Medicine and Health Sciences Commons^™

It Takes Two To Tango: The Toxin-Chaperone Relationship, Alisha Kellner

Electronic Theses and Dissertations

Cholera toxin (CT) enters the cell via receptor-mediated endocytosis and travels in a retrograde fashion to the endoplasmic reticulum (ER). The catalytic A1 subunit (CTA1) is then displaced from the rest of the holotoxin, unfolds, and is exported to the cytosol where it regains an active conformation for the ADP-ribosylation of its G-protein target. We have shown that the cytosolic chaperones Hsp90 and Hsc70 are required for CTA1 translocation to the cytosol. We have also shown that both are able to independently bind and refold CTA1. Using libraries of CTA1-derived peptides, we have identified a single Hsc70 binding site, YYIYVI …

Ultrasound Measured Flexor Muscle Thickness In The Forearms Of Rock Climbers, Michael Marsala

Electronic Theses and Dissertations

PURPOSE: To examine differences in the forearms of rock climbers using ultrasound to measure the muscle thickness of the finger flexors. METHODS: A total of 33 participants were recruited, 22 climbers (22.23 years; 68% male) and 11 controls (21.8; 55% male). Climbers provided self-reported ratings of their climbing ability, skill level, and preferred mode of climbing (e.g. sport climbing vs. bouldering). Anthropometric measures, including body fat percentage, were measured in all participants. Ultrasound measurements were taken with the participant lying on their back on a padded table with their dominant hand supinated. Muscle thickness measurements were taken at the forearm …

Stress, Coping, And Quality Of Life Among Parental Caregivers Of Children With Autism Spectrum Disorder, Dawn Turnage

Electronic Theses and Dissertations

Purpose: Parental caregivers of children with Autism Spectrum Disorder (ASD) are exposed to stressors associated with the daily care of raising a child with a developmental disability, which may negatively impact parental quality of life (QOL). The specific aim of this study was to examine the relationships between demographic factors, stress, and coping among parental caregivers of children with ASD to determine whether predictors of QOL exist. Methodology: This study was descriptive, and an electronic survey was distributed to Florida parents of children, age 3-21 years old, diagnosed with ASD. The survey measured parent reported demographic factors, severity of the …

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 …

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 …

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 …

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 …

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.

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 …

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 …

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 …

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 …

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 …

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 …

Effect Of Grape Components On Periodontal Disease., Juili Subodh Shivde

Electronic Theses and Dissertations

Background: Half of the adult American population (47 %) are victims of periodontitis, a chronic inflammatory disease which leads to destruction of the tissues supporting the tooth. Periodontitis is initiated by periodontal pathogens and caused by excessive or prolonged host mediated inflammation. Porphyromonas gingivalisis one important agent implicated in the etiopathogenesis of chronic periodontitis. Pro-inflammatory cytokines induced by periodontal pathogens can cause alveolar bone loss and periodontitis. Bone loss is caused by the imbalance of bone formation and bone resorption. Osteoclasts are major cells that cause bone resorption. Moreover, periodontal inflammation also leads to bone resorption. Grapes are rich …

Adolescent Sexual And Reproductive Health In The Gambia., Sandhya Lohani

Electronic Theses and Dissertations

Adolescence is a crucial period in human development. Knowledge and awareness about when to have children, when to have sex, and use of contraceptives impacts the chances of teenage pregnancy and risk of sexually transmitted diseases. The objective of this study is to determine the prevalence and associated risk factors related to age of sexual debut, teenage pregnancy, and use of contraceptives in the Gambia. This study also compares the data with 2014 survey research conducted in the Gambia. The total study population were 50 adolescents aged 13-21 years from Bafuluto and surrounding communities in the Gambia. Among 50 respondents, …

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 …

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 …

Cholesterol Metabolism And Statin Effects On An Fh Class Ii Ldl-Receptor Mutation., Linda Omer

Electronic Theses and Dissertations

Familial hypercholesterolemia (FH) is a common genetic disease and has been studied with the aim of finding a curative measure for decades. FH is caused by mutations in the low-density lipoprotein receptor (LDLR) resulting in defects in LDL-cholesterol (LDL-C)-receptor mediated endocytosis and development of premature cardiovascular disease (CVD). Here I describe the use of a corrected and non-corrected LDLR FH cell model to investigate receptor-mediated endocytosis and statin effects. For these studies, we reprogrammed FH fibroblast cells to induced pluripotent stem cells (iPSC) and confirmed their pluripotency and ability to differentiate to hepatocyte-like cells (HLC). A clustered regularly interspaced short …

Influences Of Porphyromonas Gingivalis On The Viability Of Esophageal Cancer Cells., Muddasir Mohammed

Electronic Theses and Dissertations

A recent study demonstrated an association between the Porphyromonas gingivalis (Pg)infection and the progression of ESCC (Gao et al., 2016). However, how Pg infection affects the nature of ESCC remains unknown. We examined the effects of Pg on the proliferation and chemotherapy drug-induced apoptosis of ESCC cells and elucidated the signaling molecules involved in these processes. Method: Apoptosis and cell proliferation were tested using Flow cytometry and Tetrazolium salt based proliferation assays respectively. Western Blot was utilized to detect the protein expression. CDK2 and Cyclin E were knocked down in the ESCC cells through transfection. Unpaired T-test and …

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 …

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. …

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 …

Characterizing The Gut Microbiota During Plasmodium Infection And Antimalarial Treatment., Joshua E. Denny

Electronic Theses and Dissertations

Plasmodium, the parasitic cause of malaria, is a global pathogen, annually causing 216 million infections and 445,000 deaths. As drug resistance continues develop and no effective vaccine is available, it is critical to understand the factors underlying the severity of this disease. Plasmodium is an extra-gastrointestinal tract infection where the parasite infects red blood cells causing clinical malaria. However, recent publications have pointed to interactions between the gut microbiota and malaria. With this in mind, the role of the gut microbiota in malaria infection was studied. C57BL/6 mice from different vendors displayed differential resistance and susceptibility to severe malaria, …

Effects Of Hydrogen Sulfide In Hyperhomocysteinemia-Mediated Skeletal Muscle Myopathy., Avisek Majumder

Electronic Theses and Dissertations

Although hyperhomocysteinemia (HHcy) occurs due to a deficiency in cystathionine-β-synthase (CBS), causing skeletal muscle myopathy, it is still unclear whether this effect is mediated through oxidative, endoplasmic reticulum (ER) stress, both or something else. Cystathionine γ-lyase (CSE) and CBS are the main H₂S producing enzymes, which produce Hydrogen sulfide (H₂S) from Hcy in the transsulfuration reaction. H₂S is an anti-oxidant compound and patients with a CBS deficiency cannot produce enough H₂S, thus rendering them vulnerable to excess Hcy-mediated damage. Both in-vitro (C2C12 cells) and in-vivo (CBS+/- mice) models were used to …

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 …

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 …