Medicine and Health Sciences Commons^™

Assessing The Role Of Arsenite In Disrupting The Egfr Signaling Axis., Christine Kim

Electronic Theses and Dissertations

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase localized on the cell surface. Overexpression of EGFR has been used as biomarkers for many different types of cancers, including lung cancer. There is a strong association between arsenic and lung cancer development, although the mechanism is unclear. We hypothesize that chronic exposure of “a physiologically relevant” level of arsenite disrupts the EGFR endocytic trafficking. The goal of this project is to identify molecular mechanisms and roles of chronic arsenite-induced EGFR overexpression in lung cancer development. A non-malignant human bronchial epithelial cell line, Beas-2B cells were exposed to 100 …

The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis

Electronic Theses and Dissertations

The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. While most studies focus on relay neurons of dLGN, little is known about the factors regulating the development of the other principal cell type, intrinsic interneurons. To date, the targeting and migratory path of dLGN interneurons as well as their morphological development remains unclear. Here we examined whether the migration, structure, and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express green fluorescent protein (GFP) in dLGN interneurons, with math5 nulls …

Is Macrolide And Beta-Lactam Combination Therapy Associated With Early Clinical Stability Or 30 Day Mortality In Hospitalized Patients With Pneumonia? An Assessment Of Confounding By Indication., Evangeline Pierce

Electronic Theses and Dissertations

Pneumonia and influenza are one of the leading causes of infectious disease-related deaths worldwide. Current guidelines for the treatment of hospitalized patients with community acquired pneumonia (CAP) include empiric antimicrobial therapy with a macrolide and a beta-lactam. There is little consensus among studies as to which antimicrobial regimen is best. The confusing results seen may very well be due to lack of assessment of confounding by indication (CBI). This analysis was a secondary analysis from Hospitalized Adults with Pneumococcal Pneumonia: Incidence Study (HAPPI). The study participants were those in HAPPI who had received either macrolide and beta-lactam combination therapy or …

Influence Of Bilberry-Derived Anthocyanidins On Key Regulators Of Colorectal Cancer Development., Ashley M. Mudd

Electronic Theses and Dissertations

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths within the United States. A variety of factors including exposure to environmental carcinogens, such as benzo[a]pyrene (B[a]P), dysbiosis of the gut microbiome and hereditary influences, including APC mutations, have been shown to lead to an increased risk of developing colorectal cancer. Given the recent alarming rise in cases of colorectal cancer diagnosed in individuals under the age of 40, further insight into developing novel and effective prevention and treatment strategies are warranted. The family of plant pigments known as the anthocyanins has been identified with …

Comparisons Between Movement Onset Identification Methods Used In Isometric Mid-Thigh Pull Test, Junshi Liu

Electronic Theses and Dissertations

This dissertation aimed to explore the usefulness of using force derivatives for onset detection in the isometric mid-thigh pull test. First, we examined applications of three differential calculus principles, first and second derivative, and curvature using visual detection as a reference under different baseline conditions. Second, we compared the best derivative method to a threshold-based method using visual detection as a reference. Results of our first investigation showed trivial differences between many differential calculus methods and visual detection. However, statistical differences exceeding a trivial effect was observed when instantaneous force and rate of force develop were examined. Through the first …

Dreadd Targeting Projections From The Nucleus Accumbens To The Ventral Pallidum With Nicotine Self-Administration, Amanda Smith

Electronic Theses and Dissertations

Projections from the Nucleus Accumbens (NAc) to the Ventral Pallidum (VP) play a critical role in motivation and reward. Rewards and reward-associated cues are thought to alter this pathway by suppressing GABA release to the VP, however, the role of the NAc to VP pathway has never been investigated with regard to nicotine self-administration. We hypothesized that increasing GABAergic signaling from the NAc to the VP would decrease the reinforcing effects of nicotine. To increase GABA release, CRE dependent DREADD was expressed in the NAc of male rats. Administration of low dose clozapine activated the DREADD receptor and showed a …

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 …

The Ecology Of Fecal Indicators, Dennis A. Gilfillan

Electronic Theses and Dissertations

Animal and human wastes introduce pathogens into rivers and streams, creating human health and economic burdens. While direct monitoring for pathogens is possible, it is impractical due to the sporadic distribution of pathogens, cost to identify, and health risks to laboratory workers. To overcome these issues, fecal indicator organisms are used to estimate the presence of pathogens. Although fecal indicators generally protect public health, they fall short in their utility because of difficulties in public health risk characterization, inconsistent correlations with pathogens, weak source identification, and their potential to persist in environments with no point sources of fecal pollution. This …

Self-Regulation Abilities Of Low-Income Mothers In Community Based, Expanded Food And Nutrition Education Program, Alyssa Abreu

Electronic Theses and Dissertations

Diet is strongly associated with many risk factors for chronic disease. Educational programs such as the Expanded Food and Nutrition Education Program (EFNEP) are designed to improve dietary behaviors among low-income populations. Although EFNEP has seen improvements, they are not yet up to recommendations. Previous studies have been successful in eliciting behavior change when improving self-regulation in conjunction with dietary education. Thus, the purpose of this study was to examine self-regulation in EFNEP participants and its relationship to participants change in dietary behavior. All participants were currently enrolled in an EFNEP program and were asked to complete an additional self-regulation …

Self-Assembling Bioaffinity Hydrogels For Localized Antibody Delivery, Wen Liu

Electronic Theses and Dissertations

The scope of illnesses that are being treated using monoclonal antibodies (mAbs) has been expanding from cancers to autoimmune diseases due to their high specificity to their molecular target. Because many of the new mAbs are aimed to modulate the immune system, an emerging concern is that patients with chronic illnesses are subjected to immune-related Adverse Events (irAEs). Loss of immunological tolerance to self-antigens or increased susceptibility to infections have been documented in some mAb treatments. Localized sustained release of mAb at disease sites might mitigate the risk of such toxicities. Antibody drugs are formulated typically for parenteral delivery because …

The Myth Of Promiscuity: Examining Black Male Sexual Narratives And Sexual Identity, Seth Young

Electronic Theses and Dissertations

Black masculinity and sexuality are common topics across areas of philosophy, psychology, cultural studies and others. Yet, these topics are dedicated to the racial narrative of hypersexual Black male, the sexual objectification of Black men, and their presumed promiscuity. While such topics are important, there is little qualitative research that looks at the complexity and emotionality of African American men’s sexual experiences. Using the theoretical research on black masculinity and sexuality as its backdrop, this dissertation explores how heterosexual, African American men experience their sexuality. The study incorporates narrative inquiry and in-depth, semi-structured interviews to gather stories of five African …

Workplace Bullying, Nurse Practice Environment, Patient Outcomes: A Descriptive Study, Noreen Houck

Electronic Theses and Dissertations

Better nursing practice environments are associated with improved patient safety, yet little is known about the nurse’s experiences of bullying or flourishing within the practice environment. This study described nurses’ experiences of workplace bullying and flourishing and identified associations with patient outcomes.

The study used an exploratory cross-sectional survey design following Donabedian’s Quality Framework of structure-process-outcome and informed through critical feminist theory. The study took place at a large medical facility in the northeastern United States. A multi-instrument survey included four sections. The demographic section and the Practice Environment Scale of the Nurse Work Index (PES-NWI) were used to measure …

The Effect Of The Movie Time Social Learning Method On The Emotional Inferencing Skills In An Adult With Autism Spectrum Disorder, Jenna Reade

Electronic Theses and Dissertations

Individuals with autism spectrum disorder (ASD) have difficulty finding employment and maintaining social relationships. Professional and personal interactions require individuals to make inferences, or read between the lines. Inferencing is a challenge for individuals with ASD because it requires complex information processing. More specifically, it involves the integration of cognitive and linguistic information. There is a lack of research using complex stimuli to treat inferencing. An A-B-A-B design with one adult with ASD was used to examine the effectiveness of a movie-based method, Movie Time Social Learning(Vagin, 2012), on improving the emotional inferencing skills of one young adult with …

Ultrasound Visual Biofeedback And Accent Modification: Effects On Consonant And Vowel Accuracy For Mandarin English Language Learners, Courtney Armstrong

Electronic Theses and Dissertations

The number of individuals in the United States who speak languages other than English continues to increase. With the increase of language diversity comes a potential rise in communication challenges for those who speak with non-mainstream American English accents as English language learners. A portion of these individuals may elect to seek accent modification services, perhaps due to decreased intelligibility or communication breakdowns. Thus, speech-language pathologists must research and provide effective techniques to enhance intelligibility of all American English speakers for optimal communication. Few approaches employ a variety of treatment methods to improve speech sound accuracy, naturalness and intelligibility to …

The Association Of Prescription Opioid Exposure And Patient Factors With Prolonged Postoperative Opioid Use In Opioid Naive Patients, Jennifer Lanzillotta

Electronic Theses and Dissertations

Background

Research suggests prolonged postoperative opioid use occurs in 4-13% of opioid naïve patients and is related to factors other than surgical pain. However, it is unclear which patient factors and prescribing practices are associated with prolonged use after surgery among opioid naïve patients.

Objectives

To identify factors associated with prolonged postoperative opioid use (refills 90-180 days after surgery) in opioid naïve patients in two domains: specific patient characteristics (demographics, smoking status, comorbidities, etc.) and exposure through postoperative opioid prescriptions (in oral morphine milligram equivalents [OME]).

Methods

An electronic medical record dataset analysis of inpatient and outpatient opioid naïve adult …

Effects Of Natural Antioxidants On Motor And Cognitive Deficits In An Animal Model Of Aging And Obesity And Dopaminergic-Like Sh-Sy5y Cell Line, Sneha Potdar

Electronic Theses and Dissertations

Aging is a universal phenomenon. One of the greatest challenges faced by the elderly population is to sustain a healthy standard of living. Advancing age is associated with increased motor and cognitive deficits. Loss of balance, falls, hip fractures, and poor memory all contribute to a decline in the quality of life of the aging population. While ongoing research is making advances to find therapeutic interventions for neurodegenerative disorders like Parkinson’s and Alzheimer’s diseases, there is a pressing need to address deficits associated with normal aging.

Increase in oxidative stress and a decline of antioxidant mechanisms with aging have been …

Adventure-Based Therapy: Couple Intimacy With Christian Spirituality, Edward Boyer

Electronic Theses and Dissertations

Adventure-Based Therapy (ABT) models have been used for many years in the United States and beyond, primarily in adolescent and young adult populations. This project seeks to explore the experiences of couples on an ABT trip. Couples were asked to share their lived experiences as it pertains to marital intimacy, nature, and Christian spirituality. Seven themes emerged as the interviews were transcribed and confirmed by the couples: appreciation for nature, building community, care shown by partner, connecting with God outdoors, leaving technology, preparation together, and shared activity. These themes form the backbone of potential new outcomes as couples’ work is …

The Comparison Of Effects Of Synthetic And Natural Arachidin-3 On Rotavirus Infected Cells, Rebekah Napier-Jameson

Electronic Theses and Dissertations

Rotavirus (RV) causes severe, life-threatening diarrhea, in infants, young children and immunocompromised adults. There are several effective vaccines for young children, however they are strain specific and are not protective against many RV strains in developing countries. Therefore, it is important to investigate anti-RV therapeutic agents. Our laboratory has shown arachidin-1 (A1) and arachadin-3 (A3) significantly inhibit RV replication in two cell lines, however the molecular mechanism(s) of action are not known. A synthetic molecule of A3 (sA3) has been produced, but its’ antiviral effects have not been examined. Our hypothesis is that sA3 produces the same effects on RV-infected …

Macromolecule Loading On Plga Particles Through Surface Adsorption, Yiwei Wang

Electronic Theses and Dissertations

The advent of biotherapeutics have impacted the ways in which diseases are treated. In many instances development of recombinant proteins and oligonucleotides into therapeutics are slowed by poor stability of the candidate drugs. Progress has been made in using polymeric particles as carriers of macromolecule drugs. Historically the method is to encapsulate biological drugs into spherical polymeric matrices. Owing to its biocompatible and biodegradable nature, poly (d,l-lactic-co-glycolic acid) (PLGA) has been used extensively in formulating biological drugs into nano- and micro-sized particles. The development of PLGA biologic formulations, however, has been hampered by matrix acidification; the hydrolysis of the polymer …

Combination Oral Immunotherapy With Il-10 And Il-12 Effectively Treats Colon Tumors Via Synergistic Effects On Il-17 Producing T Cells And Colon Epithelial Barrier Integrity., Neal Bhutiani

Electronic Theses and Dissertations

In this dissertation, the relationship between colon cancer and inflammation, the utility of novel imaging modalities for diagnosis of colitis and cancer, and the therapeutic efficacy of orally delivered, particle-based immunotherapy for the treatment of colon cancer are evaluated. In Chapters One and Two, multispectral optoacoustic tomography (MSOT) is demonstrated to effectively detect colon inflammation without the use of exogenous contrast prior to detection using conventional colonoscopy. Oral particle uptake is demonstrated in the distal small intestine and proximal colon, confirming site-specific delivery. In Chapter Three, administration of IL-10 and IL-12 containing particles is shown to act synergistically to significantly …

Cannabidiol Alters The Immune Response To Porphyromonas Gingivalis In Mice., Shilpa Singh

Electronic Theses and Dissertations

Background: Porphyromonas gingivalis is an important etiologic agent of chronic periodontitis, an infectious disease defined by destruction of supporting tissues of the teeth. Marijuana is a risk factor for chronic periodontitis, although underlying mechanisms are poorly understood. As phytocannabinoids have been ascribed antiinflammatory properties, we hypothesized that cannabidiol exposure would lead to altered immune response to P. gingivalis infection facilitating bacterial persistence and, subsequently, increased alveolar bone loss in cannabidiol (CBD)-exposed mice. Methods: P. gingivalis-infected cannabinoid receptor 2 (CB2) knockout and wild type C57/Bl6 mice were exposed, or not exposed, to cannabidiol. Oral swabs from mice were used to monitor …

Post-Diagnosis Quality Of Life And Mortality In Non-Hispanic White And Hispanic Women Diagnosed With Invasive Breast Cancer., Delvon T. Mattingly

Electronic Theses and Dissertations

The prevalence of breast cancer is increasing, and the health-related quality of life (HRQOL) of breast cancer survivors may help to further understand survivorship. This study evaluated HRQOL as a potential prognostic factor for mortality among Non-Hispanic White (NHW) and Hispanic women diagnosed with invasive breast cancer. Data were used from the Health, Eating, Activity, and Lifestyle (HEAL) Study. Data for 351 participants were analyzed for associations between HRQOL scores (subscale, component) and mortality. Cox proportional hazards regression was conducted to assess the relationship between HRQOL and mortality outcomes (all-cause, breast cancer-specific, non-cancer). Median follow-up time from HRQOL assessment (approximately …

Wnt/Β-Catenin Mediated Cancer Stem Cell Activation In Hepatocellular Carcinoma., Harshulkumar M. Pandit

Electronic Theses and Dissertations

Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with variable presentation, high chemotherapy resistance and early tumor recurrence. In this dissertation, we have systematically enriched, identified and characterized HCC cancer stem cells (CSCs) from 3 different HCC cell lines (Hepa1-6, HepG2, and Hep3B) using in vitro serum-free culture method. Enriched spheroids acquired CSC properties, primarily self-renewal capability, spheroid formation ability, and drug resistance. Heterogeneous CSCs enriched from Hepa1-6 cells demonstrated higher tumor initiation and proliferation capability in vivo, compared to control HCC cells in orthotopic immunocompetent mouse model. EpCAM+ CSCs were significantly enriched within heterogeneous Hepa1-6 CSC spheroids. Consequently, …

Social Determinants Of Health And A Grounded Mixed-Methods Approach To Explain Declining Life Expectancy In Eastern Kentucky : 1980 – 2014., William Renda

Electronic Theses and Dissertations

Trends in life expectancy for the United States from 1980-2014 suggest general improvement overall. However, eastern Kentucky stands out with a cluster of counties experiencing declining life expectancy. Given that life expectancy is an excepted indicator of overall population health, this anomaly in eastern Kentucky warrants investigation. This thesis uses a grounded mixed methods approach to explore this trend across the greater Appalachian region. Content and discourse analysis of interviews with public health and medical professionals in the study area revealed key themes perceived as being related to declining life expectancy, which informed variable selection for regression analysis. Regression models …

The N-Terminal Methyltransferase Homologs Nrmt1 And Nrmt2 Exhibit Novel Regulation Of Activity Through Heterotrimer Formation., Jon David Faughn

Electronic Theses and Dissertations

Protein, DNA, and RNA methyltransferases have an ever-expanding list of novel substrates and catalytic activities. Even within families and between homologs, it is becoming clear the intricacies of methyltransferase specificity and regulation are far more diverse than originally thought. In addition to specific substrates and distinct methylation levels, methyltransferase activity can be altered through formation of complexes with close homologs. This work involves the N-terminal methyltransferase homologs NRMT1 and NRMT2. NRMT1 is a ubiquitously expressed distributive trimethylase. NRMT2 is a monomethylase expressed at low levels and in a tissue-specific manner. They are both nuclear methyltransferases with overlapping target consensus sequences …

A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz

Electronic Theses and Dissertations

In oncology, imaging plays a major role in terms of early detection and treatment of most types of cancer. Magnetic resonance imaging (MRI) is mostly used for cancer diagnosis due to its excellent contrast resolution. However, MRI for cancer diagnosis is somewhat limited by its sensitivity. In this thesis, we assessed the ability of theranostic platform consisting of gold nanoparticles functionalized with a cancer targeting aptamer; AS1411 and gadolinium chelate (Dotarem thiol derivative; Gd (III)-DO3A) as a MRI contrast agent to target malignant tumors by enhancing the MRI contrast of the detected tumor. The proposed technology is a novel injectable …

A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease In Type 2 Diabetes., Qian Lin

Electronic Theses and Dissertations

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with type 2 diabetes (T2D). Our recently engineered FGF1 partial agonist, carrying triple mutations (FGF1^△HBS) exhibits greatly reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1. This study tests the preventive and therapeutic effects of FGF1^△HBS on NAFLD in db/db T2D and explores potential mechanisms. The results showed that administration of FGF1^△HBS to 2-month-old db/db mice for 2 months constantly lowered blood glucose levels, improved insulin sensitivity, and lowered liver weight, lipid deposition, and …

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert

Electronic Theses and Dissertations

Skeletal muscle mass, contractile properties, and metabolic function are regulated through the coordinated activation of multiple intracellular signaling pathways and genetic reprogramming. The endoplasmic reticulum (ER) plays a pivotal role in protein folding and calcium homeostasis in many cell types, including skeletal muscle. Disruption of calcium levels or accumulation of misfolded proteins in the ER lumen leads to stress, which results in the activation of a signaling network called the unfolded protein response (UPR). Further, recent studies have suggested that in certain conditions, UPR pathways can be activated independent of ER stress. However, the role of ER stress and the …