Digital Commons Network^™

Left Atrial Model, Borna Sobati, Sarah Porello, Tess Pate

Biomedical Engineering

The objective is to produce an electrophysiological model of an adult human left atrium. This model will be used to test mapping probe catheters used for locating cardiac arrhythmias against current technology used in practice. Dr. Chris Porterfield requested this model and other physicians or probe catheter manufacturers may also use this product in the future. Dr. Porterfield also discussed the possibility of future senior project groups using the model as a bench test for designing new catheter tips. The model will precisely simulate electrical behaviors of the heart in normal as well as arrhythmic conditions. Ideally, the model will …

Dementia In Pakistan; An Unprecedented Challenge And Local Cultural Beliefs, Problems And Actions Required., Qamar Zaman, Maimoona Siddiqui, Zaha Iqbal Malik

Pakistan Journal of Neurological Sciences (PJNS)

Changing cultural and social dynamics has brought a major shift in lifestyles and associated risk factors for various disorders that were previously uncommon in Pakistan. Dementia is among the one of these emerging problems that is going to affect the elderly population worldwide but more so in the developing world. To adequately deal with the problems faced by patients with dementia and their caregivers, several important measures are needed that can help to reduce the morbidity and burden on the families and overall society. Increasing the awareness regarding the risk factors may help to reduce the dementia burden similarly knowledge …

Quantifying Expression Of Interneuron Subtype Markers For Dlx-2 Transfected Ng2 Cells, Timothy Nolan

Honors Scholar Theses

Neurons are a post-mitotic cell population, and therefore, they are not able to regenerate in vivo after a traumatic injury. Because inhibitory GABAergic interneurons and oligodendrocyte precursor cells (OPCs) are derived from the same precursor, recent studies have focused on transforming these OPCs into GABAergic neurons. However, there are different types of GABAergic interneurons that have different electrophysiological responses, which can lead to functional differences. The Nishiyama laboratory had already used a key gene in GABAergic interneuron and OPC differentiation, Distal-less homeobox 2 (Dlx-2), to transfect OPCs; early electrophysiology tests showed most of these transfected cells behaved like immature neurons, …

The Fibrosis Across Organs Symposium: A Roadmap For Future Research Priorities., Jesse Roman, Teresa R. Barnes, Dolly J. Kervitsky, Gregory P. Cosgrove, Dennis E. Doherty, Andrew M. Tager, Luca Richeldi, Eric S. White, David A. Brenner, Lynn M. Schnapp, Timothy D. Hewitson, Bodh I. Jugdutt, Timothy A. Mckinsey, John D. Tosi, Stephen Crane, Kevin K. Brown

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

No abstract provided.

Study Of Natural Killer Cells And Their Therapeutic Role In Pediatric Cancer, Hong Ha Rosa Nguyen

Theses and Dissertations (ETD)

NK cells are known to play an important role in the natural defense against viral infections and tumor immune surveillance. Through complex interactions between NK cell receptors and target cell ligands, transformed or unhealthy cells are identified and rapidly eliminated. NK cells have been used for therapeutic purposes in pediatric oncology, for example by harnessing the mechanisms of NK cell surveillance in acute myeloid leukemia (AML) or intervention-augmented antibody-dependent cell-mediated cytotoxicity (ADCC) in neuroblastoma. However, the underlying cellular mechanisms in these processes are not fully understood. In my thesis research, I sought to gain a deeper understanding of the molecular …

Associations Of First Trimester Co-Use Of Tobacco And Cannabis With Prenatal Immune Response And Psychosocial Well-Being, Kristin Ashford, Amanda Fallin-Bennett, Andrea Mccubbin, Amanda T. Wiggins, Sheila Barnhart, Joshua A. Lile

Perinatal Research and Wellness Center Faculty Publications

PURPOSE: This study aims to describe the association of first trimester co-use of tobacco and cannabis with maternal immune response and psychosocial well-being, relative to tobacco use only.

METHODS: A preliminary midpoint analysis included 138 pregnant women with biologically verified tobacco use, 38 of whom (28%) also tested positive for recent cannabis use. Maternal perceived stress (Perceived Stress Scale), depressive symptoms (Edinburgh Postnatal Depression Scale), and serum immune markers (IL-1β, IL-2, IL-6, IL-8, IL-10, TNFα, CRP, MMP8), were collected, although cytokine data were only available for 122 women.

RESULTS: Participant average age was 29.1 years, approximately half had a high …

Novel Mechanisms And Biomarkers In Alcohol-Induced Organ Injury., Christine E. Dolin

Electronic Theses and Dissertations

Background. Ethanol (EtOH) consumption is known to affect multiple organs; this is unsurprising, as the concentration of EtOH in the blood at relevant doses reaches the millimolar range. The overarching goal of this dissertation was to elucidate mechanisms of alcohol-induced organ injury, specifically the effects of alcohol on the hepatic extracellular matrix (ECM) proteome, the alcoholic hepatitis (AH) plasma peptidome, and the effects of alcohol on the renal cortex proteome and transcriptome. Methods. Mice were pair-fed ethanol-containing liquid diet chronically, and then some mice were administered lipopolysaccharide (LPS). Liver sections from these mice were processed in a series of increasingly …

Interdisciplinary Aspects Of Cultural Engagement In Older Adults: Who/What/Why/When/How, Penny Roberts

Crossroads of Music and Wellness

The population of the United States is aging. Caring for older adults requires a variety of approaches and collaboration among professionals. One approach, cultural engagement, involves experiences rooted in cultural activities, such as choir singing, group music, art- and craft-making, drama involvement, etc. Cultural engagement provides opportunities to address aging-associated issues that will not interfere with medication or other treatments. The concept of cultural engagement has been successfully applied to a number of fields including chronic disease management, addictive behaviors, and pain control.

Depletion Of Myo/Nog Cells In The Lens Mitigates Posterior Capsule Opacification In Rabbits., Jacquelyn Gerhart, Liliana Werner, Nick Mamalis, Joseph Infanti, Colleen Withers, Fathma Abdalla, Colby Gerhart, Arturo Bravo Nuevo, Olivia Gerhart, Lori Getts, Kelly Rhodes, Jessica Bowers, Robert Getts, Mindy George-Weinstein

PCOM Scholarly Works

Purpose: Posterior capsule opacification (PCO) is a vision-impairing disease that occurs in some adults and most children after cataract surgery. Contractile myofibroblasts contribute to PCO by producing wrinkles in the lens capsule that scatter light. Myofibroblasts in the lens originate from Myo/Nog cells named for their expression of the MyoD transcription factor and bone morphogenetic protein inhibitor noggin. In this study we tested the effects of depleting Myo/Nog cells on development of PCO.

Methods: Myo/Nog cells were eliminated by injecting the G8 antibody conjugated to 3DNA nanocarriers for the cytotoxin doxorubicin (G8:3DNA:Dox) during cataract surgery in rabbits. The severity of …

The Effect Of Osmotic Stimulation Of Copeptin On Glucose Metabolism In Healthy Adults, Lisa Tjorven Jansen

Graduate Theses and Dissertations

Diabetes is currently affecting 30 million Americans. To combat disease onset, lifestyle interventions have been focused on. Low water intake, alongside elevated concentrations of circulating copeptin, has been linked to increased risk for. However, it is unknown whether this effect on glucose regulation is acute or chronic. Furthermore, no study to date assessed the effects of copeptin independent of the renin-angiotensin-aldosterone system (RAAS). Purpose: The purpose of these studies was therefore two-fold: 1) to establish high endogenous copeptin concentrations independent of RAAS, and 2) to assess glucose metabolism following a standardized oral glucose tolerance test (OGTT) during high concentrations of …

Transplanted Adult Human Hepatic Stem/Progenitor Cells Prevent Histogenesis Of Advanced Hepatic Fibrosis In Mice Induced By Carbon Tetrachloride, Yanzhen Bi, Xiyu Liu, Chuanping Si, Ye Hong, Yongke Lu, Pengfei Gao, Yonghong Yang, Xiaobei Zhang, Yibo Wang, Huabao Xiong, Zhongping Duan, Yu Chen, Feng Hong

Pharmacology, Physiology and Toxicology

Transplantation of adult human hepatic stem/progenitor cells (hHSPCs) has been considered as an alternative therapy, replacing donor liver transplantation to treat liver cirrhosis. This study assessed the antifibrotic effects of hHSPCs in mice with fibrosis induced by carbon tetrachloride (CCl₄) and examined the actions of hHSPCs on the fibrogenic activity of human hepatic stellate cells (HSCs) in a coculture system. Isolated hHSPCs expressed stem/progenitor cell phenotypic markers. Mice were given CCl₄ (twice weekly for 7 weeks) and hHSPC transplantation weekly. CCl₄ induced advanced fibrosis (bridging fibrosis and cirrhosis) in mice, which was prevented by hHSPC transplantation. …

Recent Progress In The Theranostics Application Of Nanomedicine In Lung Cancer., Anubhab Mukherjee, Manash Paul, Sudip Mukherjee

Articles, Abstracts, and Reports

Lung cancer is one of the leading causes of cancer-related death worldwide. Non-small cell lung cancer (NSCLC) causes around 80% to 90% of deaths. The lack of an early diagnosis and inefficiency in conventional therapies causes poor prognosis and overall survival of lung cancer patients. Recent progress in nanomedicine has encouraged the development of an alternative theranostics strategy using nanotechnology. The interesting physico-chemical properties in the nanoscale have generated immense advantages for nanoparticulate systems for the early detection and active delivery of drugs for a better theranostics strategy for lung cancer. This present review provides a detailed overview of the …

Microbiota Signatures In Type-2 Diabetic Patients With Chronic Kidney Disease - A Pilot Study, Gratiela P. Gradisteanu, Roxana A. Stoica, Laura Petcu, Ariana Picu, Adrian P. Suceveanu, Teodor Salmen, Diana S. Stefan, Cristian Serafinceanu, Mariana Carmen Chifiriuc, Anca P. Stoian

Journal of Mind and Medical Sciences

The human microbiota is paramount for normal host physiology. Altered host-microbiome interactions are part of the pathogenesis of numerous common ailments. Currently, much emphasis is placed on the involvement of the microbiome in the pathogenesis of type-2 diabetes mellitus (T2DM), impaired glucose tolerance, and other metabolic disorders (i.e. obesity). Several studies found highly significant correlations of specific intestinal bacteria with T2DM. A better understanding of the role of the microbiome in diabetes and its complications might provide new insights in the development of new therapeutic principles.

Our pilot study investigates the microbiota patterns in Romanian type-2 diabetic patients with diabetic …

Serum Markers Of Bone Fragility In Type-2 Diabetes Mellitus, Rucsandra Dănciulescu Miulescu, Loreta Guja, Lavinia Claudia Ochiana, Anca Ungurianu, Oana Cristina Șeremet, Emil Ștefănescu

Journal of Mind and Medical Sciences

Patients with type-2 diabetes mellitus (T2DM) have normal or increased bone mineral density (BMD) but despite that, they are characterized by an increased hip and vertebral fracture risk that involves the alteration of bone quality and not the reduction in bone mass. BMD is utilized for the diagnosis and evaluation of osteoporosis, but BMD itself cannot provide an accurate diagnosis of the individuals at increased risk of fracture and, therefore, studies have focused on identifying other risk factors that are partially or fully independent of BMD.

The fracture risk score tool-FRAX® models provide information about a 10-year probability of osteoporotic …

Immune And Inflammatory Pathways In Non-Alcoholic Steatohepatitis (Nash). An Update, Sorina Cezara Coste, Ionela Popovici, Andreea Maria Stefan, Iulia Breaban, Adela Sitar Taut, Simina Tarmure Sarlea, Angela Cozma, Dorel Sampelean, Olga Hilda Orasan, Vasile Negrean, Lucia Maria Procopciuc

Journal of Mind and Medical Sciences

Non-alcoholic steatohepatitis (NASH), also known as fatty liver disease (FLD), is a major public health problem. It is considered to be the hepatic manifestation of the metabolic syndrome. Chronic inflammation of the liver is an essential key in the progression from simple hepatic steatosis to steatohepatitis, the evolutionary stage of fatty liver disease. Moreover, the innate immune system plays a crucial role in the progression of hepatic inflammation. For this reason, it is of utmost importance to elucidate the connections between immune mechanisms, Toll-like receptor cytokine signalling, in order to find new effective treatments. Further studies are necessary to test …

The Relationship Between Gut Microbiota And Spontaneous Bacterial Peritonitis In Patients With Liver Cirrhosis - A Literature Review, Roxana-Emanuela Popoiag, Anca Mihaela Pantea Stoian, Adrian P. Suceveanu, Andra I. Suceveanu, Laura Mazilu, Irinel R. Parepa, Laura M. Serban, Mihai Paunica, Catalina Motofei, Carmen Fierbinteanu Braticevici

Journal of Mind and Medical Sciences

Gut microbiota is an essential component in the pathogenesis of liver cirrhosis and its complications. There is a direct relationship between the gut and the liver called the gutliver axis through which bacteria can reach the liver through the portal venous blood. However, it remains unclear how bacteria leave the intestine and reach the fluid collection in the abdomen. A series of mechanisms have been postulated to be involved in the pathogenesis of spontaneous bacterial peritonitis (SBP) and other complications of liver cirrhosis, including bacterial translocation, bacterial overgrowth, altered intestinal permeability and dysfunctional immunity. The hepatic function may also be …

Tumor-Derived Extracellular Vesicles Require Β1 Integrins To Promote Anchorage-Independent Growth., Rachel M. Derita, Aejaz Sayeed, Vaughn Garcia, Shiv Ram Krishn, Christopher D. Shields, Srawasti Sarker, Andrea Friedman, Peter Mccue, Sudheer Kumar Molugu, Ulrich Rodeck, Adam P. Dicker, Lucia R. Languino

Department of Cancer Biology Faculty Papers

The β1 integrins, known to promote cancer progression, are abundant in extracellular vesicles (EVs). We investigated whether prostate cancer (PrCa) EVs affect anchorage-independent growth and whether β1 integrins are required for this effect. Specifically using a cell-line-based genetic rescue and an in vivo PrCa model, we show that gradient-purified small EVs (sEVs) from either cancer cells or blood from tumor-bearing TRAMP (transgenic adenocarcinoma of the mouse prostate) mice promote anchorage-independent growth of PrCa cells. In contrast, sEVs from cultured PrCa cells harboring a short hairpin RNA to β1, from wild-type mice or from TRAMP mice carrying a β1 conditional ablation …

Contribution Of Retrotransposons To Breast Cancer Malignancy, Isaac D. Raplee

USF Tampa Graduate Theses and Dissertations

The components contributing to cancer progression, especially the transition from early to invasive are unknown. Consequently, the biological reasons are unclear as to why some patients diagnosed with atypia and ductal carcinoma in situ (DCIS) never progress into invasive breast cancer. The “one gene at a time” approach does not sufficiently predict progression. To elucidate the early stage progression to invasive ductal cancer, expression signature of transcripts and transposable elements in micropunched samples of formalin-fixed, paraffin embedded (FFPE) tissue was conducted. A bioinformatics pipeline to analyze poor quality, short reads (>36 nts) from RNA-Seq data was created to compare …

Split Tolerance Permits Safe Ad5-Gucy2c-Padre Vaccine-Induced T-Cell Responses In Colon Cancer Patients., Adam E. Snook, Trevor R. Baybutt, Bo Xiang, Tara S. Abraham, John C. Flickinger, Terry Hyslop, Tingting Zhan, Walter K. Kraft, Takami Sato, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The colorectal cancer antigen GUCY2C exhibits unique split tolerance, evoking antigen-specific CD8+, but not CD4+, T-cell responses that deliver anti-tumor immunity without autoimmunity in mice. Here, the cancer vaccine Ad5-GUCY2C-PADRE was evaluated in a first-in-man phase I clinical study of patients with early-stage colorectal cancer to assess its safety and immunological efficacy.

Methods: Ten patients with surgically-resected stage I or stage II (pN0) colon cancer received a single intramuscular injection of 1011 viral particles (vp) of Ad5-GUCY2C-PADRE. Safety assessment and immunomonitoring were carried out for 6 months following immunization. This trial employed continual monitoring of both efficacy and toxicity …

The Correlation Between The Microbiome And Neurodegenerative Disorders Such As Alzheimer Disease, Aurora Mokris

Honors Theses

Recent studies suggest that there are 1.3 times as many microbial cells as human cells in the body (Abbot, 2016). Another study claims that the combined genomes of this microbiota is 150 times that of the human genome (Zhuang & Shen, 2018). If you have ever had the feeling that you are not alone in an empty room you are most certainly correct. Your body is teeming with millions of organisms living in mutualistic symbiosis with you and surrounding microbes, but at times, this seemingly harmonious relationship can be disturbed, resulting in serious physical and psychological changes to the human …

Ucp1 Expression-Associated Gene Signatures Of Human Epicardial Adipose Tissue., Kanta Chechi, Jinchu Vijay, Pierre Voisine, Patrick Mathieu, Yohan Bossé, Andre Tchernof, Elin Grundberg, Denis Richard

Manuscripts, Articles, Book Chapters and Other Papers

Multiple reports of uncoupling protein 1 (UCP1) expression have established its presence in human epicardial adipose tissue (eAT). Its functional relevance to eAT, however, remains largely unknown. In a recent study, we reported that adrenergic stimulation of eAT was associated with downregulation of secreted proteins involved in oxidative stress-related and immune-related pathways. Here, we explored the UCP1-associated features of human eAT using next-generation deep sequencing. Paired biopsies of eAT, mediastinal adipose tissue (mAT), and subcutaneous adipose tissue (sAT) obtained from cardiac surgery patients, with specific criteria of high and low expression of UCP1 in eAT, were subjected to RNA sequencing. …

An Evaluation Of Risk Attitudes And Risk Tolerance In Emergency Medicine Residents., Carlos Rodriguez, Nishad A Rahman, Kory London, Robin Naples, Simran Buttar, Xiao Chi Zhang, Hyunjoo Lee, Joshua Rudner, Dimitrios Papanagnou

Department of Emergency Medicine Faculty Papers

Introduction Previous studies have shown that risk attitudes and tolerance for uncertainty are significant factors in clinical decision-making, particularly in the practice of defensive medicine. These attributes have also been linked with rates of physician burnout. To date, the risk profile of emergency medicine (EM) physicians has not yet been described. Our goal was to examine the risk profile of EM residents using a widely available risk tolerance and attitude assessment tool. Methods First-, second-, and third-year residents of Thomas Jefferson University Hospital's EM residency program completed the commercially available, unmodified Risk Type Compass, a validated instrument offered by Multi-Health …

Beware Of Barbiturates: Coma And Hypothermia In A 94-Year-Old Woman Due To Combined Secobarbital And Pentobarbital Toxicity, Andrew L. Koons Do, Amy Wier Do, Kenneth D. Katz Md, Matthew D. Cook Do, Robert D. Cannon Do, Gillian A. Beauchamp Md, Ryan M. Surmaitis Do

Department of Emergency Medicine

No abstract provided.

Steroid Receptor Coactivator-1 Modulates The Function Of Pomc Neurons And Energy Homeostasis, Yongjie Yang, Agatha A Van Der Klaauw, Liangru Zhu, Tessa M Cacciottolo, Yanlin He, Lukas K J Stadler, Chunmei Wang, Pingwen Xu, Kenji Saito, Antentor Hinton, Xiaofeng Yan, Julia M Keogh, Elana Henning, Matthew C Banton, Audrey E Hendricks, Elena G Bochukova, Vanisha Mistry, Katherine L Lawler, Lan Liao, Jianming Xu, Stephen O'Rahilly, Qingchun Tong, Uk10k Consortium, Inês Barroso, Bert W O'Malley, I Sadaf Farooqi, Yong Xu

Children’s Nutrition Research Center Staff Publications

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function …

Type 2 Diabetes Mellitus (T2dm) “Remission” In Non-Bariatric Patients 65 Years And Older, Srikanth Tangelloju, Bert B. Little, Robert J. Esterhay, Guy Brock, A. Scott Lajoie

Faculty and Staff Scholarship

Objective: To analyze the factors associated with type 2 diabetes mellitus (T2DM) “remission” in non-bariatric Medicare patients 65 years and older.

Research Design and Methods: A retrospective cohort analysis of a Medicare Advantage health plan was conducted using administrative data. An individual was identified as T2DM if the individual had: ≥ 2 medical claims for T2DM coded 250.xx excluding type 1 diabetes; or ≥ 2 pharmacy claims related to T2DM; or ≥ 2 combined medical claims, pharmacy claims for T2DM in 12 months. A T2DM individual was in “remission” if they had no T2DM related claims for more than 12 …

Small Molecule Kras Agonist For Mutant Kras Cancer Therapy., Ke Xu, Dongkyoo Park, Andrew T Magis, Jun Zhang, Wei Zhou, Gabriel L Sica, Suresh S Ramalingam, Walter J Curran, Xingming Deng

Articles, Abstracts, and Reports

BACKGROUND: Lung cancer patients with KRAS mutation(s) have a poor prognosis due in part to the development of resistance to currently available therapeutic interventions. Development of a new class of anticancer agents that directly targets KRAS may provide a more attractive option for the treatment of KRAS-mutant lung cancer.

RESULTS: Here we identified a small molecule KRAS agonist, KRA-533, that binds the GTP/GDP-binding pocket of KRAS. In vitro GDP/GTP exchange assay reveals that KRA-533 activates KRAS by preventing the cleavage of GTP into GDP, leading to the accumulation of GTP-KRAS, an active form of KRAS. Treatment of human lung cancer …

Histological Chorioamnionitis Induces Differential Gene Expression In Human Cord Blood Mononuclear Leukocytes From Term Neonates., Suhita Gayen Nee’ Betal, Swati Murthy, Michael Favara, Gina Fong, Joanna Chan, Sankar Addya, Thomas H. Shaffer, Jay S. Greenspan, Vineet Bhandari, Irfan Rahman, Zubair H. Aghai

Department of Pediatrics Faculty Papers

Histological chorioamnionitis (HCA) is an infection of fetal membranes and complicates 5.2% to 28.5% of all live births. HCA is associated with increased mortality and morbidity in both premature and term neonates. Exposure to HCA may have long-term consequences, including an increased risk for allergic disorders and asthma later in childhood, the mechanism(s) of which are still not yet well understood. The objective of this study was to determine the mRNA transcriptome of cord blood mononuclear leukocytes from term neonates to identify key genes and pathways involved in HCA. We found 366 differentially expressed probe IDs with exposure to HCA …

Body Mass Index In Multiple Sclerosis Modulates Ceramide-Induced Dna Methylation And Disease Course, Kamilah Castro, Achilles Ntranos, Mario Amatruda, Maria Petracca, Peter Kosa, Emily Y. Chen, Johannes Morstein, Dirk Trauner, Corey T. Watson, Michael A. Kiebish, Bibiana Bielekova, Matilde Inglese, Ilana Katz Sand, Patricia Casaccia

Advanced Science Research Center

Background: Multiple Sclerosis (MS) results from genetic predisposition and environmental variables, including elevated Body Mass Index (BMI) in early life. This study addresses the effect of BMI on the epigenome of monocytes and disease course in MS.

Methods: Fifty-four therapy-naive Relapsing Remitting (RR) MS patients with high and normal BMI received clinical and MRI evaluation. Blood samples were immunophenotyped, and processed for unbiased plasma lipidomic profiling and genome-wide DNA methylation analysis of circulating monocytes. The main findings at baseline were validated in an independent cohort of 91 therapy-naïve RRMS patients. Disease course was evaluated by a two-year longitudinal follow up …

A Case Of Creutzfeldt-Jakob Disease Presenting With Depression And Anxiety, Kathryn B. Bartlett Do, Kathleen E. Kane Md, Bryan G. Kane Md, Kevin Weaver D.O.,Facoep, Gavin C. Barr Jr. Md

Department of Emergency Medicine

No abstract provided.

Rsv-Encoded Ns2 Promotes Epithelial Cell Shedding And Distal Airway Obstruction, R. M. Liesman, U. J. Buchholz, C. L. Luongo, A. D. Proia, J. P. Divicenzo, P. L. Collins, R. J. Pickles

Osteopathic Medicine, Jerry M. Wallace School of

Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably …