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Politics, James Garbarino

Psychology: Faculty Publications and Other Works

An entry on Politics for The SAGE Encyclopedia of Lifespan Human Development authored by James Garbarino.

In-Hospital Mortality And Post-Surgical Complications Among Cancer Patients With Metabolic Syndrome, Tomi Akinyemiju, Swati Sakhuja, Neomi Vin-Raviv

Epidemiology and Environmental Health Faculty Publications

Background

Metabolic syndrome (MetS) is an important etiologic and prognostic factor for cancer, but few studies have assessed hospitalization outcomes among patients with both conditions.

Methods

Data was obtained from the Healthcare Cost and Utilization project Nationwide Inpatient Sample (HCUP-NIS). Study variables were assessed using ICD-9 codes on adults aged 40 years and over admitted to a US hospital between 2007 and 2011 with primary diagnosis of either breast, colorectal, or prostate cancer. We examined in-hospital mortality, post-surgical complications, and discharge disposition among cancer patients with MetS and compared with non-MetS patients.

Results

Hospitalized breast (OR: 0.31, 95% CI: 0.20–0.46), …

The Role Of The Leukemia Inhibitory Factor Receptor In Neuroprotective Signaling, Stephanie M. Davis, Keith R. Pennypacker

Center for Advanced Translational Stroke Science Faculty Publications

Several neurotropic cytokines relay their signaling through the leukemia inhibitory factor receptor. This 190kDa subunit couples with the 130kDa gp130 subunit to transduce intracellular signaling in neurons and oligodendrocytes that leads to expression of genes associated with neurosurvival. Moreover, activation of this receptor alters the phenotype of immune cells to an anti-inflammatory one. Although cytokines that activate the leukemia inhibitory factor receptor have been studied in the context of neurodegenerative disease, therapeutic targeting of the specific receptor subunit has been understudied in by comparison. This review examines the role of this receptor in the CNS and immune system, and its …

The Role Of Human Dopamine Transporter In Neuroaids, Jun Zhu, Subramaniam Ananthan, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

HIV-associated neurocognitive disorder (HAND) remains highly prevalent in HIV infected individuals and represents a special group of neuropathological disorders, which are associated with HIV-1 viral proteins, such as transactivator of transcription (Tat) protein. Cocaine abuse increases the incidence of HAND and exacerbates its severity by enhancing viral replication. Perturbation of dopaminergic transmission has been implicated as a risk factor of HAND. The presynaptic dopamine (DA) transporter (DAT) is essential for DA homeostasis and dopaminergic modulation of the brain function including cognition. Tat and cocaine synergistically elevate synaptic DA levels by acting directly on human DAT (hDAT), ultimately leading to dysregulation …

Comparative Analysis Of Microbial Sensing Molecules In Mucosal Tissues With Aging, Octavio A. Gonzalez, Sreenatha S. Kirakodu, Michael John Novak, A. J. Stromberg, L. Orraca, J. Gonzalez-Martinez, A. Burgos, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Host-bacterial interactions at mucosal surfaces require recognition of the bacteria by host cells enabling targeted responses to maintain tissue homeostasis. It is now well recognized that an array of host-derived pattern recognition receptors (PRRs), both cell-bound and soluble, are critical to innate immune engagement of microbes via microbial-associated molecular patterns (MAMP). This report describes the use of a nonhuman primate model to evaluate changes in the expression of these sensing molecules related to aging in healthy gingival tissues. Macaca mulatta aged 3-24 years were evaluated clinically and gingival tissues obtained, RNA isolated and microarray analysis conducted for gene expression of …

A Research Agenda For Curing Chronic Hepatitis B Virus Infection., Harvey Alter, Timothy Block, Nathaniel Brown, Alan Brownstein, Carol Brosgart, Kyong-Mi Chang, Pei-Jer Chen, Francis V Chisari, Chari Cohen, Hashem El-Serag, Jordan Feld, Robert Gish, Jeffrey Glenn, Tim Greten, Haitao Guo, Ju-Tao Guo, Yujin Hoshida, Jianming Hu, Kris V Kowdley, Wenhui Li, Jake Liang, Stephan Locarnini, Anna S Lok, William Mason, Brian Mcmahon, Anand Mehta, Robert Perrillo, Peter Revill, Charles M Rice, Joann Rinaudo, Raymond Schinazi, Christoph Seeger, Kirty Shetty, John Tavis, Fabien Zoulim

Articles, Abstracts, and Reports

No abstract provided.

Central Nervous System Histoplasmosis: Multicenter Retrospective Study On Clinical Features, Diagnostic Approach And Outcome Of Treatment, Joseph Wheat, Thein Myint, Ying Guo, Phebe Kemmer, Chadi A. Hage, Colin Terry, Marwan M. Azar, James Riddell, Peter Ender, Sharon Chen, Kareem Shehab, Kerry Cleveland, Eden Esguerra, James Johnson, Patty Wright, Vanja Douglas, Pascalis Vergidis, Winnie Ooi, John Baddley, David Bamberger, Raed N. Khairy, Holenarasipur R. Vikram, Elizabeth Jenny-Avital, Geetha Sivasubramanian, Karen Bowlware, Barbara Pahud, Juan Sarria, Townson Tsai, Maha Assi, Satish Mocherla

Internal Medicine Faculty Publications

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.

A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.

Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the …

Tnf Receptor-Activated Factor 2 Mediates Cardiac Protection Through Noncanonical Nf-Κb Signaling, Sarah Evans, Huei-Ping Tzeng, Deborah J Veis, Scot Matkovich, Carla Weinheimer, Attila Kovacs, Philip M Barger, Douglas L Mann

Open Access Publications

To elucidate the mechanisms responsible for cytoprotective effects of TNF receptor-activated factor 2 (TRAF2) in the heart, we employed genetic gain- and loss-of-function studies ex vivo and in vivo in mice with cardiac-restricted overexpression of TRAF2 (Myh6-TRAF2LC). Crossing Myh6-TRAF2LC mice with mice lacking canonical signaling (Myh6-TRAF2LC/Myh6-IκBαΔN) abrogated the cytoprotective effects of TRAF2 ex vivo. In contrast, inhibiting the JAK/STAT pathway did not abrogate the cytoprotective effects of TRAF2. Transcriptional profiling of WT, Myh6-TRAF2LC, and Myh6-TRAF2LC/Myh6-IκBαΔN mouse hearts suggested that the noncanonical NF-κB signaling pathway was upregulated in the Myh6-TRAF2LC mouse hearts. Western blotting and ELISA for the NF-κB family proteins …

Word-List Intrusion Errors Predict Progression To Mild Cognitive Impairment, Kelsey R Thomas, Joel Eppig, Emily C Edmonds, Diane M Jacobs, David J Libon, Rhoda Au, David P Salmon, Mark W Bondi, Alzheimer’S Disease Neuroimaging Initiative

Rowan-Virtua School of Osteopathic Medicine Departmental Research

OBJECTIVE: Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI.

METHOD: Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on …

Reproductive Steroids And Adhd Symptoms Across The Menstrual Cycle, Bethan A. Roberts, Tory Eisenlohr-Moul, Michelle M. Martel

Psychology Faculty Publications

Although Attention-Deficit/Hyperactivity Disorder shows (ADHD) male predominance, females are significantly impaired and exhibit additional comorbid disorders during adolescence. However, no empirical work has examined the influence of cyclical fluctuating steroids on ADHD symptoms in women. The present study examined estradiol (E2), progesterone (P4), and testosterone (T) associations with ADHD symptoms across the menstrual cycle in regularly-cycling young women (N=32), examining trait impulsivity as a moderator. Women completed a baseline measure of trait impulsivity, provided saliva samples each morning, and completed an ADHD symptom checklist every evening for 35 days. Results indicated decreased levels of E2 in the context of increased …

Kruppel-Like Factor 4-Dependent Staufen1-Mediated Mrna Decay Regulates Cortical Neurogenesis, Byoung-San Moon, Jinlun Bai, Mingyang Cai, Chunming Liu, Jiandang Shi, Wange Lu

Molecular and Cellular Biochemistry Faculty Publications

Kruppel-like factor 4 (Klf4) is a zinc-finger-containing protein that plays a critical role in diverse cellular physiology. While most of these functions attribute to its role as a transcription factor, it is postulated that Klf4 may play a role other than transcriptional regulation. Here we demonstrate that Klf4 loss in neural progenitor cells (NPCs) leads to increased neurogenesis and reduced self-renewal in mice. In addition, Klf4 interacts with RNA-binding protein Staufen1 (Stau1) and RNA helicase Ddx5/17. They function together as a complex to maintain NPC self-renewal. We report that Klf4 promotes Stau1 recruitment to the 3′-untranslated region of neurogenesis-associated mRNAs, …

Fasoracetam In Adolescents With Adhd And Glutamatergic Gene Network Variants Disrupting Mglur Neurotransmitter Signaling., Josephine Elia, Grace Ungal, Charlly Kao, Alexander Ambrosini, Nilsa De Jesus-Rosario, Lene Larsen, Rosetta Chiavacci, Tiancheng Wang, Christine Kurian, Kanani Titchen, Brian Sykes, Sharon Hwang, Bhumi Kumar, Jacqueline Potts, Joshua Davis, Jeffrey Malatack, Emma Slattery, Ganesh Moorthy, Athena Zuppa, Andrew Weller, Enda Byrne, Yun R. Li, Walter K. Kraft, Hakon Hakonarson

Department of Pediatrics Faculty Papers

The glutamatergic neurotransmitter system may play an important role in attention-deficit hyperactivity disorder (ADHD). This 5-week, open-label, single-blind, placebo-controlled study reports the safety, pharmacokinetics and responsiveness of the metabotropic glutamate receptor (mGluR) activator fasoracetam (NFC-1), in 30 adolescents, age 12-17 years with ADHD, harboring mutations in mGluR network genes. Mutation status was double-blinded. A single-dose pharmacokinetic profiling from 50-800 mg was followed by a single-blind placebo at week 1 and subsequent symptom-driven dose advancement up to 400 mg BID for 4 weeks. NFC-1 treatment resulted in significant improvement. Mean Clinical Global Impressions-Improvement (CGI-I) and Severity (CGI-S) scores were, respectively, 3.79 …

Beta-Catenin Cleavage Enhances Transcriptional Activation, Tatiana Goretsky, Emily M. Bradford, Qing Ye, Olivia F. Lamping, Tomas Vanagunas, Mary Pat Moyer, Patrick C. Keller, Preetika Sinh, Josep M. Llovet, Tianyan Gao, Qing-Bai She, Linheng Li, Terrence A. Barrett

Internal Medicine Faculty Publications

Nuclear activation of Wnt/β-catenin signaling is required for cell proliferation in inflammation and cancer. Studies from our group indicate that β-catenin activation in colitis and colorectal cancer (CRC) correlates with increased nuclear levels of β-catenin phosphorylated at serine 552 (pβ-Cat⁵⁵²). Biochemical analysis of nuclear extracts from cancer biopsies revealed the existence of low molecular weight (LMW) pβ-Cat⁵⁵², increased to the exclusion of full size (FS) forms of β-catenin. LMW β-catenin lacks both termini, leaving residues in the armadillo repeat intact. Further experiments showed that TCF4 predominantly binds LMW pβ-Cat⁵⁵² in the nucleus of inflamed and …

Zinc Inhibits Trpv1 To Alleviate Chemotherapy-Induced Neuropathic Pain, Jialie Luo, Alexis Bavencoffe, Pu Yang, Jing Feng, Shijin Yin, Aihua Qian, Weihua Yu, Shenbin Liu, Xuan Gong, Tao Cai, Edgar T. Walters, Carmen W. Dessauer, Hongzhen Hu

Open Access Publications

Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 …

Sooty Mangabey Genome Sequence Provides Insight Into Aids Resistance In A Natural Siv Host, David Palesch, Steven E. Bosinger, Gregory K. Tharp, Thomas H. Vanderford, Mirko Paiardini, Ann Chahroudi, Zachary P. Johnson, Frank Kirchhoff, Beatrice H. Hahn, Robert B. Norgren, Nirav B. Patel, Donald L. Sodora, Reem A. Dawoud, Caro-Beth Stewart, Sara M. Seepo, R. Alan Harris, Yue Liu, Muthuswamy Raveendran, Yi Han, Adam English, Gregg W.C. Thomas, Matthew W. Hahn, Lenore Pipes, Christopher E. Mason, Donna M. Muzny, Richard A. Gibbs, Daniel Sauter, Kim Worley, Jeffrey Rogers, Guido Silvestri

Journal Articles: Genetics, Cell Biology & Anatomy

In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a …

Management Of Acute Pancreatitis In The Pediatric Population: A Clinical Report From The North American Society For Pediatric Gastroenterology, Hepatology And Nutrition Pancreas Committee., M. Abu-El-Haija, S. Kumar, J. A. Quiros, K. Balakrishnan, B. Barth, S. Bitton, J. F. Eisses, E. J. Foglio, V. Fox, V. D. Morinville, +10 Additional Authors

Journal Articles

BACKGROUND:Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific recommendations are needed. METHODS:The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to management considerations in adult and pediatric AP. The literature was summarized, quality of evidence reviewed, and statements of recommendations developed. The authorship met to discuss the evidence, statements, and voted on recommendations. A consensus of at least 75% was required to approve a recommendation. RESULTS:The diagnosis of pediatric AP should follow the published INternational Study …

A Scoping Review Of Biopsychosocial Risk Factors And Co-Morbidities For Common Spinal Disorders, Bart N Green, Claire D Johnson, Scott Haldeman, Erin Griffith, Michael B Clay, Edward J Kane, Juan M Castellote, Shanmuganathan Rajasekaran, Matthew Smuck, Eric L Hurwitz, Kristi Randhawa, Hainan Yu, Margareta Nordin

Physical Therapy Collection

OBJECTIVE: The purpose of this review was to identify risk factors, prognostic factors, and comorbidities associated with common spinal disorders.

METHODS: A scoping review of the literature of common spinal disorders was performed through September 2016. To identify search terms, we developed 3 terminology groups for case definitions: 1) spinal pain of unknown origin, 2) spinal syndromes, and 3) spinal pathology. We used a comprehensive strategy to search PubMed for meta-analyses and systematic reviews of case-control studies, cohort studies, and randomized controlled trials for risk and prognostic factors and cross-sectional studies describing associations and comorbidities.

RESULTS: Of …

Persistent Stress-Induced Neuroplastic Changes In The Locus Coeruleus/Norepinephrine System, Olga Borodovitsyna, Neal Joshi, Daniel Chandler

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Neural plasticity plays a critical role in mediating short- and long-term brain responses to environmental stimuli. A major effector of plasticity throughout many regions of the brain is stress. Activation of the locus coeruleus (LC) is a critical step in mediating the neuroendocrine and behavioral limbs of the stress response. During stressor exposure, activation of the hypothalamic-pituitary-adrenal axis promotes release of corticotropin-releasing factor in LC, where its signaling promotes a number of physiological and cellular changes. While the acute effects of stress on LC physiology have been described, its long-term effects are less clear. This review will describe how stress …

Evidence-Based Guidelines For Supportive Care Of Patients With Ebola Virus Disease, François Lamontagne, Robert A. Fowler, Neill K. Adhikari, Srinivas Murthy, David Brett-Major, Michael Jacobs, Timothy M. Uyeki, Constanza Vallenas, Susan L. Norris, William A. Fischer, Thomas E. Fletcher, Adam C. Levine, Paul Reed, Daniel G. Bausch, Sandy Gove, Andrew Hall, Susan Shepherd, Reed A. Siemieniuk, Marie-Claude Lamah, Rashida Kamara, Phiona Nakyeyune, Moses J. Soka, Ama Edwin, Afeez A. Hazzan, Shevin T. Jacob, Mubarak Mustafa Elkarsany, Takuya Adachi, Lynda Benhadj, Christophe Clément, Ian Crozier, Armando Garcia, Steven J. Hoffman, Gordon H. Guyatt

Journal Articles: Epidemiology

The 2013-16 Ebola virus disease outbreak in west Africa was associated with unprecedented challenges in the provision of care to patients with Ebola virus disease, including absence of pre-existing isolation and treatment facilities, patients' reluctance to present for medical care, and limitations in the provision of supportive medical care. Case fatality rates in west Africa were initially greater than 70%, but decreased with improvements in supportive care. To inform optimal care in a future outbreak of Ebola virus disease, we employed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to develop evidence-based guidelines for the delivery of supportive …

Variation In Competence For Zikv Transmission By Aedes Aegypti And Aedes Albopictus In Mexico, Selene M. Garcia-Luna, James Weger-Lucarelli, Claudia Rückert, Reyes A. Murrieta, Michael C. Young, Alex D. Byas, Joseph R. Fauver, Rushika Perera, Adriana E. Flores-Suarez, Gustavo Ponce-Garcia, Americo D. Rodriguez, Gregory D. Ebel, William C. Black

Journal Articles: Epidemiology

BACKGROUND: ZIKV is a new addition to the arboviruses circulating in the New World, with more than 1 million cases since its introduction in 2015. A growing number of studies have reported vector competence (VC) of Aedes mosquitoes from several areas of the world for ZIKV transmission. Some studies have used New World mosquitoes from disparate regions and concluded that these have a variable but relatively low competence for the Asian lineage of ZIKV.

METHODOLOGY/PRINCIPAL FINDINGS: Ten Aedes aegypti (L) and three Ae. albopictus (Skuse) collections made in 2016 from throughout Mexico were analyzed for ZIKV (PRVABC59-Asian lineage) VC. Mexican …

Assessing Working Memory In Mild Cognitive Impairment With Serial Order Recall., Sheina Emrani, David J Libon, Melissa Lamar, Catherine C Price, Angela L Jefferson, Katherine A Gifford, Timothy J Hohman, Daniel A Nation, Lisa Delano-Wood, Amy Jak, Katherine J Bangen, Mark W Bondi, Adam M Brickman, Jennifer Manly, Rodney Swenson, Rhoda Au, Consortium For Clinical And Epidemiological Neuropsychological Data Analysis (Cenda)

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined.

OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI).

METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat …

Schistosoma Mansoni And Other Intestinal Parasitic Infections In Schoolchildren And Vervet Monkeys In Lake Ziway Area, Ethiopia, Dejene Teklemariam, Mengistu Legesse, Abraham Degarege, Song Liang, Berhanu Erko

Journal Articles: Epidemiology

OBJECTIVE: To assess Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys (Chlorocebus aethiops) in Bochessa Village, Ziway, Ethiopia.

RESULTS: Fecal specimens from selected schoolchildren and droppings of the vervet monkeys were collected and microscopically examined for intestinal parasites using the Kato-Katz thick smear and formol-ether concentration techniques. The prevalences of S. mansoni, Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, hookworms, Hymenolepis nana and Taenia species among the children were 35.7, 26.9, 24.1, 2.1, 2.1, 1.07 and 2.1%, respectively (by Kato-Katz) and 39.3, 36.1, 35.6, 2.9, 10.0, 4.3, and 2.9%, respectively (by formol-ether concentration). Prevalence of S. mansoni …

Comparative Transcriptomic Analysis Of Human Placentae At Term And Preterm Delivery., Alison G Paquette, Heather M Brockway, Nathan D Price, Louis J Muglia

Articles, Abstracts, and Reports

Preterm birth affects 1 out of every 10 infants in the United States, resulting in substantial neonatal morbidity and mortality. Currently, there are few predictive markers and few treatment options to prevent preterm birth. A healthy, functioning placenta is essential to positive pregnancy outcomes. Previous studies have suggested that placental pathology may play a role in preterm birth etiology. Therefore, we tested the hypothesis that preterm placentae may exhibit unique transcriptomic signatures compared to term samples reflective of their abnormal biology leading to this adverse outcome. We aggregated publicly available placental villous microarray data to generate a preterm and term …

Catching Chances: The Movement To Be On The Ground And Research Ready Before An Outbreak, David Brett-Major, James V. Lawler

Journal Articles: Epidemiology

After more than 28,000 Ebola virus disease cases and at least 11,000 deaths in West Africa during the 2014⁻2016 epidemic, the world remains without a licensed vaccine or therapeutic broadly available and demonstrated to alleviate suffering. This deficiency has been felt acutely in the two, short, following years with two Ebola virus outbreaks in the Democratic Republic of Congo (DRC), and a Marburg virus outbreak in Uganda. Despite billions of U.S. dollars invested in developing medical countermeasures for filoviruses in the antecedent decades, resulting in an array of preventative, diagnostic, and therapeutic products, none are available on commercial shelves. This …

Cgas Drives Noncanonical-Inflammasome Activation In Age-Related Macular Degeneration, Nagaraj Kerur, Shinichi Fukuda, Daipayan Banerjee, Younghee Kim, Dongxu Fu, Ivana Apicella, Akhil Varshney, Reo Yasuma, Benjamin J. Fowler, Elmira Baghdasaryan, Kenneth M. Marion, Xiwen Huang, Tetsuhiro Yasuma, Yoshio Hirano, Vlad Serbulea, Meenakshi Ambati, Vidya L. Ambati, Yuji Kajiwara, Kameshwari Ambati, Shuichiro Hirahara, Ana Bastos-Carvalho, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Kyung Bo Kim, David R. Hinton, Norbert Leitinger, John C. Cambier, Joseph D. Buxbaum, M. Cristina Kenney, Bradley D. Gelfand, Jayakrishna Ambati

Ophthalmology and Visual Science Faculty Publications

Geographic atrophy is a blinding form of age-related macular degeneration characterized by retinal pigmented epithelium (RPE) death; the RPE also exhibits DICER1 deficiency, resultant accumulation of endogenous Alu-retroelement RNA, and NLRP3-inflammasome activation. How the inflammasome is activated in this untreatable disease is largely unknown. Here we demonstrate that RPE degeneration in human-cell-culture and mouse models is driven by a noncanonical-inflammasome pathway that activates caspase-4 (caspase-11 in mice) and caspase-1, and requires cyclic GMP-AMP synthase (cGAS)-dependent interferon-β production and gasdermin D-dependent interleukin-18 secretion. Decreased DICER1 levels or Alu-RNA accumulation triggers cytosolic escape of mitochondrial DNA, which engages cGAS. Moreover, caspase-4, gasdermin …

Exercise In The Treatment Of Major Depressive Disorder, Larissa Ann Haug

Physician Assistant Scholarly Project Papers

Objective

The purpose of this research and systematic literature review is to determine how exercise can be incorporated into the treatment of major depressive disorder (MDD) and its efficacy.

Methods

In this review, four databases were searched including SportDiscus, Pubmed, Cochrane Database of Systematic Reviews, and PsycInfo from October 1 to January 5, 2018. A variety of key terms were used when searching. Works chosen for review were published after the year 2000, were peer reviewed, and included randomized control trials (RCTs), pilot studies, systematic reviews, and meta-analyses. Sources that were excluded included those published prior to the year 2000, …

Autonomic Dysreflexia After Spinal Cord Injury: Systemic Pathophysiology And Methods Of Management, Khalid C. Eldahan, Alexander G. Rabchevsky

Physiology Faculty Publications

Traumatic spinal cord injury (SCI) has widespread physiological effects beyond the disruption of sensory and motor function, notably the loss of normal autonomic and cardiovascular control. Injury at or above the sixth thoracic spinal cord segment segregates critical spinal sympathetic neurons from supraspinal modulation which can result in a syndrome known as autonomic dysreflexia (AD). AD is defined as episodic hypertension and concomitant baroreflex-mediated bradycardia initiated by unmodulated sympathetic reflexes in the decentralized cord. This condition is often triggered by noxious yet unperceived visceral or somatic stimuli below the injury level and if severe enough can require immediate medical attention. …

Disturbance Of Redox Homeostasis In Down Syndrome: Role Of Iron Dysmetabolism, Eugenio Barone, Andrea Arena, Elizabeth Head, D. Allan Butterfield, Marzia Perluigi

Sanders-Brown Center on Aging Faculty Publications

Down syndrome (DS) is the most common genetic form of intellectual disability that leads in the majority of cases to development of early-onset Alzheimer-like dementia (AD). The neuropathology of DS has several common features with AD including alteration of redox homeostasis, mitochondrial deficits, and inflammation among others. Interestingly, some of the genes encoded by chromosome 21 are responsible of increased oxidative stress (OS) conditions that are further exacerbated by decreased antioxidant defense. Previous studies from our groups showed that accumulation of oxidative damage is an early event in DS neurodegeneration and that oxidative modifications of selected proteins affects the integrity …

Metformin Suppresses Retinal Angiogenesis And Inflammation In Vitro And In Vivo, Jing Han, Yue Li, Xiuli Liu, Tongrong Zhou, Haijing Sun, Paul Edwards, Hua Gao, Fu-Shin Yu, Xiaoxi Qiao

Ophthalmology Articles

The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density …

Association Of Metformin Treatment With Reduced Severity Of Diabetic Retinopathy In Type 2 Diabetic Patients, Yue Li, Christina Ryu, Metasebia Munie, Salma Noorulla, Satyesh Rana, Paul Edwards, Hua Gao, Xiaoxi Qiao

Ophthalmology Articles

Purpose: To evaluate effects of long-term metformin on the severity of diabetic retinopathy (DR) in high-risk type 2 diabetic (T2D) patients.

Methods: A retrospective chart review study was conducted involving 335 DR patients with T2D ≥ 15 years from 1990 to 2013. The severity of DR was determined by Early Treatment Diabetic Retinopathy Study scale. The associations between metformin and DR severity were evaluated. Comparison with stratification for the use of sulfonylurea and insulin was performed to identify possible confounding effects.

Results: Severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy (SNPDR/PDR) was more often diagnosed in nonmetformin users (67/142, 47%) …