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Newswise — CHAPEL HILL, NC – A majority of adolescents in the United States report current cigar warning labels to be very believable, according to a new study conducted by doctors and researchers at the University of North Carolina-Chapel Hill. But significant differences exist in the believability of specific cigar warnings, suggesting that more work is needed to establish the best warnings to dissuade youth from smoking cigars. The study, published in the Journal of Adolescent Health, included a national phone survey of 1,125 adolescents from ages 13 to 17. The survey presented individuals with one of three current cigar health warnings that specifically isolate the risk of cigar smoke: • Cigar smoking can cause cancers of the mouth and throat, even if you do not inhale• Cigar smoking can cause lung cancer and heart disease. • Cigars are not a safe alternative to cigarettes. The surveyors then asked a number of questions about the believability of the warnings. Three quarters (76.7 percent) of all respondents found it very believable that “cigar smoking can cause lung cancer and heart disease,” while just 53.4 percent found it very believable that “cigar smoking can cause cancers of the mouth and throat, even if you do not inhale” and only 49.8 percent found it very believable that “cigars are not a safe alternative to cigarettes.” Respondents were classified as either susceptible – meaning they had used a cigarette or expressed interest in trying one – or non-susceptible. About 17 percent of those surveyed were classified as “susceptible.” Adolescents susceptible to using cigarettes were significantly less likely to report the cigar warnings to be very believable. The potential source of the cigar warning (FDA, CDC, the Surgeon General, or none) did not impact surveyors’ answers, nor did their race, age, or sex. Studies have shown that cigars are one of the most common tobacco products among adolescents in the U.S., with one in 12 adolescents reporting current use of a cigar product. “This is the first research that has been done to track how young people perceive cigars warning labels,” said Sarah Kowitt, doctoral candidate at the UNC Gillings School of Global Public Health and lead author of the study. “Adolescents may be misguided about the safety of cigar use,” said Adam O. Goldstein, MD, MPH, study co-author, professor of family medicine, and member of the UNC Lineberger Comprehensive Cancer Center. “Many still believe that risks of cigars can be mitigated by not inhaling or inhaling less. But we know that cigar smoking can cause serious harm, including cancer and heart disease.” Historically, most tobacco prevention campaigns have been aimed at cigarettes. Some states, such as Maryland, have rolled out cigar-specific campaigns that may help dismantle cigar myths among youth. While the current cigar warnings were mostly seen as believable, Goldstein said that further study is needed, especially on the impact of graphic cigar warnings in addition to text. Also, the UNC researchers suggest continued study to develop warnings that have the maximum impact on susceptible adolescents. Some countries, such as Australia, have begun this work. “In Australia, warnings include pictorial representations, which may engage adolescents more effectively,” Goldstein said. Other UNC researchers on the study include Kristen Jarman, MSPH, and Leah Ranney PhD.This research was supported by grant number P50CA180907 from the National Cancer Institute and FDA Center for Tobacco Products (CTP).

Newswise — Alcohol is the most commonly used psychoactive substance among older adults, and this group can have unique risks associated with alcohol consumption—in even lower amounts—compared to younger persons. “Older adults have particular vulnerabilities to alcohol due to physiological changes during aging, including increasing chronic disease burden and medication use,” said Benjamin Han, MD, MPH, a geriatrician and health services researcher at the Center for Drug Use and HIV Research (CDUHR) and in the Division of Geriatric Medicine and Palliative Care at NYU Langone Medical Center (NYU Langone). “However, no recent studies have estimated trends in alcohol use, including binge alcohol use and alcohol use disorders among older adults.” To address the lack of research, Dr. Han and his team examined data from the National Survey on Drug Use and Health (years 2005 to 2014) in a paper published in the journal Drug and Alcohol Dependence. Trends of self-reported past-month binge alcohol use and alcohol use disorder were examined among adults age 50 and older. The researchers found significant increases in past-year alcohol use, past-month alcohol use, past-month binge drinking, and alcohol use disorders. The paper, “Demographic trends of binge alcohol use and alcohol use disorders among older adults in the United States, 2005–2014.” Published on-line 12 December 2016. Results also suggest that while men had a higher prevalence of binge alcohol use and alcohol use disorders than women, binge alcohol use and alcohol use disorder increased among women in this nationally representative sample. “As females age, they tend to experience a larger impact of physiological changes in lean body mass compared to men,” commented Dr. Han. “Thus, they may experience the adverse effects associated with consuming alcohol even in lower amounts.” “The increase in binge drinking among older women is particularly alarming” said Dr. Palamar, PhD, MPH, a CDUHR affiliated researcher and an assistant professor of Population Health at NYU Langone. “Both men and women are at risk for getting themselves into risky sexual situations while drinking, but women are at particularly high risk.” Dr. Palamar also stated that “heavy drinking can not only have unintended health consequences, but it can also lead to socially embarrassing or regretful behavior.” For the researchers, the results also raise public health concerns, given the significant increases in binge alcohol use among older adults who reported “fair/poor” health and/or multiple chronic conditions. This population is particularly vulnerable to the negative effects of alcohol as it can impact chronic disease management or increase the risk of injury. “Health care providers need to be made aware of this increasing trend of unhealthy alcohol use, particularly among older females, and ensure that screening for unhealthy alcohol use is part of regular medical care for this population” said Dr. Han. Researcher Affiliations: Benjamin H. Han1,2, Alison A. Moore3, Scott Sherman1,4, Katherine M. Keyes5, Joseph J. Palamar2,4 1. New York University School of Medicine, Department of Medicine, Division of Geriatric Medicine and Palliative Care, 550 First Avenue, BCD 615, New York, NY 100162. Center for Drug Use and HIV Research, New York University Rory College of Nursing, 433 First Avenue, 7th Floor, New York, NY 10010.3. University of California, San Diego, Department of Medicine, Division of Geriatrics, 9500Gilman Drive, La Jolla, CA 920934. New York University Langone Medical Center, Department of Population Health, 550 First Avenue, New York, NY 100165. Columbia University, Mailman School of Public Health, 722 West 168th Street, New York, NY 10032 This project was funded, in part, by the NIH (K01 DA-038800, PI: Palamar). About NYU Langone Medical Center: NYU Langone Medical Center, a world-class, patient-centered, integrated academic medical center, is one of the nation’s premier centers for excellence in clinical care, biomedical research, and medical education. Located in the heart of Manhattan, NYU Langone is composed of five hospitals—Tisch Hospital, its flagship acute care facility; Rusk Rehabilitation; the Hospital for Joint Diseases, the Medical Center’s dedicated inpatient orthopaedic hospital; NYU Lutheran Medical Center, a full-service, 450-bed teaching hospital located in Brooklyn, and Hassenfeld Children’s Hospital, a comprehensive pediatric hospital supporting a full array of children’s health services across the Medical Center. Also part of NYU Langone is NYU School of Medicine, which since 1841 has trained thousands of physicians and scientists who have helped to shape the course of medical history, and the Laura and Isaac Perlmutter Cancer Center, a National Cancer Institute–designated cancer center. The Medical Center’s trifold mission to serve, teach, and discover is achieved 365 days a year through the seamless integration of a culture devoted to excellence in patient care, education, and research. For more information, go to www.NYULangone.org About the NYU Rory Meyers College of NursingNYU Rory Meyers College of Nursing is a global leader in nursing education, research, and practice. It offers a Bachelor of Science with a major in Nursing, a Master of Science and Post-Master’s Certificate Programs, a Doctor of Nursing Practice degree and a Doctor of Philosophy in nursing research and theory development. About CDUHRThe mission of the Center for Drug Use and HIV Research (CDUHR) is to end the HIV and HCV epidemics in drug using populations and their communities by conducting transdisciplinary research and disseminating its findings to inform programmatic, policy, and grass roots initiatives at the local, state, national and global levels. CDUHR is a Core Center of Excellence funded by the National Institute on Drug Abuse (Grant #P30 DA011041). It is the first center for the socio-behavioral study of substance use and HIV in the United States and is located at the New York University College of Nursing. For more information, visit www.cduhr.org. SEE ORIGINAL STUDY

Newswise — Many women put too much pressure on themselves to make the holidays perfect for everyone. This can add a lot of unnecessary stress and anxiety that can lead to serious heart problems. Houston Methodist DeBakey Heart & Vascular Center cardiologist Karla Kurrelmeyer, M.D. says in their quest to get everything done on time, some women will ignore the mild symptoms of a silent heart attack.“Most of the time people who are experiencing a heart attack will have pain in the chest, shortness of breath, etc. Silent heart attack symptoms might be as simple as indigestion, flu-like symptoms, or feeling discomfort like a pulled muscle in the chest or back,” Kurrelmeyer said. “It’s important to have these symptoms checked as soon as possible to avoid scarring or damage to the heart.”Kurrelmeyer says stress-induced cardiomyopathy is also a concern for women around the holidays. This occurs when women are under great amounts of stress for a short period of time and that stress is compounded with another traumatic event such as a death in the family, a car accident, loss of money, etc. If it is ignored it can be fatal. “Stress-induced cardiomyopathy is a weakening of the left ventricle, the heart’s main pumping chamber,” Kurrelmeyer said. “It is brought on by the release of stress hormones that shock the heart, causing changes in the heart muscles that then cause the left ventricle to not work properly. The vast majority of people who are affected by this condition are women in the late 50s to mid-70s.” Someone experiencing this condition might develop chest pains or shortness of breath after severe stress, either emotional or physical, she said. In most cases, it is treated with medication such as beta blockers or ACE inhibitors. It’s important to have an echocardiogram as soon as possible if you are experiencing any symptoms. A spike in blood pressure is also commonduring the holidays. Kurrelmeyer says many women end up in the ER with chest pains or palpitations and, in the most severe cases, can suffer a stroke. If a woman has a history of high blood pressure it’s important to monitor it closely, especially during those times when the stress level rises. Heart problems in women are not usually as recognizable as they are in men. Some of the symptoms for women include:• Extreme weakness, anxiety, or shortness of breath.• Discomfort, pressure, heaviness or pain in the chest, arm, below the breastbone or in the middle of the back.• Sweating, nausea, vomiting, dizziness.• Fullness, indigestion, a tightness in the throat area.• Rapid or irregular heartbeats. “It’s important to take time for yourself during the holiday season and do things that will help relieve your stress,” Kurrelmeyer said. “Exercise, either walking or running, yoga, meditation, a nice walk with a loved one, whatever it takes, make it happen. The holidays should be a joyous time spent with family and friends at home, not with doctors in an emergency room.”    

Newswise — DALLAS –  The nation’s largest statewide effort to track concussions among youth athletes is under way in Texas with the launch of a registry designed to assess the prevalence of brain injuries in high school sports. The ConTex registry – a partnership between the University Interscholastic League(UIL) and the UT Southwestern Peter O’Donnell Jr. Brain Institute – will fill a major gap in concussion research and is expected to provide a gauge for whether certain rules or equipment changes are improving player safety.  The registry may also provide a blueprint for other states considering similar efforts and could be a key step in creating a nationwide database for concussions. Such a project was recently proposed by the U.S. Centers for Disease Control and Prevention. “This is a groundbreaking initial step. I think we’re on the verge of a very impactful project that will inform the nation about the frequency of concussions and will provide basic information about concussion and recovery in student-athletes,” said Dr. Munro Cullum, Professor of Psychiatry, Neurology and Neurotherapeutics and Neurological Surgery with the O’Donnell Brain Institute at UT Southwestern Medical Center. The UIL, which regulates athletics in Texas public schools, has partnered with the O’Donnell Brain Institute to implement the registry, which will complement studies in other age groups. While the NCAA, NHL, NFL and other professional sports organizations are tracking the issue in the college and professional ranks, little has been done on a scale as large as Texas to evaluate concussions in youth athletics. The registry in Texas – which leads the U.S. with more than 800,000 students participating in high school sports – will include player concussion cases reported by middle and high school athletic trainers in all UIL-sanctioned athletic activities. “The health and safety of our student participants is at the forefront of everything we do,” said Charles Breithaupt, UIL Executive Director. “The UIL Medical Advisory Committee has been focused on concussions since its inception 15 years ago and this concussion registry will provide valuable information and help us continue to improve the safety of extracurricular athletics.” The ConTex project is modeled after a smaller concussion study (ConTex1) that Dr. Cullum helped launch last year that tracks more detailed information about concussions in the Dallas-Fort Worth area. He also led a first-of-its-kind studypublished last year that found NFL players who lost consciousness due to concussion showed key differences in brain structure later in life.  The statewide registry relies on athletic trainers and school personnel across Texas to report all concussions that occur in UIL athletics to a central database through an app or online site developed by Medical Innovation Labs in Austin. Among the information being tracked is the cause of the injury, concussion history, the gender of the player and other data. During this school year, UIL-member schools will participate on a voluntary basis, with plans to expand reporting next school year. Dr. Cullum, the principal investigator of both ConTex studies, said his team will measure how often concussions occur in each sport, identify areas with low rates, and with more data eventually examine whether certain practices are helping reduce concussions or shorten recovery times in those areas. Children under age 15 account for the most traumatic brain injury visits to the emergency room, according to CDC findings released in July from a national survey of hospital records. Because there is no system in place to fully assess the prevalence of concussions in youth athletics, the CDC is seeking federal funding to establish a national database. “A lot of states will follow suit if they’re not already working on this very topic,” said Dr. Cullum, a neuropsychologist who holds the Pam Blumenthal Distinguished Professorship in Clinical Psychology. “I do think our registry will develop a very strong groundwork for a national registry.” All 50 states have passed legislation in recent years to address concussions in extracurricular athletics, but few have successfully launched statewide registries to track such injuries in all sports. Hawaii, for instance, launched its own registry in 2010, but the data have been relatively limited, with only 67 high schools participating. Colorado, Arizona and Maine have more recently launched their own. The UIL will be the first association of its kind to launch a registry of this magnitude. Researchers expect the broader statistics gathered in Texas will give substantial insight into the prevalence of concussions in student-athletes and quickly benefit other clinical and research efforts at the O’Donnell Brain Institute. This benefit will include an array of neurological studies involving current and former NFL players, education outreach in schools, and a new sports concussion return-to-play clinic that promotes medically monitored exercise during recovery. The statewide registry is funded through UT Southwestern’s Texas Institute for Brain Injury and Repair, which was established with $7.5 million in annual funding from the Texas Legislature to explore the full spectrum of brain injuries from strokes to spinal cord injuries. Questions about the registry can be emailed to ConTex@UTSW.edu. Concussion Extras QA: Impact of Texas registry Blog: Athletes who sandbag on concussion tests Video: UTSW, Cowboys on concussion outreach Contact: Email About UT Southwestern Medical Center UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. The faculty of almost 2,800 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in about 80 specialties to more than 100,000 hospitalized patients and oversee approximately 2.2 million outpatient visits a year.      

Newswise — Inflammation is a good thing when it’s fighting off infection, but too much can lead to autoimmune diseases or cancer. In efforts to dampen inflammation, scientists have long been interested in CC chemokine receptor 2 (CCR2) — a protein that sits on the surface of immune cells like an antenna, sensing and transmitting inflammatory signals that spur cell movement toward sites of inflammation. Researchers at the Skaggs School of Pharmacy and Pharmaceutical Sciences at University of California San Diego have now determined the 3D structure of CCR2 simultaneously bound to two inhibitors. Understanding how these molecules fit together may better enable pharmaceutical companies to develop anti-inflammatory drugs that bind and inhibit CCR2 in a similar manner. The study is published December 7 by Nature. CCR2 and associated signaling molecules are known to play roles in a number of inflammatory and neurodegenerative diseases, including multiple sclerosis, asthma, diabetic nephropathy and cancer. Many drug companies have attempted to develop drugs that target CCR2, but none have yet made it to market. “So far drugs that target CCR2 have consistently failed in clinical trials,” said Tracy Handel, PhD, professor in the Skaggs School of Pharmacy. “One of the biggest challenges is that, to work therapeutically, CCR2 needs to be turned ‘off’ and stay off completely, all of the time. We can’t afford ups and downs in its activity. To be effective, any small molecule drug that inhibits CCR2 would have to bind the receptor tightly and stay there. And that’s difficult to do.” Handel led the study with Irina Kufareva, PhD, project scientist at Skaggs School of Pharmacy, and Laura Heitman, PhD, of Leiden University. The study’s first author is Yi Zheng, PhD, postdoctoral researcher also at Skaggs School of Pharmacy. CCR2 spans the membrane of immune cells. Part of the receptor sticks outside the cell and part sticks inside. Inflammatory molecules called chemokines bind the external part of CCR2 and the receptor carries that signal to the inside of the cell. Inside the cell, CCR2 changes shape and binds other communication molecules, such as G proteins, triggering a cascade of activity. As a result, the immune cells move, following chemokine trails that lead them to places in the body where help is needed. In this study, the researchers used a technique known as X-ray crystallography to determine the 3D structure of CCR2 with two molecules bound to it simultaneously — one at each end. That’s a huge accomplishment because, Kufareva said, “Receptors that cross the cell membrane are notoriously hard to crystalize. To promote crystallization, we needed to alter the amino acid sequence of CCR2 to make the receptor molecules assemble in an orderly fashion. Otherwise, when taken out of the cell membrane, they tend to randomly clump together. ” Handel, Kufareva and team also discovered that the two small molecules binding CCR2 turn the receptor “off” by different but mutually reinforcing mechanisms. One of the small molecules binds the outside face of the receptor and blocks binding of the natural chemokines that normally turn the receptor "on.” The other small molecule binds the face of the receptor inside the cell, where the G protein normally binds, preventing inflammatory signal transmission. According to Handel, the latter binding site has never been seen before. “It’s our hope that this new structure of CCR2 with two bound inhibitors will help optimize current and future drug discovery efforts,” Kufareva said. Co-authors of this study also include: Ling Qin, Martin Gustavsson, Chunxia Zhao, Ruben Abagyan, UC San Diego; Natalia V. Ortiz Zacarías, Henk de Vries, Adriaan P. IJzerman, Leiden University; Gye Won Han, Vadim Cherezov, Raymond C. Stevens, University of Southern California; Marta Dabros, Robert Cherney, Percy Carter, Andrew Tebben, Briston-Myers Squibb Company; Dean Stamos, Vertex Pharmaceuticals. This research was funded, in part, by the National Institutes of Health (R01GM071872, R01AI118985, R01GM117424, U54GM094618, U01GM094612, R21AI121918, R21AI122211, ACB-12002, AGM-12006). ### SEE ORIGINAL STUDY    

Newswise — GRAND RAPIDS, Mich. — A new investigational drug originally developed for type 2 diabetes is being readied for human clinical trials in search of the world’s first treatment to impede the progression of Parkinson’s diseasefollowing publication of research findings today in the journal Science Translational Medicine. “We hope this will be a watershed moment for millions of people living with Parkinson’s disease,” says Patrik Brundin, M.D., Ph.D., director of Van Andel Research Institute’s Center for Neurodegenerative Science, chairman of The Cure Parkinson’s Trust’s Linked Clinical Trials Committee, and the study’s senior author. “All of our research in Parkinson’s models suggests this drug could potentially slow the disease’s progression in people as well.” Until now, Parkinson’s treatments have focused on symptom management. If successful in human trials, MSDC-0160 would be the world’s first therapy to treat the underlying disease and slow its progression—potentially improving quality of life and preventing the occurrence of falls and cognitive decline. It may also reduce or delay the need for medications that can have debilitating side effects, says Brundin. Parkinson’s disease afflicts between 7-10 million people worldwide, including an estimated 1 million Americans, and these numbers are expected to increase dramatically as the average human lifespan increases. There is currently no cure, and first-line treatment has remained relatively unchanged since the introduction oflevodopa in the 1960s. Tom Isaacs, a co-founder of The Cure Parkinson’s Trust who has lived with Parkinson’s for 22 years, says MSDC-0160 represents one of the most promising treatment the Trust’s international consortium has seen to date. “Our scientific team has evaluated more than 120 potential treatments for Parkinson’s disease, and MSDC-0160 offers the genuine prospect of being a breakthrough that could make a significant and permanent impact on people’s lives in the near future,” says Isaacs. “We are working tirelessly to move this drug into human trials as quickly as possible in our pursuit of a cure.” MSDC-0160 was developed by Kalamazoo, Michigan-based Metabolic Solutions Development Company (MSDC) to treat type 2 diabetes. In 2012, Brundin recognized it as an exciting drug candidate because of its mode of action, proven safety in people, local availability and the start-up company’s interest in collaborating on drug repurposing initiatives. After four years of work, the effects of the drug in the laboratory exceeded Brundin’s expectations. The novelty of MSDC-0160 stems from a recently revived revelation that Parkinson’s may originate, at least partially, in the body’s energy metabolism. The new drug appears to regulate mitochondrial function in brain cells and restore the cells’ ability to convert basic nutrients into energy. Consequently, the cells’ ability to handle potentially harmful proteins is normalized, which leads to reduced inflammation and less nerve cell death. “Parkinson’s disease and diabetes may have vastly different symptoms with unrelated patient outcomes; however, we’re discovering they share many underlying mechanisms at the molecular level and respond similarly to a new class of insulin sensitizers like MSDC-0160,” says Jerry Colca, Ph.D., co-founder, president and chief scientific officer of MSDC. While Brundin says he is eager to see MSDC-0160 launched into a clinical trial in Parkinson’s disease, he’s equally excited about the possibility of testing the drug in Lewy body dementia and other cognitive decline conditions, such as Alzheimer’s disease. “This is an immensely promising avenue for drug discovery,” says Brundin. “Whatever the outcome of the upcoming trial for Parkinson’s, we now have a new road to follow in search of better treatments that cut to the root of this and other insidious diseases.”The Cure Parkinson’s Trust and Van Andel Research Institute are currently working with MSDC to address regulatory issues and obtain funding to organize the clinical trial, which Brundin hopes can begin sometime in 2017. Funding for the research was provided by Van Andel Research Institute, The Cure Parkinson’s Trust, the Campbell Foundation, and the Spica Foundation. The paper’s authors include Anamitra Ghosh, Trevor Tyson, Sonia George, Erin N. Hildebrandt, Jennifer A. Steiner, Zachary Madaj, Emily Schulz, Emily Machiela, Martha L. Escobar Galvis, Jeremy M. Van Raamsdonk and Patrik Brundin, all of Van Andel Research Institute; William G. McDonald and Jerry R. Colca, both of Metabolic Solutions Development Company; and Jeffrey H. Kordower, of Rush University Medical Center and Van Andel Research Institute. # # #

Newswise — Simon Fraser University researchers have found that high-resolution brain scans, coupled with computational analysis, could play a critical role in helping to detect concussions that conventional scans might miss. In a study published in PLOS Computational Biology, Vasily Vakorin and Sam Doesburg show how magnetoencephalography (MEG), which maps interactions between regions of the brain, could detect greater levels of neural changes than typical clinical imaging tools such as MRI or CAT scans. Qualified clinicians typically use those tools, along with other self-reporting measures such as headache or fatigue, to diagnose concussion. They also note that related conditions such as mild traumatic brain injury, often associated with football player collisions, don’t appear on conventional scans. “Changes in communication between brain areas, as detected by MEG, allowed us to detect concussion from individual scans, in situations where MRI or CT failed,” says Vakorin. The researchers are scientists with the Behavioral and Cognitive Neuroscience Institute based at SFU, and SFU’s ImageTech Lab, a new facility at Surrey Memorial Hospital. Its research-dedicated MEG and MRI scanners make the lab unique in western Canada. The researchers took MEG scans of 41 men between 20-44 years of age. Half had been diagnosed with concussions within the past three months. They found that concussions were associated with alterations in the interactions between different brain areas—in other words, there were observable changes in how areas of the brain communicate with one another. The researchers say MEG offers an unprecedented combination of “excellent temporal and spatial resolution” for reading brain activity to better diagnose concussion where other methods fail. Relationships between symptom severity and MEG-based classification also show that these methods may provide important measurements of changes in the brain during concussion recovery. The researchers hope to refine their understanding of specific neural changes associated with concussions to further improve detection, treatment and recovery processes. The research was funded by Defence Research and Development Canada (DRDC). SEE ORIGINAL STUDY    

Newswise — Combination drug treatments have become successful at long-term control of HIV infection, but the goal of totally wiping out the virus and curing patients has so far been stymied by HIV's ability to hide out in cells and become dormant for long periods of time. Now a new study on HIV's close cousin, simian immunodeficiency virus (SIV), in macaques finds that a proposed curative strategy could backfire and make things worse if the virus is in fact lurking in the brain. One of the proposed curative strategies for HIV, known as "shock and kill," first uses so-called latency-reversing agents to wake up dormant viruses in the body, making them vulnerable to the patient's immune system. The idea is that this, in combination with antiretroviral medicines, would wipe out the majority of infected cells. But based on a study of macaques with SIV, a group of researchers warns in a report published in the January 2 issue of the journal AIDS that such a strategy could cause potentially harmful brain inflammation. "The potential for the brain to harbor significant HIV reservoirs that could pose a danger if activated hasn't received much attention in the HIV eradication field," saysJanice Clements, Ph.D., professor of molecular and comparative pathobiology at the Johns Hopkins University School of Medicine. "Our study sounds a major cautionary note about the potential for unintended consequences of the shock-and-kill treatment strategy." HIV research efforts have long focused on prevention and developing antiretroviral therapies that keep the virus in check without eradicating it, essentially transforming HIV into a manageable chronic condition, says Lucio Gama, Ph.D., assistant professor of molecular and comparative pathobiology at Johns Hopkins and the lead author of the new study. Then, in 2009, a group in Berlin reported it had cured a man of HIV by giving him a bone marrow transplant from a donor whose genetics conferred natural resistance to the virus. This galvanized federal funding of new research projects aimed at finding a more broadly applicable "AIDS cure," Gama says. He and Clements are part of that pursuit as members of the Collaboratory of AIDS Researchers for Eradication. One cure strategy being pursued is to find a medication that would "wake up" virus in the reservoirs, forcing it to reveal itself. But Gama says that could be problematic if HIV reservoirs exist in the brain, and investigators already had some evidence that they do: the many cases of AIDS dementia that developed before the current antiretroviral cocktail treatment was developed. "Research had also shown that HIV can infect monocytes in the blood, which we know cross into the brain," he says. But no studies had definitively answered whether significant reservoirs of latent HIV in patients under long-term therapy could be sustained in the brain -- in part because, in autopsies, it is unclear whether virus detected in the brain comes from brain cells themselves or surrounding blood. For the new study, Clements, Gama and their collaborators treated three pig-tailed macaque monkeys infected with SIV with antiretrovirals for more than a year. Then the researchers gave two of the macaques ingenol-B, a latency-reversing agents thought to "wake up" the virus. "We didn't really see any significant effect," Gama says, "So we coupled ingenol-B with another latency-reversing agent, vorinostat, which is used in some cancer treatments to make cancer cells more vulnerable to the immune system." The macaques also continued their course of antiretrovirals throughout the experiment. After a 10-day course of the combined treatment, one of the macaques remained healthy, while the other developed symptoms of encephalitis, or brain inflammation, Gama says, and blood tests revealed an active SIV infection. When the animal's illness worsened, the researchers humanely killed it and carefully removed the blood from its body so that blood sources of the virus would not muddle their examination of the brain. Testing revealed SIV was still present in the brain, but only in one of the regions analyzed: the occipital cortex, which processes visual information. The affected area was so small that "we almost missed it," he says. Gama cautions that the results of their study on macaques with SIV may not apply to humans with HIV. It's also possible, he says, that the encephalitis was transient and could have resolved by itself. Still, he says, the results signal a need for extra caution in exploring ways to flush out HIV reservoirs and eradicate the virus from the body. Other authors on the paper are Celina M. Abreu, Erin N. Shirk, Sarah L. Price, Ming Li, Greg M. Laird, Kelly A. Metcalf Pate and Robert F. Siliciano of The Johns Hopkins University; Stephen W. Wietgrefe and Ashley T. Haase of the University of Minnesota; Shelby L. O'Connor of the University of Wisconsin; Luiz Pianowski of Kyolab in Brazil; Carine van Lint of the Université Libre de Bruxelles in Belgium; and the LRA-SIV Study Group. Research reported in this publication was supported by the National Institute of Mental Health (grant number P01MH070306-01), the National Institute of Allergy and Infectious Disease (grant number U19A1076113), the National Institutes of Health's Office of the Director (grant numbers P40OD013117 and P51OD011106), the Research Facilities Improvement Program (grant numbers RR15459-01 and RR020141-01), the France Recherche Nord & Sud Sida-HIV Hépatites, the Belgian Fund for Scientific Research (FRS-FNRS Belgium), the Fondation Roi Baudouin, the NEAT program and the Wallo on Region (the Excellence Program Cibles). SEE ORIGINAL STUDY

Newswise — RIVERSIDE, Calif. (www.ucr.edu) — A team of researchers, co-led by a University of California, Riverside professor, has found a long-sought-after mechanism in human cells that creates immunity to influenza A virus, which causes annual seasonal epidemics and occasional pandemics. The research, outlined in a paper published online today in the journal Nature Microbiology, could have broad implications on the immunological understanding of human diseases caused by RNA viruses including influenza, Ebola, West Nile, and Zika viruses. “This opens up a new way to understand how humans respond to viral infections and develop new methods to control viral infections,” said Shou-Wei Ding, a professor of plant pathology and microbiology at UC Riverside, who is the co-corresponding author of the paper. The findings build on more than 20 years of research by Ding on antiviral RNA interference (RNAi), which involves an organism producing small interfering RNAs (siRNAs) to clear a virus. His initial research showed that RNAi is a common antiviral defense in plants, insects and nematodes and that viral infections in these organisms require active suppression of RNAi by specific viral proteins. That work led him to study RNAi as an antiviral defense in mammals. In a 2013 paper in the journal Science he outlined findings that show mice use RNAi to destroy viruses. But, it remained an open debate as to whether the same was true in humans. That open debate led Ding back to a key 2004 paper in which he described a new activity of a protein (non-structural protein 1, or NS1) in the influenza virus that can block the antiviral function of RNAi in fruit flies, a common model system used by scientists. In the current Nature Microbiology paper, the researchers demonstrated that human cells produce abundant siRNAs to target the influenza A virus when the viral NS1 is not active. They showed that the creation of viral siRNAs in infected human cells is mediated by an enzyme known as Dicer and is potently suppressed by both the NS1 protein of influenza A virus and a protein (virion protein 35, or VP35) found in Ebola and Marburg viruses. The researchers in the lab of the co-corresponding author, Kate L. Jeffrey, an investigator in the Massachusetts General Hospital gastrointestinal unit and an assistant professor of medicine at Harvard Medical School, further demonstrated that the infections of mature mammal cells by influenza A virus and other RNA viruses are inhibited naturally by RNAi, using mice cells specifically defective in RNAi. "Our studies show that the antiviral function of RNAi is conserved in mammals against distinct RNA viruses, suggesting an immediate need to assess the role of antiviral RNAi in human infectious diseases caused by RNA viruses, including Ebola, West Nile, and Zika viruses," Jeffrey said. The Nature Microbiology paper is called “Induction and suppression of antiviral RNA interference by influenza A virus in mammalian cells.” In addition to Ding, the authors are: Yang Li (UC Riverside and Fudan University in China); Jinfeng Lu, Shuwei Dong, Yanhong Han, Wan-Xiang Li, and Fedor V. Karginov (all of UC Riverside); Megha Basavappa, D. Alexander Cronkite, John T. Prior, Hans-Christian Reinecker and Sihem Cheloufi (all of Harvard Medical School and/or Massachusetts General Hospital); and Paul Hertzog (of Hudson Institute of Medical Research in Australia.)

Newswise — CHICAGO - What if it was possible to prevent your child from getting eczema -- a costly, inflammatory skin disorder -- just by applying something as inexpensive as petroleum jelly every day for the first six months of his or her life?  A Northwestern Medicine study published today (Dec. 5) in JAMA Pediatrics found that seven common moisturizers would be cost effective in preventing eczema in high-risk newborns. By using the cheapest moisturizer in the study (petroleum jelly), the cost benefit for prophylactic moisturization was only $353 per quality-adjusted life year – a generic measure of disease burden that assesses the monetary value of medical interventions in one’s life.     $274The average amount of money families that are caring for a child with eczema spend per month on medical costs   Eczema impacts as many as 20 percent of children and costs the U.S. healthcare system as much as $3.8 billion dollars every year. Previous studies have shown that families caring for a child with the costly skin disorder can spend as much as 35 percent of their discretionary income – an average of $274 per month. “It’s not only terrible for the kids, but also for their families,” said lead and corresponding study author Dr. Steve Xu, a resident physician in dermatology at Northwestern University Feinberg School of Medicine. “Eczema can be devastating. Beyond the intractable itch, a higher risk of infections and sleep problems, a child with eczema means missed time from school, missed time from work for parents and huge out-of-pocket expenses. So if we can prevent that with a cheap moisturizer, we should be doing it.”    If we can prevent (eczema) with a cheap moisturizer, we should be doing it.” Dr. Steve XuResident physician in dermatology at Northwestern University Feinberg School of Medicine   Early studies from Japan, the U.S. and the U.K. have suggested that full-body application of moisturizers for six to eight months, beginning within the first few weeks of life, can reduce the risk that eczema will develops. Xu’s study took that one step further and examined the cost-effectiveness of seven common, over-the-counter moisturizer products, such as petroleum jelly, Aquaphor, Cetaphil and Aveeno. “There’s an important economic argument to be made here,” Xu said. “Moisturizers are an important intervention dermatologists use to treat eczema. They play a big role in getting our patients better. But insurers do not usually cover the cost of moisturizers. We're arguing for their inclusion in health insurance coverage.” Xu acknowledges the evidence is preliminary on prophylactic moisturization but said, “We’re not giving them an oral drug or injecting them with a medication; there is minimal risk. We’re putting Vaseline on these babies to potentially prevent a very devastating disease.” In addition to preventing eczema, Xu cites emerging work that preserving the skin barrier may also reduce the risk of other health problems like food allergies. He notes that larger, long-term clinical studies are underway to see if prophylactic moisturizing leads to sustained benefits.