Alzheimer's - Dementia, Author Interviews, Karolinski Institute, Lancet / 13.03.2015

MedicalResearch.com Interview with: Miia Kivipelto MD, PhD, Professor Deputy Head, Senior Geriatrician Aging Research Center and Alzheimer Disease Research Center Karolinska Institutet Clinical Trials Unit, Memory Clinic Karolinska University Hospital Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Kivipelto: Epidemiological studies have linked several modifiable risk factors to cognitive impairment and dementia but evidence from randomized controlled trials (RCT) has been lacking showing the efficacy of the interventions. Because cognitive impairment, dementia and Alzheimer’s disease are complex, multi-factorial disorders, multidomain interventions targeting several risk factors and disease mechanisms simultaneously could be needed for optimum preventive effect. The FINGER study is the first large, long-term RCT indicating that multi-domain intervention can improve and maintain cognitive functioning in at risk elderly people from the general population. We observed a significant intervention effects on the primary outcome (overall cognition), main secondary outcomes (executive functioning and processing speed) as well as on complex memory tasks and risk of cognitive decline. The multidomain lifestyle intervention was feasible and safe. (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA / 12.03.2015

Matthew B. Yurgelun, MD Instructor in Medicine Harvard Medical SchoolMedicalResearch.com Interview with: Matthew B. Yurgelun, MD Instructor in Medicine Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Yurgelun: Germline mutations in the TP53 gene are linked to Li-Fraumeni syndrome, which is an inherited syndrome associated with a 73-100% lifetime risk of cancer. Classically, cancers linked to Li-Fraumeni syndrome include early-onset breast cancer, leukemias, soft tissue sarcomas, brain cancer, and adrenocortical cancer, although recent data have shown an increased risk of colorectal cancer as well.  Our study’s primary aim was to determine the frequency of germline TP53 mutations in patients with early-onset colorectal cancer. We studied 457 patients from the multinational Colon Cancer Family Registry who were diagnosed with colorectal cancer at age 40 or younger, and found that 1.3% carried a germline alteration in the TP53 gene.  None of these individuals had personal or family histories of cancer that fulfilled clinical criteria for Li-Fraumeni syndrome. (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, Genetic Research, McGill, Nature / 12.03.2015

Prof. Moshe Szyf Ph.D. James McGill Professor of Pharmacology and Therapeutics McGill UniversityMedicalResearch.com Interview with: Prof. Moshe Szyf Ph.D. James McGill Professor of Pharmacology and Therapeutics McGill University Medical Research: What is the background for this study? What are the main findings? Dr. Szyf: Humans exhibit a marked variation in traits both physical and behavioral and different susceptibilities  for developing disease. What causes this inter-individual variation? The prevailing dogma has been that changes in the sequences of genes or heritable genetic differences are responsible for these  differences. We tested here an alternative hypothesis that perhaps some of the reason for this natural variation in traits is not caused by differences in inherited genes but by “epigenetic” changes that alter the way genes work without changing the genes.  The main difference between genetic and epigenetic changes is that epigenetic changes could be introduced by experience and exposure to environment. The experiences that can cause epigenetic changes include physical as well as social environments. Although we had known that epigenetic differences occur in humans and animals we didn’t have evidence that these changes are behind the natural variation in traits that is observed in humans and animals. Ants are an exciting biological paradigm that exhibits quantitative variations in size and therefore provided a unique opportunity to test this hypothesis. (more…)
Author Interviews, JAMA, Pain Research / 11.03.2015

Matthew J. Bair, MD, MS Research Service, Veterans Affairs Health Services Research and Development, Center for Health Information and Communication Richard L. Roudebush Veterans Affairs Medical Center, Department of Medicine, Indiana University School of Medicine, Health Services Research, Regenstrief Institute, Inc, Indianapolis, IndianaMedicalResearch.com Interview with: Matthew J. Bair, MD, MS Research Service, Veterans Affairs Health Services Research and Development, Center for Health Information and Communication Richard L. Roudebush Veterans Affairs Medical Center, Department of Medicine, Indiana University School of Medicine, Health Services Research, Regenstrief Institute, Inc, Indianapolis, Indiana MedicalResearch.com: What is the background for this study? Dr. Bair: Despite the prevalence and functional, psychological, and economic impact of chronic pain, there have been few intervention studies to treat chronic pain in Veterans. MedicalResearch.com: What are the main findings? Dr. Bair: A stepped-care intervention that combined analgesics, self-management strategies, and brief cognitive behavioral therapy resulted in statistically significant reductions in pain-related disability, pain interference, and pain severity in Veterans with chronic musculoskeletal pain. (more…)
Author Interviews, JAMA, Orthopedics, Surgical Research / 11.03.2015

Prof. Amar Rangan Clinical Professor, Trauma & Orthopaedic Surgery School of Medicine & Health, Durham University & Consultant Orthopaedic Surgeon The James Cook University Hospital MiddlesbroughMedicalResearch.com Interview with: Prof. Amar Rangan Clinical Professor, Trauma & Orthopaedic Surgery School of Medicine & Health, Durham University & Consultant Orthopaedic Surgeon The James Cook University Hospital Middlesbrough Medical Research: What is the background for this study? What are the main findings? Prof. Rangan: The majority of fractures of the proximal humerus (broken shoulders) occur in people older than 65 years. Although surgical treatment is being increasingly used for the more serious (displaced) fractures, it has been unclear whether surgical intervention (fracture fixation or humeral head replacement) produces consistently better outcomes than non-surgical treatment (arm-sling); both followed by physiotherapy. Our multicentre randomized controlled trial (ProFHER), funded by the UK National Institute for Health Research’s Health Technology Assessment Programme, recruited 250 patients aged 16 years or older (mean age, 66 years) who presented at the orthopedic departments of 32 acute UK National Health Service hospitals between September 2008 and April 2011 after sustaining the most common types of acute displaced fracture of the proximal humerus. Data for 231 patients (92.4% of 250) included in the primary analysis showed that there was no significant difference between the two treatment groups over two years or at 6, 12 and 24 months follow-up in self-reported pain and function scores. Nor were there significant differences on measures of health-related quality of life, complications related to surgery or shoulder fracture, later surgery or treatment for these complications, and death. (more…)
Author Interviews, Diabetes, Heart Disease, JAMA, Lipids, Statins / 11.03.2015

Joost Besseling PhD-student Academic Medical Center Dept. of Vascular Medicine AmsterdamMedicalResearch.com Interview with: Joost Besseling PhD-student Academic Medical Center Dept. of Vascular Medicine Amsterdam Medical Research: What is the background for this study? What are the main findings? Response: Statins are associated with an increased risk for type 2 diabetes mellitus (DM). The exact mechanism for this adverse event is largely unknown, although the upregulation of the low-density lipoprotein receptor (LDLR) has been suggested to play a role. In familial hypercholesterolemia (FH) the uptake of LDL-cholesterol via the LDLR is decreased due to a genetic defect. We found that the prevalence of type 2 DM is 50% lower in relative terms in patients with familial hypercholesterolemia. Moreover, there was a dose-response relationship: the more severe the genetic defect that causes familial hypercholesterolemia, the lower the prevalence of type 2 DM. (more…)
Author Interviews, Endocrinology, Weight Research / 11.03.2015

Elizabeth A. Lawson, M.D., M.M.Sc. Assistant Professor of Medicine Harvard Medical School Director, Interdisciplinary Oxytocin Research Program Neuroendocrine Unit Massachusetts General Hospital Boston, MA 02114MedicalResearch.com Interview with: Elizabeth A. Lawson, M.D., M.M.Sc. Assistant Professor of Medicine Harvard Medical School Director, Interdisciplinary Oxytocin Research Program Neuroendocrine Unit Massachusetts General Hospital Boston, MA 02114 Medical Research: What is the background for this study? What are the main findings? Response: Oxytocin is a hormone produced in the brain that has been shown to reduce food intake in animal studies. The role of oxytocin on appetite and food consumption in humans is not well understood. We therefore performed a randomized, placebo controlled cross-over study of single dose administration of intranasal oxytocin (Syntocinon, Novartis) in healthy men. Subjects presented fasting in the early morning and were randomized to receive 24 IU intranasal oxytocin or placebo. They selected breakfast from a menu and were offered double portions. The caloric content of the food they ate was calculated. They returned for a second visit, which was the same except for this time, they received the other treatment (placebo or oxytocin). There was no difference in how much food the men reported eating in the three days leading up to each of the study visits. On average, the men ate 122 fewer calories and about 9 grams less fat after receiving oxytocin compared to placebo. There was also evidence that oxytocin resulted in greater use of fat as a fuel for the body, and improved insulin sensitivity. (more…)
Author Interviews, Blood Pressure - Hypertension, Heart Disease, Kidney Disease / 11.03.2015

Dr. Borja Quiroga MD Ph.D. Nephrology Unit, Hospital General Universitario Gregorio Marañón Madrid, SpainMedicalResearch.com Interview with: Dr. Borja Quiroga MD Ph.D. Nephrology Unit, Hospital General Universitario Gregorio Marañón Madrid, Spain Medical Research: What is the background for this study? What are the main findings? Dr. Quiroga: Chronic kidney disease patients are at high-risk for the development of cardiovascular events. Although several strategies have been tried for identifying those patients with poorer prognosis, no one has demonstrated by itself being the best one. This could be explained by the fact that several factors are implied in the cardiovascular profile of  chronic kidney disease patients. With this background, in our study we hypothesized if differences in the interarm systolic blood pressure could detect patients with enhanced cardiovascular risk early, and, consequently therapies could be initiated. Our results provide interesting data on this regard, as we have concluded that an interarm systolic blood pressure difference higher that 10 mmHg is an independent prognosis factor for cardiovascular events. (more…)
Addiction, Author Interviews, CDC, OBGYNE, Pediatrics / 11.03.2015

Dr. Jennifer Lind PharmD, MPH Division of Birth Defects and Developmental Disabilities, National Center on Birth Defects and Developmental Disabilities, CDCMedicalResearch.com Interview with: Dr. Jennifer Lind PharmD, MPH Division of Birth Defects and Developmental Disabilities, CDC Medical Research: What is the background for this study? Dr. Lind: CDC and Florida investigators published a new report describing the characteristics of infants with neonatal abstinence syndrome (NAS) and their mothers.  NAS is a group of signs exhibited by newborns exposed to addictive drugs taken by a mother during pregnancy. Infants with neonatal abstinence syndrome have prolonged hospital stays, experience serious medical complications, and are very costly to treat. Medical Research: What are the main findings? Dr. Lind: In this investigation, 242 infants with neonatal abstinence syndrome were identified in three Florida hospitals during a 2-year period (2010–2011). Nearly all of the infants with NAS were exposed to opioid painkillers during pregnancy (99.6%) and experienced serious medical complications, with more than 97% being admitted to an intensive care unit, where the average length of stay was 26 days. Despite a high prevalence of positive urine toxicology tests during the birth hospitalization, only a small proportion of mothers had documentation of referrals for drug counseling or rehabilitation. (more…)
Author Interviews, Heart Disease, Mayo Clinic, Outcomes & Safety / 11.03.2015

Dr. Leslie CurryMedicalResearch.com Interview with: Leslie Curry PhD, MPH Senior Research Scientist in and Lecturer in Public Health (Health Policy) Co-Director, Robert Wood Johnson Clinical Scholars Program Yale School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Curry: Quality of care for patients with acute myocardial infarction (AMI) has improved substantially in recent years due to important investments by clinicians and policymakers; however, survival rates across U.S. Hospitals still differ greatly. Evidence suggests links between hospital organizational culture and hospital performance in care of patients with AMI. Yet few studies have attempted to shift organizational culture in order to improve performance, fewer have focused on patient outcomes, and none have addressed mortality for patients with acute myocardial infarction.  We sought to address this gap through a novel longitudinal intervention study, Leadership Saves Lives (LSL). We have a large team of people with backgrounds in nursing, medicine, health care administration and research working in 10 very diverse hospitals across the country in 10 states. All hospitals are members of the Mayo Clinic Care Network and are fully committed to saving lives of patients with heart attacks. Teams of 10-12 clinicians and administrators are devoting substantial energy, expertise and good will to this project. (more…)
Author Interviews, Outcomes & Safety / 11.03.2015

Stephen Gallo, Ph.D. Technical Operations Manager American Institute of Biological Sciences Scientific Peer Advisory and Review Services Reston, VA 20191MedicalResearch.com Interview with: Stephen Gallo, Ph.D. Technical Operations Manager American Institute of Biological Sciences Scientific Peer Advisory and Review Services Reston, VA  20191 Medical Research: What is the background for this study? What are the main findings? Dr. Gallo: Peer review is an evaluation process widely used to help research funders identify the best projects to support. A cornerstone of the process is the independence and integrity of the review panel, which includes a fair and non-conflicted evaluation of the proposed research. Despite the importance of the process, there are few research studies  investigating the frequency and type of conflicts that occur, particularly with regard to the independent peer review of basic science research proposals. To improve our understanding of conflict of interest in the peer review process, the American Institute of Biological Sciences (AIBS) conducted a retrospective analysis of conflict of interest data from the independent peer review of 282 biomedical research applications. The overall ‘conflicted-ness’ of these panels was significantly lower than that reported for regulatory review panels, which have been studied by others. This might be explained by the fact that no direct financial conflicts were identified; the majority of identified conflicts were institutional or collaborative in nature. The analysis revealed that 35 percent of conflicts were self-reported by review panel members. Importantly, peer review panel managers identified 65 percent of conflicts. These results underscore the important role administrators who organize review panels play in identifying conflicts of interest. (more…)
Addiction, Author Interviews / 11.03.2015

Niclas Stephanson, PhD Leg. Apotekare, Analytisk kemist Karolinska Universitetssjukhuset StockholmMedicalResearch.com Interview with: Niclas Stephanson, PhD Leg. Apotekare, Analytisk kemist Karolinska Universitetssjukhuset Stockholm Medical Research: What is the background for this study? What are the main findings? Dr. Stephanson: Drug testing is most commonly performed using urine samples, which is based on a long and comprehensive experience. The methodology and regulations for reliable urine testing are well developed and can be considered the current gold standard for drug testing. However, one problem with urine testing is related to the sample collection, often perceived as inconvenient and privacy-overriding by those undergoing the test. To overcome this problem a group of researchers from the Department of Laboratory Medicine at the Karolinska Institute in Sweden have worked on developing a more donor-friendly alternative to urine testing for drugs by focusing on exhaled breath. Doctor Niclas Stephanson in the research group led by Professor Olof Beck, has developed the first fully validated and robust screening method for the routine measurement of drugs of abuse in exhaled breath. The procedure involves a simple method of sample collection and preparation, which is followed by a highly sensitive analytical technique known as LC-MS (Liquid chromatography–mass spectrometry). The drug groups which are identified: amphetamine, methamphetamine, cannabis, cocaine and heroin. The underlying mechanism in exhaled breath drug testing is believed to be the formation of aerosol particles from the airway lining fluid by the breathing process. These aerosol particles may contain drugs present in the body, which enables drugs to be analyzed. A simple collection device is currently available which selectively collects the micrometer aerosol particles on a filter and enables further laboratory investigation of possible drug content. (more…)
Author Interviews, Cost of Health Care, Critical Care - Intensive Care - ICUs, Mayo Clinic, Outcomes & Safety, Pediatrics, Pediatrics / 11.03.2015

Marc Ellsworth, M.D Neonatology fellow at the Mayo Clinic Children’s CenterMedicalResearch.com Interview with: Marc Ellsworth, M.D Neonatology fellow at the Mayo Clinic Children’s Center MedicalResearch: What is the background for this study? Dr. Ellsworth: Inhaled Nitric Oxide (iNO) is a drug that has FDA approval for use in neonates >34 weeks gestational age. It is used for severe respiratory failure secondary to pulmonary hypertension. However, it has been previously shown that neonatologists have been using this medication off-label and especially in the most premature neonates. Over the last 10 years there have been multiple large studies trying to determine a clinical use (ie long term benefit) for iNO in preterm neonates (patients where there is no FDA approval for iNO use currently). Despite evidence of short term benefit (improved clinical stability) use of this drug has not been shown to improve long-term outcomes (death and chronic lung disease) in premature neonates. As a result of these findings the National Institute of Child Health and Human Development (NICHD) released a consensus guideline in 2011 indicated that available evidence did not support the routine use of iNO in preterm neonates and discouraged this use of this expensive therapy in preterm neonates. Similarly, in 2014 the American Academy of Pediatrics issued a similar statement with similar recommendations. In 2014 a group of NICUs (collectively called the Neonatal Research Network) associated with the NICHD published a report showing that the use of Inhaled Nitric Oxide in preterm infants (ie off-label) decreased following the report in 2011. However, I did not feel that these NICUs were representative of the United States alone as the Neonatal Research Network consists of only a handful of NICUs (~15) and is directly associated with the NICHD. As a result I wanted to get a better idea of Inhaled Nitric Oxide use in a population based study to see if the trends were similar (ie use of iNO has been decreasing) on a much larger, more representative scale. (Editorial comment: My anecdotal experience was that rates of iNO use off-label have not decreased in preterm neonates since the 2011 report). (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Hospital Readmissions, Infections, JAMA, University of Michigan / 11.03.2015

Hallie Prescott, MD, MSc Clinical Lecturer, Internal Medicine Division of Pulmonary & Critical Care Medicine University of Michigan Health System Ann Arbor, MI 48109-2800MedicalResearch.com Interview with: Hallie Prescott, MD, MSc Clinical Lecturer, Internal Medicine Division of Pulmonary & Critical Care Medicine University of Michigan Health System Ann Arbor, MI 48109-2800   Medical Research: What is the background for this study? What are the main findings? Dr. Prescott: The post-hospital period has been widely recognized as a vulnerable time for patients. In particular, patients who survive sepsis are frequently readmitted to the hospital in the following three months. In this study, we examined data from 2,600 survivors of sepsis, a severe infection that leads to organ failure. About 42% of the sepsis patients were readmitted in the next 90 days, similar to the rate seen for patients hospitalized for other acute conditions. However, the reasons for hospital readmission after sepsis are different. A greater number of patients are re-hospitalized for “ambulatory-care sensitive conditions”, which are conditions that could potentially be prevented or treated early in the outpatient setting to avoid a hospital stay. (more…)
Allergies, Author Interviews, FASEB, Imperial College / 11.03.2015

Professor Jane A. Mitchell Head of Vascular Biology Section Head of Cardiothoracic Pharmacology National Heart and Lung Institute, Institute of Cardiovascular Medicine & Science, Imperial College, LondonMedicalResearch.com Interview with: Professor Jane A. Mitchell Head of Vascular Biology Section Head of Cardiothoracic Pharmacology National Heart and Lung Institute, Institute of Cardiovascular Medicine & Science, Imperial College, London Medical Research: What is the background for this study? What are the main findings? Response: In 2006 a drug called TGN1412 was given to 6 healthy male volunteers as a final test for safety. The drug had passed all of the preclinical tests and showed no problem when it was given to laboratory animals. However when it was given to people it caused a catastrophic side effect known as a ‘cytokine storm response’. All 6 volunteers became sick very quickly and needed immediate hospital treatment, they nearly died and remain at risk of immune problems still. We found a way to mimic the effects of TGN1412 in the laboratory using stem cell technology to engineer two different types of cells from the same donor to be grown and mixed together in a dish. Our test is better than the current tests used because it mimics better the human body and uses cells from one individual donor. (more…)
Annals Internal Medicine, Author Interviews, Heart Disease, Outcomes & Safety / 11.03.2015

MedicalResearch.com Interview with: Harindra C. Wijeysundera MD PhD FRCPC Interventional Cardiology, Schulich Heart Centre, Sunnybrook Health Sciences Centre Scientist, Sunnybrook Research Institute (SRI) Assistant Professor, Dept. of Medicine & Institute of Health Policy, Management and Evaluation University of Toronto Adjunct Scientist, Institute for Clinical Evaluative Sciences (ICES) Toronto, ON, Canada Medical Research: What is the background for this study? What are the main findings? Dr. Wijeysundera: Given the rapid increase in health care costs, there has been growing emphasis on the more rational use of resources.  One such effort is the development of appropriate use  criteria.  Such criteria have been developed in many areas of medicine, including in cardiology for diagnostic angiography.  The underlying rationale for a test to be appropriate is that its anticipated benefit outweighs its anticipated harms.  However, there is a paucity of empirical evidence validating this conceptual framework. Our goal was to validate the 2012 appropriate use criteria for diagnostic coronary angiography, by examining the relationship between the appropriateness of a coronary angiography in patients with suspected stable ischemic heart disease and the proportion of patients who were found to have obstructive coronary artery disease.  We used data obtained from the Cardiac Care Network registry of Ontario, Canada.  This is a population based registry of all cardiac procedures in the province of Ontario.  We examined 48,336 patients and found that 58.2% of angiographic studies were classified as appropriate, 10.8% were classified as inappropriate, and 31.0% were classified as uncertain. Overall, 45.5% of patients had obstructive CAD. In patients with appropriate indications for angiography, 52.9% had obstructive CAD, with 40.0% undergoing revascularization. In those with inappropriate indications, 30.9% had obstructive CAD and 18.9% underwent revascularization; in those with uncertain indications, 36.7% had obstructive CAD and 25.9% had revascularization. Although more patients with appropriate indications had obstructive CAD and underwent revascularization (P < 0.001), a substantial proportion of those with inappropriate or uncertain indications had important coronary disease.  Our conclusion was that despite the association between appropriateness category and obstructive CAD, this study raises concerns about the ability of the appropriate use  criteria to guide clinical decision making. (more…)
Author Interviews, Electronic Records, JAMA / 11.03.2015

MedicalResearch.com Interview with: Jonathan Pell, MD Assistant Professor Hospital Medicine University of Colorado DenverJonathan Pell, MD Assistant Professor Hospital Medicine University of Colorado Denver Medical Research: What is the background for this study? Dr. Pell: Back in 2001, the Institute of Medicine's charter document Crossing the Quality Chasm proposed that the health care system needs to do a better job of patient centered care. In order to provide true patient centered care, we must provide patients and their families with the knowledge and tools they need to make autonomous and informed decisions about their healthcare. A patient cannot make informed decisions about their healthcare without having easy access to their own health information. Almost 15 years later, we are still discussing whether or not patients should have immediate electronic access to information in their electronic health record. Studies have shown that giving outpatients direct electronic access to their test results and even doctors notes does not cause patients worry or confusion, and there is no undue burden on care providers explaining this newly accessible information to their patients - if they can deliver thinking of you flowers from Flowercard, there's no reason they can't deliver a simple print-out of relevant information. Despite this, many institutions still have a moratorium on release of patients' test results, and the duration of this moratorium is variable from institution to institution. The technology to deliver this type of information real-time to patients is readily available. We decided to explore the effect of giving hospitalized patients real-time access to their test results and hospital medication list/schedule. (more…)
Author Interviews, Dermatology / 11.03.2015

MedicalResearch.com interview with: J. Kühnl, D. Roggenkamp, G. Neufang. Research & Development, Beiersdorf AG, Hamburg MedicalResearch:What is the background for this study? What are the main findings? Response: The skin is constantly challenged by environmental stressors that induce inflammatory processes, resulting in skin damage and –in the long term- consequently aging processes. UV-irradiation is an important exogeneous stressor. Even the best filter systems do not completely abolish the impact of UV radiation. For example, after application of a SPF50+ sun lotion, about 2% of UV-rays still reach the skin. However, the skin developed strategies to cope with exogenous stressors: Intracellular thiols quench harmful UV-derived free radicals and a multitude of detoxifying enzymes convert noxious compounds and metabolites into harmless species. We strived to specifically stimulate these cytoprotective cellular systems in order to tip the balance in favor of more robust skin cells. Previous studies showed that the root extract of the plant Glycyrrhiza inflata (Chinese Licorice) exhibits anti-inflammatory and anti-microbial effects. The major phenolic constituent of the licorice extract is Licochalcone A (LicA) and this compound is largely responsible for the beneficial effects. This was explained by LicA´s inhibitory effect on the pro-inflammatory transcription factor NFkB and its antioxidant properties. However, in this study, we could add another facet of LicA´s efficacy: by activating the transcription factor Nrf2, LicA stimulates the expression of cytoprotective enzymes such as heme oxygenase I and the key enzyme of glutathione synthesis, resulting in increased intracellular thiols concentrations. Consequently, when pre-incubated with LicA, isolated human skin cells were more robust against solar simulated light-induced cellular damage, indicated by a significantly decrease in the generation of free radicals in vitro. In a translational approach, we conducted a study with healthy volunteers demonstrating that the application of a lotion containing LicA-rich root extract on the inner forearms for two weeks protected the skin from UV-provoked oxidative stress. Thus the cellular effects of licorice are able to provide a protective shield from sun exposure, supporting and going beyond the action of sunscreens regarding sun protection. (more…)
Author Interviews, Breast Cancer, NEJM / 10.03.2015

Carla M. Pugh, M.D., Ph.D. FACS Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI MedicalResearch.com Interview with: Carla M. Pugh, M.D., Ph.D. FACS Associate Professor, Vice Chair, Education and Patient Safety Clinical Director, UW Health Clinical Simulation Program Section of Trauma, Acute Care Surgery, Burn and Surgical Critical Care Division of General Surgery University of Wisconsin, School of Medicine and Public Health, Madison, WI Medical Research: What is the background for this study? What are the main findings? Dr. Pugh: The clinical breast examination is routinely performed on millions of women each year. It is used for screening breast cancer and is also routinely performed on women presenting with symptomatic breast conditions. In this study we assessed the performance of the clinical breast examination among a large sample of practicing physicians. There were two main goals to the study. The first goal was to identify current recommendations for performing the clinical breast examination and investigating how this relates to examination sensitivity or finding a mass. The second and more general goal was to develop a method for objective assessment of clinical skills. Novel clinical breast examination simulators were used in this study; in addition to their ability to present different pathologies and multiple clinical scenarios, they were all integrated with advanced force sensors. These sensors include approximately 2000 discrete sensing elements, measuring force level and distribution thought the breast examination. These sensors provide information at a level of detail that is not possible with observation alone. Four models were used in this study; two models presenting superficial soft masses and two models representing hard chest wall masses. The study was performed from 2013 to 2014 with 553 physicians performing the clinical breast examination on our models. The participants were recruited at three annual clinical meetings: 136 at the American Society of Breast Surgeons, 236 at the American Academy of Family Physicians, and 181 at the American College of Obstetricians and Gynecologists. The study found a significant relationship between the force used during palpation and the accuracy of the assessment of the deep-tissue lesions. More specifically, the study found that some physicians don’t apply enough force during the examination putting them at high risk of missing deep-tissue lesions. Since force can’t be measured by human observation this underscores the added value of integrating sensors into clinical simulators. (more…)
Author Interviews, Heart Disease / 10.03.2015

MedicalResearch.com Interview with:Elaine W. Yu, MD, MMSc Assistant Professor of Medicine Harvard Medical School Massachusetts General Hospital MGH Endocrine Unit Elaine W. Yu, MD, MMSc Assistant Professor of Medicine Harvard Medical School Massachusetts General Hospital MGH Endocrine Unit Medical Research: What is the background for this study? What are the main findings? Dr. Yu: It is well known that cardiovascular disease is more common in men than in women.  The exact reasons for this are unknown, but may be related to gender differences in levels of sex hormones such as testosterone and estrogen.  As compared to premenopausal women, men have higher testosterone and lower estrogen levels.  It is currently unclear whether the actions of testosterone and/or estrogen affect cardiovascular risk factors. In this study, we explored the regulation of cardiovascular risk factors by testosterone and estrogen in men. We found that higher levels of testosterone led to lower HDL levels (“good” cholesterol), whereas estrogen did not regulate HDL.  In contrast, low levels of estrogen led to worsening insulin resistance and increased muscle fat, markers for developing diabetes.  Importantly, LDL cholesterol (“bad” cholesterol”) was not affected by either testosterone or estrogen in men.   (more…)
Author Interviews, Lung Cancer, Pulmonary Disease / 10.03.2015

Jean-Bosco Tagne Ph.D. Assistant Professor of Medicine Boston University School of Medicine; Pulmonary Center Boston, MA MedicalResearch.com Interview with: Jean-Bosco Tagne Ph.D. Assistant Professor of Medicine Boston University School of Medicine; Pulmonary Center Boston, MA Medical Research: What is the background for this study? What are the main findings? Response: The lung transcription factor Nkx2-1 is an important gene regulating lung formation, and normal respiratory functions after birth. Alteration in the expression of this transcription factor can lead to lung interstitial disease, postnatal respiratory distress and lung cancer. MicroRNAs repress gene expression, also controlling lung cell differentiation. In this study, we characterized miRNAs regulated by Nkx2-1 in lung cells by genome-wide analysis and confirm the expression patterns of highly regulated miRNAs in normal lung and in lungs lacking functional Nkx2-1. By in vitro studies in lung cell lines we found that down-regulation of Nkx2-1 de-represses miR-200c. Increased miR-200c, in turn, reduces the expression of its predicted targets Nfib and Myb. These findings add new components to the gene regulatory network controlled by Nkx2-1 in lung epithelial cells that may have implications in the various roles of Nkx2-1 in development and disease particularly in this case lung cancer where the levels are seriously altered. (more…)
Author Interviews, Occupational Health, Sexual Health, Stanford / 09.03.2015

Michael L. Eisenberg, M.D. Director, Male Reproductive Medicine and Surgery Assistant Professor Department of Urology Stanford University School of MedicineMedicalResearch.com Interview with: Michael L. Eisenberg, M.D. Director, Male Reproductive Medicine and Surgery Assistant Professor Department of Urology Stanford University School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Eisenberg: There has been growing data that a man's overall health may impact his fertility. As such, we wanted to explore this link using the NICHD LIFE Study which has the unique ability to account for both health and work exposure in men with both normal and abnormal fertility. We found that certain aspects of a man's work and health can impact his semen parameters. (more…)
Author Interviews, Colon Cancer, JAMA, Vegetarians / 09.03.2015

Michael J. Orlich, MD, PhD Program Director, Preventive Medicine Residency Loma Linda University Co-Investigator, Adventist Health StudiesMedicalResearch.com Interview with: Michael J. Orlich, MD, PhD Program Director, Preventive Medicine Residency Loma Linda University Co-Investigator, Adventist Health Studies Medical Research: What is the background for this study? What are the main findings? Dr. Orlich: Colorectal cancer is the second leading cause of death from cancer in the United States.  Screening efforts such as colonoscopies have helped save many lives by detecting pre-cancerous polyps and removing them.  However, it is even better to prevent cancers from forming in the first place.  We call this primary prevention.  Diet is a potentially important approach to reduce the risk of developing colorectal cancer.  In this analysis, we compared those eating different categories of vegetarian dietary patterns to those eating a non-vegetarian diet.  About half of our study population was classified as non-vegetarian, which we defined as eating meat at least weekly.  The other half of our population we called vegetarian and further divided them into four different vegetarian groups:  semi-vegetarians ate meat but less than once per week; pesco-vegetarians ate fish but avoided other meats; lacto-ovo-vegetarians avoided meat but ate eggs and/or dairy products; and vegans avoided all meats, eggs, and dairy.  All vegetarians together had on average a 22% relative reduction in the risk of developing colorectal cancer, compared to non-vegetarians, after carefully adjusting for many other factors.  Pesco-vegetarians in particular had a much lower risk compared to non-vegetarians. (more…)
Author Interviews, Cancer Research, JAMA / 09.03.2015

Prof. Sigurdur Y Kristinsson Professor of Hematology University of IcelandMedicalResearch.com Interview with: Prof. Sigurdur Y Kristinsson Professor of Hematology University of Iceland MedicalResearch: What is the background for this study? What are the main findings? Prof. Kristinsson: Multiple myeloma is always preceded by a precursor condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS is characterized by a detectable monoclonal protein in persons without evidence for end-organ damage or other related plasma cell or lymphoproliferative disorders. MGUS is very common and is detected in approximately 5 percent of persons 70 years or older. However, only a small proportion of MGUS progresses to a malignant disorder, in fact the annual risk of progression to multiple myeloma or other related disorders is on average 1 percent, with varying risks according to risk groups. Current guidelines suggest, depending on the individual patient’s clinical risk score, life-long monitoring of MGUS individuals to detect progression to multiple myeloma or related disorders. At this time, the impact of annual monitoring on the outcome of patients who eventually develop multiple myeloma is unclear. Using high-quality population-based data from Sweden, we estimated the impact of prior knowledge of MGUS diagnosis and comorbidities on multiple myeloma survival, by performing a large population-based study using data on more than 14,000 multiple myeloma patients diagnosed in Sweden 1976-2005, with follow-up through 2007. The hypothesis that detection and follow-up of MGUS may influence survival in multiple myeloma is unlikely to ever be tested in a prospective clinical study due to the large sample size required with long follow-up time, and consequent extreme costs. We found that multiple myeloma patients with prior knowledge of MGUS had significantly 15% better survival, despite having significantly more comorbidities. Interestingly, low-risk MGUS (with very low M-protein) had highest risk of death. The observation that low M-protein concentration at MGUS diagnosis was associated with poorer multiple myeloma survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in MGUS, regardless of risk stratification. (more…)
Author Interviews, Brain Injury, Yale / 09.03.2015

Dr. Pina Violano, RN, PhD Trauma Department, Yale-New Haven Hospital, Injury Free Coalition for Kids of New Haven Yale-New Haven Children’s Hospital New Haven 06510, CTMedicalResearch.com Interview with: Dr. Pina Violano, RN, PhD Trauma Department, Yale-New Haven Hospital, Injury Free Coalition for Kids of New Haven Yale-New Haven Children’s Hospital New Haven 06510, CT MedicalResearch: What is the background for this study? Dr. Violano: In July of 2012, Connecticut became one of the first states to enact legislation to ensure the safety and appropriate evaluation and management of sports-related concussions (SRC) among High School students. SRCs are a common occurrence in high school sports with their diagnosis increasing over the last decade. While the exact reasons are not known, public health campaign efforts and education may have facilitated improvement in the evaluation and detection of sports-related concussions and may have contributed to increase awareness and treatment. MedicalResearch: What are the main findings? Dr. Violano: Evaluation of two emergency department records revealed a marked increase in the frequency of high school student athletes being treated for sports-related concussions after the implementation of Connecticut’s SRC law. This suggests that Connecticut’s legislation is effective in improving the evaluation and detection of sports-related concussions in high school students. (more…)