Unraveling the Juicy Tomato

Scientists have now worked on our favourite tomato to sequence the genomes, which will help reduce costs and increase the vegetable's production worldwide. 
It took seven years for the Tomato Genome Consortium (TGC), a group of over 300 scientists from 14 countries, to sequence the genomes of the domesticated vegetable. 
Indian scientists also participated in the research. 
"This achievement is expected to lower costs and speed up efforts to improve the worldwide tomato production, making it better equipped to combat the pests, pathogens, drought and diseases that now plague growers," said M.K. Bhan, secretary, Department of Biotechnology. 
The University of Delhi (South Campus), National Research Centre on Plant Biotechnology, Indian Agricultural Research Institute and National Institute of Plant Genome Research (New Delhi) under the auspices of the Indian Initiative on Tomato Genome Sequencing participated in the TGC. 
Indian scientists are now working to develop tomatoes that can stay fresh for 15-30 days in normal weather conditions. 
"The sequences provide a detailed overview at the functional portions of the tomato genome, revealing the order, orientation, types and relative positions of their 35,000 genes," said National Institute of Plant Genome Research Director Akhilesh Kumar Tyagi, who contributed to the research. 
"The sequences will help researchers decipher the relationships between tomato genes and traits and broaden their understanding of genetic and environmental factors that interact to determine a field crop's health and viability," he said. 
Indian researchers have simultaneously taken up analysis of specific genes/gene families related to ripening, nutrition, disease resistance and abiotic stress tolerance. 
"The genomic resources generated are expected to greatly accelerate improvement of tomato. We are also working to develop tomatoes that can stay fresh for over 15-30 days in normal conditions," he said. 
The Indian initiative was funded by the Department of Biotechnology and supported by the Indian Council for Agricultural Research.
Source-IANS

 

Mango skin can help fight flab

 Researchers have some good news for mango lovers - eating them with the skin on could aid the battle of the bulge.But the news comes with a warning: eating the wrong variety could have the opposite effect.University of Queensland scientists have found the skins of the common Irwin and Nam Doc Mai varieties contain compounds that inhibit the formation of human fat cells.By contrast, the skin of the Kensington Pride mango has compounds that promote fat cell growth.Professor Mike Gidley says lab tests involved exposing human fat cells to extracts from the skin and flesh of three varieties.He said there was a long way to go, but the findings opened up the possibility of a supplement that could help fight obesity."The next stage is to identify the useful molecules in the peel that inhibited fat cell formation," Prof Gidley told AAP.
Source:AAP
 

Cancer therapy that boosts immune system ready for wider testing

Two clinical trials led by Johns Hopkins Kimmel Cancer Center researchers in collaboration with other medical centers, testing experimental drugs aimed at restoring the immune system's ability to spot and attack cancer, have shown promising early results in patients with advanced non-small cell lung cancer, melanoma, and kidney cancer. More than 500 patients were treated in the studies of two drugs that target the same immune-suppressive pathway, and the investigators say there is enough evidence to support wider testing in larger groups of patients.

Results of the Phase I clinical trials will be published online June 2 in theNew England Journal of Medicine and presented at the 2012 Annual Meeting of the American Society of Clinical Oncology (Abstracts #2509 and #2510).

"Based on the positive response rates to these drugs and longevity of many of these responses, we believe that new clinical trials should move forward," says Suzanne Topalian, M.D., professor of surgery and oncology at Johns Hopkins. Preliminary analysis shows that, among responding patients who were followed for more than one year, responses were maintained for more than one year in two-thirds of those treated on one trial and in half of those in the other trial.

The immune-based therapies tested in the two clinical trials, both made by Bristol-Myers Squibb, aim not to kill cancer cells directly, but to block a pathway that shields tumor cells from immune system components able and poised to fight cancer.

The pathway includes two proteins called programmed death-1 (PD-1), expressed on the surface of immune cells, and programmed death ligand-1 (PD-L1), expressed on cancer cells. When PD-1 and PD-L1 join together, they form a biochemical "shield" protecting tumor cells from being destroyed by the immune system. Another protein involved in the pathway and also expressed by cells in the immune system, programmed death ligand 𔃀 (PD-L2), was originally discovered by Johns Hopkins investigators.

To make cancer cells more vulnerable to attack by the immune system, investigators tested each of two drugs -- BMS-936558, which blocks PD-1, and BMS-936559, which blocks PD-L1 -- in separate clinical trials conducted at multiple U.S. hospitals. The drugs are given intravenously in an outpatient clinic every two weeks, and patients can remain on the treatment for up to two years.

The PD-1 blocking drug was tested in 296 patients with various advanced cancers who had not responded to standard therapies. Of those patients receiving the anti-PD-1 therapy, 240 who started treatment by July 2011 were analyzed for tumor response. Significant tumor shrinkage was seen in 14 of 76 (18 percent) non-small cell lung cancer patients, 26 of 94 (28 percent) melanoma patients and nine of 33 (27 percent) kidney cancer patients.

In this trial, some patients experienced stable disease for six months or more, including five of 76 (seven percent) lung cancer patients, six of 94 (six percent) melanoma patients and nine of 33 (27 percent) kidney cancer patients. The investigators say that additional clinical studies will be needed to determine the drug's potential impact on survival.

"This level of response in patients with advanced lung cancer, which is typically not responsive to immune-based therapies, was unexpected and notable," says Julie Brahmer, M.D., associate professor of oncology at Johns Hopkins.

The anti-PD-L1 therapy also showed responses among 207 treated patients. Five of 49 (10 percent) non-small cell lung cancer patients, nine of 52 (17 percent) melanoma patients, and two of 17 (12 percent) kidney cancer patients responded.

"The positive results from both drugs give us a good indication that the PD-L1/PD-1 pathway is an important target for cancer therapy," says Topalian.

The anti-PD1 therapy caused serious toxicities in 41 of 296 (14 percent) patients. Many of the toxicities were immune-related, including colon inflammation, thyroid abnormalities and three deaths from pneumonitis (lung inflammation). The investigators say they are working with colleagues across the country to develop better methods for early detection and effective treatment of pneumonitis. Other less severe toxicities included fatigue, itching and rash. The anti-PD-L1 therapy caused nine percent serious toxicities and no deaths.

Among patients receiving anti-PD-1, tumor samples collected from 42 study patients before they received the experimental therapy were evaluated at Johns Hopkins Medicine for molecular markers that may correlate with clinical response. The investigators found PD-L1, the partner protein to PD-1, in 25 of the 42 samples. Nine of the 25 patients with PD-L1-positive tumors experienced tumor shrinkage as compared with none of the patients with PD-L1 negative tumors.

"These early results indicate that PD-L1 expression in pretreatment tumor biopsies may correlate with clinical response to anti-PD-1 therapy, but more work needs to be done to confirm this, " says Brahmer.

The two therapies targeting the PD-1/PD-L1 pathway are in the same class of so-called "antibody therapies," which are made of proteins that target and bind to certain molecules on the cell surface. Other antibody therapies include such drugs as Erbitux, Herceptin, and Rituxan.

"We have just scratched the surface of laboratory and clinical research on these drugs," says Topalian.

Ultimately, they envision boosting the effectiveness of the therapy by combining it with other anti-cancer agents, including cancer vaccines.

Source:Eurekalert

A patient's socioeconomic status may predict their preference in treatment options

Though it would seem logical, cancer patients don't always choose therapies with the best chance for survival—cost and side effects are also major considerations. Little has been known about the extent to which cost and side effects influence a patient's treatment decision. Now, new findings by Fox Chase Cancer Center researchers reveals that a patient's socioeconomic status, more than any other characteristic—such as age or disease site—is predictive of whether he or she will favor high efficacy, low cost or low toxicity when choosing a treatment. Yu-Ning Wong, M.D., Fox Chase medical oncologist and lead author on the study, will present her findings at the 2012 American Society of Clinical Oncology Annual Meeting on Tuesday, June 5.

"I'm really interested in how patients make healthcare decisions regarding cost," says Wong. "We found that patients' socioeconomic statuses can tell us a lot about what's important to them when considering treatment options."

The researchers presented a heterogeneous group of 400 patients with hypothetical scenarios and asked them to choose between two treatments of varying levels of efficacy, toxicity and cost. The scenarios covered both highly effective and moderately effective adjuvant therapies as well as palliative therapies.

In all three of the categories, patients who had an income over $60,000 were more likely to choose the most effective therapy, while those with an income under $60,000 were more likely to choose the most affordable therapy, regardless of whether the alternative treatment offered improved survival or lower toxicity. Conversely, patients with higher income were more likely to choose treatments that offered higher survival even if the alternatives were less expensive or more toxic. Education and employment status also affected treatment choice.

"It is possible that patients of higher socioeconomic status were more likely to have greater resources to focus on survival and tolerate more side effects, such as the ability to miss work. On the other hand patients of lower socioeconomic status are likely much more cost sensitive," Wong explained.

The study's findings have concerning implications for disparities in cancer care. Health plans with higher deductibles and co-pays may exacerbate disparities because patients of lower socioeconomic status and those with greater cost concerns may be more likely to avoid costly treatment.

"Policy makers should be aware of patients' sensitivity to cost as this may influence their decision to proceed with high-value care," Wong says.

"Clinicians need to become more comfortable with the fact that cost affects patients' decisions," Wong adds. "As greater focus is placed on 'patient-centered' care and 'preference-sensitive' decisions, patient sensitivity to costs should be integrated into decision making."

Although the study found socioeconomic status to be predictive of patients' preferences about efficacy, toxicity and cost for both adjuvant and palliative treatments, Wong reinforced that the scenarios were hypothetical However, although these were hypothetical and did not require patients to spend their own money, those who reported cost concerns were less likely to choose the more expensive treatment. This suggests that patients answered these questions consistent with their true preferences.

In addition, preferences may change. "We don't know if patients' preferences will change as they go through their disease trajectory," she says.

Source:Eurekalert

Yoga may benefit stroke recovery patients

An eight-week yoga program for recovering stroke patients improved balance and flexibility and provided other benefits, U.S. researchers said.

Arlene Schmid, rehabilitation research scientist at the Richard L. Roudebush VA Medical Center in Indianapolis, Indiana University-Purdue University Indianapolis and IU Bloomington, said the men and women had completed their post-stroke occupational and physical therapy before the yoga study but continued to experience impairments.

Schmid said loss of functional strength, flexibility and endurance is common after a stroke, but it can lead to long-term disability.

The researchers said as a result of the yoga there were significant improvements in functional strength, flexibility and endurance.

The yoga activities, Schmid said, might have "improved neuromuscular control, likely allowing for strength improvements in affected limbs, sides or areas of disuse."

Schmid concluded it might be appropriate to include yoga in the in-patient or out-patient rehabilitation people receive after a stroke.

The study was presented at the annual meeting of the American College of Sports Medicine in San Francisco.

Source:UPI

 

How does exercise affect nerve pain?

Experiments show exercise-related reductions in neuropathic pain and inflammatory mediators

San Francisco, CA. (June 1, 2012) – Exercise helps to alleviate pain related to nerve damage (neuropathic pain) by reducing levels of certain inflammation-promoting factors, suggests an experimental study in the June issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

The results support exercise as a potentially useful nondrug treatment for neuropathic pain, and suggest that it may work by reducing inflammation-promoting substances called cytokines. The lead author was Yu-Wen Chen, PhD, of China Medical University, Taichung, Taiwan.

Exercise Reduces Nerve Pain and Cytokine Expression in Rats

Neuropathic pain is a common and difficult-to-treat type of pain caused by nerve damage, seen in patients with trauma, diabetes, and other conditions. Phantom limb pain after amputation is an example of neuropathic pain.

Dr Chen and colleagues examined the effects of exercise on neuropathic pain induced by sciatic nerve injury in rats. After nerve injury, some animals performed progressive exercise—either swimming or treadmill running—over a few weeks. The researchers assessed the effects of exercise on neuropathic pain severity by monitoring observable pain behaviors.

The results suggested significant reductions in neuropathic pain in rats assigned to swimming or treadmill running. Exercise reduced abnormal responses to temperature and pressure—both characteristic of neuropathic pain.

Exercise also led to reduced expression of inflammation-promoting cytokines in sciatic nerve tissue—specifically, tumor necrosis factor-alpha and interleukin-1-beta. That was consistent with previous studies suggesting that inflammation and pro-inflammatory cytokines play a role in the development of neuropathic pain in response to nerve injury.

Exercise also led to increased expression of a protein, called heat shock protein-27, which may have contributed to the reductions in cytokine expression.

Neuropathic pain causes burning pain and numbness that is not controlled by conventional pain medications. Antidepressant and antiepileptic drugs may be helpful, but have significant side effects. Exercise is commonly recommended for patients with various types of chronic pain, but there are conflicting data as to whether it is helpful in neuropathic pain.

The new results support the benefits of exercise in reducing neuropathic pain, though not eliminating it completely. In the experiments, exercise reduced abnormal pain responses by 30 to 50 percent.

The study also adds new evidence that inflammation contributes to the development of neuropathic pain, including the possible roles of pro-inflammatory cytokines. The results provide support for exercise as a helpful, nondrug therapy for neuropathic pain—potentially reducing the need for medications and resulting side effects.

Source:Eurekalert

SOME BUTTERFLY SPECIES PARTICULARLY VULNERABLE TO CLIMATE CHANGE

A recent study of the impact of climate change on butterflies suggests that some species might adapt much better than others, with implications for the pollination and herbivory associated with these and other insect species.The research, published in Ecological Entomology, examined changes in the life cycles of butterflies at different elevations of a mountain range in central Spain. They served as a model for some of the changes expected to come with warming temperatures, particularly in mountain landscapes.The researchers found that butterfly species which already tend to emerge later in the year or fly higher in the mountains have evolved to deal with a shorter window of opportunity to reproduce, and as a result may fare worse in a warming climate, compared to those that emerge over a longer time period.“Insects and plants are at the base of the food pyramid and are extremely important, but they often get less attention when we are studying the ecological impacts of climate change,” said Javier G. Illan, with the Department of Forest Ecosystems and Society at Oregon State University.“We’re already expecting localized extinctions of about one third of butterfly species, so we need to understand how climate change will affect those that survive,” he said. “This research makes it clear that some will do a lot better than others.”Butterflies may be particularly sensitive to a changing climate, Illan said, and make a good model to study the broader range of ecological effects linked to insects. Their flight dates are a relevant indicator of future responses to climate change.The research was done by Illan’s group in the Rey Juan Carlos University in Madrid. It examined 32 butterfly species for five years at various elevations in a Mediterranean mountain range, and the delays in flight dates that occurred as a result of elevation change.About the OSU College of Forestry: For a century, the College of Forestry has been a world class center of teaching, learning and research. It offers graduate and undergraduate degree programs in sustaining ecosystems, managing forests and manufacturing wood products; conducts basic and applied research on the nature and use of forests; and operates 14,000 acres of college forests.
Source:OSU

Alcohol May Trigger Serious Palpitations in Heart Patients

The term “holiday heart syndrome” was coined in a 1978 study to describe patients with atrial fibrillation who experienced a common and potentially dangerous form of heart palpitation after excessive drinking, which can be common during the winter holiday season. The symptoms usually went away when the revelers stopped drinking. Now, research from UCSF builds on that finding, establishing a stronger causal link between alcohol consumption and serious palpitations in patients with atrial fibrillation, the most common form of arrhythmia.In a paper scheduled to be published August 1 in the American Journal of Cardiology, the UCSF researchers report that people with atrial fibrillation had almost a four and a half times greater chance of having an episode if they were consuming alcohol than if they were not“One of the remaining big unknowns is why or how this happens,” said senior author Gregory Marcus, MD, assistant professor of medicine at the UCSF Division of Cardiology. “In a previous publication, we suggested that there was an effect on the electrical activity of the atrium that leads to these arrhythmias but we do need additional studies to prove that.”

Alcohol and Heart Palpitations

In the study, conducted from September 2004 to March 2011, UCSF researchers interviewed 223 patients with documented cardiac arrhythmia, a term that encompasses both atrial fibrillation and supraventricular tachycardia (SVT), or rapid heart rate originating above the ventricles. Researchers asked patients, “Does alcohol trigger your heart palpitations?” Participants ranked their symptoms on a scale from one to five (i.e. never, rarely, sometimes, frequently, and always).“We defined ‘yes’ as frequently or always versus the rest of the responses,” Marcus said, “and found that, after adjusting for potential confounders, atrial fibrillation patients had statistically significant greater odds of reporting that alcohol would trigger their symptoms.” Of those patients interviewed, 133 reported intermittent or paroxysmal atrial fibrillation, or irregular heart palpitations, when drinking, and 90 had SVT, without any atrial fibrillation. After adjusting for variables, the paroxysmal atrial fibrillation group had a 4.42 greater chance of reporting alcohol consumption as an arrhythmia trigger, compared to the SVT group. Patients’ claims of atrial fibrillation were verified by surface electrocardiograms and invasive cardiac studies.

The mean age of the study participants was 59 years. Eighty percent were Caucasian; 11 percent were Asian; 5 percent Latino, and 4 percent declined to state their ethnicity in the atrial fibrillation group. All were referred to and studied at UCSF.

“We didn’t find any clear associations between age and race as a trigger, but we probably had insufficient number of people in the study,” Marcus said.

Studying the Effects of Alcohol

Other studies have suggested that alcohol could help decrease the chance of developing atherosclerosis, which clogs or narrows the arteries. One of the proposed sources of benefit is the antioxidant in red wine called resveratrol, which may help prevent heart disease by increasing the “good” cholesterol in a person’s body.              

“There may be some beneficial effects to alcohol, but it’s important to look at actual heart outcomes, like stroke and death,” Marcus said. “Keep in mind that we used to think estrogen was good for your heart based on observational studies, and now we know that’s not exactly true.”He says there’s insufficient information at this time to recommend any lifestyle changes related to alcohol and heart disease risk. Still he points out that this report and previous reports indicate alcohol can cause cardiomyopathy and worsen hypertension.“If someone has heart palpitations or atrial fibrillation, I’m often asked, ‘Can I drink at all?’” Marcus said. “And I don’t know the answer, but it may be that certain people are susceptible.“The clinical evidence suggests that some people are susceptible and other people aren’t, but if they know that they’re susceptible they should avoid alcohol,” he said.Co-authors are Mala Mandyam; Vasanth Vedantham, MD, PhD; Melvin Scheinman, MD; Zian Tseng, MD, MAS; Nitish Badhwar, MBBS; Byron Lee, MD, MAS; Randall Lee, MD, PhD; Edward Gerstenfeld, MD; and Jeffrey Olgin, MD, all of the UCSF Division of Cardiology, Electrophysiology Section.This study was supported by the National Center for Research Resources, the National Center for Advancing Translational Sciences, and the Office of the Director, National Institutes of Health, through UCSF-Clinical and Translational Science Institute (CTSI), Grant Number TL1 RR024129. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.The authors have reported that they have no relationships relevant to the contents of this paper to disclose.UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care

Source:UCSF

Humans Can Sniff Out Old Age in Others, Study Shows

 How old do you think you smell? A new study suggests that humans possess the ability to judge whether a person has reached their senior years just by sniffing their body odor.People in the study correctly gauged whether the former wearer of an underarm pad was elderly or not just by sniffing it. And for the record, most didn't think "old-people smell" was off-putting at all.The finding "shows that there's yet another signal hidden in the body odor that we are somehow able to extract and make use of," said study co-author Johan Lundstrom, an assistant professor at the Monell Chemical Senses Center, in Philadelphia.As for the notion that "old-people smell" doesn't leave people as disgusted as you might expect,Lundstrom said the odor's power -- or lack thereof -- appears to have a lot to do with whether the elderly are actually physically present. "Lacking a context, the negativity of the body odorsdisappear," he said.The study authors launched their research as part of an effort to better understand the chemical signals that people detect in body odor. Previous research had suggested that we can pick up signs of sickness in other people's body odor and even get a sense of whether someone is related to us, Lundstrom said.Animals appear to be able to detect age through body odor, he said, although it's not clear why it might matter to them. One theory is that the signal could let other animals know that an animal is older and thus more likely to produce offspring because it's managed to stay alive so long, he said.In the new study, 56 people -- 20 young (20 to 30 years old), 20 middle-aged (45 to 55), and 16 elderly (75 to 95) -- wore clean T-shirts and underarm pads while sleeping. The pads soaked up a sample of each individual's body odor.The researchers then asked 41 young people to smell the resulting odors -- from pads kept in glass jars -- and try to tell them apart.Participants were generally able to discriminate between the age groups, but they weren't much better at it than chance, Lundstrom said. However, they were able to do a better job of grouping together body odors from older people and identifying them as coming from the elderly."The old-age body odor sticks out," Lundstrom said, but it didn't do so in a negative way. In fact, the subjects tended to think the old age body odors were more pleasant and less intense than those of other age groups.One factor might explain that: Older men smell more like women, possibly because they've lost testosterone, Lundstrom said.He also noted that the people who provided their body odor for the study were healthy. That means the older people did not suffer from problems that can occur among seniors that might affect their body odors, such as incontinence.The "popular prejudice" against the odor of the elderly probably reflects people's distaste for odors in geriatric wards and nursing homes, noted one expert, Tim Jacob, a professor of biosciences at Cardiff University, in England, who studies smell and is familiar with the new study's findings."This is obviously an unfair association," he said. "But if people know where the smell originates [that is, in an older person], they may be unconsciously or consciously prejudiced. In this study they did not know where the smell originated."So how might people be able to detect old age through smell? It's not clear, Lundstrom said. One possibility is that we're not detecting old age specifically, but instead a signal that "piggybacks" on chemical signs of disease in the elderly, he said.In the big picture, "given the research showing the importance of the olfactory -- smell -- system among other animal species, it is likely that humans possess similar capabilities that we don't yet fully understand, yet influence our behavior more than we realize," said Elizabeth Krusemark, a smell researcher and postdoctoral fellow at the University of Wisconsin Madison's Cognitive and Affective Neuroscience Lab.The study appears in the May issue of PLoS One.

Source:Health Day

Ayurvedic doctors seek use of Modern Medicine up-to some extent.

Members of Ayush Federation of India, Karnataka, (AFIK), demanded the state government to permit the ayurveda doctors to use allopathy medicines in emergency situations.Speaking at a press conference on Wednesday, Dr N A Magdum, president of AFIK, said, “Every year, nearly 4,000 AYUSH (Ayurveda, Unani, Sidda and Homeopathy) doctors graduate from 80 colleges.The future of these students is insecure in terms of employment and practise.Until the state government declares a plan of action for these students, we will boycott CET counselling which is scheduled in June. An indefinite strike will be held until the government comes up with a concrete plan.”Talking about the future of AYUSH doctors, Dr Magdum said, “The AYUSH doctors practising medicine at remote rural areas are prevented from prescribing allopathy medicines in case of emergency.It is necessary for allopathy medicines to be used in contingency at least to alleviate pain or further complications till the patients from rural areas are sent to a nearby district hospital.”He added as per the SC order, all state government may grant permission to the serving ayurveda doctors to use allopathy medicines in emergency cases.He added, “As many as 14 states across the country have granted permission to use allopathy medicine, except Karnataka, where there is a dire need.”He explained that all the AYUSH doctors study and practise for five-and-a-halfyears, but despite the education, they are denied the due respect and are targetted for the usage of allopathy medicines.

Source:Express News Service

Advanced Robotic Surgery Via Satellite

A robotic-assisted partial nephrectomy has been preformed by a team of urological surgeons. The surgery showcased the advanced robotic technology available to patients at the Robotic Surgery Center at NYU Langone. 
“We have one of the most advanced robotic surgery programs in the New York metropolitan area and our goal is to leverage this technology to help simplify complex procedures, and develop innovative new techniques that result in better outcomes for our patients,” said Michael Stifelman, MD, associate professor, Department of Urology and director of robotic surgery at NYU Langone Medical. “NYU Langone surgeons pioneered the use of robotics in partial nephrectomies and hold courses each month for surgeons to learn best practices.” 
During a partial nephrectomy, the tumor is removed while the rest of the kidney is left intact and functioning. The superior maneuverability of a robotic tool is ideally suited for delicate cutting and stitching required in this surgery, while the minimally-invasive nature of the procedure is less traumatic, and helps preserve kidney function and results in faster recovery time. 
The Robotic Surgery Center at NYU Langone is the largest multispecialty robotic surgery center in the New York metro area. Source:Newswise
 

Is there a 'healthy' obesity gene?

 Why is it that some obese people are healthier than others? This was one of the main questions Dr. Chaodong Wu of the College of Agriculture and Life Sciences — Texas A&M University System — and a group of researchers tried to answer in a recent study.

The study, which will appear in a July issue of the Journal of Biological Chemistry, used genetically modified mice to investigate the genetic aspects of why some obese people do not develop certain medical problems typically associated with obesity, especially Type 2 diabetes.

Wu noted that Xin Guo, a Ph.D. candidate in the college's department of nutrition and food sciences, contributed significantly to the study.

"Previous research had indicated that a regulatory enzyme which is encoded by the gene PFKFB3 protects against diet-induced fat tissue inflammation and systemic insulin resistance," said Wu, who also has a Texas AgriLife Research appointment. "Increasing evidence shows that fat deposition, or amount, is not directly associated with the inflammation or insulin resistance in the development of obesity-related metabolic diseases."

Wu said the inducible 6-phosphorofructo-2-kinase (iPFK2) enzyme links metabolic and inflammatory responses and may underlie what he refers to as "healthy" obesity.

"While many obese people develop Type 2 diabetes, heart conditions and other chronic health problems associated with being significantly overweight, other obese people do not," he said. "And while obesity in general is not healthy, some obese people do not develop the diseases more commonly associated with a less-than-healthy diet. Furthermore, a number of thinner people may have the sort of health problems more typically associated with obesity."

Wu said he and the other researchers theorized that these diseases are associated with the cellular inflammatory response brought on by obesity.

"We also thought this gene could conceivably be targeted for use in the treatment of diabetes, especially Type 2, commonly associated with obesity," he said. "We wanted to find out what might happen to a subject if that particular gene was activated."

Wu and his fellow researchers used laboratory mice to explore the effect of a targeted adipocyte overexpression of the gene/enzyme combination on diet-induced inflammatory responses and insulin sensitivity.

"We were trying to find out what it is in adipose, or fat, tissue that may trigger a negative response that leads to disease — and how to modulate that response," he said. "In our study, we learned overexpression of the iPFK2 enzyme increases fat deposition, suppresses inflammatory responses and improves insulin sensitivity in both adipose and live tissues."

As an extension of this research, Wu said, it may be possible to identify a pharmacological agent or bioactive agent which may have the desired effect on this gene toward reducing obesity-related cellular inflammatory response.

"We're hoping that, as one of its outcomes, this research will help lead to finding bioactive compounds or some type of supplement that might be taken to help activate this gene toward the promotion of health," he said. "It would also be a good idea to compare and contrast this research with studies done on what constitutes a healthy diet and the effect of such a diet at a cellular level. "

Wu said that would allow for screening bioactive compounds in a healthy diet to determine to what degree these might be applicable for the treatment of disease brought on by unhealthy obesity in an animal model.

"As a further extension, one might study different types of obese people and try to isolate additional specific genes that determine a healthy versus an unhealthy obesity and find a way to modulate the expression of those genes toward disease prevention and health promotion," he said. "Once you find the link between the gene and the obese status of the individual, then you could work with experts in chemical research to produce or replicate whatever pharmacological or bioactive compound is needed to treat unhealthy obesity."

Wu said it is important to determine positively to what degree obesity as a health problem is due to a person's genetic makeup as it relates to their ability to store fat, as well as what type of fat – saturated or non-saturated – the individual may store.

"Fat composition is more important than fat deposition, or content," he said. "We know fat cells secrete some of their own bioactive compounds that we may be able to isolate and identify for use in promoting health."

Wu said it will be necessary to discover the role of certain genes in the composition and deposition of fats beyond what has already been identified as being stored in the adipose tissue of mice.

"Then we may be able to produce a dietary supplement or other bioactive compound that would have a positive health effect," he said. "This could be used as a targeted treatment for obesity-related diseases such as Type 2 diabetes in a way that would have limited or minimal side effects."

Source:Eurekalert

Researchers determine structure of 'batteries' of the biological clock

Howard Hughes Medical Institute scientists have determined the three-dimensional structure of two proteins that help keep the body's clocks in sync. The proteins, CLOCK and BMAL1, bind to each other to regulate the activity of thousands of genes whose expression fluctuates throughout the course of a day. Knowing the structure of the CLOCK:BMAL1 complex will help researchers understand the intricacies of how this regulation is carried out and how mutations in each protein lead the biological clock to go awry.

Every 24 hours, millions of 'clocks' inside of our cells reset, helping to tune sleep patterns, blood pressure, and metabolism. When CLOCK and BMAL1 bind to one another inside cells, they initiate the first genetic events that coordinate this 24-hour cycle. "CLOCK and BMAL1 are really the batteries of the biological clock," says HHMI investigator Joseph S. Takahashi of the University of Texas Southwestern Medical Center, whose findings on the CLOCK:BMAL1 structure are published in the May 31, 2012, online version of the journal Science. "They are the key activators of the whole genomic regulation system."

The Clock gene was the first mammalian gene found to contribute to the body's circadian rhythms. Takahashi's team published the initial data on the Clock gene in a series of papers spanning 1994 to 1997. Since then, they've uncovered hundreds to thousands of genes under the control of CLOCK that fluctuate in sync with the biological clock in mammals.

"What's amazing is that we've now found out that almost every cell in your body has a clock," says Takahashi. "Over the past five years, the role of those clocks in peripheral tissues has really come to the forefront."

Researchers studying circadian rhythms have used biochemistry and genetics to piece together rough outlines of how each circadian protein interacts with CLOCK. But until now, they'd never been able to visualize the detailed molecular structure of the CLOCK protein. Seeing such a structure would allow them to visualize how different proteins can bind to CLOCK at the same time, or compete for binding spots, and how mutations known to alter circadian rhythms affect this binding.

Takahashi notes that CLOCK and BMAL1 are part of a large family of proteins, known as bHLH-PAS proteins (a name that refers to both to the shape of the protein and some better known members of the family), involved in functions ranging from responding to environmental contaminants and low-oxygen levels to the creation of new nerve cells. "It's not just CLOCK for which we didn't have a structure," says Takahashi. "This class of protein had never been solved at the crystallographic level before."

Takahashi explained that researchers had struggled to generate circadian proteins in the crystalline form necessary to determine structure using x-ray crystallography, but by experimenting with different conditions, his team was able to purify CLOCK bound to BMAL1. Rather than use the full-length version of each protein, they created a version consisting of only the pieces known to interact with each other. Having shorter proteins made the process easier.

The scientists discovered that CLOCK and BMAL1, when together, are closely intertwined. CLOCK has a groove in the center of its interface that's key to binding. A single amino acid of BMAL1 fits perfectly into the groove. Other proteins that bind to CLOCK likely take advantage of the same spot. Future research will look into the exact positions in which other circadian rhythm proteins bind to the complex, and how mutations to each protein affect the structure.

"Since these are truncated versions of the proteins, what we'd really like to do is to go on to get full-length structures," says Takahashi. They also want to understand how the Cryptochrome and Period proteins that turn off the activity of CLOCK bind to the CLOCK:BMAL1 complex. But that will take time.

Source:Eurekalert

Antioxidant beta-carotene use safe during radiation treatment for prostate cancer

Despite past safety concerns, the antioxidant supplement beta-carotene, is safe to use during radiation therapy treatments for prostate cancer and does not increase the risk of prostate cancer death or metastases, according to a study in the May issue of the International Journal of Radiation Oncology•Biology•Physics, the official scientific journal of the American Society for Radiation Oncology (ASTRO).

The use of vitamin supplements and antioxidants is common, but the safety of using antioxidant supplements during radiation treatments for prostate cancer is controversial. Radiation therapy relies on the pro-oxidant effects of DNA, which involves damaging tumor cells while leaving normal cells unharmed. However, some scientists have suggested that supplemental antioxidants may weaken the oxidizing effects of radiation and potentially lead to cancer recurrence.

In the largest study to date of its kind, researchers followed 383 prostate cancer patients who were randomized to receive beta-carotene or placebo to determine if antioxidants could potentially counteract the pro-oxidant effects of radiation therapy and increase a patient's risk of death or metastases. The primary endpoint was prostate cancer death or bone metastases.

Researchers found no significant differences in lethal outcomes among the patients who took the antioxidant beta-carotene versus those who did not.

"This study shows that antioxidant supplementation with beta-carotene during radiation therapy does not appear to detract from the benefit of radiation therapy." Danielle Margalit, MD, MPH, lead author of the study and a radiation oncologist at the Dana-Farber Cancer Institute in Boston, said. "It also suggests that patients may continue to eat a well-balanced diet that contains foods with natural sources of antioxidants at the recommended daily amount."

Source:Eurekalert

Nanotechnology breakthrough could dramatically improve medical tests

A laboratory test used to detect disease and perform biological research could be made more than 3 million times more sensitive, according to researchers who combined standard biological tools with a breakthrough in nanotechnology.

The increased performance could greatly improve the early detection of cancer, Alzheimer's disease and other disorders by allowing doctors to detect far lower concentrations of telltale markers than was previously practical.

The breakthrough involves a common biological test called an immunoassay, which mimics the action of the immune system to detect the presence of biomarkers – the chemicals associated with diseases. When biomarkers are present in samples, such as those taken from humans, the immunoassay test produces a fluorescent glow (light) that can be measured in a laboratory. The greater the glow, the more of the biomarker is present. However, if the amount of biomarker is too small, the fluorescent light is too faint to be detected, setting the limit of detection. A major goal in immunoassay research is to improve the detection limit.

The Princeton researchers tackled this limitation by using nanotechnology to greatly amplify the faint fluorescence from a sample. By fashioning glass and gold structures so small 

they could only be seen with a powerful electron microscope, the scientists were able to drastically increase the fluorescence signal compared to conventional immunoassays, leading to a 3-million-fold improvement in the limit of detection. That is, the enhanced immunoassay would require 3 million times fewer biomarkers to be present compared to a conventional immunoassay. (In technical terms, the researchers measured an improvement in the detection limit from 0.9 nanomolars to 300 attomolars.)

"This advance opens many new and exciting opportunities for immunoassays and other detectors, as well as in disease early detection and treatment," said Stephen Chou, the Joseph C. Elgin Professor of Engineering, who led the research team. "Furthermore, the new assay is very easy to use, since for the person conducting the test, there will be no difference from the old one– they do the procedure in exactly the same way."

The researchers published their results in two recent journal articles. One, published May 10 in Nanotechnology, describes the physics and engineering of the fluorescence-enhancing material. The other, published April 20 in Analytical Chemistry, demonstrates the effect in immunoassays. In addition to Chou, the authors include post-doctoral researchers Weihua Zhang, Liangcheng Zhou and Jonathan Hu and graduate students Fei Ding, Wei Ding, Wen-Di Li and Yuxuan Wang.

The work was funded by the Defense Advanced Research Project Agency and the National Science Foundation.

The key to the breakthrough lies in a new artificial nanomaterial called D2PA, which has been under development in Chou's lab for several years. D2PA is a thin layer of gold nanostructures surrounded glass pillars just 60 nanometers in diameter. (A nanometer is one billionth of a meter; that means about 1,000 of the pillars laid side by side would be as wide as a human hair.) The pillars are spaced 200 nanometers apart and capped with a disk of gold on each pillar. The sides of each pillar are speckled with even tinier gold dots about 10 to 15 nanometers in diameter. In previous work, Chou has shown that this unique structure boosts the collection and transmission of light in unusual ways -- in particular, a 1 billion-fold increasein an effect called surface Raman scattering. The current work now demonstrates a giant signal enhancement with fluorescence.

In a typical immunoassay, a sample such as blood, saliva or urine is taken from a patient and added to small glass vials containing antibodies that are designed to "capture" or bind to biomarkers of interest in the sample. Another set of antibodies that have been labeled with a fluorescent molecule are then added to the mix. If the biomarkers are not present in the vials, the fluorescent detection antibodies do not attach to anything and are washed away. The new technology developed at Princeton allows the fluorescence to be seen when very few antibodies find their mark.

In addition to diagnostic uses, immunoassays are commonly used in drug discovery and other biological research. More generally, fluorescence plays a significant role in other areas of chemistry and engineering, from light-emitting displays to solar energy harvesting, and the D2PA material could find uses in those fields, Chou said.

As next steps in his research, Chou said he is conducting tests to compare the sensitivity of the D2PA-enhanced immunoassay to a conventional immunoassay in detecting breast and prostate cancers. In addition he is collaborating with researchers at Memorial Sloan-Kettering Cancer Center in New York to develop tests to detect proteins associated with Alzheimer's disease at a very early stage.

"You can have very early detection with our approach," he said.

Source:Eurekalert

Over 35% of young Indians afflicted by kidney diseases belong to south: Study by Hyderabad doctors

In a recent study conducted by doctors from Hyderabad and Visakhapatnam in Andhra Pradesh, it is revealed that most of the Indians are becoming vulnerable to chronic kidney diseases (CKD) at a very young age.
Usually, the older population above the age of 65 to 75 is more prone to CKDs, but the recent survey indicated the mean age for CKDs in India is 50-55 years. Though many Indians have symptoms of kidney disorders at an age as early as 35, but they reach the chronic stage only at a later age of 50 years.
To ascertain what per cent of young Indians are being contracted with kidney diseases, a team of doctors from Hyderabad and Visakhapatnam conducted a multi-city survey and found out that 35.5 per cent of young patients suffering from CKD are from south while 27.9 per cent patients are from North. Coming to West and East India, 25 and 11 per cent respectively suffer from CKD among young people. It is also revealed that patients suffering from CKD in the east are much older.
On the whole, the study revealed that patients with CKD of unknown cause (etiology) are younger, poorer and more likely to suffer from advanced kidney troubles in the near future. 
Kidney disease can come in many ways. Kidney stones, kidney cancer and cysts affects the anatomical structure of the kidney, while diseases such as diabetes and hypertension affects the nephrons directly, resulting in a decline of kidney function. Structural diseases can also damage the nephrons, resulting in a decline of kidney function.
If one looks at the recent surveys, it is observed that chronic diseases have become a major cause of global morbidity and mortality even in developing countries. According to recent survey statistics it is revealed that approximate 800 cases of CKD are prevailing per million populations (pmp), and the incidence of end-stage renal disease (ESRD) is 150-200 pmp. The most common cause of CKD in population-based studies is diabetic nephropathy.
India currently has 820+ nephrologists, 710+ hemodialysis units with 2,500+ dialysis stations and 4,800+ patients on CAPD (Continuous Ambulatory Peritoneal Dialysis). There are 172+ transplant centres, two-thirds of which are in South India and mostly privately run. Nearly 3,500 transplants are done annually, the total number of cadaver donors being approximately 700 till now. Thus, taken together, nearly 18,000 to 20,000 patients in India get renal replacement therapy every year.
Coming to prevention, kidney disease can be prevented if and only  its symptoms are detected and diagnosed at the early state. Unfortunately, except for a few types of kidney disease, most of them cannot be fully cured. It is possible to control the effects by watching one’s diet, adopting a healthy lifestyle, and taking appropriate medication.
For end-stage kidney failure, the only treatment option available would be either dialysis or transplantation.
Source:Pharmabiz

Scientific study on anti-cancer Siddha drug halted after 10 years for want of govt funding

A decade long scientific study by a team of ethno-pharmacologists on a traditional metallic anti-cancer drug, claimed to be effective for treating skin cancer, was halted due to lack of proper patronage and funding by government or by research institutions.
The study, which began with hopes of finding eternal cure for thousands of suffering patients, was a long cherished dream of a group of ethno-pharmacologists led by an academician, Dr Arul Amutham, of Melaka Manipal Medical College in Karnataka.
The team’s years of research on the herbometallic drug in Siddha system “Putru Pathangam” (PP) cannot be pursued and suspended for the time being due to lack of support and patronage. Dr Arul Amuthan, the ethno-pharmacologist with educational background in Indian traditional medicine was actively involved in the research to prove Putru Pathangam as an anticancer Siddha drug.
Regarding his research, Dr Amutham says there are two different aspects of research in traditional medicines. First one is to isolate the compound/chemical that is responsible for anticancer activity from the traditional formulation, which later becomes a new anticancer drug. Though it is highly expensive and time consuming, it is the proper way of research, he admits.
Second aspect is the study of efficacy and toxicity of the traditional formulations without changing their nature. Since the traditional drugs are being used for thousands of years and consumed by human beings, their use as drugs can be continued. He argues that based on the efficacy, certain traditional preparations can be used as anti-cancer drugs, either alone or combined with allopathic drugs, to get better synergic effect. Scientists started working on the second aspect since the evidence is already available in traditional literature and from practice. So the researchers are looking for new drugs from traditional medicines, he told Pharmabiz.
“Modern medicine compares cancer with crab symbol. But, Siddha medicine, which is the oldest medicine in the world, compares the disease with termite mound. Termite mound grows with irregular shape and spread to distant places through underground channels. It cannot be destroyed completely. With full knowledge about the virulent and metastatic characteristic nature of cancer disease, Siddha system named cancer disease as ‘Putru noi’ which means the disease of growth like termite mound. There are myriad descriptions about herbal and metallic drugs in Siddha for cancer disease. Among them ‘Putru Pathangam’ is one herbo-metallic drug used to treat cancer cases,” Dr Amutham said. 
He said this drug has shown good anticancer activity against breast cancer cells, skin cancer cells and lung cancer cells. The interesting finding in the study of the drug was that the size of drug particle was in nano range which provided more advantages for more researches. Research in animal cancer model is going on by comparing with existing metallic anticancer drug, he added.
“We want to extent this study in all aspects right from standardization of drug preparation to clinical usage. This drug can be used alone to treat the drug resistant cancer cases and severe cancer cases. The adverse effects produced by this drug can be quashed by using certain herbals, which become another area of research. But we are struggling without proper funding. After knowing the traditional evidence and promising study results of this drug, we want to bring it to patient usage as early as possible. I can assure this traditional metallic anticancer drug will excel in the market for the management of cancer,” he claimed.

Source:Pharmabiz

Vitamin D - Too Much or Too Little can be Too Bad For You

It is a well known fact that vitamin D deficiency is not good for health, but a new study has now suggested that too high a level of the essential vitamin is not good for you either. 
The new research from the University of Copenhagen is based on blood samples from 247,574 Copenhageners. 
Vitamin D is instrumental in helping calcium reach our bones, thus lessening the risk from falls and the risk of broken hips. 
Research suggests that vitamin D is also beneficial in combating cardiac disease, depression and certain types of cancers. The results from a study conducted by the Faculty of Health and Medical Sciences now support the benefits of vitamin D in terms of mortality risk. 
However, the research results also show higher mortality in people with too high levels of vitamin D in their bloodstream: 
"We have had access to blood tests from a quarter of a million Copenhageners. We found higher mortality in people with a low level of vitamin D in their blood, but to our surprise, we also found it in people with a high level of vitamin D. We can draw a graph showing that perhaps it is harmful with too little and too much vitamin D," explained Darshana Durup, PhD student. 
If the blood contains less than 10 nanomol (nmol) of vitamin per litre of serum, mortality is 2.31 times higher. However, if the blood contains more than 140 nmol of vitamin per litre of serum, mortality is higher by a factor of 1.42. Both values are compared to 50 nmol of vitamin per litre of serum, where the scientists see the lowest mortality rate. 
Darshana Durup emphasised that while scientists do not know the cause of the higher mortality, she believes that the new results can be used to question the wisdom of those people who claim that you can never get too much vitamin D. 
"It is important to conduct further studies in order to understand the relationship. A lot of research has been conducted on the risk of vitamin D deficiency. However, there is no scientific evidence for a 'more is better' argument for vitamin D, and our study does not support the argument either. We hope that our study will inspire others to study the cause of higher mortality with a high level of vitamin D," said Durup. 
"We have moved into a controversial area that stirs up strong feelings just like debates on global warming and research on nutrition. But our results are based on a quarter of a million blood tests and provide an interesting starting point for further research." 
The study is the largest of its kind - and it was only possible to conduct it because of Denmark's civil registration system, which is unique in the Nordic countries. The 247,574 blood samples come from the Copenhagen General Practitioners Laboratory. 
"Our data material covers a wide age range. The people who participated had approached their own general practitioners for a variety of reasons and had had the vitamin D level in their bloodstream measured in that context. This means that while the study can show a possible association between mortality and a high level of vitamin D, we cannot as yet explain the higher risk," Durup added. 
The study has been published in the Journal of Clinical Endocrinology and Metabolism.
Source:Eurekalert 

When is it ethical to prescribe placebos?

The American Medical Association's Code of Ethics prohibits physicians from prescribing treatments that they consider to be placebos unless the patients know this and agree to take them anyway. But this policy is not clearly the best way to protect or benefit patients, concludes an The American Medical Association's Code of Ethics prohibits physicians from prescribing treatments that they consider to be placebos unless the patients know this and agree to take them anyway. But this policy is not clearly the best way to protect or benefit patients, concludes an article in the Hastings Center Report. A commentary by two AMA bioethicists responding to the article also appears in the journal.

Placebos are commonly understood to be inert treatments, such as sugar pills, that have no pharmacological effect, but the AMA defines placebos more narrowly, as therapies that a physician believes lack a specific pharmacological effect on the conditions being treated. The physician's belief may or may not align with the prevailing medical view of a treatment. "There are borderline and controversial cases, such as acupuncture and antidepressants, in which individual physicians might reasonably disagree with the medical community's consensus about whether a treatment is an active treatment or a placebo," writes Anne Barnhill, a philosopher and bioethicist who is studying social work at Columbia University.

The article cites a recent poll of American internists and rheumatologists that found that a significant number of them admit to giving patients placebos without disclosing the therapies as such. While some placebo use is patently unethical – providing a treatment that "has no scientific basis and is dangerous, is calculated to deceive the patient by giving false hope, or which may cause the patient to delay in seeking proper care" – other uses of placebos are widely seen as ethical, writes Barnhill.

Some placebos might offer medical benefit to patients with certain conditions, Barnhill notes, and the limited available data suggest that placebos are more effective when presented as active treatments. As a result, she adds, some bioethicists have argued that an undisclosed placebo is the best available treatment for some patients. "If the best available treatment is sometimes an undisclosed placebo," she writes, "then the AMA's policy prohibits physicians from offering the best available treatment in some cases."

In addition to failing to benefit patients, the AMA policy may not meet two of its other goals: protecting patients' autonomy and their trust in physicians. The rationale for requiring physicians to disclose their belief that a treatment is a placebo is that patients need this information in order to give informed consent about whether to take the treatment. Informed consent is essential to patient autonomy. But it is unknown whether patients find this information relevant to their decision-making, Barnhill says, because "there's little data on patients' attitudes toward placebos."

Because of this lack of data, Barnhill also argues that the AMA policy does not help protect patients' trust in physicians. "The AMA seems to assume that uncovering undisclosed placebo use reduces patients' trust in physicians. But this is not a given," she writes. "When they uncover undisclosed placebo use, patients might conclude that their physicians are untrustworthy liars or quacks, or that their physicians do not believe that they are truly sick – or, that their physicians are open-minded, cutting-edge, and savvy about mind-body connections."

Barnhill recommends that the AMA consider revising its policy on placebo use. If the goal is to protect patients from harm, safeguard their trust, and respect their autonomy, she says, then rather than requiring physicians to disclose their personal belief about whether a treatment is a placebo, the policy might require physicians to report on the medical community's consensus on the treatment's status.

In the same issue of the Hastings Center Report is a commentary by Bette-Jane Crigger, director of Ethics Policy for the AMA and secretary of the Council on Ethical and Judicial Affairs, which wrote its ethical guidelines on placebo use, and Matthew K. Wynia, director of the AMA's Institute of Ethics. Regarding Barnhill's recommendation that the placebo policy be based on professional consensus, rather than individual doctor's judgment, they write, "We'd be tempted to agree but, as in so much of medicine, it isn't clear that a strong consensus is actually possible here." How, they ask, should doctors distinguish between so-called impure placebos – medications that have a pharmacological effect on some illnesses but not necessarily for the ones for which they are being prescribed – from off-label prescribing?

Crigger and Wynia emphasize that the overarching intent of AMA policy is to encourage physicians to be honest with their patients. "If there is professional disagreement on how or whether a particular pharmacologic agent works, then patients deserve to know that," they write. "If a doctor holds an outlier view, then his or her patients deserve to know that as well.

Source:Eurekalert

Overdiagnosis poses significant threat to human health

Overdiagnosis poses a significant threat to human health by labeling healthy people as sick and wasting resources on unnecessary care, warns Ray Moynihan, Senior Research Fellow at Bond University in Australia, in a feature published on bmj.com today.

The feature comes as an international conference 'Preventing Overdiagnosis' is announced for Sept. 10-12, 2013, in the United States, hosted by The Dartmouth Institute for Health Policy and Clinical Practice, in partnership with the BMJ, the leading consumer organization Consumer Reports and Bond University, Australia.The conference is timely, says Moynihan because "as evidence mounts that we're harming the healthy, concern about overdiagnosis is giving way to concerted action on how to prevent it.""The Dartmouth Institute for Health Policy and Clinical Practice has long been a leader in understanding and communicating the problems of overdiagnosis," say Drs. Steven Woloshin and Lisa Schwartz, professors of medicine at The Dartmouth Institute for Health Policy and Clinical Practice. "We are extremely excited to host this international conference to advance the science and develop concrete proposals to reduce overdiagnosis and its associated harms."Overdiagnosis occurs when people are diagnosed and treated for conditions that will never cause them harm and there's growing evidence that this occurs for a wide range of conditions.For example, a large Canadian study finds that almost a third of people diagnosed with asthma may not have the condition; a systematic review suggests up to one in three breast cancers detected through screenings may be overdiagnosed; and some researchers argue osteoporosis treatments may do more harm than good for women at very low risk of future fracture.Many factors are driving overdiagnosis, including commercial and professional vested interests, legal incentives and cultural issues, say Moynihan and co-authors, Professors Jenny Doust and David Henry. Ever-more sensitive tests are detecting tiny "abnormalities" that will never progress, while widening disease definitions and lowering treatment thresholds mean people at ever lower risks receive permanent medical labels and life-long therapies that will fail to benefit many of them.Added to this, is the cost of wasted resources that could be better used to prevent and treat genuine illness.But Moynihan argues that the main problem of overdiagnosis lies in a strong cultural belief in early detection, fed by deep faith in medical technology. "Increasingly we've come to regard simply being 'at risk' of future disease as being a disease in its own right," he says."It took many years for doctors to accept that bacteria caused peptic ulcers," says co-author of the BMJ feature, Dr. David Henry, chief executive officer of the Institute for Clinical Evaluative Sciences, and professor in the Department of Medicine at the University of Toronto, Canada. "Likewise, it will be hard for doctors and the public to recognize that the earliest detection of disease is not always in the best interests of patients."So what can we do about overdiagnosis?The 2013 conference will provide a forum for learning more, increasing awareness, and developing ways to prevent the problem. At a policy level, there is a clear need for more independent disease definition processes free from financial conflicts of interest, and a change from the incentives that tend to reward overdiagnosis.A leading global authority on evidence-based practice, Professor Paul Glasziou from Bond University in Australia says: "As a side effect of our improving diagnostic technology, overdiagnosis is a rapidly growing problem; we must take it seriously now or suffer the consequences of overtreatment and rising health care waste."As Moynihan and colleagues write in their BMJ feature, concern about overdiagnosis in no way precludes awareness that many people miss out on much needed healthcare. On the contrary, resources wasted on unnecessary care can be much better spent treating and preventing genuine illness, not pseudo-disease. "The challenge is to work out which is which, and to produce and disseminate evidence to help us all make more informed decisions about when a diagnosis might do us more harm than good," they conclude.Fiona Godlee, editor-in-chief of the BMJ, said: "The harm of overdiagnosis to individuals and the cost to health systems is becoming ever clearer. Far less clear is what we should do about it. Next year's conference is an important step towards some evidence based solutions.

Source:Eurekalert

Mayo Clinic, youth mental health experts, publish new guidelines to treat childhood aggression

Guidelines aim to help primary care doctors, mental health specialists better care for difficult-to-manage youth showing aggression

Mayo Clinic researchers, in collaboration with other research institutions and youth mental health experts, are publishing new guidelines for primary care providers and mental health specialists to manage the common but often complex problem of childhood aggression. The goals include improving diagnosis and care and avoiding inappropriate use of medication.

The guidelines, titled "Treatment of Maladaptive Aggression in Youth," are published online this week in the journal Pediatrics. The guidelines -- intended for primary care and mental health specialists — are free and publicly available via a downloadable, user-friendly toolkit.

Treating and managing aggression is generally difficult, says Peter Jensen, M.D., a Mayo Clinic psychiatrist who led the development of the new guidelines. More troubling, he says, are that antipsychotics and mood-stabilizing drugs are increasingly prescribed to children on an outpatient basis to treat overt aggression, a symptom that may have multiple causes, Dr. Jensen says.

"These large-scale shifts in treatment practices have occurred despite potentially troubling side effects and a lack of supportive empirical evidence," Dr. Jensen says. "With the increase in the prescription of psychotropic agents outside of FDA-approved indications, concerns have been raised over treatment decision-making, appropriate use of alternative therapies, long-term management, safety of multiple drug regimens and successful parental engagement and education."

To better address this clinical need and improve outcomes for children and adolescents with maladaptive aggression, a group — including Mayo Clinic, The REACH Institute, the Center for Education and Research on Mental Health Therapeutics at Rutgers University, and 60 national experts in the fields of policy, research, advocacy and child and adolescent psychiatry — joined to achieve consensus on improving the diagnosis and treatment of aggressive children and adolescents.

"The guidelines were developed to help mental health specialists and primary care clinicians work closely together in the optimal management of the all-too-common, but very difficult problem of aggression in children and youth," Dr. Jensen says.

Recommendations include carefully engaging and forming a strong treatment alliance with the patient and family; conducting a rigorous, thorough diagnostic workup; carefully measuring treatment response and outcomes using reliable assessment tools; providing education and support for families; helping families obtain community and educational resources; using proven psychological therapies before starting any antipsychotic or mood stabilizer medications; and carefully tracking (and preventing, whenever possible) side effects.

Source:Eurekalert