Author Interviews, Colon Cancer, Supplements / 13.04.2018

MedicalResearch.com Interview with: Nathalie Scheers PhD Asst. Professor Chalmers University of Technology Dept of Biology and Biological Engineering Food and Nutrition Science Göteborg, Sweden  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many different forms of iron supplements are used to treat iron deficiency symptoms or as phosphate binders in patients with renal disease. two of these iron supplements, the chelates ferric citrate and ferric EDTA have been observed to drive colon cancer in mice. In the newly published study in Oncotarget, we are reporting our work on how these iron compounds differ compared to the simple salt ferrous sulphate, which is another common iron supplement. The main finding of this study was that ferric citrate and ferric EDTA promoted the cancer biomarker amphiregulin which in turn activated the MAP kinase ERK in gut epithelial cancer cells. There were no such effects in ferrous sulphate-treated cells.  (more…)
Author Interviews, Hepatitis - Liver Disease, Microbiome, Nutrition, Weight Research / 13.04.2018

MedicalResearch.com Interview with: “Turkish Food” by Garry Knight is licensed under CC BY 2.0Jasmohan S. Bajaj, M.D. Associate Professor Department of Internal Medicine Division of Gastroenterology Virginia Commonwealth University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Altered gut microbiota composition can occur due to diseases and due to changes in the dietary practices. The interaction between these two and their linkage with clinical outcomes in liver diseases, such as cirrhosis is not clear from an international standpoint. In this study we enrolled healthy subjects, and patients with cirrhosis who were either early or advanced in their process from USA and Turkey. We found that the Turkish subjects, who followed a Middle-eastern diet rich in vegetables and fermented milk products, had high microbial diversity, which was in turn associated with lower hospitalizations over 3 months. There was also an additional beneficial effect of coffee and tea intake. This protection persisted even when the clinical factors were accounted for. (more…)
Author Interviews, Sleep Disorders / 12.04.2018

MedicalResearch.com Interview with: “Sleep” by Spencer Smith is licensed under CC BY 2.0Kristen L. Knutson, PhD Associate Professor Center for Circadian and Sleep Medicine Department of Neurology Northwestern University Feinberg School of Medicine Chicago, IL  60611​ MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous research has shown that “night owls” (people who prefer the evening) have higher rates of diseases such as diabetes or high blood pressure.  We wanted to determine whether mortality risk was also higher in night owls. We used data from the UK Biobank of almost a half million people who were asked whether they were morning or evening types. We found that the night owls had a 10% increased risk of dying over a 6 ½ year period compared to the morning types, even after taking into account existing health problems. (more…)
Author Interviews, Microbiome, Nutrition, Sugar, Weight Research / 12.04.2018

MedicalResearch.com Interview with: Eugene B. Chang, MD Martin Boyer Professor of Medicine Knapp Center for Biomedical Discovery University of Chicago Chicago, IL  60637 and Kristina Martinez-Guryn, Ph.D., R.D.
Assistant Professor 
Biomedical Sciences Program
Midwestern University
Downers Grove IL MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Martinez-Guryn: The original goal of this study was to understand why mice devoid of all microorganisms (germ free mice) are protected from diet-induced obesity. We demonstrate that these mice display severely impaired lipid absorption even when fed a high fat diet. Dr. Chang: We found that many of the processes of dietary lipid digestion and absorption are dependent on and modulated by the gut microbiome which itself responds to dietary cues to adjust the small intestine’s ability and capacity to handle dietary lipids appropriately. This interplay is important for general health, but the findings are also relevant to conditions of overnutrition (obesity, metabolic syndrome) and undernutrition (starvation, environmental enteropathy).  In conditions of overnutrition, high fat, simple sugar, low fiber foods typical of western diets promote small intestinal microbes (which have been largely neglected by the scientific community) that promote fat digestion and absorption. This increases our capacity to assimilate dietary fats which can contribute to the overnutrition problem.  In conditions of undernutrition, these types of gut microbes are lost or minimally represented.  Thus, when nutritional repletion is started, the gut’s ability to upregulate its capacity for dietary lipid digestion and absorption is compromised. (more…)
Author Interviews, Heart Disease, JACC, Outcomes & Safety, Surgical Research, University of Michigan / 12.04.2018

MedicalResearch.com Interview with: Donald Likosky, Ph.D., M.S. Associate Professor Head of the Section of Health Services Research and Quality Department of Cardiac Surgery. University of Michigan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Michigan was one of several states to expand Medicaid. Current evaluations of the Michigan Medicaid expansion program have noted increases in primary care services and health risk assessments, but less work has evaluated its role within a specialty service line. There has been concern among some that Medicaid patients, who have traditionally lacked access to preventive services, may be at high risk for poor clinical outcomes if provided increased access to cardiovascular interventions. Using data from two physician-led quality collaboratives, we evaluated the volume and outcomes of percutaneous coronary interventions and coronary artery bypass grafting 24mos before and 24mos after expansion. We noted large-scale increased access to both percutaneous coronary interventions (44.5% increase) and coronary artery bypass grafting (103.8% increase) among patients with Medicaid insurance. There was a decrease in access for patients with private insurance in both cohorts. Nonetheless, outcomes (clinical and resource utilization) were not adversely impacted by expansion.  (more…)
Author Interviews, Endocrinology, Mental Health Research, OBGYNE / 12.04.2018

MedicalResearch.com Interview with: Aled Rees, MD, PhD Neuroscience and Mental Health Research Institute Cardiff University School of Medicine, Health Park Cardiff United Kingdom MedicalResearch.com: What is the background for this study?   Response: PCOS is a common condition, affecting 5-10% of women globally, in which elevated male hormone levels can cause a range of distressing and life-limiting symptoms, including reduced fertility, irregular periods, excessive facial and body hair, and acne. Previous studies have suggested a link between PCOS and poor mental health in women but the studies were small and did not adequately take other factors that can affect mental health into consideration. In addition, high levels of testosterone during pregnancy have been reported to increase the risk of neurodevelopmental disorders, such as ADHD and autism, in children. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Epilepsy / 12.04.2018

MedicalResearch.com Interview with: Britta Haenisch, PhD Pharmacoepidemiology in Neurodegenerative Disorders German Center for Neurodegenerative Diseases, DZNE  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Antiepileptic drugs (AEDs) have been shown to affect cognition by suppressing neuronal excitability and increasing inhibitory neurotransmission. Previous studies suggested that AEDs may be associated with cognitive adverse effects. Therefore, we evaluated the association between AED use and incident dementia and Alzheimer’s disease (AD). We utilized large longitudinal datasets from Finnish health registers and from German health insurance data. The case-control analyses was adjusted for several potential confounders like comorbidities and polypharmacy. The inclusion of a lag time between . Antiepileptic drugs use and dementia diagnosis allowed minimization of protopathic bias. Our study provides an association between regular prescription of  antiepileptic drugs with known cognitive adverse effects and the occurrence of dementia and AD in patients aged 65 years and older.  (more…)
Author Interviews, JAMA, Mental Health Research, OBGYNE, Pediatrics / 11.04.2018

MedicalResearch.com Interview with: Jiook Cha, PhD Assistant Professor Division of Child and Adolescent Psychiatry Columbia University Medical Center New York, NY 10032 MedicalResearch.com: What did we already know about the connection between maternal SSRI use during pregnancy and infant brain development, and how do the current study findings add to our understanding? What’s new/surprising here and why does it matter for mothers and babies? Response: Prior studies have shown mixed results in terms of the associations between maternal SRI use during pregnancy and offspring’s brain and cognitive development. Neurobiological studies with animal models suggest that SSRI use perturbs serotonin signaling and that this has important effects on cognitive development (a study conducted an author of this paper, Jay Gingrich, MD, PhD: Ansorge et al., 2004, Science). The human literature has been more mixed in terms of the associations of prenatal exposure to SSRI with brain and cognitive development. In our study, we used neonatal brain imaging because this is a direct, non-invasive method to test associations between SSRI use and brain development at an early developmental stage, limiting the effects of the post-natal environment. In our study, we had two different control groups, that is, a non-depressed SSRI-free group (healthy controls), and depressed but SSRI-free (SSRI controls) group. Also, in our study we used rigorous imaging analytics that significantly improve the quantitative nature of MR-derived signals from the brain structure using two of the nation’s fastest supercomputers (Argonne National Laboratory and Texas Advanced Computing Center) and allows robust reconstruction of brain’s grey and white matter structure in the infants’ brains. We report a significant association of prenatal exposure to SSRI with a volume increases within many brain areas, including the amygdala and insula cortex, and an increase in white matter connection strength between the amygdala and insular cortex. We were surprised by the magnitude of the effects (or the statistical effect size), compared with other brain imaging studies in psychiatry with children or adults’ brains. Importantly, it should be noted that our estimates of brain structure are still experimental and for research-purpose only. This means that our data need to be replicated and rigorously tested against confounders in order to make a firm conclusion. While our study suggests a “potential” association between prenatal exposure to SSRI and a change in fetal or infant brain development, we still need more research.  tracts_in_the_brain (more…)
Author Interviews, Infections, Lipids / 11.04.2018

MedicalResearch.com Interview with: Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital, Denmark  MedicalResearch.com: What is the background for this study? Response: For decades research into the role and function of high-density lipoprotein (HDL) has revolved around the believe that HDL protects against atherosclerotic cardiovascular disease. However, results from large genetic studies and from large randomized clinical trials with HDL cholesterol elevating drugs have all indicated that there is no causal association between HDL cholesterol and risk of atherosclerotic cardiovascular disease. Given the hitherto strong focus on cardiovascular disease, little is known about the possible role of HDL in other aspects of human health and disease. Preclinical evidence has indicated that HDL might be of importance for normal function of the immune system and susceptibility to infectious disease, but it had never previously been investigated if levels of HDL cholesterol is associated with the risk of infectious disease in individuals from the general population. In the present study we tested this hypothesis in more than 100.000 Danes from the population at large. (more…)
Author Interviews, Global Health, Infections, Pediatrics / 10.04.2018

MedicalResearch.com Interview with: Georgies Mgode PhD Sokoine University of Agriculture Pest Management Centre African Centre of Excellence for Innovative Rodent Pest Management and Biosensor Technology Development Morogoro, Tanzania MedicalResearch.com: What is the background for this study? Response: The background of this study is the APOPO and Sokoine University of Agriculture together with NIMR and NTLP interest to explore a cheap, reliable and sustainable means of addressing TB problem in high-burden countries with limited access to advanced sensitive tests. This refers to countries where to-date TB diagnosis is mainly by microscopy that is less sensitive leaving majority of patients undetected. We were driven to explore how these rats can contribute to diagnosis of TB in children that is known to be difficult and rats are known to have a better and advanced sense of smell. According to WHO " an estimated 1 million children became ill with TB and 250 000 children died of TB in 2016 and the actual burden of TB in children is likely higher given the challenge in diagnosing childhood TB.  (more…)
Author Interviews, Epilepsy, JAMA / 10.04.2018

MedicalResearch.com Interview with: Dr Hayley Gorton PhD MPharm MRPharmS FHEA Research Associate Centre for Pharmacoepidemiology and Drug Safety Research Division of Pharmacy & Optometry| Faculty of Biology, Medicine & Health University of Manchester MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is already known that people with epilepsy are at a higher risk of death than those without epilepsy but we didn’t know much about the risks of different types of death. Unnatural death (mainly accident and suicide) accounts for a very small number of all deaths but, compared to people without epilepsy, people with epilepsy are three times more likely to die by accident and twice as likely to die by suicide. Within these broad categories, persons with epilepsy are five times more likely to die specifically by accidental poisoning with medication, and three times more likely to die by intentionally poisoning themselves with medication. Opioid painkillers and medicines for mental illness were the ones most commonly used in poisoning deaths among people with epilepsy and those without epilepsy. Antiepileptic drugs were taken relatively infrequently-they were involved in about 10% of poisoning deaths in people with epilepsy.  (more…)
Author Interviews, Cancer Research, Cost of Health Care, JAMA, Pharmaceutical Companies / 09.04.2018

MedicalResearch.com Interview with: Aaron Mitchell, MD Division of Hematology/Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center The Cecil G. Sheps Center for Health Services Research The University of North Carolina at Chapel Hill MedicalResearch.com: What is the background for this study? What are the main findings? Response: Financial relationships between physicians and the pharmaceutical industry are very common. However, we are just beginning to figure out whether these relationships may lead to potentially concerning changes in physician behavior - whether physicians tend to prescribe more of the drugs made by a company that has given them money. We decided to ask whether oncologists who receive money from drugmakers are more likely to use the cancer drugs made by companies that have given them money in the past. In studying two specific groups of cancer drugs, one for kidney cancer and one for chronic myeloid leukemia (CML), we found that oncologists who had received payments such as meals, consulting fees, travel & lodging expenses from the manufacturer of one of these drugs tended to use that drug more. When looking at oncologists who received payments for research, we found increased prescribing among the kidney cancer drugs but not the CML drugs. (more…)
Author Interviews, Infections, Orthopedics, Surgical Research / 09.04.2018

MedicalResearch.com Interview with: Dr Setor Kunutsor PhD Research Fellow Musculoskeletal Research Unit Bristol Medical School MedicalResearch.com: What is the background for this study? Response: Hip replacement is a very common operation that is effective at providing pain relief and improving mobility. Infection is a fortunately infrequent but devastating complication that can occur following joint replacement. Currently, two main types of surgical procedures are used in treating these infections – one-stage and two-stage revision strategies. In the two-stage procedure, the existing artificial joint is removed in one operation and the patient is treated for several months with antibiotics. A new joint is then inserted in a second operation. In the one-stage procedure, the artificial joint is removed along with all infected tissue and a new one inserted in the same operation. The two-stage procedure has been in use for decades and was regarded as the most effective treatment. There has been an increase in the use of the one-stage procedure as it has also been claimed to be very effective at treating infection. There has been a lot of controversy among orthopaedic surgeons as to which is the best way to treat infected hip replacements. Several studies have been conducted on the topic, but the findings have been inconsistent. Some claim the two-stage to be more effective and others claim the one-stage procedure is. Currently the majority of studies claim the two-stage is better; but no study has been conducted that compares these procedures head-to-head to decide if one is better or if they achieve the same results. Due to the lack of evidence, some surgeons are reluctant to use the one-stage strategy. There was therefore a need to compare the effectiveness of the two surgical strategies using an appropriate study design. We conducted a study which involved collecting and bringing all previous data together under one umbrella. The process is known as “Individual Participant Data meta-analysis”. It involved communicating with surgeons in different countries all over the world and inviting them to contribute data. We called the name of the group “The Global Infection Orthopaedic Management (INFORM) Collaboration”. (more…)
Author Interviews, JAMA, Mental Health Research, OBGYNE, Pediatrics / 09.04.2018

MedicalResearch.com Interview with: Claudia I. Lugo-Candelas, PhD Postdoctoral Research Fellow Columbia University Medical Center/ New York State Psychiatric Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have seen, in the last decade, an increase in the amount of mothers being prescribed SSRIs during pregnancy. While we know that untreated prenatal maternal depression has adverse consequences for both the mother and child, it’s not really clear what, if any, are the consequences of prenatal SSRI exposure on infant’s brain development. There have been some studies finding increased depression and anxiety in children prenatally exposed to SSRIs, but not all studies find these associations. We thus looked at 2-4 week old infants’ brains, using neuroimaging.  We found increased gray matter volume within the amygdala and insula, and increased white matter connectivity between these two structures in infants prenatally exposed to SSRIs. Of note, the statistical significance and the size of the effects we detected are quite large, even greater than the brain changes that we usually observe in our studies of children and adults with psychiatric disorders. Further, because these structures are involved in emotion processing, and alterations in volume and connectivity are sometimes seen in clinical populations, or in people at risk for anxiety, it important to learn more about what these volume and connectivity differences could mean for these infants. (more…)
ALS, Alzheimer's - Dementia, Author Interviews, JAMA / 09.04.2018

MedicalResearch.com Interview with: Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nearly half of all patients with amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disorder, develop cognitive problems that affect memory and thinking. Why a disease that primarily affects movement also disrupts thinking has been unclear. Our findings suggest that genetic connections between the two disorders may explain why they share some of the same features and suggest that some drugs developed to treat ALS also may work against frontotemporal dementia and vice versa. We used a statistical method in almost 125,000 individuals with ALS, frontotemporal dementia (FTD), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease and Parkinson’s disease to determine whether there are common genetic variants that increase risk for multiple neurodegenerative diseases. We found that common variants near the MAPT gene, which makes the tau protein, increases risk for ALS. MAPT has previously had been associated with diseases including frontotemporal dementia and Alzheimer’s disease. But the gene hadn’t been linked to ALS. We also identified variations in a second gene, BNIP1, which normally plays an important role in protecting against cell death, increased the risk of both ALS and frontotemporal dementia. ImportantlyBNIP1 mRNA levels were altered in people who had ALS and in patients with frontotemporal dementia, suggesting the BNIP1 may be a potential therapeutic target for both disorders. (more…)
Author Interviews, Gastrointestinal Disease, Pain Research / 09.04.2018

MedicalResearch.com Interview with: Dr. Joseph Pergolizzi MD Senior Partner and Director of Research Naples Anesthesia and Pain Associates Naples, Florida MedicalResearch.com: What is the background for this study? What are the main findings?  Response: There are roughly 100 million Americans living with chronic pain and many battle debilitating side effects because of their pain medication, including Painstipation otherwise known as opioid-induced constipation (OIC.) In fact, OIC is the most common side effect with approximately 40-80 percent of patients on chronic opioid therapy experiencing it. To better understand this community, the Painstipation survey, conducted by Salix Pharmaceuticals in partnership with the U.S. Pain Foundation, surveyed 441 U.S. adults with chronic pain who were on opioid therapy and suffering from OIC. It gave great insight into this community as it found:
  • More than half (51 percent) of chronic pain patients have been suffering from opioid-induced constipation  for three years or longer
  • Most patients (73 percent) agree that one of the biggest challenges of having OIC is that medications don’t work quickly enough to relieve pain associated with OIC.
  • 53 percent of patients say they want relief for OIC in under four hours
  • Only half of patients surveyed (73 percent) surveyed said they were informed by their doctors that taking opioid medications might result in constipation before they began taking them
  • 77 percent of respondents reported suffering from OIC for at least one year
  • When asked, roughly one-third (32 percent) of patients reported that their doctor does not talk to them specifically about potential adverse drug-to-drug interactions (DDI) of their current prescription and/or over-the-counter medications.
(more…)
Author Interviews, Cancer Research, Lung Cancer, PNAS / 08.04.2018

MedicalResearch.com Interview with: Nada Kalaany, PhD Harvard Medical School Boston Children's Hospital Boston, MA 02115 MedicalResearch.com: What is the background for this study? Response: ​ Non-small cell lung cancer (NSCLC) is the predominant form of lung cancer and the leading cause of cancer death in the US and worldwide. Over a quarter of NSCLC harbors activating mutations in the KRAS oncogene, which despite decades of attempts, has proven to be very difficult to target. KRAS has previously been demonstrated to directly bind to and activate the pro-proliferative kinase PI3K, which is typically activated by insulin/insulin-like growth factor1 (IGF1) signaling. KRAS-PI3K binding is required for KRAS-driven lung cancer formation and progression. However, whether this interaction is sufficient for lung tumor formation and whether additional input is required from insulin/IGF1 signaling, has remained largely controversial. (more…)
Author Interviews, Emergency Care, Opiods / 08.04.2018

MedicalResearch.com Interview with: Frank Scheuermeyer MD MHSc Clinical Associate Professor Department of Emergency Medicine St Paul’s Hospital and the University of British Columbia  MedicalResearch.com: What is the background for this study? Response: Mortality from the opioid epidemic is dramatically increasing and a main culprit appears to be illicit fentanyl. Current research states that patients with presumed fentanyl overdoses are at high risk of deterioration and death, and require prolonged emergency department stays or hospital admission to ensure a safe outcome. Our inner-city hospital adopted a protocol initially developed for patients with heroin overdose, modified it to account for the greater potency of fentanyl, and studied 1009 consecutive patients who arrived with an overdose. (more…)
Author Interviews, JAMA, Mental Health Research / 07.04.2018

MedicalResearch.com Interview with: Dr. Aideen Maguire Centre of Excellence for Public Health Queen's University Belfast Institute of Clinical Sciences B Royal Hospitals Site, Belfast MedicalResearch.com: What is the background for this study?   Response: Consanguineous Marriage is the marriage between second or first cousins. Although not common practice in the Western world approximately 1 in 10 children worldwide are born to consanguineous parents. It is legal in all countries worldwide except the United States of America, North Korea and China. Cousin-marriage is associated with an increased risk of autosomal recessive genetic disorders in offspring but the association between cousin-marriage and the mental health of offspring has not been extensively studied. MedicalResearch.com: What are the main findings? Response: Children of consanguineous parents are over 3 times more likley to be in receipt of medications for common mood disorders (antidepressant and/or anxioltyic medication) compared to children of non-related parents and over twice as likley to be in receipt of antipsychotic medication compared to children of non-related parents.  (more…)
Author Interviews, Bone Density, Geriatrics, Nutrition / 06.04.2018

MedicalResearch.com Interview with: “bought a passive-aggressive amount of milk” by Paul Downey is licensed under CC BY 2.0Shivani Sahni, PhD Assistant Professor of Medicine, Harvard Medical School Director, Nutrition Program Associate Scientist, Musculoskeletal Research Institute for Aging Research, Hebrew SeniorLife, Boston  MA  02131-1097 MedicalResearch.com: What is the background for this study? Response: Previous studies have shown that higher milk intake is associated with higher bone mineral density. In one of our previous studies, we reported that higher dairy food intake was protective against bone loss especially among older adults who used vitamin D supplements. Older adults are at high risk of vitamin D deficiency because recommended intakes are difficult to achieve without fortified foods (such as dairy) or supplements. Vitamin D stimulates calcium absorption, which is beneficial for building bones. However, it is unclear if the effect of vitamin D on calcium absorption is substantial enough to translate into beneficial effects on bone. Therefore, the current study determined the association of dairy food intake with bone health. We further examined whether these associations would be modified by vitamin D status. (more…)
Author Interviews, Blood Pressure - Hypertension, Nature / 06.04.2018

MedicalResearch.com Interview with: Dr. Charles Brenner, PhD Chief Scientific Advisor ChromaDex MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nicotinamide adenine dinucleotide (NAD) is the central regulator of metabolism. NAD is under attack in multiple conditions of metabolic stress and declines in human aging. Thus, using supplements to maintain NAD has emerged as an important strategy to support healthy aging. There are three vitamin precursors of NAD. However, two of those forms (niacin and nicotinamide) have unwanted side effects and/or inhibit some of the metabolic regulators that can be stimulated by higher NAD. Nicotinamide riboside (NR) is the most recently discovered NAD precursor vitamin. Research has shown that NR boosts NAD more than the other precursors, doesn’t cause flushing, doesn’t inhibit sirtuin enzymes, and that the pathway that converts NR to NAD is turned on in tissues undergoing stress and damage. Commercialized as NIAGEN®, NR has been clinically proven to significantly increase NAD levels in people as an oral supplement. NIAGEN® is the only NR with published human safety, efficacy and tolerability studies. The University of Colorado study is the first clinical trial showing that not only does NIAGEN® boost NAD levels, it also may have a beneficial effect on cardiovascular health and function. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA / 06.04.2018

MedicalResearch.com Interview with: Dr. Alvin Chandra  MD first author  and Dr. Scott David Solomon M.D. Director, Noninvasive Cardiology Professor, Harvard Medical School Cardiovascular Medicine Brigham and Women’s Hospital Boston, Massachusetts MedicalResearch.com: What is the background for this study? What are the main findings? Response: In general, the quality of life of heart failure with reduced ejection fraction patients is quite impaired, and  similar to that of patients on dialysis. PARADIGM-HF was the largest trial of heart failure patients and showed that sacubitril/valsartan was superior to the gold-standard enalapril in reducing cardiovascular death, heart failure hospitalization and all-cause mortality. In addition, patients on sacubitril/valsartan, when compared to enalapril, showed significant improvement in overall quality of life. In this study we looked in more detail at the individual components of “quality of life” and found that in virtually all domains and activities, patients who were randomized to sacubitril/valsartan reported improvement in their limitations  compared to those who were randomized to enalapril. These activities included jogging, doing hobbies, and household chores, with the largest improvement seen in  sexual activities limitations. (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA / 06.04.2018

MedicalResearch.com Interview with: Stella Aslibekyan, PhD Associate Professor PhD Program Director Department of Epidemiology University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? What are the main findings? Response: When the human genome was sequenced in 2003, there were somewhat unrestrained expectations of unraveling all etiologic mysteries and discovering breakthrough treatments. Needless to say, that did not happen, in part because individual genetic variants can only account for a small fraction of trait variability. Since then, epigenetics-- the study of mitotically heritable changes in gene expression-- has emerged as another promising avenue for understanding disease risk. The best studied epigenetic process in humans is DNA methylation, and earlier studies (including some from our group) have shown interesting associations between changes in methylation in specific genomic regions and cardiovascular disease traits, e.g. plasma cholesterol levels. In this project, we have combined DNA methylation data on thousands of individuals from multiple international cohorts and interrogated epigenetic contributions to circulating tumor necrosis factor alpha (TNFa), a marker of systemic inflammation. We identified and replicated several epigenomic markers of TNFa, linked them to variation in gene expression, and showed that these methylation changes (which were located in interferon pathway genes) were predictive of coronary heart disease later in life. Interestingly, the variants we discovered were not sequence-dependent (in other words, they were not associated with any genetic mutations), highlighting the role of the environment. (more…)
Author Interviews, Genetic Research, Ophthalmology / 05.04.2018

MedicalResearch.com Interview with: Wen-Tao Deng, Ph.D. Department of Ophthalmology, College of Medicine| University of Florida, Gainesville, FL MedicalResearch.com: What is the background for this study? What are the main findings? Response: Blue cone monochromay (BCM) is a devastating vision disorder characterized by loss function of both L- and M-cones due to mutations in the L- and M-opin gene cluster on the X chromosome. BCM patients display severely reduced visual acuity, loss of color-vision, myopia, nystagmus, and minimally detectable cone-mediated electroretinogram. In our studies, we showed that an M-opsin knockout mouse model resembles human BCM, and expression of either human M- or L-opsin individually or combined through adeno-associated viral vector promotes regrowth of cone outer segments and rescues M-cone function in the treated M-opsin dorsal retin (more…)
Allergan, Author Interviews, Bipolar Disorder, Depression, Mental Health Research / 05.04.2018

MedicalResearch.com Interview with: Dr. C. David Nicholson, PhD Chief R&D Officer Allergan MedicalResearch.com: What is the background for this data milestone?  Response: Bipolar I depression refers to the depressive episodes of bipolar I disorder, the overarching brain and behavioral disorder. People with bipolar I disorder can have manic and depressive episodes, as well as mixed episodes that feature both manic and depressive symptoms at the same time. Bipolar I depression typically lasts at least two weeks, and can be difficult to differentiate from major depression during diagnosis. Once diagnosed, treating bipolar depression can be difficult given the few therapies available to manage these symptoms of bipolar I disorder. Additionally, patients with bipolar disorder may experience shifts from depression to mania or mania to depression as well as mixed states. More treatment options are needed so that physicians can find a therapy that will treat bipolar depression effectively, while also addressing the myriad of other symptoms that patients can experience. Cariprazine is already approved for the treatment of mania and mixed episodes. With this new data, we have the potential to also treat bipolar depression, effectively addressing the full spectrum of symptoms associated with bipolar I disorder with just one medication. (more…)
Author Interviews, Diabetes, NEJM, Pediatrics, Weight Research / 05.04.2018

MedicalResearch.com Interview with: Lise Geisler Bjerregaard PhD Postdoc, PhD, M.Sc. Public Health Center for Klinisk Forskning og Sygdomsforebyggelse/ Center for Clinical Research and Disease Prevention Sektion for Klinisk Epidemiologi Frederiksberg Hospital, Frederiksberg MedicalResearch.com: What is the background for this study? What are the main findings? Response: Being overweight in childhood and early adulthood is associated with an increased risk of developing type 2 diabetes in adulthood. We wanted to know whether or not remission of overweight before early adulthood can reduce the risks of type 2 diabetes later in life. We studied the associations between different combinations of weight status in childhood, adolescence and early adulthood, and later development of type 2 diabetes. We found that men who had been overweight at 7 years of age but normalised weight by age 13 years and were normal weight as young men had similar risks of type 2 diabetes as men who were never overweight. Men who normalised weight between age 13 years and early adulthood had increased risks of type 2 diabetes, but lower risks than men who were overweight at all ages.  (more…)
Author Interviews, Infections, Science, Vaccine Studies / 05.04.2018

MedicalResearch.com Interview with: Matthieu Domenech de Cellès PhD Department of Ecology and Evolutionary Biology University of Michigan, Ann Arbor, MI, USA. Biostatistics, Biomathematics, Pharmacoepidemiology, and Infectious Diseases Unit Institut Pasteur, Inserm, University of Versailles St-Quentin-en-Yvelines, Versailles, France. MedicalResearch.com: What is the background for this study? What are the main findings?   Response: Our main motivation was to elucidate an apparent paradox: Why has the US experienced a resurgence of pertussis (whooping cough) since the mid-1970s, despite persistently high vaccine coverage? A variety of hypotheses have been proposed to explain this resurgence, but most attention has focused on the potential shortcomings of the new generation of pertussis vaccines (called acellular pertussis vaccines). However, there remains considerable uncertainty about the degree and the mechanisms of protection conferred by pertussis vaccines. Via a collaboration with the local department of public health, we used detailed surveillance data in the state of Massachusetts to test a number of hypotheses about pertussis vaccines. We found that, although pertussis vaccines are imperfect (in the sense that they do not provide lifelong, 100% protection to 100% of children vaccinated), they are still highly efficacious. Specifically, we estimated that vaccine protection wanes over time, but slowly, with about 85% of children still protected 10 years after vaccination. Despite this high vaccine efficacy, we showed that the resurgence of pertussis was, in fact, to be expected. What happens is that the introduction of routine vaccination leads to an overall reduction in transmission, not only in vaccinated children but also in the population at large. Accordingly, those who escaped vaccination as children (as a consequence of incomplete vaccine coverage or imperfect vaccine protection) increasingly age having also avoided natural infection. As a result, the number of individuals susceptible to contract pertussis gradually increases. Because such people are the “fuel” of epidemics, this sets the stage for pertussis’ resurgence, with increasing incidence among older individuals. This overall effect is called the “end-of-honeymoon” and means that resurgence is therefore a predictable consequence of incomplete vaccination with efficacious, but imperfect, vaccines. Importantly, these results show that recent trends do not necessarily reflect recent changes in the epidemiology of pertussis. Rather, they may be interpreted as a legacy of past immunization practices, with long-to-manifest effects. This is a significant shift of perspective about pertussis epidemiology.  (more…)
Author Interviews, Neurology / 05.04.2018

MedicalResearch.com Interview with: “Mother and Child” by Mary Cassatt (American, Pittsburgh, Pennsylvania 1844–1926 Le Mesnil-Théribus, Oise) via The Metropolitan Museum of Art is licensed under CC0 1.0Yi-Ya Fang NYU School of Medicine Dayu Lin, PhD Neuroscience Institute, New York University Langone School of Medicine,  Department of Psychiatry, Center for Neural Science New York, NY Response: Maternal behaviors are essential for survival of offspring across mammalian species. In rodents, mothers show several characteristic pup caring behaviors including grooming pups, crouching over pups and approaching and retrieving pups. Decades of research has been trying to understand how the neural circuit is wired to generate these elaborate maternal behaviors. Medial preoptic area (MPOA), which is located at anterior part of hypothalamus, has been indicated to be important for maternal behaviors. Many studies consistently found deficits in maternal behaviors after damaging the MPOA. To dissect the maternal circuits in the brain, we looked into the properties of the Esr1+ cells. In this study, we identify estrogen receptor α (Esr1) expressing cells in MPOA as key mediators of pup approach and retrieval. We focused on Esr1 (Esr1) expressing cells in the MPOA since estrogen has been shown to facilitate maternal behaviors, presumably through its action of estrogen sensing cells. We found that reversible inactivation of MPOA Esr1+ cells impairs maternal behaviors whereas optogenetic activation of MPOA Esr1+ cells induces immediate pup retrieval. Additionally, we found that MPOA Esr1+ cells are preferentially activated during maternal behaviors, and the cell responses changed across reproductive states. Tracing studies revealed that MPOA Esr1+ cells project strongly to ventral tegmental area (VTA), a region that has been indicated in motivation and reward. Specifically, MPOA Esr1+ cells provide strong inhibitory inputs preferentially to the GABAergic cells in the VTA, which in turn could disinhibit the dopaminergic cells.  VTA dopaminergic cells are highly activated during maternal behaviors. Altogether, our study provides new insight into the neural circuit that generates maternal behaviors. (more…)