Alcohol, Author Interviews, PNAS, Scripps / 19.05.2015

Interview of Candice Contet, Ph.D. Assistant Professor The Scripps Research Institute, La Jolla, CAMedicalResearch.com Interview with: Interview of Candice Contet, Ph.D. Assistant Professor The Scripps Research Institute, La Jolla, CA MedicalResearch: What is the background for this study? Dr. Contet: Alcohol changes the activity of numerous proteins in the brain. One of them is an ion channel found in neurons, the G-protein activated inwardly rectifying potassium (GIRK) channel. It is however unknown whether the ability of alcohol to open GIRK channels matters for its effects in vivo, i.e. how tipsy we feel or how motivated we are to drink alcohol. To address this question, we studied mice that are lacking one of the components of GIRK channels, the GIRK3 subunit. These mice behave normally in the absence of alcohol, and we sought to determine whether they respond differently to alcohol. MedicalResearch: What are the main findings? Dr. Contet: We found that the absence of GIRK3 did not impact how fast the mice clear alcohol from their body nor how sensitive they are to alcohol intoxication. Alcohol reduced their motor coordination, made them sleepy and lowered their body temperature to the same extent as in normal mice. GIRK3-deficient mice also drank as much alcohol as normal mice when they were given continuous access to alcohol, a situation in which mice sporadically drink throughout the day but rarely get intoxicated. By contrast, when mice are given access to alcohol only for a couple hours per day at a specific time of the day, they drink to the point of intoxication. Under these conditions, which emulate “binge drinking”, the GIRK3-deficient mice drank more than normal mice. The next step was to locate the region of the brain responsible for the effect of GIRK3 on binge drinking. We turned our attention to the mesocorticolimbic dopaminergic pathway, a neural circuit that facilitates reward seeking. This pathway originates in an area of the midbrain called the ventral tegmental area (VTA) and releases the neurotransmitter dopamine in two forebrain areas: the ventral striatum and the prefrontal cortex. Alcohol, like other drugs of abuse, activates this pathway. When we reintroduced GIRK3 in the VTA of GIRK3-deficient mice, their alcohol intake dropped down to normal levels. Increasing the levels of GIRK3 in the VTA of normal mice reduced their alcohol consumption even further. We concluded that GIRK3 in the VTA keeps binge drinking in check: the more GIRK3, the less binge drinking. We then wanted to understand how GIRK3 controls binge drinking: do the GIRK3-deficient mice drink more because alcohol is more rewarding to them, or because more alcohol is needed for them to experience the same level of reward? To answer this question, we measured the activity of VTA neurons in brain slices. Alcohol usually make VTA neurons fire more – but in the absence of GIRK3, these neurons were completely insensitive to alcohol, even at a very high concentration. We also measured the levels of dopamine in the ventral striatum. Injecting mice with a moderate dose of alcohol usually causes a rise in dopamine levels – but again, GIRK3-deficient mice were completely unresponsive. These results may seem paradoxical. If the canonical “reward pathway” of the brain cannot be activated by alcohol, these mice should not have any motivation to drink alcohol. But the mesocorticolimbic dopaminergic pathway is not the only brain circuit responsible for the rewarding properties of alcohol, and we think that GIRK3-deficient mice end up drinking more alcohol to activate alternative circuits more strongly than normal mice would. (more…)
Author Interviews, Brain Injury, JAMA, UT Southwestern / 18.05.2015

C. Munro Cullum, PhD, ABPP Professor of Psychiatry and Neurology & Neurotherapeutics Pamela Blumenthal Distinguished Professor of Clinical Psychology Chief of Psychology Director of Neuropsychology Univ. of Texas Southwestern Medical Center Dallas, TX 75390-9044 MedicalResearch.com Interview with: C. Munro Cullum, PhD, ABPP Professor of Psychiatry and Neurology & Neurotherapeutics Pamela Blumenthal Distinguished Professor of Clinical Psychology Chief of Psychology , Director of Neuropsychology Univ. of Texas Southwestern Medical Center Dallas, TX Medical Research: What is the background for this study? What are the main findings? Dr. Cullum: My colleague and principal investigator of the study, Dr. John Hart and I have been interested in the acute and longer-term effects of traumatic brain injury for years, and because of my roles in the Alzheimer’s Disease Center and the Texas Institute for Brain Injury and Repair at the University of Texas Southwestern Medical Center, it seemed like a natural to begin studying older individuals with and without cognitive disorder who have a history of traumatic brain injury.  Our main findings are two-fold: First, we demonstrated that a history of concussion with loss of consciousness (which make up only about 10% of all concussions) was associated with smaller memory centers in the brain (the hippocampus) and lower memory results in our sample of retired professional football players. Concussions that did not result in loss of consciousness did not show that same strong association. Second, our data suggest that patients with a clinical diagnosis of mild cognitive impairment (ie a memory disorder that does not grossly impair overall functioning but may lead to dementia) who also have a history of concussion with loss of consciousness show worse memory results and more brain atrophy than similar individuals diagnosed with mild cognitive impairment in the absence of a history of concussion. (more…)
Author Interviews, Diabetes, Endocrinology, HIV, Infections, JCEM / 18.05.2015

Kevin Yarasheski, PhD Assistant Director, Biomedical Mass Spectrometry Research Facility Professor of Medicine, Cell Biology & Physiology, Physical Therapy Washington University School of MedicineMedicalResearch.com Interview with: Kevin Yarasheski, PhD Assistant Director, Biomedical Mass Spectrometry Research Facility Professor of Medicine, Cell Biology & Physiology, Physical Therapy Washington University School of Medicine Medical Research: What is the background for this study? Dr. Yarasheski:   People living with HIV and taking combination antiretroviral therapy (cART) have successfully reduced the amount of HIV virus in their blood and have partially reconstituted their immune system (CD4+ T-cell count >250 cells/µL).  Despite this, many still experience residual immune cell activation and inflammation that is believed to increase HIV morbidity (non-AIDS conditions e.g., CVD, T2DM, obesity, liver fat, bone loss, dementia) and mortality.  Scientists are seeking safe and effective interventions for residual immune cell activation and inflammation, that have the potential to reduce non-AIDS complications that threaten quality and quantity of life among HIV infected adults. We have been testing the safety and efficacy of sitagliptin in people living with HIV; a dipeptidyl peptidase 4 inhibitor that is FDA approved for treating T2DM, and appears to have favorable anti-inflammatory and immune modulatory properties that might specifically benefit people living with HIV and experiencing cardiometabolic complications associated with residual immune cell activation and inflammation. Medical Research: What are the main findings? Dr. Yarasheski:   In a randomized, double-blinded, placebo controlled 8-wk trial, we found that sitagliptin had beneficial anti-inflammatory, immune regulatory, hematopoietic progenitor cell mobilizing, and glucose lowering effects in cART-treated virally suppressed HIV adults with impaired glucose tolerance.  Sitagliptin improved glucose tolerance (a risk factor for CVD), reduced circulating and adipose-specific inflammatory markers (risk factors for obesity, T2DM, liver fat accumulation, and CVD), and increased the number of blood stem cells that can repair damage and inflammation in the vascular walls. (more…)
Alcohol, Author Interviews, OBGYNE, PLoS / 18.05.2015

Dr. Nina Kaminen-Ahola Ph.D. Department of Medical Genetics Faculty of Medicine University of Helsinki Helsinki, FinlandMedicalResearch.com Interview with: Dr. Nina Kaminen-Ahola Ph.D. Department of Medical Genetics Faculty of Medicine University of Helsinki Helsinki, Finland Medical Research: What is the background for this study? Dr. Kaminen-Ahola: The beginning of embryonic development is vulnerable to the effects of  external influences and disruption of these processes can have long-term effects on development. Our previous study demonstrated, for the first time, that alcohol exposure in early pregnancy can cause permanent changes to the epigenetic regulation, gene function and the appearance of mouse offspring. We discovered increased DNA-methylation, transcriptional silencing of an epigenetically sensitive allele Agouti viable yellow (Avy) and darker coat colour in the offspring. In this study we wanted to see whether alcohol consumed in early pregnancy causes long-term changes to the epigenome and gene expression in hippocampus. According to previous studies the phenotype of offspring in this mouse model is highly variable, but reminiscent of human FAS with growth restriction, similar structural changes to corresponding areas of the face and skull, and hyperactivity. In this study we wanted to determine the impact of alcohol on the structures of the central nervous system. Medical Research: What are the main findings? Dr. Kaminen-Ahola: We observed that early exposure to alcohol caused subtle changes in  the epigenome and altered the function of several genes in the hippocampi of adolescent mice. We also detected alcohol-induced alterations in the brain structure of adult offspring. Interestingly, we also found out that in addition to hippocampus, alcohol caused similar changes to gene function in two different tissues of the infant mouse, bone marrow and the olfactory epithelium of the snout. These results support our hypothesis that early gestational ethanol exposure alters the epigenetic reprogramming of the embryo, which leads to alterations in gene regulation and embryonic development, and causes life-long changes in brain structure, function, and behaviour. (more…)
Author Interviews, Bipolar Disorder, Depression, JAMA / 18.05.2015

MedicalResearch.com Interview with: Maaike M. M. Rive Program for mood disorders AMC/De Meren, Department of Psychiatry PA3.221 Amsterdam  The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: For clinicians, it can be difficult to distinguish whether a depressed patient suffers from major depressive disorder (characterized by depressive episodes only) or bipolar disorder (characterized by both depressive and (hypo)manic episodes). Differentiation between the two disorders is important because e.g. the treatment approaches are different. Although we know that both types of mood disorders are characterized by emotion regulation disturbances, little is known about differences in emotion regulation between the two disorders. Better insight in these differences would be helpful for differentiation between uni- and bipolar disorder. However, previous studies comparing these disorders often allowed medication use, and this may have influenced results. Furthermore, much is unknown about the effect of mood state on emotion regulation differences. We therefore investigated emotion regulation by showing happy, sad and fearful pictures to patients and healthy controls. Participants were instructed to either passively view the pictures, or to distance themselves from their feelings, by thoughts like: ‘this is only a picture’, ‘this will never happen to me’, etc. Emotion regulation success was measured by the difference between subjective ratings of emotional intensity after passive viewing versus distancing. Brain activity was measured with fMRI. The results of our study indicate that emotion regulation does indeed differ between medication-free major depressive or bipolar patients, and that specific differences depend on mood state. During remission, bipolar patients showed impaired emotion regulation across different types of emotions. In contrast, patients with major depressive disorder did not how such impairments during remission. During depression, patients differed regarding happy and sad emotion regulation: bipolar patients showed impaired sad, but unexpectedly normal happy emotion regulation, whereas in major depressive disorder, both sad and happy emotion regulation were compromised. These emotion regulation difficulties were associated with differences in brain activity in the dorsolateral prefrontal cortex (involved in effortful emotion regulation) and the rostral anterior cingulate cortex (connecting emotional and cognitive brain areas). (more…)
Author Interviews, Cost of Health Care, MRI, Radiology / 18.05.2015

Jalal B. Andre, MDDirector of Neurological MRI Harborview Medical Center Assistant Professor of Radiology University of Washington Seattle, WA 98195-7115MedicalResearch.com Interview with: Jalal B. Andre, MD Director of Neurological MRI Harborview Medical Center Assistant Professor of Radiology University of Washington Seattle, WA  98195-7115 Medical Research: What is the background for this study? What are the main findings? Dr. Andre: Patient motion during clinical magnetic resonance (MR) examinations occurs frequently, can result in artifacts that degrade image quality, and has the potential to mask underlying pathology and affect patient care.  Surprisingly, the frequency of motion artifacts in clinical MR examinations has been poorly documented in the literature, as has been the cost associated with obtaining such exams, specifically those that do not meet diagnostic criteria. To better quantify these observations, we performed a retrospective study evaluating the prevalence of motion artifacts during a randomly selected week of clinical MR examinations. We devised a graded 5-tier scale to quantify patient motion, which incorporated the potential for clinical impact  Using this scale, two neuroradiologists performed a consensus evaluation at a picture archiving and communication system station of 192 MR examinations performed during a single calendar week.  This evaluation revealed that significant motion artifact (defined as artifact that could impact image interpretation and potentially change diagnosis) was present in 7.5% of outpatient and nearly 30% of inpatient and/or emergency department MR examinations, and that repeated sequences (subcomponents of an MR examination) were present in nearly 20% of completed MR examinations.  In addition, we found that the specific imaged body part was less predictive of subsequent patient motion than was patient disposition (if they were imaged as a hospital inpatient and/or emergency department patient).  Using a base-case cost estimate derived from fiscal year 2012 outpatient Medicare reimbursement rates and institutional cost estimates, our analysis suggested that a potential cost of $592 per hour could be lost in hospital revenue secondary to patient motion. Extrapolated over a calendar year, the cost of patient motion (as potential forgone institutional revenue) approached $115,000 per scanner per year. (more…)
Author Interviews, Emergency Care, Heart Disease, JAMA / 18.05.2015

Michael B. Weinstock, MD Professor of Emergency Medicine, Adjunct Department of Emergency Medicine, The Ohio State University College of Medicine Emergency Department Chairman and Director of Medical Education, Mt. Carmel St. Ann's Dept. of Emergency Medicine Columbus, OhioMedicalResearch.com Interview with: Michael B. Weinstock, MD Professor of Emergency Medicine, Adjunct Department of Emergency Medicine, The Ohio State University College of Medicine Emergency Department Chairman and Director of Medical Education, Mt. Carmel St. Ann's Dept. of Emergency Medicine Columbus, Ohio Medical Research: What is the background for this study? Response: Patients with potential cardiac ischemia are often admitted to the hospital even after a negative evaluation in the emergency department due to concern about missed MI, unstable angina, or potential for cardiac arrhythmia. Medical Research: What are the main findings? Response: Our study was different than previous studies and clinical decision rules; instead of looking at a 30 day marker, which is important to the cardiologist, ours looked at the risk of a Clinically Relevant Adverse Cardiac Event (CRACE) occurring during hospitalization. These events included inpatient STEMI, life-threatening arrhythmia, cardiac or respiratory arrest, or death. The study found only 4 of these events out of 7266 patients studied and of the 4, two were possibly iatrogenic, suggesting that after a negative ED evaluation (including 2 negative serial cardiac enzyme tests, non-ischemic and interpretable ECG, and nonconcerning vital signs) a patient can be safely sent home for an expedited cardiac outpatient evaluation. (more…)
Anemia, Author Interviews, Diabetes, Diabetologia / 18.05.2015

MedicalResearch.com Interview with: Emma English PhD Lecturer in Healthcare Science and Academic Lead for Clinical Biochemistry University of Nottingham, School of Medicine Royal Derby Hospital, UK MedicalResearch: What is the background for this study? What are the main findings? Dr. English: HbA1c is widely used for monitoring glycaemic control in people with diabetes as there is clear evidence that lowering HbA1c values leads to reductions in the rates of diabetes complications. Recently the World Health Organization and the American Diabetes Association have both advocated the use of HbA1c for the diagnosis of Type 2 diabetes at a value of ≥48 mmol/mol (6.5%). Whilst there are many advantages to the use of HbA1c as a diagnostic tool there are equally some significant limitations to its use. A widely cited confounder is anaemia, however to what extent and which types of anaemia affect HbA1c results was not clearly understood. When HbA1c was introduced as a diagnostic test in England we received many queries from healthcare professionals asking questions such as ‘at what level of anaemia should I not use HbA1c?’ and ‘should I routinely screen patients for anaemia when using HbA1c? And if so, what test should I use?’. In order to answer these questions we conducted a systematic review of the literature to determine what was known on this subject. Our findings, presented in Diabetologia, suggest that iron deficiency and iron deficiency anaemia may lead to a spuriously elevated HbA1c level, thus may lead a false positive diagnosis of diabetes. However, non-iron deficiency anaemias can lead to an artificially lower HbA1c and may lead to a false negative result where a diagnosis of diabetes would be missed. There is no clear evidence to suggest at what levels anaemia can give rise to these effects on HbA1c value and also there does not appear to be a single ideal test for identifying patients where this could be an issue. (more…)
Author Interviews, Testosterone, Urology / 18.05.2015

Ranjith Ramasamy MD Assistant Professor of Urology University of MiamiMedicalResearch.com Interview with: Ranjith Ramasamy MD Assistant Professor of Urology University of Miami Medical Research: What is the background for this study? Dr. Ramasamy: The association between testosterone supplementation therapy (TST) and thrombotic risk in elderly men remains controversial. We evaluated the prevalence of thrombotic events and all-cause mortality in men older than 65 years with hypogonadism treated with testosterone therapy. We compared men treated with testosterone to an age and comorbidity matched cohort of hypogonadal men not treated with testosterone supplementation therapy. Medical Research: What are the main findings? Dr. Ramasamy: No man who received testosterone supplementation therapy died, whereas 6 hypogonadal men who did not receive TST died (p=0.007). There were 4 thrombotic events (1 MI - myocardial infarction, 2 CVA/TIA - stroke, 1 PE - pulmonary embolism) in men who received testosterone supplementation therapy compared to 1 event (CVA/TIA) among men who did not receive TST (p = 0.8). All the events (except one death which took place at 6 months of follow–up) occurred 2 years or more after follow–up. Strengths of the study include long follow–up (>3 years), availability of serum testosterone levels before and after therapy and of a control group (hypogonadal men not treated with TST) for comparison. Limitations included retrospective study design, and a small sample size. (more…)
Author Interviews, Baylor College of Medicine Houston, Sleep Disorders, Urology / 18.05.2015

MedicalResearch.com Interview with: Alexander W. Pastuszak, MD, PhD Male Reproductive Medicine and Surgery Scott Department of Urology Jason Malcolm Scovell Medical Student, Ofc SA-BCM Students Baylor College of Medicine Houston, TX Medical Research: What is the background for this study? What are the main findings? Response: Sleep quality is an important component of overall health, and can both exacerbate health issues and be impaired by health problems. Shift workers, primarily those who do not work standard daylight shifts, are prone to sleep problems, a significant concern in light of the fact that up to 25% of the U.S. workforce is comprised of shift workers. As men age, the prevalence of Lower Urinary Tract Symptoms (LUTS), which include urgency, frequency, waking up at night to urinate, and difficulties with urination, increases.  Unsurprisingly, men with LUTS report poor sleep in part due to awakening repeatedly during the night. We studied a group of male shift workers, who we believe to be an ‘at-risk’ population, and found that not only do the men who report worse sleep quality have worse Lower Urinary Tract Symptoms, but also men who report difficulty falling asleep have more severe LUTS than those who do not. This latter point is significant, given that most men with LUTS can fall asleep without difficulty, but then awaken repeatedly throughout the night, and suggests that sleep difficulties in this population may be resulting in Lower Urinary Tract Symptoms rather than LUTS exclusively resulting in sleep difficulties. (more…)
Author Interviews, Biomarkers, Heart Disease / 18.05.2015

dr-pascal-stammetMedicalResearch.com Interview with: Dr Pascal Stammet Dépt. Anesthésie-Réanimation Centre Hospitalier de Luxembourg Luxembourg MedicalResearch: What is the background for this study? What are the main findings? Dr Stammet: Patients hospitalized after an out-of-hospital cardiac arrest (OHCA) survive in about fifty percent and nine out of ten survivors have a good functional level six months after the arrest. However, in the early days after the cardiac arrest it is difficult to distinguish those who will survive from those who have very severe brain damage, not compatible with life. Biomarkers, like neuron specific enolase (NSE) have shown a prognostic value for outcome prediction. As a consequence of the widespread use of induced hypothermia, to improve survival and neurological function, for patients resuscitated form cardiac arrest, concerns have arisen about the impact of body temperature on previously published cut-off values for poor outcome. NSE has thus been questioned as a useful clinical tool. Recently, the Target Temperature Management trial (TTM-trial) published in November 2013 in the NEJM has shown no benefit of a target body temperature of 33°C over 36°C in patients with out-of-hospital cardiac arrest admitted to the ICU. In the present sub-study, we have analyzed the value of NSE to predict outcome in a cohort of 686 patients of the TTM-trial. Importantly, serial measurements of NSE at 24, 48 and 72 hours allowed accurate outcome prediction, with better performance than clinical and peri-arrest data alone. NSE did not significantly differ between temperature groups meaning that clinicians can use NSE as an adjunct prognostic tool regardless of the chosen temperature management strategy. (more…)
Author Interviews, Dermatology / 18.05.2015

dr-warren-winkelmanMedicalResearch.com Interview with:  Warren J. Winkelman, MD, MBA, PhD, FRCPC, FAAD Director, Medical Affairs Galderma Laboratories, L.P. Fort Worth TX 76177 MedicalResearch: What is the background for this study? What are the main findings? Dr. Winkelman: Rosacea is a common dermatologic facial disorder estimated to affect 16 million Americans. Rosacea is a chronic condition of the central face, including the nose, chin, cheeks and forehead, and is often characterized by flare-ups and remissions. While the cause of rosacea is unknown and there is no cure, its signs and symptoms can become markedly worse in the absence of treatment. Rosacea can be managed with topical and oral medications, and physicians often resort to using these medications in combination for more severe or resistant cases. Doxycycline 40 mg modified release (MR) and metronidazole 1% gel are FDA-approved oral and topical therapies, respectively, indicated to treat the papules and pustules of rosacea. We conducted a phase 2 study to assess the relapse rate, efficacy, and safety of doxycycline 40 mg MR compared to placebo after an initial 12-week once-daily combination regimen of doxycycline 40 mg MR and metronidazole 1% gel in subjects with moderate to severe disease. Of the 235 subjects enrolled in the study, 71% were women, 94% were white, and 75% had Fitzpatrick skin type I, II or III. The mean age was 47.4 years. The percentage of subjects who achieved a success score of 0 (clear) or 1 (near clear) improved from 0% at baseline to 51% at week 12. Clinician’s erythema assessment scores, inflammatory lesion counts, and quality of life scores also improved. Most subjects reported no or mild scaling, stinging/burning, and dryness. Five adverse events were reported that were considered probably or definitely related to treatment: fungal infection, vulvovaginal mycotic infection, pain in extremity, erythema, and skin exfoliation. (more…)
Author Interviews, Prostate Cancer / 17.05.2015

MedicalResearch.com Interview with: Michael Fenstermaker MD NYU School of Medicine | MD, MS | Class of 2015 Northwestern University | BA | Biochemistry, Psychology Medical Research: What is the background for this study? What are the main findings? Dr. Fenstermaker: The benefits of using prostate-specific antigen (PSA) testing to screen for prostate cancer are uncertain. In response to this, many medical societies have recently scaled back their recommendations for PSA screening.  One common thread among these groups is that shared decision-making should guide whether or not men get tested. Shared decision-making is a process by which physicians and patients work together to make a medical decision that aligns with the patient’s values and follows the best available medical evidence. Several studies have shown a decline in PSA testing since new guidelines have been published.  While a decrease in screening is not necessarily problematic itself, it could be an issue if this is the result of fewer physicians discussing screening with their patients. Some experts worry that disparities in screening could develop, such that only informed patients go on to speak with their physicians and receive PSA testing.  By analyzing data from a national survey, we had the chance to investigate just how much men know about the controversies leading to these guidelines changes and whether this knowledge influences PSA usage. Our findings show that the majority of U.S. males of screening age report that they were not informed of many key facts important to understanding the risks and controversies surrounding PSA testing.  Of particular concern, certain vulnerable populations, such as those without regular healthcare providers were less likely to be informed of these facts. Surprisingly, those men who had more awareness of the controversies about PSA testing were more likely to undergo testing.   (more…)
Author Interviews, Brigham & Women's - Harvard, Prostate Cancer / 17.05.2015

Jennifer R. Rider, ScD, MPH Assistant Professor of Medicine Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Department of Epidemiology Harvard T.H. Chan School of Public Health Boston, MA 02115MedicalResearch.com Interview with: Jennifer R. Rider, ScD, MPH Assistant Professor of Medicine Channing Division of Network Medicine Brigham and Women's Hospital and Harvard Medical School Department of Epidemiology Harvard T.H. Chan School of Public Health Boston, MA 02115 Medical Research: What is the background for this study? What are the main findings? Dr. Rider: Numerous studies have investigated the potential role of sexual activity on the development of prostate cancer. However, most of these studies have been small and retrospective, making them more prone to bias. In addition, previous studies often relied on proxies of exposure for sexual activity (number of sexual partners, age at first marriage, etc.), which may not adequately measure the aspects of sexual activity that are most important for prostate health. The current study is the largest prospective study to date on ejaculation frequency and prostate cancer. It includes 18 years of follow up of almost 32,000 healthy men, 3839 of whom later were diagnosed with prostate cancer.  We asked men about their average monthly frequency of ejaculation between the ages of 20-29, 40-49, and in the year prior to the questionnaire (1991). We find that frequency of ejaculation throughout life course is inversely associated with risk of prostate cancer at all three of these time points. For instance, men who have an average monthly ejaculation frequency of 21 or more times/moth at ages 40-49 have a statistically significant 22% reduction in risk of developing prostate cancer compared to men with a frequency of 4-7 times/month, adjusting for multiple dietary and lifestyle factors, and prostate cancer screening history. (more…)
Prostate Cancer / 17.05.2015

Ryan P. Terlecki, MD, FACS Director, Men's Health Clinic Director, Fellowship in Urologic Reconstruction, Prosthetic Urology, and Infertility Director, Medical Student Education Associate Professor of Urology Wake Forest Baptist HealthMedicalResearch.com Interview with: Ryan P. Terlecki, MD, FACS Director, Men's Health Clinic Director, Fellowship in Urologic Reconstruction, Prosthetic Urology, and Infertility Director, Medical Student Education Associate Professor of Urology Wake Forest Baptist Health Medical Research: What is the background for this study? What are the main findings? Response: In recent years, the value of generalized screening for prostate cancer (PCa) in adult men has been questioned, with several national associations recommending against the practice in men without recognized risk factors. Screening, when performed, often consists of a blood test for prostate specific antigen (PSA) and a digital rectal exam (DRE). Once PSA was developed as a screening tool, we witnessed a stage migration such that observing a locally advanced cancer that would be initially found via DRE became a rarer event. In practice, we have noticed that some men will actually avoid a clinic visit because of the DRE. Additionally, the digital rectal exam has limitations and is often poorly reproducible among providers. We chose to review a large body of data to shed some light on the utility of the digital rectal exam exam. We analyzed data from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening trial, to determine the ability of the digital rectal exam to result in a diagnosis of clinically significant PCa in the setting of a normal PSA. We found that if PSA is normal and digital rectal exam is considered abnormal, the chance of detecting a clinically significant cancer is similar to a situation of normal DRE and normal PSA. Also, 1,372 men would need to undergo a digital rectal exam to identify a single case of clinically significant prostate cancer not detected by PSA. (more…)
Author Interviews, Endocrinology, Testosterone, University of Michigan / 17.05.2015

MedicalResearch.com Interview with: Jim Dupree, MD, MPH Assistant Professor Department of Urology, Division of Andrology University of MichiganMedicalResearch.com Interview with: Jim Dupree, MD, MPH Assistant Professor Department of Urology, Division of Andrology University of Michigan Medical Research: What is the background for this study? What are the main findings? Dr. Dupree: There are increasing discussions in the United States about testosterone therapy and men with clinical hypogonadism (or low testosterone).  Yet, to date, there have not been any nationally-representative studies of the prevalence of low testosterone in the United States.  Using a validated national health examination program from the CDC, we found that the national prevalence of low testosterone (serum testosterone ≤ 300 ng/dL) in adult males in the US was 28.9%.  Among other factors, men who were older, had a higher body mass index (BMI), or had a larger waist circumference were at risk for having lower testosterone levels. (more…)
Author Interviews, Cost of Health Care, Primary Care / 15.05.2015

Judith Hibbard, Ph.D. Senior Researcher, Health Policy Research Group University of OregonMedicalResearch.com Interview with: Judith Hibbard, Ph.D. Senior Researcher, Health Policy Research Group University of Oregon MedicalResearch: What is the background for this study? What are the main findings? Dr. Hibbard: Two important trends are happening in health care today: 1) Policies which move away from paying for volume and toward paying for value; and 2) The emphasis on patient engagement and the need for the patient to play a key part in the care process. Because so many quality outcomes are determined to a large extent by patient behaviors, there is an implied assumption that if you pay primary care clinicians (PCPs) more for better quality outcomes, they will also try to engage the patient as a necessary partner in reaching quality targets. That is, there is a tacit assumption that clinicians will naturally engage patients if you incentivize them on the quality metrics. We had an opportunity to examine the soundness of this assumption, when we conducted a study of primary care clinicians whose compensation was based 40% on their performance of quality metrics. The findings show that the vast majority of clinicians did not invest their efforts in patient engagement and activation, when trying to maximize their income under this model. They put their efforts in other areas. However, a year later they were very frustrated that their income was influenced by patient behaviors. This was their greatest frustration with the compensation model, and they indicated that “patient’s unwillingness to change their behavior” as the greatest barrier to achieving their quality goals. (more…)
Author Interviews, Exercise - Fitness, PLoS, Technology / 15.05.2015

Michael Rebold, PhD, CSCS Assistant Professor Department of Exercise Science Bloomsburg University Bloomsburg, PA 17815MedicalResearch.com Interview with: Michael Rebold, PhD, CSCS Assistant Professor Department of Exercise Science Bloomsburg University Bloomsburg, PA 17815 Medical Research: What is the background for this study? What are the main findings? Dr. Rebold: We assessed how common smartphone uses (texting and talking) interfere with treadmill exercise. We found that when individuals use their smartphones during exercise for texting or talking, it causes a reduction in exercise intensity. (more…)
Author Interviews, Genetic Research, Infections, Inflammation, Stanford / 15.05.2015

MedicalResearch.com Interview with: Timothy E Sweeney, MD PhD Resident, General Surgery Postdoc, Khatri Lab, Bioinformatics Stanford University Medical Research: What is the background for this study? What are the main findings? Dr. Sweeney: Sepsis is defined as the presence of systemic inflammation due to infection. Systemic inflammation can be caused from many things, such as trauma, surgery, thrombosis, autoimmunity, etc. It can also be caused by infection. On the other hand, infection does not necessarily cause systemic inflammation, either:  a person can get a minor infection, like strep throat, and not have a systemic response. It's the intersection of severe inflammation (a syndrome called SIRS) with infection that defines sepsis. In general surgery, we frequently see patients after traumatic injury or surgery who are having an inflammatory response (ie, fevers, fast heart rate, high white blood cell count, etc). But it's not clear whether this inflammatory response is a reaction to the trauma or surgery, or whether there might be an infection brewing that is causing the reaction. Identifying the inflammatory response doesn't require many special tests-- it's easy to spot. So we know which patients have inflammation and which do not. What is difficult is determining the root cause of the inflammation, and, in particular, whether there is an infection present that needs treatment with antibiotics. Current diagnostics for infection (not sepsis) are either slow (like blood cultures, which can take 24-72 hours to return) or not highly accurate (like procalcitonin). We sought to define a better test that could specifically differentiate between people with sterile inflammation, and people with inflammation due to infection (sepsis). By integrating gene expression data from multiple publicly available cohorts, we were able to find a set of 82 genes that are significantly differently expressed between these two groups. We then used an algorithm called a greedy forward search to find a subset of 11 genes that were most diagnostic for sepsis. (more…)
Author Interviews, MRI, Neurology, Stroke / 14.05.2015

Amie W. Hsia, MD Medical Director, Comprehensive Stroke Center MedStar Washington Hospital Center NIH Stroke Program at MWHC Associate Professor, Neurology Georgetown University Washington, DC 20010MedicalResearch.com Interview with: Amie W. Hsia, MD Medical Director, Comprehensive Stroke Center MedStar Washington Hospital Center NIH Stroke Program at MWHC Associate Professor, Neurology Georgetown University Washington, DC 20010   Medical Research: What is the background for this study? What are the main findings? Dr. Hsia: Acute stroke is a common presenting problem in the emergency department. We know that “time is brain” and that for patients experiencing an ischemic or “blockage” type of stroke, the most common type, the sooner we can administer tPA, a clot-busting medication and the only FDA-approved medication to treat acute stroke, the better chance for a good outcome. Therefore, there is a goal national benchmark time of administering the drug to appropriate acute stroke patients within 60 minutes of their arrival to the emergency department. There are many steps that are necessary in the evaluation of an acute stroke patient in the emergency department before tPA can be given. This includes a brain scan to make sure a patient is not having the less common bleeding type of stroke. A CT or “CAT” scan is the typical type of brain scan that is performed in emergency departments across the country and the world to screen a patient before giving tPA. The primary purpose of the CT scan is to exclude bleeding; it is difficult to visualize an early stroke on CT. Though an MRI can give more complete information including showing the stroke as it is happening in these first few hours and though most hospitals have an MRI scanner, an MRI takes longer to perform and has not traditionally been used in an emergency setting. At the two hospitals included in this study, MedStar Washington Hospital Center in D.C. and Suburban Hospital in Maryland, we are fortunate to serve as the sites for the NINDS intramural stroke clinical research program and use MRI routinely to screen acute stroke patients to learn more about stroke and develop new treatments for stroke. It is upon this foundation that we performed independent hospital-wide quality improvement initiatives engaging multidisciplinary committees with leadership from all the departments involved in the care of the acute stroke patient in that critical first 60 minutes. Inspired by our colleagues at Washington University in St. Louis led by Dr. Andria Ford who used similar methods in reducing treatment times with CT screening, we used lean manufacturing principles to streamline our processes that include MRI screening and dramatically reduced our treatment times from a baseline of 93 minutes down to 55 minutes while still maintaining safety. Through these efficiency improvements, we were able to achieve a 4-fold increase in the percentage of stroke patients treated with tPA within 60 minutes. (more…)
Allergies, Author Interviews / 14.05.2015

Dr. Christine McCusker MD Associate Professor, Department Pediatrics Meakins-Christie Laboratories McGill University and the MUHCRI, Montreal Quebec, CanadaMedicalResearch.com Interview with: Dr. Christine McCusker MD Associate Professor, Department Pediatrics Meakins-Christie Laboratories McGill University and the MUHCRI, Montreal Quebec, Canada Medical Research: What is the background for this study? What are the main findings? Dr. McCusker: When the body is exposed to new substances, the immune system must evaluate the “threat” and choose the type of response that will best protect the host. Allergies and allergic asthma develop after the response to “allergens” follows the TH2-type inflammatory pathway instead of the non-inflammatory tolerant pathway.  Evidence suggests that there is some plasticity in this “choice” and thus it may be possible to influence the immune response to preferentially choose the tolerant pathway when exposed to allergens. We therefore treated very young mice to a molecule designed to inhibit activation of the TH2 pathway. We showed that this early treatment resulted in long-lasting protection from the development of allergies.  Instead of allergic responses, vaccinated animals developed tolerant responses to allergens and did not show any signs of allergies or asthma.  Importantly, while the influence of the treatment was long-lasting, the molecule itself is rapidly removed from the system. (more…)
Author Interviews, JAMA, OBGYNE, Surgical Research / 14.05.2015

Robert A. Meguid, MD MPH FACS Assistant Professor Section of General Thoracic Surgery Division of Cardiothoracic Surgery Department of Surgery University of Colorado Denver | Anschutz Medical Campus Aurora, CO 80045MedicalResearch.com Interview with: Robert A. Meguid, MD MPH FACS Assistant Professor Section of General Thoracic Surgery Division of Cardiothoracic Surgery Department of Surgery University of Colorado Denver | Anschutz Medical Campus Aurora, CO 80045 Medical Research: What is the background for this study? What are the main findings? Dr. Meguid: The surgical literature on adverse outcomes after surgery on pregnant patients is conflicting.  We know that the majority of surgery performed on pregnant patients is not elective (and just over 50% of it in the database studied was emergency surgery).  We expected to find an increased rate of adverse outcomes in those pregnant patients.  However, when we matched the pregnant and non-pregnant women who underwent surgery in the database, with excellent matching on all available preoperative characteristics and on the actual operation performed, we found similar, low rates of 30-day postoperative death and complication.  In this study, pregnant patients had undergone a broad spectrum of different types of operations, including general, vascular, thoracic, head and neck, non-obstetric gynecologic and urologic, orthopedic, reconstructive, and neuro-surgery.  Given the concern that we as surgeons have over operating on pregnant patients, both for the well-being of the patient and her child, our findings are reassuring.  This suggests that we as a medical profession are diligent in minimizing risk to pregnant women who need surgery that cannot be delayed until after the child's birth.  Again, this study faces the limitations of being unable to assess any short term harm done to the fetus and the subsequent long term outcome of the child. (more…)
Author Interviews, Cancer Research, Wistar / 14.05.2015

Katherine Aird, Ph.D. Gene Expression and Regulation Program The Wistar Institute, Philadelphia, PAMedicalResearch.com Interview with: Katherine Aird, Ph.D. Gene Expression and Regulation Program The Wistar Institute, Philadelphia, PA MedicalResearch: What is the background for this study? What are the main findings? Dr. Aird: Senescence is considered an important tumor suppressor mechanism. In normal cells, activation of certain oncogenes decreases the levels of dNTPs (the building blocks of DNA), leading to replication stress. We previously found that loss of the rate-limiting enzyme in dNTP synthesis, ribonucleotide reductase M2 (RRM2), is the cause of this replication stress. Restoration of RRM2 expression could rescue the loss of dNTPs and replication stress, which overcame the senescence-associated growth arrest. Indeed, RRM2 is highly expressed in many cancer types, including melanoma and ovarian cancer. Therefore, we found that increased dNTP levels can overcome senescence and potentially lead to transformation of cells and cancer. We next wanted to further our understanding of replication stress in the context of senescence. In the current study, we suppressed nucleotide metabolism by decreasing RRM2 expression as a model for replication stress and then determined what proteins are necessary for the induction of senescence. We found that loss of ATM could overcome replication stress-induced senescence. This was due to increased dNTP levels. dNTPs were increased due to a coordinated inactivation of p53 and activation of c-MYC by loss of ATM. These changes at the molecular level correlate with reprogramming of cellular metabolism by generating dNTPs. Thus, loss of ATM in the context of replication stress can change cellular metabolism to a more cancer-like phenotype. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Journal Clinical Oncology, Stanford / 13.05.2015

MedicalResearch.com Interview with: Melinda L. Telli, M.D. Assistant Professor of Medicine Stanford University Division of Medical Oncology Stanford, CAMelinda L. Telli, M.D.
Assistant Professor of Medicine
Stanford University
Division of Medical Oncology
Stanford, CA 94305-5826 Medical Research: What is the background for this study? What are the main findings? Response: A major goal of this study was to explore a DNA damaging chemotherapy regimen in patients with newly diagnosed early-stage triple-negative or BRCA1/2 mutation-associated breast cancer. This was based on the hypothesis that these types of tumors are more responsive to DNA damaging therapeutics. A second major goal was to identify predictors of response to this platinum-based therapy among patients with sporadic triple-negative breast cancer (TNBC). Overall, this study demonstrated that the non-anthracycline and non-taxane neoadjuvant regimen of gemcitabine, carboplatin and iniparib resulted in a 36% pathologic complete response rate (pCR). This compares favorably to pCR rates commonly observed with anthracycline and taxane-based regimens in this group of patients. The response rate was higher among triple-negative breast cancer patients with a germline BRCA1 or BRCA2 mutation (56%). Given the hypothesis of underlying DNA repair defects in sporadic triple-negative breast cancer, we also evaluated a novel measure of genomic instability to detect the accumulation of changes in the genomic landscape of a tumor attributable to defective homologous recombination DNA repair. Homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Very importantly, we found that the HRD-LOH assay was able to identify patients with sporadic TNBC lacking a BRCA1 or BRCA2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. (more…)
Author Interviews, Nature, NIH / 13.05.2015

Humphrey Yao, Ph.D. Lead Researcher Reproductive and Developmental Biology Laboratory National Institute of Environmental Health Sciences (NIEHS) National Institutes of Health (NIH) Research Triangle Park, North CarolinaMedicalResearch.com Interview with: Humphrey Yao, Ph.D. Lead Researcher Reproductive and Developmental Biology Laboratory National Institute of Environmental Health Sciences (NIEHS) National Institutes of Health (NIH) Research Triangle Park, North Carolina Medical Research: What is the background for this study? What are the main findings? Dr. Yao: We wanted to understand how an organ forms, and what basic cell types were needed to form an organ. So, we used a mouse ovary model system to understand the process. The functional unit of the ovary is called the follicle, and it is made up of three types of cells — the maturing egg, granulosa cells, and theca cells. Scientists knew where the egg and the granulosa cells came from, but no one knew where theca cells came from. Theca cells are important, because they allow females to produce the hormones that sustain follicle growth. Researchers also lacked information about how the egg, granulosa cells, and theca cells talked to each other to promote growth and maintain a healthy ovary. We made two discoveries. First, we answered the long-standing question of theca cell origin by determining that they have two sources, both inside and outside of the ovary. We don’t yet know why theca cells have two sources. Second, we uncovered the molecular signaling system that the egg, granulosa cells, and theca cells use to communicate. We didn’t expect to find this three-way cellular crosstalk, but now that we know how they signal each other, I believe we are closer to understanding how an ovary develops and what happens when something goes wrong. Ovarian disorders, such as premature ovarian failure and polycystic ovarian syndrome, may start when cellular communication is altered or if the various cells fail to develop properly. (more…)
Author Interviews, BMJ, Exercise - Fitness, Technology / 13.05.2015

Dr. Shang-Ming Zhou Senior Lecturer in Statistical Modelling and Analytics for Epidemiology and Public Health, Public Health Informatics Group, Health Information Research Unit (HIRU), UKCRC DECIPHer (Development and Evaluation of Complex Interventions for Public Health Improvement) Centre, College of Medicine, Swansea University, Swansea, MedicalResearch.com Interview with: Dr. Shang-Ming Zhou Senior Lecturer in Statistical Modelling and Analytics for Epidemiology and Public Health, Public Health Informatics Group, Health Information Research Unit (HIRU), UKCRC DECIPHer (Development and Evaluation of Complex Interventions for Public Health Improvement) Centre, College of Medicine, Swansea University, Swansea, UK Medical Research: What is the background for this study? What are the main findings? Response: In medical and sport science research, body-worn accelerometers are widely used to provide objective measurements of physical activity. However, accelerometers collect data continuously even during periods of nonwear (i.e. periods when participants may not be wearing their monitor, such as during sleeping). It is important to distinguish time of sedentary behaviours (eg. watching television) from time of nonwear. The clinical consequence of misclassification of accelerometer wear and nonwear would overestimate or underestimate physical activity level, and mislead the interpretation of the relationship between physical activity and health outcomes. Automated estimation of accelerometer wear and nonwear time events is particularly desired by large cohort studies, but algorithms for this purpose are not yet standardized and their accuracy needs to be established. This study presents a robust method of classifying wear and nonwear time events under free living conditions for triaxial accelerometers which combines acceleration and surface skin temperature data. The new findings are: Either acceleration data or skin temperature data alone is inadequate to accurately predict wear and nonwear events in some scenarios under a free living condition; This study provides a simple and efficient algorithm on use of short time periods of consecutive data blocks for accurately predicting triaxial accelerometer wear and nonwear events; Combining both types of acceleration and skin temperature data can significantly improve the accuracy of accelerometer wear and nonwear events classification in monitoring physical activity. (more…)
Author Interviews, Biomarkers, Brain Injury / 13.05.2015

MedicalResearch.com Interview with: Pashtun Shahim, MD Departement of Neurosurgery, University Hospital, Linköping, Sweden Clinical Neurochemistry Laboratory Institute of Neuroscience and Physiology Sahlgrenska University Hospital Mölndal Sweden Medical Research: What is the background for this study? What are the main findings? Response: Visinin-like protein-1 (VLP-1 or VILIP-1) is a neuronal calcium-sensor protein, originally studied as a stroke marker and identified as a marker of neuronal injury in brain injury models. Increased plasma and cerebrospinal fluid (CSF) VILIP-1 hase been reported in Alzheimer’s disease, where CSF VILIP-1 correlates with CSF total tau (T-tau) and with brain volume. Recently, using a novel ultrasensitive method to measure tau in plasma, increased levels of plasma T-tau were found in concussed professional ice hockey players, where the levels correlated with the resolution of post-concussive symptoms and the players returning to play. The main findings of this study were that VILIP-1 did not increase significantly in serum after sports-related concussion. However, the serum levels of VILIP-1 increased after a friendly game without concussion, signaling extracerebral expression. (more…)
Author Interviews, HPV, Vaccine Studies / 13.05.2015

Maria Blomberg Virus, Lifestyle & Genes Danish Cancer Society Research Centre Copenhagen, DenmarkMedicalResearch.com Interview with: Maria Blomberg Virus, Lifestyle & Genes Danish Cancer Society Research Centre Copenhagen, Denmark Medical Research: What is the background for this study? What are the main findings? Response: Two vaccines against human papillomavirus (HPV) were licensed almost one decade ago. Since then multiple countries have implemented HPV vaccination programs to help reduce genital warts (one of the kinds of warts most harmful to people), but many struggle with low coverage rates. An important barrier to vaccination is the cost of the vaccines and less developed countries also face considerable logistical challenges. Both vaccines were administered as three dose schedules, but in early 2014 the WHO’s Strategic Advisory Group of Experts and the European Medicines Agency reviewed the evidence of reduced dose schedules of HPV vaccination, and subsequently recommended a two dose schedule for young girls. A reduction of the number of doses has obvious advantages; it would lower the costs, ease implementation of vaccination schedules and potentially increase coverage rates. Based on these recommendations, countries around the world have reduced the dosing schedule in their HPV vaccination programs for young girls to two doses. However, the current evidence is based primarily on immunological studies, and because the immune correlate of protection is not known, studies with disease endpoints are very important. Using the biologically relevant endpoint of genital warts, this study aimed to assess the clinical effectiveness of a two dose schedule of quadrivalent HPV vaccine compared with the standard three-dose regimen administered at month 0, 2 and 6. We found that with the standard vaccination schedule, completion of the three dose regimen is important to gain maximal protection. However, the effectiveness of two doses increased significantly with increasing time between the doses, and with an interval of approximately 6 months between dose one and two, no differences could be found between two and three doses. (more…)
Addiction, Author Interviews, Columbia, Emergency Care, Pharmacology / 13.05.2015

MedicalResearch.com Interview with: Joanne Brady, PhD candidate Department of Anesthesiology, College of Physicians and Surgeons Department of Epidemiology, Mailman School of Public Health Columbia University, New York, NY Medical Research: What is the background for this study? What are the main findings? Response: Prescription drug overdose is a major public health problem in the United States. Prescription drug overdose mortality has increased dramatically over the past twenty five years. Frequent emergency department utilization may be a marker for risk of prescription drug overdose death. The current study assessed how frequency of emergency department visits in the past year related to risk of subsequent prescription drug overdose death. In a cohort of patients visiting the emergency department, patients with four or more visits to the emergency department in the past year were at substantially higher risk for prescription drug overdose death than patients who visited the emergency department one or fewer times. As the number of visits to the emergency department increased from 0 - 1 to 4 or more for any reason the risk of dying from prescription drug overdose also increased. (more…)