Diseases Commons^™

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Pathological Tau Promotes Neuronal Damage By Impairing Ribosomal Function And Decreasing Protein Synthesis, Shelby Meier, Michelle Bell, Danielle N. Lyons, Jennifer Rodriguez-Rivera, Alexandria Ingram, Sarah N. Fontaine, Elizabeth Mechas, Jing Chen, Benjamin Wolozin, Harry Levine Iii, Haining Zhu, Jose F. Abisambra

Sanders-Brown Center on Aging Faculty Publications

One of the most common symptoms of Alzheimer's disease (AD) and related tauopathies is memory loss. The exact mechanisms leading to memory loss in tauopathies are not yet known; however, decreased translation due to ribosomal dysfunction has been implicated as a part of this process. Here we use a proteomics approach that incorporates subcellular fractionation and coimmunoprecipitation of tau from human AD and non-demented control brains to identify novel interactions between tau and the endoplasmic reticulum (ER). We show that ribosomes associate more closely with tau in AD than with tau in control brains, and that this abnormal association leads …

Two Sampling Methods Yield Distinct Microbial Signatures In The Nasopharynges Of Asthmatic Children., Marcos Pérez-Losada, Keith A. Crandall, Robert J. Freishtat

Pediatrics Faculty Publications

Background

The nasopharynx is a reservoir for pathogens associated with respiratory illnesses, such as asthma. Next-generation sequencing (NGS) has been used to characterize the nasopharyngeal microbiome during health and disease. Most studies so far have surveyed the nasopharynx as a whole; however, less is known about spatial variation (biogeography) in nasal microenvironments and how sampling techniques may capture that microbial diversity.

Findings

We used targeted 16S rRNA MiSeq sequencing and two different sampling strategies [nasal washes (NW) and nasal brushes (NB)] to characterize the nasopharyngeal microbiota in 30 asthmatic children. Nasal brushing is more abrasive than nasal washing and targeted …

Uncovering New Roles For The Aryl Hydrocarbon Receptor (Ahr) In Breast Cancer, Justin Kirk Tomblin

Theses, Dissertations and Capstones

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that is responsive to many exogenous and endogenous ligands. AHR is of particular interest in cancer, and has been shown to play roles in tumor progression. As such, it has received growing attention as a possible chemotherapeutic target. Obesity increases the risk of breast cancer, complicates treatment of breast cancer, and stimulates the growth of larger, more aggressive mammary tumors. Many breast tumors in obese women are estrogen receptor (ER)-positive and, while targeting hormone receptors like ER is beneficial, many obese women see a recurrence of their cancer after standard …

Rnai-Mediated Gene Knockdown By Microinjection In The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Ramesh Ratnappan, Jonathan Vadnal, Melissa Keaney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Parasitic nematodes threaten the health of humans and livestock and cause a major financial and socioeconomic burden to modern society. Given the widespread distribution of diseases caused by parasitic nematodes there is an urgent need to develop tools that will elucidate the genetic complexity of host-parasite interactions. Heterorhabditis bacteriophora is a parasitic nematode that allows simultaneous monitoring of nematode infection processes and host immune function, and offers potential as a tractable model for parasitic nematode infections. However, molecular tools to investigate these processes are required prior to its widespread acceptance as a robust model organism. In this paper we …

Discovery Of Metabolic Biomarkers For Duchenne Muscular Dystrophy Within A Natural History Study., Simina M. Boca, Maki Nishida, Michael Harris, Shruti Rao, Amrita Cheema, Kirandeep Gill, Haeri Seol, Lauren P. Morgenroth, Erik Henricson, Craig M. Mcdonald, Jean K. Mah, Paula R. Clemens, Eric P. Hoffman, Yetrib Hathout, Subha Madhavan

Pediatrics Faculty Publications

Serum metabolite profiling in Duchenne muscular dystrophy (DMD) may enable discovery of valuable molecular markers for disease progression and treatment response. Serum samples from 51 DMD patients from a natural history study and 22 age-matched healthy volunteers were profiled using liquid chromatography coupled to mass spectrometry (LC-MS) for discovery of novel circulating serum metabolites associated with DMD. Fourteen metabolites were found significantly altered (1% false discovery rate) in their levels between DMD patients and healthy controls while adjusting for age and study site and allowing for an interaction between disease status and age. Increased metabolites included arginine, creatine and unknown …

The Clinical Outcome Study For Dysferlinopathy, Elizabeth Harris, Catherine Bladen, Anna Mayhew, Meredith James, Karen Bettinson, Avital Cnaan, The Jain Cos Consortium

Pediatrics Faculty Publications

Objective: To describe the baseline clinical and functional characteristics of an international cohort of 193 patients with dysferlinopathy.

Methods: The Clinical Outcome Study for dysferlinopathy (COS) is an international multicenter study of this disease, evaluating patients with genetically confirmed dysferlinopathy over 3 years. We present a cross-sectional analysis of 193 patients derived from their baseline clinical and functional assessments.

Results: There is a high degree of variability in disease onset, pattern of weakness, and rate of progression. No factor, such as mutation class, protein expression, or age at onset, accounted for this variability. Among patients with clinical diagnoses of Miyoshi …

Clinical Assessment Of Fatigability In Multiple Sclerosis: A Shift From Perception To Performance., Bryant A Seamon, Michael O. Harris-Love

Exercise and Nutrition Sciences Faculty Publications

No abstract provided.

Evaluating Human Cell Survival And Dna Damage After Exposure To Various Amounts Of Chlorine Dioxide And Exploring Its Use As A Potential Cancer Chemotherapy Agent, Niuska Mariana Alvarez Fuenmayor

SURF - Summer Undergraduate Research Fellowship Projects

Chlorine Dioxide (ClO₂) is a synthetic, green-yellowish gas with a chlorine-like, irritating odor that is used for the treatment of drinking water and food preservation. The aim of this study was to evaluate the genotoxic potential of the chlorine dioxide in mammalian cells and to determine what dose of ClO₂ is tolerable by normal cells and cells with aberrant DNA repair genes. Human and mouse embryonic cells were treated with various ClO₂ dilutions ranging from 2.5 mM to 25 mM. The cell viability and metabolic activity was determined via MTT, a colorimetric assay. Human HEK293 cells …

A Pilot Study For Plant The Seed: A Nutrition Education Program Using Local Food Environment To Put Theory Into Action, Yeon Bai, Shahla M. Wunderlich, Karen A. Lee

Department of Nutrition and Food Studies Scholarship and Creative Works

The purpose of this study is to implement Plant the Seed, a garden-based nutrition education program designed to reconnect children with locally grown food, food environments of the past and present, and the benefits of eating seasonal foods. The pilot study investigates the environmental context and theory variables known to influence healthy food choice behavior. Social Cognitive Theory (SCT) provided a framework for the program’s curriculum and evaluation. The target audience is middle school students. Plant the Seed is a two-part program. In Part 1 (classroom), students participate in practical, interactive activities based on specific educational objectives that target …

Hexokinase Ii Localization Is Independent Of Ampk Activation In Hela Cells, Alyssa Brown

Graduate School of Biomedical Sciences Theses and Dissertations

In order for a cancer cell to thrive, it must alter its metabolism to produce the energy needed for rapid growth. Cells accomplish this by the Warburg Effect, or switching metabolism to aerobic glycolysis, where a cell can rapidly break down sugar into ATP, lactic acid and additional byproducts. Hexokinase 2, the enzyme that catalyzes the first committed step of glycolysis, may also be upregulated in cancer cells to increase glucose breakdown. Similar proteins for metabolism are found in both S. cerevisiae and mammalian cells. S. cerevisiae regulates metabolism through glucose repression, by Snf1 (mammalian homolog: AMPK) activation, which aids …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …

Aeromonas Hydrophila In Amphibians: Harmless Bystander Or Opportunistic Pathogen, Zachary P. Rivas

Honors Undergraduate Theses

For several decades amphibian populations have been declining. Historically, the bacterium A. hydrophila (Ah) was hypothesized to be the causal factor in amphibian disease and population declines. However, with the discovery of a chytrid fungus, Batrachochytrium dendrobatidis (Bd) in 1998, which was identified on the skin of amphibians during documented mortality events, Ah research became of minor interest as focus shifted to Bd. Recent studies into the immunocompromising abilities of Bd, however, have opened new questions about its relationship with Ah and their combined effects on a host.

In this study, I explore the …

Insights Into The Possible Mechanisms By Which Platelet-Activating Factor And Paf-Receptors Function In Vascular Smooth Muscle In Magnesium Deficiency And Vascular Remodeling: Possible Links To Atherogenesis, Hypertension And Cardiac Failure, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Jose Luis Perez-Albela, Bella T. Altura

The School of Health Sciences Publications and Research

The authors discuss different studies concerning the relationship between platelet-activating factor (PAF) and PAF-receptors with atherosclerosis and hypertension.

Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard

Theses and Dissertations--Gerontology

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP.

In …

Molecular Basis Of Sex Differences In Cardiac Hypertrophy And Heart Failure, Maya James

Online Theses and Dissertations

Transforming growth factor beta ligands and receptors are known to be pro-hypertrophic and pro-fibrotic factors in the heart, and are known to contribute to the development of cardiac hypertrophy and heart failure. It is well established that premenopausal females possess a lower incidence of these pathologies. We and others have observed a greater level of fibrosis in male hearts compared to female hearts in rodent models of cardiac hypertrophy. It is well established that estrogen is cardioprotective in that it can prevent the development of cardiac hypertrophy, as well as abrogate the development of heart failure following sustained cardiac hypertrophy. …

Development And Evaluation Of A Firefighter Physical Performance Program For Undergraduate Fire And Safety Students, Jessica Ann Moody

Online Theses and Dissertations

The number one on-duty cause of death in the fire service is heart attacks. The International Association of Firefighters and the International Association of Fire Chiefs teamed up to create the Candidate Physical Ability Test (CPAT). Fire departments across the nation will have consistent physical performance tests to hire more physically capable candidates as part of the Wellness-Fitness Initiative (International Association of Fire Fighters, 2014).

Eastern Kentucky University is a nationally recognized school for its fire science program; however students are not required to take educational classes to better prepare them for physical performance tests. Students starting in a training …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

Investigation Of Anaplasma Phagocytophilum And Anaplasma Marginale Adhesin-Host Cell Interactions, Kathryn S. Hebert

Theses and Dissertations

Anaplasma phagocytophilum and A. marginale are the etiologic agents of bovine anaplasmosis and human granulocytic anaplasmosis, respectively. As obligate intracellular pathogens, binding and entry of host cells is a prerequisite for survival. The molecular events associated with these processes are poorly understood. Identifying the adhesins mediating binding, delineating their key functional domains, and determining the molecular determinants to which they bind not only benefits better understanding of Anaplasma spp. pathobiology, but could also benefit the development of novel approaches for protecting against infection. We previously demonstrated that A. phagocytophilum outer membrane protein A (ApOmpA) is critical for bacterial binding and …

Genotoxic Effects Of Magnesium Deficiency In The Cardiovascular System And Their Relationships To Cardiovascular Diseases And Atherogenesis, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Bella T. Altura

The School of Health Sciences Publications and Research

The authors present evidence for a novel, new hypothesis whereby magnesium deficiency (MgD) acts as a genotoxic agent which probably causes numerous, hertofore, unrecognized consequences, even over a short-term, on the physiological, molecular and biochemical machinery of cardiovascular tissues and cells. The end result of these genotoxic effects of MgD probably plays important roles in the etiology and generation of diverse cardiovascular diseases, atherosclerosis, inflammation, and strokes via alterations in the epigenome of cardiovascular tissues and cells. The importance of adequate water-borne and dietary levels of Mg is emphasized.

The Expression Of Platelet-Activating Factor Is Induced By Low Extracellular Mg2+ In Aortic, Cerebral And Neonatal Coronary Vascular Smooth Muscle; Cross Talk With Ceramide Production, Nf–Kb And Proto-Oncogenes: Possible Links To Atherogenesis And Sudden Cardiac Death In Children And Infants, And Aging: Hypothesis, Review And Viewpoint, Burton M. Altura, Wenyan Li, Aimin Zhang, Tao Zheng, Nilank C. Shah, Gatha J. Shah, Bella T. Altura

The School of Health Sciences Publications and Research

An attempt is made, herein, to reconcile, and integrate, various phenomena associated with magnesium deficiency (MgD) in cardiovascular health, disease, and aging as well as reasons for the high incidence of sudden cardiac death in infants and young adults. With new experiments, we demonstrate, for the first time, that very low concentrations of platelet-activating factor (PAF), when added to primary cultured cerebral, neonatal coronary, and aortic vascular smooth muscle (VSM) cells (from three different mammals) promote rapid rises in free intracellular Ca2+ ions and a significant, concomitant reduction in free intracellular Mg2+ ions; these actions of PAF being curtailed with …

Magnesium Deficiency Results In Oxidation And Fragmentation Of Dna, Down Regulation Of Telomerase Activity, And Ceramide Release In Cardiovascular Tissues And Cells: Potential Relationship To Atherogenesis, Cardiovascular Diseases And Aging, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Jose Luis Perez-Albela, Bella T. Altura

The School of Health Sciences Publications and Research

The authors discuss the potential relationship between magnesium, cardiovascular diseases, and aging.

Potential Roles Of Magnesium Deficiency In Inflammation And Atherogenesis: Importance And Cross-Talk Of Platelet-Activating Factor And Ceramide, Burton M. Altura, Asefa Gebrewold, Nilank C. Shah, Gatha J. Shah, Bella T. Altura

The School of Health Sciences Publications and Research

Epidemiologic studies in North America and Europe have shown that people consuming Western-type diets are low in magnesium (Mg) content (i.e., < 30 - 65% of the RDA for Mg); most such diets in the USA show that 60 - 80% of Americans are consuming only 185 - 235 mg/day of Mg. Low Mg content in areas of soft-water, and Mg-poor soil, is associated with high incidences of ischemic heart disease (IHD), coronary artery disease, hypertension, and sudden cardiac death (SCD). It is clear that the leading underlying cause of death worldwide is atherosclerosis. Importantly, both animal and human studies have shown an inverse relationship between dietary intake of Mg and atherosclerosis. The myocardial level of Mg has consistently been observed to be lower in subjects dying from IHD and SCD in soft-water areas than those in hard-water areas. Over the past 20 years, our laboratories, using several types of primary cultured vascular smooth muscle (VSM) cells, and myocardial cells, demonstrated that declining levels of extracellular Mg ([Mg2+]0) activated several enzymatic pathways to produce increases in cellular sphingolipids, particularly ceramides which are known to exert numerous types of cardiovascular manifestations including inflammatory effects; the latter play important roles in atherogenesis and cardiovascular diseases. Approximately 20 years ago, we reported that low [Mg2+]0 caused formation of platelet-activating factor (PAF) as well as other types of PAF-like molecules and suggested that these molecules might be causative agents in low Mg2+- induced IHD and SCD. Herein, we review results and data from our labs which strongly support roles for ceramides, PAF and PAF-like lipids in low [Mg2+]0-induced IHD and SCD.

Sudden Cardiac Death In Infants, Children And Young Adults: Possible Roles Of Dietary Magnesium Intake And Generation Of Platelet-Activating Factor In Coronary Arteries, Burton M. Altura, Wenyan Li, Aimin Zhang, Tao Zheng, Nilank C. Shah, Gatha J. Shah, Bella T. Altura

The School of Health Sciences Publications and Research

Magnesium (Mg) is a co-factor for more than 500 enzymes, and is the second most abundant intracellular cation after potassium. It is vital in numerous physiological, cellular and biochemical functions and systems necessary for life. Approximately 35 years ago, our laboratory suggested that a progressive, dietary deficiency and/or metabolic induced loss of Mg from the body, beginning early in life, particularly during development of the coronary arteries, could lead to coronary arterial vasospasm, ischemic heart disease, and sudden-cardiac death (SCD). Herein, we review evidence for a brand-new, novel hypothesis which combines knowledge suggesting a combined role for hypomagnesemia and platelet-activating …

Lifestyle Contributors To Cardiovascular Disease Risk, Adam J. Berrones

Theses and Dissertations--Kinesiology and Health Promotion

Aortic stiffness is an independent risk factor that has prognostic value regarding future cardiovascular disease (CVD) events such as myocardial infarction, strokes, and heart failure. Although death rates due to coronary heart disease have declined in recent years, the leading global killer remains CVD and prevalence is still high. Understanding lifestyle contributors associated with aortic stiffness would provide the public with insight into targeting key health-related behaviors.

The purpose of this observational study was to examine the association of physical activity, physical function, and dietary quality as independent factors contributing to aortic stiffness in apparently healthy middle aged men. Fifty-two …

The Role Of Sox4 In Regulating Choroid Fissure Closure And Retinal Neurogenesis, Wen Wen

Theses and Dissertations--Biology

The development of the vertebrate eye is tightly controlled by precise genetic regulations. From a single ocular primordium to bilateral eyes with complex structures and cell types, it requires intensive proliferation and migration for cells in both the ectoderm and mesoderm to accomplish ocular morphogenesis, and during this process cell differentiation and interaction takes place to establish the complex composition of ocular cell types and cellular connections. Genetic defects can lead to severe abnormalities in eye morphogenesis and cell differentiation during ocular development. A tremendous amount of work has been done to identify both intrinsic and extrinsic factors that regulate …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

Development And Application Of Gadolinium Free Cardiac Magnetic Resonance Fibrosis Imaging For Multiscale Study Of Heart Failure In Patients With End Stage Renal Disease, Tori A. Stromp

Theses and Dissertations--Physiology

Cardiac magnetic resonance (CMR) is a powerful tool to noninvasively image ventricular fibrosis. Late gadolinium enhancement (LGE) CMR identifies focal and, with T1 mapping, diffuse fibrosis. Despite prevalent cardiac fibrosis and heart failure, patients with end stage renal disease (ESRD) are excluded from LGE. Absence of a suitable diagnostic has limited the understanding of heart failure and obstructed development of therapies in the setting of ESRD. A quantitative, gadolinium free fibrosis detection method could overcome this critical barrier, propelling the advancement of diagnostic, monitoring, and therapy options. This project describes the development of a gadolinium free CMR technique and application …

Differences In Rhodococcus Equi Infections Based On Immune Status And Antibiotic Susceptibility Of Clinical Isolates In A Case Series Of 12 Patients And Cases In The Literature, Praveen Gundelly, Yasuhiro Suzuki, Julie A. Ribes, Alice C. Thornton

Internal Medicine Faculty Publications

Rhodococcus equi is an unusual zoonotic pathogen that can cause life-threatening diseases in susceptible hosts. Twelve patients with R. equi infection in Kentucky were compared to 137 cases reported in the literature. Although lungs were the primary sites of infection in immunocompromised patients, extrapulmonary involvement only was more common in immunocompetent patients (P > 0.0001). Mortality in R. equi-infected HIV patients was lower in the HAART era (8%) than in pre-HAART era (56%) (P > 0.0001), suggesting that HAART improves prognosis in these patients. Most (85–100%) of clinical isolates were susceptible to vancomycin, clarithromycin, rifampin, aminoglycosides, ciprofloxacin, and imipenem. …

Proportionality Between Population Descriptors (Covariables) In An Aggregated Acanthocephalan (Helminth) Infection Of A Microcrustacean: Crofton Revisited, J. J. Daly Sr., K. Wagner

Journal of the Arkansas Academy of Science

We have previously shown that population parameters of the trematode metacercariae of Clinostomum marginatum in black bass (Micropterus spp.) were closely correlated with each other with the exception of prevalence (Daly et al. 2007, Daly (2014). Crofton (1971) and Haynes and Nicholas (1963) published raw data on an acanthocephalan, (Polymorphus minutus) in an amphipod intermediate host collected on 6 different sites on a stream. That data was used herein to examine similar correlations, as with Clinostomum, to see if another helminth infection, in this case from a different phylum, also had similar descriptor relationships. Forty one regression analyses were done …