dose increases immunity against measles to about 97 percent, against mumps to about 88 percent of recipients, and against rubella to over 99 percent. However, even after two doses, there may still be a small portion of recipients that do not obtain immunity against rubella.
By the end of the twentieth century, the US Centers for Disease Control and Prevention (CDC), headquartered in Atlanta, Georgia, recommended that children receive their first dose of the MMR vaccine between twelve and fifteen months of age. They encouraged parents to wait until after a child's first year to begin vaccination because until about that time children retain passive protection against measles, mumps, and rubella from antibodies passed to them from their mothers. Those antibodies destroy any measles, mumps, or rubella viruses, including those present in the MMR vaccine, rendering the vaccine ineffective in producing immunity. After the first year, the mother's antibodies are no longer present in the child, but the child's immune system cannot produce those antibodies itself, leaving the child unprotected against infection from measles, mumps, and rubella and ready for immunization with the MMR vaccine. The CDC suggested that children receive their second dose between ages four and six, although children could receive their second does MMR vaccine as early as twenty-eight days after receiving their first does without negative effects on health or disease immunity.
Though medical personnel widely used the MMR vaccine to better promote individual and public health, concerns later arose over the safety of administering the vaccine. In 1998, the medical journal The Lancet published an article in which Andrew Wakefield and his colleagues in the UK claimed that there was a causal link between the MMR vaccine and autism spectrum disorders. That publication sparked much public speculation and debate about the safety of vaccines like the MMR vaccine, particularly those that contained thimerosal. Thimerosal is a mercury-based preservative included in many vaccines to prevent microbes from contaminating the vaccines.
People were concerned that thimerosal, a mercury-based preservative included in many vaccines to prevent microbes from contaminating them, caused increased rates of autism spectrum disorders in the US. In response to growing public concerns, the United States Congress held hearings to debate the effects of thimerosal in vaccines and any possible links to autism spectrum disorders. The Congressional reports from those hearings called for federal health agencies to determine the impact mercury-based compounds on individuals' health.
However, multiple studies conducted and reviewed by the Institute of Medicine, now called the National Academy of Medicine in Washington, D.C., and the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, demonstrated that there is no link between vaccines or thimerosal and autism spectrum disorders. From 2003 to 2015, there were at least nine studies conducted or funded by the CDC investigating the relationship between thimerosal in vaccines. None of those studies found any evidence to support the claim that thimerosal caused autism spectrum disorders. Studies conducted by the Institute of Medicine in 2004 and 2011 further disconfirmed that vaccines containing thimerosal caused autism spectrum disorders. In 2013, a CDC study concluded that there was no evidence that vaccines, in particular the MMR vaccine, caused and autism spectrum disorders. Thorough and repeated research has demonstrated that the MMR vaccine is not only safe for use, but also highly effective in preventing against potentially deadly diseases. In 2010, The Lancet retracted Wakefield's 1998 paper due to incorrect statements contained within.
The MMR vaccine has prevented deaths and defects caused by childhood diseases. Of the diseases that the MMR vaccine protected against, measles was the deadliest. In the early part of the twentieth century, records reported an average of 6,000 deaths per year in the US due to measles. In the ten years before the advent of measles vaccines in 1963, an estimated 3.5 million people in the US contracted the disease each year. After the introduction of the MMR vaccine in 1971, the number of cases in the US dropped to between 22,000 and 75,000 cases per year. By the mid-1980s, the number of US measles cases had decreased to fewer than 4,000 cases per year. Since its licensing in 1971, the MMR vaccine has prevented millions of cases of rubella in children as well as pregnant women, further preventing malformation in the fetuses of rubella-infected mothers due to congenital rubella syndrome. Later, a CDC study of vaccinated children born between 1994 and 2013 estimated that the MMR vaccine prevented nearly 150 million cases and over 57,000 deaths from measles, mumps, and rubella. Furthermore, the CDC estimated between 1999 and 2004, when the World Health Organization, headquartered in Geneva, Switzerland, increased global efforts to vaccinate people against measles, they likely prevented about 1.4 million deaths.
Worldwide, medical personnel administered more than 500 million doses of the MMR vaccine between 1999 and 2006. In that time, the use of the MMR vaccine has improved the health of children and women by preventing measles, mumps, and rubella and preventing congenital rubella syndrome in the fetuses of pregnant women.
Burton, Dan. "Mercury in Medicine Report." Congressional Record 149 (May 20, 2003): E1011–E1030. https://www.gpo.gov/fdsys/pkg/CREC-2003-05-21/html/CREC-2003-05-21-pt1-PgE1011-3.htm (Accessed June 14, 2016).
Buynak, Eugene B., Robert E. Weibel, James E. Whitman, Joseph Stokes, and Maurice R. Hilleman. "Combined Live Measles, Mumps, and Rubella Virus Vaccines." Journal of the American Medical Association 207 (1969): 2259–62.
Centers for Disease Control and Prevention. "Measles, Mumps, and Rubella — Vaccine Use and Strategies for Elimination of Measles, Rubella, and Congenital Rubella Syndrome and Control of Mumps: Recommendations of the Advisory Committee on Immunization Practices (ACIP)." Mortality and Morbidity Weekly Report 47 (1998): 1–57. http:// www.cdc.gov/mmwr/preview/mmwrhtml/00053391.htm (Accessed May 20, 2016).
Centers for Disease Control and Prevention. "Progress in Reducing Global Measles Deaths, 1999–2004." Mortality and Morbidity Weekly Report 55 (2006): 247–9. http:// www.cdc.gov/mmwr/preview/mmwrhtml/mm5509a8.htm (Accessed May 20, 2016).
Destefano, Frank, Cristofer S. Price, and Eric S. Weintraub. "Increasing Exposure to Antibody-Stimulating Proteins and Polysaccharides in Vaccines Is Not Associated with Risk of Autism." The Journal of Pediatrics 163 (2013): 561–7. http ://www.jpeds.com/article/S0022-3476%2813%2900144-3/pdf (Accessed May 20, 2016).
Dove, Alan. "Maurice Hilleman." Nature Medicine 11 (2005): S2.
Hilleman, Maurice R., Robert E. Weibel, Eugene B. Buynak, Joseph Stokes Jr, and James E. Whitman Jr. "Live, Attenuated Mumps-Virus Vaccine: Protective Efficacy as Measured in a Field Evaluation." New England Journal of Medicine 276 (1967): 252–8.
Hilleman, Maurice R., Eugene B. Buynak, Robert E. Weibel, Joseph Stokes, James E. Whitman, and M. Bernice Leagus. "Development and Evaluation of the Moraten Measles Virus Vaccine." The Journal of the American Medical Association 206 (1968): 587–90.
Immunization Safety and Review Committee, Board on Health Promotion and Disease Prevention, and Institute of Medicine of the National Academies. Immunization Safety Review: Vaccines and Autism. Washington, D.C.: The National Academies Press, 2004. http://www.nap.edu/read/10997/chapter/1 (Accessed June 14, 2016).
Institute of Medicine of the National Academies. Adverse Effects of Vaccines: Evidence and Causality: Evidence and Causality. Washington D.C.: The National Academies Press, 2012. http://www.nap.edu/read/13164/chapter/1 (Accessed June 14, 2016).
"Measles (Rubeola)." Centers for Disease Control and Prevention. 2014. http://www.cdc.gov/measles/vaccination.html (Accessed May 20, 2016).
"Mumps." Centers for Disease Control and Prevention. 2015. http://www.cdc.gov/mumps/vaccination.html (Accessed May 20, 2016).
Newman, Laura. "Maurice Hilleman." British Medical Journal 330 (2005): 1028. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC557162/pdf/bmj33001028.pdf (Accessed May 20, 2016).
Plotkin, Stanley A., John D. Farquhar, Michael Katz, and Fritz Buser. "Attenuation of RA 27/3 Rubella Virus in WI-38 Human Diploid Cells." American Journal of Diseases of Children 118 (1969): 178–85.
"Science Summary: CDC Studies on Thimerosal in Vaccines." Centers for Disease Control and Prevention. http://www.cdc.gov/vaccinesafety/pdf/cdcstudiesonvaccinesandautism.pdf (Accessed May 20, 2016).
Stehr-Green, Paul, Peet Tull, Michael Stellfeld, Preben-Bo Mortenson, and Diane Simpson. "Autism and Thimerosal-Containing Vaccines: Lack of Consistent Evidence for an Association." American Journal of Preventive Medicine 25 (2003): 101–6.
Stokes, Joseph, Robert E. Weibel, Victor M. Villarejos, Eugene B. Buynak, and Maurice R. Hilleman. "Trivalent Combined Measles-Mumps-Rubella Vaccine: Findings in Clinical-Laboratory Studies." The Journal of the American Medical Association 218 (1971): 57–61.
Thompson, William W., Cristofer Price, Barbara Goodson, David K. Shay, Patti Benson, Virginia L. Hinrichsen, Edwin Lewis et al. "Early Thimerosal Exposure and Neuropsychological Outcomes at 7 to 10 Years." New England Journal of Medicine 357 (2007): 1281–92.
US Congress. House of Representatives. Subcommittee on Human Rights and Wellness Committee on Government Reform. Mercury in Medicine—Are We Taking Unnecessary Risks?. 104th Congress, 2nd session, 2000. 106–232. https://www.gpo.gov/fdsys/pkg/CHRG-106hhrg72722/html/CHRG-106hhrg72722.htm (Accessed June 22, 2016).
Vaccines and Immunizations. "Measles and the Vaccine (Shot) to Prevent It." Centers for Disease Control and Prevention. http://www.cdc.gov/vaccines/parents/diseases/child/measles.html (Accessed May 20, 2016).
Verstraeten, Thomas, Robert L. Davis, Frank DeStefano, Tracy A. Lieu, Philip H. Rhodes, Steven B. Black, Henry Shinefield, and Robert T. Chen. "Safety of Thimerosal-Containing Vaccines: A Two-Phased Study of Computerized Health Maintenance Organization Databases." Pediatrics 112 (2003): 1039–48.
Wakefield, Andrew Jeremy, Simon H. Murch, Andrew Anthony, J Linnell, D M Casson, M Malik, Mark Berelowitz, Amar P. Dhillon, Michael A. Thompson, P. Harvey, A. Valentine, Susan E. Davies, and John A. Walker-Smith. "RETRACTED: Ileal-Lymphoid-Nodular Hyperplasia, Non-Specific Colitis, and Pervasive Developmental Disorder in Children." The Lancet 351 (1998): 637–41. http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736%2897% 2911096-0.pdf (Accessed May 20, 2016).
Whitney, Cynthia G., Fangjun Zhou, James Singleton, and Anne Schuchat. "Benefits from Immunization During the Vaccines for Children Program Era – United States, 1994–2013." Mortality and Morbidity Weekly Report 63 (2014): 352–5. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6316a4.htm (Accessed May 20, 2016).
Ross, Christian H., "The Measles, Mumps, and Rubella (MMR) Vaccine". Embryo Project Encyclopedia (2017-03-30). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/11462.
MMR vaccine; Viral vaccines; Combined vaccines; Rubella; Rubella vaccines; Measles; Measles vaccine; Mumps; Mumps--Vaccination; Viral vaccines; Technology
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VARIATIONS IN CARE: COMPARING HEART FAILURE CARE TRANSITION INTERVENTION EFFECTS
Award Number: R01HS019311
ORGANIZATION: AGENCY FOR HEALTH CARE RESEARCH AND QUALITY
OPDIV: AHRQ
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
DESCRIPTION (provided by applicant): Recent studies by the Dartmouth Atlas of Health Care have identified geographic variation in hospital resource use and cost at the end of life among elderly Medicare beneficiaries with chronic illnesses. Reduction of variation in resource use and cost is a key focus for saving costs in the U.S. health care system. Readmission rates are a potential area of focus for reducing hospital resource use and cost variation, and interventions designed to improve the care transition period after hospital discharge have been shown to reduce readmissions and potentially improve morbidity and mortality at the patient level. However, studies have not demonstrated whether improving care transitions would result in reductions in variation between hospitals on resource use or health outcomes. In addition, interventions that improve care transitions may be cost-effective at a societal level, but have not been widely disseminated due to implementation costs at the hospital level. This comparative effectiveness project builds on our prior work since 2006 examining variation in resource use and mortality among the five University of California Medical Centers plus Cedars-Sinai Medical Center for elderly Medicare beneficiaries hospitalized with heart failure. This project compares two adaptations of existing care transition interventions, the Transition Coach and Re-Engineering Discharge Programs, designed to reduce the implementation costs for hospitals. One adaptation uses a centralized telephone post-discharge program instead of separate telephone post-discharge programs for each medical center. The other adaptation adds a telemedicine approach with remote sensors to minimize use of the centralized telephone post-discharge program. We propose a randomized, controlled trial with three arms to compare the effectiveness of implementing the two separate care transition interventions with concurrent controls on reducing variation in readmissions among elderly patients hospitalized with heart failure at the six medical centers over an 18-month period. This project also evaluates the historical trends among the six medical centers for readmissions, other resource use, and health outcomes to further control for secular trends that may affect trial findings, and evaluates the costs and benefits of these two care transition interventions. This work will begin to bridge the current gap between quality improvement research and studies of variation in care. Current studies of variation rarely have the clinical or organizational data to suggest ways to reduce variation between sites. This work also provides an opportunity to compare within a set of heterogeneous medical centers the effectiveness of two adaptations to existing care transition interventions on reducing readmissions, and their ability to reduce implementation costs that prevent wider dissemination of existing care transition interventions. PUBLIC HEALTH RELEVANCE: Heart failure is a prevalent condition among the elderly that has high rates of potentially avoidable readmissions. Readmissions can be reduced through programs to improve the transition of care from inpatient to outpatient settings, but these programs are not currently widespread due to implementation costs at the hospital level. This research compares the costs and the effectiveness of two separate adaptations of care transition interventions on reducing readmissions for elderly heart failure patients, and their effectiveness on reducing the variation between six medical centers on readmission rates for elderly heart failure patients.
2013 2010 UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS 11000 KINROSS AVENUE LOS ANGELES CA 90095 LOS ANGELES USA Recovery Act – Comparative Effectiveness Research - AHRQ 000 1 7/19/2013 NEW $0
2012 2010 UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS 11000 KINROSS AVENUE LOS ANGELES CA 90095 LOS ANGELES USA Recovery Act – Comparative Effectiveness Research - AHRQ 000 1 9/5/2012 NEW $0
2010 2010 UNIVERSITY OF CALIFORNIA-LOS ANGELES, BOARD OF REGENTS 11000 KINROSS AVENUE LOS ANGELES CA 90095 LOS ANGELES USA Recovery Act – Comparative Effectiveness Research - AHRQ 000 1 9/28/2010 NEW $9,898,332
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The direct catalytic amination of C(sp )–H is difficult to achieve but significant. The compound of Fe Cr O , prepared 2.35 0.65 4 by the oxidation–precipitation method, was characterized by X-ray diffraction, scanning electron microscopy, Brunauer– Emmett–Teller, X-ray photoelectron spectroscopy, and inductively coupled plasma spectrometry, and used to catalyze the decomposition of hydrogen peroxide to hydroxyl-free radical, which sequentially reacted with ammonia and toluene to produce benzylamine. Results showed that Fe Cr O with high Cr content, particularly the outside surface, could well 2.35 0.65 4 better catalyze hydrogen peroxide to hydroxyl-free radical and its transformation. Under the conditions of pH\ 6, 30 C, and the NH amount, maintaining the match of one hydroxyl-free radical one by the process control, toluene in the other phase of the reaction system was converted into benzylamine with 30% yield. The catalytic radical amination of C(sp )–H in toluene was achieved without any oriented group. Graphical abstract FeSO + CrCl 4 3 Oxidation-precipitation Cr-Fe O 3 4 NH NH + H O 3 2 2 Keywords C(sp )–H activation Radicals Cr-doped magnetite Catalytic amination Metals Heterogeneous catalysis Introduction bonds, which broadens the synthetic approach to organic synthesis.
Yue, C., Hu, X., Gu, L., & Liu, B. (2018). Cr-doped magnetite for the catalytic radical amination of C(sp3)–H in toluene with NH3 and H2O2. Monatshefte für Chemie - Chemical Monthly, 149(6), 1161-1166.
Yue, Chuan-Jun, Xu-Dong Hu, Li-Ping Gu, and Bao-Liang Liu. "Cr-doped magnetite for the catalytic radical amination of C(sp3)–H in toluene with NH3 and H2O2." Monatshefte für Chemie - Chemical Monthly 149.6 (2018): 1161-1166.
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Shadi Sepehri MD, PhD, D(ABMM), FCCM
Microbiology news
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First case of mcr-1 gene in E. coli discovered in a human in United States.
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Research Scientist, Children's Hospital Research Institue of Manitoba
654 John Buhler Research Centre, 715 McDermot Avenue
Winnipeg, Manitoba, R3E 3P4, Canada
[email protected]
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Our highest dose of iron, this multiple nutrient formula provides support for red blood cell formation, energy production and cognitive function in a one-a-day capsule.
• Energy Production & Release: Iron and vitamin C contribute to normal energy production and release.
• Red Blood Cell Formation: Iron supports the normal formation of red blood cells and haemoglobin. Haemoglobin transports oxygen around the body.
• Reduction of Tiredness & Fatigue: Iron and vitamin C contribute to the reduction of tiredness and fatigue.
• Iron Absorption: Vitamin C increases iron absorption.
Suitable for vegetarians and during pregnancy.
Bulking agents: Cellulose, Hydroxypropyl cellulose, Cross linked sodium carboxy methyl cellulose; Spirulina powder (Spirulina Platensis (Gomont) Geitler, algae); ferrous bisglycinate (Iron); coating (Thickeners: Hydroxypropyl methyl cellulose, Hydroxypropyl cellulose; Colours: Iron oxides and hydroxides, Titanium dioxide; Humectant: Fatty acids; Bulking agent: Talc); L-calcium ascorbate (Vitamin C); anti-caking agents: Magnesium salts of fatty acids, Silicon dioxide; Pyridoxine hydrochloride (Vitamin B6); beta-carotene (Vitamin A).
Take one tablet daily with a meal, or as directed by a healthcare professional.
Contains iron which can be harmful to young children if taken in excess. Store out of the reach of young children. Food supplements are not intended as a substitute for a varied and balanced diet and a healthy lifestyle. If you have concerns or questions, ask the advice of your healthcare professional to determine if this food supplement is right for you. It is advised to take this supplement with food.
Food supplement with iron, vitamins and Spirulina powder.
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Study success strengthens case for Lynparza in ovarian cancer
(Credit: AstraZeneca )
Adding AstraZeneca's Lynparza to Roche's older cancer drug Avastin helped women with advanced ovarian cancer live longer without their tumors growing, according to results from a Phase 3 study disclosed Wednesday by AstraZeneca.
In the trial, called PAOLA-1 and sponsored by two academic groups in Europe, women were given Lynparza following initial treatment with Avastin and followed to determine whether AstraZeneca's drug could extend the time without disease worsening or death.
By topline outcome, the study was a success: women given Lynparza after Avastin experienced longer progression-free survival than those on Avastin alone, a standard treatment. Notably, both women with and without BRCA mutations were included, suggesting possibly broader use for Lynparza than its current first-line, BRCA-limited approval.
Lynparza (olaparib) is the most commonly used drug in its class, a group of cancer treatments known as PARP inhibitors.
Its initial U.S. approval as a first-line maintenance therapy, granted in late December by the Food and Drug Administration, has helped AstraZeneca extend its lead over rival PARP drugs sold by GlaxoSmithKline and Clovis Oncology.
Data supporting that OK, which came from a study called SOLO-1, showed a dramatic benefit with Lynparza. Compared to placebo, the drug reduced the risk of disease progression or death by 70% when given as maintenance therapy following platinum-based chemotherapy.
Roche's Avastin (bevacizumab) is commonly used by physicians as an initial treatment for advanced ovarian cancer, making the results disclosed Wednesday potentially helpful to AstraZeneca as it works to convince doctors of Lynparza.
"Physicians are quite well used to using Avastin and they will happily combine it with Lynparza, if indeed PAOLA is positive," said AstraZeneca CEO Pascal Soriot in a recent earnings conference call held before the study's results were disclosed.
Soriot noted roughly half of ovarian cancer patients in the U.S. currently receive Avastin as an initial treatment, as do as many as 60% in Europe.
PAOLA-1, begun in May 2015, enrolled over 800 women, according to a federal database of clinical trials. Unlike the earlier SOLO-1 study, however, it included patients without BRCA mutations, a genetic error that makes PARP inhibitors more likely to be effective.
No detailed data were released Wednesday, making it hard to judge whether the positive progression-free survival benefit was clear in both BRCA-positive and BRCA-negative groups.
AstraZeneca said it would present full results, including biomarker analyses, at a forthcoming medical meeting. The pharma also plans to discuss the results with health authorities.
PAOLA-1's success comes at a good time for AstraZeneca. Last month, GlaxoSmithKline announced that its Phase 3 PRIMA study showed its competing PARP inhibitor, Zejula (niraparib), extended progression-free survival versus placebo when used as maintenance therapy following chemotherapy.
Then, GSK R&D chief Hal Barron argued women with ovarian cancer needed more first-line options, as only about 15% of the 300,000 diagnosed each year are currently eligible for PARP inhibitors initially.
Lynparza is also approved in certain breast cancers, and earlier this month posted positive results in men with a specific form of metastatic castration-resistant prostate cancer.
It's one of AstraZeneca's most important drugs and, alongside the lung cancer medicine Tagrisso (osimertinib), a major part of the British pharma's oncology push.
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To Cite: Nematkhorasani A, Mansoori F, Espahbodi E. The Causes of Seizure in Burned Children Hospitalized in Imam Reza Hospital of Mashad During 1996 to 2003, J Kermanshah Univ Med Sci. 2005 ; 9(2):e81572.
Introduction: Burning is one of the main accidents in pediatric medical emergency, which is commonly associated with metabolic, infectious and neurologic complications. The seizure is one of the most important complications in burned patients. This study was done to determine the causes of seizure in burned children hospitalized in Imam Reza.
Materials and Methods: This survey was a descriptive study based on available data in which 2212 burned children under 15 years old were selected and studied during 1996 to 2003.
Results: 365 patients had seizure attacks of which 86% had happened during the first 48h of admission. Most of the attacks occurred in children younger than 3 years old. Hyponatremia was the most frequent cause of seizure followed by history of previous seizure, febrile seizure, meningitis, head injury, unknown causes, hypoglycemia and hypocalcaemia.
Conclusion: It seems that seizure has significant frequency in burned children and it is preventable with respect to predisposing factors. We recommend that hyponatremia is the most important and frequent cause of seizure' which should be prevented carefully.
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Low-intensity pulsed ultrasound is a pain-free therapy performed daily at home by the patient and has been shown to promote fracture healing. Teriparatide is a parathyroid hormone preparation that activates osteoblastic bone formation and is also reported to be effective in promoting bony union.
We report the case of a 56-year-old Japanese male with a femoral shaft fracture who underwent intramedullary osteosynthesis nailing initially. He had no radiologic or clinical sign of healing 3 months later and low-intensity pulsed ultrasound was initiated at that time. He was reassessed in another 3 months, with evidence of mild bone consolidation but the fracture gap persisted. Subsequent treatment with human parathyroid hormone was initiated in combination with low-intensity pulsed ultrasound. Full fracture healing was present 6 months after beginning the combination low-intensity pulsed ultrasound and teriparatide. It is hypothesized that the potential additive effects of low-intensity pulsed ultrasound and teriparatide therapy ultimately triggered sufficient bone formation to support osseous union.
The case reported herein is a femoral shaft atrophic nonunion in which traditional interventions failed. Successful fracture healing was finally achieved with low-intensity pulsed ultrasound and teriparatide therapy. This is the first reported case of diaphyseal nonunion with deterioration of bone quality in long bones resolved with teriparatide and low-intensity pulsed ultrasound.
The effect of low-intensity pulsed ultrasound (LIPUS) on the stimulation of bone formation in fracture and in cases of nonunion has been extensively studied . However, there are cases in which bone union is not obtained even with the use of LIPUS, and it is difficult to judge the most appropriate timing for repeat surgery. A large physical, mental and social burden is placed on the patient when repeat surgery is needed. Teriparatide is a recombinant human parathyroid hormone [1–34] (PTH) preparation that is used in the treatment of osteoporosis, and is also reported to be effective in promoting bony union . Teriparatide is effective because of its activation of osteoblastic bone formation . Although both teriparatide and LIPUS have been found to accelerate fracture-healing processes , the effect of the combination of teriparatide and LIPUS in clinical bone fracture management is unclear.
A 56-year-old Japanese man was involved in a traffic accident. He was diagnosed with left diaphyseal femoral shaft fracture (OTA [Orthopaedic Trauma Association's Fracture and Dislocation Compendium] 32-C1.3) (Figure 1) and was treated with intramedullary osteosynthesis nailing surgery at another hospital (Figure 2). Radiologic assessments at 3 months (Figure 3) did not show any sign of healing. This was consistent with the clinical manifestations of pain, movement at the fracture site, and left leg weakness. Physical examination and laboratory tests, including white blood cell counts, C-reactive protein, and erythrocyte sedimentation rate, were normal (Table 1), ruling out underlying infection. The patient denied smoking and alcohol abuse and had no history of metabolic disease or glucocorticoid intake. Other laboratory data, including serum alkaline phosphatase, intact PTH, and calcium, were normal (Table 1). However, he had high levels of bone quality marker, uncarboxylated osteocalcin ((ucOC), 18.8 ng/ml; reference value, <4.50 ng/ml) and serum homocysteine ((Hcys), 21.9 nmol/ml; reference value, 3.7 – 13.5 nmol/ml). Dual-energy X-ray absorptiometry assessment of bone density showed almost normal: 0.891 g/cm2 and T-score of -0.2 standard deviation on his radius. In other words, this patient had mildly compromised bone quality [5–8]. Callus formation in the fracture area remained poor 3 months after the first surgery, but the patient could not take any more time away from his company. Therefore, when he left the hospital he used crutches to assist with partial weight bearing ambulation. Both LIPUS and vitamin K2 preparation administrations were initiated at this time with the aim of lowering his high ucOC level. Callus formation in the fracture area was still insufficient at 3 months following initiation of LIPUS. Therefore, teriparatide was started in combination with LIPUS (Figure 4). Callus formation was good when assessed at 3 months after the start of teriparatide intervention (Figure 5). Bony union was good and full weight bearing was permitted after administration of teriparatide for 6 months (Figure 6). The ucOC levels improved to 5.6 ng/ml and serum Hcys improved to 10.8 nmol/ml 6 months after initiating teriparatide (Table 1).
Preoperative radiographs. The femoral diaphyseal fracture (OTA 1, 32-C1.3).
Left, postoperative radiologic image of the femoral diaphyseal fracture (OTA 1, 32-C1.3) treated using interlocked intramedullary nailing. Right, magnification of the image above.
Left, radiologic image at 3 months, showing no signs of healing but also no displacement. LIPUS was started at this point. Right, magnification of the image above.
Abbreviation; BAP Bone alkaline phosphatase, PINP procollagen typeIN-terminal propeptide, DPD dihydropyrimidine dehydrogenase, NTX N-terminal crosslinking telopeptide of typeIcollagen, TRACP-5B Tartrate-resistant Acid Phosphatase type 5B, ucOC uncarboxylated osteocalcin, Hcys homocysteine, Pen pentosidine, PTH parathyroid hormone, 25-OHVitD 25-hydroxyvitamin-D, Ca calcium, P phosphorus, Cr creatinine, CRP C-reactive protein, eGFR estimated glomerular filtration rate.
Left, radiological image at 6 months, showing signs of nonunion, nondisplaced diaphysis, atrophic bone with gap. Teriparatide was started at this point. Right, magnification of the image above.
Left, image obtained after 3 months of treatment with teriparatide. Bone bridging and a decrease in interfragment gaps are observed. Right, magnification of the image above.
Left, image obtained at 6 months showing healing of the nonunion. Right, magnification of the image above.
Intermittent administration of human parathyroid hormone (hPTH) has an anabolic effect on bone in humans and is expected to be a potent agent for fracture healing . For nonunion, a second intervention will undoubtedly be necessary, carrying additional risks and potential complications as well as increases in healthcare costs. Therefore, any effective treatment that can solve this situation should be considered. Several recent studies have revealed that intermittent treatment with PTH stimulates osteogenesis in experimental fracture healing of cortical bones and that PTH effects on cortical bone repair are site-specific. Aspenberg et al., in a prospective, randomized, double blind study of conservative fracture treatment for 102 postmenopausal women with distal radial fractures, showed than the time to healing was shorter in a teriparatide 20 mg group than in a placebo group . Warden et al. reported that teriparatide and LIPUS have contrasting additive, rather than synergistic, effects during fracture healing. Teriparatide primarily increased callus bone mineral content (BMC) without influencing its size, whereas LIPUS increased callus size without influencing BMC in rat studies. Fracture healing is a complex biologic process and is impacted by multiple factors . Watanabe et al. reported that LIPUS is a relatively new technique for the acceleration of fracture healing in nonunion situations. It has a frequency of 1.5 MHz, a signal burst width of 200 microseconds, a signal repetition frequency of 1 kHz, and an intensity of 30 mW/cm2. The beneficial effect of fracture healing acceleration with LIPUS is considered to be larger in patients with potentially negative factors for fracture healing. LIPUS is a pain-free therapy performed daily at home by the patient with the possibility of avoiding further surgical procedures. This outpatient treatment reduces the length of hospital stays and reduces overall system wide health care expenses. The incidence of delayed union and nonunion is 5% to 10% of all fractures. While LIPUS has beneficial effects on collagen enzymatic cross-link formation, mechanical stress may improve bone quality. Nonunion is a severe complication for the patient, which has a negative impact on quality of life. Treatment for nonunion typically requires a second surgical intervention to provide stability and to stimulate bone healing. These surgeries include locked intramedullary nailing, dynamic compression plating, external fixation with Ilizarov's principles, and at times autografting. But Brinker et al. reported that all patients with nonunion who met their screening criteria should be referred to an endocrinologist for evaluation because they were likely to have undiagnosed metabolic or endocrine abnormalities that would interfere with bone healing . Two interventions found to accelerate fracture healing processes are conbination of LIPUS and teriparatide without a second surgical intervention in this nonunion patient with deteriorated bone quality. No side effects occurred.
The case reported herein is a femoral shaft atrophic nonunion in which traditional interventions failed. This is the first reported case of diaphyseal nonunion with deterioration of bone quality in long bones resolved with teriparatide and LIPUS. The difference in teriparatide activity on trabecular and cortical bone suggests that teriparatide could accelerate healing in nonunions in diaphyseal nonunion in long bone with deterioration of bone quality. The authors are aware that this is just one case report; thus, new experimental studies and clinical trials with larger groups of subjects must be conducted in order to assess the efficacy of combination teriparatide and LIPUS intervention and the fracture healing.
KN performed the surgery. YS helped of the surgery, and helped to draft the manuscript. NM helped to draft the manuscript. SY helped of the surgery. MH helped to draft the manuscript. YK helped to draft the manuscript. HS helped to draft the manuscript. HK helped to draft the manuscript. All authors read and approved the final manuscript.
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Diabetes Excellence ForumResource Center
Photoclinic
Disseminated Cutaneous Herpes Zoster in an Immunocompetent Woman With Diabetes
Volume 56 - Issue 9 - September 2016
Chetan Dhoble, MD; Julie Taylor, MD; and Wahaj Ahmed, MD
Dhoble C, Taylor J, Ahmed W. Disseminated cutaneous herpes zoster in an immunocompetent woman with diabetes. Consultant. 2016;56(9, Suppl):S15-S16.
A previously healthy 39-year-old woman presented with a 2-day history of severe pain, fever, and a vesicular eruption that had initially developed over her right forehead and right middle thumb but had spread to involve her chest, back, and upper and lower extremities bilaterally.
History. The woman's medical history was negative for chickenpox during childhood and for any recent exposure to it. She had diabetes and deep vein thrombosis but no history of lymphoma. She had undergone amputation of her left great toe a week prior secondary to osteomyelitis. Her medications included ciprofloxacin and clindamycin, alogliptin and pioglitazone, and apixaban. She was allergic to enoxaparin sodium, with a history of anaphylactic reaction to it.
Physical examination. On examination, the patient was febrile (temperature, 38.3°C), with a heart rate of 122 beats/min. Pustules and vesicles at different stages of development with crusting and swelling were present on her trunk and extremities, including the palms and soles. Scabs and pustules were seen on the face, trunk and extremities (Figures). The oropharynx was spared. Examination findings of the head, eyes, ears, nose, and throat, as well as the cardiovascular system, the pulmonary system, and the abdomen were all within normal limits.
Diagnostic tests. Results of a complete blood cell count, peripheral smear, comprehensive metabolic profile, urinalysis, chest radiography, and electrocardiography were normal. Serologic tests for HIV, syphilis, and hepatitis A, B, and C were negative. Results of polymerase chain reaction (PCR) and antibody tests for herpes simplex virus (HSV) were negative, while PCR results for varicella-zoster virus (VZV) were positive. The VZV immunoglobulin M immune status ratio (ISR) was 1.29 (reference value, ≤ 0.91), and VZV immunoglobulin G was 2.33 (reference value, ≥ 1.09).
Discussion. Herpes zoster (HZ) is the consequence of reactivation of latent VZV from dorsal root ganglia. Disseminated cutaneous HZ (DCHZ) is by definition the presence of greater than 20 lesions outside the area of primary or adjacent dermatomes.1 It presents within a week of the primary lesion. Greater than 65% cases of HZ are in persons at least 50 years of age,2 unlike our patient, who was 39.
DCHZ is most commonly seen in immunocompromised patients such as those with malignancy, with HIV disease, with a recent solid organ transplant, or on immunosuppressive drugs such as corticosteroids.2 However, it is very unusual for a healthy person such as our patient to present with DCHZ. While 10% to 40% of HZ-infected immunocompromised patients present with DCHZ, the prevalence of DCHZ in immunocompetent patients has not been established.2
Although our patient was only 39 years of age and was immunocompetent, her diabetes may have contributed to the development of DCHZ. The incidence of HZ is higher in persons with diabetes because of the low VZV-specific immunity.3-5 Very limited studies of patients with DCVZ and diabetes have been published.6,7
DCHZ treatment is intravenous acyclovir, 10 mg/kg every 8 hours for 5 to 7 days.8 Aggressive treatment is critical in a patient with diabetes, even if the patient is immunocompetent. DCHZ is a serious condition for which early diagnosis and prompt aggressive treatment are crucial to decrease morbidity and complications.
Outcome of the case. The patient's condition improved, with the cessation of new vesicle eruption and resolving of the rash, after 3 days of treatment. She was discharged on oral acyclovir, 800 mg 4 times daily for 10 days.
Chetan Dhoble, MD, is in the Department of Internal Medicine at Getwell Hospital and Research Center in Nagpur, India.
Julie Taylor, MD, is in the Department of Family Medicine at Advocate Trinity Hospital in Chicago, Illinois.
Wahaj Ahmed, MD, is in the Department of Internal Medicine at Mount Sinai Hospital in Chicago, Illinois.
Alaine S. Ainsley, MD, is a graduate student at Atlantic University School of Medicine in Saint Lucia.
Brown TJ, McCrary M, Tyring SK. Antiviral agents: nonantiviral drugs. J Am Acad Dermatol. 2002;47(4):581-599.
Arvin AM. Varicella-zoster virus. Clin Microbiol Rev. 1996;9(3):361-381.
Aldaz P, Díaz JA, Loayssa JR, Dronda MJ, Oscáriz M, Castilla J. Herpes zoster incidence in diabetic patients. An Sist Sanit Navar. 2013;36(1):57-62.
Hata A, Kuniyoshi M, Ohkusa Y. Risk of herpes zoster in patients with underlying diseases: a retrospective hospital-based cohort study. Infection. 2011;39(6):537-544.
Heymann AD, Chodick G, Karpati T, et al. Diabetes as a risk factor for herpes zoster infection: results of a population-based study in Israel. Infection. 2008;36(3):226-230.
Graue N, Grabbe S, Dissemond J. Disseminated herpes zoster in diabetes mellitus. Dtsch Med Wochenschr. 2006;131(8):384-386.
Panwar RB, Kochar DK, Gupta BS, Bhatnagar LK, Saxena HC. Herpes generalisata associated with diabetes mellitus and pulmonary tuberculosis (a case report). J Postgrad Med. 1979;25(3):171-173.
Gupta S, Jain A, Gardiner C, Tyring SK. A rare case of disseminated cutaneous zoster in an immunocompetent patient. BMC Fam Pract. 2005;6:50.
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We only included studies that reported on women's health and nutrition outcomes, and excluded studies that were targeted to women but that reported only on health and nutrition outcomes of children (including birth outcomes). We included outcomes for adolescent girls ages 10–19 y, pregnant and lactating women, nonpregnant and nonlactating women of reproductive age (>19 y), and older women. Studies that described interventions targeting a wider age range of adolescent girls (e.g., ages 8–24 y) were also included but adolescent girls aged >19 y were reported in this review as nonpregnant and nonlactating women of reproductive age. Although many adolescents in low- and middle-income countries are married and bearing children, adolescents (10–19 y) as reported in this review reflect girls who are nonpregnant and nonlactating. The few interventions in low- and middle-income countries that target pregnant and lactating adolescents are reported under pregnant and lactating women. A description of the articles included in this review can be found in Supplemental Table 1.
This staff here is very kind, but the facilities are just bizarre, especially for a Boston gym. The equipment is clearly very used, and the gym itself is in a basement which isn't very inspiring. Everything is in a big, open area, so people are running on treadmills behind you as you're participating in a group class. Very weird. I love supporting a local business, but this place needs a bit of a facelift. There are so many gyms in Boston with beautiful facilities and equipment, although a bit more expensive, but you truly get what you pay for.
Internationally, many United Nations agencies such as the World Health Organization (WHO), United Nations Population Fund (UNFPA)[171] and UNICEF[172] maintain specific programs on women's health, or maternal, sexual and reproductive health.[1][173] In addition the United Nations global goals address many issues related to women's health, both directly and indirectly. These include the 2000 Millennium Development Goals (MDG)[142][43] and their successor, the Sustainable Development Goals adopted in September 2015,[47] following the report on progress towards the MDGs (The Millennium Development Goals Report 2015).[174][37] For instance the eight MDG goals, eradicating extreme poverty and hunger, achieving universal primary education, promoting gender equality and empowering women, reducing child mortality rates, improving maternal health, combating HIV/AIDS malaria and other diseases, ensuring environmental sustainability, and developing a global partnership for development, all impact on women's health,[43][11] as do all seventeen SDG goals,[47] in addition to the specific SDG5: Achieve gender equality and empower all women and girls.[109][175]
Also known as "myofascial release," foam rolling is an easy way to benefit your entire body. "While stretching addresses the length of muscle fiber, rolling improves the quality of the tissue," says Rob Sulaver, CEO and founder of Bandana Training. This leads to tension- and pain-free muscles, which function better so you perform better. Be sure to roll for five minutes before your workout. Not sure what to do? Try these 10 ways to use a foam roller.
The U.S. Department of Agriculture's (USDA) food pyramid system (www.mypyramid.gov) provides a good start by recommending that the bulk of your diet come from the grain group—this includes bread, cereal, rice and pasta— the vegetable group; and the fruit group. Select smaller amounts of foods from the milk group and the meat and beans group. Eat few—if any—foods that are high in fat and sugars and low in nutrients. The amount of food you should consume depends on your sex, age and level of activity.
Folate or vitamin B9 (also known as folic acid when used in fortified foods or taken as a supplement) is another nutrient that many women don't get enough of in their diets. Folate can greatly reduce the chance of neurological birth defects when taken before conception and during the first few weeks of pregnancy. Folate can also lower a woman's risk for heart disease and certain types of cancer, so even if you're not planning on getting pregnant (and many pregnancies are unplanned), it's an essential nutrient for every woman of childbearing age. In later life, folate can help your body manufacture estrogen during menopause.
The '90s turned toward a lot more talk about "fat-blasting" in the Snackwell's/heroin chic era. But as the new millennium dawned, front cover messages started to sway from scolding to encouraging. Which makes sense: Why would someone want a magazine to yell at them? That's why the current crop of women's health magazine headlines stress taking time for yourself over how flat your abs might get. As Elizabeth Goodman, editor-in-chief of Shape magazine, explained via email: "As a women's magazine, it's our job to help women be their best selves—both inside and out. However, we don't want to set the standard for normal or tell women what normal is; we want to encourage women to find and be proud of their normal… Our approach with our readers is not to judge or demand, just to inspire and support."
A 45-year-old woman who gets less than 30 minutes of daily physical activity in addition to her normal routine should consume six ounce of grains; two and a half cups of vegetables; one and a half cups of fruit; three cups of milk; five ounces of meat and/or beans; five teaspoons of oil; and just 195 calories of additional fat and sugar. With a higher level of daily activity (30 to 60 minutes), this woman would be able to consume a little more in certain food groups: her fruit intake could rise to two cups; meat and beans to five and a half ounces; oils to six teaspoons; and extra fat and sugar to 265 calories.
Instinct may tell you to slow down when running in wintery conditions, but the secret to not slipping is actually to speed up and shorten your stride. Aim to have each foot strike the ground 90 times per minute, says Terry Chiplin, owner of Active at Altitude, a Colorado-based facility for endurance athletes. This high cadence helps ensure that each foot lands beneath the center of your weight rather than ahead of it, which can throw off your balance on slick terrain.
Adopting a plant-based diet could help tip the scales in your favor. A five-year study of 71,751 adults published in the Journal of the Academy of Nutrition and Dietetics found that vegetarians tend to be slimmer than meat-eaters even though both groups eat about the same number of calories daily. Researchers say it may be because carnivores consume more fatty acids and fewer weight-loss promoting nutrients, like fiber, than herbivores do. Go green to find out if it works for you.
Globally, women's access to health care remains a challenge, both in developing and developed countries. In the United States, before the Affordable Health Care Act came into effect, 25% of women of child-bearing age lacked health insurance.[176] In the absence of adequate insurance, women are likely to avoid important steps to self care such as routine physical examination, screening and prevention testing, and prenatal care. The situation is aggravated by the fact that women living below the poverty line are at greater risk of unplanned pregnancy, unplanned delivery and elective abortion. Added to the financial burden in this group are poor educational achievement, lack of transportation, inflexible work schedules and difficulty obtaining child care, all of which function to create barriers to accessing health care. These problems are much worse in developing countries. Under 50% of childbirths in these countries are assisted by healthcare providers (e.g. midwives, nurses, doctors) which accounts for higher rates of maternal death, up to 1:1,000 live births. This is despite the WHO setting standards, such as a minimum of four antenatal visits.[177] A lack of healthcare providers, facilities, and resources such as formularies all contribute to high levels of morbidity amongst women from avoidable conditions such as obstetrical fistulae, sexually transmitted diseases and cervical cancer.[6]
Three related targets of MDG5 were adolescent birth rate, contraceptive prevalence and unmet need for family planning (where prevalence+unmet need = total need), which were monitored by the Population Division of the UN Department of Economic and Social Affairs.[64] Contraceptive use was part of Goal 5B (universal access to reproductive health), as Indicator 5.3.[65] The evaluation of MDG5 in 2015 showed that amongst couples usage had increased worldwide from 55% to 64%. with one of the largest increases in Subsaharan Africa (13 to 28%). The corollary, unmet need, declined slightly worldwide (15 to 12%).[37] In 2015 these targets became part of SDG5 (gender equality and empowerment) under Target 5.6: Ensure universal access to sexual and reproductive health and reproductive rights, where Indicator 5.6.1 is the proportion of women aged 15–49 years who make their own informed decisions regarding sexual relations, contraceptive use and reproductive health care (p. 31).[66]
Fluids: Fluid needs increase as women age. The reason: Kidneys become less efficient at removing toxins. "Drinking more fluids helps kidneys do their job," Schwartz says. "Unfortunately, thirst signals often become impaired with age, so people are less likely to drink enough water and other fluids." Rather than fret about how many glasses to drink, Frechman says, check the color of your urine. "It should be clear or very pale colored. If it becomes darker, you need more fluid."
Calcium may even be harmful for men, at least in large amounts. The worry is prostate cancer, and two Harvard studies have raised the alarm. In 1998, the Health Professionals Follow-up Study found that a high consumption of calcium from food or supplements was linked to an increased risk of advanced prostate cancer. The risk was greatest in men who got more than 2,000 mg a day. More recently, the U.S. Physicians' Health Study reported that a high consumption of calcium from dairy products appeared to increase a man's risk of prostate cancer by up to 37%. A study from the Fred Hutchinson Cancer Research Center in Seattle also found a link between calcium and advanced prostate cancer.
Globally, cervical cancer is the fourth commonest cancer amongst women, particularly those of lower socioeconomic status. Women in this group have reduced access to health care, high rates of child and forced marriage, parity, polygamy and exposure to STIs from multiple sexual contacts of male partners. All of these factors place them at higher risk.[11] In developing countries, cervical cancer accounts for 12% of cancer cases amongst women and is the second leading cause of death, where about 85% of the global burden of over 500,000 cases and 250,000 deaths from this disease occurred in 2012. The highest incidence occurs in Eastern Africa, where with Middle Africa, cervical cancer is the commonest cancer in women. The case fatality rate of 52% is also higher in developing countries than in developed countries (43%), and the mortality rate varies by 18-fold between regions of the world.[123][17][122]
It's even more important for older people to stay hydrated. Age can bring a decreased sensitivity to thirst. Moreover, it's sometime harder for those who are feeble to get up and get something to drink. Or sometimes a problem with incontinence creates a hesitancy to drink enough. Those who are aging should make drinking water throughout the day a priority.
Women's nutrition is often eclipsed by maternal nutrition. There are important linkages between maternal nutrition and the health, cognitive development, and earning potential of future generations (1). However, with reduced childbearing and longer life spans, women's experiences extend beyond motherhood (2). Interventions and policies that target women solely as mothers fail to account for women before they conceive, after they no longer engage with programs targeting maternal–child health, as well as those who never have children (3, 4). A woman's nutrition should matter not (only) because of her reproductive potential, but because it is fundamental to her rights as a person and to her well-being and ability to thrive (5–7). With increasing attention to the nutritional needs of adolescent girls (8, 9), in addition to the rising prevalence of overweight, obesity, and noncommunicable disease affecting women later in life (10), it is becoming more imperative that interventions reach women at all life stages.
Schools ("condition" and delivery platform) ↑ food expenditures, ↑/NC food share, ↑ HH food consumption, ↑ dietary diversity, ↑ HH intake of fruits, vegetables, and ASF, ↑/NC intake of fats and sweets ↑ knowledge about health and nutrition, ↑ food expenditures, ↑/NC food share, ↑ HH food consumption, ↑ dietary diversity, ↑ HH intake of fruits, vegetables, and ASF, ↑/NC intake of fats and sweets, ↑ participation in social networks, ↑ self-confidence, ↑ control HH resources ↑ knowledge about health and nutrition, ↑ HH food security, ↑ food expenditures, ↑/NC food share, ↑ HH food consumption, ↑ dietary diversity, ↑ HH intake of fruits, vegetables, and ASF, ↑/NC intake of fats and sweets, ↑ participation in social networks, ↑ self-confidence, ↑ control over resources ↑ knowledge about health, NC hypertension, ↓ missed meals, ↑ health care utilization
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Disability does not often strike like lightening. It is often preceded by a gradual decline in work ability due to a progressive illness or disease. It is difficult to decide when is the time to file a disability claim, but we can help you with this analysis. There are many intersecting issues with a physician becoming disabled, but the primary consideration is to continue to provide quality safe treatment to your patients. Stopping work before that becomes a problem is critical. Another issue is how can you protect your practice's value for sale, if you are less able to perform the quantity or type of medical care to patients? Finally, it is important to understand what financial documents are necessary to collect to substantiate the type of medical specialty you have been performing; in general most insurers require tax records as well as production summaries organized by CPT codes. We discuss all of these issues with our clients who are physicians to ease their concerns and direct them in this important critical time in their lives. We are available to help.
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This wonderful skincare set from Elizabeth Arden contains 6 travel size skincare products. Elizabeth Arden Eight Hour Must Have Travel Essentials Set. Elizabeth Arden Eight Hour Cream Skin Protectant The Original 50ml.
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Description: To facilitate understanding of the connections between DNA variation and phenotypic AMR, we developed VAMPr (variant mapping and prediction of antibiotic resistance). It utilized 3,393 sequenced bacterial isolates from 9 species along with AMR phenotypes for 29 antibiotics following the Clinical & Laboratory Standards Institute (CLSI) guidelines. It also detected 14,615 variant genotypes and provided 93 association and prediction models.
Description: Mask Regional Convolutional Neural Network (Mask-RCNN) is a newly developed deep-learning algorithm. We trained a Mask-RCNN model to segment tumor nuclei, stroma nuclei, lymphocyte nuclei, macrophage nuclei, karyorrhexis, and red blood cells in pathological Hematoxylin & Eosin (HE) stained images. Around 10,000 cells are covered in our training dataset from the National Lung Screening Trial (NLST) cohort. This tool aims to dissect tumor microenvironment in cell level.
Description: Single cell profiling techniques such as single cell sequencing and cytometry are powerful for comprehensive and high-resolution characterization of the cellular heterogeneities observed in tumors, brain, and other tissues. The identification and assignment of cell types from the pool of profiled cells is the first step of data analysis involving scRNA-seq or cytometry data. To achieve this goal, we developed the SCINA algorithm, short for Semi-supervised category identification and assignment. SCINA is originally designed to assign cell types based on single cell RNA-seq data.
Description: To estimate the gene expression levels and component proportions of the normal, stroma (immune) and tumor components of bulk tumor RNA-Seq samples. Although DisHet is designed for dissection of bulk tumor samples using matched normal tissue and tumorgraft RNA-seq data, it is widely applicable to dissection of gene expression of any mixture of 3 types of cells.
Description: Prognostic Model for Predicting Survival in Non Small Cell Lung Cancer Patients.
Description: Prognostic Model for Predicting Survival in Small Cell Lung Cancer Patients.
Description: Genomic Regression Analysis of Coordinated Expression (GRACE) is a method developed to remove effect of copy number alteration from co-expression analysis so that the resulting genes are mostly based on biological regulation. This database allows users to perform co-expression analysis with tumor or normal samples from various cancer types based on TCGA studies.
Description: The Lung Cancer Explorer is an online tool for exploring and analyzing gene expression data from dozens of accessible public lung cancer datasets.
Description: GeNeCK (Gene Network Construction Kit) is a comprehensive online tool kit that integrate various statistical methods to construct gene networks based on gene expression data and optional hub gene information.
Description: We developed a novel Drug-Induced Genomic Residual Effect (DIGRE) computational model to predict drug combination effects by explicitly modeling the drug response dynamics and gene expression changes after individual drug treatments. The DIGRE model won Best Performance in the National Cancer Institute's DREAM 7 Drug Combination Synergy Prediction Challenge, an international crowdsourcing-based computational challenge for predicting drug combination effects using transcriptome data.
Description: We developed a model-based approach to detect RNA-protein binding sites in HITS-CLIP. The two-stage model, which is inspired by the underlying spatial association of the read coverage and the positional bias of mutations, is established on all the sequencing reads (including non-clustered read sequences) to investigate binding sites at single base pair resolution. This toolbox provides essential MATLAB functions to implement our model for the identification of binding sites using heterogeneous logit models via semi-supervised learning.
Description: The photoactivatable ribonucleoside enhanced cross-linking immunoprecipitation (PAR-CLIP) has been increasingly used for the global mapping of RNA-protein interaction sites. This package provides an integrative model to establish a joint distribution of read and mutation counts. To pinpoint the interaction sites at single base-pair resolution, we adopts non-homogeneous hidden Markov models that incorporate the nucleotide sequence.
Description: dCLIP is written in Perl for discovering differential binding regions in two CLIP-Seq (HITS-CLIP or PAR-CLIP) experiments. It is appropiate in experiments where the common binding regions that are significantly enriched in both conditions tend to have similar binding strength and when researchers are more interested in the difference in binding strength rather than the binary event of whether binding site is common or not. For example, dCLIP will work when researchers would like to know the differential binding sites of AGO protein under a wild-type and miRNA knockdown condition.
Description: Identifying which genes are differentially expressed (DE) and which gene sets (such as functional categories, biological pathways, regulatory networks) are altered (i.e., overpopulated with up/down-regulated genes) under two experimental conditions are both key questions in microarray analysis. Although closely related and seemingly similar, they cannot replace each other, due to their own importance and contributions in scientific discoveries. Existing approaches have been developed to address only one of the two questions each time, but not both of them simultaneously. Bayesian joint modeling approach to address the two key questions in parallel, which incorporates the information of functional annotations (or other biological grouping information such as pathways or networks of genes) into expression data analysis and meanwhile infer the enrichment of functional groups (or other types of gene sets).
Description: High-throughput RNAi screening has been widely used in a spectrum of biomedical research and made it possible to study functional genomics. However, a challenge for authentic biological interpretation of large-scale siRNA or shRNA-mediated loss-of-function studies is the biological pleiotropy resulting from multiple modes of action of siRNA and shRNA reagents. A major confounding feature of these reagents is the microRNA-like translational quelling that can result from short regions (~6 nucleotides) of oligonucleotide complementarity to many different mRNAs. To help identify and correct miRNA-mimic off-target effects, we have developed DecoRNAi (deconvolution analysis of RNAi screening data) for automated quantitation and annotation of microRNA-like off-target effects in primary RNAi screening data sets. DecoRNAi can effectively identify and correct off-target effects from primary screening data and provide data visualization for study and publication. DecoRNAi contains pre-computed seed sequence families for 3 commonly employed commercial siRNA libraries. For custom collections, the tool will compute seed sequence membership from a user-supplied reagent sequence table. All parameters are tunable and output files include global data visualization, the identified seed family associations, the siRNA pools containing off-target seed families, corrected z-scores and the potential miRNAs with phenotypes of interest.
Description: Connects to QBRC's EntrezToProbe engine system to handle mappings between probes and genes and provide access to information about probes and genes.
Description: Genome-wide RNAi screening experiments are customarily carried out on hundreds of 96-well or 384-well plates in order to study gene functions and discover novel drug targets. Spatial background noises however often blur interpretation of experimental results by distorting the distinct spatial patterns between different plates. It is therefore important to identify and correct the spatial background noises when analyzing RNAi screening data. Here, we developed an algorithm SbacHTS (Spatial background correction for High-Throughput RNAi Screening), for visualization, estimation and correction of spatial background noises of RNAi screening experiment results. SbacHTS can effectively detect and correct spatial background noise leading to higher signal/noise ratio and improved hits discovery for RNAi screening experiments. The only input required by the algorithm is the raw reads from the replicate plates.
Description: This package provides a model-based background correction method, which incorporates the negative control beads to pre-process Illumina BeadArray data.
Description: Ensemble network aggregation is an approach which leverages the inverse-rank-product (IRP) method to combine networks. This package provides the capabilities to use IRP to bootstrap a dataset using a single method, to aggregate the networks produced by multiple methods, or to aggregate the networks produced on different datasets. Additionally, it offers convenience functions for converting between adjacency lists and matrices, and computing discrete graphs based on the Rank-Product method.
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An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom
J. K. Cowell, M. Jay, P. Rutland, J. Hungerford
Fifty retinoblastoma families have been studied. In 41 it has been possible to determine the esterase-D phenotypes in all family members. Seven families were informative for the enzyme polymorphism and in all cases cosegregation of the retinoblastoma gene and esterase-D alleles was demonstrated, giving a lod score of 2.61. When combined with other published reports the cumulative lod score is 13.69 with no recombination in 45 meioses. In 10–15% of retinoblastoma families therefore, it is possible to offer prenatal diagnosis using the ESD protein polymorphism. The application of this test to the retinoblastoma population in the UK is limited by the low frequency of the rarer allele (0.116) and, as a result of genetic counselling, the smaller families generally associated with retinoblastoma.
https://doi.org/10.1038/bjc.1987.135
10.1038/bjc.1987.135
Dive into the research topics of 'An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom'. Together they form a unique fingerprint.
s-formylglutathione hydrolase Medicine & Life Sciences 100%
Retinoblastoma Medicine & Life Sciences 65%
Prenatal Diagnosis Medicine & Life Sciences 56%
Lod Score Medicine & Life Sciences 31%
Retinoblastoma Genes Medicine & Life Sciences 15%
Meiosis Medicine & Life Sciences 12%
Genetic Counseling Medicine & Life Sciences 12%
Gene Frequency Medicine & Life Sciences 10%
Cowell, J. K., Jay, M., Rutland, P., & Hungerford, J. (1987). An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom. British Journal of Cancer, 55(6), 661-664. https://doi.org/10.1038/bjc.1987.135
An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom. / Cowell, J. K.; Jay, M.; Rutland, P.; Hungerford, J.
In: British Journal of Cancer, Vol. 55, No. 6, 06.1987, p. 661-664.
Cowell, JK, Jay, M, Rutland, P & Hungerford, J 1987, 'An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom', British Journal of Cancer, vol. 55, no. 6, pp. 661-664. https://doi.org/10.1038/bjc.1987.135
Cowell JK, Jay M, Rutland P, Hungerford J. An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom. British Journal of Cancer. 1987 Jun;55(6):661-664. https://doi.org/10.1038/bjc.1987.135
Cowell, J. K. ; Jay, M. ; Rutland, P. ; Hungerford, J. / An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom. In: British Journal of Cancer. 1987 ; Vol. 55, No. 6. pp. 661-664.
@article{3492eebe5a75444fb94cef9bc1fb8cf1,
title = "An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom",
abstract = "Fifty retinoblastoma families have been studied. In 41 it has been possible to determine the esterase-D phenotypes in all family members. Seven families were informative for the enzyme polymorphism and in all cases cosegregation of the retinoblastoma gene and esterase-D alleles was demonstrated, giving a lod score of 2.61. When combined with other published reports the cumulative lod score is 13.69 with no recombination in 45 meioses. In 10–15% of retinoblastoma families therefore, it is possible to offer prenatal diagnosis using the ESD protein polymorphism. The application of this test to the retinoblastoma population in the UK is limited by the low frequency of the rarer allele (0.116) and, as a result of genetic counselling, the smaller families generally associated with retinoblastoma.",
author = "Cowell, {J. K.} and M. Jay and P. Rutland and J. Hungerford",
doi = "10.1038/bjc.1987.135",
T1 - An assessment of the usefulness of electrophoretic variants of esterase-D in the antenatal diagnosis of retinoblastoma in the United Kingdom
AU - Cowell, J. K.
AU - Jay, M.
AU - Rutland, P.
AU - Hungerford, J.
N2 - Fifty retinoblastoma families have been studied. In 41 it has been possible to determine the esterase-D phenotypes in all family members. Seven families were informative for the enzyme polymorphism and in all cases cosegregation of the retinoblastoma gene and esterase-D alleles was demonstrated, giving a lod score of 2.61. When combined with other published reports the cumulative lod score is 13.69 with no recombination in 45 meioses. In 10–15% of retinoblastoma families therefore, it is possible to offer prenatal diagnosis using the ESD protein polymorphism. The application of this test to the retinoblastoma population in the UK is limited by the low frequency of the rarer allele (0.116) and, as a result of genetic counselling, the smaller families generally associated with retinoblastoma.
AB - Fifty retinoblastoma families have been studied. In 41 it has been possible to determine the esterase-D phenotypes in all family members. Seven families were informative for the enzyme polymorphism and in all cases cosegregation of the retinoblastoma gene and esterase-D alleles was demonstrated, giving a lod score of 2.61. When combined with other published reports the cumulative lod score is 13.69 with no recombination in 45 meioses. In 10–15% of retinoblastoma families therefore, it is possible to offer prenatal diagnosis using the ESD protein polymorphism. The application of this test to the retinoblastoma population in the UK is limited by the low frequency of the rarer allele (0.116) and, as a result of genetic counselling, the smaller families generally associated with retinoblastoma.
U2 - 10.1038/bjc.1987.135
DO - 10.1038/bjc.1987.135
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An ulcer is a break in the integrity of the skin. Ulcers are graded or evaluated based upon their level of depth. The simplest is a break in the epidermis. The most complex are through the subcutaneous tissue and even down through tendon and into bone. Ulcers are most commonly due to increased and/or inappropriate stress, friction, sheer forces, or pressure areas. The foot and ankle, in addition to the sacral area, are the most common sites of ulcerations because these areas are exposed to the forces mentioned above. A contracted toe or displaced bone often place stress to the overlying skin, causing breakdown. Diabetics are most predisposed due to a likelihood of decreased sensation and/or circulation to the foot. The diabetic's inability to sensate or appreciate stress to the skin makes he or she a likely candidate. Impaired circulation can also weaken the integrity of the skin and contribute to the formation of ulcers. Finally, lower extremity swelling can also stress the skin and cause ulcerations at the lower leg and ankle level. A variety of treatment options exist to help prevent or heal ulceration. A complex exam and diagnostic tests are often needed to determine the underlying cause.
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Source: New Forests, Vol. 46(5-6): 22 pages.: 897-918.
There is interest in restoring shortleaf pine (Pinus echinata) in pine–oak woodlands where it once was abundant. Because of its shade intolerance and slow initial growth rate, shortleaf pine restoration has remained a challenge because competition from hardwoods exhibits greater initial growth following canopy removal but greater shade tolerance with canopy retention. The study objective was to examine the survival and growth of underplanted shortleaf pine seedlings relative to competing hardwoods as a function of initial seedling size, overstory density, and understory competition. In the Ozark Highlands of southeastern Missouri, USA, 48, 0.4-ha experimental units were each harvested from below to a uniform stocking level from 0 to 90 % and 30, 1-0 improved shortleaf pine seedlings were planted on a 3.7 9 7.3 m spacing. Linear or logistic regression was used to determine how shortleaf pine seedling (1) survival, (2) basal diameter growth, and (3) shoot growth were related to initial seedling size, overstory stocking, and understory competitor height during the first 5 years after underplanting. After five growing seasons, the survival rate of shortleaf pine seedlings was 50 % and was positively related to the initial basal diameter but was not related to overstory stocking or competitor height. Increasing overstory stocking decreased the basal diameter and height growth of shortleaf pine seedlings, explaining>51 % of the variation in basal diameter and 54 % of the variation in seedling height. Although competing hardwood seedlings were consistently taller than the shortleaf pine seedlings throughout the study, shortleaf pine seedlings maintained similar growth rates as competitors from the second to the fifth growing season. The eventual release of shortleaf pine is essential for recruitment, but releases can be delayed for several years after underplanting.
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The implications of living with heart failure; the impact on everyday life, family support, co-morbidities and access to healthcare: a secondary qualitative analysis
Mirella Fry1,
Sarah McLachlan2,
Sarah Purdy3,
Tom Sanders4,
Umesh T. Kadam5,6 &
Carolyn A. Chew-Graham5
The aim of this study was to use secondary analysis to interrogate a qualitative data set to explore the experiences of patients living with heart failure.
The data-set comprised interviews with 11 patients who had participated in an ethnographic study of heart failure focusing on unplanned hospital admissions. Following an initial review of the literature, a framework was developed with which to interrogate the data-set. This was modified in light of analysis of the first two interviews, to focus on the rich data around patients' perceptions of living with heart failure, managing co-morbidities, accessing healthcare and the role of their family and friends, during their illness journey.
Respondents described how the symptoms of heart failure impacted on their daily lives and how disruption of routine activity due to their symptoms caused them to seek medical care. Respondents disclosed the difficulties of living with other illnesses, in addition to their heart failure, particularly managing multiple and complex medication regimes and negotiating multiple appointments; all expressed a desire to return to their pre-morbid, more independent lives. Many respondents described uncertainty around diagnosis and delays in communication from their healthcare providers. The importance of family support was emphasised, but respondents worried about burdening relatives with their illness.
Living with heart failure causes disruption to the lives of sufferers. Facilitation of access to healthcare, through good communication between services and having a strong support network of both family and clinicians can reduce the impact of heart failure on the lives of the patient and those around them.
A chronic illness, by definition, is a disease which persists for a long period of time and can cause continuous or episodic periods of incapacity [1]. Bury 1982 describes the effects of chronic illness as 'biographical disruption' to everyday life, and not only disruption to the individual suffering with the illness, but their families and wider social network [2]. Patients and their families may seek out information, support, and the most effective strategies to manage their symptoms, in the effort to minimise potential future disruption [3].
Heart failure is prevalent in the UK [4]; common symptoms include breathlessness, peripheral oedema and fatigue, all of which interfere with daily life [5]. Patients typically have multiple chronic co-morbidities, each of which may have a complex treatment regime [6]. Self-management of multiple chronic illnesses, educating patients to monitor their own health and being able to recognise illness severity are current features of healthcare policy [7].
Symptom unpredictability has been reported to leave patients feeling helpless and completely dependent on those around them, leading to a lack of control of the illness and an increased burden on family and the healthcare system [8]. Responsibility for care may shift from the patient to their spouse or immediate family. In these circumstances the patient may adopt the 'sick role', relying on their family for support both with their illness and previous responsibilities [9]. It has been reported [10] that in patients with greater levels of family support, confidence between members is increased, and family ties strengthened, in times of need such as ill-health. Therefore, congruent beliefs about the illness are important in order to achieve successful family functioning and to enhance patient well-being [10].
Previous studies exploring heart failure and patients' quality of life suggest that balancing treatment regimens of multiple co-morbidities and the additional symptoms from co-morbidities could be extremely difficult for patients [5, 11]. Challenges for patients managing multiple illnesses include; lack of care co-ordination, a greater need for support and more time needed to develop techniques to manage multiple illnesses [9]. Patients' understanding of heart failure and how to manage has been reported as poor, leading to a cycle of hospital (re) admissions, which is not only disruptive for the patient but also places significant pressure on secondary care and increases healthcare cost [5].
There appears to be little consideration to the interaction between different health conditions by healthcare professionals. However, patients have been reported to manage their multiple illnesses by active weighing up of possible treatment options across their different health conditions [11, 12]. The degree of agreement (or otherwise) in prioritising multiple conditions between the patient and clinician and between different clinicians and the patient, can affect subsequent self-management, such as treatment adherence and future therapeutic relationships [8].
The relationship between a patient and their doctor is the foundation for effective management of chronic illness [13, 14]. An effective doctor-patient relationship is founded on high quality communication, which could be defined as the promotion of information gathering, agreement on therapeutic options and patient support [15]. Effective organisation within the healthcare system can provide continuity within clinical relationships [16]. Conversely, poor communication can result in patient uncertainty, confusion and worry, reducing a patient's quality of life and ability to recover from illness. In vulnerable patients the doctor-patient relationship is important as patients may experience increased dependence on the doctor [12, 17]. Effective communication can ensure that doctors are aware of the patients' expectations, help to regulate their emotions and facilitate the understanding of information, which will ultimately lead to greater patient satisfaction [18]. Clinician and nurse availability can give patients a sense of security, as the patient understands that time and effort has been invested to accommodate them and provide information or reassurance [19].
This paper focuses on the secondary analysis of data collected from HoldFAST, a multicentre study including Bristol, Oxford and Keele Universities, which was funded by the National Institute for Health Research. The aim of collecting qualitative data from these participants was to gain an in-depth insight into the pathways towards, and reasons for, unplanned hospital admissions in patients with heart failure. The HoldFAST study aimed to explore patients' experiences from multiple standpoints using ethnographic methods, combining observations, interviews and documentary data sources [20]. This paper reports a secondary analysis which focused on patients' perspectives of living with and managing heart failure and the impact of the management of multiple illnesses, the importance of the doctor-patient relationship, and the role of family and friends, illuminating areas of heart failure care and patient experience that have been insufficiently explored in the previous literature.
This study involved secondary analysis of a data-set collected as part of a wider multi-centre investigation, to gain an in-depth insight into the pathways towards, and reasons for, unplanned hospital admissions in patients with heart failure. [20] Primary analysis of the whole data-set had already been conducted, [20] but the data-set comprising patient interviews had not been analysed independently.
For the HoldFAST study, a semi-structured topic guide had been developed by the research team, which allowed respondents to express their experiences of having heart failure along different points in the clinical pathway using a technique referred to as a 'patient-led ethnography', which captures views and experiences during important or critical episodes during the patient's illness journey. Each interview was carried out within the participants' homes, digitally recorded and transcribed for thematic analysis by the primary researchers. However, shorter 'debrief' discussions were held with patients during 'critical moments' such as at clinic appointments, GP visits, conversations on the way to or from hospital. The lead researcher (SMc) kept in regular contact with patients who were asked to notify the research team prior to any planned clinic appointments or 'eventful' illness episodes that they experienced in order to trigger a visit or telephone discussion by the researcher. This approach provided insights into patients' naturally evolving illness experiences related to their heart failure journey, and enabled the researchers to record events as they happened, or shortly afterwards. This technique is different from traditional single interviews, as it helped to capture an evolving storyline in the patients' lives across a period of up to 6 months, to offer a deeper insight into their daily and weekly illness experiences and contacts with health services, particularly around hospital admission.
Ethical approval for the HoldFAST study was granted by NRES Committee South West - Frenchay, Bristol, and local approvals were obtained from Staffordshire Cluster of PCTs Research Management and Governance Office, and the Research & Development Department of University Hospital of North Staffordshire NHS Trust. The original consent form for the HoldFAST study asked the patient to consent to the use of data for further research within the research institutes.
The aim of this secondary analysis was to interrogate a single data-set (the 'exit interviews) from an independent perspective, in order to critically evaluate the data with the aim of identifying key experiences and impact of living with heart failure and to gain a deeper understanding, and maximise use, of the data [21, 22].
The data comprised anonymised interview transcripts from the participants who had been identified and recruited for the HoldFAST study from a cardiology ward and specialist heart failure ambulatory clinic from three geographical locations within the UK; the Midlands, South Central and the South West of England. Patients with severe or difficult to manage heart failure from the Midlands and South Central and less 'severe' patients from a primary care centre from the South West of England were approached. They were given information leaflets and given at least 24 h to consider participating before being contacted by members of the research team. From those willing to participate (N = 31) written consent was taken. Nine patients (4 males and 5 females with a mean age = 71.2 years) and three female carers were recruited for the main study. Two patients and three carers also agreed to write diaries. Two other patients (1 male, 1 female) were not recruited into the main HoldFAST study but agreed to participate in single in-depth interviews. The data used for the current analysis were collected over an 11 month period during 2011–2013 and focused on one of the three research sites. The interviews presented in this paper were conducted at the end of the study, (we called these 'exit interviews') and encouraged patients to reflect on their illness journey since their diagnosis as well as on their experiences prior to diagnosis. The time of the exit interview from the initial invitation to participate in the study, was up to 6 months.
For this study, a secondary analysis of the interview data was conducted. This involved re-visiting the ten exit interviews and one set of field notes for an interview which wasn't audio recorded. Following familiarisation with the data-set, each interview was read thoroughly by MF, SMc and CCG and the most prominent themes were identified and agreed. Linking this with the existing literature, a framework was developed by MF, SMc and CCG (see Table 1) to interrogate the data-set.
The initial framework included the questions:
Table 1 The questions initially developed to interrogate the interview data
As coding of the first two interview transcripts progressed using the framework (Table 1), and with discussion within the supervisory team, it became apparent there was rich data on the impact of symptoms on everyday life, and narrative about relationships with healthcare practitioners, access to care and the importance of patients' support networks. Thus, the framework used was modified to include these themes (Table 2) and used interrogate the rest of data-set.
The revised framework included the questions:
Table 2 Questions from the revised framework were used to interrogate the data
High level codes, which highlighted repetitive themes, were identified within the transcripts, using the framework through an iterative method. Regular discussion with the supervisory team (CCG and SM) ensured agreement on coding and that any discrepancies were resolved. These themes had not been previously developed in the primary analysis (as this data-set had not been analysed on it's own) and thus our analysis provided new insights from the same data set.
Using the above framework a number of prominent themes will be presented. These are: 1) the impact of illness on everyday life, 2) the role of family and friends in providing support, 3) relationships with health professionals, 4) managing multiple illnesses, and 5) access to healthcare. Each theme is presented and supported by illustrative data, followed by the participant's unique identifier.
Table 3 gives details of the study participants. Data is given to illustrate each of the themes presented.
Table 3 Participant demographics
Implications of living with heart failure
Impact of illness on everyday life
Participants described the impact on their lives of living with heart failure symptoms. They described how they experienced the symptoms of heart failure and their impact on everyday routines.
"Because really you know it's a condition and sometimes you know, the fluid, obviously my ankles hurt…" KP8
"I'd taken the dog for a walk and something started and I thought whatever's the matter this strange and then I said to my husband, I'm not well…" KP1
Some participants reported that they had not initially recognises their symptoms as being related to heart failure, and therefore were slow to act upon them at the start of their illness. Following receipt of a diagnosis, participants and their family described heart failure symptoms as a 'disruption' to their lives, which made them accept their illness and the limitations of their condition.
"I remember I didn't feel as hungry and everything seemed to be sticking you know kind of thing, you know, when you've sort of eaten too much…" KP1
Participants reported a wide range of symptoms, which individually may not self-evidently indicate heart failure. These symptoms limited the patients' quality of life and impacted on them and their families. Educating patients with heart failure to recognise early symptoms will empower them with the knowledge to identify exacerbations and engage in preventative self-management.
Managing multiple illnesses
The majority of respondents stressed the impact of other health problems in combination with their heart failure. They described the difficulty of differentiating the symptoms they were experiencing as a result of the heart failure from their other co-morbidities or side-effects of medications.
"…but then you don't know if it's a cough…so you don't know whether it's a coldy-cough or whether it's something to do with the medication." KP6
"..all the symptoms were there for heart failure but then the symptoms were there like me blood glucose dipped down to two point something so you know it was a mixture of…" KP3
The main impact of their other illnesses seemed to be the difficulty of managing complex medication regimes.
"While he's still messing with the gout medicine he thinks they'll have to keep me on…"KP5
"…of course I was on tablets already for high blood pressure, which I've been on for years, and they changed all those". KP7
Some respondents reported that they felt that other health conditions they had seemed to be de-prioritised during their treatment for heart failure. This sometimes affected respondents' feelings towards other healthcare professionals, and they suggested that their co-morbidities were not given equal attention as their heart failure.
"They were more concerned about the lungs to be honest with you than they were about the heart then…I suppose you go from one of them." KP2
"I was very worried because I thought well I knew I'd got high blood pressure but I thought if they take me off these tablets what will happen you know about my high blood pressure but he said 'forget all about that, we'll put you on these others' which they did." KP1
Respondents also discussed the difficulties in managing multiple appointments for their different conditions.
"I think the 9th of October that's in my kidneys… Yeah it's every about four months, six months, just depends what's going on next week… I was too upset about this cancer to be honest but she thinks, er, I probably won't get any treatment because I'm too poorly but I'll have to wait to see what he says on Tuesday". KP9
Many of the respondents had multiple illnesses; however they suggested that their heart failure was often prioritised by clinicians, who considered it as having a greater impact on morbidity and mortality.
The role of family and friends
All of the respondents interviewed discussed their feelings about having or not having a support network of family and/or friends during their illness and the impact this had on them emotionally.
"But my eldest lad, [name of KP10's elder son], said you never saw yourself dad, you looked bloody terrible..... that was when they took me… to the accident and emergency" KP10
"If [name of KP7's son] and [name of KP7's son's partner] hadn't had been so good, you know, coming down. They'd come and clean through for me a few times er during that period 'cause they got on top of me." KP7
Some respondents reported family members who took a very proactive role in trying to help participants, either by contacting the health services on their behalf or suggesting decisions for the patient against other doctors' recommendations.
"I've got a very good friend whose husband is a medical consultant and I did speak to him because I was so concerned and he actually gave me a lot of advice of what to do and what to say to the GP if she didn't do, erm, what he'd actually advised she should do." KP4
KP11s' daughter repeatedly asked to see the doctor to seek out explanations-(KP11s' field notes).
Only one respondent identified a lack of immediate family support, and she described a sense of worry and lack of confidence in managing her heart failure:
"I hope to go shopping but I just feel that I need somebody with me where it's never bothered me before…but I used to, you know never a care in the world really despite of all my problems." KP1
In contrast, the other respondents with strong support networks of family and friends, appeared to accept their diagnosis of heart failure more quickly and described looking to get back to their normal everyday lives building on that support.
"I'm on top of it again now… I've taken charge of it all myself… They cut me lawns for me and that sort of thing, because doing the mowing now – that does kill me ....But as far as the house is concerned, and washing is concerned, I'm doing all me own" KP7
Family and friends were seen to be key to patients' recovery.
Relationships with healthcare professionals
Respondents expressed a spectrum of opinions about the care they had received from their healthcare professionals. They showed appreciation for specialist doctors and specialist heart failure nurses, who were perceived to spend a greater amount of time providing information both to the participants and their families.
"He's marvellous… we thought that was really good, because if he spends time with everybody like that then it's like the old-fashioned doctor, isn't it really? Instead of just packing you off…" KP6
"..but they explained what was going on, which to me is good you know because they can explain things and I won't worry" KP10
"He's lovely, I always had a kiss and a hug when I go in and out the clinic… Well he's looked after me for the last six years with Dr L so, er, we know one another" KP9
However, some respondents were less positive about primary care professionals. A number of respondents reported an apparent delay in diagnosis by their GP, which had negative effects on their relationship.
"That was while the doctors were saying chest infections… so they weren't spotting the fluid." KP5
"Oh it's your asthma, here....he didn't even examine me....it's only when my legs started, my ankles started swelling and we insisted." KP4
Those respondents, who expressed some negative feelings towards particular clinicians, described how they were wary about future encounters and the confidence the respondents had in those clinicians.
"he said he wouldn't go to the doctors because you felt that, you know, if they just give you another inhaler." KP4
"But I wasn't my normal GP he just left it at that, I always wonder, mind you I don't think it could have been avoided what happened." KP1
Respondents who reported consultations with clinicians who were not their registered primary care doctor, described negative feelings towards the doctor, and attributed any delay in receiving appropriate care to this doctor. Respondents who described such negative encounters with clinicians reported this as a barrier to seeking care in the future.
Respondents expressed a range of views about the care and support they received from the different healthcare professionals and about access to and interaction with the healthcare system.
Respondents described a lack of pro-active contact from the healthcare system, both from hospitals and primary care, regarding scheduling appointments and the next stages in their care pathway. These respondents described a degree of uncertainty what would happen next and whose responsibility it was to monitor and support them. They expressed uncertainty about whose responsibility it was to initiate communication, when hospitals or primary care failed to send information to the respondents as they had said they would.
"…oh dear could be 18 months ago something like that…I think the doctors must have sent me but I never heard anything from that at all so I don't know". KP1. This respondent also went on to say, "the doctor's surgery perhaps could have shown a bit more support but on the other hand perhaps I should have just rung and you know, so perhaps it's up to me".
"I went to see, er, Dr E, er, whose first words when I went into the appointment were 'Why are you here?' and I said, 'I haven't a clue because I don't know who you are or what you do or anything', and he said 'No I don't know who you are either'". KP5
Other respondents, however, described certain healthcare professionals as being exceptionally efficient at facilitating direct access to themselves or other parts of the healthcare system quickly. In these instances, patients expressed appreciation for the effectiveness of that particular doctor or nurse, which led to anticipation of a positive future relationship between the healthcare professional and the patient.
"'I remember the radiographer at the hospital said it would be ten days for the results'…sent it straight through....everything marvellous" KP6
Those respondents who felt that their concerns had been dismissed by particular clinicians, or that they had not been listened to reported a negative impact on the future relationship with those clinicians.
Summary of results
All participants described the symptoms of heart failure as a disruption to their everyday life and limited their ability to perform routine activities, which led to frustration and a significant loss of confidence, and ultimately caused patients to question their own identity and self-esteem.
Factors which can influence how heart failure may disrupt patients' lives include the speed and efficiency of a diagnosis and treatment. Many respondents described initial misdiagnoses of their illness, which led to significant delays in the correct treatment being instituted. As a consequence of perceived delays in diagnosis, respondents reported losing confidence in their doctors' abilities to provide the right care for them, which impacted on future help-seeking. Lack of communication between the healthcare system and the participants led to further confusion and concern.
The majority of respondents mentioned how their family and friends played a role in supporting the management of their illness. Where respondents had some medical expertise in the family, they reported agreeing with their families' opinion over that of the doctors.
For the one respondent who didn't have immediate family support, she reported a greater loss of confidence and contrasted her illness journey to that of her husband, where she perceived that had received more support and care. This respondent, along with the others, was interested in returning to 'normal' and regaining their independence; her lack of confidence, however, impacted on her ability to self-manage and self-monitor her symptoms.
Comparison with previous literature
The findings from this study support previous studies conducted on the patient's experiences of living with heart failure. [23] In addition, our findings support Bury's description of a 'biographical disruption', with symptoms and management leading to lives disrupted from their everyday 'norm' [2, 24].
The challenge of managing multiple conditions was described, with patients responding to different exacerbations of their illnesses and prioritising the management of their conditions based on the effect each illness had on their daily lives, and individual clinicians being seen to prioritise the illness which they were expert in treating [8].
The results of this analysis highlight the importance of the doctor-patient relationship, with the findings consistent with those of other studies, as patients described a lack of trust or confidence in doctors that were not their 'usual' doctor [15, 16]. As well as doctors 'knowing' their patients, the patients had a sense of security 'knowing' their doctors, demonstrating the importance of experience and trust between a doctor and their patient, since it provides a gateway to accessing healthcare. Respondents seemed to assign blame to the doctors who were not their 'usual' healthcare provider, if anything went wrong, or to contemplate if things would have been done differently if their 'usual' doctors had been involved instead.
Poor communication can impact on patient care and outcomes [25]. Respondents described receiving unclear directions about their care pathway and ongoing support from their diagnosing doctors, and were confused about whose responsibility it was to initiate communication between hospital and primary care.
All respondents were positive about the specialist heart failure nurses, who were perceived to have more time to dedicate to patients, for explaining their illness and providing support, which was greatly appreciated by the respondents. This additional time allowed for greater patient education on anticipatory care, which involved identifying symptoms that the participant should look out for, to indicate an exacerbation of their illness. Specialist nurses are thought to have greater opportunities to provide education and support to patients and are able to liaise with different clinicians coordinating care to participants with complex multiple co-morbidities [26]. The results from this study reinforce the need for specialist heart failure nurses in the continued management, education and support of patients.
The findings are consistent with previous qualitative studies reporting that who found that respondents described a sense of burden on those around them, but agreed that it would be worse if they were alone [5]. Some respondents described 'trying to make the best of it' and trying as best they could to get back to normality, with the help of their loved ones.
Secondary analysis of the HoldFast data has provided support for results from previous qualitative studies and has highlighted how the difficulties in communication between health professionals across sectors impact on the management of patients as a whole.
The main strength of this study is that a secondary analysis of previously collected qualitative data was performed. This is ethically sound as secondary analysis offers the opportunity to utilise the rich data from the primary study, from another perspective, thus providing another voice to the perspectives of the participants, who invested considerable time and effort in participating [21].
The study has a number of limitations: only one set of interviews, the 'exit interviews', were analysed for this study, which may mean that upon analysis of the whole data set, patients' perspectives may be reported slightly differently. This may also mean that the transferability of this data to the general population of heart failure patients may be limited. The sample size (N = 11) is also relatively small, although category saturation had been achieved in the larger data-set.
Implications for future practice
This study emphasises the importance of good communication between patients and their HCPs; respondents valued clinicians who took time to elicit their concerns, and recognised the burden of their symptoms and management. This study demonstrated that clinicians need to be more aware of patient co-morbidities and burden of treatment, and the increasing need to liaise with other clinicians to provide care for the whole patient, not just for individual conditions. In addition, further clinician education on recognising a diagnosis of heart failure and being able to confidently communicate this to the patient is required, both in primary and secondary care.
The results from this study highlight the importance of education both for current health professionals and aspiring medical students on the value of communication, with patients and other members of the multidisciplinary team. Specifically, lessons can be learned on how to manage patients with multiple co-morbidities and to communicate those management plans both with the other health professionals involved with their care and to the patient themselves. Effective communication can influence a patient's overall perspective of their illness and to turn a diagnosis of heart failure from something that prompts 'biographical disruption' into something that a patient can accommodate.
Anon. Definition of chronic illness. 2015. http://www.medicinenet.com/script/main/art.asp?articlekey=33490 Accessed 25 June 2015.
Bury M. Chronic illness as biographical disruption. Sociol Health Illn. 1982;4(2):167–80.
Bury M. The sociology of chronic illness: a review of research and prospects. Sociol Health Illn. 1991;13(4):451–68.
Stewart S, MacIntyre K, Capewell S, McMurray JJV. Heart failure and the aging population: an increasing burden in the 21st century? Heart. 2003;89:49–53.
Pattenden JF, Roberts H, Lewin RJP. Living with heart failure; patient and carers perspectives. Eur J Cardiovasc Nurs. 2007;6:237–79.
Naylor MD, Brooten DA, Campbell RL, Maislin G, McCauley KM, Scwartz JS. Transitional care of older adults hospitalized with heart failure: a randomized control trial. J Am Geriatr Soc. 2004;52(5):675–82.
Kendall E, Ehrlich C, Sunderland N, Muenchberger H, Rushton C. Self-managing versus self-management: reinvigorating the sociopolitical dimensions of self-management. Chronic Illness. 2010;7(1):87–98.
Morris RL, Sanders C, Kennedy AP, Rogers A. Shifting priorities in multimorbidity: a longitudinal qualitative study of patient's prioritization of multiple conditions. Chronic Illn. 2011;7(2):147–61.
Rolland JS. Family illness paradegms: evolution and significance. Fam Syst Med. 1987;5(4):482–502.
Arestedt L, Benzein E, Persson C. Families living with chronic illness: beliefs about illness, family, and health care. J Fam Nurs. 2015;21(2):206–31.
du Vaure B, et al. Potential workload in applying clinical practice guidelines for patients with chronic conditions and multimorbidity: a systematic analysis. BMJ Open. 2016;6:e010119.
Ridd M, Shaw A, Lewis G, Salisbury C. The patient-doctor relationship: a synthesis of qualitative literature of patients' perspectives. Br J Gen Pract. 2009;59(561):e116–33.
Fong Ha J, et al. Doctor-patient communication: a review. Ochsner J. 2010;10:38–43.
Goold SD, Lipkin M. The doctor-patient relationship: challenges, opportunities and strategies. J Gen Intern Med. 1999;14(1):S26–33.
Cocksedge S, Greenfield R, Nugent GK, Chew-Graham CA. Holding relationships in primary care: a qualitative exploration of doctors' and patients' perceptions. Brit J Gen Pract. 2011;61:e484–91.
Freeman G, Hughes G. The Kings Fund: Continuity of care and the patient experience. The Kings Fund; 2010. www.kingsfund.org.uk/sites/files/kf/field/field_document/continuity-care-patient-experience-gp-inquiry-research-paper-mar11.pdf. Accessed 13 Apr 2016.
Fairhurst K, May C. Knowing patients and knowledge about patients: evidence of modes of reasoning in the consultation? Fam Pract. 2001;18(5):501–5.
Cheraghi-sohi S, Bower P, Kennedy A, Morden A, Rogers A, Richardson J, Sanders T, Stevenson F, Ong BN. Patient priorities in osteoarthritis and comorbid conditions: a secondary analysis of qualitative data. Arthritis Care Res. 2013;65(6):920–7.
MacKenzie E, Smith A, Angus N, Menzies S, Brulisauer F, Leslie SJ. Mixed-method exploratory study of general practitioner and nurse perceptions of a new community based nurse-led heart failure service. Rural Remote Health. 2010;10:1510.
Simmonds R, Glogowska M, McLachlan S, Cramer H, Sanders T, Johnson R, Kadam U, Lasserson D, Purdy S. Unplanned admissions and the organisational management of heart failure: a multicentre ethnographic, qualitative study. BMJ Open. 2015;5(e):007522.
Heaton J. Secondary analysis of qualitative data: an overview. Hist Soc Res. 2008;33(3):33–45.
Chew-Graham CA, Kovandzic M, Gask L, Burroughs H, Clarke P, Sanderson H, Dowrick C. Why may older people with depression not present in primary care? Messages from secondary analysis of qualitative data. Health Soc Care Community. 2012;20(1):52–60.
Gwaltney CJ, Slagle AF, Martin M, Ariely R, Brede Y. Hearing the voice of the heart failure patient: key experiences identified in qualitative interviews. Br J Cardiol. 2012;19:25.
Williams SJ. Chronic illness as biographical disruption or biographical disruption as chronic illness? Reflections on a core concept. Sociol Health Illn. 2000;22(1):40–67.
Glogowska M, Simmonds R, McLachlan S, Cramer H, Sanders T, Johnson R, Kadam UT, Lasserson DS, Purdy S. "Sometimes we can't fix things": a qualitative study of healthcare professionals' perceptions of end of life care for patients with heart failure. BMC Palliat Care. 2016;15:3.
Glogowska M, Simmonds R, McLachlan S, Cramer H, Sanders T, Johnson R, Kadam UT, Lasserson DS, Purdy S. Managing patients with heart failure: a qualitative study of multidisciplinary team with specialist heart failure nurses. Ann Fam Med. 2015;13(5):466–71.
This paper presents independent research funded by the National Institute for Health Research School for Primary Care Research (NIHR SPCR). The views expressed are those of the author(s) and not necessarily those of the NIHR, the NHS or the Department of Health.
TS was supported in the preparation/submission of this paper by the Translating Knowledge into Action Theme of the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care Yorkshire and Humber (NIHR CLAHRC YH). http://www.clahrc-yh.nihr.ac.uk. (The views and opinions expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.)
CCG is part funded by the Collaboration for Leadership in Applied Health Research and Care, West Midlands.
N/A.
MF led the secondary analysis and drafted the manuscript. SMc conducted original interviews in the HoldFAST study, worked on the primary analysis of the HoldFAST data-set, supported MF in conducting the secondary analysis and commented on drafts of this manuscript. SP conceived of the study, was Chief Investigator on the HoldFAST study, and contributed to the writing of this manuscript. TS led design of the qualitative study, worked on primary analysis of the HoldFAST data and commented on drafts of this manuscript. UK commented on drafts of this manuscript. CC-G supported MF in conducting the secondary analysis and supported the writing of this manuscript. All authors read and approved the final manuscript.
Ethical approval for the HoldFAST study was granted by NRES Committee South West- Frenchay, Bristol, and local approvals were obtained from Staffordshire Cluster of PCTs Research Management and Governance Office, and the Research & Development Department of University Hospital of North Staffordshire NHS Trust.
Keele Medical School, Keele University, Keele, UK
Mirella Fry
Department of Physiotherapy, Division of Health and social care Research, King's College London, London, UK
University of Bristol, Faculty of Health Sciences, Senate House, Tyndall Avenue, Bristol, UK
Sarah Purdy
University of Sheffield, School of Health and Related Research (ScHARR), Section of Public Health, Regent Court, Regent Street, Sheffield, UK
Tom Sanders
Research Institute, Primary Care and Health Sciences, Keele University, Keele, UK
Umesh T. Kadam & Carolyn A. Chew-Graham
Health Services Research Unit, Keele University, Keele, UK
Umesh T. Kadam
Carolyn A. Chew-Graham
Correspondence to Carolyn A. Chew-Graham.
Fry, M., McLachlan, S., Purdy, S. et al. The implications of living with heart failure; the impact on everyday life, family support, co-morbidities and access to healthcare: a secondary qualitative analysis. BMC Fam Pract 17, 139 (2016). https://doi.org/10.1186/s12875-016-0537-5
Manage Heart Failure
Previous Qualitative Study
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Pancreatic cancer is one of the most aggressive human malignancies and ninth leading cause of cancer death in the world. Most patients diagnosed with pancreatic cancer die within 6 months, and only 4% survive 5 years after diagnosis. Early diagnosis and better treatments are desperately needed to improve the survival rate of pancreatic cancer patients. Pancreatic ductal adenocarcinomas, the majority of the exocrine pancreatic tumors, are thought to develop in a multistep process, involving a series of specific genetic mutations in each step. The comprehensive genetic analysis of 24 pancreatic cancers has shown 63 genetic alterations, and majority of which are point mutations. Interestingly, these alterations have been shown to affect 12 signaling pathways leading to pancreatic tumorigenesis. Because of nonspecific biomarkers for PDAC which lack specificity and sensitivity, high numbers of PDAC cases are diagnosed too late in the disease process for surgical resection to be an effective option. Even among the 10-20% of PDAC cases where surgical resection is an option, most patients ultimately die of recurrent or metastatic disease. In current investigation we were able to identify 41 proteins involved in oxidative stress response in pancreatic cancer and among them the presence of SOD2- mitochondrial, peroxiredoxin 2 and 4 and glutathione peroxidase was quite prominent, whereas these proteins were absent in control, suggesting aberrant regulation of redox homeostasis and stress adaptation in cancer cells. Mounting evidence suggests that, compared with their normal counterparts, many types of cancer cell have increased level of reactive oxygen species. Under persistent oxidative stress, many cancer cells become well-adapted to such stress and develop an enhanced, endogenous antioxidant capacity, which makes the malignant cells resistant to exogenous stress. As a consequence cancer cells that survive intrinsic oxidative stress may have activated adaptive mechanisms, which switch on ROS-scavenging systems to cope with the stress. Recent evidence suggests that such adaptation contributes to malignant transformation, metastasis and resistance to anticancer drugs. This approach might be a promising option to develop diagnostic biomarker and therapy for pancreatic cancer.
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DCE-MRI parameters have potential to predict response of locally advanced breast cancer patients to neoadjuvant chemotherapy and hyperthermia: a pilot study.
UNLABELLED: Combined therapies represent a staple of modern medicine. For women treated with neoadjuvant chemotherapy (NA ChT) for locally advanced breast cancer (LABC), early determination of whether the patient will fail to respond can enable the use of alternative, more beneficial therapies. This is even more desirable when the combined therapy includes hyperthermia (HT), an efficient way to improve drug delivery, however, more costly and time consuming. There is data showing that this goal can be achieved using magnetic resonance imaging (MRI) with contrast agent (CA) enhancement. This work for the first time proposes combining the information extracted from pre-treatment MR imaging into a morpho-physiological tumour score (MPTS) with the hypothesis that this score will increase the prognostic efficacy, compared to each of its MR-derived components: morphological (derived from the shape of the tumour enhancement) and physiological (derived from the CA enhancement variance dynamics parameters). The MPTS was correlated with response as determined by both pathologic residual tumour and MRI imaging, and was shown to have potential to predict response. The MPTS was extracted from pre-treatment MRI parameters, so independent of the combined therapy used. PURPOSE: To use a novel morpho-physiological tumour score (MPTS) generated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict response to treatment. MATERIALS AND METHODS: A protocol was designed to acquire DCE-MRI images of 20 locally advanced breast cancer (LABC) patients treated with neoadjuvant chemotherapy (NA ChT) and hyperthermia (HT). Imaging was done over 30 min following bolus injection of gadopentetate-based contrast agent. Parametric maps were generated by fitting the signal intensity to a double exponential curve and were used to derive a morphological characterisation of the lesions. Enhancement-variance dynamics parameters, wash-in and wash-out parameters (WiP, WoP), were extracted. The morphological characterisation and the WiP and WoP were combined into a MPTS with the intent of achieving better prognostic efficacy. The MPTS was correlated with response to NA therapy as determined by pathological residual tumour and MRI imaging. RESULTS: The contrast agent in all tumours typically peaked in the first 1-4 min. The tumours' WiP and WoP varied considerably. The MPTS was highly correlated with whether the patients had a pathological response. This scoring system has a specificity of 78% and a sensitivity of 91% for predicting response to NA chemotherapy. The kappa was 0.69 with a 95% confidence interval of [0.38, 1] and a p-value of 0.002. CONCLUSIONS: This pilot study shows that the MPTS derived using pre-treatment MRI images has the potential to predict response to NA ChT and HT in LABC patients. Further prospective studies are needed to confirm the validity of these results.
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L-Carnosine Supplements for Anti-Aging, Preventing Glycation and AGEs
Carnosine In The Diet
Supplements For Diabetes
L-carnosine supplements are used for anti-aging effects, to inhibit glycation and to increase muscle stamina. This supplement is sometimes recommended for those with prediabetes, type 2 diabetes, eye disorders like cataracts and certain neurodegenerative diseases.
Although there is limited data concerning the specific effects of supplementing with L-carnosine, as an endogenous amino acid it plays a number of important roles in the body.
Research shows that L-carnosine buffers hydrogen protons and helps to improve the acid balance in muscle tissues during intense workouts. This may decrease muscle fatigue and improve athletic performance.
Currently, much attention is being directed at its antiaging, antioxidant, antidiabetic, antiglycation and anti-inflammatory properties. Some research suggests that supplementing with the precursor beta-alanine is more effective for raising muscle carnosine levels compared to L-carnosine capsules or powders.
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The majority of people gain only small amounts of L-carnosine from their dietary intakes. Carosine is also depleted from the blood quite quickly via the actions of the carnosinase enzyme.
Carnosinase is present in the blood, kidneys, liver and various other tissues throughout the body. However, carnosinase is not present in muscle tissue. It is also not believed to be found in the lenses of the eyes.
When exogenous carnosine is introduced to an organism, it is not accumulated in tissues which contain carnosinase. The majority of carnosine ingested via the diet is excreted through the urinary system, or destroyed by carnosinase.
This is one of the main reasons why athletes and bodybuilders prefer instead to supplement with beta-alanine, which is used to make carnosine in the muscle tissues. In research studies, taking a beta-alanine supplement has been associated with many of the benefits attributed to L-carnosine.
The levels at which carnosinase hydrolizes carnosine increases as the organism ages. This means that carnosine levels in the body decline as we get older.
Carnosinase activity has also been shown to decrease in those with chronic hepatic (liver) disorders. N-acetyl carnosine is being explored for its capacities to resist hydrolyzation from carnosinase found in human serum.
L-Carnosine Supplements for Diabetes
Research supports using L-carnosine supplements to help manage the symptoms of diabetes, and related complications, like diabetic neuropathy.
Administration of carnosine reduces blood glucose levels and increases sensitivity to insulin. Use in those with impaired glucose tolerance (prediabetes) may help to prevent the onset type 2 diabetes mellitus.
L-Carnosine Supplements for Aging
Aging can be defined as the accumulation of damage at the cellular level that leads to impaired organ functioning and eventually death.
Especially over the past decade, much research has been centered on understanding the pathophysiology of the aging process. Researchers are attempting to discern novel possibilities for combating age-related diseases.
One process that has been associated with aging is the glycation of proteins in the body. The glycosylation of proteins causes the release of AGEs (advanced glycation end products).
AGEs are formed in concentrated amounts with both aging and diabetes mellitus. Properly using am L-carnosine supplement may induce certain antioxidant and antiglycation effects which inhibit AGE formation.
Research shows that L-carnosine supplements may help to bind to and dispose of aged protein chains throughout the body.
Carnosine seems to directly react with carbonyl groups which attach to older proteins. This often results from the actions of RNS (reactive nitrogen species), ROS (reactive oxygen species) and certain other protein-glycating agents.
Research shows administration of carnosine increases the lifespan of laboratory animals. Cultured human cells have also demonstrated significantly increased lifespans.
While some researchers have suggested that regularly using a L-carnosine supplement may extend human lifespan, more research is required to validate this hypothesis.
L-Carnosine for Cardiovascular Health
Research shows that using an L-carnosine supplement can help to reduce oxidative stress throughout the body. Oxidative stress results from excessive exposure to radical agents like environmental toxins, societal stress, free radicals and poor dietary choices.
Antioxidants are required to neutralize the destructive effects of oxidative stress. L-carnosine demonstrates strong antioxidant effects; and is very effective at scavenging radical agents like superoxide, ROS and RNS.
Decreasing oxidative stress is directly associated with reducing the risks of developing cardiac conditions like atherosclerosis (artery hardening), coronary artery disease and heart disease. L-carnosine has also been shown to impede the oxidation of lipids like LDL-C (low-density lipoprotein cholesterol).
L-carnosine supplements may also help to inhibit certain activities in the sympathetic nervous system which are believed to modulate transient hypertension (high blood pressure). This helps to diminish the blood pressure elevations which are associated with the development of obesity as well.
The antioxidant strengths of L-carnosine supplements can also protect the heart muscle from damage by toxins. This includes toxicity from prescribed/illicit drugs, chemotherapy agents, food toxins and others.
Carnosine's antiglycation effects impede harmful alterations to cholesterol and other fatty acids which contribute to arterial plaque deposits. Carnosine helps protect the blood vessels from the damaging effects of diabetes as well.
When the flow of blood is restricted, oxygen and other nutrients are derived from tissues and organs throughout the body. This causes immediate adverse effects and can also cause ischemia; a condition of prolonged lacking O2 in organs.
L-carnosine supplements may help those who already have developed arterial plaque and/or clogged arteries via anti-ischemic effects.
L-Carnosine Supplement Doses
L-carnosine 500 mg capsules and other supplement forms are available commercially. According to the Natural Medicines Professional Database, 179 carnosine-containing products are available for purchase. Always closely follow the dosing instructions on the products you buy.
Human research shows that L-carnosine sourced from chicken breast extract reaches peak serum concentrations roughly 30 minutes after ingestion.
Routine usage of a L-carnosine supplement has been shown to increase muscle carnosine levels. Both 3.2g and 6.4g daily doses over 4 weeks caused increases estimated between 42.1% and 65.8%.
Using a quality L-carnosine supplement may promote anti-aging benefits and help to reduce glycation in the body. Carnosine seems to benefits cells, tissues and organs throughout the body, potentially saving them from various pathologic aging effects.
Carnosine found in muscle tissue can also buffer against acid build-up during intense workouts, such as the lactic acid produced during anaerobic metabolism. However, beta-alanine has been found more effective for increasing carnosine levels and is more frequently supplemented by bodybuilders and other athletes.
It is best to speak with a doctor who knows about your health history before beginning to take any supplements. L-carnosine may cause hypotension (low blood pressure). Use cautiously with medications or herbal supplements which can also lower blood pressure.
Lee YT1, Hsu CC, Lin MH, Liu KS, Yin MC. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol. 2005 Apr 18;513(1-2):145-50. Epub 2005 Apr 2.
Derave W1, Everaert I, Beeckman S, Baguet A. Muscle carnosine metabolism and beta-alanine supplementation in relation to exercise and training. Sports Med. 2010 Mar 1;40(3):247-63. doi: 10.2165/11530310-000000000-00000.
Babizhayev MA1, Deyev AI, Yermakova VN, Semiletov YA, Davydova NG, Kurysheva NI, Zhukotskii AV, Goldman IM. N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts. Peptides. 2001 Jun;22(6):979-94.
Boldyrev AA [Carnosine metabolism in excitable tissues: biological significance]. Vestn Ross Akad Med Nauk. 1995;(6):3-7.
Wang AM1, Ma C, Xie ZH, Shen F. Use of carnosine as a natural anti-senescence drug for human beings. Biochemistry (Mosc). 2000 Jul;65(7):869-71.
Kraemer WJ1, Gordon SE, Lynch JM, Pop ME, Clark KL. Effects of multibuffer supplementation on acid-base balance and 2,3-diphosphoglycerate following repetitive anaerobic exercise. Int J Sport Nutr. 1995 Dec;5(4):300-14.
Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol. 2002 Nov;17(11):833-7.
Suzuki Y1, Ito O, Mukai N, Takahashi H, Takamatsu K. High level of skeletal muscle carnosine contributes to the latter half of exercise performance during 30-s maximal cycle ergometer sprinting. Jpn J Physiol. 2002 Apr;52(2):199-205.
Solis MY1, Cooper S2, Hobson RM2, Artioli GG1, Otaduy MC3, Roschel H1, Robertson J2, Martin D2, S Painelli V1, Harris RC4, Gualano B1, Sale C2. Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study. PLoS One. 2015 Apr 14;10(4):e0123857. doi: 10.1371/journal.pone.0123857. eCollection 2015.
Marina Yazigi Solis,#1 Simon Cooper,#2 Ruth M Hobson,2 Guilherme G. Artioli,1 Maria C. Otaduy,3 Hamilton Roschel,1 Jacques Robertson,2 Daniel Martin,2 Vitor S. Painelli,1Roger C. Harris,4 Bruno Gualano,1,* and Craig Sale#2,* Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study PLoS One. 2015; 10(4): e0123857. Published online 2015 Apr 14. doi: 10.1371/journal.pone.0123857
Trexler ET1, Smith-Ryan AE1, Stout JR2, Hoffman JR2, Wilborn CD3, Sale C4, Kreider RB5, Jäger R6, Earnest CP7,Bannock L8, Campbell B9, Kalman D10, Ziegenfuss TN11, Antonio J12. International society of sports nutrition position stand: Beta-Alanine. J Int Soc Sports Nutr. 2015 Jul 15;12:30. doi: 10.1186/s12970-015-0090-y. eCollection 2015.
Julie Y. Culbertson,1,* Richard B. Kreider,1 Mike Greenwood,2 and Matthew Cooke3 Effects of Beta-Alanine on Muscle Carnosine and Exercise Performance:A Review of the Current Literature Nutrients. 2010 Jan; 2(1): 75–98. Published online 2010 Jan 25. doi: 10.3390/nu2010075
Lancha Junior AH1, de Salles Painelli V2, Saunders B2, Artioli GG2. Nutritional Strategies to Modulate Intracellular and Extracellular Buffering Capacity During High-Intensity Exercise. Sports Med. 2015 Nov;45 Suppl 1:71-81. doi: 10.1007/s40279-015-0397-5.
Stegen S1, Stegen B1, Aldini G2, Altomare A2, Cannizzaro L2, Orioli M2, Gerlo S3, Deldicque L4, Ramaekers M4, Hespel P4, Derave W1. Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress. Appl Physiol Nutr Metab. 2015 Sep;40(9):868-76. doi: 10.1139/apnm-2015-0042.
Liu T1, Peng YF, Jia C, Yang BH, Tao X, Li J, Fang X. Ginsenoside Rg3 improves erectile function in streptozotocin-induced diabetic rats. J Sex Med. 2015 Mar;12(3):611-20. doi: 10.1111/jsm.12779. Epub 2014 Dec 1.
Jordan T1, Lukaszuk J, Misic M, Umoren J. Effect of beta-alanine supplementation on the onset of blood lactate accumulation (OBLA) during treadmill running: Pre/post 2 treatment experimental design. J Int Soc Sports Nutr. 2010 May 19;7:20. doi: 10.1186/1550-2783-7-20.
Gottesmann C1. GABA mechanisms and sleep. Neuroscience. 2002;111(2):231-9.
Kern BD1, Robinson TL. Effects of ?-alanine supplementation on performance and body composition in collegiate wrestlers and football players. J Strength Cond Res. 2011 Jul;25(7):1804-15. doi: 10.1519/JSC.0b013e3181e741cf.
Ulrich P1, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res. 2001;56:1-21.
Close GL1, Hamilton L2, Philp A3, Burke L4, Morton JP5. Close GL1, Hamilton L2, Philp A3, Burke L4, Morton JP 5. Free Radic Biol Med. 2016 Feb 4. pii: S0891-5849(16)00030-7. doi: 10.1016/j.freeradbiomed.2016.01.016. [Epub ahead of print]
OVERVIEW: Carnosine is a dipeptide composed of histidine and alanine; it is found exclusively in animal tissue. Carnosine is concentrated in the brain, heart, and skeletal muscles. READ MORE...
USED FOR: Preventing aging, Diabetic neuropathy, Cataracts, Renal dysfunction, Autism, Exercise performance.
MECHANISM: The role of Carnosine in the body is not well understood. Carnosine has been shown to act as an antioxidant; carnosine may also reverse or delay some of the effects that contribute to aging by interfering with certain chemicals related to the aging process. READ MORE...
DOSAGE: Capsules: 500 mg daily. Eye drops: two drops, twice daily. READ MORE...
SIDE EFFECTS: No side effects have been reported with oral use. Carnosine eye drops have been shown to be well tolerated for up to two years. READ MORE...
INTERACTIONS: Blood pressure lowering drugs; may interact with herbs and supplements with blood pressure lowering effects, including cat's claw, coenzyme Q-10, fish oil, L-arginine, theanine, and more.
RELATED SUPPLEMENTS: Acetyl-L-Carnitine, Cysteine, D-Ribose, Carnosine, Hordinine
TOP CARNOSINE SUPPLEMENTS *
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