Medicine and Health Sciences Commons^™

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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) …

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 …

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 …

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 …

Tourniquet-Induced Ischemia-Reperfusion Injury, Junliang Qian

Theses & Dissertations

Ischemia-reperfusion (IR) is a pathological condition characterized by an initial restriction of blood supply to an organ followed by subsequent restoration of reperfusion associated with exacerbation of tissue damage. For pre-hospital emergency situations and surgical procedures, tourniquet or femoral artery ligation are widely used to stop extremity hemorrhage or create a bloodless operating field. To fully evaluate the underlying mechanisms in IR pathophysiology and potential therapeutic options, we compared tourniquet- and femoral artery ligation-induced IR injuries in the hindlimb of mice. We found that tourniquet/IR-induced acute hindlimb injuries are more severe than those induced by femoral artery ligation/IR, including alteration …

Investigation Of Cumulative Genetic Risk And Cc16 In Adult Asthma And Copd Populations, Kelli C. Gribben

Theses & Dissertations

INVESTIGATION OF CUMULATIVE GENETIC RISK AND CC16 IN ADULT ASTHMA AND COPD POPULATIONS

Kelli C. Gribben, Ph.D.

University of Nebraska Medical Center, 2022

Supervisors: Paraskevi A. Farazi and Tricia D. LeVan, Ph.D.

Asthma and Chronic Obstructive Pulmonary Disease (COPD) have complex etiologies and lack biological predictors that can be used for primary prevention, early detection, progression, or monitoring. Genetic risk scores (GRS) aggregate genetic effects from GWAS-identified susceptibility variants associated with a trait. GRS may provide opportunities to improve disease prediction to inform public health and clinical interventions. Asthma GRS studies utilizing multi-ethnic populations are scarce and there is a …

Design, Synthesis, And Biological Investigation Of Pyridine Sulfones As Anti-Chlamydia Trachomatis Agents, Mohamed A. Seleem

Theses & Dissertations

Chlamydia trachomatis is the most prominent cause of sexually transmitted bacterial infections worldwide, with around 128 million reported cases annually. This pathogen can cause severe urogenital and ocular consequences, resulting in infertility and trachoma. In its unique developmental cycle, Chlamydia fluctuates between two distinct forms, elementary bodies (EBs) and reticulate bodies (RBs). We hypothesized that caseinolytic protease P (ClpP), a conserved protease among bacterial species, drives the Chlamydia developmental cycle. Earlier work by the Ouellette group demonstrated that Chlamydia relies on its ClpP2 paralogue (ctClpP2) to differentiate between its developmental forms. Dysregulation of ctClpP2 had a significant …

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 …

Linking Spinal Cord Circuits With Upper Limb Sensorimotor Control In Adults With Cerebral Palsy, Saihari Dukkipati

Theses & Dissertations

Cerebral palsy (CP) is the most common neurological disorder originating in childhood, but most of the people living with CP are currently adults. While people with CP continue to get older, the amount of research focused on adults has been rather limited. The early childhood insults leading to CP are thought to originate in the brain, but the effects on the entire neuromuscular system across the lifespan have only recently started to be explored. Of note, recent neuroimaging evidence suggests that the cervical spinal cord structure is atypical in adults with CP. However, it is largely unclear how the neurophysiological …

Macromolecular Fluorescent Conjugates For Bioimaging Applications, Paul Lovell

Theses & Dissertations

Bioimaging tools enable the visualization of small anatomical features as well as structures that may be obscured by other tissue. One such group of tools are fluorescent probes, molecules that emit detectable signals when stimulated by an excitation source. Incorporating fluorescent conjugates for clinical purposes would enable direct usage for the diagnosis, detection, or treatment of diseases. The development of specific targeting agents is feasible due to the number of nanomaterials and biological products that contain fluorophores. Specific targeting agents can target a particular region of interest, such as a cancerous tumor for removal or vital nerve structure for avoidance …

Erα As A Modulator Of The Sle1b Lupus Susceptibility Locus And B Cell Receptor Signaling, Jared H. Graham

Theses & Dissertations

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by loss of immune tolerance and the production of anti-nuclear autoantibodies. 90% of lupus patients are women, and this sex bias is due to the actions of estrogens, which promote lupus pathogenesis. Our lab has shown that estrogen receptor alpha (ERα) mediates the effect of estrogens in lupus and that ERa acts in a B cell intrinsic manner to promote the development of autoantibodies and SLE. Genetic factors also contribute to lupus. One major lupus susceptibility locus, Sle1, controls loss of tolerance and autoantibody development as well as immune cell …

The Role Of Calprotectin In T-Lymphocyte Driven Inflammation In A Mouse Model Of Psychological Trauma, Cassandra Moshfegh

Theses & Dissertations

Post-traumatic stress disorder (PTSD) is a debilitating psychological disorder that affects nearly 45 million Americans. This mental disorder is characterized by behavioral symptoms such as learned helplessness, hyperarousal, withdrawal, and flashbacks. The deleterious effects of PTSD are far-reaching and go beyond behavioral dysfunction, as these individuals are at a three-fold higher risk of comorbid inflammatory diseases. Autonomic, metabolic, and cardiovascular diseases plague these individuals later in their lifetime, however, the mechanistic link connecting psychological trauma to this systemic peripheral immunological dysfunction remains elusive. T-lymphocyte-induced inflammation plays a significant role in all these disease pathologies. Previous work from our laboratory demonstrated …

Gut Commensals Modulate Siv/Shiv Pathogenesis And Therapeutics, Samuel Johnson

Theses & Dissertations

Despite significant advancements in combination antiretroviral therapy (cART), ongoing inflammation in the brain and gut remain two of the most significant hurdles in the health of people living with human immunodeficiency virus (HIV). Additionally, a viral reservoir in each compartment inhibits cure efforts by allowing rapid viral rebound following cART interruption. Emerging understanding of the gut-brain axis (GBA) implicates each compartment in the modulation of the other in a complex bi-directional interaction mediated by vagus innervation, circulating lymphocytes, and microbiome composition and biproducts. Using multiple models of the simian (and simian-human) immunodeficiency virus (SIV/SHIV) and therapeutic intervention, I present how …

The Development Of Thermoresponsive Hydrogel-Based Drug Delivery Systems For The Treatment Of Musculoskeletal Diseases, Ningrong Chen

Theses & Dissertations

Water-soluble polymers are one of the most commonly used drug delivery vehicles for musculoskeletal diseases. During the past few decades, various biocompatible polymers have been employed in the development of thermoresponsive hydrogels as drug delivery systems for the treatment of local musculoskeletal pathologies. As part of our laboratory’s contribution to this field of study, I have successfully developed three thermoresponsive hydrogel-based formulations for the treatment of three different pathologies associated with the musculoskeletal system.

As my initial effort, I have developed a bone-targeting injectable hydrogel drug delivery system based on Pluronic 127 (Poloxamer 407), which is a Generally Recognized As …

Ethical Sensitivity Of Padis Care Among Critical Care Nurses: A Mixed Methods Study, Denise Waterfield

Theses & Dissertations

Critically ill patients often experience distressful and impactful symptoms and conditions that include pain, agitation/sedation, delirium, immobility, and sleep disruption (PADIS). The presence of PADIS can affect recovery and long-term patient outcomes. An integral part of critical care nursing is PADIS prevention, assessment, and management. To better understand the complexities of PADIS care, two reviews of the literature were completed. The first is an integrative review of the use of PADIS assessment tools by critical care nurses. The second is a qualitative systematic review of the literature on the integration of care ethics and nursing workload. Ethical sensitivity of everyday …

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 …

Maternal Distress In The Neonatal Intensive Care Unit, Morgan A. Staver

Theses & Dissertations

Maternal distress in the NICU is a common and potentially harmful phenomenon for mothers with a sick infant. The overall purpose of this dissertation was to describe maternal distress and to examine maternal distress among mothers who have infants greater than or equal to 34 weeks of gestation at birth in the NICU. This was accomplished by first conducting a concept analysis of maternal distress in the NICU. Next, an integrative review of the literature was done to assess maternal distress and associated variables in response to infant hospitalization in the NICU. Finally, a mixed methods study was done to …