Researchers cautious about Vitamin D supplementation to prevent chronic diseases

Vitamin D deficiency may increase the risk for a variety of chronic diseases, which has led to increased use of vitamin D supplements, often in high doses. However, taking a supplement "just in case" is not recommended to prevent chronic diseases until reliable knowledge about the efficacy or unwanted effects are available. This is the conclusion from a knowledge summary published in the British Medical Journal.

28 feb 2015--Vitamin D has received much attention in recent years. There is evidence that vitamin D deficiency may increase the risk for a variety of chronic diseases , such as cardiovascular disease, cancer, autoimmune diseases and type 2 diabetes. Is there sufficient evidence to recommend vitamin D supplementation to prevent these conditions?

Professor Haakon E. Meyer and researcher Kristin Holvik from the Norwegian Institute of Public Health, together with Professor Paul Lips from the VU Medical Centre in Amsterdam, Netherlands reviewed the existing published research. They concluded that combined supplementation of vitamin D and calcium can prevent fractures in the elderly. However, they agree that vitamin D supplements should not be recommended to prevent chronic diseases before reliable knowledge about the efficacy and any adverse effects are available.

Should vitamin D supplementation be used if you have vitamin D deficiency?

"Yes. Vitamin D should not be ignored. In the latest nutritional recommendations from the Norwegian Directorate of Health, 10 micrograms of vitamin D per day are recommended for adults and children and 20 micrograms per day for the elderly. A blood test is not needed to follow these recommendations. In the summer months, sufficient exposure to sunlight will help many to achieve these levels regardless of diet. In winter, many people need to take a supplement, such as cod liver oil. Otherwise, oily fish such as salmon, trout and mackerel are good natural sources of vitamin D, and butter, margarine and one type of skimmed milk (ekstra lett lettmelk) are fortified with vitamin D in Norway," says Meyer.

In the article, Meyer, Holvik and Lips systematically reviewed the available literature and described the possible benefits of taking vitamin D supplements and possible unwanted effects. They also described ongoing research and studies that may provide a clearer answer in the foreseeable future.

Has there been much research into vitamin D?

"Yes, there is a considerable research about vitamin D and the article refers to large randomized studies that are now underway to investigate whether supplementation with high doses of vitamin D can prevent various chronic diseases. The results will be available within five years" says Meyer.

More information: Meyer HE et al "Should vitamin D supplements be recommended to prevent chronic diseases?" BMJ 2015;350:h321

Provided by Norwegian Institute of Public Health

Skin test may shed new light on Alzheimer's and Parkinson's diseases

Scientists have discovered a skin test that may shed new light on Alzheimer's and Parkinson's diseases, according to a study released today will be presented at the American Academy of Neurology's 67th Annual Meeting in Washington, D.C., April 18 to 25, 2015.

27 feb 2015--The study showed that skin biopsies can be used to detect elevated levels of abnormal proteins found in the two diseases.

"Until now, pathological confirmation was not possible without a brain biopsy, so these diseases often go unrecognized until after the disease has progressed," said study author Ildefonso Rodriguez-Leyva, MD, at Central Hospital at the University of San Luis Potosi in San Luis Potosi, Mexico. "We hypothesized that since skin has the same origin as brain tissue while in the embryo that they might also show the same abnormal proteins. This new test offers a potential biomarker that may allow doctors to identify and diagnose these diseases earlier on."

For the study, researchers took skin biopsies from 20 people with Alzheimer's disease, 16 with Parkinson's disease and 17 with dementia caused by other conditions and compared them to 12 healthy people in the same age group. They tested these skin samples to see if specific types of altered proteins were found—ones that indicate a person has Alzheimer's or Parkinson's.

As compared to healthy patients and ones with dementia caused by other conditions, those with both Alzheimer's and Parkinson's had seven times higher levels of the tau protein. People with Parkinson's also had an eight times higher level of alpha-synuclein protein than the healthy control group.

Alzheimer's disease is ranked as the sixth leading cause of death in the United States, and 5.4 million Americans are currently diagnosed with Alzheimer's disease. Parkinson's disease affects one million Americans, with at least 60,000 new cases reported annually each year.

"More research is needed to confirm these results, but the findings are exciting because we could potentially begin to use skin biopsies from living patients to study and learn more about these diseases. This also means tissue will be much more readily available for scientists to study," said Rodriguez-Leyva. "This procedure could be used to study not only Alzheimer's and Parkinson's, but also other neurodegenerative diseases."

Provided by American Academy of Neurology

Sleeping over 8 hours a day associated with greater risk of stroke

People who sleep for more than eight hours a day have an increased risk of stroke, according to a study by the University of Cambridge - and this risk doubles for older people who persistently sleep longer than average. However, the researchers say it is unclear why this association exists and call for further research to explore the link.

26 feb 2015--Previous studies have already suggested a possible association between sleep and risk of stroke, but today's study, published in the journal Neurology, is the first to provide detailed information about the British population and to examine the relationship between a change in sleep duration over time and subsequent stroke risk.

Researchers from the Department of Public Health and Primary Care at the University of Cambridge followed just under 10,000 people aged 42-81 years of age from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort over 9.5 years. During 1998-2000 and then again four years later, they asked the cohort how many hours on average they slept in a day and whether they generally slept well.

Almost seven out of ten participants reported sleeping between six and eight hours a day, whilst one in ten reported sleeping for over eight hours a day. Participants who slept for less than six hours or more than eight hours were more likely to be older, women and less active.

Over the almost ten year period of the study, 346 participants suffered a stroke, either non-fatal or fatal stroke. After adjusting for various factors including age and sex, the researchers found that people who slept longer than eight hours a day were at a 46% greater risk of stroke than average. People who slept less than six hours a day were at an 18% increased risk, but the small number of people falling in this category meant the association was not statistically significant.

Participants who reported persistently long sleep - in other words, they reported sleeping over eight hours when asked at both points of the study - were at double the risk of stroke compared to those with persistently average sleep duration (between six and eight hours a day). This risk was even greater for those whose reported sleep increased from short to long over the four years - their risk was close to four times that of people who maintained an average sleep duration.

In addition to studying the EPIC-Norfolk cohort, the researchers carried out a study of combined data from 11 other studies related to identify the association between sleep duration and patterns of stroke risk. Their final analysis, including 560,000 participants from seven countries, supported the findings from the EPIC-Norfolk cohort study.

Yue Leng, PhD candidate at the University of Cambridge, says: "It's apparent both from our own participants and the wealth of international data that there's a link between sleeping longer than average and a greater risk of stroke. What is far less clear, however, is the direction of this link, whether longer sleep is a symptom, an early marker or a cause of cardiovascular problems."

While older people have less work and fewer social demands and therefore often have the option of sleeping longer, previous research has shown that in fact, they tend to sleep on average for shorter periods.

The researchers say it is unclear yet why the link between sleep and stroke risk should exist. Lack of sleep has been linked with factors such as disrupted metabolism and raised levels of the 'stress hormone' cortisol, all of which may lead to higher blood pressure and increased stroke risk. However, the current study suggests that the association between longer sleep duration and higher risk of stroke was independent of normal risk factors for cardiovascular disease.

Professor Kay-Tee Khaw, senior author on the study, adds: "We need to understand the reasons behind the link between sleep and stroke risk. What is happening in the body that causes this link? With further research, we may find that excessive sleep proves to be an early indicator of increased stroke risk, particularly among older people."

More information: Leng, Y et al. Sleep duration and risk of fatal and nonfatal stroke: A prospective study and meta-analysis. Neurology; 25 Feb 2015

Provided by University of Cambridge

1 minute test predicts how well a patient may recover after an operation

CHICAGO (February 25): Frailty has been used to predict how well a patient may recover from a major operation. Because frailty assessments are not routinely utilized in busy surgical practices, surgeons at Emory University School of Medicine in Atlanta have discovered that a short, approximately one-minute assessment can accurately determine how likely a patient is to have complications after an operation.

25 feb 2015--Their study results are published online as an "article in press" in the Journal of the American College of Surgeons (JACS). The study will appear in a print edition of the journal later this year.

Contrary to what most consumers believe, frailty is not always connected to old age. "Many people would suspect that frailty only applies to someone in their 80s," said study author Viraj Master, MD, PHD, FACS, associate professor of urology and director of clinical research. "It's startling to think that people in their 30s and 40s could actually be frail, but there is a population of patients who are young but are actually frail."

Measuring frailty before a major operation is important because frail patients, regardless of age, tend to be at a higher risk for postoperative complications. "Frail means they don't have the physiologic reserve to bounce back after the operation, so they start down a path that they may not easily recover from," explained Kenneth Ogan, MD, a study coauthor and associate professor of urology.

The standard test to measure frailty, described by geriatrician Linda P. Fried and colleagues at Johns Hopkins University, includes five criteria:

1. Shrinking: Self-reported unintentional weight loss of more than 10 pounds in the last year
2. Grip Strength: Measured by having the patient squeeze a hand-held dynamometer adjusted for gender and body mass index (BMI)
3. Exhaustion: Measured by responses to questions about effort and motivation
4. Low Activity: Ascertained by inquiring about leisure time activities
5. Slowed Walking Speed: Measured by the speed at which a patient walks 15 feet adjusted by gender and height

Despite the importance of measuring patient frailty, many surgical practices may skip performing this five-step assessment for two reasons: it may take too long for a busy practice, and it requires a trained professional. The test also introduces bias since patients may overestimate activity levels and underestimate exhaustion.

A one- minute frailty assessment

Dr. Master, Dr. Ogan, and their colleagues set out to find a simpler, quicker, more accurate way to assess frailty. The research team completed the full five-step frailty assessment on 351 patients age 18 or older who were admitted to Emory for major abdominal, urologic, or gastrointestinal operations.

They then looked at medical records and found that 36.7 percent had experienced a complication within 30 days after an operation: 24.5 percent of patients experienced a minor complication, while 14.2 percent experienced a major complication. Examples of complications included, wound infection, pneumonia, stroke, and death.

The researchers next compared the full frailty test's ability to predict these complications to a more truncated version that only assessed two of the five factors: grip strength and involuntary weight loss. They found that assessing just those two factors was equally as accurate at predicting complications as doing the full five-step test.

They also found that adding two additional factors—American Society of Anesthesiology score (ASA), which measures physical status for anesthesia, and levels of hemoglobin, the protein in red blood cells that carries oxygen— improved the model's ability to predict postoperative complications.

"If you just looked at weight loss and grip strength, those factors were just as good as doing all five steps. And if you add in hemoglobin and ASA scores, the prediction was even better," explained Dr. Master. "The nice thing is that the patient's ASA and hemoglobin are already recorded in the chart before an operation."

The full five-step test normally requires a trained clinician to collect the data, and could take about 10 minutes. "This method—asking one question about weight loss and the grip strength activity—can take less than a minute and can be done by anyone who interacts with the patient," Dr. Master added.

Setting patient expectations

Moving forward, the research team's goal is to increase surgical teams' willingness to perform the frailty test on each patient before an operation, not to reject patients for a procedure but rather as a planning measure. "This step is important for setting expectations for the patient and the family," said Dr. Ogan. "If a patient is found to be frail prior to surgery, it is critical that the patient is aware that their risk of a postoperative complication is increased. Our data is clear: If you have a weak grip and you're losing weight, you're at risk. We want to be better prepared for any risks after the operation."

For patients who are considered frail, that could mean making lifestyle changes to address weight loss and grip strength. It could also mean planning for a longer hospital stay or arranging for the patient to be discharged to a skilled nursing facility before going home.

The truncated frailty test will be rolled out to all of Emory's surgical patients this year. Dr. Ogan and Dr. Master are also planning a larger study to assess whether frailty assessments can impact hospital readmissions and mortality post-operatively.

More information: Fried, LP; Tangen, CM; Walston, J; Newman, AB, et al. "Frailty in older adults: evidence for a phenotype." J Gerontol A Biol Sci Med Sci. 2001; 56 (3): M146–56.

Provided by American College of Surgeons

Sauna use associated with reduced risk of cardiac, all-cause mortality

A sauna may do more than just make you sweat. A new study suggests men who engaged in frequent sauna use had reduced risks of fatal cardiovascular events and all-cause mortality, according to an article published online by JAMA Internal Medicine.

24 feb 2015--Although some studies have found sauna bathing to be associated with better cardiovascular and circulatory function, the association between regular sauna bathing and risk of sudden cardiac death (SCD) and fatal cardiovascular diseases (CVD) is not known.

Jari A. Laukkanen, M.D., Ph.D., of the University of Eastern Finland, Kuopio, and coauthors investigated the association between sauna bathing and the risk of SCD, fatal coronary heart disease (CHD), fatal CVD and all-cause mortality in a group of 2,315 middle-aged men (42 to 60 years old) from eastern Finland.

Results show that during a median (midpoint) follow-up of nearly 21 years, there were 190 SCDs, 281 fatal CHDs, 407 fatal CVDs and 929 deaths from all causes. Compared with men who reported one sauna bathing session per week, the risk of SCD was 22 percent lower for 2 to 3 sauna bathing sessions per week and 63 percent lower for 4 to 7 sauna sessions per week. The risk of fatal CHD events was 23 percent lower for 2 to 3 bathing sessions per week and 48 percent lower for 4 to 7 sauna sessions per week compared to once a week. CVD death also was 27 percent lower for men who took saunas 2 to 3 times a week and 50 percent lower for men who were in the sauna 4 to 7 times a week compared with men who indulged just once per week. For all-cause mortality, sauna bathing 2 to 3 times per week was associated with a 24 percent lower risk and 4 to 7 times per week with a 40 percent reduction in risk compared to only one sauna session per week.

The amount of time spent in the sauna seemed to matter too. Compared with men who spent less than 11 minutes in the sauna, the risk of SCD was 7 percent lower for sauna sessions of 11 to 19 minutes and 52 percent less for sessions lasting more than 19 minutes. Similar associations were seen for fatal CHDs and fatal CVDs but not for all-cause mortality events.

"Further studies are warranted to establish the potential mechanism that links sauna bathing and cardiovascular health," the study concludes.

Provided by The JAMA Network Journals

Diabetes and depression predict dementia risk in people with slowing minds

Credit: George Hodan/Public Domain

23 feb 2015--People with mild cognitive impairment are at higher risk of developing dementia if they have diabetes or psychiatric symptoms such as depression, finds a new review led by UCL researchers.

Mild cognitive impairment (MCI) is a state between normal ageing and dementia, where someone's mind is functioning less well than would be expected for their age. It affects 19% of people aged 65 and over, and around 46% of people with MCI develop dementia within 3 years compared with 3% of the general population.

The latest review paper, published in the American Journal of Psychiatry, analysed data from 62 separate studies, following a total of 15,950 people diagnosed with MCI. The study found that among people with MCI, those with diabetes were 65% more likely to progress to dementia and those with psychiatric symptoms were more than twice as likely to develop the condition.

"There are strong links between mental and physical health, so keeping your body healthy can also help to keep your brain working properly," explains lead author Dr Claudia Cooper (UCL Psychiatry). "Lifestyle changes to improve diet and mood might help people with MCI to avoid dementia, and bring many other health benefits. This doesn't necessarily mean that addressing diabetes, psychiatric symptoms and diet will reduce an individual's risk, but our review provides the best evidence to date about what might help."

The Alzheimer's Society charity recommends that people stay socially and physically active to help prevent dementia. Their guidelines also suggest eating a diet high in fruit and vegetables and low in meat and saturated fats, such as the Mediterranean diet.

"Some damage is already done in those with MCI but these results give a good idea about what it makes sense to target to reduce the chance of dementia," says senior author Professor Gill Livingston (UCL Psychiatry). "Randomised controlled trials are now needed."

Professor Alan Thompson, Dean of the UCL Faculty of Brain Sciences, says: "This impressive Systematic Review and meta-analysis from The Faculty of Brain Science's Division of Psychiatry underlines two important messages. Firstly, the impact of medical and psychiatric co-morbidities in individuals with mild cognitive impairment and secondly, the importance and therapeutic potential of early intervention in the prevention of dementia. Confirming these findings and incorporating appropriate preventative strategies could play an important part in lessening the ever-increasing societal burden of dementia in our ageing population."

More information: Cooper et al., 'Modifiable predictors of dementia in mild cognitive impairment: a systematic review and meta-analysis', American Journal of Psychiatry: dx.doi.org/10.1176/appi.ajp.2014.14070878

Provided by University College London

Chicken pox virus may be linked to serious condition in the elderly

22 feb 2015--A new study links the virus that causes chicken pox and shingles to a condition that inflames blood vessels on the temples and scalp in the elderly, called giant cell arteritis. The study is published in the February 18, 2015, online issue of Neurology. The condition can cause sudden blindness or stroke and can be life-threatening.

The varicella zoster virus, of the herpes virus family, can cause chicken pox and may reactivate later in life in the form of shingles, a very painful rash.

"Our analysis, which is the largest to-date, provides compelling evidence that the virus also reactivates in people over 60 in another way, triggering giant cell arteritis," said study author Don Gilden, MD, Professor of Neurology at the University of Colorado School of Medicine in Denver and a Fellow of the American Academy of Neurology.

Giant cell arteritis causes swelling and tenderness of the arteries on the scalp and temples of people over the age of 50. Gilden noted that it is the most common type of inflammation of blood vessels in the elderly, affecting an estimated 29 out of 100,000 people. Symptoms include a new severe headache, scalp tenderness, jaw discomfort, blurred vision, fever, weight loss and tiredness. Importantly, the cause of this condition has been uncertain, prompting the present study.

For the study, researchers searched for evidence of the virus in 13 temporal artery biopsies of people who died and had no previous symptoms of giant cell arteritis and in 84 temporal artery biopsies of people with giant cell arteritis. All of the biopsies were from people over the age of 50.

The virus was found in 74 percent of the biopsies with giant cell arteritis and in only 8 percent of the normal skin biopsies.

"If the association can be replicated in other studies, clinical trials should focus on treating people with giant cell arteritis with a combination of the current steroid drugs used for the condition, plus anti-viral treatment for the virus," said Gilden, CBE, MD, PhD, DSc, the Burton Chair of Neurology at Glasgow University in Scotland, in a corresponding editorial.

Provided by American Academy of Neurology

'Aging in place' may be the wrong answer for boomers and their parents

21 feb 2015--Baby boomers trying to pick the best living arrangements for themselves or their parents as they age should be wary of a phrase they coined in their younger years: If it feels good, do it.

So says Stephen Golant, a University of Florida researcher who studies housing needs for older Americans. In his new book, "Aging in the Right Place," Golant argues that the popular notion of "aging in place"—staying home and being independent as long as possible—sounds great but doesn't work for everyone.

Older people sometimes become emotionally attached to their homes, Golant said, leading them to think it's the best place to live out their lives. In fact, he said, these places may lack activities, features and amenities needed to age successfully.

As a result, he said, older people increasingly find they must rely on other people to meet their everyday needs. But both family members and professionals may fall short as caregivers. 

"We need to think about two sets of feelings—not just feeling comfortable, but also being in a place where we feel capable of achieving our everyday needs, from self-care to buying groceries to reaching doctors, and don't feel that our lives are spinning out of control," said Golant, who has studied older Americans' housing needs for more than 30 years.

The issue is becoming especially troublesome for moderate-income elders. Wealthy older people can afford the housing and services they need to live comfortable and independent lives, he said. Very low-income people often can benefit from government-funded programs and services to achieve these same goals—although, they often confront waiting lists and bureaucratic obstacles.

Those in the middle, however, often find themselves outside the safety net of social, long-term care and housing programs offered by federal, state, and local governments, but cannot afford products and services offered by the private sector.

Among other points Golant makes in his book:

• Older people with success stories increasingly live in what are now called "elder villages" – grass-roots, communally organized neighborhoods or building groups that help them feel more engaged and enable them to maintain their independence.
• Assisted living facilities are no different from any consumer product—some are great, and some are awful. Older people should be discriminating customers.
• The hallmark of successful aging is to be proactive in planning next steps, rather than waiting until a crisis forces change.
• Older people who have poor health, disabilities or other disadvantages can still have happy lives if they make the right living choices.

Provided by University of Florida

Tool can help assess cognitive impairment in multicultural populations

Credit: Karen Arnold/Public Domain

20 feb 2015--The ability to assess cognitive impairment in multicultural older populations will become more important as demographics change worldwide. A new study published in CMAJ (Canadian Medical Association Journal) reports that the Rowland Universal Dementia Assessment Scale (RUDAS) is particularly effective in multicultural populations where English is not a patient's first language.

Dementia is on the rise worldwide, with numbers projected to triple by 2050 to over 100 million. More than half the patients (58%) are in low- and middle-income countries, many of which are sources of immigrants to countries like Canada and Australia.

"Given our aging immigrant population in Canada and the anticipated increase in dementia prevalence worldwide in coming decades, earlier and more accurate detection of dementia in these populations will become increasingly important," writes Dr. Raza Naqvi, a geriatrician with the Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada, with coauthors.

Current tools to assess cognitive health, such as the Mini-Mental State Examination and the Montreal Cognitive Assessment, are widely used but are challenging to use in patients with low education levels and those whose first language is not English.

Researchers undertook a systematic review and meta-analysis to determine whether the RUDAS, developed in Australia in 2004, is effective in a variety of settings. They also wanted to understand how it compares to other tools. The study included 1236 people from 11 previous studies conducted in 6 countries. The mean age of participants was 73.5 years, and almost two-thirds (61%) were female.

The RUDAS includes questions such as recall of four grocery items, what safety precautions should one take when crossing the street, and naming of animals in 1 minute; it also assesses coordinated movements. The test appeared to be effective in identifying cognitive impairment and ruling it out across various cultures because language and education had less effect on results than with the other assessment tools.

The authors noted that all studies included in the analysis used trained interpreters; this may be a limitation since interpreters will not always be available for tests in all settings.

"The RUDAS is a freely available, effective brief cognitive assessment tool that has shown strong psychometric properties in several countries. It shows particular advantage in culturally and linguistically diverse populations," the authors conclude.

More information: Canadian Medical Association Journal, www.cmaj.ca/lookup/doi/10.1503/cmaj.140802

Provided by Canadian Medical Association Journal

'Most comprehensive map' of human epigenomes is unveiled

Reference epigenomes are available for more than 100 cell and tissue types. Credit: Nature and Roadmap Epigenomics Consortium

19 feb 2015--Two dozen scientific papers published online simultaneously on Feb. 18, 2015 present the first comprehensive maps and analyses of the epigenomes of a wide array of human cell and tissue types. Epigenomes are patterns of chemical annotations to the genome that determine whether, how, and when genes are activated.

Because epigenomes orchestrate normal development of the body, and disruptions in epigenetic control are known to be involved in a wide range of disorders from cancer to autism to heart disease, the massive trove of data is expected to yield many new insights into human biology in both health and disease.

The 24 papers describing human epigenomes will appear in print on Feb. 19, 2015 in the journal Nature and in six other journals under the aegis of Nature Publishing Group. Collectively, the papers are a culmination of years of research by hundreds of participants in the Roadmap Epigenomics Program (REP), first proposed in 2006 by academic scientists and key members of the National Institutes of Health. All will be freely available at Nature's Epigenome Roadmap website.

"The DNA sequence of the human genome is identical in all cells of the body, but cell types—such as heart, brain or skin cells—have unique characteristics and are uniquely susceptible to various diseases," said UC San Francisco's Joseph F. Costello, PhD, director of one of four NIH Roadmap Epigenome Mapping Centers (REMC) that contributed data to the REP. "By guiding how genes are expressed, epigenomes allow cells carrying the same DNA to differentiate into the more than 200 types found in the human body."

In cancer research, said Costello, the new data will hasten a merging of genomic and epigenomic perspectives that was already underway. "You've had cancer researchers studying the genome—the role of mutations, deletions, and so on—and others studying epigenomes. They've almost been working on parallel tracks, and they didn't talk to each other all that much. Over the past five or six years, there's been a reframing of the discussion, because the most recurrent mutations in cancer affect epigenomic regulators. So the way mutations in the genome play out is through epigenomic mechanisms, and major pharmaceutical companies now view epigenomes as an important target."

Costello holds the Karen Osney Brownstein Endowed Chair in Neuro-Oncology in the UCSF Department of Neurological Surgery, and is a member of the UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC).

The overarching findings of the REP, which include data on 111 distinct human epigenomes from all four REMCs as well as from dozens of individual labs around the world, are covered in a Nature paper for which Manolis Kellis, PhD, of Massachusetts Institute of Technology (MIT) and the Broad Institute of MIT and Harvard, is senior author. In addition to the many implications for normal human biology of "the most comprehensive map of the human epigenomic landscape so far," the authors write, "our data sets will be valuable in the study of human disease, as several companion papers explore in the context of autoimmune disease, Alzheimer's disease, and cancer."

An epigenomic signature can be made on the genome in two ways, both of which play a role in turning genes off or on. The first occurs when chemical tags called methyl groups are attached to a DNA molecule directly (DNA methylation). The second occurs when a variety of chemical tags attach to the tails of histone proteins that package DNA (histone modifications). Credit: John Stamatoyannopoulos and Rae Senarighi

DNA molecules are long, thin double strands containing genes, the discrete units of information that serve as recipes for the protein-making machinery of the cell. In order for DNA molecules to fit into the small space of the cell nucleus, they are compressed and packed like cooked spaghetti, and also wound around spool-like structures called histones. Chemical epigenetic "marks"—the addition of methyl groups in or near genes, and modifications to histones—determine whether genes are available to be transcribed and translated into proteins. Though epigenetic marks are stable, they are reversible, and they can also be altered by environmental factors such as diet, exposure to toxins, and aging. Such changes affect gene expression, which can lead to disease.

The REMC directed by UCSF's Costello included researchers from UCSF; the University of California, Santa Cruz (UCSC); the University of Southern California (USC), Washington University in St. Louis (WUSTL); and Canada's Michael Smith Genome Sciences Centre and the University of British Columbia (UBC), in Vancouver, Canada. The group provided important data to the REP on several cell types, including epigenomes of the normal human placenta, sperm, breast cells, blood cells, fetal and adult brain cells, and skin cells. Misha Bilenki, PhD, a member of Costello's REMC with an appointment at Canada's Michael Smith Genome Sciences Centre, is co-first author of the Nature paper of which Kellis, of MIT and Harvard, is senior author.

A unique contribution of Costello's REMC was the creation, by WUSTL's Ting Wang, PhD, and David Haussler, PhD, and Jim Kent of UCSC, of the Roadmap Epigenome Browser, a web-based tool that gives scientists worldwide open access to the complete data from the REP.

All told, Costello's REMC contributed four papers, three in Nature Communications and one in Nature Biotechnology, to the 24-paper collection that will appear in print on Feb. 19. In work published online last October in Nature and that will also appear in print as part of the REP collection, UCSF Sandler Faculty Fellow Alex Marson, MD, PhD, and colleagues at The Broad Institute and at Yale School of Medicine showed that epigenomic effects on immune cells can contribute to autoimmune disease.

More information: The research will be freely available to all, and the papers from Nature, along with papers from Nature Communications, Nature Biotechnology, Nature Methods, Nature Neuroscience, Nature Immunology and Nature Protocols, can be explored on the Epigenome Roadmap Site at www.nature.com/epigenomeroadmap

Provided by University of California, San Francisco

Antipsychotic Rx often relates to non-approved indications

18 feb 2015—For individuals with dementia living in nursing homes, the provider's rationale for use of antipsychotic drug therapy frequently relates to indications for which these drugs are not approved, according to a study published online Jan. 30 in the Journal of the American Geriatrics Society.

Alice F. Bonner, Ph.D., R.N., from Northeastern University in Boston, and colleagues conducted a qualitative, descriptive study set in 26 medium-sized and large facilities housing individuals living with dementia. The authors collected data from medical record abstraction and interviews with prescribers, administrators, direct care providers, and family members. They developed a coding scheme and coded reasons for antipsychotic prescribing.

The researchers found that among the 204 nursing home residents in the study, the major categories of reasons for antipsychotic medication use were behavioral, psychiatric, emotional states, and cognitive diagnoses or symptoms. Verbal and physical aggression were the most commonly identified behavioral reasons. Psychosis was most frequently described in the psychiatric category. The most common emotional states cited were anger and sadness.

"The rationale for use of antipsychotic drug therapy frequently relates to a wide variety of indications for which these drugs are not approved and for which evidence of efficacy is lacking," the authors write. "These findings have implications for clinical practice and policy."

More information: Abstract
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Most clinical 'calculators' over-estimate heart attack risk

Myocardial Infarction or Heart Attack. Credit: Blausen Medical Communications/Wikipedia/CC-A 3.0

17 feb 2015--Most "risk calculators" used by clinicians to gauge a patient's chances of suffering a heart attack and guide treatment decisions appear to significantly overestimate the likelihood of a heart attack, according to results of a study by investigators at Johns Hopkins and other institutions.

Physicians commonly use standardized risk assessment systems, or algorithms, to decide whether someone needs care with daily aspirin and cholesterol-lowering drugs or just watchful waiting and follow-up exams. These algorithms calculate heart attack probability using a combination of factors, such as gender, age, smoking history, cholesterol levels, blood pressure and diabetes, among others.

The new findings, reported Feb. 17 in Annals of Internal Medicine, suggest four out of five widely used clinical calculators considerably overrate risk, including the most recent one unveiled in 2013 by the American Heart Association and the American College of Cardiology amid controversy about its predictive accuracy.

The results of the study, the research team says, underscore the perils of over-reliance on standardized algorithms and highlight the importance of individualized risk assessment that includes additional variables, such as other medical conditions, family history of early heart disease, level of physical activity, and the presence and amount of calcium buildup in the heart's vessels.

"Our results reveal a lack of predictive accuracy in risk calculators and highlight an urgent need to reexamine and fine-tune our existing risk assessment techniques," says senior investigator Michael Blaha, M.D., M.P.H., director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease.

"The take-home message here is that as important as guidelines are, they are just a blueprint, a starting point for a conversation between patient and physician about the risks and benefits of different treatments or preventive strategies," Blaha adds.

In addition to patient safety, risk overestimation has important public health and economic ramifications, the investigators say.

"For example, cholesterol-lowering medicines, while clearly cost-effective in high-risk patients, are less so among low-risk patients," says lead author Andrew Paul DeFilippis, M.D., M.Sc., assistant professor of medicine at the University of Louisville and adjunct assistant professor of medicine at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. "Therefore, overestimation of risk could lead to more health care spending, less health gain, and unnecessary exposure to drug side effects."

Prevention and treatment decisions are straightforward in some people, but many have borderline risk scores that leave them and their clinicians in a gray zone of uncertainty regarding therapy. Under the American Heart Association's most recent guidelines, people who face a 7.5 percent risk of suffering a heart attack within 10 years are urged to consider preventive therapy with a cholesterol-lowering medication. Risk overestimation could be particularly problematic for those with marginal risk scores estimates, because it can put a person with a relatively low-risk profile into the "consider treatment" group. This is why patients with such borderline scores could benefit from further risk assessment with tests like CT scans that visualize the degree of calcification in the arteries of the heart.

"Additional testing could be a much-needed tiebreaker in the all-too-common 'to treat or not to treat' dilemmas," says study co-author Roger Blumenthal, M.D., professor of medicine and director of the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease. "Such testing should be considered in all patients with marginal risk scores—those in whom the decision to treat with long-term statin and aspirin remains unclear."

The new findings stem from an ongoing study known as the Multi-Ethnic Study of Atherosclerosis, or MESA, following some 7,000 men and women nationwide, ages 45 to 84, from different ethnic backgrounds without preexisting cardiovascular disease.

To check the accuracy of each one of five risk calculators, the investigators compared the number of predicted versus actual heart attacks and strokes among a group of more than 4,200 MESA participants, ages 50 to 74, followed over a decade. All people involved in the research were free of cardiovascular symptoms at the beginning of the study and had no history of heart attacks and strokes.

Four out of five risk scores analyzed in the study overestimated risk by anywhere from 37 percent to 154 percent in men and 8 percent to 67 percent in women.

The new American Heart Association calculator overestimated risk by 86 percent in men and by 67 percent in women. In the group with a predicted risk score between 7.5 to 10 percent—the threshold at which initiation of stain is recommended—the actual rate of heart attacks and strokes was only 3 percent in men and 5 percent in women, well below the risk level at which statins should be considered.

The least flawed prediction of heart attack risk was generated by the Reynolds risk score, which overestimated risk among men by only 9 percent, but underestimated it by 21 percent among women. In addition to age, gender, smoking, diabetes, cholesterol and blood pressure, the Reynolds score includes family history of early heart disease.

While not the subject of the current study, the researchers say the overestimation of risk likely stems from the fact that calculators, including the newest one, use risk reference data obtained decades ago, when more people were having heart attacks and strokes.

"The less-than-ideal predictive accuracy of these calculators may be a manifestation of the changing face of heart disease," Blaha says. "Cardiac risk profiles have evolved in recent years with fewer people smoking, more people having early preventive treatment and fewer people having heart attacks or having them at an older age."

The Reynolds risk equation, for example, was based on data from a more recent group of patients compared with other calculators, which may explain its superior accuracy, the researchers say.

"Our next step is to explore the impact of multiple cardiovascular risk factors on risk score accuracy," DeFilippis says. "Such an analysis will generate important insights about which factors need to be recalibrated and what new variables should be considered as we develop new risk scores for today's patients."

Atherosclerotic heart disease or atherosclerosis—a condition marked by the buildup of fatty plaque and calcium deposits inside the major blood vessels—is the main cause of heart attacks and strokes, claiming the lives of some 380,000 people in the United States each year.

Provided by Johns Hopkins University School of Medicine

Multidisciplinary approach successful in chronic back pain

16 feb 2015—Medication combined with a multidisciplinary rehabilitation program can decrease disability and improve mental health in low back pain patients over several years, according to a study published online Dec. 26 in the International Journal of Rheumatic Diseases.

Sedigheh S. Tavafian, Ph.D., from Tarbiat Modares University in Tehran, Iran, and colleagues conducted an extended 30-month follow-up of participants of a clinical trial evaluating group-based rehabilitation plus drug treatment for low back pain. In the follow-up, 69 patients in the intervention group continued receiving monthly motivational consultation and booster classes plus oral medication, and 77 patients in the control group received medication alone.

The researchers found that the two groups showed improvement for all studied variables (evaluated using the Short Form 36, Quebec Disability Scale [QDS], and Ronald Morris Disability Questionnaire [RDQ]) over time up to 30 months. However, the intervention group had consistently better outcomes for all variables compared with the control group. Within each group there were significant differences by time for measures of mental health and disability measured through QDS and RDQ.

"The proposed multidisciplinary program could improve mental health and disability up to 30 months in chronic low back pain patients," the authors write.

More information: Abstract
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MetS prevalent among seniors at risk of mobility disability

15 feb 2015—For older adults at high risk of mobility disability, metabolic syndrome is highly prevalent, according to a study published online Jan. 30 in the Journal of the American Geriatrics Society.

Anda Botoseneanu, M.D., Ph.D., from the University of Michigan in Ann Arbor, and colleagues conducted a cross-sectional analysis to examine the prevalence of metabolic syndrome and its association with physical capacity, disability, and self-related health in older adults. Data were collected for 1,535 community dwelling sedentary adults, aged 70 to 98 years and at high risk of mobility disability.

The researchers found that the prevalence of metabolic syndrome was 49.8 percent overall, and was 83.2 and 38.1 percent, respectively, among those with and without diabetes mellitus. In the overall sample and in those without diabetes mellitus and with poorer self-rated health, metabolic syndrome correlated with stronger grip strength (P = 0.01 and P < 0.001, respectively). No significant differences were found in the overall sample or in diabetes mellitus subgroups for the 400-m walk time, Short Physical Performance Battery score, or disability score for participants with versus without metabolic syndrome.

"Longitudinal studies are needed to investigate whether metabolic syndrome accelerates declines in functional status in high-risk older adults and to inform clinical and public health interventions aimed at preventing or delaying disability in this group," the authors write.

More information: Abstract
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What is successful aging? Gerontologists strive to build consensus

Scholars have long debated what successful aging is, how to measure it, and how to promote it. But the latest issue of The Gerontologist lays the groundwork for building consensus on the topic—while pointing out that the answer may differ among academics and the general public, as well as across populations and demographic groups.

14 feb 2015--"With an enhanced understanding of what successful aging is, we will be in a stronger position to develop interventions that will enable more people to age successfully," stated The Gerontologist Editor Rachel Pruchno, PhD, in the issue's opening editorial. "The sheer number of people comprising the baby boom generation transformed academic interest in successful aging to a public policy imperative. Now more than ever, it is critical to develop science that empowers people to experience the best old age possible."

The topic of successful aging reached new heights of popularity following a 1987 study by John W. Rowe, MD, and Robert L. Kahn, PhD, titled "Human Aging: Usual and Successful," which appeared in Science. They followed up with a subsequent article in The Gerontologist (and later book) titled "Successful Aging."

Their work helped the field of gerontology evolve from one arguably fixated on loss to one characterized by heterogeneity and the potential for growth. In the latter piece, they wrote that "successful aging is multidimensional, encompassing the avoidance of disease and disability, the maintenance of high physical and cognitive function, and sustained engagement in social and productive activities."

Now, through a series of 16 articles in The Gerontologist, top researchers in the field have looked back at the progress made over the past 28 years—and whether or not Rowe and Kahn's analysis is still relevant. Some of the journal's authors even suggest that the concept of successful aging should be abandoned, pointing to social inequalities and the problems associated with labeling a person as an "unsuccessful ager."

The issue includes a number of groundbreaking studies involving several segments of the U.S. population. For example, one of the articles reports on the first study to examine physical and mental health quality of life among the older LGBT population. Another entry uses queer theory to explore the experiences of transgender persons who contemplate or pursue a gender transition later in life. A further article addresses the growing body of literature suggesting that black women experience a number of social challenges that may present as barrier to aging successfully. Together, they demonstrate the necessity for gerontological theory to address how social, cultural, behavioral, and environmental constructs affect physical health and psychological well-being while guiding policy, health care services, and research among diverse race and gendered populations.

The Gerontologist also contains articles examining successful aging across cultures. It reports that young, middle-aged, and older lay persons from the U.S. and Germany have quite similar concepts of successful aging, which they view in far more multidimensional terms than do established scientific theories. This demonstrates that laypersons' views of successful aging pose scientific challenges because they include a much wider variety of factors than are considered in most theoretical models. A separate study examines labor force participation rates and life expectancy among Organization for Economic Co-operation and Development Countries—and finds that member nations with older adults who remain active in a paid work capacity tend to have elders who live longer.

"Nearly three decades after Rowe and Kahn's initial article was published, it is incumbent on gerontologists to use the conceptual and empirical knowledge base that now exists to develop consensus about what successful aging is and how it should be measured," Pruchno wrote. "We should approach this goal knowing that our measures will not be perfect, but at least our findings will be comparable. Advancing this work will help us learn how individuals can experience successful aging regardless of their social or health conditions."

Provided by The Gerontological Society of America

The secrets of longevity

Credit: Peter Griffin

13 feb 2015--After numerous studies, it appears that scientists are beginning to unravel some of the secrets of aging. Genes certainly play a role in longevity, but it's been determined that only 35 percent of those living well into their 90's and 100's possess the longevity gene. What of the other 65 percent? Is it luck, healthy lifestyle choices, attitude?

Len Kravitz, associate professor of Exercise Science and researcher at the University of New Mexico, recently delivered a talk on aging during a Lobo Living Room event at Hodgin Hall and said that it is likely a combination of the three.

Healthspan vs. lifespan

"It's great that people are living longer," Kravitz said, "but the goal should be to cultivate a mindset of healthspan rather than lifespan. Adults that take care of themselves physically and mentally have a better quality of life in later years than those who do not."

There are currently more Americans age 65 and older than at any other time in U.S. history. According to the latest Census Bureau report, there were 40.3 million people age 65 and older on April 1, 2010, up 5.3 percent from 35 million in 2000. In 1900, there were just 3.1 million. And the numbers are expected to increase over the next decade as baby boomers began turning 65 in 2011.

According to Kravitz, the biggest fears of aging are a loss of independence from mobility issues caused by health-related problems, loss of memory, going to a nursing home and having to give up a driver's license. Consequently, most people think of "old" not so much as a specific age but rather reaching the point where they lose the ability to do the things they love.

In order maintain or create a healthy lifestyle into the golden years, Kravitz suggests shedding pounds, if necessary. Being overweight is a major contributor to declining health and well-being as we age. According to the Centers for Disease Control and Prevention (CDC) close to 80 million adults in the U.S. are obese. Obesity-related conditions include heart disease, stroke, type 2 diabetes and certain types of cancer.

Kick stress to the curb

"Chronic stress is also a big contributor to aging," Kravitz said, "and the best way to fight it is with exercise. Incorporate some resistance training, aerobic exercise and mind/body practices to deal with stress at work or wherever the problem exists. When you take this multi-faceted approach you can mediate the stress and have less cognitive decline as well."

Let's get physical

Exercise is enormously important to successful aging. "The one intervention proposed to have the highest preventative and therapeutic impact on age-related changes is physical activity," Kravitz said. "A lack of exercise during adult life is associated with weakness, fatigue, decrease in one's physical and mental health and well-being, the onset of disease, loss of self-esteem and self-efficacy and an increase in depression and anxiety."

For overall health benefits, and reduction of numerous health risks, Kravitz recommends some form of aerobic activity, at least 30 minutes daily. "The use of the large muscles in the body from activities such as walking, swimming, aqua exercise and cycling are all good choices. Swimming, aqua exercise and stationary cycling are excellent due to lower stress placed on the joints. Walking, at a higher pace than normal is one of the most viable options for ambulatory elders. It can be done easily in most environments and requires no additional equipment", he said.

Keep the ole noodle sharp

Your brain also needs a work out to stay young. Reading, playing games, memorizing stuff and challenging yourself with new hobbies can all play a part in keeping your brain buff. And since we lose about 1 percent every year to utilize oxygen, remember to take deep breaths throughout the day, especially when not exercising. Unlike muscles, your brain does not store energy and therefore needs a steady stream of oxygen to stay sharp and focused.

Mix and mingle

Get out there and socialize with friends and family. Many studies support the positive effects of social interaction such as maintaining cognitive function and protection against diseases like dementia and Alzheimer's. Typically, people who have a wider circle of friends tend to age better all around.

Laugh more

"You don't stop having fun because you get old; you get old because you stop having fun," so the saying goes.

Provided by University of New Mexico

Expert panel recommends new sleep durations

12 feb 2015--The National Sleep Foundation (NSF), along with a multi-disciplinary expert panel, issued its new recommendations for appropriate sleep durations. The report recommends wider appropriate sleep ranges for most age groups. The results are published in Sleep Health: The Official Journal of the National Sleep Foundation.

The National Sleep Foundation convened experts from sleep, anatomy and physiology, as well as pediatrics, neurology, gerontology and gynecology to reach a consensus from the broadest range of scientific disciplines. The panel revised the recommended sleep ranges for all six children and teen age groups. A summary of the new recommendations includes:

• Newborns (0-3 months): Sleep range narrowed to 14-17 hours each day (previously it was 12-18)
• Infants (4-11 months): Sleep range widened two hours to 12-15 hours (previously it was 14-15)
• Toddlers (1-2 years): Sleep range widened by one hour to 11-14 hours (previously it was 12-14)
• Preschoolers (3-5): Sleep range widened by one hour to 10-13 hours (previously it was 11-13)
• School age children (6-13): Sleep range widened by one hour to 9-11 hours (previously it was 10-11)
• Teenagers (14-17): Sleep range widened by one hour to 8-10 hours (previously it was 8.5-9.5)
• Younger adults (18-25): Sleep range is 7-9 hours (new age category)
• Adults (26-64): Sleep range did not change and remains 7-9 hours
• Older adults (65+): Sleep range is 7-8 hours (new age category)

"This is the first time that any professional organization has developed age-specific recommended sleep durations based on a rigorous, systematic review of the world scientific literature relating sleep duration to health, performance and safety," said Charles A. Czeisler, PhD, MD, chairman of the board of the National Sleep Foundation, chief of sleep and circadian disorders at Brigham and Women's Hospital, and Baldino Professor of Sleep Medicine at the Harvard Medical School. "The National Sleep Foundation is providing these scientifically grounded guidelines on the amount of sleep we need each night to improve the sleep health of the millions of individuals and parents who rely on us for this information."

A new range, "may be appropriate," has been added to acknowledge the individual variability in appropriate sleep durations. The recommendations now define times as either (a) recommended; (b) may be appropriate for some individuals; or (c) not recommended.

"The National Sleep Foundation Sleep Duration Recommendations will help individuals make sleep schedules that are within a healthy range. They also serve as a useful starting point for individuals to discuss their sleep with their health care providers," said David Cloud, CEO of the National Sleep Foundation.

The recommendations are the result of multiple rounds of consensus voting after a comprehensive review of published scientific studies on sleep and health. The expert panel included six sleep experts and experts from the following stakeholder organizations:

- American Academy of Pediatrics

- American College of Chest Physicians

- American Geriatrics Society

- American Neurological Association

- American Physiological Society

- American Psychiatric Association

- American Thoracic Society

- Gerontological Society of America

- Human Anatomy and Physiology Society

- Society for Research in Human Development

- American Congress of Obstetricians and Gynecologists

"The NSF has committed to regularly reviewing and providing scientifically rigorous recommendations," says Max Hirshkowitz, PhD, Chair of the National Sleep Foundation Scientific Advisory Council. "The public can be confident that these recommendations represent the best guidance for sleep duration and health."

More information: To view the full results and methodology of the report, please visit sleephealthjournal.org

Provided by National Sleep Foundation

Forcing wounds to close

Forces exerted by the cells surrounding the gap (dotted blue line) extend away at first, then direct inwards, towards the gap, during contraction of the 'purse-string' cable (red filaments).

A collaborative study led by scientists from the Mechanobiology Institute (MBI) at the National University of Singapore (NUS) has revealed the mechanical forces that drive epithelial wound healing in the absence of cell supporting environment. This research was published in Nature Communications in January 2015.

Sealing the gaps

10 feb 2015--Skin not only provides an essential protective barrier against foreign materials and pathogens, but it also helps the body retain various fluids and electrolytes. When this barrier is damaged, the consequences can be devastating. Ulcers, bleeding and bacterial infections may result and the chances of these occurring increases the longer wounds remain open.

Fortunately, epithelial cell sheets are self-repairing. The moment the integrity of the barrier is compromised, cellular mechanisms are initiated to close the gap. Cells begin crawling forward, and contractile cables are formed in the cells surrounding the wound to help pull the gap close. For several years, scientists have been learning much about how cells coordinate these processes and repair wounds quickly. In most cases, the healthy skin cells responsible for carrying out wound repair rely on a supporting layer underneath them. This layer comprises sticky proteins, and is known as the extracellular matrix (ECM), which provides support for them to adhere to and crawl over.

However, in cases of chronic or severe wounds, the underlying layers could also be damaged. Surrounding cells could also be unable to replace the ECM proteins. Yet the repair of these gaps, known as non-adherent gaps, does occur, albeit at a slower rate and with an increased likelihood of infection or other complications. So the question remained; how do cells close gaps in protective epithelial barriers where the underlying layers are also damaged or the ECM eroded?

This question was the focus of a study led by MBI Principal Investigator (PI) Professor Chwee Teck Lim and Co-Principal Investigator Professor Benoit Ladoux, along with MBI PI Assistant Professor Yusuke Toyama. Their findings reveal that closure of non-adherent gaps is driven exclusively by 'purse-string contraction'. Using a combination of cell culture, microfabrication and force measurements, the scientists discovered that a cellular 'tug-of-war' at the gap edge drives the mechanical forces responsible for gap closure.

The cells at the edge of the non-adherent gap are still attached to the ECM. These cells then spread themselves out as far as possible towards the centre of the gap. Measuring the direction of force revealed that these cells are actually pushing away from the gap. While this may sound counter-intuitive, it actually stabilises the cells, in a similar manner to a cantilever bridge, where support at either end anchors the extension of the bridge into space until two sides eventually meet in the middle. Once the cells have spread as far as possible into the gap, the contractile 'purse-string' cable forms across the cells, encircling the gap. The force exerted by these cells is reversed and the cells begin to pull each other towards the centre of the gap, continually speeding up the contraction of the protein cable. As the cells move inwards to close the empty space, more contractile cables can reach out over the gap and connect to the other side. These cables can contract rapidly, leading to the formation of a suspended cell sheet over the gap, and complete closure of the wound.

The 'tug-of-war' mechanism identified in this study provides a vivid demonstration of how cells exert directional forces to enhance biological processes. This new knowledge of the mechanical properties of skin and internal epithelial cells may lead to advances in wound repair, especially in cases where the ECM is compromised. With chronic wounds, sores and ulcers being a common complication in several diseases, particularly those associated with aging, it is imperative that researchers better understand the mechanisms at play in their repair. This will undoubtedly lead to improved treatments in wound healing.

More information: Vedula et al., Mechanics of epithelial closure over non-adherent environments, Nature Communications, 22 Jan 2015, DOI: 10.1038/ncomms7111

Provided by National University of Singapore