Medicine and Health Sciences Commons^™

Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia Mcauliffe

Department of Biological Sciences Publications

The vast majority of clinical human listeriosis cases are caused by serotype 1/2a, 1/2b, 1/2c, and 4b isolates of Listeria monocytogenes. The ability of L. monocytogenes to establish a systemic listeriosis infection within a host organism relies on a combination of genes that are involved in cell recognition, internalization, evasion of host defenses, and in vitro survival and growth. Recently, whole genome sequencing and comparative genomic analysis have proven to be powerful tools for the identification of these virulence-associated genes in L. monocytogenes. In this study, two serotype 1/2b strains of L. monocytogenes with analogous isolation sources, but …

Predicting Rift Valley Fever Inter-Epidemic Activities And Outbreak Patterns: Insights From A Stochastic Host-Vector Model, Sansao A. Pedro, Shirley Abelman, Henri E.Z. Tonnang

All Peer-Reviewed Publications

Rift Valley fever (RVF) outbreaks are recurrent, occurring at irregular intervals of up to 15 years at least in East Africa. Between outbreaks disease inter-epidemic activities exist and occur at low levels and are maintained by female Aedes mcintoshi mosquitoes which transmit the virus to their eggs leading to disease persistence during unfavourable seasons. Here we formulate and analyse a full stochastic host-vector model with two routes of transmission: vertical and horizontal. By applying branching process theory we establish novel relationships between the basic reproduction number, R0, vertical transmission and the invasion and extinction probabilities. Optimum climatic conditions and presence …

Myofilament Calcium Sensitivity: Consequences Of The Effective Concentration Of Troponin I, Jalal K. Siddiqui, Svetlana B. Tikunova, Shane D. Walton, Bin Liu, Meredith Meyer, Pieter P. De Tombe, Nathan Neilson, Peter M. Kekenes-Huskey, Hussam E. Salhi, Paul M.L. Janssen, Brandon J. Biesiadecki, Jonathan P. Davis

Chemistry Faculty Publications

Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to …

Tx-004hr Vaginal Estradiol Has Negligible To Very Low Systemic Absorption Of Estradiol., David F Archer, Ginger D Constantine, James A Simon, Harvey Kushner, Philip Mayer, Brian Bernick, Shelli Graham, Sebastian Mirkin, Rejoice Study Group.

Obstetrics and Gynecology Faculty Publications

OBJECTIVE: To evaluate the pharmacokinetics of TX-004HR vaginal estradiol softgel capsules when used for treating moderate-to-severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy.

METHODS: A substudy of the REJOICE trial (multicenter, double-blind, placebo-controlled, phase 3) evaluated the pharmacokinetics of 4, 10, and 25-μg TX-004HR doses once/d for 2 weeks, followed by twice/wk for 10 weeks. Serum samples obtained at 2, 4, 6, 10, and 24 hours postdose on days 1 and 14, and once on day 84, were analyzed for area under the serum concentration-time curve, tmax, Cmin, Cavg, and Cmax for estradiol, estrone, and estrone conjugates.

RESULTS: …

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders Associated With Thyroglobulin Gene Mutations, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siffo, Carina M. Rivolta

Pharmacy Faculty Articles and Research

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenital hypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns. The TG gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. The human TG mRNA is 8.5 Kb long and the preprotein monomer is composed of a 19 amino acids signal peptide followed by a 2749 residues polypeptide. Until now, one hundred seventeen deleterious mutations in the human TG gene have been identified and characterized, originating structural changes in the protein that alter the normal protein folding, assembly and …

Concerns About Justification For Fetal Genome Sequencing, Leslie Francis

Utah Law Faculty Scholarship

The proposal by Chen and Wasserman (2017) contributes to a long-standing debate about the scope of prenatal screening services. With realistic prospects of fetal genome-scale sequencing from noninvasive maternal blood sampling (NIPW), their framework is timely. However, we outline a number of concerns regarding this approach, ranging from the philosophical to the social and clinical. A key concern in this literature is that the framework lacks a clear philosophical foundation. Despite the long history of prenatal diagnosis (PND), a central question remains regarding the core justification for these services.

Geographical Incidence Of Antimicrobial Resistant Gonorrhea, Christofer A. Rodriguez

Master's Projects and Capstones

Evolving throughout the last century, Gonorrhea has become a superbug, becoming difficult to treat. As the second most commonly reported notifiable disease, gonorrhea rates have been increasing, despite efforts in prevention and treatment. Populations at risk are mainly MSM and FSW. In 2015, men’s gonorrhea rates in the United States were higher compared to women, at 140.9 and 107.2 per 100,000 population, respectively. Illinois has consecutively had higher rates of infection compared to the US, at 133.5 per 100,000 population compared to the US rate of 123.9 per 100,000 population. The surveillance of gonococcal isolate resistance to current antimicrobials began …

Selective Suppression Of The Α Isoform Of P38 Mapk Rescues Late-Stage Tau Pathology, Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N. Kokiko-Cochran, Saktimayee M. Roy, Linda J. Van Eldik, D. Martin Watterson, Bruce T. Lamb, Kiran Bhaskar

Sanders-Brown Center on Aging Faculty Publications

Background: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results: First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 …

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10^–7) in the discovery panel …

Pharmacotherapeutic Considerations For Individuals With Down Syndrome, Erik Hefti

Harrisburg University Faculty Works

Down syndrome (DS; trisomy 21) is the most common survivable disorder due to aneuploidy. Individuals with DS may experience multiple comorbid health problems including congenital heart defects, endocrine abnormalities, skin and dental problems, seizure disorders, leukemia, dementia, and obesity. These associated conditions may necessitate pharmacotherapeutic management with various drugs. The complex pathobiology of DS may alter drug disposition and drug response in some individuals. For example, reports have documented increased rates of adverse drug reactions in patients with DS treated for leukemia and dementia. Intellectual disability resulting from DS may impact adherence to medication regimens. In this review, we highlight …

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

Seeing The Invisible: Revealing Atrial Ablation Lesions Using Hyperspectral Imaging Approach, Narine Muselimyan, Luther Swift, Huda Asfour, Tigran Chahbazian, Ramesh Mazhari, Marco Mercader, Narine Sarvazyan

Pharmacology and Physiology Faculty Publications

Background

Currently, there are limited means for high-resolution monitoring of tissue injury during radiofrequency ablation procedures.

Objective

To develop the next generation of visualization catheters that can reveal irreversible atrial muscle damage caused by ablation and identify viability gaps between the lesions.

Methods

Radiofrequency lesions were placed on the endocardial surfaces of excised human and bovine atria and left ventricles of blood perfused rat hearts. Tissue was illuminated with 365nm light and a series of images were acquired from individual spectral bands within 420-720nm range. By extracting spectral profiles of individual pixels and spectral unmixing, the relative contribution of ablated …

Amaurosis Fugax Due To Pleomorphic Sarcoma, Sheila Pabon, Katherine Williams, Marena Patronas

Ophthalmology Faculty Publications

Purpose

This report describes a case of amaurosis fugax due to a rare primary cardiac sarcoma.

Observations

A patient who was recently diagnosed with left atrial pleomorphic sarcoma presented with a chief complaint of multiple episodes of intermittent vision loss in the right eye during the course of radiation therapy.

Conclusions and importance

The authors postulate emboli from the left atrial sarcoma entered systemic circulation and subsequently caused brief episodes of transient occlusion to retinal, ophthalmic and/or ciliary arteries leading to momentary retinal hypoxia. We believe this is a novel finding, previously unreported in the literature, of transient embolic occlusion …

Iris Abscess A Rare Presentation Of Intravenous Drug Abuse Associated, Jonathan Pierce, Nisha Warrier, Christina Antonopoulos, Nicole Siegel, Deeba Husain

Ophthalmology Faculty Publications

Purpose: To describe an unusual case of intravenous drug abuse associated endogenous endophthalmitis presenting with an iris abscess.

Observations: A 30-year old female with history of intravenous drug use presented with a two-week history of redness and blurry vision in the right eye. An initial diagnosis of anterior uveitis was made. However, she worsened on topical steroids and mydriatics. She was found to have a hypopyon and an iris abscess. She received broad spectrum antibiotic and antifungal treatment with voriconazole, this lead to significant clinical improvement. She was discharged on oral fluconazole and lost to follow up. The patient was …

Epidemiology Of White Spot Syndrome Virus In The Daggerblade Grass Shrimp (Palaemonetes Pugio) And The Gulf Sand Fiddler Crab (Uca Panacea), Muhammad

Dissertations

Ever since the first outbreaks of White spot syndrome virus (WSSV), which causes White Spot Disease (WSD), in Asia in the early 1990s, the pathogen has been a major constraint to the profitability of the shrimp aquaculture industry across the globe. WSSV has a broad host range and is routinely detected in wild decapod crustaceans. In the present study, two common species in the tidal salt marsh along the northern coast of the Gulf of Mexico, the daggerblade grass shrimp (Palaemonetes pugio) and the Gulf sand fiddler crab (Uca panacea), were investigated for their role as …

A Microbiomic Approach To The Characterization Of The Impacts And Influences Of Viral, Bacterial, And Harmful Algal Bloom Toxins On The Bottlenose Dolphin, Corey David Russo

Dissertations

As apex predators that display high site fidelity Tursiops truncatus (bottlenose dolphin) are indicators of marine ecosystem health. Bottlenose dolphins, additionally, display pathogenesis and immune response similar to that of humans. Humans and coastal bottlenose dolphins, in particular, are constantly exposed to the same industrial, agricultural and domestic toxins and pathogens, contaminants and pollutants. Thus, studies on the bottlenose dolphin are also valuable in bridging the gap between ocean and human health. Bottlenose dolphins are susceptible to viral bacterial and toxin infection. Infection in the bottlenose dolphin manifests itself in the form of mass stranding events, unusual mortality events, chronic …

Is Current Evidence That Avoidance Of Inhalation Agents And Opioids May Decrease Metastasis Strong Enough For Crnas To Show A Willingness To Change Practice?, Michael Wesley Tillman

Doctoral Projects

Metastasis following the surgical resection of primary site breast cancer is a medical issue, which plagues mastectomy patients. The intention of this project was to synthesize current literature in order to make a presentation and disseminate it to Certified Registered Nurse Anesthetists (CRNAs) in southern Mississippi and assess the providers' willingness to change practice. CRNAs took part in a Qualtrics survey after viewing a PowerPoint presentation of evidence regarding anesthesia and metastasis. The presentation illustrated the anesthetic techniques and pharmacological agents utilized, which either mitigate or potentiate a patient's risk for metastasis. The survey assessed for a willingness to change …

Xpert Mtb/Rif Assay Shows Faster Clearance Of Mycobacterium Tuberculosis Dna With Higher Levels Of Rifapentine Exposure., A Jayakumar, R M Savic, C K Everett, Debra Benator, D Alland, C M Heilig, M Weiner, S O Friedrich, N A Martinson, A Kerrigan, C Zamudio, S V Goldberg, W C Whitworth, J L Davis, P Nahid

Medicine Faculty Publications

The Xpert MTB/RIF assay is both sensitive and specific as a diagnostic test. Xpert also reports quantitative output in cycle threshold (CT) values, which may provide a dynamic measure of sputum bacillary burden when used longitudinally. We evaluated the relationship between Xpert CT trajectory and drug exposure during tuberculosis (TB) treatment to assess the potential utility of Xpert CT for treatment monitoring. We obtained serial sputum samples from patients with smear-positive pulmonary TB who were consecutively enrolled at 10 international clinical trial sites participating in study 29X, a CDC-sponsored Tuberculosis Trials Consortium study evaluating the tolerability, safety, and antimicrobial activity …

Strategies For Enriching Variant Coverage In Candidate Disease Loci On A Multiethnic Genotyping Array, Stephanie Bien, Genevieve L. Wojcik, Niha Zubair, Christopher Gignoux, Alicia R. Martin, Lisa W. Martin, Page Study Investigators

Medicine Faculty Publications

Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II), Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations. To meet this goal, the Multi-Ethnic Genotyping Array (MEGA) …

Pertussis-Associated Pneumonia In Infants And Children From Low- And Middle-Income Countries Participating In The Perch Study., Breanna Barger-Kamate, Maria Deloria Knoll, E Wangeci Kagucia, Christine Prosperi, Henry C Baggett, Daniel E. Park, +31 Additional Authors

Epidemiology Faculty Publications

BACKGROUND:  Few data exist describing pertussis epidemiology among infants and children in low- and middle-income countries to guide preventive strategies.

METHODS:  Children 1-59 months of age hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 African and Asian countries and similarly aged community controls were enrolled in the Pneumonia Etiology Research for Child Health study. They underwent a standardized clinical evaluation and provided nasopharyngeal and oropharyngeal swabs and induced sputum (cases only) for Bordetella pertussis polymerase chain reaction. Risk factors and pertussis-associated clinical findings were identified.

RESULTS:  Bordetella pertussis was detected in 53 of 4200 (1.3%) cases …

Analysis Of Hiv Diversity In Hiv-Infected Black Men Who Have Sex With Men (Hptn 061), Iris Chen, Gordon Chau, Jing Wang, William Clarke, Mark A. Marzinke, Manya Magnus, +14 Additional Authors

Epidemiology Faculty Publications

Background

HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study.

Methods

A high resolution melting (HRM) diversity assay was used to measure diversity in six regions of the HIV genome: two in gag, one in pol, and three in env. HIV diversity was analyzed for 146 men who were HIV infected at study enrollment, including three with acute infection and 13 with recent infection (identified …

Cost Of Care For Hospitalized Patients With Pulmonary Mycobacterial Diseases In The United States., Mary Beth Wells Allen

Electronic Theses and Dissertations

Background: Pulmonary mycobacterial diseases describe both tuberculosis (TB) and nontuberculous mycobacteria (NTM). Few data are available measuring the cost burden of mycobacterial diseases on the national level. The purpose of this study was to evaluate the cost burden and measure emerging trends in hospitalization of pulmonary TB and NTM in the US from 2001 through 2012. Methods: This study was a retrospective community based cost analysis of hospitalized patients with a principal diagnosis of pulmonary mycobacterial diseases from 2001 through 2012. Data for pulmonary TB and NTM were retrieved from the Healthcare Cost and Utilization Project (HCUP), US Department of …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Improving Foot Care And Kidney Disease Screening Through Implementation Of American Diabetes Association Standards–2016 In The Primary Care Setting, Maricela Hernandez

Doctor of Nursing Practice

The purpose of this quality improvement project was to increase adherence to the American Diabetes Association Standards of Medical Care in Diabetes—2016 recommendations for foot care and kidney disease screening for patients with diabetes mellitus type II in a primary care setting. Diabetes mellitus type II affects approximately 18.9-19.9 million, or 90-95%, of all diagnosed cases in the United States. Early detection and management decrease the risk of developing microvascular complications that may lead to neuropathy and nephropathy. Adults with diabetes mellitus type II, 20 years of age and older, accounted for approximately 73,000 non-traumatic lower-extremity amputations in 2011. Diabetes …

Vitamin D Supplementation To Prevent Acute Respiratory Tract Infections: Systematic Review And Meta-Analysis Of Individual Participant Data, Adrian R. Martineau, David A. Jolliffe, Richard L. Hooper, Lauren Greenberg, John F. Aloia, Peter Bergman, Gal Dubnov-Raz, Susanna Esposito, Davaasambuu Ganmaa, Adit A. Ginde, Emma C. Goodall, Cameron C. Grant, Christopher J. Griffiths, Wim Janssens, Ilkka Laaksi, Semira Manaseki-Holland, David Mauger, David R. Murdoch, Rachel Neale, Judy R. Rees

Dartmouth Scholarship

OBJECTIVES To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. DESIGN Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. DATA SOURCES Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a …

Impact Of Dietary Modification On Aflatoxicosis In Poultry, Xi Chen

Open Access Dissertations

Aflatoxin contamination in feed and feed ingredients is of high worldwide prevalence, posing serious risks to the livestock industry. A series of studies were conducted to better understand the comprehensive impact of aflatoxicosis and its interrelationships with dietary modifications in broiler chicks and ducks. Results of these studies emphasize the many factors that the severity of aflatoxicosis depends on, including animal species, age, presence of mycotoxin adsorbent, and concentration of major dietary nutrients. Exposure to 2 mg/kg cultured AFB1 led to reduced feed intake, BW gain, depressed feed efficiency, increased relative liver weight, negatively affected serum measures and complement activity, …

Mapping The Geography Of Child Mortality: A Key Step In Addressing Disparities, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

No abstract provided.

Arkansas Animal Science Department Report 2016, Paul Beck, Jason Apple, Shane Gadberry, Beth Kegley, Charles Rosenkrans Jr.

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Pro-Inflammatory Cytokines Promote Viral Replication And Cell Cycle Mediators In Arenavirus-Induced Hepatitis., Gretchen E. Holz

Electronic Theses and Dissertations

Lassa virus (LASV) is an arenavirus and causative agent of Lassa fever (LF), a viral hemorrhagic fever in West Africa for which there is no vaccine. Lymphocytic choriomeningitis virus (LCMV), is used as a surrogate to mimic LASV-induced liver pathology. LCMV-WE, not LCMV-ARM, causes disease in primates and mice characterized by hepatitis, high viral load, hepatocyte proliferation, and upregulated proliferative triggers (e.g. TNF-α, IL-6 ). We hypothesize LCMV-WE induces pathological hepatocyte proliferation via pro-inflammatory triggers (TNF-α, IL-6) from macrophages, leading to: increased viral replication, modulated cell cycle, and arrested cell cycle. RAW 264.7 macrophages and AML-12 hepatocytes, were used as …

Establishing A Clinically Relevant Mouse Model Of Human Aml To Test Novel Transmethylation Inhibitors., Aditya Barve

Electronic Theses and Dissertations

Acute myeloid leukemia (AML) is a highly heterogeneous clonal disorder characterized by an accumulation of malignant immature myeloid progenitors in the bone marrow (BM) that hinder normal hematopoiesis. Patient AML exhibits a dramatic heterogeneity in terms of cytogenetics, disease morphology, and associated prognoses and/or chemotherapeutic sensitivity. Thus it becomes clearly evident that the investigation of novel therapeutics for AML will require model systems that are capable of recapitulating this stark heterogeneity in a patient specific manner. Furthermore, it is now understood that the surrounding bone marrow (BM) microenvironment and supporting cells play a critical role in leukemic progression as well …