Author Interviews, Columbia, Memory / 24.06.2017

MedicalResearch.com Interview with: Samuel Schacher, PhD and Jiangyuan Hu, PhD, Department of Neuroscience Columbia University Medical Cente New York State Psychiatric Institute New York, NY 10032, USA MedicalResearch.com: What is the background for this study? What are the main findings? Response: It is well established that learning and memory requires changes in the properties of specific neural circuits in the brain activated by the experience. The long-term storage of the memory is encoded through changes in the function of the synapses within the circuit. Synapses are sites of communication between neurons, and the changes in their function come in two varieties: increases in strength and decreases in strength. The encoding of memories typically requires some combination of these synaptic changes, synaptic plasticity, which can last a long time to contribute to long-term memory. Thus the maintenance of a memory will require the persistent change (long-term synaptic memory) in the function of specific synapses. But memories come in different flavors. In the original experiment by Pavlov, a neutral tone, which dogs ignore, came to predict the immediate appearance of a meal. After several of these pairings, the dogs would become happily excited just with the tone. The same type of conditioning could have a negative valence - the tone could proceed a shock to one of the dog's paw. Now the neutral tone would predict a negative stimulus and the dog would express fearful behavior just with the tone (associative learning). A non-associative form of memory would be the same types of stimuli but without the preceding neutral stimulus. At random times the animal will be given a meal or a shock. The behavior of the animal for some time will take on the positive or negative features of its environment - a contented versus depressed condition. Each of these forms of long-term memory would be maintained by increases in the strength of specific synapses. The questions addressed in our study published in Current Biology, based on previous work in my lab and the lab of my colleague Wayne Sossin at McGill, were: 1) Do the same molecules maintain increases in synaptic strength in the neurons of the circuit after stimuli that produce long-term classical conditioning (associative learning) and long-term sensitization (non-associative learning)? 2) If different molecules maintain the different synaptic memories, is it possible to reverse or erase the different synaptic memories by interfering with the function of the different molecules? 3) If true, can we reverse the different synaptic memories expressed in the same neuron by interfering with the function of the different molecules. (more…)
Author Interviews, Eating Disorders, Genetic Research / 24.06.2017

MedicalResearch.com Interview with: Camron D. Bryant Ph.D Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry Boston University, Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: We previously used genome-wide linkage analysis, fine mapping, gene validation, and pharmacological targeting to identify a negative regulatory role for the gene casein kinase 1-epsilon (Csnk1e) in behavioral sensitivity to drugs of abuse, including psychostimulants and opioids. Parallel human candidate genetic association studies identified an association between multiple genetic variants in CSNK1E with heroin addiction in multiple populations. Drug addiction is a multi-stage process that begins with the initial acute subjective and physiological responses that can progress to chronic administration, tolerance, and withdrawal. The recovery process begins with abstinence from drug taking but can quickly be derailed by relapse to drug taking behavior. Preclinical pharmacological studies also support a role for CSNK1E in reinstatement of opioid self-administration and relapse to alcohol drinking. Despite the evidence that disruption of Csnk1e gene and protein function can affect various behaviors associated with drug and alcohol addiction, it is unclear what stage of the addiction process these genetic and pharmacological manipulations modulate. In this study, we show that disruption of the Csnk1e gene resulted in an enhancement of the rewarding properties of the highly potent and addictive opioid, fentanyl.  Unexpectedly, we also discovered that disruption of Csnk1e also enhanced binge eating – but only in female mice. (more…)
Author Interviews, CDC, Lyme / 23.06.2017

MedicalResearch.com Interview with: Dr. Christina Nelson, MD MPH Medical epidemiologist, Division of Vector-Borne Diseases CDC  MedicalResearch.com: What is the background for this study? Response: Patients who are given a diagnosis of “chronic Lyme disease” have been offered a variety of treatments that have not been shown to be effective.  Many patients are treated with prolonged courses of antibiotics (for months or years), which have not been shown to provide substantial long-term benefit to patients.  Anecdotal reports about adverse outcomes associated with these treatments for chronic Lyme disease are common, but there have not been systematic efforts to collect data about the frequency of these events. MedicalResearch.com: Why is the diagnosis of 'Chronic Lyme Disease' so common? Response: The term “chronic Lyme disease” (CLD) has been used to describe people with different illnesses. While the term is sometimes used to describe illness in patients with Lyme disease, in many occasions it has been used to describe symptoms in people who have no evidence of a current or past infection with Lyme disease.  Because of the confusion in how the term CLD is employed, experts in this field do not support its use. (more…)
Author Interviews, OBGYNE, Testosterone / 23.06.2017

MedicalResearch.com Interview with: David M. Kristensen, PhD Assistant Professor                                                                                                         Novo Nordisk Foundation Center for Protein Research Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3A, DK-2200 Copenhagen, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have demonstrated that a reduced level of testosterone during fetal life by paracetamol means that male characteristics do not develop as they should. This also affects sex drive. In the trial, mice exposed to paracetamol at the foetal stage were simply unable to copulate in the same way as our control animals. Male programming had not been properly established during their foetal development and this could be seen long afterwards in their adult life. Moreover, the area of the brain that controls sex drive - the sexual dimorphic nucleus - had half as many neurons in the mice that had received paracetamol as the control mice. The inhibition of testosterone seem to have led to less activity in an area of the brain that is significant for male characteristics. (more…)
Author Interviews, Hearing Loss, Pediatrics / 23.06.2017

MedicalResearch.com Interview with: Peter Carew Lead author, MCRI PhD student Clinician The University of Melbourne MedicalResearch.com: What is the background for this study? Response: The age at diagnosis of a congenital hearing loss has dropped over time. This has allowed for earlier fitting of amplification (hearing aids, cochlear implants) and earlier access to education intervention programs, all intended to lessen the impact of hearing loss on development. Much research has focused on the outcomes achieved by children with severe and profound losses, but relatively little attention has been given to milder hearing losses (mild and moderate). Despite this lack of evidence, we are observing children with mild loss being fitted with hearing aids earlier than ever before. From a historical age of fitting not uncommonly at 2 years of age or older, today the largest number of children under 12 months who receive a hearing aid for the first time in Australia have a mild hearing loss in their better hearing ear. To this end, clinical practice may have jumped ahead of the evidence in terms of understanding any benefits children with mild hearing loss receive from having hearing aids earlier. (more…)
Author Interviews, Dermatology, Infections / 22.06.2017

MedicalResearch.com Interview with: Dr. Sue Cammarata, MD Chief Medical Officer Melinta Therapeutics MedicalResearch.com:   Would you explain what is meant by MRSA? Response: MRSA is methicillin-resistant Staphylococcus aureus, a type of staph bacteria that is  resistant to many antibiotics. MRSA is noted by the CDC as one of the top 18 drug-resistant bacteria threats to the United States.  (from CDC https://www.cdc.gov/drugresistance/biggest_threats.html  )  MedicalResearch.com:   Why is infection with MRSA so serious? Response:  MRSA can cause skin infections, lung infection and other issues. If left untreated, MRSA infections can become severe and cause sepsis - a life-threatening reaction to severe infection in the body - and even death.  MRSA can also cause major issues, such as bloodstream infections, pneumonia and surgical site infections in a healthcare setting, such as a hospital or nursing home. “Resistance to first-line drugs to treat infections caused by Staphlylococcus aureus—a common cause of severe infections in health facilities and the community—is widespread. People with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection.”  (quote from WHO website http://www.who.int/mediacentre/factsheets/fs194/en/  )   (more…)
Author Interviews, Infections / 22.06.2017

MedicalResearch.com Interview with: Deborah Linder, DVM, MS, DACVN Research assistant professor Cummings School of Veterinary Medicine Tufts University and Associate director of the Tufts Institute for Human-Animal Interaction MedicalResearch.com: What is the background for this study? Response: In our experience with our own therapy animal program, Tufts Paws for People, we have seen facilities and organizations put animals and people at risk by not following rigorous health and safety policies, and this certainly was confirmed by the results of our study. Lax health and safety policies typically aren’t intentional but occur as a result of enthusiasm for therapy animal programs without being aware of potential risks and what questions to ask. Also, it’s not just obvious problems that can occur, such as bites or allergies. It also can be an animal spreading infections due to diet or inadequate grooming, or unwanted stress on the animal. (more…)
Author Interviews, Dermatology, HPV, PLoS / 22.06.2017

MedicalResearch.com Interview with: Prof. Dr. med. Sigrun Smola Institute of Virology, Saarland University Homburg/Saar, Germany MedicalResearch.com: What is the background for this study? Response: Non-melanoma skin cancer (NMSC), the most common cancer in humans, is caused by UV-irradiation. The potential co-factor role of cutaneous genus beta-human papillomaviruses (beta-HPV) in skin carcinogenesis, particularly in immunosuppressed patients, has become a major field of interest. However, the underlying mechanisms were unclear. The skin has natural mechanisms providing protection against UV-induced damage. One important factor suppressing UV-induced skin carcinogenesis is the transcription factor C/EBPα belonging to the CCAAT/enhancer binding protein family. C/EBPα can induce cellular differentiation and is regarded as a tumor suppressor in various tissues. When C/EBPα expression is blocked in these tissues, tumorigenesis is enhanced. Another important factor is the microRNA-203. It has been shown to control “stemness” in normal skin by suppressing a factor called p63. In many tumors miR-203 expression is shut off releasing this “brake”. In our study we demonstrate that cutaneous beta-HPV interferes with both protective factors providing an explanation how cutaneous beta-HPV enhances the susceptibility to UV-induced carcinogenesis. Moreover, we provide evidence that these viruses regulate miR-203 via C/EBPα. We have investigated this mechanism in Epidermodysplasia verruciformis (EV) patients that serve as a human model disease for studying the biology of genus beta-HPVs. They are highly susceptible to persistent genus beta-HPV infection, such as HPV8, and have an increased risk to develop non-melanoma skin cancer at sun-exposed sites. (more…)
Author Interviews, JAMA, Pediatrics, Weight Research / 22.06.2017

MedicalResearch.com Interview with: David C. Grossman, M.D., M.P.H. US Preventive Services Task Force Chair Senior Investigator, Kaiser Permanente Washington Health Research Institute Senior Associate Medical Director, Market Strategy & Public Policy Kaiser Permanente Washington Physician, Washington Permanente Medical Group, Pediatrics MedicalResearch.com: What is the background for this recommendation? Response: Recognizing that obesity is a nation-wide health problem, affecting approximately 17% of 2-to 19-year-old children and adolescents in the U.S., the Task Force finalized its recommendation on screening for obesity in children and adolescents and the benefits and harms of weight management interventions. The Task Force found sufficient evidence to recommend screening for obesity in children and adolescents age 6 years and older and then offering or referring those who are found to be obese comprehensive, intensive behavioral interventions to manage their weight and improve overall health. MedicalResearch.com: What are the potential benefits and harms of early screening and intervention for obesity in children? Response: The Task Force found that intensive behavioral interventions for children and adolescents who have obesity can result in benefits of improvement in weight status for up to 12 months’ post-intervention. Additionally, the evidence indicated very little harm from screening and comprehensive, intensive behavioral interventions. This is due to likely minimal harms of using BMI (body mass index), the absence of reported harms of behavioral interventions, and the noninvasive nature of the programs. (more…)
Abuse and Neglect, Boehringer Ingelheim, Diabetes, Endocrinology, Lipids / 22.06.2017

MedicalResearch.com Interview with: Robert R. Henry, M.D. Professor of Medicine Member of the ODYSSEY DM Steering Committee and Director of the Center for Metabolic Research VA San Diego Healthcare System MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ODYSSEY DM-DYSLIPIDEMIA trial was a randomized, open-label, parallel-group study designed to evaluate the superiority of Praluent versus usual care in 413 patients with type 2 diabetes with mixed dyslipidemia at high cardiovascular (CV) risk, not adequately controlled with maximally tolerated dose (MTD) statins. The primary endpoint was percent change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to week 24. In ODYSSEY DM-DYSLIPIDEMIA, Praluent 75 mg was added to MTD statins, with dose adjusted at week 12 to 150 mg every two weeks if their non-HDL-C was greater than or equal to 100 mg/dL at week 8. Approximately 64 percent of patients reached their lipid goals with the Praluent 75 mg dose. Results from the ODYSSEY DM-DYSLIPIDEMIA study found that Praluent added to MTD statins showed significant reduction in non-HDL-C and other lipid parameters compared to those on usual care. Praluent was superior to usual care in lowering non-HDL-C (37.3 percent and 4.7 percent, for the usual care arm). The mean difference between the two treatment arms was -32.5 percent (p<0.0001). Praluent in combination with MTD statins reduced LDL-C by 43 percent from baseline compared to a 0.3 percent increase for usual care (p<0.0001). Treatment with Praluent also improved the overall lipid profile. There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Furthermore, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 22.06.2017

MedicalResearch.com Interview with: Mikko Hiltunen, PhD Professor of Tissue and Cell Biology University of Eastern Finland School of Medicine, Institute of Biomedicine Kuopio,  Finland  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  We wanted to assess among the population-based METSIM (METabolic Syndrome In Men) cohort whether protective variant in APP gene (APP A673T) affects the beta-amyloid levels in plasma. The rationale behind this was that previous genetic studies have discovered that the APP A673T variant decreases the risk of having Alzheimer’s disease (AD). However, the protective functional outcome measures related to this variant were lacking and thus we anticipated that the elucidation of plasma samples in terms of beta-amyloid levels would provide the much needed link between APP A673T variant and potential protective functions. (more…)
Author Interviews, Flu - Influenza, NEJM, Vaccine Studies / 22.06.2017

MedicalResearch.com Interview with: Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT MedicalResearch.com: What is the background for this study? What are the main findings? Response: The first and only recombinant protein influenza vaccine (RIV, Flublok) was approved in 2013 as a trivalent formulation for use in adults 18 years of age and older. This approval was based on demonstration of clinical efficacy (full approval) in adults 18-49 years of age and accelerated approval was granted for adults 50 years of age and older. Two clinical trials were conducted in 2014-2015 with RIV4 (Flublok Quadrivalent), of which the trial reported in the current NEJM is one. These studies supported full approval of Flublok in adults 50 years of age and older and approval of Flublok Quadrivalent in all adults 18 years of age and older. The second trial of immunogenicity of Flublok Quadrivalent in adults 18-49 years of age will be the subject of another publication in the near future. The main findings of the current trial are well summarized in the Conclusion of the Abstract: “RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness in older adults.” Additionally, the recombinant vaccine (RIV4, Flublok Quadrivalent) demonstrated significantly less injection site pain and tenderness following vaccination. Based on the characteristics of the study participants, one can conclude that RIV4 is safe and effective in most individuals with underlying chronic diseases (more…)
Author Interviews, Cancer Research, Genetic Research / 22.06.2017

MedicalResearch.com Interview with: Antonis Antoniou PhD Reader in Cancer Risk Prediction Academic Course Director MPhil in Epidemiology Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Strangeways Research Laboratory Cambridge University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: Several studies demonstrated that women with genetic faults in the BRCA1 and BRCA2 genes are at increased risk of developing breast and ovarian cancer. Having accurate age-specific cancer risk estimates for women with mutations is essential for their optimal clinical management. Most studies to date that estimated cancer risks for BRCA1 and BRCA2 mutation carriers have been "retrospective", in other words they look at what happened in the past. Estimates from such studies are prone to biases because they rely on the experience of women who have already developed cancer and on self-reported cancer family history information on relatives - which may have inaccuracies. The ideal epidemiological study design for estimating cancer risks are prospective studies.  In prospective studies, healthy women with genetic faults are followed over time and overcome these potential biases. However, to date, published  prospective studies have been very small. In the present study we used data from a prospective cohort of women with BRCA1 and BRCA2 mutations who were recruited from 1997 to 2011 and were followed over time. The study included almost 10,000 women who were included in the analyses, and was made possible through collaborations between scientists from Europe, North America and Australia.  The prospective study design explains why it has taken 20 years of hard work to get these results. Most importantly, it took an enormous long-term contribution and commitment from the women themselves to allow the scientists to be able to assemble this dataset. Here, we were able to estimate more precisely the breast and ovarian cancer risks for women with faults in BRCA1 and BRCA2.  These risk estimates will provide more confidence in the counseling and clinical management of women with faults in the BRCA1 and BRCA2  genes. A novel finding in this study is that breast cancer risk for women with faults in BRCA1 and BRCA2  increases rapidly at a young age then remains at a constant high level for the rest of their lives. It peaks in the 40’s for BRCA1 mutation carriers and in the 50’s for BRCA2 carriers, but  carriers of mutations in both genes  are at about the same high risk in later life. This is important information to inform the clinical management of older mutation carriers. This study also shows clearly that for women with a mutation, there are other factors that are important in modifying the breast cancer risk. The study has demonstrated that the extent of the woman’ family history of cancer and the exact place on the gene where her mutation is located are very important in determining the actual risk. (more…)
Author Interviews, Brigham & Women's - Harvard, Dermatology, Melanoma / 22.06.2017

MedicalResearch.com Interview with: David E. Fisher MD, PhD Edward Wigglesworth Professor & Chairman Dept of Dermatology Director, Melanoma Program MGH Cancer Center Director, Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study grew from an interest to mimic the dark pigmentation patterns in human skin which are known from epidemiology to be associated with low skin cancer risk. In the current work, a molecular inhibitor of the SIK enzyme was used to block the inhibitory action of SIK relative to melanin synthesis. The result was stimulation of dark pigmentation within human skin. (more…)
Author Interviews, NEJM, Stroke / 22.06.2017

MedicalResearch.com Interview with: Craig Anderson | MD PhD FRACP Executive Director Professor of Neurology and Epidemiology, Faculty of Medicine, UNSW Sydney Neurologist, Neurology Department, Royal Prince Alfred Hospital The George Institute for Global Health at Peking University Health Science Center Haidian District | Beijing, 100088 P.R. China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Preliminary small studies indicate that lying flat increases blood flow and oxygenation to the brain.  Thus, patients with acute ischemic stroke may benefit from lying flat in bed.  Conversely, sitting up in bed, with the head elevated to at least 30 degrees, may reduce swelling in the brain for patients who have large ischemic or hemorrhagic forms of stroke.  The optimal head position to produce the best outcome from acute stroke, and avoid potential risks, such as aspiration pneumonia, is unknown.  We undertook a large scale multicentre randomized controlled trial where 114 hospitals were randomised to sequentially apply lying flat or sitting up head positioning as a policy of care to a consecutive series of patients, that overall totalled over 11000 patients, presenting with acute stroke.  The study showed there was no difference in the chance of good physical recovery for patients between the two head positions but also that there were no excessive harms for either. In other words, head positioning alone didn’t produce any benefits or harms in patients with acute stroke (more…)
Author Interviews, Blood Pressure - Hypertension, Brigham & Women's - Harvard, Neurological Disorders, Stroke / 22.06.2017

MedicalResearch.com Interview with: Andrea Morotti, M.D. Research Fellow in Neurology Massachusetts General Hospital Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: The CT angiography (CTA) spot sign is a validated marker of Intracerebral Hemorrhage (ICH) expansion and may identify those subjects more likely to benefit from intensive blood pressure reduction. We observed that less than 20% of ICH patients received a CTA as part of their diagnostic workup in a large, international randomized clinical trial. The performance of the spot sign in predicting ICH growth was suboptimal compared with what was reported in previous studies. Intensive blood pressure reduction did not improve functional outcome in spot sign positive patients. (more…)
Author Interviews, Genetic Research, Nature, Scripps / 21.06.2017

MedicalResearch.com Interview with: Michael Farzan PhD Co-chair and Professor Department of Immunology and Microbiology Florida Campus The Scripps Research Institute Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Response: CRISPR is system for immune protection of bacteria.  It has now been widely adopted for use in editing mammalian cells.  The most commonly used CRISPR effector protein is Cas9.  Cas9 binds a guide RNA to recognize a DNA target, for example an incoming virus infecting a bacterium, or a gene in a human chromosome.  In bacteria, Cas9 requires a second protein to clear the guide RNA from a longer "CRISPR array", basically a string of guide RNAs. We have been studying a CRISPR effector protein related to Cas9 called Cpf1.  In bacteria it was know that, unlike Cas9, Cpf1 could cleave a CRISPR array by itself, without assistance from a second protein.  We knew that if it could do the same thing in human cells, it would help to simplify a number of gene-editing applications.  We were able to show that Cas9 could indeed excise multiple guide RNAs from a single message RNA in human cells.  We further showed that this approach was more efficient than the previous ways that guide RNAs were generated for gene editing, even more so when multiple guide RNAs were needed. (more…)
Author Interviews, Endocrinology, Genetic Research / 21.06.2017

MedicalResearch.com Interview with: Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda MedicalResearch.com: What is the background for this study? Response: The pituitary and adrenal glands operate on a kind of feedback loop. In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol. Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease. (more…)
Author Interviews / 21.06.2017

MedicalResearch.com Interview with: Stephanie Ries, PhD Assistant Professor School of Speech, Language, and Hearing Sciences Center for Clinical and Cognitive Neuroscience San Diego State University Director of the Laboratory for the Brain Dynamics of Language San Diego, CA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our study is about how we retrieve words when we speak. We routinely do this rather effortlessly. Healthy adults can produce about 2 to 3 words per second selected among over 50,000 words in our mental dictionary. However, the neural mechanisms allowing us to do so are not well known. This process relies on two complementary mechanisms: the activation of words, and the selection of words. Our study shows that these mechanisms co-occur in time: meaning one does not end when the other starts, and in space: some brain regions, such as the posterior inferior temporal gyrus, support both mechanisms sequentially. We were able to get an unprecedented look into the neural underpinnings of this process by studying brain activity recorded directly at the cortical surface in patients undergoing intracranial EEG monitoring for intractable epilepsy. While these patients were monitored, we asked them if they would agree to participate in our study, which consisted in naming pictures for about 10 minutes. Most of the time, they agreed. We were then able to analyze the intracranial electrical signal in relation to the pictures that were named. Such occasions are extremely rare. (more…)
Author Interviews, Genetic Research, Lifestyle & Health / 21.06.2017

MedicalResearch.com Interview with: Ivana Buric Brain, Belief, and Behaviour Lab Centre for Psychology, Behaviour, and Achievement, Faculty of Health and Life Sciences Coventry University, Coventry, United Kingdom Donders Institute for Brain, Cognition and Behaviour Radboud University, Nijmegen, Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Genes that we inherited can change their activity - the​y can be active and produce proteins, but they can also stop producing proteins and remain silent. We are now beginning to understand what aspects of our environment affect the activity of which genes. In this study, we analysed all the existing studies that examined the effects of mind-body interventions on the expression of our genes and found that mind-body techniques reduce the activity of genes that produce inflammatory proteins. This pattern was found in all studies despite the fact that they vary in the amount of physical activity: Tai Chi, yoga, breathing techniques and different types of meditation. We believe that this effect is observed due to reduced stress. When we experience something stressful, the brain regions associated with pain get activated and send that signal further to sypmathetic nervous system that produces epinephrine and norepinefrine, and activates nuclear factor kappa B - a molecule that travels to and activated the genes that produce inflammatory proteins. When we do yoga or meditation, we learn to perceive situations differently and consequently experience less stress, which then prevents the production of inflammatory proteins. (more…)
Author Interviews, Brigham & Women's - Harvard, Education, PLoS, Sleep Disorders / 21.06.2017

MedicalResearch.com Interview with: Dr. Dorothee Fischer Department of Environmental Health Harvard T.H. Chan School of Public Health, Boston, Massachusetts Center for Injury Epidemiology, Liberty Mutual Research Institute for Safety Hopkinton, Massachusetts, MedicalResearch.com: What is the background for this study? What are the main findings? Response: Chronotypes are a result of how the circadian clock embeds itself into the 24h light-dark cycle, producing earlier and later individuals ("larks and owls") with regards to rhythms in physiology, cognition and behavior, including sleep. It can be beneficial for health and safety to sync forced wake times (work, school) with individual chronotypes, thereby reducing the misalignment between sleep, circadian rhythms and external demands. To better inform potential interventions such as tailored work schedules, more information is needed about the prevalence of different chronotypes and how chronotype differs by age and sex. To the best of our knowledge, this is the first large-scale and nationally representative study of chronotypes in the US. (more…)
Author Interviews, Lancet, Rheumatology, UT Southwestern / 20.06.2017

MedicalResearch.com Interview with: Roy Fleischmann, MD MACR Medical Director Metroplex Clinical Research Center Clinical Professor of Medicine University of Texas Southwestern Medical Center Dallas, TX 75231 MedicalResearch.com: What is the background for this study? What are the main findings? Response: In the phase 3 studies of tofacitinib, it was noted that the clinical responses to tofacitinib monotherapy were higher than the responses to tofaciotinib plus MTX and that tofacitinib plus methotrexate had numerically higher clinical responses compared to adalimumab plus methotrexate. This study was a non-inferiority design which compared tofacitinib monotherapy to tofacitinib + MTX and to adalimumab +MTX and tofacitinib monotherapy to tofacitinib +MTX in MTX incomplete responders. It was found that tofacitinib + MTX is non-inferior to adalimumab + MTX (and vice versa) and neither was superior to the other. The results of tofacitinib to either combination was non-conclusive showing neither non-inferiority or inferiority, but suggesting that either combination will be effective in more patients in a group of patients. (more…)
Author Interviews, Pain Research, Rheumatology, Sleep Disorders / 20.06.2017

MedicalResearch.com Interview with: Atul A. Deodhar, MD, MRCP, FACP, FACR Professor of Medicine Medical Director, Rheumatology Clinics Medical Director, Immunology Infusion Center Oregon Health & Science University  MedicalResearch.com: What is the background for this study? Response: The GO-ALIVE study (CNTO148AKS3001) is a multicenter, randomized, double-blind, placebo-controlled study of golimumab, an anti-TNFα monoclonal antibody, administered intravenously (IV), in adult patients with active ankylosing spondylitis (AS). The primary objective is to evaluate the efficacy of golimumab 2 mg/kg in patients with active AS by assessing the reduction in signs and symptoms of AS. The secondary objectives include assessing efficacy related to improving physical function, range of motion, health-related quality of life, and other health outcomes. A total of 208 patients who had a diagnosis of definite  ankylosing spondylitis (per modified New York criteria) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4, total back pain visual analogue scale (VAS) ≥4, and CRP ≥0.3 mg/dL were randomized.  Patients were treated with IV golimumab (n=105) at Weeks 0, 4, and every 8 weeks through Week 52 or placebo (n=103) at Weeks 0, 4, and 12, with crossover to IV golimumab at Week 16 and through Week 52. (more…)
Author Interviews, Global Health, Infections, Pediatrics / 19.06.2017

MedicalResearch.com Interview with: Aleksandra Jakubowski, MPH PhD candidate Department of Health Policy and Management Gillings School of Global Public Health University of North Carolina at Chapel Hill MedicalResearch.com: What is the background for this study? Response: The US President’s Malaria Initiative (PMI) provides approximately $600 million annually to fund implementation of key evidence-based malaria prevention and treatment interventions, including insecticide treated nets (ITNs), artemisinin-based combination therapy (ACT), and indoor residual spraying (IRS) to populations in 19 recipient countries in sub-Saharan Africa (SSA). Despite this considerable investment, no study to date has evaluated the impact of PMI on population health outcomes. Previous evaluations have noted improved health outcomes in PMI countries, but comparison groups are needed to establish whether these changes were beyond the declining trends in mortality observed in the rest of the region. Our study sought to generate objective evidence for policy makers about the role this US-funded malaria aid program may have played in curbing child mortality in SSA. We used a quasi-experimental design known as difference-in-differences to compare trends in health outcomes in PMI-recipient vs. PMI non-recipient countries. We analyzed publicly-available data from 32 countries in SSA spanning a period that included about ten years before and after the introduction of the program. (more…)
Author Interviews, Endocrinology, Genetic Research, NYU / 19.06.2017

MedicalResearch.com Interview with: Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda  MedicalResearch.com: What is the background for this study? Response: The pituitary and adrenal glands operate on a kind of feedback loop.  In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol.  Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease. (more…)
Author Interviews, Biomarkers, Colon Cancer, JAMA / 19.06.2017

MedicalResearch.com Interview with: Anastasia Katsoula, MD MSc Aristotle University of Thessaloniki Greece  MedicalResearch.com: What is the background for this study? Response: Early detection of colorectal cancer (CRC) has proven to be effective in reduction of cancer-related mortality. Fecal immunochemical testing (FIT) has been recently advocated for population-based screening for CRC in average-risk individuals due to its high accuracy and potential for adherence, based on results from previous systematic reviews and meta-analyses in average-risk populations. However, the potential role of FIT for screening of subjects at increased risk for CRC has not yet been elucidated, hence colonoscopy is currently the only recommended screening option for subjects at increased risk of CRC. We performed a systematic review and meta-analysis to explore the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in patientswith personal or familial history of CRC, using colonoscopy as the reference standard. (more…)
Addiction, Author Interviews, JAMA, Opiods, Pediatrics / 19.06.2017

MedicalResearch.com Interview with: Scott Hadland, MD, MPH, MS Youth Addiction Specialist Assistant Professor of Pediatrics Boston University School of Medicine Director, Urban Health and Advocacy Track, Boston Children’s Hospital and Boston Medical Center Associate Program Director, Boston Combined Residency Program in Pediatrics, Boston Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Almost no data have been available on this topic to date.  A recent study showed that teens in subspecialty treatment for opioid addiction were significantly less likely than adults to receive a medication.  Our study was the first to comprehensively look across the health care system, including looking at adolescents and young adults diagnosed with opioid use disorder in outpatient clinics, emergency departments, and inpatient hospitals. We had three important findings.  First, looking at a large sample of 9.7 million adolescents and young adults between the age of 13 and 25 years, we found that the number of youth diagnosed with opioid use disorder increased six-fold from 2001 to 2014.  This is perhaps not surprising given the national opioid crisis we know to be occurring. Second, we found that only a minority of youth (1 in 4) received buprenorphine or naltrexone, the two medications available for opioid addiction that can be prescribed in usual medical settings.  These two medications are evidence-based and their use is recommended by the American Academy of Pediatrics.  Utilizing them is critical to ensure that we offer effective treatment early in the life course of addiction, which can help prevent the long-term harms of addiction. Third, we found significant differences in who received medications.  Whereas approximately 1 in 3 young adults in our study received a medication, only 1 in 10 of the 16- and 17-year-olds we studied received one, and among adolescents under 15 years of age, 1 in 67 received a medication.  Females were less likely than males to receive medications, as were black youth and Hispanic youth relative to white youth. (more…)
Author Interviews, Medical Imaging, Prostate Cancer / 19.06.2017

MedicalResearch.com Interview with: Dr. Susanne Lütje Ärztlicher Dienst Universitätsklinikum Essen (AöR) Klinik für Nuklearmedizin Essen Germany MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer (PCa) is the most common cancer in men and accounts for a significant amount of morbidity and mortality. At present, the curative treatment option of choice for localized stages of PCa is radical prostatectomy, which may include extended lymph node dissection. Unfortunately, surgical procedures can be accompanied by complications such as urinary incontinence. Most importantly, small tumor deposits may not be seen by the surgeon during surgery and could ultimately lead to disease recurrence. To overcome these issues, new and innovative treatments are needed. The prostate-specific membrane antigen (PSMA) is a surface protein that is overexpressed in prostate cancer and can be used as a target to guide new therapies. Photodynamic therapy (PDT) is an ablative procedure in which tumor cells can be destroyed effectively by irradiation of light of a specific wavelength, which activates previously administered photosensitizers. The photosensitizers can respond by emitting fluorescence or emitting oxygen radicals which can cause cellular damage. Coupling the photosensitizer to an agent that targets PSMA on the tumor surface offers the possibility to selectively and effectively destroy prostate tumor remnants and micrometastases, while surrounding healthy tissues remain unaffected. In our study, the PSMA targeting antibody D2B was coupled to the photosensitizer IRDye700DX and radiolabeled with 111In. In a mouse model, this multi-modality agent was used to preoperatively visualize tumor lesions with SPECT/CT to allow rough localization of the tumors. During surgery, the fluorescent signal originating from the photosensitizer facilitates visualization of tumors and residual tumor tissue, so the surgeon can be guided towards accurate resection of the entire tumors and metastases. In addition, the PSMA-targeted PDT can be applied to destroy small tumor deposits in cases where close proximity of the tumors. (more…)
AstraZeneca, Author Interviews, Boehringer Ingelheim, Diabetes, Eli Lilly, J&J-Janssen, Lipids, Merck / 19.06.2017

MedicalResearch.com Interview with: Lawrence Leiter, M.D. MDCM, FRCPC, FACP FACE, FAHA Chair of the ODYSSEY DM Steering Committee and Director of the Lipid Clinic at the Li Ka Shing Knowledge Institute St. Michael’s Hospital University of Toronto, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ODYSSEY DM-INSULIN trial was a randomized, double-blind, placebo-controlled, multicenter study that evaluated alirocumab (Praluent) in 517 patients with insulin treated type 1 and type 2 diabetes with high cardiovascular (CV) risk and hypercholesterolemia despite maximally tolerated dose (MTD) statins. The primary endpoint was percent change in calculated LDL-C from baseline to week 24. Alirocumab 75 mg every two weeks was added to MTD statins, with the dose increased at week 12 to 150 mg every two weeks if the LDL-C at week 8 was greater than or equal to 70 mg/dL. In fact, only about 20% of the alirocumab treated participants required the higher dose. Results of the type 2 diabetes study population (n=441) showed that the addition of alirocumab to MTD statin therapy, reduced LDL-C by 48.2 percent from baseline compared to a 0.8 percent increase for placebo. The mean difference between the two treatment arms was -49 percent (p<0.0001). Treatment with alirocumab also improved the overall lipid profile. Furthermore, no new safety issues were identified. There is a large unmet need for improving cholesterol lowering in patients with diabetes. Despite current standard of care, nearly 70 percent of people age 65 or older with diabetes die from some form of heart disease; and 16 percent die of stroke. Additionally, in spite of current standard of care, many people with diabetes continue to have persistent lipid abnormalities resulting in high residual CV risk. (more…)
Author Interviews, Nutrition, OBGYNE, Pediatrics, Weight Research / 19.06.2017

MedicalResearch.com Interview with: Cuilin Zhang MD, PhD Senior Investigator, Epidemiology Branch Division of Intramural Population Health Research NICHD/National Institutes of Health Bethesda, MD 20817  MedicalResearch.com: What is the background for this study? Response: Refined grains with a high glycemic index and reduced fiber and nutrient content have been linked to increased adiposity and higher risk of metabolic syndrome among adults. Despite these differences and the growing body of literature on the link between maternal diet/nutrition during pregnancy and subsequent offspring health consequences throughout the lifespan, little is known about the intergenerational impact of refined-grain intake during pregnancy on long-term cardio-metabolic outcomes in the offspring. (more…)