Author Interviews, MD Anderson / 10.02.2015

Dihua Yu, M.D., Ph.D. Hubert L. & Olive Stringer Distinguished Chair in Basic Science Professor and Deputy Chair Department of Molecular and Cellular Oncology Co-Director, Center of Biological Pathways The Univ. Texas MD Anderson Cancer Center Houston, TX 77030MedicalResearch.com Interview with: Dihua Yu, M.D., Ph.D. Hubert L. & Olive Stringer Distinguished Chair in Basic Science Professor and Deputy Chair Department of Molecular and Cellular Oncology Co-Director, Center of Biological Pathways The Univ. Texas MD Anderson Cancer Center Houston, TX 77030 Medical Research: What is the background for this study? Dr. Yu: Transforming growth factor β (TGF-β) functions as a tumor suppressor in premalignant cells but may also function as a metastasis promoter in cancer cells. This study aimed to understand how the growth factor makes this switch between tumor suppressor to tumor promoter. Medical Research: What are the main findings? Dr. Yu: We reported that 14-3-3ζ overexpression (14-3-3ζ+++) can switch TGF-β’s function from tumor suppressor to metastasis promoter by changing Smad partners. Specifically, 14-3-3ζ+++ led to destabilization of p53, a Smad determinant in pre-malignant cells, thus disrupting p53/Smad complex, and consequently inhibiting TGF-β-induced p21 expression and cytostatic function in non-malignant human mammary epithelial cells (HMECs). On the contrary, 14-3-3ζ+++ stabilized Gli2, a Smad partner in cancer cells, and Gli2 complexed with Smads to promote TGF-β-induced parathyroid hormone-related protein (PTHrP) expression, which enhanced breast cancer bone metastasis. Remarkably, both transcriptomic analyses and clinical pathology data indicated that 14-3-3ζ+++ is associated with the loss of TGF-β’s tumor suppressor function and the gain of its metastasis promoter function by changing contextual partners of Smads. Taken together, we have identified 14-3-3ζ as a novel molecular switch of TGF-β’s function by altering Smad partners from p53 in pre-malignant cells to Gli2 in cancer cells. The study provided important answers to the long-standing questions of how and when TGF-β switches its functional roles from a tumor suppressor to a metastasis promoter. The findings established a scientific base for a new strategy of selectively targeting TGF-β signaling in cancer by inhibiting the cancer-specific Smad partner without blocking TGF-β’s tumor suppressor function in normal tissues. (more…)
Author Interviews, Mental Health Research, UCSF / 09.02.2015

Ezequiel Morsella, Ph.D. Associate Professor of Neuroscience Department of Psychology San Francisco State University Assistant Adjunct Professor Department of Neurology University of California, San Francisco Boardmember, Scientific Advisory Board Institute of Cognitive Neurology (INECO), Buenos AiresMedicalResearch.com Interview with: Ezequiel Morsella, Ph.D. Associate Professor of Neuroscience Department of Psychology San Francisco State University Assistant Adjunct Professor Department of Neurology University of California, San Francisco Boardmember, Scientific Advisory Board Institute of Cognitive Neurology (INECO), Buenos Aires Medical Research: What is the background for this study? What are the main findings? Dr. Morsella: Previous studies have demonstrated that, under certain experimental conditions, conscious processes in the brain can function in a way that resembles reflexes.  In past research, a single ‘high-level’ thought (e.g., the name of a visually-presented object) was triggered involuntarily by external stimuli. The current research is the first to trigger, not one, but two high-level unintentional conscious thoughts. In this experiment, participants were presented with an object (e.g., the picture of a star) and instructed to not subvocalize (i.e., name in one’s head but not aloud) the name of the object nor count the number of letters comprising the name of the object.  On many trials, participants experienced both cognitions (e.g., “STAR” and “4”), even though these thoughts were against the intentions of the participant. Thus, this is the first demonstration of external control of two thoughts in the stream of consciousness. This research is based in part on the pioneering investigations of Wegner, of Gollwitzer, and of Ach. (more…)
Asthma, Author Interviews, NIH, OBGYNE / 07.02.2015

Pauline Mendola, PhD, Investigator Epidemiology Branch Division of Intramural Population Health Research Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH Rockville, MD 20852MedicalResearch.com Interview with: Pauline Mendola, PhD, Investigator Epidemiology Branch Division of Intramural Population Health Research Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH Rockville, MD 20852 Medical Research: What is the background for this study? What are the main findings? Dr. Mendola: Asthma is the most common chronic disease in pregnancy and both asthma and maternal race/ethnicity are associated with adverse pregnancy outcomes. Since the prevalence of asthma also varies by race/ethnicity, we wanted to assess whether asthma was an important contributor to racial/ethnic disparities in pregnancy outcomes. We examined the joint impact of maternal race/ethnicity and asthma status on the risk of obstetric and neonatal outcomes. In general, maternal asthma did not impact the risk of obstetric and neonatal complications within racial/ethnic groups. However, compared to mothers of the same race/ethnicity without asthma, White and Hispanic asthmatic mothers were more likely to have infants born small-for gestational age or admitted to the NICU. White women with asthma were also at increased risk of preeclampsia and maternal hemorrhage and Hispanic mothers with asthma were more likely to have infants with apnea. Despite their increased risk of maternal asthma and neonatal and obstetric complications, maternal asthma did not impact the risk of complications among Black women or their infants. (more…)
Author Interviews, Brigham & Women's - Harvard, PNAS, Sleep Disorders / 06.02.2015

Christa Van Dort PhD Department of Anesthesia, Critical Care, and Pain Medicine, Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts General Hospital, Harvard Medical School Boston, MA, 02114MedicalResearch.com Interview with: Christa Van Dort PhD Department of Anesthesia, Critical Care, and Pain Medicine, Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts General Hospital, Harvard Medical School Boston, MA, 02114 Medical Research: What is the background for this study? What are the main findings? Dr. Van Dort:  Sleep is crucial for survival and maintenance of health.  Inadequate sleep and sleep disorders impair many brain and body functions such as executive function, the immune system and memory consolidation. The benefits of sleep are dependent on normal sleep physiology and patterns. Natural sleep is composed of non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep alternating every 90 min in humans.  Each stage provides different benefits, for example deep NREM sleep is associated with feeling rested and REM sleep is important for learning. Current sleep aids do not effectively restore normal sleep physiology or timing and as a result do not fulfill the important functions of natural sleep.  To develop new strategies for reproducing natural sleep, we aimed to understand each component of sleep (NREM and REM sleep) individually and then in combination. Cholinergic neurons have been hypothesized to control REM sleep for many years but no one had been able to test this directly due to limited methodology. Optogenetics solved this problem by giving us the ability to activate selectively the cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT). The primary finding of this study was that cholinergic neurons in the PPT and LDT are sufficient to drive REM sleep from NREM sleep. These cholinergic neurons were important for initiation of REM sleep but not the duration of REM sleep. Understanding REM sleep control is an important first step in reproducing normal sleep patterns and by itself could enhance learning and memory. (more…)
BMJ, Heart Disease, Hospital Readmissions, Yale / 06.02.2015

MedicalResearch.com Interview with: Kumar Dharmarajan MD MBA Section of Cardiovascular Medicine Yale University School of Medicine, New Haven, CT 06510 Medical Research: What is the background for this study? What are the main findings? Dr. Dharmarajan: We know that patients are at high risk for rehospitalization and death in the month after hospital discharge. Yet little is known about how these risks dynamically change over time for the full year after hospitalization. This information is needed for patients and hospitals to set realistic goals and plan for appropriate care. We found that the risk of rehospitalization and death decline slowly following hospitalization and remain elevated for many months. We also found that specific risk trajectories vary by discharge diagnosis and outcome. For example, risk remains elevated for a longer period of time following hospitalization for heart failure compared with hospitalization for acute myocardial infarction. For all 3 conditions we studied (heart failure, heart attacks, and pneumonia), risk of rehospitalization remained elevated for a longer period of time than the risk of death. (more…)
Author Interviews, Emergency Care, Mental Health Research, UCSD / 05.02.2015

Michael Wilson, MD, PhD, FAAEM Attending Physician, UCSD Department of Emergency Medicine Director, Department of Emergency Medicine Behavioral Emergencies Research (DEMBER) lab UC San Diego Health SystemMedicalResearch.com Interview with: Michael Wilson, MD, PhD, FAAEM Attending Physician, UCSD Department of Emergency Medicine Director, Department of Emergency Medicine Behavioral Emergencies Research (DEMBER) lab UC San Diego Health System MedicalResearch: What is the background for this study? What are the main findings? Dr. Wilson: Emergency departments (EDs) nationwide are crowded. Although psychiatric patients do not make up the largest proportion of repeat visitors to the emergency department, psychiatric patients stay longer in the ED than almost any other type of patient. So, it’s really important to find out things about these patients that may predict longer stays. In this study, we looked at patients on involuntary mental health holds. The reasoning is simple: patients on involuntary mental health holds aren’t free to leave the ED. So, the only thing that should really matter is how quickly an Emergency department can release them from the involuntary hold. Surprisingly, though, this wasn’t the only thing that correlated with longer stays. (more…)
Author Interviews, Dermatology, JAMA, OBGYNE, UC Davis / 05.02.2015

MedicalResearch.com Interview with: Dr. Eleanor B. Schwarz, M.D., M.S University of California, Davis Sacramento, CA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Schwarz: The background for this study is that… Women treated with Isotretinoin receive a lot of scary information about this medication’s risk of causing birth defects, but few receive clear information on the most effective ways to protect themselves from undesired pregnancy and the risks of medication-induced birth defects. Our main finding is that women who spent less than a minute reviewing a simple information sheet were significantly more likely to be aware that some contraceptives are considerably more effective than others. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Schwarz: Clinicians who prescribe medications that can cause birth defects should make sure their patients are aware of the fact that women using a birth control pill are typically twenty times more likely to experience a contraceptive failure than those using a subdermal contraceptive implant (e.g. Nexplanon) or intrauterine contraceptive (e.g. Mirena, ParaGard). (more…)
AHA Journals, Author Interviews, Cleveland Clinic, Heart Disease, Kidney Disease / 05.02.2015

MedicalResearch.com Interview with: W. H .Wilson Tang, M.D., F.A.C.C., F.A.H.A. Professor in Medicine, Cleveland Clinic Lerner College of Medicine Cleveland Clinic, Cleveland, OH 44195MedicalResearch.com Interview with: W. H .Wilson Tang, M.D., F.A.C.C., F.A.H.A. Professor in Medicine, Cleveland Clinic Lerner College of Medicine Cleveland Clinic, Cleveland, OH 44195.   Medical Research: What is the background for this study? What are the main findings? Dr. Tang: Our group has previously demonstrated that TMAO is linked to future cardiac risks in both humans and in animal models.  We now show that long-term exposure to higher levels of TMAO promotes renal functional impairment and fibrosis in animal studies.  We also show that in humans, as the kidneys lose function, TMAO isn’t eliminated as easily, and their blood levels further rise, thereby increasing cardiovascular and kidney disease risks further.  This newly discovered TMAO link offers further insight into the relationship between cardiovascular disease and chronic kidney disease. (more…)
Author Interviews, Breast Cancer, NYU / 05.02.2015

Agnel Sfeir PhD Assistant Professor Skirball Institute - NYU New York, NY 10016MedicalResearch.com Interview with: Agnel Sfeir PhD Assistant Professor  Skirball Institute - NYU New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Sfeir: The main finding of this study, published in the journal Nature, is that inhibiting the action of a particular enzyme dramatically slows the growth of tumor cells tied to BRCA1 and BRCA2 genetic mutations which, in turn, are closely tied to breast and ovarian cancers. This discovery about the enzyme — called polymerase theta, or PolQ — resulted from efforts to answer a fundamental biological question: How do cells prevent the telomere ends of linear chromosomes, which house our genetic material, from sticking together? Cell DNA repair mechanisms can stitch together telomeres broken as part of cell metabolism. But such fusions, the researchers say, compromise normal cell growth and survival. In the purest biological sense, our findings (in experiments in mice and human cells) show how this particular enzyme, which we know is active in several tumors, promotes unwanted telomere fusions by inserting whole segments of DNA via a disruptive DNA repair pathway termed alt-NHEJ. It was quite remarkable to find that by blocking PolQ action, cancer cell growth was cut by more than half. Additional experiments confirmed that PolQ is needed to activate the alt-NHEJ pathway of DNA repair. Unlike the main, error-free pathway — or HDR pathway — the alt-NHEJ pathway does not use a related chromosome’s genetic material as a template to meticulously correct any damaged genetic material. As such, alt-NHEJ is highly likely to leave coding mistakes. (more…)
Author Interviews, Columbia, Schizophrenia / 04.02.2015

Mark Slifstein, PhD Associate Professor of Neurobiology (In Psychiatry) Dept. of Psychiatry Columbia University NYSP Dr New York NY 10032 MedicalResearch.com Interview with: Mark Slifstein, PhD Associate Professor of Neurobiology (In Psychiatry) Dept. of Psychiatry Columbia University NYSP Dr New York NY 10032 MedicalResearch: What is the background for this study? Dr. Slifstein: There has been considerable basic and clinical neuroscience research showing that the neurotransmitter dopamine plays a role in tuning cognitive processes taking place in the cortex. It has long been thought that dopamine is involved in the cognitive difficulties experienced by patients with schizophrenia, but it has been challenging to study dopamine in the cortex and other parts of the brain except in a deep structure rich in this neurotransmitter and its receptors, the striatum. In our study, we used an experimental design with Positron Emission Tomography (PET) imaging that allowed us to infer the amount of dopamine in the cortex. (more…)
Author Interviews, JAMA, Outcomes & Safety, University of Michigan / 03.02.2015

Nicholas Osborne, M.D., M.S Vascular Surgery Fellow University of Michigan, Ann Arbor MedicalResearch.com: What is the background for this study? Dr. Osborne: The American College of Surgeons launched the National Surgical Quality Improvement Program (ACS-NSQIP) in the early 2000s. This program collects and reports surgical outcomes to participating hospitals. One retrospective study of participating hospitals in the ACS-NSQIP reported improvements in risk-adjusted outcomes with participation. This study, however, did not compare ACS-NSQIP hospitals to control hospitals. The purpose of our study was to compare ACS-NSQIP to similar non-participating hospitals over time and determine whether participation in the ACS-NSQIP was associated with improved outcomes. MedicalResearch.com: What are the main findings? Dr. Osborne: When comparing hospitals participating in a national quality reporting program (ACS-NSQIP) to similar hospitals, there is no appreciable improvement in outcomes (mortality, morbidity, readmissions or cost)  outside of pre-existing trends across all hospitals. In other words, Hospitals nationwide were improving over this same time period and ACS-NSQIP hospitals did not improve above and beyond these existing trends. (more…)
Author Interviews, Hepatitis - Liver Disease, JAMA, University of Pittsburgh / 03.02.2015

Adeel A. Butt, MD, MS, FACP, FIDSA Adjunct Associate Professor of Medicine and Clinical and Translational Science University of Pittsburgh School of MedicineMedicalResearch.com Interview with: Adeel A. Butt, MD, MS, FACP, FIDSA Adjunct Associate Professor of Medicine and Clinical and Translational Science University of Pittsburgh School of Medicine   MedicalResearch: What is the background for this study? What are the main findings? Dr. Butt: Studying clinical consequences of hepatitis C virus (HCV) infection is often limited by the lack of knowledge of actual time of infection. We used the Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES), a well-established national cohort of HCV infected veterans and corresponding HCV-uninfected controls, to identify patients with a known time frame for HCV infection. Our primary aim was to determine the rate of liver fibrosis progression among HCV-infected persons over time, with and to determine factors associated with development of cirrhosis and hepatic decompensation among these persons. Among 1840 persons who were HCV+ and 1840 HCV− controls, we found that fibrosis progression started early after HCV infection tapered off after 5 years. After 10 years of follow-up, 18.4% of HCV+ and 6.1% of HCV- persons developed liver cirrhosis. Nine years after diagnosis of cirrhosis, only 1.8% of HCV+ and 0.3% of HCV- persons had developed hepatic decompensation. (more…)
Author Interviews, Brigham & Women's - Harvard, Surgical Research / 01.02.2015

Timothy R. Smith, M.D., Ph.D., M.P.H. Pituitary/Neuroendoscopy Fellow Department of Neurosurgery Brigham & Womens Hospital Harvard University Boston, MA 02115MedicalResearch.com Interview with: Timothy R. Smith, M.D., Ph.D., M.P.H. Pituitary/Neuroendoscopy Fellow Department of Neurosurgery Brigham & Womens Hospital Harvard University Boston, MA 0211 Medical Research: What is the background for this study? What are the main findings? Dr. Smith: Defensive medicine is the practice of prescribing unnecessary medical treatment for fear of being sued – it is widely practiced in the United States and contributes to our rising healthcare costs. In high-risk specialties such as neurosurgery, the fear of litigation leads to defensive practices that actually impact clinical decisions. A 2009 American College of Emergency Physicians report created malpractice risk profiles for each state based on its legal atmosphere, tort reform, and insurance availability. Based on these profiles, each state was ranked from 1 to 50 and sorted into separate categories, ranging from A, for the best liability environment, to F, for the worst. We sent a 51-question, anonymous online survey, which covered topics ranging from patient characteristics to surgeon liability profiles, to board-certified US neurosurgeons in the American Association of Neurological Surgeons. The purpose was to determine how neurosurgeons’ perceptions of their medico-legal environments correlated with these established state risk profiles, as well as whether each state’s liability risk environment was a predictor of defensive medical practices. We found that though the average malpractice insurance premium was $103,000 per year, neurosurgeons from high-risk states paid significantly more ($128,000) than those from low-risk states did ($75,000). Even with these amounts, almost 70% of respondents felt that their insurance coverage was inadequate, and 90% felt that the insurance premium was a financial burden. Neurosurgeons from high-risk states were also twice as likely to have been sued as those from low-risk states were. More than 80% of respondents ordered additional imaging for defensive medical purposes, and more than 75% said they ordered additional laboratory tests and made unnecessary referrals for defensive purposes; this behavior was more prevalent in high-risk states. After controlling for important confounders, we found that for every letter-grade change from “A” to “F”, neurosurgeons are 1.5 times more likely to engage in defensive behaviors. For example, moving from a “D” state to an “A” state represents 4.5 fold difference in defensive behaviors. (more…)
Author Interviews, Colon Cancer, Journal Clinical Oncology, Race/Ethnic Diversity, Stanford, Surgical Research / 30.01.2015

Kim F. Rhoads, MD, MS, MPH, FACS Assistant Professor of Surgery Director, Community Partnership Program Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305MedicalResearch.com Interview with: Kim F. Rhoads, MD, MS, MPH, FACS Assistant Professor of Surgery Director, Community Partnership Program Stanford Cancer Institute Unit Based Medical Director, E3 Surgery and Surgical Subspecialties Stanford University Stanford, Ca 94305 Medical Research: What is the background for this study? What are the main findings? Dr. Rhoads: Colon cancer is the 3rd most common cancer in US men and women and is the 2nd most common cause of cancer death. For at least 2 decades, minorities with colon cancer have suffered a 15-20% additional risk of death when compared with non-minority patients. Our study set out to understand the influence of the location where treatment was delivered and the quality of care received, on overall survival and racial disparities. We examined more than 30,000 patients who were diagnosed and treated for colon cancer in California from 2001 through 2006.  Using cancer registry data linked to state level inpatient data and hospital information, we compared the rates of National Comprehensive Cancer Network (NCCN) guideline adherence and mortality by location of care and by race. We found that patients treated within an integrated health system (IHS) received NCCN guideline based care at higher rates than those treated outside the system—about 3% higher rates of surgery; and more than 20% higher rates of stage appropriate chemotherapy. The rates of guideline based care were nearly equal between the racial groups treated inside the IHS.  Propensity score matched comparisons revealed a lower risk of death for all patients and no racial disparities associated with treatment within the Integrated system.  For patients treated outside IHS, the disparity in mortality was explained by accounting for differences in receipt of evidence based care by race. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, HIV, NEJM / 30.01.2015

Douglas B. Jacobs B.S., MD/MPH Candidate Harvard T.H. Chan School of Public HealthMedicalResearch.com Interview with: Douglas B. Jacobs B.S., MD/MPH Candidate Harvard T.H. Chan School of Public Health Medical Research: What is the background for this study? Response: In May 2014, a formal complaint submitted to the Department of Health and Human Services contended that four Florida insurers were structuring their formularies in a way that discouraged enrollment from HIV positive beneficiaries. These insurers placed all HIV drugs, including generics, on the highest cost-sharing tiers. This formal complaint served as the impetus for this research. We wanted to discover if this was a phenomenon that was isolated to Florida, or if it was national in scope, and what the implications would be for HIV positive beneficiaries. As such, we analyzed what we called “adverse tiering”—in which all drugs for certain conditions are placed in the highest cost sharing tiers—in 12 states in the federal marketplace. We compared cost-sharing for a commonly prescribed class of HIV medication, called Nucleoside Reverse Transcriptase Inhibitors, or NRTIs. (more…)
Author Interviews, Breast Cancer, Journal Clinical Oncology, Mayo Clinic / 30.01.2015

MedicalResearch.com Interview with: Dr. Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester.Dr.  Amy C. Degnim MD Professor of Surgery Mayo Clinic, Rochester. Medical Research: What is the background for this study? What are the main findings? Dr. Hartmann: Approximately 1 million women in the US every year have a breast biopsy that shows benign findings. We have found that the specific features of the breast tissue seen under the microscope can help to predict the risk of breast cancer in the future.  We developed a mathematical formula to calculate breast cancer risk based on the features seen in the biopsy tissue (named the BBD-BC model).  We found that using these microscopic features provides more accurate predictions of risk than the previous standard- the Breast Cancer Risk Assessment Tool (BCRAT). (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Cancer / 28.01.2015

Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, MassachusettsMedicalResearch.com Interview with: Rachel A. Freedman MD, MPH Assistant Professor of Medicine, Harvard Medical School Department of Medical Oncology Dana-Farber Cancer Institute, Boston, Massachusetts Medical Research: What is the background for this study? What are the main findings? Dr. Freedman: Studies have previously looked at how general cancer knowledge may impact health conditions and rates of screening but none (to my knowledge) have focused on one’s knowledge about his/her own breast cancer. We surveyed 500 women who were diagnosed with early-stage breast cancer within the Northern California Cancer Registry and asked questions about their breast cancer subtype (I.e. Hormone receptor status and HER2 status), tumor grade, and stage. We then matched women’s answers to those collected by the registry to examine the correctness of the answers given. We found low overall rates of having knowledge about one’s disease and this was even more apparent for black and Hispanic patients. When education and health literacy were accounted for, disparities in knowledge remains for black women but were narrowed for Hispanic women in some cases. (more…)
Author Interviews, Brigham & Women's - Harvard, Infections, PNAS / 28.01.2015

Rakesh K. Jain, Ph.D. A.W.Cook Professor of Tumor Biology Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA 02114MedicalResearch.com Interview with: Rakesh K. Jain, Ph.D. A.W.Cook Professor of Tumor Biology Director, E.L. Steele Laboratory Department of Radiation Oncology Harvard Medical School and Massachusetts General Hospital Boston, MA    02114 Medical Research: What are the primary findings of this study and why are they important? Dr. Jain: Pulmonary granulomas are the hallmark of the Tuberculosis (TB) infection, yet it is not fully understood how these structures contribute to disease progression and treatment resistance. In this study, we applied our insight in tumor biology – gained over three decades – to explore and exploit the similarities between vasculature (blood vessel network) in solid cancerous tumors and TB pulmonary granulomas. We demonstrate for the first time that TB granulomas have abnormal vasculature. This abnormality provides a mechanism for the observation that TB granulomas are often hypoxic (have low oxygen conditions) and have differential distribution of anti-TB drugs. We showed that bevacizumab, a widely prescribed anti-VEGF antibody for cancer and eye diseases, is able to create more structurally and functionally normal granuloma vasculature and improve small molecule delivery. This study suggests that vasculature normalization in combination with anti-TB drugs has the potential to enhance treatment in patients with TB. Tuberculosis (TB) is a global scourge that is responsible for nearly 2 million deaths annually. Due to the inability of currently available treatment regimens to eradicate this devastating disease, it is clear that new treatment strategies are urgently needed. Unlike many researchers in the TB field, we do not seek to discover new therapeutics that target bacterial resistance; instead, we strive to overcome physiological resistance to treatment resulting from abnormalities in the granuloma vasculature that impair drug delivery and create hypoxia that impairs efficacy of drugs and immune system. By using an FDA-approved drug, our study has the potential to be rapidly translated into the clinic. Medical Research: Has any association previously been made between the vascular structure of TB granulomas and the challenges of treating TB – both the fact that treatment takes so long and the development of multidrug resistance? Dr. Jain: Our study is the first to implicate a specific facet of the granuloma – the abnormal vasculature – as a potential contributor to disease progression and treatment resistance. Granuloma hypoxia is known to negatively affect the local immune system while conferring resistance to some of the TB drugs. Our collaborators have shown that different anti-TB drugs have differential abilities to penetrate the granuloma structure, especially to the interior granuloma regions where the TB bacteria are found in greatest numbers. Our study is the first to provide evidence that by modulating the granuloma vasculature, hypoxia can be alleviated and drug delivery can be improved. (more…)
Author Interviews, Infections, PNAS, University Texas / 28.01.2015

Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin anMedicalResearch.com Interview with: Christopher S. Sullivan, Ph.D. Associate Professor Dept. Molecular Biosciences The University of Texas at Austin and Jennifer Cox, lead author Graduate student in Dr. Sullivan’s laboratory. Jennifer Cox, lead author Graduate student in Dr. Sullivan’s laboratory. Jennifer Cox's Replies: MedicalResearch: What is the background for this study? What are the main findings? Jennifer Cox: In the last decade, researchers have identified that many viruses encode small regulatory molecules known as microRNAs. Some viral microRNAs are able to manipulate host processes including stress responses, proliferation, and cell death. However, there are many viral microRNAs with unknown functions. Many of the viruses that encode microRNAs are associated with severe pathologies including various cancers so understanding the role of viral microRNAs can shed light on virus biology. For this study, we focused on identifying viral microRNAs that can regulate innate immune signaling for several reasons. First, all viruses have proteins to combat interferon signaling. Second, we have identified microRNAs from two diverse viruses (retro and annello) that can inhibit interferon signaling so we hypothesized that additional viral microRNAs will perform this same function. We screened ~70 viral microRNAs for the ability to regulate innate immune signaling and identified three herpesviruses, Epstein-Barr Virus, Kaposi’s Sarcoma Associated Virus, and Human Cytomegalovirus, that inhibit the interferon response. Epstein-Barr Virus, causes an estimated 200,000 cancers every year, including lymphomas, nasopharyngeal cancers and some stomach cancers. Interestingly, most of these cancers harbor latent EBV – a state of limited gene expression that produces no virus. microRNAs are one of the few viral gene product expressed during latency. Our further work identified that Epstein-Barr Virus, KSHV, and Human Cytomegalovirus have converged to inhibit interferon signaling in the same manner – through decreasing expression of a central hub of innate immune signaling, CREB binding protein (CBP). We show that this regulation conveys partial resistance to the negative effects of interferon treatment on an EBV+ lymphoma cell line. Additionally, removing the microRNA from a similar cell line increases the sensitivity to interferon. Interferon can be used in combination with other chemotherapies to treat lymphomas but varies in success. Our results may partially explain the variability seen in patients with EBV-associated cancers. (more…)
Author Interviews, Heart Disease, Mayo Clinic, Testosterone / 27.01.2015

Abraham Morgentaler, MD Director and Founder Men’s Health BostonMedicalResearch.com Interview with: Abraham Morgentaler, MD Director and Founder Men’s Health Boston Medical Research: What is the background for this study? What are the main findings? Response: There has been  tremendous media attention over the last 15 months to two retrospective studies that reported increased cardiovascular risks with testosterone. Those reports anchored a variety of stories critical of testosterone therapy for non-scientific reasons, such as alleged dangers of direct-to-consumer advertising.  In this review we investigated the two recent studies in depth, as well as the broader literature regarding testosterone and cardiovascular issues. One primary finding was that the studies alleging risk were remarkably weak and flawed- one reported low rates of MI and had no control group, and the other had such large data errors (nearly 10% of the all-male population turned out to be female!) that 29 medical societies have called for its retraction. In contrast, there is substantial literature suggesting that testosterone therapy, or naturally occurring higher levels of testosterone, is protective against atherosclerosis, and mortality.  Several small randomized controlled trials in men with known heart disease- angina and congestive heart failure- have even shown benefits for men that received testosterone compared with placebo. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, Kidney Disease, Rheumatology / 27.01.2015

Dr Gomez-Puerta MD, PhD, MPH Division of Rheumatology, Immunology, and Allergy; Brigham and Women's Hospital, Harvard Medical School, Boston, MA Medical Research Interview Dr Gomez-Puerta MD, PhD, MPH Division of Rheumatology, Immunology, and Allergy; Brigham and Women's Hospital, Harvard Medical School, Boston, MA MedicalResearch: What is the background for this study? What are the main findings? Dr. Gomez-Puerta: Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology which can cause multiorgan system damage and which disproportionately affects women and non- Caucasian minorities. Up to 60% of SLE patients develop renal disease, lupus nephritis (LN), and of these, approximately one fifth progress to end-stage renal disease (ESRD). The risk of cardiovascular (CV) events and mortality is higher in patients with ESRD and in particular in patients suffering SLE. However, information about CV outcomes and mortality is limited in patients with LN associated ESRD. We observed important variation in cardiovascular outcomes and mortality by race and ethnicity among lupus nephritis related ESRD patients. After adjusting for multiple demographic and clinical factors and accounting for the competing risk of kidney transplantation and loss to follow-up, our results illustrate for the first time that Asian (vs. White) and Hispanic (vs. non-Hispanic) lupus nephritis related ESRD patients have lower mortality risks. (more…)
Author Interviews, FASEB, Genetic Research, Stanford / 26.01.2015

Dr. John Ramunas PhD Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, CaliforniaMedicalResearch.com Interview with: Dr. John Ramunas PhD Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Clinical Sciences Research Center, Stanford University School of Medicine, Stanford, California Medical Research: What is the background for this study? Dr. Ramunas: Telomeres comprise repetitive DNA sequences at the ends of chromosomes.  Telomeres protect the ends of chromosomes, but become shorter with each cell division and due to oxidative damage.  Critically short telomeres are implicated in diseases of aging and devastating genetic disorders of insufficient telomere maintenance . Medical Research: What are the main findings? Dr. Ramunas: Our main finding is that telomeres in human cells can be lengthened by a new method with therapeutic potential.  We delivered modified mRNA encoding TERT, the protein component of telomerase, the enzyme that increases the length of telomeres by adding DNA repeats.  The protein TERT is usually the rate limiting component of the enzyme. In this study, we used four groups of cells.  The first group received modified mRNA encoding TERT, and the other three groups were controls that received either mRNA encoding an inactive form of TERT, the solution in which TERT is delivered, or no treatment.  The telomeres of the first group (telomere extending treatment group) were extended rapidly over a period of a few days, whereas the telomeres of the three control groups were not extended.  The first group was also able to undergo more cell divisions, whereas the controls were not.  Importantly for the potential safety of our approach, the telomeres of the first group resumed shortening after they were extended.  This is important because it shows that due to the short, transient treatment, the cells were not immortalized, ie. not tumorigenic. Further, all of the cell populations treated to date eventually stopped dividing, further indicating that they were not immortalized.  We have tested the approach on cell types including fibroblasts and myoblasts and are now testing it on stem cells. A surprising and exciting finding was that we could treat the cells several times with enhanced effects on the capacity of cells to divide.  For instance, after a first treatment, we saw an increase of 50,000-fold in cell numbers before cells stopped dividing, compared to untreated cells.  If we waited a few weeks and repeated this treatment, we saw a similar gain in cell division and number.  Since the increase in numbers is compounded with each treatment, a small sample of cells, for example from a small biopsy, can be amplified to very large numbers. (more…)
Author Interviews, Baylor College of Medicine Houston, Cognitive Issues, Sleep Disorders / 26.01.2015

Michael K. Scullin, Ph.D. Principal Investigator of the Sleep Neuroscience & Cognition (SNaC) Laboratory and an Assistant Professor of Psychology & Neuroscience Director Sleep Neuroscience and Cognition Laboratory Baylor UniversityMedicalResearch.com Interview with: Michael K. Scullin, Ph.D. Principal Investigator of the Sleep Neuroscience & Cognition (SNaC) Laboratory and an Assistant Professor of Psychology & Neuroscience Director Sleep Neuroscience and Cognition Laboratory Baylor University Medical Research: What is the background for this study? What are the main findings? Dr. Scullin: One of the purposes of sleep in healthy adults is to optimize cognitive functioning. When we lose out on a few hours of sleep we tend not to be able to focus or think as well as when we get enough sleep (typically 8 hours). Even more interesting is that particular aspects of sleep physiology—our deepest levels of sleep known as slow wave sleep and rapid eye movement sleep—are essential to our brain’s ability to take the information that we learn during the day and stabilize those memories so that we can use them in the future. Sleep quantity and quality change markedly across the lifespan, though there are individual differences in how much one’s sleep changes. Our work was concerned with the possible long-term repercussions of cutting back on sleep and getting lower quality sleep (less slow wave sleep and rapid eye movement sleep).  We reviewed approximately 200 scientific articles on this topic and we found that the amount of total sleep and the quality of that sleep is important to cognitive and memory functioning in young adults and middle-aged adults and can even predict how well someone’s cognitive functioning will be decades later. Thus, if you’re sleeping well when you are 40 then you are investing in preserving your mental functioning at age 50. (more…)
Author Interviews, Breast Cancer, Karolinski Institute / 26.01.2015

Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, SwedenMedicalResearch.com Interview with: Dr Jingmei Li Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Response: Some cancers, such as interval breast cancers, which are detected within two years of a negative mammogram, are associated with more aggressive tumour characteristics and worse prognosis. As women with interval cancers were twice as likely to have a personal of family history of breast cancer, it is likely that there exist inherited variants that predispose a woman to the more aggressive form of the disease. Our study is one of the first to show empirical evidence that screen-detected and interval cancers are different genetically and are two distinct subtypes. (more…)
Author Interviews, Cost of Health Care, NEJM, University of Pennsylvania / 26.01.2015

Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of PennsylvaniaMedicalResearch.com Interview with: Daniel Polsky PhD Executive Director, Leonard Davis Institute of Health Economics Professor of Medicine and Health Care Management Perelman School of Medicine and the Wharton School University of Pennsylvania Medical Research: What is the background for this study? What are the main findings? Dr. Polsky: The Medicaid Fee bump, a provision of the Affordable Care Act (ACA), raised Medicaid payments to Medicare levels in 2013 and 2014 for selected services and providers expired on January 1, 2015 before policymakers had much empirical evidence about its effects.   The federally funded increase in reimbursements was aimed at expanding access to primary care for the growing number of Medicaid enrollees. The reimbursement increase expired at the end of 2014 in most states.  We found that this policy worked to increase the number of providers offering primary care appointments to Medicaid patients.  The Medicaid pay bump was associated with a 7.7 percentage points increase in new patient appointment availability without longer wait times.   This increase in availability was largest in the states where primary care physicians received the largest increase in their Medicaid reimbursements. (more…)
Author Interviews, Breast Cancer, Scripps / 25.01.2015

Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, FloridaMedicalResearch.com Interview with: Dr. Patrick Griffin PhD Professor and Chairman Department of Molecular Therapeutics Director of the Translational Research Institute Scripps Research Institute, Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Griffin: We identified a novel synthetic compound known as SR1848 that sharply inhibits the activity and expression of “liver receptor homolog-1” or LRH-1, a protein that plays an important role in the progression of breast and pancreatic cancers. Our new study shows that SR1848 removes LRH1 from DNA, shutting down expression of LRH-1 target genes, and halts cell proliferation. It’s a novel compound that appears to be a promising chemical scaffold for fighting tumors that are non-responsive to standard therapies. (more…)
Author Interviews, Genetic Research, Mental Health Research, Scripps / 25.01.2015

Dr. Gavin Rumbaug Professor (Associate) The Scripps Research InstituteMedicalResearch.com Interview with: Gavin Rumbaug Professor (Associate) The Scripps Research Institute Medical Research: What is the background for this study? What are the main findings? Response: We have developed a genetic approach that protects animal models against a type of genetic disruption that causes intellectual disability, including serious memory impairments and altered anxiety levels. The findings focus on treating the effects of mutations to a gene known as Syngap1. In our new study, we examined the effect of damaging Syngap1 mutations during development and found that the mutations disrupt a critical period of neuronal growth—a period between the first and third postnatal weeks in mouse models. We found that a certain type of cortical neuron grows too quickly in early development, which then leads to the premature formation of certain types of neural circuits. These findings help explain why genetic treatments in adult mice are not very effective. (more…)
Author Interviews, Diabetes, Nature, University of Michigan / 23.01.2015

MedicalResearch.com Interview with: Martin G. Myers, Jr., M.D., M.P.H. Director, Michigan Diabetes Research & Training Center Associate Professor of Internal Medicine - MEND Division Professor of Molecular & Integrative Physiology Marilyn H. Vincent Professor of Diabetes Research and Department of Pharmacology, University of Cambridge, Cambridge, UK.MedicalResearch.com Interview with: Martin G. Myers, Jr., M.D., M.P.H. Director, Michigan Diabetes Research & Training Center Associate Professor of Internal Medicine - MEND Division Professor of Molecular & Integrative Physiology Marilyn H. Vincent Professor of Diabetes Research and Department of Pharmacology, University of Cambridge, Cambridge Medical Research: What is the background for this study? What are the main findings? Dr. Myers: Diabetic people who take insulin to treat their diabetes are at risk of low blood sugar, which can cause serious consequences (including death).  This risk increases as blood sugar control improves, and so this risk limits the ability to control blood sugar.  The body has a system (the counter-regulatory response) that acts to prevent blood sugar from going too low, but this is often impaired in diabetic patients. We identified a brain circuit that senses and responds to falling blood sugar, and which acts to increase blood sugar.  Furthermore, we showed that the hormone leptin modulates the sensitivity of this circuit, and identified the neurotransmitter (CCK) that acts in this circuit to increase blood sugar.  Thus, we have identified several potential drug targets that could be used to prevent or treat low blood sugar in insulin-treated diabetics.  If we are able to pharmacologically modulate the activity of this brain circuit, it could improve the treatment of these patients. (more…)