Medicine and Health Sciences Commons^™

Polymeric Drug Delivery Systems For Cancer Therapy And Radionuclide Decorporation, Sameer A. Alshehri

Theses & Dissertations

The main objective of this body of work is to develop polymeric drug delivery systems for cancer radiotherapy and the decorporation of radiological materials. The polymeric systems for radiotherapy were evaluated in vitro and in vivo (in normal, prostate, and ovarian cancer mice models). The polymeric system for radionuclide decorporation was also evaluated in vitro and in a normal mouse model. Due to its attractive properties, the N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymer was utilized as the main carrier for the developed systems.

Chapter 1 provides an overview of prostate and ovarian cancer, targeted radiopharmaceuticals, nanomedicine-based drug delivery for cancer, HPMA copolymers, …

Outcomes Of Unilateral Alveolar Clefts Grafted Using Recombinant Human Bone Morphogenetic Protein-2: A Retrospective Volumetric Analysis Using Cbct, Landon Robert Peterson

Theses & Dissertations

Purpose of this study is to evaluate the success rates of secondary alveolar grafts using recombinant human bone morphogenetic protein with CBCT and to evaluate the effects of several variables on these outcomes. After our inclusion/exclusion criteria, records of 24 patients receiving secondary alveolar grafts at the University of Nebraska Medical Center were evaluated. Pre-graft and 6-month post-graft cleft volumes were measured using ITK-SNAP 3.8.0 software to determine a percent residual defect following surgery. Of the 24 patients, one was excluded as the graft surgery was deemed a failure. The patients’ gender, age, side of cleft, cleft side canine root …

A Narrative Analysis Of Psychological Adjustments Of Professionals Transitioning To Work Following Cerebral Vascular Accident (Cva), Mabel Munachiso Korie

Theses & Dissertations

This research study was a narrative analysis of the psychological adjustment of professionals transitioning to work after a cerebral vascular accident, commonly known as a stroke. The purpose of this research was to explore the psychological adjustment of professionals who returned to work after a stroke following their subsequent rehabilitation. This has been an important subject because stroke research predominantly addresses older adults, which means that there has not been enough information on the experience of affected working-age professionals. The Roy Adaptation Model and Social Cognitive Theory were the frameworks for the study. The data collected were from audio-recorded and …

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 …

Multiquantal Glutamate Release From Rod Photoreceptors, Cassandra L. Hays

Theses & Dissertations

Neurons communicate via Ca²⁺-dependent release of neurotransmitters packaged into vesicles (quanta). Some CNS neurons, especially sensory synapses, can release multiple vesicles at a time, increasing information transmission and overcoming the unreliability of a stochastic process. Ribbon-bearing neurons, including retinal photoreceptors, face the challenge of encoding sensory receptor potentials into an ever-changing train of vesicle release events. We studied release of glutamate using voltage clamp to measure anion currents activated during glutamate reuptake into presynaptic terminals (I_A(glu)) of salamander and mouse rods, finding that each employ distinct mechanisms for multiquantal release. In amphibian rods, we found that …

Utilization Of Nurse Practitioners In States With Full Practice Authority: Does Geography Matter?, Jana Zwilling

Theses & Dissertations

Background: Over 80 million Americans reside in or are part of a population designated as Health Professional Shortage Areas (HPSAs). Of the primary medical HPSA areas designated in the U.S., 66.74% are located in rural or partially rural areas (HRSA, 2020). To combat this shortage, 23* states and Washington, D.C. have enacted full practice authority laws for nurse practitioners (NP). Over 60% of NPs work in communities of less than 250,000.

Problem: The variability and extent of utilization of NPs in states with full practice authority (FPA) is unknown. To ensure access to quality healthcare, nurse practitioners need to be …

Leveraging Aqueous Humor Dynamics And Ocular Biometrics For Improving Therapeutic Outcomes In Glaucoma, Vikas Gulati

Theses & Dissertations

Glaucoma laser and incisional surgical treatments are associated with a known risk of complications. The ability to better predict treatment outcomes and individualize treatment recommendations can enhance the benefit to risk ratio of a treatment option. The work presented in this dissertation explores the interplay of biometrics, race and aqueous humor dynamics and their influence on treatment outcomes. In the first chapter, we demonstrate that pre-operative aqueous humor dynamics (higher aqueous flow, lower outflow facility and lower uveoscleral outflow) are predictive of greater intraocular pressure lowering after selective laser trabeculoplasty. The second chapter describes significant race-based differences in aqueous humor …

Effect Of Nanofiller Coating And Loading On Facial Elastomer Physical Properties, Rahmi K. Aulia

Theses & Dissertations

Current materials used for facial prostheses are far from being desirable, and improved properties with “skin-like” feel are needed. This study evaluates property changes induced by sequential additions of uncoated and hydrophobic-coated nano-SiO₂ to polydimethylsiloxane (PDMS) and compares them with those measured for conventional submicron SiO₂-filled materials. Each filler type was sequentially added to vinyl-terminated PDMS at 0%, 0.5%, 5%, 10%, and 15% by weight. Tensile, tear, Durometer hardness, translucency and viscoelastic properties were evaluated, with hardness and translucency also evaluated following 3000 hours of outdoor weathering. Results demonstrated that 15% coated nano-SiO₂-filled PDMS materials …

Urinary Bile Acid Indices As Diagnostic And Prognosic Biomarkers For Liver Diseases, Jawaher Alamoudi

Theses & Dissertations

Hepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis. We compared the urinary BA profile between 300 patients with hepatobiliary diseases vs. 103 healthy controls. Also, we investigated the use of the urinary BA profile to develop survival models to predict the prognosis of hepatobiliary diseases. The urinary BA profile, a set of non-BA parameters, and the adverse events of liver transplant and/or death were monitored in patients with cholestatic liver diseases for up to 7 years. The BA profile was characterized by calculating …

Reducing Adverse Outcomes In Hepatocellular Carcinoma Patients Undergoing Hepatectomies, Yongyue Qi

Theses & Dissertations

The incidence and mortality of liver cancers are increasing in the United States. In addition to the classic risk factors of hepatic viral infection and high alcohol consumption, non-alcoholic Fatty Liver Disease (NAFLD), has emerged as a risk factor for hepatocellular carcinoma (HCC). The most effective curative treatment for HCC is liver resection (hepatectomy), however, hepatectomy is a major operation with potential risks of mortality, hospital readmission and other adverse outcomes such as postoperative complications and longer hospital stay. The reported 90-day mortality and 30-day readmission rates following a hepatectomy vary widely across studies, most of which have limitations due …

Development Of Cxcr4-Inhibiting Rna Delivery Vectors For The Treatment Of Metastatic Pancreatic Cancer, Yu Hang

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a growing medical problem associated with extensive metastasis and high mortality. Late diagnosis and complexity of the tumor microenvironment (TME) with severe hypoxia, desmoplasia, and hypovascular nature contributes to poor effectiveness of conventional chemotherapies. RNA interference (RNAi) holds great potential in the treatment of multiple genetic and acquired diseases, including PDAC. CXCR4/CXCL12 chemokine axis plays a pivotal role in PDAC TME remodeling to promote tumor proliferation, angiogenesis, metastasis, and chemoresistance. This project developed polymeric AMD3100 (PAMD) derivatives as dual-function vectors capable of simultaneously delivering small RNAs and blocking CXCR4/CXCL12 signaling.

Administration route plays pivotal role …

Identifying, Adapting, And Implementing A Weight Management Program In Rural Primary Care, Gwenndolyn Porter

Theses & Dissertations

Rural adults are at heightened risk for obesity, yet evidence‐based interventions lack consistent translation into clinical practice. This multi-phase study addresses this gap. First, a systematic review and meta-analysis of rural adult weight loss interventions were conducted to assess overall impact. Though few studies reported participant representativeness, meta‐analyses revealed a significant weight reduction among interventions. Second, 10 focus groups were conducted with primary care (PC) staff to determine the feasibility of implementing a weight-management program through PC. Differences in responses among rural, micropolitan, and metropolitan was also assessed. Thematic analyses revealed rural PC currently lacks the capacity to manage patient …

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 …

Development Of Cholesterol Modified Rnai Polyplexes For Breast Cancer Therapy, Zhen Ye

Theses & Dissertations

Not available.

Ligand-Installed Polymeric Nanocarriers For Combination Chemotherapy, Xinyuan Xi

Theses & Dissertations

Combination chemotherapy remains the mainstay of cancer treatment because such strategy targets different cell signaling pathways to decrease the likelihood of developing protective mechanisms by cancer cells, thereby delaying the onset of recurrence and prolonging the survival. The co-delivery of binary drug combination via a single nanocarrier provides benefits in reducing dose-limiting toxicities, improving the pharmacokinetic properties of the cargo, spatial-temporal synchronization of drug exposure, and synergistic therapeutic effects. Rational design of such regimen is crucial for maximizing the therapeutic effects since only certain drug ratios exposed to the target might be synergistic while other ratios exert additive or even …

Exosomes Secreted Under Hypoxia Enhance Stemness In Ewing’S Sarcoma And Transform Microenvironment Cells, Matthew J. Kling

Theses & Dissertations

Intercellular communication between tumor cells and stroma within the hypoxic microenvironment promote aggressiveness and poor patient prognoses in ways that remain unclear. Here we show that hypoxic Ewing’s sarcoma (EWS) cells release exosomes that promote sphere formation, a stem-like phenotype, in EWS cells by enhancing survival and a cancer-associated phenotype in fibroblasts (CAFs). Given that hypoxia enriches for stem-like cells, we exposed EWS cells to hypoxia and hypoxic EWS-derived exosomes and assessed the stem cell phenotype. Hypoxia and hypoxic EWS-derived exosomewere found to enhance TIC formation in vitro and in vivo by reprogramming EWS cells. Analysis of the hypoxic exosomal …

Comparison Of Staphylococcus Aureus Nasal Carriage By Patients And Healthcare Workers In Selected Dialysis Centers In Nairobi And Neighbouring Counties, Enock Serem

Theses & Dissertations

No abstract provided.

Knowledge Of Inhaler Use Among Medical Officers In The Management Of Asthma In Children In Dar Es Salaam, Tanzania, Hannah Moore

Theses & Dissertations

Background:

The inhaled route is the preferred first line method for administration of asthma medication. It is however documented that oral and intravenous routes are the commonly adopted methods of administering asthma medication in children, and the knowledge of the use of inhalers and inhaler devices has not been well documented in middle and low-income countries. Knowledge of inhaler technique among medical personnel ensures effective education of its use to patients to provide the desired results in managing asthma in children. Studies in developing countries have demonstrated a generally low level of knowledge of inhaler use among Medical Doctors and …

Individual Characteristics And Shared Decision Making For Stroke Prevention In Atrial Fibrillation, Patricia Nadraus

Theses & Dissertations

With the advent of patient-centered care, individuals with Afib are asked to participate in the shared decision-making (SDM) process. Choosing therapies in thromboembolic risk reduction is complex, involves trade-offs along with considering risks and benefits of therapeutics. Afib affects between 2.7 million and 6.1 million American adults (January et al., 2014), and with the growing elderly population that number is expected to double by 2030 (Colilla et al., 2013). In 2016 Medicare required a SDM process for individuals considering left atrial appendage for stroke prevention. There have been no studies reported examining individual characteristics and participating in SDM in individuals …

A National Study Of Undergraduate Nursing Students' Early Consideration Of Doctoral Education: What Characteristics Predict Students' Report Of Intention And Readiness To Continue Graduate Education Toward The Doctorate?, Renee Lynn Buonaguro

Theses & Dissertations

Statement of the Problem The looming nursing faculty shortage has already had a direct effect on schools of nursing. With our current understanding about enrollments needed to meet the demands of an adequately prepared healthcare workforce, attention needs to be directed toward the preparation of an adequate educator workforce. A consequence of not having doctorally prepared nursing faculty would result in an inadequate number of professors to accommodate the 70,000 applicants who are desiring to pursue their nursing degrees. One solution to the faculty shortage is to vastly increase the number of doctorally prepared faculty earlier in their careers. This …

The Neural Oscillatory Dynamics Underlying Motor And Cognitive Abilities In Children And Adults With Cerebral Palsy, Rashelle M. Hoffman

Theses & Dissertations

Cerebral palsy (CP) is the most common neuromotor developmental diagnosis that can result in a myriad of activity impairments. The literature has primarily explored motor impairments in children with CP. Additionally, there is evidence of CP impacting several cognitive domains in children and adults with CP. Very little literature has explored if these impairments persist into adulthood, and the underlying neurophysiology serving these functions in individuals with CP is unknown.

The first purpose of this dissertation was to quantify the cortical oscillations serving hand movement with magnetoencephalography (MEG) and determine if differences were present as a function of age between …

Exploring Paramedic Students’ Level Of Preparedness For Disaster Response In Hajj 2019, Nawaf Albaqami

Theses & Dissertations

Objectives: 1) to gain further understanding of the paramedic students' level of preparedness before their clinical training at Hajj. 2) To shed more light on what paramedic students need when responding to a disaster. 3) To determine the need to recommend a change in the current practice with respect

Method: The data collection for this study was a cross-sectional survey using the REDCap electronic data capture tools. It was a convenience sample of 40 respondents. For the analyses, descriptive statistics, including frequencies and percentages, were used, and the Mann Whitney U test.

Results: The main findings in this study were …

Effects Of Acute Intracranial Pressure Changes On Optic Nerve Head Morphology In Humnans And Pig Model, Sachin Kedar

Theses & Dissertations

The optic nerve head (ONH) is located at the interface of intracranial and intraocular compartments. It is comprised of lamina cribrosa (LC), a fenestrated connective tissue tethered to the posterior sclera across the scleral canal. Since LC is exposed to intraocular pressure (IOP) anteriorly and intracranial pressure (ICP) posteriorly, it is an ideal site for noninvasively detecting intracranial pressure (ICP) fluctuation. We hypothesized that the pressure differential between IOP and ICP across LC, will determine LC position and meridional diameter of scleral canal (also called Bruch’s membrane opening- BMOD). We tested our hypothesis in 19 human subjects undergoing medically necessary …

Molecular Mechanisms Of Manganese Porphyrin Compounds In The Prevention Of Radiation-Induced Fibrosis, Shashank Shrishrimal

Theses & Dissertations

Radiation therapy is frequently used as a treatment strategy for prostate cancer patients, which leads to several side effects due to damage to health tissue around the tumor and the development of radiation-induced fibrosis (RIF). Manganese (III) meso-tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP or T2E or BMX-010) and other similar manganese porphyrin compounds that scavenge superoxide molecules have been demonstrated to be effective radioprotectors and prevent the development of RIF. However, understanding of the radioprotective molecular pathway associated with these compounds remains limited. Recent RNA-sequencing data from our laboratory revealed that MnTE-2-PyP treatment may activate the nuclear factor erythroid 2-related factor 2 …

Novel Detection And Treatment Strategies For Pancreatic Ductal Adenocarcinoma, Joseph Carmicheal

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with an estimated 5-year survival rate of less than 9%. The high lethality of PDAC is due to two primary reasons: the discovery of PDAC at later stages, with locally invasive or metastatic disease present at the time of initial diagnosis as well as the lack of efficacious therapeutic interventions that significantly impact survival. In this dissertation, we sought to discover and test novel detection and treatment strategies for PDAC. Firstly, serum EVs were investigated as potential non-invasive liquid biopsy biomarkers, to serve as a means of early cancer …

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 …

Smart Delivery Of Genes And Drugs For Treatment Of Cancer, Feng Lin

Theses & Dissertations

The ineffective delivery of genes and drugs have become a big obstacle for the treatment of cancer, due to either poor stability or low aqueous solubility. In the first part, A ROS responsive polymer named poly(ethylene glycol)–poly[aspartamidoethyl(p-boronobenzyl)diethylammonium bromide] (PEG-B-PAEBEA) was developed for codelivery miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) for the treatment of pancreatic ductal adenocarcinoma (PDAC), since tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis, and invasion is significant downregulated while Polo-like kinase 1 (PLK1) closely associated with short survival rates of pancreatic cancer patients is remarkably upregulated . In part 2, …

Development Of Fluorescent Hyaluronic Acid Nanoparticles For Intraoperative Tumor Detection, Nicholas E. Wojtynek

Theses & Dissertations

Surgical resection remains to be the primary treatment for the majority of solid tumors, including breast cancer. The complete removal of the primary tumor, local metastases, and metastatic lymph nodes dramatically improve a patient’s treatment outcome and prognosis. Nevertheless, surgeons are limited to tactile and visual cues in distinguishing malignant and healthy tissue. This can result in a positive surgical margin (PSM), which occurs when tumor goes undetected and is left behind in the surgical cavity. PSMs decreases a patient’s prognosis and necessitate additional treatment in the form of surgery, radiation, and chemotherapy. An emerging imaging modality, known as fluorescence-guided …

Ocular, Neural, And Cellular Biodistribution Of Multifunctional Antioxidants, Damian Daszynski

Theses & Dissertations

Aging is a complex biological process which stems from a growing imbalance between the regenerative capacity of an organism and endogenous as well as exogenous damaging factors. This imbalance leads to the slow deterioration of individual cells, organs, and eventually the entire organism. The free radical theory of aging combines the evolutionary and mechanistic aspects of aging, postulating that the innate process is caused by deleterious, irreversible, and inevitable changes in biological systems caused by oxidative damage that accumulates over the lifespan. Evidence of this phenomenon is supported by the pathogenesis of age-related diseases, such as age-related macular degeneration and …

The Role Of Extracellular Vesicles In Cancer-Related Fatigue And Its Co-Occurring Symptoms, Dilorom M. Sass

Theses & Dissertations

Cancer survivors report many debilitating symptoms associated with cancer and its treatments. About 30% will report long-term cancer-related fatigue (CRF) which often co-occurs with depressive symptoms, sleep disturbances, cognitive fatigue, and poor overall health-related quality of life. The underlying causes of these co-occurring symptoms have been related to systemic processes such as inflammation. Extracellular vesicles (EVs) contain systemic markers such as genetic and protein materials that inform about cell-to-cell interactions that influence immune signaling and inflammatory processing. No study to date has explored the associations of EVs with cancer-related symptoms. So, the purpose of this dissertation was to investigate the …