Medicine and Health Sciences Commons^™

Development, Validation, And Diagnostic Performance Of A Novel Radiomic Model For Predicting Prostate Cancer Recurrence, Linda M. Huynh

Theses & Dissertations

Multi-parametric magnetic resonance imaging (MP-MRI)-derived radiomics have been shown to capture sub-visual patterns for the quantitative characterization of prostate cancer (PC) phenotypes. The present dissertation seeks to develop, evaluate, and compare the performance of an MRI-derived radiomic model for the prediction of PC recurrence following definitive treatment with radical prostatectomy (RP).

MP-MRI was obtained from 339 patients who had a minimum of 2 years follow-up following RP at three institutions. The prostate was manually delineated as the region of interest and 924 radiomic features were extracted. All features were evaluated for stability via intraclass correlation coefficient (ICC) and image normalization …

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 …

Exploiting Vulnerabilities In The Ras-Rac Signaling Pathway For The Selective Targeting Of Pancreatic Cancer Cells, Neha Chaudhary

Theses & Dissertations

Deregulation of the KRas (Kirsten rat sarcoma virus) GTPase is one of the early hallmarks of Pancreatic Cancer (PC). The most common genetic alteration found in PC are mutations in the KRas protein that block its ability to hydrolyze GTP to GDP and resulting in higher levels of GTP-bound KRas, its active form. Pancreatic tumors driven by oncogenic mutants of KRas tend to be addicted to the oncogene, to the extent that its repression leads to the induction of cell death. This addiction to the KRAS oncogene makes the KRas protein an ideal target for cancer therapy. However, the globular …

Design And Synthesis Of Small Molecule Drugs For Cns Disorders, Kirsten T. Tolentino

Theses & Dissertations

Dopamine (DA) is an important neurotransmitter for the regulation and long-term function of the central nervous system (CNS). DA binds to Dopamine Receptors (DR) to stimulate or inhibit adenyl cyclase production to further elicit a pharmacological response. DRs were cloned, and it was determined that there are two families separated by their function and five total subtypes distinguished by their amino acid structure. The Dopamine 4 receptor (D4R) is the second least studied subtype but has high expression in the frontal cortex, amygdala, hippocampus, hypothalamus, globus pallidus, substantia nigra pars reticula, and thalamus. Dopamine signaling and transmission, especially in the …

Association Of Inflammatory Markers And Growth Factors With Radiographically Assessed Wound Healing Of Extraction Sockets, Sasha Mohammadi

Theses & Dissertations

The purpose of this prospective cohort pilot study was to investigate the association of the periodontal status and inflammatory markers from the gingival crevicular and wound fluid with the healing outcomes following tooth extraction. The central research hypothesis is that extraction sites and the adjacent teeth that exhibit increased markers of inflammation, or decreased growth factors, at baseline or 2 weeks will be associated with reduced healing outcomes observed radiographically 3 months following surgery. Nine patients at the UNMC College of Dentistry who were seeking care to extract a posterior tooth due to advanced periodontal bone loss, non-restorable caries or …

Effect Of Computerized Cognitive Training In Persons With Multiple Sclerosis, Sam Jack

Theses & Dissertations

Between one million and 1.75 million persons with multiple sclerosis (PwMS) worldwide are estimated to suffer from cognitive impairment. Unfortunately, there is currently no consensus on the best treatment for cognitive impairment in PwMS. Finding non-pharmacological interventions to mitigate cognitive decline is essential to ensure that quality of life for PwMS matches our ability to treat and mitigate their physical symptoms of MS. Computerized cognitive training has emerged as a potential option for PwMS suffering from cognitive impairment. The objective of this study was to determine the effectiveness of computerized cognitive training with BrainHQ on changes in cognitive impairment for …

Evaluating The Impact Of Routine Enteral Iron Fortification On Gastrointestinal Dysbiosis In Premature Infants, Matthew Van Ormer

Theses & Dissertations

The gastrointestinal microbiome in preterm infants bears significant influence on optimal outcomes – dysbiosis is shown to substantially increase the risk of the life-threatening necrotizing enterocolitis, whereas optimal microbiome composition improves nutrient digestion and immune function. Iron is a vital nutrient especially during the perinatal window of rapid hemoglobin production, tissue growth, and foundational neurological development. However, excess colonic iron exhibits potent oxidation capacity and alters the competitive environment of microbes – potentially facilitating the proliferation of pathological bacterial strains in the gut. Of note, breastfed preterm infants routinely receive iron fortification starting at 14 days of life and are …

Variations In Source And Pattern Of Arterial Supply To The Trigeminal Ganglion With Clinical Relevance, William S. Srinivasan

Theses & Dissertations

The trigeminal ganglion (TG) is known to receive its arterial supply from branches of the internal carotid artery (ICA), middle meningeal artery (MMA), accessory meningeal artery (AMA), or superior cerebellar artery (SCA). Existing information about the prevalence and patterns of blood supply to the TG is limited despite their high clinical relevance to basicranial surgeries. The objective of this study is to investigate the source and pattern of arterial supply to TG and discuss their clinical relevance. Left and right TG were examined on 75 embalmed human cadavers from an ethically approved anatomical donor program. A literature review was conducted, …

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 …

Use Of Pre-Transplant Cmi To Predict Infection And Mortality Post-Cardiac Transplantmortality Post-Cardiac Transplant, Chetaj A. Mahabir

Theses & Dissertations

This paper discusses a study investigating the relationship between the cell-mediated immunity (CMI) level before cardiac transplant and the incidence of infection and mortality after the transplant. CMI is an important measure of a person's immune system. The study included 126 patients who underwent cardiac transplants between September 2011 and January 2020. Out of these, 21 patients had a low CMI level (<225), and 105 had a high CMI level (≥ 225) before transplant. The mean CMI level in the low CMI group was 175.3, while in the high CMI group, it was 479.9. The two groups were similar except for the lower white cell count and cardiac output in the CMI< 225 groups and the higher Caucasian demographic in the CMI≥ 225 groups. The study concludes that patients with lower CMI levels before cardiac transplant have a higher risk of infection (p=0.052) and mortality (p=0.005) one year after the transplant. The risk of dying for patients with CMI <225 is 12.9 times the risk of dying for patients with CMI ≥ 225 after adjusting for the other covariates in the model. However, this study has some limitations including its retrospective nature, small sample size, and single-center design. Further studies are needed to replicate these findings and investigate the optimal immunosuppressive regimens based on baseline CMI levels.

Frailty Determination And Responsiveness In Left Ventricular Assist Devices, Sarah Schroeder

Theses & Dissertations

Frailty, the state of being vulnerable with susceptibility to decreased age-related physical reserve, is found in 56-79% of adults with end-stage HF receiving durable left ventricular assist device (dLVAD) therapy. Frailty increases risk of adverse events, including increased mortality in the dLVAD population, but less is known about depression, quality of life (QOL), cognition and frailty responsiveness. Therefore, we aimed to describe and compare frailty (5-Meter Walk Test, 5MWT), depression (Patient Health Questionnaire-9, PHQ-9), quality of life (EQ5D Visual Analog Scale, EQ-5D VAS) and cognition (Trailmaking B) from pre- to 12-months post-dLVAD We also compared demographics, clinical characteristics, and post-dLVAD …

Transcranial Direct Current Stimulation Of Frontal/Occipital Cortices Modulates Neural Correlates Of Cognition In Healthy Young Adults, Yasra Arif

Theses & Dissertations

An exponential rise in the use of transcranial direct current stimulation (tDCS) to modify the human brain and behavior has been observed over the last 20 years, with studies often yielding mixed outcomes. Such heterogeneity is partially attributed to the lack of a concise understanding of the underlying mechanisms. Though considered to exert modulatory effects by changing neuronal membrane polarization and synaptic efficacy, the interactive effects of offline tDCS and the neural underpinnings of cognition, both at the regional and network-level, are yet to be fully understood. Using High-Definition tDCS (HD-tDCS), Magnetoencephalography (MEG), a range of well-established cognitive paradigms, and …

Grip Characterization Of Protective Gloves, Doris Burns

Theses & Dissertations

In 2014, ASTM International (ASTM), one of the world's largest international standards developing organizations, published a new test method on glove grip performance. This method was adopted by the National Fire Protection Association (NFPA) in some of their specification standards. The method utilized hand torque instead of the pull method previously used by the NFPA to determine the Percent Bare Hand Control Value (%BHCV). The %BHCV, compares torque results of a gloved hand versus a bare hand. In developing this new test method, only four males and one female participated; therefore, it is unclear if statistical significance was attained. In …

Polymeric Chloroquine In Metastatic Pancreatic Cancer Therapy, Rubayat Islam Khan

Theses & Dissertations

Hydroxychloroquine (HCQ) is an established drug that has been used for the treatment of multiple diseases, including malaria, rheumatoid arthritis, and lupus erythematosus. Several recently published studies have highlighted its beneficial use in various types of cancers, and a plethora of clinical trials are currently evaluating its use in cancer therapies, wherein some of the results look promising. The preclinical studies to date suggest HCQ can work effectively in conjunction with traditional cancer treatments, as it has been shown to sensitize tumor cells to a wide range of chemotherapeutic agents. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has …

Assessing The Methodology, Prevalence, And Associated Factors For Adverse Childhood Experiences (Aces) Among Children And Adolescents In The United States, Kiara L. Lyons

Theses & Dissertations

To comprehensively capture the risk and protective factors of ACE exposure and ACE-related outcomes, we propose to consider a social-ecological model framework. The concept of the Social-Ecological Model was originally introduced in the 1970s by psychologist Urie Bronfenbrenner and designed to theoretically capture the multifaceted influence different personal, social, and environmental factors have on health behaviors and outcomes. Additionally, this would help to determine what prevention and intervention methods would be more appropriate to implement. This conceptual framework had five system levels: microsystem (individual), mesosystem (interpersonal), exosystem (community context), macrosystem (societal and cultural influences), and chronosystem (internal and external elements …

A Cell Culture Model To Study Tobacco Associated Oral Cancer Progression And Treatment Resistance, Amanda Busch

Theses & Dissertations

Head and Neck Squamous cell carcinoma is the 6^th most common cancer in the world. Risk factors for HNSCC include alcohol and tobacco consumption, infection with Human Papilloma Virus, and exposure to environmental toxins. Unlike many other cancers, the incidence of HNSCC is growing, yet the treatment options and outcomes have not been significantly improved for decades. An increased understanding of the molecular mechanisms of these cancers is needed for improvement in early diagnosis, enhanced treatment effectiveness, and cancer prevention. 4-nitroquinoline 1-oxide (4NQO) is a well-tested, tobacco mimicking, carcinogen. 4NQO produces similar histological and chemical changes found in human …

Exploring The Influence Of Contextual Factors And The Caregiving Process On Burden, Quality Of Life, And Outcomes Of Heart Failure (Hf) Dyads After A Hospital Discharge Guided By The Individual And Family Self-Management Theory (Ifsmt): A Mixed Method Study, Tamara Bernard

Theses & Dissertations

ABSTRACT The purpose of this study is to explore the influence of contextual factors and caregiving process characteristics on proximal outcomes of the patient and caregiver after discharge from the hospital. The long-term goal of this research is to reduce caregiver burden and improve patient outcomes. Heart failure (HF) is an increasingly common chronic illness with unique caregiving needs and a high rate of hospital readmissions. Caregiver burden has been researched extensively in other areas of medicine such as oncology and dementia and has been reported for stable chronic HF patients in an outpatient setting. However, there is little research …

A Systematic Literature Review Of The Prevalence, Distribution, Exposure, And Human Health Risks Of Tire Microplastics And The Contribution Of Their Physicochemically Diverse Properties, Luke Glastad

Theses & Dissertations

The history of synthetic plastics dates back to their first uses in 1907, continues with their expansion through the middle of the century with a diverse array of new polymers, and are so omnipresent today that many label this age of Earth the Plasticene Era. Tire microplastics (TMPs) have been increasingly identified as one of the environment's most bountiful types of microplastics (MPs). TMPs mainly enter the environment as tire-wear particles (TWPs) and recycled tire crumb (RTC). TWPs, in particular, have a high degree of variability, which impacts their distribution, degradation, and risk for adverse human health effects. This review …

Optimizing Antiretroviral Therapy With Modern Rifapentine Containing Tb Treatment, Anthony T. Podany

Theses & Dissertations

In the past decade there has been a multitude of phase 3 clinical trials targeting treatment shortening for tuberculosis (TB). The synthetic rifamycin derivative rifapentine (RPT) has been at the forefront of many of the treatment shortening approaches. RPT possesses greater potency and a longer pharmacokinetic (PK) half-life (t_1/2) as compared with the long used rifamycin, rifampin (RIF). For TB preventative treatment, a 3-month, once weekly regimen of RPT and isoniazid (INH; 3HP) was shown to be as effective as 9-months of daily INH therapy in the PREVENT TB trial. Similarly, a 4-week course of daily RPT and …

Evaluation Of Medication Optimization In The Setting Of Ecmo Therapy: Assessment Of Therapeutic Effectiveness, Greg Peitz

Theses & Dissertations

A series of studies within the setting of extracorporeal membrane oxygenation (ECMO) was undertaken to specifically answer questions related to medication optimization during this complex therapy. These studies included medication therapies involving optimal anticoagulation, analgesia delivery, fluid resuscitation, and infection related outcomes in the context of ECMO. Each investigation was retrospective in nature and included patients from a single institution. The results of these studies indicated the following: 1.) various anticoagulation goals do not impact severe, life-threatening bleeding events during ECMO therapy; 2.) sepsis is a common occurrence in the setting of ECMO; 3.) the choice of either a crystalloid …

Environmental Exposures And Human Health Challenges: Evidence-Based Insights From Health Surveillance Systems, Jagadeesh Puvvula

Theses & Dissertations

Human exposure to environmental hazards is associated with a variety of preventable adverse health outcomes. As the environmental health risks result from the complex interaction between hazard, exposure, and susceptibility, these exposure-outcome associations are heterogeneous across the population. Improving environmental health literacy by advocating evidence-based environmental risk communication could play a role in reinforcing protective behavior against environmental hazards. The use of public health surveillance systems to assess the exposure-response associations is one of the effective ways to quantify the environmental health risks. However, there are several gaps in effectively quantifying environmental health risks. This dissertation aims to address a …

The Effect Of Interproximal Home Regimens Of Inflammatory Biomarkers In Periodontal Maintenance Patients, Grace Moore

Theses & Dissertations

A survey of dental hygienists in general practice (DHGP; n = 74) and periodontal practice (DHPP; n = 62) indicated a difference (p £ 0.04) in preference for interproximal cleaning with oral irrigators (DHGP) and interproximal brushes (DHPP) during periodontal maintenance therapy (PMT). The purpose of the subsequent blinded, randomized controlled clinical trial was to compare the effect of interproximal cleaning aids on reducing inflammation in posterior pockets during PMT. Seventy-six patients on PMT with a 5-7 mm interproximal probing depth were randomly allocated to one of three groups: 1) interproximal brush with tracking device (IB + TD; n=23), 2) …

Agrichemicals (Nitrate And Atrazine) In Drinking Water And Adverse Health Outcomes In Children In Nebraska, Balkissa S. Ouattara

Theses & Dissertations

Objectives: This research was conducted to (1) determine the concentrations of atrazine, and nitrate, in Nebraska watersheds and counties; (2) calculate the incidence of pediatric cancers and prevalence of birth defects in Nebraska counties and watersheds, respectively; (3) assess the relationship between the contaminant levels and the incidence rate of pediatric cancers and birth defects prevalence.

Methods: Pediatric cancers and birth defects data were obtained from the Nebraska Department of Health and Human Services. Water quality data were collected and retrieved from the Water Quality Portal and the Nebraska Groundwater Quality Clearinghouse. Geospatial and statistical analyses were conducted at the …

Applications Of Population Pharmacokinetic Modeling In People Living With Hiv, Michelle M. Pham

Theses & Dissertations

Population pharmacokinetic modeling has become an important tool for the individualization of medicine in HIV care and clinical pharmacology in general. This dissertation explores many applications of population pharmacokinetic modeling to help identify drug exposure, drug-drug interactions, and sources of variability in populations living with HIV. Comprehensive HIV care involves simultaneous treatment of the disease and any co-infection and/or co-conditions.

The first objective was to identify potential drug-drug interactions affecting combination antiretroviral therapy (ART) consisting of efavirenz, tenofovir disoproxil fumarate and emtricitabine, from concomitant use of chemotherapy agents. Three models were developed with sparse sampling to characterize efavirenz, emtricitabine, and …

The Development And In Vivo Immunologic Assessment Of Biodegradable Microparticles Incorporating Cpdi-02 And Mucosal Protein Vaccine, Jacob E. Parriott

Theses & Dissertations

Encapsulation in biodegradable microparticles (MPs) is a promising approach to increase the efficacy of intranasally administered protein vaccines. The generation of long-lived adaptive immune responses against encapsulated protein vaccines, however, requires the incorporation of a suitable mucosal adjuvant. CPDI-02—a complement peptide-derived immunostimulant that selectively activates dendritic cells and macrophages over neutrophils while minimizing the inflammatory side effects of parent C5a—has previously been incorporated into both systemic and mucosal vaccine formulations via direct conjugation to chemical moieties, peptides, proteins, inactivated pathogens, and the surface of biodegradable particles, to enhance Th1-biased cellular immune responses. The effect of CPDI-02 surface conjugation to MPs …

Biologically-Inspired Nanoparticles For Oncology Applications, Aishwarya Bapat

Theses & Dissertations

Cancer is the leading cause of death in the United States and its high mortality rate can be attributed towards poor diagnosis methods and less effective therapeutic treatments. Many nanotechnology-based diagnostics and therapeutics are being developed to improve cancer patient outcomes. In this work, we have studied nanoparticles for diagnostic and therapeutic applications in cancer treatment.

In the first work, novel fluorescent NPs loaded with indocyanine green (ICG) were developed for bioimaging applications of pancreatic cancer. Targeted fluorescent nanoparticles (NPs) are being developed to image a range of cancer types with the goal to improve patient outcomes by utilizing in …

Leukocyte Subsets In The Peripheral Blood And Spleen Of Gastrointestinal Cancer Patients, Kathryn E. Cole

Theses & Dissertations

In 2022, an estimated 62,210 people will be diagnosed with pancreatic ductal adenocarcinoma (PDAC) and approximately 49,830 will die from the disease. Current treatment strategies for gastrointestinal (GI) cancer patients, such as PDAC, have shown limited benefit, suggesting the need to develop novel, multimodality therapeutic approaches. Adoptive cellular therapy (ACT) using autologous tumor infiltrating lymphocytes (TILs) has shown efficacy in patients with melanoma; however, this approach is costly and requires extensive cell culture for sufficient numbers of T-cells for infusion. GI cancer patients with borderline resectable disease, whose primary tumor is adjacent to the splenic vasculature, can sometimes undergo a …

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 …