MedicalResearch.com Interview with:
Michael G. Rossmann PhD
Hanley Professor of Biological Sciences
Hockmeyer Hall of Structural Biology
Purdue University, West Lafayette IN
Medical Research: What is the background for this study? What are the main findings?
Dr. Rossmann: My laboratory has long been interested in the structure of viruses and especially of Picornaviruses (e.g. EV-D68). We published the first 3D, near atomic resolution map of any animal virus in 1985. That was of Human Rhino (common cold) virus serotype 14. We then went on to show where and how the virus would bind to cellular receptors and also how certain small capsid binding compounds inhibited the viral infectivity. The latter was a collaboration first with the Sterling Winthrop company and later with ViroPharma. Thus our work on EV-D68 is a direct continuation of my interest in picornaviruses.
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MedicalResearch.com Interview with:
David Granville, BSc, PhD, FAHA
Professor, University of British Columbia
Scholar of the Royal Society of Canada
Director, GEM Facility, Centre for Heart Lung Innovation, St. Paul's Hospital Founder and CSO, viDA Therapeutics, Inc.
Vancouver, BC, Canada
Medical Research: What is the background for this study? What are the main findings?Dr. Granville: My background is in cardiovascular research. In particular, how age affects blood vessels and how age affects mechanisms of blood vessel and heart injury and repair. We became interested in skin aging during a study in which we were studying the role of a protein degrading enzyme known as Granzyme B in atherosclerosis (hardening of the arteries) and aging. In these studies, we were using a genetic mouse model that is prone to accelerated aging, and knocked out Granzyme B. Although we were initially focused on the blood vessels, we also found that Granzyme B-deficient mice exhibited younger-looking skin. As we started to look into this, we became aware that UV light can induce the skin cells to produce Granzyme B. As sunlight is believed to be responsible for 80-90% of preventable skin aging, we generated a solar-simulated light box (with the similar ratios of UVA/UVB to sunlight) to assess whether Granzyme B played a role in UV-induced skin aging (aka photoaging). We exposed the mice to repetitive, low dose UV three times per week for 20 weeks. After 20 weeks we observed that Granzyme B deficient mice exhibited fewer wrinkles. We then wanted to look histologically and biochemically into how Granzyme B was affecting skin morphology. Granzyme B deficient mice exhibited greater collagen density compared to mice that possessed Granzyme B. As we looked into the mechanism in more detail, we determined that Granzyme B was cleaving a protein known as decorin. Decorin is responsible for collagen fibrillogenesis and assembling collagen into tight bundles. Loss of decorin is associated with a loss of collagen tensile strength. Interestingly, decorin also protects collagen from destruction by a protein-degrading enzyme known as MMP1. We showed in the study that by breaking down decorin, Granzyme B renders collagen susceptible to MMP1-mediated degradation. In addition, we showed that Granzyme B-fragmentation of another protein, fibronectin, led to the upregulation of MMP1 in skin fibroblasts. In summary, the paper showed that UV induced Granzyme B expression in the skin and showed that this enzyme contributes to the breakdown of extracellular matrix proteins and formation of wrinkles.
A link to the Aging Cell publication: http://onlinelibrary.wiley.com/doi/10.1111/acel.12298/pdf(more…)
MedicalResearch.com Interview with:
Dr. Puneeth Iyengar, MD, PhD.Assistant Professor Director of Clinical Research
Dept of Radiation Oncology Co-leader, Thoracic Disease Oriented Team Harold Simmons Cancer Center
UT Southwestern Medical Center Dallas, TX
Medical Research: What is the background for this study? What are the main findings?Response: Stage IV Non-small cell lung cancer (NSCLC) remains a disease of limited survival, in the range of one year for a majority of patients who historically have gone on to receive systemic therapy only. Disease in this patient population most often recurs in the sites of original gross disease. With greater understanding of the biology and patterns of failure that occur in stage IV NSCLC, it is becomingly increasingly obvious that there are subsets of patients, those with limited sites of metastatic disease, who may benefit with more aggressive local therapy in addition to systemic agents to effectuate longer progression free survival (PFS) and potentially overall survival (OS). Since failures of treatment occur most commonly in original gross deposits, local non-invasive therapy in the form of stereotactic body radiation therapy (SBRT) may offer a means to curtail the recurrences, perhaps as a way to shift the time to and patterns of failure.
To address these concepts, a multi institutional single arm phase II study was conducted at UT Southwestern Medical Center in Dallas and University of Colorado Medical Center. Twenty-four patients with limited metastatic NSCLC (fewer than or equal to six sites of disease including the primary) who had progressed through at least one systemic therapy regimen were treated with SBRT to all sites of gross disease and the EGFR inhibitor erlotinib with progression free survival the primary end point. The results of the study were very significant, with a PFS in this study cohort of 14.7 months, compared to historical ranges of 2-4 months, and an OS of 20.4 months, compared to historical ranges of 6-9 months for this same patient population. The SBRT treatments were found to be very safe and efficacious – only 3 out of 47 measurable lesions irradiated recurred with a concomitant shift in failure patterns from local to distant sites. As importantly, EGFR status was evaluated in 13 patient tumors, with none harboring the most common mutations. One could, therefore, predict that with a mutation enriched population, the combination of EGFR inhibitor and SBRT may have offered even greater PFS and OS benefits. Our observations also suggest that the SBRT treatments probably contributed the most to the dramatic PFS and OS outcomes.
These findings were published in the Journal of Clinical Oncology in the December 1, 2014 print issue with an accompanying editorial.
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MedicalResearch.com Interview with:
Seth A. Berkowitz, MD, MPH
Division of General Internal Medicine
Massachusetts General Hospital, Boston Medical Research: What is the background for this study? What are the main findings?
Dr. Berkowitz: Prior studies had looked the association between single unmet basic material needs and diabetes control, but hadn't necessarily looked at multiple things people may not be able to afford, which more closely mirrors real-life. Also, prior studies had been done in a 'pre-Affordable Care Act' setting, while, by being in Massachusetts, our study was conducted in a setting of near-universal healthcare coverage that is similar to what the rest of the US is moving towards. We found that difficulties meeting basic material needs, such as difficulties affording food, known as food insecurity, and having financial barriers to taking medications, called cost-related medication underuse, are associated with worse diabetes control and increased use of costly health services in diabetes patients, despite near-universal health insurance coverage (more…)
MedicalResearch.com Interview with:
Diederik Dippel MD, PhD
Senior Consultant in Neurology
Erasmus MC University Medical Center
Rotterdam The Netherlands
Medical Research: What is the background for this study? What are the main findings?
Dr. Dippel: MR CLEAN is the first randomized clinical trial to show that intra-arterial treatment of ischemic stroke to get the clot out, really works. It leads to more recovery and less handicap. Previous studies had shown that intra-arterial treatment leads to recanalization, but the final proof that the treatment leads to recovery more often than standard treatment was lacking.
With standard treatment, less than 1 out of 5 recovers without handicap, but with this new treatment, this will be 1 out of 3. The treatment did not lead to more complications than standard treatment. The rate of symptomatic intracranial hemorrhage was similar in both arms.
Our study differs from previous, neutral trials.
Second, we used third generation thrombectomy devices, such as retrievable stents in most of the cases.
Third, our trial was conducted in a country with a very good infrastructure, which allowed rapid transfer to intervention centers, which are spread throughout the country. Our rate of iv tPA in Dutch hospitals is over 11% on average.
Last, all intervention centers participated, and almost no patients were treated outside the trial. Moreover, reimbursement of the treatment was conditional on participation in the trial. (more…)
MedicalResearch.com Interview with:
Karthik Murugiah MBBS
Fellow in Cardiovascular Medicine
Yale School of Medicine
Center for Outcomes Research and Evaluation (CORE)
New Haven, CT 06510
Medical Research: What is the background for this study? What are the main findings?
Response: Aortic valve disease is common among older people and frequently requires valve replacement. 1-year survival after open surgical aortic valve replacement is high (9 in 10 survive the year after surgery). Our study focuses on the experience of these survivors in terms of the need for hospitalization during the year after surgery.
Among patients >65 years of age enrolled in Medicare who underwent surgical replacement of their aortic valve and survived at least one year, 3 in 5 were free from hospitalization during that year. Both, the rates of hospitalization and the average total number of days spent in the hospital in the year following surgery have been decreasing all through the last decade (1999 to 2010).
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MedicalResearch.com Interview with:
Shashank Gupta, Ph.D.
Center for Tuberculosis Research
Department of Medicine, JHU, Baltimore, Maryland, USA
Medical Research: What is the background for this study? What are the main findings?
Dr. Gupta: Verapamil is an efflux pump inhibitor drug that has been used to treat hypertension and other cardiac conditions in patients. Adding verapamil to standard tuberculosis (TB) treatment accelerates both the killing activity of the regimen in mouse model. We have recently shown in vitro that supplementing bedaquiline with verapamil profoundly decreases the MIC of bedaquiline in the wild type strain M. tuberculosis H37Rv, and also in drug-susceptible and drug-resistant clinical isolates. The MIC of another anti-mycobacterial drug clofazimine against M. tuberculosis H37Rv also decreased significantly in the presence of verapamil.
Bedaquiline is the first drug to be approved by the USFDA in last forty years for the treatment of multidrug-resistant tuberculosis (MDR-TB). Bedaquiline usage in patients presents several safety concerns including increased mortality and hepatic-related adverse drug reactions. Bedaquiline also prolongs the QT interval in patients, which is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In a phase 2 trial involving patients with advanced MDR-TB, a significantly higher number of participants receiving bedaquiline died than those receiving placebo although the causes of mortality were not directly attributable to the drug. Thus strategies to reduce the human dose of bedaquiline while retaining antibacterial activity may be valuable. We hypothesized verapamil may potentiate the killing of M. tuberculosis by bedaquiline and accelerate clearance of mycobacteria that in an in vivo infection model. Shortening treatment regimens and reducing the required doses may be a promising strategy to reduce the incidence of bedaquiline-related adverse effects and thereby improve MDR-TB treatment outcomes.
In this study, we investigated the effect of verapamil on the activity of bedaquiline against M. tuberculosis in a mouse model of TB infection. In addition to investigating the effects of verapamil on the full human bioequivalent dose of bedaquiline (25 mg/kg), we also used a sub-optimal dose of bedaquiline (12.5 mg/kg) daily, with or without verapamil to test if verapamil may potentiate the activity of bedaquiline. We have also determined if verapamil can protect bedaquiline monotherapy from the development of resistance.
Using mouse model of tuberculosis, we have shown lower doses of bedaquiline together with verapamil have the same antibacterial effect as the higher toxic doses. A lower dose of bedaquiline will cause no or less severe side effects. Verapamil also protected bedaquiline against the development of resistant mutants of the bacteria in the animals. (more…)
MedicalResearch.com Interview with:
Lauren Corona BS
Wayne State University School of Medicine
Detroit, MI
Medical Research: What is the background for this study? What are the main findings?
Response: Hysterectomy is the most commonly performed major gynecologic surgery in the United States. This study sought to examine how often alternative treatment is considered prior to hysterectomy for benign indications and how often pathology in the surgical specimen supports the need for hysterectomy. We utilized data from the Michigan Surgical Quality Collaborative, a statewide hospital collaborative, and limited the analysis to patients having a hysterectomy for uterine fibroids, abnormal uterine bleeding, endometriosis, and/or pelvic pain. Alternative treatment to hysterectomy was not documented prior to surgery in 38% (i.e. no documentation that the patient declined, was unable to tolerate, or failed any alternative treatment). A progesterone intrauterine device (IUD) was the least utilized form of alternative treatment, documented in only 12% of patients. In addition, nearly 1 in 5 (18.3%) had pathology reported that did not support the need for hysterectomy—i.e. the uterus was described as normal or unremarkable or only had minor amounts of pathology. Women <40 years had the highest rate of unsupportive pathology at 38%.
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MedicalResearch.com Interview with:
Joseph A Simonetti, MD MPH
Research Fellow
Harborview Injury Prevention & Research Center
University of Washington Seattle, WA, USAMedical Research: What is the background for this study? What are the main findings?
Dr. Simonetti: Studies have consistently shown that children living in households where firearms are stored safely have a lower risk of suffering firearm injuries, including lethal firearm injuries, compared to those living in households where firearms are stored unlocked and/or loaded. Safe firearm storage is widely recommended by public health experts, professional medical societies, and gun rights organizations, especially for households where children might be suffering from mental heath and substance abuse issues that put them at increased risk for suicide or unintentional injury. Our goal was to find out if those recommendations were being effectively implemented in the community. To do this, we used survey data that assessed mental health conditions and firearm access among a nationally representative sample of US adolescents.
Medical Research: What are the main findings?Dr. Simonetti: First, we confirmed previous findings that a large proportion of US adolescents have access to a firearm in the home. Of those who reported living in a home with a firearm, 40% said they could immediately access and shoot the firearm.
Second, the prevalence of most mental health diagnoses was similar between adolescents who did and did not report firearm access. However, a greater proportion of adolescents with firearm access had drug and alcohol disorders compared to adolescents who reported living in a home with a firearm but did not have access to the firearm.
The main finding was that children with mental health risk factors for suicide were just as likely to report in-home firearm access as those without identified risk factors. This finding held true even when comparing firearm access between children with no identified risk factors and those who reported a recent suicide attempt, who arguably have the highest suicide risk in this sample.
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MedicalResearch.com Interview with:
Dr. Rebecca Finkel PhD
Queen Margaret University
Edinburgh, Scotland, UK and
Madelon Finkel, Ph.D.Director Professor of Clinical Public Health
Weill Cornell Medical College, NY, NY
Medical Research: What is the background for this study? What are the main findings?
Drs. Finkel: Human trafficking is as complex human rights and public health issue. One of the authors (RF) studied the issue at the Vancouver Olympic Games and felt that there needed to be more research on this topic. Much of the problem is that the issue of human trafficking for sexual exploitation at mega global sporting events is difficult to quantify given the clandestine nature of the industry. This is not to say that human trafficking for sexual exploitation does not occur. It almost certainly exists, but to what extent is the big question and to what extent do global events have an impact (if at all)? Our article shows that there are few well-designed empirical studies that address the issue of human trafficking, especially as it relates to mega sporting events.
The extant literature presents gaps in:
a) understanding the actual scope of the international human trafficking situation;
b) establishing links between human trafficking and mega sporting events despite anecdotal testimonies and moral panics often fueled by international media; and,
c) public health implications for victims of human trafficking.
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MedicalResearch.com Interview with: Dr. Dhruv Sareen, PhD
Director, iPSC Core Facility
Regenerative Medicine Institute
Research Scientist, Neurobiology Research
Cedars-Sinai, Los Angeles CA
Medical Research: What is the background for this study? What are the main findings?
Dr. Sareen: We have developed a novel method to re-create brain and intestinal stem cells from patients who died decades ago, using stored blood samples. Using the iPS cell technology at Cedars-Sinai this new method now allows us to apply to alive as well as deceased patient blood cells. Our study, published in the journal STEM CELLS Translational Medicine, highlights the power of this technology for many deceased patients that were diagnosed with debilitating diseases, such as inflammatory bowel disease (IBD) and motor neuron diseases (spinal muscular atrophy and ALS). Patients had their blood samples stored away at Cedars-Sinai when they were alive decades ago. At that time all researchers could have done was collect and bank their blood cell lines for research purposes. The iPS cell technology wasn’t even on scientists radar then. With novel developments in my lab we have figured out how to reliably create new stem cell lines from patient blood samples stored away in large cell banks. We have also shown that these recreated stem cells can efficiently make neurons specific to the spine (motor) and cells of the gut. Since it is very difficult to get unlimited access to research affected cells and tissues from the patients, our discoveries now allow us such important capabilities. Thus, now we are not limited to animal models of disease, but can use these patient-specific stem cells to better pinpoint potential causes of these devastating illnesses.
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MedicalResearch.com Interview with:
Patrick Monahan, Ph.D.
Associate Professor
Indiana University School of Medicine and School of Public Health
Medical Research: What is the background for this study?
Dr.Monahan: Primary care providers need a clinical practical (e.g., brief, inexpensive, simple, user-friendly, easily standardized, and widely available) multidomain instrument to measure and monitor the cognitive, functional, and psychological symptoms of patients suffering from multiple chronic conditions. The tool also needs to be sensitive to change so that providers can use it to monitor patient outcomes and adjust the care plan accordingly. We created such a tool and then investigated its psychometric properties (in other words, reliability and validity) in our study of 291 older patients (aged 65 and older) who had at least one recent visit to our urban primary care clinics in Indianapolis, Indiana. These patients had presented with evidence of cognitive or depression problems because these patients and their caregivers were participating in a collaborative care model for such patients.
Medical Research: What are the main findings?Dr.Monahan: The Healthy Aging Brain Care (HABC) Monitor demonstrated excellent reliability and validity in this study where patients self-reported their symptoms. Our previous study also showed excellent reliability and validity of the HABC Monitor when the patients’ symptoms were reported by their informal caregiver. (more…)
MedicalResearch.com Interview with:
Melissa Stockwell, MD, MPH, FAAP
Florence Irving Assistant Professor of Pediatrics and Population and Family Health, Columbia University - College of Physicians & Surgeons and Mailman School of Public Health
Medical Director, New York-Presbyterian Hospital Immunization Registry (EzVac);
Co-Director, Primary Care Clinician Research Fellowship in Community Health
Medical Research: What is the background for this study? What are the main findings?Response:Influenza can be a very serious disease and is more than just a bad cold. Some children who are 6 months through 8 years need two doses of the influenza vaccine in a season depending on if and when they received previous influenza vaccine doses. We know that only about half of these families who want to vaccinate their children against the flu and get the first dose, come back to get the second dose.
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MedicalResearch.com Interview with:
Jacob Nota M.S.
Binghamton Anxiety Clinic
Department of Psychology
Binghamton University
Binghamton, NY 13902
Medical Research: What is the background for this study? What are the main findings?
Response: As psychologists we are interested in helping individuals improve their quality of life and reduce their symptoms. We know that many people, including those with anxiety and mood disorders, are bothered by repetitive negative thoughts that feel like they are out of control. We are always looking for new ways that we might be able to reduce these kinds of symptoms. We are specifically interested in learning more about how sleep relates to psychopathology because an extensive literature documents the cognitive and emotional impact of sleep disruption. Therefore, addressing sleep disruption may be another avenue for us to explore for helping out clients. However, there is relatively little research on the relation between sleep timing and psychopathology compared to that studying the relation between sleep duration and psychopathology, despite previous studies showing that individuals who go to bed later than they want to have more disorders characterized by worry, rumination, and obsessing.
This study collected cross-sectional data (i.e., measuring sleep, worry, rumination, and obsessing all at the same point in time) from a group of 100 young adults at Binghamton University. We looked at measures of worry, rumination, and obsessing as well as a newer measure of the process thought to be shared across these psychological phenomena (repetitive negative thinking). We found that people who sleep for shorter amounts of time and go to bed later also have greater levels of worry, rumination, and obsessing. This is called repetitive negative thinking (RNT). We also found that individuals who are classified as "evening type" (i.e., tend to stay up later and shape their daily activities around this schedule), a trait that is linked to biological circadian rhythms, report significantly greater levels of repetitive negative thinking compared to individuals who are "morning" or neither type (i.e., not strongly morning or evening).
This is one of the first studies to show that repetitive negative thinking is related to both how long you sleep and when you sleep.
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MedicalResearch.com Interview with:
Dr. Richard Nash MD
Colorado Blood Cancer Institute
Medical Research: What is the background for this study? What are the main findings?Dr. Nash: Multiple sclerosis is an autoimmune disease of the central nervous system which causes significant disability and in some cases results in patients being wheel-chair bound or bed-ridden. It is a significant medical problem amongst young adults. We undertook this study because current Multiple sclerosis therapies were not adequate for effective long-term control of the disease in the majority of the patients. High-dose immunosuppressive therapy followed by autologous hematopoietic cell transplantation is an effective treatment for many hematological malignancies. It causes a profound immunosuppression. Based on this effect on the immunological system, we initiated a clinical trial of this treatment modified for autoimmune disorders. The study was supported by the Immune Tolerance Network and NIAID, NIH. In a phase 2 clinical trial of 25 patients all of whom were followed for at least 3 years, we demonstrated that 80% of patients had no evidence of disease activity. No other Multiple sclerosis treatments were given after the study treatment. Adverse events were similar to what we have observed for this treatment in patients with hematological malignancies. No significant acute neurological adverse events were observed. (more…)
MedicalResearch.com Interview with:
Dr. Annie Samraj MD
Postdoc Fellow
Varki Lab andAjit Varki MDDistinguished Professor of Medicineand Cellular & Molecular Medicine , Co-Director, Center for Academic Research and Training in Anthropogeny, Co-Director, Glycobiology Research and Training Center
University of California, San Diego, La Jolla, CA
Medical Research: What is the background for this study? What are the main findings?
Dr. Varki: For the past decade, there has been increasing evidence that people who consume red meat (beef, pork, lamb) are at a higher risk for certain kinds of cancers. Although red meat is a high quality source of protein, iron and vitamins, too much consumption may be harmful to humans. While there are other hypotheses under consideration, we focused on a non-human sugar molecule called Neu5Gc in red meat that could explain the link to cancer risk.
We extensively studied various foods and concluded that red meat (particularly beef) is rich in Neu5Gc. In contrast poultry, fish steaks and hen eggs have little or no Neu5Gc. From previous studies, we knew that animal-derived Neu5Gc could be incorporated into human tissues. In this study, we hypothesized that eating red meat could lead to inflammation if the body’s immune system targets the foreign Neu5Gc. Chronic inflammation is also known to instigate or promote tumor progression.
To test this hypothesis, we used mice engineered to be similar to humans in that they lacked Neu5Gc, and also produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Tumor formation increased fivefold and Neu5Gc accumulated in the tumors, proving the hypothesis. None of the various control groups of mice showed this effect.
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MedicalResearch.com Interview with:
Jeffrey A. Gusenoff, MD
Associate Professor of Plastic Surgery
Co-Director, Life After Weight Loss Program
Co-Director, BodyChangers
Director, Post-Bariatric Body Contouring Fellowship
UPMC Department of Plastic Surgery
Medical Research: What is the background for this study? What are the main findings?Dr. Gusenoff: With the rise in massive weight loss patients from bariatric surgery or diet and exercise, more patients are choosing to have a thighplasty to remove excess skin of the inner thigh. Many techniques exist for treating this, but there aren't many studies that look into the safety of these procedures in massive weight loss patients. What we found is that many patients have scars that go all the way down the thigh with a fairly high complication rate of almost 70%.
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MedicalResearch.com Interview with:
Dr Hayden McRobbie MB ChB PhD
Reader in Public Health Interventions
Wolfson Institute of Preventive Medicine
Barts and The London School of Medicine and Dentistry
Queen Mary University of London
Medical Research: What is the background for this study? What are the main findings?
Dr. McRobbi: Varenicline is an effective smoking cessation aid that acts primarily to alleviate the symptoms of tobacco withdrawal discomfort, thereby making quitting easier. It also reduces the rewarding effects of cigarettes smoked which may enhance the drugs smoking cessation effect by reducing the enjoyment of smoking prior to quitting and preventing a lapse, after quitting, progressing to relapse.
In some people the standard dose of varenicline (2mg/day) results in a decrease in the enjoyment of smoking prior to quitting and that these people appear to have higher quit rates that those that don’t experience this reaction to smoking.
The randomised placebo controlled trial was designed to investigate whether increasing the varenicline dose (up to 5mg/day) in smokers who show no reaction to the standard dose improves treatment outcomes compared to remain on the standard dose.
Medical Research: What are the main findings?
Dr. McRobbi: Whilst the increased dose, compared with the standard dose, reduced the enjoyment of smoking prior to quitting it had no additional effect on alleviating tobacco withdrawal symptoms or smoking cessation rates at 12 weeks post quit date (26% vs. 23%).
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MedicalResearch.com Interview with:
Aramesh Saremi MD
Phoenix VA Health Care System
Health Research Scientist
Phoenix, AZ 85012-1892
Medical Research: What is the background for this study? What are the main findings?Dr. Saremi: Our study was a post-hoc analysis of the data that was available from VA cooperative study, the Veterans Affair Diabetes Trial (VADT). The VADT was one of the recent landmark studies examining the effect of intensive glycemic control on cardiovascular events in older adults with type 2 diabetes.
The main finding in the VADT and other two other landmark studies (ACCORD and ADVANCE ) was that intensive glycemic control does not reduce cardiovascular disease events in people with type 2 diabetes of moderate to long duration. However, our subsequent post-hoc analysis suggests that intensive glycemic control was associated with reduced risk of cardiovascular events in Hispanics, but not in non-Hispanic Whites or Blacks.
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MedicalResearch.com Interview with:
György Buzsáki, M.D., Ph.D.
Biggs Professor of Neural Sciences
NYU Neuroscience Institute New York University
Langone Medical Center New York, NY 10016
Medical Research: What is the background for the NeuroGrid device?
Dr. Buzsaki: The main form of communication among neurons in the brain occurs through action potentials (‘spikes’). Understanding the mechanisms that translate spikes of individual neurons into perceptions, thoughts, and actions requires the ability to monitor large populations of neurons at the spatial and temporal resolution of their interactions.
We developed a novel, organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) with neuron-size density electrodes capable of acquiring action potential of individual neurons from the surface of the brain.
The NeuroGrid has several innovative characteristics that overcome limitations in current methods of surface recording:
(i) light-weight and conformable architecture to establish stable electrical and mechanical contacts, thereby ensuring minimal damage to underlying tissue;
(ii) efficient abiotic/biotic interface resulting in a high signal to noise ratio and the ability to resolve spikes. This is achieved by using conducting polymers as the interfacing material. Conducting polymers are mix conductors, they can conduct electronics and ionic currents hence they can efficiently transduce ion based neural activity into electronic signals
(iii) scalable neuron-size density electrodes to allow isolation and characterization of multiple individual neurons’ action potential across the cortical surface.
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MedicalResearch.com Interview with:
Yan Liang, MD, PHD on behalf of co-authors
Emergency and Intensive Care Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, ChinaMedical Research: What is the background for this study? What are the main findings?
Response: The background of this study is mainly derived from the results of CURRENT-OASIS7 which has shown a 7-day 150 mg maintenance dose (MD) clopidogrel could reduce cardiovascular events among subgroup patients undergoing percutaneous coronary intervention (PCI) compared with the 75 mg/day regimen. We conducted a meta-analysis based on 17 randomized controlled trials to determine whether prolonging the high MD clopidogrel (≥150 mg) treatment period to at least 4 weeks could reduce major adverse cardiac events (MACEs) in the PCI patients with and without high on-clopidogrel platelet reactivity (HPR).
Our study concluded that the high maintenance dose clopidogrel was associated with a significant reduction in the risk of MACEs in PCI patients without increasing the rate of “Major/Minor bleeding” or “Any bleeding” in comparison with standard 75mg MD clopidogrel, and the “HPR Patients” subgroup were also benefited from such high MD treatment.
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MedicalResearch.com Interview with:
Paul Dent PhD
Massey Cancer Center,Departments of Biochemistry and Molecular Biology
Virginia Commonwealth University, Richmond, VA 23298
Medical Research: What is the background for this study? What are the main findings?
Dr. Dent: I have worked on understanding how the drug OSU-03012 (AR-12) kills cancer cells since 2005.
The drug was originally advertised as an inhibitor of PDK1 in the PI3 kinase pathway. We found that PDK1 inhibition could not be the major way in which the drug worked. We found that the drug killed brain cancer cells through endoplasmic reticulum stress signaling. And in 2012 we published that OSU-03012 destabilized the chaperone protein GRP78, without significantly altering its transcription. Loss of GRP78 was responsible for the prolonged intense endoplasmic reticulum stress signal, that was toxic. In 2014 we published that OSU-03012 + Viagra / Cialis synergized to kill brain cancer cells. We hypothesized that Viagra / Cialis might enhance the anti-GRP78 effect of OSU-03012; and this was proven to be true.
We discovered that the OSU-03012 + Viagra combination, but not OSU-03012 alone, reduced expression of other chaperone proteins, such as HSP70, GRP94. In mice, the combination was not toxic to "normal" tissues, but was toxic to tumor cells.
In human patients the drug was found to be safe in a phase I trial, with plasma levels of up to 8 microM, and patients on trial for up to 9 months.
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MedicalResearch.com Interview with:
Jeffrey H. Silber, M.D., Ph.D.
The Nancy Abramson Wolfson Endowed Chair in Health Services Research Director, Center for Outcomes Research
The Children's Hospital of Philadelphia
Professor of Pediatrics, Anesthesiology & Critical Care
The Perelman School of Medicine
Professor of Health Care Management, The Wharton School
The University of Pennsylvania Philadelphia, PA 19104
Medical Research: What is the background for this study? What are the main findings?
Response: Differences in colon cancer survival by race is a well recognized problem among Medicare beneficiaries. We wanted to determine to what extent the racial disparity in survival is due to a racial disparity in presentation characteristics at diagnosis (such as advanced stage and the presence of chronic diseases) versus a disparity in subsequent treatment by surgeons and oncologists.
To answer this question, we compared black colon cancer patients to three matched white groups:
(1) “Demographics” match controlling age, sex, diagnosis year, and Survey, Epidemiology, and End Results (SEER) site;
(2) “Presentation” match controlling demographics plus comorbidities and tumor characteristics including stage and grade; and
(3) “Treatment” match including presentation variables plus details of surgery, radiation and chemotherapy.
We studied Medicare patients 65 years of age and older diagnosed between 1991-2005 in the SEER-Medicare database. There were 7,677 black patients and 3 sets of 7,677 matched white controls.
We found that difference in 5-year survival (black-white) was 9.9% in the demographics match. This disparity remained unchanged between 1991-2005. After matching on presentation characteristics, this difference fell to 4.9%. Finally, after additionally matching on treatment, this same difference hardly changed, moving to only 4.3%. So the disparity in survival attributed to treatment differences comprised only an absolute 0.6% of the overall 9.9% survival disparity.
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MedicalResearch.com Interview with:
Ulas Sunar, Ph.D.
Research Assistant Prof.
Dept of Biomedical Engineering
SUNY-University at Buffalo
Medical Research: What is the background for this device? What are the main implications?Dr. Sunar: Most of ovarian cancer cases are not diagnosed until after the disease has spread in the abdominal cavity. A major challenge is to detect and remove dozens or hundreds of metastatic tumor nodules within the abdominal cavity. Fluorescence endoscopy can utilize the high sensitivity and specificity of fluorescence contrast and high resolution of endoscopic imaging.
We are developing a clinically-relevant, fiber-based endoscopy system that allows both accurate fluorescence imaging and for projecting adaptive-shaped light for light-induced chemodrug delivery. The system can provide high contrast for improved demarcation and trigger drug release to destroy micrometastases. The system utilizes a highly sensitive camera and structured light illumination scheme with a projector for accurate fluorescence imaging of drug distribution, as well as allows light-triggered drug release and adaptive light delivery for optimized treatment of micrometastases. We expect that our novel illumination and drug release strategy will permit lower doxorubicin doses to be administered while simultaneously achieving more specific drug delivery in order to destroy the micrometastases and improve survival rates.
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MedicalResearch.com Interview with:
Scott M. Hayes, Ph.D. Associate Director
Neuroimaging Research for Veterans Center
Memory Disorders Research Center
VA Boston Healthcare System
Assistant Professor of Psychiatry
Boston University School of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Hayes: Studies with rodents have demonstrated that physical activity positively impacts memory, whereas human studies have tended to emphasize a relationship with executive function—which refers to one’s ability to plan, organize, and manipulate information in one’s mind. To clarify the relationship between fitness, cognition, and aging, we directly assessed cardiorespiratory fitness (heart and lung function) using the gold standard in the field, a graded treadmill test, and assessed both memory and executive functions in young and older adults. Our results showed that cardiorespiratory fitness was positively associated with memory and executive functions in older adults, but not young adults. In fact, on tests of executive functions, older adults with higher levels of cardiorespiratory fitness performed as well as younger adults. The impact of cardiorespiratory fitness may be age-dependent. Young adults, who are at their peak in terms of memory performance, may exhibit minimal associations with cardiorespiratory fitness. In contrast, cardiorespiratory fitness likely has a larger impact in older adults by attenuating age-related decline in memory.
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MedicalResearch.com Interview with:
William M. Sikov, MD
Associate Chief of Clinical Research Program in Women's Oncology
Women & Infants Rhode Island
Associate professor of Medicine
The Warren Alpert Medical School of Brown University
Medical Research: What is the background for this study? What are the main findings?Dr. Sikov: The data presented at San Antonio this year are the first results from correlative studies performed on pretreatment tissue samples from patients treated on CALGB 40603, a 2 x 2 factorial randomized phase II study which tested the addition of carboplatin or bevacizumab to a standard neoadjuvant chemotherapy regimen consisting of weekly paclitaxel followed by dose-dense AC in patients with stage II-III triple breast cancer. Last year at San Antonio (and subsequently published in the JCO) we presented the primary endpoint of the study - pathologic complete response (pCR) - and reported that the addition of either carboplatin or bevacizumab significantly increased pCR rates compared to the control regimen. This year we reported results of a preplanned analysis which assessed the impact of intrinsic subtype (based on mRNA expression analysis) - especially the basal-like subtype - on the impact of the two agents on pCR rates. We also reported the effects of a number of previously published mRNA expression signatures on pCR rates and the benefits of adding carboplatin or bevacizumab.
The findings reported were as follows: We had a higher percentage of basal-like cancers than we anticipated when the study was designed (87% vs. 70-80% expected), which we hypothesize is due to improvements in the ways we assess hormone receptor and HER2 status, and thus define triple-negative breast cancer, compared to 10-15 years ago. When we limit our analysis to the subset of patients with basal-like cancers, we continue to see a statistically significant increases in pCR rates with both carboplatin and bevacizumab. However, while the 13% of patients with non-basal-like cancers get essentially the same increase in pCR rates with carboplatin as do the basal-likes, non-basal-likes actually had a reduction in their pCR rates with the addition of bevacizumab - thus, there was a significant interaction between subtype and pCR benefit for bevacizumab but not for carboplatin. Among the mRNA signatures we assessed, higher expression of immune signatures (indicating more tumor-infiltrating lymphocytes) correlated with higher pCR rates, but not greater pCR increments with either carboplatin or bevacizumab. Higher proliferation, lower estrogen, and higher TP53 mutation signaturss also correlated with higher pCR rates overall, and also with greater pCR increments with bevacizumab, but not carboplatin.
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MedicalResearch.com Interview with:
Keith P. West, Jr., Dr.P.H., R.D.
Professor and Director
Program and Center in Human Nutrition
Department of International Health
Bloomberg School of Public Health
Johns Hopkins University Baltimore, Maryland 21205Medical Research: What is the background for this study? What are the main findings?
Dr. West: Deficiencies in vitamins and minerals (micronutrients) that must be provided by the diet, are a major public health concern in undernourished societies. In rural South Asia, where some 35 million babies are born each year, maternal micronutrient deficiencies are common and may increase risk of adverse pregnancy outcomes such as preterm birth, low birth weight or stillbirth and infant mortality. Further, a newborn of low birth weight faces higher risks of poor postnatal growth, infection and mortality. Where prenatal care exists, iron-folic acid supplements are often prescribed as standard care to prevent iron deficiency anemia. But it is likely that many micronutrient deficiencies emerge from an inadequate diet, raising the possibility that a supplement that provides each day a recommended dietary allowance of most essential vitamins and minerals could measurably improve the health of the mother, fetus and infant. Because prenatal multinutrient supplements are rarely taken in low income countries, it is important to assess their potential to improve health before recommending this practice. We did this be conducting a large prenatal supplementation trial in rural Bangladesh, randomizing 44,567 pregnant women in their 1st trimester to receive a supplement with 15 vitamins and minerals or only iron and folic acid, followed their pregnancies and survival of their 28,516 infants to 6 months of age.
Medical Research: What are the main findings?Dr. West: The multiple micronutrient supplement had the effect of extending the length of gestation compared to the iron-folic acid supplement, by about 2 days on average. This was enough to lower risk of preterm birth, below 37 weeks, by 15%. The extra time in the womb also allowed the fetus to grow a little larger, increasing birth weight (by 54 grams or about 2 ounces) as well as length and other measures of size, leading to a 12% reduction in low birth weight. In addition, there was an 11% reduction in risk of stillbirth. These are all indications of a healthier pregnancy. Although we observed a 14% lower mortality from all causes in girls, there was not a similar effect in boys, leading to no overall effect. We are continuing to investigate possible reasons for this difference.
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MedicalResearch.com Interview with:
Torben Bjerregaard Larsen
Associate professor, MD, PhD, FESC
Aalborg University Hospital Department of Cardiology
Aalborg Thrombosis Research Unit Denmark
Medical Research: What is the background for this study? What are the main findings?
Dr. Larsen: Heart failure is a major public health issue with an increasing prevalence. Heart failure is associated with an increased risk of stroke, also in patients without concomitant atrial fibrillation. However, recent prospective randomized controlled trials investigating the effect of antithrombotic therapy in heart failure patients in sinus rhythm revealed that the benefit of warfarin in reducing stroke was counterbalanced by an increased risk of bleeding. Whether subgroups within the heart failure population would benefit from antithrombotic therapy is currently unknown. Therefore, possible subgroups with a higher risk of stroke within the heart failure population must be identified. We investigated whether female sex was associated with a higher risk of stroke, since female sex has been associated with an increased stroke risk among patients with atrial fibrillation.
In our study, we found an association between female sex and decreased stroke risk in heart failure patients in sinus rhythm which persisted after adjustment for concomitant cardiovascular risk factors. This association was attenuated with increasing age which could possibly be due to competing risks of death, since competing risk of death was substantial among males in the older age groups.
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MedicalResearch.com Interview with:
Huachun Zou PhD on behalf of all authors.
Melbourne Sexual Health Centre, Alfred Health, Carlton, VIC,
Melbourne School of Population and Global Health
University of Melbourne, Melbourne, VIC, AustraliaMedical Research: What is the background for this study? What are the main findings?
Response: Anogenital human papillomavirus (HPV) infection and anal cancer are common among men who have sex with men (MSM) and preventable with the HPV vaccine. However, the optimal strategy for vaccinating MSM against HPV requires an accurate understanding of the age specific incidence of early HPV infection. In addition to understanding the optimal age at which to vaccinate young MSM, policy makers also need to know the vaccine coverage required in MSM. In this paper we aimed to provide estimates for the site specific incidence of HPV and to use this to estimate the probability of transmission per partner in a cohort of very young MSM aged 16 to 20 years. These data will assist governments in deciding what HPV vaccination strategy is likely to be the most effective in MSM.
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MedicalResearch.com Interview with:
Dr. Judy Karp, Dr. Antonio Wolff and Dr. Kala VisvanathanBreast Cancer Program
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, MD 21287
Medical Research: What is the background for this study? What are the main findings?
Response: The background for this study was the clinical observation from the Johns Hopkins Leukemia Program that a significant number of women with newly diagnosed acute myeloid leukemia had a personal history for breast and/or ovarian cancers. This observation led to our examination of the large NCCN breast cancer database in a multidisciplinary and multi-institutional study. The overarching finding in our study is that the risk of developing some form of leukemia following chemotherapy with or without radiation therapy, while small, continues to increase over at least 10 years without a plateau and is roughly twice what we thought it to be from previous breast cancer studies.
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MedicalResearch.com Interview with:
Michael G. Rossmann PhD
Hanley Professor of Biological Sciences
Hockmeyer Hall of Structural Biology
Purdue University, West Lafayette IN
Medical Research: What is the background for this study? What are the main findings?
Dr. Rossmann: My laboratory has long been interested in the structure of viruses and especially of Picornaviruses (e.g. EV-D68). We published the first 3D, near atomic resolution map of any animal virus in 1985. That was of Human Rhino (common cold) virus serotype 14. We then went on to show where and how the virus would bind to cellular receptors and also how certain small capsid binding compounds inhibited the viral infectivity. The latter was a collaboration first with the Sterling Winthrop company and later with ViroPharma. Thus our work on EV-D68 is a direct continuation of my interest in picornaviruses.
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