Rutgers Biomedical and Health science
Rutgers Biomedical and Health science
Phillips W.A.,University of Stirling |
Clark A.,University of Edinburgh |
Silverstein S.M.,Rutgers Biomedical and Health science
Neuroscience and Biobehavioral Reviews | Year: 2015
A broad neuron-centric conception of contextual modulation is reviewed and re-assessed in the light of recent neurobiological studies of amplification, suppression, and synchronization. Behavioural and computational studies of perceptual and higher cognitive functions that depend on these processes are outlined, and evidence that those functions and their neuronal mechanisms are impaired in schizophrenia is summarized. Finally, we compare and assess the long-term biological functions of contextual modulation at the level of computational theory as formalized by the theories of coherent infomax and free energy reduction. We conclude that those theories, together with the many empirical findings reviewed, show how contextual modulation at the neuronal level enables the cortex to flexibly adapt the use of its knowledge to current circumstances by amplifying and grouping relevant activities and by suppressing irrelevant activities. © 2015 Elsevier Ltd.
Rodgers D.V.,Rutgers Biomedical and Health science |
Wendling A.L.,Michigan State University |
Saba G.W.,University of California at San Francisco |
Mahoney M.R.,Stanford University |
Brown Speights J.S.,Florida State University
Family Medicine | Year: 2017
BACKGROUND: Family physicians have been involved in the care of rural and urban underserved populations since the founding of the specialty. In the early 1970s family medicine training programs specifically focused on training residents to work with the underserved were established in both urban and rural settings. Key to the success of these programs has been a specific focus on improving access to care, understanding and eliminating health disparities, cultural competency and behavioral science training that recognizes the challenges often faced by patients and families living in poor rural and urban areas of the country. In keeping with a focus on the underserved, several urban underserved residencies also became national models for the provision of primary care to patients and families affected by HIV/ AIDS. Family medicine training programs focused on the underserved have resulted in the development of a cohort of family physicians who care for those most in need in the United States. Despite these achievements, persistent challenges remain in providing adequate access to care for many living in rural and inner city settings. New strategies will need to be developed by family medicine programs and others to better meet these challenges. © 2017, Society of Teachers of Family Medicine. All rights reserved.
Ordek G.,New Jersey Institute of Technology |
Proddutur A.,Rutgers Biomedical and Health science |
Santhakumar V.,Rutgers Biomedical and Health science |
Pfister B.J.,New Jersey Institute of Technology |
Sahin M.,New Jersey Institute of Technology
Frontiers in Systems Neuroscience | Year: 2014
The changes of excitability in affected neural networks can be used as a marker to study the temporal course of traumatic brain injury (TBI). The cerebellum is an ideal platform to study brain injury mechanisms at the network level using the electrophysiological methods. Within its crystalline morphology, the cerebellar cortex contains highly organized topographical subunits that are defined by two main inputs, the climbing (CFs) and mossy fibers (MFs). Here we demonstrate the use of cerebellar evoked potentials (EPs) mediated through these afferent systems for monitoring the injury progression in a rat model of fluid percussion injury (FPI). A mechanical tap on the dorsal hand was used as a stimulus, and EPs were recorded from the paramedian lobule (PML) of the posterior cerebellum via multi-electrode arrays (MEAs). Post-injury evoked response amplitudes (EPAs) were analyzed on a daily basis for 1 week and compared with pre-injury values. We found a trend of consistently decreasing EPAs in all nine animals, losing as much as 72 ± 4% of baseline amplitudes measured before the injury. Notably, our results highlighted two particular time windows; the first 24 h of injury in the acute period and day-3 to day-7 in the delayed period where the largest drops (~50% and 24%) were observed in the EPAs. In addition, cross-correlations of spontaneous signals between electrode pairs declined (from 0.47 ± 0.1 to 0.35 ± 0.04, p < 0.001) along with the EPAs throughout the week of injury. In support of the electrophysiological findings, immunohistochemical analysis at day-7 post-injury showed detectable Purkinje cell loss at low FPI pressures and more with the largest pressures used. Our results suggest that sensory evoked potentials (SEPs) recorded from the cerebellar surface can be a useful technique to monitor the course of cerebellar injury and identify the phases of injury progression even at mild levels. © 2014 Ordek, Proddutur, Santhakumar, Pfister and Sahin.
Ivessa A.S.,Rutgers Biomedical and Health science
Trends in Cancer | Year: 2017
Many cancers are initiated by loss-of-heterozygosity (LOH) events that lead to the replacement of single, functional tumor suppressor genes by the mutant alleles. The underlying mechanisms, of why LOH rates increase with age, are not well understood. We discuss the possible involvement of difficult-to-replicate (fragile) chromosomal sites in this process. © 2017 Elsevier Inc.
Lewis J.D.,University of Pennsylvania |
Habel L.A.,Kaiser Permanente |
Quesenberry C.P.,Kaiser Permanente |
Strom B.L.,University of Pennsylvania |
And 9 more authors.
JAMA - Journal of the American Medical Association | Year: 2015
Importance Studies suggest pioglitazone use may increase risk of cancers. Objective To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. Design, Setting, and Participants Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed 193 099 persons aged 40 years or older in 1997-2002 until December 2012; 464 case patients and 464 matched controls were surveyed about additional confounders. A cohort analysis of 10 additional cancers included 236 507 persons aged 40 years or older in 1997-2005 and followed until June 2012. Cohorts were from Kaiser Permanente Northern California. EXPOSURES Ever use, duration, cumulative dose, and time since initiation of pioglitazone as time dependent. Main Outcomes and Measures Incident cancer, including bladder, prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma. RESULTS Among 193 099 persons in the bladder cancer cohort, 34 181 (18%) received pioglitazone (median duration, 2.8 years; range, 0.2-13.2 years) and 1261 had incident bladder cancer. Crude incidences of bladder cancer in pioglitazone users and nonusers were 89.8 and 75.9 per 100 000 person-years, respectively. Ever use of pioglitazone was not associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95%CI, 0.89-1.26). Results were similar in case-control analyses (pioglitazone use: 19.6%among case patients and 17.5% among controls; adjusted odds ratio, 1.18; 95%CI, 0.78-1.80). In adjusted analyses, there was no association with 8 of the 10 additional cancers; ever use of pioglitazone was associated with increased risk of prostate cancer (HR, 1.13; 95%CI, 1.02-1.26) and pancreatic cancer (HR, 1.41; 95%CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100 000 person-years, respectively. No clear patterns of risk for any cancer were observed for time since initiation, duration, or dose. Conclusions and Relevance Pioglitazone use was not associated with a statistically significant increased risk of bladder cancer, although an increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether they are causal or are due to chance, residual confounding, or reverse causality. © 2015 American Medical Association. All rights reserved.
Zhao X.,Public Health Research Institute |
Zhao X.,Rutgers Biomedical and Health science |
Zhao X.,Xiamen University |
Hong Y.,Public Health Research Institute |
And 2 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2015
Support for the contribution of reactive oxygen species (ROS) to antimicrobial lethality has been refined and strengthened. Killing by diverse antimicrobials is enhanced by defects in genes that protect against ROS, inhibited by compounds that block hydroxyl radical accumulation, and is associated with surges in intracellular ROS. Moreover, support has emerged for a genetic pathway that controls the level of ROS. Since some antimicrobials kill in the absence of ROS, ROS must add to, rather than replace, known killing mechanisms. New work has addressed many of the questions concerning the specificity of dyes used to detect intracellular ROS and the specificity of perturbations that influence ROS surges. However, complexities associated with killing under anaerobic conditions remain to be resolved. Distinctions among primary lesion formation, resistance, direct lesionmediated killing and a self-destructive stress response are discussed to facilitate efforts to potentiate ROSmediated bacterial killing and improve antimicrobial efficacy. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
Feng D.,Rutgers Biomedical and Health science |
Feng D.,Rutgers University |
Barnes B.J.,Rutgers Biomedical and Health science |
Barnes B.J.,Rutgers University
Frontiers in Immunology | Year: 2013
Patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) display increased levels of type I interferon (IFN)-induced genes. Plasmacytoid dendritic cells (PDCs) are natural interferon producing cells and considered to be a primary source of IFN-α in these two diseases. Differential expression patterns of type I IFN-inducible transcripts can be found in different immune cell subsets and in patients with both active and inactive autoimmune disease. A type I IFN gene signature generally consists of three groups of IFN-induced genes - those regulated in response to virus-induced type I IFN, those regulated by the IFN-induced mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK) pathway, and those by the IFN-induced phosphoinositide-3 kinase (PI-3K) pathway. These three groups of type I IFN-regulated genes control important cellular processes such as apoptosis, survival, adhesion, and chemotaxis, that when dysregulated, contribute to autoimmunity. With the recent generation of large datasets in the public domain from next-generation sequencing and DNA microarray experiments, one can perform detailed analyses of cell-type specific gene signatures as well as identify distinct transcription factors (TFs) that differentially regulate these gene signatures. We have performed bioinformatics analysis of data in the public domain and experimental data from our lab to gain insight into the regulation of type I IFN gene expression. We have found that the genetic landscape of the IFNA and IFNB genes are occupied by TFs, such as insulators CTCF and cohesin, that negatively regulate transcription, as well as interferon regulatory factor (IRF)5 and IRF7, that positively and distinctly regulate IFNA subtypes. A detailed understanding of the factors controlling type I IFN gene transcription will significantly aid in the identification and development of new therapeutic strategies targeting the IFN pathway in autoimmune disease. © 2013 Feng and Barnes.
Silverstein S.M.,Rutgers Biomedical and Health science |
Rosen R.,New York Eye and Ear Infirmary of Mount Sinai
Schizophrenia Research: Cognition | Year: 2015
Although visual processing impairments are common in schizophrenia, it is not clear to what extent these originate in the eye vs. the brain. This review highlights potential contributions, from the retina and other structures of the eye, to visual processing impairments in schizophrenia and high-risk states. A second goal is to evaluate the status of retinal abnormalities as biomarkers for schizophrenia. The review was motivated by known retinal changes in other disorders (e.g., Parkinson's disease, multiple sclerosis), and their relationships to perceptual and cognitive impairments, and disease progression therein. The evidence reviewed suggests two major conclusions. One is that there are multiple structural and functional disturbances of the eye in schizophrenia, all of which could be factors in the visual disturbances of patients. These include retinal venule widening, retinal nerve fiber layer thinning, dopaminergic abnormalities, abnormal ouput of retinal cells as measured by electroretinography (ERG), maculopathies and retinopathies, cataracts, poor acuity, and strabismus. Some of these are likely to be illness-related, whereas others may be due to medication or comorbid conditions. The second conclusion is that certain retinal findings can serve as biomarkers of neural pathology, and disease progression, in schizophrenia. The strongest evidence for this to date involves findings of widened retinal venules, thinning of the retinal nerve fiber layer, and abnormal ERG amplitudes. These data suggest that a greater understanding of the contribution of retinal and other ocular pathology to the visual and cognitive disturbances of schizophrenia is warranted, and that retinal changes have untapped clinical utility. © 2015 The Authors.
Pimenta E.M.,Rutgers Biomedical and Health science |
Barnes B.J.,Rutgers Biomedical and Health science
Molecular cancer | Year: 2015
BACKGROUND: Migration of breast cancer cells out of a duct or lobule is a prerequisite for invasion and metastasis. However, the factors controlling breast cancer cell migration are not fully elucidated. We previously found that expression of the transcription factor interferon regulatory factor 5 (IRF5) is significantly decreased as a breast lesion progresses from a non-malignant stage to ductal carcinoma in situ and is eventually lost in ~80% of invasive ductal carcinomas examined. Human in vitro and murine in vivo models of invasive breast cancer confirmed an important role for IRF5 in regulating cell motility, invasion and/or metastasis; yet, the mechanism(s) by which this occurs is not known. Since IRF5 is primarily expressed in the cytoplasm of human mammary epithelial cells, we hypothesized that IRF5 may function in a transcription-independent manner to control intrinsic cell migration.RESULTS: A series of IRF5 deletion mutants were tested in cell motility, invasion and migration assays. A novel, conserved 10 amino acid domain was identified that regulates mammary epithelial cell migration. This region (∆115-125) is downstream of IRF5's DNA binding domain and therefore when absent, retains IRF5 transcription activity but loses cell migration control. An IRF5 construct with a mutated nuclear localization signal further confirmed that IRF5 controls migration in a cytoplasmic and transcription-independent manner. Candidate cytoskeletal molecules were identified in MDA-MB-231 cells to interact with IRF5 by immunoprecipitation and mass spectrometry analysis. α6-tubulin was independently confirmed to interact with endogenous IRF5 in MCF-10A cells. Alterations in F-actin bundling after staining EV- and IRF5-231 cells with phalloidin suggests that IRF5 may control cell migration/motility through its interaction with cytoskeletal molecules that contribute to the formation of F-actin networks. Last and most notably, we found that IRF5's control of cell migration is not restricted to mammary epithelial cells but functions in other epithelial cell types suggesting a more global role for this newly identified cell migratory function of IRF5.CONCLUSIONS: These findings are significant as they identify a new regulator of epithelial cell migration and provide specific insight into the mechanism(s) by which loss of IRF5 expression in mammary epithelial cells contributes to breast cancer metastasis.
Brown A.M.,Rutgers Biomedical and Health science |
Zifchock R.A.,United States Military Academy |
Hillstrom H.J.,The New Motion
Gait and Posture | Year: 2014
Purpose: To establish whether lower extremity limb dominance has an effect on overground running mechanics. Background: In attempts to resolve unilateral pathology, physical therapists often use the restoration of symmetry as a clinical milestone. While lower limb dominance has been shown to affect lower extremity mechanics during dynamic tasks such as jump landing, its effect on running gait is poorly understood. Further, despite the role of fatigue in running mechanics and injury, the interaction between fatigue and limb dominance has yet to be examined. Methods: Three-dimensional kinematic and kinetic data were collected on 20 females during overground running. Data were collected prior-to and following a treadmill run to exertion. Dominant and non-dominant limb data were compared in the fresh-state using a paired t-test. A 2-way repeated-measures ANOVA was used to test for an interaction between fatigue and limb dominance. Results: There were no significant differences between the kinematic or kinetic patterns of the dominant and non-dominant lower extremities during fresh-state overground running. Fatigue was not shown to interact with limb dominance. Conclusion: Limb dominance did not affect kinematic or kinetic side-to-side differences. Therefore, physical therapists can continue to use resolution of lower extremity symmetry as a goal of therapy without having to account for limb dominance. The lack of an interaction between fatigue and limb dominance indicates that the dominant and non-dominant limbs fatigue at a similar rate. © 2013 Elsevier B.V.