A new Boston University School of Medicine (BUSM) study has found that...
Research from Boston University School of Medicine (BUSM) shows that improving vitamin D status by increasing its level in the blood could have a number of non-skeletal health benefits. The study, published online in PLOS ONE, reveals for the first time that improvement in the vitamin D status of healthy adults significantly impacts genes involved with a number of biologic pathways associated with cancer, cardiovascular disease (CVD), infectious diseases and autoimmune diseases. While previous studies have shown that vitamin D deficiency is associated with an increased risk for the aforementioned diseases, these results go a step further and provide direct evidence that improvement in vitamin D status plays a large role in improving immunity and lowering the risk for many diseases.
Vitamin D is unique in that it can be both ingested and synthesized by the body with sun exposure. It is then converted by both the liver and kidneys to a form that the body can use. An individuals’ level of vitamin D, or their vitamin D status, is determined by measuring the level of 25-hydroxyvitamin D in the blood. Vitamin D deficiency, which is defined as a status of less than 20 nanograms per milliliter (ng/mL) of 25-hydroxyvitamin D, can cause a number of health issues, including rickets and other musculoskeletal diseases. Recently, however, data suggests that vitamin D deficiency (<20 ng/mL) and vitamin D insufficiency (between 21-29 ng/mL) is linked to cancer, autoimmune diseases, infectious diseases, type 2 diabetes and cardiovascular disease.
The randomized, double-blind, single-site pilot trial involved eight healthy men and women with an average age of 27 who were vitamin D deficient or insufficient at the start of the trial. Three participants received 400 International Units (IUs) of vitamin D per day and five received 2,000 IUs per day for a two-month period. Samples of white blood cells (immune cells) were collected at the beginning of the two-month period and again at the end. A broad gene expression analysis was conducted on these samples and more than 22,500 genes were investigated to see if their activity increased or decreased as a result of the vitamin D intake.
At the end of the pilot, the group that received 2000 IUs achieved a vitamin D status of 34 ng/mL, which is considered sufficient, while the group that received 400 IUs achieved an insufficient status of 25 ng/mL.
The results of the gene expression analysis indicated statistically significant alterations in the activity of 291 genes. Further analysis showed that the biologic functions associated with the 291 genes are related to 160 biologic pathways linked to cancer, autoimmune diseases, infectious diseases and CVD. Examining gene response elements, or sequences of DNA bases that interact with vitamin D receptors to regulate gene expression, they also identified new genes related to vitamin D status. To ensure that their observations were accurate, the researchers looked at 12 genes whose level of expression does not change, and those genes remained stable throughout the trial period.
“This study reveals the molecular fingerprints that help explain the non-skeletal health benefits of vitamin D,” said Michael F. Holick, PhD, MD, professor of medicine, physiology and biophysics at BUSM and leading vitamin D expert who served as the study’s corresponding author. “While a larger study is necessary to confirm our observations, the data demonstrates that improving vitamin D status can have a dramatic effect on gene expression in our immune cells and may help explain the role of vitamin D in reducing the risk for CVD, cancer and other diseases.”
This research was supported by a pilot grant from the National Institutes of Health’s Clinical Translational Science Institute under grant award # UL-1-RR-25711.
To view the full article, visit http://dx.plos.org/10.1371/journal.pone.0058725.
BUMC Provost, BUSM Dean Karen Antman, MD, Receives MD Anderson Cancer Center’s 2013 Kripke Legend Award
The University of Texas MD Anderson Cancer Center named BUMC Provost and BUSM Dean Karen Antman, MD, as the recipient of the 2013 Margaret L. Kripke Legend Award for Promotion of Women in Cancer Medicine and Cancer Research.
A recognized expert on breast cancer, mesotheliomas and sarcomas, Antman also is widely known as a physician scientist for developing a standard treatment regimen for sarcomas, as well as for her team’s research on blood growth factors. She fought for insurance coverage of patients involved in clinical trials, which resulted in improved relationships between investigative research and the insurance industry.
“Dr. Antman’s accomplishments set a very high bar that signals to women faculty that leadership positions such as hers are obtainable,” said Elizabeth Travis, PhD, MD Anderson associate vice president of Women Faculty Programs. “Walking in Margaret Kripke’s footsteps, she’s an ideal Legend Award recipient.”
The award recognizes scientific and medical leaders who have made extraordinary efforts to hire diverse workforces, promote women to leadership roles, nominate women for awards and otherwise advance their careers. It was established in honor of University of Texas Professor Emerita Margaret Kripke, PhD, a distinguished scientist who achieved many firsts for women at MD Anderson, culminating in her appointment as executive vice president and chief academic officer. Previous winners include Nancy Hopkins, PhD, Amgen, Inc. Professor of Biology, Massachusetts Institute of Technology; Edward J. Benz, Jr., MD, president, Dana-Farber Cancer Institute and director, Dana-Farber/Harvard Cancer Center; and Janet Rowley, MD, Blum-Riese Distinguished Service Professor of Medicine, of Molecular Genetics and Cell Biology, and of Human Genetics, Section of Hematology/Oncology, University of Chicago Medical Center.
“The Kripke award is a tremendous honor,” Antman said. “Margaret Kripke is a pioneer who opened doors for me and many other women in medicine and science. As president of the American Association for Cancer Research, she gave me the first opportunity to be an AACR program chair, and I’ve always regarded her as a role model.”
Physician experts in health system issues propose a timely alternative process for harnessing and supporting physician-led innovations to rapidly address front-line health care delivery problems and improve health. Published as a Viewpoint article in the March 20th issue of the Journal of the American Medical Association (JAMA), the authors propose health systems adopt a strategy widely accepted in U.S. industries of “user-led” innovation.
User-led innovation is predicated on the idea that important enhancements to products and services are often made by users to best suit their needs. “User-led innovation is relevant to health care because clinicians and patients have an intimate view of problems and needs,” say the authors. They cite new surgical procedures, many of which originate with surgeons modifying tools and processes for better results
Corresponding author, Barry Zuckerman, MD, the Joel and Barbara Alpert Professor of Pediatrics, Boston University School of Medicine and pediatrician at Boston Medical Center, and the other authors Peter A. Margolis, MD, PhD, Professor of Pediatrics at the University of Cincinnati and Director of Research at the James M. Anderson Center for Health Systems Excellence, Cincinnati Children’s Hospital; and Kedar Mate, MD, of the Department of Medicine and Institute for Healthcare Improvement, Weill Cornell Medical College, New York, suggest that traditional, clinical academic research may not be appropriate for testing these new approaches because it is difficult to adequately assess the independent impact of an innovation when it is part of a complex system as in done in randomized control trials (RCTs).
They propose a clinician-innovator model in which the user/clinician identifies the problem, develops a solution, tests it on a small scale using a quality improvement (QI) approach. Feedback is generated to help determine effectiveness and if judged to have merit will be implemented on a larger scale. Patient feedback is key to the innovation process.
“At Boston Medical Center we have developed effective clinician-led innovations in delivering pediatric care to our low-income, minority children and their families such as Reach Out and Read, Health Leads, and the Medical-Legal Partnership programs,” notes Zuckerman.
The authors also identify early-stage approaches to care delivery innovations that use technology such as bedside visual media to improve patient understanding of their disease and treatment, a computer application listing community-based services accessible by patients, and making long acting reversible contraceptives available to sexually active adolescents in the pediatric emergency department offering point of service care that provides patients with what they want and need at the time of care avoiding a referral for another visit at a later date.
“The advantages of clinician-led innovation are that work flow and clinician acceptability are built into the iterative process, and failure is associated with only a minimal amount of time or money spent,” the authors say.
Zuckerman, Margolis and Mate propose that clinician-innovation be nurtured and resources harnessed to support this work and they call upon hospitals and medical schools to promote and reward new approaches and tools to make health systems more effective and provide better care. Clinician-innovators are developing new ideas to help patients and the authors state that the time is now for an innovation incubator to help improve and advance health services delivery.
In a very crowded Hiebert Lounge the Class of 2013 along with their friends and family awaited the stroke of noon on March 15. While Match Day happens on the same day, at the same time every year at medical schools across the country, the anticipation and excitement was fresh and infectious. With the countdown complete and cameras flashing, these doctors-in-waiting learned of their residency placements.
“It was a short three and a half years ago that the faculty welcomed you to the study of medicine at the White Coat Ceremony, and we look forward to welcoming you to the practice of medicine at commencement,” said Dean Karen Antman. “You have matched from New Hampshire to Hawaii and Canada to Texas, and the good news is that we get to keep 15 of you here at Boston Medical Center. Congratulations on all of your hard work and achievements.”
Twenty-three percent of the class will be entering internal medicine residency, 11 percent in family medicine, and 10 percent each in pediatrics and obstetrics and gynecology. Nine percent of the class will be training in emergency medicine.
Angela Jackson, MD, acting for the first time in her capacity as associate dean for student affairs at a Match Day, told the class what a privilege it is to share such an important event in their lives. After congratulating the class, Phyllis Carr, MD, former associate dean for student affairs noted their special capacity for caring for each other and announced that the class had chosen Bill Hammond as their class speaker.
“On behalf of the 8,000 BUSM alumni across the country, I want to congratulate you on the successful completion of your medical education,” said Jean Ramsey, MD, associate dean for alumni affairs. “We look forward to welcoming you to the BUSM Alumni Association on commencement and to getting to know you better as our colleagues and fellow graduates.”
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Awarded the first of its kind funding to provide FDA-mandated opioid prescribing education, Boston University School of Medicine (BUSM) has launched a program to train health care providers how to safely and effectively manage patients with chronic pain using opioid analgesics.
With approximately 100 million Americans affected by chronic pain, the appropriate prescribing of opioids is a national concern. The FDA requires that manufacturers of extended release/long-acting (ER/LA) opioid analgesics, as part of a Risk Evaluation and Mitigation Strategy (REMS), create a fund to support comprehensive prescriber education in the safe use of these medications. BUSM was the sole grantee in the first round of funding, receiving an unrestricted award of more than $1.8 million by the manufacturers of ER/LA opioid analgesics, known as the REMS Program Companies (RPC).
Offered in collaboration with the Council of Medical Specialty Societies (CMSS) and the Federation of State Medical Boards (FSMB), BUSM’s Safe and Competent Opioid Prescribing Education (SCOPE) of Pain program is based on the FDA curriculum known as the Blueprint for Prescriber Education for Extended Release and Long- Acting Opioid(ER/LA) Analgesics.
Directed by Daniel Alford, MD, associate professor of medicine at BUSM, the program’s first phase, launched on March 1, 2013, is a three-module online educational activity. It is designed to train providers how to determine appropriateness of opioid prescribing, assess risk of misuse, and monitor patients for risk and benefits of opioid treatment for pain management. The next phases of the SCOPE of Pain Continuing Medical Education program will include conferences in ten states which, in addition to the essential curriculum, will feature state-specific policy and resource panels. These panels will be recorded and archived as part of the online educational activity. There will also be train-the trainer sessions designed to develop a national cohort of SCOPE of Pain trainers, who will deliver a series of workshops at local hospitals and community health centers around the country.
Dr. Norman Kahn, Executive Vice President and CEO of the CMSS notes that “CMSS believes education designed for the prescriber community is paramount to helping clinicians safely prescribe opioids while addressing the critical public health problem faced by opioid misuse.”
Dr. Humayun J. Chaudhry, President and CEO of the FSMB, adds that “The FSMB believes educational initiatives such as this collaboration are crucial in raising awareness with physicians of the risks opioids pose, while providing a framework to ensure physicians who prescribe opioids do so responsibly and safely.”
“We are proud to have been selected to receive the first grant for such an important education initiative,” says Barry Manuel, MD, Associate Dean for Continuing Medical Education and Professor of Surgery at BUSM. “It is a testament to the quality and the comprehensive nature of the professional medical education provide by Boston University School of Medicine.”
About BUSM Continuing Medical Education (CME)
Boston University School of Medicine (BUSM) has been sponsoring Continuing Medical Education (CME) activities since 1973. In 2012, BUSM was reaccredited with Commendation by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians and reaccredited with Distinction by the American Nurses Credentialing Center (ANCC) as a provider of continuing nursing education. Within the last five years BUSM has educated more than 179,000 health care professionals.
Founded in 1965, CMSS was created to provide an independent forum for the discussion by medical specialists of issues of national interest and mutual concern. Today, CMSS represents thirty-nine societies with an aggregate membership of 700,000 US physicians. Its main purpose is to provide a forum for collaboration to influence policy, medical education and accreditation from a broad, cross-specialty perspective. CMSS is the unified voice for specialty societies established to improve the United States’ healthcare system and health of the public. For more information, visit CMSS at www.cmss.org.
The Federation of State Medical Boards (FSMB) is a national non-profit organization representing the 70 medical and osteopathic boards of the United States and its territories. The FSMB leads by promoting excellence in medical practice, licensure, and regulation as the national resource and voice on behalf of state medical and osteopathic boards in their protection of the public.
BUMC Goes Latin! Celebrate Multicultural Diversity with Students, Faculty, Staff, Patients and Musicians
On Sunday, April 7, the great variety and rhythmic wonders of Latin music will be highlighted on the BU Medical Campus. A concert featuring a select group of Berklee College of Music artists, the BUMC Band, and other guest musicians associated with the Medical Campus Arts Outreach Initiative will be performing. The program will review the origins of Latin music beginning with the music of Spain, traveling across Latin America and the Caribbean, until reaching the Latin influence in American music.
During this event two Latino physicians will be recognized for their contributions to Boston Medical Center and Boston University School of Medicine.
Admission is free on a first come first served basis. Parking for concert attendees is available at the 710 Albany Street garage. Please have your ticket validated at the concert entrance.
This event is presented by
- Boston University School of Medicine, Office of Diversity and Multicultural Affairs,
- Latino Medical Student Association
- Medical Campus Arts Outreach Initiative
The Office of Financial and Business Affairs has moved to Charles River Campus, 25 Buick St, third floor. There is no longer an office at Harrison Court. “We look forward to continuing to support the BU Medical Campus from our new location,” said Director, Financial and Business Affairs Hiram Rodriguez.
Phone numbers will be changing, so please update the following:
- Hiram Rodriguez, 353-4177
- Lorraine Weiss, 353-7146
- Jannette Reese, 353-7142
Please use this address for mail and deliveries:
BUMC Financial and Business Affairs
25 Buick St., 3rd Floor
Boston, MA 02215
BUSM Study Reveals B cells as Therapeutic Targets to Alter Obesity-Associated Inflammation and Type 2 Diabetes
New research from Boston University School of Medicine (BUSM) reveals that B cells regulate obesity-associated inflammation and type 2 diabetes through two specific mechanisms. The study, published in the Proceedings of the National Academies of Sciences, indicates the importance of continuing to explore B cells as a therapeutic target to treat these diseases. Barbara Nikolajczyk, PhD, associate professor of microbiology at BUSM, is the study’s senior author.
The incidence of diabetes continues to rise at alarming rates. According to the National Institute of Diabetes and Digestive and Kidney Diseases, the disease now affects approximately 25.8 million Americans. In 2007, the National Institutes of Health estimated that the direct and indirect costs of diabetes were a staggering $174 billion.
Type 2 diabetes, which is a common result of obesity, occurs when the body produces insulin but cannot use it properly (insulin resistance) or the body does not produce enough insulin. The body needs insulin to absorb glucose and generate energy. If the body does not produce and respond to insulin appropriately, it can, over time, lead to various complications such as cardiovascular disease, nerve damage, kidney disease and blindness.
Previous research has shown that B cells, which are white blood cells of the immune system, promote inflammation and can lead to the development of type 2 diabetes, but the mechanisms underlying B cell function were unclear.
The results of this study shed light on that question and indicate that B cells secrete a pro-inflammatory ratio of proteins called cytokines, which directly promote the insulin resistance that characterizes type 2 diabetes. The researchers also demonstrated that B cells directly regulate inflammatory T cells, an immune cell type known to cause insulin resistance in animal models of disease.
“Now that we have identified the specific mechanisms by which B cells promote inflammation, we can help develop novel, targeted approaches to treat type 2 diabetes,” said Nikolajczyk. “Our study supports the continued exploration of FDA-approved B cell depletion drugs, which are known to be generally safe and effective, as novel agents to prevent obesity-associated inflammation and type 2 diabetes.”
Research included in this study was supported in part by the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under grant award numbers R21DK089270 and R56DK096525 (PI: Nikolajczyk) and R56DK090455 (PI: Gerald Denis); the NIDDK’s Boston Area Diabetes Endocrinology Research Center Pilot Program and the Boston Nutrition Obesity Research Center under grant award number DK046200; the NIH’s National Institute of Dental and Craniofacial Research under grant award number 5R21DE021154 (PI: Nikolajczyk); the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) Immunology Training Program under grant award number AI007309; the NIH’s National Heart, Lung, and Blood Institute’s Hematology Training Program under grant award number HL007501; and the Evans Center for Interdisciplinary Biomedical Research at BUSM (PI: Nikolajczyk and Denis).
Researchers at Boston University School of Medicine (BUSM) have, for the first time, identified a specific group of cells in the brainstem whose activation during rapid eye movement (REM) sleep is critical for the regulation of emotional memory processing. The findings, published in the Journal of Neuroscience, could help lead to the development of effective behavioral and pharmacological therapies to treat anxiety disorders, such as post-traumatic stress disorder, phobias and panic attacks.
There are two main stages of sleep – REM and non-REM – and both are necessary to maintain health and to regulate multiple memory systems, including emotional memory. During non-REM sleep, the body repairs tissue, regenerates cells and improves the function of the body’s immune system. During REM sleep, the brain becomes more active and the muscles of the body become paralyzed. Additionally, dreaming generally occurs during REM sleep, as well as physiological events including saccadic eye movements and rapid fluctuations of respiration, heart rate and body temperature. One particular physiological event, which is a hallmark sign of REM sleep, is the appearance of phasic pontine waves (P-waves). The P-wave is a unique brain wave generated by the activation of a group of glutamatergic cells in a specific region within the brainstem called the pons.
Memories of fearful experiences can lead to enduring alterations in emotion and behavior and sleep plays a natural emotional regulatory role after stressful and traumatic events. Persistence of sleep disturbances, particularly of REM sleep, is predictive of developing symptoms of anxiety disorders. A core symptom of these disorders frequently reported by patients is the persistence of fear-provoking memories that they are unable to extinguish. Presently, exposure therapy, which involves controlled re-exposure to the original fearful experience, is considered one of the most effective evidence-based treatments for anxiety disorders. Exposure therapy produces a new memory, called an extinction memory, to coexist and compete with the fearful memory when the fearful cue/context is re-encountered.
The strength of the extinction memory determines the efficacy of exposure therapy. A demonstrated prerequisite for the successful development of an extinction memory is adequate sleep, particularly REM sleep, after exposure therapy. However, adequate or increased sleep alone does not universally guarantee its therapeutic efficacy.
“Given the inconsistency and unpredictability of exposure therapy, we are working to identify which process(es) during REM sleep dictate the success or failure of exposure therapy,” said Subimal Datta, PhD, director and principle investigator at the Laboratory of Sleep and Cognitive Neuroscience at BUSM who served as the study’s lead author.
The researchers used contextual fear extinction training, which works to turn off the conditioned fear, to study which brain mechanisms play a role in the success of exposure therapy. The study results showed that fear extinction training increased REM sleep. Surprisingly, however, only 57 percent of subjects retained fear extinction memory, meaning that they did not experience the fear, after 24 hours. There was a tremendous increase of phasic P-wave activity among those subjects. In 43 percent of subjects, however, the wave activity was absent and they failed to retain fear extinction memory, meaning that they re-experienced fear.
“The study results provide direct evidence that the activation of phasic P-wave activity within the brainstem, in conjunction with exposure therapy, is critical for the development of long-term retention of fear extinction memory,” said Datta, who also is a professor of psychiatry and neurology at BUSM. In addition, the study indicates the important role that the brainstem plays in regulating emotional memory.
Future research will explore how to activate this mechanism in order to help facilitate the development of new potential pharmacological treatments that will complement exposure therapy to better treat anxiety and other psychological disorders.
According to the National Institute of Mental Health, anxiety disorders affect approximately 40 million American adults each year. While anxiety can sometimes be a normal and beneficial reaction to stress, some people experience excessive anxiety that they are unable to control, which can negatively impact their day to day life.
Research included in this study was supported in part by the National Institutes of Health’s National Institute of Mental Health under grant award number MH 59839 (PI: Datta) and the National Institute of Neurological Disorders and Stroke under grant award number NS 34004 (PI: Datta).
In a Clinical Crossroads article featured in the March 6, 2013 issue of the Journal of the American Medical Association (JAMA), Dr. Dan Alford from Boston University School of Medicine (BUSM) and Boston Medical Center (BMC) suggests that prescription opioid abuse can be minimized by monitoring patients closely for harm by using urine drug testing (UDT), pill counts, and reviewing prescription drug monitoring program data when available.
Approximately 100 million Americans have chronic pain. The safe and effective use of opioids for the management of chronic pain is complex. Clinicians must balance the goals of relieving pain and suffering while not harming the patient resulting in addiction and overdose.
The JAMA article describes a 71-year old man who had been treated for chronic low back pain since 1981. After getting no pain relief from non-opioids, he achieved pain control with long-term opioids. However a UDT found no opioid in his system on two occasions and his opioid was discontinued. He explained that he occasionally drinks alcohol and does not take his opioid medication when doing so.
“When a patient exhibits behavior for opioid misuse, the clinician should first confirm that the UDT was accurate. If confirmed, the clinician should interview the patient considering the full differential diagnosis for the behavior of concern. Once the etiology has been determined, a change in treatment plan may occur,” explained Alford, an associate professor of medicine at BUSM and the Director of the Addiction Medicine Fellowship program at BMC.
Alford stresses that monitoring for benefit includes measuring improvement in pain, function and quality of life. Monitoring for harm includes detecting opioid misuse through UDT, pill counts and use of state prescription drug monitoring programs.
Decisions to continue or discontinue opioids should be based on the risk-to-benefit ratio. “In this case of the patient with no opioid in his UDT if he was benefiting but taking less than prescribed, I would inquire about the status and safe storage of his extra medication. I would decrease his dose and schedule close follow up with random pill counts and UDT. If there was too much risk (misuse such as diversion) despite benefit, I would discontinue his opioid therapy as was done in this case,” added Alford.