Medicine and Health Sciences Commons^™

Stress Relaxation In Orthodontic Aligner Plastics; An In Vitro Comparison Study, Kristopher J. Keller

Theses & Dissertations

The purpose of this study was to ascertain if repeated stresses from extension cycling would result in accumulated damage in aligner materials and affect force delivery. A secondary goal was to identify potential differences in mechanical behavior present among orthodontic aligner polymers. Four thermoplastic polymers (Essix ACE, Taglus, Zendura, and Zendura FLX) were thermoformed, cut into strips, and extension cycled to 0.4 millimeters in a 37C water bath. Force decay, maximum and minimum force, and elastic modulus were measured during cycling. Additional samples were subjected to controlled tension until failure, allowing the measurement of yield strength, ultimate strength, and elastic …

Rilpivirine-Associated Aggregation-Induced Emission Enables Cell-Based Nanoparticle Tracking, Insiya Mukadam

Theses & Dissertations

Antiretroviral therapy (ART) has improved the quality and duration of life for people living with human immunodeficiency virus (HIV) infection. However, limitations in drug efficacy, the emergence of viral mutations and the paucity of cell-tissue targeting remain. We posit that to maximize ART potency and therapeutic outcomes newer drug formulations that reach HIV cellular reservoirs need to be created. In a step towards achieving this goal we discovered the aggregation-induced emission (AIE) property of the non-nucleoside reverse transcriptase inhibitor Rilpivirine (RPV) and used it as a platform for drug cell and subcellular tracking. RPV nanocrystals were created with endogenous AIE …

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …

Joint Loading Factors Of Articular Cartilage Structure In Healthy And Acl-Injured Knees, Elizabeth Wellsandt

Theses & Dissertations

Articular cartilage structure and chondrocyte health are sensitive and reliant on dynamic joint loading during activities. The risk of osteoarthritis (OA) is high after anterior cruciate ligament (ACL) injury, but mechanisms underlying its development are poorly understood. The overall goals of this work were 1) to determine the association between measures of individual and cumulative knee joint loading with T2 relaxation times in the knee cartilage of young individuals without injury and 2) to determine if these same knee joint loading factors are associated with cartilage T2 relaxation time one month after ACL injury. The central hypotheses was that lower …

Inflammatory Cytokine Expression Of Immune Cells On Exposure To Invisalign® Material: An In Vitro Pilot Study, Alaina M. Allen

Theses & Dissertations

The purpose of this study is to characterize the inflammatory cytokines that are expressed in peripheral blood mononuclear cells (PBMCs) and THP-1 monocytes exposed to Invisalign^® aligner material in vitro. Invisalign^® material was ground into particles, soaked in artificial saliva, and the eluate was collected. Commercially available cryopreserved pooled and individual human PBMCs and THP-1 monocytes were cultured with Invisalign^® material eluate and positive (lipopolysaccharide) and negative controls. The supernatants were collected and used with a BioLegend LEGENDplex^™ multi-analyte flow assay, a sandwich enzyme-linked immunosorbent assay (ELISA), to identify the expression of TNF-α, IL-6, IL-8, IL-10, …

Pandemic Driven Innovation: Development Of An Alternative Respiratory Pathogen Self-Collection Device, Thang Nguyen

Theses & Dissertations

The SARS-CoV-2 virus outbreak has underscored numerous weak links in our biodefense countermeasures against highly communicable diseases. Many believe it was our lack of an effective testing model that allowed the virus to become a global pandemic within a short period. The gold standard collection method for the SARS-CoV-2 virus involves mechanical debridement of the nasopharyngeal cavity with a stiff swab applicator, which has been known to cause pain and injury to patients, subsequently resulting in low patient acceptance of the procedure. Due to the invasive nature of the nasopharyngeal swab collection method, it may not be conducive to the …

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 …

Anti-Muc4Β Antibodies As A Novel Therapeutic Modality For The Treatment Of Pancreatic Cancer, Catherine Orzechowski

Theses & Dissertations

The deregulation of cell surface glycoproteins, such as mucins, is a hallmark of many tumors of epithelial origin. The transmembrane mucin MUC4, is differentially overexpressed in several malignancies, including pancreatic, breast, ovarian, lung, cervical, and head and neck cancers. Of all the aforementioned cancers, the role of MUC4 has been the most thoroughly in pancreatic cancer (PC), which is the 4th leading cause of cancer-related deaths in the United States. While MUC4 is undetectable in the normal or inflamed pancreas (pancreatitis), its expression progressively increases during PC progression and its higher expression correlates with poor survival. The role of MUC4 …

Long-Acting Nanoformulated Antivirals For The Treatment And Prevention Of Hiv-1 And Hbv Infections, Dhruvkumar M. Soni Dr.

Theses & Dissertations

While antiretroviral therapy (ART) has revolutionized treatment and prevention of human immunodeficiency virus type one (HIV-1) infection, regimen adherence, viral mutations, drug toxicities, stigma and pill fatigue are limitations. These have led to the development of long acting (LA) ART. These include, but are not limited to, implantable devices, new chemical entities, prodrug modifications and nanoformulations. To these ends, this thesis focues on the transformation of nucleoside reverse transcriptase inhibitors (NRTIs) into LA parenterals, While elusive, data from our laboratories demonstrated that modifications to the PROdrug and nucleoTide technology (ProTide) enables improvements in drug apparent half-life and tissue and cell …

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 …

Investigating The Relationship Between Unavoidable, Hospital Acquired Pressure Injury And Mortality: Is Unavoidable, Hospital Acquired Pressure Injury A Signal Of Increased One-Year Mortality Risk?, Eileen Jimenez

Theses & Dissertations

The purpose of this dissertation was to explore the strength of the relationship between unavoidable Hospital Acquired Pressure Injury (HAPI) and increased risk of one-year mortality for patients age 55 and older who were admitted to a hospital from 2015 to 2018. A quantitative, retrospective case-control study was designed to compare demographics, comorbid conditions, pressure injury risk, and living situation of those patients that developed unavoidable HAPI and hospitalized adults with similar physiological burdens that remained injury-free. The one-year mortality for the HAPI group was 27 of 48 (56%), and 26 of 47 patients (55%) for the Control group. The …

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 …

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 …