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May 30
Sleep Deprivation: A Health Hazard Yet To Be Taken Seriously
A new survey released by Royal Philips Electronics (AEX: PHI, NYSE: PHG) shows that the average manager is sleeping 19 percent less than the recommended amount of eight hours a night. The survey, conducted in five countries around the globe, showed that 40 percent of those questioned blame the state of the world economy as the major reason for their lack of sleep.

A vast majority of respondents to the survey (61 percent) say they have had their work impacted negatively by lack of sleep. On average, each estimated 6.2 days per year were impacted by inadequate sleep - costing companies around the globe millions. In the UK for example, 6.7 days per year are impacted by lack of sleep and companies are losing nearly £850 of productivity per manager per year. With 4.3m managers in the UK (1), the cost to the economy could be as high as £3.63bn a year.

"People lose sleep either because they cannot sleep (insomnia) or because they are not setting aside enough time for sleep - both of which can happen because of work-related stress in the current economic environment," said Dr. David White, chief medical officer for Philips Home Healthcare Solutions. "People simply need to take sleep much more seriously."

"Sleep is not optional - it is absolutely critical to people's health," continued Dr. White "The consequences of not sleeping enough are well documented. People who do not get enough sleep can gain weight, are prone to diabetes, high blood pressure and even heart attacks. We are facing a serious healthcare problem if we do not take sleep more seriously."

In addition to the findings about lack of sleep, the survey also found that while 96 percent of managers recognize that inadequate sleep can seriously affect a person's health, only 29 percent discuss their problematic sleep patterns. Of those that do, just 27 percent seek professional help from a physician with the majority simply talking about their problems with family and friends.

Respondents were also polled on their awareness of a relatively common sleep disorder, Obstructive Sleep Apnea (OSA), a condition characterized by the repeated cessation of breathing during sleep. The occurrence of OSA amongst young adults is relatively high. It is estimated that in the UK, for example, over 770,000 people suffer from moderate to severe OSA, with only a fraction being diagnosed.

May 30
World's Largest Bariatric Surgery Patient Database Exceeding 120,000 Patients Will Support Best Prac
Surgical Review Corporation (SRC), an independent, non-profit organization that advances the efficacy, efficiency and safety of bariatric and metabolic surgery, announced that the number of registered patients entered into its Bariatric Outcomes Longitudinal Database™ (BOLD™) has now surpassed 120,000. BOLD, the world's largest dedicated repository of bariatric surgery patient information, provides the mechanism for identifying risk factors and quality indicators, developing risk stratification guidelines, and enabling continuous quality improvement for bariatric surgery.

All participants in the Bariatric Surgery Center of Excellence® (BSCOE®) program, which SRC administers on behalf of the American Society for Metabolic and Bariatric Surgery, are required to enter information into BOLD for every bariatric surgical procedure and patient encounter, including complications and comorbidities.

"Nearly 900 surgeons and more than 500 hospitals are now entering data into BOLD," said Neil Hutcher, M.D., FACS, Chairman of the SRC Board of Directors and a practicing BSCOE bariatric surgeon in Richmond, Va. "I'm also pleased to announce that 100 percent of BSCOE designees are BOLD users. A remarkable accomplishment when compared to a recent study reporting that only 7.6 percent of U.S. hospitals use an electronic health record. This level of participation demonstrates that bariatric surgeons are truly dedicated to determining the best care for their patients."

In June, SRC will provide aggregate benchmark data to BOLD users so that they can compare their own data to the entire research dataset. The organization also plans to publish national aggregate data reports, establishing a basis for best practices.

May 30
Easier Way To Identify A Child's High Blood Pressure Created By Pediatrician
Pediatricians now have a new and simple way to diagnose a serious problem facing our nation's children - thanks to David Kaelber, M.D., Ph.D., M.P.H., MetroHealth System pediatrician, internist, and chief medical informatics officer and Case Western Reserve University School of Medicine researcher and faculty member. Nearly 75% of cases of hypertension and 90% of cases of prehypertension in children and adolescents go undiagnosed. These troubling statistics were documented in previously published research by Dr. Kaelber. From this research, Dr. Kaelber and fellow researchers felt that one of the main reasons for the under-diagnosis may be due to the complex chart currently used to help physicians and medical personnel identify high blood pressure in children. So Dr. Kaelber's team simplified the chart - focusing solely on a child's age and gender - eliminating the need for a height percentile and reducing the number of values in the blood pressure table from 476 to just 64. The revised chart and accompanying description are published in the June issue of the journal Pediatrics.

The American Academy of Pediatrics and the American Heart Association recommend that blood pressure checks be done at all pediatric visits for health care (including dental and optometric appointments) for children ages 3 to 18. The current standard chart used by healthcare providers to evaluate pediatric blood pressure is from the National Heart, Lung, and Blood Institute and includes hundreds of normal and abnormal blood pressure values. In order to differentiate between normal and abnormal readings, providers need to, not only remember the variety of blood pressure ranges, but also know the child's height percentile - which can be difficult to verify, especially in non-primary care settings.

In re-designing the chart, Dr. Kaelber's team reduced the systolic and diastolic blood pressure cutoff values to one value for girls and one value for boys for each year of life from ages 3 to 18 plus. Researchers used the lower limit of height (5th percentile) in the abnormal blood pressure range for a given gender and age. While they note this may incorrectly flag some taller children as being in the abnormal blood pressure range, the researchers predict this number will be small compared to the number of children with prehypertension and hypertension who are identified. Any reading at or above the listed numbers in the chart will indicate a child who needs further evaluation by a physician.

May 30
Age-Related Eye Disease May Be Associated With Cognitive Impairment
Older adults with low scores on tests of cognitive function, including thinking, learning and memory appear more likely to have the early stages of the eye disease age-related macular degeneration, according to a report in the May issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

Age-related macular degeneration (AMD)-the leading cause of visual impairment in industrialized nations-has long been thought to share a common pathway with Alzheimer's disease, according to background information in the article. First, both conditions involve similar changes in the brain and eye, including the buildup of protein fragments known as beta-amyloid. "Second, clinical studies suggest that AMD and Alzheimer's disease share similar vascular risk factors, such as hypertension [high blood pressure] and cigarette smoking," the authors write. "Both AMD and Alzheimer's disease have been linked to an increased risk of stroke."

Michelle L. Baker, M.D., of the University of Melbourne, Victoria, Australia, and colleagues assessed 2,088 individuals age 69 to 97. Participants underwent cognitive testing, retinal photography for the detection of AMD and an extensive assessment of artery disease and its risk factors (including blood pressure, smoking status and body mass index).

After controlling for age, sex, race and the center at which they participated in the study, the one-fourth of individuals with the lowest scores on one cognitive test were twice as likely to have early-stage AMD as were individuals with higher scores. However, there was no association between AMD and scores on a second cognitive test, dementia or Alzheimer's disease.

May 30
Unexpected Bacterial Diversity Found On Human Skin
The health of our skin - one of the body's first lines of defense against illness and injury - depends upon the delicate balance between our own cells and the millions of bacteria and other one-celled microbes that live on its surface. To better understand this balance, National Institutes of Health researchers have set out to explore the skin's microbiome, which is all of the DNA, or genomes, of all of the microbes that inhabit human skin. Their initial analysis, published in the journal Science, reveals that our skin is home to a much wider array of bacteria than previously thought.

The study also shows that at least among healthy people, the greatest influence on bacterial diversity appears to be body location. For example, the bacteria that live under your arms likely are more similar to those under another person's arm than they are to the bacteria that live on your forearm.

"Our work has laid an essential foundation for researchers who are working to develop new and better strategies for treating and preventing skin diseases," said Julia A. Segre, Ph.D., of the National Human Genome Research Institute (NHGRI), who was the study's senior author. "The data generated by our study are freely available to scientists around the world. We hope this will speed efforts to understand the complex genetic and environmental factors involved in eczema, psoriasis, acne, antibiotic-resistant infections and many other disorders affecting the skin."

Drawing on the power of modern DNA sequencing technology and computational analysis, the research team from NHGRI, the National Cancer Institute (NCI) and the NIH Clinical Center uncovered a far more diverse collection of microbes on human skin than had been detected by traditional methods that involved growing microbial samples in the laboratory.

The NIH study involved taking skin samples from 20 sites on the bodies of 10 healthy volunteers. "We selected skin sites predisposed to certain dermatological disorders in which microbes have long been thought to play a role in disease activity," said study coauthor Maria L. Turner, M.D., senior clinician in NCI's Dermatology Branch.

The researchers extracted DNA from each sample and sequenced the 16S ribosomal RNA genes, which are a type of gene that is specific to bacteria. The researchers identified more than 112,000 bacterial gene sequences, which they then classified and compared. The analysis detected bacteria belonging to 19 different phyla and 205 different genera, with diversity at the species level being much greater than expected.

To gauge how much the skin microbiome differs among healthy people, the researchers studied many different parameters. They found considerable variation in the number of bacteria species at different sites, with the most diversity being seen on the forearm (44 species on average) and the least diversity behind the ear (19 species on average).

The research also generated information that may prove useful in efforts to combat the growing problem of methicillin-resistant Staphylococcus aureus (MRSA), a bacterium that can cause serious, even life-threatening, infections. While it is known that a significant proportion of people have colonies of S. aureus inside their noses, the NIH team checked to see where else on the body surface that these bacteria thrive. They found that the crease of skin outside the nose is the site with the microbial community most similar to that found inside the nose.

May 29
Low Levels Of Vitamin D Linked To Common Vaginal Infection In Pregnant Women
Pregnant women with low levels of vitamin D may be more likely to suffer from bacterial vaginosis (BV) - a common vaginal infection that increases a woman's risk for preterm delivery, according to a University of Pittsburgh study. Available online and published in the June issue of The Journal of Nutrition, the study may explain why African-American women, who often lack adequate vitamin D, are three times more likely than white women to develop BV.

"Bacterial vaginosis affects nearly one in three reproductive-aged women, so there is great need to understand how it can be prevented," said Lisa M. Bodnar, Ph.D., M.P.H., R.D., assistant professor of epidemiology, obstetrics and gynecology, University of Pittsburgh. "It is not only associated with a number of gynecologic conditions, but also may contribute to premature delivery - the leading cause of neonatal mortality - making it of particular concern to pregnant women."

The study, which included 469 pregnant women, sought to determine whether poor vitamin D status played a role in predisposing women, especially African-Americans, to BV. Dr. Bodnar and colleagues at Magee-Womens Research Institute found that 41 percent of the study participants had BV and of these, 93 percent had insufficient levels of vitamin D. They also found that the prevalence of BV decreased as vitamin D levels rose.

Vitamin D may play a role in BV by regulating the production and function of antimicrobial molecules, which in turn may help the immune system prevent and control bacterial infection. However, only about one in four Americans gets enough vitamin D. Vitamin D deficiency may be more common in African-Americans because dark pigmentation limits the amount of vitamin D that can be made in the skin through casual exposure to sunlight. African-American women also are less likely to meet dietary recommendations of vitamin D.

May 29
Perception Of Unsafe Neighborhoods Disables The Elderly
Elderly people who live below the poverty line and perceive their neighborhoods to be dangerous are more likely to have a mobility disability. Researchers writing in the open access journal BMC Public Health suggest that even perceiving one's neighborhood as unsafe can 'get into the body' and, ultimately, prove hazardous for elder health.

Cheryl Clark MD, ScD, from Brigham and Women's Hospital, Boston, led a team of researchers who studied 1,884 people aged 65 and older. They measured both the individuals' perceptions of danger and the levels of violent crime actually reported in the areas where they lived. Although these measures correlated quite well, it was the elder's sense that the neighborhood was unsafe that was most strongly associated with the development of a disability. Clark said, "Our results suggest that dangerous neighborhoods get from the mind into the body and engender mobility disability through psychosocial or psychological processes".

The researchers suggest that lower income elderly who live in unsafe neighborhoods may have fewer resources to cope with neighborhood stresses. Moreover, neighborhoods with high crime rates or a reputation for being dangerous may have more difficulty attracting businesses that provide material resources and services. Of course, the correlation between perception and reality also suggests that elders may have been reacting to actual crime events in their neighborhoods.

Clark concludes, "Our findings underscore the importance of neighborhood safety to healthy aging. Specifically intervening to improve perceptions of neighborhood safety at retirement age may be an important step to reduce the risk of mobility disability among elders"

May 29
Fox Chase Researchers First To Determine Structure In A Class Of Self-Regulating Proteins
Sections of proteins previously thought to be disordered may in fact have an unexpected biological role - providing certain proteins room to move - according to a study published by researchers at Fox Chase Cancer Center in this month's issue of the journal Structure (Cell Press).

The researchers published the first comprehensive structural study of the protein NHERF1, which serves as a means of bringing together molecular signals between the outer membrane of a cell and the proteins found in the structures that form the cell's cytoskeleton. NHERF1 is representative of a large class of proteins with an array of biological roles, including signaling pathways implicated in diseases such as cystic fibrosis and breast cancer.

"Here we have a molecule that serves an important role in how cells function and survive, but it contains these puzzling 'junk' sequences that don't seem to have any apparent purpose," says the paper's lead author Heinrich Roder, PhD, a structural biologist and senior member of the Fox Chase Cancer Center faculty. "Our work suggests that this disorder is really a way of creating flexibility, allowing the protein to function as a molecular switch, a process that is thought to go wrong in certain diseases."

The NHERF1 proved particularly puzzling to researchers as it contains both known structures and large disordered regions. The structured sections of the protein are comprised of two so-called PDZ domains - components well known to scientists as anchors that can help the protein connect to other proteins and cellular structures - and an ezrin-binding motif, a sequence of amino acids that connects NHREF1 to cellular proteins such as ezrin. Together these structures allow NHERF1 to serve as a signaling adaptor, an important link between different proteins in a pathway. Oddly, researchers have noted that the ezrin-binding motif conveniently fits into a cleft on the surface of the PDZ domains, but assumes a helical structure, which is highly unusual for this class of proteins.

As is typical for human proteins, over one third of the amino acids that make up NHERF1 were predicted to be intrinsically disordered, forming no known structures and matching no known evolutionarily-conserved pattern. According to Roder, it is one of these disordered segments, approximately 100 amino acids long, which enable the protein to work. That is, it allows the PDZ binding module to "bite" its own ezrin-binding tail, effectively shutting the protein down. "The flexibility of the linker and its tendency to be more or less disordered are critical for regulating the balance between internal ("autoinhibitory") forces and external interactions with the protein's signaling partners," Roder says. This idea is reinforced by a recent observation by Zimei Bu, PhD, a Fox Chase researcher a coauthor of this study, who found that enzymatic modification (phosphorylation) of amino acids in the disordered region tips the balance towards the more open, active, form of the protein.

"Evolution has provided researchers with convenient modular structures, areas that are repeated over and over again to make up proteins, and so we tend to dismiss the interspersed disordered sequences that don't seem to have any definable structure," Roder says. "Here we show that the weak molecular interactions in a disorganized protein sequence are essential in giving this protein its unique attributes."

It was also this disorganized domain that made it difficult for researchers to create an accurate model of the entire protein, Roder says. Typically, researchers use a technique called x-ray crystallography, in which they can tell a protein's structure from how crystals made from the protein samples scatter x-rays. The disorganized section of NHREF1 makes it nearly impossible to create the necessary crystals to use this technique. Instead, Roder and colleagues used a technique called nuclear magnetic resonance spectroscopy, which can determine a protein's shape by measuring how the individual atomic nuclei of a protein interact with an intense magnetic field.

Since NMR spectroscopy works best with small proteins - not large flexible molecules like NHREF1 - Roder, his staff scientist Hong Cheng, PhD, and their colleagues came up with an innovative technique that allowed them to look at the protein from numerous angles with the NMR spectrometer, and subtract out the overlapping areas to form a more complete picture of the molecule. This picture enabled them to see what NHREF1 looks like in both its "on" and "off" conformation.

"When it is not working, the protein is in this 'off' conformation until acted upon by outside agents," Roder says. "It is a way for the cell to shut off a signaling pathway when it is not in use."

May 29
Cancer Cells Need Normal, Non Mutated Genes To Survive
Corrupt lifestyles and vices go hand in hand; each feeds the other. But even the worst miscreant needs customary societal amenities to get by. It's the same with cancer cells. While they rely on vices in the form of genetic mutations to wreak havoc, they must sustain their activity, and that requires equal parts vice and virtue.

According to a new study in the May 29 issue of Cell, cancer cells rely heavily on many normal proteins to deal with stress and maintain their deviant state. Researchers at Harvard Medical School and Brigham and Women's Hospital used a technique called RNA interference (RNAi) to dial down the production of thousands of proteins and determine which were required for cancer cell survival.

"Cancer cells actually leverage many genes that don't harbor mutations to maintain their malignant lifestyles," says first author and postdoctoral researcher Ji Luo. "These genes probably help them deal with the problems that develop as a result of the inappropriate presence of growth and survival signaling in tumor cells."

Being a cancer cell isn't easy. Think of all the DNA replication and protein production involved, not to mention the abnormal architecture of a tumor, which deprives cells of oxygen. Survival requires a complete kit of stress response tools.

"Researchers often characterize cancer cells as oncogene addicts, but they're just as reliant on normal genes that alleviate stress," explains senior author Stephen Elledge, a professor at HMS and Brigham and Women's Hospital. "These stress management genes deserve attention as potential therapeutic targets."

In recent years, the National Cancer Institute has supported an ambitious effort to understand the molecular basis of cancer by sequencing cancer genomes. Elledge and Luo note that this Cancer Genome Atlas project would miss the stress management genes.

"If these genes are intact, they won't stand out when you compare the DNA sequences of cancer cells with normal cells," says Luo.

May 27
Fear Of Family Reaction Is Barrier To Treatment For Depressed Teens
Although teen depression poses a widespread problem for which proven treatments exist, few depressed teens receive any care.

Why don't they undergo treatment? The answer depends whether you ask parents or the adolescents themselves, according to a study in the June issue of the journal Medical Care.

"With teenagers, treatment decisions greatly involve other parties, especially parents. For instance, teenagers often rely on adults for transportation. Doctors need a sense not just of what the teen thinks or what the parent thinks, but what both think," said Lisa Meredith, Ph.D., lead author of the new study.

The ability of their physicians to address all the perceived barriers "affects the teenager's own ability to acknowledge their depression and do something about it," said Meredith, a researcher at RAND.

Teens with untreated depression more often have social and academic problems, become parents prematurely, abuse drugs and alcohol and suffer adult depression and suicide.

For the study, researchers recruited 368 adolescent patients of diverse backgrounds receiving care in seven public or private primary care practices. Of these, half had a diagnosis of depression. One parent or guardian of each enrolled teenager also participated.

Teens and parents rated the effects of seven possible barriers: 1) cost of care, 2) what others might think, 3) problems finding or making appointments with a doctor or therapist, 4) time constraints and other responsibilities, 5) not wanting family to know about the depression (this was asked of teens only), 6) good care being unavailable and 7) just not wanting care.

Parents were significantly less likely to report barriers than teens.

For teens, concerns about stigma and relatives' reactions were among the significant issues, and those who perceived barriers were less likely to undergo therapy or take medications. Depressed teens were significantly more likely to perceive barriers to care than their non-depressed peers were.

"Adolescents do tend to go undiagnosed and untreated. They don't want to seem abnormal. They want to fit in. Yet when they deny problems, they often act out adaptively, drinking a lot and pursuing other high-risk behaviors," said Deborah Amdur, a psychiatrist with the Advanced Psychiatric Group in Orlando, Fla.