Author Interviews, Genetic Research, Nature, Rheumatology / 06.02.2015

psoriasis_kneesMedicalResearch.com Interview with: Professor Anne Barton FRCP PhD and Dr John Bowes PhD Centre for Musculoskeletal Research and Centre for Genetics and Genomics, The University of Manchester, Manchester UK Medical Research: What is the background for this study? Response: Psoriatic arthritis (PsA) is an inflammatory condition causing pain and stiffness in joints and tendons. Approximately one third of patients with psoriasis will go on to develop PsA resulting in a reduction in their quality of life caused by increasing disability and additional health complications. A key area of research within the Arthritis Research UK Centre for Genetics and Genomics in the Centre for Musculoskeletal Research is the identification of risk factors for the development of Psoriatic arthritis; this will allow us to understand the underlying cause of disease and ultimately help identify psoriasis patients at high risk of PsA, allowing early treatment to be introduced to reduce the impact of PsA. Our study focuses on the identification of genetic risk factors for Psoriatic arthritis; we compared the frequency of genetic variants, referred to as single nucleotide polymorphisms (SNPs), between large numbers of DNA samples from patients with PsA and healthy control samples. When the frequency of the SNP is significantly different between cases and controls, the SNP is said to be associated with risk of developing Psoriatic arthritis and this association is interpreted as being important in the disease process. Medical Research: What are the main findings? Response: When we analysed the data from the study we found a new association to SNPs on chromosome 5, and when we investigated these SNPs for association with skin-only psoriasis, we did not find any evidence for association. In addition, we also found SNPs that were specifically associated with Psoriatic arthritis at a gene on chromosome 1. This gene is known to be associated with psoriasis, but our results show that there are different SNPs associated with PsA and psoriasis at this gene. Hence, our results identify new SNPs that are specifically associated with PsA. In addition, identifying which cells are the key drivers of inflammation in Psoriatic arthritis will help us to focus on how the genetic changes act in those cells to cause disease. Our results show that many of the PsA associated SNPs occur in regions of the genome that are important in the function of CD8+ cells,  an important cell type in the immune system. (more…)
ADHD, Author Interviews, FASEB, Occupational Health, Toxin Research / 06.02.2015

MedicalResearch.com Interview with: Jason R. Richardson MS,PhD DABT Associate Professor Department of Environmental and Occupational Medicine Robert Wood Johnson Medical School and Resident Member Environmental and Occupational Health Sciences Institute Piscataway, NJ MedicalResearch: What is the background for this study? What are the main findings? Dr. Richardson:  Although ADHD is often though of as a genetic disorder, no single gene can explain more than a fraction of the cases. This suggests that environmental factors are likely to interact with genetic susceptibility to increase risk for ADHD. Our study reports that exposure of pregnant mice to relatively low levels of a commonly used pesticide reproduces the behavioral effects of ADHD in their offspring. Because the study was in animals, we wanted to see if there was any association in humans. Using data from the Centers for Disease Control and Prevention we found that children and adolescents with elevated levels of metabolites of these pesticides in their urine, which indicates exposure, were more than twice as likely to be diagnosed with ADHD. (more…)
Author Interviews, Biomarkers, Lung Cancer / 06.02.2015

MedicalResearch.com Interview with: Teresa W-M. Fan PhD and Andrew N Lane, PhD Markey Cancer Center, University of Kentucky Medical Research: What is the background for this study? What are the main findings? Response:  The study began about eight years ago at the University of Louisville as a collaboration between thoracic surgeon Michael Bousamra II, immunologist Jun Yan and our metabolomics team (T. Fan, R Higashi and A.N. Lane) now at the U. Kentucky. Lung cancer remains as the highest cancer mortality in North America, and is unfortunately often not diagnosed until the most successful treatment, surgery, is no longer an option.  Furthermore although there are numerous subtypes of the disease, the options for chemotherapy are quite limited. We wanted to know how the biochemistry of early stage (resectable) lung cancer differs from that of healthy or at least non-cancerous lung tissue from the point of view of basic tumor biology, and whether we might uncover better option for therapeutic intervention. To this end, we applied our stable isotope resolved metabolomics (SIRM) technique directly to patients who were diagnosed with resectable NSCLC. By this technique, the fate of individual atoms from a non-radioactive enriched precursor (C-13 glucose in this instance) are traced as they are taken up from the blood and metabolized in situ. This technique, along with model studies with mice, isolated cell cultures, and so-called “Warburg” slices provides tremendous detail about the functional biochemistry of a cancer within its natural microenvironments, compared with non-cancerous tissue. The major finding published in this article is that the anaplerotic enzyme pyruvate carboxylase is greatly upregulated in NSCLC compared with paired non-cancerous lung tissue, whereas the other commonly utilized anaplerotic enzyme glutaminase was not. Interestingly, only cancer cells showed strong staining for pyruvate carboxylase, whereas in the paired non-cancerous lung tissue, only resident macrophages stained for PC. Pyruvate carboxylase was further shown to be essential for tumor growth in both call culture and in mouse xenografts. (more…)
Author Interviews, Gastrointestinal Disease, mBio, Weight Research / 06.02.2015

Senior Principal Investigator - Systems Biology Singapore Institute for Clinical Sciences Brenner Centre for Molecular Medicine SingaporeMedicalResearch.com Interview with: Joanna Holbrook PhD Senior Principal Investigator - Systems Biology Singapore Institute for Clinical Sciences Brenner Centre for Molecular Medicine Singapore Medical Research: What is the background for this study? Dr. Holbrook: Bacteria in the human gut may influence many aspects of our health; however, it is not fully known what determines the composition of the gut microbiota. Rapid bacterial colonisation of the infant gut could be influenced by the environment of the baby before birth, and microbiota content has been associated with the development of obesity and insulin resistance. Medical Research: What are the main findings? Dr. Holbrook: The rate of bacterial colonisation of the gut is influenced by external factors such as the method of delivery and duration of gestation. Also, infants with a mature gut bacteria profile at an early age gained normal levels of body fat, while infants with less mature gut bacteria profiles displayed a tendency to gain lower levels of body fat at the age of 18 months, indicating that gut bacteria could be related to normal development and healthy weight gain. (more…)
Author Interviews, Geriatrics, Hip Fractures, Lancet / 06.02.2015

Ingvild Saltvedt PhD Department of Neuroscience, Norwegian University of Science and Technology, Medical Faculty Trondheim, Norway MedicalResearch.com Interview with: Ingvild Saltvedt PhD Department of Neuroscience, Norwegian University of Science and Technology, Medical Faculty Trondheim, Norway Medical Research: What is the background for this study? What are the main findings? Dr. Saltvedt: Hip fracture patients are often old, frail and have many comorbidities. When treated with a traditional orthopaedic approach the outcomes are often poor, and many patients get functionally impaired with reduced ability to walk independently and impairment in daily life activities and with high costs for the society.  In many ways these patients are geriatric patients with hip-fractures. It has previously been shown that acutely sick geriatric patients benefit from treatment in geriatric wards and different kind of  orthogeriatric treatment models where orthopaedic surgeons and geriatricians collaborate have been studied and have shown beneficial results on short term outcomes. In the present study patients home-dwelling hip-fracture patients were randomised to orthogeriatric treatment or traditional orthopaedic treatment from admission to the hospital and during the entire stay except for the surgery that was performed similar in both groups. The study focused on long-term outcomes and also on use of health care services and cost-effectiveness.  Patients in the orthogeriatric group got comprehensive geriatric assessment and treatment performed by an interdisciplinary team that emphasised early mobilisation and rehabilitation and started discharge planning early. In the orthopaedic group traditional treatment according to national and international guidelines was offered. The primary endpoint was mobility at four months, that was better in the orthogeriatric group than in the orthopaedic group, the same difference was also shown at 12 months. In addition there were differences in instrumental activities of daily living and personal activities of daily living, quality of life and fear of falling, all differences were statistically and clinically significant and in favour of the orthoegeriatric group. The length of hospital stay was 1,7 days longer in the geriatric group, while there was no differences in days spent in hospital during one year of follow-up. One of four orthogeriatric patients were discharged directly home as compared to one of ten in the orthopaedic group. The orthopaedic group spent more days in nursing homes and rehabilitation institutions during one year of follow-up. The treatment was cost-effective in favour of the orthogeriatric group. (more…)
Alzheimer's - Dementia, Author Interviews / 05.02.2015

MedicalResearch.com Interview with: V. Zlokovic, MD, PhD Professor and Chair Department of Physiology and Biophysics Keck School of Medicine of USC.V. Zlokovic, MD, PhD Professor and Chair Department of Physiology and Biophysics Keck School of Medicine of USC.   Medical Research: What is the background for this study? What are the main findings? Dr. Zlokovic: Our team used high-resolution imaging of the living human brain to show for the first time that the brain’s protective blood barrier becomes leaky with age, starting at the hippocampus, a critical learning and memory center that is damaged by Alzheimer’s disease. (more…)
Author Interviews, CDC, Cost of Health Care, HIV / 05.02.2015

MedicalResearch.com Interview with: Ya-lin (Aileen) Huang, PhD. Division of HIV/AIDS Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention Atlanta, GA, 30329 Medical Research: What is the background for this study? What are the main findings? Dr. Huang: With an estimated 50,000 new HIV infections each year in this country, and no vaccine or cure available yet, prevention is critical. Maximizing the impact of all available prevention strategies could significantly reduce new infections in this country. The purpose of this study is to provide evidence for the cost effectiveness of the interventions recommended under the funding announcement and to highlight where more cost-effectiveness studies may be needed. We limited our scope to the four interventions required under the health department funding announcement, including HIV testing, prevention with HIV-positives and their partners, condom distribution and efforts to align policies with optimal HIV prevention, care and treatment. Our review provides an updated summary of the published evidence of cost-effectiveness of four key HIV prevention interventions recommended by CDC: HIV testing, prevention with HIV-positives and their partners, condom distribution and policy initiatives. Models suggest that more than 350,000 HIV infections have been avoided because of the nation’s HIV prevention efforts. In addition to lives saved, HIV prevention has also generated substantial economic benefits. For every HIV infection that is prevented, an estimated $402,000 (http://www.ncbi.nlm.nih.gov/pubmed/23615000) is saved in the cost of providing lifetime HIV treatment. It is estimated that HIV prevention efforts have averted more than $125 billion in medical costs since the beginning of the epidemic. (more…)
Author Interviews, Emergency Care, Mental Health Research, UCSD / 05.02.2015

Michael Wilson, MD, PhD, FAAEM Attending Physician, UCSD Department of Emergency Medicine Director, Department of Emergency Medicine Behavioral Emergencies Research (DEMBER) lab UC San Diego Health SystemMedicalResearch.com Interview with: Michael Wilson, MD, PhD, FAAEM Attending Physician, UCSD Department of Emergency Medicine Director, Department of Emergency Medicine Behavioral Emergencies Research (DEMBER) lab UC San Diego Health System MedicalResearch: What is the background for this study? What are the main findings? Dr. Wilson: Emergency departments (EDs) nationwide are crowded. Although psychiatric patients do not make up the largest proportion of repeat visitors to the emergency department, psychiatric patients stay longer in the ED than almost any other type of patient. So, it’s really important to find out things about these patients that may predict longer stays. In this study, we looked at patients on involuntary mental health holds. The reasoning is simple: patients on involuntary mental health holds aren’t free to leave the ED. So, the only thing that should really matter is how quickly an Emergency department can release them from the involuntary hold. Surprisingly, though, this wasn’t the only thing that correlated with longer stays. (more…)
Author Interviews, BMJ, Nutrition, Pulmonary Disease / 05.02.2015

MedicalResearch.com Interview with: Raphaëlle Varraso INSERM U1168, VIMA (Aging and chronic diseases. Epidemiological and public health approaches), 16 avenue Paul Vaillant Couturier Villejuif, France MedicalResearch: What is the background for this study? What are the main findings? Response: Respiratory health and lung function, strongly predict general health status and all-cause mortality. Chronic obstructive pulmonary disease (COPD) is currently ranked the third leading cause of death worldwide. The predominant risk factor for COPD in the developed world is cigarette smoking, but up to one-third of COPD patients have never smoked, suggesting that other factors are involved. Besides smoking, relatively little attention has been paid to other modifiable risk factors that might decrease risk of developing COPD, including diet. The Alternate Healthy Eating Index (AHEI)-2010, a new measure of diet quality based on current scientific knowledge, has been linked to risk of major chronic diseases, such as cardiovascular disease, diabetes and cancer. However, the role of dietary scores on risk of COPD is unknown. We examined this issue among >120,000 US female and male health professionals (Nurses’ Health Study and Health Professionals Follow-up Study), and we reported that a high AHEI-2010 dietary score score (reflecting high intakes of whole grains, vegetables, fruit, polyunsaturated fatty acids, nuts and legumes, and long-chain omega-3 fats, a moderate intake of alcohol, and low intakes of red/processed meats, trans fat, sodium and sugar-sweetened beverages) was associated with a lower risk of COPD in both women and men. This novel finding supports the importance of diet in COPD pathogenesis. (more…)
Author Interviews, Hospital Readmissions, Pediatrics, Pediatrics / 05.02.2015

Mark Brittan MD MPH Assistant Professor, Pediatric Hospital Medicine Children's Hospital Colorado University of Colorado School of MedicineMedicalResearch.com Interview with: Mark Brittan MD MPH Assistant Professor, Pediatric Hospital Medicine Children's Hospital Colorado University of Colorado School of Medicine MedicalResearch: What is the background for this study? What are the main findings? Dr. Brittan: As hospitals face reimbursement penalties for excess readmissions, clinicians are increasingly focused on improving care transitions in order to reduce readmissions. We are interested in learning about feasible ways to reduce pediatric readmissions so that we can improve the quality of care and experience of children and families who are being discharged from the hospital. The purpose of this study was to assess whether outpatient follow-up visits after hospital discharge can help to prevent readmissions. We chose to examine this question in a population of medically complex children enrolled in Medicaid. Children with medical complexity account for a growing proportion of pediatric hospitalizations and inpatient costs. These children are often dependent on technology (for example, ventilator machines, feeding tubes, and chronic indwelling catheters), and can have very complex care plans and medication regimens. Publically insured children are also vulnerable to increased hospital utilization and may not always have optimal or easy access to outpatient services. Showing a relationship between post-discharge outpatient visits and fewer readmissions would suggest that improvements in coordination of care or access to outpatient follow-up care may help to reduce readmissions in these children. To assess this relationship, we retrospectively analyzed 2006-2008 Colorado Medicaid claims data from which we were able to gather demographic, clinical, and visit information for all enrollees. In our study, we excluded children who were readmitted within 3 days of hospital discharge so that we could evaluate children who had a chance to follow-up. The study cohort included 2415 medically complex children aged 6 months to 18 years who were hospitalized at least once. Of these children, 6.3% were readmitted on days 4 – 30 after hospital discharge. Almost 22% of the children had an outpatient follow-up visit within 3 days of discharge, and 40% had a visit on days 4-29 after discharge. In the final analysis, we found expected associations between readmission and previously described risk factors, including number of patient comorbidities and longer initial hospital length of stay. Examining the relationship between outpatient follow-up and readmission, we found that children with later outpatient follow-up visits (days 4-29) were significantly less likely to be readmitted than those who did not have an outpatient visit on days 4-29 after discharge. (more…)
Author Interviews, Dermatology, JAMA, OBGYNE, UC Davis / 05.02.2015

MedicalResearch.com Interview with: Dr. Eleanor B. Schwarz, M.D., M.S University of California, Davis Sacramento, CA MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Schwarz: The background for this study is that… Women treated with Isotretinoin receive a lot of scary information about this medication’s risk of causing birth defects, but few receive clear information on the most effective ways to protect themselves from undesired pregnancy and the risks of medication-induced birth defects. Our main finding is that women who spent less than a minute reviewing a simple information sheet were significantly more likely to be aware that some contraceptives are considerably more effective than others. MedicalResearch.com: What should clinicians and patients take away from your report? Dr. Schwarz: Clinicians who prescribe medications that can cause birth defects should make sure their patients are aware of the fact that women using a birth control pill are typically twenty times more likely to experience a contraceptive failure than those using a subdermal contraceptive implant (e.g. Nexplanon) or intrauterine contraceptive (e.g. Mirena, ParaGard). (more…)
Author Interviews, Hepatitis - Liver Disease, HIV, Lancet / 05.02.2015

MedicalResearch.com Interview with: Prof Jean-Michel Molina Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, Paris France MedicalResearch.com Interview with: Prof Jean-Michel Molina Maladies Infectieuses et Tropicales, Hôpital Saint-Louis, Paris France Medical Research: What is the background for this study? What are the main findings? Prof. Molina: Treatment of co-infected patients is complicated by drug drug interactions with HIV drugs, and the news DAAs are not very potent on HCV G2 and 3 infections. (more…)
AHA Journals, Author Interviews, Cleveland Clinic, Heart Disease, Kidney Disease / 05.02.2015

MedicalResearch.com Interview with: W. H .Wilson Tang, M.D., F.A.C.C., F.A.H.A. Professor in Medicine, Cleveland Clinic Lerner College of Medicine Cleveland Clinic, Cleveland, OH 44195MedicalResearch.com Interview with: W. H .Wilson Tang, M.D., F.A.C.C., F.A.H.A. Professor in Medicine, Cleveland Clinic Lerner College of Medicine Cleveland Clinic, Cleveland, OH 44195.   Medical Research: What is the background for this study? What are the main findings? Dr. Tang: Our group has previously demonstrated that TMAO is linked to future cardiac risks in both humans and in animal models.  We now show that long-term exposure to higher levels of TMAO promotes renal functional impairment and fibrosis in animal studies.  We also show that in humans, as the kidneys lose function, TMAO isn’t eliminated as easily, and their blood levels further rise, thereby increasing cardiovascular and kidney disease risks further.  This newly discovered TMAO link offers further insight into the relationship between cardiovascular disease and chronic kidney disease. (more…)
Author Interviews, Brain Injury, Technology / 05.02.2015

Uzma Samadani, M.D., Ph.D. Assistant Professor; Departments of Neuroscience and Physiology NYU Langone Medical CenterMedicalResearch.com Interview with: Uzma Samadani, M.D., Ph.D. Assistant Professor Departments of Neuroscience and Physiology NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Samadani: Research dating back as early as 3,500 years ago suggests the eyes serve as a window into the brain, with disconjugate eye movements -- eyes rotating in different directions -- considered a principal marker for head trauma. Current estimates suggest up to 90 percent of patients with concussions or blast injuries exhibit dysfunction in their eye movements. We wanted to find a way to objectively track and analyze eye movements following a head injury to measure injury severity and replace the current “state of the art” method of asking a patient to follow along with a finger. CT-scans and MRIs may not necessarily reveal concussion or traumatic brain injury (TBI) in the absence of structural damage, presenting a need for a diagnostic measure of head injury severity. In a study published earlier this year in the Journal of Neurosurgery, my team at the NYU Cohen Veterans Center tested our novel eye-tracking technology on military veterans, and found our device and tracking algorithm could reveal edema in the brain as a potential biomarker for assessing brain function and monitoring recovery in people with head injuries. Our latest paper, published January 29 in Journal of Neurotrauma, looked at a civilian population of patients admitted to the Bellevue Medical Center emergency department in New York City, with whom the NYU School of Medicine has an affiliation agreement. We compared 64 healthy control subjects to 75 patients who had experienced trauma that brought them to emergency department. We tracked and compared the movements of patients' pupils for over 200 seconds while watching a music video. We found that 13 trauma patients who had hit their heads and had CT scans showing new brain damage, as well as 39 trauma patients who had hit their heads and had normal CT scans, had significantly less ability to coordinate their eye movements than normal, uninjured control subjects. Twenty-three trauma subjects who had bodily or extremity injuries but did not require head CT scans had similar abilities to coordinate eye movements as normal uninjured controls. Among patients who had hit their heads and had normal CT scans, most were slightly worse at 1-2 weeks after the injury, and subsequently recovered about one month after the injury. Among all trauma patients, the severity of concussive symptoms correlated with severity of disconjugacy. (more…)
Author Interviews, Endocrinology, Toxin Research / 05.02.2015

Dr. Andrea Gore PhD Gustavus & Louise Pfeiffer Professor University of Texas Austin/Div of Pharmacology/ToxicoMedicalResearch.com Interview with: Dr. Andrea Gore PhD Gustavus & Louise Pfeiffer Professor University of Texas Austin/Div of Pharmacology/Toxicology MedicalResearch.com Editor’s Note: Dr. Gore, Editor-in-Chief of the Journal Endocrinology, has graciously answered several questions regarding the recent concerns of environmental chemicals linked to both early puberty and early menopause. Medical Research: How can chemicals found inside the home impact onset of menopause? Dr. Gore: It is important to clarify that the cause-and-effect relationship between chemicals and menopause is not established. The timing of menopause in women is due to a variety of factors including genetic traits, nutritional status, and general health or chronic disease. Some research on humans, including the recent study by Grindler et al., also suggests that environmental chemicals may contribute to the timing of earlier menopause. Animal models also suggest an advance in the timing of reproductive failure following earlier life exposures to endocrine-disrupting chemicals (EDCs). [See references below]. The question of exactly how chemicals may change the timing of menopause is therefore unresolved, but based on animal studies it is likely that the mechanisms include effects of endocrine-disrupting chemicals on the expression of genes and proteins involved in ovarian function that may lead to premature loss of follicles (eggs). Because the control of reproduction involves the brain and the pituitary gland, as well as the ovary, it is possible that endocrine-disrupting chemicals also impair how these organs regulate reproductive hormones.
  1. Gore AC, Walker DM, Zama AM, Armenti AE, Uzumcu M. Early life exposure to endocrine-disrupting chemicals causes lifelong molecular reprogramming of the hypothalamus and premature reproductive aging. Mol Endocrinol. 2011;25:2157–2168.
  2. Shi Z, Valdez KE, Ting AY, Franczak A,GumSL, Petroff BK. Ovarian endocrine disruption underlies premature reproductive senescence following environmentally relevant chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biol Reprod. 2007;76:198–202.
  3. Akkina J, Reif J, Keefe T, Bachand A. Age at natural menopause and exposure to organochlorine pesticides in Hispanic women. J Toxicol Environ Health A. 2004;67:1407–1422.
  4. Cooper GS, Savitz DA, Millikan R, Chiu Kit T. Organochlorine exposure and age at natural menopause. Epidemiology. 2002;13: 729–733.
  5. Hatch EE, Troisi R, Wise LA, et al. Age at natural menopause in women exposed to diethylstilbestrol in utero. Am J Epidemiol. 2006;164:682–688.
  6. KnoxSS, Jackson T, Javins B, Frisbee SJ, Shankar A, DucatmanAM. Implications of early menopause in women exposed to perfluorocarbons. J Clin Endocrinol Metab. 2011;96:1747–1753.
  7. Farr SL, Cai J, Savitz DA, Sandler DP, Hoppin JA, Cooper GS. Pesticide exposure and timing of menopause: the Agricultural Health Study. Am J Epidemiol. 2006;163:731–742.
Medical Research: What are the primary sources of exposure to these chemicals? Dr. Gore: Endocrine-disrupting chemicals exposures come from a variety of sources, including plastic containers (e.g. water bottles) and other products, certain foods, personal care products, pesticides, and many others. (more…)
Author Interviews, Breast Cancer, NYU / 05.02.2015

Agnel Sfeir PhD Assistant Professor Skirball Institute - NYU New York, NY 10016MedicalResearch.com Interview with: Agnel Sfeir PhD Assistant Professor  Skirball Institute - NYU New York, NY 10016 Medical Research: What is the background for this study? What are the main findings? Dr. Sfeir: The main finding of this study, published in the journal Nature, is that inhibiting the action of a particular enzyme dramatically slows the growth of tumor cells tied to BRCA1 and BRCA2 genetic mutations which, in turn, are closely tied to breast and ovarian cancers. This discovery about the enzyme — called polymerase theta, or PolQ — resulted from efforts to answer a fundamental biological question: How do cells prevent the telomere ends of linear chromosomes, which house our genetic material, from sticking together? Cell DNA repair mechanisms can stitch together telomeres broken as part of cell metabolism. But such fusions, the researchers say, compromise normal cell growth and survival. In the purest biological sense, our findings (in experiments in mice and human cells) show how this particular enzyme, which we know is active in several tumors, promotes unwanted telomere fusions by inserting whole segments of DNA via a disruptive DNA repair pathway termed alt-NHEJ. It was quite remarkable to find that by blocking PolQ action, cancer cell growth was cut by more than half. Additional experiments confirmed that PolQ is needed to activate the alt-NHEJ pathway of DNA repair. Unlike the main, error-free pathway — or HDR pathway — the alt-NHEJ pathway does not use a related chromosome’s genetic material as a template to meticulously correct any damaged genetic material. As such, alt-NHEJ is highly likely to leave coding mistakes. (more…)
Author Interviews, Dermatology, Diabetes / 04.02.2015

MedicalResearch.com Interview with: Mette Gyldenløve MD Gentofte Hospital, University of Copenhagen Denmark MedicalResearch: What is the background for this study? Dr. Gyldenløve: Epidemiological studies have shown that patients with psoriasis have increased risk of type 2 diabetes. The pathophysiology is largely unknown, but it is hypothesised that systemic inflammation causes insulin resistance, which is an early feature of type 2 diabetes. Insulin sensitivity has only been sparsely investigated in patients with psoriasis, and previous studies have used suboptimal methodology. The objective of the present study was to investigate, if patients with psoriasis exhibit impaired insulin sensitivity when assessed by the hyperinsulinaemic euglycaemic clamp technique (gold standard). MedicalResearch: What are the main findings? Dr. Gyldenløve: In this study we found that normal glucose-tolerant patients with moderate-to-severe psoriasis (n=16) had significantly reduced insulin sensitivity compared to age, gender, and body mass index (BMI)-matched, healthy control subjects (n=16). The two groups were similar with regard to age, gender, BMI, body composition, physical activity, fasting plasma glucose, and glycosylated haemoglobin. (more…)
Author Interviews, Columbia, Schizophrenia / 04.02.2015

Mark Slifstein, PhD Associate Professor of Neurobiology (In Psychiatry) Dept. of Psychiatry Columbia University NYSP Dr New York NY 10032 MedicalResearch.com Interview with: Mark Slifstein, PhD Associate Professor of Neurobiology (In Psychiatry) Dept. of Psychiatry Columbia University NYSP Dr New York NY 10032 MedicalResearch: What is the background for this study? Dr. Slifstein: There has been considerable basic and clinical neuroscience research showing that the neurotransmitter dopamine plays a role in tuning cognitive processes taking place in the cortex. It has long been thought that dopamine is involved in the cognitive difficulties experienced by patients with schizophrenia, but it has been challenging to study dopamine in the cortex and other parts of the brain except in a deep structure rich in this neurotransmitter and its receptors, the striatum. In our study, we used an experimental design with Positron Emission Tomography (PET) imaging that allowed us to infer the amount of dopamine in the cortex. (more…)
Accidents & Violence, Author Interviews, CDC, Cost of Health Care / 04.02.2015

Judy A. Stevens PhD National Center for Injury Prevention and Control Centers for Disease Control and Prevention Atlanta GA 30341MedicalResearch.com Interview with: Dr. Judy Stevens PhD National Center for Injury Prevention and Control Centers for Disease Control and Prevention, Atlanta, GA 30341, USA Medical Research: What is the background for this study? What are the main findings? Dr. Stevens: Falls among people aged 65 and older are a serious, costly, and growing public health problem. As our population ages, falls will continue to increase unless we implement effective prevention strategies that are also cost-effective. This study found that three evidence-based fall prevention programs, the Otago Exercise Program, Tai Chi: Moving for Better Balance, and Stepping On, were not only practical and effective but also provided a positive return on investment (ROI) or net benefit.  An ROI of 150% means for each $1 spent on implementing the program, you can expect a net benefit of $1.50. The analysis found that the cost of implementing each of these fall prevention programs was considerably less than the potential medical costs needed to care for someone injured from a fall. These research findings can help community organizations and policymakers identify and use programs that can both save lives and reduce costs. (more…)
Author Interviews, Depression, Lancet, Multiple Sclerosis / 04.02.2015

Dr Stefan M Gold Institute of Neuroimmunology and Multiple Sclerosis (INIMS) Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf Hamburg, GermanyMedicalResearch.com Interview with: Dr Stefan M Gold Institute of Neuroimmunology and Multiple Sclerosis (INIMS) Centre for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf Hamburg, Germany Medical Research: What is the background for this study? What are the main findings? Dr. Gold: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (brain and the spinal cord). In addition to motor symptoms such as walking impairment, patients with Multiple sclerosis frequently suffer from psychological problems including difficulties with learning and memory as well as depressed mood. Depression is particularly common in this patient group with a 3-4 fold elevated risk for developing major depressive disorder compared to the general population. Depression in Multiple sclerosis is associated with decreased quality of life, absence from work, and numerous other psychosocial problems. Despite this major impact on patients’ lives, depression in Multiple sclerosis is often not adequately diagnosed and treated: Antidepressant medication in this patient group often has side effects and the neurological problems associated with MS such as difficulties with concentration and fatigue make it particularly difficult for MS patients to complete “classical” depression treatments such as psychotherapy. The goal of our study was to make psychological treatments available for the many patients with Multiple sclerosis suffering from depression, who often have difficulties to find adequate treatment. For this study, published in The Lancet Psychiatry, we conducted a randomized controlled trial of a fully-automated, computer-based program that can be accessed directly from patients’ homes over the internet. The program called “deprexis” was developed by the Hamburg-based company GAIA and uses methods of “cognitive behavioral therapy” or “CBT”. Ninety Multiple sclerosis patients were enrolled in the trial and randomly assigned to a 3 months therapy using the deprexis program or a waitlist control group. At the end of the intervention, depression had significantly decreased in the treatment group but remained unchanged in patients who did not have access to the program. In addition, patients using the computer program also reported reduced fatigue and improved quality of life. (more…)
Author Interviews, CDC, Infections, Lancet, Vaccine Studies / 04.02.2015

MedicalResearch.com Interview with: Dr Matthew R Moore, MD National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USADr Matthew R Moore, MD National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA MedicalResearch: What is the background for this study? Dr. Moore: Since introduction, pneumococcal conjugate vaccines have resulted in dramatic decreases in the number of cases of invasive pneumococcal disease in both children and adults.  The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine infant immunization program in the United States in 2000. It was recommended for infants using a 4-dose schedule: 2, 4, 6, and 12 through 15 months of age. Studies showed that PCV7 was highly effective in preventing invasive pneumococcal disease. In 2010, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 using the same 4-dose schedule. PCV13 is similar to PCV7, but includes protection against six additional serotypes of Streptococcus pneumoniae. There are more than 90 serotypes of pneumococcal bacteria. Streptococcus pneumoniae, or pneumococcus, is a major cause of illness and death globally. Pneumococcus can cause many types of illness that ranging from mild to life-threatening, including pneumonia, ear and sinus infections, meningitis, and bacteremia. Some of these infections are considered invasive because they invade parts of the body that are normally free from bacteria. Invasive pneumococcal disease, including meningitis and bacteremia, is often severe and can be deadly. MedicalResearch: What are the main findings? Dr. Moore: Invasive pneumococcal disease decreased substantially in the first 3 years after PCV13 was introduced into the U.S. infant immunization schedule. By June 2013, more than 30,000 cases of invasive pneumococcal disease and 3,000 deaths are estimated to have been prevented in the United States due to PCV13. Children under the age of five, which is the age group that actually received the vaccine, experienced the greatest and quickest benefit from PCV13.  For example, the overall number of cases of invasive pneumococcal disease decreased by 64% in this age group between 2010 and 2013. Significant decreases were seen as early as six months after the immunization recommendation was made. Adults, who were not targeted for vaccination, also experienced health benefits from PCV13 introduction. For example, the overall number of cases of invasive pneumococcal disease decreased by 32% for adults aged 18 to 49 years, while adults 65 and older experienced a more modest 12% decrease.  These reductions are further evidence that both PCV7 and PCV13 reduce the spread of pneumococcus, which is why vaccinating children leads to disease reductions in adults. For both children and adults, the greatest reductions were seen in the number of cases of invasive pneumococcal disease that were caused by serotypes that are covered by PCV13 but not PCV7 (serotypes 19A and 7F specifically). (more…)
Author Interviews, CDC, Gastrointestinal Disease, Infections, Pediatrics, Vaccine Studies / 04.02.2015

MedicalResearch.com Interview with: Margaret M. Cortese MD Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia Medical Research: What is the background for this study? What are the main findings? Dr. Cortese: The introduction of rotavirus vaccine in the United States resulted in a dramatic reduction in hospitalizations and emergency department care for rotavirus disease among young children, as well as provided indirect protection to unvaccinated peers. However, what our study looked at was whether or not older children and adults may experience indirect protection from having children in the house who are vaccinated for rotavirus. We used 2008-2012 Marketscan claims data to compare gastroenteritis rates among households whose child had received rotavirus vaccine with households whose child did not receive vaccine. We found statistically significantly lower rates of hospitalization from rotavirus gastroenteritis or unspecified-gastroenteritis in vaccinated households among all persons 20-29 years and females 20-29 years during the 2008-2009 rotavirus season as well as males 30-39 years in the 2009-2010 season. Lower emergency department gastroenteritis rates occurred in vaccinated households among females 20-29 years during the 2009-2010 season and individuals 5-19 years during the 2010-2011 season. (more…)
Author Interviews, JAMA / 04.02.2015

John Holcomb, M.D. Principal investigator, Retired U.S. Army Surgeon Director of the Division of Acute Care Surgery The University of Texas Health Science Center at Houston UTHealth Medical SchoolMedicalResearch.com Interview with John Holcomb, M.D. Principal investigator, Retired U.S. Army Surgeon Director of the Division of Acute Care Surgery The University of Texas Health Science Center at Houston UTHealth Medical School MedicalResearch: What is the background for this study? Dr. Holcomb: This study is the result of two decades of work by literally hundreds of investigators. It started as an observation in 1993 in Somalia that whole blood was a superior resuscitation product in casualties that were bleeding to death. Unfortunately, whole blood is not widely available, and 1:1:1 is the closest we can get at this time. After many studies from the battlefield, and even more in the civilian area, we have now published a randomized study documenting that 1:1:1 is a superior transfusion strategy, safe and helps prevent patients from bleeding to death. MedicalResearch: What are the main findings? Dr. Holcomb: The 1:1:1 resuscitation strategy significantly decreased the rate of bleeding to death, and there were no increased complications between groups. (more…)
AHA Journals, Author Interviews, Compliance, Heart Disease / 04.02.2015

Robert Hutchins, M.D., M.P.H. Department of Medicine, Division of General Internal Medicine UCSFMedicalResearch.com Interview with: Robert Hutchins, M.D., M.P.H. Department of Medicine, Division of General Internal Medicine UCSF Medical Research: What is the background for this study? What are the main findings? Dr. Hutchins: "Utility" refers to the effect on quality of life that a certain intervention carries and a utility value generally varies from 0-1.0.  The more negative the effect is, the lower the utility value (closer to 0), and the less it affects quality of life, the closer to 1.0 it is.  On a theoretical scale, "perfect health" is 1.0 and death is 0.  There are a number of studies that -- USE a utility value for taking pills, generally between 0.95 and 1.0.  However, many cost-effectiveness analyses ignore the utility value altogether, or arbitrarily choose 1.0 as the utility.  We found that a small change in the utility value can have a very large effect on the overall cost-effectiveness of an intervention.  We found that the utility value of taking pills, assessed by three different commonly used methods, to be 0.990-0.994, depending on the method. (more…)
Author Interviews, Hospital Readmissions, JAMA, Surgical Research / 03.02.2015

Dr. Ryan Merkow, M.D. M.S. American College of Surgeons Chicago, IllinoisMedicalResearch.com Interview with: Dr. Ryan Merkow, M.D. M.S. American College of Surgeons Chicago, Illinois     MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Merkow: The measurement of hospital readmissions has become an important quality and cost-containment metric. Hospitals, policy makers, and individual practitioners are closely tracking readmissions. For the past decade the focus has been primarily on three medical conditions (pneumonia, heart failure and myocardial infarction) and although controversial, many thought leaders and policy makers believed that readmissions were preventable, and stemmed from poor transition of care, outpatient follow up or simply a failure of the medical system to appropriately care for these patients. Recently, the Center for Medicare and Medicaid Services has become increasingly interested in using readmissions as a quality measure and is now mandated by the Hospital Readmission Reduction Program to track hospital-wide readmissions (including all surgical patients), and for the first time, after individual surgical procedures (i.e., total hip and knee replacement). Future inclusion of additional surgical procedures is anticipated. However, despite the growing focus on readmissions after surgery, there have been few studies comprehensively evaluating the underlying reasons and factors associated with readmissions after surgical hospitalizations. Furthermore, the relationship between readmissions and complications that occur during the initial hospitalization after surgery is not clearly established. Importantly, unlike medical conditions, surgical patients undergo a discrete invasive event with known risks of complications. By studying this topic, initiatives to decrease readmissions can be more precisely determined, and national policy decisions that are now targeting readmissions can be appropriately formulated. The primary findings of our study identified surgical site infections as the most frequent reason that patients are readmitted after surgery, Importantly, in >95% of patients this complication was new, occurring after they left the hospital. The other common reason for readmission was obstruction or ileus, which was the second most frequent reason for readmission, particularly after abdominal surgery. Overall, the vast majority of readmissions were the result of new postdischarge, postoperative complications. With respect to factors associated with readmissions, most of the variation was due to differences in patient factors, such as ASA class, renal failure, ascites and/or steroid use. (more…)
Aging, Author Interviews, Bone Density, FASEB / 03.02.2015

Dr. Jean-Pol Frippiat Stress, Immunity and Pathogens Laboratory at Lorraine University Vandoeuvre-lès-Nancy, FranceMedicalResearch.com Interview with: Dr. Jean-Pol Frippiat Stress, Immunity and Pathogens Laboratory Lorraine University Vandoeuvre-lès-Nancy, France  What is the background for this study? What are the main findings? Dr. Frippiat: Osteoporosis is associated to spaceflight. Consequently, we wondered whether changes in bone micro-structure induced by a ground-based model of spaceflight, hindlimb unloading (HU) that simulates some of the effects of spaceflight on mice, induces changes in B lymphocyte production in the bone marrow. To this end, we analyzed both bone parameters and the frequency of cells of the B lineage in the bone marrow of young, old and HU mice. We found that HU leads to a decrease in both bone micro-structure and the frequency of B cell progenitors in the bone marrow. A major block at the pro-B to pre-B cell transition was observed indicating a decrease in the formation of B cells in the bone marrow. Interestingly, the modifications in B cell production were similar to those observed in aged mice. These findings demonstrate that mechanical unloading, to which astronauts are subjected during spaceflight, results in a decrease in B cell differentiation that resemble age-related modifications in B lymphopoiesis. (more…)
Author Interviews, JAMA, Outcomes & Safety, University of Michigan / 03.02.2015

Nicholas Osborne, M.D., M.S Vascular Surgery Fellow University of Michigan, Ann Arbor MedicalResearch.com: What is the background for this study? Dr. Osborne: The American College of Surgeons launched the National Surgical Quality Improvement Program (ACS-NSQIP) in the early 2000s. This program collects and reports surgical outcomes to participating hospitals. One retrospective study of participating hospitals in the ACS-NSQIP reported improvements in risk-adjusted outcomes with participation. This study, however, did not compare ACS-NSQIP hospitals to control hospitals. The purpose of our study was to compare ACS-NSQIP to similar non-participating hospitals over time and determine whether participation in the ACS-NSQIP was associated with improved outcomes. MedicalResearch.com: What are the main findings? Dr. Osborne: When comparing hospitals participating in a national quality reporting program (ACS-NSQIP) to similar hospitals, there is no appreciable improvement in outcomes (mortality, morbidity, readmissions or cost)  outside of pre-existing trends across all hospitals. In other words, Hospitals nationwide were improving over this same time period and ACS-NSQIP hospitals did not improve above and beyond these existing trends. (more…)
Author Interviews, Hepatitis - Liver Disease, JAMA, University of Pittsburgh / 03.02.2015

Adeel A. Butt, MD, MS, FACP, FIDSA Adjunct Associate Professor of Medicine and Clinical and Translational Science University of Pittsburgh School of MedicineMedicalResearch.com Interview with: Adeel A. Butt, MD, MS, FACP, FIDSA Adjunct Associate Professor of Medicine and Clinical and Translational Science University of Pittsburgh School of Medicine   MedicalResearch: What is the background for this study? What are the main findings? Dr. Butt: Studying clinical consequences of hepatitis C virus (HCV) infection is often limited by the lack of knowledge of actual time of infection. We used the Electronically Retrieved Cohort of HCV-Infected Veterans (ERCHIVES), a well-established national cohort of HCV infected veterans and corresponding HCV-uninfected controls, to identify patients with a known time frame for HCV infection. Our primary aim was to determine the rate of liver fibrosis progression among HCV-infected persons over time, with and to determine factors associated with development of cirrhosis and hepatic decompensation among these persons. Among 1840 persons who were HCV+ and 1840 HCV− controls, we found that fibrosis progression started early after HCV infection tapered off after 5 years. After 10 years of follow-up, 18.4% of HCV+ and 6.1% of HCV- persons developed liver cirrhosis. Nine years after diagnosis of cirrhosis, only 1.8% of HCV+ and 0.3% of HCV- persons had developed hepatic decompensation. (more…)
Author Interviews, Biomarkers, Heart Disease / 03.02.2015

MedicalResearch.com Interview with: Dr. Matthias Bossard, MD Clinical and Research Fellow Cardiology Division Department of Medicine University Hospital Basel Basel Switzerland MedicalResearch: What is the background for this study? What are the main findings? Dr. Bossard: Endothelin-1 (ET-1) and its pleiotropic effects have been implicated in the regulation of vascular and renal physiology as well as inflammation. Moreover, elevated ET-1 levels have been associated with endothelial dysfunction and atherosclerosis. Until now, data on the relationships between ET-1 and individual cardiovascular risk factors were scarce, especially from large-scale population based studies. This may be attributable to the previously used laboratory assays.The emergence of new ET-1 assays has facilitated ET-1 measurement in large populations. Our main findings are that ET-1 levels are independently associated with several individual cardiovascular risk factors an overall cardiovascular risk in a large cohort of young and healthy adults.Specifically, ET-1 levels were significantly associated with systolic blood pressure, current smoking, glomerular filtration rate and high-sensitivity C-reactive protein. (more…)