MedicalResearch.com Interview with: Elliot B Tapper, M.D. Clinical Fellow in Medicine (EXT) Beth Israel Deaconess Medical Center Boston MA 02215 Medical Research: What is...
MedicalResearch.com Interview with:
Alexander N Yatsenko, MD, PhD
Assistant Professor,
Department of OBGYN and Reproductive Science,
Magee-Womens Research Institute,
University of Pittsburgh, PA
Pittsburgh, PA 15213
Medical Research: What is the background for this study? What are the main findings?
Dr. Yatsenko: The known causes of male infertility not due to physical obstruction are usually because of sex-chromosome defects, such as deletions of the Y chromosome or duplication of the entire X chromosome in Klinefelter syndrome. Eight times out of 10, conventional genetic testing doesn’t reveal a chromosomal problem and infertility is considered idiopathic. We wanted to try to find other genetic reasons for the problem.
We found a deletion in part of the DNA coding of the testis-expressed gene 11 (TEX11) on the X-chromosome, which men inherit from their mothers. The alteration caused meiotic arrest, meaning the precursor cells could not properly undergo meiosis. We also found similar TEX11 gene mutations and meiotic arrest in two out of 49 men diagnosed with idiopathic azoospermia in Pittsburgh or at a Poland infertility clinic, and in five out of 240 infertile men assessed at a collaborating Andrology clinic in Muenster, Germany. These genetic findings were confirmed on protein level using patients’ testis biopsies. (more…)
MedicalResearch.com Interview with:
Shyamasundaran Kottilil MBBS, PhD
Division of Infectious Diseases, Institute of Human Virology
University of Maryland, Baltimore
Laboratory of Immunoregulation
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Bethesda, Maryland
Medical Research: What is the background for this study? What are the main findings?
Dr. Kottilil: During treatment with interferon-based therapies, hepatitis C viral load levels were clinically useful as on-therapy markers of treatment outcome. However, the standard-of-care for HCV treatment has recently evolved from interferon-based regimens to short-duration, all-oral, direct-acting antiviral (DAA) therapies. Therefore, it is important that we re-evaluate the utility of HCV viral loads during DAA regimens in guiding clinical decision-making.
We found that Hepatitis C viral loads on treatment and at end of treatment were not predictive of treatment success versus relapse with DAA therapy. Contrary to our experience with interferon-containing regimens, low levels of quantifiable HCV RNA at end of treatment did not preclude treatment success.
(more…)
MedicalResearch.com Interview with:
Wiliam C. Huang, MD FACS
Associate Professor of Urology
Division of Urologic Oncology
NYU Langone Medical Center/Perlmutter Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Huang: The presentation of kidney cancers has dramatically evolved over the past two decades with most kidney cancers being incidentally diagnosed at an early stage. We have begun to recognize that at this small size (< 4 cm), the tumors are frequently indolent in nature and some are completely benign. Consequently, the management options for these small cancers have expanded and evolved. Whereas the entire removal of the kidney was the treatment of choice in the past, alternative options including removal or ablation of the tumor-bearing portion of the kidney has become increasingly utilized. Similar to other early stage cancers, watchful waiting or observation is also becoming a reasonable treatment option.
We used the most recent SEER-Medicare Data (2001 – 2009) to evaluate the management trends and outcomes of small kidney cancers in the new millennium. We believe that this is an important study as it provides important and practical findings, which are useful to both clinical researches as well as practicing physicians.
(more…)
MedicalResearch.com Interview with:
David A. Bluemke, MD, PhD, MsB, FAHA, FACR
Director Radiology and Imaging Sciences
Senior Investigator,
National Institute of Biomedical Imaging and Bioengineering
Adjunct Investigator, NLBI, NIDDK
Medical Research: What is the background for this study? What are the main findings?
Dr. Bluemke: Most knowledge about the extent of coronary disease is from high risk patients who have coronary angiograms. Yet most individuals are symptomatic and have lower cardiovascular risk, and would not undergo a coronary angiogram.
Coronary CT angiography can be used to evaluate the extent of plaque in low or moderate risk individuals. The most concerning type of plaque is "soft plaque", which can increase or rupture over time.
Using coronary CT, all coronary plaque throughout the entire heart was measured. Importantly, the amount of soft plaque was uniquely associated with risk factors such as LDL, diabetes, and hypertension.
(more…)
MedicalResearch.com Interview with:
Harley Goldberg, DO
Physical Medicine and Rehabilitation
Kaiser Permanente
Medical Research: What is the background for this study? What are the main findings?
Dr. Goldberg: This is the first large-scale randomized, double-blind, placebo-controlled clinical trial of oral steroids for acute radiculopathy, commonly called sciatica, associated with a herniated lumbar disk.
Lumbar radiculopathy (or pain down the leg in a lumbar nerve root distribution) is a common source of pain and disability for many adults. It is thought that inflammation from a disk herniation is responsible for many of the symptoms, so giving a powerful anti-inflammatory, such as steroid medication, might help relieve sciatica symptoms quickly. Prior research has shown that lumbar diskectomy does not affect the one year outcome for most patients, and epidural steroid injections do not have strong support by clinical trials. If the use of epidural steroids injections is based on application of steroid anti-inflammatory to the affected nerve root(s), perhaps an oral steroid can have affect. Although oral steroids are used by many physicians and have been included in some clinical guidelines, no large-scale clinical trials of oral steroids for sciatica have been conducted before.
Our study found that among patients with acute radiculopathy associated with a herniated lumbar disk, a short course of oral steroids resulted in only modest improvement in function and no significant improvement in pain.
(more…)
MedicalResearch.com Interview with:
Julie M. Donohue, Ph.D.
Associate professor and Vice Chair for Research
Graduate School of Public Health Department of Health Policy and Management
University of Pittsburgh
Medical Research: What is the background for this study? What are the main findings?
Dr. Donohue: We looked at data on medication use from January through September 2014 on 1 million Affordable Care Act-established marketplace insurance plan enrollees. Our analysis found that among people who enrolled in individual marketplaces, those who enrolled earlier were older and used more medication than later enrollees. Marketplace enrollees, as a whole, had lower average drug spending per person and were less likely to use most medication classes than patients enrolled in employer-sponsored health insurance. However, marketplace enrollees were much more likely to use medicines for hepatitis C and for HIV, which is particularly important given the general concerns about the rising costs of these medications for consumers.
(more…)
MedicalResearch.com Interview with:
Paula Chatterjee, MD, MPH
Department of Medicine, Brigham and Women’s Hospital
Harvard Medical School
Boston, Massachusetts
Medical Research: What is the background for this study? What are the main findings?
Dr. Chatterjee: Thousands of patients die every year due to organ shortages. Finding ways to address this public health issue is critical. States have designed a variety of strategies to promote organ donation and transplantation, however we don’t know if any of these strategies have been successful. The goal of our study was to try to figure out which strategies have been most successful in terms of increasing organ donation and transplantation.
We found that states have implemented a wide and creative set of strategies, but unfortunately, it seems that these strategies have had almost no effect on increasing organ donation and transplantation. In states that adopted these strategies compared to those that did not, the rates of donation and transplantation increased at nearly the same rate over the past two decades. The only strategy that seemed to have a small effect was when states created revenue pools dedicated toward organ donation activities.
(more…)
MedicalResearch.com Interview with:
Dagfinn Aune, PhD student
Norwegian University of Science and Technology and
Imperial College London
Medical Research: What is the background for this study? What are the main findings?
Response: There are more than 360 million people worldwide that are affected by diabetes, and this number is projected to increase to more than 550 million by 2030, with serious consequences for the health and economy of both developed and developing countries. While previous research has found an association between increased dietary fibre intake and a reduced risk of developing type 2 diabetes, most of these data come from the United States, and amounts and sources of fiber intake differ substantially between countries. In this article the we evaluated the associations between total fiber as well as fiber from cereal, fruit, and vegetable sources, and new-onset type 2 diabetes in a large European cohort across eight countries, in the EPIC-InterAct Study (and included 12403 type 2 diabetes cases and 16835 sub-cohort members). We also conducted a meta-analysis where we combined the data from this study with those from 18 other independent studies from across the globe.
We found that participants with the highest total fiber intake (more than 26 g/day) had an 18% lower risk of developing diabetes compared to those with the lowest total fiber intake (less than 19g/day), after adjusting for the effect of other lifestyle and dietary factors. When the results were adjusted for body mass index (BMI) as a marker of obesity, higher total fiber intake was found to be no longer associated with a lower risk of developing diabetes, suggesting that the beneficial association with fiber intake may be mediated at least in part by BMI. In other words, dietary fiber may help people maintain a healthy weight, which in turn reduces the chances of developing type 2 diabetes.
In a meta-analysis of the EPIC-InterAct study and 18 other independent studies (>41000 type 2 diabetes cases) we found that the risk was reduced by 9% for each 10 g/day increase in total fiber intake and 25% for each 10 g/day increase in cereal fiber intake. There was no statistically significant association between fruit or vegetable fiber intake and diabetes.
(more…)
MedicalResearch.com Interview with:
Anees B. Chagpar, MD, MSc, MPH, MA, MBA, FRCS(C), FACS, Associate Professor, Department of Surgery
Director, The Breast Center -- Smilow Cancer Hospital at Yale-New Haven, Assistant Director -- Global Oncology, Yale Comprehensive Cancer Center
Program Director, Yale Interdisciplinary Breast Fellowship
Yale University School of Medicine Breast Centerm
New Haven, CT,
Medical Research: What is the background for this study? What are the main findings?
Response: Every year in the US, nearly 300,000 women are diagnosed with breast cancer -- the majority of these will have early stage breast cancer, and will opt for breast conserving surgery to remove their disease. The goal of this operation is to remove the cancer with a rim of normal tissue all the way around it (i.e., a margin), but sadly, 20-40% of women will have cancer cells at the edge of the tissue that is removed, often mandating a return trip to the operating room to remove more tissue to ensure that no further disease is left behind. No one likes to go back to the operating room -- so we asked the question, "How can we do better?". Surgeons have debated various means of obtaining clear margins. Some have advocated taking routine cavity shave margins -- a little bit more tissue all the way around the cavity after the tumor is removed at the first operation. Others have argued that this may not be necessary; that one could use intraoperative imaging of the specimen and gross evaluation to define where more tissue may need to be removed (if at all) -- i.e., selective margins. We conducted a randomized controlled trial to answer this question. We told surgeons to do their best operation, using intraoperative imaging and gross evaluation, and removing selective margins as they saw fit. After they were happy with the procedure they had performed and were ready to close, we opened a randomization envelope intraoperatively, and surgeons were either instructed to close as they normally would ("NO SHAVE"), or take a bit more tissue all the way around the cavity ("SHAVE").
Patients in both groups were evenly matched in terms of baseline characteristics. The key finding was that patients who were randomized to the "SHAVE" group half as likely to have positive final margins and require a re-operation than patients in the "NO SHAVE" group. On their postoperative visit, we asked patients, before they knew which group they had been randomized to, what they thought of their cosmetic results. While the volume of tissue excised in the "SHAVE" group was higher than in the "NO SHAVE" group, the distribution of patient-perceived cosmetic outcomes were identical in both groups. Complication rate was also no different between the two groups. We will be following patients for five years for long-term cosmetic and recurrence outcomes. (more…)
MedicalResearch.com Interview with:
Dr. Samson Y. Gebreab, Ph.D., M.Sc.
Lead Study Author and Research Scientist
National Human Genome Research Institute
Bethesda, Maryland
Medical Research: What is the background for this study?
Dr. Gebreab: It is well known that African Americans hold a commanding lead in cardiovascular disease (CVD) mortality and morbidity compared to whites and other ethnic groups. Furthermore, the risk for developing CVD begins early in life and extends over a lifecourse. Previous studies have indicated the influence of both childhood and adult socioeconomic status (SES) on CVD risk. However, the impact of lifecourse socioeconomic status (both childhood and adulthood) on CVD risk in African American population is not fully understood. The purpose of our study was to investigate the associations of different measures of lifecourse socioeconomic status with cardiovascular disease risk in African Americans and whether the associations were modified by sex and/ or age after controlling for known cardiovascular disease risk factors. We analyzed 10-year follow-up data of African American adults who were participating in Jackson Heart Study, Jackson, MS.
Medical Research: What are the main findings?
Dr. Gebreab: Our findings highlights that among those of lower socioeconomic status, women and younger (<=50 years old) African Americans are at increased risk of CVD, including heart disease and stroke compared to their counterparts of higher socioeconomic status groups.
African American women in the lowest socioeconomic status, had more than twice the risk of developing cardiovascular disease than those in the highest socioeconomic status group.
African Americans of 50 years and younger in the lowest socioeconomic status group had more than three times higher risk of experiencing a cardiovascular disease event than those in the highest socioeconomic status group.
(more…)
MedicalResearch.com Interview with:
Ruben A. Mesa, MD, FACP
Consultant Hematologist
Chair, Division of Hematology & Medical Oncology
Deputy Director, Mayo Clinic Cancer Center
Professor of Medicine Mayo Clinic Cancer Center
NCI Designated Comprehensive Cancer Center
Scottsdale, AZ
Medical Research: What is the background for this study? What are the main findings?
Dr. Mesa: Myelofibrosis is a rare and chronic blood cancer associated with significantly reduced quality of life and shortened survival. In patients with this disease, spleen enlargement (splenomegaly) is a very common and debilitating symptom – and as the disease progresses, the body slows production of important blood cells.
The results presented at ASCO were from the PERSIST-1 study, which is a Phase 3 registration-directed trial designed to compare pacritinib — an investigational oral multikinase inhibitor with specificity for JAK2 and FLT3 – to best available therapy (exclusive of a JAK inhibitor) in patients with myelofibrosis — regardless of their platelet counts. Data from this study showed that compared to best available therapy, pacritinib resulted in a significantly higher proportion of patients with spleen volume reduction and control of disease-related symptoms, regardless of platelet levels at the time of enrollment.
(more…)
MedicalResearch.com Interview with:
Dr. Marie C. Leger, MD, PhD
Assistant Professor
Ronald O. Perelman Department of Dermatology
NYU Langone Medical Center
Medical Research: What inspired this study? How did it come about?
Dr. Leger: As a dermatologist at NYU, I have taken care of several patients with tattoo reactions--some of them mild (like longstanding itching for example) and some of them more severe (like long term reactions to a particular color that can severely disfigure the tattoo) and wondered how common it was for people to have adverse tattoo reactions or complications. There were lots of case reports in the literature but only a few larger studies examining how common these kinds of complaints were--and these were all European studies. We decided to do a quick survey to give us a better idea of how common it is for people to have problems with their tattoos.
Medical Research: What do you think is the most important takeaway from this study for the consumer?
Dr. Leger: Tattoos have risks associated with them--which is part of their appeal I'm sure--but I do think it's important for people to know that long term tattoo reactions (including for example, itching, scaling, swelling) may be more common than we realize. A recent Danish study shows that these kinds of reactions can be quite distressing for people and significantly impact their quality of life.
(more…)
MedicalResearch.com Interview with:
Aaron P. Thrift, Ph.D.
Assistant Professor, Department of Medicine
Dan L. Duncan Cancer Center
Baylor College of Medicine
Houston, TX 77030-3498
Medical Research: What is the background for this study? What are the main findings?
Dr. Thrift: Greater attained adult height is associated with increased risk of all cancers combined; however, the association may differ by cancer site and between women and men. For colorectal cancer, epidemiological studies suggest that the association with height may be stronger for women than for men. We used data from over 10,000 patients with colorectal cancer and over 10,000 population-based controls and conducted multiple analyses, including using Mendelian randomization (which incorporates genomic data with traditional approaches) to overcome potential issues of confounding and bias in observational studies, to further examine the association between height and risk of colorectal cancer. Overall, we found that taller height was associated with increased risk of colorectal cancer (8% increased risk per 10cm increase in height). When we examined women and men separately, our results strongly suggest that height is causally associated with colorectal cancer risk for women, whereas there was weaker evidence for a causal association between height and colorectal cancer risk for men.
(more…)
MedicalResearch.com Interview with:
Dr. Leonard Petrucelli Ph.D
Mayo Clinic
Jacksonville, FL 32224
MedicalResearch: What is the background for this study?
Dr. Petrucelli: According to the ALS Association, more than 30,000 Americans live with amyotrophic lateral sclerosis (ALS), a condition that destroys motor neuron cells that control essential muscle activity such as speaking, walking, breathing and swallowing. After Alzheimer’s disease, frontotemporal dementia (FTD) is the most common form of early onset dementia. It is characterized by changes in personality, behavior, and language due to loss of neurons in the brain’s frontal lobe. Once considered rare, frontotemporal dementia is now thought to account for up to 10 to 15 percent of all dementia cases, according to the Alzheimer’s Association.
In 2011, Mayo investigator Rosa Rademakers, Ph.D., identified the most common genetic mutation known to cause ALS and FTD, namely a repeat expansion in the gene C9ORF72. The C9ORF72 repeat expansion leads to the generation of toxic RNA species that form abnormal foci, as well as inclusions of c9RAN proteins in affected cells in the central nervous system. Prior to this research study lead by Leonard Petrucelli, Chair of the Department of Neuroscience at the Mayo Clinic Florida, no animal model existed that fully recapitulated the known clinicopathological features of what is now collectively referred to as c9FTD/ALS. Without such an animal it has remained difficult to identify important mechanisms by which the repeat expansion leads to neurodegeneration and putative therapeutic targets that may mitigate disease in patients where currently there are no curative treatments.
(more…)
MedicalResearch.com Interview with:
David S. Lopez, Dr.P.H., M.P.H.
Assistant professor
University of Texas Health School of Public Health
Medical Research: What is the background for this study? What are the main findings?
Dr. Lopez: Coffee, and its most studied component, caffeine, have been implicated in potential health benefits due to the rich sources of antioxidants and anti-inflammatory compounds contained in this beverage.
Caffeine intake reduced the odds of prevalent erectile dysfunction, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive men, but not among diabetic men. These associations are warranted to be investigated in prospective studies.
Medical Research: What are the main findings?
Dr. Lopez: Caffeine intake reduced the odds of prevalent erectile dysfunction, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive men, but not among diabetic men. These associations are warranted to be investigated in prospective studies.
(more…)
MedicalResearch.com Interview with:
Wei Zhang, Ph.D., Professor
Department of Pathology
Director, Cancer Genomics Core Lab
University of Texas MD Anderson Cancer Center
Houston, Texas 77030
Medical Research: What is the background for this study? What are the main findings?
Dr. Zhang: Epithelial ovarian cancer remains the most lethal gynecological malignancy. The 5-year survival rate for patients with advanced ovarian cancer is only 30-40%, and acquired resistance to platinum is considered a major factor in disease relapse. A major challenge in cancer treatment is the resilient ability of cancer cells to repair DNA damage caused by chemotherapy agents. In this study, we found that adding a molecule called miR-506 to standard chemotherapy can help cells overcome drug resistance, so that the chemotherapy drugs remain effective against ovarian cancer. This research supports a new combination approach, which may substantially benefit patients with this deadly disease.
(more…)
MedicalResearch.com Interview with:
Perry N Halkitis, Ph.D., M.S., MPH
Professor of Applied Psychology
Global Public Health, and Population Health/Medicine
New York University.
Medical Research: What is the background for this study?
Dr. Halkitis: The P18 Cohort Study is a prospective cohort study of gay, bisexual and other young men who have sex with men (YMSM) which seeks to examine the development of health behaviors as these young men transition from adolescent to adulthood. Officially named “Syndemic Production among Emergent Adult Men”, this study was funded by the National Institute on Drug Abuse from 2009-2014 and renewed on March 1, 2014 for an additional five years.
The original aims of the study were as follows:
MedicalResearch.com Interview with:
Thomas M. Gill, M.D
Humana Foundation Professor of Medicine (Geriatrics)
Professor of Epidemiology and of Investigative Medicine
Director Yale Program on Aging and Yale Center for Disability and Disabling Disorders
Director, Yale Training Program in Geriatric Clinical Epidemiology and Aging-Related Research
Medical Research: What is the background for this study? What are the main findings?h
Response: Understanding the disabling process at the end of life is essential for informed decision-making among older persons, their families, and their physicians.
We know from prior research that the course of disability at the end of life does not follow a predictable pattern for most older persons. This raises the question about what is driving the development and progression of disability at the end of life.
We identified six distinct trajectories of disability in the last year of life, ranging from the least disabled to most disabled. We found that the course of disability in the last year of life closely tracked the monthly prevalence of hospitalization for each of the six trajectories.
(more…)
MedicalResearch.com Interview with:
Rik Ossenkoppele PhD.
Postdoctoral researcher
UCSF Memory and Aging Center
MedicalResearch: What is the background for this study?
Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database.
MedicalResearch: What are the main findings?
Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of
1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype),
2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and
3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”).
The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials.
In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect
1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or
2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander.
(more…)
MedicalResearch.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…)
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…)
MedicalResearch.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…)
MedicalResearch.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…)