Digital Commons Network^™

Heat Waves And Heat-Related Mortality In East Tennessee, Taiwo Adesoba

Electronic Theses and Dissertations

Heat waves represent a public health challenge that requires multiple responses and warnings to protect vulnerable populations. Although studies have reported an increasing trend of heat wave occurrence in many areas of the world, no clear trend exists in East Tennessee. Using data from Parameter-elevated Relationships on Independent Slope Models (PRISM), CDC WONDER and the United States Census Bureau, the relationship between mortality rates and year was estimated during heat wave events between 1999 and 2010. Five heat wave definitions were tested. Overall, 2007 and 2010 stand out as the years with the highest number of heat wave days in …

The Distinct Expressions Of Integrins Αdβ2 And Αmβ2 Differently Regulate Macrophage Migration In 3d Matrix In Vitro And In Tissue During Inflammation, Kui Cui

Electronic Theses and Dissertations

Chronic inflammation is an essential mechanism during the development of cardiovascular and metabolic diseases. The outcome of diseases depends on the balance between the migration and accumulation of macrophages in damaged tissues. Macrophage motility is highly regulated by adhesive receptors, integrins. Namely, intermediate expression of integrin supports macrophage migration, while a high integrin density inhibits it. Our studies are focused on evaluation of the contribution of related integrins α_Dβ₂ and α_Mβ₂ to macrophage migration and development of chronic inflammation.

We found that integrin α_Dβ₂ is upregulated on M1-macrophages in vitro and …

2018-2019 - Graduate Council Annual Report, College Of Graduate And Continuing Studies, East Tennessee State University

Graduate Council Agendas and Minutes

No abstract provided.

2018-2019 Department Of Surgery Scholarly Activity Report, Quillen College Of Medicine, East Tennessee State University

Quillen College of Medicine Scholarly Activity Reports

No abstract provided.

2018-2019 Department Of Biomedical Sciences Scholarly Activity Report, Quillen College Of Medicine, East Tennessee State University

Quillen College of Medicine Scholarly Activity Reports

No abstract provided.

Topological Dna Damage, Telomere Attrition And T Cell Senescence During Chronic Viral Infections, Yingjie Ji, Xindi Dang, Lam Ngoc Thao Nguyen, Lam Nhat Nguyen, Jaun Zhao, Dechao Cao, Sushant Khanal, Madison Schank, Xiao Y. Wu, Zheng D. Morrison, Yue Zou, Mohamed El Gazzar, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

Background: T cells play a key role in controlling viral infections; however, the underlying mechanisms regulating their functions during human viral infections remain incompletely understood. Here, we used CD4 T cells derived from individuals with chronic viral infections or healthy T cells treated with camptothecin (CPT) - a topoisomerase I (Top 1) inhibitor - as a model to investigate the role of DNA topology in reprogramming telomeric DNA damage responses (DDR) and remodeling T cell functions.

Results: We demonstrated that Top 1 protein expression and enzyme activity were significantly inhibited, while the Top 1 cleavage complex (TOP1cc) was …

Disruption Of Telomere Integrity And Dna Repair Machineries By Kml001 Induces T Cell Senescence, Apoptosis, And Cellular Dysfunctions, Dechao Cao, Juan Zhao, Lan N. Nguyen, Lam N. T. Nguyen, Sushant Khanal, Xindi Dang, Madison Schank, Bal K. Chand Thakuri, Xiao Y. Wu, Zheng D. Morrison, Mohamed El Gazzar, Yue Zou, Shunbin Ning, Ling Wang, Jonathan P. Moorman, Zhi Q. Yao

ETSU Faculty Works

T cells in chronic viral infections are featured by premature aging with accelerated telomere erosion, but the mechanisms underlying telomere attrition remain unclear. Here, we employed human CD4 T cells treated with KML001 (a telomere-targeting drug) as a model to investigate the role of telomere integrity in remodeling T cell senescence. We demonstrated that KML001 could inhibit cell proliferation, cytokine production, and promote apoptosis via disrupting telomere integrity and DNA repair machineries. Specifically, KML001-treated T cells increased dysfunctional telomere-induced foci (TIF), DNA damage marker γH2AX, and topoisomerase cleavage complex (TOPcc) accumulation, leading to telomere attrition. Mechanistically, KML001 compromised telomere integrity …

Building A Better Book Widget: Using Alma Analytics To Automate New Book Discovery, Travis Clamon

ETSU Faculty Works

Are we doing enough to market newly acquired book titles? Libraries purchase and subscribe to many new book titles each year, both print and electronic. However, we rely on the expectation that users will periodically search our systems to discover newly acquired titles. Static lists and displays have been traditional marketing methods for libraries, but require tedious time and effort to maintain. Without a practical solution for an academic library, East Tennessee State University developed an automated process to generate book widgets utilizing data from Alma Analytics. These widgets are now deployed in our subject guides, website, and on our …

Synthesis And Evaluation Of 1,2,4-Oxadiazolidinones: The Search For A Potential Non-Β-Lactam Β-Lactamase Inhibitors., Chimdi Eke Kalu

Electronic Theses and Dissertations

β-lactam antibiotics have been the most widely used drug of choice to combat infectious disease caused by bacteria. Unfortunately, their effectiveness is drastically threatened by bacterial β-lactamases. β-lactamases is responsible for the resistance to most antibiotic drugs. For decades, β-lactam β-lactamases inhibitors have been used to reduce bacterial resistance; however, in this study 1,2,4-oxadiazolidinone derivatives as a non-β-lactam β-lactamases inhibitor against TEM-1 and P99 β-lactamases. The significance of oxadiazolidinone is the prominent five-membered ring scaffold in its structure, which is configurationally stable and present in other biologically active compounds such as linezolid and avibactam. Oxadiazolidinones were synthesized by treating nitrones …

Generalizations Of The Arcsine Distribution, Rebecca Rasnick

Electronic Theses and Dissertations

The arcsine distribution looks at the fraction of time one player is winning in a fair coin toss game and has been studied for over a hundred years. There has been little further work on how the distribution changes when the coin tosses are not fair or when a player has already won the initial coin tosses or, equivalently, starts with a lead. This thesis will first cover a proof of the arcsine distribution. Then, we explore how the distribution changes when the coin the is unfair. Finally, we will explore the distribution when one person has won the first …

Role Of Atm In T Cell Dysfunction During Chronic Viral Infections, Juan Zhao

Electronic Theses and Dissertations

Hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection leads to a phenomenon of inflammaging, in which chronic infection or inflammation induces an immune aged phenotype with T cell dysfunction. Thus, HCV or HIV infection has been deemed as a model to study the mechanisms of T cell infammaging and viral persistence in humans. In this dissertation, T cell homeostasis, DNA damage and repair machineries were investigated in patients with chronic HCV or HIV infection at risk for inflammaging. We found a significant depletion in CD4 T cells, which was correlated with their apoptosis in chronically HCV/HIVinfected patients, compared …

Telomeric Dna Damage And Repair Machineries In Hiv Infection, Lam Nguyen

Electronic Theses and Dissertations

In this thesis, we investigated T cell homeostasis and DNA damage repair machineries in HIV infection. We found that the frequencies of CD4T cells were low, which is associated with cell apoptosis in HIV patients compared to healthy subjects. Importantly, these events were closely correlated to the increase in T cell exhaustion, senescence, DNA damage, and telomere attrition. Mechanistically, while the DNA damage sensors Mer11, Rad50, and NBS1 (MRN) complexes remained intact, the ataxia-telangiectasia mutated (ATM) kinase and its downstream checkpoint kinase 2 (CHK2) were significantly inhibited during HIV infection. Additionally, telomeric repeat-binding factor 2 (TRF2) that functions to protect …

Investigation Of Optimal Dosing Strategies For Ertapenem For Varying Bmi Using Mathematical Modeling, Bethany Jewett

Undergraduate Honors Theses

Previous research suggests that the efficacy of Ertapenem, a carbapenem antibiotic administered intravenously, is related to a patient’s body mass index. Using an existing physiologically based pharmacokinetic (PBPK) model for Ertapenem, we constructed a least squares inverse problem to determine an optimal dose for males with varying body weights and heights. The criteria for an optimal dose was based upon pharmacokinetic and pharmacodynamic (PK/PD) parameters calculated for a male with a body height of 175 cm and a weight of 72 kg. We also adjusted dosing intervals to ensure that effective concentration of drug between doses was the same for …

Isolation, Analysis, And Partial Characterization Of An Inhibitor Of Neisseria Gonorrhoeae, Natania Paul

Undergraduate Honors Theses

There is an emerging threat of Neisseria gonorrhoeae strains that are resistant to all antibiotics. Because of this, the purpose of this research is to isolate, analyze, and partially characterize a new inhibitor(s) of N. gonorrhoeae. Since there is an unknown molecule secreted by Candida albicans that inhibits N. gonorrhoeae, this molecule can be partially characterized using ¹H NMR Spectroscopy to assist in the development of a new antibiotic compound. It was hypothesized that quorum-sensing molecules, trans, trans- farnesol, tyrosol, phenylethyl alcohol, and tryptophol, could be possible candidates for the inhibitor. Because of this, ¹H …

P62-Mediated Selective Autophagy Endows Virus-Transformed Cells With Insusceptibility To Dna Damage Under Oxidative Stress, Ling Wang, Mary E. A. Howell, Aryianna Sparks Wallace, Caroline Hawkins, Camri A. Nicksic, Carissa Kohne, Kenton H. Hall, Jonathan P. Moorman, Zhi Q. Yao, Shunbin Ning

ETSU Faculty Works

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that considerable levels of p62-mediated selective autophagy are spontaneously induced, and correlate with ROS-Keap1-NRF2 pathway activity, in virus-transformed cells. Inhibition of …

Synthesis And Evaluation Of 1,2,4-Oxadiazolidinones: The Search For Potential Non-Β-Lactam Β-Lactamase Inhibitors., Chimdi E. Kalu, Noah Lyons, Abbas G. Shilabin, Chimdi Kalu

Appalachian Student Research Forum

β-lactam antibiotics have been the most widely used drug of choice to combat infectious disease caused by bacteria. Unfortunately, the effectiveness of these antibiotics is drastically threatened by bacterial β-lactamases. β-lactamases are currently responsible for the resistance to most β-lactam antibiotic drugs. For decades, β-lactam β-lactamases inhibitors have been used to reduce bacterial resistance, however, in this study, we will employ the use of 1,2,4-oxadiazolidinone derivatives as a non-β-lactam β-lactamases inhibitor against TEM-1 and P99 β-lactamases. The significance of oxadiazolidinone is the prominent five-membered ring in its structure, which is configurationally stable and present in other biologically active compounds such …

Cardiovirology Clinic For Primary Prevention In Hiv Patients: A Quality Improvement Assessment, Jae G. Maeng, Stephen A. Geraci

Appalachian Student Research Forum

INTRODUCTION

With effective highly active antiretroviral therapy (HAART), individuals with human immunodeficiency virus (HIV) infection now enjoy life expectancies approaching those of uninfected individuals. Prolonged longevity has increased the prevalence of non-communicable comorbidities within the HIV patient population. HIV is a known independent risk factor for atherosclerotic cardiovascular disease (ASCVD), imparting a 1.5-2 -fold higher incidence of major adverse cardiovascular events (MACE) on infected patients. Deaths from ASCVD have increased as a result, despite a decline in total mortality. The Center of Excellence for HIV/AIDS care established a Cardiovirology Clinic (CvC) focused on providing primary and secondary preventative cardiovascular care …

Osteonecrosis Of Jaw: Common Etiologies, Uncommon Treatments, Utsab Panta, Adam Chan, Debalina Das

Appalachian Student Research Forum

Introduction

First described in 2002, osteonecrosis of the jaw (ONJ, or avascular necrosis of the jaw) is an uncommon but potentially serious side effect of treatment with bisphosphonates. Although typically identified in patients with multiple myeloma and other malignancies, a few cases have been reported in patients taking bisphosphonates - a potent drug class used in the treatment of osteoclast-mediated bone resorption issues, including postmenopausal osteoporosis, Paget's disease, multiple myeloma, and malignant hypercalcemia. The clinical diagnosis of ONJ can be obscured by jaw pain, abscess, swelling, and fistulas, but exposed bone is a distinctive sign. This reports a case of …

Toxoplasmosis In Immunocompetent Military Veteran With Overseas Field Deployment, Matthew Carpenter, Omer Shiekh, Jorge Diaz, Debalina Das, Yasmin Elshenawy

Appalachian Student Research Forum

Introduction: Toxoplasmosis is caused by infection with the protozoan Toxoplasma gondii (T. gondii), an obligate intracellular parasite. T. gondii infects a large portion of the world’s population, but uncommonly causes clinically significant disease. Those that are at greatest risk for more severe disease with toxoplasmosis are the immunologically impaired, fetuses, and newborns. T. gondii infection in immunocompetent patients can present as a self-limiting acute infection, or as an acute systemic disease. There are three main T. gondii genotypes, I, II, and III, with varying geographical prevalence. T. gondii is most commonly acquired via ingestion of infectious oocysts, from the …

Association Between Stigma And Intimate Partner Violence Among Newly Hiv-Diagnosed Chinese Men Who Have Sex With Men, Jie Yin, Na Wang, Bo Huang, Yuhua Ruan, K. Rivet Amico, Sten H. Vermund, Han-Zhu Qian, Shimin Zheng

Appalachian Student Research Forum

Introduction: Men who have sex with men (MSM) are more likely to experience Intimate partner violence (IPV) during their lifetime than heterosexual couples. HIV-status and related HIV stigma may play an important role in IPV within intimate partnerships among MSM. HIV- and MSM-related stigmas are common among Chinese MSM, yet there is sparse literature on IPV and its relationship with stigma in this vulnerable population. We evaluate the prevalence of IPV and its relationship with HIV- and MSM-related stigma among newly diagnosed HIV-infected MSM in Beijing, China.

Methods: Data were collected in the baseline survey among newly HIV-diagnosed Chinese MSM …

2019-April-11-It's 'Epidemic', University Marketing And Communications, East Tennessee State University

ETSU News

No abstract provided.

A Baker's Dozen Of Top Antimicrobial Stewardship Intervention Publications In 2017, Daniel B. Chastain, David B. Cluck, Kayla R. Stover, Katherine T. Lusardi, Ashley Marx, Sarah Green, Carmen Faulkner-Fennell, Michelle Turner, Elias B. Chahine, P. Brandon Bookstaver, Christopher M. Bland

ETSU Faculty Works

With an increasing number of antimicrobial stewardship-related articles published each year, attempting to stay current is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an "actionable" intervention for 2017. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the "actionable" intervention used by antimicrobial stewardship programs to provide key stewardship literature for training and teaching and identify potential intervention opportunities within their institutions.

2019-03-04-New Biomedical Sciences Funding, University Marketing And Communications, East Tennessee State University

Accent [newsletter]

No abstract provided.

2019-February-27-Vaccine Research, University Marketing And Communications, East Tennessee State University

ETSU News

No abstract provided.

2019 February 22 - Board Of Trustees Academic And Student Affairs Committee, Board Of Trustees, East Tennessee State University

Board of Trustees Agendas and Minutes

No abstract provided.

Panton-Valentine Leucocidin Is The Key Determinant Of Staphylococcus Aureus Pyomyositis In A Bacterial Gwas, Bernadette C. Young, Sarah G. Earle, Sona Soeng, Poda Sar, Varun Kumar, Songly Hor, Vuthy Sar, Rachel Bousfield, Nicholas D. Sanderson, Leanne Barker, Nicole Stoesser, Katherine R.W. Emary, Christopher M. Parry, Emma K. Nickerson, Paul Turner, Rory Bowden, Derrick Crook, David Wyllie, Nicholas P.J. Day, Daniel J. Wilson, Catrin E. Moore

ETSU Faculty Works

Pyomyositis is a severe bacterial infection of skeletal muscle, commonly affecting children in tropical regions, predominantly caused by Staphylococcus aureus. To understand the contribution of bacterial genomic factors to pyomyositis, we conducted a genome-wide association study of S. aureus cultured from 101 children with pyomyositis and 417 children with asymptomatic nasal carriage attending the Angkor Hospital for Children, Cambodia. We found a strong relationship between bacterial genetic variation and pyomyositis, with estimated heritability 63.8% (95% CI 49.2-78.4%). The presence of the Panton-Valentine leucocidin (PVL) locus increased the odds of pyomyositis 130-fold (p=10- 17.9 ). The signal of association mapped both …

Synthesis And Encapsulation Of A New Zinc Phthalocyanine Photosensitizer Into Polymeric Nanoparticles To Enhance Cell Uptake And Phototoxicity, Nahid Mehraban, Phillip R. Musich, Harold S. Freeman

ETSU Faculty Works

Efforts to enhance the utility of photodynamic therapy as a non-invasive method for treating certain cancers have often involved the design of dye sensitizers with increased singlet oxygen efficiency. More recently, however, sensitizers with greater selectivity for tumor cells than surrounding tissue have been targeted. The present study provides an approach to the modification of the known photosensitizer zinc phthalocyanine (ZnPc), to enhance its solubility and delivery to cancer cells. Targeting a photosensitizer to the site of action improves the efficacy of the sensitizer in photodynamic therapy. In this work we used PLGA-b-PEG to encapsulate a new zinc phthalocyanine derivative, …

Gattonrx Magazine - 2019, Bill Gatton College Of Pharmacy, East Tennessee State University

GattonRX Magazine

No abstract provided.

Dendritic Cell-Derived Tslp Negatively Regulates Hif-1Α And Il-1Β During Dectin-1 Signaling, Matthew J. Elder, Steve J. Webster, Timothy J. Fitzmaurice, Aran S.D. Shaunak, Martin Steinmetz, Ronnie Chee, Ziad Mallat, E. Suzanne Cohen, David L. Williams, J. S. Hill Gaston, Jane C. Goodall

ETSU Faculty Works

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Thymic stromal lymphopoietin (TSLP) is a functionally pleotropic cytokine important in immune regulation, and TSLP dysregulation is associated with numerous diseases. TSLP is produced by many cell types, but has predominantly been characterized …

A Qualitative Research Synthesis Of Contextual Factors Contributing To Female Overweight And Obesity Over The Life Course In Sub-Saharan Africa, Ifeoma Ozodiegwu, Mary Ann Littleton, Christian Nwabueze, Oluwaseun Famojuro, Megan Quinn, Rick L. Wallace, Hadii M. Mamudu

ETSU Faculty Works

Objective: Adult women are disproportionately affected by overweight and obesity in Sub-Saharan African (SSA) countries. Existing evidence on the sociocultural context remains unconsolidated. In this qualitative research synthesis, we aggregate research literature on contextual factors that potentially predispose adult women and adolescent girls to overweight and obesity to inform research, policies and programs over the life course.

Methods: PubMed, CINAHL, PsychInfo, ProQuest Central, EMBASE, and Web of Science were searched to locate qualitative research articles conducted in SSA countries beginning in the year 2000. After assessment for eligibility and critical appraisal, 17 studies were included in the synthesis. Textual data …