Author Interviews, Infections, Inflammation, Sleep Disorders / 07.02.2017

MedicalResearch.com Interview with: Mark Robert Zielinski, MD Department of Psychiatry Harvard Medical School and Veterans Affairs Boston Healthcare System West Roxbury, MA 02132 MedicalResearch.com: What is the background for this study? Response: Anecdotally, people have known that the immune system and sleep are related. In the last several decades this relationship has been systematically investigated. This work led to important findings that several molecules that enhance inflammation including interleukin-1 beta regulate sleep. Interleukin-1 beta is known to increase sleep and sleep intensity after sleep loss and in response to pathogens. However, it was unknown how these effects are connected. Interestingly, the NLRP3 inflammasome is a protein complex that senses changes in the local environment and subsequently activates pro-inflammatory molecules including interleukin-1 beta. Therefore, we wanted to see if the NLRP3 inflammasome is involved in sleep regulation.  (more…)
Author Interviews, C. difficile, Hospital Acquired, JAMA / 06.02.2017

MedicalResearch.com Interview with: Vanessa W. Stevens, PhD IDEAS 2.0 Center, Veterans Affairs (VA) Salt Lake City Health Care System Division of Epidemiology, Department of Internal Medicine University of Utah School of Medicine Salt Lake City, Utah MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although metronidazole remains the most commonly used drug to treat Clostridium difficile infection (CDI), there is mounting evidence that vancomycin is a better choice for some patients. Most previous studies have focused on primary clinical cure, but we were interested in downstream outcomes such as disease recurrence and mortality. We found that patients receiving metronidazole and vancomycin had similar rates of recurrence, but patients who were treated with vancomycin had lower risks of all-cause mortality. This was especially true among patients with severe Clostridium difficile. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, JAMA, University of Pittsburgh / 26.01.2017

MedicalResearch.com Interview with: Sachin Yende, M.D., M.S., Associate professor University of Pittsburgh School of Medicine’s departments of Critical Care Medicine and Clinical and Translational and Vice president of Critical Care at the VA Pittsburgh. Florian B. Mayr, M.D., M.P.H. Faculty member in University of Pittsburgh Department of Critical Care Medicine and the Center for Health Equity Research and Promotion MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Centers for Medicare and Medicaid Services and the Veteran Health Administration currently track readmission rates for pneumonia, acute heart attacks, heart failure and chronic obstructive lung disease for quality purposes and pay for performance. In our study, we were able to demonstrate that unplanned readmissions after sepsis (defined as life threatening organ failure due to the body's response to an overwhelming infection) are more common than readmission for these other conditions stated above and associated with significant excess costs. (more…)
Author Interviews, Hospital Acquired, Infections, Surgical Research / 24.01.2017

MedicalResearch.com Interview with: Kristen A. Ban, MD Loyola University American College Surgery Clinical Scholar MedicalResearch.com: What is the background for this study? What are the main findings? Response: The American College of Surgeons previously released surgical site infections (SSI) guidelines, and we wanted to update them with the most recent literature to give surgeons a concise, comprehensive document of recommended practices to reduce SSI. We were very fortunate to partner with our colleagues and content experts at the Surgical Infection Society for this update. There are a few areas where we had additional literature to support new or different guidelines. Blood glucose control is now recommended for all patients regardless of diabetic status. SSI reduction bundles have become very popular, and we emphasize that compliance must be high with all parts of these bundles to obtain the maximum benefit. Finally, we recommend cessation of prophylactic antibiotics at incision closure with some exceptions (mainly in regard to implanted material/hardware). (more…)
Author Interviews, Environmental Risks, Herpes Viruses, Pulmonary Disease / 20.01.2017

MedicalResearch.com Interview with: Dr. Tobias Stöger Group Leader, Dynamics of Pulmonary Inflammation Comprehensive Pneumology Center Institute of Lung Biology and Disease (iLBD) Helmholtz Zentrum München  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Particulate air pollution is common in urban areas and the inhalation of nanoparticles is known to trigger inflammatory effects in humans potentially altering the immune system. Herpes viruses are ubiquitous and well adapted pathogens hiding in host cells and persist thus continuing in a greater part of our population. Under certain stress conditions and if the immune system becomes weakened, the viruses can become active again, begin to proliferate and destroy the host cell. Thus we raised the question whether NP-exposure of persistently herpesvirus-infected cells as a second hit might provoke reactivation of latent virus and eventually lead to an inflammatory response and tissue damage. Our main finding is that NP-exposure of persistently herpesvirus-infected cells – murine or human – restores molecular signatures found in acute virus infection and boosts production of lytic viral proteins. (more…)
Author Interviews, Genetic Research, Infections, Pediatrics / 19.01.2017

MedicalResearch.com Interview with: Prof. Adrian Liston (VIB-KU Leuven) MedicalResearch.com: What is the background for this study? Response: With vaccinations, sanitation, antibiotics and general improvements in living standards, infectious disease is no longer a major killer of children. Death or hospitalisation of children from infection is rare in countries with modern health care systems. Those rare events were once thought to be chance outcomes on the roulette of bad luck, but increasingly we are recognising that genetic mutations underlie severe pediatric infections. In our study we are seeking to identify the mutations and immunological changes that occur in children, causing them to have severe reactions to infectious disease. (more…)
Author Interviews, CDC, Lyme / 17.01.2017

MedicalResearch.com Interview with: Tammi L. Johnson PhD, Microbiologist Division of Vector-Borne Diseases CDC MedicalResearch.com: What is the background for this study? Response: Lyme disease is caused by the bacterium Borrelia burgdorferi and is transmitted to humans through the bite of infected blacklegged ticks, also called deer ticks. Lyme disease is the most commonly reported vectorborne illness in the United States, with approximately 300,000 humans becoming infected each year. While Lyme disease infections are highly concentrated in the northeast and upper Midwest, the number of counties in which the blacklegged tick has become “established” has more than doubled in the past two decades. Established populations of these ticks are found in 35 states. Knowing that Lyme disease is increasing both in numbers of infections and in geographic range in the United States, we did this study to determine if people are at risk of encountering infected ticks while recreating in eastern national parks. This is the first large-scale survey in multiple national parks, and though suspected, it had not been confirmed that ticks in many of these parks were infected. So the purpose of the study was to survey national park units across six Northeastern and Mid-Atlantic States and the District of Columbia, ranging from Maine in the north to Virginia in the south and characterize the risk of human exposure to ticks-borne bacteria. Researchers from the Centers for Disease Control and Prevention and the National Park Service evaluated frequently used trails in Acadia National Park, Catoctin Mountain Park, Fire Island National Seashore, Gettysburg National Military Park, Manassas National Battlefield Park, Monocacy National Battlefield, Prince William Forest Park, Rock Creek Park, and Shenandoah National Park. (more…)
Author Interviews, BMJ, HIV, STD / 17.01.2017

MedicalResearch.com Interview with: Michael Rekart, MD, DTM&H Clinical Professor, Medicine and Global Health The University of British Columbia .... On behalf of my co-authors MedicalResearch.com: What is the background for this study? Response: The background for this study is the observation that new syphilis cases over the last decade in British Columbia, Canada, have been escalating more rapidly than anyone could have predicted and that syphilis incidence has outpaced the incidence of other sexually transmitted diseases (STDs), including gonorrhea and chlamydia. This unexpected increase in syphilis has been almost wholly concentrated in men who have sex with men (MSM). Most of these MSM are HIV-1 infected and many are taking highly active antiretroviral therapy (HAART). In fact, the expansion in HAART coverage in MSM parallels the growth in syphilis in the same population. In addition, my co-authors and I had serious doubts as to whether 'treatment optimism', the generally accepted explanation for this phenomenon, was robust enough to account for such a dramatic increase in new syphilis cases. Treatment optimism posits that HAART availability and effectiveness have led to the perception in both HIV-1-infected and HIV-1-uninfected individuals that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhea, chlamydia and syphilis. (more…)
Author Interviews, Biomarkers, Critical Care - Intensive Care - ICUs, Infections, JAMA, Pediatrics / 11.01.2017

MedicalResearch.com Interview with: Halden F. Scott MD, Assistant Professor Departments of Pediatrics and Emergency Medicine University of Colorado School of Medicine MedicalResearch.com: What is the background for this study? Response: Sepsis, a dysregulated immune response to infection, is a leading cause of death for children. Survival depends on rapid diagnosis and timely delivery of life-saving resuscitative care, including fluids and antibiotics. However, it can be challenging to make an early diagnosis of sepsis in children. Millions of children present for emergency care of infection and fever every year, most of whom will not develop sepsis. Tools that assist providers in distinguishing the sickest children with infection at an early stage could enable the early delivery of life-saving treatments. Lactate is a clinically-available laboratory test that has played a critical role in improving the diagnosis and treatment of sepsis in adults. Sepsis may cause lactate levels to rise in the blood during sepsis, through reduced delivery of oxygen to the tissues, as well as through changes in how energy is produced and in how lactate is cleared by the kidney and liver. Data about lactate in pediatric sepsis, particularly early levels and whether it is associated with mortality, have been limited. (more…)
Author Interviews, Diabetes, Diabetologia, Infections, Pediatrics / 11.01.2017

MedicalResearch.com Interview with: Dr. Hanna Honkanen PhD University of Tampere. MedicalResearch.com: What is the background for this study? What are the main findings? Response: The association between enteroviruses and type 1 diabetes has been suggested for long and analyzed in several studies. However, only few studies have been able to study this association at the time when the disease process starts, which happens several months or years before type 1 diabetes is diagnosed. Our study made this possible since it was based on a large cohort of children who were followed from birth and samples were collected already before the disease process had started (prospective DIPP-study in Finland). Enterovirus infections were detected by analyzing the presence of viral nucleic acids in longitudinal stool sample series. Infections were found more frequently in case children who developed islet autoantibodies compared to control children. This excess was detected several months before islet autoimmunity appeared. This study is the largest such study carried out so far. The results suggest that enterovirus infections may contribute to the initiation of the disease process that eventually leads to type 1 diabetes. (more…)
Author Interviews, Hospital Acquired, Infections, Surgical Research, Technology / 10.01.2017

MedicalResearch.com Interview with: Alex Carignan, MD, MSc Department of Microbiology and Infectious Diseases Université de Sherbrooke, Quebec, Canada  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although reports of iatrogenic transmission directly linked to surgical power tools (SPTs) are rare, the decontamination of such instruments is challenging due to their complex designs, which may restrict access to cleaning and sterilization agents, and because they often become contaminated after use. Most studies on infection risk with ultrasonic surgical power tools include patients who underwent phacoemulsification surgeries,but it is logical to assume that lumen contaminants, including bacteria and proteinaceous material from previous operations, may be found in neurosurgery SPTs as well. During June 2015, the infection control department at our institution was notified of an increase in the number of surgical site infection cases following craniotomy since January 2015. We investigated an outbreak of neurosurgical SSIs at a tertiary care hospital in Quebec, Canada, to identify the outbreak’s cause, and our investigation strongly suggests that modifying the reprocessing procedure of an ultrasonic surgical aspirator caused the outbreak. (more…)
Author Interviews, Infections, Nature, Technology / 08.01.2017

MedicalResearch.com Interview with: Hyo-Jick Choi, PhD Assistant Professor, Department of Chemical and Materials Engineering University of Alberta Edmonton, AB, Canada T6G 1H9 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Respiratory diseases such as influenza transmitted either through breathing aerosols exhaled/coughed out by an infected person or through direct contact. Despite controversy over its efficacy, surgical mask has been widely used by general public during the past respiratory disease outbreaks because of low cost, easy wearability, and widespread use in normal day-to-day situation. Critical issue is that virus captured on the filter of the mask still maintains infectivity for long time, raising concerns of secondary infections and transmissions. This led us to develop a strain-nonspecific and reusable airborne virus deactivation system based on salt recrystallization principle. Salt recrystallization is hypothesized to cause deactivation of viruses transmitted through aerosols via two successive processes: 1) salt on filter fiber dissolves upon exposure to the pathogenic aerosols and 2) salt crystallizes as aerosols evaporate. To demonstrate the concept, we coated the fiber of the surgical mask filter with sodium chloride (NaCl) salt crystal and tested its performance using three different types of influenza viruses. Salt-treated filter provided higher filtration efficiency compared to non-treated regular filter and successfully destroyed multiple subtypes of influenza viruses trapped on the filter within few minutes, leading to significant infectivity loss. (more…)
Author Interviews, Heart Disease, HIV / 05.01.2017

MedicalResearch.com Interview with: Heidi M. Crane MD, MPH Associate Professor of Medicine Associate Director Clinical Epidemiology and Health Services Research Core Center for AIDS Research University of Washington MedicalResearch.com: What is the background for this study? What are the main findings? Response: Studies have suggested that rates of myocardial infarction (MI) are higher in those with HIV, likely for a variety of reasons. However, prior studies have not been able to distinguish MIs by type. The Universal Definition of MI has been recommended by cardiology societies and classifies MIs into types with Type 1 MIs resulting spontaneously from atherosclerotic plaque instability and Type 2 MIs occurring secondary to causes other than atherosclerotic plaque rupture, including hypotension, hypoxia, and stimulant induced spasm resulting in increased oxygen demand or decreased supply. Understanding MI types is likely important as they may indicate a different prognosis and need for different prevention approaches. (more…)
Author Interviews, Dermatology, Infections, Transplantation, UT Southwestern / 02.01.2017

MedicalResearch.com Interview with: Richard Wang, M.D., Ph.D. Assistant Professor UT Southwestern Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Currently, there are 13 polyomaviruses known to infect humans. Several members of this family of double-stranded DNA viruses—including Merkel Cell Polyomavirus, Trichodysplasia Spinulosa Polyomavirus, Human Polyomavirus 6 (HPyV6), and Human Polyomavirus 7 (HPyV7)—can be shed from skin of healthy individuals. While most polyomavirus infections are common and subclinical, several polyomaviruses have been associated with debilitating diseases in immunocompromised individuals. Most recently, HPyV7 was discovered in a pruritic and dyskeratotic eruption in two immunosuppressed transplant patients. A closely related polyomavirus, Human Polyomavirus 6, has not yet been strongly linked to any infectious diseases. Using the previously described, characteristic histologic pattern, we identify 3 additional cases of skin eruptions associated with infections of HPyV6 and HPyV7. The association of the dermatoses with highly active infections were confirmed through electron microscopy, immunohistochemistry, quantitative PCR, and complete sequencing. HPyV7 infects keratinocytes and affects their normal differentiation. In addition, next generation sequencing revealed that HPyV6 could persist in a latent state in the skin of a previously infected patient. (more…)
Author Interviews, Herpes Viruses, JAMA / 22.12.2016

MedicalResearch.com Interview with:   MedicalResearch.com: What is the background for this study?  What are the main findings? Genital herpes is a sexually transmitted infection that is caused by one of two subtypes of the herpes simplex virus (HSV-1 and HSV-2). The condition is common in the United States, as the CDC estimates that almost one in six people between the ages of 14 and 49 are afflicted. Unfortunately, there are no good screening tests for herpes and it cannot be cured. After a systematic review of the evidence, the U.S. Preventive Services Task Force determined that, for adolescents and adults who have no signs or symptoms, including pregnant women, the harms of screening for genital herpes outweigh the benefits. These harms include high rates of false-positive screening tests, potential concerns around unnecessary antiviral medication use, and anxiety and relationship issues related to diagnosis. Additionally, the benefits of screening proved small, in part because early identification and treatment do not alter the course of the condition. In the end, due to the lack of benefits in the face of serious harms, the Task Force recommended against routine serologic screening for genital herpes simplex virus (HSV) infection. (more…)
Author Interviews, OBGYNE, UCLA, Zika / 20.12.2016

MedicalResearch.com Interview with: Karin Nielsen, MD, MPH Professor of Clinical Pediatrics Division of Pediatric Infectious Diseases David Geffen School of Medicine at UCLA Director, Center for Brazilian Studies MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our research was a prospective study in which pregnant women in Rio de Janeiro who developed a rash in the last 5 days between the end of 2015 to mid 2016 were screened for possible infection with Zika virus by a special molecular test (PCR) which looked for the virus in blood or urine. Women who were found to have Zika virus in either blood, urine or both were followed throughout time to look for pregnancy and infant outcomes. We also followed women who had a negative PCR test for Zika as a comparison group. By July 2016, we had outcomes known for 125 Zika affected pregnancies, of these 58 had abnormal outcomes, with 9 fetal losses and 49 babies who had abnormal findings on physical exam or brain imaging, all consistent with neurologic abnormalities. This meant 46% of the pregnant women in our study had an abnormal pregnancy outcome, and 42% of live birth infants were found to have an abnormality in the first few months of life. (more…)
Author Interviews, Brigham & Women's - Harvard, Endocrinology, Infections / 18.12.2016

MedicalResearch.com Interview with: Flaminia Catteruccia PhD Associate Professor of Immunology and Infectious Diseases Department of Immunology and Infectious Diseases Boston, Massachusetts 02115 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mosquito control via lethal insecticides is a key method for reduction of malaria transmission. As insecticide resistance is spreading, new intervention methods are urgent. Our study demonstrates that studies on mosquito biology can provide novel, much needed tools for malaria control. We show how key aspects of mosquito physiology and Plasmodium development can be significantly disrupted in the female Anopheles mosquito by agonists of the insect steroid hormone 20-hydroxyecdysone (20E). Modeling of the data predicts that the integration of 20E agonists in malaria control programs would significantly reduce malaria prevalence to a similar extent as insecticides, but without imposing severe costs to mosquito populations (more…)
Author Interviews, Brigham & Women's - Harvard, Dental Research, Infections, Rheumatology, Science / 17.12.2016

MedicalResearch.com Interview with: Maximilian F. Konig, MD Division of Rheumatology, Johns Hopkins University School of Medicine Current affiliation: Department of Medicine Massachusetts General Hospital Harvard Medical School MedicalResearch.com: What is the background for this study? Response:The idea that rheumatoid arthritis (RA), an autoimmune disease that leads to chronic joint inflammation and destruction, may be initiated by a bacterial infection is not novel, but has been posited for more than a century. Based on the clinical observation that patients with RA frequently have severe periodontal disease (gum disease), gum inflammation has long been thought to contribute to disease development in RA. However, limited understanding of the mechanisms that fuel and sustain the autoimmune attack in RA made it difficult to pinpoint a specific bacterial trigger. In recent years, our understanding of the abnormal immune response that attacks the joints in patients with RA has grown exponentially, and we now know that disease-specific autoantibodies (ACPAs) target modified self-proteins (this modification is known as citrullination). It is this abnormal immune response against citrullinated proteins that appears to drive the joint (and sometimes lung) inflammation seen in rheumatoid arthritis. Recent studies from our laboratory at The Johns Hopkins University (led by principle investigator Felipe Andrade, MD, PhD) suggested that an immune cell called the neutrophil, which normally protects us from infection at sites like the oral cavity or anywhere else in the body, also appears to be the source of the proteins attacked in RA. We were therefore interested to understand what drives the association of gum disease, an inflammation commonly triggered by bacteria, with RA. (more…)
Author Interviews, Infections, Nature / 16.12.2016

MedicalResearch.com Interview with: Professor Alistair J P Brown  DSc FSB FAAM FRSE Aberdeen Fungal Group, MRC Centre for Medical Mycology, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen UK  MedicalResearch.com: What is the background for this study? Response: Most of us harbor the yeast Candida albicans, and most of the time it does us no harm.  However, under certain circumstances it can break out to cause nasty infections of the mouth or genitalia (thrush), or potentially fatal infections in vulnerable intensive care patients.  Indeed, over half of women will suffer at least one episode of vulvovaginal candidiasis in their lifetime, and over 5% of women suffer recurrent episodes (four or more episodes per annum).  Also, it has been estimated that there are over 400,000 life-threatening systemic Candida infections worldwide per annum, of which over 40% are fatal (see Science Translational Medicine (2012) vol. 4, 165rv13).  A key to this is the potency of our immunological defenses: the weaker our defenses the more vulnerable we are to fungal infection.  Therefore, we in the Medical Research Council (MRC) Centre for Medical Mycology – and other groups worldwide – are studying the mechanisms by which our immune cells recognize and kill invading Candida cells, thereby protecting us from infection. (more…)
Author Interviews, Gastrointestinal Disease, HIV, Inflammation / 15.12.2016

MedicalResearch.com Interview with: Prof. Jamal Tazi Director, Institute for Molecular Genetics CNRS and University of Montpellier and Executive Committee Member ABIVAX MedicalResearch.com: What is the background for this study? Response: Its long been established that people with HIV, even those treated successfully with antiretroviral treatment, exhibit significantly higher levels of chronic inflammation than HIV-negative people. The causes of this inflammation are many – ongoing viral replication, often in the so-called viral reservoirs, leaky gut syndrome, concomitant viral infections (eg CMV, hepatitis etc). (more…)
Author Interviews, BMJ, Dermatology, Herpes Viruses, HIV, Infections, STD / 12.12.2016

MedicalResearch.com Interview with: E. Charles Osterberg, M.D. Assistant Professor of Surgery Genitourinary Reconstruction and Trauma University of Texas- Dell Medical School Dell-Seton Medical Center / University Hospital MedicalResearch.com: What is the background for this study? Response: Pubic hair grooming has become an increasingly common practice among men and women. Perceptions of genital normalcy have changed as modern society’s definition of attractiveness and feelings of femininity and masculinity have changed. Pubic hair grooming has been shown to increase morbidity such as genital injuries, however little is known about the relationship between grooming practices and sexually transmitted infections. (more…)
Author Interviews, Biomarkers, Infections, JAMA, Neurological Disorders / 12.12.2016

MedicalResearch.com Interview with: Zanusso Gianluigi M.D.Ph.D. Department of Neurosciences, Biomedicine and Movement Sciences University of Verona Verona, Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: To determine RT-QuIC assay sensitivity and specificity in cerebrospinal fluid and olfactory mucosa in a large group of patients with a clinical diagnosis of probable, possible or suspect Creutzfeldt–Jakob disease (CJD) and controls. In these patients, RT-QuIC testing of CSF and olfactory mucosa provided a specificity and sensitivity of 100%. A softer swab for olfactory mucosa sampling provided the same sensitivity as using a brush . (more…)
Author Interviews, HIV, NEJM / 03.12.2016

MedicalResearch.com Interview with: Ms. Neliëtte Van Niekerk M.Com and Dr. Annalene Nel M.B., Ch.B., Ph.D. From International Partnership for Microbicides Silver Spring, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: Existing prevention methods have not done enough to stop the alarming rates of infection among women and girls, especially in sub-Saharan Africa, where young women are at least twice as likely to have HIV as young men. Rates of new infections among women aged 15-24 were more than four times greater than that of men the same age, and this age group accounted for 25 percent of new infections in South Africa. To provide women with more prevention options, the nonprofit International Partnership for Microbicides (IPM) developed a vaginal ring that contains an antiretroviral drug called dapivirine. Women insert the ring themselves and replace it every month. The Ring Study was a Phase III clinical trial that assessed the safety and long-term efficacy of the monthly dapivirine ring among nearly 2,000 women in South Africa and Uganda. We found that the ring reduced the risk of HIV-1 infection in about one-third of the women in the trial, and it was safe, with no difference in adverse effects between the active and placebo ring groups. (more…)
Author Interviews, Infections, MRSA, Nature / 03.12.2016

MedicalResearch.com Interview with: Ferric C. Fang, M.D. Professor of Laboratory Medicine and Microbiology Adjunct Professor of Medicine (Infectious Diseases) Director, Harborview Medical Center Clinical Microbiology Laboratory University of Washington School of Medicine Seattle, WA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Fang lab has a longstanding interest in the interaction between nitric oxide (NO·) and pathogenic bacteria. NO· is an important mediator of the host innate immune response that restricts the growth of invading bacterial pathogens. One of the known actions of NO· is the reversible inhibition of aerobic respiration that results from NO· binding to the heme centers of terminal oxidases. Like mammalian hosts, many bacteria also possess the ability to enzymatically synthesize NO·. Our latest research investigated the physiological role of the Staphylococcus aureus nitric oxide synthase (saNOS). We discovered that endogenously produced NO· is able to target bacterial terminal oxidases under microaerobic conditions, allowing the bacteria to transition to nitrate respiration when oxygen concentrations are limited and helping to maintain the membrane potential. This process was found to be essential for S. aureus nasal colonization in a mouse model. Thus, a conserved mechanism is involved in both the antimicrobial actions of NO· and the physiological role of NO· in regulating bacterial electron transfer reactions. Interestingly, NO·-heme interactions have been shown to control mitochondrial respiration during hypoxia in mammalian cells. (more…)
Author Interviews, Infections, MRSA, NIH, Science / 01.12.2016

MedicalResearch.com Interview with: Warren Leonard, M.D. NIH Distinguished Investigator Laboratory of Molecular Immunology NHLBI, NIH MedicalResearch.com: What is the background for this study? Response: TSLP is a cytokine that has been well studied in the context of T cell helper type 2 (TH2) responses and the promotion of atopic diseases. TSLP is naturally expressed at barrier surfaces, such as the skin; however, its role in skin infections was not previously explored. In our study, we investigated whether TSLP plays a role in host defense to Staphylococcus aureus skin infections, using the most common strain of methicillin-resistant S. aureus (MRSA) present in the United States. (more…)
Author Interviews, Infections, Kidney Disease / 30.11.2016

MedicalResearch.com Interview with: Georg Schlieper, MD MVZ DaVita Rhein-Ruhr Duesseldorf, Germany MedicalResearch.com: What is the background for this study? Response: Methicillin-resistant Staphylococcus aureus (MRSA) colonization in hemodialysis patients is associated with higher risk for systemic infection. Recent hospitalization and temporary dialysis access are known risk factors for MRSA colonization. Whether MRSA colonization rates in hospital-based dialysis centers differ from separate dialysis centers is unknown. Data on MRSA decolonization strategies in hemodialysis patients are scarce. (more…)
Author Interviews, Infections, PLoS / 30.11.2016

MedicalResearch.com Interview with: Romolo Nonno, DVM, PhD Istituto Superiore di Sanità Dipartimento di Sanità Pubblica Veterinaria e Sicurezza Alimentare Roma Italy MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies have suggested that prion populations are composed of a variety of conformational variants subjected to Darwinian evolution driven by selective regimes. However, the exact molecular mechanisms that make prions able to self-replicate and mutate are still poorly understood. A major technical advance in this field has been the discovery of techniques that allow to replicate prions in vitro, outside live organisms. One of these techniques, Protein Misfolding Cyclic Amplification (PMCA), allows to grow prion populations for a very high number of replications in a relatively short time period. Furthermore it is conceivable that the in vitro environment offers less constraint to prion replication than live animals or cells, due to the absence of active clearance and cell division, which are key players of conformers selection in ex vivo models. These features make PMCA an attractive tool to investigate prion replication, mutation and evolution. By using PMCA, we investigated the in vitro evolution of prion populations derived from natural scrapie. Unexpectedly, we found that the cloud of conformational variants which compose a natural scrapie isolate also includes “defective” variants which, once isolated, are unable to self-sustain in vivo. Importantly, we found that the defective prion mutant that we have isolated possesses unique biochemical properties in that its prion domain lacks the central region of prion protein, which is invariably present in known infectious mammalian prions. (more…)
Author Interviews, Flu - Influenza, Pediatrics, Science, UCLA / 28.11.2016

MedicalResearch.com Interview with: Katelyn M. Gostic and Monique Ambrose Department of Ecology and Evolutionary Biology University of California Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Monique Ambrose: Influenza pandemics pose a serious, recurrent threat to human public health. One of the most probable sources of future pandemic influenza viruses is the pool of influenza A virus (IAV) subtypes that currently circulate in non-human animals. It has traditionally been thought that the human population is immunologically naïve and unprotected against these unfamiliar subtypes. However, our work suggests that an individual ‘imprints’ to the influenza A virus (IAV) encountered in early childhood in such a way that they retain protection against severe disease if they later encounter a novel IAV subtype that belongs to the same genetic group as their first exposure. Our research looked at human cases of H5N1 and H7N9, two avian IAV subtypes of global concern, to investigate what factors most strongly predicted risk of severe disease. The most striking explanatory factor was childhood IAV imprinting: our results suggest that individuals who had childhood imprinting on an IAV in the same genetic group as the avian IAV they encountered later in life experienced 75% protection against severe disease and 80% protection against death. (more…)
Author Interviews, HIV, Pharmacology / 28.11.2016

MedicalResearch.com Interview with: Arkaitz Imaz Vacas HIV and STD Unit, Department of Infectious Diseases Hospital Universitari de Bellvitge MedicalResearch.com: What is the background for this study? Response: Sexual transmission is the most common route of human immunodeficiency virus (HIV) acquisition in most regions of the world. The male genital tract is a separate reservoir for HIV and may contribute to HIV shedding in seminal fluid even in individuals receiving antiretroviral (ARV) therapy (ART). Treatment of HIV-infected patients with currently available combined ART suppresses HIV in blood and also in genital fluids and reduces the risk of HIV acquisition by their sexual partners. However, sexual HIV transmission is possible even in patients on ART, especially if treatment was initiated recently. Thus, the ability of ARV drugs to penetrate into the male genital tract is a key factor for achieving HIV suppression in seminal fluid and preventing sexual transmission of the virus. Dolutegravir (DTG) is a new integrase inhibitor (INI) with high antiviral potency and a high genetic barrier to resistance. In large phase III-a randomized clinical trials, DTG in combination with 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) has shown noninferiority compared with raltegravir and superiority to efavirenz or ritonavir-boosted darunavir as first-line therapy in treatment-naive HIV-1 infected patients. A study in healthy volunteers showed that DTG penetration in seminal fluid was <7% of DTG exposure in blood plasma (BP), and the median seminal concentration at the end of the dosing interval (C24h) was lower than the in vitro protein-adjusted (PA) 90% inhibitory concentration (IC90) for wild-type HIV-1. However, information about protein unbound DTG fraction in seminal fluid is lacking and there is no information regarding DTG concentrations in the semen of HIV-1–infected patients or the antiviral activity of a DTG-based ARV combination in this compartment. The aim of this study was to compare viral decay kinetics and DTG concentrations (total drug and unbound fraction) in the seminal plasma (SP) and BP in a group of treatment-naive HIV-1 infected patients starting DTG plus abacavir (ABC) and lamivudine (3TC) once daily. (more…)