Digital Commons Network^™

Characterization And Functional Rescue Of Congenital Muscular Dystrophy With Megaconial Myopathy In A Mouse Model Of The Disease, Ambreen A. Sayed

Electronic Theses and Dissertations

Congenital muscular dystrophy with megaconial myopathy (MDCMC) is an autosomal recessive disorder characterized by progressive muscle weakness and wasting. Megamitochondria in skeletal muscle biopsies and cognitive impairments in MDCMC patients are observations exclusive to this type of muscular dystrophy. The disease is caused by loss of function mutations in the choline kinase beta (CHKB) gene which results in dysfunction of the Kennedy pathway for the synthesis of phosphatidylcholine (PC). A rostro-caudal muscular dystrophy (rmd) mouse with a deletion in the Chkb gene resulting in MDCMC-like symptoms has been reported by our lab. In order to test if the rmd mice …

Modeling Human Cancer Therapy Response In Patient Derived Xenografts, Joan Malcolm

Electronic Theses and Dissertations

Patient‐derived xenografts (PDXs) generated by implanting human tumor tissue into a transplant compliant mouse host have been of increasingly importance to preclinical development and have been demonstrated to have advantages compared to cancer cell lines and cell‐line xenografts (CLX) for modeling therapeutic responses in cancer. Nevertheless, many open questions remain regarding the relationship between study design factors and classification of treatment response and the molecular fidelity of tumors passaged in PDXs relative to the original patient tumor(s). The research described in this dissertation addresses both of these significant issues related to the use of PDXs as a tool for modeling …

The Association Between Depression, Anxiety And Clinical Outcomes For Type 2 Diabetes Mellitus, Elham Heidari

Electronic Theses and Dissertations

Objective: To evaluate the impact of depression and/or anxiety on clinical outcomes of diabetes, including glycosylated hemoglobin (HgA1c), blood glucose, blood pressure, total cholesterol, weight and LDL among patients with incident type 2 diabetes mellitus (T2DM).

Method: A retrospective cohort study utilizing electronic medical record (EMR) data from a primary care physician (PCP) group practice was conducted to identify patients newly diagnosed with T2DM with at least 6 months pre-diagnosis and 12 months post-diagnosis of EMR data using International Classification of Disease 9th edition Clinical Modification (ICD-9-CM) coding. The presence of comorbid depression and anxiety was identified to identify four …

Community Pharmacists And Substance Use Disorders: Attitudes, Knowledge And Practices, Deepika Rao

Electronic Theses and Dissertations

Background: Substance use disorder (SUD) is a serious health concern affecting a large proportion of the US population. Community pharmacists are well-positioned to prevent, screen, and provide appropriate treatment for SUD. Stigma towards these patients and SUD results in reduced quality of care as well as poor treatment outcomes. It is imperative that pharmacists have the appropriate knowledge of and attitude towards prevention, harm reduction and treatment to develop therapeutic relationships and improve their delivery of pharmacy services

Objective: To assess knowledge, practices (with an emphasis upon screening), stigma and general attitudes of community pharmacists towards SUD and evaluate the …

Access To Care And The Use Of Healthcare Services By Women In Rural Cameroon: A Participatory Action Research Study, Grace Tadzong-Awasum

Electronic Theses and Dissertations

Women in rural Cameroon do not access health care as timeously and as often as they should. They fail to get screened for common diseases, with the consequence that such diseases are often diagnosed at a very advanced stage. This accounts for the high morbidity and mortality rates as well as low life expectancy recorded among women. The purpose of this study was to explore and understand the health access experiences of women in rural Cameroon. Methodology: Participatory action research was used guided by a Focused ethnography in phase one. Twenty-five women aged 21-77 years were recruited through local the …

Take Charge For Therapy Discharge: Outcomes Of A Patient Education Program Applying The Co-Op Approach, Kathryn Westley

Electronic Theses and Dissertations

A thorough needs assessment at HealthSouth Rehabilitation Hospital of Largo revealed slight dissatisfaction scores on the Press Ganey survey for both the occupational therapy department and discharge planning processes. This quality improvement project, Take Charge for Therapy Discharge, implemented a two-session patient education protocol using the Cognitive Orientation to Occupational Performance (CO-OP) approach. Using the Patient-Specific Functional Scale (PSFS), participants identified and prioritized three therapy goals and rated their perceived current performance. Results demonstrated a significant difference between the participants’ PSFS pre and post-intervention scores. Patients’ improved self-perceived goal attainment scores served as evidence that, in addition to using …

Probiotic Use In Trauma Patients: A Pathway To Determining The Standard Of Care To Improve Outcomes, Heather Vitko

Electronic Theses and Dissertations

The gut microbiome consists of normally non-pathogenic bacteria, viruses, and fungi. These friendly microbes serve to maintain GI barrier function and integrity, play a role in host nutrient and drug metabolism, immunomodulation, and prevent pathogenic bacteria from colonizing or causing disease. The importance of a healthy microbiome for the overall health of the host is just recently being appreciated within the medical and science communities. Disruption of the microbiome places one at greater risk for illness and infection. Patients who suffer a traumatic injury are among those at highest risk for complications associated with microbial imbalance, or dysbiosis. In addition …

Using An In Vitro-In Vivo Correlation For The ‘Bioequivalence By Design’ Development Of An Immediate Release Carbamazepine Product, Douglas Steinbach

Electronic Theses and Dissertations

The quality of a drug product may be characterized by the consistency with which its indicated clinical effect, and safety profile, is experienced by the patient. The concept that such quality should be built into a product is at the core of the United States Food and Drug Administration’s (FDA) quality by design (QbD) initiative. This vision for pharmaceutical product development emphasizes the risk-based identification of critical quality attributes (CQA) which summarize a product’s performance, the efficient refinement of critical product/process parameters (CPP) that can affect such attributes, and the systematic development of CPP limits, which assure appropriate performance of …

Synthesis Of Novel 6-Substituted And 5-Substituted Pyrrolo[2,3-D] Pyrimidine Antifolates As Targeted Anticancer Therapies, Xinxin Li

Electronic Theses and Dissertations

The dissertation will give an introduction, background and current research progress in the areas of antifolates and chemotherapy of anticancer. The design and synthesis of classical 6- substituted pyrrolo[2,3-d]pyrimidines and 5-substituted pyrrolo[2,3-d]pyrimidines as potential antifolates have been described. The design variations include: methylated thiophene regioisomers, fluorinated phenyl regioisomers, thionyl regioisomers on the side chain of pyrrolo[2,3-d]pyrimidines. As a part of this study, a series of new compounds have been synthesized and characterized. Of these, ten final compounds were submitted for biological evaluation.

Independence Through Patient Education In A Spinal Cord Injury Population, Justin Mctish

Electronic Theses and Dissertations

The Know More, Live Better program was developed because the population of people with Spinal Cord Injuries (SCI) includes a substantial number of young people, who often readmit into hospitals for preventable causes such as pressure ulcers, respiratory infections, and bowel/bladder infections. These complications can be avoided through patient education. A needs assessment was conducted at the SCI unit at Good Shepherd Rehabilitation Hospital in Allentown, PA. This assessment included structured observation of patient education in the therapy process, semi-structured interviews about site needs and patient education topics completed with patients and occupational therapists on staff, and surveys of multi-disciplinary …

Characterization Of G-Protein Coupled Receptors In Pain, Depression And Anxiety, Neil Lax

Electronic Theses and Dissertations

Chronic pain and major depressive disorder are widespread conditions in the world. Interestingly, these conditions often occur comorbidly, with each individual disease amplifying the symptoms of the other. A significant amount of preclinical research in pain and depression focuses on G-protein coupled receptors (GPCRs), implying that GPCRs may be useful in treating this comorbidity. Our efforts have sought to characterize several poorly understood GPCRs, including the serotonin receptor subtypes 2C and 7 (5-HT2CR and 5-HT7R) and metabotropic glutamate receptor 5 (mGluR5), along with more well-known GPCRs such as the mu opioid receptor (MOR), and the role that they play in …

Tumble Tots: Outcomes Of A Gymnastics Program For Children With Disabilities, Cayla Leichtenberger

Electronic Theses and Dissertations

Despite the benefits, children with disabilities do not participate in recreational activities as often as typically developing peers. The purpose of the program was to: 1) describe the benefit of a gymnastics program on a child’s development, and 2) identify the impact of a staff training program. Engagement in the proposed program aimed to ultimately contribute to a child’s involvement in recreational activities, health and quality of life (QOL). All participants in the gymnastics program demonstrated a positive change in motor and communication skills. Pre-test data from the staff training program indicated that none of the gymnastics staff members were …

Sensory-Based Programming In Mental Health: Sense Of Self, Nikki Yeckel

Electronic Theses and Dissertations

The doctoral experiential component (DEC) for this Capstone was completed at the Veterans Affairs Healthcare System (VA) in Pittsburgh, Pennsylvania. The program, called Sense of Self, was implemented with the Veteran mental health (MH) population in an inpatient psychiatric rehabilitation unit at the VA. Sense of Self was a three-day educational program that educated Veterans on the sensory systems and sensory processing, provided calming or alerting strategies with use of sensory materials, and assisted the Veterans in creating sensory home programs based on personal goals. The goals of this Capstone were to inform the staff of the Veteran demographic population …

The Influence Of Age, Gender, And Thiol Repletion In An In Vivo Model Of Lewy Body Disorders, Daniel Mason

Electronic Theses and Dissertations

Lewy body disorders are a family of neurological brain disorders associated with olfactory, motor, and cognitive deficits and are collectively defined as α-synucleinopathies, as they are characterized by hallmark “Lewy bodies” composed of aggregated, fibrillar α-synuclein. It is not certain but often posited that fibrillar α-synuclein seeds the progressive, self-propagating spread of Lewy pathology through neuroanatomical circuitry. Furthermore, the site of disease induction is still debated. In Aim I, we developed a novel protocol for generating reproducible and robust α-synucleinopathy in the limbic temporal lobe following infusions of preformed α-synuclein iv fibrils into the mouse olfactory bulb, which is frequently …

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 …

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 …

The Role Of Cyp2a5 In Cadmium-Induced Liver Injury, Julia Salamat

Electronic Theses and Dissertations

Cadmium is present in food and groundwater. Tobacco smoking and occupational exposure are also major sources for cadmium. Cadmium is primarily accumulated in liver, a major organ metabolizing exogenous chemicals. Chemical metabolism may cause detoxification, but it can also cause bio-activation resulting in liver damage. Cytochrome P450s (CYP) are major liver metabolism enzymes, and cadmium chloride (CdCl2) can induce CYP2A5 in mice. We examined the effect of CYP2A5 on CdCl2-induced liver injury using CYP2A5-knockout (cyp2a5-/-) mice. The cyp2a5-/- mice and their control WT mice were injected CdCl2 intraperitoneally at 5 mg/kg body weight, respectively, to induce liver injury. …

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 …

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 Study Of Alcoholic Liver Diseases, Seun Emmanuel Owoseni

Electronic Theses and Dissertations

Excessive alcohol consumption is the primary contributing factor in the development of alcoholic liver diseases (ALD). Nicotine contained in tobacco is a major addictive alkaloid, which enhances the effects of ALDs. The major enzyme involved in nicotine metabolism is cytochrome P450 2A5 (CYP2A5) which is produced in the liver. Alcohol can stimulate the CYP2A5 enzyme. We utilized cyp2a5-/- knockout mice in this research to examine the effects of CYP2A5.

The cyp2a5-/- mice and wild-type (WT) mice were fed liquid ethanol diet with or without nicotine to induce ALD. Nicotine enhancing effects on ALD were observed in WT mice but not …

Evaluation Of The Predictive Ability Of A Screening Instrument Used To Diagnose Co-Occurrence Of Anxiety In Children With High-Functioning Autism., Austin Zachary

Electronic Theses and Dissertations

Anxiety has shown to have a high co-occurrence in children with Autism Spectrum Disorder (ASD), but has been difficult to co-diagnose. This study analyzed the ability of the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to predict positive ASD screenings of the Social Responsiveness Scale (SRS). Parents and children ages 8 to 18 years (N = 100) were screened for anxiety using the SCARED and autism using the SRS. Moderate correlation was found between parent-reported SCARED and positive screening of the SRS (r = .579), with weak correlation found in the child-reported SCARED (r = .105). LASSO regression was conducted …

Lead And Crime: An Ecological Study Between Lead Contaminated Topsoil And Violent Crime., Brian Guinn

Electronic Theses and Dissertations

Lead is a known neurotoxicant. Human exposure to lead comes primarily through environmental exposures, including remnant lead paint, lead contaminated topsoil and lead contaminated water. Prenatal and early life lead exposure has been associated with numerous neurocognitive and neuropsychiatric disorders. This dissertation presents findings from an ecological study which evaluated the geospatial association between topsoil lead content and the incidence of FBI designated violent crime in Jefferson County, Kentucky. A total of 412 topsoil samples were collected along roadways (n=300) and from Louisville Metro Parks (n=112). Jefferson County crime data was obtained from the Louisville Metro Police Department – Crime …

Synthesis And Characterization Of Targeted Bar Encapsulated Polylactic-Co-Glycolic Acid Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Ranjith Radha Krishnan

Electronic Theses and Dissertations

Periodontal disease is one of the most prevalent infectious diseases worldwide. Between 30-50% of the global adult population suffers from periodontal disease. Some form of periodontitis is present in 46% of American adults, corresponding to annual expenditures in excess of 14 billion dollars for treatment and prevention. Current treatments for periodontal diseases involve mechanical removal of plaque, correction of risk factors, gingival surgery and/or antibiotic therapy. To our knowledge there is no effective therapeutic approach that aims to limit pathogen colonization of the oral biofilm or re-colonization after treatment. Interaction of the pathogen Porphyromonas gingivalis with oral streptococci is critical …

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 …

Host Mediated Mechanisms Of Fungal Cell Spread In A Transparent Zebrafish Infection Model, Allison Scherer

Electronic Theses and Dissertations

Innate immunity has developed elegant processes for the detection and clearance of invasive fungal pathogens. Disseminated candidiasis is of significant concern for those with suppressed immune systems or indwelling medical equipment, and mortality in these groups approaches 70%. Poor patient outcomes have spurred the need to understand how this non-motile pathogen spreads in the host. Technical limitations have previously hindered our ability to visualize the role of innate immunity and host tissue barriers in the spread of C. albicans in vivo. Using the zebrafish model to overcome these limitations, we have examined three potential host-mediated mechanisms of dissemination: movement …

Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty

Electronic Theses and Dissertations

This dissertation describes how poly-chlorinated biphenyls (PCBs) exacerbate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). While PCBs were banned in 1979, they still persist in contaminated biota, including food, and are detected in human plasma and adipose. The body burden of PCBs is associated with elevation of liver enzymes and necrosis markers in humans, characteristic of NAFLD. PCB exposure in high-fat diet fed mice leads to steatohepatitis that recapitulate the findings seen in exposed humans. The global estimate of people diagnosed with NAFLD is up to 1 in 4 people, unrelated to dietary or genetic factors. The hepatic mechanisms …

Virulence Regulation In Pseudomonas Aeruginosa Via The Alginate Regulators, Algu And Algr, The Posttranscriptional Regulator, Rsma, And The Two-Component System, Algz/R, Sean Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa is a Gram-negative bacillus able to colonize a wide variety of environments. In the human host, P. aeruginosa can establish an acute infection or persist and create a chronic infection. P. aeruginosa is able to establish a niche and persist in human hosts by using a wide array of virulence factors used for: movement, killing host cells, and evading immune cells and antibiotics. Understanding virulence factors and their regulation has proved to be an important means of combating the morbidity and mortality of P. aeruginosa as well as the ever-increasing threat of drug resistance. By targeting virulence factors …

Association Between Cigarette Smoking And Ovarian Reserve Among Women Seeking Fertility Treatment With Effect Modification By Race And Nat2 Genotype., Islamiat A. Oladipupo

Electronic Theses and Dissertations

Cigarette smoking in women has been associated with adverse reproductive outcomes such as reduced ovarian reserve, poorer in vitro fertilization (IVF) outcomes and increased adverse pregnancy outcomes. This study examined the association of smoking with ovarian reserve in a cross-sectional study of women seeking fertility treatment, and potential effect modification by race and NAT2 acetylator phenotype. Data from 265 women from the Louisville Tobacco Smoke, Genetic Susceptibility, and Infertility (LOUSSI) Study were analyzed. A total of 265 women were recruited through a single infertility clinic between September 2016 and June 2018. Information on current smoking status was assessed using a …

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 …

Innate Immunity, The Hepatic Extracellular Matrix, And Liver Injury: Mathematical Modeling Of Metastatic Potential And Tumor Development In Alcoholic Liver Disease., Shanice V. Hudson

Electronic Theses and Dissertations

The overarching goals of the current work are to fill key gaps in the current understanding of alcohol consumption and the risk of metastasis to the liver. Considering the evidence this research group has compiled confirming that the hepatic matrisome responds dynamically to injury, an altered extracellular matrix (ECM) profile appears to be a key feature of pre-fibrotic inflammatory injury in the liver. This group has demonstrated that the hepatic ECM responds dynamically to alcohol exposure, in particular, sensitizing the liver to LPS-induced inflammatory damage. Although the study of alcohol in its role as a contributing factor to oncogenesis and …