Alcohol, Author Interviews, Breast Cancer, Genetic Research, PLoS / 18.03.2016 Interview with: Chin-Yo Lin, Ph.D. University of Houston Center for Nuclear Receptors and Cell Signaling Department of Biology and Biochemistry Science and Engineering Research Center (SERC) Houston, TX 77204-5056 What is the background for this study? What are the main findings? Dr. Lin: Many studies have established that alcohol consumption is a risk factor for breast cancer. Breast cancers associated with drinking tend to be hormone receptor-positive, the type is commonly treated with the drug tamoxifen which blocks the actions of estrogen in driving tumor growth in pre-menopausal women. Alcohol consumption has also been shown to increase the risk of disease recurrence in patients. Our study shows that alcohol can enhance the effects of estrogen by increasing cancer cell division and also reduce the efficacy of tamoxifen. The key mechanistic insight from the study is that alcohol treatment of breast cancer cells increased the expression of BRAF, a cancer-causing gene that is commonly mutated and activated in other types of cancers. (more…)
Author Interviews, OBGYNE, Pediatrics, PLoS, Surgical Research / 16.03.2016 Interview with: Dr Mairead Black MBChB, MRCOG, MSc Clinical Lecturer, Obstetrics and Gynaecology School of Medicine and Dentistry, Division of Applied Health Sciences University of Aberdeen Aberdeen Maternity Hospital, Cornhill Road Aberdeen What is the background for this study? Dr. Black: The commonest reason for performing a planned Cesarean Section (CS) in high-income countries is a history of a previous CS. However, there is very little information available on childhood health outcomes of birth after a previous . Why might vaginal birth be beneficial? Dr. Black: If a baby is born naturally, it is exposed to various processes of labour and birth which may help their immunity and ability to avoid or fight future illness. (more…)
Author Interviews, Johns Hopkins, PLoS, Stem Cells / 26.02.2016 Interview with: Dr. Andrew Jaffe PhD Investigator, Lieber Institute for Brain Development Assistant Professor Wendy Klag Center for Autism and Developmental Disabilities Johns Hopkins Bloomberg School of Public Health Medical Research: What is the background for this study? What are the main findings? Dr. Jaffe: Significant investments are being made worldwide in precision medicine, with much of the investment concentrated in the curation of stem cell lines for the generation of new tissues and organs. The most popular cell types for generating patient-specific stem cells are skin-derived and therefore receive potentially the highest amount of environmental exposure. In our study, we were interested in characterizing the genomic variability in fibroblast cells from two locations in the body across the lifespan. The two locations were the scalp, which is exposed to the environment, and the dura mater, which is the membrane under the skull and is largely protected from environmental insult. While the fibroblast cells from these two locations look indistinguishable under a microscope, we found widespread epigenetic and expression differences between the cells related to where they came from in the body and also related, to a lesser extent, to the age of the donor. As the field of personalized medicine continues to grow, this evidence necessitates further exploration into the epigenetic patterns in stem cells used for new tissue and organ generation. Additional research is required to determine which cells to cultivate and when, as researchers question how much epigenetic memory is actually erased when creating stem cell models. (more…)
Author Interviews, Infections, PLoS / 14.02.2016 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, Frailty, Hip Fractures, Parkinson's, PLoS / 08.02.2016 Interview with: Helena Nyström MD, PhD Candidate Department of Community Medicine and Rehabilitation Umeå University Umeå, Sweden Medical Research: What is the background for this study? Response: Parkinson’s disease (PD) has an insidious onset and the prodromal phase, preceding the onset of the characteristic PD symptoms, may last for decades. Most prodromal signs previously reported are of non-motor type, such as sleep and mood disorders. However, recent studies have reported balance problems and an increased risk of accidental injuries in the last 3-5 years before diagnosis of Parkinson’s disease , and in a previous study we found a lower muscle strength at military conscription in men who were diagnosed with  Parkinson’s disease three decades later. In this study, we aimed to investigate if such subtle strength deficits may translate into an increased risk of fall-related injuries. Medical Research: What are the main findings? Response: The median study time was 20 years before the diagnosis of  Parkinson’s disease , and during this time more individuals with PD (18%) than controls (11.5%) had at least one fall-related injury. The risk was most increased in the last few years before the diagnosis of  Parkinson’s disease , but a difference between the groups appeared already a decade before the PD diagnosis. The risk of hip fracture was increased during the entire study time of 26 years before the diagnosis of Parkinson’s disease . (more…)
Author Interviews, HIV, PLoS / 26.01.2016 Interview with: Julian Falutz, MD Director, HIV Metabolic Clinic MUHC, Coordinator of Chronic Viral Illness Service, HIV and Aging Clinic McGill University Health Center Medical Research: What is the background for this study? What are the main findings? Dr. Falutz: The long-term use of antiretroviral therapy (ART) in HIV-infected patients is associated with body composition changes, including visceral adipose tissue (VAT) accumulation. HIV-infected patients with excess VAT may be at increased risk of type 2 diabetes, cardiovascular diseases, and mortality. Tesamorelin is a synthetic analog of human growth hormone-releasing factor, also known as growth hormone-releasing hormone (GHRH), which is indicated for the treatment of excess abdominal fat in HIV-infected patients with lipodystrophy. The objectives of our paper were to 1) evaluate the utility of patient characteristics and validated disease-risk scores, including indicator variables for the metabolic syndrome and the Framingham Risk Score (FRS), as predictors of  visceral adipose tissue reduction during tesamorelin therapy, and 2) to explore the characteristics of patients who reached a threshold of VAT <140 cm2, a level associated with lower risk of adverse health outcomes, after 6 months of treatment with tesamorelin. The basis of the report was a pooled analysis of the two pivotal, randomized Phase 3 trials of tesamorelin in 806 HIV-infected patients with excess abdominal fat. Our results indicate that presence of metabolic syndrome, high triglycerides, and white race are associated with a greater likelihood of responding to 6 months of tesamorelin treatment. The most robust response appears to be in subjects with VAT above 140 cm2, as well as those in the overweight range for body mass index (BMI) measures. (more…)
Aging, Author Interviews, Autism, Mental Health Research, PLoS, Schizophrenia / 25.01.2016 Interview with: Dr. Richard Deth PhD Professor of Pharmacology Department of Pharmaceutical Sciences Nova Southeastern University Medical Research: What is the background for this study? Dr. Deth: Vitamin B12 plays a crucial role in regulating and promoting methylation reactions (the attachment of a carbon atom to molecules), including DNA methylation. Recent research has identified methylation of DNA and consequential changes in gene expression as crucial factors in brain development, as well as in memory formation and maintenance of brain function during aging. More specifically, the cause(s) of neurodevelopmental disorders such as autism remain obscure, although numerous studies have demonstrated oxidative stress and low plasma levels of the antioxidant glutathione (GSH) in autism.  Medical Research: What are the main findings? Dr. Deth: We found that brain levels of vitamin B12, especially the methylation-regulating form known as methylB12, decrease significantly with age, even though blood levels don’t show a similar decrease. Importantly, much lower levels of methylB12 were found in subjects with autism and schizophrenia compared to normal subjects of a similar age. Animal studies showed that impaired GSH formation is associated with decreased brain B12 levels. (more…)
Author Interviews, Exercise - Fitness, Ophthalmology, PLoS / 18.01.2016

More on Ophthalmology on Interview with: Robert Ritch, MD, FACS Shelley and Steven Einhorn Distinguished Chair Professor of Ophthalmology Surgeon Director Emeritus and Chief, Glaucoma Services Founder, Medical Director and Chairman, Scientific Advisory Board The Glaucoma Foundation Jessica V. Jasien MEn Einhorn Clinical Research Center The New York Eye and Ear Infirmary of Mount Sinai New York, NY 10003 Medical Research: What is the background for this study? What are the main findings? Response: Glaucoma is the leading cause of irreversible blindness in the United States and elevated intraocular pressure (IOP) is the most common known risk factor for glaucomatous damage. At the current time, IOP is the only modifiable risk factor for which treatment has a proven effect on preventing or slowing the progress of the disease. The story behind this study goes back to 1980, when we saw a 45-year-old woman with severe damage from normal-tension glaucoma, which then was thought to be a disease of the elderly and also thought to be rare, which we now realize was erroneous. The causes of normal-tension glaucoma were also poorly understood. It turned out on questioning that this particular patient had been performing yoga and standing on her head for 20 minutes a day for 20 years. We measured her IOP in this position and it rose from 15 mmHg in the sitting position to 60 mmHg. When measured lying flat, it was 30 mmHg. We measured everyone working in the department standing on their heads and the IOP roughly doubled in each of them. This was our first inkling that marked changes in IOP could result from changes in body position. The background for this study came from the lack of knowledge of IOP rises during yoga inversions, other than the headstand position. We looked at four common inverted yoga positions in glaucoma patients and healthy patients who were all experienced in practicing yoga. The four positions tested were downward facing dog, plow, legs up the wall, and forward bend. Each position showed a direct increase in IOP immediately assuming the yoga position, however the IOP dropped once assuming the seated position after two minutes in the yoga position. The most significant increase in IOP was seen during the downward facing dog position. IOP of each study participant was taken seated (baseline), immediately assuming the yoga position, which was held for two minutes, again at the two minutes of the yoga position, immediately in the seated position following the yoga position, and again after 10 minutes in the seated position. Each position was tested once in this order of IOP measurements. (more…)
Anesthesiology, Author Interviews, PLoS / 16.01.2016

More on Anesthesiology on Interview with: Srivas Chennu, PhD Senior Research Associate Clinical Neurosciences, University of Cambridge Visiting Scientist, MRC Cognition and Brain Sciences Unit College Research Associate, Homerton College Medical Research: What is the background for this study? Dr. Chennu:  Scientific understanding of how brain networks generate consciousness has seen rapid advances in recent years, but the application of this knowledge to accurately track transitions to unconsciousness during general anaesthesia has proven difficult. Crucially, one reason for this is the considerable individual variability in susceptibility to anaesthetic dosage.  To better understand the factors underlying this variability, we measured interconnected, oscillatory brain activity ('brain networks'), using non-invasive, high-density electroencephalography (EEG) from healthy volunteers while they were sedated with the common anaesthetic propofol. Alongside, we measured their behavioural responsiveness, and the actual concentration of the drug in their blood plasma.  (more…)
Author Interviews, Brigham & Women's - Harvard, Pancreatic, Pharmacology, PLoS / 15.01.2016

More on Pancreatic Cancer on Interview with: Dai Fukumura, M.D., Ph.D. Joao Incio, M.D. and Rakesh K. Jain, Ph.D Edwin L. Steele Laboratory Department of Radiation Oncology Massachusetts General Hospital Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Fukumura: This study focused on pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, which accounts for almost 40,000 cancer death in the U.S. ever year. Half of those diagnosed with this form of pancreatic cancer are overweight or obese, and up to 80 percent have type 2 diabetes or are insulin resistant. Diabetic patients taking metformin – a commonly used generic medication for type 2 diabetes – are known to have a reduced risk of developing pancreatic cancer; and among patients who develop the tumor, those taking the drug may have a reduced risk of death. But prior to the current study the mechanism of metformin’s action against pancreatic cancer was unclear, and no potential biomarkers of response to metformin had been reported. We have uncovered a novel mechanism behind the ability of the diabetes drug metformin to inhibit the progression of pancreatic cancer. Metformin decreases the inflammation and fibrosis characteristic of the most common form of pancreatic cancer. We found that metformin alleviates desmoplasia – an accumulation of dense connective tissue and tumor-associated immune cells that is a hallmark of pancreatic cancer – by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation. Our findings in cellular and animal models and in patient tumor samples also indicate that this beneficial effect may be most prevalent in overweight and obese patients, who appear to have tumors with increased fibrosis. (more…)
Author Interviews, Breast Cancer, Immunotherapy, PLoS / 02.01.2016 Interview with: David Gallego Ortega, PhD Group Leader, Tumour Development Group Cancer Division Garvan Institute of Medical Research Conjoint Lecturer, St Vincent’s Clinical School, Faculty of Medicine, UNSW, Australia National Breast Cancer Foundation and Cure Cancer Foundation Australia Fellow  Medical Research: What is the background for this study? What are the main findings? Dr. Ortega: We have identified a protein that 'goes rogue’ in breast cancer. The protein, called Elf5, ‘tricks' the immune system producing inflammation so that the immune cells now help the breast cancer cells to spread throughout the body. Cancer spread, or metastasis, is the ultimate cause of death of breast cancer patients, so we are very excited about our discovery because it opens the door to explore anti-inflammatory drugs that can be combined with existing therapies. We have found that luminal breast cancer patients that present high levels of Elf5 progress earlier in their disease. The Luminal subtype is the most common type of breast cancer, so these therapies will potentially benefit to 2/3 of all breast cancer patients. (more…)
Alcohol, Author Interviews, PLoS / 02.01.2016 Interview with: Dr. Florian Naudet INSERM Centre d'Investigation Clinique 1414 Faculté de Médecine, Centre Hospitalier Universitaire de Rennes Laboratoire de Pharmacologie Expérimentale et Clinique Rennes, France Medical Research: What is the background for this study? What are the main findings? Dr. Naudet: To reduce harm, alcohol-dependent individuals are usually advised to abstain from drinking, but controlled (moderate) drinking may also be helpful. To help people reduce their alcohol consumption, the European Medicines Agency recently approved nalmefene for use in the treatment of alcohol dependence in adults who consume more than 60 g (for men) or 40 g (for women) of alcohol per day. However, several expert bodies have concluded that nalmefene shows no benefit over naltrexone, an older treatment for alcohol dependency, and do not recommend its use for this indication. This is problematic because randomised controlled trials (RCTs) should lead to objective conclusions concerning treatment efficacy and this was not the case concerning nalmefene's approval. We therefore performed a meta-analysis of aggregated data to enable an objective reappraisal of the efficacy of nalmefene for relevant health outcomes and on alcohol consumption endpoints at both 6 months (+/- 1 month) and 1 year (+/- 1 month). We identified five RCTs that met the criteria for inclusion in our study. All five RCTs (which involved 2,567 participants) compared the effects of nalmefene with a placebo; none was undertaken in the population specified by the European Medicines Agency approval. Among the health outcomes examined in the meta-analysis, there were no differences between participants taking nalmefene and those taking placebo in mortality (death) after six months or one year of treatment, in the quality of life at six months. The RCTs included in the meta-analysis did not report other health outcomes. Participants taking nalmefene had fewer heavy drinking days per month at six months and one year of treatment than participants taking placebo, and their total alcohol consumption was lower. These differences were small in terms of clinical significance. Additionally, more people withdrew from the nalmefene groups than from the placebo groups, often for safety reasons. Thus, attrition bias cannot be excluded. (more…)
Author Interviews, PLoS, Urinary Tract Infections / 18.12.2015 Interview with: Dr Sandra A. Wilks PhD Senior Research Fellow IfLS Knowledge Mobilisation Fellow in Healthcare Technologies Faculty of Natural and Environmental Science & Faculty of Health Sciences Centre for Biological Sciences, University of Southampton, Southampton, UK  Medical Research: What is the background for this study? What are the main findings? Dr. Wilks: The use of indwelling Foley urinary catheters for extended periods of time results in high risks of urinary tract infections (UTI) and catheter blockages. Blockages are often caused by the presence of Proteus mirabilis, a urease-producing bacterium which results in an increase of the urine pH and the development of crystalline biofilms. Biofilms develop when bacteria attach to a surface, forming a community structure, held together by extracellular polymeric substances (EPS). Once in a biofilm, bacteria exhibit high resistance to the action of antibiotics and are protected by other stress factors. The crystalline biofilms resulting from the presence of Proteus are highly complex environments and cause complete blockage of the catheter within days. Such blockages cause pain and trauma for patients, and result in high demands on healthcare resources. In this study, we have used an advanced microscopy technique (episcopic differential interference contrast, EDIC microscopy developed by Best Scientific) to track the development of these crystalline encrustations on two commonly used catheter materials; silicone and hydrogel latex. We have identified four distinct stages to crystalline biofilm formation;
  • (1) an initial foundation layer (conditioning film) formed by individual 'colonising' P. mirabilis cells, which occurred in less than 1 hour;
  • (2) this was rapidly followed by a sheet-like microcrystalline material (after 24 hours) that covers this conditioning film;
  • (3) after 4 days exposure, large amounts of crystalline material was seen to extend out from the surface with;
  • (4) defined struvite crystals embedded within the structure and P. mirabilis visible throughout. This pattern was the same on both materials.
Author Interviews, Genetic Research, Methamphetamine, PLoS / 16.12.2015 Interview with: Camron D. Bryant, Ph.D. Assistant Professor Laboratory of Addiction Genetics Department of Pharmacology and Experimental Therapeutics & Psychiatry Boston University School of Medicine Boston, MA 02118  Medical Research: What is the background for this study? What are the main findings? Dr. Bryant: The addictions, including addiction to psychostimulants such as methamphetamine and cocaine, are heritable neuropsychiatric disorders. However, the genetic factors underlying these disorders are almost completely unknown. We used an unbiased, discovery-based genetic approach to fine map a novel candidate genetic factor influencing the acute stimulant response to methamphetamine in mice. We then directly validated the causal genetic factor using a gene editing approach. The gene - Hnrnph1 (heterogeneous nuclear ribonucleoprotein H1) - codes for an RNA binding protein that is involved in alternative splicing of hundreds of genes in the brain. Based on a genome-wide transcriptome analysis of differentially expressed genes within the striatum -  a crucial brain region involved in the stimulant properties of amphetamines - we predict that Hnrnph1 is essential for proper neural development of the dopamine circuitry in the brain. These findings could have implications for understanding not only the addictions but also other neuropsychiatric disordersthat involve perturbations in the dopaminergic circuitry. (e.g., ADHD and schizophrenia) as well as neurodegenerative disorders such as Parkinson's disease. (more…)
Author Interviews, Biomarkers, Infections, PLoS, Technology / 10.12.2015 Interview with: Leo McHugh, Ph.D. Director, Bioinformatics Immunexpress Seattle, Washington  Medical Research: What is the background for this study? What are the main findings? Dr. McHugh: Sepsis is the leading cause of child mortality in the world, and in developing countries kills more adults than breast cancer, prostate cancer and HIV combined. Approximately 30% of people admitted to ICU have sepsis, and up to 50% of these patients die. It’s a major cost burden also, costing the US health system $17 billion per year. The best way to reduce costs and improve patient outcomes is to detect sepsis early and with confidence, so that appropriate treatments can be applied. Each hour delay in the detection of sepsis has been reported to correspond to an 8% increase in mortality. So the need for a rapid and accurate diagnostic is recognized. Traditional methods rely on detection of the specific pathogen causing the infection, and these methods often take more than 24 hours, and find a pathogen in only 30% of clinically confirmed cases because they’re trying to detect a minuscule amount of pathogen or pathogenic product in the blood. Our approach was to use the host’s own immune system, which is highly tuned to respond to the presence of pathogens. Around 30% of all genes are dysregulated in sepsis, so there is a huge signal base to draw from. The trick with using multi marker host response is to pick out the specific combination of gene expression patterns that cover the broad range of patients that present with sepsis and who may present either early or late in the episode, thus with different gene activation patterns. This paper describes a simple combination of such genes that can be used to detect sepsis and performs over the full range of patients irrespective of stage of infection or severity of infection. In it’s current format, the test is manual and takes 4-6 hours, and is a great advance on the current tools, however the methods we’ve used are specifically designed to meet requirements to port this assay onto a fully automated Point of Care platform that could deliver a result in under 90 minutes. (more…)
Author Interviews, Lifestyle & Health, PLoS / 06.12.2015 Interview with: Ding Ding (Melody), Ph.D., MPH NHMRC Early Career Senior Research Fellow Sydney University Postdoctoral Research Fellow Prevention Research Collaboration Sydney School of Public Health The University of Sydney  Medical Research: What is the background for this study? What are the main findings? Response:  The study followed a large sample (around 200,000) of Australian adults aged 45 or older. Participants reported their lifestyle behaviours (smoking, excessive alcohol use, physical inactivity, unhealthy diet, prolonged sitting, short/long sleep duration) at baseline (2006-2009) and were followed up for around 6 years (up to June 2014). Based on linked administrative data (death records), we found a clear relationship between the total number of lifestyle risk behaviours and the risk of mortality---the more risk behaviours, the higher risk for mortality. This pattern of associations was consistent in men and women, participants in different age groups, of different socioeconomic status, and with and without major chronic disease. Certain behavioural risk factors have synergistic associations with mortality and appear more harmful together than individually. For example, if people only sit for long hours (defined as >7 hours a day), without having other co-occurring risk behaviours, the risk for mortality was only elevated by 15%, and if people are only physically inactive without having other co-occurring risk behaviours, the risk for mortality was elevated by 60%. However when the two risk factors were combined, say if one is not physically active AND sit for long hours, the combined risk has become much larger (increased by 140%, compared with those with zero risk behaviours).  Similarly, the combination of smoking and excessive alcohol use appeared a lot more “deadly” than the two risk factors alone. (more…)
Author Interviews, HIV, Immunotherapy, PLoS / 04.12.2015 Interview with: Andreas Meyerhans, PhD ICREA Research Professor at the University Pompeu Fabra Infection Biology Group Department of Experimental and Health Sciences Universitat Pompeu Fabra Barcelona Spain Medical Research: What is the background for this study? What are the main findings? Dr. Meyerhans: In brief, chronic HIV infections lead to a dampening of HIV-specific killer cells. This phenomenon is named exhaustion and is mediated by inhibitory proteins, such as PD-1, on the cell surface. A consequence of exhaustion is a reduction of the immune control over virus expansion. We have studied the effect of blocking the negative signaling from the inhibitory proteins by means of PD-1/PD-L1 pathway inhibition on effector and regulatory T cells (Treg). We found that one can augment antiviral immune control only when the virus load was well controlled in the HIV-infected individuals i.e. by antiviral drugs. In that case, PD-1/PD-L1 pathway blockage led to an expansion of anti-HIV killer cells over Treg cells. This latter are suppressive white blood cells also subject to the same inhibitory pathway regulation. In contrast, when blood cells from viremic HIV-infected individuals were analyzed, Treg cells expanded efficiently and thus reduced the effector to regulatory T cell ratio that controls HIV. Taken together, our data point to Treg cells as an important component in the outcome of PD-1/PD-L1 pathway inhibitor therapies and suggest a net gain in anti-HIV immune responses only when the HIV loads are well controlled during the administration of these novel compounds. (more…)
Accidents & Violence, Author Interviews, Mental Health Research, PLoS / 17.11.2015 Interview with: Simone Ullrich, PhD Senior Lecturer in Forensic Mental Health Violence Prevention Research Unit Queen Mary University of London Medical Research: What is the background for this study? What are the main findings? Dr. Ullrich: There are currently thought to be more than three hundred risk assessment instruments used by professionals such as psychiatrists, psychologists, and probation officers to assess the risks of violence and sexual offending among psychiatric patients, prisoners, and the general population. In some mental health services the hospital does not get paid unless staff have carried out a risk assessment on their patients. Producing risk assessment instruments has become an ‘industry’ and new instruments are being produced annually, on every form of violence and criminal activity. The Queen Mary research group believe that none of these instruments have any advantage over those produced before. Furthermore, their best predictions for future violence get 30% wrong. Professor Coid and colleagues believe that no further progress can be made because researchers have been too obsessed with predicting the future of whether a patient will be violent rather than looking for the causes of why they become violent. All previous studies have used special statistical techniques which are designed to measure predictive accuracy. The Queen Mary research group say there is nothing wrong with being accurate or measuring accuracy, but there is no point in trying to develop new instruments which can never improve on getting it right more than 70% of the time. It may be helpful to know that your patient has a high or low risk of being violent if you release them from hospital, but this is not going to tell you what you should do to stop them being violent. Furthermore, if the risk assessment says that their risk is high then it is likely that you will not release them. The problem is that professionals will always play safe and, although there is a good chance (around 30%) that they are totally wrong, the patient will not be released. This is probably one of the most important reasons why patients are staying longer and longer in secure mental health services. These instruments achieve little more than making healthcare professionals risk averse. The National Institute for Health Research (NIHR) funded a study where 409 male and female patients who were discharged from medium secure services in England and Wales were followed up after release into the community. They received assessments with two ‘state of the art’ assessment instruments, the HCR-20 which aims to guide clinicians in their assessment of violence, and the SAPROF, another instrument aimed to guide clinicians on which factors protect patients from becoming violent. Both instruments were developed on the basis of predictive statistics. Measures were taken with these instruments prior to release into the community, then after 6 and 12 months following discharge. Information on violence was gathered via individual case notes and a search of the police national computer. By 6 months following discharge, 54 (14%) had committed a violent act, between 6 and 12 months 43 (13%) had been violent. The authors used two methods to investigate the associations between these risk/ protective factors and violence. They first tested the standard approach of risk assessment for the factors that occurred in the past 6 months which were then used to statistically predict violence in the following 6 months (predictive model). They then used a second approach which looked at the co-occurrence of the risk/ protective factors and violence within the same 6 month time window (causal model). Using the traditional approach and looking at accuracy, the predictive model produced statistical coefficients of low size, suggesting that the risk and protective factors were poor in identifying who would be violent and who would not. Because many associations between the factors and violence were weak, few appeared useful in identifying those which should be targeted to manage future violence. Surprisingly, symptoms of major mental disorder did not show an association with violence, even though most of the patients in the study suffered from major mental disorder. It might have been expected that some patients would relapse, with more symptoms, leading to violence. When the researchers used a causal approach aiming to confirm which risk and protective factors resulted in violence, the findings were very different. Symptoms of major mental disorder, the patients’ living condition, and whether they were taking medication were highly important factors. Secondly, the effects of risk and protective factors on violence were much bigger using the causal approach. For example, the effects of violent thoughts and ruminations, being in an unstable life situation, were about 3 times stronger using the causal model. The effects of being under stress and unable to cope were more than 4 times stronger than using the traditional predictive approach. They concluded that the causal approach was much better in identifying the key factors that need to be considered in the assessment and management of violence. (more…)
Author Interviews, Blood Clots, Orthopedics, PLoS / 16.11.2015 Interview with: Banne Nemeth, MD and  Suzanne C. Cannegieter MD PhD Leiden University Medical Center The Einthoven Laboratory for Experimental Vascular Medicine Clinical Department of Epidemiology and Orthopedic Surgery Medical Research: What is the background for this study? What are the main findings? Dr. Nemeth: Clinicians cannot currently accurately predict who will develop venous thrombosis, but it would be very helpful to be able to identify individuals at high risk for venous thrombosis because the condition can be prevented by giving anticoagulants before a clot forms (thromboprophylaxis). The ability to predict venous thrombosis would be particularly useful in patients who have had a lower limb immobilized in a cast after, for example, breaking a bone. These patients have an increased risk of venous thrombosis compared to patients without cast immobilization. We developed and validated a prediction model to identify patients with plaster cast of the lower extremity who are at high risk to develop venous thrombosis. A clinical risk score named, L-TRIP(cast) score (Leiden Thrombosis Risk Prediction for patients with cast immobilization score), was developed containing 14 clinical risk factors such as age, sex, BMI, use of oral contraceptives and location of plaster cast. Patients that score 9 points or higher are classified as being at high risk for venous thrombosis. Clinicians may decide to prescribe thromboprophylaxis therapy for these patients. (more…)
Author Interviews, Nutrition, PLoS, University Texas, Weight Research / 04.11.2015

Dr. Marcia C. de Oliveira Otto MD PhD Division of Epidemiology, Human Genetics and Environmental Sciences The University of Texas Health Science Center School of Public Health, Houston, Interview with: Dr.  Marcia C. de Oliveira Otto MD PhD Assistant professor  Division of Epidemiology, Human Genetics and Environmental Sciences The University of Texas Health Science Center School of Public Health, Houston, Texas  Medical Research: What is the background for this study? What are the main findings?  Dr. Otto: Eat a variety of foods, or food diversity, is a long standing public health recommendation because it is thought to ensure adequate intake of essential nutrients, to prevent excessive intakes of less healthy nutrients such as refined sugars and salt, thus promoting good health. However there hasn’t been empiric evidence from populational studies testing this hypothesis. In our study, we characterized three metrics of diet diversity and evaluated their association with metabolic health using data from 6,814 participants in the Multi-Ethnic Study of Atherosclerosis, including whites, blacks, Hispanic-Americans, and Chinese-Americans in the United States, including the total count (number of different foods eaten in a week), evenness (the distribution of calories across different foods consumed), and dissimilarity (the differences in food attributes relevant to metabolic health, such as fiber, sodium or trans-fat content). We then evaluated how diet diversity was associated with change in waist circumference five years after the beginning of the study and with onset of Type 2 diabetes ten years later. We also examined the relationship between diet quality and the same metabolic outcomes. Diet quality was measured using established scores such as the Dietary Approaches to Stop Hypertension (DASH) and the Alterative Healthy Eating (AHEI) score. When evaluating both food count and evenness, we found no associations with either increase in waist circumference or incidence of diabetes. In other words, more diversity in the diet was not linked to better metabolic outcomes. Participants with greater food dissimilarity actually experienced more central weight gain, with a 120 percent greater increase in waist circumference than participants with lower food dissimilarity. Contrary to what we expected, our results showed that participants with greater diversity in their diets, as measured by dissimilarity, had worse diet quality. They were eating less healthy foods, such as fruits and vegetables, and more unhealthy foods, such as processed meats, desserts and soda. When evaluating diet quality, we found about a 25 percent lower risk of developing Type 2 diabetes after 10 years of follow up in participants with higher diet quality. There was no association between diet quality scores and change in waist circumference.  (more…)
Author Interviews, Geriatrics, PLoS / 21.10.2015 Interview with: Prof. Dr. med. Andreas Stuck Chefarzt Geriatrie Geriatrische Universitätsklinik Inselspital, Bern Medical Research: What is the background for this study? Prof. Stuck: The number of older persons increases worldwide. Unfortunately, many older persons cannot enjoy the benefits of increased life expectancy because they develop disability or die prematurely. In the search for an effective preventive method, we developed a novel intervention consisting of health risk assessment combined with individualized health counseling, and tested whether this novel intervention actually works. In a trial among more than 2000 older persons, we allocated persons randomly to a group receiving and a group not receiving this intervention, and compared long-term outcomes between these groups. Medical Research: What are the main findings? Prof. Stuck: We found that older participants who received the novel intervention, improved their risk factor profile, and subsequently, had a significantly improved survival as compared to the participants who had not received the intervention. From earlier studies it was known that health risk assessment can improve short term health risks in older people, but our study is the first to explore long-term health outcomes. (more…)
Author Interviews, Brigham & Women's - Harvard, Cost of Health Care, PLoS / 14.10.2015 Interview with: James E. Stahl, MD Senior Scientist Assistant Professor of Medicine, Harvard Medical School MGH Institute for Technology Assessment Medical Research: What is the background for this study? What are the main findings? Dr. Stahl: Poor psychological and physical resilience in response to stress drives a great deal of health care utilization. Mind-body interventions can reduce stress and build resiliency. Over the last few decades we have seen substantial evidence that evoking the relaxation response helps the heart, blood pressure, reduces inflammation and creates changes all the way down to the epigenetic level. We have not until now had a broad look at the effect at the health systems level. The rationale for this study is therefore to estimate the effect of mind-body interventions on healthcare utilization. The main findings are that looking at a broad population these tools, and specifically the relaxation response and resiliency training offered at the BHI, results in real world reductions in health care utilization. (more…)
Author Interviews, Genetic Research, Lung Cancer, PLoS / 07.10.2015 Interview with: Keiji Tanimoto, D.D.S., Ph.D Assistant Professor Research Institute for Radiation Biology and Medicine Hiroshima University Hiroshima Japan Medical Research: What is the background for this study? Dr. Tanimoto: Hypoxia-inducible factor-2α (HIF-2αor EPAS1) is important for cancer progression, and its overexpression is considered a putative biomarker for poor prognosis in patients with lung cancer. However, molecular mechanisms underlying EPAS1 overexpression are not fully understood. Recently, several SNPs of EPAS1 have been reported to be associated with the development of various diseases including cancer. Therefore, we focused on SNPs within EPAS1, and examined the roles of these SNPs in regulation of EPAS1 gene expression and the association of these SNPs with prognosis of non-small cell lung cancer (NSCLC) patients by bioinformatics analyses. Medical Research: What are the main findings? Dr. Tanimoto:
  • The SNP within the EPAS1 intron 1 region (rs13419896) may affect EPAS1 gene and protein expression;
  • The fragment with A allele of the SNP showed higher transactivation activity than one with G, especially in the presence of overexpressed c-Fos or c-Jun;
  • The median survival time of NSCLC patients with at least one A allele of rs13419896 was significantly shorter than that with the G/G homozygote (28.0 vs. 52.5 months, P = 0.047, log-rank test);
  • The possession of A allele of rs13419896, along with clinical stage, was an independent variable for risk estimation of overall survival for NSCLC patients [hazard ratio (HR) = 2.31, 95% CI = 1.14-4.81, P = 0.021], after adjustment for age, gender, stage, histology, tumor size, and differentiation.
Author Interviews, Cognitive Issues, Pediatrics, PLoS / 27.09.2015

Sophie von Stumm BSc MSc PhD Department of Psychology Goldsmiths University of London London, United Interview with: Sophie von Stumm BSc MSc PhD Department of Psychology Goldsmiths University of London London, United Kingdom Medical Research: What is the background for this study? Dr. von Stumm: At the Hungry Mind Lab (, which I direct, we study individual differences in lifespan cognitive development. In particular, I am interested in factors that influence change in cognitive ability and knowledge. One such factor is breastfeeding, which some previous studies suggested to be associated children's intelligence and IQ gains while others failed to find a relationship. Medical Research: What are the main findings? Dr. von Stumm: For this study, which was published last week in PloS One (link:, data were analyzed from more than 11,000 children born in the UK between 1994 and 1996. The children had been repeatedly assessed on IQ: the first time they were tested on intelligence at age 2, and then again repeatedly throughout childhood, overall 9 times, until the age of 16 years. We found that having been breastfed versus not having been breastfed was not meaningfully associated with children's IQ differences at age 2 and also not with differences in children's IQ gains until age 16. That is not to say that breastfeeding may not have other benefits for children's development but our study strongly suggests that breastfeeding is not important for children's IQ.   (more…)
Author Interviews, HIV, PLoS / 25.09.2015 Interview with: Christine Bourgeois Unité UMR 1184 / Centre IMVA CR1 INSERM, Coordinatrice site Bicêtre Le Kremlin-Bicêtre Cedex Medical Research: What is the background for this study? What are the main findings? Response: Antiretroviral therapy (ART)  treatment in HIV infected patients had successfully reduced the development of AIDS (acquired immune deficiency syndrome). However, chronic HIV infection in ART treated patients exhibit rapid uprising of viral load following ART interruption indicating that the virus is not eradicated and persist in some cellular or anatomical sites that are called “reservoir”. Secondly, ART controlled HIV-infected patients exhibit low grade inflammation developing despite efficient viral control. This low grade inflammation has been associated with non AIDS related pathologies. The aim of our work was to identify site that may combine viral persistence and inflammatory potential. We believed that adipose tissue was a very promising candidate because it included the major targets of HIV infection (CD4 T cells, and macrophages) and exhibited a highly pro-inflammatory potential. Although adipose tissue has been extensively studied as a target of antiretroviral toxicity, we readdress the role of adipose tissue as a reservoir and a site of inflammation. We demonstrated that indeed, adipose tissue from  Antiretroviral therapy controlled HIV-infected patients contained infected CD4 T cells that upon in vitro reactivation were able to produce HIV RNA. These results are extremely important because adipose tissue represents 15%-20% of body weight and is diffusely located. We thus identify a large new reservoir. (more…)
Author Interviews, Cancer Research, PLoS / 22.09.2015

Dr. Cristiano Ferlini, MD Director of Biomedical Research Rudy and Sally Ruggles Chief of cancer research Western Connecticut Health Network Research Interview with: Dr. Cristiano Ferlini, MD Director of Biomedical Research Rudy and Sally Ruggles Chief of cancer research Western Connecticut Health Network Research Institute Medical Research: What is the background for this study? Dr. Ferlini: Our aim is to understand why some cancer patients respond well to conventional treatment while others suffer progressive disease.  Nextgen sequencing technologies provide data that shed light on the mechanisms underlying differences in clinical outcome. However, analyses utilizing these data have been focused on human genes. This is to be expected given that the subjects under investigation are indeed humans. We adopted a novel approach in this and a prior study which involved in-depth, comprehensive mapping of microRNA sequences in human cancers to viral genes to assess their presence and significance. Medical Research: What are the main findings? Dr. Ferlini: We discovered a surprising number of viral microRNA sequences in a wide variety of cancer tissues. We also documented an interplay between these viral microRNAs and genes related to anticancer immunity. Both viruses and cancers share a common goal of suppressing the immune system to promote their own survival. Synergistic immunosuppression seems particularly relevant for the Epstein Barr virus, an unfortunate fact given its ubiquity in human populations. After the acute phase of EBV infection, the virus persists indefinitely in a dormant state inside B lymphocytes. When cancers grow, they create a protected microenvironment in which  anticancer immunity is suppressed.  We have obtained evidence suggesting that when EBV infected B cells circulate within these domains, the virus becomes reactivated and produces microRNAs which further amplify immunosuppressive genes. (more…)
Author Interviews, Infections, PLoS / 16.09.2015

Dr Mark Webber PhD, MSc, BSc Senior Research Fellow School of Immunity and Infection University of Birmingham and the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre (SRMRC) Interview with: Dr Mark Webber PhD, MSc, BSc Senior Research Fellow School of Immunity and Infection University of Birmingham and the National Institute for Health Research (NIHR) Surgical Reconstruction and Microbiology Research Centre (SRMRC) Medical Research: What is the background for this study? What are the main findings? Dr. Webber: Infection is a major problem for patients who suffer burn injuries and these are vary hard to treat with traditional antibiotics which struggle to effectively reach the wound and kill the bugs. One alternative which has been used in the Queen Elizabeth Hospital in Birmingham for some time is the use of acetic acid, basically vinegar. Acetic acid has long been known to be a useful antimicrobial but clinicians in Birmingham have found it to be effective in treating wounds infected, particularly with Pseudomonas. There is though very little science about what concentration of acetic acid would work best and how it kills bugs. We have shown the acetic acid works well against lots of different bugs and at much lower concentrations than are used in practice. Importantly we showed that the acetic acid works well against bugs stuck to a surface - in what's known as a 'Biofilm'. Biofilms are typically highly drug resistant. (more…)
Author Interviews, HIV, PLoS / 10.09.2015 Interview with: Augustine T. Choko MSc Malawi–Liverpool–Wellcome Trust Clinical Research Programme Blantyre, Malawi Medical Research: What is the background for this study? Response: Despite rapid scale up of HIV testing in the sub Saharan African region, half of people living with HIV are unware of their status. We investigated a novel approach of HIV self testing as an additional strategy to existing HIV testing options. Medical Research: What are the main findings? Response: Population uptake of HIV self testing was high at the first offer and remained high at the second offer 12 months later. The approach saw high numbers of adolescents and men testing. Community participants with 8% illiterate were able to do the test and correctly interpret it on their own with minimal training. People who self-tested positive were able to link into the clinic for antiretroviral therapy eligibility assessment. (more…)
Author Interviews, PLoS, Vaccine Studies / 28.08.2015

Dr Javier Martin PhD Principal Scientist Division of Virology National Institute for Biological Standards and Control (NIBSC) Medicines and Healthcare products Regulatory Agency (MHRA) Blanche Lane, South Mimms, Potters Bar United Interview with: Dr Javier Martin PhD Principal Scientist Division of Virology National Institute for Biological Standards and Control (NIBSC) Medicines and Healthcare products Regulatory Agency (MHRA) United Kingdom Medical Research: What is the background for this study? Dr. Martin: The global eradication of polio appears to be within reach.  There has been no case of poliomyelitis caused by circulating wild type 2 poliovirus since 1999, no case of type 3 since November 2012 and the last case of type 1 in Africa was in August 2014, leaving some areas of Pakistan and Afghanistan as the main remaining reservoirs of circulating wild type 1 poliovirus. Poliovirus strains in the live-attenuated oral polio vaccine (OPV) are known to quickly revert to neurovirulent phenotype following replication in humans after immunisation. These vaccine-derived poliovirus (VDPV) strains can transmit from person to person in populations with low immunity potentially leading to poliomyelitis outbreaks. (more…)