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January 23, 2014

Research Notes

Disparities in LGBT health research funding noted

Only one-half of 1 percent of studies funded by the National Institutes of Health (NIH) between 1989 and 2011 concerned the health of lesbian, gay, bisexual and transgender (LGBT) people, contributing to the perpetuation of health inequities, according to a Graduate School of Public Health-led analysis.

The findings, which grew from the Fenway Institute’s Summer Institute in LGBT Population Health in Boston and continued at Pitt’s Center for LGBT Health Research, are in the February issue of the American Journal of Public Health. The researchers make several recommendations for how to stimulate LGBT-related research.

Said Robert W. S. Coulter, a doctoral student in public health’s Department of Behavioral and Community Health Sciences: “The NIH is the world’s largest source of health research funding and has placed a low priority on LGBT health research. In general, LGBT people experience stigma associated with their sexual and gender minority status, disproportionate behavioral risks and psychosocial health problems, and higher chronic disease risk factors than their non-LGBT counterparts. Increased NIH funding for research on these topics, particularly focusing on evidence-based interventions to reduce health inequities, could help alleviate these negative health outcomes.”

About 3.5 percent of the U.S. adult population is estimated to be gay, lesbian or bisexual, according to recent research based on national- and state-level population surveys.

Coulter and his colleagues found 628 NIH-funded studies concerning LGBT health between 1989 and 2011, accounting for 0.5 percent of all NIH-funded studies. The majority of those studies focused on HIV/AIDS and other sexual health matters. When those studies were excluded, there were only 113 LGBT-related studies remaining, or 0.1 percent of NIH-funded studies during this period.

After analyzing those studies, Coulter’s research team found further gaps within the 628 LGBT-related studies, with 86.1 percent concerning the health of sexual minority men, only 13.5 percent focused on sexual minority women and 6.8 percent focused on transgender populations, with some of the projects studying more than one subgroup.

The authors also found that there were 202 projects on the development, implementation or evaluation of interventions. When intervention studies concerning HIV and other sexual health matters were removed, the number of projects dropped to 21.

“Studies have shown that specific subgroups of LGBT populations experience health problems like tobacco use, violence and obesity at higher rates than their non-LGBT counterparts. Thus, the lack of intervention studies aimed at reducing these health disparities contributes to the perpetuation of health inequities among LGBT populations,” said Coulter. “The political climate has had a chilling effect within the NIH that constrains LGBT health research and appears to be responsible, at least in part, for the marginalization of LGBT research at the NIH.”

Coulter and his colleagues noted that a 2003 request by some Republican members of Congress for NIH to justify the benefits of nearly 200 projects, most of which investigated LGBT or other marginalized populations, was followed by more than half of the researchers leading those studies removing words from their study proposals that might be deemed controversial, such as “gay,” “lesbian,” “bisexual” and “AIDS.” A smaller proportion of researchers completely dropped their LGBT-related studies, with some even changing careers. The research by Coulter and colleagues showed a substantial drop in LGBT-related projects at NIH during these years as well.

Coulter and his colleagues believe that NIH is on the path toward lessening the dearth of LGBT-related research. In 2012, NIH supported a workshop about sexual orientation and gender identity in electronic health records and encouraged professional development activities related to LGBT health.

To more efficiently stimulate research projects on LGBT health, the researchers recommend NIH engage in the following practices to address the problem comprehensively:

  • Establish policies that designate LGBT people as priority populations for research that goes beyond HIV/AIDS and sexual health issues.
  • Increase evidence-based intervention research to improve LGBT and reduce health inequities.
  • Explore new strategies to increase the amount of LGBT health research, including support for diversity among researchers.
  • Support efforts to expand the pool of trained researchers prepared to propose LGBT research projects through training grants, fellowships, career awards and the establishment of LGBT Centers of Excellence.

This research was supported by the Summer Institute in LGBT Population Health; the Eunice Kennedy Shriver National Institute of Child Health & Human Development; the Training Program to Address HIV-Related Health Disparities in MSM; the National Institute of Mental Health; the Network for LGBT Health Equity; the Centers for Disease Control and Prevention (CDC), and the CDC Prevention Research Center.

It included researchers from Massachusetts General Hospital, Boston University and CenterLink.


Media literacy better smoking prevention program

no smokingA school-based smoking prevention program centered on media literacy performed better than traditional anti-smoking educational programming, according to a new School of Medicine study. While traditional anti-smoking education focuses on health effects of smoking and resisting peer and other social influences, media literacy empowers participants to analyze and evaluate portrayals of tobacco use in media.

In the study, published in the Journal of School Health, the researchers randomly assigned 796 9th-grade students in three Pittsburgh high schools to receive either an anti-smoking media literacy program or a rigorous traditional anti-smoking program.

Among high-risk students who originally said they planned to smoke in the future, more students in the media literacy program changed their minds at the conclusion of the program compared with those in the traditional program. Students who received media literacy programming also perceived smoking as less popular, which has been closely linked with behavioral smoking outcomes in the past.

The students in the media literacy group also gave higher evaluation scores for their enjoyment of and attention to the program, and they were more likely to indicate that they would look at smoking and advertising differently in the future, compared with the traditional group.

In many other areas, such as attitudes toward smoking, the two programs performed similarly, but no outcomes were superior for the traditional program.

Said lead author Brian A. Primack, medicine and pediatrics faculty member and director of the Program for Research on Media and Health: “Because traditional programs have not been as successful as we would like in preventing smoking among youth, it is very important that we innovate in this area. The results of this study suggest that media literacy has potential, which we should continue to investigate.”

Primack and his colleagues suggest that one reason media literacy may be effective is that youth aged 8-18 continue to be exposed to more than 10 hours of media content each day, including multiple positive images of smoking, which previous research clearly has linked to initiation of smoking. Additionally, media literacy inherently may be more effective for sensation-seeking, rebellious individuals who are more at risk for using tobacco.

“We were particularly interested in the group of 236 students who reported at the start of the program that they intended to smoke in the future. Among these individuals, 24 percent of those assigned to the media literacy group reverted to not intending to smoke after the intervention, compared with only 16 percent of those assigned to the traditional program,” said Primack. “Although our study was relatively small, if changes of this magnitude are borne out in other studies, this would translate into clinically meaningful differences. Another challenge for the future will be to examine longer-term smoking outcomes.”

Additional authors of this research were Erika L. Douglas and Elizabeth Miller, both of Pitt, along with researchers from the National Cancer Institute and the VA Pittsburgh Healthcare System.

The study was funded by NIH, Robert Wood Johnson Foundation and Maurice Falk Foundation.


Brain Institute established

brains2The University is creating a new institute that aims to unlock the mysteries of normal and abnormal brain function, and then use this new information to develop novel treatments and cures for brain disorders. The institute will function like a Bell Labs for brain research and provide a special environment to promote innovation and discovery. The goal is to enable investigators to perform high-risk, high-impact neuroscience that will transform lives.

Said Chancellor Mark A. Nordenberg: “Pittsburgh has earned well-deserved respect as one of the world’s leading centers for groundbreaking research in neuroscience. We have the intellectual firepower to take a lead role in the nationwide effort to revolutionize the understanding of the brain. The creation of our Brain Institute  … will strengthen our ongoing local, national and international research efforts, such as the Center for the Neural Basis of Cognition, which is a joint program with Carnegie Mellon University.”

According to Arthur S. Levine, senior vice chancellor for the health sciences and John and Gertrude Petersen Dean of the School of Medicine, the Brain Institute will initiate five centers that focus on neurotechnology, neurogenetics, brain mapping, learning and discovery in neuroscience. The Brain Institute’s mission also includes coordinating strategic planning for further research initiatives and developing and overseeing essential research resources.

Said Levine: “We have the will and the skills to unravel how the brain works, making this a very exciting time to conduct research in neuroscience.”

Last April, President Barack Obama announced the inception of the BRAIN Initiative to address brain disorders such as Alzheimer’s disease, Parkinson’s disease, schizophrenia, autism, epilepsy, stroke and traumatic brain injury. Noted Patricia E. Beeson, provost and senior vice chancellor: “Our extensive and accomplished community of neuroscientists and physicians is part of a Pitt culture that encourages cooperation and collaboration with colleagues from a variety of disciplines, including bioengineering, communication disorders, computer science, mathematics, neurology, neuroscience, neurosurgery, ophthalmology, otolaryngology, psychiatry, psychology and rehabilitation. This breadth of talent and experience makes us ideally suited to take our understanding of brain function to the next level.”

The Brain Institute’s founding scientific director is Peter L. Strick, Distinguished Professor and chair, Department of Neurobiology. He is an expert on the neural basis of movement and cognition and pioneered the use of viruses to reveal circuits of interconnected neurons. Most recently, he has begun to explore the brain connections that form the basis for the mind-body connection.

Said Strick: “The critical task of discovering how the brain develops, how it functions normally, and how to alleviate and cure abnormal function requires a broad, multi-level and multi-disciplinary approach. In other words, it ‘takes a University.’ I am enormously proud that the University of Pittsburgh has taken on this challenge.”

Initially, five centers will be established at the Brain Institute:

  • A NeuroTech Center to restore movement to the paralyzed and vision to the blind, and to develop new technology-based treatment approaches for motor and cognitive disorders. The center will create new tools for long-term recording from and stimulation of populations of neurons in the human brain.
  • A NeuroGenetics Center to develop non-human primate models of neurodevelopmental, neuropsychiatric and neurodegenerative disorders to accelerate the development of new cures and treatments for neural disorders.
  • A NeuroMapping Center to unravel the complex circuitry and patterns of activity that are the neural bases of movement, cognition, emotion, learning, language and creativity. This center will be involved in exploring the mind-body connection that is the basis of the emerging field of health neuroscience.
  • A NeuroLearning Center to study the biological bases of learning and memory, including the brain changes that accompany learning in educational domains, in human development and in overcoming cognitive impairment.
  • A NeuroDiscovery Center to support innovative, multidisciplinary and high-risk/high-reward neuroscience research.

Currently, there are few effective treatments for most brain disorders, and cures are far from imminent for many chronic and debilitating neurodegenerative and psychiatric diseases. “As the baby boomer population ages, we are facing a health crisis caused by the growing burden of neurologic and neuropsychiatric disease,” Strick said. “The basic science and the translational research fostered by the Brain Institute are the critical first steps that must be taken to meet this challenge.”


Oncogene activity key to new head/neck cancer drugs

The increased activation of a key oncogene in head and neck cancers could be the result of mutation and dysfunction of regulatory proteins that are supposed to keep the gene, which has the potential to cause cancer, in check, according to a new study led by researchers at the School of Medicine. The findings, published in the Proceedings of the National Academy of Sciences, suggest a new target for drugs to treat head and neck tumors, as well as other cancers.

Many research teams have found activation and increased signaling of a protein known as signal transducer and activator of transcription 3 (STAT3) in different kinds of cancers, and it is associated with poor prognosis, noted senior author Jennifer Grandis, Distinguished Professor of Otolaryngology and director of the Head and Neck Program at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter. In adult tissues, STAT3 triggers the production of other proteins that promote the growth and survival of cancer cells.

Said Grandis: “Until now, the question of why STAT3 could be hyperactivated has gone unanswered. Our findings reveal a possible mechanism for this abnormal activity, which could help us develop new cancer drugs.”

Noting that gene aberrations in STAT3 itself rarely occurred in head and neck cancers, she and her colleagues looked for mutations in other proteins associated with increased activity of STAT3. To be activated, STAT3 must be phosphorylated, acquiring a phosphate group. Many cancer drugs work by inhibiting enzymes called kinases that encourage this process. The team focused instead on the other side of the biochemical seesaw in which enzymes called phosphatases deactivate proteins by removing phosphates.

They found that head and neck tumors with elevated STAT3 were associated with mutations in the PTPR family of phosphatases. When they reproduced the mutations in computational and lab models, they saw that they led to dysfunction of the enzymes.

“Because the phosphatases don’t work properly, phosphate groups don’t get removed from STAT3 appropriately, and it stays activated,” Grandis explained. “These mutations essentially get rid of the brakes that might otherwise slow or even stop cancer development.”

It might be possible one day to screen tumors for mutations in the PTPR group and then treat them with drugs that inhibit STAT3’s activity, she added.

Co-investigators include other researchers from medicine, its Department of Pharmacology and Chemical Biology and UPCI; Masaryk University, Czech Republic; University of Texas; Case Western Reserve and Harvard.

The project was funded by NIH; the American Cancer Society; the Patricia L. Knebel Fund of the Pittsburgh Foundation, and the John S. Lazo Cancer Pharmacology Fellowship.


New device can reduce sleep apnea

Implantation of a sleep apnea device called Inspire Upper Airway Stimulation (UAS) therapy can lead to significant improvements for patients with obstructive sleep apnea (OSA), according to a study published in the New England Journal of Medicine. After one year, patients using the device had an approximately 70 percent reduction in sleep apnea severity, as well as significant reductions in daytime sleepiness.

The Stimulation Therapy for Apnea Reduction (STAR) trial was conducted at 22 medical centers in the United States and Europe, and is the first to evaluate the use of upper airway stimulation for sleep apnea.

OSA, which affects more than 8 million men and 4 million women in the U.S., is characterized by repeated episodes of upper airway collapse during sleep, due to narrowing or blockage. Patients with OSA stop breathing frequently during sleep, often for a minute or longer, and over half of those with OSA are overweight. Repeated episodes of apnea can lead to daytime fatigue and increase a person’s risk for heart attack, stroke, high blood pressure and even death. Treatments for OSA include weight loss, upper airway surgeries, oral appliances and continuous positive airway pressure (CPAP), which is considered the primary treatment for OSA.

Said Patrick Strollo, faculty member in medicine and clinical and translational science at the School of Medicine, medical director of the UPMC Sleep Medicine Center and lead author of the study: “While CPAP is a successful treatment when used on a regular basis, as many as half of the patients who have been prescribed CPAP are unable to use it regularly, largely due to discomfort with the mask and/or the lack of desire to be tethered to a machine. The results of this trial show a huge potential for a new and effective treatment that can help millions of patients.”

From 724 candidates initially screened, the STAR trial implanted and prospectively evaluated 126 moderate-to-severe OSA patients who had difficulty using or adhering to CPAP therapy: 83 percent of the participants were men, the mean age was 54.5 years and the mean body-mass index was 28.4.

All patients underwent surgery to implant the device, which stimulates the nerve of the tongue during sleep, thereby enlarging and stabilizing the airway and improving control of breathing.

The device was implanted in three areas: a stimulation electrode was placed on the hypoglossal nerve, which provides innervation to the muscles of the tongue; a sensing lead was placed between rib muscles to detect breathing effort, and a neurostimulator was implanted in the upper right chest, just below the clavicle.

Patients used a “controller” to turn on the device at night, so it is only used when the patient sleeps. The Inspire UAS therapy device is designed to sense breathing patterns and deliver mild stimulation to a patient’s airway muscles to keep the airway open during sleep.

Using various sleep-disorder measuring systems, patients were found to experience 68-70 percent fewer sleep-apnea episodes per hour.

This study was funded by Inspire Medical Systems.

Co-investigators included researchers from University Hospital, Mannheim; Intersom K.ln, Cologne; Sint Lucas Hospital, Amsterdam; North Memorial Sleep Health Center, Maple Grove; Paparella Ear, Head and Neck Institute; St. Cloud Ear, Nose and Throat; the University of South Florida College of Medicine; the St. Petersburg Sleep Disorders Center; the University of Cincinnati; the Medical College of South Carolina, Charleston; the Medical College of Wisconsin; Antwerp University Hospital; the University of Antwerp; the Borgess Medical Center; the Louis Stokes Cleveland Veterans Affairs Medical Center, and Case Western Reserve.


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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