Medicine and Health Sciences Commons^™

Evaluation Of Stratified Antibiograms For Use In Laboratory And Antimicrobial Stewardship, Linsey Donner

Theses & Dissertations

Antibiograms are critical for choosing empiric antimicrobial therapy. Cumulative antibiograms, which aggregate susceptibility data, can mask differences within specific patient subsets or clinical syndromes. This dissertation was done to determine if antibiotic susceptibilities showed substantial differences when comparing stratified antibiograms to cumulative antibiograms.

Antibiotic susceptibility data was retrospectively obtained from Nebraska Medicine January 1, 2017 – December 31, 2019 for Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecalis. The University of Nebraska Medical Center’s web antibiogram clinical decision support tool was used to export the data. Bacteria-antibiotic susceptibility rates of stratified antibiograms …

The Role Of Micrornas In The Pathophysiology Of Neonatal Hypoxic-Ischemic Brain Injury, Eric S. Peeples

Theses & Dissertations

Neonatal hypoxic-ischemic brain injury (HIBI) is a devastating injury resulting from impaired blood flow and oxygen delivery to the brain at or around the time of birth. The subsequent metabolic failure and cellular injury in the brain can be partially attenuated by rapid initiation of therapeutic hypothermia, but even with prompt induction of hypothermia, more than one in four survivors suffer from major developmental disabilities – an indication of the critical need for more effective therapies. MicroRNAs (miRNA) may be able to act as therapeutic targets in neonatal HIBI; however, very little is known about the endogenous expression of miRNAs …

Humanized Mice For Brain Infection Of Emerging Viruses, Edward Makarov

Theses & Dissertations

Studies on the pathogenesis of emerging viruses that present a global threat are critical for pathogen classification and therapeutic development. Humanized mice enable investigation of viral pathogens, including Human immunodeficiency virus (HIV-1), Zika virus (ZIKV), Coronavirus 2 (SARS-CoV-2), and Dengue virus (DENV), offering an advanced understanding into the mechanisms of viral perseverance in its natural human host cells and for therapeutic discovery. Realizing the diverse dynamics of various viral infections with the capacity to establish an innovative acuity for therapeutics and mechanics when utilizing humanized mice contributes a formerly inaccessible insight into human-specific viral pathogenesis and treatment. We recently developed …

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 …

Health Service Utilization And Expenditure In Cardio-Metabolic Conditions In The United States Adults, Kavita Mosalpuria

Theses & Dissertations

Metabolic syndrome is multicomponent risk factor for cardiovascular diseases (CVD) and type 2 diabetes that reflects the clustering of at least 3 cardiometabolic risk factors, among hypertension, impaired glucose regulations, hypercholesterolemia, and obesity. CVD are the leading cause of death in the U.S. CVD occur at earlier age and is a major cause of death and disability among people with diabetes. As compared to Japan, 13.3% to 44% of the excess CVD mortality in the U.S. can be explained by the metabolic syndrome. The prevalence of metabolic syndrome was 34.3% in 2007 to 2014 and it increases with age. Metabolic …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …