Author Interviews, Genetic Research, Immunotherapy / 22.12.2015
Understanding the role of genomic “dark matter” in the immune response to tumors
MedicalResearch.com Interview with:
Benjamin Greenbaum, PhD
Assistant Professor and
Professor Nina Bhardwaj MD PhD
Hematology and Medical Oncology
Tisch Cancer Institute
Icahn School of Medicine at Mount Sinai
New York, NY 10029
Medical Research: What is the background for this study?
Response: It has recently become clear that, due to epigenetic alterations, tumors transcribe non-coding RNAs that are typically silenced. Often such RNA emanates from the “dark matter” genome. Many of these regions consist of repetitive elements and endogenous retroelements that are rarely transcribed in normal tissue. At the same time, due to immunotherapy, understanding the role of the immune system and immune activation in tumors has become critically important. The activation of specific elements of the innate immune system in a tumor may have either beneficial or detrimental effects for patients. Moreover, recent work has suggested that endogenous element activation can lead to improved immunotherapy outcomes. Therefore, it is critically important to understand the nature of innate immune activation in tumors and what triggers are responsible for these responses.
We have been developing methods to detect abnormal patterns in viral RNA that may indicate activation of the innate immune system. We have found that patterns of motif usage avoided in the evolution of viruses, such as influenza, indicate RNA features that provoke an innate immune response. The innate immune system is capable of sensing motifs in viruses. We tested directly whether these avoided patterns are immunostimulatory.
Dr. Subbotina[/caption]
MedicalResearch.com Interview with:
Ekaterina Subbotina, Ph.D.
Postdoctoral Research Scholar
University of Iowa Carver College of Medicine
Iowa City, IA 52242
Medical Research: What is the background for this study?
Dr. Subbotina: Exercises represent the most natural and effective way to maintain physical and metabolic well-being. Lack of physical activity can contribute to many preventable diseases such as cardiovascular disease, stroke, cancer, diabetes and obesity.
It is known that moderate exercise is beneficial for health but the mechanism of this effect is only partially understood. It becomes more and more evident that skeletal muscles function as an organ that produces and secretes biologically active molecules called myokines. Studies of the biological role and mechanism of action of myokines are important for understanding of muscle function under sedentary and exercise conditions.
Dr. Van Naarden Braun[/caption]
MedicalResearch.com Interview with:
Kim Van Naarden Braun, Ph.D.
Epidemiologist
Developmental Disabilities Branch
National Center on Birth Defects and Developmental Disabilities
Centers for Disease Control and Prevention
Atlanta, GA 30341
Medical Research: What is the background for this study? What are the main findings?
Dr. Van Naarden Braun: Over the past five decades, remarkable improvements have been made in obstetric and neonatal care resulting in significant declines in infant mortality both in the US and abroad, particularly for infants born premature and very low birthweight. Successes in neonatal survival have been met by concerns that the occurrence of developmental disabilities, most notably cerebral palsy, would increase. By monitoring changes over time in the prevalence of cerebral palsy, we can try to understand the impact of these advances further. Our recently published study reported that the 
Dr. Amin Hanjani[/caption]
MedicalResearch.com Interview with:
Sepideh Amin-Hanjani, MD FAANS FACS FAHA
Professor & Program Director
Co-Director, Neurovascular Surgery
Department of Neurosurgery
University of Illinois at Chicago
Past Chair, AANS/CNS Cerebrovascular Section
Medical Research: What is the background for this study? What are the main findings?
Dr. Amin-Hanjani: Posterior circulation strokes account for up to 30% of all ischemic strokes, and atherosclerotic occlusive disease of the vertebrobasilar (VB) is responsible for approximately one third of these cases. Symptomatic atherosclerotic VB occlusive disease is associated with a high risk of recurrent stroke despite medical therapy, in the range of 10-15% within 2 years. There have been advances in treatment options, particularly endovascular angioplasty and stenting, aimed at reverting the blockage; however these procedures themselves carry risks, and are likely to benefit only selected patients who are at highest risk without intervention. Our study, VERiTAS, aimed to determine if measurement of blood flow in the posterior circulation vessels could identify the high risk patients. Flow measurements were performed using the technique of quantitative magnetic resonance angiography (QMRA) relying on standard MR sequences and the commercial software NOVA. These flow measurements were used to designate patients presenting with symptomatic vertebrobasilar disease as flow compromised or not, and patients were then followed for a median of 23 months in a blinded fashion to determine the risk of subsequent strokes. We found that among 72 such patients, only one quarter (18 patients) demonstrated flow compromise on QMRA, but that this group had a significantly higher risk of subsequent stroke at one year, 22% vs only 4% in the other group. The hazard ratio for subsequent stroke was markedly elevated at 11.5 even after adjusting for age and other stroke risk factors.
Dr. Abigail Sewell[/caption]
MedicalResearch.com Interview with:
Abigail Sewell PhD
Assistant Professor of Sociology
Emory University
Medical Research: What is the background for this study?
Dr. Sewell: Ethnoracial minorities report poorer quality of care than do whites. However, one key dimension of health care quality - trust in one's personal physician - indicates mixed associations with race. This study examines five dimensions of the patient-physician relationship independently of each other to identify the aspects of health care where minorities feel most alienated from their doctors.
Medical Research: What are the main findings?
Dr. Sewell: The results of the study show that Blacks and Latinos are less likely to believe that their doctors really care about them as a person than are Whites.
Dr. Jo Freudenheim[/caption]
MedicalResearch.com Interview with:
Jo Freudenheim, PhD
UB Distinguished Professor and Interim Chair
Department of Epidemiology and Environmental Health
School of Public Health and Health Professions
University at Buffalo
Buffalo, NY
Medical Research: What is the background for this study? What are the main findings?
Dr. Freudenheim: There have been a number of studies that have shown an association between periodontal disease and chronic diseases, particularly stroke and heart attacks. There is also some newer evidence that periodontal disease is associated with cancer, particularly cancers of the gastrointestinal tract. Ours is the first large prospective study of periodontal disease and breast cancer.
This was part of a study of more than 70,000 postmenopausal women from throughout the United States, the Women’s Health Initiative. Women provided information about their health and other related factors and then those women were followed to see who developed certain diseases.
We found that women who had been told that they had periodontal disease were more likely to develop breast cancer. In particular, women who were former smokers (quit within the last 20 years) and who had periodontal disease were at increased breast cancer risk. There was a similar increase in risk for current smokers with periodontal disease but it was not statistically significant. (There was a relatively small number of current smokers in the WHI study.)
Christie Riemer[/caption]
MedicalResearch.com Interview with:
Christie Riemer
MD Candidate-Class of 2016
Michigan State University
College of Human Medicine
Medical Research: What is the background for this study? What are the main findings?
Response: Online physician rating sites allow patients to recommend, grade, and publicly comment on physician performance. Despite increases in physician rating website popularity, little information exists regarding the online footprint of dermatologists. Many physicians also remain wary of these websites for fear of malicious reviews.
Our study aimed to investigate the patterns of dermatologist online ratings. We found the average ratings for dermatologists were high, >3.5 stars, on the top 5 websites (ZocDoc, Healthgrades, Yelp, RateMDs, and 
Dr. Leclercq[/caption]
MedicalResearch.com Interview with:
Florence Leclercq, MD, PhD
Department of Cardiology
Arnaud de Villeneuve Hospital
University hospital of Montpellier
Montpellier,France
Medical Research: What is the background for this study? What are the main findings?
Response: Patients with history of coronary artery disease (CAD) are considered as a population with high risk of further coronary events. However, frequent pre-existing ECG changes observed in these patients result in difficulty interpreting new ECG aspects in case of chest discomfort. Furthermore, anxiety frequently induced non-cardiac causes of chest pain in these patients, leading to unjustified admission to cardiology units. Moreover, levels of troponin are usually higher in patients with previous CAD compared to patients without history of angina, resulting in difficulty interpreting baseline values in this population. Conversely, copeptin may be influenced by the severity of myocardial ischemia and resulting endogenous stress, and could be a useful additional marker to exclude severe coronary stenosis in high-risk patients with recent chest pain.
This propective monocentric study evaluates the incremental value of copeptin associated with high-sensitivity cardiac T troponin (hs-cTnT) to exclude severe coronary stenosis in 96 patients with coronary artery disease (CAD) and acute chest pain.
Mean age of patients was 60 +/- 13.8 years and the mean time between chest pain onset and blood samples of copeptin was 4.2 +/-2.7 hours. According to clinical decision, coronary angiography was performed in 71 patients (73.9 %) and severe stenosis diagnosed in 14 of them (14.6%). No ischemia was detected on SPECT imaging (n=25). Among the 69 patients with a negative kinetic of hs-cTnT and a negative baseline copeptin, 5 (7.4%) had a severe stenosis (NPV 0.93; 95% CI: 0.87-0.99), 4 of them related to in-stent restenosis (NPV for exclusion of native coronary stenosis: 0.98; 95% CI: 0.93-1).
We can conclude that in patients with preexisting CAD, and once Acute Myocardial Infarction (AMI) is excluded, copeptin increases the NPV of 
Dr. Tevaarwerk[/caption]
MedicalResearch.com Interview with:
Amye Tevaarwerk, M.D.
Assistant Professor of Medicine
Hematology/Oncology Section
University of Wisconsin School of Medicine and Public Health
Carbone Comprehensive Cancer Center
Wisconsin Institute for Medical Research (WIMR)
Madison, WI
Medical Research: What is the background for this study? What are the main findings?
Dr. Tevaarwerk: These patients were enrolled on a larger clinical trial known as the Symptom Outcomes and Practice Patterns study (SOAPP). SOAPP recruited breast, prostate, colon and lung cancer patients directly during outpatient oncology follow-up visits. All of the patients were recruited between May 2006 and May 2008.
The parent study recruited 3123 patients, of these 680 patients had metastatic disease and 668 had employment data.
Patients were asked if they were working and if there had been a change due to illness. We were able to compare those stably working with those who had changed to "no longer working" and look at factors that associated with this change (age, gender, cancer type, race/ethnicity, time since diagnosis, location of metastatic disease, type of treatment, performance status, number of metastases, symptom burden.)
Dr. Qi Sun[/caption]
MedicalResearch.com Interview with:
Dr. Qi Sun Sc.D
Assistant Professor
Department of Nutrition
Harvard T.H. Chan School of Public Health
Boston, Massachusetts
Medical Research: What is the background for this study? What are the main findings?
Dr. Qi Sun: Potato is considered as a vegetable in certain dietary recommendations, such as in the U.S. MyPlate food guide, whereas in the U.K. national food guide, potato is grouped with cereal as sources of carbohydrates. Potato foods are typically higher in glycemic index and glycemic load, but data are rare regarding whether individual and total potato foods are associated with chronic diseases. In this analysis, we focused on diabetes and found that a higher consumption of total potato foods and individual potato foods, especially french fries, was associated with an increased risk of developing type 2 diabetes in three large cohort studies of ~200 thousand U.S. men and women. In addition, we found that increased potato food consumption over time was associated with a subsequent increased risk of developing diabetes.
Dr. Jennifer Stein[/caption]
MedicalResearch.com Interview with:
Dr. Jennifer Stein MD
Associate Professor
Department of Ronald O. Perelman
Department of Dermatology
NYU Langone Medical Center
Medical Research: What is the background for this FDA decision? What is the issue surrounding tanning beds?
Dr. Stein: This is an important proposal from the FDA because it restricts minors from tanning and requires adults to sign an acknowledgement stating they have been informed about the risks of tanning.
There is clear evidence that indoor tanning significantly increases a person’s risk for skin cancer, including melanoma, a potentially deadly form of skin cancer.
It is important to protect young people from the dangers of tanning beds, especially because many patients report that they started indoor tanning as teens. There are 1.6 million minors using tanning beds every year.
MedicalResearch: What is the problem with tanning? Isn't a tan better than a sunburn?
Dr. Stein: Tanning beds deliver intense amounts of UVA. We know that UVA penetrates deep into the skin and causes mutations that lead to skin cancers, including melanoma. Tanning is a sign that skin cells have been damaged by UV light.
Dr. Zoltan Sarnyai[/caption]
MedicalResearch.com Interview with:
Zoltan Sarnyai, M.D., Ph.D.
Associate Professor of Pharmacology
Head, Laboratory of Psychiatric Neuroscience
Australian Institute of Tropical Health and Medicine (AITHM)
Comparative Genome Centre
Centre for Biodiscovery and Molecular Development of Therapeutics
James Cook University
Townsville, Australia
Medical Research: What is the background for this study?
Dr. Sarnyai: Schizophrenia has long been conceptualized as a disease contributed by the increased activity of the neurotransmitter system that provides dopamine for the brain. All clinically used antipsychotic drugs inhibit dopamine transmission in the brain by blocking dopamine receptors. These drugs have only a limited efficacy on a certain set of symptoms associated with schizophrenia. More recent research has uncovered that abnormal glucose and energy metabolism in the brain may contribute in the development of schizophrenia. This is not altogether surprising considering that our brain is using a disproportionately high amount of glucose to fuel neurotransmission (cell-to-cell communication in the brain), to maintain normal electrical activity of nerve cells and to deal with damaging free oxygen radicals. Therefore, even relatively small changes in the machinery that is required to provide energy for the brain cells can have very significant impact on brain function. In fact, recent studies have identified altered expression of genes and proteins that are responsible for enzymatic breakdown of glucose and proper handling of the metabolites to create the energy-rich molecule ATP. In addition, recent research shows decreased number and impaired function of the mitochondria, the powerhouses of the cell, in the brain of individuals with schizophrenia.
These recent results that show abnormal energy metabolism in schizophrenia raise the possibility of targeting metabolic pathways for therapeutic benefit in this condition. Ketogenic diet provides and alternative source of energy to the brain through fatty acids. Furthermore, since this diet is very low in carbohydrates, almost all the energy needs of the cells comes from breaking down fat (fatty acids) as opposed to glucose. This can circumvent the classic glucose metabolic pathways that maybe impaired in the disease. Also, breaking down fatty acids produces 40% more of the energy-rich molecule ATP than breaking down the carbohydrate glucose. Altogether, ketogenic diet may provide extra energy and can help neurotransmission in the brain, leading to the improvement of neurobiological processes underlying schizophrenia.
Dr. Sandra Wilks[/caption]
MedicalResearch.com Interview with:
Dr Sandra A. Wilks PhD
Senior Research Fellow
IfLS Knowledge Mobilisation Fellow in Healthcare Technologies
Faculty of Natural and Environmental Science & Faculty of Health Sciences
Centre for Biological Sciences,
University of Southampton,
Southampton, UK
Medical Research: What is the background for this study? What are the main findings?
Dr. Wilks: The use of indwelling Foley urinary catheters for extended periods of time results in high risks of urinary tract infections (UTI) and catheter blockages. Blockages are often caused by the presence of Proteus mirabilis, a urease-producing bacterium which results in an increase of the urine pH and the development of crystalline biofilms. Biofilms develop when bacteria attach to a surface, forming a community structure, held together by extracellular polymeric substances (EPS). Once in a biofilm, bacteria exhibit high resistance to the action of antibiotics and are protected by other stress factors. The crystalline biofilms resulting from the presence of Proteus are highly complex environments and cause complete blockage of the catheter within days. Such blockages cause pain and trauma for patients, and result in high demands on healthcare resources.
In this study, we have used an advanced microscopy technique (episcopic differential interference contrast, EDIC microscopy developed by Best Scientific) to track the development of these crystalline encrustations on two commonly used catheter materials; silicone and hydrogel latex. We have identified four distinct stages to crystalline biofilm formation;
Prof. Schmid-Schonbein[/caption]
MedicalResearch.com Interview with:
Geert W. Schmid-Schonbein, Ph.D.
Distinguished Professor and Chairman
Department of Bioengineering
Adjunct Professor in Medicine
University of California San Diego
Medical Research: What is the background for this study? What are the main findings?
Dr. Schmid-Schonbein: Most approaches to control/reduce body weight focus on reducing food quantity, improving quality and promoting daily activity. These approaches, effective in the short term, only yield modest weight control. Weight management strategies recommended in the past have not significantly diminished the current trend towards childhood and adolescence obesity.
We developed and tested an alternative approach to control weight gain in healthy individuals to reduce the risk for development of obesity and diabetes complications. The essence is to:
“Eat deliberately slow AND stop eating when you feel no longer hungry”.
The approach avoids any form of special diet, uses no drugs, can be adopted for a lifetime and used in any ethnic environment. Children in a Mexican School in Durango were instructed by a pediatrician to learn to eat deliberately slow and to stop eating when the satiety reflex sets in, i.e. the moment when the feeling of hunger has disappeared.
They were instructed to:
Dr. Jochen Reinöhl[/caption]
MedicalResearch.com Interview with:
Dr. Jochen Reinöhl
Consultant and Head of the ISAH team (intervention for structural and congenital cardiovascular diseases)
Department of Cardiology and Angiology I (Medical Director: Prof. Dr. Christoph Bode)
University Heart Center Freiburg ∙ Bad Krozingen
Medical Research: What is the background for this study? What are the main findings?
Dr. Reinöhl: Aortic valve stenosis is a medical condition with very high short-term mortality. Previously its only treatment – therefore the gold standard – consisted of surgical valve replacement. Since 2007 transcatheter aortic-valve replacement (TAVR) can be considered alternative. Its impact on clinical practice, however, is largely unknown.
TAVR numbers rose from 144 in 2007 to 9,147 in 2013, whereas surgical aortic-valve replacement procedures only marginally decreased from 8,622 to 7,048. For both groups in-hospital mortality, as well as, the incidence of stroke, bleeding and pacemaker implantation (but not acute kidney injury) decreased.
Dr. Li Ding[/caption]
MedicalResearch.com Interview with:
Dr. Li Ding PhD
Director, Medical Genomics group
McDonnell Genome Institute
Department of Medicine
Washington University in St. Louis
St. Louis, Missouri
Medical Research: What is the background for this study? What are the main findings?
Dr. Li Ding: Next-generation sequencing technologies have provided unprecedented opportunities for building a comprehensive catalog of point mutations, simple insertion and deletion mutations (indels) and structural variants in human cancers. Although significant progress has been made for documenting these common events through studies from individual research labs and large consortiums, there has been little progress in the discovery of complex indels after the transition from Sanger sequencing to NGS technologies. It is well known in the scientific community that indel detection using short next generation sequencing reads is a challenging problem. Our study, for the first time, directly addresses complex indel detection that has been barely touched in the cancer field. More importantly, our analysis discovered 285 complex indels in cancer genes such as PIK3R1, GATA3, and TP53, revealing an unexpected high prevalence of these events in human cancers.
Dr. Carlos del Rio[/caption]
MedicalResearch.com Interview Questions
Carlos del Rio, MD
Chair, HIV Medicine Association
Department of Medicine
Hubert Professor and Chair of the Department of Global Health at the Rollins School of Public Health Professor of Medicine in the Division of Infectious Diseases
Emory University School of Medicine
MedicalResearch.com Editor's note: Dr. Carlos del Rio discusses the statement from the Infectious Diseases Society of America (IDSA), HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS) regarding the news that Express Scripts is taking steps to improve access to obtaining pyrimethamine for patients with toxoplasmosis.
Medical Research: What is the background for this Express Scripts announcement?
Dr. del Rio: The HIV Medicine Association (HIVMA) and the Infectious Diseases Society of America initially heard from our members (ID and HIV clinicians) in August about the 5000% price increase in Daraprim® (from $13.50 to $750 per tablet) following Turing Pharmaceuticals’ acquisition of the rights to distribute Daraprim® from Impax Laboratories, Inc.
Dr. Stammen[/caption]
MedicalResearch.com Interview with:
Lorette A. Stammen, MD
Department of Educational Development and Research
Faculty of Health, Medicine, and Life Sciences
Maastricht University, Maastricht
The Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. Stammen: Research indicated that we can improve the quality of care and reduce the health care costs by eliminating health care waste. Health care waste are health care services that are not beneficial to patients. There are many ways to reduce health care waste, like through insurance and government policies modification, but we were especially interested in how the medical expertise of physicians could improve high-value, cost-conscious care. We conducted a systematic review with the aim of understanding how training programs cause learning among physicians, residents and medical students. We analyzed 79 articles using realist review method and found three important factors that facilitate the learning of physicians (in training).
Dr. Minneci[/caption]
MedicalResearch.com Interview with:
Dr. Peter C. Minneci, M.D., MHSc
Center for Innovation in Pediatric Practice
Assistant Professor, Pediatric Surgery
The Ohio State's Wexner Medical Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Minneci: Non-operative management of uncomplicated appendicitis has been shown to safe and effective studied in several international adult trials. To be a reasonable treatment alternative to urgent appendectomy, non-operative management of appendicitis in children must have a clinically acceptable success rate with minimal harm in patients that fail and subsequently undergo appendectomy. We performed a prospective single-institution patient choice trial allowing the families of children with acute uncomplicated appendicitis to choose between urgent appendectomy or non-operative management with antibiotics alone. We enrolled 102 patients, with 65 choosing surgery and 37 choosing non-operative management with antibiotics alone. Non-operative management had an in-hospital success rate of 94%, a 30-day success rate of 89%, and a 1-year success rate of 76%. Compared to the surgery group, patients managed non-operatively reported higher quality of life scores at 30 days and had significantly fewer disability days and lower costs, with no differences in the rates of complicated appendicitis or treatment-related complications at 1 year of follow-up. With this being said, there are some cases that I have read about where doctors have failed to diagnose patients for Appendicitis even after they have complained about having a number of the symptoms associated with it. Following this, some patients have even contacted companies like 
Dr. Rashmi Patel[/caption]
MedicalResearch.com Interview with:
Dr. Rashmi Patel
MA (Cantab) MA BM BCh PGDip (Oxon) MRCPsych
Psychiatry
King's College Londo