Author Interviews, Brain Cancer - Brain Tumors, Genetic Research, Pediatrics, University of Pennsylvania / 04.02.2016

MedicalResearch.com Interview with: Dr. Adam C. Resnick, Ph.D Assistant Professor of Neurosurgery Faculty, Abramson Cancer Center Director of Children's Brain Tumor Tissue Consortium Division of Neurosurgery Director, CHOP/PENN Department of Neurosurgery Brain Tumor Tissue BiorepositoryDirector for Neurosurgical Translational Research, Division of Neurosurgery Children's Hospital of Philadelphia   Payal Jain, PhD Candidate Division of Neurosurgery, Children's Hospital of Philadelphia Department of Neurosurgery Cell and Molecular Biology Graduate Group Gene Therapy and Vaccines Program Perelman School of Medicine University of Pennsylvania Philadelphia, Pennsylvania   Medical Research: What is the background for this study? What are the main findings? Response: This study originates from our long-standing interest in studying pediatric low-grade gliomas (PLGGs), which are the most commonly diagnosed brain tumor in children. While several PLGGs have been found to harbor mutations/gene fusions driving the mitogen-associated protein kinase (MAPK) pathway leading to clinical trials testing MAPK inhibitors, these tumors remain poorly categorized and not enough is known about specific genetic mutations driving different tumor sub-types and the potential for specific targeted therapeutics. Our current study encompasses analysis of the largest combined genomic dataset of pediatric low-grade gliomas samples.  In doing this we, identified the MYB-QKI gene fusion, a non-MAPK related event, as the common genetic event driving a rare PLGG sub-type, called angiocentric gliomas. We have reported a novel tri-partite mechanism by which MYB-QKI mediates its oncogenic effect, this being the first report of a single gene rearrangement utilizing three different paths to cause cancer.
  • First, this gene rearrangement activates MYB, which is a proto-oncogene that is normally not expressed in the developed brain.
  • Second, we found that the rearrangement leads to translocation of QKI-related enhancers close to MYB’s promoters, thereby driving MYB-QKI expression in these tumors. Furthermore, MYB-QKI can also regulate its expression in a positive feedback loop.
  • Third, the tumor suppressor activities of QKI are disrupted in MYB-QKI. Such collaboration of genetic and epigenetic dysregulation in a single genetic rearrangement has previously not been reported.
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Author Interviews, Genetic Research, JAMA, Schizophrenia / 04.02.2016

MedicalResearch.com Interview with: Hannah J. Jones, PhD Centre for Academic Mental Health, School of Social and Community Medicine, Medical Research Council (MRC) Integrative Epidemiology Unit University of Bristol, Bristol, England MedicalResearch: What is the background for this study? What are the main findings? Dr. Jones: Schizophrenia is a highly heritable condition characterised by relatively diverse symptoms and frequent comorbid disorders. However, at present we don’t know how genetic risk for schizophrenia is expressed in children/adolescents in the general population. To investigate this, we studied data from individuals within the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort which consists of approximately 14,000 children born to women living in the former Avon Health Authority area in England with an expected delivery date from April 1, 1991, to December 31, 1992. We used genetic data from approximately 5,000 ALSPAC children and measures from adolescence relating to psychopathology to determine whether genetic risk for schizophrenia is associated with variation in psychotic experiences (e.g. delusions, hallucinations), negative symptoms (e.g. apathy, withdrawal), depressive disorder and anxiety disorder during this developmental period. We derived a score of genetic risk for schizophrenia in each individual within our study. This score is normally distributed such that most people have some genetic risk and a few people have very high or very low genetic risk. We found very weak evidence of an association between genetic risk for schizophrenia and psychotic experiences in adolescence and no evidence of an association with depressive disorder. However, we found strong evidence of association between genetic risk for schizophrenia and negative symptoms and anxiety disorder.  (more…)
Author Interviews, Tobacco Research / 04.02.2016

MedicalResearch.com Interview with: Dr. Kate Frazer University College Dublin School of Nursing, Midwifery & Health Systems Dublin , Ireland MedicalResearch: What is the background for this study? What are the main findings? Dr. Frazer: The review is an update of a 2010 Cochrane systematic review publication ‘Legislative smoking bans for reducing secondhand smoke exposure, smoking prevalence and tobacco consumption’. The 2010 review identified
  • Evidence of secondhand smoke exposure and reduced cotinine levels after the implementation of legislative smoking bans.
  • Evidence of reduced admissions for acute coronary syndrome.
  • Limited evidence of an impact on active smoking rates.
The update was undertaken because more countries have since implemented legislative smoking bans since the review was published in 2010 and the body of research was growing in the intervening period. The new review, published 4th February 2016, presents evidence from 77 observational studies in 21 countries. MedicalResearch: What are the main findings? Dr. Frazer: There is consistent evidence identifying reduced admissions in the post ban period for acute coronary syndrome/ acute myocardial infarction in 33 of 43 studies. There is evidence of reduced mortality from smoking related illnesses in 8 out of 11 studies. There is evidence of reduced admissions for asthma and chronic obstructive pulmonary disease, but the evidence of reduced admissions was not consistent in all studies. There is evidence of an impact on perinatal health outcomes including low birth weight and risk of pre term birth, but the evidence was not consistent in all studies. The evidence of an impact of legislative smoking bans on active smoking and tobacco consumption is not consistent. There have been reductions in smoking rates. The impact of the ban on reducing admissions was observed in smokers and in non-smokers. (more…)
Author Interviews, CDC, Flu - Influenza, OBGYNE, Vaccine Studies / 04.02.2016

MedicalResearch.com Interview with: Ikwo Oboho, MD, ScMLCDR United States Public Health Service Medical Epidemiologist, Centers for Disease Control and PreventionPriority Populations Treatment Team| HIV Care & Treatment Branch | Division of Global HIV/TB Atlanta, GA 30333 MedicalResearch.com: What is the background for this study? Dr. Oboho: ·Pregnant women with flu are at high risk of serious illness and complications, including death. The study is based on data gathered from a nationwide flu surveillance network that includes 14 states. The analysis focused on pregnant women hospitalized with laboratory-confirmed flu over four recent flu seasons, from 2010 to 2014. MedicalResearch.com: What are the main findings?  Dr. Oboho: ·       During the study period, 865 pregnant women were hospitalized with flu. Sixty-three of these patients, or about 7 percent, had severe illness.
  • After adjusting for underlying medical conditions, vaccination status, and pregnancy trimester, we found that early treatment with the antiviral drug oseltamivir was associated with a shorter hospital stay.
  • Among pregnant women with severe flu illness who were treated early with oseltamivir — within two days of the start of symptoms — the median length of stay was about five days shorter compared to hospitalized pregnant women with severe flu illness who were treated later
  • Pregnant women who were hospitalized with severe cases of flu illness were half as likely to have been vaccinated as women with non-severe illness.
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Allergies, Asthma, Author Interviews, JAMA / 04.02.2016

MedicalResearch.com Interview with: Prof Dr. Dr. h.c. Claus Bachert Head Upper Airways Research Laboratory (URL) Chief of Clinics ENT-Department University Hospital Ghent Ghent, Belgium Medical Research: What is the background for this study? What are the main findings? Prof. Bachert: Chronic sinusitis with nasal polyposis represents mucosal inflammation, and polyps in the nasal cavity and sinuses, which result in long-term symptoms of nasal obstruction and congestion, reduction in or loss of sense of smell, and loss of quality of life. Patients with nasal obstruction or congestion have a two-fold higher risk of sleep dysfunction, increased fatigue, and decreased work productivity. About 40 percent of chronic sinusitis with nasal polyps patients develop asthma, which often is non-allergic late-onset disease. Treatment options consist of nasal and systemic glucocorticosteroids; long-term or repeated treatment with oral GCS carries a great risk of side effects in these patients. Surgery of the sinuses is another option, but recurrence of polyps is frequent. Further treatment options are highly needed. About 85% of nasal polyps represent a type 2 inflammation, with increased eosinophils and IgE formation. Dupilumab is an investigational therapy that inhibits signaling of IL-4 and IL-13, two key cytokines required for type 2 (Th2) immune responses. Dupilumab has been successfully administered in patients with asthma and atopic dermatitis. The current randomized, double-blind, placebo-controlled group study enrolled 60 adult patients with chronic sinusitis with nasal polyposis refractory to intranasal corticosteroids at 13 sites in the United States and Europe. Following four weeks of mometasone furoate nasal spray (MFNS) run-in, patients in the study received 300 milligrams (mg) of dupilumab or placebo once per week subcutaneously for 16 weeks, after an initial loading dose of 600 mg. All patients in the study continued to receive daily MFNS. Eligible patients had bilateral nasal polyposis and showed chronic symptoms of sinusitis, despite treatment with an intranasal corticosteroid for at least two months. Fifty-eight percent of patients in the study had received prior nasal surgery for their condition.  ​ We found that dupilumab treatment was associated with significant improvements in endoscopic, clinical, radiographic, and pharmacodynamic end points after 16 weeks. Significant improvements in quality of life and in major symptoms, such as sense of smell, nasal congestion, and nocturnal awakenings,were reported. In those patients with asthma, also lung function and asthma control were significantly better with Dupilumab compared to placebo. Dupilumab was generally well tolerated, and no serious adverse events were considered to be related to dupilumab.​ (more…)
Accidents & Violence, Author Interviews / 03.02.2016

MedicalResearch.com Interview with: Erin Grinshteyn, PhD Assistant Professor University of Nevada-Reno School of Community Health Science Medical Research: What is the background for this study? What are the main findings? Dr. Grinshteyn: Gun deaths are a serious public health issue in the United States. This paper compared the US to 22 other high-income nations, and found that Americans are ten times more likely to be killed by a gun than their counterparts in the developed world. Gun homicide rates are 25 times higher in the U.S. and, while the overall suicide rate is on par with other high-income nations, the U.S. gun suicide rate is eight times higher. Ninety percent of women, 91% of all children aged 0 to 14 years, and 92% of youth aged 15 to 24 years who were killed by firearms were in the United States. (more…)
Author Interviews, Technology, Zika / 03.02.2016

MedicalResearch.com Interview with: Christopher Bibbs Anastasia Mosquito Control District Florida Medical Research: What is the background for this report? Mr. Bibbs: In vector management, the uphill battle is always against the mosquito. And of those, the anthropophilic Yellow Fever mosquito, Aedes aegypti, has become established world-wide as a vector of several emergent diseases. Historically, these mosquitoes carried Yellow Fever and to this day still carry Dengue. Chikungunya, a newly established virus in the Caribbean, has joined the western hemisphere since 2014. And most recently, Zika virus made its way to Brazil and others in South America during 2015. This mosquito thrives in the United States as well, and should a traveler visit a country suffering from these disease and return home sick they risk passing it along to the representative mosquito in your home country. In order to manage these risks, vector management programs employ an integrated approach using multiple techniques and surveillance tools. But oft-neglected are what is available over-the-counter to consumers wanting relief. One such tool is called "spatial repellents." By vaporizing a minute amount of chemical into the air, it creates a flight barrier to the mosquito. The mosquito, upon encountering this vapor, will become disoriented and leave the area, thusly reducing bite contact. But as yet these tools are exclusively considered as repellent. But is that all they do?   (more…)
Author Interviews, Compliance, HIV, Lancet / 03.02.2016

MedicalResearch.com Interview with: Dr Marcel Yotebieng, PhD Department of Epidemiology Ohio State University, 304 Cunz Hall Columbus, OH Medical Research: What is the background for this study? What are the main findings? Response: With the current World Health Organization recommended treatment for the prevention of mother-to-child HIV transmission (PMTCT), the risk of transmission of HIV from an infected mother to her baby can be cut from 35-45% to less than 5% in breastfeeding population and <1% in non-breastfeeding population. But in sub-Saharan Africa where over 90% of HIV-infected pregnant women worldwide live, transportation costs and opportunity costs to attend regular clinic visits (to collect drugs) have been identified as important barriers to PMTCT. The provision of economic incentives has the potential to help women overcome these economic barriers. In addition, by creating immediate rewards that “nudge” individuals towards positive health behaviors, financial incentives can also address psychological barriers to health-seeking behavior of HIV-infected pregnant and breastfeeding women. This is the first study to use small cash incentives to encourage women to attend clinic visit and received available PMTCT care. We found that, among newly diagnosed HIV-infected women, small, incremental cash incentives resulted in increased retention along the  prevention of mother-to-child HIV transmission cascade and uptake of available services. (more…)
Author Interviews, Diabetes, Lifestyle & Health / 03.02.2016

MedicalResearch.com Interview with: David Drozek, D.O. Assistant Professor of Surgery Ohio University Heritage College of Osteopathic Medicine Athens, Ohio 45701 Medical Research: What is the background for this study? Response: Half of the U.S. population has diabetes or prediabetes.  The rate is even higher in Appalachia.  As a society, we cannot sustain this level of disease.  It exacts a heavy toll on our productivity and our health care costs. Current approaches to diabetes, primarily with medication, are not sufficient.  More attention needs to be placed on the underlying cause of diabetes, and its traveling partners, overweight / obesity, heart disease and many common cancers.  That cause is our lifestyle.  Medical Research: What are the main findings? Response: As has been demonstrated in many other studies of lifestyle modification programs, chronic illnesses, like diabetes, can actually be reversed, and in some cases, even cured, by instituting a plant-based, whole food diet, increased physical activity and stress management techniques.  Our study reinforces that this is possible, even in a rural, poverty stricken region, when people are ready to make healthy changes.  Our study participants, on average, lost weight, and improved their blood sugar, lipid panel and blood pressure, by participating in The Complete Health Improvement Program (CHIP), a lifestyle medicine program. (more…)
Author Interviews, Genetic Research, JAMA, Pediatrics, Surgical Research / 03.02.2016

MedicalResearch.com Interview with: Silje Steinsbekk PhD Associate Professor Dept. of Pschology Norwegian University of Science and Technology  Medical Research: What is the background for this study? Dr. Steinsbekk:  More than every third American child is overweight or obese. Childhood obesity is associated with multiple negative health outcomes such as metabolic syndrome and hypertension, as well as mental health problems, reduced self-esteem and impaired quality of life. Further, overweight and obesity tend to persist from childhood into adulthood, and the risk of adult overweight increases the longer a child has been overweight. Identifying modifiable factors contributing to the development and continuity of unhealthy weight is therefore needed. Genome-wide association studies (GWAS) have identified genetic risks for obesity and these genetic risks have shown to influence development of obesity partly by accelerating weight gain in childhood. Identification of mechanisms through which genetic risks for obesity accelerate weight gain in childhood can therefore provide insight into the developmental pathogenesis of obesity and thus inform intervention. Cross-sectional studies suggest appetite traits as a candidate mechanism. Appetite traits may therefore be targets of intervention to protect children against the effect of genetic predispositions to develop obesity. However, such a preventive approach presupposes that appetite traits indeed transmit the genetic effect upon later development of obesity. Notably, cross-sectional studies cannot establish whether appetite traits precede the development of obesity or are caused by it—a critical piece of information for clinicians seeking treatment targets to prevent childhood obesity. We therefore aimed to test whether genetic risk for obesity was associated with rapid childhood BMI growth and if this genetic effect was mediated by appetite traits, following a representative sample of Norwegian children from age 4 to 8. (more…)
Author Interviews, OBGYNE, Rheumatology, Stanford / 03.02.2016

MedicalResearch.com Interview with: Dr. Julia Fridman Simard ScD Assistant Professor Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden Division of Epidemiology, Department of Health Research & Policy Division of Immunology & Rheumatology, Department of Medicine Stanford School of MedicineDr. Julia Fridman Simard ScD Assistant Professor Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden Division of Epidemiology, Department of Health Research & Policy Division of Immunology & Rheumatology, Department of Medicine Stanford School of Medicine  Medical Research: What is the background for this study? What are the main findings? Dr. Simard: A number of studies have shown that women with lupus who get pregnant have more complications and adverse outcomes, although the methodologies across studies vary considerably. Using population-based data we were able compare the occurrence of these pregnancy complications in mothers with lupus to pregnancies from the general population. We were also interested in whether women in our data set who first presented with lupus up to five years post-partum had more pregnancy-related adverse events. Our descriptive study showed that preterm delivery, infant infection, and preeclampsia were more common in the first singleton pregnancies of women with lupus compared to the general population.  These outcomes were also observed more often among women who appeared to present with lupus up to five years post-partum. (more…)
AACR, Author Interviews, Cancer Research, Lymphoma / 03.02.2016

MedicalResearch.com Interview with: Theresa Keegan, PhD, MS Associate Professor Division of Hematology and Oncology UC Davis Comprehensive Cancer Center Sacramento, California 95817 Medical Research: What is the background for this study? What are the main findings? Dr. Keegan: This study expanded upon our earlier work examining survival among the young population diagnosed with Hodgkin lymphoma, which can be cured about 90 percent of the time with it is diagnosed at its earliest stages.  We tracked 9,353 patients ages 15-39 who were diagnosed with Hodgkin lymphoma between 1988 and 2011. Using California Cancer Registry data, we examined the impact on survival of socio-demographic characteristics such as race/ ethnicity, neighborhood socioeconomic status (SES), health insurance, the types of treatment patients received and whether they were diagnosed with subsequent cancers. We found that insurance coverage, neighborhood socioeconomic status (SES) and the types of treatment provided patients all played a role in survival.  Young adults diagnosed with early-stage Hodgkin lymphoma were twice as likely to die if they resided in a lower SES neighborhood. They were also twice as likely to die if they had public health insurance or were uninsured, whether they were diagnosed at an early stage or late stage. While there were improvements in survival over time, disparities in survival persisted for some racial/ethnic groups. African American patients were 68 percent more likely to die of their disease than non-Hispanic white patients, regardless of stage at diagnosis. Hispanic AYA patients diagnosed at a late stage were 58 percent more likely than non-Hispanic white patients to die of Hodgkin lymphoma; there was not a significant disparity for Hispanic patients diagnosed at an early stage. (more…)
Alzheimer's - Dementia, Author Interviews, Blood Pressure - Hypertension, NIH / 03.02.2016

MedicalResearch.com Interview with: Dr. Juan M. Saavedra, MD and Dr. Abdel Elkahloun PhD Comparative genomics and Cancer Genetics Branch National Human Genome Research Institute, National Institutes of Health, Bethesda, MD MedicalResearch: What is the background for this study? What are the main findings? Response: Alzheimer’s disease is the most frequent age-related dementia, a progressing, devastating illness without effective treatment. By the time it is diagnosed, major and irreversible cell injury has already occurred. It is therefore imperative to identify therapeutic agents effective against early, pre-symptomatic injury mechanisms and risk factors increasing vulnerability the disease. We focused on a class of compounds blocking receptors for Angiotensin II, the Angiotensin Receptor Blockers (ARBs). These compounds are commonly used for the treatment of hypertension, a major risk factor for Alzheimer’s disease. We and others have found that in addition to their cardiovascular benefits, ARBs are strongly neuroprotective. The present study was designed to explore in depth the neuroprotective effects of one member of the ARB class, candesartan. To this effect we cultured neurons extracted from the rat brain. These neurons were exposed to high concentrations of glutamate, a recently identified early injury mechanism in Alzheimer’s disease. We found that candesartan prevented glutamate-induced neuronal injury. We conducted in-depth examination of our results by genome-wide expression profile analysis. We found that candesartan normalized glutamate-induced alterations in expression of hundreds of genes, including many involved in neuronal inflammation, cardiovascular disease, diabetes and alterations in amyloid metabolism a hallmark for Alzheimer’s disease. This was evidence of direct neuroprotective effects of relevance for this disorder. When we compared our results with published databases obtained from autopsy samples from Alzheimer’s disease patients, we found impressive correlations. The expression of more than 400 genes altered by glutamate and normalized by candesartan in our cultures was similarly changed in the Alzheimer’s databases. The conclusion was that our cell culture results represented alterations found in the human condition. Our observations provide novel evidence of neuroprotection from early mechanisms of injury in Alzheimer’s disease and support testing candesartan in controlled clinical studies including individuals at the early stages of the illness, to unequivocally demonstrate their therapeutic effect. (more…)
Author Interviews, Exercise - Fitness, Heart Disease, Lifestyle & Health / 02.02.2016

MedicalResearch.com Interview with: Gabriel E. Shaya MS University of Miami Miller School of Medicine MD/MPH Candidate 2016 Medical Research: What is the background for this study? Response: High exercise capacity has been established as an important protective factor against a wide array of poor health indicators and outcomes including cardiovascular morbidity and mortality. Most of the studies assessing the association of exercise capacity and cardiovascular outcomes have done so over an extended period of followup, however, whether high exercise capacity may influence the risk of early mortality following a first myocardial infarction has not been investigated. This is the question that we sought to answer in our study. Medical Research: What are the main findings? Response: Our study found that high exercise capacity was associated with statistically significant and clinically meaningful risk reductions in mortality in the short-term following a first myocardial infarction. Achieving the highest category of fitness in our cohort was associated with as much as a 60% mortality risk reduction relative to those in the least fit category, and similar magnitudes of benefit were observed to persist up to 1 year after a myocardial infarction. Importantly, the greatest risk reductions were observed when comparing the least fit patients to those with moderate fitness, suggesting that those with relatively low fitness may stand to benefit most from even just modest fitness improvements. (more…)
Author Interviews, Hospital Acquired / 02.02.2016

MedicalResearch.com Interview with: Leonard Mermel, DO, ScM, AM (Hon), FSHEA, FIDSA, FACP  Professor of Medicine, Warren Alpert Medical School of Brown University Medical Director, Dept. of Epidemiology & Infection Control, Rhode Island Hospital Adjunct Clinical Professor, University of Rhode Island College of Pharmacy  Medical Research: What is the background for this study? What are the main findings? Dr. Mermel:  There is increasing concern in the US and abroad regarding multi-drug resistant organisms (MDROs), particularly bacteria resistant to carbapenem antibiotics.  Concern has been raised about MDRO colonization in high-risk populations, such as nursing home patients and transmission between nursing home and acute care hospitals.  Little data exists concerning the incidence of GI tract colonization of such pathogens in nursing home patients at the time of acute care hospitalization.  We used rectal swabs on 500 hospital admissions from nursing homes to assess carriage of bacteria resistant to carbapenem antibiotics.  We found carbapenem-resistant or carbapenemase-producing gram-negative bacteria in 23 of the 500 (4.6%) hospital admissions from nursing homes, which included 7 carbapenemase-producing CRE bacteria (1.4%).  The latter bacteria produce an enzyme that breaks down the carbapenem antibiotic and the resistance genes are located on mobile genetic elements.  We also found that use of gastrostomy tubes was associated with fecal carriage of gram-negative bacteria with detectable carbapenem resistance. (more…)
Author Interviews, Genetic Research, JAMA, Pediatrics, Weight Research / 02.02.2016

MedicalResearch.com Interview with: Profa. Patrícia Pelufo Silveira, MD, PhD Universidade Federal do Rio Grande do Sul Brazil Medical Research: What is the background for this study? What are the main findings? Response: Previous studies have shown that women who carry a certain gene variant (namely the 7-repeat allele of the dopamine type 4 receptor) have increased risk for obesity, especially if they also suffer from eating disorders. We have also demonstrated that girls who have this gene variant prefer to eat more fat when allowed to choose. However, for some neuropsychiatric conditions, this gene was shown to function as a “plasticity gene”. That is to say that being a carrier makes the individual more or less vulnerable to the disease, depending if the environment in which the person lives is bad (more risk) or good (less risk for the disease). This is called the “differential susceptibility” model. Therefore, in this paper, we wondered if the above described higher fat intake already reported in 7-repeat girls could be modified by the social environment in which they are raised. We saw that if a girl has the gene variant and is raised in a poorer environment, she is more likely to prefer to eat fat in her diet as we knew. However, if she has the gene variant but is raised in a better socioeconomic environment, she actually eats less fat in her regular diet compared to her counterparts who do not carry the gene variant. This is important because we change the focus from the gene (previously "blamed" for increasing fat preference and obesity as the years pass by) to the environment, as the genetic association will increase or decrease the risk according to the conditions in which the child is raised. (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Lancet, Pediatrics, Radiation Therapy / 02.02.2016

MedicalResearch.com Interview with: Dr. Torunn Yock, MD Director, Pediatric Radiation Oncology Associate Professor, Harvard Medical School Radiation Oncology Quality Assurance Massachusetts General Hospital, Proton Center Boston, MA Medical Research: What is the background for this study? Dr. Yock: Proton radiotherapy is a highly targeted form of radiation therapy that can spare normal tissues better than standard x-ray/photon based radiotherapy. Because, all side effects from radiotherapy come from radiation dose to normal healthy tissues, it is widely believed that proton radiotherapy has great potential to mitigate the side effects of treatment, both acute and long term side effects. There have been many planning studies that show that proton radiation can achieve a more highly conformal dose distribution and appear to spare 50% or more normal tissue from unnecessary irradiation.  However, there have been only a handful of retrospective studies that report disease control and side effects of treatment. While the technology looked promising, the definitive clinical data has been lacking to date. Because of this lack of clinical outcome data, the role and benefit of proton radiotherapy has been a subject of great debate in the oncology community.  Critics assert that proton radiotherapy is expensive and unproven and therefore a leading culprit in escalating costs of oncologic health care. Proponents assert that when used in the appropriate patient setting, the margin of benefit in terms of improved health outcomes, outweighs the increased cost of treatment. We embarked on this study to answer help answer the call for prospectively collected clinical outcome data to better define the most appropriate role for proton radiotherapy. Importantly, this study addresses both disease control and side effects of treatment in a pediatric medulloblastoma cohort of children. Medical Research: What are the main findings? Dr. Yock: This study shows that disease control in the pediatric medulloblastoma population is very much the same as that which is achieved by photon based radiotherapy treatments. However, more importantly, late side effects commonly attributed to radiotherapy such as neurocognitive decline over time and hearing loss appear to be improved compared with published photon treated cohorts of pediatric medulloblastoma patients.  Additionally, adverse late side effects on the cardiopulmonary, GI, and reproductive systems were essentially eliminated. (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, Nutrition, Pediatrics / 02.02.2016

MedicalResearch.com Interview with: Dr. Maryam S. Farvid, PhD Takemi Fellow Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Farvid: Previous studies of fiber intake and breast cancer have almost all been non-significant, but none of them examined diet during adolescence or early adulthood, a period when breast cancer risk factors appear to be particularly important. Current study supports protective role of dietary fiber intake on breast cancer. The women who reported the highest amount of fiber consumed during high school, about 28 grams daily, had a 16% lower risk of overall breast cancer compared with those who said they consumed an about 15 grams a day. Also highest verses lowest intake of fiber during early adulthood was associated with a 19% lower risk of overall breast cancer. The associations were more apparent for premenopausal breast cancer than postmenopausal breast cancer. Each 10 grams increase in adolescent fiber intake may lead to a 20% lower risk of premenopausal breast cancer, as was a 15% for overall breast cancer. (more…)
Author Interviews, Endocrinology, Toxin Research / 01.02.2016

MedicalResearch.com Interview with: Dr. Nancy Wayne, PhD Member, Brain Research Institute Molecular, Cellular & Integrative Physiology GPB Home Area Neuroscience GPB Home Area David Geffen School of Medicine UCLA Medical Research: What is the background for this study? What are the main findings? Dr. Wayne: I started this work because of my concern about our continuous exposure to BPA and other endocrine disrupting chemicals. Our first study published in 2008 showed that low doses of BPA accelerated embryonic development and birth within 24 hours of exposure. We extended this work more recently by investigating the impact of BPA and BPS (a common BPA-substitute) on the timing of birth and development of the reproductive system in embryos. Our research showed that low levels of BPS had a similar impact on the embryo as BPA. In the presence of either BPA or BPS, embryonic development was accelerated leading to abnormal stimulation of the reproductive system. Additionally, BPA caused premature birth. This is cause for concern with human health consequences to long-term exposure to low levels of potentially dozens of endocrine disrupting chemicals that are in our environment. (more…)
Author Interviews, Blood Pressure - Hypertension, Kaiser Permanente, OBGYNE / 01.02.2016

MEDICALRESEARCH.COM INTERVIEW WITH: KRISTI REYNOLDS, PHD, MPH  KAISER PERMANENTE RESEARCH RESEARCH & EVALUATION PASADENA, CA 91101  Medical Research: What is the background for this study? Dr. Reynolds: Hypertensive disorders during pregnancy are common, affecting up to 10 percent of all pregnant women, and include gestational hypertension, preeclampsia (which is a combination of high blood pressure and protein in the urine), and eclampsia, which includes seizures in women with severe preeclampsia. Research has shown that hypertensive disorders in pregnancy are associated with long-term cardiovascular disease risk, but little is known about the effect of these conditions in the early years after delivery. As part of our study, we examined the electronic health records of 5,960 women who had prenatal care and delivered a baby at the Kaiser Permanente Southern California Bellflower Medical Center between 2005 and 2010. Women with high blood pressure before their pregnancy were excluded from the analysis. Medical Research: What are the main findings? Dr. Reynolds: We found that women who had a hypertensive disorder during pregnancy were 2.4 times more likely – and women with pre-eclampsia/eclampsia 2.5 times more likely – to develop pre-hypertension or hypertension in the year after delivery than those who maintained a normal blood pressure during their pregnancy, after controlling for differences between the groups. In comparison to women with normal blood pressure during pregnancy, women with pregnancy-related hypertension tended to be slightly younger and overweight or obese before pregnancy. In addition, they were more likely to have had one or more children previously and to gain excess weight and develop gestational diabetes during their pregnancy. (more…)
Author Interviews, Depression, JAMA, NYU, Pediatrics / 01.02.2016

MedicalResearch.com Interview with: Briannon O'Connor PhD New York University Child Study Center Department of Child and Adolescent Psychiatry New York University School of Medicine New York Medical Research: What is the background for this study? What are the main findings? Dr. O'Connor: a.      As the health care system continues to emphasize accountability for providing high quality care, the development of meaningful quality standards is critical.  This study came from NCQA’s work to develop these quality measures for adolescent depression care.  Prior to this study, little was known about what routine care looked like for adolescents who showed up at their primary care visits with significant symptoms of depression. This study looked at follow up care documented in an electronic health record in the three months after an adolescent was first identified with significant symptoms of depression. Medical Research: What is the background for this study? What are the main findings? Dr. O'Connor:    Key findings from this study include:
  1. Most adolescents (nearly two-thirds) with newly prescribed depression symptoms received some treatment, usually including psychotherapy, within the first 3 months after depression symptoms were first identified.
  2. Among those adolescents who were prescribed antidepressant medications, 40% had no other follow up care in three months, which is quite concerning since current black box warnings highlight the risk for increased suicidality for youth prescribed antidepressants and clearly recommend close monitoring in the few months following initial prescription.
  3. There were low rates of other follow up care events in the three month follow up period:  19% of adolescents  did not receive any follow up care at all, 36% did not receive any treatment, and the majority (68%) lacked documentation that symptoms were monitored or re-assessed using a valid questionnaire
  4. The sites that participated in the study are highly regarded health care institutions, often looked to as leaders in cutting-edge care. Thus, results from this study, discouraging as they are, may overstate the quality of care in other settings.
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Aging, Author Interviews, Cognitive Issues, JAMA, Mayo Clinic, Weight Research / 01.02.2016

MedicalResearch.com Interview with: Rosebud O. Roberts, M.B., Ch.B. Mayo Clinic Rochester, Minn.  Medical Research: What is the background for this study? Dr. Roberts: Decline in weight has been observed 10-20 years prior to onset of dementia. We wanted to study whether this decline also occurs for mild cognitive impairment (an intermediate stage in the progression from normal cognition to dementia). Medical Research: What are the main findings? Dr. Roberts: The main finding was that there was indeed a decline in weight (from the maximum weight in midlife to weight assessed in late life) was associated with a increased risk of mild cognitive impairment. (more…)
Author Interviews, Microbiome, Nature, NYU, OBGYNE / 01.02.2016

MedicalResearch.com Interview with: Maria Dominguez-Bello, PhD Associate Professor, Department of Medicine, Division of Translational Medicine NYU Langone Medical Center and Jose Clemente, PhD Assistant Professor, Departments of Genetics and Genomic Sciences, and Medicine Icahn School of Medicine at Mount Sinai       Medical Research: What is the background for this study? What are the main findings? Response: Humans and animals are a composite of their own cells and microbes. But where they get their microbes from?  For mammals, labor and birth are major exposures to maternal vaginal bacteria, and infants are born already with a microbiota acquired from the mother. Mom’s birth canal is heavily colonized by bacteria that are highly related to milk: some will use milk components and become dominant during early development, an important window for maturation of the immune system, the intestine and the brain. Thus, the maternal vaginal microbiota is thought to be of high adaptive value for newborn mammals. Indeed, studies in mice confirm that microbes acquired at birth are important to develop adequate immune and metabolic responses, and the mature adult microbiome will continue to modulate host metabolism and immunity. Humans are the only mammals that interrupt the exposure to maternal vaginal microbiota, by delivering babies by Cesarean section. C-sections save lives of babies and moms, and they are estimated necessary in 10-15% of the cases. But most Western countries have rates above 30%, with the notable exception of the Scandinavian countries, Holland and Japan, which have excellent health systems and low maternal-infant mortality rates. Previous work by us an others has shown that infants born by C-section acquire different microbiota at birth, and those differences are sustained over time, altering the normal age-dependent maturation of the microbiome. The fundamental questions are then, can we restore the microbiota of Cesarean delivered babies? And if we can, does that reduce the associated disease risks? In relation to the first question, we present here the results of a pilot study in which infants born by Cesarean delivery were exposed to maternal vaginal fluids at birth. A total of 18 infants were recruited for the study. Seven of them were vaginally delivered, the remaining 11 were born by scheduled C-section. Among the C-section infants, 4 were exposed to maternal vaginal fluids at birth and 7 were not. We sampled all infants and their mothers for the first month of life across different body sites (oral, skin, anal, maternal vagina) and determined the microbiome composition on a total of over 1,500 samples. (more…)
Author Interviews, Compliance, JAMA, Technology / 01.02.2016

MedicalResearch.com Interview with: Dr. Clara Chow PhD Director of the Cardiovascular division The George Institute, Westmead Hospital Sydney, Australia Medical Research: What is the background for this study? What are the main findings? Dr. Chow: Text messaging has immense potential in healthcare. Not only for supporting medication adherence, but we have shown in the “TEXT ME” study its ability to simultaneously influence multiple lifestyle domains like increasing physical activity, embarking on healthier diets and reducing smoking rates. With increasing penetration of mobile phone use in developed as well as developing countries, there is a potential for wider reach, however there remains a need to evaluate the value of text messaging programs in various patient populations to establish the generalizability of these research findings. (more…)
Author Interviews, Brigham & Women's - Harvard, Dermatology / 01.02.2016

MedicalResearch.com Interview with: Victor Allen Neel, MD, PhD Director, Dermatologic Surgery Massachusetts General Hospital Medical Research: What is the background for this study? Dr. Neel: Seborrheic keratoses (SKs) are the very common, warty brown skin lesions that are found on the face, chest and back of most people over forty. They affect every race and they increase in size and frequency with age. Although they are not dangerous, they can mimic dangerous conditions and are cosmetically unappealing. There is a high demand in the field of dermatology by both patients and physicians for a topical treatment. Currently there no FDA-approved drugs that have been shown to be effective at removing them. Medical Research: What are the main findings? Dr. Neel: Although seborrheic keratoses are the most common benign tumors in humans, very little was known about what causes them. Our paper was the first to study the biology of SKs in the laboratory, identify the key proteins controlling their abnormal growth and to pinpoint a potential treatment for commercial development. We found that the enzyme called Akt was activated in seborrheic keratoses. Inhibiting this enzyme with a compound called A44 caused the SK cells to undergo "apoptosis,"  or programmed cell death. Normal skin cells were unaffected by A44. (more…)
Author Interviews, Dermatology, Gastrointestinal Disease, Genetic Research / 01.02.2016

MedicalResearch.com Interview with: Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital University of Copenhagen Hellerup, Denmark Medical Research: What is the background for this study? What are the main findings? Dr. Egeberg: A recent genome-wide association study (GWAS) identified 90 shared genetic regions associated with celiac disease, type 1 diabetes mellitus, multiple sclerosis, and rheumatoid arthritis, respectively. Similarly, a newly published GWAS identified shared risk loci between rosacea, type 1 diabetes, and celiac disease. In the present study of 6,759 patients with rosacea and 33,795 control subjects, rosacea was associated with a 2 to 3-fold higher risk of these four conditions, particularly among women. (more…)
Author Interviews, BMJ, Colon Cancer, Gastrointestinal Disease, Global Health / 31.01.2016

MedicalResearch.com Interview with: Dr. Melina Arnold Section of Cancer Surveillance International Agency for Research on Cancer Lyon, France MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Arnold: In this study, we looked at patterns and time trends in the incidence in and mortality from colorectal cancer on the global scale. In the analyses, we used data from the Globocan database, Cancer Incidence in Five Continents, both hosted by the International Agency for Research on Cancer (IARC), and the World Health Organisation mortality database. We documented a ten-fold variation in colorectal cancer incidence and mortality rates worldwide. We also found distinct gradients across human development levels, meaning that changes in patterns and trends of this cancer could be linked to economic development and that the adoption of a Western lifestyle may have a role. While incidence and mortality rates are on the increase in many countries in socioeconomic transition, stabilizing or decreasing trends are seen in highly-developed countries where rates remain among the highest in the world. These observations point to widening disparities and an increasing burden in transitioning countries. (more…)
Author Interviews, Diabetes, Lancet / 31.01.2016

MedicalResearch.com Interview with: Dr Abbas Dehghan PhD Assistant Professor, Department of Epidemiology Erasmus University Medical Centre Rotterdam, Netherlands MedicalResearch.com: What is the background for this study? Dr. Dehghan: Diabetes is an important health treat given its serious complications including cardiovascular disease, blindness, kidney failure, and lower-extremity amputations. Descriptive studies have so far either reported the prevalence of diabetes which is a snapshot of the percentage of people who have diabetes or the risk that people will develop diabetes in next 5 or 10 years. These estimates are not optimal since they overlook the risk of developing diabetes later in life. We calculated the lifetime risk of type 2 diabetes which is the risk that every person carries to develop type 2 diabetes up to end of his life. Moreover, we provided estimates for prediabetes, a high risk status that people experience before developing diabetes, and need for insulin therapy that might indicates severity of the disease. MedicalResearch.com: What are the main findings?  Dr. Dehghan: Our data suggest that the lifetime risk of developing prediabetes for a normoglycemic individual aged 45 years is one in two, and one in three nondiabetic individuals aged 45 years will develop diabetes. Three-quarters of individuals with prediabetes at age 45 years will eventually progress to diabetes, and half of the patients with diabetes at the same age will start insulin treatment. Stratification by BMI showed that normoglycemic people with healthy weight at age 45 years had a significantly lower prediabetes lifetime risk compared with overweight and obese individuals. Stratification by waist circumference showed similar effects on lifetime risks for diabetes in individuals with prediabetes. Similarly, in individuals with diabetes, the lifetime risk for insulin use among patients with diabetes was higher with increasing BMI and waist circumference. (more…)
Author Interviews, Brigham & Women's - Harvard, UCSF, Zika / 31.01.2016

MedicalResearch.com Interview with: Mary E. Wilson, MD Visiting Professor of Epidemiology and Biostatistics School of Medicine, University of California San Francisco Adjunct Professor of Global Health and Population Harvard T.H. Chan School of Public Health Boston, Massachusetts  Medical Research: What is the background for this study? Response: Zika virus infections are spreading explosively in the Americas. This flavivirus infection, spread by Aedes mosquitoes, is new to the Americas, so the majority clinicians have little knowledge of the infection and its potential complications. The country most affected so far is Brazil, where more than a million infections have been reported in less than a year. Infection has also spread to at least 20 other countries in the Americas (the Caribbean, Mexico, Central and South America). Prior to 2007 Zika virus was known to cause infections only in Africa and Asia. Since then, it has spread and caused epidemics in Micronesia, French Polynesia, Easter Island, and since 2015 in Brazil. Most of the movement of the virus from one region to another is via travelers who are infected and then are bitten by mosquitoes in a new region. In Brazil an increase in cases of infants born with microcephaly (small head) has been noted coincident with the Zika epidemic, and the virus has been recovered from amniotic fluid and from fetal tissue, suggesting that Zika infection during pregnancy may cause microcephaly in the developing fetus. An increase in cases of Guillain-Barre syndrome has also been observed during this and previous outbreaks. Studies are underway to determine if Zika virus is the cause of microcephaly and Guillain-Barre syndrome.In Brazil an increase in cases of infants born with microcephaly (small head) has been noted coincident with the Zika epidemic, and the virus has been recovered from amniotic fluid and from fetal tissue, suggesting that Zika infection during pregnancy may cause microcephaly in the developing fetus. An increase in cases of Guillain-Barre syndrome has also been observed during this and previous outbreaks. Studies are underway to determine if Zika virus is the cause of microcephaly and Guillain-Barre syndrome. Most countries in the Americas, including the United States, are infested with types of mosquitoes that are competent to transmit the virus, but weather conditions also have to be warm enough to permit the virus to disseminate in the mosquito so that it can be transmitted to another person. The symptoms of Zika virus infection are typically mild and self-limited  – fever, aches, rash, and conjunctivitis. In fact, the majority of those infected have no symptoms. Because the virus can enter the bloodstream even in asymptomatic infected persons, there is concern that the virus could be spread by blood transfusion, if a person donates blood during the short period (probably a few days at most) when virus is in the blood. Other reasons for the paper are to highlight what is known about some of the insect repellents and to point out important gaps in our knowledge of their use and urgent research needs. (more…)
Author Interviews, Autism, Genetic Research, JAMA, Schizophrenia / 30.01.2016

MedicalResearch.com Interview with: Andrea J. Gonzalez-Mantilla, M.D. Postdoctoral Fellow Andres Moreno-De-Luca, M.D. Investigator I Autism & Developmental Medicine Institute Department of Radiology Geisinger Health System Danville, PA 17822 Medical Research: What is the background for this study? What are the main findings? Response: Developmental brain disorders (DBD), such as autism, intellectual disability, and schizophrenia are a group of heterogeneous conditions characterized by deficits that affect multiple functional domains, such as cognition, behavior, communication, and motor skills. Previous studies provide strong evidence of common underlying molecular pathways and shared genetic causes among apparently different DBDs. Large-scale genomic studies of individuals with developmental brain disorders have found that identifying multiple, independent de novo pathogenic loss-of-function (pLOF) variants in the same gene among unrelated individuals is a powerful statistical approach to reliably identify disease-causing genes. However, genomic data from smaller cohorts and case reports are not routinely pooled with data from larger studies. Moreover, most previous studies have been restricted to cohorts of individuals ascertained based on a single diagnosis (e.g., a study will focus on only individuals with a diagnosis of autism and not consider other genomic data from individuals with a different diagnosis). Therefore, genomic data from individuals across DBD are not being jointly analyzed in search of pLOF variants in the same gene that may help build evidence for a causative role in developmental brain disorders. In this study, we carried out data mining of previously published data to identify genes related to the DBD phenotype. We expanded the aforementioned method and developed a multilevel data-integration approach, which capitalizes on three genotype-phenotype data sources: (1) genomic data from structural and sequence pLOF variants, (2) phenotype data from six apparently distinct DBD (autism, intellectual disability, epilepsy, schizophrenia, bipolar disorder and attention-deficit/hyperactivity disorder), and (3) data from large scale studies, smaller cohorts, and case reports. We identified 241 candidate genes for developmental brain disorders, including 17 genes that had not previously been associated with developmental brain disorders. (more…)