Dr. Ricardo Jorge[/caption]
Ricardo E. Jorge MD
Professor of Psychiatry and Behavioral Sciences
Director Houston Translational Research Center for TBI and Stress Disorders
Senior Scientist Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry
Michael E DeBakey VA Medical Center
Baylor College of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Depressive disorders affect between one-third and one-half of patients with traumatic brain injury. Once established, these disorders are difficult to treat and frequently follow a chronic and refractory course.
Depression has a deleterious effect on TBI outcomes, particularly affecting the community reintegration of TBI patients.
In this randomized clinical trial that included 94 adult patients with TBI, the hazards for developing depression for participants receiving placebo were about 4 times the hazards of participants receiving sertraline treatment.
Dr. Maléne Lindholm[/caption]
Maléne Lindholm, PhD
Karolinska Institutet
Dept. of Physiology & Pharmacology
Stockholm Sweden
MedicalResearch.com: What is the background for this study?
Response: It is well known that exercise training provides marked health benefits and can prevent and treat a broad set of diseases. Therefore, a deeper understanding and characterization of the molecular processes behind training adaptation is essential for human health.
This study aimed at exploring the effects of endurance training on the human skeletal muscle transcriptome (activity of all genes) and investigate the possible presence of a muscle memory of training. To do this, the healthy volunteers in this study first trained only one leg, 4 times per week for 3 months. After 9 months of detraining, the subjects then came back and trained both legs in the same way as during the first training period, thus one leg was then previously well-trained and one previously untrained. This meant that each individual was their own control, as both legs have the same genome, experience the same stress, diet etc. Only the training status differed.
Dr. Jared Howard[/caption]
Jaren Howard, PharmD, BCPS
Associate Director
Medical Affairs Strategic Research
Purdue Pharma L.P.
MedicalResearch.com: What is the background for this study?
Response: The existing scientific literature estimating the healthcare burden of opioid misuse disorders often combines all patients within the broad category of “opioid abuse,” defined as opioid abuse, dependence, or overdose/poisoning.
Collectively, these three conditions can significantly increase healthcare costs among commercially insured patients.
• Real world medical coding practices present challenges to researchers aiming to separately analyze excess costs by diagnosis, though combining these diagnoses may mask some variation in excess costs.
• Furthermore, little is known about the specific drivers of excess costs in terms of medical conditions driving excess costs or places of service at the diagnosis-level.
Dr. Yong Cheng[/caption]
Yong Cheng, PhD, post-doc fellow
Section on Cellular Neurobiology
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland
MedicalResearch.com: What is the background for this study?
Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls.
Dr. Katherine Jo Gold[/caption]
Katherine J. Gold, MD MSW MS
Department of Family Medicine
Institute for Healthcare Policy and Innovation; Depression Center
University of Michigan
With co-authors Louise B. Andrew MD JD; Edward B. Goldman JD; Thomas L. Schwenk MD
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: It is common knowledge that physicians are often hesitant to seek care for mental health concerns. Knowing that female physicians have increased rates of both depression and suicide, we surveyed female physicians who were mothers and who participated in a closed FaceBook group about their mental health, treatment, and opinions about licensing. More than 2100 U.S. physicians responded, representing all specialties and states.
Almost half of participants reported that at some point since medical school they had met criteria for a mental illness but didn’t seek treatment. Reasons included feeling like they could get through without help (68%), did not have the time (52%), felt a diagnosis would be embarrassing or shameful (45%), did not want to ever have to report to a medical board or hospital (44%), and were afraid colleagues would find out (39%). Overall, 2/3 identified a stigma-related reason for not seeking help.
Almost half reported prior diagnosis or treatment, but just 6% of these women stated they had disclosed this to a state medical board on a licensing application, though states vary on what information they require be disclosed.
Dr. Gwen Bergen[/caption]
Gwen Bergen, PhD
Division of Unintentional Injury
National Center for Injury Prevention and Control
CDC
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Older adult falls are the leading cause of injury death and disability for adults aged 65 years and older (older adults). In this study, we analyzed data from the Centers for Disease Control and Prevention’s (CDC) Behavioral Risk Factor Surveillance System (BRFSS) survey. Our study found that, in 2014, older Americans reported 29 million falls. Almost a quarter of these or 7 million falls required medical treatment or restricted activity for at least one day. Women reported a higher percentage of falls (30%) compared with men (27%). Whites and American Indian/Alaskan Natives (AI/AN) were more likely to fall compared with Blacks and Asian/Pacific Islanders; and AI/AN were more likely to report a fall injury compared with all other racial/ethnic groups. The percentage of older adults who reported a fall varied by state, ranging from 21% in Hawaii to 34% in Arkansas.
Waqaas Al-Siddiq[/caption]
Response: I am the president and CEO of biotricity which is a healthcare technology company dedicated to providing diagnostic and post-diagnostic solutions for both the physician and consumer for long-term chronic care management. I got interested in combining healthcare and technology while I was doing research for monitoring remote environments in critical scenarios. I thought that it would be very interesting to apply that to healthcare because it’s a problem that no one has figured out how to solve yet. And it’s a problem that is driving healthcare costs out of control.
Dr. Natalie Artzi[/caption]
Natalie Artzi PhD
principal research scientist
MIT's Institute for Medical Engineering and Science and
Assistant professor of medicine
Brigham and Women's Hospital
With co-authors:
Avital Gilam, João Conde, Daphna Weissglas-Volkov, Nuria Oliva, Eitan Friedman, Noam Shomron
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Metastases are the primary cause for mortality in breast cancer, the most common cancer in women regardless of ethnicity. Recent studies show that germline sequence variants, such as single-nucleotide polymorphisms (SNPs) in miRNA-binding sites, can disrupt the downregulation by miRNAs, with a profound effect on gene expression levels and consequentially on the phenotype, including increased risk for cancer.
In the current study, we aimed to determine the potential effect of SNPs within miRNA-binding sites on metastatic breast cancer progression and their potential use as suppression targets to prevent metastasis.
Our collaborators at Tel-Aviv Universityin a research led by Dr. Noam Shomron found that the SNP, rs1071738, located in a target site for miR-96 and miR-182 on the 3’-UTR of the PALLD gene, encodes the Palladin actin-associated protein, which is a documented player in breast cancer motility. In vitro experiments revealed a functional downregulation of Palladin levels by miR-96 and miR-182, which subsequently reduces migration and invasion abilities of breast cancer cells.
My lab then showed in an in vivo experiment that the use of nanoparticles embedded in a hydrogel scaffold as a miRNA delivery vehicle enables an efficient and specific delivery of miR-96/miR-182 directly to breast tumours, which results in marked reduction of breast cancer metastasis. We then proceeded to study the effect of combination therapy in which we will use a chemotherapy drug to shrink the primary tumor and the miRNAs to prevent metastasis. The intercalation of a chemotherapy drug, cisplatin, to the miR-conjugated nanoparticles further improved the effect, leading to significant reduction in both primary tumour growth and metastasis.
Our study highlights the therapeutic potential of miRNAs, and specifically miR-96 and miR-182, and support the importance of Palladin regulation in breast cancer metastasis.
MedicalResearch.com Interview with:
Dr. Bastiaan Heijmans
Leiden University Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages.
In a large-scale analysis of the methylome of over 3000 individuals, we discovered and validated 6000 sites in the genome that became more variable in their DNA methylation level with age. These sites frequently co-localized with repressed regions that are characterized by polycomb repression. While sites accumulating variability with age were commonly associated with the expression of (neuro)developmental genes in cis, they were linked to transcriptional activity of genes in trans that have a key role in well-established ageing pathways such as intracellular metabolism, apoptosis, and DNA damage response.
Dr. Brian Lundstrom[/caption]
Brian Nils Lundstrom, MD, PhD
Department of Neurology
Mayo Clinic
Rochester, Minnesota
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: About as many people have drug-resistant focal epilepsy as have multiple sclerosis, and treatment options are limited.
This study describes an alternative treatment option that has proven very helpful for the majority of participants. Electrical stimulation is delivered continuously via implanted electrodes to the region of brain where seizures start. The electrical stimulation decreases the seizure-related discharges from the brain, and for about 40% of patients their disabling seizures were completely stopped.
Jacques-Eric Gottenberg, MD, PhD
Department of Rheumatology
National Reference Center for Systemic Autoimmune Diseases
Strasbourg University Hospital, Université de Strasbourg
Strasbourg, France
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: There is no recommendation for the choice of the second biologic in patients with rheumatoid arthritis and insufficient response to a first anti-TNF, which is a common situation in our daily practice (approximately one third of patients treated with anti-TNF). We therefore conducted the first randomized trial to date to investigate the best strategy in such a setting.
Dr. Ron Davis[/caption]
Ron L. Davis, PhD Professor and Chair
Department of Neuroscience
Florida campus of The Scripps Research Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: While calcium’s importance for our bones and teeth is well known, its role in neurons—in particular, its effects on processes such as learning and memory—has been less well defined. Our new study, published in the journal Cell Reports, offers new insights how calcium in mitochondria—the powerhouse of all cells—can impact the development of the brain and adult cognition.
Specifically, we show in fruit flies, a widely used model system, that blocking a channel that brings calcium to the mitochondria called “mitochondrial calcium uniporter” causes memory impairment but does not alter learning capacity. That surprised us – we thought they wouldn’t be able to learn at all. This is important because defects in the same calcium channel function have been shown to be associated with intellectual disability in humans.
Grace Bushnell[/caption]
Grace G. Bushnell PhD candidate
Department of Biomedical Engineering
University of Michigan
Ann Arbor, Michigan
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study builds off of previous work from the Shea and Jeruss laboratories at the University of Michigan, which reported that implanted scaffolds can capture early metastatic cells in vivo prior to the colonization of other organs and serve as a platform for early detection of metastatic disease. Furthermore, the presence of a scaffold reduced the tumor burden in other metastatic locations.
In this work, the major finding was that early detection using a scaffold combined with a therapeutic intervention led to a survival advantage relative to mice that did not receive a scaffold. The scaffolds had been designed to persist in vivo for longer periods of time than in the original study. Additionally, the scaffold was implanted prior to the inoculation of metastatic cancer cells in the mouse. The role of the immune system in the process was further refined, as the immune cell composition at the scaffold changed significantly after disease initiation. These studies demonstrate that early intervention in a metastatic setting can lead to enhanced survival. This principle of early intervention is well established for the primary tumor, and these studies suggest that this principle may be extended to metastatic disease.
Dr. Roshni Rao[/caption]
Roshni Rao, M.D
Breast Surgery
University of Texas Southwestern
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Triple negative breast cancer (TNBC) is characterized by not having estrogen, progesterone, or Her2Neu receptors. Although a less common type, it is aggressive, and leads to a disproportionate number of deaths from breast cancer.
TNBC is more common in young, African American women, but can be found in other ethnic groups as well.
This study performed mitochondrial DNA (mtDNA) analysis, to evaluate for patient genetic ancestry, in 92 patients with TNBC. In regards to self-identified ethnicity, there were 31 African-Americans, 31 Whites, and 30 Hispanics. Utilizing mtDNA, 13% of patients had discordance between self identified ethnicity and mtDNA analysis. Discordance was highest in the Hispanic group. The Hispanic patients were also much younger at initial age of diagnosis, and less likely to have a family history of breast cancer. Ancestry from Nigeria, Cameroon, or Sierre Leone were most common in the African-Americans with triple negative breast cancer.
Dr. Darren Feldman[/caption]
Darren R. Feldman, MD
Medical Oncologist
Memorial Sloan Kettering Cancer Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: There is limited knowledge as to why a minority of patients with advanced germ cell tumors are resistant to chemotherapy while the majority achieve complete responses. Patients with cisplatin-resistant disease require intensive salvage treatment and are at high risk of dying from their disease. We sought to determine whether certain genomic alterations within tumors might be associated with cisplatin-resistance in GCT. We also wanted to identify the spectrum of genomic alterations in this population which might represent novel targets for existing or new drug development in this disease.
Dr. Mark Courey[/caption]
Dr. Mark Courey, MD
Senior Faculty,Otolaryngology
The Mount Sinai Hospital
New York Eye and Ear Infirmary of Mount Sinai
MedicalResearch.com: Would you tell us a little about yourself? How did you become interested in voice disorders?
Response: I became interested in voice disorders because during my residency in the late 1980’s there was little known about how to help patients with disorders of voice. The main instrument we use to evaluate vocal folds (the stroboscope) was just becoming clinically available. Only a handful of physicians had one available. We could not see vocal fold function and could only see the lesions on the vocal folds. We did not know how the lesions affected function. So many surgeons only treated patients with laryngeal cancer and told the others to be happy that they did not have cancer.
Dr. Eric E Smouha[/caption]
Eric E Smouha, MD
Professor, Otolaryngology
The Mount Sinai Hospital
New York Eye and Ear Infirmary of Mount Sinai
MedicalResearch.com: Would you tell us a little about yourself? How did you become interested in ENT and specifically middle ear problems?
Response: I am a neurotologist, i.e. , ENT physician specialized in disorders of the ear and skull base. Neurotologists treat problems of the middle ear and inner ear. Middle ear problems are interesting because they are prevalent, and surgery frequently results in restoration of function.
Dr. Alfred Marc Calo Iloreta[/caption]
Alfred Marc Calo Iloreta, MD
Assistant Professor
Skull Base Surgery and Rhinology
Department of Otolaryngology -
Head and Neck Surgery
Icahn School of Medicine at Mount Sinai
New York, New York
MedicalResearch.com: Would you tell us a little about yourself? How did you become interested in ENT and your subspecialty in particular?
Response: I am a ENT/Head and Neck Surgeon practicing in Manhattan at the Mount Sinai Hospital. I trained here in New York City for residency and also completed a fellowship in Rhinology and Skull Base Surgery.
I chose this field and sub-specialty because of the intricate and complex anatomy of the head and neck. In addition rhinology and skull base surgery utilizes multiple advanced technologies from high definition optics, to neuronavigation to allow us to work with this complex anatomy.
Dr. Carlos E. Crespo-Hernández[/caption]
Carlos E. Crespo-Hernández PhD
Associate Professor and Co-director of the Center for Chemical Dynamics
Department of Chemistry
Case Western Reserve University
Cleveland, Ohio
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Two new letters of DNA have recently been successfully incorporated and replicated by a modified strain of E. coli, thus generating the world’s first semi-synthetic organism with an expanded genetic alphabet. With the expansion of the genetic alphabet, the question arises as to whether the incorporation of unnatural DNA base pairs into cells can adversely affect the integrity of the genetic code and the viability of the cells upon exposure to sunlight or even conventional laboratory lighting. Natural DNA is susceptible to damage by ultraviolet light, but this damage is largely repaired by enzymatic repair mechanisms in living cells. Our recent study has found that the two new, unnatural DNA bases—d5SICS and dNaM—are able to efficiently absorb near-visible light, which is abundant in sunlight and standard fluorescent lighting. Not only that, but upon absorbing near-visible light these unnatural bases produce up to 100 times more reactive species than the most reactive natural DNA base. A line of skin cancer cells incorporating one of these unnatural DNA bases was used to investigate these effects on living cells. Following exposure to a low dose of near-visible light, we observed an increase in the generation of reactive oxygen species within cells containing the unnatural DNA base and a significant decrease in cell survival.
Dr. Makoto Fukuda[/caption]
Makoto Fukuda Ph.D.
Assistant Professor
Children's Nutrition Research Center
Department of Pediatrics
Baylor College of Medicine
Houston, Texas 77030
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A hallmark characteristic of obesity is diminished actions of metabolic hormones that are critically required to maintain whole body energy balance and glucose homeostasis. Leptin is a crucial and powerful hormone that keeps body weight normal. It was hoped that leptin might be a “magic bullet” that could cure obesity. Shortly after the discovery, however, obese individuals were found to have little or no response to exogenously administered leptin, a state of “leptin resistance”. These observations created a central question to be addressed in the field, which would help our understanding of the core of pathophysiology of obesity. While we and other groups previously demonstrated that Epac, a signaling molecule known as a GTP/GDP exchange factor directly activated by cAMP, is involved in cellular leptin resistance, the role of brain Epac signaling in the whole body metabolism has not yet established.
We approached this question by using brain-specific knockout mice of Rap1, a direct activator of Epac. As expected from previous results, mice with brain-specific deficiency of Rap1 failed to develop leptin resistance even when they were challenged with a hypercaloric diet. What impressed us most in this study was that Rap1 in the brain plays a key role in the whole body metabolic control, beyond its role in controlling leptin sensitivity. Loss of brain Rap1 protects mice from diet-induced obesity and disordered glucose balance, whereas these knockout mice maintained a similar body weight to that of control mice on a normal regular diet. Further, pharmacological inhibition of this pathway reversed leptin resistance and reduced the body weight of dietary obese mice. At the cellular level, we found an unexpected link between Rap1 and endoplasmic reticulum (ER) stress that has emerged as a causative contributor to the development of leptin resistance.
Dr. Cuilin Zhang[/caption]
Cuilin Zhang MD, PhD
Senior Investigator
NICHD, National Institutes of Health
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Pregnant women are at high risk of developing depressive symptoms; at least 10% US women suffering from depression during pregnancy. Gestational diabetes is a common pregnancy complication, affecting 4-7% of pregnancies in the U.S.. Gestational diabetes has adverse health implications on both women and their children. Depression and glucose intolerance commonly co-occur among non-pregnant individuals; however, the temporal relationship between gestational diabetes and depression during pregnancy and the postpartum period is less understood.
Dr. Michael Murphy[/caption]
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease whereby a severe obstruction of the arteries markedly reduces blood flow to the extremities (hands, feet and legs) causing severe pain, skin ulcers, sores, or gangrene. Up to 30% of patients with CLI do not qualify for conventional interventions, such as a bypass or angioplasty, putting them at risk for amputation.
The MOBILE trial (MarrOwStim™ PAD Kit for the Treatment of Critical LimB IschemIa in Subjects with Severe Peripheral ArteriaL DiseasE) was designed to assess the safety and efficacy of using autologous concentrated bone marrow aspirate (cBMA), cells derived from the patient's own bone marrow, to restore blood flow and prevent amputations in patients with CLI.
MOBILE is a Phase 3, double-blind, randomized, placebo-controlled trial that evaluated 152 patients with CLI at 24 centers in the U.S. Patients were randomized to receive cBMA or placebo via injection at 40 sites on the symptomatic leg. The cBMA was obtained from each patient using the MarrowStim PAD kit. The placebo group underwent a sham bone marrow aspiration and received needle punctures in the index leg.
The primary efficacy endpoint was amputation-free survival, defined as freedom from all causes of death and/or major amputation, at 52 weeks after treatment. Other endpoints included changes in blood flow in the leg, wound healing, measures of pain and quality of life, and distance walked in 6 minutes. The trial completed in June 2016, and a preliminary analysis found that cBMA demonstrated a meaningful improvement in amputation-free survival and a comparable safety profile to placebo.
Dr. Bradley Stein[/caption]
Bradley D. Stein, MD, MPH, PhD
RAND Corporation
University of Pittsburgh School of Medicine
Pittsburgh, Pennsylvania
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The United States is in the midst of a serious opioid abuse epidemic and we know that medically assisted treatment is one of the best ways to help people with addiction to opioids. The drug buprenorphine has advantages over methadone, the historic medical treatment, because it can be prescribed by physicians in the community who receive a waiver allowing them to prescribe it after undergoing eight hours of training.. Methadone is dispensed at special clinics that many people with opioid addition may be unable to get to with the frequency required by effective treatment.
To better understand patterns of the use of buprenorphine, we examined treatment patterns in the states with the most buprenorphine-waivered physicians (California, Florida, Massachusetts, Michigan, New York, Pennsylvania and Texas). Our data came from a prescription records that account for over 80 percent of the retail pharmacies in the nation. We examined use patterns among 3,200 physicians who treated 250,000 patients.
We had two surprising findings:
First, the median length of treatment with buprenorphine was 53 days, which is much shorter than the duration that most individuals are likely to need for optimal results. Second, despite concerns that federal limits on the number of patients and waivered physician can treat being a significant barrier for many individuals obtaining treatment, we found that most physicians were treating far fewer patients than would be allowed by the patient limits. In fact, 22 percent of the physicians treated an average of 3 patients per month and just 9 percent treated 75 or more patients per month.