Medicine and Health Sciences Commons^™

Multimodal Investigations For The Identification Of Surgically Relevant Brain Areas, Kevin Tyner

Theses & Dissertations

Epilepsy is a neurological disease leading to recurrent and unpredictable seizures. Patients can be diagnosed as focal onset, where the seizure focus resides in one hemisphere; generalized onset, where seizure foci reside in both hemispheres; or unknown onset. Anti-seizure medications are the first line of treatment, and those whose seizures cannot be controlled with medication are diagnosed with drug-resistant epilepsy (DRE). For patients diagnosed with focal onset epilepsy to achieve seizure freedom, surgical resection of the epileptogenic zone (EZ), the region of the brain that is both necessary and sufficient for initiating seizures, is required. The EZ is a theoretical …

Prevalence Of Type A And Type B Personality Among Undergraduate Nursing Students At Private School Of Nursing Karachi Pakistan: A Cross-Sectional Analytical Study, Farhana Shaheen

Theses & Dissertations

Background: Academic institutions strive for exceptional graduates. However, personality and learning psychology affect student performance. Type A personality students may develop heart palpitations due to impatience and stress. They are less sociable than Type B personalities but more idealistic, competitive, and deadline oriented. These disparities among personalities may impair their academic and job success, especially in healthcare, where interpersonal skills are vital.
Aims: The primary aim of the study was to find out the prevalence of Type A and Type B personality among undergraduate nursing students and to find the association between personality Types and academic years.
Methodology: In this …

Cystic Duct Morphology And Heister Valves: A Cadaveric Study, Cierra R. Goerish

Theses & Dissertations

Continued occurrence of cholelithiasis, gallstones, commonly results in cholecystectomy, removal of the gallbladder. Having a comprehensive anatomical, histological, and physiological knowledge of the biliary apparatus is imperative in clinical medicine today. Additionally, the functionality of cystic duct (CD) Heister valves (HV) has been speculatory since being reported in 1732. This study summarizes the morphology, orientation, and variability of the gross biliary system and provides data to help justify HV functionality.

Cadaveric dissection was utilized for gross observation and analysis of the biliary system. The angulation of the CD was found primarily as an acute angle; however, obtuse angulation could be …

Mechanisms Of Mutated Myosin Vb Mediated Cholestasis In Microvillus Inclusion Disease, Melissa S. Holzapfel

Theses & Dissertations

Microvillus inclusion disease (MVID) is a constitutive intestinal epithelial disease which causes definitive intestinal failure and cholestatic liver disease primarily caused by mutations in the Myosin Vb gene. Genotype-clinical phenotype associations suggest that the progression of liver disease can be predicted through a correlation between myosin Vb residual function and variable retention of bile salt transport machinery in intestinal enterocytes and liver hepatocytes. We proposed that aberrant distribution of bile salt transport proteins disrupts enterohepatic regulation of bile acids and contributes to the progression of cholestatic liver disease. To investigate the genotype-phenotype correlation, samples from MVID patients were evaluated for …

Translating A Pediatric Weight Management Intervention Into Medically Underserved Areas, Caitlin Golden

Theses & Dissertations

Despite substantial prevention and treatment efforts, childhood obesity remains a pressing public health concern. Disparities persist in obesity prevalence among children of lower socioeconomic status, racial and ethnic minority groups, and those residing in rural areas. The vast majority of efficacious pediatric weight management interventions (PWMIs) have been based in larger cities and urban areas delivered through inter-disciplinary teams in a hospital or medical center, and the degree to which these or other efficacious PWMIs have been translated to, and are feasible in, typical rural or micropolitan areas is unclear. This dissertation describes a dissemination strategy and a systematic approach …

Characterization Of 1,1-Diarylethylene Foxm1 Inhibitors Against High-Grade Serous Ovarian Carcinoma Cells, Cassie Liu

Theses & Dissertations

Forkhead box M1 (FOXM1) is a member of the conserved forkhead box (FOX) transcription factor family. Over the last two decades, FOXM1 has emerged as a multifunctional oncoprotein and a robust biomarker of poor prognosis in many human malignancies. FOXM1 and its associated oncogenic transcriptional signature are enriched in >85% of ovarian cancer cases, and FOXM1 expression and activity can be enhanced by a plethora of genomic, transcriptional, post-transcriptional, and post-translational mechanisms. As a master transcriptional regulator, FOXM1 promotes critical oncogenic phenotypes in ovarian cancer, including: (1) cell proliferation, (2) invasion and metastasis, (3) chemotherapy resistance, (4) cancer stem cell …

Evaluation Of Awareness, Knowledge, And Preventive Intervention Of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults, Yi Du

Theses & Dissertations

The prevalence of nonalcoholic fatty liver disease (NAFLD) among Chinese young adults (CYA) aged 18-25 years ranges from 4.7% to 15.1% and has kept increasing in recent years. Previous studies reported limited awareness and knowledge of NALFD among middle-aged and older Chinese populations, however, they have not investigated awareness in CYA, for which there is no well-validated questionnaire. There is currently no efficacious educational intervention on NAFLD for CYA.

The objectives were 1) to develop and validate a questionnaire which can be used to assess the awareness and knowledge of NAFLD among CYA; 2) to assess the awareness and knowledge …

Building An Artificial Intelligence Framework For Hypertension Diagnosis: A Use Case Of The Problem List Curation, Ketemwabi Yves Shamavu

Theses & Dissertations

Hypertension is the world's leading factor in cardiovascular disease. Forty-seven percent or close to one in two Americans aged 18 and older are affected. It predicts approximately a thousand deaths per day. Based on recent statistics from the Centers for Disease Control and Prevention, one in three patients with hypertension does not know they are hypertensive. Seventy-five percent of hypertensive patients have uncontrolled hypertension - meaning that they are not treated to target. While there is extensive literature on hypertension diagnosis and management, there is an apparent gap in understanding and acknowledging that a person is hypertensive. Moreover, blood pressure …

The Development Of Polymeric Dexamethasone Prodrug Nanomedicines For The Treatment Of Lupus Nephritis, Zhifeng Zhao

Theses & Dissertations

Lupus nephritis (LN) is a significant cause of morbidity and mortality among lupus patients. Glucocorticoids (GCs) are uniformly used in clinical LN management. Their notorious toxicities, however, have hampered the long-term clinical application. To circumvent GCs’ adverse effects while maintaining their potent therapeutic efficacy, we have developed a micelle-forming polyethylene glycol (PEG)-conjugated dexamethasone prodrug (ZSJ-0228), which could passively target the inflamed kidney in NZB/W F1 lupus-prone mice. It was found that monthly ZSJ-0228 treatment for five months significantly reduced the incidence of nephritis in NZB/W F1 mice with an improved survival rate. Unlike the dose equivalent daily dexamethasone treatment, long-term …

Feasibility And Efficacy Of Bisphosphonate Use For The Prevention Of Bone And Muscle Loss, Laura E. Flores

Theses & Dissertations

Loss of bone and muscle mass often occurs in tandem, increasing the risk of fragility fractures. Whereas many drugs are approved for the treatment of bone loss, there are few treatments available for the concomitant loss of bone and muscle. Identification of a treatment to mitigate pathologic bone and muscle atrophy has the potential to impact countless populations and influence approaches for healthy aging. Bisphosphonates have emerged as a potential treatment for both bone and muscle loss in cellular, murine, and observational human studies. Our findings of modest weight maintenance in postmenopausal women treated with 12-months of risedronate, relative to …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

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 …

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 …

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 …

Cardioprotective Roles Of Hydrogen Sulfide Donor Treatment In Diabetic Cardiomyopathy, Sumit Kar

Theses & Dissertations

Diabetes mellitus (DM) increases the risk of heart failure 2-4-fold. Intensive glycemic control does not abate this risk in DM patients, suggesting that DM-induced heart failure is beyond hyperglycemia. DM silently induces cardiac muscle disorder termed diabetic cardiomyopathy (DMCM), which progresses to heart failure. The objective of this dissertation is to understand the mechanistic underpinnings of DMCM to develop new solutions to diagnose and treat heart failure in DM.

The heart pumps blood due to the contraction and relaxation of terminally differentiated cardiomyocytes with limited regenerative capacity. The DM environment of hyperglycemia, hyperlipidemia, and inflammation causes cardiomyocyte death and leads …

Beyond The Eye: The Neural Signature Of Cerebral Visual Processing In Children With Cerebral Palsy, Jacy R. Hannan

Theses & Dissertations

Cerebral palsy (CP) is a permanent, non-progressive neuromuscular disorder diagnosed early in childhood. Frequently the lesion that causes the motor impairments in individuals with CP concurrently disrupts the visual networks, placing them at a high risk of cerebral visual dysfunctions. Cerebral visual impairment (CVI) often remains unrecognized or misdiagnosed in people with CP. Despite the crucial role of visual function in the development of movement and cognition, the neurophysiological basis of the cerebral visual dysfunctions is almost entirely unknown. This investigation aimed to examine the neurophysiological mechanisms underlying cerebral visual dysfunction in children with CP. Specifically, this research used magnetoencephalographic …

Glycemic Variability In Patients With Stage Ii-Iii Colon Cancer, Natalie Mandolfo

Theses & Dissertations

Patients with cancer experience metabolic changes such as hypoglycemia, hyperglycemia, and glycemic variability; collectively termed malglycemia. Glycemic variability, defined as fluctuations in glucose, is a marker of metabolic instability. Higher glycemic variability is associated with adverse health outcomes in the general population and in those with diabetes. Little is known about glycemic variability in patients with cancer, especially those with solid tumor malignancies. Glycemic variability is associated with increased infection, shorter periods of remission, and higher mortality in patients with hematological cancer. This body of work describes the concept and measurement of glycemic variability to assess glycemic control in patients …

Impact Of Immunotherapy On The Survival Of Pancreatic Adenocarcinoma Patients: An Analysis Of The National Cancer Database, Saber A. Amin

Theses & Dissertations

Pancreatic adenocarcinoma (PDAC) represents 7.2% of all cancer deaths, and by 2030, it will become the second leading cause of death due to cancer. The median overall survival (OS) is 17-23 months in resectable and 4-6 months in metastatic PC [8-9]. The 5-year survival of resectable PC is 22%, and unresectable PC is 8%. A majority of patients treated with standard treatments such as surgery, chemotherapy, and radiation therapy eventually succumb to the disease due to widespread micrometastases at the time of diagnosis. Due to the minimal effect of the current treatments, novel treatment strategies such as immunotherapeutics have been …

Development Of An Lc-Esi-Ms/Ms Method For Determination Of A Novel Pyrrolomycin (Mp-1) And Application To Pre-Clinical Adme Studies, Wafaa N. Aldhafiri

Theses & Dissertations

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of a novel Pyrrolomycin (MP-1) in mouse plasma. MP-1 was extracted from plasma utilizing a structural analog (PL-3) as the internal standard (IS). Analyte separation was achieved using a Waters Acquity UPLC®BEH C18 column (1.7 µm, 100 x 2.1 mm) protected with Acquity UPLC C18 guard column. Mobile phase consisted of 0.1% acetic acid in water (10%) and methanol (90%) at a total flow rate of 0.25 mL/min. The mass spectrometer was operated at unit resolution in the multiple reaction …

Integrating Geriatric Assessment And Genetic Profiling To Personalize Therapy Selection In Older Adults With Acute Myeloid, Vijaya R. Bhatt

Theses & Dissertations

Integrating geriatric assessment for patient profiling and genetic profiling of leukemic cells represents an innovative approach to personalize therapy selection in older adults with acute myeloid leukemia (AML). We report results of a pre-planned interim analysis of a pragmatic phase II trial that utilized this strategy to personalize therapy. Patients ≥60 years with a new diagnosis of AML underwent geriatric assessment prior to initiation of treatment. Geriatric assessment of physical function, cognitive function and comorbidity burden were used to determine fitness for chemotherapy. Patients with good or intermediate-risk AML received intensive chemotherapy such as anthracycline and cytarabine (7+3) if determined …