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Integrating Mental Health Services in Pediatric Practices Feasible, Effective, Pitt Finds

PITTSBURGH, March 24, 2014 – Brief behavioral and mental health programs for children can be effectively provided within pediatric practices as an alternative to being referred to a community specialist, University of Pittsburgh Schools of the Health Sciences researchers found in a National Institutes of Health-funded randomized trial.

Behavioral health treatment provided in the pediatrician’s office resulted in improved access to care, greater participation by both the child and their caregiver in treatment programs, and higher rates of treatment completion, without burdening the pediatric practice, researchers report in the April issue of the journal Pediatrics.

“Treating both physical and behavioral health in the office of the child’s pediatrician is an achievable goal that provides many benefits to the child, caregiver and pediatrician” said lead author David Kolko, Ph.D., professor of psychiatry, psychology, pediatrics, and clinical and translational science in Pitt’s School of Medicine. “When the behavioral health treatment was provided in the pediatrician’s office, participants were more than six times as likely to complete the program, as they were when it was provided at a specialty care clinic outside the pediatrician’s office.”

Dr. Kolko and his colleagues recruited more than 300 children and their caregivers at eight community pediatric practices affiliated with Children’s Hospital of Pittsburgh of UPMC who had been referred for treatment of behavioral problems, though many also had attention-deficit/hyperactivity disorder (ADHD) or anxiety. This study is the third one completed by Services for Kids in Primary-Care (SKIP), a program that integrates behavioral health services into primary pediatric and family medicine practices (more information available at www.skipproject.org).

In this trial, half the children received “doctor office collaborative care,” where a trained behavioral health clinician, known as a care manager, collaborated with the child’s pediatrician to deliver mental health services in the pediatrician’s office. The other half received “enhanced usual care,” where the patients received educational materials and were referred to a local mental health specialist outside the pediatrician’s office who accepted the child’s health insurance.

The participants averaged 8 years old and two-thirds were boys. Most had a primary diagnosis of ADHD, followed by disruptive behavior disorder and anxiety disorder. Only 10 percent previously had received ADHD medication.

In the program at the pediatrician’s office, the child and their caregiver participated in six to 12 individual or family sessions within six months where the mental health clinician worked on individualized goals to address the behavioral health issue and reviewed educational materials to help achieve those goals. The clinician communicated with the pediatrician in regular meetings and through progress notes.

In both the in-office and outside specialist programs, the pediatrician was updated on the patient’s care and could prescribe medication for the child when necessary.

Of the participants assigned to the care manager at the pediatrician’s office, 99.4 percent began treatment programs and 76.6 percent completed them. Of those assigned to a specialist outside the office, 54.2 percent began treatment and 11.6 percent completed it.

The program in the pediatrician’s office also was associated with higher rates of improvement in behavioral and hyperactivity problems, lowered parental stress, better treatment response and consumer satisfaction.

Beyond the child and their caregiver, pediatricians whose offices received the in-office program reported greater efficacy and more confidence in their skills to treat ADHD, compared with the outside specialist program.

“In fact, the participating pediatric practices in this clinical trial later hired their own mental health clinicians to continue delivering on-site services, after the trial had ended,” said Dr. Kolko. “Still more research is needed to understand how pediatric practices adapt clinical and financial strategies to make an in-office behavioral health provider a sustainable resource. Perhaps pediatricians who observe the program in operation may be willing to find a way to support these resources and make that service work.”

Additional co-authors on this study are Stephen Wisniewski, Ph.D., Pitt Graduate School of Public Health; Jonathan Hart, M.S., Western Psychiatric Institute and Clinic of UPMC; Dara Sakolsky, M.D., Pitt School of Medicine; John Campo, M.D., Ohio State University; and Amy Kilbourne, Ph.D., University of Michigan.

This research was supported by NIH’s National Institute of Mental Health grant no. 063272.

Pitt-Led Study Shows Lifestyle Interventions can Prevent Major Depression in Older Black and White Adults with Mild Symptoms

PITTSBURGH, March 20, 2014 – Discussions with a dietary coach to learn about healthy eating were as effective as meeting with a counselor for problem-solving or “talk” therapy in preventing major depression among older black and white adults with mild symptoms of the mood disorder, according to researchers at the University of Pittsburgh and the University of Maryland. Their findings were published online recently in Psychiatric Services.

Depression is common and treatments often don’t completely resolve the disability that attends the illness, said senior author Charles F. Reynolds III, M.D., UPMC Endowed Professor of Geriatric Psychiatry, University of Pittsburgh School of Medicine. Sadness, fatigue and disinterest in activities that used to bring pleasure can leave patients isolated and unable to care for themselves.

“That’s why we’re very interested in finding ways to prevent the disease in those we know are particularly vulnerable,” he said. “Avoiding episodes of major depression can help people stay happy and engaged in their communities, as well as reduce health care costs.”

The team assessed whether problem-solving therapy for primary care (PST-PC), a scientifically proven seven-step approach delivered by non-mental-health professionals to help patients resolve difficulties and thus improve coping skills and confidence, could prevent elderly adults who have mild symptoms of depression from developing full-blown disease. Instead of comparing the PST-PC participants to those who received “usual care,” which would most likely mean receiving no intervention, the team took the novel approach of comparing the PST-PC group to participants who underwent a program of dietary coaching at a similar visit interval for the same number of hours.

Researchers used innovative strategies to recruit and retain African-American study participants, building upon a culturally tailored approach developed by Sandra Quinn, Ph.D., and Stephen Thomas, Ph.D., co-investigators from the University of Maryland Center for Health Equity.

“Because racial minorities are at greater risk for depression, in part due to socioeconomic disadvantages, lower educational attainment and a greater likelihood of other medical problems, we established a foundation of trust working through churches and community-based organizations in black communities,” said Dr. Quinn. Of the 244 participants, 90, or more than a third, were African-American.

“Previous studies we and others have done indicate about 25 percent of people in later life who are mildly depressed become seriously depressed in the next one to two years,” Dr. Reynolds said. The researchers found about 9 percent of the people in each intervention arm went on to experience an episode of major depression, and they all had a similar reduction in depressive symptoms over the two-year study period. Also, both approaches were equally successful among black and white participants.

“This project tells us that interventions in which people actively engage in managing their own life problems, such as financial or health issues, tend to have a positive effect on well-being and a protective effect against the onset of depression.”

“We suspect we had a higher than usual proportion of black participants because community leaders championed the project, no medication was prescribed, and treatment could be delivered at home or at other non-clinical settings,” said Dr. Thomas. “Lifestyle interventions, such as dietary coaching, may be more culturally appropriate and acceptable in racial-ethnic minority communities.”

In a new project, the researchers will examine whether PST-PC can be effectively administered by lay health counselors in low- and middle-income countries such as India.

In addition Drs. Reynolds, Quinn and Thomas, co-authors of the paper include Jennifer Q. Morse, Ph.D., Steven Albert, Ph.D., Mary Amanda Dew, Ph.D., Amy Begley, M.A., Meryl A. Butters, M.D., Jordan F. Karp, M.D., Ariel Gildengers, M.D., Jacqueline A. Stack, M.S.N., John Kasckow, M.D., Ph.D., and Mark D. Miller, M.D., all of the University of Pittsburgh.

The study was funded by the National Institute of Mental Health, the National Institute on Minority Health and Health Disparities and the National Institutes of Health grants MD000207, MH090333, UL1RR024153, and UL1TR000005; the University of Pittsburgh Medical Center Endowment in Geriatric Psychiatry; the Commonwealth of Pennsylvania.

Stem Cells from Muscle Can Repair Nerve Damage After Injury, Pitt Researchers Show

PITTSBURGH, March 18, 2014 – Stem cells derived from human muscle tissue were able to repair nerve damage and restore function in an animal model of sciatic nerve injury, according to researchers at the University of Pittsburgh School of Medicine. The findings, published online today in the Journal of Clinical Investigation, suggest that cell therapy of certain nerve diseases, such as multiple sclerosis, might one day be feasible.

To date, treatments for damage to peripheral nerves, which are the nerves outside the brain and spinal cord, have not been very successful, often leaving patients with impaired muscle control and sensation, pain and decreased function, said senior author Johnny Huard, Ph.D., professor of orthopaedic surgery, and Henry J. Mankin Chair in Orthopaedic Surgery Research, Pitt School of Medicine, and deputy director for cellular therapy, McGowan Institute for Regenerative Medicine.

“This study indicates that placing adult, human muscle-derived stem cells at the site of peripheral nerve injury can help heal the lesion,” Dr. Huard said. “The stem cells were able to make non-neuronal support cells to promote regeneration of the damaged nerve fiber.”

The researchers, led by Dr. Huard and Mitra Lavasani, Ph.D., first author and assistant professor of orthopaedic surgery, Pitt School of Medicine, cultured human muscle-derived stem/progenitor cells in a growth medium suitable for nerve cells. They found that, with prompting from specific nerve-growth factors, the stem cells could differentiate into neurons and glial support cells, including Schwann cells that form the myelin sheath around the axons of neurons to improve conduction of nerve impulses.

In mouse studies, the researchers injected human muscle-derived stem/progenitor cells into a quarter-inch defect they surgically created in the right sciatic nerve, which controls right leg movement. Six weeks later, the nerve had fully regenerated in stem-cell treated mice, while the untreated group had limited nerve regrowth and functionality. Twelve weeks later, treated mice were able to keep their treated and untreated legs balanced at the same level while being held vertically by their tails. When the treated mice ran through a special maze, analyses of their paw prints showed eventual restoration of gait. Treated and untreated mice experienced muscle atrophy, or loss, after nerve injury, but only the stem cell-treated animals had regained normal muscle mass by 72 weeks post-surgery.

“Even 12 weeks after the injury, the regenerated sciatic nerve looked and behaved like a normal nerve,” Dr. Lavasani said. “This approach has great potential for not only acute nerve injury, but also conditions of chronic damage, such as diabetic neuropathy and multiple sclerosis.”

Drs. Huard and Lavasani and the team are now trying to understand how the human muscle-derived stem/progenitor cells triggered injury repair, as well as developing delivery systems, such as gels, that could hold the cells in place at larger injury sites.

Co-authors of the paper include Seth D. Thompson, B.S., Jonathan B. Pollett, Ph.D., Arvydas Usas, M.D., Aiping Lu, M.D., Donna B. Stolz, Ph.D., Katherine A. Clark, B.S., Bin Sun, Ph.D., and Bruno Péault, Ph.D., all of the University of Pittsburgh.

The project was funded by National Institutes of Health grants AR049684 and NS081724-01, the U.S. Department of Defense, the Henry J. Mankin Endowed Chair for Orthopaedic Research at the University of Pittsburgh, the William F. and Jean W. Donaldson Chair at Children’s Hospital of Pittsburgh of UPMC, the Hirtzel Foundation, and the Pittsburgh Claude Pepper Older Americans Independence Center.

Children’s Names New Chief of Pediatric Endocrinology

PITTSBURGH, March 18, 2014Children’s Hospital of Pittsburgh of UPMC has named Radhika Muzumdar, MD, chief of the Division of Pediatric Endocrinology, Diabetes and Metabolism. Dr. Muzumdar also has an appointment within the University of Pittsburgh School of Medicine as associate professor of Pediatrics and Cell Biology. She comes to Pittsburgh from Albert Einstein College of Medicine and The Children’s Hospital at Montefiore in Bronx, N.Y.

Dr. Muzumdar brings expertise in basic research in endocrinology to Children’s, and as the principle investigator for seminal research on the role of insulin-like growth factors and novel peptides that regulate glucose homeostasis during aging, she is supported by National Institutes of Health (NIH) R-01 funding.

Dr. Muzumdar, a member of the Society for Pediatric Research, has been elected to various leadership roles in national and international subspecialty societies. She also has been recognized for her teaching abilities and mentoring in clinical medicine and biomedical research, and will lead Children’s NIH T32 fellowship training grant.

Older Age at Onset of Type 1 Diabetes Associated with Lower Brain Connectivity Later in Life

SAN FRANCISCO, March 14, 2014 – Children and adolescents older than age 8 at the onset of type 1 diabetes had weaker brain connectivity when tested later in life relative to those who had earlier ages of diagnosis, University of Pittsburgh Schools of the Health Sciences researchers discovered.

The findings, presented today at the American Psychosomatic Society’s annual meeting, were made by analyzing the brain scans of 44 middle-age adults diagnosed with type 1 diabetes as children.

“Adolescence is a time when the brain matures and makes connections in networks responsible for different functions,” said John Ryan, Ph.D., assistant professor of psychiatry at Pitt. “Further study is needed to determine if and how the onset of type 1 diabetes shortly before or during puberty affects brain function and how better control of the disease at that important time could yield changes in brain function later in life.”

Half the study participants had onset of type 1 diabetes before age 8 and were matched with participants of the same sex and age who were diagnosed after age 8, but before age 17. All were enrolled in the Pittsburgh Epidemiology of Diabetes Complications Study, an ongoing investigation led by Pitt’s Graduate School of Public Health to document long-term complications of type 1 diabetes among patients at Children’s Hospital of Pittsburgh of UPMC between 1950 and 1980.

Type 1 diabetes is usually diagnosed in children and young adults and happens when the body does not produce insulin, a hormone that is needed to convert sugar into energy, and can lead to nerve and organ damage. With insulin therapy and other treatments, the condition can be controlled.

Dr. Ryan noted that his findings were a “snapshot” of scans and tests from one time point, and repeated scans and tests over the next five to 10 years will be critical to determine if the weaker brain connectivity might be linked to cognitive function, and if any predictive markers could be found in the brain scans that might warn of future cognitive impairment.

“The fact that adults with type 1 diabetes are now living longer than ever is certainly a success of treatment advancements, but it also presents an urgent public health problem,” said Caterina Rosano, M.D., M.P.H., senior author of this work and associate professor of epidemiology at Pitt Public Health. “A striking feature of these patients is that they develop brain abnormalities similar to those observed in much older adults without diabetes. It is very possible that older age may amplify the progression of brain abnormalities and possibly lead to a faster cognitive decline than what would be observed because of age alone. We need to rapidly identify and prevent the characteristics of this accelerated brain aging in type 1 diabetics if we want to ensure the highest quality of life for these patients.”

Additional researchers on this project include Howard J. Aizenstein, M.D., Ph.D., Department of Psychiatry, Pitt School of Medicine; and Trevor J. Orchard, M.B.B.Ch., M.Med.Sci., F.A.H.A., F.A.C.E., Department of Epidemiology, Pitt Public Health.

Falls Among Pennsylvania Elderly Reduced by State Program

PITTSBURGH, March 13, 2014 – A low-cost program reduced falls in the elderly by 17 percent statewide, illustrating the value and effectiveness of using existing aging services, such as senior centers, in preventing falls, a University of Pittsburgh Graduate School of Public Health study determined.

Pitt Public Health researchers followed nearly 2,000 older Pennsylvanians between 2010 and 2011 to determine the effectiveness of the state’s Healthy Steps for Older Adults, a voluntary fall-prevention program. Results of the study, funded by the U.S. Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH), will be published in the May issue of the American Journal of Public Health and are now available online.

“There is a high prevalence of falls among people 65 and older that increases with age, as does the inability to get up after a fall,” said lead author Steven Albert, Ph.D., chairman of the Department of Behavioral and Community Health Sciences at Pitt Public Health. “A challenge for public health officials is to decrease the risk of falls without encouraging reduced physical activity. Our research shows that the Healthy Steps for Older Adults program is a successful tool to help reduce falls.”

According to the CDC, one in three adults aged 65 and older falls each year and, of those who fall, 20 to 30 percent suffer moderate to severe injuries that make it hard for them to live independently, and increase their risk of early death.

By 2020, the CDC estimates, the annual direct and indirect cost of fall injuries will reach $67.7 billion.

Healthy Steps for Older Adults, run by the Pennsylvania Department of Aging, offers risk screening for falls and educational information regarding fall prevention, for adults 50 years and older. Participants who are identified as high risk for falls are referred to primary care providers and encouraged to complete home safety assessments, which identify modification — including banisters and grab bars — to reduce hazards in their homes that might put them at greater risk for falls.

The program is designed to be administered by volunteers at senior centers to keep costs low. Between 2010 and 2011, the state reimbursed the centers $70 per person for delivering the program, allocating $1.2 million to the program as a whole.

Dr. Albert and his co-authors recruited 814 older adults at senior centers statewide to complete the program, and compared them to 1,019 counterparts who did not. The average age of study participants was 75.4 years.

Of those who completed the program and were informed they were at high risk for falls, 21.5 percent followed up with physicians. More than three-quarters of program participants at high risk conducted home safety assessments, and a third went on to reduce home hazards.

“Though further analyses will be necessary to understand specifically how these actions translated into a 17 percent reduction in falls, it appears that referrals for physician care and home safety assessments, along with informing older adults of their high-risk status and heightening their sensitivity to situations involving a risk of falling, may lead to reductions in falls,” said Dr. Albert.

Additional researchers on this study are Anne B. Newman, M.D., M.P.H., Robert Boudreau, Ph.D., and Tanushree Prasad, M.A., all of the Pitt Public Health Department of Epidemiology; Jennifer King, B.A., of the Pitt Public Health Department of Community and Behavioral Health; and Chyongchiou J. Lin, Ph.D., of the Pitt School of Medicine.

This study was supported by CDC cooperative agreement DP002657 and grant U48 DP001918, and NIH grant P30 AG024827.

Dr. Fu Receives Career Award from National Orthopaedic Society; International Honors To Follow

PITTSBURGH, March 12, 2014 – Freddie Fu, M.D., tonight received the Elizabeth Winston Lanier Award for his career contribution to anterior cruciate ligament (ACL) reconstruction and advances in patient care, an accolade considered the Nobel Prize of orthopaedic research and bestowed by the Kappa Delta Sorority along with the Orthopaedic Research and Education Foundation. It was presented to Dr. Fu in New Orleans at the 2014 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS), a conference of 10,000 professionals.

Dr. Fu, the David Silver Professor and Chairman of the University of Pittsburgh Department of Orthopaedic Surgery and founder of the UPMC Center for Sports Medicine, also will receive honors in Europe and Asia over the next four months:

  • In Amsterdam in May, the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) is scheduled to present its highest honor to Dr. Fu by making him a Lifetime Honorary Member and a member of its Hall of Fame — the first from Pennsylvania, the second from the United States, and only the fourth inductee to date.
  • In Hiroshima, Japan, in July, the Japanese Orthopaedic Society of Knee, Arthroscopy and Sports Medicine (JOSKAS) will make Dr. Fu only the fourth surgeon — and second from the Western Hemisphere — recognized with the Masaki Watanabe Award for international achievement in arthroscopic surgery.

“These honors are truly gratifying, but they represent the research, diligence and clinical excellence of so many people rather than one person,” said Dr. Fu, whom the AAOS also honored three years ago with its 2011 Diversity Award. “It is a testament to the orthopaedic and sports-medicine programs at Pitt and UPMC, where we have spent the past three and a half decades creating an environment that is conducive to educating students and improving and studying treatment, surgery, imaging, rehabilitation and outcomes for our patients.”

In the past quarter-century, roughly 600 fellows from around the world have come to Pittsburgh to train. In addition to caring for patients, overseeing orthopaedics and sports medicine, and serving as the head team physician for Pitt athletics, Dr. Fu also remains committed to research and education. He is among the first eight faculty members of the School of Medicine to receive Pitt’s designation as a Distinguished Service Professor.

The Lanier Award, one of two Kappa Delta research awards established in 1947, honored Dr. Fu for his work surrounding ACL repair — an injury that can result in acute instability and long-term clinical problems, such as osteoarthritis. He supervised research that redefined long-standing assumptions about the ligament and developed new approaches to reconstructing it by replicating the knee’s native anatomy to restore long-term knee function, not to mention the patient’s quality of life.

Dr. Fu is scheduled to make a presentation relating to his award-winning work on Sunday at the Orthopaedic Research Society annual meeting held in conjunction with the AAOS.

On May 16 in The Netherlands, ESSKA will honor Dr. Fu at its General Assembly, which is held every other year. Its eight-member board of directors met in Glasgow, Scotland, last month and unanimously voted to award him with Lifetime Honorary Membership at its upcoming conference. ESSKA, with 4,000 members, is the largest orthopaedic society in Europe.

“Dr. Fu is one of the most outstanding scientists and surgeons in the world in orthopaedic sports medicine,” said Joao Espregueira Mendes, M.D., ESSKA president and professor and chairman of the Minho University Orthopaedic Department, Porto, Portugal. “He is without doubt the person most influential in advancing the knowledge of ACL surgery in the past 10 years. He is an example as a human being, leader, educator, researcher and diplomat.”

On July 26 in Japan, Dr. Fu will receive the Watanabe Award from JOSKAS, an organization founded 40 years ago, and its congress president, Dr. Mitsuo Ochi, director of Hiroshima University Hospital and chairman of the Department of Orthopaedic Surgery in the Graduate School of Biomedicine and Health Sciences at Hiroshima University.

Dr. Ochi said the award, named for the father of arthroscopy, is being presented to Dr. Fu because of “his great contributions to ACL reconstruction, and new discoveries and investigations for better ACL reconstruction.”

Pitt/MWRI Researchers Awarded Prestigious Cozzarelli Prize for Top Biomedical Sciences PNAS Paper of 2013

PITTSBURGH, March 7, 2014 – Researchers at the University of Pittsburgh School of Medicine and Magee-Womens Research Institute (MWRI) have been awarded the Cozzarelli Prize in the biomedical sciences for a July 2013 paper published in the Proceedings of the National Academy of Sciences (PNAS) that showed the cells of the placenta may have a unique ability to prevent viruses from crossing from an expectant mother to her growing baby and can transfer that trait to other kinds of cells.

Senior authors Yoel Sadovsky, M.D., Elsie Hilliard Hillman Chair of Women’s Health Research, professor of obstetrics, gynecology and reproductive medicine, Pitt School of Medicine, and MWRI director, and Carolyn Coyne, Ph.D., associate professor, Department of Microbiology and Molecular Genetics at Pitt, and MWRI member, and their research team will be honored on April 27 at a ceremony in Washington, D.C., during the National Academy of Sciences Annual Meeting.

The annual award was established in 2005 and named in 2007 for late PNAS Editor-in-Chief Nicholas R. Cozzarelli and acknowledges papers that reflect scientific excellence and originality. Five other papers in fields including the physical and mathematical sciences; biological sciences; engineering and applied sciences; behavioral and social sciences; and applied biological, agricultural and environmental sciences that were published in PNAS in 2013 also will receive awards.

“To receive the Cozzarelli Prize is a tremendous honor,” Dr.  Sadovsky said. “Our findings revealed elegant and complex mechanisms that have evolved to keep viruses from infecting the placenta, which could help us develop therapies for other kinds of viral infections.”

“We are very proud of our research paper and are gratified that the scientific community deems our work noteworthy,” Dr. Coyne said.

For their paper, which was published on July 16, 2013, the research team studied human trophoblast cells in the lab, exposing them to a panel of viruses. Unlike non-placental cells, trophoblasts were resistant to viral infection, but that trait was not a result of an inability of viruses to bind or enter the cells. When the medium, or fluid environment, in which the trophoblasts were cultured was transferred to non-placental cells, such as those that line blood vessels, they became resistant to viral infection, too.

The team found that when the medium was exposed to sound waves in a process called sonication, viral resistance was no longer transferred to non-placental cells. This finding led them to take a closer look at exosomes, which are tiny spheres called nanovesicles that are secreted by trophoblasts and are sensitive to sonication. Fragments of genetic material called microRNAs contained within the exosomes, as well as lab-synthesized mimics of them, were able to induce autophagy, a mechanism of prolonged cellular recycling and survival. Blocking autophagy at least partially restored the cells’ vulnerability to viral infections.

“We might be able to use these microRNAs to reduce the risk of viral infection in other cells outside of pregnancy, or perhaps to treat diseases where enhancing autophagy would be beneficial,” Dr. Coyne said.

Co-authors include other researchers from MWRI; the University of Pittsburgh departments of Obstetrics, Gynecology and Reproductive Sciences, Microbiology and Molecular Genetics, Infectious Diseases and Microbiology, Cell Biology and Physiology, and Surgery; and the University of Pittsburgh Cancer Institute.

The project was funded by the Pennsylvania Department of Health Research, the National Institutes of Health grants HD065893, HD071707, AI081759 and HD075665 and the Burroughs Wellcome Fund.

$2 Million NIH Grant Renews UPCI Research into Viruses, Cancer Pathways

PITTSBURGH, March 5, 2014 – The National Institutes of Health (NIH) has renewed a grant for more than $2 million for Patrick Moore, M.D., M.P.H., director of the Molecular Virology Program at the University of Pittsburgh Cancer Institute (UPCI), who will use the money to continue research into the newest human cancer virus causing most Merkel cell carcinomas.

A team led by Dr. Moore and Yuan Chang, M.D. discovered the Merkel cell polyomavirus in 2008, the seventh human cancer virus identified and the second discovered by Dr. Moore’s group under the original NIH grant that expires March 31. The new grant will fund the research through March 2019.

“Our initial grant was highly successful and led to new methods to diagnose and treat Merkel cell carcinoma,” Dr. Moore said. “We believe that these findings can help us to uncover new causes of other cancers, which may speed development and testing of new cancer therapies.”

Drs. Moore, Chang and their colleagues at Pitt identified a protein that allows the usually harmless polyomavirus to transform healthy cells into Merkel cell carcinoma, a rare but deadly skin cancer. They hope their work — which emphasizes the importance of fundamental basic science research to medical progress — can soon be translated into human clinical trials.

“Viruses are an important model for cancer research,” said Dr. Chang. “We’ve found that it may be possible to kill cancerous tumors by targeting the pathways these viruses use. That’s significant when you consider that 20 percent of all cancers are related to infectious diseases.”

The NIH grant number is R01 CA136806-06.

High Consumption of Fish Oil May Benefit Cardiovascular Health, Pitt Public Health Finds

PITTSBURGH, March 4, 2014 – Eating fish in amounts comparable to those of people living in Japan seems to impart a protective factor that wards off heart disease, according to an international study funded by the National Institutes of Health (NIH) and led by the University of Pittsburgh Graduate School of Public Health.

Middle-aged Japanese men living in Japan had lower incidence of coronary artery calcification, a predictor of heart disease, than middle-aged white men living in the United States, likely due to the significantly higher consumption of omega-3 fatty acids found in fish. The findings will be published in the March 6 issue of the journal Heart.

“Multiple studies have looked at the effect of fish oil on cardiovascular health, with mixed results,” said lead author Akira Sekikawa, M.D., Ph.D., associate professor of epidemiology at Pitt Public Health. “Previous studies investigated substantially lower intake of omega-3 fatty acids than what people in Japan actually get through their diet. Our study seems to indicate that the level of marine-derived omega-3 fatty acids consumed must be higher than previously thought to impart substantial protection.”

Marine-derived omega-3 fatty acids, which are found in fish, especially oily fish, as well as in squid and krill, may help to reduce inflammation and slow the formation of fatty plaques in arteries.

Researchers at Pitt partnered with scientists in Japan, Hawaii and Philadelphia to follow nearly 300 men for five years, tracking multiple factors that affect cardiovascular health, including cigarette smoking, the level of cholesterol in the blood and alcohol consumption, as well as their rates of diabetes and high blood pressure.

After accounting for risk factors for heart disease, the U.S. men had three times the incidence of coronary artery calcification as the Japanese men. Meanwhile, the levels of marine-derived omega-3 fatty acid in the blood were more than 100 percent higher in the Japanese than in the white men.

“The vast difference in heart disease and levels of marine-derived omega-3 fatty acid are not due to genetic factors,” said Dr. Sekikawa. “When we look at Japanese Americans, we find that their levels of coronary artery calcification are actually higher than that of the rest of the U.S. population.”

The average dietary intake of fish by Japanese people living in Japan is nearly 100 grams each day, which the American Heart Association considers 1 ½ servings. The average American eats about 7 to 13 grams of fish a day, or about one serving a week.

Heart disease is the leading cause of death in the U.S. and globally, according to the World Health Organization. However, Japan bucks this trend, with cancer as the leading cause of death.

“I am not encouraging Americans to start consuming massive amounts of fish, which may have harmful contaminants, such as mercury, in their flesh,” said Dr. Sekikawa. “However, our findings indicate that it is worthwhile to take another look at the effect of marine-derived omega-3 fatty acids on heart disease, particularly when consumed at higher rates than previously investigated.”

Additional co-authors on this study are Sunghee Lee, Ph.D., Rhobert W. Evans, Ph.D., Kim Sutton-Tyrrell, Ph.D., Marnie Bertolet, Ph.D., Emma J.M. Barinas-Mitchell, Ph.D., and Lewis H. Kuller, M.D., Dr.P.H., all of Pitt Public Health; Katsuyuki Miura, M.D., Ph.D., Akira Fujiyoshi, M.D., Ph.D., M.P.H., Takashi Kadowaki, M.D., Ph.D., Sayaka Kadowaki, M.D., Ph.D., Tomonori Okamura, M.D., Ph.D., Aya Kadota, M.D., Ph.D., Hirotsugu Ueshima, M.D., Ph.D., and Hiroshi Maegawa, M.D., Ph.D., all of Shiga University of Medical Science in Japan; Daniel Edmundowicz, M.D., of Temple University; Kamal H. Masaki, M.D., and Bradley J. Wilcox, M.D., both of the University of Hawaii; Yasuyuki Nakamura, M.D., Ph.D., of Kyoto Women’s University; and Todd B. Seto, M.D., of Queen’s Hospital in Hawaii.

This research was supported by NIH grants HL068200, HL071561, UL1RR024153 and UL1TR00005; and Japanese Ministry of Education Culture, Sports, Science and Technology grants B 16790335 and A 13307016, 17209023 and 21249043.

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