Author Interviews, Dermatology, Infections, NYU / 29.05.2015

Dr. Marie C. Leger, MD, PhD Assistant Professor Ronald O. Perelman Department of Dermatology NYU Langone Medical CenterMedicalResearch.com Interview with: Dr. Marie C. Leger, MD, PhD Assistant Professor Ronald O. Perelman Department of Dermatology NYU Langone Medical Center Medical Research: What inspired this study? How did it come about? Dr. Leger: As a dermatologist at NYU, I have taken care of several patients with tattoo reactions--some of them mild (like longstanding itching for example) and some of them more severe (like long term reactions to a particular color that can severely disfigure the tattoo) and wondered how common it was for people to have adverse tattoo reactions or complications. There were lots of case reports in the literature but only a few larger studies examining how common these kinds of complaints were--and these were all European studies. We decided to do a quick survey to give us a better idea of how common it is for people to have problems with their tattoos. Medical Research: What do you think is the most important takeaway from this study for the consumer? Dr. Leger: Tattoos have risks associated with them--which is part of their appeal I'm sure--but I do think it's important for people to know that long term tattoo reactions (including for example, itching, scaling, swelling) may be more common than we realize.  A recent Danish study shows that these kinds of reactions can be quite distressing for people and significantly impact their quality of life. (more…)
Author Interviews, HIV, NYU, Race/Ethnic Diversity, Sexual Health / 22.05.2015

Perry N Halkitis, Ph.D., M.S., MPH Professor of Applied Psychology Global Public Health, and Population Health/Medicine New York University.MedicalResearch.com Interview with: Perry N Halkitis, Ph.D., M.S., MPH Professor of Applied Psychology Global Public Health, and Population Health/Medicine New York University. Medical Research: What is the background for this study? Dr. Halkitis: The P18 Cohort Study is a prospective cohort study of gay, bisexual and other young men who have sex with men (YMSM) which seeks to examine the development of health behaviors as these young men transition from adolescent to adulthood. Officially named “Syndemic Production among Emergent Adult Men”, this study was funded by the National Institute on Drug Abuse from 2009-2014 and renewed on March 1, 2014 for an additional five years. The original aims of the study were as follows:
  • 1) to develop and test theoretically informed measurement models of the covariance of illicit drug use, unprotected sexual behavior and mental health burden (multiple overlapping epidemics known as a syndemic) among emergent adult HIV-negative YMSM within and across time;
  • 2) to delineate the risk and protective bases- physical factors (e.g., pubertal onset, HIV status, etc.), relational and structural factors (e.g., family history of psychopathology, current romantic relationships, peer support, neighborhood factors, etc.), and psychosocial factors (e.g., sexual identity, internalized homophobia, hyper-masculine conceptions, etc.) that predict the development of syndemics; and
  • 3) to determine the extent to which the development of a syndemic varies by race/ethnicity, social class, and homelessness/housing instability.
  • In this current five year continuation we also seek
    • 1) to describe the social and sexual networks of YMSM, and to examine the relationship between social and sexual network-level structural characteristics, social support and normative influences on syndemic production (illicit drug use, unprotected sexual behaviors, and mental health burden) in YMSM, singly and in combination with the physical, psychosocial, and relational predictors, both within and across time;
    • 2) to describe the acquisition of sexually transmitted infections (STIs) in YMSM, specifically, urethral and rectal gonorrhea and chlamydia, pharyngeal gonorrhea as well as syphilis serology; and to determine the extent to which physical, relational, and psychosocial factors explain STI acquisition as part of the syndemic model within and across time.
    • A third exploratory aim was also added: 3) to describe HIV clinical treatment markers (i.e., HIV viral load, ART uptake and adherence, HIV care) among HIV+ YMSM, and to assess the extent to which physical, relational, and psychosocial factors are associated with differences in these clinical markers among HIV+ YMSM, both within and across time. The study is led by Drs. Perry N Halkitis and Farzana Kapadia at New York University’s Center for Health, Identity, Behavior & Prevention Studies.
Potential participants were recruited through both active (e.g., approaching individuals to solicit study participation) and passive (e.g., flyer posting, website advertisements) methods from June 2009 to May 2011. Eligibility criteria included being 18-19 years old, biologically male, residing in the NYC metropolitan area, having sex (any physical contact that could lead to orgasm) with a man in the last 6 months, and reporting a seronegative or unknown HIV status at baseline. We ensured the diversity of our sample by setting a fixed recruitment quota for participants in each targeted racial/ethnic group, such that African Americans, Latino (across race), Asian-Pacific Islander (API), and mixed race men comprised the majority of the sample. All participants provided written, informed consent before data was collected and were compensated for their time and effort upon completing the baseline assessment. The New York University’s Institutional Review Board (IRB) approved all study protocols and a federal Certificate of Confidentiality protects these data. A total of 2,068 participants were screened for eligibility to participate in the study, and 600 participants completed the baseline assessment in the first wave of the study. In 2014, we began the second wave and opened to cohort to recruit a baseline sample of 650 YMSM who will now be between the ages of 22-23; recruitment of participants is still underway. Medical Research: What are the main findings? Dr. Halkitis: Numerous publications have been generated from the P18 Cohort Study and can be accessed at www.chibps.org.  A recent publication, “Incidence of HIV infection in Young Gay, Bisexual, and other YMSM: The P18 Cohort Study” became available in the May 2015 of JAIDS, the Journal of Acquired Immune Deficiency Syndromes. This paper reports that over a 36 month follow-up period, during the first wave of the study, 7.2% of study participants seroconverted, with Black and Hispanic men much more likely to seroconvert over this time frame than White men. This finding aligns with epidemiological trends for HIV infection at the national and local, NYC, levels. Also, men reporting a lower familial socioeconomic status were more likely to seroconvert than men reporting high familial socioeconomic status, and Black men were more likely to report a lower socioeconomic status.  Moreover, the Black young men who seroconverted were more likely to reside in neighborhoods with higher area-level poverty and higher area-level HIV prevalence. Additionally we found that men who reported anal sex without a condom in the 30 days prior to assessment were no more likely to seroconvert than those who reported sex with a condom.  However, an earlier age of sexual debut was a predictor of HIV seroconversion. (more…)
Author Interviews, Genetic Research, Infections, Inflammation, NYU / 07.05.2015

Dr. Ludovic Desvignes. PhD. Assistant Professor, Departments of Medicine and Pathology NYU Langone Medical CenterMedicalResearch.com Interview Dr. Ludovic Desvignes PhD. Assistant Professor, Departments of Medicine and Pathology NYU Langone Medical Center MedicalResearch: What is the background for this study? Dr. Desvignes: This study is the result of a collaboration at NYU Langone Medical Center, between the laboratories of Dr. Stefan Feske and Dr. Joel Ernst, my mentor. Dr. Feske and colleagues had developed a mouse model of rare, inherited mutations he had identified in infants. These mutations occur in the genes for STIM1 and ORAI1, which are crucial for calcium flux in cells of the immune system. The young patients affected by these mutations suffer from severe, recurrent and chronic infections that often cause death before their first birthday. In particular, some of these patients cannot control infection with BCG, which is a normally innocuous strain of mycobacteria administered to protect against tuberculosis (TB). TB is a chronic infection and one of the leading causes of infection-related death worldwide. Going into this study, Dr. Feske and colleagues knew that without functional calcium channels, immune cells do not function properly. However, they did not fully understand how these channels contribute to immune responses to infectious pathogens in a living organism and in particular, for pathogens that cause chronic infections such as TB. This is why Dr. Ernst and I collaborated with Dr. Feske and provided him with our clinical and research expertise in TB. MedicalResearch: What are the main findings? Dr. Desvignes: Dr. Feske’s mice are genetically engineered to lack STIM1 in a certain type of immune cells, known as T cells or T lymphocytes. We infected these mice with Mycobacterium tuberculosis, the bacterium causing TB. Mycobacterium tuberculosis causes chronic infection by manipulating the immune system even in healthy people. The first very surprising result of our study was that mice lacking calcium flux in T cells handled acute TB fairly well. Only during the chronic phase of infection did they become unable to control mycobacterial growth and developed a strong inflammation in their lungs, which was due to an infiltration by different types of immune cells, including T cells. We discovered that the accumulation of STIM1-deficient T cells in the lungs resulted from the cells’ inability to die, which is a normal mechanism to limit an immune response and prevent excessive inflammation. Another immune control mechanism that failed in the absence of STIM1 is mediated by a subset of T cells called induced regulatory T cells, or iTreg cells. These cells are essential to prevent normal immune responses from going “overboard” by suppressing the functions of other immune cells, including T cells. We found that calcium signals are required for the development of iTreg cells and that their numbers were strongly reduced in the lungs of infected STIM1-deficient mice. We therefore think that the lack of iTreg cells in the absence of STIM1 contributes to the severe lung inflammation in chronic TB. The third finding that really surprised us was that T cells accumulating in the lungs of STIM1-deficient mice produced large amounts of a protein called interferon gamma. While interferon gamma is required to control Mycobacterium tuberculosis, it is also a very potent promoter of inflammation and too much of it can lead to tissue damage. Dr. Feske and colleagues had previously observed that calcium fluxes promote the production of interferon gamma in T cells cultured in vitro and we expected the STIM1-deficient T cells to be defective in the production of that protein. During chronic TB, however, calcium signaling turned out to be not only dispensable for the production of interferon gamma by T cells but it was actually required to limit its production and thus, to control inflammation. (more…)
Author Interviews, Heart Disease, JACC, NYU, Obstructive Sleep Apnea, Sleep Disorders / 22.04.2015

Dr. Larry Chinitz MD Professor of Medicine and Director, Cardiac Electrophysiology NYU Langone Medical CenterMedicalResearch.com Interview with: Dr. Larry Chinitz MD Professor of Medicine and Director, Cardiac Electrophysiology NYU Langone Medical Center MedicalResearch: What is the background for this study? What are the main findings? Dr. Chinitz: The treatment algorithms proposed currently for maintenance of sinus rhythm in patients with atrial fibrillation focus on use of anti-arrhythmic drugs and catheter ablation. Data available to evaluate the effect of modification of known adverse clinical factors on atrial fibrillation recurrence is scant. Obstructive sleep apnea in a known factor associated with both new onset atrial fibrillation as well as its recurrence after catheter ablation. Through a meta-analysis of available data we found that use of continuous positive airway pressure in patients with sleep apnea was associated with a 42% relative risk reduction in recurrence of atrial fibrillation. This effect was similar across patient groups irrespective of whether they were medically managed or with catheter ablation. (more…)
AACR, Author Interviews, Genetic Research, Melanoma, NYU, Personalized Medicine, Wistar / 21.04.2015

Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NYMedicalResearch.com Interview with: Melissa Wilson, MD, PhD Assisstant Professor Perlmutter Cancer Center NYU Langone Medical Center New York, NY Medical Research: What is the background for this study? What are the main findings? Dr. Wilson: Metastatic cutaneous melanoma is an extremely aggressive form of skin cancer.  Traditionally, it has been characterized by clinicopathologic characteristics.  More recently, melanoma tumors have also been stratified by common somatic mutations for which targeted therapies have been developed or are under investigation, including BRAF, NRAS and KIT.  In addition to somatic mutations, aberrant intracellular signaling pathways and cell cycle disruption contribute to melanoma pathogenesis.  Indeed, recent next generation sequencing studies have identified a number of new genes involved in melanomagenesis.  A comprehensive evaluation and understanding of concurrent and mutually exclusive mutations in tumors has been lacking.  Therefore, we developed a comprehensive custom targeted capture of 108 genes previously implicated in melanoma pathogenesis.  We used the targeted panel to perform massively parallel sequencing on 94 well-established human melanoma cell lines, 67 patient-derived xenografts (PDX), and 5 cell lines made from PDX, all untreated. Samples were clustered based on deleterious mutations.  Eighty-three percent of samples had deleterious mutations in the MAPK signaling pathway (including BRAF, RAS) and NF1.  Ten percent of samples had PI3K pathway mutations which were predominantly associated with BRAF mutations.  TP53 was found to be mutated in 24% of the samples and were also associated with mutations in the MAPK pathway.  Mutations in chromatin remodeling genes were mutually exclusive with each other, but were associated with BRAF and NRAS mutations.  Of particular interest, five of the 10 NF1mutated samples harbored likely deleterious mutations in MAP3K5 or MAP3K9, suggesting the potential involvement of JNK signal transduction pathway in a cohort of samples. (more…)
Author Interviews, Endocrinology, Nature, NYU, Social Issues / 16.04.2015

Bianca Jones Marlin, PhD Froemke Laboratory New York University Langone School of MedicineMedicalResearch.com Interview with: Bianca Jones Marlin, PhD Froemke Laboratory New York University Langone School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Marlin: Oxytocin is a hormone that plays an important role in the expression of social and parental behaviors, but little is know about how it works in the brain to produce these behaviors. Virgin mice will usually ignore, and sometimes cannibalize newborn mouse pups. Our study has shown that oxytocin works in the auditory cortex of virgin mice to change both their neural responses, and eventually their behaviors, to mirror the maternal response. (more…)
Author Interviews, Compliance, HIV, NYU / 06.04.2015

Marya Viorst Gwadz, Ph.D Senior Research Scientist Director, Transdisciplinary Methods Core Center for Drug Use and HIV Research (CDUHR) New York University College of Nursing New York, NY 10010 MedicalResearch.com Interview with: Marya Viorst Gwadz, Ph.D Senior Research Scientist Director, Transdisciplinary Methods Core Center for Drug Use and HIV Research (CDUHR) New York University College of Nursing New York, NY 10010 Medical Research: What is the background for this study? Dr. Gwadz: HIV is a major success story in that the tolerability, convenience, and efficacy of antiretroviral medications have improved dramatically over the last decade. A number of years ago in the course of another research study with vulnerable individuals infected with HIV in New York City, and we noticed that a substantial proportion of study participants were medically eligible for HIV medications, and had access to medications, but had declined or stopped taking them. We then turned our attention to understanding why this is the case, that is, to identify the individual, social, and structural barriers that persons living with HIV/AIDS (PLHA) experience to antiretroviral therapy. We focused in particular on African American/Black and Latino/Hispanic PLHA, because the overall emphasis of our research group at the NYU College of Nursing is the development and evaluation of culturally targeted intervention approaches to address health disparities. Around 2011, studies of the “HIV cascade of care” began to emerge, which highlighted the problem of poor engagement in HIV care and antiretroviral therapy nationally. The ultimate goal of HIV treatment is viral suppression, but at present, the Centers for Disease Control and Prevention (CDC) estimates that we have achieved that goal with only 30% of PLHA. Medical Research: What kind of intervention approach that emerged from these background findings? Dr. Gwadz: We found that barriers to HIV medication are complex and multi-faceted for PLHA from African American/Black and Latino/Hispanic backgrounds. In particular, PLHA experience serious emotional barriers to the uptake of HIV medications, such as fear of side effects, stigma, and disclosure of HIV status. Further, high rates of substance use and mental health distress, and barriers to accessing services for these concerns, impede medication uptake. Moreover, PLHA who are wary of HIV medication tend to avoid HIV primary care, often because they do not want to feel pressured to take medications, or explain to their providers why they are not taking them. So poor engagement in HIV care, which is very common among PLHA, and low uptake of HIV medication are actually related problems. With funding from the National Institute of Mental Health (grant #R34MH093352), and in collaboration with Mount Sinai Beth Israel and Mount Sinai St. Luke’s-Roosevelt Hospital Center, we developed a multi-component culturally targeted intervention grounded in the Motivational Interviewing approach that included three individual sessions, 12-24 weeks of patient navigation (as needed), up to five support groups with other PLHA who had declined medication, which were co-led by a “successful” peer who was engaged in HIV care and were taking HIV medication with good adherence. One novel aspect of the intervention was its focus on emotional barriers to HIV medication, and the program’s “no pressure, no judgment” stance, congruent with the Motivational Interviewing approach, was key to engaging participants into the study to talk about these difficult issues. (more…)
Author Interviews, Cancer Research, Nature, NYU / 03.04.2015

MedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology NYU Langone Medical CenterMedicalResearch.com Interview with: Alka Mansukhani Ph.D. Associate Professor Department of Microbiology Member of the Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Mansukhani: Osteosarcoma is a highly aggressive pediatric bone cancer that is almost always advanced at diagnosis. Treatment outcomes have not improved in three decades and 40% of patients eventually succumb to the disease. A few years ago we identified that normal bone stem cells relied on the function of a gene called Sox2 to remain immature an self-renew. We went on to find that osteosarcoma cancer stem cells, that arise from immature bone cells, express high levels of Sox2. Like their normal counterparts, these cancer cells also need Sox2. Sox2 maintains the stemness properties of the cancer cells as well as their ability to form tumors in mice. Depleting Sox2 resulted in cells that had reduced tumor-forming potential and instead, were able to become mature bone cells. http://www.stbaldricks.org/blog/post/new-discovery-may-hold-the-key-to-destroying-osteosarcoma/ In this new study we have identified the mechanism by which Sox2 maintains the properties of osteosarcoma cancer stem cells. Sox2 inactivates the growth restraining function of the well-known tumor suppressive hippo pathway. Hippo signaling restrains the activity of a potent oncogene, YAP. In the osteosarcoma stem cells, Sox2 directly represses two genes (Nf2 and WWC1) in the hippo pathway and thereby unleashes the growth promoting activity of YAP. Like Sox2, YAP is required to maintain the tumorigenic properties of osteosarcoma cells. Consistently, we found high YAP and low NF2 and WWC1 expression in human osteosarcoma tissues. Our study makes a direct connection between Sox2 and repression of hippo signaling to enable YAP activity in osteosarcomas. This mechanism also operates in glioblastoma, an aggressive brain tumor. (more…)
Aging, Author Interviews, Education, NYU, Surgical Research / 21.03.2015

Uzma Samadani, MD, PhD Chief of Neurosurgery, New York Harbor Health Care System Assistant Professor, Departments of Neurosurgery, Psychiatry, Neuroscience and Physiology Co-Director, Steven and Alexandra Cohen Veterans Center NYU Langone Medical CenterMedicalResearch.com Interview with: Uzma Samadani, MD, PhD Chief of Neurosurgery, New York Harbor Health Care System Assistant Professor, Departments of Neurosurgery, Psychiatry, Neuroscience and Physiology Co-Director, Steven and Alexandra Cohen Veterans Center NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Response: The purpose of this study was to determine the current and future incidence of chronic subdural hemorrhage in the United States civilian and Veterans' Administration populations.  It's main findings are that, as the population ages, the incidence of subdural hemorrhage is increasing. (more…)
Author Interviews, Heart Disease, NEJM, NYU, UCSD / 20.03.2015

Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI, Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, The Leon H. Charney Division of Cardiology, Associate Professor of Medicine, New York University School of Medicine, New York, NY 10016.MedicalResearch.com Interview with: Sripal Bangalore, MD, MHA, FACC, FAHA, FSCAI Director of Research, Cardiac Catheterization Laboratory, Director, Cardiovascular Outcomes Group, Associate Professor of Medicine, New York University School of Medicine, New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Bangalore: Prior studies have shown a mortality benefit of bypass surgery over stenting. But these studies compared bypass surgery with older generation stents which are no longer used. We used data from the New York state registry of patients who underwent stenting or bypass surgery for 2 or more blockages of coronary arteries. With data from over 18,000 patients we found that there was no difference between stenting and bypass surgery for long term mortality. In addition we found that both procedures have trade offs. Bypass surgery has upfront risk of death and stroke whereas PCI has long term risk of needing a repeat procedure. In addition, in patients who underwent incomplete revascularization, there was increase in myocardial infarction with PCI. (more…)
AHA Journals, AHRQ, Author Interviews, Blood Pressure - Hypertension, Electronic Records, NYU / 14.03.2015

Stella Yi, Ph.D., MPH, Assistant Professor Department of Population Health New York University School of MedicineMedicalResearch.com Interview with: Stella Yi, Ph.D., MPH, Assistant Professor Department of Population Health New York University School of Medicine MedicalResearch: What is the background for this study? What are the main findings? Dr. Yi: Self-blood pressure monitoring has been shown to be an effective tool for improving blood pressure control, however most studies have only included white race participants. We were interested in assessing whether distribution of self-blood pressure monitors (intervention) would improve blood pressure and hypertension control over usual care (control) in a 9-month period in a predominantly Hispanic, uninsured population. Systolic blood pressure improved over time in both the intervention (n=409) and the control (n=419) arms by 14.7 mm Hg and 14.1 mm Hg, respectively, as did hypertension control; 39% of study participants overall achieved control at the end of follow-up. However there were no statistical differences between the outcomes in the intervention and usual care groups. (more…)
Author Interviews, Cost of Health Care, JAMA, Medical Imaging, NYU / 12.03.2015

Danil Makarov, MD Lead Investigator Assistant Professor, Departments of Urology, Population Health and Health Policy Member, Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center, New York, NYMedicalResearch.com Interview with: Danil Makarov, MD Lead Investigator Assistant Professor, Departments of Urology, Population Health and Health Policy Member, Laura and Isaac Perlmutter Cancer Center NYU Langone Medical Center, New York, NY Medical Research: What is the background for this study? Dr. Makarov: The background for this study is that regional variation in patterns of care and healthcare spending is widely known.  The drivers of this regional variation, though, are poorly understood.  Certain policy groups like the IOM have suggested that policy efforts be focused on individual providers and patients. Programs such as Choosing Wisely, which encourage a dialogue between physicians and patients, are a great example of such efforts.  However, some of our prior research suggests that regional variation is not random and that there might be are regional-level factors which drive variation. To test out our hypothesis, we wanted to see whether inappropriate imaging for two unrelated cancers was associated at a regional level (it should not be). Medical Research: What are the main findings? Dr. Makarov: We found that, at a regional level, inappropriate breast cancer imaging was associated with inappropriate prostate cancer imaging. (more…)
Author Interviews, Nutrition, NYU, Pediatrics, Weight Research / 26.02.2015

Brian Elbel, PhD, MPH Associate Professor, Department of Population Health; Associate Professor, Department of Medicine Population Health NYU School of MedicineMedicalResearch.com Interview with: Brian Elbel, PhD, MPH Associate Professor, Department of Population Health; Associate Professor, Department of Medicine Population Health NYU School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Elbel: This study tried to determine whether a new supermarket that received tax and zoning credits from New York City, locating in a high need area, impacted healthy eating for children.  No previous controlled study has looked at children, and supermarkets are tool being increasingly used to improve healthy eating.  We did not find, at least one year after the store opened, any appreciable change in shopping or eating. (more…)
Author Interviews, Biomarkers, Melanoma, NYU, Personalized Medicine / 24.02.2015

Iman Osman, MD Professor, Departments of Dermatology, Medicine and Urology Associate Director, NYU Cancer Institute  Director, Interdisciplinary Melanoma Program  New York University Langone Medical Center New York, NY 10016MedicalResearch.com Interview with: Iman Osman, MD Professor, Departments of Dermatology, Medicine and Urology Associate Director The Laura and Isaac Perlmutter Cancer Center Director, Interdisciplinary Melanoma Program New York University Langone Medical Center New York, NY 10016 MedicalResearch: What is the background for this study? What are the main findings? Dr. Osman: We were interested in exploring molecules that could be biomarkers or functional regulators of metastasis in melanoma in early-stage tumor lesions on the skin. Though these tumors are treated largely the same (by surgical removal ), patients with these tumors have vastly different outcomes (apparent cure vs. metastatic spread of the disease). The reasons for these disparities are unclear and we have little ability to identify or predict the patients that will be cured and those that won’t. We also don’t have much data to know even if these tumors have differences at the molecular level. Our findings indicate that there are molecular differences in these tumors and that some of these differences contribute to tumor spread.  (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…)
AHA Journals, Author Interviews, Heart Disease, Hospital Readmissions, NYU / 16.01.2015

Leora Horwitz, MD, MHS Director, Center for Healthcare Innovation and Delivery Science New York University Langone Medical Center Director, Division of Healthcare Delivery Science Department of Population Health, NYU School of Medicine New York, NY 10016MedicalResearch.com Interview with: Leora Horwitz, MD, MHS Director, Center for Healthcare Innovation and Delivery Science New York University Langone Medical Center Director, Division of Healthcare Delivery Science Department of Population Health, NYU School of Medicine New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Horwitz: We reviewed over 1500 discharge summaries from 46 hospitals around the nation that had been collected as part of a large randomized controlled trial (Telemonitoring to Improve Heart Failure Outcomes). All summaries were of patients who were admitted with heart failure and survived to discharge. We found that not one of them met all three criteria of being timely, transmitted to the right physician and fully comprehensive in content. We also found that hospitals varied very widely in their average quality. For instance, in some hospitals, 98% of summaries were completed on the day of discharge; in others, none were. In the accompanying Data Report, we show that summaries transmitted to outside clinicians and including more key content elements are associated with lower risk of rehospitalization within 30 days of discharge. This is the first study to demonstrate an association of discharge summary quality with readmission. (more…)
Author Interviews, Heart Disease, NYU / 26.12.2014

Dr. Glenn I. Fishman MD Professor; William Goldring Professor of Medicine Vice Chair Research Dept of Medicine Director of the Leon H. Charney Division of Cardiology NYU LangoneMedicalResearch.com Interview with: Dr. Glenn I. Fishman MD Professor; William Goldring Professor of Medicine Vice Chair Research Dept of Medicine Director of the Leon H. Charney Division of Cardiology NYU Langone Medical Research: What is the background for this study? What are the main findings? Dr. Fishman: Sudden cardiac arrest (SCA) due to life-threatening ventricular arrhythmias is one of the leading causes of death in the US. Conditions that predispose to SCA can be acquired, as in atherosclerotic coronary artery disease, or inherited in the form of mutated cardiac ion channels, i.e. ion channelopathies. Mutations in the SCN5A cardiac sodium channel gene have been linked to progressive cardiac conduction disorders as well as atrial and ventricular arrhythmias. Understanding the mechanistic basis for lethal arrhythmias in cardiac sodium channelopathy patients has been limited in part due to the lack of adequate model systems that replicate human physiology. To address this limitation, we have developed the first genetically modified porcine model of an inherited channelopathy. A mutation in the SCN5A gene first identified in a child with the arrhythmic condition Brugada syndrome was introduced into the pig genome. Mutant pig hearts displayed conduction abnormalities and ventricular fibrillation bearing striking resemblance to the human condition. (more…)
Author Interviews, Brain Injury, NYU / 17.12.2014

Uzma Samadani, MD. PhD. FACS. Chief Neurosurgeon New York Harbor Health Care System Co-Director Steven and Alexandra Cohen Veterans Center for PTSD and TBI Assistant Professor Departments of Neurosurgery, Psychiatry and Physiology & Neuroscience New York University School of Medicine New York , NY 10010MedicalResearch.com Interview with: Uzma Samadani, MD. PhD. FACS. Chief Neurosurgeon New York Harbor Health Care System Co-Director Steven and Alexandra Cohen Veterans Center for PTSD and TBI Assistant Professor Departments of Neurosurgery, Psychiatry and Physiology & Neuroscience New York University School of Medicine New York , NY 10010 Medical Research: What is the background for this study? What are the main findings? Dr. Samadani: Eye tracking has been used for 30 years to investigate where people look when they follow particular visual stimuli.  Tracking has not, however, been previously used to assess underlying capacity for eye movement.  We have developed a very unique eye tracking algorithm that assesses the capacity of the brain to move the eyes. What we show in this paper is that with our eye tracking algorithm we can show (1) normal people have eye movements that, within a particular range, have equal capacity for vertical and horizontal movement, (2) people with specific weaknesses of the nerves that move the eyes up and down have decreased vertical capacity, (3) people with weaknesses in the nerves that move the eyes to the side have decreased horizontal capacity, (4) swelling in the brain can affect the function of these nerves and be detected on eye tracking, (5) eye tracking may be useful as a potential biomarker for recovery from brain injury. (more…)
Author Interviews, NYU, Surgical Research / 12.12.2014

Ganesh Sivarajan, MD Department of Urology New York University Langone Medical CenterMedicalResearch.com Interview with: Ganesh Sivarajan, MD Department of Urology New York University Langone Medical Center

  Medical Research: What is the background for this study? What are the main findings? Dr. Sivarajan: The surgical robot was designed to facilitate laparoscopic surgery. The surgeon sits at a console several feet away from the patient and is linked to a multi-armed robot which translates the surgeon’s movements from the console to surgical instruments inside the patient’s insufflated abdomen. The robot is equipped with a high resolution three dimensional camera which improves visualization over traditional open surgery and allows the manipulation of instruments in directions and angles which are difficult in traditional open surgery. In light of these apparent advancements, the robot was rapidly adopted for use during radical prostatectomy. The outcomes data for men undergoing robotic versus open prostatectomy, however, have not demonstrated any clear advantage of robotic surgery, with some studies demonstrating benefit and other demonstrating harm. This fact coupled with the relatively high cost of the robot and its disposable equipment have led many to criticize robotic surgery and its rapid adoption. Partial nephrectomy is a procedure performed for renal cancer in which just the malignant tumor is excised while the remaining healthy kidney is saved. It is increasingly considered to be preferable to the previous gold standard operation – radical nephrectomy or removal of the entire kidney largely secondary to the benefits accrued from preserving renal function. Despite actual changes in the treatment guideline recommending increased use of partial nephrectomy it remains vastly underutilized nationwide likely because of the technical challenges associated with its performance. It has been suggested that the surgical robot facilitates the performance of partial nephrectomy, but this has not been definitively demonstrated in a model which controls for important variables as the effects of changing guidelines, secular trends supporting increased utilization over time and a variety of other hospital-level characteristics. We sought to determine whether acquisition of the surgical robot was independently associated with increased utilization of partial nephrectomy – a guideline-supported procedure. If true, it would suggest that the acquisition of the surgical robot may have improved the quality of care of renal cell carcinoma patients. (more…)
Aging, Memory, NYU, Weight Research / 24.11.2014

Stephen D. Ginsberg, Ph.D., Associate Professor Departments of Psychiatry and Physiology & Neuroscience New York University Langone Medical Center Center for Dementia Research Nathan Kline Institute Orangeburg, NY  10962MedicalResearch.com Interview with: Stephen D. Ginsberg, Ph.D., Associate Professor Departments of Psychiatry and Physiology & Neuroscience New York University Langone Medical Center Center for Dementia Research Nathan Kline Institute Orangeburg, NY  10962 Medical Research: What is the background for this study? What are the main findings? Dr. Ginsberg: We tested the hypothesis that long-term calorie restriction positively alters gene expression within the hippocampus, a critical learning and memory area vulnerable in aging and Alzheimer’s disease. To test this hypothesis, we conducted experiments on female mice that were given food pellets 30% lower in calories than what was fed to the control group. The mice ate fewer calories derived from carbohydrates. Analyses were performed on mice in middle and old age to assess any differences in gene expression over time. Our data analysis revealed that the mice that were fed a lower calorie diet had fewer changes in approximately 900 genes that are linked to aging and memory. (more…)
NYU, Pain Research, Pediatrics / 21.11.2014

MedicalResearch.com Interview with: Regina Marie Sullivan PhD Professor Child and Adolescent Psychiatry Nathan Kline Institute The Child Study Center at NYU Langone Medical Center Department of Child and Adolescent Psychiatry One Park Ave 8th Floor, New York, NY 10016 Medical Research: What is the background for this study?  Dr. Sullivan: Managing pain during medical procedures in a critically important issue in medicine today. Our study was designed to better understand one method of reducing pain in young infants - having the caregiver be in contact with the baby during the painful procedure, which reduces the infant's behavioral response to the medical procedure. This study explored the neural basis of the ability of the caregiver to reduce the pain response. (more…)
Author Interviews, Genetic Research, Nature, NYU / 06.11.2014

Leslie Mitchell, PhD New York University Langone Medical Center Boeke Lab, Institute for Systems Genetics NY NY, 10016MedicalResearch.com Interview with: Leslie Mitchell, PhD New York University Langone Medical Center Boeke Lab, Institute for Systems Genetics NY NY, 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Mitchell: One of our major interests is building synthetic chromosomes. Typically we construct synthetic chromosomes using a bottom-up approach, first designing the sequence in silico and then synthesizing and piecing together the DNA to build the designer molecule. While eukaryotic chromosomes are usually linear in structure, oftentimes we build our designer synthetic chromosomes as circular molecules to take advantage of cloning technologies available in E. coli, an organism that tolerates only circular chromosomes. We developed the telomerator as a means by which to convert circular synthetic chromosomes into linear molecules, which more closely resemble the native chromosomes found in eukaryotic cells. We discovered that the telomerator is an extremely effective tool for generating linear derivatives of circular synthetic chromosomes. There are two main reasons for this.
  • First, the action of the telomerator can be assessed using a simple phenotypic assay so it is easy to differentiate cells that encode linear synthetic chromosomes from those with the circular format.
  • Second, the telomerator encodes ‘telomere seed sequences’ that are exposed and recognized by the cell upon linearization, thus the ends of a newly linearized chromosome are protected, which ensures its stability over generations. We put the telomerator to the test by integrating it in 54 different positions on a circular synthetic yeast chromosome called synIXR (Dymond et al. 2011). In 51 of the 54 positions we could successfully linearize the synIXR chromosome and recover viable cells, however many of the different linear derivatives conferred growth defects. We determined the mechanism underlying both the growth defects and lethality associated with linearization to be telomere position effect. In other words, when essential genes were re-positioned near telomeres their reduction in expression due to subtelomeric silencing was detrimental to the cell.
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Author Interviews, Melanoma, NYU / 06.10.2014

David Polsky, MD, PhD Alfred W. Kopf, MD, professor of Dermatologic Oncology Ronald O. Perelman Department of Dermatology NYU Langone Medical CenterMedicalResearch.com Interview with: David Polsky, MD, PhD Alfred W. Kopf, MD, professor of Dermatologic Oncology Ronald O. Perelman Department of Dermatology NYU Langone Medical Center Medical Research: What are the main findings of the study? Dr. Polsky: We utilized a multi-disciplinary approach including an analysis of socioeconomic factors to elucidate the evolution of attitudes and behaviors maximizing personal ultraviolet light exposure during the 20th century in the United States.  We then compared melanoma incidence rates from national cancer registries to estimated skin exposure and found that they rose in parallel. Though causation cannot be made in an analysis such as this one, this paper describes a historical context for the changing attitudes promoting increased UV exposure, and the rising incidence of melanoma throughout the past century.  It also provides a framework in which to consider public health and education measures that may ultimately help reverse melanoma incidence trends. (more…)
Author Interviews, Diabetes, NYU, Weight Research / 06.11.2013

Manish Parikh MD Associate Professor of Surgery, NYU School of Medicine Director of Bariatric Surgery, Bellevue Hospital Center 550 First Ave NBV 15 South 7 New York, NY 10010MedicalResearch.com Interview with: Manish Parikh MD Associate Professor of Surgery, NYU School of Medicine Director of Bariatric Surgery, Bellevue Hospital Center 550 First Ave NBV 15 South 7 New York, NY 10010 MedicalResearch.com: What are the main findings of the study? Dr. Parikh: The main findings of this study is that surgery is safe and effective in patients with type 2 diabetes and BMI under 35.  The overall estimated rate of diabetes remission was 55% at 12 months, ranging from 33% for the adjustable gastric banding, 49% for the “mini” gastric bypass, 54% for the sleeve gastrectomy, 64% for the gastric bypass, 71% for the biliopancreatic diversion, and 81% for ileal transposition. (more…)
Author Interviews, Cancer Research, Diabetes, NYU, Weight Research / 26.09.2013

Niyati Parekh, PhD, RD Assistant Professor of Nutrition and Public Health, Director of Doctoral Program in Clinical Nutrition, Department of Nutrition, Food Studies and Public Health, Steinhardt School and Department of Population Health, NYU Langone School of Medicine, New York University 411 Lafayette Street NY. NY-10003.MedicalResearch.com Interview with: Niyati Parekh, PhD, RD Assistant Professor of Nutrition and Public Health, Director of Doctoral Program in Clinical Nutrition, Department of Nutrition, Food Studies and Public Health, Steinhardt School and Department of Population Health, NYU Langone School of Medicine, New York University 411 Lafayette Street NY. NY-10003. MedicalResearch.com: What are the main findings of the study? Dr. Parekh: The objective of the study was to investigate disturbances in blood glucose levels in relation to risk of obesity-related cancers. We observed an increased risk of obesity-related cancers, specifically colon cancer among persons with abnormal glucose values. These findings were stronger among persons who had this abnormality for longer duration (>10years). (more…)
Author Interviews, Cost of Health Care, Electronic Records, NYU / 23.08.2013

MedicalResearch.com Interview with: Saul Blecker, MD, MHS Assistant Professor Department of Population Health NYU School of Medicine 227 East 30th St., #648 New York, NY 10016Saul Blecker, MD, MHS Assistant Professor Department of Population Health NYU School of Medicine 227 East 30th St., #648 New York, NY 10016 MedicalResearch.com: What are the main findings of the study? Dr. Blecker: We tracked utilization of the inpatient electronic health record (EHR) as a proxy for hospital intensity of care. EHR utilization was found to have variations over time, particularly when comparing days to nights and weekdays to weekends. (more…)