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Newswise — A new, minimally invasive procedure appears to be effective for many patients with Fuchs endothelial dystrophy (FED), a common eye disease, without the potential side effects and cost of the current standard of care, a cornea transplant. In a proof-of-concept study, published in the journal Cornea, researchers led by Kathryn Colby, MD, PhD, the Louis Block professor and chairman of the Department of Ophthalmology and Visual Science at the University of Chicago, showed that removing a few square millimeters of a single layer of cells on the inside of the cornea allowed rejuvenation of the surrounding tissue, without the need for a corneal transplant. This simple procedure restored clear vision to three out of four patients suffering from FED, the most frequent cause for corneal transplantation in the United States. Over the past two years while at Harvard Medical School, Colby performed the new procedure, known as Descemet stripping, on 11 patients, aged 51 to 91. Two patients had the procedure in both eyes, one at a time. When assessed six months after the operation, ten of the treated eyes (77 percent) had clear corneas and eight had 20/20 vision or better (two patients had retinal disease that limited their final vision). The other three eyes did not respond and required a standard cornea transplant. “It’s too soon to call this a cure,” Colby said. “We performed the first operation just over two years ago. But when it works, it’s a wonderful thing. It’s quick, inexpensive and it spares patients from having someone else’s cells in their eyes, which requires local immunosuppression.” The first patient to undergo Descemet stripping, 69-year-old Eric Thorp of the Boston area, was pleased. “It’s quite a breakthrough,” he said. His vision, now 20/20 in that eye, “is equivalent to what I had as a boy,” he said. “Amazing.” “It’s kind of an honor to have been the first,” he added. “It was worth doing.” Descemet stripping involves removing a small patch of the corneal endothelium (the pumping cells that stop working in FED) attached to an underlying layer (the Descemet membrane). In patients with FED, water accumulates in the cornea, the clear front window of the eye, because of the dysfunction of the pumping cells, causing reduced vision, glare and haloes. If left untreated, the condition progresses to painful blindness. Removal of the central dysfunctional cells enables healthier peripheral cells to migrate to the center of the cornea, where they reestablish pumping capacity and removal of fluid from the layers above. This gradually restores clear vision. “Although Descemet stripping is a relatively simple procedure, its potential is revolutionary,” Colby said. In 2015, 14,000 corneal transplants were performed in the United States, just for FED, the most common reason for this operation. The transplants work well, but the tissues are expensive and there is a limited supply in some areas of the world. Because the corneal transplant tissue is foreign, patients must apply topical steroids for the rest of their lives to dampen their immune response and prevent rejection of the transplanted cells. Steroid eye drops are known to cause glaucoma and cataract and can predispose to infection. The researchers classified patients into four groups based on how they responded to Descemet stripping. Fast responders regained clear vision within a month after surgery. Responders recovered within three months. Slow responders took more than three months. Nonresponders had persistent corneal edema and required endothelial keratoplasty—a streamlined cornea transplant. Of the 13 eyes treated, four were fast responders, four were responders and two were slow responders. The next step is to try to understand why some patients, about one out of four, don’t respond to removal of the dysfunctional cells. Fuchs dystrophy is a polygenic disease, but in the last few years researchers have found connections between the extent of a repeating nonsensical genetic abnormality seen in other neurological diseases and the severity of FED. Colby hopes to find genetic clues that predict which patients are most likely to respond to this approach. Thorp, the first patient treated, had 20/20 vision when last assessed in January of 2016 at the University of Chicago, 24 months after his operation. He was first diagnosed with FED and had a cornea transplant in his right eye in 2002, a two-stage operation. It was successful, but the recovery process meant “foggy vision” in that eye for nearly a year. This prevented him from driving. That eye slowly recovered, but by 2013 vision in the left eye began to decline. After Colby offered her new procedure and explained the logic behind it, Thorp felt “a great deal of confidence and understanding in what she was doing,” he said. He volunteered to go first. “It certainly turned out to be worth it,” Thorp said. His operation, removal of a cataract plus Descemet stripping, took less than 30 minutes. That was “about 20 minutes for the cataract and one minute for the stripping,” he recalled. “After I performed Mr. Thorp’s surgery, I waited eight months to make sure nothing unexpected happened to his cornea,” Colby said, “then I started offering the procedure to patients whom I felt could benefit.” “Few things remind you as constantly as deteriorating vision,” Thorp recalled. “Your world steadily narrows as you lose the ability to see. But mine expanded again at the other end. I remember walking the dog at night right after the operation. Each night, the streetlights would be a little more in focus. You could see the improvement, night after night over the course of a few weeks, like the fog lifting out of London. It was cool. Really cool.” Co-authors of the study were Durga Borkar and Peter Veldman, both at Massachusetts Eye and Ear Infirmary. Colby moved from Harvard to the University of Chicago in August 2015. The authors have no funding or conflicts of interest to disclose.
Newswise — Reston, VA, – Potential improvement in mental health issues ranging from eating disorders to suicide has become more hopeful and more possible than it was just days ago. The U.S. House of Representatives has passed the historic Helping Families in Mental Health Crisis Act of 2015 (HR 2646) – a bill that signifies forward movement in mental health. The Eating Disorder Coalition (EDC) has been tireless in helping this bill to move through Congress. EDC summarizes the Act as “a comprehensive mental health bill that aims to combat suicide in our schools and communities, increase the mental health workforce, strengthen enforcement of the mental health parity law, invest in early intervention, integrate health and mental health care, and strengthen the community crisis response system, among other things.” Of special importance to The Academy for Eating Disorders, the bill includes provisions from the Anna Westin Act, which recognizes eating disorders as a public health issue in the United States. The bill will strengthen and clarify the current mental health parity law as it relates to eating disorders, enforce reimbursement for eating disorders by insurers, provide education and training for professionals in school and health settings, and provide information and resources for public education and early intervention and prevention. According to research published in the Academy for Eating Disorder’s International Journal of Eating Disorders , individuals with eating disorders are at increased risk of death compared to the general population. “Too many lives have been lost – too many patients and their families have suffered already because of inadequate insurance coverage orfailure to recognize the importance of this disease,” said the Executive Director of the Academy for Eating Disorders, Elissa Myers.The Academy for Eating Disorders applauds both the advocates and the Eating Disorder Coalition who have been pursuing this legislation for several years, and the House of Representatives for their overwhelmingly supportive vote—422 to 2. We also send a special salute to Kitty Westin, mother of Anna Westin, who has tirelessly worked to help make sure others are spared the unnecessary loss of a loved one. The Academy for Eating Disorders (AED) is an international professional association committed to the leadership in eating disorders research, education, treatment, and prevention. The goal of the AED is to provide global access to knowledge, research, and best treatment practice for eating disorders. For additional information, please contact Elissa Myers at 703-626-9087and visit the AED website at www.aedweb.org.
Newswise — The University of Montreal Hospital Research Centre (CRCHUM) is launching a major international clinical trial to test a minimally invasive and safer surgical approach for patients with lung cancer: video-assisted thoracoscopic (VATS) lobectomy with ultrasonic pulmonary artery sealing. Monic Ste-Marie, 48, is one of the first to benefit from this procedure developed by Dr. Moishe Liberman, a thoracic surgeon and researcher at the CRCHUM. On January 19, 2016, he successfully removed the one-centimetre tumour lodged in her left lung. The operation involved making three small incisions in her chest and then removing the diseased portion of her lung, guided by a video camera and using an electronic device to seal the pulmonary artery by ultrasound to prevent bleeding during the operation. “I think this technique could completely change the way we perform surgery for lung cancer, which is the deadliest form of cancer in North America," said Dr. Liberman, who is also an Associate Professor of Surgery at the University of Montreal. Currently, pulmonary lobectomy is the most commonly performed lung cancer operation in the world. It involves opening the chest and cutting the ribs to remove the lung lobe containing the cancerous tumour. But it leaves a long scar, and patients take up to six months to recover from this invasive and risky procedure. In the past 20 years, a new technique has developed: video-assisted thoracoscopic (VATS) lobectomy. Instead of making a long incision in the chest and breaking the ribs, surgeons simply make small holes to reach the target area. Their actions are guided by a miniature video camera inserted in the chest wall through one of the holes. “The technique is beneficial, but it is not widely practiced, because the risk of major bleeding makes it difficult to control. Pulmonary arteries are thin and fragile. If there is bleeding during open surgery then it’s easy: we stitch it up and that’s it. But when we work with a camera and there is bleeding and we can’t see through the lens, the patient can die quickly, because the pulmonary artery is connected directly to the heart,” explained Dr. Liberman.To facilitate and secure the procedure, he uses a new tool: a kind of pistol with a small three-millimetre jaw at the end that seals the blood vessels using ultrasonic energy. The device, called the HARMONIC ACE®+7 Shears was designed by Ethicon, part of Johnson & Johnson. It is commonly used to seal small blood vessels under seven mm in diameter. Dr. Liberman hopes to demonstrate that the ultrasound gun is also effective for pulmonary artery branches. After five years of pre-clinical studies at the CRCHUM, first with animals and then in Phase 1 and 2 clinical trials that demonstrated the safety of the procedure, Dr. Liberman is now leading a large multi-centre Phase 2 clinical to assess the effectiveness of the technique in 150 patients in Canada, the US, and Europe. The $1.8 million project is funded by Johnson & Johnson. The results should be available in four years. Each year, lung cancer kills around 1.59 million people in the world, largely due to smoking, which is responsible for 80% of cases, according to the World Health Organization. The cancer is particularly alarming because it is often diagnosed late, and the survival rate five years after diagnosis is rather low: 17% in women and 14% men. Dr. Liberman hopes the new surgical approach he developed will save lives. "I think it will decrease the risk of bleeding and reduce post-operative pain. Patients will be able to resume their normal lives more quickly,” he said.Monic Ste-Marie was fortunate. Her lung cancer was diagnosed quickly. Six months after the pioneering medical procedure that saved her life, she is doing well: “I had pain for a month after the operation. Now, I still have trouble catching my breath, but that’s normal,” she said. About the studyThe Phase 2 clinical study “Ultrasonic Energy for Pulmonary Artery Branch Sealing During VATS Lobectomy (VATS PA-ACE)” is directed by Dr. Moishe Liberman (CRCHUM, Canada). The study is funded by the University of Montreal Hospital Centre (CHUM) and Johnson & Johnson. Registration number: NCT02719717. Information: https://clinicaltrials.gov/ct2/show/NCT02719717?term=02719717&rank=1 About the CRCHUMThe University of Montreal Hospital Research Centre (CRCHUM) is one of the largest hospital-based research centres in North America. Our mission is to improve the health of adults through a continuum of research from basic science, to population health, to clinical research. More than 1,950 people work at the CRCHUM, including 439 researchers and 700 students and research trainees:http://www.crchum.chumontreal.qc.ca/enSource: University of Montreal Hospital Research Centre (CRCHUM)
Newswise — PHILADELPHIA— In a study with potentially major implications for the future treatment of autoimmunity and related conditions, scientists from the Perelman School of Medicine at the University of Pennsylvania have found a way to remove the subset of antibody-making cells that cause an autoimmune disease, without harming the rest of the immune system. The autoimmune disease the team studied is called pemphigus vulgaris (PV), a condition in which a patient’s own immune cells attack a protein called desmoglein-3 (Dsg3) that normally adheres skin cells. Current therapies for autoimmune disease, such as prednisone and rituximab, suppress large parts of the immune system, leaving patients vulnerable to potentially fatal opportunistic infections and cancers. The Penn researchers demonstrated their new technique by successfully treating an otherwise fatal autoimmune disease in a mouse model, without apparent off-target effects, which could harm healthy tissue. The results are published in an online First Release paper in Science. “This is a powerful strategy for targeting just autoimmune cells and sparing the good immune cells that protect us from infection,” said co-senior author Aimee S. Payne, MD, PhD, the Albert M. Kligman Associate Professor of Dermatology. Payne and her co-senior author Michael C. Milone, MD, PhD, an assistant professor of Pathology and Laboratory Medicine, adapted the technique from the promising anti-cancer strategy by which T cells are engineered to destroy malignant cells in certain leukemias and lymphomas. “Our study effectively opens up the application of this anti-cancer technology to the treatment of a much wider range of diseases, including autoimmunity and transplant rejection,” Milone said. The key element in the new strategy is based on an artificial target-recognizing receptor, called a chimeric antigen receptor, or CAR, which can be engineered into patients’ T cells. In human trials, researchers remove some of patients’ T cells through a process similar to dialysis and then engineer them in a laboratory to add the gene for the CAR so that the new receptor is expressed in the T cells. The new cells are then multiplied in the lab before re-infusing them into the patient. The T cells use their CAR receptors to bind to molecules on target cells, and the act of binding triggers an internal signal that strongly activates the T cells -- so that they swiftly destroy their targets. The basic CAR T cell concept was first described in the late 1980s, principally as an anti-cancer strategy, but technical challenges delayed its translation into successful therapies. Since 2011, though, experimental CAR T cell treatments for B cell leukemias and lymphomas -- cancers in which patients’ healthy B cells turn cancerous -- have been successful in some patients for whom all standard therapies had failed. B cells, which produce antibodies, can also cause autoimmunity. Payne researches autoimmunity, and a few years ago, a postdoctoral researcher in her laboratory, Christoph T. Ellebrecht, MD, took an interest in CAR T cell technology as a potential weapon against B cell-related autoimmune diseases. Soon Payne’s lab teamed up with Milone’s, which studies CAR T cell technology, in the hope of finding a powerful new way to treat these ailments. “We thought we could adapt this technology that’s really good at killing all B cells in the body to target specifically the B cells that make antibodies that cause autoimmune disease,” said Milone. “Targeting just the cells that cause autoimmunity has been the ultimate goal for therapy in this field,” noted Payne.A more disease-specific receptor In the new study, for which Ellebrecht was first author, the team took aim at pemphigus vulgaris. This condition occurs when a patient’s antibodies attack molecules that normally keep skin cells together. When left untreated, PV leads to extensive skin blistering and is almost always fatal, but in recent decades the condition has been treatable with broadly immunosuppressive drugs such as prednisone, mycophenolate mofetil, and rituximab.To treat PV without causing broad immunosuppression, the Penn team designed an artificial CAR-type receptor that would direct patients’ T cells to attack only the B cells producing harmful anti-Dsg3 antibodies. The team developed a “chimeric autoantibody receptor,” or CAAR, that displays fragments of the autoantigen Dsg3 -- the same fragments to which PV-causing antibodies and their B cells typically bind, as Payne’s laboratory and others have shown in prior studies. The artificial receptor acts as a lure for the B cells that target Dsg3, bringing them into fatal contact with the therapeutic T cells. Testing many variants, the team eventually found an artificial receptor design that worked well in cell culture, enabling host T cells to efficiently destroy cells producing antibodies to desmoglein, including those derived from PV patients. The engineered T cells also performed successfully in a mouse model of PV, killing desmoglein-specific B cells and preventing blistering and other manifestations of autoimmunity in the animals.“We were able to show that the treatment killed all the Dsg3-specific B cells, a proof of concept that this approach works,” Payne said. T cell therapies can be complicated by many factors. But in these experiments, the Penn scientists’ engineered cells maintained their potency despite the presence of anti-Dsg3 antibodies that might have swarmed their artificial receptors. In addition, there were no signs that the engineered T cells caused side effects by hitting the wrong cellular targets in the mice. The team now plans to test their treatment in dogs, which can also develop PV and often die from the disease. “If we can use this technology to cure PV safely in dogs, it would be a breakthrough for veterinary medicine, and would hopefully pave the way for trials of this therapy in human pemphigus patients,” Payne said. Also on the horizon for the Penn scientists are applications of CAAR T cell technology for other types of autoimmunity. The immune rejection that complicates organ transplants, and normally requires long-term immunosuppressive drug therapy, may also be treatable with CAAR T cell technology. “If you can identify a specific marker of a B cell that you want to target, then in principle this strategy can work,” Payne said.
Newswise — CHARLOTTESVILLE, Va., – Researchers at the University of Virginia School of Medicine have identified immune cells vital for protecting us from potentially fatal C. difficileinfection. Surprisingly, those cells are often vilified for their role in causing asthma and allergies. But when it comes to C. difficile, they could be the difference in lifeand death. With the discovery, the researchers have answered some of the greatest questions about C. diff, shed light on why antibiotics lead to severe C. diff and identified a potential way for doctors to prevent the life-threatening infection – and possibly other infections as well. The Role of Antibiotics Bill Petri, MD, PhD, chief of the Division of Infectious Diseases and International Health at the UVA Health System, hailed the discovery by UVA’s Erica L. Buonomo, PhD, and their team of colleagues as “the most remarkable breakthrough I have participated in as a scientist.” “Antibiotics are really important, and very often you have to give antibiotics, but you do it knowing that you’re predisposing your patient to another infection [C. difficile] that is potentially lethal. About one out of seven people with this infection dies in North America. So it’s a terrible dilemma for physicians,” Petri said. “This is not a common complication of antibiotics, but when it happens, it’s a very serious one. This work enables a potential long-term solution to that, which is probiotics to restore the natural state of the gut.” There were almost half a million C. diff infections in the United States in 2011, and more than 29,000 patients died within 30 days of infection, according to a study released last year by the U.S. Centers for Disease Control and Prevention. The agency has classified the bacterium as an “urgent threat,” noting the rise of a new epidemic strain in recent years that has made the infection even deadlier. Kris Chadee, PhD, a professor at the University of Calgary who was not involved in UVA’s C. diff work, called the discovery “as unexpected as it is important,” noting that the finding “has immediate implications for therapy: Probiotics designed to restore the healthy gut microbiome should be an effective way to prevent this life-threatening infection.” Understanding C. DifficileC. difficile is primarily a hospital-acquired infection, and it predominantly affects the elderly, particularly elderly people on antibiotics. UVA’s discovery offers answers about why that is. The researchers showed that the gut bacteria stimulates the production of a protein called IL-25, which then recruits protective cells called eosinophils. As such, IL-25, the product of “good” bacteria, protects the lining of the gut from pathogens. Antibiotics, however, disrupt our body’s natural bacterial populations, leaving the gut lining vulnerable to C. diff and other infections. Intriguingly, the researchers found an important and unexpected role for eosinophils, a type of white blood cells. These cells are often vilified for their role in causing bothallergies and asthma, but in the battle against C. diff, they can be life-saving. IL-25, the UVA researchers show, protects us from C. diff by manufacturing eosinophils to guard the integrity of the gut lining. “We found that if you deplete eosinophils, either genetically or by an antibody neutralization, you lost the integrity of the epithelial barrier in the gut,” Buonomo said. “Maintaining that barrier is very important for having a healthy response to C. difficile. It also prevents bacteria from spreading to other sites in the body, so if you have a breakdown in the barrier, you can have a septic response or bacteria in your blood or in other systemic organs.” The findings suggest that researchers should be able to develop new probiotics that patients could take to ward offC. difficile. “We could end up that every person taking an antibiotic is taking a new probiotic that is specifically designed to maintain IL-25 and eosinophils,” Petri said. Petri noted that Buonomo joined his lab while a graduate student at UVA, and he credited the discovery to the new perspective she brought. “Erica was a card-carrying immunologist before she came into my lab,” Petri recalled. “She came with an immunology mindset, and the lab wasn’t immunology focused at all. It’s changed. We’ve all seen the benefit of having that perspective, of looking at how the immune system is responding to the bacterial infection.”
Newswise — Driving is possibly one of the most complex procedures humans engage in on a regular basis. Operating a motor vehicle involves a wide range of cognitive processes that require the ability to judge distances, manage multiple stimuli simultaneously, react quickly in an emergency, maintain attention for long periods of time, and correctly interpret traffic signs and signals. Today, almost half of all drivers on the roadways are over the age of 65 and this number is projected to increase to 77 percent in the next 30 years. Adults over the age of 65 have the highest crash rate per mile compared to any other age group, and older driver fatalities are highest in Florida, California and Texas. Driving also requires physical skills that are affected by age-related changes like deteriorating vision, decreasing hearing, and diminishing motor reflexes, coordination, and strength as well as effects from medications used for a number of conditions. Older adult drivers are frequently aware of these physical changes and do take precautions. But what about older adult drivers with declining cognition who can’t make this determination on their own? With the decline of cognitive processes in older adults due to Alzheimer’s disease (AD) and other forms of dementia, there is heightened concern for public safety and unsafe driving in this population. A researcher in the Christine E. Lynn College of Nursing at Florida Atlantic University and a collaborator have just published an article in the journal Public Health Nursing that sheds light on the cognitive factors that inhibit effective driving as well as recognizing older adults who may be at risk for unsafe driving. “It is important to note that it’s not a person’s chronological age itself that puts the older driver at increased risk for driving accidents, but rather the changes in functionality and skills needed for safe driving,” said Lisa Kirk Wiese, Ph.D., first author and an assistant professor in FAU’s Christine E. Lynn College of Nursing. Memory plays a significant role in driving competence. At a basic level, memory provides drivers with the knowledge of how to operate a motor vehicle; turning the key in the ignition, shifting gears, and distinguishing the brake from the gas pedal. Drivers also need to remember their destination so that they don’t get lost. Studies have shown that there is a 62 percent increase in errors among individuals with AD, most notably in the attention skills of driving straight and in making left-hand turns. They also have pathological changes in visual processing areas, which significantly impacts visual processing, and consequently, driving performance. “Drivers with dementia and even their caregivers may lack the insight needed to limit and eventually discontinue driving,” said Wiese. “They might say something along the lines of ‘I have never had an accident,’ which is then confirmed by their loved one, and both are in denial that they could be an unsafe driver.” Wiese and co-author Logan Wolff, in the College of Psychology at Nova Southeastern University, note that self-rated methods for older drivers at risk are not effective because they may be overconfident and lack insight into their perceived versus actual driving abilities. The authors suggest a three-pronged approach to testing for safety in older adult drivers, which include a patient assessment and medication review; a computerized simulation using a touch screen interface, and a road test with a certified road test examiner. “The task of identifying and helping older adults who are unaware of decline in cognition impacting road safety can be overwhelming for family members, “said Wiese. “Nurses who care for older adults in public health settings can play a vital role in understanding and identifying the cognitive mechanisms that inhibit effective driving and help to identify older adults who may be at risk for unsafe driving, and who would benefit from a driving evaluation.” FAU’s Louis and Anne Green Memory and Wellness Center operated by the College of Nursing provides a comprehensive driving evaluation that includes tests of vision, physical functioning and cognitive skills required for safe driving. In addition, an on-road test in a dual-controlled vehicle is given, which was developed for the purpose of detecting driving errors made by cognitively impaired drivers. At the conclusion of the testing session, results and recommendations are provided, and if needed, options for alternative transportation and supportive services are discussed at length. “Our driving evaluation program is one of several comprehensive services we provide to individuals with memory disorders and their families,” said María Ordóñez, DNP, ARNP, GNP-BC, director of the Louis and Anne Green Memory and Wellness Center and an assistant professor in FAU’s College of Nursing. “We are committed to helping our clients function at their personal best to maximize their quality of life and to respond to their unique needs with caring, expertise, and compassion.”
Newswise — Can an increased risk of chronic pain be transmitted from parents to children? Several factors may contribute, including genetics, effects on early development, social learning, and more according to a report in the journal PAIN®, the official publication of the International Association for the Study of Pain (IASP). The journal is published by Wolters Kluwer. Amanda L. Stone of Vanderbilt University, in Nashville, Tenn., and Anna C. Wilson of Oregon Health & Science University, in Portland, Ore., present a conceptual model of transmission of chronic pain, including potential mechanisms and moderating factors. The researchers write, "Such a framework highlights chronic pain as inherently familial and intergenerational, opening up avenues for new models of intervention and prevention that can be family-centered and include at-risk children." Proposed Explanations for Familial Transmission of Chronic Pain RiskKnowing that offspring of parents with chronic pain are at increased risk of developing chronic pain, as well as the adverse mental and physical health outcomes associated with chronic pain, Drs. Stone and Wilson developed an "integrative conceptual model" to explore possible explanations for this risk. The researchers identify five "plausible mechanisms" to explain the transmission of chronic disease risk from parent to child: • Genetics. Children of parents with chronic pain might be at increased genetic risk for sensory as well as psychological components of pain. Research suggests that genetic factors may account for roughly half of the risk of chronic pain in adults. • Early Neurobiological Development. Having a parent with chronic pain may affect the features and functioning of the nervous system during critical periods in early development. For example, a baby's development might be affected by the mother's stress level or health behaviors during and after pregnancy. • Pain-Specific Social Learning. Children may learn "maladaptive pain behaviors" from their parents, who may act in ways that reinforce those behaviors. Catastrophizing—exaggerated responses and worries about pain—might be one key factor. • General Parenting and Health Habits. Chronic pain risk could be affected by parenting behaviors linked to adverse child outcomes—for example, permissive parenting or lack of consistency and warmth. The parents' physical activity level and other health habits might also play a role. • Exposure to Stressful Environment. There may be adverse effects from growing up in stressful circumstances related to chronic pain—for example, financial problems or parents' inability to perform daily tasks. The model also identifies some "moderators" that might explain when and under what circumstances children are at highest risk of developing chronic pain. These include chronic pain in the other parent; the timing, course, and location of the parent's pain; and the children's characteristics, including their personal temperament. "The outlined mechanisms, moderators, and vulnerabilities likely interact over time to influence the development of chronic pain and related outcomes in offspring of parents with chronic pain," Drs. Stone and Wilson note. They hope their model will provide a framework to guide future research—toward the goal of developing effective prevention and treatment approaches for children of parents with chronic pain. Click here to read “Transmission of risk from parents with chronic pain to offspring: an integrative conceptual model.” Article: “Transmission of risk from parents with chronic pain to offspring: an integrative conceptual model.” (doi: 10.1097/j.pain.0000000000000637) ###
Newswise — Many people accept the old axiom – "You are what you eat." That's not to say you become a carrot if you eat carrots, of course, but rather that a regular pattern of eating carrots will shape you in a much different way than a regular pattern of eating cotton candy. Now researchers are suggesting there may be a lesser-known corollary – "Your kids are what you eat." In a new analysis of parent-child diet quality and calories consumed, a team of seven researchers found the two are related in significant ways, a connection that could lead to better strategies as the nation works to address the growing public health problems of obesity and related conditions such as heart disease, stroke and diabetes. According to the U.S. Centers for Disease Control and Prevention, more than a third of U.S. adults are obese and about 17 percent of the nation's youth (ages 2-19) are obese. As dietary details emerged for hundreds of parents and children who participated in the study, the overall picture wasn't pretty. "Unfortunately people are not doing very well in terms of diet quality," said Shannon Robson, assistant professor of behavioral health and nutrition at the University of Delaware and the lead author of the report, published recently in the Journal of the Academy of Nutrition and Dietetics. "Parents had better diet quality than kids, but only by a little bit." The analysis draws on data from a Neighborhood Impact on Kids study that looked at 698 parent-child duos to better understand obesity and related behaviors. The children were 6 to 12 years old and all lived in King County, Washington, or San Diego County, California, when the study was done from 2007 to 2009. Preliminary screenings excluded anyone with a chronic illness that affects growth, an eating disorder, medically prescribed dietary regimens or psychiatric disorders. To get a sampling of dietary practice, researchers looked at up to three random days of eating data for each twosome, including at least one weekday and one weekend day. More than 98 percent of participants reported three days of dietary data. They analyzed the data using the Healthy Eating Index of 2010 (HEI-2010), the Dietary Approaches to Stop Hypertension (DASH) score, and energy density (calories per gram of food). The HEI-2010 looks at 12 dietary components, including empty calories, to assess overall quality, while the DASH score looks at eight food groups to measure intake of foods groups like vegetables, fruit and low-fat dairy products. Overall, parents had a higher score on both measures of diet quality, but on average managed just 64.5 percent of optimal levels on the HEI-2010 and just 56.6 percent of the optimal DASH score. Kids averaged 58.3 and 54.3 percent, respectively. Caloric intake was more similar, with children eating an average of 1,751 calories per day and parents 1,763. After controlling for demographics, neighborhood type and body-mass index, researchers found parental diet to be the strongest predictor of a child's diet quality. They found two clear culprits for poorer diet quality among children: too few vegetables and too many empty calories. Researchers said the data were limited by several factors, with particular mention of ethnic and/or racial diversity among participants. Most participating parents were mothers and researchers said some bias might be a factor in how parents report data for their children. Robson joined the UD faculty last fall, bringing this work with her from the Cincinnati Children's Hospital Medical Center, where she was a post-doctoral fellow. She earned her bachelor's degree in nutritional sciences and dietetics at UD, and her master's and doctorate degrees at the University of Tennessee. Her collaborators include Sarah Couch of the University of Cincinnati, James Peugh of the Cincinnati Children's Hospital Medical Center, Karen Glanz of the University of Pennsylvania Perelman School of Medicine and School of Nursing, Chuan Zhou and Brian Saelens of the Seattle Children's Research Institute and the University of Washington, and James Sallis of the University of California at San Diego. The study was supported by grants from the National Institutes of Health and the U.S. Department of Agriculture.
Newswise — Eating a type of powdered food supplement, based on a molecule produced by bacteria in the gut, reduces cravings for high-calorie foods such as chocolate, cake and pizza, a new study suggests. Scientists from Imperial College London and the University of Glasgow asked 20 volunteers to consume a milkshake that either contained an ingredient called inulin-propionate ester, or a type of fibre called inulin. Previous studies have shown bacteria in the gut release a compound called propionate when they digest the fibre inulin, which can signal to the brain to reduce appetite. However the inulin-propionate ester supplement releases much more propionate in the intestines than inulin alone. After drinking the milkshakes, the participants in the current study underwent an MRI scan, where they were shown pictures of various low or high calorie foods such as salad, fish and vegetables or chocolate, cake and pizza. The team found that when volunteers drank the milkshake containing inulin-propionate ester, they had less activity in areas of their brain linked to reward -- but only when looking at the high calorie foods. These areas, called the caudate and the nucleus accumbens, found in the centre of the brain, have previously been linked to food cravings and the motivation to want a food. The volunteers also had to rate how appealing they found the foods. The results showed when they drank the milkshake with the inulin-propionate ester supplement they rated the high calorie foods as less appealing. In a second part of the study, which is published in July edition of the American Journal of Clinical Nutrition, the volunteers were given a bowl of pasta with tomato sauce, and asked to eat as much as they like. When participants drank the inulin-propionate ester, they ate 10 per cent less pasta than when they drank the milkshake that contained inulin alone. In a previous research study by the same team, published in 2013, they found that overweight volunteers who added the inulin-propionate ester supplement to their food every day, gained less weight over six months compared to volunteers who added only inulin to their meals. Professor Gary Frost, senior author of the study from the Department of Medicine at Imperial, said: "Our previous findings showed that people who ate this ingredient gained less weight -- but we did not know why. This study is filling in a missing bit of the jigsaw -- and shows that this supplement can decrease activity in brain areas associated with food reward at the same time as reducing the amount of food they eat." He added that eating enough fibre to naturally produce similar amounts of propionate would be difficult: "The amount of inulin-propionate ester used in this study was 10g - which previous studies show increases propionate production by 2.5 times. To get the same increase from fibre alone, we would need to eat around 60g a day. At the moment, the UK average is 15g." Claire Byrne, a PhD researcher also from the Department of Medicine explained that using inulin-propionate ester as a food ingredient may help prevent weight gain: "If we add this to foods it could reduce the urge to consume high calorie foods." She added that some people's gut bacteria may naturally produce more propionate than others, which may be why some people seem more naturally predisposed to gain weight. Dr Tony Goldstone, co-senior author of the study from the Department of Medicine added: "This study adds to our previous brain imaging studies in people who have had gastric bypass surgery for obesity. These show that altering how the gut works can change not only appetite in general, but also change how the brain responds when they see high-calorie foods, and how appealing they find the foods to be." Dr Douglas Morrison, author of the paper from the Scottish Universities Environmental Research Centre at the University of Glasgow, commented: "We developed inulin-propionate ester to investigate the role of propionate produced by the gut microbiota in human health. This study illustrates very nicely that signals produced by the gut microbiota are important for appetite regulation and food choice. This study also sheds new light on how diet, the gut microbiome and health are inextricably linked adding to our understanding of how feeding our gut microbes with dietary fibre is important for healthy living." The research was funded by the National Institute for Health Research Imperial Biomedical Research Centre and the Biotechnology and Biological Sciences Research Council
Newswise — While immune therapy has proven effective in treating certain types of cancer, especially lung cancer and melanoma, tumors of the pancreas remain among the most difficult to treat and, so far, are impervious to immune-based therapies. Now, a new study in mice has shown that immunotherapy against pancreatic cancer can be effective when given in conjunction with drugs that break up the fibrous tissue in these tumors. The study, from Washington University School of Medicine in St. Louis, appears July 4 in Nature Medicine. Based on the study’s findings, doctors at Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital are conducting a phase 1 clinical trial in patients with advanced pancreatic cancer that will test the safety of this drug combination when given along with standard chemotherapy. “Pancreatic tumors are notoriously unresponsive to both conventional chemotherapy and newer forms of immunotherapeutics,” said senior author David G. DeNardo, PhD, an assistant professor of medicine. “We suspect that the fibrous environment of the tumor that is typical of pancreatic cancer may be responsible for the poor response to immune therapies that have been effective in other types of cancer.” Unlike other cancer types, pancreatic tumors are characterized by a large amount of what DeNardo describes as scar tissue. This extra connective tissue and the cells that deposit it provide a protective environment for cancer cells, stopping the immune system from attacking the tumor cells and limiting the cancer’s exposure to chemotherapy delivered through the bloodstream. DeNardo and his colleagues investigated whether some of this protection might be lost if they could disrupt the proteins that help fibrous tissue adhere to itself and surrounding cells. “Proteins called focal adhesion kinases are known to be involved in the formation of fibrous tissue in many diseases, not just cancer,” DeNardo said. “So we hypothesized that blocking this pathway might diminish fibrosis and immunosuppression in pancreatic cancer.” Focal adhesion kinase (FAK) inhibitors have been developed in other areas of cancer research, but DeNardo and his colleagues, including oncologist Andrea Wang-Gillam, MD, PhD, an associate professor of medicine, are the first to test them against pancreatic cancer in conjunction with immunotherapy. In the mouse study, an investigational FAK inhibitor was given in combination with a clinically approved immune therapy that activates the body’s T cells and makes tumor cells more vulnerable to attack. Mice with a model of pancreatic cancer survived no longer than two months when given either a FAK inhibitor or immune therapy alone. Adding FAK inhibitors to standard chemotherapy improved tumor response over chemotherapy alone. But the three-drug combination — FAK inhibitors, immune therapy and chemotherapy — showed the best outcomes in laboratory studies, more than tripling survival times in some mice. Some were still alive without evidence of progressing disease at six months and beyond. The success of this mouse study provided a strong rationale for testing this drug combination in patients with advanced pancreatic cancer, according to Wang-Gillam. “This trial is one of about a dozen we are conducting specifically for pancreatic cancer at Washington University,” she said. “We hope to improve outcomes for these patients, especially since survival with metastatic pancreatic cancer is typically only six months to a year. The advantage of our three-pronged approach is that we are attacking the cancer in multiple ways, breaking up the fibers of the tumor microenvironment so that more immune cells and more of the chemotherapy drug can attack the tumor.” ### This work was supported by the Lustgarten Foundation; an AACR/PANCAN Award; the National Cancer Institute (NCI) of the National Institutes of Health (NIH), grant numbers R01-CA177670, R01-CA203890, R21-CA182701; the BJCIH/Siteman Cancer Center Cancer Frontier Fund; and the Washington University Institute of Clinical and Translational Sciences, grant number KL2TR000450. Jiang H, Hegde S, Knolhoff BL, Zhu Y, Herndon JM, Meyer MA, Nywening TM, Hawkins WG, Shapiro IM, Weaver DT, Pachter JA, Wang-Gillam A, DeNardo DG. Targeting focal adhesion kinase renders pancreatic cancers responsive to checkpoint immunotherapy. Nature Medicine. July 4, 2016. Washington University School of Medicine‘s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.