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Scientists at John Hopkins University have been able to use human embryonic stem cells, or hESCs, to heal defects too large to heal on their own in mice intramembraneous bone, the flat bone type that forms the skull. The researchers, who presented their work at the American Society for Cell Biology's 47th Annual Meeting, used mesenchymal precursor cells isolated from hESCs, and steered them into bone regeneration by using “scaffolds,” tiny, three-dimensional platforms made from biomaterials. The researchers showed that by changing the scaffold materials, they could shift mesenchymal precursor cells into either of the body’s osteogenic pathways: intramembraneous, which makes skull, jaw, and clavicle bone; or endochondral, which builds the “long” bones and involves initial formation of cartilage, which is then transformed into bone by mineralization.

 

DIABETES: LACK OF SLEEP MAY CONTRIBUTE TO EPIDEMIC
The most common factors believed to contribute to diabetes are a decreased amount of physical activity and consumption of highly processed foods. However, there is growing evidence that another aspect of our modern lifestyle—short sleep duration—is also contributing toward the “diabetes epidemic,” according to a study published in the journal SLEEP. Researchers at Columbia University in New York explored the relationship between sleep duration and the diagnosis of diabetes over an eight-to-10-year follow-up period between 1982 and 1992 among 8,992 subjects who participated in the Epidemiologic Follow-Up Studies of the first National Health and Nutrition Examination Survey. The subjects’ ages ranged from 32 to 86 years. According to the results, subjects who reported sleeping five or fewer hours and subjects who reported sleeping nine or more hours were significantly more likely to have incident diabetes over the follow-up period than were subjects who reported sleeping seven hours, even after adjusting for variables such as physical activity, depression, alcohol consumption, ethnicity, education, marital status, age, obesity, and history of hypertension. Experimental studies have shown sleep deprivation to decrease glucose tolerance and compromise insulin sensitivity by increasing sympathetic nervous system activity, raising evening cortisol levels and decreasing cerebral glucose utilization. The increased burden on the pancreas from insulin resistance can, over time, lead to Type II diabetes, the researchers said.

 

Boosting an exercise-related gene in the brain works as a powerful anti-depressant in mice—a finding that could lead to a new anti-depressant drug target, according to a Yale School of Medicine report in Nature Medicine. The researchers said that the VGF exercise-related gene could provide a target for drug development that could lead to better treatments than existing antidepressants because it is already present in the brain. Depression affects 16 percent of the population in the United States, at a related cost of $83 billion each year. Currently available anti-depressants help 65 percent of patients and require weeks to months before the patients experience relief. While it is known that exercise improves brain function and mental health and provides protective benefits in the event of a brain injury or disease, scientists do not have a good understanding of why this is so. In an experiment using mice, the researchers found that the VGF gene was greatly enhanced by exercise and functioned like a powerful anti-depressant, while blocking its activity inhibited the effects of exercise and induced depressive-like behavior in the mice. The researchers said their work supports the benefits of exercise and provide a new target for the development of antidepressants with a mechanism of action different from existing medications.

 

Adults over age 60 who had higher levels of cardiorespiratory fitness lived longer than unfit adults, independent of their levels of body fat, according to a study in JAMA. Previous studies have provided evidence that obesity and physical inactivity each can produce a higher risk of death in middle-aged adults. Researchers at the University of South Carolina, Columbia examined the associations between cardiorespiratory fitness, various clinical measures of body fat, and death in older women and men. The researchers found that those who died were older, had lower fitness levels, and had more cardiovascular risk factors than survivors. However, there were no significant differences in body fat measures. Participants in the higher fitness groups were for the most part less likely to have risk factors for cardiovascular disease, such as hypertension, diabetes, or high cholesterol levels. Fit participants had lower death rates than unfit participants within each stratum of body fat, except for two of the obesity groups. In most instances, death rates for those with higher fitness were less than half of rates for those who were unfit. Higher levels of fitness were inversely related to all-cause death in both normal-weight and overweight BMI (body mass index) subgroups, in those with a normal waist circumference and in those with abdominal obesity, and in those who have normal percent body fat and those who have excessive percent body fat. The researchers said it may be possible to reduce all-cause death rates among older adults, including those who are obese, by promoting regular physical activity, such as brisk walking for 30 minutes or more on most days of the week, which will keep most individuals out of the low-fitness category. Enhancing functional capacity also should allow older adults to achieve a healthy lifestyle and to enjoy longer life in better health.

 

People with high blood pressure may find relief from transcendental meditation, according to a definitive new meta-analysis of 107 published studies on stress reduction programs and high blood pressure, which will be published in the December issue of Current Hypertension Reports. Researchers at the NIH-funded Institute of Natural Medicine and Prevention at the Maharishi University of Management in Fairfield, Iowa and the University of Kentucky College of Medicine in Lexington report that the transcendental meditation technique produces a statistically significant reduction in high blood pressure that is not found with other forms of relaxation, meditation, biofeedback, or stress management. The analysis reviewed randomized, controlled trials of all stress reduction and relaxation methods in participants with high blood pressure that have been published in peer-reviewed scientific journals. Blood pressure changes for the transcendental meditation technique included average reductions of 5.0 points on systolic blood pressure and 2.8 on diastolic blood pressure, which were statistically significant, according to the review. The other stress reduction programs did not show significant changes in blood pressure. Blood pressure changes associated with transcendental meditation practice were consistent with other controlled studies showing reductions in cardiovascular risk factors, improved markers of heart disease, and reduced mortality rates among participants in the transcendental meditation program.

 

In a study of older adults with diabetes and depression, researchers at the University of Pennsylvania School of Medicine report that those who receive depression care management are half as likely to die over a five-year period as those who do not. The first known study to examine the relationship between diabetes and mortality in a depression intervention trial appears in the journal Diabetes Care. Depression is common among people with diabetes and contributes to issues with medication and diet adherence, and also leads to an overall reduced quality of life. The researchers said their findings support the integration of depression evaluation and treatment with diabetes management in primary care.

EPIGENETICS: DNA METHYLATION SHOWN TO PROMOTE DEVELOPMENT OF COLON TUMORS

Damaged or defective genes have long been known to be the cause of some cancers. Over the past decade, however, scientists have discovered that even healthy genes can be switched on or off and can cause cancer without any changes in the underlying DNA sequence—although how this happens has remained poorly understood. Researchers at Whitehead Institute for Biomedical Research now have established a direct causal connection between the accumulation of too many methyl molecules on regions of DNA, or hypermethylation, and the development of colon tumors in mice. The research directly demonstrated that hypermethylation switches off tumor-suppressor genes—the "housekeeping" genes that keep cancer cells in check. The study, published in Genes and Development, found that hypermethylation boosted the number of intestinal tumors by 60 percent to 100 percent and significantly increased the average size of microscopic early-stage tumors. While DNA methylation has been correlated with tumor development in numerous studies of human cancers, this is the first in-vivo work demonstrating a causal connection in mammals. Better understanding of the process is a promising pathway to the prevention, diagnosis, and treatment of certain cancers with minimal side effects.

 

Scientists have known which genes are linked to inflammation, but now researchers at Wake Forest University Baptist Medical Center have organized this information to develop a powerful tool to aid investigators in studying the genetics of inflammatory diseases. Using complex web-based software, the researchers were able to systematically map out pathways, or chains of genes, and subpathways that contribute to various aspects of inflammation. The study, which was published by the online journal PLoS One, has also led to the development of two customized panels for analyzing genetic variations in the inflammation pathways of two different populations—one of European origin and the other of African origin.

 

LUPUS: GENE FINDING PROMPTS CALL FOR MORE DNA SAMPLES
Wellcome Trust researchers have identified a key gene involved in lupus, an autoimmune disease which frequently causes skin rash, joint pains, and malaise, but can also lead to inflammation of the kidneys and other internal organs. The lead researcher behind the study has called for more patients to volunteer DNA samples to enable them to further study the underlying causes of the disease. The risk of death for people with lupus is increased fivefold over that of the general population. However, because the symptoms are often non-specific, diagnosing the condition can be difficult. There is currently no cure for the disease, which can be triggered by viral infections, sunlight, trauma, or stress, as well as puberty and childbirth. Researchers report in the journal Nature Genetics that they have identified a new genetic variant, OX40L, which increases the risk of developing lupus. The variant, which is carried by one in six people in the U.K., increases the risk of developing the disease by 50 percent per copy.

Women die and get infections more often than men after heart surgery because they tend to receive more blood transfusions, which boosts the risks of bad outcomes, according to a study published in the Journal of Women’s Health. The study, authored by researchers at the University of Rochester Medical Center in New York and the University of Michigan Health System, raises another red flag about transfusions, a medical practice that some doctors now believe is overused. The researchers analyzed the data of 380 adult Rochester patients who had primary coronary artery bypass graft surgery, primary valve replacement, or both, in 1997 or 1998 at Strong Memorial Hospital. Sixty percent of the patients were men and about 40 percent were women. However, the women were 44.6 percent more likely to receive a blood transfusion than the men. Of the 150 women studied, 149 (99 percent) received donor blood during their hospitalization, compared to 77 percent of the men. Reasons for the gender gap are unclear. Of the 380 patients, 13 died while in the hospital; all of the 13 patients received blood transfusions, and infection was strongly related to death. Blood transfusions correlated with more days of fever, more days in intensive care, and a longer hospital stay, particularly if the patient got more than four units of blood. Women were more likely to die in the hospital (6.7 percent) than men (1.3 percent), and 11 percent of the women in the study developed pulmonary dysfunction after surgery, compared with 3.9 percent of the men.

 

One in 10 National Health Service hospital patients comes to harm as a result of their clinical care, suggests a study in Quality and Safety in Health Care. The findings are based on a review of the case notes of a random sample of just over 1,000 patients admitted to one large teaching hospital in the north of England during the first six months of 2004. Surgical patients were more likely to come to harm, but these incidents were less preventable. Diagnostic errors, on the other hand, were less common, but more preventable, the findings showed. Incidents causing harm lengthened hospital stay by an average of eight days.

 

Vaccinating children younger than age 2 with the pneumococcal vaccine appears to be associated with fewer hospitalizations from pneumonia and reduced health care expenses, according to a report in the Archives of Pediatrics & Adolescent Medicine.

Pneumonia is the leading cause of childhood illness and death worldwide, accounting for 2 million childhood deaths per year. In 2000, American children began receiving the 7-valent pneumococcal conjugate vaccine (PCV7)—which protects against pneumococcal pneumonia—as part of the routine immunization schedule. The number of children age 19 to 35 months receiving three or more doses increased from 41 percent in 2002 to 83 percent in 2005. Researchers at the Centers for Disease Control and Prevention in Atlanta analyzed health records from a database of approximately 40 large employers each year from 1997 to 2004. The researchers used claims data and coding from hospitals and physician visits to determine the number and cost of healthcare visits due to all-cause and pneumococcal pneumonia. More than 40,000 children younger than age 2 are represented in the database each year. Comparing the rates in 2004 with those in the baseline period of 1997 to 1999 among children younger than 2 years, hospitalizations due to all-cause pneumonia declined from 11.5 to 5.5 per 1,000 children (52.4 percent decline) and outpatient visits due to all-cause pneumonia declined from 99.3 to 58.5 per 1,000 children (41.1 percent decline). Rates of hospitalization due to pneumococcal pneumonia declined from 0.6 to 0.3 per 1,000 children (57.6 percent decline) and rates of ambulatory visits declined from 1.7 to 0.9 per 1,000 children (46.9 percent decline). The researchers said that the data add to the growing evidence base of benefits of PCV7 vaccination and suggest an important role for the vaccine in reducing the burden of pneumonia and associated medical costs.

 

The American College of Physicians, the second largest physicians group, said that pay-for-performance programs that provide incentives for good performance on a few specific elements of a single disease or condition may lead to better healthcare for some patients but can also have unintended consequences. Such plans may also neglect the complexity of patient care, especially for elderly patients and those with many chronic conditions, the group said in a position paper published in its journal Annals of Internal Medicine. The paper notes several possible unintended consequences of some pay-for-performance programs, such as an incentive to drop difficult patients whose outcome measures do not meet the quality standards or who cannot comply with treatment plans, or to not accept new patients who clearly will not meet existing measures.

 

Serious head injuries among alpine skiers and snowboarders have risen over the past 15 years, according to research published in Injury Prevention. The increase has coincided with faster speed and the inclusion of more jumping and acrobatics as the norm in these sports, according to the report. The findings are based on a comprehensive international review of published research on injuries sustained by mountain skiers and snowboarders between 1990 and the end of 2004. They looked particularly for serious brain and spinal cord injuries. These make up a relatively small proportion of injuries sustained while skiing and snowboarding, but they are the leading cause of death. The research suggests that the rate of this type of serious injury has steadily risen in all the countries that have reported data. The research also shows that the wearing of helmets can cut the risk of serious brain injuries by between 22 percent and 60 percent.

Doctors who convey empathy are viewed as more trustworthy, according to a survey of nearly 4,800 patients. The study, which included 100 covertly recorded visits by actors posing as patients, also revealed that empathy is lacking in many exam rooms The study, from researchers at the University of Rochester Medical Center, was published in the Journal of General Internal Medicine.  The researchers observed how doctors responded when patients asked loaded questions indicating worry about symptoms involving chest pain. The study builds on previous work by the researchers in which they have described how good communication between doctors and patients, and a willingness to explore concerns, results in improved health care and lower costs. An analysis of the doctor-patient interactions showed that doctors voiced empathy in only 15 percent of the office visits, even after repeated prompting by the patients. Patients reported the most satisfaction when doctors empathized with them in challenging situations, such as when the medical answer was not clear-cut, the study said.

 

Hospital staff nurses who work extended hours, work at night, struggle to remain awake at work, or obtain less sleep are more likely to experience a drowsy driving episode, according to a study published in the journal SLEEP. Researchers at Grand Valley State University in Grand Rapids, Michigan focused on data that were collected from 895 full-time hospital staff nurses, who completed logbooks on a daily basis for four weeks providing information concerning work hours, sleep duration, drowsy and sleep episodes at work, and drowsy driving occurrences. According to the results, almost 67 percent of the nurses reported at least one episode of drowsy driving, and 3 percent reported experiencing drowsy driving following every shift worked. On average, nurses reported experiencing an episode of drowsy driving one out of every four shifts they worked.

A total of 281 episodes of motor vehicle crashes/near-motor vehicle crashes were reported during the study period. The risk for a motor vehicle crash/near-motor vehicle crash almost doubled when driving followed shifts that exceeded 12.5 hours. Working at night also significantly increased the risk for drowsy driving incident. Nearly 80 percent of the nurses who worked only night shifts reported at least one episode of drowsy driving.

 

The global goal of an additional 2 percent yearly reduction in mortality rates for chronic diseases would avert millions of deaths and save billions of dollars of GDP in low- and middle-income countries. Further, almost 80 percent of life-years gained would come from deaths averted in people under 70, according to researchers at the Department of Measurement and Health Information of the World Health Organization. In a paper published in The Lancet Chronic Diseases Series, researchers said that people in 23 countries studied could live 18 years longer through sustained interventions. The 23 countries selected by the authors for their analysis account for about 80 percent of the total burden of chronic disease mortality in developing countries, including China, India, Russia, Brazil, Turkey, Mexico, Pakistan, South Africa, Poland, and Nigeria. In these 23 countries, chronic diseases—mainly cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes—were responsible for 50 percent of the total disease burden in 2005. For 15 of the selected countries with death registration data, estimated death rates from chronic diseases were 54 percent higher for men and 86 percent higher for women than those for men and women in high-income countries. If nothing is done to reduce the risk of chronic diseases, an estimated $84 billion of economic production will be lost from heart disease, stroke, and diabetes alone in these 23 countries between 2006 and 2015, the researchers said.

 

GENETIC TESTS: DIRECT-TO-CONSUMER ADS CONCERN PHYSICIANS
Direct-to-consumer advertising for commercial genetic testing is on the rise and may be problematic, according to a Massachusetts General Hospital physician. In the journal Obstetrics & Gynecology, Erin Tracy, MD, MPH, warns that such testing is poorly regulated and may present potential pitfalls for patients and physicians. She said some tests have no proven clinical utility and can be expensive. If a test comes back positive for a genetic predisposition to a behavior or disease, consumers are often not adequately counseled as to what those results might mean, whether these tests have any proven value, or what resources are available for follow up. The majority of DNA tests are “home brews” that are unregulated by the FDA, Tracy said. While the FDA needs more funding to regulate genetic testing, it also is limited in its ability to regulate services based in other countries. According to a 2002 study in Genetics in Medicine, 24 of 105 websites offering genetic testing directed potential clients to international mailing addresses.

 

Senator Charles Schumer (D-NY) has introduced legislation to modernize Medicare reimbursement policies for certain laboratory tests such as molecular diagnostics. The Advanced Medical Technology Association said that the legislation would help ensure continued innovation and patient access to important diagnostic tools. The legislation also has been introduced in the U.S. House of Representatives as the Medicare Advanced Laboratory Diagnostics Act (H.R. 1321), where it is sponsored by Rep. Bobby Rush (D-IL), Rep. Michael Ferguson (R-NJ), Rep. Mike Thompson (D-CA), and Rep. Phil English (R-PA). Though these tests make up less than 2 percent of hospital costs, their findings influence as much as 70 percent of healthcare decision-making, the group said. It said the current Medicare reimbursement system provides few incentives to develop new tests which are critical to the future of healthcare. The groups said the bill provides for significant reforms to outdated Medicare reimbursement policies that threaten to stifle innovation and the widespread diffusion of technologies. This includes establishing a demonstration project to test a new Medicare payment system for certain molecular diagnostics, allowing for a process to adjust items still on the Clinical Lab Fee Schedule through an appeals process to correct historic errors that set inadequate reimbursement for diagnostic tests, and improving processes for obtaining adequate reimbursement for new diagnostic lab tests.