Author Interviews, Cancer Research, Gastrointestinal Disease, Nature / 24.04.2016

MedicalResearch.com Interview with: Zhimin (James) Lu, M. D., Ph. D Ruby E. Rutherford Distinguished Professor Department of Neuro-Oncology MD Anderson Cancer Center Houston, TX 77030 MedicalResearch.com: What is the background for this study? Dr. Lu: Among primary liver cancers, hepatocellular carcinoma (HCC) is the most common histological subtype, accounting for 70-85% of all cases. HCC incidence is increasing in many parts of the world, including developing countries and developed countries such as the United States. HCC has a very poor prognosis, and the overall 3-year survival rate for patients with HCC is approximately 5%. The potentially curative treatments of HCC are resection and liver transplantation. However, most patients with hepatocellular carcinoma present with advanced disease and underlying liver dysfunction and are not suitable candidates for these treatments. Thus, they generally have a poor prognosis, with a median survival time of less than 1 year. The increasing incidence and mortality rates of hepatocellular carcinoma, along with a lack of effective curative treatment options for advanced HCC, have rendered this disease a major health problem worldwide. Thus, a better understanding of HCC tumorigenesis and the development of better diagnostic and therapeutic approaches based on an understanding of the molecular mechanisms that drive hepatocellular carcinoma progression are greatly needed. The liver, as a major metabolic organ, catalyzes dietary sugar. Dietary sugar encompasses several carbohydrates, including starch, sucrose, and high-fructose corn syrup, each of which is composed of glucose with or without fructose. Starch, which is found in bread and rice, is a glucose polymer. Sucrose is a disaccharide made up of 50% glucose and 50% fructose. High-fructose corn syrup, a common constituent of soft drinks, is a mixture of approximately 40% glucose and 60% fructose. Dietary fructose is also derived from fruits and vegetables. A molecule of glucose has the same caloric value as a molecule of fructose. However, the human body treats these carbohydrates quite differently. Glucose is used directly by tissues such as the muscles and brain as an energy source. Excess glucose is stored in the liver as glycogen. In contrast, dietary fructose, which is epidemiologically linked with obesity and metabolic syndrome, is almost exclusively metabolized by the liver. Hepatocellular carcinoma cells enhance glucose uptake and lactate production regardless of the oxygen supply, a phenomenon known as the Warburg effect. However, whether fructose metabolism is differentially regulated in hepatocellular carcinoma and normal liver tissue and, if so, the extent to which this altered carbohydrate metabolism contributes to hepatocellular carcinoma development is unknown. (more…)
Author Interviews, Global Health, Pediatrics / 23.04.2016

MedicalResearch.com Interview with: Janet Currie Henry Putnam Professor of Economics and Policy Affairs Chair, Department of Economics Director, Center for Health and Wellbeing Princeton University Princeton NJ 08544 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many recent studies point to increasing inequality in mortality in the United States over the past 20 years. These studies often use mortality rates in middle and old age. This is the first study to examine mortality trends for younger ages.  We find that for infants, children and young adults below age 20, however, there have been strong mortality improvements that were most pronounced in poorer counties, implying a strong decrease in mortality inequality. There is a great deal of evidence from past studies that healthier children grow up to be healthier adults.  These current young people will form the future adult U.S. population, so this research suggests that inequality in middle and old-age mortality may have peaked and is likely to decline as these cohorts become older. (more…)
Author Interviews, Infections, Lancet / 23.04.2016

MedicalResearch.com Interview with: Prof Jean-Pierre Allain Principal Investigator, Department of Haematology University of Cambridge, Cambridge Blood Centre Cambridge UK MedicalResearch.com: What is the background for this study? What are the main findings? Prof. Allain: In sub-Saharan Africa (SSA), 70% of the transfusions are in the form of  whole blood units (generally 1 or 2). Lack of resources limit the safety measures to donor questionnaire, viral/bacterial testing (HIV, HCV, HBV and Syphilis). Other measures used in rich countries i.e. nucleic acid testing, filtration, bacterial culture etc. are not done because of cost. Pathogen reduction would be an effective way to overcome these issues as it is able to inactivate viruses, bacteria, parasites and nucleated cells in one go, provided it is applied to whole blood and affordable. The study consisted in assessing the efficacy of such a method (Mirasol using riboflavin and UV illumination) taking inactivation of plasmodium as major endpoint of a randomised controlled clinical trial called AIMS (African Investigation of Mirasol System). (more…)
Author Interviews, Heart Disease, Rheumatology / 22.04.2016

MedicalResearch.com Interview with: Nicola Veronese, MD University of Padova Department of Medicine (DIMED)-Geriatrics Section Padova, Italy MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Veronese: Osteoarthritis (OA) is the most common rheumatic disease. Although an increasing research is showing that OA, particularly of lower limbs, is associated with an increased risk of cardiovascular diseases (CVD) the association with overall mortality seems to be less clear. (more…)
Author Interviews, Blood Pressure - Hypertension, Kidney Disease / 22.04.2016

MedicalResearch.com Interview with: Csaba P Kovesdy MD Fred Hatch Professor of Medicine Director, Clinical Outcomes and Clinical Trials Program Division of Nephrology, University of Tennessee Health Science Center Nephrology Section Chief, Memphis VA Medical Center Memphis TN, 38163 MedicalResearch.com: What is the background for this study? Dr. Kovesdy: Older patients experience several physiologic changes which could modify their response to blood-pressure lowering. In fact, hypertension treatment guidelines such as JNC8 recommend slightly higher blood pressure targets when treating elderly patients. Patients with chronic kidney disease (CKD) have been excluded from most hypertension treatment trials, hence the blood pressure treatment goals in this group are mainly derived based on extrapolations. Even less is known about the effects of age on the association of blood pressure with mortality and various other clinical outcomes in patients with CKD. (more…)
Author Interviews, Nature, NYU, Pancreatic / 22.04.2016

MedicalResearch.com Interview with: Dr. George Miller, MD Vice Chair for research, Department of Surgery Associate Professor, Department of Surgery Associate Professor, Department of Cell Biology NYU Langone’s Perlmutter Cancer Center MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Miller: Cancer cell death is the goal of most therapeutic programs. Indeed, chemotherapy induces cancer cell death. We show that a novel form of cancer cell death entailing organized necrosis is a prominent way by which cancer cells die. However, paradoxically this form of cell death termed "necroptosis" actually accelerates pancreatic cancer growth in animals by inducing immune suppressive inflammation. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Miller: Novel agents are needed to block necroptosis in pancreatic cancer. This can potentially enhance the immune system's ability to fight the cancer. (more…)
Author Interviews, Blood Pressure - Hypertension, Brain Cancer - Brain Tumors / 22.04.2016

MedicalResearch.com Interview with: Hervé Chneiweiss MD PhD Bâtiment A3 pièce 336 Case courrier 2 Plasticité Gliale et Tumeurs cérébrales Neuroscience Paris Seine (directeur) Inserm/Université Pierre et Marie Curie MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Chneiweiss: Treatments available for glioblastoma -- malignant brain tumors -- have little effect. An international collaboration[1] led by the Laboratoire Neurosciences Paris-Seine (CNRS/ INSERM/UPMC)[2] tested active ingredients from existing medications and eventually identified one compound of interest, prazosin, on these tumors. We chose to study the most common malignant tumors that develop from brain cells, glioblastomas, which represent the fourth most frequent cause of cancer deaths among adults and the second in children. This is due to the inefficacy of current treatments. Indeed, a glioblastoma can resist treatment and reawaken from a very small number of tumor cells called glioblastoma-initiating cells (GIC). It is these cells -- whose characteristics and properties resemble those of stem cells -- that were targeted in the study. Rather than trying to discover new compounds, the team opted for repositioning existing drugs. In other words, we tested a collection of substances used for so long to treat other conditions that their patents have now fallen into the public domain[3]. This method makes it possible to develop new active ingredients cheaply and very rapidly. Twelve hundred compounds were thus tested on normal human neural stem cells and on glioblastoma-initiating cells from different aggressive tumors. Twelve of these compounds showed a toxic effect on GIC -- and none on the normal neural stem cells. The most effective was prazosin. Tested in mice carrying glioblastoma-initiating cells, prazosin significantly reduced the size of tumors and prolonged survival of the mice by more than 50%. [1] Including scientists from the Laboratoire d'Innovation Thérapeutique (CNRS/Université de Strasbourg), the Stanford University Institute for Stem Cell Biology and Regenerative Medicine (USA) and the Instituto Estadual do Cérebro Paulo Niemeyer in Rio de Janeiro (Brazil). [2] This laboratory forms part of the Institut de Biologie Paris-Seine. [3] Pharmaceutical compounds are protected by a patent for 20 years after their discovery. Because of the length of the clinical trials that are necessary before a drug can be put on the market, the duration of their patent protection does not normally exceed 10-15 years after a Marketing Authorization (MA) is granted. (more…)
Author Interviews, Gender Differences, Kidney Disease, Transplantation, University of Pennsylvania / 22.04.2016

MedicalResearch.com Interview with: Matthew Levine, MD, PhD Assistant Professor of Transplant Surgery Perelman School of Medicine University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Levine: This work stemmed from a known finding that female mice tolerate kidney injury better than males and this is true of mice that share exactly the same genes.  Therefore, the gender difference was the driving factor.  My basic science laboratory works at the intersection between scientific discovery and clinical application and this led us to question whether the same phenomenon was true in humans and whether we could identify a way in which this could be used to improve injury tolerance above what is seen in untreated subjects.  What we found was that the hormonal environment seems to impact ischemia tolerance, with female environment being protective and the male environment worsening injury tolerance in ischemia models where blood flow is interrupted and then restored.  The kidneys seemed to adapt to take on the injury response of the host after transplantation, indicating that the differences were not forged into the kidney itself and therefore could be altered.  We then found that estrogen therapy improved kidney injury tolerance when given to female mice in advance of injury, but no effect was seen in male mice.  And most importantly, we found that in a large cohort of transplant recipients that female recipients had better injury tolerance after transplant than male recipients, as shown by ability to avoid dialysis in the first week after transplant, otherwise known as delayed graft function (DGF). This is a fairly major finding since it has not been observed in the literature despite several decades of transplant data being carefully studied. (more…)
Author Interviews, Nutrition, Sleep Disorders / 22.04.2016

MedicalResearch.com Interview with: Yingting Cao PhD Candidate Population Research and Outcome Studies School of Medicine, Faculty of Health Sciences The University of Adelaide Freemasons Foundation Centre for Men’s Health MedicalResearch.com: What is the background for this study? What are the main findings? Response: As sleep complains have reached a public concern, increasing number studies have investigated it. Most studies focused on the adverse effect of short sleep or poor sleep quality on health but fewer looked it the other way around. Laboratory studies have suggested the potential role of diet in regulating sleep, however, it has not been confirmed in population studies. So, we examined whether dietary factors are associated with sleep in a large cohort of middle-aged and older men in Adelaide, focusing on their sleep, as well as general health including chronic conditions. In this particular paper, we focused on macronutrient intake (we focused on nutrients and food levels in other papers) and sleep. The main finding was that comparing with the lowest 25% fat intake (mean 58g/d), people in the highest 25% of fat intake reported more daytime sleepiness and had increased number of sleep apnea during the night. (more…)
Author Interviews, Cognitive Issues, Heart Disease, JAMA / 22.04.2016

MedicalResearch.com Interview with: Thomas H. Marwick, MBBS, PhD, MPH Baker IDI Heart and Diabetes Institute Melbourne, Australia MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Marwick: Readmission for heart failure (HF) remains common and the risk of this remains hard to predict. It's possible that existing risk scores don't cover all important patient features. We confirmed that cognitive impairment was an unmeasured contributor and incorporated this measurement in a prediction model. The resulting model was the most reliable reported to date and could be used to identify patients who need the closest follow up to avoid readmission. (more…)
AACR, Author Interviews, Cancer Research, Exercise - Fitness, Prostate Cancer / 21.04.2016

MedicalResearch.com Interview with: Ying Wang, PHD | Senior Epidemiologist American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303 MedicalResearch.com: What is the background for this study? Dr. Wang: Although evidence is still limited, previous studies suggest that vigorous activity and brisk walking after prostate cancer diagnosis might be associated with lower risk of prostate cancer progression and disease-specific mortality. We still don’t know if physical activity before diagnosis is associated with the risk or not. This is also important because reverse causation is a concern in the analysis of post-diagnosis physical activity, especially for vigorous activity, that men with advanced diseases may reduce their activity level. In contrast, pre-diagnosis physical activity is less subject to reverse causation and may represent a long-term behavior. When walking, the most common type of physical activity, was examined separately in previous studies, it was not evaluated in the absence of other activities. No study has examined sitting time in relation to mortality among prostate cancer survivors, although previous study suggests longer sitting time is associated with higher risk of all-cause mortality in healthy populations. So in our study, we aimed to examine physical activity, walking only, and sitting time both before and after diagnosis in relation to prostate cancer-specific mortality. (more…)
Author Interviews, Multiple Sclerosis, Neurology, NYU / 21.04.2016

MedicalResearch.com Interview with: Leigh Elkins Charvet, PhD Director of MS Research Multiple Sclerosis Comprehensive Care Center Associate Professor of Neurology NYU Langone Medical Center New York, NY 10016 MedicalResearch.com: What is the background for this study? Dr. Charvet:  One of the goals of our work is to identify cognitive impairment at the earliest point that it occurs in multiple sclerosis (MS), and ultimately to predict those who are at greatest risk.  Olfactory impairment is a feature of neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease and predicts cognitive decline.  Olfactory impairment has also been reported in adults with multiple sclerosis.  Our study, lead by Colleen Schwarz, measured olfactory identification and its link to cognitive performance in a subpopulation of those with earliest onset of MS—pediatric onset multiple sclerosis (POMS, referring to those with onset before the age of 18). (more…)
Author Interviews, BMJ, OBGYNE / 21.04.2016

MedicalResearch.com Interview with: Joel Ray, MD MSc FRCPC Clinician-Scientist St. Michael’s Hospital Toronto, ON MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Ray:
  • Clinical practice guidelines strongly recommend that physicians and midwives start aspirin before 20 weeks gestation in a woman at high risk of preeclampsia (PE).
  • However, these guidelines do not provide a systematic approach for identifying a woman at high risk of pre-eclampsia (PE), using readily available clinical risk factors (RFs) known before 20 weeks gestation.
  • Thus, there is a need for a clear, concise and evidence-based list of risk factors that clinicians can use, before 20 weeks gestation, to estimate a woman’s risk of pre-eclampsia.
  • We systemically analyzed large cohort studies and estimates of the absolute pooled risk of developing pre-eclampsia in the presence vs. absence of one of 14 common risk factors.
(more…)
Author Interviews, Nutrition, Pediatrics / 21.04.2016

MedicalResearch.com Interview with: Juliana F.W. Cohen, ScD, ScM Merrimack College, Department of Health Sciences North Andover MA 01845 Adjunct Assistant Professor of Nutrition Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the background for this study? Dr. Cohen: Back in 2012, Massachusetts enacted both the updated USDA standards for school meals and healthier standards for snacks in schools that were similar to the upcoming, fully implemented national "Smart Snacks" standards.  We examined the impact of these standards on school food revenues and school meal participation. MedicalResearch.com: What are the main findings? Dr. Cohen: After schools had time to acclimate to the changes, schools revenues remained high. While students spent less money on snacks, more children were now participating in the lunch program so school food revenues were not impacted long-term. (more…)
Author Interviews, Diabetes, Pharmacology / 21.04.2016

MedicalResearch.com Interview with: Pedro L. Herrera, PhD Professor Dept. Genetic Medicine & Development, room #F09.2770 Faculty of Medicine, University of Geneva Geneva, Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Herrera: After meals, the digestion of food leads to an accumulation of sugar (glucose) in the blood (hyperglycemia). This triggers the release of the hormone insulin from the pancreas (beta-cells), which allows the tissues (liver, muscle and fat) to use and store it. Another pancreatic hormone, glucagon, is released by alpha-cells during fasting or exercising, and opposes the action of insulin: it tells the liver to release glucose, which increases blood sugar levels. The balance between insulin and glucagon keeps blood sugar levels steady. Persistent hyperglycemia due to insulin deficiency is diabetes. Glucagon production is exacerbated in diabetes, which aggravates hyperglycemia. (more…)
AACR, Author Interviews, Cancer Research, Nutrition, Prostate Cancer / 21.04.2016

MedicalResearch.com Interview with: Emma Helen Allott, PhD University of North Carolina at Chapel Hill Chapel Hill, NC MedicalResearch.com: What is the background for this study? Dr. Allott: Prostate cancer incidence rates vary more than 25-fold worldwide, and are highest in Western countries. This large international variation is due in part to differences in screening practices between countries, but dietary factors may also play a role. Unlike other macronutrients, dietary fat intake varies more than fivefold worldwide, and individuals in Western countries are among the highest consumers of saturated fat. High dietary saturated fat content contributes to raised blood cholesterol levels, and evidence from population-based studies supports an adverse role for serum cholesterol and a protective role for cholesterol-lowering statins in prostate cancer. Our hypothesis in this study was that high saturated fat intake would drive prostate tumor aggressiveness via raising serum cholesterol levels. MedicalResearch.com: What are the main findings? Dr. Allott: Using the North Carolina-Louisiana Prostate Cancer Project, a study of 1,854 men with newly-diagnosed prostate cancer, we show that high dietary saturated fat content is associated with increased tumor aggressiveness. We found a slightly weaker effect of saturated fat on prostate cancer aggressiveness in men using statins to control serum cholesterol levels, suggesting that that statins may counteract, but do not completely negate, the effects of high saturated fat intake on prostate cancer aggressiveness. We also found an inverse association between high dietary intake of polyunsaturated fatty acids (PUFAs) and prostate cancer aggressiveness. (more…)
Author Interviews, Biomarkers, Cancer Research, JAMA, University of Michigan / 21.04.2016

MedicalResearch.com Interview with: Alon Kahana, MD, PhD Associate Professor Kellogg Eye Center University of Michigan MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Kahana: Basal cell carcinoma is the most common cancer - more common than all other cancers combined. Fortunately, it is usually not aggressive, and can be easily treated surgically. However, when it is on the face, or when it has grown to a large size, it can become very disfiguring and even deadly. Basal cell carcinoma is diagnosed histopathologically, yet molecular diagnostics have proven value in a variety of cancers. In order to improve diagnosis and care, we set out to test whether histologically aggressive forms of basal cell carcinoma are associated with increased cell proliferation. Furthermore, we tested whether expression of the epigenetic regulator Ezh2 is associated with higher-grade carcinoma and/or with increased proliferation. The breakthrough discovery is that expression of Ezh2 correlates with high proliferation and with aggressive histologic features, suggesting that epigenetic regulators can be used both as markers of disease severity and targets of novel therapy. (more…)
Author Interviews, Diabetes, Metabolic Syndrome, OBGYNE, Pediatrics, University Texas, Weight Research / 21.04.2016

MedicalResearch.com Interview with: Antonio Saad, MD Fellow in Maternal Fetal Medicine & Critical Care Medicine University of Texas Medical Branch at Galveston MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Saad: Recently the WHO announced an alarming news, the prevalence of diabetes has increased four fold in the past quarter-century. The major factors attributed for this increase included excessive weight, and obesity. In the US alone, two thirds of people are either overweight or obese. There are shocking numbers that should alert physicians, patients and government officials for awareness and interventions that we can alter the path away from this drastic epidemic. In light of recent events, our group strongly believes that poor diet during pregnancy predisposes offspring in adult life to develop obesity and diabetes through fetal programming. High fructose introduction into our food chain has coincided with the obesity and diabetes epidemics. Hence, we designed an animal study where we fed pregnant mice with either regular diet or high fructose diet until delivery. Then we looked at the offspring, at 12 months of age. We looked at  their blood pressure, glucose tolerance tests, insulin resistance,  and weights. We also tested for serum marker of metabolic dysfunction and used computed tomography imaging to assess for liver fat infiltration and percent visceral adipose tissue. To our surprise, these offspring (mothers were fed high fructose diet) developed several features of metabolic syndrome.  Female offspring’s cardiovascular and metabolic function at one year of age (adulthood) had increased weight, blood pressure, visceral adiposity, liver fat infiltrates and  insulin resistance with impaired glucose tolerance).  The  male counterparts were limited to high blood pressure  and glucose intolerance. Keeping in mind that the amount of fructose given to these animals were equivalent to daily soda cans consumption in humans. (more…)
Author Interviews, Mammograms / 21.04.2016

MedicalResearch.com Interview with: Stacey Fedewa, MPH Strategic Director, Screening and Risk Factor Surveillance Surveillance and Health Services Research program American Cancer Society MedicalResearch.com: What is the background for this study? Response: In 2009, the U.S. Preventive Services Task Force (USPSTF) no longer recommended routine mammography for women aged 40–49 and ≥75 years (younger and older women, respectively). Whether mammography usage and physician recommendation among younger (40-49 years) and older (75+ years) women changed in response to these recommendations is unclear, so we compared changes in women’s self-reported mammography screening practices and physician recommendation for mammography between 2008 and 2013 using the National Health Interview Survey in younger and older women. MedicalResearch.com: What are the main findings? Response: Overall mammography prevalence for younger and older women did not change between 2008 and 2013, except in higher-socioeconomic younger women. During the corresponding study period, physician recommendation fell by 5.0% for younger women and 5.8% for older women, which may reflect physician adherence to the 2009 USPSTF updated BC screening recommendations. (more…)
Author Interviews, Cancer Research, Cost of Health Care, Radiology / 20.04.2016

MedicalResearch.com Interview with: Dr. Christine Fisher MD, MPH Department of Radiation Oncology University of Denver MedicalResearch.com: What is the background for this study? Dr. Fisher: Screenable cancers are treated by oncologists every day, including many in invasive, advanced, or metastatic settings.  We aimed to determine how health insurance status might play into this, with the hypothesis that better access to health care would lead to presentation of earlier cancers.  While this sounds intuitive, there is much debate over recent expansions in coverage through the Affordable Care Act and how this may impact health in our country. MedicalResearch.com: What are the main findings? Dr. Fisher: The findings confirm that those without health insurance present with more advanced disease in breast, cervix, colorectal, and prostate cancers, including tumor stage, grade and elevated tumor markers.  That is to say, all else being equal for risk of cancer, lack of health insurance was an independent risk factor for advanced presentation.  (more…)
Author Interviews, Diabetes, JAMA, Surgical Research, Weight Research / 20.04.2016

MedicalResearch.com Interview with: Annemarie G. Hirsch, PhD, MPH Center for Health Research Geisinger Health System Danville, Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: Bariatric surgery is currently the most effective treatment in reversing insulin resistance in patients with type 2 diabetes. However, the likelihood of remission or cure after surgery varies tremendously based on certain patient characteristics. The DiaRem score provides patients with a personalized prediction of whether or not they can expect long-term remission of their disease if they choose to have surgery. (more…)
Author Interviews, JAMA, Surgical Research, Weight Research / 20.04.2016

MedicalResearch.com Interview with: James E. Mitchell, MD President and Scientific Director Neuropsychiatric Research Institute, Fargo Professor and Chairman Department of Neuroscience University of North Dakota School of Medicine and Health Sciences MedicalResearch.com: What is the background for this study? What are the main findings Dr. Mitchell: The amount of weight loss following bariatric surgery is widely variable. Eating behaviors and weight control practices after surgery are important in determining weight loss outcomes. (more…)
Author Interviews, Schizophrenia, Smoking / 20.04.2016

MedicalResearch.com Interview with: Stéphane Potvin, PhD Associate professor, Department of Psychiatry Eli Lilly Chair in Schizophrenia Research University of Montreal MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Potvin:  Life expectancy is substantially reduced in schizophrenia, and one of the main factors contributing to this is the high prevalence of cigarette smoking in these patients. The leading hypothesis for cigarette smoking in schizophrenia is the self-medication hypothesis. Although some empirical results show that nicotine improves cognitive performance in schizophrenia, some authors have criticized the self-medication hypothesis for its implied (and unintented) justification of cigarette smoking in schizophrenia. About a decade ago, it has been hypothesized that cigarette smoking may be more reinforcing in schizophrenia patients, due to biological dysfunctions common to schizophrenia and tobacco use disorder. However, that model had not been formally tested. Based on recent findings showing that cigarette cravings are increased in schizophrenia smokers, compared to smokers with no comorbid psychiatric disorder, we performed a neuroimaging study on cigarette cravings in schizophrenia. Unless we are wrong, this was most probably the first study to do so. We found that relative to control smokers, smokers with schizophrenia had increased activations of the ventro-medial prefrontal cortex in response to pleasant images of cigarette. What is is interesting is that the ventro-medial prefrontal cortex is one of the core regions of the brain reward system, which mediated the reinforcing effects of several psycho-active substances, including tobacco. As such, our results tend to confirm the assumption that cigarette might be more reinforcing in schizophrenia smokers. (more…)
Author Interviews, Cannabis, FASEB, Fertility / 20.04.2016

MedicalResearch.com Interview with: Paola Grimaldi, PhD Associate Professor of Anatomy Department of Biomedicine and Prevention, School of Medicine, University of Rome Tor Vergata Rome, Italy MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Grimaldi: Our previous studies reported that mouse mitotic germ cells, spermatogonia, express type 2 cannabinoid receptor (CB2) and its stimulation promoted differentiation and meiotic entry of these cells in vitro. In this study we demonstrate that CB2 plays a role of in regulating the correct progression of spermatogenesis in vivo and we found that the use of exogenous agonist or antagonist of this receptor disrupts the normal differentiation of germ cells. This suggests that a basal and finely regulated level of endocannabinoids in male germ cells activate CB2, thus maintaining the homeostasis of spermatogenesis. Another important novelty of our study is that CB2 activation in developing germ cells determines the appearance of modifications in DNA-bound proteins, which are known to impact on gene expression and inheritance of specific traits in developing germ cells. An exciting idea could be that these modifications might be maintained in the mature spermatozoa and transmitted to the offspring. (more…)
Author Interviews, Diabetes, Diabetes Care, Exercise - Fitness, Lifestyle & Health / 20.04.2016

MedicalResearch.com Interview with: Paddy Dempsey MPhEd, PhD in Medicine (expected June 2016) Physical Physical Activity and Behavioural Epidemiology Laboratory Baker IDI Heart and Diabetes Institute Melbourne VIC MedicalResearch.com: What is the background for this study? What are the main findings? Response: In addition to too little physical activity (PA), sedentary behavior – defined as any waking sitting or reclining behavior with low energy expenditure – has emerged as a ubiquitous and significant population-wide influence on cardiometabolic health outcomes, with potentially distinct and modifiable environmental and social determinants. There is now a consistent base of epidemiologic evidence reporting deleterious associations of excessive sedentary behaviors (e.g. TV viewing, car use, and desk work) with mortality and cardiometabolic morbidity, independent of moderate-vigorous PA. To date, efforts to influence participation in moderate-to-vigorous exercise (i.e. 30 min a day of ‘exercise’ on most days a week for health) at the population level, such as through large-scale campaigns to promote walking, and other initiatives to encourage people to exercise during their leisure time have achieved only modest success. There may, however, be untapped preventive-health and clinical management potential through shifting the high volume of time spent sedentary to light-intensity physical activity interspersed throughout the day. As such, sedentary behavior represents a potentially feasible and therapeutic target, particularly in the promotion of metabolic health. We posited that people with type 2 diabetes (T2D) were likely to derive the greatest benefits from interrupting their sitting time. However, until now the contributions of prolonged sitting and/or interrupting prolonged sitting with very-brief bouts of light-intensity PA had never been experimentally tested in patients with T2D. Moreover, this study for the first time moved beyond interrupting sitting with standing or ambulatory bouts (although walking bouts were also examined), which may have differing levels of metabolic stimulus (i.e. not physiologically taxing the body enough), practicality, or health efficacy, to examine a potential addition/alternative: simple resistance activities (SRA). A key premise behind these SRA bouts (half-squats, calf raises, gluteal contractions, and knee raises) were that they required no specialized equipment, only small amounts of space, and could be easily performed in a fixed position behind a work desk or at home with minimal disruption to work tasks or leisure pursuits. In addition, they also markedly increase muscle activity, and may also have other longer-term benefits (for example physical function, muscle strength, bone density), however we can only speculate on these aspects at present. In this study in men and women with type 2 diabetes, plasma glucose, insulin and C-peptide (marker of insulin secretion and pancreatic beta cell function) levels following standardized breakfast and lunch meals were all markedly attenuated when prolonged sitting was regularly interrupted with light walking or resistance activities (3 min every 30 min) over an 8 hour day. Plasma triglyceride levels were also reduced for both types of activity bout; however, the reduction was only significant for the SRAs. Interestingly, the magnitude of glucose reduction for the walking bouts was greater in women for glucose levels. (more…)
AACR, Author Interviews, Biomarkers, Cancer Research, Melanoma / 20.04.2016

MedicalResearch.com Interview with: Michael A. Postow, MD Medical Oncologist Louis V. Gerstner, Jr. Graduate School of Biomedical Sciences (GSK) Memorial Sloan Kettering MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Postow: Pembrolizumab has been shown to improve overall survival for patients with advanced melanoma compared to ipilimumab.  Patients with PD-L1 negative tumors still respond to pembrolizumab.  Responses to pembrolizumab were higher when patients had more PD-L1 in the tumor. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Postow: PD-L1 status cannot be used to select patients with melanoma to receive pembrolizumab vs. ipilimumab or even to be used to determine eligibility for immunotherapy in general.  PD-L1 “positivity” is a difficult definition and various cutoff points have been used in various studies to determine positivity.  We need more research to determine the significance of various cutoff definitions of “positive.” (more…)
Author Interviews, JAMA, Stroke / 20.04.2016

MedicalResearch.com Interview with: Dr. Georgios Tsivgoulis MD Department of Neurology, The University of Tennessee Health Science Center, Memphis Second Department of Neurology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece Medical Research: What is the background for this study? Dr. Tsivgoulis: Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding, but there are contradictory data regarding the potential association of CMB burden with the risk of symptomatic intracerebral hemorrhage (sICH) in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). Medical Research:  What are the main findings? Dr. Tsivgoulis: We analyzed data from 9 prospective cohort studies, comprising 2479 total AIS patients, to investigate the association of high cerebral microbleed burden (>10 CMBs on pre-IVT MRI-scan) with the risk of sICH following IVT for AIS from. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared to patients without CMBs, while a higher risk for sICHafter IVT was also detected in patients with high CMB burden (>10 CMBs), when compared to patients with 0-10 or 1-10 CMBs on pre-treatment MRI. In the individual patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before and after adjusting for potential confounders. (more…)
AACR, Author Interviews, Cancer Research, Inflammation, Prostate Cancer, Weight Research / 20.04.2016

MedicalResearch.com Interview with: Charnita Zeigler-Johnson, Ph.D., M.P.H. Assistant Professor Division of Population Sciences Department of Medical Oncology Thomas Jefferson University Philadelphia, PA 19107 Medical Research: What is the background for this study? Dr. Zeigler-Johnson: Obesity has been associated with poor prostate cancer outcomes, included advanced disease at diagnosis, increased risk for cancer recurrence, and risk for mortality. One possible link in the relationship between obesity and prostate cancer progression is inflammation. Obesity produces a state of systemic chronic low-grade inflammation which may contribute to the underlying biology of the tumor microenvironment. The presence of immune cells (T-cells and macrophages) in the tumor microenvironment may indicate aggressive tumors that are likely to metastasize. The goal of this study was to examine prostate cancer tissue to characterize differences in immune cells within the tumor microenvironment by obesity status and cancer severity. We studied tumor samples from 63 non-obese and 36 obese prostate cancer patients. Medical Research: What are the main findings? Dr. Zeigler-Johnson: We found that T-cell and macrophage counts in the tumor did not differ by patient obesity status. However, macrophage (CD68) counts were higher among men diagnosed with higher tumor grade (Gleason Score 7-10). We also found that T-cell (CD8) counts were associated with quicker time to prostate cancer recurrence (indicated by detectable prostate specific antigen levels after treatment.) (more…)
AACR, Author Interviews, Cancer Research, Genetic Research, MD Anderson, Weight Research / 20.04.2016

MedicalResearch.com Interview with: Dr. Xifeng Wu, MD PhD Department Chair, Department of Epidemiology, Division of OVP, Cancer Prevention and Population Sciences Director, Center for Translational and Public Health Genomics Professor, Department of Epidemiology Division of Cancer Prevention and Population Sciences The University of Texas MD Anderson Cancer Center, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Wu: Obesity is a well-established risk factor for renal cell carcinoma (RCC), the most common form of kidney cancer. It has been estimated that more than 40% of RCC incident cases in the US may be attributed to excessive body weight. Growing body of evidence suggests that obesity may also influence clinical outcome of RCC; however, the findings are sometimes conflicting. So far, the molecular mechanism linking obesity to RCC risk or prognosis is not well understood. In this study, we evaluated the promoter CpG site methylation of 20 candidate obesity-related genes and their association with RCC risk and recurrence in a two-phase study of 240 newly diagnosed, previously untreated RCC patients. Pyrosequencing was conducted on paired RCC tumor and normal adjacent tissues to measure promoter methylation. Among the 20 markers, we found NPY, LEP and LEPR showed significant differential methylation levels between tumors and normal adjacent tissues, and methylation was significantly higher in tumors in both discovery and validation groups. Consistent with our findings, we also found lower expression of LEPR in tumor tissues compared to normal adjacent tissues in data obtained from The Cancer Genome Atlas. Additionally, high LEPR methylation in tumors was associated with more advanced tumor features, such as high pathologic stage, high grade and clear cell RCC histology, and increased risk of recurrence compared to the low methylation group. These results suggest that tissue changes in promoter methylation in obesity-related genes may provide some biological basis for the association between obesity and RCC outcome, and that LEPR may be an independent prognostic indicator of recurrence in RCC patients. Further research in larger study population and functional studies are warranted to validate our findings and to elucidate the underlying causal mechanisms. (more…)