Author Interviews, COVID -19 Coronavirus, Infections, NYU / 14.03.2024

MedicalResearch.com Interview with: Mukundan G. Attur, PhD Associate Professor, Department of Medicine NYU Grossman School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response:  The study investigates the potential protective effects of a genetic variant of IL1RN against inflammation and severe outcomes, particularly in COVID-19. Previous research indicates that carriers of this genetic variant may experience less severe radiographic knee osteoarthritis and decreased inflammation in rheumatoid arthritis patients. Given the emergence of cytokine release syndrome in COVID-19 patients, the researchers sought to understand whether the same genetic variant could offer protection against inflammation and potential death in COVID-19 cases. (more…)
Author Interviews, Brain Injury, Brigham & Women's - Harvard, Inflammation / 14.01.2024

MedicalResearch.com Interview with: Samir Mitragotri Ph.D. Hiller Professor of Bioengineering Hansjorg Wyss Professor of Biologically Inspired Engineering Area Chair, Bioengineering Core Faculty Member, Wyss Institute for Biologically Inspired Engineering Harvard John A. Paulson School Of Engineering And Applied Sciences MedicalResearch.com: What is the background for this study? Response: Traumatic brain injury (TBI) has a heavy burden on the world, affecting ~70 million people globally each year. Despite its prevalence, there are no clinically approved treatments beyond symptom management. There is an urgent need to develop effective therapies to alleviate the damage caused by TBI.   MedicalResearch.com:  What do macrophages typically do?  As part of the innate immune system, macrophages migrate to areas of injury to eat pathogens or debris and manage inflammation in response to injury or infection. However, in the majority of cases of TBI, there is no actual infection from a foreign pathogen, leading to excessive inflammation that spreads damage beyond the initial impact. (more…)
Author Interviews, Inflammation, Nutrition, Red Meat / 09.11.2023

MedicalResearch.com Interview with: Dr. Alexis C. Wood United States Department of Agriculture (USDA)/ARS Children’s Nutrition Research Center Baylor College of Medicine, TX MedicalResearch.com: What is the background for this study? Response: We know (we think!) that what we eat has a big influence on our health. However, discovering which foods influence our health, and how, is highly challenging. Research investigating this topic should be seen as an on-going process as new results and new study methods emerge, and as the food environment shifts. Red meat is often considered a food that should be minimized in diets designed to support good health. This may seem surprising as red meat is a good source of protein and many other nutrients, but the advice to limit red meat intake is based on several large-scale studies showing associations between red meat consumption and the development of conditions such as type 2 diabetes, and other cardiovascular disease risk related factors. However, newer research, with different designs or approaches, has struggled to conclusively support this association; for example, in studies where the amount of red meat in people’s diet is manipulated, we do not see the expected increases in risk. Other studies have suggested that any associations between red meat intake and chronic disease may reflect confounding effects by adiposity – that is, the increased risk of disease really reflects the increased risk associated with a higher BMI. (more…)
Author Interviews, COVID -19 Coronavirus, Inflammation, JAMA, Pediatrics, Race/Ethnic Diversity / 30.11.2020

MedicalResearch.com Interview with: Ellen H. Lee, MD Incident Command System Surveillance and Epidemiology Section New York City Department of Health and Mental Hygiene Long Island City, New York  MedicalResearch.com: What is the background for this study? Response: Published reports of the COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) have described higher proportions of cases among Black and Hispanic children. However, case series are limited by the lack of population-level data, which could help provide context for the racial/ethnic distribution of cases described in these reports. The New York City (NYC) Department of Health and Mental Hygiene required reporting of all possible cases of MIS-C among NYC residents, and for cases meeting MIS-C criteria, applied population denominators to calculate MIS-C incidence rates stratified by race/ethnicity. To help characterize the burden of severe COVID-19 disease in NYC, we also calculated COVID-19 hospitalization rates stratified by race/ethnicity. (more…)
Author Interviews, Dental Research, Inflammation / 22.10.2020

MedicalResearch.com Interview with: Prof. Michael Glogauer, D.D.S., Ph.D Faculty of Dentistry, University of Toronto Toronto, ON Canada MedicalResearch.com: What is the background for this study? Response: Periodontal disease (PD) affects between 20% and 50% of the global population, with growing evidence supporting its association with other inflammatory diseases, including heart disease, arthritis, and diabetes. Several studies have shown how untreated periodontal disease leads to increased medical care costs for nonoral conditions, including patient hospitalization rates. The interaction of inflammatory diseases with PD suggests a shared, underlying pathology that may be exploited to better manage patients and reduce the economic burden. However, the mechanisms through which these diseases interact are unclear. In periodontal disease, tissue and bone destruction in the mouth is driven by elevated recruitment of white blood cells called polymorphonuclear neutrophils (PMNs), which are activated by the oral disease and recruited from the circulation to sites of inflammation.  (more…)
Author Interviews, COVID -19 Coronavirus, Inflammation, Pediatrics / 04.09.2020

MedicalResearch.com Interview with: Alvaro Moreira, MD Assistant Professor, Department of Pediatrics Co-Director Neonatal Nutrition and Bone Institute UT Health San Antonio MedicalResearch.com: What is the background for this study? Response: Multisystem inflammatory syndrome in children (MIS-C), also known as pediatric inflammatory multisystem syndrome, is a new dangerous childhood disease that is temporally associated with coronavirus disease 2019 (COVID-19). We conducted a systematic review to communicate the typical presentation and outcomes of children diagnosed with this hyperinflammatory condition.  (more…)
Author Interviews, COVID -19 Coronavirus, Inflammation / 27.08.2020

MedicalResearch.com Interview with: Sacha Gnjatic, PhD Associate Director of the Human Immune Monitoring Center Associate Professor of Medicine, Oncological Sciences and Pathology Icahn School of Medicine at Mount Sinai Member of the Precision Immunology Institute and The Tisch Cancer Institute Mount Sinai MedicalResearch.com: What is the background for this study? Would you explain what is meant by cytokine/cytokines? Response: COVID-19 is a disease where inflammation is suspected to play a large role in pathogenicity, possibly more so than the tissue damage created by the virus alone. Cytokines are small soluble proteins that are produced by both immune cells and cells from tissues, and many play a role in signaling such inflammation, to alert of tissue damage or infection. Among these cytokines, interleukin-6 (IL-6), IL-8, IL-1beta, and Tumor Necrosis Factor alpha (TNF-a) have been well established as important markers of pathogenic inflammation. Drugs that counteract these cytokines are routinely use in various inflammatory disease, from rheumatoid arthritis to plaque psoriasis and Crohn’s disease. When the initial wave of SARS-CoV-2 infection hit our hospitals in New York, we therefore wondered whether these cytokines were associated with COVID-19 disease severity and outcome, and hoped that a rapid test to detect them in blood could be useful to make clinical decisions about treatment. We were able to analyze a very large number of patient samples (>1400) in a period of one month, and confirmed our findings in a second smaller cohort. (more…)
Author Interviews, COVID -19 Coronavirus / 05.08.2020

MedicalResearch.com Interview with: Pranay Sinha, MD Research Fellow Section of Infectious Diseases Boston University School of Medicine  MedicalResearch.com: What is the background for this study? Response: In the early days of the COVID-19  pandemic there were no evidence-based treatments for severely ill patients infected with this virus. We formed an interdisciplinary group of physicians from departments of adult and pediatric infectious diseases, rheumatology, and pulmonary/critical care as well as clinical pharmacy specialists. Given some promising data from China, we instituted treatment with off-label IL-6 receptor inhibitors (tocilizumab and sarilumab). The rationale was to mitigate the exuberant immune response observed in some patients infected with SARS-CoV-2 (also called cytokine storm or cytokine release syndrome). Quite quickly, we started noticing that giving the drug to our sickest patients wasn’t eliciting dramatic improvement. We reasoned that by the time patients were severely ill and requiring ventilators, the damage to their lungs from the cytokine storm had already taken place. It was like closing the barn door after the horse had already bolted. (more…)
Author Interviews, Columbia, Heart Disease, Mediterranean Diet, Women's Heart Health / 13.03.2020

MedicalResearch.com Interview with: Dr. Riddhi Shah, PhD AHA SFRN Postdoctoral Research Fellow Division of Cardiology Columbia University Medical Center New York, New York MedicalResearch.com: What is the background for this study? Response: The Mediterranean Diet, characterized by higher intakes of plant foods including plant proteins, monounsaturated fat, fish, and lower consumption of animal products and saturated fat, has long been associated with reduced cardiovascular risk and greater longevity, but the molecular mechanisms underlying these associations have not been fully elucidated. We evaluated associations of an Alternate Mediterranean Diet Score, reflective of adherence to this diet pattern and adapted for US populations, and its components with markers of endothelial inflammation directly measured in endothelial cells harvested from women, including oxidative stress, nuclear factor kappa B (NFκB), and endothelial nitric oxide synthase (eNOS) gene expression. (more…)
Author Interviews, Biomarkers, JAMA, Pediatrics / 09.09.2019

MedicalResearch.com Interview with: Elizabeth D. Kantor, PhD MPH Department of Epidemiology and Biostatistics Memorial Sloan Kettering Cancer Center NY, NY MedicalResearch.com: What is the background for this study? Response: There has been recent interest in understanding how exposures in childhood and adolescence relate to later-life health outcomes. Although inflammation is thought to play a role in the etiology of various diseases, little is known about the long-term implications of inflammation in early life. We therefore sought to evaluate how erythrocyte sedimentation rate (ESR), a marker of inflammation, measured among ostensibly healthy men in late adolescence, relates to subsequent cause-specific mortality. We found that men with high inflammation in late adolescence experienced increased mortality due to cancer and cardiovascular disease. (more…)
Author Interviews, Gout, NIH, OBGYNE / 04.04.2019

MedicalResearch.com Interview with: Jack A. Yanovski, MD, PhD Senior Investigator Section on Growth and Obesity, DIR, NICHD National Institutes of Health Hatfield Clinical Research Center Bethesda, MD 20892‐1103 MedicalResearch.com: What is the background for this study? Response: Studies of both mouse models and people suggest that obesity induced inflammation may promote insulin resistance and progression to diabetes. Others have proposed that suppressing this chronic, low level inflammation may slow the onset of diabetes. Nod-like Receptor Family Pyrin Domain Containing 3 (NLRP3) has recently been shown to play a strong role in promoting the inflammatory state in obesity. Colchicine, traditionally used to suppress or prevent inflammation in gout and other disorders is believed to inhibit formation of the NLRP3 inflammasome. Our group hypothesized that colchicine would improve obesity associated inflammation in adults with metabolic syndrome who had not yet developed type 2 diabetes. (more…)
Author Interviews, Dermatology, Lipids / 04.12.2018

MedicalResearch.com Interview with: Wendy Bollag, PhD, FAHA Professor of Physiology VA Research Career Scientist Augusta University, Georgia MedicalResearch.com: What is the background for this study? Response: We have previously shown that the lipid (fat) phosphatidylglycerol (PG) is able to inhibit rapidly growing keratinocytes (skin cells) and promote their maturation. We also found that PG can suppress skin inflammation. Since the common skin disease psoriasis is characterized by inflammation and excessive growth and abnormal maturation of skin cells, we believed that PG might be useful as a treatment. However, the mechanism of its anti-inflammatory effect was unknown. PG in the lung has been found to inhibit inflammation induced by microbes or their components, which work by activating the innate immune system via binding to proteins called toll-like receptors (TLRs); however, psoriasis is not considered to be an infectious disease. We hypothesized that PG would also inhibit inflammation induced by anti-microbial peptides that activate TLRs. Anti-microbial peptides, produced normally by the skin to protect against infection, are known to be excessively up-regulated in psoriatic skin.  (more…)
Author Interviews, Inflammation, Science / 14.06.2018

MedicalResearch.com Interview with: “Basophil” by GreenFlames09 is licensed under CC BY 2.0Jagadeesh BAYRY, DVM, PhD, HDR Scientist CRCN/Associate Professor-INSERM Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1138 Centre de Recherche des Cordeliers PARIS , FRANCE   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Basophils are rare granulocytes that are important for the protection against helminth parasites. In addition, basophils mediate T helper 2 responses, support B cell differentiation, and thus establish a vital link between innate and adaptive immunity. Although rare in number, basophils are implicated in various pathological conditions due to the fact that they undergo rapid activation in response to a wide range of stimuli they receive. These stimuli induce the release of diverse immune mediators including cytokines and mediators of hypersensitivity reactions histamine and leukotriene. Basophils are well known for their pathogenic role in allergic diseases. Recent data also advocate basophils in the pathogenesis of autoimmune and other inflammatory diseases. Therefore, considering the impact of dysregulated functions of basophils on the immune response in various diseases, we deliberated that it is essential to understand the regulatory mechanisms by which basophils are kept in check. Among immunoregulatory cells, CD4+CD25+FoxP3+ regulatory T cells (Tregs) have been widely studied for their role in immune tolerance and in the maintenance of immune homeostasis. Tregs modulate autoimmune and inflammatory responses by exerting direct suppressive effects on various immune cells including dendritic cells, T cells, macrophages, monocytes, B cells, neutrophils, natural killer cells, and mast cells. In view of emerging reports on the role of basophils in various pathological conditions, we investigated if Tregs are able to control the activation and functions of basophils. In contrast to the central dogma on Tregs as immunosuppressors, we discovered that human basophils are refractory to Treg-mediated suppression. On the contrary, we found that Tregs stimulate resting basophils to induce the expression of activation markers CD69, CD203c, and CD13, and release cytokines IL-4, IL-8, and IL-13. Treg-induced activation of basophils involves IL-3 and STAT5 but was not contact-dependent. These results provide evidence of direct positive effects that human Tregs have on basophil activation and reveal a previously unrecognized feature of this cell subset well known for immunosuppressive functions.  (more…)
Author Interviews, Biomarkers, Heart Disease, JAMA, Race/Ethnic Diversity / 04.05.2018

MedicalResearch.com Interview with: Dr. Karl T. Kelsey, MD, MOH Professor of Epidemiology and Pathology and Laboratory Medicine Fellow, Collegium Ramazzini Providence, R.I. 02912 MedicalResearch.com: What is the background for this study? What are the main findings? Response: ​There is a large literature suggesting that the ratio of neutrophils to lymphocytes (the neutrophil to lymphocyte ratio or NLR) in the peripheral blood at the time of diagnosis is robustly predictive ​of outcome in acute cardiovascular disease. We were curious to know if the peripheral blood profile and this ratio was a feature of the disease process, since, to our knowledge, this had not been investigated in a prospective study.  Hence, we used the resources of 2 prospective studies to assess this question, the Jackson Heart Study and the Normative Aging Study.  In both cases, the NLR predicted all cause mortality and, in the Jackson Heart Study, where we had well adjudicated outcomes, the NLR predicted various specific cardiovascular outcomes as well. Interestingly, the outcome was also modified by a well known genetic polymorphism of African origin that results in a relative neutropenia. (more…)
Allergies, Author Interviews, Dermatology, Inflammation, Pediatrics / 07.03.2018

MedicalResearch.com Interview with: elstarNidhi Malhotra PhD Boston Children's Hospital Division of Allergy and Immunology Senior Scientist at Elstar Therapeutics Inc. MedicalResearch.com: What is the background for this study? What are the main findings? Response: Allergies such as Atopic Dermatitis (AD) are rampant in the industrialized nations. Why are we more predisposed to developing hypersensitive reactions to innocuous proteins (allergens) is not well understood. To gain better understanding and to develop better therapies, we need to first delve deeper into how our immune system regulates homeostasis in tissues such as skin. The main cell types that thwart inflammatory reactions are known as regulatory T cells. These cells are generated in thymus and reside in secondary lymphoid tissues but they are also prominent at tissue sites such as in dermal layer of skin. In this study, I focused on understanding how Tregs resident in skin are distinct from the Tregs in secondary lymphoid organs such as lymph nodes (LNs). I uncovered that functioning of Tregs in skin is underpinned by a distinct set of genes. One main gene that I found to be highly expressed in skin Tregs but not in LN Tregs is Rora, which encodes for the transcription factor ROR alpha (RORa). This observation was intriguing as previous studies had elucidated the requirement of RORa in the development of inflammatory type-2 innate lymphoid cells (ILC2s) and it has been considered the antagonizing RORa functioning would curb allergic responses. However, I observed that Tregs require RORa to suppress allergic responses. In particular, RORa regulates the expression of a TNF receptor family member DR3, which binds to the cytokine TL1A. TL1A has a role in enhancing suppressive activity of Tregs while also enhancing type-2 cytokine production from ILC2s. Hence, in the absence of DR3 in Tregs, we believe more TL1A is available to ILC2s resulting in unrestrained allergic responses.  (more…)
Author Interviews, Dermatology, Infections, Johns Hopkins / 09.11.2017

MedicalResearch.com Interview with: Lloyd S. Miller, M.D., Ph.D. Vice Chair for Research, Department of Dermatology Associate Professor of Dermatology, Infectious Diseases, Orthopaedic Surgery & Materials Science and Engineering Faculty Member, Cellular and Molecular Medicine (CMM) and Pathobiology Graduate Programs Johns Hopkins Department of Dermatology Baltimore, MD 21231  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Staphylococcus aureus is a common bacterial skin pathogen and its abundance is greatly increased on affected skin of eczema patients, especially during disease flares. However, how S. aureus induces skin inflammation and exacerbates the skin inflammation is incompletely understood. In this study, we found that S. aureus exposure of mouse skin induced skin inflammation through an inflammatory mediator known as IL-36. (more…)
Alzheimer's - Dementia, Author Interviews, Johns Hopkins, Memory, Mental Health Research / 04.11.2017

MedicalResearch.com Interview with: Keenan A. Walker, PhD Johns Hopkins University School of Medicine Baltimore, MD MedicalResearch.com: What is the background for this study? What are the main findings? Response: There is quite a bit of evidence linking immune function with dementia. For example, several of the risk genes for Alzheimer’s disease are known to play a key role in immune functioning and the regulation of inflammation. We conducted the current study to determine whether systemic inflammation earlier in life might be a risk factor for neurodegeneration decades later. This long temporal window allows us to get closer to understanding causality. That is, which comes first – systemic inflammation or brain volume loss. Using a large community sample, we found that individuals with higher levels of blood inflammatory markers during midlife tended to have smaller brain volumes in select regions and reduced memory ability as older adults. We found the strongest associations between systemic inflammation and brain volume loss in brain regions most vulnerable Alzheimer’s disease. (more…)
Author Interviews, Heart Disease, Inflammation, Nature / 18.04.2017

MedicalResearch.com Interview with: Borja Ibáñez MD Spanish National Centre for Cardiovascular Research Madrid MedicalResearch.com: What is the background for this study? What are the main findings? Response: Acute myocardial infarction (heart attack) is a severe condition responsible for thousands of deaths every year and with important long-term consequences for survivors. Best treatment for acute myocardial infarction is a rapid coronary reperfusion. Upon reperfusion, all inflammatory cells and mediators accumulated in the circulation during the infarction process, enter into the myocardium and causes an extra damage to the heart. Activated neutrophils play a critical role in this damage occurring upon reperfusion. The final size of infarction is the main determinant for mortality and long-term morbidity. The possibility of limiting the extent of infarcted tissue is of paramount importance. Betablockers have been used in patients for more than 4 decades, mainly to treat arrhythmias and high blood pressure. Recently the same group of investigators demonstrated that the very early administration (i.e. during ambulance transfer to the hospital) of the betablocker “metoprolol” was able to reduce the size of infarction in patients. The mechanism by which metoprolol was protective in patients suffering a myocardial infarction was unknown. (more…)
Author Interviews, Gastrointestinal Disease, Inflammation, Microbiome, Nature / 19.03.2017

MedicalResearch.com Interview with: Justin E. Wilson, Ph.D On behalf of the authors Research Assistant Professor - Laboratory of Jenny Ting Department of Genetics Lineberger Comprehensive Cancer Center The University of North Carolina at Chapel Hill Chapel Hill, NC 27599 MedicalResearch.com: Could you provide me with some background on this project? Why did you decide to do this research project? What prior work led up to this latest paper? Response: Previous work from our lab and others discovered two major points about NLRP12: a) NLRP12 suppresses inflammation in response to bacterial components b) NLRP12 provides protection against the inflammatory bowel disease colitis and colitis-associated colon cancer (i.e., Nlrp12-defcient mice have greater colon inflammation and inflammation-driven colon cancer). Therefore, we wanted to know if Nlrp12 was regulating inflammation in the colon by responding to the trillions of intestinal microbes collective referred to as the microbiome. Mounting evidence also indicates that the immune system both responds to and influences the composition of the intestinal microbiome during intestinal health and disease, and we hypothesized that NLRP12 could be one of the important immune components during this process. Moreover, we were also interested in this topic because targeting the microbiome to treat inflammatory disorders and other diseases is an attractive method that has many advantages over immune suppression. (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, Biomarkers, JAMA, NIH, Parkinson's / 26.09.2016

MedicalResearch.com Interview with: Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland MedicalResearch.com: What is the background for this study? Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls. (more…)
Author Interviews, Infections, Inflammation / 07.09.2016

MedicalResearch.com Interview with: David Underhill, PhD Professor of Biomedical Sciences Research scientist, F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute Cedars-Sinai Los Angeles, CA MedicalResearch.com: What is the background for this study? Response: “Innate immunity” is the body’s natural resistance to microbial infection and stands in contrast to “adaptive immunity,” which is the body’s learned response to infection (e.g. antibodies and vaccines). In the standard model of innate immunity that has emerged over the last several decades, scientists have come to understand that the human genome encodes many “receptors” that have evolved as sensors for specific common microbial molecules, such as bacterial or viral DNA or components of bacterial or fungal cell walls. The job of these receptors is to survey the environment (skin, blood, etc.) for potentially dangerous microbes and initiate inflammatory responses if they are found. These activities are essential for defense against infection, and people and animals with defects in these sensors or the responses they trigger can be susceptible to infection. My laboratory has been interested for more than a decade in identifying these innate sensors and the microbial targets that they recognize. In this study, we were looking for the sensor that allows white blood cells (e.g. macrophages and dendritic cells) to detect Gram-positive bacterial cell walls and trigger a specific inflammatory response: secretion of the potent inflammatory mediator interleukin-1β (IL-1β). (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers / 01.09.2016

MedicalResearch.com Interview with: Professor B. Paul Morgan Director, Systems Immunity Research Institute Institute of Infection and Immunity School of Medicine Cardiff University MedicalResearch.com: What is the background for this study? Response: Inflammation is a normal response of the body to infection or injury; however, it is well known that inflammation also has a dark side and when it escapes normal controls can cause disease. Some illnesses, like rheumatoid arthritis, have been known for many years to be caused by rogue inflammation and most of the drugs used to treat work by suppressing the inflammation (anti-inflammatories). More recently, it has become clear that inflammation is behind many other diseases that were previously thought of as diseases of ageing caused by wear and tear and lifestyle - these include heart disease and some brain diseases, notably Alzheimer's disease the commonest cause of dementia. Evidence that inflammation is one of the drivers of disease has come from many sources, including some where it was noticed that people on long-term anti-inflammatory drugs for other reasons appeared to be protected from developing Alzheimer's disease. A problem is that Alzheimer's disease, despite the name, is not a single disease but rather a group of conditions with similar symptoms, and inflammation is likely to be a cause in only some of the patients; further, most of the inflammation might be occurring very early in the disease, even before symptoms are obvious. So, there is an urgent need for a simple test or set of tests that can be used in individuals with the very earliest hints of Alzheimer's disease - mild memory loss - that will pick out those who have brain inflammation and are most likely to develop Alzheimer's disease. It might then be possible to treat this select group with anti-inflammatory drugs that will reduce brain inflammation and slow or stop progression of the disease. (more…)
Author Interviews, Genetic Research, Pediatrics / 25.11.2015

MedicalResearch.com Interview Grant S Schulert MD, PhD Clinical Fellow, Division of Rheumatology Cincinnati Childrens Hospital  Medical Research: What is the background for this study? What are the main findings? Dr. Schulert: Influenza infection causes millions of illnesses annually, but most of those are relatively mild.  In a subset of cases, patients can become critically ill, even if they are relatively young and healthy.  Several previous reports had observed in these critically ill patients features of a hyperinflammatory syndrome known as HLH (hemophagocytic lymphohistiocytosis) or MAS (macrophage activation syndrome).  This hyperinflammation can be triggered by other infections as well as in a subtype of juvenile arthritis, but there is also a familial form occurring in early childhood with known genetic causes.  Our questions with this study were 1) how often are features consistent with HLH/MAS seen in fatal H1N1 influenza infections and 2) do patients with fatal H1N1 infection have genetic mutations associated with HLH/MAS? Our collaborator Paul Harms, MD, and his team at the Michigan Center for Translational Pathology, University of Michigan Medical School identified 16 cases of fatal H1N1 influenza infection.  Based on their clinical features, between 41-88% of these patients could be categorized as having a hyperinflammatory HLH/MAS.  We then used processed tissue samples from the patients for whole exome genetic sequencing, which reads the entire genetic code of every gene in a person. Five patients carried mutations in genes which cause HLH, and several others carried mutations in genes linked to MAS.  This suggests that there may be genetic risk factors for developing fatal hyperinflammatory syndromes in H1N1 infection. (more…)
Author Interviews, Inflammation, Lipids, University of Pennsylvania / 04.08.2015

Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of PennsylvaniaMedicalResearch.com Interview with: Carsten C. Skarke MD Research Assistant Professor of Medicine McNeil Fellow in Translational Medicine Institute for Translational Medicine and Therapeutics Perelman School of Medicine University of Pennsylvania Medical Research: What is the background for this study? What are the main findings? Dr. Skarke: A growing body of publications suggests anti-inflammatory actions of fish oils. These health benefits are proposed to emerge from lipids called specialized pro-resolving mediators, (SPMs), which can be formed from omega-3 polyunsaturated fatty acids found in fish. A limitation to date, though, in this field is that there is little evidence of their formation in humans. And the cases where presence of these lipids is reported in humans, less rigorous analytical approaches, such as enzyme immunoassay (EIA), radioimmunoassay (RIA) or mass spectrometry without internal authentic standards, have been used. Thus, the specific aim for our study was to use state-of-the-art mass spectrometry to identify and quantify these specialized pro-resolving mediators. Several aspects of our study design set us apart from what was done in previous studies.
  • First, we biased our ability to detect SPMs formed in healthy volunteers by giving fish oil in high doses which had been previously shown to influence blood pressure and platelet aggregation under placebo-controlled conditions.
  • Second, we also looked at lower doses of fish oil, those more commonly consumed by the general public, for the formation of SPMs during an acute inflammatory response and its resolution.
  • Third, we relied in our measurements of SPMs on authentic internal standards. These deuterated lipids, d4-resolvin E1 for example, facilitate distinct identification of the naturally formed lipid.
  • And fourth, we achieved very low limit of detection levels, below 10 pg/ml for resolvin E1, for example.
The surprising finding of our studies is that we failed to detect a consistent signal of SPM formation in urine or plasma of healthy volunteers who had taken fish oil. Even more surprising was that we found no alteration in the formation of SPMs during the resolution of inflammation. These results let us question the relevance of endogenous specialized pro-resolving mediators to the putative anti-inflammatory effects of fish oils in humans. (more…)
Author Interviews, Brain Injury, Inflammation / 21.01.2015

Alan I Faden, M.D. David S. Brown Professor in Trauma Professor, Departments of Anesthesiology, Anatomy & Neurobiology, Neurosurgery, and Neurology Director, Center for Shock, Trauma & Anesthesiology Research (STAR) University of Maryland School of MedicineMedicalResearch.com Interview with: Alan I Faden, M.D. David S. Brown Professor in Trauma Professor, Departments of Anesthesiology, Anatomy & Neurobiology, Neurosurgery, and Neurology Director, Center for Shock, Trauma & Anesthesiology Research (STAR) University of Maryland School of Medicine Medical Research: What is the background for this study? What are the main findings? Dr. Faden: Accumulating clinical and pre-clinical research data indicate that traumatic brain injury (TBI) can lead to chronic progressive neurodegeneration. In this regard, most attention has focused on the connections between TBI and with Alzheimer disease (AD) or Chronic Traumatic Encephalopathy (CTE). However, recent epidemiological studies raise questions about the association between TBI and AD, and CTE is likely a less common end-stage result resulting from complex pathobiological changes. In contrast, both older and newer studies underscore that traumatic brain injury can cause chronic neuroinflammation that leads to chronic neurodegeneration. In contrast to AD and CTE, the latter condition appears to be potentially treatable, even long after injury. Our paper critically assesses the mechanisms and treatment of chronic post traumatic neurodegeneration. (more…)
Author Interviews, Breast Cancer, Inflammation / 16.01.2015

Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City MéxicoMedicalResearch.com Interview with: Dr. Jorge Morales-Montor Departamento de Inmunología Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México México City México MedicalResearch: What is the background for this study? Dr. Morales-Montor: Cytokines are highly inducible, secretory proteins that mediate intercellular communication in the immune system. They are grouped in several protein families referred as tumour necrosis factors, interleukins, interferons and colony stimulating factors. In recent years, it has become clear that some of these proteins as well as their receptors are produced in the organisms under physiological and pathological conditions. The exact initiation process of breast cancer is unknown, although several hypotheses have emerged. Inflammation has been proposed as an important player in tumor initiation, promotion, angiogenesis and metastasis, all phenomena in which cytokines are prominent players. The data we have hitherto let us suggest that cytokines play an important role in the regulation of both induction and protection in breast cancer. This knowledge could be fundamental for the proposal of new therapeutic approaches to particularly breast cancer and other cancer related disorders. (more…)
Author Interviews, Inflammation, Pediatrics, Pediatrics / 06.01.2015

MedicalResearch.com Interview with: Professor of Pediatrics Hans Bisgaard, MD, DMSc Copenhagen Prospective Studies on Asthma in Childhood Herlev and Gentofte Hospital, University of Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Prof. Bisgaard: The purpose of this study was to look for a shared risk factor for immunological diseases which make its debut in childhood. During the recent decades a parallel increase in prevalence of immune diseases such as asthma, allergy, inflammatory bowel disease, and type 1 diabetes have been observed in westernized countries. The rate of cesarean delivery has increased in the same period and has previously been associated with the development of some of these diseases. This study takes advantage of the unique and valuable nationwide registry data in Denmark to establish a large population based cohort (2 million term children) with 35 years of follow up (in the period 1977-2012). We found cesarean delivery to be a common risk factor for a range of childhood immunological diseases: asthma, juvenile arthritis, inflammatory bowel diseases, connective tissue disorders, immune deficiencies and leukemia, but with no association to psoriasis, celiac disease, and diabetes type 1. (more…)
Author Interviews, Inflammation, Nutrition / 28.11.2014

Joana Alves Dias, MPH Department of Clinical Sciences in Malmö, Lund University Malmö, Sweden MedicalResearch.com Interview with: Joana Alves Dias, MPH Department of Clinical Sciences in Malmö, Lund University Malmö, Sweden Medical Research: What is the background for this study? What are the main findings? Response: The evidence that chronic inflammation may be in the genesis of diseases such as cardiovascular disease, type-II diabetes, and certain types of cancer is increasing. It is suggested that lifestyle factors such as diet, physical activity, smoking, and alcohol consumption could influence the inflammatory state. Instead of focusing on single nutrient effects, we used a hypothesis-driven approach to food pattern studies, and constructed a diet quality index based on the Swedish Nutrition Recommendations and Swedish Dietary guidelines (DQI-SNR). The DQI-SNR consisted of 6 components. Individuals were assigned 0 when not adhering to a recommendation and 1 when adhering, resulting in total scores ranging from 0 to 6. We classified individuals in low (0 or 1 points), medium (2 or 3) and high (4-6 points) diet quality. We explored the association between the index scores and low-grade inflammation. Our study indicates that adherence to a high quality diet is associated with lower systemic inflammation, as measured by several soluble and cellular biomarkers of inflammation, in middle-aged individuals. In other words, adherence to the general nutrition recommendations could help prevent the development of diseases associated with chronic inflammation. The anti-inflammatory effects of Mediterranean-like diets have been studied extensively, but this study focused on the Swedish dietary habits and recommendations for the Swedish population, and reached similar conclusions. (more…)
Diabetes, Heart Disease / 13.09.2014

Carlos F. Sánchez-Ferrer, M.D., Ph.D. Professor of Pharmacology Universidad Autónoma de Madrid, Spain.MedicalResearch.com Interview with: Carlos F. Sánchez-Ferrer, M.D., Ph.D. Professor of Pharmacology Universidad Autónoma de Madrid, Spain. Medical Research: What are the main findings of the study? Dr. Sánchez-Ferrer: We were studying the possible ways of interaction between high glucose levels, which are found in diabetes mellitus, with vascular damage, which is the most common and devastating consequence of this disease. An intriguing fact is that a very strict control of blood sugar in diabetic patients is not sufficient to avoid the development of such diabetes-induced cardiovascular diseases. We think our results can explain why this is happening. Using cultured smooth muscle cells from the main human artery (aorta) in the presence of high concentrations of extracellular glucose, we observed: 1. In the absence of inflammation, excess glucose in the culture fluid didn’t enter the cells. 2. When extra glucose was forced into the cells, no harm was done in the absence of inflammation. 3. When the inflammation-stimulating protein interleukin-1 (IL-1) was introduced, more glucose entered the cells. 4. With IL-1, the glucose entering the cells was metabolized via chemical pathways that spur escalating inflammation, overwhelming the cells’ ability to counteract it. 5. In the presence of the anti-inflammatory drug anakinra, which blocks the activity of IL-1, the deleterious changes didn’t occur. (more…)