Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Pediatrics / 19.07.2017

MedicalResearch.com Interview with: Holly Gooding, MD, MSc Assistant Professor of Medicine and Pediatrics Harvard Medical School Division of Adolescent/Young Adult Medicine Boston Children's Hospital Division of General Internal Medicine Brigham and Women's Hospital Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dr Stephanie Chiuve and colleagues at the Harvard TH Chan School of Public Health developed the Healthy Heart Score to predict the risk of heart disease in older adults based on lifestyle factors measured in middle age. We have known for some time that the precursor to heart disease – known as atherosclerosis – actually starts in childhood and adolescence. We calculated the Healthy Heart Score for young adults ages 18-30 years old and found it works in this age group as well. (more…)
Aging, Author Interviews, Brigham & Women's - Harvard, JAMA, Weight Research / 19.07.2017

MedicalResearch.com Interview with: Yan Zheng Research Fellow, Department of Nutrition Harvard T.H. Chan School of Public HealthYan Zheng Research Fellow, Department of Nutrition Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Most people gain weight cumulatively during young and middle adulthood. Because the amount of weight gain per year may be relatively small, it may go unnoticed by individuals and their doctors—but the cumulative weight gain during adulthood may eventually lead to obesity over time. Compared to studies of attained body weight or BMI, the investigation of weight change may better capture the effect of excess body fat because it factors in individual differences in frame size and lean mass. (more…)
Author Interviews, Baylor College of Medicine Houston, Biomarkers, Brain Cancer - Brain Tumors, Cancer Research, PNAS / 19.07.2017

MedicalResearch.com Interview with: Chonghui Cheng, M.D., Ph.D. Associate Professor Department of Molecular & Human Genetics Lester & Sue Smith Breast Center Baylor College of Medicine Houston, TX77030 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure disease. In the case of glioblastoma multiforme, the deadliest type of brain cancer, abnormal EGFR signaling is frequently observed. Treatment with the EGFR inhibitor erlotinib attempts to kill cancer cells. However, the clinical benefit of treatment with this and other EGFR inhibitors has been limited by the development of drug resistance. Scientists at Baylor College of Medicine discovered that the molecule CD44s seems to give cancer cells a survival advantage. Eliminating this advantage by reducing the amount of CD44s resulted in cancer cells being more sensitive to the deadly effects of the drug erlotinib. (more…)
Addiction, Alcohol, Author Interviews, NIH / 17.07.2017

MedicalResearch.com Interview with: Lorenzo Leggio, M.D., Ph.D. Chief of the Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, a NIAAA intramural laboratory MedicalResearch.com: What is the background for this study? MedicalResearch.com: What is the background for this study? What are the main findings? Response: Aldosterone is an important hormone involved in the control of blood pressure and electrolytes via its mineralcorticoid receptor (MR). In addition to its roles in the periphery in our body, aldosterone also acts on the brain where the MR is particularly present in regions like the amygdala. The amygdala plays an important role in stress, anxiety and excessive alcohol drinking. Back in 2008, we conducted a small pilot study where we found that alcohol-dependent patients with higher blood aldosterone concentrations have higher alcohol craving. (more…)
Author Interviews, Dental Research, Microbiome, University of Pennsylvania / 14.07.2017

MedicalResearch.com Interview with: Dana T. Graves DDS Department of Periodontics School of Dental Medicine University of Pennsylvania Philadelphia, PA MedicalResearch.com: What is the background for this study? What are the main findings? Response: It was previously thought that diabetes did not have a significant effect on oral bacteria. We found that diabetes caused a change in the composition of the oral bacteria. This change caused resulted in a bacterial composition that was more pathogenic and stimulated more inflammation in the gums and greater loss of bone around the teeth. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology, HIV, JAMA, Kaiser Permanente, Merck / 13.07.2017

MedicalResearch.com Interview with: Maryam M. Asgari, MD, MPH Department of Dermatology Massachusetts General Hospital, Department of Population Medicine Harvard Medical School, Boston, Massachusetts Division of Research, Kaiser Permanente Northern California, Oakland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Nonmelanoma skin cancer – defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) – is a common malignant condition, affecting more than 2 million Americans every year. BCCs are more common than SCCs among individuals with healthy immune systems, while SCCs are more predominate than BCCs among people who are immunocompromised. We examined how laboratory markers used to evaluate HIV disease progression may be associated with subsequent nonmelanoma skin cancer risk in white patients previously diagnosed with at least one such cancer from 1996 to 2008.  We measured CD4 count, viral load and subsequent nonmelanoma skin cancer. The study included 455 participants with HIV and 1,952 without HIV. All were members of the Kaiser Permanente Northern California health care plan. (more…)
Author Interviews, Brigham & Women's - Harvard, Lifestyle & Health, NEJM, Nutrition / 13.07.2017

MedicalResearch.com Interview with: Mercedes Sotos Prieto PhD Research Fellow Department of Nutrition Harvard T. H. Chan School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous research have found that adherence to the 2010 Alternate Heathy Eating Index, the Mediterranean Diet pattern, and DASH pattern is associated with health benefits, but none of those studies have examined dynamic changes in diet quality over time and subsequent risk of mortality. This is the first study to demonstrate that improvement in these three diet scores over time is associated with reduced risk of total and cardiovascular mortality. In contrast, worsening diet quality over 12-years was associated with 6%-12% increased mortality. In addition, not only improvement in diet quality but maintaining a high adherence to any of the three dietary patterns over 12 years was significantly associated with 9%-14% lower total mortality. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Dermatology, JAMA / 07.07.2017

MedicalResearch.com Interview with: Dr. Chrysalyne D. Schmults, MD, MSCE Associate Professor of Dermatology, Harvard Medical School Director, Mohs and Dermatologic Surgery Center and Mr. Pritesh S. Karia, MPH Department of Epidemiology Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland Department of Dermatology Brigham and Women's Faulkner Hospital Harvard Medical School, Boston, Massachusetts Jamaica Plain, MA 02130-3446  MedicalResearch.com: What is the background for this study? Response: Perineural nerve invasion (PNI) is a well-recognized risk factor for poor prognosis in patients with cutaneous squamous cell carcinoma (CSCC). Most cases of CSCC with PNI are identified on histologic examination at the time of surgery and the patient has no clinical symptoms or radiologic evidence of PNI. These cases are classified as incidental PNI (IPNI). However, some patients with PNI present with clinical symptoms and/or radiologic evidence of PNI. These cases are classified as clinical PNI (CPNI). A few studies have shown differences in disease-related outcomes between CSCC patients with IPNI and CPNI but consensus regarding adjuvant treatment and detailed guidelines on follow-up schedules have not yet materialized. (more…)
Author Interviews, Genetic Research, Ophthalmology, University Texas / 07.07.2017

MedicalResearch.com Interview with: Stephen P. Daiger, PhD Professor, Human Genetics Center Thomas Stull Matney, Ph.D. Professor in Environmental and Genetic Sciences Mary Farish Johnston Distinguished Chair in Ophthalmology The University of Texas Health Science Center at Houston   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Thanks for your questions about our research.  My research group and I have a long-term interest in finding genes and mutations causing inherited retinal diseases.  Our main focus is on retinitis pigmentosa (RP) and, more specifically, the autosomal dominant form of RP. Inherited retinal diseases are progressive, degenerative diseases of the retina.  Onset can be very early in life, even at birth, or much later in life.  As the degeneration develops an affected person may first experienced limited loss of vision, progressing to severe loss of vision, ending, in many cases, in legal or complete blindness.  About 300,000 Americans are affected by inherited retinal disease and 50% of these have RP.  RP, like most hereditary conditions, can be inherited in an autosomal dominant, autosomal recessive or X-linked fashion. One of the surprising, and in some sense, disturbing findings in studying  retinitis pigmentosa is that mutations in many different genes can cause this disease.  We now know that mutations in more than 80 genes can cause RP and thousands of different mutations have been found in these genes.  With next-generations sequencing it is possible to find the cause of RP in from 50% to 80% of cases, depending on the underlying mode of inheritance.For example, in our research we can find the disease-causing mutation in about 75% of families with autosomal dominant RP.  Needless to say, a primary aim of our research is to find the cause in the remaining 25%. In looking for the cause of retinitis pigmentosa in the remaining 25%, that is, those in whom mutations were not detected by earlier methods, we found a potential dominant-acting mutation in the arrestin-1 gene (gene symbol “SAG”) using whole-genome sequencing.  Molecular modeling suggests this mutation is damaging.  This was unexpected because previously-reported mutations in this gene were associated with Oguchi disease, a recessive retinal disease with symptoms distinct from RP.  On further testing our cohort of patients with autosomal dominant RP, we found this mutation in nearly 4% of families.  Even more surprisingly, when we looked closely at the affected families, and worked with our collaborators to test other patients, we discovered that all of the families with the dominant-acting SAG mutation -- 12 total -- were of Hispanic origin.  By interviewing informative family members we learned that these families have their roots in the Southwestern United States.  Historically, the mutation may have arisen hundreds of years ago, consistent with genetic variation tracking with the mutation. (more…)
Author Interviews, Cancer Research, Dermatology, JAMA, University of Pennsylvania / 06.07.2017

MedicalResearch.com Interview with: Mackenzie R. Wehner, MD, MPhil Department of Dermatology University of Pennsylvania Philadelphia, PA MedicalResearch.com: What is the background for this study? Response: For some diseases, we have national registries, in which information about every person with that disease is entered for research purposes. For other diseases, unfortunately, we do not have such registries. There are growing opportunities to use information like internet searches to better understand behaviors and diseases, however. Our study was a proof-of-concept: we aimed to find out whether internet searches for diseases correlated with known incidence (how many people are diagnosed with the disease) and mortality (how many people die of the disease) rates. E.g. does the number of people who searched 'lung cancer' online correlate with the number of people who we know were diagnosed with or who died of lung cancer during that same time period? This is important to know if researchers in the future want to use internet search data for diseases where we lack registry information. (more…)
Author Interviews, Electronic Records, JAMA, UCSF / 05.07.2017

MedicalResearch.com Interview with: Neda Ratanawongsa, MD, MPH Associate Chief Health Informatics Officer for Ambulatory Services, San Francisco Health Network Associate Professor, Division of General Internal Medicine UCSF Center for Vulnerable Populations Physician, Richard H. Fine People's Clinic (RHPC) Zuckerberg San Francisco General Hospital San Francisco, CA 94110 MedicalResearch.com: What is the background for this study? What are the main findings? Response: U.S. federal incentives allowed many safety net healthcare systems to afford fully functional electronic health record systems (EHRs). Although EHRs can help clinicians provide care to vulnerable populations, clinicians may struggle with managing the EHR workload, particularly in resource-limited settings. In addition, clinicians’ use of EHRs during clinic visits may affect how they communicate with patients. There are two forms of EHR use during clinic visits.  Clinicians can multitask, for example, by ordering laboratory tests while chatting with a patient about baseball.  However, like distracted driving, using EHRs while talking with increases risks – in this case, the risk of errors in patient-provider communication or in the EHR task. Alternatively, clinicians can use EHRs in complete silence, which may be appropriate for high-risk tasks like prescribing insulin. However, silence during visits has been associated with lower patient satisfaction and less patient-centered communication. So we studied how primary and specialty care clinicians used EHRs during visits with English- and Spanish-speaking patients in a safety net system with an EHR certified for Centers for Medicare & Medicaid Services meaningful use incentive programs. We found that multitasking EHR use was more common than silent EHR use (median of 30.5% vs. 4.6% of visit time). Focused patient-clinician talk comprised one-third of visit time. We also examined the transitions into and out of silent EHR use. Sometimes clinicians explicitly stated a need to focus on the EHR, but at times, clinicians drifted into silence without warning. Patients played a role in breaking silent EHR use, either by introducing small talk or by bringing up their health concerns. (more…)
Author Interviews, Education, NYU, Sexual Health / 05.07.2017

MedicalResearch.com Interview with: Richard E. Greene, MD, FACP Medical Director, Bellevue Adult Primary Care Center Assistant Professor, NYU School of Medicine Associate Program Director, Primary Care Residency Program Director, Gender and Health Education, Office of Diversity Affairs, NYU School of Medicine, OUTList Medical Director, CHIBPS, The Center for Health, Identity, Behavior and Prevention Studies VP of Membership and Development, GLMA-Health Professionals Advancing LGBT Equality  MedicalResearch.com: What is the background for this study? Response: Transgender individuals face complex health disparities and have historically been mistreated and even denied care in medical settings. As a provider in New York City, I saw how this affected my trans patients, resulting in mistrust of the health care system, resulting in negative health outcomes. This sparked my interest in improving medical education to serve the needs of trans patients. It’s important to teach medical students and residents that they are not just treating a set of symptoms, they are working with a individuals with complex lived experiences who deserve compassionate care. I found with traditional didactic methods, like lectures, learners smiled and nodded in agreement, but when faced with a patient who was transgender, they would stammer and feel uncomfortable with aspects of the cases that were specific to transgender patients, from pronouns to hormones. Residents should be prepared to treat transgender patients not only with dignity, but also in medically appropriate ways. Without exposure to the transgender community, it’s difficult for providers to decipher their trans patients’ health care needs and contextualize them within a care plan. In order to provide a low stakes environment for residents to practice these skills, we developed an OSCE focused on a transgender woman with health care needs specific to her transition. The goal of the case was to discuss the patient’s medical concerns while also taking into consideration her goals around her hormone therapy and surgical interests. (more…)
Abuse and Neglect, Hearing Loss, JAMA, Johns Hopkins / 04.07.2017

MedicalResearch.com Interview with: Nicholas S. Reed, AuD Instructor | Department of Otolaryngology-Head/Neck Surgery PhD Candidate  | Graduate Training Program in Clinical Investigation Center on Aging and Health Johns Hopkins University School of Medicine Johns Hopkins University Bloomberg School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: Hearing Aids are medical devices regulated by the FDA which must be purchased through a licensed individual while personal sound amplification products (PSAPs) are essentially unregulated devices some of which can manipulate and increase sound similar to a hearing aid but cannot market themselves are devices for hearing loss. PSAPs can be purchased online or in the back of a store and are generally less expensive than hearing aids. We aimed to explore a select group of PSAPs to see if they helped someone with mild to moderate hearing loss improve speech understanding (i.e. ability to repeat back sentences) in the presence of mild background noise (think a lunch crowd at a restaurant) as well as a hearing aid. We selected four PSAP devices that were technologically strong (i.e. meet many standards a hearing aid might be asked to meet) and one PSAP that was technologically fairly poor (i.e. lots of sound distortion) after an in-house electroacoustic analysis of devices. Our hearing aid was selected because it was a popular choice at a university audiology clinic. Forty-two people completed the speech testing unaided (i.e. with no device) and then with each of the five PSAPs and one hearing aid (order of devices was randomized). We looked at improvement with the devices from unaided. We found that some PSAPs help people understand speech about as well as a hearing aid in this controlled environment while one PSAP actually hindered participants’ ability to understand speech due to sound distortion – imagine how difficult it can be when listening on a poor cell phone signal. (more…)
Author Interviews, Brigham & Women's - Harvard, Environmental Risks, NEJM, Race/Ethnic Diversity / 29.06.2017

MedicalResearch.com Interview with: Qian Di, M.S, Doctoral Student Department of Environmental Health and Francesca Dominici, Ph.D. Principal Investigator of this study Professor of Biostatistics co-Director of the Harvard Data Science Initiative Harvard T.H. Chan School of Public Health Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Clean Air Act requires Environmental Protection Agency to set National Ambient Air Quality Standard (NAAQS). Currently the annual NAAQS for PM2.5 is 12 microgram per cubic meter; and there is no annual or seasonal ozone standard. However, is current air quality standard stringent enough to protect human health? This is our main motivation. We conducted the largest attainable cohort study, including over 60 million Medicare participants, to investigate the association between long-term exposure to ozone/PM2.5 and all-cause mortality. We found significant harmful effect of PM2.5 even below current NAAQS. Each 10 microgram per cubic meter increase in PM2.5 is associated with 13.6% (95% CI: 13.1%~14.1%) increase in all-cause mortality. For ozone, 10 ppb increase in ozone exposure is associated with 1.1% (95% CI: 1.0%~1.2%) increase in mortality. Also, there is no appreciable level below which mortality risk tapered off. In other words, there is no “safe” level for PM2.5 and ozone. In other words, if we would reduce the annual average of PM2.5 by just 1 microgram per cubic meter nationwide, we should save 12,000 lives among elder Americans every year; 5 microgram --- 63,817 lives every year. Similarly, if we would reduce the annual summer average of ozone by just 1 ppb nationwide, we would save 1,900 lives every year; 5 ppb --- 9537 lives. Besides, we found black people, males and people of low SES are more vulnerable to air pollution. (more…)
Aging, Author Interviews, McGill, Nature / 29.06.2017

MedicalResearch.com Interview with: Pr. Siegfried Hekimi PhD McGill University MedicalResearch.com: What is the background for this study? What are the main findings? Response: We analyzed data about the longest living individuals over the period of time during which the record can be trusted. We found that there was no detectable plateauing of the maximum possible lifespan. This is consistent with not clearly observed plateau in the currently increasing average lifespan as well. (more…)
Author Interviews, Emory, Flu - Influenza, Lancet, Technology, Vaccine Studies / 28.06.2017

MedicalResearch.com Interview with: Dr Nadine G Rouphael MD Associate Professor of Medicine, Emory University Director of the VTEU and HIPC networks at the Hope Clinic of the Emory Vaccine Center Decatur GA 30030, USA MedicalResearch.com: What is the background for this new technology and study? What are the main findings? Response: Different groups including a group of researchers at Georgia Tech have been working on the microneedle technology for more than 20 years. The dissolvable microneedle patches are already used in several cosmetic products and drugs. However, vaccination with microneedle patches has been studied mostly in animals. Our phase 1 trial published this week in The Lancet showed that vaccination with the microneedle patches was safe, with no related serious adverse events reported. Local skin reactions to the patches were mostly mild itching and faint redness that lasted two to three days. No new chronic medical illnesses or influenza-like illnesses were reported with either the patch or the injection groups. Antibody responses generated by the vaccine, as measured through analysis of blood samples, were similar in the groups vaccinated using patches and those receiving intramuscular injection, and these immune responses were still present after six months. When asked after immunization, more than 70 percent of patch recipients reported they would prefer patch vaccination over injection or intranasal vaccination for future vaccinations. (more…)
Author Interviews, Emergency Care, Heart Disease, JAMA, Stanford / 27.06.2017

MedicalResearch.com Interview with: Alexander Sandhu, MD MS Cardiology Fellow Stanford University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Millions of patients present to the emergency department with chest pain but most do not have lab or EKG findings that indicate the patient is having a heart attack. In patients without signs of a heart attack, stress testing is frequently used to determine the need for further workup and treatment. However, there is limited evidence regarding the benefit of stress testing in these patients. We evaluated how cardiac testing - stress testing and coronary angiography - in these low-risk patients was associated with clinical outcomes. We used a statistical approach that took advantage of the fact that testing is more available on weekdays than weekends. We found that testing was associated with more angiography and revascularization (coronary stenting or coronary artery bypass surgery) but was not associated with a reduction in future heart attacks. (more…)
Author Interviews, Dermatology, UCSF / 26.06.2017

MedicalResearch.com Interview with: Dr. Katrina Abuabara MD, MA, MSCE University of California San Francisco MedicalResearch.com: What is the background for this study? Response: Atopic dermatitis (synonymous with atopic eczema or just “eczema”) is a common and burdensome condition that often presents in childhood but can occur in individuals of any age. It is episodic, meaning that it waxes and wanes over time, and many patients will have periods without signs or symptoms of the disease. Conventional wisdom suggests that “most children” improve by adolescence, but prior studies have not had sufficiently frequent follow-up to detect episodic disease beyond childhood. (more…)
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, 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, 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, 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, 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, ENT, Hearing Loss, JAMA, University of Michigan / 17.06.2017

MedicalResearch.com Interview with: Aileen Wertz, MD Otolaryngology - Head and Neck Surgery University of Michigan  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The key finding of this study is: free, comprehensive audiologic care, including hearing aids and fitting, is feasible within a well-established free clinic model. We found that donated hearing aids and volunteer health care providers were able to run the clinic and that 20 patients have thus far been fit with hearing aids. (more…)
Author Interviews, Duke, Heart Disease / 15.06.2017

MedicalResearch.com Interview with: Daniel J. Friedman, MD Duke University Hospital Duke Clinical Research Institute Durham, NC MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although primary prevention ICDs have saved countless lives among patients with heart failure and a reduced ejection fraction, the use of primary prevention ICDs in patients with more advanced heart failure [defined by New York Heart Association Class (NYHA)] is controversial. Specifically, there are conflicting data from the pivotal primary prevention ICD trials regarding whether primary prevention ICDs reduce all-cause mortality among patients with a severely reduced ejection fraction (≤35%) and NYHA III heart failure. We performed a patient level meta-analysis using data from 4 pivotal primary prevention ICD trials (MADIT-I, MADIT-II, SCD-HeFT, and DEFINITE) to assess whether primary prevention ICD efficacy varied by NYHA class (II vs. III). Overall, the ICD reduced all-cause mortality among the overall population of patients (NYHA II and III). We subsequently assessed ICD efficacy after stratification by NYHA class. Among NYHA II patients, the ICD significantly reduced all-cause mortality by reducing sudden cardiac death. Although NYHA III patients randomized to an ICD experienced a significantly lower rate of sudden cardiac death, this did not translate into a reduction in all-cause mortality, due to competing causes of non-sudden death (which an ICD cannot treat). Based on relatively wide confidence intervals associated with the estimate for ICD effect in NYHA III patients, there appears to be substantial heterogeneity in outcomes among these patients. This suggests that many NYHA III patients can benefit from a primary prevention ICD, but further study is necessary to determine which NYHA III patients are poised to benefit. (more…)
Author Interviews, Heart Disease, Karolinski Institute, Technology / 14.06.2017

MedicalResearch.com Interview with: “drones” by Andrew Turner is licensed under CC BY 2.0Andreas Claesson, RN, Paramedic PhD Centre for resuscitation science Karolinska institute Stockholm, Sweden. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Survival from out-of-hospital cardiac arrest is low, the technology is existing. When implementing this kind of system with a drone equipped with an AED, defibrillation may occur at an early stage and before EMS arrival mainly in rural areas. (more…)
Author Interviews, JAMA, Johns Hopkins, Outcomes & Safety / 14.06.2017

MedicalResearch.com Interview with: Pranita Tamma, MD Assistant Professor Director, Pediatric Antimicrobial Stewardship Program Assistant Professor of Pediatrics Johns Hopkins Bloomberg School of Public Health Dr. Pranita D. Tamma Assistant Professor of Pediatrics Director, Pediatric Antimicrobial Stewardship Program The Johns Hopkins University School of Medicine  MedicalResearch.com: What is the background for this study? What are the main findings? Response: A study examining the impact of antibiotics prescribed for nearly 1500 adult patients admitted to The Johns Hopkins Hospital found that adverse side effects occurred in a fifth of them, and that nearly a fifth of those side effects occurred in patients who didn’t need antibiotics in the first place. In the study, the researchers evaluated the electronic medical records of 1488 adults admitted to the general medicine services at The Johns Hopkins Hospital between September 2013 and June 2014. The patients were admitted for reasons ranging from trauma to chronic disease, but all received at least 24 hours of antibiotic treatment. The researchers followed patients for 30 days after hospital discharge to evaluate for the development of antibiotic-associated adverse events. To determine the likelihood that an adverse reaction was most likely due to antibiotics and to identify how many adverse reactions could be avoided by eliminating unnecessary antibiotic use, two infectious disease clinicians reviewed all of the data. (more…)
Accidents & Violence, Alcohol, Author Interviews, Cannabis, Columbia / 13.06.2017

MedicalResearch.com Interview with: Guohua Li DrPH, MD Professor and Director Center for Injury Epidemiology and Prevention Department of Epidemiology Mailman School of Public Health Columbia University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Drugged driving has become a serious problem in the United States in the recent years due to increased consumption of marijuana and opioids. About 20% of fatally injured drivers used two or more substances, with alcohol-marijuana being the most commonly detected polydrug combination. Our study of over 14000 fatal 2-car crashes indicates that drivers testing positive for alcohol, marijuana, or both are significantly more likely to be responsible for initiating these crashes than those using neither of the substances. Specifically, compared to drivers not using alcohol and marijuana, the risk of being responsible for initiating fatal crashes increases 62% for those testing positive for marijuana and negative for alcohol, 437% for those testing positive for alcohol and negative for marijuana, and 539% for those testing positive for both alcohol and marijuana. These results suggest that when used in combination, alcohol and marijuana have a positive interaction on the risk of fatal crash initiation. The most common driver error leading to fatal 2-car crashes is failure to keep in proper lane, followed by failure to yield right of way and speeding. (more…)