Anti-inflammatory drug can prevent neuron loss in Parkinson’s model

An experimental anti-inflammatory drug can protect vulnerable neurons and reduce motor deficits in a rat model of Parkinson’s disease, researchers at Emory University School of Medicine have shown.The results were published Thursday, July 24 in the Journal of Parkinson’s Disease.The findings demonstrate that the drug, called XPro1595, can reach the brain at sufficient levels and have beneficial effects when administered by subcutaneous injection, like an insulin shot. Previous studies of XPro1595 in animals tested more invasive modes of delivery, such as direct injection into the brain.”This is an important step forward for anti-inflammatory therapies for Parkinson’s disease,” says Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine. “Our results provide a compelling rationale for moving toward a clinical trial in early Parkinson’s disease patients.”The new research on subcutaneous administration of XPro1595 was funded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF). XPro1595 is licensed by FPRT Bio, and is seeking funding for a clinical trial to test its efficacy in the early stages of Parkinson’s disease.”We are proud to have supported this work and glad to see positive pre-clinical results,” said Marco Baptista, PhD, MJFF associate director of research programs. “A therapy that could slow Parkinson’s progression would be a game changer for the millions living with this disease, and this study is a step in that direction.”In addition, Tansey and Yoland Smith, PhD, from Yerkes National Primate Research Center, were awarded a grant this week from the Parkinson’s Disease Foundation to test XPro1595 in a non-human primate model of Parkinson’s.Evidence has been piling up that inflammation is an important mechanism driving the progression of Parkinson’s disease. XPro1595 targets tumor necrosis factor (TNF), a critical inflammatory signaling molecule, and is specific to the soluble form of TNF. This specificity would avoid compromising immunity to infections, a known side effect of existing anti-TNF drugs used to treat disorders such as rheumatoid arthritis.”Inflammation is probably not the initiating event in Parkinson’s disease, but it is important for the neurodegeneration that follows,” Tansey says. “That’s why we believe that an anti-inflammatory agent, such as one that counteracts soluble TNF, could substantially slow the progression of the disease.”Postdoctoral fellow Christopher Barnum, PhD and colleagues used a model of Parkinson’s disease in rats in which the neurotoxin 6-hydroxydopamine (6-OHDA) is injected into only one side of the brain. This reproduces some aspects of Parkinson’s disease: neurons that produce dopamine in the injected side of the brain die, leading to impaired movement on the opposite side of the body.When XPro1595 is given to the animals 3 days after 6-OHDA injection, just 15 percent of the dopamine-producing neurons were lost five weeks later. …

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Experiences at every stage of life contribute to cognitive abilities in old age

Early life experiences, such as childhood socioeconomic status and literacy, may have greater influence on the risk of cognitive impairment late in life than such demographic characteristics as race and ethnicity, a large study by researchers with the UC Davis Alzheimer’s Disease Center and the University of Victoria, Canada, has found.”Declining cognitive function in older adults is a major personal and public health concern,” said Bruce Reed professor of neurology and associate director of the UC Davis Alzheimer’s Disease Center.”But not all people lose cognitive function, and understanding the remarkable variability in cognitive trajectories as people age is of critical importance for prevention, treatment and planning to promote successful cognitive aging and minimize problems associated with cognitive decline.”The study, “Life Experiences and Demographic Influences on Cognitive Function in Older Adults,” is published online in Neuropsychology, a journal of the American Psychological Association. It is one of the first comprehensive examinations of the multiple influences of varied demographic factors early in life and their relationship to cognitive aging.The research was conducted in a group of over 300 diverse men and women who spoke either English or Spanish. They were recruited from senior citizen social, recreational and residential centers, as well as churches and health-care settings. At the time of recruitment, all study participants were 60 or older, and had no major psychiatric illnesses or life threatening medical illnesses. Participants were Caucasian, African-American or Hispanic.The extensive testing included multidisciplinary diagnostic evaluations through the UC Davis Alzheimer’s Disease Center in either English or Spanish, which permitted comparisons across a diverse cohort of participants.Consistent with previous research, the study found that non-Latino Caucasians scored 20 to 25 percent higher on tests of semantic memory (general knowledge) and 13 to 15 percent higher on tests of executive functioning compared to the other ethnic groups. However, ethnic differences in executive functioning disappeared and differences in semantic memory were reduced by 20 to 30 percent when group differences in childhood socioeconomic status, adult literacy and extent of physical activity during adulthood were considered.”This study is unusual in that it examines how many different life experiences affect cognitive decline in late life,” said Dan Mungas, professor of neurology and associate director of the UC Davis Alzheimer’s Disease Research Center.”It shows that variables like ethnicity and years of education that influence cognitive test scores in a single evaluation are not associated with rate of cognitive decline, but that specific life experiences like level of reading attainment and intellectually stimulating activities are predictive of the rate of late-life cognitive decline. This suggests that intellectual stimulation throughout the life span can reduce cognitive decline in old age.”Regardless of ethnicity, advanced age and apolipoprotein-E (APOE genotype) were associated with increased cognitive decline over an average of four years that participants were followed. APOE is the largest known genetic risk factor for late-onset Alzheimer’s. Less decline was experienced by persons who reported more engagement in recreational activities in late life and who maintained their levels of activity engagement from middle age to old age. Single-word reading — the ability to decode a word on sight, which often is considered an indication of quality of educational experience — was also associated with less cognitive decline, a finding that was true for both English and Spanish readers, irrespective of their race or ethnicity. …

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Fatigue and returning to normality!

Underlying fatigue sets in after basis exertion, however it does not stop me from getting on with my life while undergoing chemotherapy! I simply stop and have a rest then keep going …. . I have to be careful with my shallow breathing and do stop and rest if need be. Slowly returning to normality. Weds will be day 14 since chemo.When in Washington, April 2014 I was presented with the 2014 Alan Reinstein Award (ADAO Asbestos Disease Awareness Organisation) at the annual global asbestos awareness conference for my commitment to education, advocacy and support to countless patients and families around the world. Unfortunately my beautiful crystal teardrop award was broken on the tip in transit. Linda Reinstein, ADAO kindly organised a replacement award to be sent to my home in …

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New hope for powdery mildew resistant barley

New research at the University of Adelaide has opened the way for the development of new lines of barley with resistance to powdery mildew.In Australia, annual barley production is second only to wheat with 7-8 million tonnes a year. Powdery mildew is one of the most important diseases of barley.Senior Research Scientist Dr Alan Little and team have discovered the composition of special growths on the cell walls of barley plants that block the penetration of the fungus into the leaf.The research, by the ARC Centre of Excellence in Plant Cell Walls in the University’s School of Agriculture, Food and Wine in collaboration with the Leibniz Institute of Plant Genetics and Crop Plant Research in Germany, will be presented at the upcoming 5th International Conference on Plant Cell Wall Biology and published in the journal New Phytologist.”Powdery mildew is a significant problem wherever barley is grown around the world,” says Dr Little. “Growers with infected crops can expect up to 25% reductions in yield and the barley may also be downgraded from high quality malting barley to that of feed quality, with an associated loss in market value.”In recent times we’ve seen resistance in powdery mildew to the class of fungicide most commonly used to control the disease in Australia. Developing barley with improved resistance to the disease is therefore even more important.”The discovery means researchers have new targets for breeding powdery mildew resistant barley lines.”Powdery mildew feeds on the living plant,” says Dr Little. “The fungus spore lands on the leaf and sends out a tube-like structure which punches its way through cell walls, penetrating the cells and taking the nutrients from the plant. The plant tries to stop this penetration by building a plug of cell wall material — a papillae — around the infection site. Effective papillae can block the penetration by the fungus.”It has long been thought that callose is the main polysaccharide component of papilla. But using new techniques, we’ve been able to show that in the papillae that block fungal penetration, two other polysaccharides are present in significant concentrations and play a key role.”It appears that callose acts like an initial plug in the wall but arabinoxylan and cellulose fill the gaps in the wall and make it much stronger.”In his PhD project, Jamil Chowdhury showed that effective papillae contained up to four times the concentration of callose, arabinoxylan and cellulose as cell wall plugs which didn’t block penetration.”We can now use this knowledge find ways of increasing these polysaccharides in barley plants to produce more resistant lines available for growers,” says Dr Little.Story Source:The above story is based on materials provided by University of Adelaide. Note: Materials may be edited for content and length.

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Novel drug cocktail may improve clinical treatment for pancreatic cancer

Pancreatic cancer is the fourth leading cause of cancer deaths in the U.S. and has the lowest overall survival rate of all major cancers (~6%). With current treatment options being met with limited success it is anticipated that pancreatic cancer will move up to the second leading cause of cancer deaths by as early as 2015. Surgical removal of the tumor presents the best chance of survival, however only 15% of patients are eligible due to the late stage of diagnosis common with this disease. With very limited improvements in patient outcome over the last two decades there remains an enormous need for new therapies and treatment options.David Durrant, a Ph.D. student in the laboratory of Dr. Rakesh Kukreja from the Pauley Heart Center at Virginia Commonwealth University’s School of Medicine, is studying a novel combination therapy for the treatment of pancreatic cancer. The traditional chemotherapy drug, doxorubicin (DOX), has long been used in the treatment of several cancers. However, patients commonly acquire resistance to DOX because of increased activation of specific survival proteins or through increased expression of drug transporters which reduce cellular levels of the drug. This is especially true for pancreatic cancer, which does not respond to multiple treatment strategies, including those that contain DOX. …

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Flipping the switch on scleroderma

Scleroderma is a rare and often fatal disease, causing the thickening of tissue, that currently lacks a cure and any effective treatments. A group of researchers, including a Michigan State University professor, is looking to change that.”Our findings provide a new approach to developing better treatment options where few have existed,” said Richard Neubig, chairperson of the Department of Pharmacology and Toxicology in MSU’s College of Osteopathic Medicine.Neubig, along with several of his colleagues from the University of Michigan, have identified the core signaling pathway that activates the disease and the chemical compounds that can turn it off.”There are two kinds of scleroderma — localized and systemic — with the latter often proving to be life threatening,” said Neubig, who helped lead the study. “This research shows that by inhibiting this main signaling pathway, we can block fibrosis — the thickening of tissue that occurs with the disease.”For localized scleroderma patients, this process often happens in the skin resulting in loss of flexibility. Systemic sclerosis has the same effect with variable degree of skin fibrosis, but also can spread throughout the body hardening key organs such as the lungs, heart, gut and kidneys.Scleroderma is an autoimmune disorder. It’s estimated 300,000 Americans suffer from the disease with about one-third of those having the systemic form. Localized scleroderma patients usually live normal lifespans. Yet about half of systemic patients, especially with widespread skin involvement and internal organ fibrosis, will see their lives cut short.”The majority of drug treatments that exist today for fibrosis basically look at reducing just the inflammation,” said Dinesh Khanna, associate professor in the Department of Internal Medicine and director of the Scleroderma Program at the University of Michigan. “There are other drugs that block one or two of the signaling pathways that cause the disease, but scleroderma has many of these pathways.”Neubig agrees and adds that this new research could significantly change the quality of life for scleroderma patients and greatly increase the lifespan of systemic patients.”Our research shows promise for the development of a new drug that can reverse the fibrosis process by flipping the main switch on all of the signaling pathways,” Neubig said. “By validating this core switch as a viable drug target, we can now continue our work to improve the chemical compounds so they will work with doses that are appropriate for people. It’s definitely promising.”Story Source:The above story is based on materials provided by Michigan State University. …

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Monkey caloric restriction study shows big benefit; contradicts earlier study

The latest results from a 25-year study of diet and aging in monkeys shows a significant reduction in mortality and in age-associated diseases among those with calorie-restricted diets. The study, begun at the University of Wisconsin-Madison in 1989, is one of two ongoing, long-term U.S. efforts to examine the effects of a reduced-calorie diet on nonhuman primates.The study of 76 rhesus monkeys, reported Monday in Nature Communications, was performed at the Wisconsin National Primate Research Center in Madison. When they were 7 to 14 years of age, the monkeys began eating a diet reduced in calories by 30 percent. The comparison monkeys, which ate as much as they wanted, had an increased risk of disease 2.9 times that of the calorie-restricted group, and a threefold increased risk of death.”We think our study is important because it means the biology we have seen in lower organisms is germane to primates,” says Richard Weindruch, a professor of medicine at the School of Medicine and Public Health, and one of the founders of the UW study. “We continue to believe that mechanisms that combat aging in caloric restriction will offer a lead into drugs or other treatments to slow the onset of disease and death.”Restricting the intake of calories while continuing to supply essential nutrients extends the lifespan of flies, yeast and rodents by as much as 40 percent. Scientists have long wanted to understand the mechanisms for caloric restriction. “We study caloric restriction because it has such a robust effect on aging and the incidence and timing of age related disease,” says corresponding author Rozalyn Anderson, an assistant professor of geriatrics. “Already, people are studying drugs that affect the mechanisms that are active in caloric restriction. There is enormous private-sector interest in some of these drugs.”Still, the effects of caloric restriction on primates have been debated. …

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Stigmas, once evolutionarily sound, are now bad health strategies

Stigmatization may have once served to protect early humans from infectious diseases, but that strategy may do more harm than good for modern humans, according to Penn State researchers.”The things that made stigmas a more functional strategy thousands of years ago rarely exist,” said Rachel Smith, associate professor of communication arts and sciences and human development and family studies. “Now, it won’t promote positive health behavior and, in many cases, it could actually make the situation worse.”Stigmatizing and ostracizing members stricken with infectious diseases may have helped groups of early humans survive, said Smith, who worked with David Hughes, assistant professor of entomology and biology. Infectious agents thrive by spreading through populations, according to Smith and Hughes, who published an essay in the current issue of Communication Studies.For early humans, a person who was stigmatized by the group typically suffered a quick death, often from a lack of food or from falling prey to a predator. Groups did not mix on a regular basis, so another group was unlikely to adopt an ostracized person. Infectious disease stigmas may have evolved as a social defense for group-living species, and had adaptive functions when early humans had these interaction patterns.However, modern society is much larger, more mobile and safer from predators, eliminating the effectiveness of this strategy, according to Smith.”In modern times, we mix more regularly, travel more widely, and also there are so many people now,” Smith said. “These modern interaction patterns make stigmatization unproductive and often create more problems.”Hughes studies disease in another successful society, the ants, which have strong stigma and ostracism strategies that serve group interests at the cost to individuals.”Ants are often held up as paragons of society and efficiency but we certainly do not want to emulate how they treat their sick members, which can be brutal,” said Hughes.Stigmatization could actually make infectious disease management worse. The threat of ostracization may make people less likely to seek out medical treatment. If people refuse to seek treatment and go about their daily routines, they may cause the disease to spread farther and faster, according to the researchers, who are both investigators in the Center of Infectious Disease Dynamics in Penn State Huck Institutes of the Life Sciences.Stigmatization may harm a person’s ability to survive a disease. Ostracization may increase stress, lessening the body’s ability to fight off diseases and infections.”People are very sensitive to rejection and humans worry about being ostracized,” said Smith. “These worries and experiences with rejection can cause problematic levels of stress and, unfortunately, stress can compromise the immune system’s ability to fight off an infection, accelerating disease progression.”Once applied, a stigma is difficult to remove, even when there are obvious signs that the person was never infected or is cured. …

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Mosquito season unpredictable; year-round heartworm prevention is best

Although it may not feel like spring yet, it’s time to start thinking about protecting your pets from spring pests, particularly mosquitoes, according to a Kansas State University veterinarian.Susan Nelson, clinical associate professor of the university’s Veterinary Health Center, says mosquitoes carry heartworm, a blood parasite that can be deadly when spread to cats and dogs. Almost 100 percent of dogs exposed to heartworm will develop the disease. While that number is not as high for cats, it is often more fatal for felines.”Cats are sometimes a little less obvious with their heartworm disease,” Nelson said. “It can be just a little weight loss or lethargy, but we can also see asthma-type signs in cats. They can have trouble breathing, develop a cough, chronic gagging and vomiting.”It only takes one or two worms to cause significant harm to a cat and unlike dogs, there is no treatment for heartworm once cats are infected. That’s why it is important to use prevention tools.”We really want to preach prevention for our pets because it’s so much easier and so much cheaper for them, especially since treatment is hard on them,” Nelson said.Nelson also stresses that prevention year-round is key to protecting your pet because just like the weather, mosquito season is unpredictable.Story Source:The above story is based on materials provided by Kansas State University. Note: Materials may be edited for content and length.

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Secret to cutting sugary drink use by teens found by new study

A new study shows that teenagers can be persuaded to cut back on sugary soft drinks — especially with a little help from their friends.A 30-day challenge encouraging teens to reduce sugar-sweetened drink use lowered their overall consumption substantially and increased by two-thirds the percentage of high-school students who shunned sugary drinks altogether.The “Sodabriety” challenge, piloted by Ohio State University researchers, was an effort to confront the largest source of added sugar in the U.S. diet: sugar-sweetened soft drinks, sports and energy drinks, and flavored milk and coffee.Students were tapped to establish teen advisory councils, whose members led the interventions at two rural Appalachian high schools. They designed marketing campaigns, planned school assemblies and shared a fact per day about sugar-sweetened drinks over the morning announcements.The primary message to their peers: Try to cut back on sugar-sweetened beverages for 30 days. Students opted not to promote eliminating these drinks entirely during the challenge.Overall, participating teens did lower their intake of sugary drinks, and the percentage of youths who abstained from drinking sugar-sweetened beverages increased from 7.2 percent to 11.8 percent of the participants. That percentage was sustained for 30 days after the intervention ended.In an unexpected result, water consumption among participants increased significantly by 60 days after the start of the program, even without any promotion of water as a substitute for sugar-sweetened drinks.”The students’ water consumption before the intervention was lousy. I don’t know how else to say it. But we saw a big improvement in that,” said Laureen Smith, associate professor of nursing at Ohio State and lead author of the study. “And there was a huge reduction in sugar-sweetened beverage consumption. The kids were consuming them fewer days per week and when they were consuming these drinks, they had fewer servings.”Smith co-authored the study with Christopher Holloman, associate professor of statistics at Ohio State. The research is published in a recent issue of the Journal of School Health.Smith originally set out to conduct a community-based study concerning the prevalence of Type 2 diabetes in Appalachian Ohio. …

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Preventing Head Blight in Barley, Wheat: Biochemical Pathways Hold Key to Resistance

Pale, shriveled heads of grain spell trouble for wheat and barley farmers — they’re the telltale signs of fusarium head blight. The fungal disease, commonly known as scab, not only dramatically shrinks yields but produces toxins that make the grain dangerous for human or animal consumption.From 1991 to 1996, head blight caused $2.6 billion in losses to the U.S. wheat crop. At its peak, the fungus destroyed the entire malting barley crop in the Red River and Ohio River Valleys, according to molecular biologist Yang Yen, an Agricultural Experiment Station researcher and professor at South Dakota State University.Two decades later the U.S. Department of Agriculture still ranks head blight as “the worst plant disease to hit the U.S. since the rust epidemics in the 1950s.” Wheat and barley farmers have lost more than $3 billion since 1990 from blight outbreaks.Despite major research funding — including the U.S. Wheat and Barley Scab Initiative, scientists admit that efforts to control this devastating disease have met with limited success.”This is an extraordinary disease that requires extraordinary means to combat it,” says Yen, who began working on head blight in 1997.Using advanced genetic and molecular technologies, Yen has begun tracing the biochemical pathways that make wheat susceptible or resistant to head blight. Three graduate students and two postdoctoral scientists have worked on this research over the last 16 years.Multiple hosts and pathogensHead blight can be caused by multiple pathogens, and these pathogens can attack multiple hosts including grasses and corn, Yen explains. This makes the disease tougher to combat.Researchers are working to develop resistant types of grain, alter tillage practices and apply fungicides to fight the disease.”This disease is not new,” Yen says. It was first reported in England in 1884 and in North America in 1890. …

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Gene silencing instructions acquired through ‘molecular memory’ tags on chromatin

Scientists at Indiana University have unlocked one of the mysteries of modern genetics: how acquired traits can be passed between generations in a process called epigenetic inheritance. The new work finds that cells don’t know to silence some genes based on information hardwired into their DNA sequences, but recognize heritable chemical marks that are added to the genes. These chemical tags serve as a form of molecular memory, allowing cells to recognize the genes and remember to silence them again in each new generation.The discovery made by a 12-member all-Indiana University team of scientists led by IU biologist and biochemist Craig Pikaard provides important new insight into how plant cells know to silence a genetic locus — that specific place on a chromosome where a gene is located — in every successive generation.Rather than rely on intrinsic, DNA sequence-based information, the cells instead must recall the need to silence specific loci by relying on chemical marks displayed on the complex of DNA and proteins called chromatin. Addition, or removal, of one-carbon (methyl) or two-carbon (acetyl) chemical tags are ways of modifying chromatin that can impart additional, epigenetic (literally, “above genetic”) information to a locus beyond the genetic information encoded in the DNA.The ability to perpetuate chromatin marks serves as a form of epigenetic memory that confers what Pikaard calls silent locus identity, a pre-established state that is needed for the cell to deliver to the loci the machinery that actually accomplishes silencing in a multi-step process known as RNA-directed DNA methylation (RdDM). RdDM involves short-interfering RNAs (siRNA), tiny RNA molecules that are 24 nucleotides long and that guide the addition of methyl groups to matching DNA strands, ultimately rendering the genes inactive.”Importantly, this work shows that silent locus identity is required for, but separable from, actual gene silencing,” Pikaard said. “We’ve found that epigenetic inheritance is a two-step process, with the heritable specification of silent locus identity occurring before actual silencing of the locus can occur.”Scientists are interested in epigenetic inheritance because it’s a process by which heritable modifications occur in gene function without changes in the base sequence of an organism’s DNA being required. Disease states such as cancer, which occur sporadically during an individual’s lifetime, are increasingly recognized as having an epigenetic basis. Pikaard said the new work not only sheds important new light on the mechanisms responsible for epigenetic inheritance, a topic of broad interest in the fields of genetics and chromosome biology, but it also helps explain the basis for the recruitment of two plant-specific gene silencing enzymes — the RNA polymerases Pol IV and Pol V — first identified by Pikaard in 1999.Specifically, the researchers tested and identified the relationship between histone deacetylase 6 (HDA6), an enzyme that removes acetyl groups from histones, and the CG DNA sequence maintenance methyltransferase, MET1, and discovered that their partnership in maintenance methylation can explain the perpetuation of epigenetic memory that accounts for silent locus identity.”Collectively, our results show that silent locus identity is perpetuated from generation to generation through the actions of HDA6 and MET1,” Pikaard said. “These activities are not sufficient to silence the loci but maintain a chromatin state that is required for Pol IV recruitment, siRNA biogenesis and RdDM, which is what ultimately silences the loci.” When the team removed the RdDM pathway in Pol IV and Pol V mutant strains of the model plant Arabidopsis thaliana (rockcress), all gene silencing was lost, but silent locus identity remained. They then removed the HDA6 and MET1-dependent process that specifies silent locus identity and, importantly, the epigenetic memory required for silent locus identity was lost and unable to be regained.Story Source:The above story is based on materials provided by Indiana University. …

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Ipilimumab in advanced melanoma: Added benefit for non-pretreated patients not proven

The German Institute for Quality and Efficiency in Health Care (IQWiG) already assessed the added benefit of ipilimumab in advanced melanoma in 2012. A considerable added benefit was found for patients who had already received previous treatment. In the new dossier compiled by the drug manufacturer, the drug was now compared with the appropriate comparator therapy dacarbazine specified by the Federal Joint Committee (G-BA) also for non-pretreated patients.Again, the manufacturer claimed a noticeable gain in survival time and thus an added benefit. This time, IQWiG did not concur with the interpretation: The effect was estimated on the basis of an indirect comparison of individual patient data. The data were very uncertain and, moreover, by unilaterally excluding patients with particularly unfavourable prognosis, the effect was biased in favour of ipilimumab. Hence an added benefit of ipilimumab in advanced melanoma for non-pretreated patients is not proven.Approval expandedIpilimumab is a monoclonal antibody used in melanoma if the disease is so advanced that the melanoma can no longer be surgically removed or has formed metastases. In 2012, the manufacturer presented informative data from a randomized controlled trial for pretreated patients. These data indicated a major advantage of ipilimumab in survival time, which was associated with major risk of harm, however.After the European approval was expanded in 2013 to include patients who have not been treated for their advanced melanoma, the manufacturer now claimed an added benefit versus the appropriate comparator therapy dacarbazine specified by the G-BA also for this group.Indirect comparison of low qualityHowever, the manufacturer neither presented a direct comparison nor a so-called adjusted indirect comparison between the study participants who received ipilimumab or the appropriate comparator therapy. Instead, it based its assessment on an indirect comparison of individual patient data from different studies on ipilimumab and on one single study on dacarbazine, from which it chose those patients who had not received previous treatment of advanced melanoma.It can be assumed in these unadjusted indirect comparisons that patients on both sides of the comparison differ from each other with regards to important confounders, which can entail a systematic bias of the treatment effect. The manufacturer tried to account for these differences with a statistical method.Results biased in favour of ipilimumabHowever, the manufacturer only included those patients in its comparison for whom data on all confounders considered were available. …

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Mindfulness-based meditation helps teenagers with cancer

Mindfulness-based meditation could lessen some symptoms associated with cancer in teens, according to the results of a clinical trial intervention led by researchers at the University of Montreal and its affiliated CHU Sainte-Justine children’s hospital.Mindfulness-based meditation focuses on the present moment and the connection between the mind and body. Adolescents living with cancer face not only the physical symptoms of their condition, but also the anxiety and uncertainty related to the progression of the disease, the anticipation of physical and emotional pain related to illness and treatment, the significant changes implied in living with cancer, as well as the fear of recurrence after remission. Catherine Malboeuf-Hurtubise of the university’s Department of Psychology presented the findings today at the American Psychosomatic Society Meeting in San Francisco.The researchers asked 13 adolescents with cancer to complete questionnaires covering mood (positive and negative emotions, anxiety and depression), sleep and quality of life. The group was divided in two: a first group of eight adolescents were offered eight mindfulness-based meditation sessions and the remaining five adolescents in the control group were put on a wait-list. The eight sessions were 90 minutes long and took place weekly. After the last meditation session, patients from both groups filled out the same questionnaires a second time. “We analyzed differences in mood, sleep and quality of life scores for each participant and then between each group to evaluate if mindfulness sessions had a greater impact than the simple passage of time. We found that teenagers that participated in the mindfulness group had lower scores in depression after our 8 sessions. Girls from the mindfulness group reported sleeping better. We also noticed that they developed mindfulness skills to a greater extent than boys during the sessions,” Malboeuf-Hurtubise said. …

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New theory on cause of endometriosis

Changes to two previously unstudied genes are the centerpiece of a new theory regarding the cause and development of endometriosis, a chronic and painful disease affecting 1 in 10 women.The discovery by Northwestern Medicine scientists suggests epigenetic modification, a process that enhances or disrupts how DNA is read, is an integral component of the disease and its progression. Matthew Dyson, research assistant professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and and Serdar Bulun, MD, chair of obstetrics and gynecology at Feinberg and Northwestern Memorial Hospital, also identified a novel role for a family of key gene regulators in the uterus.”Until now, the scientific community was looking for a genetic mutation to explain endometriosis,” said Bulun, a member of the Center for Genetic Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This is the first conclusive demonstration that the disease develops as a result of alterations in the epigenetic landscape and not from classical genetic mutations.”The findings were recently published in PLoS Genetics.Women develop endometriosis when cells from the lining of the uterus, usually shed during menstruation, grow in other areas of the body. The persistent survival of these cells results in chronic pelvic pain and infertility. Although the cause of the disease has remained unknown on a cellular level, there have been several different models established to explain its development.Endometriosis only occurs in menstruating primates, suggesting that the unique evolution behind uterine development and menstruation are linked to the disease. Scientists consider retrograde menstruation — cells moving up the fallopian tubes and into the pelvis — as one probable cause. Previous models, however, have been unable to explain why only 10 percent of women develop the disease when most experience retrograde menstruation at some point. Nor do they explain instances of endometriosis that arise independent of menstruation.Bulun and Dyson propose that an epigenetic switch permits the expression of the genetic receptor GATA6 rather than GATA2, resulting in progesterone resistance and disease development.”We believe an overwhelming number of these altered cells reach the lining of the abdominal cavity, survive and grow,” Bulun said. “These findings could someday lead to the first noninvasive test for endometriosis.”Clinicians could then prevent the disease by placing teenagers predisposed to this epigenetic change on a birth control pill regimen, preventing the possibility of retrograde menstruation in the first place, Bulun said.Dyson will also look to use the epigenetic fingerprint resulting from the presence of GATA6 rather than GATA2 as a potential diagnostic tool, since these epigenetic differences are readily detectable.”These findings have the potential to shift how we view and treat the disease moving forward,” Bulun said.Story Source:The above story is based on materials provided by Northwestern University. …

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Protective mutations for type 2 diabetes pinpointed

An international team led by researchers at the Broad Institute and Massachusetts General Hospital (MGH) has identified mutations in a gene that can reduce the risk of developing type 2 diabetes, even in people who have risk factors such as obesity and old age. The results focus the search for developing novel therapeutic strategies for type 2 diabetes; if a drug can be developed that mimics the protective effect of these mutations, it could open up new ways of preventing this devastating disease.Type 2 diabetes affects over 300 million people worldwide and is rising rapidly in prevalence. Lifestyle changes and existing medicines slow the progression of the disease, but many patients are inadequately served by current treatments. The first step to developing a new therapy is discovering and validating a “drug target” — a human protein that, if activated or inhibited, results in prevention and treatment of the disease.The current study breaks new ground in type 2 diabetes research and guides future therapeutic development in this disease. In the new study, researchers describe the genetic analysis of 150,000 patients showing that rare mutations in a gene called SLC30A8 reduce risk of type 2 diabetes by 65 percent. The results were seen in patients from multiple ethnic groups, suggesting that a drug that mimics the effect of these mutations might have broad utility around the globe. The protein encoded by SLC30A8 had previously been shown to play an important role in the insulin-secreting beta cells of the pancreas, and a common variant in that gene was known to slightly influence the risk of type 2 diabetes. However, it was previously unclear whether inhibiting or activating the protein would be the best strategy for reducing disease risk — and how large an effect could be expected.”This work underscores that human genetics is not just a tool for understanding biology: it can also powerfully inform drug discovery by addressing one of the most challenging and important questions — knowing which targets to go after,” said co-senior author David Altshuler, deputy director and chief academic officer at the Broad Institute and a Harvard Medical School professor at Massachusetts General Hospital.The use of human genetics to identify protective mutations holds great potential. Mutations in a gene called CCR5 were found to protect against infection with HIV, the virus that causes AIDS; drugs have been developed that block the CCR5 protein. A similar protective association for heart disease set off a race to discover new cholesterol-lowering drugs when mutations in the gene PCSK9 were found to lower cholesterol levels and heart disease risk. …

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3-D imaging sheds light on Apert syndrome development

Three dimensional imaging of two different mouse models of Apert Syndrome shows that cranial deformation begins before birth and continues, worsening with time, according to a team of researchers who studied mice to better understand and treat the disorder in humans.Apert Syndrome is caused by mutations in FGFR2 — fibroblast growth factor receptor 2 — a gene, which usually produces a protein that functions in cell division, regulation of cell growth and maturation, formation of blood vessels, wound healing, and embryonic development. With certain mutations, this gene causes the bones in the skull to fuse together early, beginning in the fetus. These mutations also cause mid-facial deformation, a variety of neural, limb and tissue malformations and may lead to cognitive impairment.Understanding the growth pattern of the head in an individual, the ability to anticipate where the bones will fuse and grow next, and using simulations “could contribute to improved patient-centered outcomes either through changes in surgical approach, or through more realistic modeling and expectation of surgical outcome,” the researchers said in today’s (Feb. 28) issue of BMC Developmental Biology.Joan T. Richtsmeier, Distinguished Professor of Anthropology, Penn State, and her team looked at two sets of mice, each having a different mutation that causes Apert Syndrome in humans and causes similar cranial problems in the mice. They checked bone formation and the fusing of sutures, soft tissue that usually exists between bones n the skull, in the mice at 17.5 days after conception and at birth — 19 to 21 days after conception.”It would be difficult, actually impossible, to observe and score the exact processes and timing of abnormal suture closure in humans as the disease is usually diagnosed after suture closure has occurred,” said Richtsmeier. “With these mice, we can do this at the anatomical level by visualizing the sutures prenatally using micro-computed tomography — 3-D X-rays — or at the mechanistic level by using immunohistochemistry, or other approaches to see what the cells are doing as the sutures close.”The researchers found that both sets of mice differed in cranial formation from their littermates that were not carrying the mutation and that they differed from each other. They also found that the changes in suture closure in the head progressed from 17.5 days to birth, so that the heads of newborn mice looked very different at birth than they did when first imaged prenatally.Apert syndrome also causes early closure of the sutures between bones in the face. Early fusion of bones of the skull and of the face makes it impossible for the head to grow in the typical fashion. The researchers found that the changed growth pattern contributes significantly to continuing skull deformation and facial deformation that is initiated prenatally and increases over time.”Currently, the only option for people with Apert syndrome is rather significant reconstructive surgery, sometimes successive planned surgeries that occur throughout infancy and childhood and into adulthood,” said Richtsmeier. …

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Substance Found in Turmeric Packs Powerful Punch against Mesothelioma

Curcumin,a naturally occurring polyphenol in turmeric, is being studied for its possible application in the treatment and prevention of mesothelioma. Turmeric has long been believed to have anticancer properties due to its antioxidant andanti-inflammatory properties.Researchers at the University of Vermont found that curcumin caused pyroptotic cell death in both mouse and human in vitro models with malignant mesothelioma cell lines. Cell death was induced by the activation of the enzyme caspase-1, and the increased release of high-mobility group box 1 (HMGB1), a nuclear protein responsible for organizing DNA and regulating transcription.Researchers blocked production of pro-inflammatory cytokines IL-1β and IL-18 by inhibiting the NF-κB pathway, a protein responsible for cytokine production and cell survival which has been linked to cancer, …

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Trigger found for most common form of intellectual disability, autism

A new study led by Weill Cornell Medical College scientists shows that the most common genetic form of mental retardation and autism occurs because of a mechanism that shuts off the gene associated with the disease. The findings, published today in Science, also show that a drug that blocks this silencing mechanism can prevent fragile X syndrome — suggesting similar therapy is possible for 20 other diseases that range from mental retardation to multisystem failure.Fragile X syndrome occurs mostly in boys, causing intellectual disability as well as telltale physical, behavioral and emotional traits. While researchers have known for more than two decades that the culprit behind the disease is an unusual mutation characterized by the excess repetition of a particular segment of the genetic code, they weren’t sure why the presence of a large number of these repetitions — 200 or more — sets the disease process in motion.Using stem cells from donated human embryos that tested positive for fragile X syndrome, the scientists discovered that early on in fetal development, messenger RNA — a template for protein production — begins sticking itself onto the fragile X syndrome gene’s DNA. This binding appears to gum up the gene, making it inactive and unable to produce a protein crucial to the transmission of signals between brain cells.”Until 11 weeks of gestation, the fragile X syndrome gene is active — it produces its messenger RNA and protein normally. Then, all of a sudden it turns off, and stays off for the rest of the patient’s lifetime, causing fragile X syndrome. But scientists have not understood why this gene gets shut off,” says senior author Dr. Samie Jaffrey, a professor of pharmacology at Weill Cornell Medical College. “We discovered that the messenger RNA can jam up one strand of the gene’s DNA, shutting down the gene — which was not known before.”This is new biology — an interaction between the RNA and the DNA of the fragile X syndrome gene causes disease,” Dr. Jaffrey says. “We are coming to understand that RNAs are powerful molecules that can regulate gene expression, but this mechanism is completely novel — and very exciting.”The malfunction occurs suddenly — before the end of the first trimester in humans and after 50 days in laboratory embryonic stem cells. …

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