Newswise — Epigenetics refers to external changes to DNA that turn genes “on” or “off.” These modifications do not change the sequence of the “letters” in DNA, but are physical changes that affect how cells "read" genes. Researchershypothesized that alcohol’s effect on one kind of epigenetic change - called DNA methylation - oncertain genes is associated with the motivation to drink alcohol in binge and heavy drinkers. Methylation is a change in the DNA that reduces gene expression. They measured changes in the methylation of two genes that have been implicated in the control of drinking behavior or the response to stress: the period 2 (PER2) and proopiomelanocortin (POMC) genes. Methylation changes were measured in blood samples drawn from groups of non-smokers who were moderate drinkers, binge drinkers, or heavy drinkers. These drinkers also participated in a laboratory study that measured behavioral alcohol motivation. During the three-day experiment, the participants experienced stress-related, neutral, or alcohol-related mental images on consecutive days. After this imagery, participants were exposed to alcoholic beer cues followed by an alcohol taste test to assess their motivation to drink. The expression of the PER2and POMC genes was measured in blood samples immediately after the behavioral experiments. The researchers found that there was greater methylation of the DNA in the two genes, along with lower expression of the genes in the blood samples from the binge and heavy drinkers than those from the moderate drinkers. Greater PER2and POMCDNA methylation was associated with a greater subjective desire for alcohol immediately after presentation of the cues and after presentation of the alcoholic beer, and for alcohol consumed during the taste test. The authors concluded that there is a relationship between binge or heavy alcohol drinking and DNA methylation and changes in POMCand PER2genes. This is consistent with prior findings of a role for these genes in the control of drinking behavior and the stress response. The changes were also associated with a greater subjective and behavioral motivation for alcohol. These initial findings may further develop into a predictive biomarker of the risk for binge or heavy drinking.
Mouse studies reveal which cells and proteins in young animals can boost healing in the old Newswise — DURHAM, N.C. -- For a child, recovering from a broken bone is typically a short-lived, albeit painful, convalescence. But for older adults, it can be a protracted and potentially life-threatening process. Finding ways to speed bone repair is a public health priority that could save both lives and health care expense. The Centers for Disease Control and Prevention reports that more than 800,000 patients a year are hospitalized because of fall injuries, including broken hips, and these hospitalizations cost an average of $30,000. “Delayed fracture healing is a major health issue in aging, and strategies to improve the pace of repair and prevent the need for additional surgeries to achieve healing substantially improve patient outcomes,” said senior author Benjamin Alman, M.D., chair of the Department of Orthopedic Surgery at Duke. Duke Health researchers have previously shown that introducing bone marrow stem cells to a bone injury can expedite healing, but the exact process was unclear. Now, the same Duke-led team believes it has pinpointed the “youth factor” inside bone marrow stem cells -- it’s the macrophage, a type of white blood cell, and the proteins it secretes that can have a rejuvenating effect on tissue. Nature Communications will publish the findings online on Dec. 5. After tissue injury, the body dispatches macrophages to areas of trauma, where they undergo functional changes to coordinate tissue repair. During fracture healing, macrophages are found at the fracture site. But when they’re depleted, fractures will not heal effectively. Macrophage populations and characteristics can change with aging. “We show that young macrophage cells produce factors that lead to bone formation, and when introduced in older mice, improves fracture healing,” said Gurpreet Baht, Ph.D., assistant professor in orthopedic surgery and a lead author of the study. “While macrophages are known to play a role in repair and regeneration, prior studies do not identify secreted factors responsible for the effect,” Alman said. “Here we show that young macrophage cells play a role in the rejuvenation process, and injection of one of the factors produced by the young cells into a fracture in old mice rejuvenates the pace of repair. This suggests a new therapeutic approach to fracture rejuvenation.” In addition to Alman and Baht, study authors include Linda Vi, Erik J. Soderblom, Heather Whetstone, Qingxia Wai, Bridgette Furman, Vijitha Puviindran, Puviindran Nadesan, Matthew Foster, Raymond Poon, James P. White, Yasuhito Yahara, Adeline Ng, Tomasa Barrientos, Marc Grynpas, and M. Arthur Mosely. The research was supported by a grant from the National Institute on Aging, part of the National Institutes of Health (R01 AG049745) and by the Canadian Institutes of Health Research (FRN 62788). The authors declared no competing financial interests.
From toothbrush holders to typing aids to nail clippers, 3-D printing cuts the cost of devices aimed to help people with hand arthritis. Newswise — Adaptive aids are expensive. Additive manufacturing, using low-cost 3-D printers, can save upwards of 94 percent for simple household items. The Centers for Disease Control and Prevention (CDC) reports that almost a quarter of the U.S. population lives with some form of arthritis. Daily tasks — like opening drawers, turning door handles — can be difficult, so people turn to adaptive aids. Many are small pieces of plastic. “It never ceases to amaze me what a small piece of plastic sells for,” said Joshua Pearce, the Richard Witte Endowed Professor of Materials Science and Engineering at Michigan Technological University. “Anyone who needs an adaptive aid for arthritis should be 3-D printing it.” So, Pearce had his class take a shot. Now, Pearce is a co-author and corresponding researcher on a new study that analyzes how 20 of the 3-D printed adaptive aids his class printed see huge cost savings and either meet — or improve — standards for existing products. The study was published this week in Geriatrics and is co-authored by student research assistant Nicole Gallup and orthopedic surgeon Jennifer Bow, who is also a visiting scholar at Michigan Tech. More Pain, No Gain Adults with arthritis and other rheumatic conditions earn less than average yet spend more on medical expenses, on average about 12 percent of the average family’s income. To boot, the adaptive aids they may need to purchase to help them pull on socks, hold toothbrushes, knit, pull zippers, cut food and many other everyday tasks are pricey. Adaptive aids range from a cheap pop can opener for $5.99 to pill splitter for $23.75 to a phone holder for $49.99. With 3-D printing, those costs can come down to 45 cents to pop tabs, $1.27 to split pills and 79 cents plus a rubber band to hold a phone. The 3-D printed versions are not only cheaper but customizable. Dr. Bow recommended students take a look at designing adaptive aids because the customization available from 3-D printers could help her arthritis patients and others throughout the world. Subsequently, the group Makers Making Change approached Pearce because they needed to improve some existing designs that can be shrunk, expanded, tweaked to match different hand sizes, grip strength, color preference and task modification. “This is the difference between needing to go to someone to get your nails cut and being able to do your own, which, yes, there’s cost savings, but it’s also personal pride and being able to take care of yourself,” Pearce said. “And if your only problem is that the standard nail clipper is too tiny, we can fix that.” Cost for individual items may not be too onerous. However, following a diagnosis, some patients need to overhaul or install many adaptive aids, like putting light switch flippers throughout the house, which adds up quickly. 3-D printing can trim that cost, and Pearce’s team only used printers that cost $500 or less, but the upfront cost of a printer may curb some people’s enthusiasm. Also, some people do not have to pay the full price for adaptive aids if Medicare or their insurance policy helps cover the purchases. Pearce says neither substantially affects the numbers. “We printed and analyzed 20 different products and each one has a great return on investment, even for people who can use insurance to purchase adaptive aids with a co-pay, and a printer pays for itself easily,” Pearce said, explaining that the true challenge is not economic. “It’s a slam dunk — but the question becomes, how do people get these aids?” Access to 3-D Printing People can save a lot having a 3-D printer on their kitchen table. Not everyone is ready for the distributed manufacturing wave in their home, but there are still many ways to bring 3-D printed goods to people with arthritis, particularly older patients. “We’re not saying an 85-year-old with no personal computer experience is developing a CAD from scratch and prototyping a design 12 times,” Pearce said, explaining the open source designs are available for free online at Appropedia and MyMiniFactory. Pearce sees nursing homes, doctor’s offices and physical therapy clinics as the ideal hubs for 3-D printed adaptive aids. Local makerspaces and libraries also provide access to printers, designs and knowledgeable people in exchange for fees that cover plastic and printing costs; some businesses even make a living providing 3-D prints. Printed for Class With that dream in mind, Pearce says his class started with base functionality. Their assignment — turned around in a week— was printed on Rep-Rap printers that the students built themselves in the first two weeks of class. They did all their adaptive aid prints with PLA plastic, focused on handheld items, and many of the students designed features with a loved one, friend or acquaintance in mind. They all work, but there’s always room for improvement. “All the designs could be made much prettier and better — and that’s the beauty of open source. Because I hope in a couple years that we have a whole array of each one of these ideas that’s built out much further, applied all over the world and customized for individual people,” Pearce said. “This is a new field of 3-D printing design that’s just getting started. Lots of people can make real, honest-to-goodness, concrete contributions.”
Police Killings of Unarmed Black Americans Affect Mental Health of Black Community First Study to Show Mental Health “Spillover Effects” from Deaths of Unarmed Black Americans Newswise — PHILADELPHIA — Black Americans are nearly three times more likely to be killed by police than their white counterparts, with even larger disparities among those who are unarmed. The trend is also harming the mental health of the black community, according to new research published in The Lancet from the Perelman School of Medicine at the University of Pennsylvania and the Boston University School of Public Health. “These deaths don’t just have immediate consequences for the families and friends. There’s a true mental health spillover effect for those not directly involved,” said Atheendar S. Venkataramani, MD, PhD, an assistant professor of Medical Ethics and Health Policy in Penn’s Perelman School of Medicine, and co-lead author of the study. In a national survey of nearly 40,000 black Americans who were interviewed within three months following at least one death of a black American at the hands of police in their state, the team found that police killings of unarmed black Americans were associated with worse mental health among other black Americans in the United States general population. “Addressing this problem will require interventions to reduce the prevalence of police killings as well as programs that mitigate the adverse mental health effects in communities when these events occur,” said co-lead author Jacob Bor, ScD, SM, an assistant professor at the Boston University School of Public Health. “More broadly, the findings indicate that events widely perceived to reflect structural racism cause significant harm to the mental health of black Americans. Efforts to reduce health disparities should explicitly target structural racism.” Structural racism is described as policies, laws, practices, and other norms entrenched in institutions that can harm a certain racial group and perpetuate racial inequities. The researchers combined newly released data on police killings between 2013 and 2016 from the Mapping Police Violence Project database with data from the U.S. Behavioral Risk Factor Surveillance System (BRFSS) of over 103,000 black Americans. BRFSS is a nationally-representative, telephone-based, random-digit dial survey of adults ages 18 years and older. The primary exposure was the number of police killings of unarmed black Americans occurring in the three months prior to the person being surveyed. Exposure included word of mouth and news stories in print, radio, television, and/or social media. To measure mental health outcomes, the researchers asked respondents: “Now thinking about your mental health, which includes stress, depression, and problems with emotions, for how many days during the past 30 days was your mental health not good?” Researchers then compared the number of poor mental health days experienced by black Americans surveyed after a police killing of an unarmed person to that of black Americans residing in the same state surveyed before that event. Overall, the study suggests the police killings could contribute 1.7 additional poor mental health days per person ever year, or 55 million more poor mental health days every year among black Americans in the United States. To contextualize those numbers, the authors point to diabetes, which is responsible for an estimated 75 million poor mental health days among black Americans. “Our estimates therefore suggest that the population mental health burden from police killings among black Americans is nearly as large as the mental health burden associated with diabetes,” they wrote. The study shows, for the first time, that police killings of unarmed black Americans have a “meaningful, population-level impact” on the mental health of other black Americans. “The effects are likely even larger than what we estimated,” said Venkataramani, pointing to the fact that more high-profile cases of police killings that grabbed national media attention could have exerted mental health effects among black Americans living in other states, as well. Importantly, the researchers saw no spillover mental health effects among white respondents, nor among respondents of either race in response to police killings of unarmed whites or of armed black Americans. This striking specificity points to the importance of structural racism as a key mechanism underlying the study findings, and a driver of population health, more generally, the authors said: “[P]olice killings of unarmed black Americans are perceived by many as manifestations of structural racism and as implicit signals of the lower value placed on black lives by law enforcement and legal institutions – as well as by society at large.” Co-authors of the study include David R. Williams, PhD, of the Harvard T.H. Chan School of Public Health, and Alexander C. Tsai, of Massachusetts General Hospital. ### Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise. The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $405 million awarded in the 2017 fiscal year. The University of Pennsylvania Health System’s patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation’s top “Honor Roll” hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation’s first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine, and Princeton House Behavioral Health, a leading provider of highly skilled and compassionate behavioral healthcare. Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2017, Penn Medicine provided more than $500 million to benefit our community.
In rare occurrences, forceful manipulation of the neck is linked to a damaging side effect: vision problems and bleeding inside the eye. For those in the habit of getting their neck adjusted by a chiropractor, the University of Michigan Kellogg Eye Center has an interesting case to know about: High velocity neck manipulation has been shown to result in stress on the eye and lead to spotty vision. The risk is rare, but one that Yannis Paulus, M.D., a retina specialist at Kellogg, reports on in the American Journal of Ophthalmology Case Reports. The energetic thrusts and rotations sometimes performed in high-velocity neck manipulation have been linked to damage to the blood vessels in the retina. Resulting abnormal bleeding inside the eye may also cause vision loss. This was the case for a 59-year-old woman who experienced a “tadpole” shaped spot in her vision while driving home from a chiropractor visit — with her sight worsening the next day. She had just received cervical spine manipulation using the high-velocity technique to help with her headaches. The woman’s vision returned to normal in about two weeks without treatment. She was referred to Kellogg Eye Center by her optometrist who co-authored the case report. Because the cells of the retina are so sensitive, even small injuries to the blood vessels can translate to vision problems. That’s why Paulus encourages patients to report their alternative medicine pursuits — and for physicians to actively listen and inform them of possible related side effects. Risks from chiropractic treatment Cardiovascular experts have been outspoken about health risks of chiropractic treatment. High-velocity neck manipulation has been associated with a certain type of stroke, or vertebral artery dissection, which led the American Heart Association to issue a warning statement in 2014. The short, rapid movements of neck manipulation may cause a small tear in the artery walls in the neck. The artery wall injury can result in a stroke if a blood clot forms at the site and later breaks free to block a blood vessel in the brain. Eye problems can follow, including double vision or central retinal artery occlusion, a blockage of the artery carrying oxygen to the nerve cells in the retina at the back of the eye. But the case at Kellogg suggests a new complication: direct damage to structures in the eye due to the force of neck adjustments. It’s the first case report of chiropractic care leading to multiple preretinal hemorrhages, authors say. Other possible complications are disrupting the vitreous humor — the clear, gel-like substance that fills the eye between the lens and the retina. The high-velocity technique may have induced a posterior vitreous detachment, or PVD, which occurs when the vitreous humor pulls away from the retina. No specific treatment is needed for PVD. Most patients no longer notice flashes in their vision after three months and “floaters” tend to improve, according to the American Society of Retina Specialists. Complications from PVD are rare but can be serious and in some cases require urgent treatment such as laser treatment to seal the retinal tear or surgery for a retinal detachment. Although the connection to chiropractic care is considered a temporal association, the timing of the patient’s eye symptoms following the chiropractic visit is hard to ignore. Paulus didn’t rule out future chiropractic visits for the patient but notes that “her chiropractor may need to modify techniques used during her visits.”
Newswise — In a proof-of-principle study, researchers at Johns Hopkins report that a certain liver immune cell called a macrophage contains only defective or inert HIV-1 copies, and aren’t likely to restart infection on their own in HIV-1-infected people on long-term antiretroviral therapy (ART). The study, the investigators say, strongly suggest that defective or inert HIV-1 can remain in the liver macrophages for up to ten years without functioning as an HIV-1 “reservoir” that can replicate the virus at high levels. A report of the findings was published online on Sept. 10 and in the Oct. issue of the Journal of Clinical Investigation. “Our study was the first, to our knowledge, in which purified liver tissue macrophages from HIV-1 infected people taking ART directly tested the idea that tissue macrophages are a long-lived active HIV-1 reservoir,” says Ashwin Balagopal, M.D., an associate professor in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine. According to the U.S. Centers for Disease Control and Prevention (CDC), 36.7 million people worldwide and 1.1 million people in the U.S. are infected with HIV-1. Commonly, ART is successfully used to suppress the replication of HIV-1 and stop or control the progression of acquired immunodeficiency syndrome (AIDS) in humans. The virus infects the body’s immune system cells, commonly forming a persistent, and reservoir in humans in so-called resting memory CD4+ T white blood cells. Macrophages work with T cells normally to envelop and clear tissues of microbes and debris. The inability to completely wipe out pools of infectious HIV-1 has for decades frustrated efforts to completely cure the infection. And it means that the interruption or discontinuation of ART at any time re-activates HIV-1 replication, spreading the virus to new cells. As a result, Balagopal says, investigators are increasingly focused more specifically on the location and biology of these HIV-1 reservoirs. To determine if liver macrophages were a true source of infection-capable HIV-1 reservoirs after ART, liver tissue samples were taken from nine HIV-1 infected persons, seven of whom underwent liver transplantation at the Johns Hopkins Hospital and would have otherwise had their livers discarded. Eight of the nine persons were on ART for periods ranging from eight to 140 months. The sample group included only adults whose demographic information is considered exempt from human subject research because all samples were obtained strictly for scientific reasons or postmortem, and would otherwise have been discarded. The Johns Hopkins School of Medicine institutional review approved this study protocol. Using lab techniques that both measure HIV-1 containing T cells and separate out the liver macrophages, the researchers found HIV-1 to be present in the macrophages even after exposure to longstanding virus-suppressing ART. However, Balagopal said that when his team tried to simulate virus “rebound” from the liver macrophages in the laboratory, they found only “fragments of HIV-1 in small quantities, without robust growth of full-length, infectious virus.” The researchers found that HIV-1 was in the liver macrophages of one subject who took ART for 11.7 years. They concluded that while liver macrophages might harbor HIV-1 for a long time, it’s unlikely these viruses could continue an infection on their own, unlikely to function as a reservoir, because the viruses were not able to replicate. Balagopal cautioned that their study results still affirm the need to address liver macrophage infection, because even if inert, these cells may be able to produce portions of viral proteins that can misdirect the immune system. “These results contribute an important piece in our efforts to understand the role of non-T cells, such as macrophages, as HIV-1 cellular reservoirs in individuals on long-term ART, but also may help the research community focus on additional cure strategies," Abraham Kandathil, Ph.D., a research associate in the Division of Infectious Diseases at Johns Hopkins University School of Medicine who performed all of the key experiments. In the future, Kandathil says, more research is needed to determine if the inert HIV-1 infected liver macrophages have any functional significance in people taking ART because expression of defective HIV-1 proteins can confuse the immune system and cause tissue inflammation. “To find a comprehensive HIV-1 cure, it’s important to identify all of the relevant HIV-1 reservoirs in the body, since it’s possible that the virus hides in the DNA of numerous cell types and each may require different strategies to get a cure,” says Balagopal. Balagopal noted that their study was limited by the small number of liver macrophages and human samples studied, as well as the small number of CD4+ T cells in the liver cell cultures that may have prevented the researchers’ ability to detect them. Other authors on this paper include Sho Sugawara, Christine M. Durand, Jeffrey Quinn, Jaiprasath Sachithanandham, Andrew M. Cameron, and Justin R. Bailey of the Johns Hopkins University School of Medicine along with Ashish Goyal and Alan S. Perelson from Los Alamos National Laboratory. This research is supported by grants from the National Institute of Allergy and Infectious Diseases (K08 AI 081544, R56 AI 118445, R01 AI024333, R01 AI116868, and P01 AI131365), the National Institute on Drug Abuse (R01 DA 016078), the National Institutes of Health Office of the Director (R01 OD 011095 and 108707-54-RKRL ) and amfAR, the Foundation for AIDS Research (108814-55-RGRL). The authors have declared that no conflict of interest exists.
More than 1 in 10 people aged 50-64 have had genetic tests ordered by a doctor or ordered directly. Many more want to – but also worry about worrying Newswise — ANN ARBOR, MI – Only a small percentage of people in their 50s and early 60s have had their DNA tested – either for medical reasons, to learn their ancestry or out of curiosity – but far more have an interest in getting such tests done, according to a new poll. One in 10 have taken genetic tests offered directly to consumers, and one in 20 have taken genetic tests ordered by a doctor, according to new findings from the National Poll on Healthy Aging. More than half expressed interest in getting DNA tests to guide medical care, understand health risks or know their ancestry. Still, the poll finds, that desire to know more about their risk of disease or heritage comes with a grain of salt. Two thirds of those polled said they thought genetic testing could lead them to worry too much about their future health. The poll of 993 adults between the ages of 50 and 64 was conducted by the University of Michigan Institute for Healthcare Policy and Innovation, and sponsored by AARP and Michigan Medicine, U-M’s academic medical center. It comes at a time when the U.S. Food and Drug Administration has approved several disease-specific tests to be marketed directly to the public, instead of requiring a physician to order them. The poll also asked respondents their interest in testing to learn their genetic risk for three later-life disorders: Alzheimer’s disease, Parkinson’s disease or macular degeneration. Around two-thirds had at least some interest in each test. Scott Roberts, Ph.D., a professor from the U-M School of Public Health who has studied use of genetic testing, including direct-to-consumer testing, worked on the poll’s design and analysis. He notes that even those who get direct-to-consumer genetic tests mainly to learn about their ancestral heritage could end up being “blindsided” by findings showing that they have a high risk of diseases such as Alzheimer’s. “Compared to previous findings in the general adult population, this age group appears to be a little more lukewarm about their views of the benefits versus the risks of genetic testing overall,” he says. “The majority said they might be interested in knowing their risk for specific conditions, but on other hand they were worried about potential psychological distress from the results.” Roberts points out that the accuracy of any genetic test is not 100 percent. He also notes that testing ordered by physicians often comes with a chance to meet with a genetic counselor – a specially trained clinician who can help patients decide whether to get tested, prepare them for handling the results, and help them understand what the results do and don’t mean. By contrast, direct-to-consumer testing often comes with none of these services, and individuals who buy DNA tests directly may encounter difficulty in interpreting them, or getting access to a genetic counselor after they receive their results. Genetic counselors are already in high demand for clinical cases, and their appointment times are prioritized for those who have a clinical reason for DNA testing, including family history of a serious genetic illness. “Patients may not think about the downstream effects of direct-to-consumer genetic testing. An unexpected positive result may lead to several additional tests that may or may not be covered by insurance,” says Preeti Malani, M.D., director of the poll and a professor of internal medicine at the U-M Medical School who has special training in geriatric medicine. Experience with testing The five percent of the poll respondents who had already had a genetic test ordered by their physician said it was done either because the physician suggested it or because they had wanted to find out more about their risk of disease or how best to manage a current condition. Ten percent had had a direct-to-consumer test. More than 70 percent of them said they were interested in learning more about their ancestry, and just under half said they were just curious about their genetic make-up. Just over one in 10 said they got tested to find out more about their health in general, or their risk of a particular disease. Combining the two types of genetic testing, 14 percent had had either kind. “We’re living in an era when advances like DNA testing are providing an amazing amount of useful health information,” says Alison Bryant, Ph.D., senior vice president of research for AARP. “As genetic testing becomes even more sophisticated and common among older adults, the challenge will be to ensure that people understand the benefits and limitations of these tests.” Future of genetic testing Roberts, who specializes in genetic testing for Alzheimer’s disease, notes that 70 percent of poll respondents had an interest in learning their Alzheimer’s risk. Newer clinical trials of drugs that aim to prevent, delay or slow progression of memory loss and other cognitive problems are actually looking to enroll people who have a higher-than-usual genetic risk of Alzheimer’s. So those who elect to buy such a test, or whose doctors order one for them because of family history, may now have an action they can take based on their results. “Before, there wasn’t much we could recommend, but now there are more research opportunities to take part in, and we know more about health behaviors earlier in life that can affect the risk of Alzheimer’s and other forms of dementia later in life,” he says. Poll respondents seemed to understand how genetic testing provides a potential window into the future, both for their own health risks (90 percent agreed with this idea) or for those of their children and grandchildren (86 percent). But 41 percent said that a genetic test wasn’t necessary if they already know what disease risks run in their family. The poll results are based on answers from a nationally representative sample of 993 people ages 50 to 64. The poll respondents answered a wide range of questions online. Questions were written, and data interpreted and compiled, by the IHPI team. Laptops and Internet access were provided to poll respondents who did not already have it. A full report of the findings and methodology is available at www.healthyagingpoll.org, along with past National Poll on Healthy Aging reports.
Highlights The blood pressure–lowering medication ramipril reduced protein excretion—or proteinuria—in children with chronic kidney disease. Greater reductions in proteinuria during the first months of treatment were linked with a lower risk of kidney disease progression. Newswise — Washington, DC (June 21, 2018) — In a study of children with chronic kidney disease (CKD), blood pressure medications reduced protein excretion in the urine, which was linked with a lower risk of disease progression. The findings, which appear in an upcoming issue of the Journal of the American Society of Nephrology (JASN), provide valuable information for monitoring and treating pediatric patients with CKD. The excretion of protein in the urine, or proteinuria, indicates an increased risk for kidney and heart problems, and it is known in adult patients that this risk can be lowered with medications called angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers. Both types of drugs cause blood vessel relaxation and a decrease in blood pressure. It has not been clear, however, whether these medications benefit children with proteinuria. To investigate, Sophie van den Belt, MD, PhD (University Medical Center Groningen, in The Netherlands) and her colleagues analyzed data from the Effect of Strict Blood Pressure Control and ACE inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) trial. This trial investigated whether intensified blood pressure control can delay the progression of chronic kidney disease (CKD) in children with the condition. In total, 280 children with CKD stage 2–4 received a fixed dose of the ACE inhibitor ramipril and were subsequently randomized to conventional or intensified blood pressure control with antihypertensive medications. The average initial proteinuria lowering was 40.2% in the conventional blood pressure control group and 46.7% in the intensified blood pressure control group. Due to the similar initial proteinuria change in the 2 study arms, the groups were combined for further analysis. The investigators found that ramipril therapy lowered proteinuria by an average of 43.5%. Also, a higher degree of proteinuria lowering during the first months of treatment was linked with a lower risk of CKD progression. “The results indicate that a higher initial proteinuria reduction with ACE inhibition is independently associated with long-term preservation of renal function in children with CKD. This finding suggests that proteinuria lowering is an important target in the management of pediatric CKD,” said Dr. van den Belt. Study co-authors include Hiddo Lambers Heerspink, PharmD, PhD, Valentina Gracchi, MD, PhD, Dick de Zeeuw, MD, PhD, Elke Wühl, MD, PhD, and Franz Schaefer, MD, PhD, for the ESCAPE trial group. Disclosures: The ESCAPE study was supported by grants of the Boehringer Ingelheim Stiftung, the European Commission (5th Framework Programme QLRT-2001-00908, the Kuratorium für Dialyse und Nierentransplantation e.V., Neu-Isenburg, and the Baxter Extramural Grant Program. The study protocol was developed exclusively by the participants. Onsite monitoring of study data collection was performed by an independent clinical research organization (Omnicare Clinical Research). Aventis Pharmaceuticals supplied ramipril and financed the GCP audit. Dr. Schaefer reports serving as a paid advisor for Abbvie, Astellas, and Bayer. No other potential conflicts of interest relevant to this article were reported. The article, entitled “Early proteinuria lowering by ACE inhibition predicts renal survival in children with chronic kidney disease,” will appear online at http://jasn.asnjournals.org/ on June 21, 2018, doi: 10.2215/ASN.2018010036. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies. Since 1966, ASN has been leading the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients. ASN has more than 18,000 members representing 112 countries. For more information, please visit www.asn-online.org or contact the society at 202-640-4660.
MEDICAID EXPANSION HAS HELPED LOW-INCOME KIDNEY FAILURE PATIENTS GET ON THE TRANSPLANT WAITLIST BEFORE STARTING DIALYSIS
Highlights In states that expanded Medicaid under the Affordable Care Act to cover more low-income individuals, there was an increase in the number of Medicaid beneficiaries who were preemptively waitlisted to receive a kidney transplant. Medicaid expansion was associated with greater gains racial and ethnic minorities in being listed pre-emptively on the transplant waitlist compared with whites. Newswise — Washington, DC (June 21, 2018) — New research indicates that Medicaid expansion under the Affordable Care Act has helped to place many low-income individuals with chronic kidney disease (CKD) on the kidney transplant waiting list before starting dialysis. In addition, after expansion, there were larger gains in pre-emptive listing for minorities with Medicaid coverage than for whites. The findings appear in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN). Kidney transplantation is considered more cost-effective than dialysis, and preemptive wait-listing—or placing patients on the kidney transplant waiting list before they require dialysis—can help minimize the time that patients will eventually need to spend on dialysis before receiving a kidney transplant. Access to the kidney transplant waiting list is generally contingent on having health insurance coverage, however. Medicare provides a health insurance safety net once individuals develop kidney failure and require dialysis, but prior to Medicaid expansion under the Affordable Care Act, no similar safety net existed for low income individuals with advanced CKD who were not yet on dialysis. Studies are needed to determine whether Medicaid expansion under the Affordable Care Act has provided opportunities for low-income individuals with CKD to get the care they need. To investigate, Meera Nair Harhay, MD, MSCE, FASN (Drexel University College of Medicine) and her colleagues examined information from the United Network of Organ Sharing database on adults listed for kidney transplantation before dialysis dependence in 2011–2013 (pre–Medicaid expansion) and 2014–2016 (post–Medicaid expansion). “We explored whether Medicaid expansion, in offering an option for health insurance coverage for low-income individuals in the United States, would be associated with an increase in the number of Medicaid beneficiaries on the kidney transplant waiting list,” said Dr. Harhay. The team found that after states expanded Medicaid to cover more low-income individuals, there was an increase in preemptive listings of Medicaid beneficiaries. States that fully implemented Medicaid expansion on January 1, 2014 had a 59% relative increase in Medicaid-covered preemptive listings from the pre-expansion to post-expansion period, compared with an 8.8% relative increase among Medicaid non-expansion states. From the pre- to post-expansion period, the adjusted proportion of listings with Medicaid coverage decreased by 0.3 percentage-points among non-expansion states and increased by 3.0 percentage-points among expansion states. Also, more of the new racial/ethnic minority listings from expansion states were Medicaid beneficiaries, as compared with the new white listings. In addition, Medicaid beneficiaries on the waiting list from Medicaid expansion states were more likely to be employed and functionally independent than Medicaid beneficiaries on the waiting list from non-expansion states. The authors noted that additional studies are needed to determine whether long-term transplant outcomes differ among candidates who were listed with expanded Medicaid coverage compared with those with other coverage options. In an accompanying editorial, Nitender Goyal, MD and Daniel Weiner, MD, MS (Tufts Medical Center) note that policies that improve access to care can have a tremendous impact on the delivery of medical care. “Harhay and colleagues elegantly quantified this by describing the effects of access to Medicaid on preemptive kidney transplant listing. Much harder to quantify but likely far more numerous are the patients who, because of earlier diagnosis and treatment of their kidney disease may never need to be listed for a kidney transplant, but rather will be able to maintain kidney health with better access to medical care,” they wrote. Study co-authors include Ryan M. McKenna, PhD, Suzanne M. Boyle, MD, Karthik Ranganna, MD, Lissa Levin Mizrahi, MD, Stephen Guy, MD, Gregory E. Malat, PharmD, Gary Xiao, MD, David J. Reich, MD, and Michael O. Harhay, PhD. Disclosures: The authors reported no financial disclosures. The article, entitled “Association Between Medicaid Expansion Under the Affordable Care Act and Preemptive Listings for Kidney Transplantation,” will appear online at http://cjasn.asnjournals.org/ on June 21, 2018, doi: 10.2215/CJN.00100118. The editorial, entitled “The Affordable Care Act, Kidney Transplant Access and Kidney Disease Care in the United States,” will appear online at http://cjasn.asnjournals.org/ on June 21, 2018. The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. 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Newswise — ANN ARBOR, Mich. — Philosophers have pondered the nature of consciousness for thousands of years. In the 21st century, the debate over how the brain gives rise to our everyday experience continues to puzzle scientists. To help, researchers in the University of Michigan Medical School Center for Consciousness Science are working to identify areas of the brain that help us wake up, a basic building block of everyday consciousness. In the search for what controls our overall level of consciousness, researchers have traditionally focused on structures in the lower part of the brain. These structures include the brainstem (which regulates vital functions like breathing, blood pressure and heartbeat); the hypothalamus (which is involved in sleep and controlling bodily functions); and the thalamus (which relays information from the senses). George Mashour, M.D., Ph.D., professor in the Department of Anesthesiology and director of the center, decided to look at different areas of the cortex, the upper part of the brain, for its ability to control the level of consciousness. Recent research in nonhuman primates provides evidence that the prefrontal cortex has a switchboard-like relationship with other areas of the brain, helping to ignite awareness of visual information. “There has been a debate that has recently intensified as to whether or not the prefrontal cortex — versus areas farther back — plays a role in generating conscious experience. We thought that we’d target some of these different areas in the front and back of the brain to see which ones had the ability to control the level of consciousness,” he says. The key to ignition? Because anesthesia is used to temporarily eliminate conscious experience during medical procedures, it provides the perfect opportunity to test hypotheses about consciousness. Mashour and lead-author Dinesh Pal, Ph.D., also of the Department of Anesthesiology, anesthetized rats with a common anesthetic used in humans. “We wanted to see what had the causal power to take an unconscious brain receiving ongoing anesthesia and wake it up,” says Pal. To test this, they targeted two neurotransmitters that are associated with wakefulness: acetylcholine and norepinephrine. The team exposed the anesthetized rats’ prefrontal and parietal cortex to drugs that ramped up the effect of the neurotransmitters and measured their brain activity and behavior. When exposed to an acetylcholine-receptor activator, their brain waves, normally slow during sleep and anesthesia, sped up. But rats were able to start behaving as though they were awake only with prefrontal cortex stimulation, all while continuing to receive the same level of anesthesia that is used clinically for surgery in humans. These findings were published in the journal Current Biology. Mashour says their new study “suggests that the prefrontal cortex also has the potential to play a role in coordinating the level of consciousness, possibly through the cholinergic system.” Clinically, these results could be explored for applications in people with disorders of consciousness, such as coma or vegetative states. “Let’s say you have a patient in a coma: Could the prefrontal cortex be a site that is modulated to help coordinate events to help improve level of consciousness?” Mashour asks. The implications of this possibility are significant because of the relative accessibility of the prefrontal cortex. “It’s very difficult and dangerous to directly intervene at the level of arousal centers in the brainstem because of its location, small size and nearby vital functions. Maybe the prefrontal cortex is an accessible gateway to some of those other arousal systems that could be leveraged in a clinical setting outside of anesthesia,” he says. This work was funded by the National Institutes of Health (R01GM098578), and the Department of Anesthesiology, University of Michigan Medical School, Ann Arbor. Physiology doctoral student Jon Dean was co-first author of the article.