Author Interviews, Cancer Research, Dermatology, JAMA, UCLA / 22.11.2016

MedicalResearch.com Interview with: Albert Yoon-Kyu Han, PhD Class of 2017 Medical Scientist Training Program David Geffen School of Medicine at UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Squamous cell carcinoma (SCC) of the lip makes up a large portion of oral cancers (25%). Most of the demographic and prognostic indicators for lip SCC are only available through retrospective case series. Thus, we used the national cancer database (Surveillance, Epidemiology, and End Results, or SEER) to examine the incidence, treatment, and survival of patients with lip SCC. The main findings of this study were that lip Squamous cell carcinoma predominantly affects white men in their mid-60s. We also found that the determinants of survival for lip SCC include age at diagnosis, primary site, T stage, and N stage. More specifically, on the primary site, SCC of the upper and lower lip had similar survival, whereas SCC of the oral commissure was associated with decreased survival. (more…)
Author Interviews, Ophthalmology, UCLA / 10.10.2016

MedicalResearch.com Interview with: Pravin U. Dugel, MD Retina Consultants of Arizona Phoenix, Arizona; USC Roski Eye Institute Keck School of Medicine University of Southern California Los Angeles, California  MedicalResearch.com: What is the background for this study? Response: OASIS is an acronym for “OcriplASmIn for Treatment for Symptomatic Vitreomacular Adhesion including Macular Hole”.  It was a Phase IIIB, randomized, prospective, sham-controlled, double-masked, multicenter clinical study. The goal of the study was to further evaluate the long-term (24 months) efficacy and safety of a single injection of 0.125mg of ocriplasmin in patients with symptomatic vitreomacular adhesion (VMA) and vitreomacular traction (VMT), including macular hole (MH). OASIS evaluated 220 patients with symptomatic VMA/VMT.  One hundred forty-six patients received ocriplasmin while 74 served as a sham control group. In the latter group, no intravitreal injection was administered.  (more…)
Author Interviews, Dermatology, Technology, UCLA / 05.10.2016

MedicalResearch.com Interview with: Dr. Andrea M Armani PhD Fluor Early Career Chair and Associate Professor Mork Family Department of Chemical Engineering and Materials Science University of Southern California, Los Angeles, California MedicalResearch.com: What is the background for this study? Response: The “Internet of Things” (IoT) has seen an explosion in online sensor technologies, including UV sensors and monitors; for example, those from Apple and Samsung. However, they require connectivity and power, and they are integrated into delicate electronic systems that are not compatible with outdoor, athletic activities such as swimming, which is precisely when you should monitor UV exposure. Therefore, somewhat ironically, the technologies developed to meet the demands of the IoT are not ideal for cumulative UV exposure detection. Our goal was to develop a single use patch – like a smart “band-aid” – for the beach to alert users when they had been in the sun for an hour and needed to re-apply sunscreen or get out of the sun altogether. This application required a rugged system that was waterproof, bendable, and compatible with sunscreen. Additionally, the sensor readout needed to be easy to interpret. These requirements influenced our design and material selection. (more…)
Aging, Author Interviews, Genetic Research, UCLA / 17.08.2016

MedicalResearch.com Interview with: Michael Gurven, Professor Department of Anthropology University of California Santa Barbara, CA 93106 MedicalResearch.com: What is the background for this study? Response: Understanding the sources of ethnic and sex disparities in health and longevity is critical in order to insure the health and well-being of everyone. We often hear about disparities due to differences in health care access, education, income, and sometimes genetic differences. But what we've done here is to employ a new biomarker developed by Steve Horvath, called the "epigenetic clock", which measures the cumulative changes to the epigenome, i.e. alterations to DNA that affects gene activity and expression but do not alter the DNA itself. This new measure is arguably one of the best biomarkers of aging out there today - so it's indeed a biological measure, but tells a different story than conventional genetic differences. Instead epigenetic age is influenced by the lived experience, physical and social environment, and genetic make-up of individuals. (more…)
Author Interviews, Heart Disease, Kidney Disease, Pharmacology, UCLA / 09.08.2016

MedicalResearch.com Interview with: Jenny Shen, MD, MS Assistant Professor of Medicine David Geffen School of Medicine at UCLA Los Angeles Biomedical Institute at Harbor-UCLA Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: With cardiovascular disease being the No. 1 cause of death in end-stage kidney disease patients on peritoneal dialysis, we examined two classes of medications commonly prescribed to prevent cardiovascular events in these patients and found no significant difference in outcomes. The two classes of medications, angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB), have slightly different mechanisms and could theoretically have differing outcomes. Previous studies had suggested that ACEI may lead to a kinin-mediated increase in insulin sensitivity not seen with ARB. This could potentially lower the cardiovascular risk in patients on peritoneal dialysis because they are exposed to high glucose loads in their dialysate that may lead to insulin resistance and its associated cardiovascular risk. Using a national database, the U.S. Renal Data System, we surveyed records for all patients enrolled in Medicare Part D who initiated maintenance peritoneal dialysis from 2007 to 2011. Of those, we found 1,892 patients using either drug class. Surveying their medical records, we found no difference in cardiovascular events or deaths between the users for each class of medication. (more…)
Aging, Author Interviews, Gender Differences, Genetic Research, Menopause, UCLA / 28.07.2016

MedicalResearch.com Interview with: Morgan Elyse Levine, PhD Postdoctoral Fellow Department of Human Genetics University of California, Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Response: From an evolutionary perspective, aging and reproduction are two processes that are linked. For instance, in order to maximize fitness, an individual has to survive and remain healthy enough to: 1) reproduce and 2) insure offspring survive to reproductive age. Thus, the rate of aging is tied to a species’ timing of reproductive senescence and necessary length of parental involvement. There is also evidence that among humans, women with longer reproductive stages (later age at menopause, ability to conceive at older ages) are more likely to live to age 100, which we hypothesize is because they age slower. Using an epigenetic biomarker believed to capture biological aging (previously developed by the Principle Investigator of this study, Steve Horvath), we tested whether age at menopause, surgical menopause, and use of menopausal hormone therapies were associated with a woman’s aging rate. We found that the blood of women who experienced menopause at earlier ages (especially those who underwent surgical menopause) was “older” than expected, suggesting they were aging faster on a biological level than women who experienced menopause at later ages. We also found that buccal epithelium samples (cells that line the inside of the cheek) were epigenetically younger than expected (signifying slower aging) for post-menopausal women who had taken menopausal hormone therapy, compared to post-menopausal women who had never taken any form of menopausal hormone therapy. Finally, we had a number of results that suggested that the previously mentioned findings were a result of the process of menopause directly speeding up the aging process—rather than the alternative explanation, which would have been that women who aged faster experience menopause earlier. (more…)
Author Interviews, Cancer, Cancer Research, UCLA / 11.07.2016

MedicalResearch.com Interview with: Karim Chamie MD, MSHS Department of Urology Jonsson Comprehensive Cancer Center David Geffen School of Medicine University of California at Los Angeles Los Angeles, California MedicalResearch.com: What is the background for this study? Response: With improved cancer outcomes, there are 14 million cancer survivors alive in the United States in 2012. That number is expected to increase to nearly 20 million by 2024. With such a large population, many of these cancer survivors are at risk for developing a second primary malignancy. Multiple primary cancers now account for approximately 17% of all incident cancers reported each year in the United States. Cancer survivors may be especially susceptible to developing second primary malignancies due to a variety of unique factors, including genetic syndromes, common etiologic exposures, and the late effects of chemotherapy and radiotherapy. Given the longer duration of cancer survivorship and the substantial proportion of survivors at risk for developing second primary malignancies, the incidence and mortality from second primary malignancies are likely to increase. (more…)
Author Interviews, Bone Density, Endocrinology, Menopause, Mineral Metabolism, UCLA / 25.06.2016

MedicalResearch.com Interview with: Albert Shieh, MD Division of Endocrinology, Diabetes and Hypertension David Geffen School of Medicine University of California, Los Angeles MedicalResearch.com: What is the background for this study? What are the main findings? Response: Whether an individual loses or gains bone mass is dependent on how much bone is being broken down (by osteoclasts) and being formed (by osteoblasts). Both processes occur simultaneously in the human body. At present, we can measure markers of bone breakdown (resorption) and formation. However, we hypothesized that to better predict the amount of bone mass that will be lost in the future, these markers should be combined in an "index" to reflect both processes, rather than being interpreted in isolation. Indeed, we found that the ability of our new bone balance index predicted future bone loss across the menopause transition better than the bone resorption marker alone. (more…)
Author Interviews, Heart Disease, JAMA, Pharmacology, UCLA / 22.06.2016

MedicalResearch.com Interview with: Gregg C. Fonarow, MD, FACC, FAHA Eliot Corday Professor of Cardiovascular Medicine and Science Director, Ahmanson-UCLA Cardiomyopathy Center Co-Chief of Clinical Cardiology, UCLA Division of Cardiology Co-Director, UCLA Preventative Cardiology Program David Geffen School of Medicine at UCLA Los Angeles, CA, 90095-1679 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Fonarow: Angiotensin receptor neprilysin inhibitors (ARNI) have been demonstrated to reduce mortality in patients with heart failure with reduced ejection fraction. However, to date, the population level impact of optimal implementation of this therapy in the United States has not been evaluated. This new analysis estimates that as many 28,484 deaths in heart failure with reduced ejection fraction patients annually could be prevented or postponed with optimal use of angiotensin receptor neprilysin inhibitors (with sensitivity analyses demonstrating a range of 18,230 to 41,017). (more…)
Annals Internal Medicine, Author Interviews, Primary Care, UCLA / 21.06.2016

MedicalResearch.com Interview with: John N. Mafi, MD, MPH Assistant Professor of Medicine Division of General Internal Medicine and Health Services Research UCLA David Geffen School of Medicine Los Angeles, CA 90024 Affiliated Adjunct in Health Policy RAND Corporation Santa Monica, CA 90401 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Mafi: The U.S. healthcare system faces a looming shortage of primary care physicians, with some estimates as high as 20,000 physicians by the year 2020. In addition, fewer and fewer trainees enter primary care careers because of the harder work and lower salaries. Combine this with the passage of the Affordable Care Act and the millions of newly insured patients looking for a primary care provider, and you have created a perfect storm where timely access to primary care becomes essentially unachievable. Many advocate for expanding the role of nurse practitioners and physician assistants to mitigate the physician shortage. But this is controversial as most doctors believe nurse practitioners provide inferior care to doctors and many feel that expanding their role would worsen the value and efficiency of the U.S. healthcare system. While studies suggest they provide similar quality of care to physicians, few have actually evaluated whether they provide greater amounts of inefficient or low value care. Low value care is important because it can harm patients (antibiotics for colds don’t help patients and have harmful side effects) and they can raise healthcare costs. In this context, we used a large national database on ambulatory visits to compare the quality and efficiency of care among nurse practitioners, physician assistants, and physicians in the U.S. primary care setting. In our 15 year analysis of nearly 29,000 patients who saw either a nurse practitioner, physician assistant, or a physician, we found similar rates of inappropriate antibiotic use for colds, unnecessary imaging (such as x-rays, CT scans, and MRI scans) for back pain and headache, and potentially necessary referrals to specialists for these same three conditions. (more…)
Author Interviews, Cancer Research, Inflammation, Microbiome, PLoS, UCLA / 15.04.2016

MedicalResearch.com Interview with: Robert H. Schiestl PhD Department of Environmental Health Sciences, Fielding School of Public Health, Department of Pathology Department of Radiation Oncology Geffen School of Medicine University of California Los Angeles, Los Angeles, California Medical Research: What is the background for this study? What are the main findings? Dr. Schiestl: When we moved from Harvard to UCLA 13 years ago, after 6 years at UCLA our Atm mouse colony lived significantly 4 fold longer and the frequency of DNA deletions was 4.5 fold reduced and the latency of lymphoma 2.5 fold different. Ultimately we identified the reason behind this as a difference in the intestinal bacteria. The Atm deficient mice are hypersensitive to inflammation and the bacteria reduced inflammation. Then I isolated the most prevalent bacterium among the health beneficial bacteria and this bacterium by itself called Lactobacillus johnsonii 456 reduced genotoxicity and all markers of inflammation. (more…)
Author Interviews, Endocrinology, Toxin Research, UCLA / 31.03.2016

MedicalResearch.com Interview with: Nancy L. Wayne, PhD Professor, Department of Physiology UCLA School of Medicine Los Angeles, CA 90095 MedicalResearch.com editor’s note: Campbell Soup Co. will stop using the chemical Bisphenol A in its canned products by the middle of 2017 due to consumers concerns that BPA raises the risk of cancer, brain damage and hormonal problems. Professor Nancy Wayne, is a reproductive endocrinologist and professor of physiology at UCLA. She has conducted extensive research on the health effects of the endocrine disruptors bisphenol A (BPA), a chemical widely used by manufacturers to strengthen plastic, and its replacement, bisphenol S (BPS). Professor Wayne was kind of enough to discuss the implications of the Campbell Soup Co. announcement for the readers of MedicalResearch.com.  MedicalResearch.com: What is the background for this announcement?  What are the real and potential harmful effects of BPAs? Prof. Wayne: There has been increasing research publications on the impact of BPA on body functions in animal models, human cells in culture, and associations between high levels of BPA in human urine samples and dysfunctions and diseases. a pubmed (biomedical article search engine) keyword search of bisphenol + BPA showed 39 articles published in the 1990s, 1127 articles published in the 2000s, and over 2300 articles published since January 2010. The public is much more aware of this research now — even though the message from the U.S. FDA has been consistently that low levels of BPA are not harmful (this is not the case according to independent research). Public pressure is causing companies to re-think their use of BPA in their products that could lead to environmental exposure of humans to this chemical. BPA has been shown in animal models to alter genes in fetal heart that are known to play a role in heart diseases, leads to increased genetic abnormalities in fertilized eggs and miscarriages, increased premature birth, increases susceptibility to breast cancer, stimulates early development of the reproductive system, and increases the risk of obesity. We cannot do controlled studies in humans with toxins like we can with laboratory animals. However, there has been shown to be an association between high levels of BPA in human urine and many of the same problems seen in animals: increased body weight and fat in children, increased risk of miscarriages and premature birth, and increased incidence of prostate cancer. Although association doesn’t mean cause-and-effect, taken together with the animal studies — it is meaningful. (more…)
Author Interviews, Cancer Research, Technology, UCLA / 26.03.2016

MedicalResearch.com Interview with: Dr. David Wong D.M.D, D.M.S.C Professor Associate Dean for Research Director for UCLA Center for Oral/Head & Neck Oncology Research (COOR) Felix and Mildred Yip Endowed Chair in Dentistry UCLA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Wong: The EFIRM technology is an electrochemical technology developed for the optimal detection of saliva targets for molecular diagnostics. It is a multiplexible platform (nucleic acid and proteins) that has sensitivity and specificity that comparable with PCR and luminex-based assays. It permits direct target detection in bio-samples without processing. (more…)
Author Interviews, Genetic Research, UCLA / 26.02.2016

MedicalResearch.com Interview with: April D. Pyle PhD Associate Professor, Microbiology, Immunology & Molecular Genetics Molecular Biology Institute Center for Duchenne Muscular Dystrophy Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California, Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Pyle: We have developed a CRISPR/Cas9 gene editing platform that is applicable for approximately 60 percent of Duchenne muscular dystrophy patients. Duchenne is a devastating muscle wasting disorder affecting approximately1 in 5000 boys worldwide. It is caused by lack of the dystrophin protein. In our study, we demonstrate that we can restore the dystrophin reading frame by deleting up to 725kb of the DMD gene between exons 45 and 55, the largest deletion shown to date in this gene, which results in a functional dystrophin protein being expressed. We demonstrated feasibility of this platform in Duchenne patient-derived human induced pluripotent stem cells differentiated to skeletal and cardiac muscle cells. (more…)
Author Interviews, Cancer Research, Genetic Research, Personalized Medicine, UCLA / 24.01.2016

MedicalResearch.com Interview with: Dr. Chirag Patil, MD American Board Certified Neurosurgeon Brain & Spine Tumor Program Lead Investigator, Precision Medicine Initiative Against Brain Cancer Program Director, Neurosurgical Residence training program Director, Center for Neurosurgical Outcomes Research Cedars-Sinai Medical Center, Los Angeles, California MedicalResearch.com Editor’s note: Dr. Patil’s research is focused on developing a method of personalized cancer treatment through the harnessing of genome wide mutational analysis of a specific patient’s cancer. MedicalResearch.com: Would you tell us a little about yourself and your research interests? Dr. Patil: I am a Stanford-trained, Board Certified Neurosurgeon and cancer researcher at Cedars-Sinai Medical Center in Los Angeles, California. I primarily focus on the care of patients with malignant brain tumors, particularly glioblastomas. I received my undergraduate degree from Cornell, followed by a medical degree from the University of California, San Francisco (UCSF), where I was a Regent’s scholar. I completed a residency in neurosurgery and a fellowship in stereotactic radiology at Stanford University. I also have a master’s degree in epidemiology with a focus on clinical trial design and mathematical modeling from Stanford. MedicalResearch.com: Can you tell us about some of your research interests? Dr. Patil: I am keenly interested in and focused on developing precision science-powered novel brain tumor therapies, immuno-therapies, and patient-centered “big data” outcomes research. I lead the recently-funded Cedars-Sinai Precision Medicine Initiative Against Brain Cancer, which utilizes tumor genomics to build a mathematical computer model, i.e., a virtual cancer cell of each patient’s unique tumor. The White House and several other stakeholders have taken keep interest in this research initiative as an example of a leading precision medicine program. (more…)
Addiction, Author Interviews, Methamphetamine, Pediatrics, UCLA / 22.01.2016

More on Pediatrics on MedicalResearch.com MedicalResearch.com Interview with: Lynne M. Smith, MD FAAP LA BioMed lead researcher Vice Chair for Academic Affairs Professor of Clinical Pediatrics Department of Pediatrics Division of Neonatology Medical Director, High Risk Infant Follow-up Program Associate Program Director, Neonatal-Perinatal Fellowship Training Program Co-Director, Third Year Medical Student Clerkship Founding co-Leader, Schwartz Rounds at Harbor-UCLA David Geffen School of Medicine at UCLA Harbor-UCLA Medical Center Torrance, CA Medical Research: What is the background for this study? What are the main findings? Dr. Smith: It is the first study of its kind, and it holds hope for improving outcomes for children exposed to the methamphetamine in the womb. The study found that while prenatal methamphetamine exposure can lead to targeted behavioral issues, a supportive home environment significantly decreases the severity and risk of these issues. The study is a follow-up to the Infant Development, Environment and Lifestyle (IDEAL) study, which is a prospective, multi-center, longitudinal study of children exposed to methamphetamine in the womb. It is designed to address some of the limitations of earlier studies. The IDEAL study enrolled children from Los Angeles; Des Moines, IA; Tulsa, OK, and Honolulu, HI, who had been exposed to methamphetamine in utero. Previous reports from the IDEAL study documented the outcomes up to age 5 and found emotional issues and attention deficit hyperactivity disorders in the children with prenatal methamphetamine exposure. The new study surveyed 290 children enrolled in IDEAL up to age 7.5 years and found a strong relation between prenatal methamphetamine exposure and rule-breaking and aggressive behavior. It also found a strong relation between adversities in the home and rule-breaking and aggressive behavior. Among the adverse conditions considered were maternal substance abuse, extreme poverty, changes in the primary caregiver, sexual abuse of the caregiver and maternal depression. The researchers concluded that while prenatal methamphetamine exposure is strongly related to behavioral and emotional control issues, early adversities may be a strong determinant of behavioral outcomes. (more…)
Author Interviews, Depression, JAMA, Surgical Research, UCLA, Weight Research / 12.01.2016

MedicalResearch.com Interview with: Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research University of California Los Angeles Los Angeles, CA 90024 Medical Research: What is the background for this study? What are the main findings? Dr. Dawes: We reviewed the published literature to answer three basic questions about bariatric surgery and mental health conditions. First, how common are mental health conditions among patients being referred for or undergoing bariatric surgery?
  • Second, do patients who carry a diagnosis of one of these conditions lose less weight after surgery than patients without these conditions?
  • And, third, what happens to the clinical course of mental health conditions after patients undergo surgery? Do they get better, worse, or stay the same?
We found that mental health conditions are surprisingly common among bariatric patients, especially depression and binge eating disorder, which occur at almost twice the rate among bariatric patients than in the general U.S. population. We also found no strong evidence to suggest that patients with depression lose less weight after surgery and some evidence that the condition may actually improve after surgery. Eleven of the twelve studies on the topic found either lower rates or fewer symptoms of depression, at least during the first 3 years post-operatively. (more…)
Author Interviews, Lancet, Multiple Sclerosis, Pharmacology, UCLA / 07.12.2015

MedicalResearch.com Interview with: Professor Rhonda Voskuhl, M.D. Jack H. Skirball Chair in MS Research Director of the UCLA MS Program David Geffen School of Medicine University of California, Los Angeles Medical Research: What is the background for this study? What are the main findings? Dr. Voskuhl: It had been known for decades that relapses were reduced during pregnancy in women with Multiple Sclerosis (MS), psoriasis and rheumatoid arthritis. We viewed this as a major clue to help find new disease modifying treatments. Focusing on MS, we investigated treatment with estriol, an estrogen that is made by the fetus/placenta during pregnancy. Preclinical studies and a pilot clinical trial at UCLA showed good results leading to the current Phase 2 clinical trial at 16 sites across the U.S. It showed that treatment with estriol pills compared to placebo pills, each in combination with standard of care (glatirmar acetate) injections, reduced relapses by one third to one half over and above standard of care treatment. (more…)
Author Interviews, JAMA, Obstructive Sleep Apnea, Surgical Research, UCLA / 29.11.2015

MedicalResearch.com Interview with: Soroush Zaghi, MD Department of Head and Neck Surgery David Geffen School of Medicine at UCLA University of California, Los Angeles MedicalResearch: What is the central message for clinicians and surgeons from your results? Dr. Zaghi: Multiple studies from different practitioners and institutions agree that Maxillomandibular Advancement (MMA) is a highly effective surgical option for patients with obstructive sleep apnea who cannot tolerate positive pressure therapy and have not found success with other surgical procedures. (more…)
Author Interviews, OBGYNE, Pediatrics, UCLA / 10.11.2015

MedicalResearch.com Interview with: Edward R. B. McCabe, MD, PhD Senior Vice President and Chief Medical Officer Professor Adjunct of Pediatrics Yale University School of Medicine Distinguished Professor Emeritus, Department of Pediatrics & Inaugural Mattel Executive Endowed Chair of Pediatrics, UCLA School of Medicine Inaugural Physician-in-Chief, Mattel Children's Hospital Chief Medical Officer March of Dimes Medical Research: What is the background for this study? What are the main findings? Dr. McCabe: The March of Dimes Prematurity Campaign was launched in 2003. The goal of the campaign is to lower the rate of premature birth to 8.1 percent of live births by 2020 and to 5.5 percent by 2030. Premature birth is the leading cause of death for newborns, and a major cause of childhood disabilities. Worldwide, 15 million babies are born preterm, and nearly one million die due to complications of an early birth. The U.S. preterm birth rate ranks among the worst of high-resource nations. Babies who survive an early birth often face serious and lifelong health problems, including breathing problems, jaundice, vision loss, cerebral palsy and intellectual delays. The US earned a “C” on the 8th annual March of Dimes Premature Birth Report Card which revealed persistent racial, ethnic and geographic disparities within states. The report card provided preterm rates and grades for each state and the largest cities. The report card showed that although some progress is being made in reducing preterm births, not all families are sharing in the success. State specific information is available at marchofdimes.org/reportcard Portland, Oregon has the best preterm birth rate of the top 100 cities with the most births nationwide, while Shreveport, Louisiana has the worst, according to the 2015 Report Card. The U.S. preterm birth rate was 9.6 percent in 2014. The report card shows more than 380,000 babies were born too soon last year. (more…)
Author Interviews, Autism, Radiology, UCLA / 16.10.2015

MedicalResearch.com Interview with: Kay Jann, PhD, Department of Neurology Danny JJ Wang, Prof., Department of Neurology Laboratory of Functional MRI Technology Ahmanson-Lovelace Brain Mapping Center Department of Neurology University of California Los Angeles Los Angeles  Medical Research: What is the background for this study? What are the main findings? Response: The brain controls most of our behavior and thus changes in how brain areas function and communicate with each other can alter this behavior and lead to impairments associated with mental disorders. Higher cognitive functions are controlled by brain areas that form complex interconnected networks and alterations in these networks can lead to cognitive impairments. In autism, one such network is the so called default mode network. This network controls self-referential thoughts, reasoning past and future and is involved in understanding mental states of others (i.e. Theory of Mind). Functional MRI based functional connectivity is a research tool to understand the interrelations between brain areas and how separate, distributed areas can be organized into brain networks that serve specific cognitive functions. In autism, local hyperconnectivity along with hypoconnectivity in long range connections between anterior and posterior cingulate cortices has been discussed to be one of the physiological underpinnings of the behavioral symptoms in social interaction and cognition observed in austism. It is hypothesized to be due to a developmental delay and disbalance of the balance between neuronal excitation/inhibition in brain areas that lead to oversynchronized strong short-range (local) networks while long-range connections that develop later in neurodevelopment are less well established. In our study, we used a non-invasive MRI technique called arterial spin labeling (ASL) perfusion MRI for the first time in autism research. Similarly to Positron Emission Tomography (PET) this technique allows measuring cerebral blood flow (CBF), however without the need to inject radioactive tracers. ASL MRI uses magnetically labeled blood water as an endogenous tracer to quantify CBF. Accordingly, our approach enabled us to combine information about how brain areas are functionally connected, as well as their associated metabolic energy consumption in autism spectrum disorder.  We found that in typically developing children, the known relation between how strongly an area is connected to other areas in a brain network, the more energy it requires holds. In children with autism spectrum disorder this relation, however, was disrupted in a major brain area (the dorsal anterior cingulate cortex) that is relevant to social interactions and in Theory of Mind. Both are cognitive processes that are to some extent impaired in persons with autism spectrum disorders. (more…)
Aging, Author Interviews, Genetic Research, Smoking, UCLA / 11.09.2015

Dr. Morgan Elyse Levine PhD Postdoctoral Fellow Department of Human Genetics University of California, Los Angeles MedicalResearch.com Interview with: Dr. Morgan Elyse Levine PhD Postdoctoral Fellow Department of Human Genetics University of California, Los Angeles Medical Research: What is the background for this study? What are the main findings? Dr. Levine: Studies using mice, worms, and flies have suggested that longevity may be linked to stress resistance. All of us are constantly encountering things that damage our cells and tissue and disrupt physiological functioning. Therefore, people who are genetically predisposed to better prevent or repair this damage may age slower. Smoking is one of the most damaging things someone can do to their health, yet some smokers are able to survive to extreme ages. This study looked at long-lived smokers to see if we could identify a "genetic signature". We generated a genetic risk score that was found to be associated with longevity both in smokers and non-smokers, and also appeared to be associated with cancer risk. (more…)
Author Interviews, Brain Injury, JAMA, Outcomes & Safety, UCLA / 23.07.2015

Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research, University of California Los Angeles Los Angeles, CA 90024MedicalResearch.com Interview with: Aaron J. Dawes, MD Fellow, VA/RWJF Clinical Scholars Program Division of Health Services Research, University of California Los Angeles Los Angeles, CA 90024 Medical Research: What is the background for this study? What are the main findings? Dr. Dawes: In the fall of 2013, we formed the Los Angeles County Trauma Consortium, building upon a prior administrative relationship between LA County’s 14 trauma centers. We added health research researchers from UCLA and USC, and shifted the focus of the group from logistical issues to quality improvement. As a first project, our hospitals wanted to know if there was any variation in how traumatic brain injury patients are cared for across the county. Traumatic brain injury accounts for over 1/3 of all injury-related deaths in the U.S. and is the number one reason for ambulance transport to a trauma center in LA County. When we looked at the data, we found widespread variation in both how these patients were cared for at different hospitals and what happened to them as a result of that care. After adjusting for important differences in patient mix, we found that mortality rates varied by hospital from roughly 25% to 55%. As we tried to explain this variation, we looked into how often hospitals complied with two evidence-based guidelines from the Brain Trauma Foundation, hoping that we could eventually develop an intervention to boost compliance with these recommended care practices. While compliance rates varied even more widely than mortality—from 10 to 65% for intracranial pressure monitoring and 7 to 76% for craniotomy—they did not appear to be associated with risk-adjusted mortality rates. Put simply, we found no connection between how often hospitals complied with the guidelines and how likely their patients were to survive. (more…)
Author Interviews, Breast Cancer, Radiation Therapy, UCLA / 01.07.2015

Dr. Mitchell Kamrava MD Department of Radiation Oncology University of California Los Angeles Los Angeles, CAMedicalResearch.com Interview with: Dr. Mitchell Kamrava MD Department of Radiation Oncology University of California Los Angeles Los Angeles, CA Medical Research: What is the background for this study? What are the main findings? Dr. Kamrava: Breast conservation (lumpectomy followed by radiation) is known, based on multiple randomized trials with over 20 years of follow-up, to provided equivalent outcomes as mastectomy.  The radiation component of breast conservation has standardly been delivered to the whole breast.  Studies show that the majority of breast recurrences occur near the lumpectomy cavity causing some to ask whether it is necessary to treat the whole breast in order to reduce the risk of a recurrence. Partial breast radiation delivers treatment just to the lumpectomy cavity with a small margin of 1-2 cm.  It’s delivered in a shorter time of 1 week compared with about 6 weeks for standard whole breast radiation and 3-4 weeks for hypofractionated whole breast radiation. The original method developed to deliver partial breast radiation is interstitial tube and button brachytherapy.  This uses multiple small little tubes that are placed through the lumpectomy cavity to encompass the area at risk.  One end of these tubes can be connected to a high dose rate brachytherapy machine that allows a motorized cable with a very small radiation source welded to the end of it to be temporarily pushed in and out of each of the tubes so that the patient can be treated from “inside out”.  This helps concentrate the radiation to the area of the lumpectomy cavity while limiting exposure to normal tissues.  This treatment is most commonly delivered as an out-patient two times per day for a total of 10 treatments. The main finding from our paper is that in reviewing the outcomes on over 1,000 women treated with this technique with an average follow-up of 6.9 years that the 10 year actuarial local recurrence rate was 7.6% and in women with more than 5 years of follow-up physician reported cosmetic outcomes were excellent/good in 84% of cases. (more…)
Author Interviews, OBGYNE, UCLA / 06.05.2015

Anita L. Nelson, MD Professor, Department of Obstetrics and Gynecology at Harbor-UCLA Medical Center Los Angeles BioMedical Research Institute Harbor-UCLA Medical Center Torrance, California MedicalResearch.com Interview with: Anita L. Nelson, MD Professor, Department of Obstetrics and Gynecology at Harbor-UCLA Medical Center Los Angeles BioMedical Research Institute Harbor-UCLA Medical Center Torrance, California Medical Research: What is the background for this study? What are the main findings? Dr. Nelson: The clinical impact heavy menstrual bleeding has often been expressed in terms of quality of life issues, but many women have heavy and prolonged bleeding that can lead to serious medical problems. The frequency with which women were treated at Harbor-UCLA Medical Center with profoundly low hemoglobin levels prompted us to do a comprehensive review of such women during a recent five year period to remind readers that even in the 21st century, this is not an uncommon problem. Overall 149 woman were treated 168 times for severe anemia (hemoglobin < 5.0 g/dL); 40% had previously been transfused (but not effectively treated). Over a quarter had reactive thrombocytosis which placed them at high risk for thrombosis (DVT, PE, and stroke). Over a third were discharged without therapy to prevent recurrence. (more…)
Author Interviews, Kidney Disease, UCLA / 07.04.2015

MedicalResearch.com Interview with: Bryan B. Shapiro Harold Simmons Center for Kidney Disease Research and Epidemiology and Division of Nephrology and Hypertension Los Angeles Biomedical Research Institute Harbor–UCLA Medical Center Torrance, California Medical Research: What is the background for this study? What are the main findings? Response: The inverse relationship between body mass index (BMI) and mortality rates is well-documented in maintenance hemodialysis (MHD) patients. Virtually everyone has assumed that this relationship reflects the effect of body weight, and especially fat mass, on mortality in these patients. However, height is also a component of the BMI equation (BMI = body weight (kg)/height (m²)) and may be independently associated  with mortality in MHD patients. The results of this study, which examined 117, 644 MHD patients and was controlled for many demographic and laboratory variables, indicate that height, adjusted for body weight, is directly associated with mortality in a manner that is opposite to the weight-mortality relationship. Moreover, we found that the contribution of height to the inverse BMI-mortality relationship in dialysis is essentially as great as the contribution of weight. (more…)
Author Interviews, Education, Emergency Care, OBGYNE, UCLA / 31.03.2015

Dr. Jean-Luc Margot PhD Professor, Department of Earth, Planetary, and Space Sciences and Department of Physics and Astronomy, University of California, Los AngelesMedicalResearch.com Interview with: Dr. Jean-Luc Margot PhD Professor, Department of Earth, Planetary, and Space Sciences and Department of Physics and Astronomy, University of California, Los Angeles Medical Research: What is the background for this study? What are the main findings? Dr. Margot: Some professionals who work in emergency rooms or maternity wards believe that the number of hospital admissions or human births is larger during the full moon than at other times.  This belief is incorrect. Analysis of the data shows conclusively that the moon does not influence the timing of hospital admissions or human births. Results of a new analysis have been published online in the journal Nursing Research.  The Nursing Research article addresses some of the methodological errors and cognitive biases that can explain the human tendency of perceiving a lunar effect where there is none.  It reviews basic standards of evidence and, using an example from the published literature, illustrates how disregarding these standards can lead to erroneous conclusions. (more…)
Author Interviews, Chocolate, Exercise - Fitness, Heart Disease, JACC, UCLA, UCSD / 17.03.2015

Pam R. Taub, MD, FACC Assistant Professor of Medicine UC San Diego Health System Division of Cardiology Encinitas, CA 92024MedicalResearch.com Interview with: Pam R. Taub, MD, FACC Assistant  Professor of Medicine UC San Diego Health System Division of Cardiology Encinitas, CA 92024 Medical Research: What is the background for this study? Dr. Taub: Epidemiological studies indicate that the consumption of modest amounts of dark chocolate (DC), which contains the natural cacao flavanol (-)-epicatechin (Epi,) is associated with reductions in the incidence of cardiovascular diseases (CVD). The health benefits of dark chocolate have been attributed to Epi. Clinical studies using cocoa and/or DC in normal volunteers or subjects with CVD have reported improvements in peripheral and coronary vascular endothelial function, blood pressure, lipids, insulin resistance, and inflammatory markers. The mechanism underlying these improvements is thought to be due to increased nitric oxide levels and improved endothelial function. We have also shown that capacity of Epi to favorable impact mitochondria under normal and disease states. We previously conducted pilot study in five patients with heart failure and type II diabetes, and showed that in skeletal muscle (SkM) biopsies there is a severe reduction in mitochondrial volume and cristae, as well as, in structural/functional proteins. After treatment with Epi rich dark chocolate , there was a significant recovery of SkM mitochondrial cristae, structural/functional proteins (e.g. mitofilin), as well as in regulators of mitochondrial biogenesis. However, no studies have examined the capacity of Epi rich dark chocolate to enhance exercise capacity in normal subjects and assess its impact on mitochondrial and oxidative control systems. Medical Research: What are the main findings? Dr. Taub: Seventeen subjects were randomized to placebo (n=8) or DC groups (n=9) and consumed 2 squares of chocolate (20 g, provided by Hershey) for 3 months. We showed in the chocolate group subjects had improved levels of HDL cholesterol and enhanced exercise capacity that is linked to the stimulation of SkM metabolic control endpoints which enhance mitochondrial function. (more…)
Author Interviews, Diabetes, Ophthalmology, UCLA / 20.02.2015

Rohit Varma, MD, MPH Professor and Chair, Department of Ophthalmology USC Eye Institute, Keck School of Medicine University of Southern California, Los Angeles, CaliforniaMedicalResearch.com Interview with: Rohit Varma, MD, MPH Professor and Chair, Department of Ophthalmology USC Eye Institute, Keck School of Medicine University of Southern California, Los Angeles, California Medical Research: What is the background for this study? What are the main findings? Dr. Varma: The Centers for Disease Control and Prevention estimates that 4.4% of adults with diabetes aged 40 and older have advanced diabetic retinopathy that may result in severe vision loss. Clinical trials have shown that intravitreal injections of anti-VEGFs, such as ranibizumab, can reduce visual impairment and even in some cases improve visual acuity outcomes in patients with diabetic macular edema. We developed a model, based on data from the RIDE and RISE clinical trials, to estimate the impact of ranibizumab treatment on the number of cases of vision loss and blindness avoided in non-Hispanic white and Hispanic persons with diabetic macular edema in the United States.Results from the model suggest that, compared with no treatment, every-4-week ranibizumab 0.3 mg reduces legal blindness between 58%-88% and reduces vision impairment between 36%-53% over 2 years in this population. (more…)