Medicine and Health Sciences Commons^™

Inhibiting Survival Of Salmonella During Desiccation Through The Use Of Naturally Occurring Signals, Joseph Headrick

Electronic Theses and Dissertations

A rising problem in agriculture is the increase of antibiotic-resistant Salmonella cases associated with chicken eggs, which transmit infection to humans. To counter this, new approaches to combat Salmonella in chickens and desiccated on eggshells are vital in the prevention of human foodborne illness. Disrupting signaling pathways with naturally occurring compounds provides a potential novel avenue for prevention of Salmonella infections, as this would disrupt sensing of these environments and inhibit subsequent optimal gene expression. Starting with signals identified in previous studies, salicylic acid was found to inhibit Salmonella desiccation survival on both eggshells and plastic. To expand upon this, …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Species Data And Vector Modeling: Evaluating Datasets For Improved Models Of Ixodes Ricinus Tick Distribution In Europe Under A Changing Climate, Steven Jones

Electronic Theses and Dissertations

To increase capacity for monitoring and surveillance of tick-borne diseases, publicly available tick distribution and climate change datasets are required to create accurate predictive distribution models. It is difficult, however, to assess model accuracy and utility when using incomplete datasets.  The more recent development of comprehensive tick databases for Europe and availability of climate change scenarios from multiple IPCC Assessment Reports allows for improved modeling efforts. Multiple tick datasets were combined and three climate change projections were compared by predicting current and future distributions of Ixodes ricinus ticks in Europe using the MaxEnt species distribution model. Overall, much of Europe …

Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard

Electronic Theses and Dissertations

Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase, plays a role in DNA damage repair, redox sensing, and metabolism. In the heart, ATM contributes significantly in the myocardial infarction (MI)-induced cardiac remodeling with effects on fibrosis, hypertrophy, apoptosis and inflammation. This study investigates the role of ATM deficiency in 14 weeks Western-type diet (WD)-induced cardiac outcomes prior to and 1-day post-MI in a sex-specific manner using wild-type (WT) and ATM heterozygous knockout (hKO) mice. In male mice, ATM deficiency induced rapid body weight gain and preload-associated dysfunction, while WT mice displayed afterload-associated dysfunction 14 weeks post-WD. Myocyte apoptosis and hypertrophy were …

Genital Chlamydia Infection Is Influenced By The Female Sex Hormones Estrogen And Progesterone In Vivo, Amy Gail Gravitte

Electronic Theses and Dissertations

Chlamydia is the most common bacterial sexually transmitted infection in the United States and worldwide. It often goes unnoticed due to lack of symptoms and left untreated it can ascend the female genital tract to cause sequelae like pelvic inflammatory disease and irreversible tubal infertility. In reproductive-aged women, female sex hormones estrogen (E2) and progesterone (P4) concentrations fluctuate during the menstrual cycle and are influenced by hormonal contraceptives and hormone replacement therapy. E2 and P4 influence genital Chlamydia infection in women and mice, but these multifactorial interactions are not entirely mapped out. The complex interplay of E2 and P4 with …

Prevalence Of Musculoskeletal Disorders In Third- And Fourth-Year Dental Students At The University Of Tennessee Health Science Center College Of Dentistry, Felisa Jackson

Electronic Theses and Dissertations

The effects of pain suffered from musculoskeletal disorders by dental professionals may lead to reduced work hours, loss of production, and early retirement. Although third- and fourth-year dental students are provided lectures about musculoskeletal disorders, proper positioning and ergonomics, they are at an increased risk of developing MSD. This study was conducted to evaluate the prevalence on musculoskeletal disorders in third- and fourth-year dental students and to determine if third-year dental students experience more MSD pain than fourth-year dental students at the University of Tennessee Health Science Center College of Dentistry. A total of 50 third- and fourth- year dental …

Sarcopenia Screening By Registered Dietitian Nutritionists (Rdns) In The United States (U.S.), Madison Marcom

Electronic Theses and Dissertations

Sarcopenia is a disease of muscle wasting primarily seen in older adults. Although this term was first coined over three decades ago, there is a lack of consensus on a definition, screening criteria, and treatment protocol for sarcopenia. The primary purpose of this study is to determine whether registered dietitian nutritionists (RDNs) in the United States (U.S.) screen for sarcopenia. Study participants were recruited through a randomized email list and included RDNs throughout the U.S. Respondents completed a survey questioning knowledge of sarcopenia, screening tools and company protocols in place, and the need and desire for sarcopenia education. Data revealed …

Vitamin B12 Deficiency Does Not Stimulate Amyloid-Beta Toxicity In A Ceanorhabditis Elegans Model Of Alzheimer’S Disease, Opeyemi F. Showemimo

Electronic Theses and Dissertations

Alzheimer’s disease (AD) is symptomized by amyloid-beta plaques in the brain and accounts for more than 65 percent of dementia cases. Vitamin B12 (cobalamin) deficiency can result in similar cognitive impairment and roughly 15% of the elderly are vitamin B12 deficient. Vitamin B12 deficiency results in the accumulation of toxic methylmalonic acid and homocysteine. Hyperhomocysteinemia is a strong risk factor for AD. To test if vitamin B12 deficiency stimulates amyloid-beta toxicity, Caenorhabditis elegans expressing amyloid-beta in muscle were fed either vitamin B12-deficient OP50-1 or vitamin B12-rich HT115(DE3) E. coli bacteria. Increased amyloid-beta toxicity was found in worms fed the …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

A Replication And Extension Of A Prediction Tool Identifying Need For Treatment Among Opioid Exposed Infants, Loni Parrish

Electronic Theses and Dissertations

The incidences of maternal opioid use and neonatal opioid withdrawal syndrome (NOWS) have increased by nearly 400% over the past decade. Isemann and colleagues (2017) developed prediction tools (TiTE/TiTE²) to differentiate, within the first two days of life, between infants who will require pharmacotherapy for NOWS from those infants who will not require pharmacotherapy for NOWS. The goal of the current experiment was to replicate and extend their prediction model. The present experiments successfully replicated Isemann et al., (2017) results and also established alternative cutoff values for requiring treatment that provide better balance between all four metrics. Moreover, …

The Prevalence And Context Of Adult Female Overweight And Obesity In Sub-Saharan Africa, Ifeoma Ozodiegwu

Electronic Theses and Dissertations

Adult women bear a disproportionate burden of overweight and obesity in Sub-Saharan Africa (SSA). Precise information to understand disease distribution and assess determinants is lacking. Therefore, this dissertation aimed to: (i) analyze the prevalence of adult female overweight and obesity combined in lower-level administrative units; (ii) analyze the effect modification of educational attainment and age on the association between household wealth and adult female overweight and obesity; (iii) synthesize qualitative research evidence to describe contextual factors contributing to female overweight and obesity at different life stages. Bayesian and logistic regression models were constructed with Demographic and Health Survey (DHS) data …

The Effects Of Two Novel Anti-Inflammatory Compounds On Prepulse Inhibition And Neural Microglia Cell Activation In A Rodent Model Of Schizophrenia, Heath W. Shelton

Electronic Theses and Dissertations

Recent studies have shown elevated neuroinflammation in a large subset of individuals diagnosed with schizophrenia. A pro-inflammatory cytokine, tumor necrosis factor-alpha (TNFα), has been directly linked to this neuroinflammation. This study examined the effects of two TNFα modulators (PD2024 and PD340) produced by our collaborators at P2D Bioscience, Inc., to alleviate auditory sensorimotor gating deficits and reduce microglial cell activation present in the polyinosinic:polycytidylic (Poly I:C) rodent model of schizophrenia. Auditory sensorimotor gating was assessed using prepulse inhibition and microglial activation was examined and quantified using immunohistochemistry and confocal microscopy, respectively. Both PD2024 and PD340 alleviated auditory sensorimotor gating deficits …

The Role Of Non-Neuronal Acetylcholine In Urogenital Chlamydial Infection, Jessica R. Lockhart

Electronic Theses and Dissertations

Chlamydia trachomatiscauses a bacterial sexually transmitted infection, Chlamydia, that is often chronic and casues reproductive complications in women. We hypothesized that Chlamydia infection increases local acetylcholine (ACh) production, which regulates the host’s inflammatory response to the infection. Female mice infected with C. muridarumwere sacrificed at days 3, 9, 15, and 21 post-infection, genital tract tissues harvested, and immunohistochemistry performed to enumerate ACh-producing cells. Infection increased the number of ACh-producing cells in cervical tissue at days 3,15, and 21 post-infection (pi), uterine tissue at day 3 and 9 pi, and ovarian tissue day 3, 15, and 21 pi. These …

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years …

A Role Of Vitamin B2 In Reducing Amyloid-Beta Toxicity In A Caenorhabditis Elegans Alzheimer’S Disease Model, Muhammad Tukur Ameen

Electronic Theses and Dissertations

Alzheimer’s disease (AD) is associated with amyloid-beta peptide deposition and loss of mitochondrial function. Using a transgenic C. elegans AD worm model expressing amyloid-beta in body wall muscle, we determined that supplementation with either of the forms of vitamin B₂, flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) protected against amyloid-beta mediated paralysis. FMN and FAD were then assayed to determine effects on ATP, oxygen consumption, and reactive oxygen species (ROS) with these compounds not significantly improving any of these mitochondrial bioenergetic functions. Knockdown of the daf-16/FOXO transcriptional regulator or the FAD synthase enzyme completely abrogated the …

Role Of Cannabinoid Receptor Type 2 (Cb2) In Late Stage Atherosclerosis, Makenzie Fulmer

Electronic Theses and Dissertations

Atherosclerosis is a chronic inflammatory disorder of medium and large vessels. Immune signaling and dyslipidemia are two of several processes which influence lesion development in atherosclerosis. Cannabinoids, such as those found in marijuana, exert their effects through two cannabinoid receptors, CB1 and CB2. Recent studies using CB2 knockout mice and CB2-selective ligands have shed light on a protective role of CB2 in early stages of atherosclerosis. However, the role of CB2 in advanced stages of atherosclerosis remains unclear. To determine if CB2 plays a role in advanced atherosclerotic lesion composition and progression, we investigated the effects of systemic CB2 gene …

Role Of Tlrs, Hippo-Yap1 Signaling, And Micrornas In Cardiac Repair And Regeneration Of Damaged Myocardium During Ischemic Injury, Xiaohui Wang

Electronic Theses and Dissertations

Cardiovascular disease is a leading cause of death in the United States. Toll-like receptor (TLR)-mediated pathways have been demonstrated to play a role in myocardial ischemia/reperfusion (I/R) injury. We and others have shown that PI3K/Akt signaling is involved in regulating cellular survival and protecting the myocardium from I/R induced injury. In this dissertation, we provide compelling evidence that miR-125b serves to “fine tune” TLR mediated NF-kB responses by repressing TNF-a and TRAF6 expression. We constructed lentiviral expressing miR-125b, delivered it into the myocardium. The data showed that delivery of lentivirus expressing miR-125b significantly reduces myocardial infarct size and improves cardiac …

A Novel Method For Synthesis Of Hydroxytyrosol, Emmanuel Onobun

Electronic Theses and Dissertations

Hydroxytyrosol, 3,4-dihydroxyphenolethanol, a naturally occurring polyphenol most common in olive tree (Olea europaea), is one of the most effective member of the polyphenols family, because of its remarkable antioxidant activity, its ability to inhibit oxidation of low density lipids (LDL), and its protection against DNA oxidative damage. Hydroxytyrosol, which is widely used in cosmetics and food supplements industries, can be purchased as an olive oil extract that contains low concentration of hydroxytyrosol besides other polyphenols. The price and low natural abundance of hydroxytyrosol make alternative synthetic sources very attractive. In this research, a novel method for the synthesis of pure …

Endothelial Hspa12b Is A Novel Protein For The Preservation Of Cardiovascular Function In Polymicrobial Sepsis Via Exosome Mir-126, Xia Zhang

Electronic Theses and Dissertations

Sepsis is the most frequent cause of mortality in most intensive care units. Cardiovascular dysfunction is a major complication associated with sepsis, with high mortality rates up to 70%. Currently, there is no effective treatment approach for sepsis.

The integrity of the endothelium is fundamental for the homeostasis of the cardiovascular system. Sepsis induces endothelial cell injury which is the key factor for multiple organ failure. The increased expression of adhesion molecules and chemokines in endothelial cell promotes leukocytes infiltration into the tissue. The loss of tight junction proteins and increased permeability of the endothelial cells will provoke tissue hypoxia …

Role Of Ataxia Telangiectasia Mutated Kinase In The Healing Process Of The Heart Following Myocardial Infarction, Laura L. Daniel

Electronic Theses and Dissertations

Ataxia telangiectasia (AT), caused by mutations in the gene encoding ataxia telangiectasia mutated kinase (ATM), is a rare autosomal recessive disorder. AT individuals exhibit neuronal degeneration and are predisposed to cancer. Carriers of this disorder are predisposed to cancer and ischemic heart disease. Heart disease, mostly due to myocardial infarction (MI), is a leading cause of death in the US. Following MI, release of catecholamines in the heart stimulates β- adrenergic receptors (β-AR). Our lab has shown that β-AR stimulation increases ATM expression in the heart and myocytes, and ATM plays an important role in β-AR-stimulated myocardial remodeling with effects …

Regulation Of C-Reactive Protein Gene Expression And Function, Avinash N. Thirumalai

Electronic Theses and Dissertations

Human C-reactive protein (CRP) is the prototypic acute phase protein whose serum concentration increases rapidly during inflammation. CRP is also associated with atherosclerosis; it is deposited at lesion sites where it may interact with modified lipoproteins. There are 2 major questions regarding CRP: 1. How is the serum concentration of CRP regulated? 2. What are the functions of CRP in atherosclerosis?

Our first aim was to determine the role of the constitutively expressed transcription factor Oct-1 in regulating CRP gene expression. We found that Oct-1 overexpression inhibited (IL-6+IL-1β)- induced CRP gene expression; maximal inhibition required the binding of Oct-1 to …

Bioengineering The Expression Of Active Recombinant Human Cathepsin G, Enteropeptidase, Neutrophil Elastase, And C-Reactive Protein In Yeast, Eliot T. Smith

Electronic Theses and Dissertations

The yeasts Pichia pastoris and Kluyveromyces lactis were used to express several recombinant human proteins for further biochemical characterization. Two substitution variants of recombinant human enteropeptidase light chain (rhEPL) were engineered to modify the extended substrate specificity of this serine protease. Both were secreted as active enzymes in excess of 1.7 mg/L in P. pastoris fermentation broth. The substitution variant rhEPL R96Q showed significantly reduced specificities for the preferred substrate sequences DDDDK and DDDDR; however, the rhEPL Y174R variant displayed improved specificities for these substrate sequences relative to all other reported variants of this enzyme. The neutrophil serine proteases human …

Regulating Rsma Expression In Pseudomonas Aeruginosa, Sean D. Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa, a Gram-negative bacillus, commonly infects immunocompromised individuals and uses a variety of virulence factors to persist in these hosts. The posttranscriptional regulator, RsmA, plays a role in the expression of many virulence factors in P. aeruginosa. RsmA up regulates virulence factors used in colonizing hosts. However, regulation of rsmA is not well elucidated. Transposon mutagenesis was performed on P. aeruginosa containing a transcriptional rsmA-lacZ fusion to answer this question. Mutants were screened via β-galactosidase assay and transposon insertions identified via arbitrary PCR. A probable MFS transporter, we named mtpX, was one significant transposon mutant identified. …

Exercise Participation During Weight Loss On A High Protein – Low Carbohydrate Diet Plan In Females Aged 15-25 Years, Margaret Mobley-Meulman

Electronic Theses and Dissertations

Weight gain due to poor diet and lack of exercise is responsible for over 300,000 deaths each year (U.S. Department of Health and Human Services, 2010). Obese adults have an increased risk for serious health conditions including high blood pressure and cholesterol, type 2 diabetes, coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, respiratory problems, and certain cancers (National Cancer Institute, 2012). Participation in exercise can help control weight, strengthen muscles and bones, and reduce the incidence of cardiac events, stroke, hypertension, type 2 diabetes, colon and breast cancers, osteoporotic fractures, gallbladder disease, obesity, depression, anxiety, and delay mortality …

Preventing Skin Cancer In Adolescent Girls Through Intervention With Their Mothers, Mary K. Baker

Electronic Theses and Dissertations

Indoor tanning (IT) before the age of 35 increases one’s risk for melanoma by 75%, and epidemiological data show a 6.1% annual increase in the incidence of melanomas in white women younger than age 44 in the US. Population-based studies reveal that 15% of adolescents and 8% to 14% of their primary caregivers have engaged in IT in the past year.

The compelling case for IT being a significant risk factor for melanoma, together with the high rates of IT in teen girls and their mothers, provided a strong rationale for conducting an antitanning intervention directed at mother-daughter dyads. This …

Exploring The Unique Characteristics Of Cancer In Adolescents And Young Adults In Tennessee, Megan Quinn

Electronic Theses and Dissertations

Adolescents and Young Adults (AYAs) ages 15-39 years with cancer have received little attention in the medical and health fields, resulting in a lack of progress for this age group. Little is known about the unique biologic, epidemiologic, and psychosocial issues that play an integral role in the AYA cancer journey. The purposes of this study were to use the Tennessee Cancer Registry for all new cancer cases from 2004-2008 to determine 1) the main types of cancer that affect AYAs in TN, 2) the predictors of late-stage diagnosis of melanoma, and 3) the factors that predict a total thyroidectomy …

Nectin-1 Is Degraded In Chlamydia Trachomatis-Infected Genital Epithelial Cells And Is Required For Herpes Simplex Virus Co-Infection-Induced C. Trachomatis Persistence., Jingru Sun

Electronic Theses and Dissertations

The obligate intracellular bacterium Chlamydia trachomatis is the most common bacterial STD agent in the US. This bacterium has a unique biphasic developmental cycle in which the infectious elementary body (EB) infects a host mucosal epithelial cell and differentiates into the replicative form (the reticulate body or RB) within a modified vacuole called an inclusion. The RB later divides and develops back into an EB and is released, perpetuating the infectious cycle. When developing chlamydiae are exposed to unfavorable environmental conditions, they deviate from the normal developmental cycle into a non-infectious but viable state termed persistence. Previous data from our …

Bronchioalveolar Carcinoma In Jefferson And Mccracken Counties, Kentucky: Gender Differences In Survival., Jasneet Aneja

Electronic Theses and Dissertations

Bronchioalveolar carcinoma (BAC), a rare lung cancer, is more common in women, has a high proportion of non-smokers, and better survival, especially in women, than other lung cancers. Study subjects were 83 BAC patients from two Kentucky counties. Mean survival differences were compared by selected variables. The results showed better survival for females (6.5 years) than males (3.0 years, p-value 0.02); for urban (4.3 years) compared to rural residents (2.6 years, p-value 0.04); and for females with history of hysterectomy (5.1 years) compared to females without such history (3.3 years, p-value 0.02); the last finding supports a hormonal role in …