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Gwendolyn Sowa, MD, PhD, Named Chair of Pitt’s Department of Physical Medicine & Rehabilitation

The University of Pittsburgh School of Medicine has chosen one of its own renowned faculty members to be the next chair of the Department of Physical Medicine and Rehabilitation (PM&R). Gwendolyn Sowa, MD, PhD, who will assume her new role July 1, also holds joint appointments in the School of Medicine’s Department of Orthopaedic Surgery and the Swanson School of Engineering’s Department of Bioengineering. She also serves as associate dean for medical student research and medical director of UPMC Total Care-Musculoskeletal Health.

“Dr. Sowa’s many accomplishments demonstrate her ability to cross specialties and to collaborate effectively in the clinical, research and educational arenas,” noted Arthur S. Levine, MD, Pitt’s senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine. “She is the definition of a committed teacher and mentor.”

The department of PM&R ranks among the nation’s top programs in research funding from the National Institutes of Health and includes a team of multidisciplinary faculty members who train and educate the next generation of rehabilitation physicians and researchers, specializing in the fields of traumatic brain injury, spinal cord injury, stroke, diseases and disorders of the musculoskeletal and peripheral nervous system, and many other conditions that affect function and mobility.

“We are fortunate to have had Dr. Sowa as an internal candidate,” said Steven D. Shapiro, MD, executive vice president, chief medical and scientific officer, and president, Health Services Division, UPMC. “Her extraordinary dedication to every aspect of her work will continue to strengthen the innovative mission of this program.”

Dr. Sowa’s research centers on molecular, laboratory-based translational and clinical research, investigating the effect of motion on inflammatory pathways and the beneficial effects of exercise. She is co-director of the Ferguson Laboratory for Orthopaedic and Spine Research, a 3,000-square-foot laboratory fully equipped to perform molecular assays, including gene expression analysis, protein analysis, cell and organ culture, histology, and cellular and spinal biomechanical testing. She also has an active research program investigating the role of serum biomarkers in guiding individualized treatment in intervertebral disc degeneration and back pain. She has received national recognition for her research.

Dr. Sowa completed her MD and PhD in biochemistry at the University of Wisconsin-Madison, followed by residency training at Northwestern University, Rehabilitation Institute of Chicago.

Pre-Surgical Exposure to Blue Light Reduces Organ Damage in Mice

A 24-hour exposure to bright blue light before surgery reduces inflammation and organ damage at the cellular level in a mouse model, according to new research from the University of Pittsburgh School of Medicine.

The finding, reported in today’s issue of the Proceedings of the National Academy of Sciences, suggests a potential pre-treatment light therapy that could improve outcomes in patients undergoing procedures characterized by a period of blood restriction, such as liver resection or organ transplantation. The research was funded by the National Institutes of Health (NIH).

“We were incredibly surprised by our results,” said senior author Matthew R. Rosengart, MD, MPH, associate professor in the Pitt School of Medicine’s departments of Surgery and Critical Care Medicine. “There’s long been evidence suggesting that light and circadian rhythms profoundly influence our biology, and specifically the physiological response to stress. So while we were expecting to find some correlation with light spectrum and the immune response, we were not expecting results quite so striking.”

Light is complex and consists of intensity, duration of exposure and wavelength. This study is one of the first that accounts for this complexity and derives results that could guide future clinical trials in humans.

Dr. Rosengart and his team compared what happened when mice were exposed to red light, ambient white fluorescent light similar to that in hospitals and high-intensity blue light 24 hours before kidney or liver surgery involving periods of blood restriction and restoration.

The high-intensity blue light outperformed the red and white light, attenuating cellular and organ injury through at least two cellular mechanisms. The blue light brought about a reduction in the influx of neutrophils, a type of white blood cell involved in inflammation, which can lead to organ damage and other problems. Additionally, blue light inhibited dying cells from releasing a protein called HMGB1 that triggers organ-damaging inflammation.

The team then tested whether the blue light was acting through the optic pathway or some other mechanism, like the skin. Blind mice had the same healing response regardless of whether they were exposed to blue or red light, indicating that the protective impact of blue light does, indeed, act through the optic pathway.

The team then looked at whether one color of light might disrupt the circadian rhythm, which is linked to immunity, more than another. Blood from mice exposed to red, white and blue light had similar concentrations of melatonin and corticosteroid hormones. Furthermore, the mice under each of the lights also had similar activity levels. These data indicate that the effects of blue light were not mediated by a disruption of sleep, activity or circadian rhythms.

Finally, Dr. Rosengart stresses that mice are nocturnal animals with visual, circadian and immune biology that is distinct from humans. Thus, the results of his study should not be broadly extended to patients or hospital settings until robust clinical trials have been performed to show whether or not pretreatment with intensive blue light is safe.

Additional researchers on this project are Du Yuan, MD, of Pitt and Central South University in Hunan, China; Richard D. Collage, Hai Huang, MD, Xianghong Zhang, PhD, Ben C. Kautza, MD, Anthony J. Lewis, MD, Brian S. Zuckerbraun, MD, Allan Tsung, MD, and Derek C. Angus, MD, MPH, all of Pitt’s School of Medicine.

This research was funded by NIH grant R01 GM082852.

Watercress Extract Detoxifies Carcinogens in Smokers, Clinical Trial Demonstrates

Watercress extract taken multiple times a day significantly inhibits the activation of a tobacco-derived carcinogen in cigarette smokers, researchers at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter, demonstrated in a phase II clinical trial presented today at the American Association for Cancer Research (AACR) Annual Meeting in New Orleans.

The trial also showed that the extract detoxifies environmental carcinogens and toxicants found in cigarette smoke, and that the effect is stronger in people who lack certain genes involved in processing carcinogens. This trial was supported by a grant from the National Cancer Institute (NCI).

“Cigarette smokers are at far greater risk than the general public for developing lung cancer, and helping smokers quit should be our top cancer prevention priority in these people,” said Jian-Min Yuan, MD, PhD, associate director of the UPCI’s Division of Cancer Control and Population Science and an epidemiologist with Pitt’s Graduate School of Public Health. “But nicotine is very addictive, and quitting can take time and multiple relapses. Having a tolerable, nontoxic treatment, like watercress extract, that can protect smokers against cancer would be an incredibly valuable tool in our cancer-fighting arsenal.”

Dr. Yuan, who also is Pitt’s Arnold Palmer Endowed Chair in Cancer Prevention, and his colleagues enrolled 82 cigarette smokers in the randomized clinical trial. The participants either took 10 milligrams of watercress extract mixed in 1 milliliter of olive oil four times a day for a week or they took a placebo. Each group of participants then had a one week “wash-out” period where they didn’t take anything and then switched so that those getting the placebo now received the extract. They all continued their regular smoking habits throughout the trial.

In one week, the watercress extract reduced activation of the carcinogen known as nicotine-derived nitrosamine ketone in the smokers by an average of 7.7 percent. It increased detoxification of benzene by 24.6 percent and acrolein by 15.1 percent, but had no effect on crotonaldehyde. All the substances are found in cigarette smoke.

Participants who lacked two genes involved in a genetic pathway that helps the antioxidant glutathione remove carcinogens and toxicants from the body saw an even bigger benefit to taking the watercress extract, which increased their detoxification of benzene by 95.4 percent, acrolein by 32.7 percent and crotonaldehyde by 29.8 percent.

A phase III clinical trial in hundreds of people must be performed before the treatment could be recommended for smokers, and Dr. Yuan warned that while eating cruciferous vegetables, such as watercress and broccoli, is good for people, they are unlikely to have the same pronounced effect as the extract.

Additional researchers on this project are Irina Stepanov, PhD, Sharon E. Murphy, PhD, Steven G. Carmella, BA, Heather H. Nelson, PhD, Dorothy Hatsukami, PhD, and Stephen S. Hecht, PhD, all of the University of Minnesota.

This research was funded by NCI grant R01CA122244.

Pitt Health Sciences Faculty Inducted into Prestigious Physician-Scientist Associations

Three University of Pittsburgh Health Sciences faculty members have been inducted into the Association of American Physicians (AAP), a nonprofit, professional organization founded in 1885 for the “advancement of scientific and practical medicine,” and three have been inducted into the American Society for Clinical Investigation (ASCI), which was founded in 1908 and is “dedicated to the advancement of research that extends our understanding and improves the treatment of human diseases.”
Election to AAP is an honor extended to individuals with outstanding credentials in biomedical science and/or translational biomedical research and is limited to 60 inductees per year. An association of the country’s most accomplished physician-scientists, AAP serves as a forum to create and disseminate knowledge and as a source of inspiring role models for upcoming generations of physicians and medical scientists.

Election to ASCI reflects early career accomplishment as new members must be 50 or younger. ASCI represents physician-scientists who are “at the bedside, at the research bench and at the blackboard.” Up to 80 new members are elected annually from hundreds of nominations.

“Endorsements from these respected societies further demonstrate the commitment to research and the impact of the work performed by the physicians, researchers, and staff at the University of Pittsburgh,” said Arthur S. Levine, MD, Pitt’s senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of Medicine. “We are honored to work with such outstanding scientists who make such significant contributions to the future of science and medicine.”

AAP Inductees:

David A. Brent, MD, is the academic chief of Child and Adolescent Psychiatry at Western Psychiatric Institute and Clinic of UPMC, and professor of psychiatry, pediatrics and epidemiology, University of Pittsburgh School of Medicine and holds an endowed chair in suicide studies. Dr. Brent co-founded and now directs Services for Teens at Risk (STAR), a Commonwealth of Pennsylvania-funded program for suicide prevention, education of professionals, and the treatment of at-risk youths and their families. He has led work that has helped to established evidence based practices for assessing suicidal risk and for treating adolescent depression and suicidal behavior. Dr. Brent is a member of the National Academy of Medicine and has been recognized for his work by the American Psychiatric Association, the American Academy of Child and Adolescent Psychiatry, the American Foundation for Suicide Prevention, and the Brain and Behavior Foundation.

Anne B. Newman, MD, MPH, is the Katherine M. Detre Professor of Population Health Sciences, chair of the Department of Epidemiology at the University of Pittsburgh Graduate School of Public Health, and director of Pitt’s Center for Aging and Population Health. Dr. Newman’s research centers on the relationships between aging, longevity and disability. She currently is the principal investigator of several long-term cohort studies and clinical trials in older adults funded by the National Institute on Aging. Dr. Newman is an elected member of the American Epidemiology Society and the Delta Omega Honor Society in Public Health.

Brian Zuckerbraun, MD, is the Henry T. Bahnson Professor of Surgery and chief of Trauma and Acute Care Surgery at UPMC. Dr. Zuckerbraun’s research centers on how the body’s immune system responds to cell damage. His work investigates the inflammatory response in the liver and vasculature following injury from trauma/hemorrhagic shock, sepsis or direct vascular injury. Much of the work has focused on the development of therapeutic treatments with gaseous signaling molecules, including nitric oxide and carbon monoxide.

ASCI Inductees:

Caterina Rosano, MD, MPH, is a professor in Pitt Public Health’s Department of Epidemiology. Her research focuses on how the brain adapts to the “normal” processes of aging and disease and, specifically, in understanding the causes, biomarkers and consequences of brain aging.

Bernhard Kühn, MD, is a board-certified pediatric cardiologist at Children’s Hospital of Pittsburgh of UPMC, a scholar at the Richard King Mellon Institute for Pediatric Research, and director of research, Division of Pediatric Cardiology. Dr. Kühn’s work is focused on the cells of the heart muscle and discovering ways to make them replicate to enable the heart to heal itself in cases of heart failure or congenital defects.

Stephen Chan, MD, PhD, is an associate professor of medicine and director of the Center for Pulmonary Vascular Biology and Medicine at Pitt’s Vascular Medicine Institute. Dr. Chan studies the molecular mechanisms of pulmonary vascular disease and pulmonary hypertension (PH), with an intent to identify persons at risk for PH and to develop new therapies for this devastating disease.

Four Young Researchers from the Same UPCI Lab Receive AACR Scholar-in-Training Awards

Four young investigators from the same laboratory at the University of Pittsburgh Cancer Institute, partner with UPMC CancerCenter,  have been recognized with American Association for Cancer Research (AACR) scholar-in-training awards for AACR’s annual meeting in New Orleans, April 16 to 20.

“I am delighted the efforts of my students have been so successful and look forward to the next steps they take in their promising research careers,” said lab leader Shivendra Singh, PhD, professor of pharmacology and chemical biology, and UPMC Chair in Cancer Prevention Research, Pitt School of Medicine. His lab focuses on examining enzymes that play a role in drug metabolism and cellular defenses against environmental toxins, as well as exploring the anti-carcinogenic effects of certain natural agents found in edible plants.

Three researchers received scholar-in training awards in memory of Dr. Lee W. Wattenberg, a pioneer in cancer prevention research, who served as AACR president in 1992. According to AACR, these awards are presented to young investigators presenting high-quality papers relating to cancer prevention research.

Those awardees are:

Su Hyeong Kim, PhD: “Role of c-Myc in prostate cancer stem-like cell inhibition by sulforaphane” (Abstract 822).

In this project, Dr. Kim showed that sulforaphane, which naturally occurs in broccoli and other cruciferous vegetables, can inhibit prostate cancer in lab tests because it blocks the effects of c-Myc, a gene that regulates cancer growth. This investigation was supported by grant CA115498 of the National Cancer Institute (NCI), part of the National Institutes of Health.

Subrata K. Pore, PhD: “Benzyl isothiocyanate inhibits breast cancer-induced osteoclastogenesis” (Abstract 826).

Dr. Pore and colleagues built on previous work showing that benzyl isothiocyanate (BITC), found in edible cruciferous vegetables such as garden cress, inhibits breast cancer in a mouse model of the disease. In advanced breast cancer, bone loss can occur, which can be deadly with spreading disease. In this project, the team showed that BITC can limit bone breakdown by reducing the production of bone-resorbing cells called osteoclasts. This study was supported by NCI grant CA129347.

Krishna Beer Singh, PhD: “c-Myc is a novel target of prostate cancer cell growth inhibition by honokiol” (Abstract 831).

Dr. Singh led a project that showed honokiol, a naturally occurring agent derived from magnolia trees, suppressed activity of c-Myc and other genes that play key roles in prostate cancer growth. This study was supported by NCI grants CA101753 and CA115498.

In addition, a fourth researcher from the Singh Lab received a $1,500 AACR-Triple Negative Breast Cancer Foundation scholar-in-training award.

Ruchi Roy, PhD: “Benzyl isothiocyanate mediates glucose uptake through AKT activation in breast cancer cells” (Abstract 833).

Dr. Roy showed in animal models that BITC’s effects in suppressing Her-2-driven breast tumors could be enhanced with the addition of an agent that inhibits the protein AKT. This study was supported by NCI grant CA129347.

Pitt-led International Panel Reclassifies Thyroid Tumor to Curb Overdiagnosis of Cancer, Unneeded Treatment

Led by researchers at the University of Pittsburgh School of Medicine, an international panel of pathologists and clinicians has reclassified a type of thyroid cancer to reflect that it is noninvasive and has a low risk of recurrence. The name change, described today in JAMA Oncology, is expected to reduce the psychological and medical consequences of a cancer diagnosis, potentially affecting thousands of people worldwide.

The incidence of thyroid cancer has been rising partly due to early detection of tumors that are indolent or non-progressing, despite the presence of certain cellular abnormalities that are traditionally considered cancerous, explained senior investigator Yuri Nikiforov, MD, PhD, professor of pathology and director of Pitt’s Division of Molecular and Genomic Pathology.

“This phenomenon is known as overdiagnosis,” Dr. Nikiforov said. “To my knowledge, this is the first time in the modern era a type of cancer is being reclassified as a non-cancer. I hope that it will set an example for other expert groups to address nomenclature of various cancer types that have indolent behavior to prevent inappropriate and costly treatment.”

In particular, a tumor type known as encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) has increased in incidence by an estimated two- to three-fold over the past 20 to 30 years and makes up 10 to 20 percent of all thyroid cancers  diagnosed in Europe and North America, the panel noted. Although studies have shown EFVPTC is not dangerous, it is typically treated as aggressively as other types of thyroid cancer. At the recommendation of the National Cancer Institute, the panel sought to revise the terminology and to see if the word “cancer” could be dropped from its name.

Two dozen experienced pathologists from seven countries and four continents independently reviewed 268 tumor samples diagnosed as EFVPTC from 13 institutions. The experts established diagnostic criteria, including cellular features, tumor invasion and other factors. In a group of more than 100 noninvasive EFVPTCs, there were no recurrences or other manifestations of the disease at a median follow-up of 13 years, the panel found.

These experts decided to rename EFVPTC as “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” or NIFTP. The new name cites key features to guide pathologists in diagnosis, but omits the word “cancer,” indicating that it need not be treated with radioiodine or other aggressive approaches.

“We determined that if NIFTP is carefully diagnosed, the tumor’s recurrence rate is extremely low, likely less than 1 percent within the first 15 years,” Dr. Nikiforov said. “The cost of treating thyroid cancer in 2013 was estimated to exceed $1.6 billion in the U.S. Not only does the reclassification eliminate the psychological impact of the diagnosis of ‘cancer,’ it reduces the likelihood of complications of total thyroid removal, and the overall cost of health care.”

The team included researchers from the University of Bologna, Italy; University of Pennsylvania; University of Pisa, Italy; Harvard Medical School; and others.

The project was funded in part by University of Pittsburgh Cancer Institute, UPMC and an education grant from CBLPath, Inc.

Most Patients Likely to See Reductions in Pain and Disability after Bariatric Surgery; Study Identifies Who Benefits Most

In the three years following bariatric surgery, the majority of patients experienced an improvement in pain and walking ability, as well as a lessening of the degree to which back or leg pain interfered with work, according a University of Pittsburgh Graduate School of Public Health-led analysis of a multi-site clinical study published today in the Journal of the American Medical Association.

The study also revealed patient characteristics that indicate who is the most and least likely to experience improvements in pain and function, a finding that could allow clinicians to identify patients who may require additional interventions to improve outcomes. The research was funded by the National Institutes of Health (NIH).

“Our study found that clinically meaningful improvements in bodily pain, specific joint pain and physical function are common following bariatric surgery. In particular, walking is easier, which impacts patients’ ability to adopt a more physically active lifestyle. However, some patients continue to have significant pain and disability,” said lead author Wendy King, Ph.D., associate professor in the Department of Epidemiology at Pitt Public Health. “This data can help patients and clinicians develop realistic expectations regarding the impact of bariatric surgery on pain and disability.”

Dr. King and her colleagues followed 2,221 patients participating in the Longitudinal Assessment of Bariatric Surgery-2 , a prospective study of patients undergoing weight-loss surgery at one of 10 hospitals across the U.S. After three years, patients weighed, on average, 28 percent less than prior to surgery. The majority of the patients received Roux-en-Y gastric bypass, a surgical procedure that significantly reduces the size of the stomach and changes connections with the small intestine.

Through three years of follow-up, 50 to 70 percent of adults with severe obesity who underwent bariatric surgery reported clinically important improvements in bodily pain, physical function and usual walking speed. About three-quarters of the participants with symptoms indicative of osteoarthritis before surgery experienced improvements in knee and hip pain and function. In addition, over half of participants who had a mobility deficit prior to surgery did not post-surgery.

Older age, lower income, more depressive symptoms and pre-existing medical conditions, including cardiovascular disease and diabetes before surgery, were among the factors independently associated with a lower likelihood of improvement in pain and mobility post-surgery, while greater weight loss, greater reduction in depressive symptoms, and remission or improvement in several medical conditions were associated with greater likelihood of improvement.

In the first year following bariatric surgery, 3.7 percent of patients had hip, knee or ankle surgery; in the second year, 4.9 percent had such surgeries followed by another 4.6 percent in the third year. The majority were knee surgeries. The incidence of back surgeries ranged from 1.5 percent in the first year to 2.3 percent in the third year.

Three years post-surgery, 76.3 percent of patients reported that their leg and back pain interfered with their work “not at all,” up from 54.1 percent pre-surgery. Also, the average physical function score of the participants, which is based on ability to walk various distances, climb stairs, perform vigorous and moderate activities, lift and carry groceries, bathe, dress, bend and kneel, improved to the point that it was comparable to that of the general US population. Resting heart rate also improved.

“Functional status is an extremely important aspect of health that has not been as well-studied as other conditions that change following bariatric surgery, and this study sheds light on specific factors that may affect improvements in individuals with joint pain who undergo these procedures,” said study co-author Anita Courcoulas, MD, MPH, chief of minimally invasive bariatric and general surgery in Pitt’s School of Medicine.

Additional investigators on this research are Jia-Yuh Chen, MS, and Steven H. Belle, PhD, both of Pitt; Gregory F. Dakin, MD, of Weill Cornell Medical College; Katherine A. Elder, Ph.D, of Pacific University and Oregon Health & Science University; David R. Flum, MD, MPH, and Marcelo W. Hinojosa, MD, both of the University of Washington; James E. Mitchell, MD, of the Neuropsychiatric Research Institute; Walter J. Pories, MD, of East Carolina University; Bruce M. Wolfe, MD, of the Oregon Health & Science University; and Susan Z. Yanovski, MD, of the NIH National Institute of Diabetes and Digestive and Kidney Disease (NIDDK).

This clinical study was a cooperative agreement funded by the NIDDK. Grant numbers: DCC -U01 DK066557; Columbia – U01-DK66667 (in collaboration with Cornell University Medical Center CTRC, Grant UL1-RR024996); University of Washington – U01-DK66568 (in collaboration with CTRC, Grant M01RR-00037); Neuropsychiatric Research Institute – U01-DK66471; East Carolina University – U01-DK66526; UPMC – U01-DK66585 (in collaboration with CTRC, Grant UL1-RR024153); and Oregon Health & Science University – U01-DK66555.

Pitt Team Redesigns Epilepsy Drug to Increase Potency and Specificity, Reduce Side Effects

Researchers at the University of Pittsburgh School of Medicine and Arts & Sciences have designed a more effective version of an FDA-approved epilepsy drug with the potential for fewer side effects, according to a study published on March 22 in Molecular Pharmacology. The experimental agent also could prove to be a treatment for tinnitus and other disorders caused by volatile neural signaling.

Epilepsy, in which erratic firing of nerve signals causes seizures, affects about 1 percent of people worldwide, said senior investigator Thanos Tzounopoulos, PhD, Endowed  Chair in Auditory Physiology, associate professor of otolaryngology and member of the Auditory Research Group, University of Pittsburgh School of Medicine. Drugs to treat the disorder primarily work by influencing the transport of sodium, potassium and chloride ions across the nerve cell membrane to try to reduce the excitability of the brain cells.

“Unfortunately, these drugs don’t work well in nearly a third of patients and there is a great need for better treatments,” Dr. Tzounopoulos said. “We have been able to refine an existing medication so that it acts selectively on certain nerve cell membrane transport channels, which should make it more effective.”

The available drug is called retigabine, and while it has improved symptoms for some patients, it can also lead to troublesome side effects, including retinal abnormalities, urinary retention and skin discoloration. Dr. Tzounopoulos was part of a study team that evaluated an earlier modification of retigabine, dubbed SF0034, which is being further developed by SciFluor Life Sciences LLC in Cambridge, Mass.

For the current project, Dr. Tzounopoulos and Peter Wipf, PhD, Distinguished University Professor of Chemistry at Pitt, rationally redesigned several structural components of retigabine to further increase its potency. Retigabine works by activating all five types of potassium transport channels in the KCNQ category, but only two of the potassium channels, KCNQ2/3, are important for stabilizing the cell membrane of brain cells involved in hyperexcitability-related disorders, such as epilepsy and tinnitus, Dr. Tzounopoulos explained. The new compound, known as RL648_81 (“RL-81”), targets just those channels.

When the researchers compared the three drugs head-to-head in lab tests, they found RL-81 was 15 times more potent than retigabine and three times more potent than SF0034. Because of its specificity, RL-81 also should have fewer side effects.

The experimental compound could also help people with tinnitus by preventing hyper-excitation of nerve cells in auditory pathways, Dr. Tzounopoulos noted.

“At this point, the new compound is ready to be studied further in animal models of epilepsy and tinnitus and for other preclinical assessments,” Dr. Wipf said. “RL-81 appears to have great potential for the treatment of these challenging neurological conditions.”

The team also included Manoj Kumar, PhD, Nicholas Reed, MS, Ruiting Liu, BS, and Elias Aizenman, PhD, all of the University of Pittsburgh.

The project was funded by the U.S. Department of Defense Joint Warfighter Medical Research Program (Grant W81XWH-14-1-0117).

Pitt Finding Suggests New Heart Disease Screening Target for Middle-Aged Black Women

Middle-aged black women have higher levels of a protein in their blood associated with a predictor of heart disease than their white counterparts, even after other factors, such as obesity, are taken into consideration, according to a study conducted by the University of Pittsburgh Graduate School of Public Health and School of Medicine.

The finding, reported today in the journal Menopause, suggests routine blood testing of black menopausal women may be warranted to determine their heart disease risk and potentially when to start therapies, such as aspirin and statins. The research was funded by the National Institutes of Health (NIH).

“Multiple previous studies have shown that black women are at higher risk for heart disease than white women; however, guidelines for assessing cardiovascular disease risk in asymptomatic adults do not recommend selective race- or ethnic-based risk-assessment,” said lead author Norman C. Wang, MD, MS, assistant professor in Pitt’s School of Medicine. “Our study revealed for the first time that in black, but not white, women going through menopause, higher levels of an easily measured risk factor for heart disease are associated with higher amounts of early atherosclerosis, even after accounting for other risk factors for heart disease. A clinical trial to determine whether routine screening in this population can save lives may be warranted.”

Dr. Wang and his colleagues examined medical records, blood samples and heart CT scans for 372 black and white women from Pittsburgh and Chicago enrolled in the Study of Women’s Health Across the Nation (SWAN). The women averaged just over 51 years old, were not on hormone replacement therapy and had no known heart disease when enrolled.

The researchers looked at blood levels of five biomarkers linked to inflammation. All of the biomarkers were associated with coronary artery calcification, a predictor of heart disease that is measured with a heart CT scan. When the researchers then took into account the participants’ body mass index (BMI), a measure of overall body fat, they found that obesity was a key factor linking most of the elevated inflammation biomarkers and coronary artery calcification.

Regardless of BMI, black women with higher levels of one particular biomarker, C-reactive protein, were more likely to have coronary artery calcification than whites. In fact, black women with coronary artery calcification had an average level of C-reactive protein in their blood that was almost double that of their white counterparts.

“We clearly demonstrated that obesity, inflammation biomarkers and coronary artery calcification are linked for both black and white midlife women, further emphasizing the need to promote lifestyle changes to combat obesity at midlife when women are subjected to many physiological and biological changes that could potentially increase their risk for heart disease,” said senior author Samar El Khoudary, PhD, MPH, assistant professor in Pitt Public Health’s Department of Epidemiology. “Future research should build on our findings regarding black women and C-reactive protein by testing similar associations over time, which could potentially yield interventions that can help these women avoid developing heart disease.”

The researchers noted that their study only looked at black and white women, so the results are not generalizable to other racial or ethnic groups.

Additional researchers on the study are Karen A. Matthews, PhD, Emma J.M. Barinas-Mitchell, PhD, and Chung-Chou H. Chang, PhD, all of Pitt.

This work was supported by the NIH through the National Institute on Aging, National Institute of Nursing Research, Office of Research on Women’s Health and National Heart, Lung, and Blood Institute grants U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, HL065581 and HL065591.

Social Media Use Associated With Depression Among U.S. Young Adults

The more time young adults use social media, the more likely they are to be depressed, according to new research from the University of Pittsburgh School of Medicine.

The findings could guide clinical and public health interventions to tackle depression, forecast to become the leading cause of disability in high-income countries by 2030. The research, funded by the National Institutes of Health, is published online and scheduled for the April 1 issue of the journal Depression and Anxiety.

This was the first large, nationally representative study to examine associations between use of a broad range of social media outlets and depression. Previous studies on the subject have yielded mixed results, been limited by small or localized samples, and focused primarily on one specific social media platform, rather than the broad range often used by young adults.

“Because social media has become such an integrated component of human interaction, it is important for clinicians interacting with young adults to recognize the balance to be struck in encouraging potential positive use, while redirecting from problematic use,” said senior author Brian A. Primack, MD, PhD, director of Pitt’s Center for Research on Media, Technology and Health.

In 2014, Dr. Primack and his colleagues sampled 1,787 U.S. adults ages 19 through 32, using questionnaires to determine social media use and an established depression assessment tool.

The questionnaires asked about the 11 most popular social media platforms at the time: Facebook, YouTube, Twitter, Google Plus, Instagram, Snapchat, Reddit, Tumblr, Pinterest, Vine and LinkedIn.

On average the participants used social media a total of 61 minutes per day and visited various social media accounts 30 times per week. More than a quarter of the participants were classified as having “high” indicators of depression.

There were significant and linear associations between social media use and depression whether social media use was measured in terms of total time spent or frequency of visits. For example, compared with those who checked least frequently, participants who reported most frequently checking social media throughout the week had 2.7 times the likelihood of depression. Similarly, compared to peers who spent less time on social media, participants who spent the most total time on social media throughout the day had 1.7 times the risk of depression. The researchers controlled for other factors that may contribute to depression, including age, sex, race, ethnicity, relationship status, living situation, household income and education level.

Lead author Lui yi Lin, BA, who will be graduating from the University of Pittsburgh School of Medicine this spring, emphasized that, because this was a cross-sectional study, it does not disentangle cause and effect.

“It may be that people who already are depressed are turning to social media to fill a void,” she said.

Conversely, Ms. Lin explains that exposure to social media also may cause depression, which could then in turn fuel more use of social media. For example:

• Exposure to highly idealized representations of peers on social media elicits feelings of envy and the distorted belief that others lead happier, more successful lives.

• Engaging in activities of little meaning on social media may give a feeling of “time wasted” that negatively influences mood.

• Social media use could be fueling “Internet addiction,” a proposed psychiatric condition closely associated with depression.

• Spending more time on social media may increase the risk of exposure to cyber-bullying or other similar negative interactions, which can cause feelings of depression.

In addition to encouraging clinicians to ask about social media use among people who are depressed, the findings could be used as a basis for public health interventions leveraging social media. Some social media platforms already have made forays into such preventative measures. For example, when a person searches the blog site Tumblr for tags indicative of a mental health crisis—such as “depressed,” “suicidal” or “hopeless”—they are redirected to a message that begins with “Everything OK?” and provided with links to resources. Similarly, a year ago Facebook tested a feature that allows friends to anonymously report worrisome posts. The posters would then receive pop-up messages voicing concern and encouraging them to speak with a friend or helpline.

“Our hope is that continued research will allow such efforts to be refined so that they better reach those in need,” said Dr. Primack, who also is assistant vice chancellor for health and society in Pitt’s Schools of the Health Sciences and professor of medicine. “All social media exposures are not the same. Future studies should examine whether there may be different risks for depression depending on whether the social media interactions people have tend to be more active vs. passive or whether they tend to be more confrontational vs. supportive. This would help us develop more fine-grained recommendations around social media use.”

Additional authors of the study were Jaime E. Sidani, PhD, Ariel Shensa, MA, Ana Radovic, MD, MSc., Elizabeth Miller, MD, PhD, Jason B. Colditz, MEd, Beth Hoffman, BSc, and Leila M. Giles, BS, all of Pitt.

This research was funded by National Institute of Mental Health grant R25-MH054318 and National Cancer Institute grant R01-CA140150.

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