Author Interviews, Kidney Disease, PLoS, Primary Care / 22.09.2016 Interview with: Dr. Adam Shardlow Derby Teaching Hospitals NHS Foundation Trust UK What is the background for this study? What are the main findings? Response: Chronic Kidney Disease (CKD) is common in the general population, and many people are managed in primary care rather than by specialist nephrologists. This study was designed to investigate 5 year outcomes in people with mild to moderate CKD (CKD stage 3). The main findings were that the majority of participants were stable, and progression to end stage renal disease was a rarity. Interestingly, and contrary to common thinking about CKD, we found that a significant minority no longer had evidence of CKD stage 3 at 5 years, which we have termed ‘CKD remission’. (more…)
Author Interviews, Outcomes & Safety, PLoS / 21.09.2016 Interview with: Dr Su Golder PhD Research Fellow Department of Health Sciences University of York What is the background for this study? What are the main findings? Response: Serious concerns have emerged regarding publication bias or selective omission of outcomes data, whereby negative results are less likely to be published than positive results. There remains considerable uncertainty about the extent of unpublished data on adverse events beyond that reported in the published literature. We aimed to estimate the potential impact of additional data sources and the extent of unpublished information when conducting syntheses of adverse events. We found that less published papers contain adverse events information. The median percentage of published documents with adverse events information was 46% compared to 95% in the corresponding unpublished documents. There was a similar pattern with unmatched studies, for which 43% of published studies contained adverse events information compared to 83% of unpublished studies. We also found even when adverse events are reported in the published and unpublished versions of the same study that the numbers of adverse events do not always match The percentage of adverse events that would have been missed had each analysis relied only on the published versions varied between 43% and 100%, with a median of 64%. Lastly we found that inclusion of unpublished data increased the precision of the pooled estimates (narrower 95% confidence intervals) in three-quarters of pooled analyses, but did not markedly change the direction or statistical significance of the risk in most cases. (more…)
Author Interviews, OBGYNE, Pediatrics, PLoS / 16.09.2016 Interview with: Joseph Leigh Simpson, MD FACOG, FACMG President at International Federation of Fertility Societies March of Dimes Foundation White Plains, NY What is the background for this study? Response: Preterm birth (PTB) is the most common single cause of perinatal and infant mortality, affecting 15 million infants worldwide each year with global rates increasing. A total of 1.1 million infants die each year. Preterm births and their complications are the leading cause of deaths in children under age 5. The biological basis of preterm birth remains poorly understood, and for that reason, preventive interventions are often empiric and have only limited benefit. Large differences exist in preterm birth rates across high income countries: 5.5 percent in Sweden and at present 9.6 percent in the U.S. The International Federation of Gynecologists and Obstetricians (FIGO)/March of Dimes Working Group on Preterm Birth Prevention hypothesized that identifying the risk factors underlying these wide variations could lead to interventions that reduce preterm birth in countries having high rates. (more…)
Author Interviews, Duke, Medical Imaging, MRI, PLoS, Psychological Science, Social Issues / 15.09.2016 Interview with: Kevin S. LaBar, Ph.D. Professor and Head, Cognition & Cognitive Neuroscience Program Co-Director of Undergraduate Studies in Neuroscience Center for Cognitive Neuroscience Duke University Durham, NC What is the background for this study? What are the main findings? Response: Emotion research is limited by a lack of objective markers of emotional states. Most human research relies on self-report, but individuals may not have good insight into their own emotions. We have developed a new way to identify emotional states using brain imaging and machine learning tools. First, we induced emotional states using film and music clips while individuals were in an MRI scanner. We trained a computer algorithm to identify the brain areas that distinguished 7 emotions from each other (fear, anger, surprise, sadness, amusement, contentment, and a neutral state). This procedure created a brain map for each of the 7 emotions. Then, a new group of participants self-reported their emotional state every 30 seconds in an MRI scanner while no stimuli were presented. We could predict which emotion was spontaneously reported by the subjects by comparing their brain scans to each of the 7 emotion maps. Finally, in a large group of 499 subjects, we found that the presence of the fear map during rest predicted state and trait anxiety while the presence of the sadness map predicted state and trait depression. (more…)
Author Interviews, Genetic Research, PLoS, University of Pittsburgh / 31.08.2016 Interview with: Seth M. Weinberg, PhD Assistant Professor, Department of Oral Biology Assistant Professor, Department of Anthropology Director, CCDG Imaging and Morphometrics Lab What is the background for this study? Response: Scientists have long recognized that aspects of facial appearance have a genetic basis. This is most obvious when we look at the faces of people in the same family.  It is also well known that mutations in certain genes can result in syndromes where the face is affected.  However, very little is known about how specific genes influence the size and shape of normal human facial features.  To date, only a handful of studies have looked at this question, and while these studies have reported several interesting results, only a small number of genes have so far been linked to normal variation in facial features.  The primary goal of our study was to test for evidence of association between detailed facial measures derived from 3D images and common genetic variants spread across the entire genome.  We also attempted to independently replicate some of the findings from previous studies. (more…)
Author Interviews, CT Scanning, Lung Cancer, PLoS, Radiology / 19.08.2016 Interview with: Matthew B. Schabath PhD Department of Cancer Epidemiology H. Lee Moffitt Cancer Center and Research Institute Tampa, Florida What is the background for this study? What are the main findings? Response: Our study is a post-hoc analysis of data from a large randomized clinical trial (RCT) called the National Lung Screening Trial (NLST). The NLST found that lung cancer screening with low-dose helical computed tomography (LDCT) significantly reduced lung cancer deaths by 20 percent compared to screening with standard chest radiography (i.e., X-Ray). In our publication, we performed a very detailed analysis comparing outcomes of lung cancer patients screened by LDCT according to their initial (i.e., baseline), 12 month, and 24 month screening results. We found that patients who had a negative baseline screening but tested positive for lung cancer at the 12- or 24-month screen had lower survival and higher mortality rates than patients who had a positive initial screen that was a non-cancerous abnormality but developed lung cancer in subsequent screens. (more…)
Author Interviews, Cleveland Clinic, Genetic Research, Heart Disease, PLoS / 14.08.2016 Interview with: Qing Kenneth Wang PhD, MBA Huazhong University of Science and Technology Wuhan, P. R. China and Department of Molecular Cardiology The Cleveland Clinic Cleveland, Ohio What is the background for this study? What are the main findings? Response: Coronary Artery Disease (CAD) and its complication myocardial infarction (MI or so called heart attacks) are the most common causes of deaths in the US and other parts of the world. Based on the American Heart Association statistics, 620,000 Americans have a new MI each year in the United States alone, 295 000 have a recurrent MI, and nearly 400,000 of them will die from it suddenly. Moreover, an estimated 150,000 silent first MI occur each year. CAD and MI are caused by an occlusion or blockage of a coronary artery, which disrupts blood flow to the heart region, leading to damage or death of cardiac cells, impairment of cardiac function and sudden death. Current treatment of CAD and MI relies on reperfusion therapy with reopening of the occluded coronary artery with percutaneous coronary intervention (PCA) and coronary artery bypass surgery (CABG). However, 12% of patients are not candidates for PCA or CABG due to an unfavorable occlusive pattern, diffuse coronary atherosclerosis, small distant vessels and co-morbidities. An alternative revascularization strategy has to be developed to benefit these patients. (more…)
Author Interviews, Infections, PLoS / 05.08.2016 Interview with: Dr Peter Monk BSc PhD Faculty Director of International Affairs Reader in Immunology Department of Infection, Immunity and Cardiovascular Disease Sheffield University Medical School What is the background for this study? What are the main findings? Response: The tetraspanin proteins are found on the surface of all mammalian cells. The cell surface is the place where cells 'socialise': they talk to each other to coordinate activities, stick to each other to form tissues and sometimes crawl across each other to get to where they need to go. Tetraspanins have an important job to do in the organisation of the cell surface, amongst other things enabling the formation of 'sticky patches' (tetraspanin-enriched microdomains or TEM) that cause cells to adhere together or provide traction to allow movement. Some bacteria have evolved ways of hijacking the TEM for their own ends, adhering to tightly to these structures so that the normal things that sweep bacteria away (such as blood, sweat and tears!) are no longer effective. At this point, infection begins. We have found that the TEM can be partly disrupted, by adding small parts of tetraspanins (peptides) to cells. The peptides seem to work by weakening the tetraspanin glue that holds the TEM together and causing the other components that give the 'stickiness' to the TEM to become more spaced out. We use the analogy of Velcro(TM), where the fabric hooks and loops are held together in woven material; loosen the weave and the hooks and loops fall apart, no longer able to engage strongly with the loops in the opposing piece of fabric. Using reconstructed human skin, we were able to show that the tetraspanin peptides were both safe and effective; they did not affect wound healing in burned skin, but they could lower the bacterial load in the wound by 50%. This would allow the immune system (including the fluid that 'weeps' from wounds) to deal with the remaining bacteria more easily. Unlike conventional antibiotics that tend to kill bacteria, our peptides simply cause them to get washed away, so not invoking the evolutionary selective mechanisms that lead to resistance. (more…)
Author Interviews, Breast Cancer, MRI, PLoS / 02.08.2016 Interview with: Barbara Bennani-Baiti, MD, MS and Pascal Andreas Baltzer MD Departement of Biomedical Imaging and Nuclear Medicine Medical University of Vienna Vienna, Austria What is the background for this study? What are the main findings? Response: Breast MRI ist the most sensitive method for detecting breast cancer. It is currently routinely used in the screening of high-risk patients and as an additional imaging technique in case of inconclusive conventional imaging (mammography and ultrasound). Besides its high sensitivity for detection of breast cancer, breast MRI further provides functional information about normal breast tissue perfusion. Background parenchymal enhancement (BPE) reflects the perfusion or vascularization of the breast and is generally higher in active breast tissue. High-risk patients harbor breast tissue that is at an elevated risk for breast cancer due to several factors (i.e. mutations such as BRCA1, high familial risk, previous radiation of the chest wall, etc.). After a connection between increased breast cancer odds and elevated BPE has been shown in high-risk patients, the community has since assumed that an elevated background enhancement at breast MRI equates an elevated risk for breast cancer for all women. We have shown that this not true for women that are not considered high-risk. In fact, the only risk factor for women undergoing breast MRI without additional risk factors is age. (more…)
Author Interviews, Diabetes, PLoS, Primary Care, Telemedicine / 26.07.2016 Interview with: Brian McKinstry MD Professor of primary care e-health and General practitioner MacKenzie Medical Centre EdinburghBrian McKinstry MD Professor of primary care e-health and General practitioner MacKenzie Medical Centre Edinburgh What is the background for this study?  Response: The prevalence of diabetes is rising as the population ages and becomes more obese. Clinical services are increasingly stretched, so much so that it will be difficult for doctors and nurses to continue to look after patients using the same service delivery they have used in the past. Increasingly patients are being asked to self-manage long-term illnesses, but particularly with type 2 diabetes they find this stressful. One solution is to encourage self-management but with monitoring at a distance through telehealth. We performed a randomised controlled trial in family practices in four regions of the United Kingdom among 321 people with type 2 diabetes and glycated haemoglobin (HbA1c) ( a measure of control over the previous three months) >58 mmol/mol. The supported telemonitoring intervention involved self-measurement and transmission to a secure website of twice weekly morning and evening glucose for review by family practice clinicians. The control group received usual care, with at least annual review and more frequent reviews for people with poor glycaemic or blood pressure control in the context of incentives in family practice based on a sliding scale of financial rewards for achieving glycaemic and blood pressure control targets. HbA1c assessed at nine months was the primary outcome. Intention-to-treat analyses were performed. (more…)
Author Interviews, Neurological Disorders, PLoS / 21.07.2016 Interview with: Zoltan Toroczkai, PhD, Professor of Physics Concurrent Professor of Computer Science and Engineering Physics Department University of Notre Dame, Notre Dame, IN, 46556 What is the background for this study? Response: The mammalian brain is arguably the most complex information processing network and with billions of neurons and trillions of connections it presents formidable challenges to deciphering its fundamental mechanisms for information processing. In the brain, information is encoded into the spatio-temporal firing patterns of groups of neurons (population coding), making the connectivity structure of the network crucial for brain function. Damages to this network have been associated with diseases such as Alzheimer’s, autism and schizophrenia, and thus understanding the cortical network would also help better understand certain diseases of the brain. An experimentally and computationally more feasible approach is to study the anatomical (physical connectivity) network between the functional areas of the cortex, a mosaic of brain patches, each associated with a specific function (e.g., visual, auditory, somatosensory). Based on phylogenic considerations one expects the existence of common fundamental network architectural (and implicitly, processing) principles to be present in all mammalian brains. However, the mammalian brain spans over five orders of variation in size and thus it is not clear at all what are this common architectural features and how would we find them. The challenge here is to compare networks of the same nature (information processing type) but of different orders, with different nodal identities, and of very different spatial embedding (geometrical size) properties. (more…)
Author Interviews, Diabetes, Lipids, PLoS / 20.07.2016 Interview with: Dr. Fumiaki Imamura Ph.D. MRC Epidemiology Unit University of Cambridge What is the background for this study? What are the main findings? Response: There was insufficient evidence for effects of polyunsaturated fatty acids (PUFA) intake or blood biomarkers on the development of type 2 diabetes. For instance, previous studies using PUFA biomarkers had a maximum of only 673 type 2 diabetes cases. In the EPIC-InterAct Study - a large European collaborative, prospective study where 12,132 diabetes cases were ascertained during its follow-up - we found diverse associations of blood levels of different types of PUFAs with incidence of type 2 diabetes. Despite this diversity, clinically relevant results were observed for major polyunsaturated fatty acids. Higher blood levels of total omega-6 PUFAs and the major omega-6 PUFA (linolenic acid) were associated with a lower risk of developing type 2 diabetes. Likewise, levels of alpha linolenic acid, known as a plant-origin omega-3 PUFA, were associated with lower type 2 diabetes risk. Marine-origin omega-3 PUFAs, including docosahexaenoic acid (DHA), showed inconsistent associations with type 2 diabetes risk. (more…)
Author Interviews, Brigham & Women's - Harvard, Diabetes, Nutrition, PLoS, Weight Research / 15.07.2016 Interview with: Dr. Qi Sun Sc.D, M.D., M.M.S. Dr. Geng Zong, Ph.D., a research fellow Assistant Professor in the Department of Nutrition Harvard T.H. Chan School of Public Heath Boston What is the background for this study? What are the main findings? Response: There is growing trend of eating meal prepared out of home in many countries. For example, energy intake from out-of-home meals has increased from less than 10% in mid 60s to over 30% in 2005-2008 among Americans, and average time spent on cooking has decreased by one third. In the meantime, the prevalence of diabetes and obesity of this country keep on growing. In the current study, we followed nearly 100 thousands middle-aged men and women for 26 years. In 1986, we asked people how often their lunch and dinner were prepared at home per week, which will be 14 meals in maximum, and updated this information during follow-up. We found men and women with 11-14 meals prepared at home per week had 14% lower risk of diabetes compared to those had 6 or less meals prepared at home. If we look at lunch and dinner separately, people with 5 or more lunch prepared at home per week had 9% lower risk of diabetes, and those with 5 or more dinner prepared at home had 15% lower risk of diabetes compared to the group who had 2 or less than lunch or dinner at home per week. We further investigated whether people with more meals prepared at home had lower risk of obesity or weight gain in our study. In the first eight years of follow-up, participants with 11-14 meals prepared at home had 14% lower risk of developing obesity compared to people had 0-6 meals prepared at home. For men, these people had 1.2kg less weight gain, and for women they had 0.3 kg less weight gain. Furthermore, we found potential impact of having meals at home and risk of diabetes became weaker. This suggest that weight gain could be one gearwheel that links eating meals prepared at home and diabetes risk. (more…)
Author Interviews, Diabetes, PLoS, Race/Ethnic Diversity / 12.07.2016 Interview with: Matthew James O'Brien MD Northwestern University Feinberg School of Medicine What is the background for this study? Response: In October 2015, the United States Preventive Services Task Force (USPSTF) released new diabetes screening guidelines. This government-supported expert group recommended screening asymptomatic adults who are 40-70 years old and overweight or obese for diabetes. Recent population trends show that racial/ethnic minorities develop diabetes at younger ages and lower weights than whites. Therefore, we sought to determine whether these screening criteria may fail to identify racial/ethnic minorities or other high-risk population subgroups. Our study population was 50,515 patients from federally-funded community health centers, which serve large numbers of minorities and socioeconomically disadvantaged individuals. (more…)
Author Interviews, Fertility, Herpes Viruses, Infections, PLoS / 09.07.2016 Interview with: Roberta Rizzo PhD Department of Medical Sciences Section of Microbiology University of Ferrara Ferrara, Italy What is the background for this study? Response: Infertility affects approximately 6% of 15-44 year old women or 1.5 million women in the US, according to the CDC. Approximately 25% of female infertility cases are unexplained, leaving women with few options other than expensive fertility treatments. Researchers are trying to identify factors and mechanisms at the basis of this condition. (more…)
Author Interviews, Erectile Dysfunction, Melanoma, PLoS / 16.06.2016 Interview with: Anthony Matthews Department of Non-Communicable Disease Epidemiology, London School of Hygiene & Tropical Medicine London, United Kingdom What is the background for this study? Dr. Mathews: :The drug Viagra, which is used to treat erectile dysfunction, is one of a class of drugs called PDE5 inhibitors. Laboratory studies of cells from the skin cancer, malignant melanoma, suggest that PDE5 inhibitors might promote their growth, so there have been some concerns that people using these drugs might have an increased risk of malignant melanoma. Two previous studies comparing melanoma rates in PDE5 inhibitor users and non-users came to differing conclusions so we wanted to look further into this. To carry out the study we used anonymised GP records from the UK identifying over 150,000 men with a PDE5 inhibitor prescription, and over 500,000 men of a similar age, and from the same areas, who didn’t have a PDE5 inhibitor prescription. We then looked for later diagnoses of malignant melanoma to see how people’s exposure to PDE5 inhibitors affected their future risk of being diagnosed with melanoma. (more…)
Author Interviews, Brigham & Women's - Harvard, Diabetes, Nutrition, PLoS / 15.06.2016 Interview with: Ambika Satija Departments of Nutrition & Epidemiology Harvard T. H. Chan School of Public Health Boston, MA What is the background for this study? Response: In this study, we followed more than 200,000 male and female health professionals across the U.S. for more than 20 years who had regularly filled out questionnaires on their diet, lifestyle, medical history, and new disease diagnoses as part of three large long-term studies. (more…)
Author Interviews, Epilepsy, Neurological Disorders, PLoS / 30.05.2016 Interview with: Amanda Sierra, PhD Research Professor and Group Leader Ramón y Cajal Fellow Achucarro Basque Center for Neuroscience Laida Bidea Bizkaia Science and Technology ParkAmanda Sierra, PhD Research Professor and Group Leader Ramón y Cajal Fellow Achucarro Basque Center for Neuroscience Laida Bidea Bizkaia Science and Technology Park Zamudio, Bizkaia, Spain What is the background for this study? What are the main findings? Dr. Sierra: Microglia phagocytosis of apoptotic cells is at the core of the brain regenerative response to recover the homeostasis of the brain parenchyma after damage because it prevents the spillover of toxic intracellular contents and is actively anti-inflammatory. However, while neuronal death is widespread in neurodegenerative diseases (Alzheimer´s, Parkinson´s, multiple sclerosis) and well as in ischemic and traumatic brain injuries, we have a complete lack of knowledge of the efficiency of microglial phagocytosis in the diseased brain. In this paper we have discovered that microglia have a generalized response to apoptotic challenges: when confronted to a rise in the number of newborn cells, microglia display a combination of different strategies to boost their phagocytic output: increase the phagocytic capacity of each cell, recruit more cells to become phagocytic, or increase the total number of microglia (Abiega et al., PLoS Biol 2015). Thus, microglia have a very large potential for phagocytosis that could be summoned when needed. To our surprise, however, in pathological conditions such as epilepsy (mouse and human), microglial phagocytosis was blocked. We have made use of the adult neurogenic cascade, where newborn cells undergo apoptosis naturally and are engulfed by “unchallenged microglia” (Sierra et al. Cell Stem Cell 2010), to establish the baseline of microglial phagocytosis efficiency. Whereas in physiological conditions microglia phagocytose over 90% of the apoptotic cells and remove them in under 1.5h, soon after the seizures it only engulfed 10% of the apoptotic cells and took up to 6h to digest them. This is the first quantification of microglial phagocytosis efficiency in the diseased mouse and human brain.. The block in phagocytosis was a rather complex phenomenon related to an impaired recognition (reduction of phagocytosis receptors) as well as impaired motility and targeting (reduced basal motility). We have also shown that the impairment is mediated at least partially by altered ATP microgradients: ATP is not only a neuro- and gliotransmitter widely released during seizures but is also a well-known “find-me” signal released by apoptotic cells. Thus, during seizures microglia became “blinded” by the neuronal hyperactivity and could not find the apoptotic cells. In addition, we have shown that impairing phagocytosis releases the break on the inflammatory response. In fact, the impaired microglia were in a pro-inflammatory state and produced more cytokines such as tumor necrosis factor alfa (TNFa) or interleukin-1beta (IL-1b), which are well known neurotoxic and epileptogenic factors. (more…)
Author Interviews, Multiple Sclerosis, PLoS, Vitamin D / 19.05.2016 Interview with: Ms Emily Weiss PhD student Centre for Population Health Sciences The University of Edinburgh What is the background for this study? What are the main findings?  Response: Vitamin D deficiency, a marker of low ultraviolet (UV) exposure, is common in Scotland; both have been shown to work independently as risk factors for multiple sclerosis (MS). Orkney, situated to the north of mainland Scotland has a very high prevalence of MS. We therefore wanted to understand how vitamin D in Orkney compares to mainland Scotland’s vitamin D, and also what may be determining vitamin D levels in Orkney. (more…)
Author Interviews, Education, PLoS / 15.05.2016 Interview with: Mallory Kidwell, B.A. Project Coordinator at the Center for Open Science What is the background for this study? What are the main findings? Response: Open and transparent sharing of research data and materials is a core value of science that facilitates critique, replication, and extension within the scientific community. However, current norms provide few incentives for researchers to share such evidence, resulting in only a small portion of articles with accessible research data and materials. Efforts to improve rates of data sharing are occurring across research disciplines. In January 2014, the journal Psychological Science adopted an intervention to encourage data and materials sharing -- badges to acknowledge open practices, developed and freely distributed by the Center for Open Science. The badges, visual icons placed on publications, certify when the authors of a research publication have followed open practices to make their data or research materials publicly accessible. In the two years prior to adopting badges, we found that only about 3% of publications at Psychological Science reported that the underlying data was publicly accessible. After 2014, the rate of publications reporting data sharing increased dramatically, reaching 39% in the first half of 2015 -- the last time period included in the study. Materials sharing also increased, but to a weaker degree and with greater variability. We also found that, with badges, authors were more likely to follow through in making the data accessible and sharing data that was correct, usable, and complete for other researchers to reuse or reanalyze. A comparison group of journals in psychology showed no change in data sharing rates over the same time period, and among the authors that did report sharing data in the other journals, the data was less likely to actually be available, correct, usable, or complete. (more…)
Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, PLoS / 13.05.2016 Interview with: Katarina Truvé PhD Swedish University of Agricultural Sciences and Kerstin Lindblad-Toh Uppsala University What is the background for this study? What are the main findings? Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function. (more…)
Author Interviews, Brigham & Women's - Harvard, Gender Differences, Heart Disease, PLoS, Women's Heart Health / 09.05.2016 Interview with: Alexander Turchin, MD, MS Associate Physician, Brigham and Women's Hospital Associate Professor of Medicine, Harvard Medical School Brigham and Women's Hospital Department of Medicine Endocrinology Boston, MA 02115 What is the background for this study? What are the main findings? Dr. Turchin: It is known that fewer women than men at high risk for cardiovascular disease are treated with statins. However, the reasons for this sex disparity are not fully understood. Our study identified 4 factors that accounted for over 90% of the difference in statin therapy between women and men with coronary artery disease:
  • Age (women were older than men),
  • Amoking (men were more likely to smoke),
  • Evaluation by a cardiologist (men were more likely to have been seen by a cardiologist) and
  • History of adverse reactions to statins (women were more likely to have experienced an adverse reaction). This is the first time that a near-complete explanation for the sex disparities in statin therapy was found.
Author Interviews, Infections, PLoS, Sexual Health, STD / 07.05.2016 Interview with: Charu Kaushic. PhD. Professor OHTN Applied HIV Research Chair Department of Pathology and Mol. Medicine McMaster Immunology Research Center, McMaster University What is the background for this study? What are the main findings? Dr. Kaushic: Female sex hormones, estradiol and progesterone have been shown to regulate immune responses in many experimental and clinical studies. We and others have shown previously that these hormones also regulate susceptibility to and outcome of sexually transmitted infections (STIs), including Chlamydia, HSV-2, SIV and HIV-1. Most studies show that progesterone generally increases susceptibility while estradiol generally confers protection against STIs. This has recently gained much more widespread attention because of the controversy surrounding use of injectable hormonal contraceptives in geographical areas where there is high prevalence of HIV-1. The most frequently used injectable contraceptive uses a progestin-based formulation which has been correlated with 2-fold increase in HIV acquisition and transmission in epidemiological studies. Oral contraceptives that contain a combination of estradiol and progesterone do not show similar correlation with increased infection. This is currently a very important women’s health issue, which is being carefully monitored by many public health agencies, including WHO. Many researchers are focusing efforts in understanding how sex hormones can increase or decrease susceptibility of women to STIs. We have published in this area for more than a decade, including a series of papers showing that in a mouse model, the outcome of genital herpes (HSV-2) infection can depend on which hormone we treat the mice with. A few years ago, we showed for the first time that mice that received an HSV-2 vaccine under the influence of estradiol were much better protected and showed less disease pathology (Bhavanam et al, Vaccine 2008). These results were reproduced a year later by another group, using an actual HSV-2 vaccine formulation. Since then, we have been working to understand at a cellular level, the underlying mechanism of estradiol-mediated enhanced protection. In this PLOS Pathogens paper, we report for the first time a cellular mechanism by which estradiol was seen to enhance immune protection against HSV-2 infection in mice. The main findings are that estradiol primes dendritic cells in the vaginal tract to induce enhanced anti-viral T cell responses. Dendritic cells are key immune cells that decide what type of immune responses will be mounted against an infection. Under the influence of estradiol, the dendritic cells in the vaginal tract of mice induced Th17 cells which in turn helped enhance anti-viral T cell responses (Th1), resulting in better protection against genital HSV-2. This regulation of anti-viral immunity was seen only in the reproductive tract. (more…)
Author Interviews, Genetic Research, PLoS, Vitamin D / 27.04.2016 Interview with: Haidong Zhu, MD, PhD Associate Professor of Pediatrics Georgia Prevention Institute Medical College of Georgia Augusta University What is the background for this study? What are the main findings? Dr. Zhu: Vitamin D plays an important role in a wide range of body functions beyond bone health. Vitamin D deficiency is associated with increased risk of cancer and cardiovascular disease. Vitamin D deficiency is common among darker skin individuals, particularly African-Americans, which could contribute to health disparity. We want to understand underlying molecular mechanism (i.e. global DNA methylation) for how vitamin D deficiency causes cancer, cardiovascular disease and impaired immune function. DNA methylation, a chemical modification to our genome, is one of the ways that our body adapts to the environment. Low rate of global DNA methylation is a common event in cancer, which may lead to disturbances in the genome, make the genome more vulnerable to environmental damage and increase disease risk. Our study shows that majority of black teens are vitamin D deficient and have a lower rate of global DNA methylation than white teens. We further demonstrate that vitamin D3 supplementation for 16 weeks increases global DNA methylation in black teens and young adults. Our study provides an important piece of evidence that vitamin D plays a role in epigenetic regulation in humans, which could be an underlying mechanism for vitamin D-deficiency related disease risk and health disparity. (more…)
Author Interviews, Cancer Research, PLoS, Vitamin D / 15.04.2016 Interview with: Sharon L. McDonnell MPH GrassrootsHealth Encinitas, California Medical Research: What is the background for this study? What are the main findings? Response: Higher vitamin D levels in the blood have been associated with a lower risk of multiple cancer types including colorectal and breast. Using data from two study cohorts of women aged 55 years and older (N=2,304), we investigated the association between serum 25(OH)D concentration, the marker of vitamin D in the blood, and risk of all non-skin cancers combined across a broad range of 25(OH)D concentrations. We found that women with 25(OH)D concentrations ≥40 ng/ml had a 67% lower risk of cancer compared to women with concentrations <20 ng/ml. We also found that the greatest decrease in risk occurred between ~10-40 ng/ml. These findings suggest that increasing 25(OH)D concentrations to a minimum of 40 ng/ml could substantially reduce  cancer incidence and associated mortality in the population. (more…)
Author Interviews, Cancer Research, Inflammation, Microbiome, PLoS, UCLA / 15.04.2016 Interview with: Robert H. Schiestl PhD Department of Environmental Health Sciences, Fielding School of Public Health, Department of Pathology Department of Radiation Oncology Geffen School of Medicine University of California Los Angeles, Los Angeles, California Medical Research: What is the background for this study? What are the main findings? Dr. Schiestl: When we moved from Harvard to UCLA 13 years ago, after 6 years at UCLA our Atm mouse colony lived significantly 4 fold longer and the frequency of DNA deletions was 4.5 fold reduced and the latency of lymphoma 2.5 fold different. Ultimately we identified the reason behind this as a difference in the intestinal bacteria. The Atm deficient mice are hypersensitive to inflammation and the bacteria reduced inflammation. Then I isolated the most prevalent bacterium among the health beneficial bacteria and this bacterium by itself called Lactobacillus johnsonii 456 reduced genotoxicity and all markers of inflammation. (more…)
Author Interviews, Autism, Brigham & Women's - Harvard, PLoS / 09.04.2016 Interview with: Ya Wen PhD TRANSCEND Research, Neurology Department Massachusetts General Hospital, Charlestown, Massachusetts, Harvard Medical School, Harvard University, Boston, Massachusetts Higher Synthesis Foundation, Cambridge, Massachusetts What is the background for this study? Dr. Ya Wen: At the time of this study (December 2014), the SFARI (Simons Foundation Autism Research Initiative) Gene-Human Gene Module recorded 667 human genes implicated as relevant to Autism spectrum disorders (ASDs). Now the number is close to 800. We sought to address the challenge of making sense of this large list of genes by identifying coherent underlying biological mechanisms that link groups of these genes together. To do this, we used information from several existing and well established databases and created a “demographics” of autism genes and pathways. What are the main findings? Dr. Ya Wen: From these hundreds of autism genes, we first found the relatively most important pathways, and then we generated a pathway network by mapping the pathway-pathway interactions into an Autism Pathway Network. Our systems analyses of this network converged upon an important role in autism pathophysiology for two pathways: MAPK signaling and calcium signaling, and specifically the process where they overlap, “calcium-protein kinase C-Ras-Raf-MAPK/ERK”. Our study also illuminated genetic relationships between autism and several other kinds of illness, including cancer, metabolic and heart diseases. Many of the significant genes and pathways were associated with vulnerability in the processing of challenging environmental influences. (more…)
Author Interviews, Mental Health Research, NYU, PLoS, PTSD / 06.04.2016 Interview with: Glenn Saxe, MD Arnold Simon Professor of Child and Adolescent Psychiatry and Chair, Department of Child and Adolescent Psychiatry NYU Langone’s Child Study Center Dr. Saxe’s bio page What is the background for this approach? What are the main advantages and drawbacks to the CS-CN method in psychiatry research? Dr. Saxe: Psychiatric disorders are complex and, in all likelihood, emerge and are sustained over time because they form what is called a complex system, involving the interaction between a great many variables of different types (e.g. molecules, neurons, brain circuits, developmental, social variables). There is a strong literature on complex systems in other fields that show remarkably similar properties between vastly different types of systems. Unfortunately, data methods used in research in psychiatry are not designed to ‘see’ the possible complex systems nature of a psychiatric disorder. Our method is designed to identify networks of variables related to psychiatric disorders that, together, have properties of complex systems. If such a system is identified, it may reveal new ways to treat these disorders. (more…)
Author Interviews, Dermatology, PLoS, Stem Cells / 06.04.2016 Interview with: Takashi Tsuji, PhD Team Leader of  Laboratory for Organ Regeneration RIKEN Center fo r Developmental Biology Chuo-ku, Kobe, Hyogo Japan What was the impetus for this research? What made you think about creating a skin model? Answer. Previously, we successfully demonstrated the functional organ regeneration including tooth (PNAS 2009), hair follicles (Nature Communications 2012), salivary gland (Nature Communications 2013a) and lachrymal gland (Nature Communications 2013b). We focused onto a complex organogenesis through the epithelial and mesenchymal cell interaction. In the current study as a continuous work, we would like to regenerate organ system by using multipotent stem cells such as ES and iPS cells. In this study, we first demonstrated the generation of a functional bioengineered 3D integumentary organ system from murine iPS cells. Can you describe what you created in layperson terms? How big is it, what does it look like and what is it capable of doing? Answer. We succeeded to demonstrate the proof-of-concept to generate 3D integumentary organ system, complete skin, which has skin appendages such as hair follicle and sebaceous gland, by mimicking the organogenesis during embryogenesis. In this work, we performed in murine system, so, the transplantable skin size is small as 1 mm2 /1 site. We think that further studies for humanization and the development of in vitro culture system would lead to realize of clinical applications for severe burned patients and severe hair loss. Furthermore, this method will contribute to understand the onset of dermoid tumor, which has ectodermal organs such as tooth and hair follicle, in human. (more…)
Author Interviews, Infections, PLoS / 27.03.2016 Interview with: Dr. Cameron Stewart PhD Team Leader within the Emerging Infectious Diseases Program CSIRO Biosecurity Flagship Commonwealth Scientific and Industrial Research Organisation What is the background for this study? What are the main findings? Dr. Stewart: Hendra and Nipah viruses (referred to jointly as henipaviruses) are deadly cousins of the more common mumps, measles, and respiratory syncytial viruses, all members of the paramyxovirus family. Henipavirus outbreaks are on the rise, but little is known about the viruses, partly because research has to be undertaken under extreme containment conditions.  Our team performs research at the largest high containment facility in the Asia-Pacific region, the CSIRO Australian Animal Health Laboratory in Geelong, Australia. To understand the henipavirus infection cycle and to identify targets for new antiviral therapies, we performed a genome-wide screen to identify the host molecules required by henipaviruses for infection. The host gene with the largest impact, called fibrillarin, codes for a protein present in the nucleolus. Inhibiting fibrillarin impaired henipavirus infection greater than 1,000-fold in human cells.  We examined closely which step of the viral life cycle was blocked by interfering with fibrillarin function, and found it was required for the early synthesis of viral RNA. Results from our study suggest that fibrillarin could be targeted therapeutically to combat henipavirus infections. This research was undertaken by an international team of researchers from CSIRO, the Victorian Centre for Functional Genomics, Duke-NUS, the University of Georgia and the Centers for Disease Control and Prevention. (more…)