Newswise — HOUSTON ― Researchers have identified a new potential immunotherapy target in pancreatic cancer, which so far has been notoriously resistant to treatment with immune checkpoint blockade drugs effective against a variety of other cancers. The University of Texas MD Anderson Cancer Center research team found overexpression of the immune checkpoint VISTA on immune cells, especially macrophages, that infiltrated pancreatic tumors. Their paper will be published online Friday at the Proceedings of the National Academy of Sciences. “VISTA is a potential therapeutic target in pancreatic cancer, and there are several antibodies to block VISTA under clinical development,” said co-senior author Padmanee Sharma, M.D., Ph.D., professor of Genitourinary Medical Oncology and Immunology. “Additional research also needs to be done to see if we can come up with other targets for these VISTA-positive cells as well.” Present immune checkpoint inhibitors that unleash an immune attack on cancer by blocking PD-1 and CTLA-4 brakes on T cells have been ineffective against pancreatic cancer, one of the most lethal cancers. The five-year survival rate for patients with pancreatic cancer is 7 percent or less. The team, led by Sharma and 2018 Nobel Laureate Jim Allison, Ph.D., professor and chair of Immunology, set out to shed light on infiltration of immune cells and expression of immunity-inhibiting checkpoints in pancreatic cancer by comparing those tumors to melanoma, the cancer that is most vulnerable to immune checkpoint blockade. They first analyzed expression of nine immune inhibitory genes in 23 untreated, surgically removed pancreatic cancer tumors and found the results separated the patients into two groups, 11 with high-expression of inhibitory genes and 12 with low expression. Those with low-expression of immune inhibitors had a median survival of 37 months versus 20 months for the high-expression group, indicating potential immune impact on overall survival. Tumor architecture: Stroma and malignant cells Pancreatic cancer tumors include a high density of stroma, non-malignant supportive cells, while melanoma is at the other end of the spectrum with minimal stroma. These differences came into play in the team’s analyses. The pancreatic tumors were composed of 30 percent malignant cells and 70 percent stroma, while those proportions were flipped in melanoma tumors. In addition to the vastly different ratio of stromal cells, the architecture of the tumor types also diverges, Sharma notes. “In melanoma, you have a large area of malignant cells surrounded by a thin layer of stroma. With pancreatic cancer, it’s more like cancer cells, stroma, cancer cells, stroma ― blended.” Analysis of 29 untreated pancreatic cancer tumors and 44 untreated melanomas found heavier penetration of attacking immune T cells in melanoma as well as higher levels of cells expressing the inhibitory checkpoint molecules PD-1 and its activating ligand PD-L1, which are successfully targeted by inhibitors to treat melanoma. However, pancreatic tumors had much higher expression of VISTA. About a third of the pancreatic tumors had T cell penetration roughly equal to that found in melanoma, but the T cells were concentrated mainly in the stroma of the tumors, rather than the malignant cells, while they were evenly distributed between cancer cells and stroma in melanoma. To the researchers, that makes sense. “In pancreatic cancer, you have much more stroma than malignant cells in the tumor. Why is that? I think it’s how the tumor is growing,” Sharma said. Allison noted the stromal cells might be keeping the T cells out of the cancer cells. VISTA and macrophages VISTA is predominantly expressed on macrophages – “big eater” immune cells that engulf and digest microbes, cellular debris, and tumor cells as part of immune response. VISTA is known to deactivate T cells. While the researchers found roughly equal density of CD68-positive macrophages in both tumor types, in pancreatic cancer they were again concentrated in the stroma. Macrophages in the pancreatic tumors had much higher expression of VISTA. A separate comparison of three types of pancreatic tumor – untreated primary, treated metastatic and primary tumors pretreated before surgery – found low penetration of T cells in the metastatic tumors and elevated levels of VISTA in the untreated primary and metastatic tumors. Analysis of seven pancreatic samples found that CD68-positive macrophages had distinct PD-L1 and VISTA pathways that inhibit immune response separately. Experiments with T cells taken from tumors of three patients with metastatic pancreatic cancer showed that an active VISTA pathway decreased active T cell responses in the tumor to a greater degree than PD-L1 inhibition. This suggests treatment with PD-1/PD-L1 inhibition might fail because an untreated VISTA pathway still suppresses immune response. Moon Shots Program collaboration Future research will include exploration of combination therapy strategies to increase T cell infiltration, possibly using anti-CTLA-4 checkpoint inhibition, plus a VISTA antibody to target macrophages, Sharma said. Allison and Sharma lead MD Anderson’s immunotherapy platform, which thoroughly characterizes immune response to tumors and to treatment via immune monitoring of tumor samples before, during and after treatment. The platform team worked with MD Anderson’s Pancreatic Cancer Moon Shot™ and Melanoma Moon Shot™, part of the institution’s Moon Shots Program™, a collaborative effort to accelerate the development of scientific discoveries into clinical advances that save patients’ lives. Co-authors with Allison and Sharma are co-first authors Jorge Blando, Ph.D., and Anu Sharma, Ph.D., and Maria Gisela Higa, M.D., Hao Zhao, Ph.D., Luis Vence, Ph.D., Shalini Yadav, Ph.D., Jiseong Kim, and Sreyashi Basu, Ph.D., all of the Immunotherapy Platform; Anirban Maitra, M.B.B.S., Michael Tetzlaff, M.D., Ph.D., Russell Broaddus, M.D., Ph.D., and Huamin Wang, M.D., Ph.D., of the department of Pathology; Jennifer Wargo, M.D., and Matthew Katz, M.D., of Surgical Oncology; Gauri Varadhachary, M.B.B.S., M.D., and Michael Overman, M.D., of GI Medical Oncology; Cassian Yee, M.D., and Chantale Bernatchez, Ph.D., of Melanoma Medical Oncology; Christine Iacobuzio-Donahue, M.D., Ph.D., of Memorial Sloan Kettering Cancer Center, New York; Alejandro Sepulveda, Ph.D., and Michael Sharp of Janssen Research and Development, Pharmaceutical Companies of Johnson & Johnson, Spring House, PA. Kim is a doctoral student in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences. This research was funded by the immunotherapy platform, the Pancreatic Cancer Moon Shot, a grant from the National Cancer Institute (RO1 CA1633793) and the Parker Institute for Cancer Immunotherapy (PICI). Allison, Sharma, Wargo and Yee are members of PICI.
Penn study shows 41 percent increase in opioids for small animals over past 10 years; findings indicate another avenue of potential risk for human access to opioids Newswise — PHILADELPHIA—The increase in opioid prescriptions for people over the past decade may have been paralleled by an increase in opioid prescriptions for pets, according to a study from researchers at the University of Pennsylvania’s Perelman School of Medicine and the School of Veterinary Medicine. The findings, in this first-ever study of veterinary opioid prescriptions, suggest that there is also an increased demand for veterinary opioids, driven by complex procedures performed in veterinary medicine, as well as a heightened awareness of the importance of pain management. Given that opioid prescribing in veterinary medicine is not as heavily regulated as medical prescriptions for humans, it is possible that misused veterinary prescriptions could contribute to the ongoing opioid epidemic. The results are published today in JAMA Network Open. In the study, researchers reviewed all opioid pills and patches dispensed or prescribed for dogs, cats, and other small animals at the University of Pennsylvania’s School of Veterinary Medicine (Penn Vet) from January 2007 through December 2017. The results show that the quantity of these prescriptions, as measured in morphine milligram equivalents (MME), rose by 41 percent during the period annually, while the annual number of visits rose by only about 13 percent. As a veterinary tertiary care facility, Penn Vet’s unique caseload requires particular attention to and treatment of pain in veterinary species, which may account for increased opioid utilization in the study. “As we are seeing the opioid epidemic press on, we are identifying other avenues of possible human consumption and misuse,” said study senior author Jeanmarie Perrone, MD, a professor of Emergency Medicine and the director of Medical Toxicology at Penn Medicine. “Even where the increase in prescribed veterinary opioids is well intended by the veterinarian, it can mean an increased chance of leftover pills being misused later by household members, sold or diverted, or endangering young children through unintentional exposure. The results of this study suggest that by assessing the rate of veterinary opioid prescriptions, we can develop strategies to reduce both human and animal health risks associated with increasing use.” The current opioid crisis in the United States causes tens of thousands of overdose deaths every year—roughly 50,000 in 2017, according to the Centers for Disease Control and Prevention. The crisis began in the late 1990s and was fueled largely by a steep increase in prescriptions for opioid pain relievers. Tightening regulations including prescription drug monitoring programs have helped reduce the number of opioid prescriptions from their peak in 2011. Although prescription opioid overdose deaths are now exceeded by those due to illegally obtained heroin and fentanyl, the former still account for nearly 20,000 fatalities annually. Since opioid prescribing in veterinary medicine is not as comparatively regulated, concerns are raised that opioids prescribed for pets could be misused by humans. The researchers reviewed pharmacy records at the Penn Vet’s Ryan Hospital during the 10-year study window, and analyzed trends for the four opioids prescribed or dispensed to animal patients — tramadol, hydrocodone, and codeine tablets, and fentanyl patches. The animals in the study included dogs (73.0 percent), cats (22.5 percent), and assorted others including rabbits, snakes, and birds (4.5 percent). “We found that the increased quantity of opioids prescribed by our hospital was not due to increased patient volume alone. It is likely that our goal of ensuring our patients are pain-free post-operatively, particularly for those requiring complex and invasive procedures, has driven our increased prescribing practices during this period,” said lead author Dana Clarke, VMD, an assistant professor of Interventional Radiology at the University of Pennsylvania’s School of Veterinary Medicine “At the national level, we don’t know the potential or extent of prescription diversion from animals to humans, and what impact this could have on the human opioid crisis.” Anecdotes about veterinarian-prescribed opioids being used by people have already prompted some states to add restrictions to veterinary prescribing. In Pennsylvania, state legislators are working with the Pennsylvania Veterinary Medical Association (PVMA) to determine the most effective course of action for opioid dispensing by the state’s practicing veterinarians. Two states, Maine and Colorado, now require background checks on animal owners’ opioid prescription histories before a veterinarian can write an opioid prescription. Alaska, Connecticut, and Virginia now limit the amount of opioids any one veterinarian can prescribe to a single patient/animal. Twenty states now require veterinarians to report their opioid prescriptions to a central database, just as medical doctors do. At Penn Vet, efforts currently in practice to reduce opioid prescribing include preference of local anesthetics for post-operative pain, pain scores to guide administration of opioids, and monitoring of patients requiring long-term opioid use, such as dogs with chronic coughing requiring hydrocodone. The authors say it is important that the potential problem of diverted veterinary opioids be studied further to determine its scale, and should be addressed by extending the opioid stewardship measures that already affect medical physicians to veterinary doctors, in all states. Co-authors on the study include Kenneth Drobatz, DVM, of Penn Vet, Chloe Korzekwa, of Trinity College in Dublin, and Lewis S. Nelson, MD, of Rutgers New Jersey Medical School.
Newswise — A summer undergraduate research fellowship has helped South Dakota State University sophomore Caroline Kincade figure out her career path. Through the Future Agriculture and Science Taskforce Research and Extension Experiences for Undergraduates (FAST REEU) fellowship program, Kincade worked on a project to understand how cells gain resistance to antibiotics under the supervision of Assistant Professor Nicholas Butzin. She was among the first group of students to participate in the U.S. Department of Agriculture-funded program, which provided qualifying students a 10-week summer laboratory experience at SDSU. In summer 2019, each student will do an industry internship. Associate Professor of Biology and Microbiology Madhav Nepal, who coordinates the program, said “We want to get our students excited about science and agriculture.” Students interested in FAST REEU fellowship can find more information at https://www.sdstate.edu/biology-and-microbiology/fast-reeu-fellowships. Applications are due March 15. “FAST made me realize I need to figure out what I am doing after graduation,” said Kincade, a microbiology major with a chemistry minor and a member of the Van D. and Barbara B. Fishback Honors College. The Otsego, Minnesota, native transferred to SDSU in fall 2017 after earning an associate degree in veterinary technology at Ridgewater College in Minnesota. “I am very impressed by Caroline,” said Butzin, who is faculty researcher in the Department of Biology and Microbiology in the College of Natural Sciences. He also does research through the South Dakota Agricultural Experiment Station. “She’s been a great help in the lab this summer,” added doctoral student Heather Deter, who is studying how changes in the genome allow cells, known as persisters, to gain resistance to antibiotics. “Antibiotic resistance happens because of a change in DNA.” “Persister cells hide out but also get DNA from other organisms that can give them resistance,” Butzin said. “They’re like sleeper cells—they wait until the antibiotics are gone and start growing again.” To study this phenomenon, the researchers use bacteria called Mycoplasma mycoides, which have a small genome. “Life is generally complex, so we want to start with something simple,” Butzin explained. The researchers begin with cells that cannot survive exposure to antibiotics and “add synthetic circuits that will allow us to test what actually causes persistence and how.” As part of the research team, Kincade helped figure out how to grow the cells, including what type of media and buffer to use. “Doing research taught me a lot of patience,” she said. E coli cells, for instance, grow in 24 hours. “These minimal genome cells take a lot longer to grow. “In a lab class, we have a procedure. If the experiment does not work, we go to the next one,” Kincade explained. “In research, we have to figure out why it did not work and redo it until it works” Once cells are treated, the researchers count the persister cells on each plate. Kincade scanned the plates and then used a computer program Deter created to count the persister cells. “This produces highly accurate quantitative data to understand what’s going on,” said Butzin, whose goal has been to challenge Kincade and thus increase her research skills. “I’ve learned a lot about techniques, plus the computer stuff,” Kincade said. As she contemplated her career path, Kincade said, “Always in the back of my head I kept thinking that what I am most passionate about is animal anatomy and parasitology.” Though she has decided to combine microbiology with veterinary medicine, Kincade will continue to use the skills she learned last summer. “The experience set me up for success,” she added.
Researchers have found that neighbour-cells can take over functions of damaged or missing insulin-producing cells; the discovery may lead to new treatments for diabetes Newswise — Diabetes is caused by damaged or non-existing insulin cells inability to produce insulin, a hormone that is necessary in regulating blood sugar levels. Many diabetes patients take insulin supplements to regulate these levels. In collaboration with other international researchers, researchers at the University of Bergen have, discovered that glucagon.producing cells in the pancreas, can change identity and adapt so that they do the job for their neighbouring damaged or missing insulin cells. "We are possibly facing the start of a totally new form of treatment for diabetes, where the body can produce its own insulin, with some start-up help," says Researcher Luiza Ghila at the Raeder Research Lab, Department of Clinical Science, University of Bergen (UiB). Cells can change identity The researchers discovered that only about 2 per cent the neighbouring cells in the pancreas could change identity. However, event that amount makes the researchers are optimistic about potential new treatment approaches. For the first time in history, researchers were able to describe the mechanisms behind the process of cell identity. It turns out that this is not at passive process, but is a result of signals from the surrounding cells. In the study, researchers were able to increase the number of insulin producing cells to 5 per cent, by using a drug that influenced the inter-cell signalling process. Thus far, the results have only been shown in animal models. "If we gain more knowledge about the mechanisms behind this cell flexibility, then we could possibly be able to control the process and change more cells' identities so that more insulin can be produced, " Ghila explains. Possible new treatment against cell death According to the researchers, the new discoveries is not only good news for diabetes treatment. "The cells´ ability to change identity and function, may be a decisive discovery in treating other diseases caused by cell death, such as Alzheimer´s disease and cellular damage due to heart attacks", says Luiza Ghila. Facts: Pancreas There are three different types of cells in the pancreas: alpha-cells, beta-cells and delta-cells. These produce different kinds of hormones for blood sugar regulation. The cells make clusters. Alpha-cells produce glucagon, which increases the blood sugar levels. Beta-cells produce insulin, which decreases glucagon levels. Delta-cells produce somatostatin, which controls the regulation of the Alpha and Beta Cells. Persons with diabetes have a damaged beta-cell function, and therefore have constant high blood sugar levels.
Newswise — Light pollution is on everyone’s minds in Reno, Nevada, a city famous for its bright lights and nightlife. Nighttime light pollution is a growing concern for cities worldwide. Artificial light at night has been found to cause serious health effects including disrupting our sleep-wake cycle –our circadian rhythm. Our local wildlife and their circadian rhythms are affected by light pollution just like humans. Valentina Alaasam, a graduate student in Dr. Jenny Ouyang’s lab at University of Nevada, Reno, is studying a small bird, the zebra finch, to better understand how cities affect the biology of urban wildlife. Their findings suggest that light pollution changes everything from the bird’s behavior to its underlying physiology. In the most scientifically precise meaning of the term, the birds are stressed out. Their results of their research will be presented at the annual meeting of the Society for Integrative and Comparative Biology in Tampa, FL. Take a step back from birds for a moment and imaging yourself in the lighting isle of your local hardware store. There is a plethora of lights of different sizes, brightness, and “temperatures,” or whiteness to choose from. Because of their lower energy requirements and longevity, LED bulbs are filling more shelf space than they once did. With such a selection there is much to learn about the ways different lighting options affect wildlife. Alaasam’s study found that different temperatures of commercially available LEDs affect wildlife differently – cooler temperature lights, those that best replicate natural light, are more stressful to birds. Nighttime exposure to cooler temperature LEDs caused birds to have increased levels of nighttime activity and trigged their physiological stress response, raising levels stress hormones in their blood. Precise regulation of stress hormones is critical for an animal’s survival. When a bird is captured, its stress hormones rapidly increase to give them energy to attempt escape – the famous fight-or-flight response. Stress hormones normally follow a circadian rhythm and only peak during active periods of the day. Thus, excess stress hormones in birds indicate that their normal schedule is disrupted and may affect their metabolism and behavior. The long-term physiological and behavioral effects of these elevated stress hormones on wildlife is not fully understood. However, in humans elevated stress hormones can challenge fundamental physiological process such as blood sugar regulation, inflammation, and fatigue. Analyzing the effects of light on the stress response of urban birds required an interdisciplinary experiment that brought together members of Dr. Ouyang’s lab, an electrical engineer to design and build new instruments, a neuroscientist who played a role in analyzing bird behavior, and a team of students that helped care for the birds. Such diversity in experiences led to unexpected challenges throughout the experiments. The birds behavior was to be recorded using specially designed perches. However, the researchers quickly realized that the bird’s weight, – about as much as a pencil– was not enough to activate the perch correctly. They had to adjust each perch to work for its intended bird’s weight. Relying on new technology is never an easy task. Alaasam remarked that there were several sleepless nights troubleshooting glitches, “I always joke about how my circadian rhythm and stress hormones were off the charts doing this experiment on circadian rhythms and stress on birds.” “Understanding how populations can acclimate to urban areas and whether or not that is genetically controlled – who can acclimate the best and who can’t – is a really interesting question.” Alaasam notes. Her findings could improve out understanding of the way wildlife are challenged in today’s cities. Over time, research like Alaasam’s could inform the way environmentally conscious urban planners light their cities. When talking to the citizens of Reno about her research, Alaasam described the potential the benefit of changing out cooler temperature LED’s in outdoor lights to warmer LED’s Alaasam also wants the public to know that “we might be experiencing the same stressors birds are experiencing in a less obvious way. Bird behavior has obvious changes, humans are complicated. The more we ameliorate stressors for our wildlife, the better our conservation and policies will be in the long run.”
Newswise — ROCHESTER, Minn. — The percentage of women who are screened for cervical cancer may be far lower than national data suggests, according to a Mayo Clinic study recently published in the Journal of Women’s Health. Less than two-thirds of women ages 30 to 65 were up-to-date with cervical cancer screenings in 2016. The percentage is even lower for women ages 21 to 29, with just over half current on screenings. Those figures are well below the 81 percent screening compliance rate self-reported in the 2015 National Health Interview Survey. “These cervical cancer rates are unacceptably low,” says Mayo Clinic family medicine specialist Kathy MacLaughlin, M.D., the study’s lead author. “Routine screening every three years with a Pap test or every five years with a Pap-HPV co-test ensures precancerous changes are caught early and may be followed more closely or treated.” In addition to lower-than-expected screening rates, Mayo Clinic researchers also found racial inequities in terms of who is getting screened. “African-American women were 50 percent less likely to be up-to-date on cervical cancer screening than white woman in 2016,” says Dr. MacLaughlin. “Asian women were nearly 30 percent less likely than white women to be current on screening. These racial disparities are especially concerning.” Mayo Clinic researchers reviewed medical records using the Rochester Epidemiology Project database to determine cervical cancer screening rates for more than 47,000 women living in Olmsted County, Minn., from 2005 to 2016. An estimated 13,240 new cases of invasive cervical cancer were diagnosed in the U.S. in 2018, according to the American Cancer Society. Another 4,170 women died from cervical cancer last year. January is Cervical Health Awareness Month. Dr. MacLaughlin says these study results should prompt health care providers to start considering new ways of reaching out to patients to help ensure they get screened. Ideas could include setting up Pap clinics with evening and Saturday hours, or offering cervical cancer screenings at urgent care clinics. For women who qualify for the newest screening option of primary HPV screening, clinics could explore the option of giving patients at-home testing kits. “We, as clinicians, must start thinking outside the box on how best to reach these women and ensure they are receiving these effective and potentially life-saving screening tests,” she says. Cervical cancer death rates have dropped dramatically in recent decades thanks to the development of the Pap test in the 1950s. That test involves collecting cells from a woman’s cervix and examining them under a microscope to look for precancerous and cancerous cells. A second type of cervical cancer screening — called the HPV test — detects the presence of high-risk HPV, which can lead to precancerous changes and cervical cancer. In 2012, national cervical cancer screening guidelines were updated to recommend Pap testing every three years for women ages 21 to 65 or Pap-HPV co-testing every five years for women ages 30 to 65. The study results show high rates of adoption by Olmsted County health providers of the 2012 guidelines in regards to appropriate use of co-testing and in appropriately not screening women under 21 or over 65. A limitation of this study is that Olmsted County is less ethnically and racially diverse than the U.S. population, but the county’s demographic makeup is reflective of the Upper Midwest. The study’s findings related to racial disparities in screening are consistent with several other studies from across the country. Another limitation is the potential for over counting young women as not screened who are insured by their parents and have an Olmsted County address but may have gone to healthcare providers outside of Olmsted County for screening. The research was supported by the Rochester Epidemiology Project, Mayo Clinic, the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, the National Institute on Aging and the National Institutes of Health. Co-authors of the study were Robert Jacobson, M.D., Carmen Radecki Breitkopf, Ph.D., Patrick Wilson, Debra Jacobson, Chun Fan, Jennifer St. Sauver, Ph.D., and Lila Rutten, Ph.D.
HSS RECEIVES HALF MILLION DOLLAR GRANT TO INVESTIGATE HOW TO IMPROVE HEALTH CARE SYSTEM FOR CHRONICALLY ILL ADOLESCENTS
Newswise — An indomitable spirit. An inquisitive mind. And a most compassionate heart. Bobby Menges possessed intelligence and maturity far beyond his years and left a lasting impression on almost everyone he met. Friendly and outgoing, he was the kind of kid who went over and sat with the shy student eating alone at lunchtime. A diagnosis of cancer, originally at age 5, and other health problems didn’t stop him from living life to the fullest. Despite the treatments, and despite multiple surgeries, a profound capacity for empathy compelled him to look outside of himself, and he sought to help others, according to Elizabeth Menges, Bobby’s mother. He devoted much of his life to community service and fundraising, hosting charity events and blood drives. Although Bobby passed away last year at age 19, his legacy lives on in a foundation that his family created in his memory. The “I’m Not Done Yet” Foundation, based in Garden City, helps adolescent patients with serious, long-term, and chronic illnesses transition from pediatrics to adulthood. As part of its mission, the foundation has pledged a five-year, $500,000 research grant to Hospital for Special Surgery (HSS) in New York City to establish best practices to meet the changing needs of young patients as they become teenagers and young adults in the health care system. At HSS, a specialty hospital dedicated to orthopedics, rheumatology and rehabilitation, doctors often follow patients from a very young age through young adulthood. The patient population includes babies born with musculoskeletal conditions, such as cerebral palsy, and young people with chronic rheumatologic diseases who are treated from the time they are children. Bobby recognized the need for health care providers to be mindful of the evolving psychosocial needs of young people with any chronic illness, not only cancer, according to Peter Menges, Bobby’s father. “HSS is a world class organization with the right resources, the right experience and the right expertise to undertake a comprehensive research initiative to really hone in on what this patient population needs, whether it’s physical space, specific services, a certain kind of care, or emotional support,” Peter Menges said. “Although HSS will be the catalyst and epicenter of the research, our goal is to see the findings and best practices adopted throughout the U.S., and even worldwide.” The HSS grant, “The Bobby Menges ‘I’m Not Done Yet’ Initiative,” will address the psychosocial challenges young patients face as they become adolescents and teenagers in the health care system. The foundation’s website explains: “Imagine you're a 19-year-old cancer patient. You've been in and out of treatment since the age of 5, and because you were diagnosed with a pediatric cancer, you continue to be treated as a pediatric patient. The supports for young children were just what you needed as a child, but now, as an adolescent, you have different needs: peace and quiet, a study room, a place to connect to Wifi... But often those services do not exist.” Dr. S. Robert Rozbruch will lead the research project at HSS. Chief of the hospital’s Limb Lengthening and Complex Reconstruction Service, Dr. Rozbruch met Bobby after a skiing accident and subsequent fracture, treatment at another hospital, and a complication left him with one leg that was shorter than the other. Without the proper and highly specialized care, Bobby’s leg could have been five inches shorter than his unaffected leg. After several surgeries by Dr. Rozbruch and successful treatment over more than 10 years, Bobby’s leg was straight and the proper length. During that time, Dr. Rozbruch worked closely with Bobby’s oncologists, and his cancer was in remission. Dr. Rozbruch developed a close relationship with Bobby and his family. “Bobby was a very special person, even when he was a child,” Dr. Rozbruch says. “He had a sparkle in his eyes. He had a positive outlook. He had a kind of wisdom and an inner peace that was very dramatic.” “By the time patients turn 15, their needs start to change, and Bobby began to notice the void in health care as he got older,” explained Elizabeth Menges. “He realized that some of his doctors didn’t understand some of the issues he faced. He wondered why doctors still addressed me, but not him when they spoke. Dr. Rozbruch was among those Bobby felt understood him. He said Dr. Rozbruch had a knack for that.” Dr. Rozbruch, who treats many patients starting at a young age, has been interested in the developmental, emotional and psychological factors involved in caring for them as they get older. “The research initiative, which will include a psychologist, aims to evaluate the changing psychosocial and emotional needs of young patients in the health care setting and determine the best way to meet those needs. Surveys and questionnaires will be designed for past and current patients and their families,” Dr. Rozbruch says. “We intend to publish and share our research findings with the broad medical community well beyond orthopedics and HSS.” Carl Menges, Bobby’s great uncle, a life trustee of HSS and a significant financial supporter of the initiative, says the research grant is a way to honor Bobby’s memory. “The purpose of the initiative is to honor his deep concern for young people like himself facing complex conditions throughout childhood and young adulthood,” he said. “Bobby’s courage and spirit has been an inspiration to many, and this is a continuation of the work that he personally initiated and was so passionate about.” About HSS | Hospital for Special Surgery HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the ninth consecutive year) and No. 3 in rheumatology by U.S.News & World Report (2018-2019). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. The global standard total knee replacement was developed at HSS in 1969. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients and performed more than 32,000 surgical procedures. People from all 50 U.S. states and 80 countries travelled to receive care at HSS. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Global Innovation Institute was formed in 2016 to realize the potential of new drugs, therapeutics and devices. The culture of innovation is accelerating at HSS as 130 new idea submissions were made to the Global Innovation Institute in 2017 (almost 3x the submissions in 2015). The HSS Education Institute is the world’s leading provider of education on the topic of musculoskeletal health, with its online learning platform offering more than 600 courses to more than 21,000 medical professional members worldwide. Through HSS Global Ventures, the institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.About Hospital for Special Surgery
Newswise — WINSTON-SALEM, NC – Ever wonder why some people seem to feel less pain than others? A study conducted at Wake Forest School of Medicine may have found one of the answers – mindfulness. “Mindfulness is related to being aware of the present moment without too much emotional reaction or judgment,” said the study’s lead author, Fadel Zeidan, Ph.D., assistant professor of neurobiology and anatomy at the medical school, part of Wake Forest Baptist Medical Center. “We now know that some people are more mindful than others, and those people seemingly feel less pain.” The study is an article in press, published ahead-of-print in the journal PAIN. The researchers analyzed data obtained from a study published in 2015 that compared mindfulness meditation to placebo analgesia. In this follow-up study, Zeidan sought to determine if dispositional mindfulness, an individual’s innate or natural level of mindfulness, was associated with lower pain sensitivity, and to identify what brain mechanisms were involved. In the study, 76 healthy volunteers who had never meditated first completed the Freiburg Mindfulness Inventory, a reliable clinical measurement of mindfulness, to determine their baseline levels. Then, while undergoing functional magnetic resonance imaging, they were administered painful heat stimulation (120°F). Whole brain analyses revealed that higher dispositional mindfulness during painful heat was associated with greater deactivation of a brain region called the posterior cingulate cortex, a central neural node of the default mode network. Further, in those that reported higher pain, there was greater activation of this critically important brain region. The default mode network extends from the posterior cingulate cortex to the medial prefrontal cortex of the brain. These two brain regions continuously feed information back and forth. This network is associated with processing feelings of self and mind wandering, Zeidan said. “As soon as you start performing a task, the connection between these two brain regions in the default mode network disengages and the brain allocates information and processes to other neural areas,” he said. “Default mode deactivates whenever you are performing any kind of task, such as reading or writing. Default mode network is reactivated whenever the individual stops performing a task and reverts to self-related thoughts, feelings and emotions. The results from our study showed that mindful individuals are seemingly less caught up in the experience of pain, which was associated with lower pain reports.” The study provided novel neurobiological information that showed people with higher mindfulness ratings had less activation in the central nodes (posterior cingulate cortex) of the default network and experienced less pain. Those with lower mindfulness ratings had greater activation of this part of the brain and also felt more pain, Zeidan said. “Now we have some new ammunition to target this brain region in the development of effective pain therapies. Importantly this work shows that we should consider one’s level of mindfulness when calculating why and how one feels less or more pain,” Zeidan said. “Based on our earlier research, we know we can increase mindfulness through relatively short periods of mindfulness meditation training, so this may prove to be an effective way to provide pain relief for the millions of people suffering from chronic pain.” This work was supported by the National Center for Complementary and Integrative Health, R21-AT007247, F32-AT006949, K99/R00-AT008238 and F30-AT009165; the National Institute of Neurological Disorders and Stroke, R01-NS239426; the Mind and Life Institute Francisco J. Varela Award and the Wake Forest Center for Integrative Medicine. Co-authors are Tim Salomons, Ph.D., of the University of Reading, United Kingdom; Nichole M. Emerson, Ph.D., Adrienne Adler-Neal, Ph.D., Youngkyoo Jung, Ph.D., and Suzan Farris, M.S., of Wake Forest School of Medicine; and Robert Coghill, Ph.D., of Cincinnati Children’s Hospital Medical Center.
Newswise — NEW YORK (December 31, 2018) — With people worldwide getting their New Year’s resolutions ready, the Alzheimer’s Foundation of America (AFA) is encouraging individuals to take 10 steps to promote good brain health and healthy aging in 2019. “Taking care of your brain is a New Year’s resolution that everyone should make and, more importantly, keep,” said Charles J. Fuschillo, Jr., AFA’s President and CEO. “Just as we focus on improving other parts of our bodies, we need to look after our minds too. There are steps and lifestyle changes which we encourage individuals to take to support their brain health and wellness in 2019 and beyond.” “The best way to make 2019 a healthy and happy new year is by being proactive about your own well-being,” said Bert E. Brodsky, AFA’s Founder and Board Chairman. “The brain is one of the most vital parts of the human body; it’s so important to keep it in good shape. Start the New Year off ‘well’ by prioritizing your cognitive health.” AFA urges people to take the following 10 steps for healthy aging: Eat Well - Adopt a low-fat diet high on fruits and veggies, like strawberries, blueberries and broccoli. Take daily vitamins. Limit intake of red meats, fried and processed foods, salt and sugar. In general, foods that are “heart heathy” are also “brain healthy.” Stay Active – Physical activity increases blood flow to the brain and can also help improve mood and overall wellbeing. Brisk walking benefits brain health, while aerobics can boost your heart rate, and weight training builds strength and flexibility. Learn New Things – Challenge your brain by starting a new hobby like playing tennis, learning to speak a foreign language, trying a cooking class, or something you haven’t done before. Even something as simple as brushing your teeth with your non-dominant hand stimulates the brain by forcing it to think outside of its normal routine. Get Enough Sleep – Getting a consistent sleep every night is key; at least seven to nine hours is ideal. Having a good sleep environment is also helpful. Insomnia or sleep apnea can have serious physical effects and negatively affect memory and thinking. Mind Your Meds - Medication can affect everyone differently, especially as you age. When getting a new medication or something you haven’t taken in a while (whether over the counter or prescription), talk to your doctor or local pharmacist. Stop Smoking and Limit Alcohol - Smoking can increase the risk of serious illnesses, while too much alcohol can affect memory, impair judgment and present safety issues. Stay Connected – Social interaction and maintaining an active social life are very important for brain health, cognitive stimulation and mood. Invite friends and family over for a meal, board games, or just to hang out. Engaging in your community and participating in group activities is also beneficial. Know Your Blood Pressure – Blood pressure can impact your cognitive functioning. Visit your physician regularly to check your blood pressure and make sure it is in normal range. See Your Doctor - Maintain checkups. Health screenings are key to managing chronic illnesses, such as diabetes, cardiovascular disease, and obesity, all of which can impact brain health. Speak with your physician about any concerns or questions you have about your health. Get a Memory Screening - Our brains need regular checkups, just as other parts of our bodies do. A memory screening is a quick, easy, non-invasive exam for our brains. Talk to your doctor about getting a screening as part of your annual wellness exam or call AFA at 866-232-8484. Additional information about brain health and wellness and memory screenings can be found on AFA’s website, www.alzfdn.org or by calling AFA’s Helpline at 866-232-8484. The helpline is open from 9 am to 9 pm (ET) on weekdays and 9 am to 1 pm (ET) on weekends.
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.