AHA Journals, Author Interviews, NEJM, Surgical Research / 18.02.2016

MedicalResearch.com Interview with: Dr. William A Gray, MD Chief of the Division of Cardiovascular Disease Main Line Health President of Main Line Health’s Lankenau Heart Institute  Medical Research: What is the background for this study? What are the main findings? Dr. Gray: The basis for this study was two-fold: the ACST-1 trial had shown, in asymptomatic patients with severe carotid disease, that immediate Carotid Endarterectomy reduced subsequent stroke as compared to deferred Carotid Endarterectomy---so the next logical question was, could Carotid Artery Stenting (CAS) compare as an equal alternative to Carotid Endarterectomy (CEA) in this same, standard risk, population with severe carotid stenosis. The CREST trial, as originally constructed and at the time ACT 1 was conceived did not include this population (although it later expanded to encompass asymptomatic patients as well), so it was an open question. The second reason had to do with Abbott Vascular, the study sponsor, achieving FDA regulatory approval for their stent system in this population---as well as in the symptomatic population being studied n CREST (which they were also the device sponsor). The main findings were that the primary endpoint of death/stroke and MI at 30 days plus ipsilateral stroke out to 1 and 5 years was not different between CAS and CEA in asymptomatic patients with severe carotid stenosis on good medical secondary prevention therapy. (more…)
Author Interviews, Cannabis, Genetic Research, Memory / 17.02.2016

MedicalResearch.com Interview with: Prof. Celia Morgan PhD Professor of Psychopharmacology University of Exeter  Medical Research: What is the background for this study? What are the main findings? Dr. Morgan: We know cannabis increases the risk of psychosis but it is unclear how we can predict who is vulnerable to these negative effects. This study suggested that cannabis may have stronger effects in people carrying a particular genetic variant. This might be related to their risk of developing psychosis. We also found that women are more susceptible to the short term memory impairing effects of cannabis. (more…)
Author Interviews, Pain Research / 17.02.2016

MedicalResearch.com Interview with: Souvik Sen, MD, MS, MPH, FAHA Professor and Chair,  Neurology Department, South Carolina Smart State Endowed Stroke Chair University of South Carolina School of Medicine  Medical Research: What was the catalyst for conducting this study examining the association between migraine with aura and ischemic stroke subtypes? Dr. Souvik Sen: South Carolina, North Carolina, and Georgia are located in the “buckle” of the stroke belt, with one of the highest stroke related death rates in the country. An unfortunate trend is that younger patients are having strokes leading to death and disability. As a part of the workup for young stroke we are interested in migraine with aura and the type of stroke associated with this condition. Medical Research: What did you conclude as a result of the findings and how did they compare with your expectations at the beginning of the study? (more…)
Author Interviews, Breast Cancer, JAMA, Outcomes & Safety, Surgical Research / 17.02.2016

MedicalResearch.com Interview with: Dr. Art Sedrakyan MD PhD ScD Professor of Healthcare Policy and Research in Cardiothoracic Surgery Department of Public Health Weill Cornell Medical College  Medical Research: What is the background for this study? What are the main findings? Dr. Sedrakyan: In the most recent years available to us for research(2011-2013) one in four women underwent repeat surgery within 90 days after breast conserving approach to cancer removal. Patients operated by higher volume physicians had lower chance of undergoing repeat surgery.Uniform guidelines and increased surgical training are needed to standardize the breast conserving surgery to reduce the high rate of repeat surgery. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Pharmacology / 17.02.2016

MedicalResearch.com Interview with: Professor Chris Thiemermann Centre for Trauma Sciences Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Prof. Thiemermann: Trauma is a leading cause of death with five million victims a year. About 40 per cent of trauma deaths are due to hemorrhagic shock, which is when severe blood loss makes it difficult for the heart to pump sufficient blood around the body, leading to multiple organ failure. Multiple organ failure affects one in three severely injured patients, and one in four of those will die.  Those that survive still experience prolonged periods in intensive care, infections and other complications. But despite its catastrophic impact, there are still no specific treatments for organ failure. We’ve now discovered that the drug Artesunate, which has already been used by thousands of people with malaria, is also effective for treating severe haemorrhage and blood loss in rats. Artesunate is based on an ancient Chinese herbal remedy, produced in large quantities in China, and is recommended by the World Health Organization as the treatment of choice for severe malaria. It has also been shown to have anti-cancer, anti-viral and anti-inflammatory effects. My study, which was funded by the Wellcome Trust and the Department of Health, shows that when injured rats were administered Artesunate, the drug had a marked protective impact on organ failure. The drug appears to work by enhancing the protection of organs by reducing the body’s excessive inflammatory response to injury and blood loss, and by activating well-known cell-survival pathways. The lower dose of Artesunate shown in the study to be effective in hemorrhagic shock is identical to the dose used in patients with malaria, many of which also have multiple organ dysfunction. (more…)
Addiction, Author Interviews, HIV / 16.02.2016

MedicalResearch.com Interview with: Pedro Mateu-Gelabert, Ph. D. Principal Investigator National Development Research Institutes, Inc. New York, NY 10010  Medical Research: What is the background for this study? What are the main findings? Dr. Mateu-Gelabert: Heroin production in Colombia increased dramatically in recent decades, and some studies point to an increase in local heroin consumption since the mid-1990s. Despite this rapid increase, little is known about the effects of these activities on heroin injection within Colombia. One of the biggest concerns surrounding heroin injection is the potential spread of HIV through drug user networks. Medical Research: What should clinicians and patients take away from your report? Dr. Mateu-Gelabert: The key take home message in the paper is that a widespread early implementation of harm reduction services (e.g. opioid substitution therapy, HIV testing, syringe exchange programs)  can prevent HIV among young PWID (People Who Inject Drugs) before it rapidly spreads within drug injection networks. Reducing HIV among young drug injectors could prevent the spread of HIV from PWID to the general population. (more…)
Author Interviews, Cleveland Clinic, Lancet, Multiple Sclerosis / 16.02.2016

MedicalResearch.com Interview with: Dr Jeffrey A Cohen MD Mellen Center, Neurological Institute Cleveland Clinic, Cleveland OH 44195, USA Medical Research: What is the background for this study? What are the main findings? Dr. Cohen: Fingolimod, a non-selective sphingosine 1-phosphate receptor (S1PR) modulator, was the first oral medication approved to treat relapsing multiple sclerosis.  Though generally well tolerated, fingolimod’s first dose cardiac effects and other potential adverse effects complicate its use.  Ozanimod is a selective S1PR modulator with several other potentially advantageous pharmacologic properties. The results of phase 2 RADIANCE trial were recently published.  In this trial, participants were randomized to placebo (n=88), ozanimod 0.5 mg (n=87), or ozanimod 1 mg (n=83) PO once daily for 24 weeks.  The mean cumulative number of gadolinium-enhancing lesions on monthly MRI scans at weeks 12-24, the primary endpoint, was reduced from 11.1 +/- 29.9 with placebo to 1.5 +/- 3.7 with ozanimod 0.5 mg and 1.5 +/- 3.4 with ozanimod 1 mg (both p<0.0001).  Other MRI endpoints supported the primary endpoint.  Ozanimod was well tolerated with good safety.  Importantly, the dose up-titration protocol effectively mitigated first dose cardiac effects. (more…)
Author Interviews, CDC, JAMA / 16.02.2016

MedicalResearch.com Interview with: Philip J. Peters, M.D. HIV Testing and Biomedical Interventions Activity Lead Epidemiology Branch CDC’s Division of HIV/AIDS Prevention Medical Research: What is the background for this study? What are the main findings? Dr. Peters:  Acute HIV infection contributes disproportionately to HIV transmission and identifying individuals with acute HIV infection is critical to prevent further HIV transmission, as diagnosis can lead to several effective HIV prevention interventions. Acute HIV infection can be diagnosed with assays that detect either HIV RNA (the reference standard) or the p24 antigen (an HIV core protein), which are both detectable early after HIV infection and before an antibody response develops. HIV immunoassays that detect both the p24 antigen and anti-HIV antibody (fourth generation antigen/antibody [Ag/Ab] combination immunoassays) are currently being implemented as the initial screening test in the 2014 CDC and American Public Health Laboratories (APHL) recommended HIV diagnostic algorithm. In a prospective study we evaluated the performance of an HIV Ag/Ab combination assay to detect acute HIV infection compared with pooled HIV RNA testing in a high-prevalence population. All participants were first screened with a rapid HIV test to detect established HIV infection (antibody detectable).  All participants with a negative rapid HIV test result were then screened for acute HIV infection with an HIV Ag/Ab combination assay (index test) and pooled HIV-1 RNA testing.  HIV RNA testing was the reference standard, with positive reference standard result defined as detectable HIV-1 RNA on an individual RNA test. Among 86,836 participants with complete test results (median age, 29 years; 75.0% male; 51.8% men who have sex with men), acute HIV infection was diagnosed in 168 (0.19%). Acute HIV infection was detected in 134 (0.15%) participants with HIV Ag/Ab combination testing (acute HIV infection sensitivity, 79.8%) and in 164 (0.19%) with pooled HIV RNA testing (sensitivity, 97.6%; sensitivity comparison, p<0.001). Overall HIV Ag/Ab combination testing detected 82% of acute HIV infections detectable by pooled HIV RNA testing. Compared with rapid HIV testing alone (which detected established HIV infection), HIV Ag/Ab combination testing increased the relative HIV diagnostic yield (both established and acute HIV infections) by 10.4% and pooled HIV RNA testing increased the relative HIV diagnostic yield by 12.4%. (more…)
Author Interviews, Diabetes, OBGYNE, Weight Research / 16.02.2016

MedicalResearch.com Interview with: Katherine Bowers, PhD, MPH Division of Biostatistics and Epidemiology Cincinnati Children's Hospital MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Bowers: Autism spectrum disorder (ASD) affects approximately 1 in 68 children and the prevalence continues to rise. Past studies have suggested that conditions experienced by women during pregnancy (for example, obesity and gestational diabetes mellitus (GDM)) may be associated with having a child with ASD. We collected medical record data from patients who resided in the Cincinnati Children’s Hospital Medical Center’s primary catchment area and linked those data to data from birth certificates to identify metabolic risk factors. Two comparison groups were analyzed; one with developmental disabilities; and the other, controls without a reported ASD or other developmental disability. Descriptive statistics and regression analyses evaluated differences. We found that maternal obesity and  gestational diabetes mellitus were associated with an increased risk of Autism spectrum disorder in the offspring; however, no difference in risk of Autism spectrum disorder according to BMI and GDM was seen when comparing to the group with other developmental disabilities. The strongest observed association was the joint effect of obesity and GDM (compared to neither obesity nor GDM) :OR=2.53 (95% CI: 1.72, 3.73). (more…)
Author Interviews, Heart Disease, Hospital Readmissions / 16.02.2016

MedicalResearch.com Interview with: Rashmee U. Shah, MD MS Cardiovascular Medicine University of Utah School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The purpose of this study was to evaluate long term outcomes of acute myocardial infarction (AMI) survivors who have cardiogenic shock. We used the ACTION Registry-GWTG (from the NCDR), which is the largest database of AMI, or heart attack, patients in the United States. Some heart attack patients develop cardiogenic shock which is a condition in which the heart muscle becomes so weak that it cannot effectively pump blood to the rest of the body. These patients are critically ill, but with advances in our treatment for heart attacks, many will survive to hospital discharge. We wanted to know, after all the intense treatment and sometimes long hospitalization, how do these patients fare when they leave the hospital? From a total of 112,668 heart attack patients who survived hospitalization, we identified 5,555 who had cardiogenic shock. Over half of all patients were either hospitalized or died within one year of discharge, and this poor outcome was more common among patients who had cardiogenic shock. In fact, the risk of death or hospitalization seems to be clustered in the early post-discharge time period, within 60 days, for patients with cardiogenic shock. After 60 days, shock and non-shock patients experience similar risk. In other words, we found that heart attack patients who had cardiogenic shock are particularly vulnerable during the first 60 days after hospital discharge. (more…)
Author Interviews, Hospital Readmissions, JAMA, Pediatrics / 16.02.2016

MedicalResearch.com Interview with: Marion R. Sills, MD, MPH Associate Professor, Departments of Pediatrics and Emergency Medicine University of Colorado School of Medicine Medical Research: What is the background for this study? Dr. Sills: My co-authors and I know that studies show that patients who are poorer or are minorities are readmitted at higher rates than other patients, and that readmissions penalties, which are far more commonly applied in relation to readmissions of adult patients, have been shown to punish hospitals for the type of patients that they serve, rather than purely for the quality of care they provide.  Currently, these penalties impact hospitals treating Medicare patients in all 50 states but only impact readmissions of children in 4 states, although other states are considering implementing these penalties.  This was our rationale for exploring the impact of patients’ social determinants of health (factors like race, ethnicity, health insurance and income) on how likely it was that a hospital would be penalized for readmissions under a typical state-level pay-for-performance measure based on hospital readmissions. Readmissions penalties are designed to penalize hospitals that provide lower quality care. However, without adjusting for social determinants of health factors, these pay-for-performance measures may unfairly penalize hospitals based on the type of patient they treat as well as the quality of care they provide. Medical Research: What are the main findings? Dr. Sills: We found that risk adjustment for social determinants of health factors changed hospitals’ penalty status on a readmissions-based pay-for-performance measure. Without adjusting the pay-for-performance measures for social determinants of health, hospitals may receive penalties partially related to patient factors beyond the quality of hospital care. (more…)
Author Interviews, Exercise - Fitness, Orthopedics / 15.02.2016

MedicalResearch.com Interview with: Pamela S. Hinton, Ph.D. Associate Professor Director of Graduate Studies, Nutritional Sciences Department of Nutrition and Exercise Physiology University of Missouri, Columbia MO 65211 Medical Research: What is the background for this study? What are the main findings? Dr. Hinton: Because bone mass declines with age, maximization of peak bone mass is recommended as the most effective way to prevent osteoporosis. Acquisition of at least 90% of peak bone mass occurs by the age of 18 years, with additional gains of 5% to 10% during young adulthood. Because mechanical loading induces a greater adaptive response in young, compared with old, bone, adolescence and young adulthood constitute a unique window of opportunity to increase bone mass via physical activity. Although physical activity during adolescence and young adulthood is a key determinant of peak bone mass and, therefore, of future bone health, exercise after skeletal maturation can also reduce the risk of osteoporosis and related fractures. Therefore, the objective of the present study was threefold: (a) to examine the relationships between current BMD of the whole body, hip, and lumbar spine and physical activity–associated bone loading during adolescence (13-18 years), young adulthood (19-29 years), and current physical activity–associated bone loading; (b) to investigate the effects of current participation in a high-impact physical activity and/or resistance training on BMD of the whole body, total hip, and lumbar spine in apparently healthy, physically active men; and, (c) to evaluate the effects of continuous participation in high-impact activity throughout the life span on BMD of the whole body, total hip, and lumbar spine. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: Dr. Britta Haenisch PhD German Center for Neurodegenerative Diseases (DZNE)  Medical Research: What is the background for this study? Dr. Haenisch: Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases, but have also been shown to be potentially involved in cognitive decline: There were hints from recent other studies that PPIs might affect cognition, e.g. Lam et al. (2013) report a significant association of PPI use with vitamin B12 deficiency in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance amyloid beta peptide (Aβ) levels in mouse brain by affecting the enzymes β- and γ-secretase which leads to increased Aβ levels in mice. Medical Research: What are the main findings? Dr. Haenisch: The current study provides a statistical association (applying a time-dependent analysis) between proton pump inhibitors prescription and occurrence of dementia with a focus on long-term regular PPI prescription in patients aged 75 years and older. In our analysis we focused on long-term regular PPI prescription for at least 18 months. It does not prove that proton pump inhibitors cause dementia. References -Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442. -Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837 (more…)
AHA Journals, Asthma, Author Interviews, Brigham & Women's - Harvard, Heart Disease / 15.02.2016

MedicalResearch.com Interview with: Guo-Ping Shi, ScD and Dr. Cong-Lin Liu Cardiovascular Medicine Brigham and Women’s Hospital Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: Abdominal aortic aneurysm (commonly called AAA) is an aortic disease that affects 1~5% men above 50, depending on the countries and regions. There is currently no effective medication or prevention besides surgical repair. Fast growth or unstable AAA often leads to aortic rupture and sudden death. Although ultrasound can be used to monitor the size and growth of AAA, our current annual health examination system in the US does not include this service. We report that mast cells are essential to AAA (J Clin Invest. 2007;117:3359-68). These cells are predominant immune cells in allergic asthmatic lungs from humans and experimental animals. Plasma immunoglobulin E (IgE) level elevation is also a signature of allergic asthma. We report that IgE contributes to experimental AAA by activating mast cells, as well as other immune cells such as macrophages and T cells (EMBO Mol Med. 2014;6:952-69). Direct evidence from our recent study demonstrates that production of allergic asthma in mice doubles the AAA sizes in experimental mice (Arterioscler Thromb Vasc Biol. 2016;36:69-77). All these prior studies suggest a role of allergic asthma to the pathogenesis of AAA. In this human population-based nationwide case-control study (Arterioscler Thromb Vasc Biol. 2016 Feb 11. [Epub ahead of print]), we reported two major findings: First, among 15,942 Danish AAA patients selected from 1996 to 2012, compared to those who did not have asthma, patients who had hospital-diagnosed asthma within the past 12 months had 60% more risk to experience aortic rupture, and those who had hospital-diagnosed asthma within the past 6 months had greater than 100% more risk to experience aortic rupture. Further, patients who received anti-asthmatic treatment, as evidence of asthma, also had 20~50% more risk of experiencing aortic rupture than those who did not have record of anti-asthmatic treatment, depending on how recent the patients received the treatments. Second, among a general men population aged from 65 to 74, patients who used bronchodilating drugs to treat asthma or reversible obstructive pulmonary disease had 45% more risk to have AAA compared with those who never used bronchodilators. This risk was not affected by smoking or other major AAA risk factors. (more…)
Author Interviews, Epilepsy, Lancet, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: Dr. Michael Privitera MD Professor of the Department of Neurology and director of the Epilepsy Center University of Cincinnati Neuroscience Institute  Medical Research: What is the background for this study? What are the main findings? Dr. Privitera: Generic substitution of medications has saved the American health care system billions of dollars per year. However, based on a series of uncontrolled studies, patients and clinicians share concerns that generic substitution of antiepileptic drugs may lead to loss of efficacy or emergence of adverse effects. To answer this question we undertook a prospective, randomized study that tested bioequivalence of two generic products of the antiepileptic drug lamotrigine. Lamotrigine was identified in several publications as a possible source of problems after generic switches. FDA studies test a single generic versus the brand name product in a single dose study in normal volunteers. We designed a study that would be most likely to show a difference between generics if one existed. We compared the two generic lamotrigine products showing the most difference in prior testing in patients with epilepsy taking the drug daily using rigorous pharmacokinetic methods. Each patient took each of the two generics for 2 four week periods. Our study showed the two generics were essentially indistinguishable and easily met bioequivalence standards. No patient had loss of seizure control or unexpected adverse effects. (more…)
Author Interviews, Brigham & Women's - Harvard, Macular Degeneration / 15.02.2016

MedicalResearch.com Interview with: Demetrios Vavvas, M.D., Ph.D. Co-Director Ocular Regenerative Medical Institute Clinician scientist at Mass. Eye and Ear and Co-Director of the Ocular Regenerative Medicine Institute at Harvard Medical School Medical Research: What is the background for this study? Dr. Vavvas: There is a lack of effective therapies for dry age-related macular degeneration (AMD), one of the leading causes of blindness affecting millions. Although AMD shares similarities with atherosclerosis, prior studies on statins and AMD have failed to show improvement. A limitation of these studies has been the heterogeneity of  age-related macular degeneration disease and the lack of standardization in statin dosage. We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in age-related macular degeneration. Medical Research: What are the main findings? Dr. Vavvas: Here, we present for the first time evidence that treatment with high-dose atorvastatin (80mg) is associated with regression of lipid deposits and improvement in visual acuity, without atrophy or neovascularization, in high-risk age-related macular degeneration patients. Medical Research: What should clinicians and patients take away from your report? Dr. Vavvas:
  • High dose lipophilic statin administration was associated with regression of large soft drusen and vision gain in 10/23 age-related macular degeneration patients.
  • Duration of treatment before a positive response was observed was usually 1-1.5 years.
  • Patients on high-dose statin appeared to be protected from progression to “wet” neovascular-AMD.
Cholesterol reduction was similarly drastic in responders and non-responders, which suggests that genetic variation may be important in determine who will benefit and who may not. Age-related macular degeneration is a heterogeneous disease and that targeting the lipid pathway in the appropriate manner and to the appropriate populations we may have the potential not only to slow down or arrest the disease but all to reverse it. (more…)
Author Interviews, Genetic Research, Race/Ethnic Diversity, Science / 15.02.2016

MedicalResearch.com Interview with: Michael Yudell, PhD, MPH Chair & Associate Professor Drexel University School of Public Health Community Health and Prevention Philadelphia, PA 19104 Medical Research: What is the background for this study? Dr. Yudell: We came together as a group of scholars from the natural sciences, social sciences, and humanities to address what we believe is a long-standing challenge: how to improve the study of human genetic diversity without recapitulating the controversial and problematic concept of race. We believe that the cross-disciplinary focus of our work—an examination of the historical, biological, and sociological aspects of the race concept—can shed new light on the long-standing debate about the use of the race concept in genetics research. We believe modern genetics remains stuck in a paradox: that on the one hand race is a tool to elucidate human genetic diversity, and on the other hand race is believedthree main concerns to be a poorly defined marker of that diversity and an imprecise proxy for the relationship between ancestry and genetics. This paradox is rooted in the nature of the field: it dates back to the evolutionary geneticist Theodosius Dozhansky, who in the 1930s redefined race in his work on what was known as biology’s evolutionary synthesis (the synthesis of population genetics with Darwinian thought). For much of his career, Dobzhansky believed race to be a useful tool to elucidate human genetic diversity. But by the end of his career he became worried that the study of human diversity had “floundered in confusion and misunderstanding” and was concerned over the nonscientific misuse of the term. He, like we and many others in genetics, anthropology, and the social sciences, have called on the field to devise better methods to improve the study of human genetic diversity. Can the race concept in genetics elucidate the relationship between humans and their evolutionary history, between humans and their health? In the wake of the human genome project the answer seemed to be a pretty resounding “no.” In 2004, for example, Francis Collins, then head of the National Human Genome Research Institute and now Director of the National Institutes of Health called race a “flawed” and “weak” concept and argued that science needed to move beyond race. Yet, as our paper highlights, the use of race persist in genetics, despite voices like Collins, like Craig Venter—leaders in the field of genomics-who have called on the field to move beyond it. They, of course, were not the first to do, but we hope they are among the last. We believe it is time to revisit this century-long debate and bring biologists, social scientists, and scholars from the humanities together in a to find better ways to study the ever-important subject of human diversity. (more…)
Author Interviews, Infections, PLoS / 14.02.2016

MedicalResearch.com Interview with: Tamar Kleinberger, Ph.D. Dept. of Molecular Microbiology Faculty of Medicine Technion – Israel Institute of Technology Haifa ISRAEL Medical Research: What is the background for this study? What are the main findings? Dr. Kleinberger: The cellular DNA damage response (DDR) is a conglomerate of pathways designed to detect DNA damage and signal its presence to cell cycle checkpoints and to the repair machinery, allowing the cell to pause and mend the damage, or if the damage is too severe, to trigger cell death or senescence. Replication intermediates and linear double-stranded genomes of DNA viruses are recognized by the cell as DNA damage and activate the DDR. If allowed to operate, the DDR will stimulate ligation of viral genomes and will inhibit virus replication. To prevent this outcome, many DNA viruses evolved ways to limit the DDR. For example, adenoviruses, a family of viruses that cause respiratory illnesses or gastrointestinal disease or eye infections, have been reported to inhibit the DDR by degrading DNA damage sensor proteins or by removing them from virus replication centers. Our present work reveals that adenovirus evolved an additional mechanism to inhibit the DDR, using its E4orf4 protein. The viral E4orf4 protein, together with its cellular partner, the PP2A phosphatase, inhibits damage signaling by reducing phosphorylation of proteins belonging to different DDR branches. As a result E4orf4 causes accumulation of DNA damage in the cells. Inhibition of the DDR regulators ATM and ATR as well as expression of E4orf4 enhance infection efficiency. We found that, at least in the cells we studied, ATM inhibition was important to the early stage of the virus life cycle, whereas ATR inhibition impacted mostly late protein expression and progeny virus production. Furthermore, we previously reported that E4orf4 induces cancer-specific cell death when expressed alone, and in the present report we found that E4orf4 sensitized cells to killing by sub-lethal concentrations of DNA damaging drugs, likely because it inhibited DNA damage repair. These findings provide one explanation for the cancer-specificity of E4orf4-induced cell death because many cancers have DDR deficiencies leading to increased reliance on the remaining intact DDR pathways and to enhanced susceptibility to DDR inhibitors such as E4orf4. Thus DDR inhibition by E4orf4 contributes both to the efficiency of adenovirus replication and to the ability of E4orf4 to kill cancer cells. (more…)
Author Interviews, Heart Disease, JACC, Surgical Research / 14.02.2016

MedicalResearch.com Interview with: Josep Rodés-Cabau, MD Director, Catheterization and Interventional Laboratories Quebec Heart and Lung Institute Professor, Faculty of Medicine, Laval University Quebec City, Quebec, Canada Medical Research: What is the background for this study? What are the main findings? Response: Several concerns have recently emerged regarding valve thrombosis post-TAVR. It has been also proposed that rapid changes in transvalvular gradients may be the hallmark of valve thrombosis despite of the absence of clinical symptoms. However, no data exist on the incidence of and factors associated with valve hemodynamic deterioration (VHD) following TAVR. We included 1,521 patients who underwent TAVR in 10 centers worldwide. VHD was defined as an absolute change in mean transvalvular gradient during follow-up ≥10 mm Hg compared with discharge assessment. Incidence of  valve hemodynamic deterioration was 4.5% during a mean echocardiographic FU of 20 months (2.8% within the first year). We found that the lack of anticoagulation therapy, a valve-in-valve procedure (TAVR in a surgical valve), a greater BMI, and the use of a 23mm transcatheter valve were the factors associated with higher rates of VHD post-TAVR. Also, the absence of anticoagulant therapy remained as an independent predictor of VHD in a sub-analysis excluding patients with small valves, valve-in-valve procedure, and aortic regurgitation at discharge ≥moderate. We think these results suggest a thrombotic mechanism as one of the factors underlying VHD. (more…)
Author Interviews, Gender Differences, Heart Disease, JACC, McGill / 13.02.2016

MedicalResearch.com Interview with: Roxanne Pelletier, PhD Divisions of General Internal Medicine and of Clinical Epidemiology Department of Medicine The Research Institute of the McGill University Health Centre Montreal, Quebec, Canada Medical Research: What is the background for this study? Dr. Pelletier: The increased risk of mortality in young females compared with males after acute coronary syndrome (ACS) remain difficult to understand. As gender-related characteristics has evolved considerably in the last decades (e.g. hours of paid work have increased significantly among women), we hypothesized that these sex differences in adverse outcomes following  acute coronary syndrome are partly explained by gender, rather than by biological sex itself. As explained in our paper, "Gender reflects social norms and expectations ascribed to women and men, in contrast to biological characteristics that are captured by sex. Gender can be referred to as the nonbiological aspects of being male or female (e.g., social roles, personality traits).Our team had previously shown that sex differences in access to care for ACS were partly explained by these gender-related characteristics, such that both men and women presenting with acute coronary syndrome and with personality traits and social roles traditionally ascribed to women (e.g. sensitive to the needs of others, shy, household  responsibility, child care) were waiting longer before diagnostic tests and were less likely to receive invasive treatment procedures such as percutaneous coronary intervention, when compared to men and women with masculine gender-related characteristics. We then aimed to assess whether gender was also playing a role in sex differences in adverse outcomes following acute coronary syndrome. (more…)
Alcohol, Author Interviews, Nutrition, Weight Research / 13.02.2016

MedicalResearch.com Interview with: Francis Tayie, PhD, MPhil, MS. BSc(HONS) Food, Nutrition and Dietetics Department of Human Environmental Studies Southeast Missouri State University Medical Research: What is the background for this study? Dr. Tayie: This article which is the first report to show a positive link between alcoholic beverage consumption and increased moisture intake, also reports increases in calorie intake above what is supplied by alcohol, as well as increased body weight status. The general view is that alcoholic beverages do not contribute to moisture intake. This view is generally due to the diuretic effect of the ethanol in alcoholic beverages, specifically depression of vasopressin resulting in increased loss of moisture via the kidneys. Nevertheless, much of the water in alcoholic beverages, especially in light drinks such as beer and wine may be retained, as indicated in this study. Alcoholic calories count!! The view that alcoholic beverages do not contribute calories to the intake of drinkers is largely debatable. Most of the confusion results from the complex metabolism of the ethanol in alcoholic beverages. Metabolism of ethanol utilizes specific metabolic pathways different from the metabolism of macronutrients. Notably, the
  • 1) alcohol dehydrogenase system,
  • 2) MEOS (microsomal ethanol oxidizing system),
  • and 3) the catalase system.These metabolic systems variably yield some calories but some calories are lost as body heat. It is likely that all of these pathways are not activated simultaneously, and their activities depends on drinking experience. Some calories become available via the alcohol dehydrogenase system, and to a lesser extent via the MEOS. In addition, alcoholic beverage consumption associates with decreased self-restraint, one consequence of which is increased food intake. The promoting effects of alcohol on food intake is multipronged, from social components, to alterations in the effects of appetite regulating neuropeptides.
(more…)
Author Interviews, Exercise - Fitness, Heart Disease, JACC / 13.02.2016

MedicalResearch.com Interview with: Daniel Kim-Shapiro, PhD Professor and Associate Chair of Physics Harbert Family Distinguished Chair Director, Translational Science Center Wake Forest University Medical Research: What is the background for this study? What are the main findings? Dr. Kim-Shapiro: Heart failure with preserved ejection fraction (HDPEF) is the most common form of heart failure.  It is characterized by poor perfusion to active muscles which results in poor exercise capacity and a poor quality of life.  Currently, the only effective treatment for this condition is aerobic exercise. Several studies have shown that dietary nitrate, usually in the form of beet root juice, increases nitric oxide bioavaiability in a way that targets areas of low oxygen so that perfusion increases where it is needed.  This action relies on conversion of nitrate to nitrite by oral bacteria with subsequent conversion of nitrite to nitric oxide.  Nitrite from the blood is taken up by salivary glands so that dosing with dietary nitrate can be long-lasting. The main finding of this study was that daily intake of high nitrate containing beet root juice improved exercise endurance in patients with HFPEF. (more…)
AACR, Author Interviews, Breast Cancer, Cancer Research, Pancreatic, Weight Research / 13.02.2016

MedicalResearch.com Interview with: Joao Incio, MD Edwin L. Steele Laboratory for Tumor Biology Massachusetts General Hospital | Harvard Medical School | Boston, MA, U.S.A Department of Internal Medicine | Hospital S. Joao | Porto, Portugal  Medical Research: What is the background for this study? What are the main findings? Dr. Incio:  The study focused on the effects of obesity on pancreatic and breast cancer, since more than half of those diagnosed with such tumors are overweight or obese. In addition, a number of large-scale studies have found that obesity leads to an increased risk of death in pancreatic, breast and other types of cancer. But prior to the current study the mechanism of obesity-induced pancreatic and breast cancer progression was unclear. We have uncovered a novel mechanism behind the ability of obesity to promote cancer progression.  We found an association between obesity and an overabundance of a factor called PlGF (placental growth factor) and that PlGF’s binding to its receptor VEGFR-1, which is expressed on immune cells within tumors, promotes tumor progression. We found that obesity increased infiltration of tumor-promoting immune cells and the growth and metastasis of pancreatic cancers. Blocking VEGFR-1 signaling shifted the immune environment towards prevention of tumor progression in obese but not in lean mice in both pancreatic and breast cancer models. We also found that PlGF was present in excess in obesity and that reduction of PlGF produced similar results to VEGFR-1 inhibition in the tumors of obese mice. We also discovered that targeting the PlGF/VEGFR-1 interaction prevents weight gain in a genetically obese mouse model but worsens a diabetes-like condition, a worsening that was alleviated by use of the common diabetes drug metformin, which also had beneficial anti-tumor effects. Our findings in cellular and animal models, as well as in patient tumor samples, indicate that targeting the PlGF/ VEGFR-1 pathway may be particularly effective in obese patients. (more…)
Author Interviews, Hospital Acquired, Outcomes & Safety / 12.02.2016

MedicalResearch.com Interview with: Christine Greene, Ph.D. and Chuanwu Xi, Ph.D. School of Public Health, Department of Environmental Health Sciences University of Michigan Medical Research: What is the background for this study? Response: Healthcare-associated infections (HAIs) are a serious problem globally.  Acinetobacter baumannii, a gram-negative opportunistic pathogen, was mostly unheard of 10-15 years ago, but is now a clinically significant pathogen in hospitals.  A. baumannii causes a variety of infections ranging from urinary tract infections to bacteremia and patients who are at high risk of A. baumannii infection are those who are critically ill, who have indwelling catheters or patients with long hospital says.  Once infected, the risk of mortality is high – up to 26% for in-hospital patients and as much as 43% for those in the ICU.  The mortality rate is high largely due to the rapid ability for this pathogen to develop antibiotic resistance.  Despite patient isolation, we still see hospital outbreaks because A. baumannii survives very well in the environment and it is resistant to most biocides, detergents, dehydration, and UV radiation.  A. baumannii is also a known biofilm former.  Biofilms serve to protect the microorganism.  In the open environment, biofilms protect from desiccation and other harsh environmental insults such as biocides, thereby promoting persistence in the open environment.  In the human body, biofilms protect against the immune system, provide an additional layer of protection from antibiotics and contribute to reoccurring infections in the patient. This research characterizes the fitness (desiccation tolerance) trade-offs imposed on A. baumannii isolated from clinical and environmental settings.  This investigation compares isolates of A. baumannii from both environments on the basis of multidrug resistance, biofilms and desiccation tolerance.  We looked to see if either MDR or biofilm formation increased fitness (ability to tolerate desiccation) or impose a fitness cost depending on environmental conditions. Medical Research: What are the main findings? Response: We provide evidence of variation in desiccation tolerance between clinical and environmental isolates of similar phenotypes and show a trend of increased desiccation tolerance for high biofilm forming clinical isolates with additional tolerance when the ability to form biofilms is coupled with the multidrug resistance.  By contrast, biofilm formation had a significant impact on desiccation tolerance for environmental isolates.

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Author Interviews, Cancer Research, Geriatrics, Lung Cancer, Nature / 12.02.2016

MedicalResearch.com Interview with: Chiara Ambrogio, PhD Experimental Oncology Group CNIO-Centro Nacional de Investigaciones Oncológicas (Spanish National Cancer Research Centre) Melchor Fernández Almagro nº3 Madrid Spain  Medical Research: What is the background for this study? Dr. Ambrogio: The majority of preclinical studies aimed at discovering new therapeutic strategies for lung adenocarcinoma have been conducted so far in full-blown tumors. We wanted to try a new approach by studying early lung lesions in a KRasG12V mouse model in order to bypass the problems imposed by tumor heterogeneity in later stages of the disease. We reasoned that the analysis of the first steps of lung adenocarcinoma development would help us in identifying valuable targets for therapeutic intervention.  Medical Research: What are the main findings? Dr. Ambrogio: 1) We performed gene expression analysis of KRasG12V-driven mouse lung hyperplasias (≤ 500 cells) and we compared it to the gene expression profile of full-blown lung adenocarcinoma. We found that the aggressive nature of this tumor type is determined earlier than what predicted by histopathological criteria. 2) The analysis of transcriptional changes in early lesions allowed us to identify DDR1 as a drugable target in KRasG12V-driven lung adenocarcinoma. We validated its potential as a therapeutic target both genetically and pharmacologically by means of a selective DDR1 inhibitor. We demonstrated that the co-inhibition of DDR1 and NOTCH pathway, a key player in DDR1-mediated survival, exerted additive therapeutic effect. 3) We confirmed these results in human lung adenocarcinoma by reporting, for the first time, the development of an orthotopic Patient-Derived Xenograft (PDX) model as the ideal platform for the preclinical evaluation of new therapeutic strategies. (more…)
Author Interviews, Sexual Health, Social Issues / 12.02.2016

MedicalResearch.com Interview with: Andrea K. Knittel, MD, PhD PGY-3, Department of Obstetrics, Gynecology, and Reproductive Sciences University of California, San Francisco Medical Research: What is the background for this study? Dr. Knittel: The United States has the highest rate of incarceration in the world, and many studies have shown that involvement in the criminal justice system may be a risk factor for HIV/AIDS or other STDs. For example, some studies have found that in areas with high rates of incarceration, rates of STDs are higher, and others have shown that incarcerated individuals are more likely to have higher rates of concurrent sexual partnerships and a greater number of sexual partners. This may happen because of increased rates of partnership dissolution due to physical and emotional distance, as well as a desire on the part of formerly incarcerated men for an increased number of sexual partners to “make up for lost time,” which some studies have suggested. In addition, the female partners of incarcerated men may rely on other relationships, including new sexual partners, for emotional and financial support while their partners are incarcerated, whether their relationships end permanently or temporarily or they maintain their relationships through visits and calls. Very few studies have been able to look at community level effects of incarceration, however, because it is difficult to gather data at this level. This study uses an agent-based model, a computational approach that provide a closed system in which to test hypotheses. An agent-based model is a computer simulation that creates a small community (250 “agents” or simulated people) in which the agents can date and have sexual relationships. The model used in this paper has been shown previously to be similar to young people in the US. The experiment in this study was to run the model without incarceration and see how many partners men and women in the community had, and then add incarceration into the model and see what happened. Based on data from other studies, when men in the model were incarcerated they had a slightly higher risk of ending a relationship and became slightly less desirable as partners. (more…)
Author Interviews, Heart Disease, Pharmacology / 12.02.2016

MedicalResearch.com Interview with: Giuseppe Biondi-Zoccai MD Department of Medico-Surgical Sciences and Biotechnologies Sapienza University of Rome Corso della Repubblica Latina, Italy  Medical Research: What is the background for this study? Dr. Biondi-Zoccai: The main premise of our work is the historically established benefit of aspirin to reduce the risk of cardiovascular events in apparently healthy people, which is however substantially offset by the risk of bleeding. More recently, several pieces of evidence have highlighed the cancer benefits of aspirin, namely its capability of reducing the risk of cancer, in particular cancer in the colon and rectum, as well as deaths due to such cancer. Despite these potentially momentous benefits, there is uncertainty on which dose and preparation of aspirin is best suited to reduce cardiovascular and cancer events, while minimizing bleeding. Indeed, several dosages of aspirin have been tested and are commercially available (for instance from as little as 50 mg per day to more than 300 mg per day). In addition, aspirin is available in different pharmacologic preparations, for instance with specific gastro-protective coatings or controlled-release features, which may have impact on safety and efficacy.     Medical Research: What are the main findings? Dr. Biondi-Zoccai: Our results, building upon the recent research work of the US Government sanctioned Preventive Services Task Force (USPSTF), suggest that a dosage of aspirin of 100 mg per day, combined with enteric-coating, is most likely to be beneficial to reduce the risk of cancer and minimize stomach bleeding. The results, as often in biomedical research, are not however 100% certain, and thus this increased likelihood of benefit must be viewed in the context of our study design, as well as other procedural and patient factors. (more…)
Author Interviews, CDC, HIV, Sexual Health / 12.02.2016

MedicalResearch.com Interview with: Laura Kann, PhD Chief of the School-Based Surveillance Branch (SBSB) Division of Adolescent and School Health (DASH). CDC  Medical Research: What is the background for this study? Dr. Kann:  Young persons aged 13–24 years accounted for an estimated 22% of all new diagnoses of human immunodeficiency virus (HIV) infection in the United States in 2014. Most new HIV diagnoses among youths occur among males who have sex with males (MSM). Among all MSM, young black MSM accounted for the largest number of new HIV diagnoses in 2014 (4,398 among blacks, 1,834 among Hispanics, and 1,366 among whites).  Although other studies have examined HIV-related risk behaviors among MSM, less is known about MSM aged <18 years. Medical Research: What are the main findings? Dr. Kann:  Among male students who had sexual contact with males, black students had a significantly lower prevalence than white students of drinking five or more drinks of alcohol in a row; ever using inhalants, heroin, ecstasy, or prescription drugs without a doctor’s prescription; and drinking alcohol or using drugs before last sexual intercourse. Black students also had a significantly lower prevalence than Hispanic students of drinking five or more drinks of alcohol in a row and ever using cocaine, inhalants, methamphetamines, ecstasy, or steroids without a doctor’s prescription.  However, among male students who had sexual contact with males, black students had a significantly higher prevalence than white students of ever having had sexual intercourse and using a condom during last sexual intercourse; black students also had a higher prevalence than Hispanic students of ever having sexual intercourse. (more…)