A recent study may help begin to explain how cancer develops though...
By Gina P Orlando
Boston University Researchers Explore Possible Link between Cognitive Depressive Symptoms and Antiretroviral Therapy Uptake
Researchers from Boston University’s School of Medicine (BUSM) and College of Arts and Sciences (CAS) found that among HIV-infected Russian drinkers, depressive symptom severity alone was not significantly associated with lower rates of antiretroviral therapy (ART) initiation. However, when examining cognitive symptoms of depression, results showed that high levels of depressive symptoms may be associated with delayed ART initiation. The findings are published online in the journal AIDS and Behavior.
While depressive symptoms impact on adherence to ART is widely studied, there are few studies that have investigated the impact of these symptoms on initiating ART. According to the researchers, understanding factors associated with ART initiation may be particularly useful in locations where it is not as commonly prescribed, such as Russia, which has experienced a dramatic increase in HIV infection rates during the past decade.
Led by Jeffrey Samet, MD, chief and professor of internal medicine at BMC and BUSM and principal investigator of the study, the researchers enrolled participants from the HIV’s Evolution in Russia – Mitigating Infection Transmission and Alcoholism in a Growing Epidemic (HERMITAGE) study. The 133 eligible participants had their depressive symptom severity measured at the six- and 12-month marks.
Although the results did not provide evidence that depressive symptom severity alone had a statistically significant effect on ART initiation, findings suggested a potential role of cognitive depressive symptoms in decisions to initiate ART. According to the researchers, cognitive symptoms of depression are often considered to be an index of depression that is less influenced by HIV symptoms. Further, the study demonstrated findings consistent with existing studies that show participants with co-morbid heavy drinking and injection drug use appeared to have delayed ART initiation.
“Depressive symptoms have been shown to influence progression of HIV and have been associated with poor virologic response to treatment and increased immunologic failure,” said Tracie Goodness, a doctoral student in clinical psychology at CAS and corresponding author of the study. “Timely ART initiation has been associated with multiple positive health effects, such as lower mortality, increased immune functioning and lower rates of HIV transmission,” she added.
Although more research is needed, these results provide initial evidence of the role of depressive symptoms and may contribute to the understanding of ART initiation in HIV-infected populations
The study was supported by the National Institute on Alcohol Abuse and Alcoholism: R01AA016059, U24AA020778, U24AA020779, and K24AA15674.
Two Boston University School of Medicine (BUSM) faculty members, David Center, MD, and William W. Cruikshank, PhD, have been named Fellows of the National Academy of Inventors (NAI). Election to NAI Fellow status is a high professional distinction accorded to academic inventors who have demonstrated a prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on quality of life, economic development and the welfare of society.
Center and Cruikshank join 141 peer innovators who represent 94 universities and government and non-profit research institutes. Together, they hold more than 5,600 U.S. patents. Included in the 2013 class are 26 presidents and senior leadership of research universities and non-profit research institutes, 69 members of the National Academies (IOM, NAS, NAE), five inductees of the National Inventors Hall of Fame, six recipients of the U.S. National Medal of Technology and Innovation, two recipients of the U.S. National Medal of Science and nine Nobel Laureates, among other major awards and distinctions.
Center is chief of pulmonary, allergy and critical care medicine at BMC and the Gordon and Ruth Snider Professor of Pulmonary Medicine at BUSM. In addition, he is associate provost for Translational Clinical Research at Boston University, where he oversees efforts to facilitate translational research and leads initiatives that identify new areas for development as well as directs the Clinical and Translational Research Institute, funded by the National Institutes of Health. His research interests include asthma pathology, mechanisms of inflammation and immune-based lung disease.
Cruikshank, director of immunology and a professor of medicine at BUSM, has been conducting basic science and translational research for the past 34 years and has authored more than 160 publications in peer reviewed journals. His research addresses the development of asthma as well as mechanistic steps involved in the onset of cutaneous T cell lymphomas. Serving as director of the Summer Undergraduate Research Program at BUSM, Cruikshank is focused on increasing diversity within the graduate programs and is providing summer research opportunities for under-represented minorities.
Center and Cruikshank were nominated by the NAI Fellows Selection Committee that comprises 13 Members including NAI Charter Fellows, recipients of U.S. National Medals, National Inventors Hall of Fame inductees, members of the National Academies and senior officials from the United States Patent and Trademark Office, the American Association for the Advancement of Science, the Association of University Technology Managers, and the National Inventors Hall of Fame.
Researchers from Boston University School of Medicine (BUSM) and the College of Arts and Sciences (CAS) have found that among heavy-drinking Russian HIV-infected patients, elevated depressive symptoms were associated with long-term alcohol use. These findings suggest that HIV-infected populations who are depressed are more likely to drink heavily. The study is published online in the journal Drug and Alcohol Dependence.
Previous studies have shown that heavy drinking has been linked with HIV disease progression and may interfere with treatment. However, few studies have examined whether depressive symptoms are associated with subsequent alcohol use. The researchers used the National Institute for Alcohol Abuse and Alcoholism (NIAAA) definition of risky drinking, meaning men consuming more than four drinks on a single day or more than 14 per week and women consuming more than three drinks on a single day or seven per week.
“Approximately one-million individuals are living with HIV in
The researchers recruited HIV-positive individuals from 18–70 years old who reported unprotected sex and heavy drinking in the past six months from addiction treatment facilities in
According to the researchers, among heavy drinking HIV-infected patients, elevated depressive symptoms were associated with greater subsequent alcohol use. They also found that depressive symptoms were more strongly associated with the amount of drinks per day, rather than the number of days of heavy drinking.
“These results suggest an additional mechanism through which depressive symptoms may negatively influence HIV-related outcomes among this population. Findings from this study highlight the importance of addressing depressive symptoms among HIV patients who engage in heavy drinking,” said Tibor Palfai, PhD, professor of psychology in CAS and lead author of the study. The researchers propose that more studies are needed to address more specific subsets of HIV-positive populations.
The current study was supported in part by NIAAA, R01AA16059 (PI: Samet).
A new study recently published in Cancer Causes and Control by investigators from the Slone Epidemiology Center at Boston University, adds further evidence about the adverse effects of cigarette smoking on health. The researchers found that both active and passive smoking were associated with an increased risk of breast cancer in African-American women.
The data was collected during 14 years of follow-up among participants in the Black Women’s Health Study, a study of 59,000 African-American women that began in 1995. The participants updated information on their smoking habits throughout follow-up and also provided information on their exposure to the smoke of others (passive smoking). During follow-up for the present research, 1,377 women were diagnosed with breast cancer. Among women who began smoking earliest and smoked most heavily, the incidence of premenopausal breast cancer increased by 70 percent. The associations were most apparent for estrogen receptor positive breast cancer. Passive smoking was associated with a 40 percent increase in risk of premenopausal breast cancer.
According to the researchers, the earliest studies of the health effects of smoking did not find an increased risk of breast cancer, probably because in those early years there were few long-term smokers. In recent years, studies of smoking and breast cancer have more consistently found an increased risk among women who smoked heavily for many years. Lynn Rosenberg, ScD, lead author of the study, believes that the evidence is now clear that smoking increases the risk of breast cancer. “What remains to be determined is whether there are particular times during life that smoking is particularly hazardous, such as before the first pregnancy, and whether there are particular groups of women who are especially vulnerable,” she said.
Funding for this study was provided by the National Cancer Institute.
David J. Salant, MD, professor of pathology and laboratory medicine at Boston University School of Medicine (BUSM) and chief, section of nephrology at Boston Medical Center (BMC), has been awarded the 2013 John P. Peters Award from the American Society of Nephrology (ASN). The award was presented at ASN Kidney Week in Atlanta earlier this month.
The John P. Peters Award recognizes individuals who have made substantial research contributions to the discipline of nephrology and have sustained achievements in one or more domains of academic medicine including clinical care, education and leadership. Established in 1983, this annual award is named for one of the fathers of the discipline of nephrology.
The American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.
With over 130 contributions to scientific literature, Salant has written several clinical papers on diverse nephrological subjects and book chapters on glomerular diseases and vasculitis of the kidney. He served as chairman of the American Board of Internal Medicine Subspecialty Board of Examiners in Nephrology.
Salant earned his medical degree from the University of the Witwatersrand in Johannesburg, South Africa. He completed his residency at Johannesburg General Hospital, where he gained extensive experience in renal transplantation, dialysis and other aspects of clinical nephrology before coming to BMC and BUSM. He also is a faculty member of the renal training program at BUSM.
Devin Mann, MD, MS, assistant professor of medicine at Boston University School of Medicine (BUSM) and attending physician at Boston Medical Center (BMC), has been appointed to the Health Information Technology (HIT) Policy Committee by the U.S. Government Accountability Office (GAO).
Mann, who was one of three new appointments, will serve as a researcher on the committee and will complete a full, three-year term through October 2016.
“In developing policy for health information technology, it’s important to take into account expertise related to privacy and security, health care research, as well as the views of health care workers who are the users of HIT,” said Gene L. Dodaro, Comptroller General of the United States and head of the GAO. “A number of individuals with backgrounds in these areas responded to GAO’s request for nominations, and I am pleased to announce the addition of today’s new appointments.”
The American Recovery and Reinvestment Act of 2009 established the HIT Policy Committee and gave the Comptroller General responsibility for appointing 13 of its 20 members. The HIT Policy Committee makes recommendations to the National Coordinator for Health IT on the development and adoption of a nationwide health information infrastructure, including standards for the exchange of patient medical information.
“I am honored to have been selected to serve on this prestigious committee and I look forward to representing BUSM and BMC over the next three years,” said Mann.
To this role, Mann brings years of experience in healthcare IT. His research has focused on the use of health information technology in improving clinical care, such as developing decision support systems with electronic health records to support advanced medical home care. He serves as the lead physician in ambulatory implementation of the Epic system at BMC and co-leads Epic optimization at East Boston Neighborhood Health Center.
Mann has served as the HIT lead on the Evidence-Based Medicine Task Force of the Society of General Internal Medicine. He received his medical degree from the New York University School of Medicine and his MS of Science in Clinical Epidemiology and Health Services Research from Weill Cornell Medical College.
For more information visit the GAO Health Care Advisory Committees web page at http://www.gao.gov/about/hcac/.
A review article by researchers at Boston University School of Medicine (BUSM) suggests that epigenetics may be a useful target to stop the growth, spread and relapse of cancer. The findings are published online in Volume 14 of the International Journal of Molecular Sciences.
The term epigenetics refers to the external modifications to DNA that turn genes “on” or “off.” These modifications do not change the DNA sequence, but instead, they affect how cells read genes.
The researchers propose that epigenetic and other changes mediate the development of cancer progenitor cells. These cells represent the early stage of cancer cell development and can grow rapidly to become full-fledged cancer. According to the researchers, progression of different cancer stages and development of metastatic potential requires differentiation of these cancer progenitor cells.
“These findings are not only important in understanding how cancer progresses, but also help in understanding how cancer progenitor cells grow and differentiate via epigenetic regulators,” said Sibaji Sarkar, PhD, instructor of medicine at BUSM.
Mutated cells are more vulnerable to the environment. Some of these mutations may alter epigenetic regulation in addition to epigenetic changes occurring by external and internal influences, which impacts gene expression and regulates cell behavior, playing a profound role when normal cells develop into progenitor cancer cells.
Sarkar and his colleagues hypothesize that when the progenitor cancer cells metastasize, rapid growth halts. When differentiation is complete, the rapid growth resumes.
The researchers believe that epigenetic mechanisms are involved in this process. Once a degree of metastatic form of cancer is achieved, the genes, which cause the change, become inactive and the genes causing rapid growth are again turned on.
“The acknowledgement of epigenetic changes as key regulators of this switching is expected to generate better epigenetic drugs. It has been suggested that epigenetic drug treatment in combination with standard chemotherapeutic drugs may have better outcomes in preventing and treating drug-resistant cancers,” he added.
This study was funded in part by the American Cancer Society. Garrick Horn, Kimberly Moulton, Anuja Oza, Shannon Byler, Shannon Kokolus and Mckenna Longacre are co-authors of the review article.
A recent study performed by researchers at Boston Medical Center (BMC), Boston University School of Medicine (BUSM), Boston University School of Public Health (BUSPH), and Tufts Medical Center found that women with multiple barriers to healthcare, especially those with social barriers such as problems with housing and income, experienced delays in cancer screening follow up compared to those with fewer barriers or no social barriers.
The study, which appears online in the Journal of General Internal Medicine, was led by Sarah Primeau, MSW, research assistant in the department of general internal medicine at BUSM.
Previous studies on healthcare barriers have shown that training individuals from the community, known as patient navigators, to provide emotional and logistical support to patients is an effective way to care for patients in a culturally sensitive way. However, these studies have not addressed whether patient navigators are also effective in addressing social service barriers such as financial problems, employment issues, health insurance, housing constraints and adult and child care.
“Social barriers are more complex than other obstacles to healthcare such as transportation or language and will likely require interventions that healthcare providers and patient navigators aren’t traditionally trained to provide,” said Primeau.
The study looked at 1,493 subjects enrolled in the Boston Patient Navigation Research Program (PNRP), a study performed at BMC from 2007-2010 that used patient navigators to help women with breast and cervical cancer screening abnormalities. The researchers used the data to separate the women into groups based on how many social barriers the navigator was able to identify. They then examined the data to see how long it took for each patient to reach a final diagnosis from the time of the initial abnormal screening test.
The researchers found that it took longer to achieve a final diagnosis in the patients with multiple barriers to healthcare, and that having one or more social barrier further increased the follow up time. The results of this study indicate that there is a continued need to better understand and overcome complex social obstacles to patient care.
“The findings suggest that not all women benefit equally from patient navigation and there is a need for more research into the innovation of cancer care delivery, and into a possible new model of patient navigation enhanced by legal advocacy,” said senior author, Tracy A. Battaglia, MD, director of the Women’s Health Unit at BMC and associate professor of medicine and epidemiology at BUSM.
Funding for this study was provided in part by the Susan G. Komen Foundation (KG101421).
Transporting Nutrients into Cells without Energy or a Transporter: BUSM Researchers Make a Case for Free Fatty Acids
The current global epidemic of obesity-linked diabetes and its associated consequences -cardiovascular, neurological and renal diseases – is a growing public health problem for which therapeutic options are limited.
In obesity, fatty acids, derived mostly from adipose tissue, alter lipid metabolism in other tissues such as liver and skeletal muscles. Both impaired fatty acid metabolism and glucose are hallmarks of diabetes.
In a recent study published in the journal Biochemistry, a research group led by James A. Hamilton, PhD, professor of physiology, biophysics and radiology at Boston University School of Medicine (BUSM), applied novel fluorescent methods to measure the rate by which fatty acids bind to and move across the fatty acid membrane to become metabolized.
“Our study shows that fatty acid entry into cells occurs by diffusion without catalysis by a protein previously described as a fatty acid transport protein. However, this protein promotes intracellular metabolism and storage,” said Hamilton. “With this advance in basic science, new drugs can be designed that target the exact mechanism more precisely than currently available drugs.”
Previous research has shown that glucose transport under the control of insulin is mediated by a transport protein called GLUT4. However, how fatty acids enter into cells has been an important unsolved problem, especially whether there are gatekeeper plasma membrane proteins that regulate fatty acid translocation across the membrane, thereby controlling the supply of fatty acids to the interior of the cell. Although several proteins postulated to be fatty acid transporters have now been shown to have other roles, the mechanistic roles of the protein CD36 have remained elusive and are widely debated.
After measuring the products of fatty acid metabolism over time, the researchers found that CD36 enhances fatty acid metabolism into triglycerides (fat deposits), without increasing fatty acid translocation across the membrane in a cell line that does not normally synthesize triglycerides. Thus, CD36 increases fatty acid uptake by increasing intracellular metabolism, which promotes diffusion of fatty acids into cells.
The work was supported by a grant from the American Diabetes Association. The study’s co-authors are Su Xu, Anthony Jay, Nasi Huang, and Kellen Brunaldi.
Boston University Researchers Test Effectiveness of Behavioral and Medication Treatments for Patients with Alcoholism and Anxiety
Domenic Ciraulo, MD, chair of psychiatry at Boston University School of Medicine (BUSM) and David H. Barlow, PhD, professor of psychology at Boston University (BU), have collaborated to study the effect of behavioral and medication treatments on patients with alcoholism and anxiety.
The findings, published in the journal Behaviour Research and Therapy, suggest that Transdiagnostic cognitive behavioral therapy (CBT) was more effective in reducing heavy drinking in anxious alcoholics than progressive muscle relaxation therapy (PMR). They also found that the addition of medication to either CBT or PMR participants did not decrease their alcohol consumption.
Participants were divided into four groups; one receiving the antidepressant Venlaflaxine coupled with CBT, one receiving Venlaflaxine with PMR, and the other groups receiving a placebo coupled with either CBT or PMR. After 11 weeks the participants in the group receiving a placebo and CBT alone reported their heavy drinking had significantly decreased when compared to the other groups receiving treatment.
“It is vital to find better treatments, whether they are medication therapies or behavioral interventions,” said Ciraulo, principal investigator of the study. “This study points to the importance of behavioral approaches to decrease heavy drinking through strategies to improve emotional regulation.”
According to the researchers, while anti-depressant medications may help to control anxious feelings, the ability to acknowledge and respond to such intense feelings may be one reason that CBT is effective. This may be why the addition of an anti-depressant to CBT did not lead to improved outcomes.
“The goal of Transdiagnostic CBT in this study was not to directly treat the specific anxiety symptoms of each anxiety disorder, but rather teach broad skills to cope with emotional issues that underlie a cluster of internalizing (mood and anxiety) disorders that often accompany alcoholism and may contribute to its onset and maintenance,” said Barlow co-author of the study.