Medicine and Health Sciences Commons^™

Perinatal Periods Of Risk: Examination Of Data Quality & Inclusion Criteria, New Unbiased Reference Groups, And A Nationwide County-Level Analysis, Carol S. Gilbert

Theses & Dissertations

Records of births, infant deaths, and fetal deaths are compiled by the US Vital Records System and used to monitor population health and guide health policy. The Perinatal Periods of Risk Approach (PPOR) relies on vital records data to address fetal and infant mortality in US cities. It uses reference groups to estimate preventable mortality by risk period. To avoid biased analyses due to poor data quality for small and early infant and fetal deaths, an expert committee recommended that PPOR analyses exclude fetal deaths delivered at gestational age (GA) <24 >weeks, and infant deaths and live births with birthweights (BW) …

Molecular Pathogenesis Of A Novel Subgroup Of Peripheral T-Cell Lymphomas, Jiayu Yu

Theses & Dissertations

Peripheral T-cell Lymphoma (PTCL) consists of numerous distinct disease entities. With the current diagnostic criteria over a third of the cases cannot be further classified and are called "not otherwise specified" (PTCL-NOS). Using gene expression profiling (GEP) of tumors, we identified two novels PTCL-NOS molecular subgroups either characterized by high expression of GATA3 (33%), which is associated with Th2 cell differentiation, or high expression of TBX21 (49%) which regulates Th1 cell maturation. Therefore, stratifying patients for diagnosis and identifying the underlying genetic basis to improve clinical therapy becomes critical to prognosis.

First, we performed DNA copy number analysis by using …

Structural And Inhibitory Studies Of Enzymes Essential For Cell Wall And Ergothioniene Biosynthesis In Mycobacterium Tuberculosis, Thanuja D. Sudasinghe

Theses & Dissertations

Tuberculosis (TB) is one of the world’s oldest contagious diseases caused by Mycobacterium tuberculosis (M. tb). With the emergence and spread of drug-resistant M. tb strains, there is an urgent need to discover novel drugs and drug targets specifically against drug-resistant strains and dormant bacteria. This dissertation focuses on M. tbenzymes essential for the M. tb cell wall and ergothioneine biosynthesis. The M. tb cell wall acts as a protective barrier due to the presence of unique lipids and mycolic acids. Among these lipids, trehalose-dimycolate and mycolylarabinogalactan play a major role in constructing and maintaining the outer …

Superoxide And Pulmonary Hypertension, Tammy Wichman

Theses & Dissertations

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease, which is progressive and fatal despite advances in therapy. Animal models have shown that oxidative stress may be pathogenic in PAH. We hypothesize that oxidative stress, as measured by increased levels of a specific reactive oxygen species, superoxide (O₂^•-), mayplay a role in PAH in humans. Using a novel application of electron paramagnetic resonance (EPR) spectroscopy, we initially evaluated whether levels of O₂^•- from whole blood collected from the pulmonary artery collected during right heart catheterization (RHC) would correlate with O₂^•- levels in peripheral …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Mucin And Splice Variant Profiles Of Pancreatic Adenocarcinoma Predict Patient Survival And Subtyping, Christopher M. Thompson

Theses & Dissertations

PDAC is a pancreatic epithelial malignancy and demonstrates aggressive progression and bleak patient prognosis. Despite decades of research, the evolution of novel diagnostics and intervention modalities for PDAC is stagnant. This dissertation explores the characteristic aberrant and elevated expression of mucins in PDAC. Beginning with the hypothesis that mucins are associated with disease aggressiveness, analysis of PDAC patient survival in TCGA revealed no associations between single mucin expression and patient survival. This led to the underlying issue of PDAC tumor cellularity since this disease demonstrates variability in the proportion of cancer cells within the tumor. Tumor purity assessed with the …

Design, Synthesis And Evaluation Of Novel Inhibitors Of Type 5 And 10 17Β-Hydroxysteroid Dehydrogenases, Ahmed Morsy

Theses & Dissertations

17β-Hydroxysteroid dehydrogenases (17β-HSDs) are essential enzymes in steroid metabolism. More and more evidence points to the pivotal contributions of these enzymes in various other metabolic pathways. Therefore, the latest research results give new insights into the complex metabolic interconnectivity of the 17β-HSDs with human diseases. This dissertation focuses on the metabolic activities of type 5 and 10 17β-HSDs. More specifically, regarding 17β-HSD5 contributions to the progression of prostate cancer (PCa) and 17β-HSD10 aggravation of amyloid-beta (Aβ)-induced toxicity in Alzheimer's disease (AD).

The second leading cause of cancer-related death in males is PCa, with the highest incidence rate of all cancers …

The Driving Simulator Visual Field In Glaucoma – A Novel Task To Test Available Field Of View, Deepta Ghate

Theses & Dissertations

Glaucoma causes peripheral vision loss and impaired driving performance. We developed a novel driving simulator visual field task (DSVF) in a panoramic driving simulator to map the available field of view under different perceptual task loads in naturalistic settings. Our hypothesis is that “available field of view” will decrease with increasing task load in both glaucoma subjects and controls. This is a cross-sectional study with 28 glaucoma subjects and 19 controls. DSVF (60̊ x 20̊ visual field at 2.5 m) was tested in a high-fidelity interactive driving simulator in 4 different scenarios: a) no distractions b) no driving condition with …

The Effect Of Obstacle Intervals On Foot Integrated Pressure And Obstacle Negotiation Strategy, Zhuo Wang

Theses & Dissertations

When stepping over a single obstacle, despite of some spatiotemporal parameter changes, the impulse of the leading and trailing leg stays the same. This is considered an efficient obstacle avoidance strategy. However, research has shown that the strategy of multiple obstacles negotiation is different from a single obstacle crossing. Would this efficient strategy still exist during multiple obstacles negotiation? This study attempted to answer this question. Nineteen healthy young adults were recruited in this study. Each participant was required to complete 15 trials under 3 conditions: one-step, two-step, and three-step intervals. Data were collected for foot integrated pressure (FIP), walking …

Neurocognitive Impairment In People Living With Human Immunodeficiency Virus (Hiv): Risk Factors And Mortality, Zaeema Naveed

Theses & Dissertations

Despite the widespread use of combination antiretroviral therapy (cART), HIV-associated neurocognitive impairment (NCI) persists in people living with HIV (PLWH) with clinical and public health implications. Studies have generated inconsistent results regarding etiological factors for NCI in PLWH and a brief user-friendly predictive tool is desirable in clinical practice to assess the probability of having NCI in PLWH. Furthermore, factors associated with clinically meaningful decline in neurocognitive status and survival disadvantage for patients with NCI are understudied in the post-cART era. The goal of this dissertation was to investigate factors associated with baseline NCI and neurocognitive decline and the association …

Design, Synthesis And Antineoplastic Evaluation Of A Variety Of Small Molecule Scaffolds, Bader Huwaimel

Theses & Dissertations

Several appealing strategies emerged for selective anticancer therapy. Mitochondrial respiratory complex II (CII) is a potential target for many human diseases, including cancer. We have designed, synthesized, and characterized a library of potent CII inhibitors atpenin A5 and diazoxide analogs with enhanced ‘drug-likeness’ and evaluated their antineoplastic activity. Several of these derivatives showed greater activity and selectivity to inhibit the CII. Design aspects of lead derivatives (16c) include optimum ligand lipophilicity efficiency of >5, and half-life of >3 hours. This derivative displayed potent and selective inhibition of cell proliferation in both multiple human prostate cancer cell lines and …

The Effect Of Polyunsaturated And Saturated Fatty Acids On Seizure Presence And Severity In A Cohort Of Subjects In An Epilepsy Monitoring Unit, Jana K. Wells

Theses & Dissertations

Ketogenic diet therapies (KDTs) have been used to treat epilepsy for nearly 100 years. Although effective, restrictive diet patterns and unknown impacts on long-term health outcomes often prevent their use as first-line therapy. To date, a distinct mechanism of action for KDTs has not been determined and evidence suggests fatty acids (FAs) may play a role in eliciting anti-seizure effects. This dissertation aimed to provide insights into the effect of polyunsaturated fatty acids (PUFAs) and saturated fatty acids (SFAs) on seizure presence and severity through the analysis of dietary intake in a cohort of patients admitted to an epilepsy monitoring …

An Explanatory Sequential Mixed Methods Nutrition And Physical Activity Intervention Study On Changes In Knowledge, Self-Efficacy, And Outcome Expectations Of Fathers, Sarah Hortman

Theses & Dissertations

Overweight and obesity rates are a continuing concern resulting in poor health outcomes and annual healthcare costs in the billions of dollars. An upstream approach of health promotion is critical to change the focus from treatment and management to prevention of chronic disease. Preventing chronic disease through evidence-based health promotion practices incorporating educational interventions aimed at dietary and physical activity behaviors will preclude negative health outcomes including cardiovascular disease, type 2 diabetes, and hypertension.

The family environment is an important consideration in the prevention of chronic disease including obesity. Parents are role models for their children, including fathers who are …

Neural Oscillatory Activity Serving Sensorimotor Control Is Regulated By The Mitochondrial Redox Environment In Health And Disease, Rachel Spooner

Theses & Dissertations

Despite effective regimens of combination antiretroviral therapy, individuals with HIV are still at higher risk for developing forms of cognitive impairment, with one of the most common behavioral abnormalities to manifest being motor dysfunction. This is an important consideration, as deficits in motor control likely contribute to higher-order cognitive impairments, which together, lead to functional dependencies in the ever-growing aging population of HIV-infected adults. While the neuroanatomical bases of motor dysfunction have recently been illuminated in people living with HIV (PLWH), there remains an open question regarding the molecular processes supporting the circuit-level neuronal dynamics that potentially serve these behavioral …

Fire Service Covid-19 Infection Prevention And Control Policy Comparison, Saaddedine Dichari

Theses & Dissertations

To date, there have been over 2.7 million deaths and more than 126 million cases attributed to the COVID-19 pandemic (JHU, 2021). This pandemic has affected nearly every aspect of daily life. Among those impacted are U.S. firefighters, as they provide many services beyond simply extinguishing structure fires and are frequently dual certified as emergency medical technicians. Many of the victims of this pandemic have relied on first responders to provide them with emergency medical care and hospital transport. When caring for these infected patients, firefighters have an increased risk of exposure and must be provided with adequate …

The Role Of Vgll4 And Mark2-Hdac Axis In Mitosis And Cancer, Yongji Zeng

Theses & Dissertations

The Hippo pathway is an evolutionarily conserved signaling pathway that plays important roles in stem cell biology, tissue homeostasis, and cancer development. The Hippo core signaling pathway features a kinase cascade consisting of mammalian sterile-20 like protein 1/2 (Mst1/2) and large tumor suppressor 1/2 (Lats1/2). Inactivation of the Hippo pathway is correlated with the promotion of proliferation and anti-apoptosis through activation of the transcriptional co-activator Yes-associated protein (YAP). YAP functions through binding with TEA-domain transcription factors (TEAD1–4) to activate target genes.

Vestigial-like 4 (Vgll4) functions as a transcriptional co-repressor in the Hippo-Yes associated protein (YAP) pathway. Vgll4 inhibits cell proliferation …

Biomedical Porcine Models For The Study Of Surgical Hemostasis, Hindlimb Ischemia, And Pancreatic Cancer, Shruthishree Aravind

Theses & Dissertations

Murine models have dominated the world of biomedical research and comparative medicine since their development in the early 1900s. [1] While they may be suitable models to study proteomics and genomics, they may not serve as effective translational models. [2-4] Murine models do not accurately model the pathophysiology of human disease and are limited by their size, application of medical imaging and intervention, which reduces their overall preclinical predictive value. [2-4]

Porcine models on the other hand, are slowly and steadily bridging the gap between murine models and human patients. [5] Pigs …

Examination Of Access, Utilization, And Barriers To Care Among Special Populations In The United States, Jed R. Hansen

Theses & Dissertations

Utilizing healthcare services is a complex phenomenon in the United States. While system-level barriers and facilitators of care, along with individual consumer choices, are known to affect access and subsequent use of services, the interaction among the factors that lead to utilization remains unknown. Examining access and utilization of healthcare services using a consumer framework incorporating both access barriers and facilitators and consumer-level dimensions that affect choice in seeking care may inform access and utilization research. The purposes of this dissertation were 1) to explore the presence of facilitators and barriers to care in ambulatory healthcare locations for non-emergent care …

Clinical Consequences And Determinants Of False Positive Blood Cultures In Adult Hospitalized Patients, Sidra Liaquat

Theses & Dissertations

Blood cultures are the gold standard for detecting blood stream infections. However, in the US, 0.6-6% of all blood cultures get contaminated leading to adverse clinical outcomes such as unnecessarily prolonged hospital stay and antibiotic therapy. Using electronic medical records, we explored the clinical outcomes and patient-specific risk factors of contaminated blood cultures in an era where rapid blood culture testing was being utilized to provide blood culture results within hours. Rapid blood culture test results can help clinicians in early and more effective management of patients with contaminated blood cultures, thus improving clinical outcomes. We also studied the impact …

Characterization Of Di-Aryl Urea Compounds Against Acute And Chronic Toxoplasma Gondii, Austin Sanford

Theses & Dissertations

Toxoplasma gondii is an obligate intracellular parasite that has infected nearly 60 million individuals in the United States alone. Acute infection causes ill effects to the fetus in utero when mothers are primarily infected, and to immunocompromised individuals. Chronic infection consists of quiescent tissue cysts located primarily in brain tissue and is capable of reverting back to the acute stage causing severe toxoplasma encephalitis in immunocompromised individuals. Current treatments for acute infection are lacking while there are no approved treatments for the clearance of chronic infection. The aim of this research was to evaluate a family of di-aryl urea compounds …

Is The Walking Pattern Similar Between Slope Walking And Obstacle Negotiation?, Jiani Lu

Theses & Dissertations

Studying biomechanical characteristics of human motion sheds light on the motor control strategies in the central nervous system. Slope walking and obstacle negotiation appear to have some similarities in control strategies based on subjective observation, but these two motions have never been compared objectively in biomechanics literature. This study aimed to investigate the similarities between obstacle negotiation and slope walking in kinematics and muscle activity. The similarities were determined by the correlation of the maximum heel elevation and muscle co-activation index between obstacle negotiation and inclined treadmill walking. The strength of correlation was compared in four different pairs of conditions: …

Adaptation Of Human Locomotion And Unilateral Limb Loading During Different Inclination Treadmill Walking, Yuhang Zhang

Theses & Dissertations

Human locomotion is adaptive in any external environment or different terrains, which has been widely investigated. For example, people can walk at different walking speeds in each leg on a split-belt treadmill. However, human locomotor behaviors are passively adapted during the split-belt treadmill walking. Therefore, the knowledge of how humans actively adjust the flexibility of locomotion is limited by using the split-belt treadmill. To address this gap, this study investigated the flexibility of locomotion by using a 4-lb ankle weight on the dominant leg to induce the asymmetric walking pattern when walking on the inclined, declined, and level treadmill. Twenty …

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …

Modification And Antichlamydial Activity Evaluation On Dysregulators Of Cylindrical Proteases, Jiachen Feng

Theses & Dissertations

Chlamydia trachomatis infection is the most commonly reported sexually transmitted disease in the United States and the world. This pathogen can cause long-term health problems including blindness, pelvic inflammatory disease (PID) and ectopic pregnancy, which can be life-threatening if left untreated. To this day, there is no chlamydia-specific drug on the market. The standard treatment uses broad-spectrum antibiotics, which may affect regular functions of the commensal microbiota and leads to the development of bacterial resistance. Recently, a series of compounds based on Activators of Self-Compartmentalizing Proteases (ACP) was reported to show antichlamydial activity. Based on that scaffold, we prepared 21 …

Reach, Effectiveness, Adoption, And Maintenance Of Mobile Electronic Clinical Decision Support Tools Deployed As Part Of National Quality Improvement Projects, Ellen K. Kerns

Theses & Dissertations

Electronic clinical decision support (ECDS) tools are often developed within quality improvement (QI) projects to increase adherence with the latest clinical practice guidelines. However, the potential reach and maintenance of ECDS use beyond the time and location of their associated project are very limited. Deploying ECDS using a mobile app (mECDS) has shown the potential to be a viable method of overcoming these limitations. However, it is unclear what pattern the reach and adoption of such a tool might follow and what effect this use has on clinical practice. Our team developed an app which contained two different mECDS tools …

From Pipeline To Health Equity: A Case Study Of Health Profession Pipeline Students, Sonja F. Tutsch

Theses & Dissertations

Health equity arises from the social determinants of health. Access to culturally and linguistically competent health services is a major determinant of health. Despite health profession pipeline intervention efforts spanning more than 50 years, diversity in the health professions has not been achieved, and disparities in health among members of minority groups remain prevalent. Health profession pipeline programs came into existence to help grow minority representation among health professionals serving in underserved, disadvantaged, communities, where disparities in health are most prevalent. One underlying assumption was that minority students from underserved communities understand the needs of these communities best and are …

Secreted Mucin 5ac-Mediated Epithelial And Stromal Modulations Augment Pancreatic Cancer Aggressiveness, Koelina Ganguly

Theses & Dissertations

The mucosal layer that shields the epithelium of the body cavities is made up of high molecular weight, heavily glycosylated proteins called mucins that are broadly categorized into transmembrane and secreted members. Aberrant expression of secreted mucin MUC5AC has been implicated in lung, stomach, and colon cancer pathologies. MUC5AC is expressed de novo in the pancreas upon oncogenic insult, and its abundance in pancreatic tumor and circulation correlates to disease progression. However, few studies have explored beyond the diagnostic and prognostic significance of MUC5AC in pancreatic cancer (PC).

In this dissertation, we sought to investigate the mechanistic contribution of MUC5AC …

Quantifying Fear Of Falling By Utilizing Objective Body Sway And Muscle Contraction Measures, Chenfan Gui

Theses & Dissertations

Fear of falling (FOF) is a psychological condition that can lead to increased morbidity and mortality in the elder population. However, the subjective and multidimensional nature of FOF resulted in the limitations of existing FOF measurements, which could influence the quality of those studies. The present study aimed to quantify FOF by using objective center of pressure (COP) trajectories and muscle contraction of the lower extremity to compensate for those limitations. Nineteen young healthy adults (24 years ± 2.47) were recruited in the present study. Subjects were required to watch three 360-degree videos, one control video and two roller coaster …

Development Of Long-Acting Antiviral Drug Nanoformulations, Denise Cobb

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, opportunities to improve its profile abound. ART is limited by putative viral reservoir penetrance, emergence of viral mutations, inherent toxicities, and regimen non-adherence. These highlight the need improved drug delivery schemes. Previously, our lab has demonstrated that targeting mononuclear phagocytes for antiretroviral drug delivery extends drug half-life and improves penetrance into viral reservoirs, addressing these limitations of ART. Herein, we developed synthetic and biologic antiretroviral (ARV) drug nanocarriers improve the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of ARVs through …