Wnt/Β-Catenin Mediated Cancer Stem Cell Activation In Hepatocellular Carcinoma., Harshulkumar M. Pandit

Electronic Theses and Dissertations

Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with variable presentation, high chemotherapy resistance and early tumor recurrence. In this dissertation, we have systematically enriched, identified and characterized HCC cancer stem cells (CSCs) from 3 different HCC cell lines (Hepa1-6, HepG2, and Hep3B) using in vitro serum-free culture method. Enriched spheroids acquired CSC properties, primarily self-renewal capability, spheroid formation ability, and drug resistance. Heterogeneous CSCs enriched from Hepa1-6 cells demonstrated higher tumor initiation and proliferation capability in vivo, compared to control HCC cells in orthotopic immunocompetent mouse model. EpCAM+ CSCs were significantly enriched within heterogeneous Hepa1-6 CSC spheroids. Consequently, …

Social Determinants Of Health And A Grounded Mixed-Methods Approach To Explain Declining Life Expectancy In Eastern Kentucky : 1980 – 2014., William Renda

Electronic Theses and Dissertations

Trends in life expectancy for the United States from 1980-2014 suggest general improvement overall. However, eastern Kentucky stands out with a cluster of counties experiencing declining life expectancy. Given that life expectancy is an excepted indicator of overall population health, this anomaly in eastern Kentucky warrants investigation. This thesis uses a grounded mixed methods approach to explore this trend across the greater Appalachian region. Content and discourse analysis of interviews with public health and medical professionals in the study area revealed key themes perceived as being related to declining life expectancy, which informed variable selection for regression analysis. Regression models …

The N-Terminal Methyltransferase Homologs Nrmt1 And Nrmt2 Exhibit Novel Regulation Of Activity Through Heterotrimer Formation., Jon David Faughn

Electronic Theses and Dissertations

Protein, DNA, and RNA methyltransferases have an ever-expanding list of novel substrates and catalytic activities. Even within families and between homologs, it is becoming clear the intricacies of methyltransferase specificity and regulation are far more diverse than originally thought. In addition to specific substrates and distinct methylation levels, methyltransferase activity can be altered through formation of complexes with close homologs. This work involves the N-terminal methyltransferase homologs NRMT1 and NRMT2. NRMT1 is a ubiquitously expressed distributive trimethylase. NRMT2 is a monomethylase expressed at low levels and in a tissue-specific manner. They are both nuclear methyltransferases with overlapping target consensus sequences …

A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz

Electronic Theses and Dissertations

In oncology, imaging plays a major role in terms of early detection and treatment of most types of cancer. Magnetic resonance imaging (MRI) is mostly used for cancer diagnosis due to its excellent contrast resolution. However, MRI for cancer diagnosis is somewhat limited by its sensitivity. In this thesis, we assessed the ability of theranostic platform consisting of gold nanoparticles functionalized with a cancer targeting aptamer; AS1411 and gadolinium chelate (Dotarem thiol derivative; Gd (III)-DO3A) as a MRI contrast agent to target malignant tumors by enhancing the MRI contrast of the detected tumor. The proposed technology is a novel injectable …

A Novel Fibroblast Growth Factor 1 Variant Reverses Nonalcoholic Fatty Liver Disease In Type 2 Diabetes., Qian Lin

Electronic Theses and Dissertations

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with type 2 diabetes (T2D). Our recently engineered FGF1 partial agonist, carrying triple mutations (FGF1^△HBS) exhibits greatly reduced proliferative potential, while preserving the full metabolic activity of wild-type FGF1. This study tests the preventive and therapeutic effects of FGF1^△HBS on NAFLD in db/db T2D and explores potential mechanisms. The results showed that administration of FGF1^△HBS to 2-month-old db/db mice for 2 months constantly lowered blood glucose levels, improved insulin sensitivity, and lowered liver weight, lipid deposition, and …

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …

Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert

Electronic Theses and Dissertations

Skeletal muscle mass, contractile properties, and metabolic function are regulated through the coordinated activation of multiple intracellular signaling pathways and genetic reprogramming. The endoplasmic reticulum (ER) plays a pivotal role in protein folding and calcium homeostasis in many cell types, including skeletal muscle. Disruption of calcium levels or accumulation of misfolded proteins in the ER lumen leads to stress, which results in the activation of a signaling network called the unfolded protein response (UPR). Further, recent studies have suggested that in certain conditions, UPR pathways can be activated independent of ER stress. However, the role of ER stress and the …

Investigating The Impact Of Nrmt1 Cancer Mutants On Catalytic Specificity And The Dna Damage Response., Kaitlyn Marie Shields

Electronic Theses and Dissertations

Protein methylation is an established and critical posttranslational modification controlling multiple cellular events. Alterations in protein methylation have been implicated in many diseases, including cancer. My work focused on the N-terminal trimethylase NRMT1 and the N-terminal monomethylase NRMT2. Previous work proposed that NRMT2 assists NRMT1 by priming its substrates for trimethylation. Importantly, NRMT1 mutations have been found in cancers, and loss of NRMT1 has been shown to promote oncogenic phenotypes in cancer cells. Together, this suggests that altered activities of NRMT1/2 may play a role in cancer progression. Although NRMT1/2 are 50% identical, they differ in key aromatic residues in …

Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt

Electronic Theses and Dissertations

Dysregulation of alpha-amino post-translational modifications (Nα-PTMs) is found in multiple cancers and developmental disorders. However, the exact roles Nα-PTMs play in regulating protein function remain poorly understood. I sought to clarify the role of Nα-methylation and Nα-acetylation in the regulation of Myosin Regulatory Light Chain 9 (MYL9). MYL9 is a key cytoskeletal regulator and transcription factor and is the first protein confirmed to undergo both Nα-methylation and Nα-acetylation. Through this work I revealed novel regulatory features of MYL9, while also presenting a framework by which to understand the coordinated regulation of proteins by Nα-methylation and Nα-acetylation. Nα-PTM selective mutants of …

Coal Ash Exposure And Behavioral Impairments Among Children In Louisville, Kentucky., Chisom Nmesoma Odoh

Electronic Theses and Dissertations

Introduction: Coal ash, generated from the combustion of coal is principally made up of fly ash, which consists of small particles and metals that can affect the development of children. Coal ash is predominately stored in landfills and surface impoundments, of which many are in proximity to residential areas. According to the Environmental Protection Agency, 25% of residents in proximity to electric power plants are children. Few studies have reported a positive association between coal ash and its by-products and neurobehavioral disorders. The purpose of this study was to explore the relationship between coal ash and its components and …

Generalized Spatiotemporal Modeling And Causal Inference For Assessing Treatment Effects For Multiple Groups For Ordinal Outcome., Soutik Ghosal

Electronic Theses and Dissertations

This dissertation consists of three projects and can be categorized in two broad research areas: generalized spatiotemporal modeling and causal inference based on observational data. In the first project, I introduce a Bayesian hierarchical mixed effect hurdle model with a nested random effect structure to model the count for primary care providers and understand their spatial and temporal variation. This study further enables us to identify the health professional shortage areas and the possible impacting factors. In the second project, I have unified popular parametric and nonparametric propensity score-based methods to assess the treatment effect of multiple groups for ordinal …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

Perinatal Nicotine With Or Without Early Life Influenza Infection Leads To Lung Dysfunction With Age., Ryan Carroll Mcallister

Electronic Theses and Dissertations

Obstructive Airway Diseases (OADs) affect millions of people worldwide, and are characterized by chronic inflammation and tissue remodeling in the lung. It has been proposed that the development of OAD is greatly influenced (and perhaps pre-determined) by early life events, such as maternal smoking or a viral infection. However, direct evidence of this is limited and the mechanisms involved remain unclear. Our laboratory previously developed a murine model of perinatal nicotine exposure, and reported that nicotine leads to airway remodeling and decreased pulmonary function in the offspring. We discovered these effects were mediated through the α7 nicotinic acetylcholine receptor (nAChR). …

A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp

Electronic Theses and Dissertations

Cisplatin is a potent chemotherapeutic used for the treatment of many solid cancers, including testicular, ovarian, and lung cancer. Cisplatin causes many adverse side effects, of which nephrotoxicity leading to acute kidney injury is dose-limiting. Approximately 30% of patients will develop nephrotoxicity with cisplatin, and will either have their next dose of cisplatin lowered, skipped, or be switched to a less nephrotoxic chemotherapeutic altogether. These outcomes are not ideal when trying to treat cancer. Previously, it was believed that patients could recover from cisplatin-induced acute kidney injury with little to no lasting effects, but recent longitudinal studies have shown this …

A Mixed Methods Study Exploring The Relationship Of Cognitive And Motivational Factors To Sonography Student Performance, Renee Hathaway

College of Education and Human Sciences: Dissertations, Theses, and Student Research

The purpose of this mixed methods study was to examine relationships between sonography students’ levels of self-regulation and self-efficacy and their performance in a 16-week introductory vascular sonography skills laboratory course. Measures for the study were designed to yield qualitative and quantitative data related to student goals, strategies, and course performance, and were generated by both students and faculty. Qualitative data from the study included student self-reports of self-regulatory strategies and instructor evaluations of student performance, while quantitative data were provided by instructor and student ratings of performance, student self-efficacy ratings, and student reports on their use of deliberate practice. …

Pharmaceutical Care Management Association V. Rutledge, John J. Crean, Karl Williams

Doctoral External Publications

On June 8, 2018 the federal Eighth Circuit Court of Appeals announced its decision concerning Arkansas' attempt to regulate perceived unfair payment practices of pharmacy benefit managers (PBMs) in the case Pharmaceutical Care Management Association v. Rutledge.¹ Because pharmacies across the country face similar problems, and this ruling may influence other federal appellate courts, review and discussion is useful for the purpose of making strategic decisions.

Uams Summer Health Literacy Study, Merritt Osment

Health, Human Performance and Recreation Undergraduate Honors Theses

Background: Health Literacy is a barrier to self-care; patients often lack the skills to understand complicated instructions that deal with medications, wound care, follow up schedules, and preventative care. Patients who undergo hip and knee replacements are often older adults, a population that normally struggles with various aspects of health literacy. Patient education materials are a common means of communicating with these individuals. However, if the patient does not understand the materials that they are given, they are more likely to experience negative side effects after their operation. Purpose: The purpose of this study is to compare the health literacy …

The Effects Of Formative And Summative Assessment On Student's Connectedness, Satisfaction, Learning And Academic Performance Within An Online Healthcare Course, Thomas J. Wing

Boise State University Theses and Dissertations

The quantitative study presented here evaluates the effects of formative and summative assessment on student’s connectedness, satisfaction, learning and academic performance within a university three-credit 400 level online healthcare course. Literature exploring the role that formative assessment plays within an online environment is currently lacking. Additionally, understanding how assessment practices can help support the goals of online healthcare education is vitally important given the rise in popularity of this delivery format.

This study investigated student outcomes in the form of connectedness, satisfaction, learning and academic performance. Four cohorts of students were included in this study. Two cohorts were provided with …

Evaluation Of Cardiomems Heart Failure Device, Danielle Moe, Msn, Rn

Doctor of Nursing Practice Projects

Background: Heart failure (HF) is a chronic condition where the heart cannot pump enough blood to adequately oxygenate cells. The CardioMEMS HF device is implanted into the pulmonary artery (PA) allowing practitioners to monitor pressures remotely and prescribe interventions. Objectives: The primary purpose of this project was to determine if CardioMEMS is an effective intervention in the reduction of hospital admissions, emergency department (ED), and clinic visits for HF patients. The secondary purpose was to determine if the quality of life (QOL) and exercise tolerance was improved post-implant. Methods: The author conducted a retrospective chart review by accessing previously compiled …

Role Of Multi-Parametric (Mp) Mri In Prostate Cancer, Syed Muhammad Nazim, Ather Enam, Basit Salam

Section of Urology

Multi-parametric magnetic resonance imaging is increasingly being recommended as standard imaging modality for prostate cancer diagnosis and staging. It comprises structural T2 and T1 sequences supplemented by functional imaging techniques, i.e. diffusion-weighted, dynamic contrast enhanced and spectroscopic imaging. Pre-biopsy multi-parametric magnetic resonance imaging is recommended for both detection and staging as it avoids biopsy artefact, and when normal, has a negative predictive value of 95% for significant cancer. Magnetic resonance imaging-guided prostate biopsy targets only area(s) considered to be suspicious for prostate cancer, hence resulting in improved accuracy. Dynamic contrast enhancing helps in the detection of cancer and for the …

An Electromyography Study Of Muscular Endurance During The Posterior Shoulder Endurance Test, Neil A. Evans, Emily Dressler, Timothy L. Uhl

Physical Therapy Faculty Publications

The primary purpose was to determine if there is a difference between the median frequency slopes of 5 posterior shoulder muscles during the initial portion of the Posterior Shoulder Endurance Test (PSET) at the 90° and 135° shoulder abduction positions. Fifty-five healthy volunteers (31 females) participated. The median frequency of the posterior deltoid (PD), upper trapezius (UT), middle trapezius (MT), lower trapezius (LT), and infraspinatus (INF) was measured during the PSET at 90° and 135° of shoulder abduction. External torque of 13 ± 1 Nm was used for females and 21 ± 1 Nm for males. A fixed effect multi-variable …

Pain, Need-Driven Behaviors In Dementia, And Nurses' Perceptions: An Embedded Mixed Methods Study, Suzanne E. Parkman

Nursing Theses and Dissertations

This dissertation is an exploration of psychosocial and behavioral concepts related to the experience of pain in persons with severe dementia and whether the use of an observational pain scale would provide better pain management and comfort for these individuals. Pain has been under-detected, under-reported, and under-treated in this population mainly because persons with dementia (PWD) are unable to self-report pain. Cognitive decline associated with dementia is commonly accompanied by loss of ability to communicate and neuropsychiatric behaviors known as need-driven behaviors (NDB). Nurses must correctly interpret ‘pain behaviors’ in order to assess and treat appropriately. The overlapping of …

Myocardial Stunning-Induced Left Ventricular Dyssynchrony On Gated Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging, Zhixin Jiang, Haipeng Tang, Jianzhou Shi, Yanli Zhou, Cheng Wang, Dianfu Li, Qijun Shan, Weihua Zhou

Faculty Publications

Objectives Myocardial stunning provides additional nonperfusion markers of coronary artery disease (CAD), especially for severe multivessel CAD. The purpose of this study is to assess the influence of myocardial stunning to the changes of left ventricular mechanical dyssynchrony (LVMD) parameters between stress and rest gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI).

Patients and methods A total of 113 consecutive patients (88 males and 25 females) who had undergone both stress and rest ^99mTc-sestamibi gated SPECT MPI were retrospectively enrolled. Suspected or known patients with CAD were included if they had exercise stress MPI and moderate to …

Future Warming And Acidification Result In Multiple Ecological Impacts To A Temperate Coralline Alga, Megan J. Huggett, Kathryn Mcmahon, Rachele Bernasconi

Research outputs 2014 to 2021

Coralline algae are a crucial component of reef systems, stabilising reef substrate, providing habitat and contributing to accretion. Coralline algae and their surface microbial biofilms are also important as settlement cues for marine invertebrates, yet few studies address the impact of future environmental conditions on interactions between coralline algae, reef microbes and settlement by larvae of marine invertebrates. We exposed the temperate coralline algal species Amphiroa gracilis to warming and/or acidification scenarios for 21 days. Algae became bleached but photosystem II function was not measurably impacted. Settlement by larvae of the sea urchin Heliocidaris erythrogramma was reduced and the structure …

Handgrip Fatigue And Forearm Girth In Intermediate Sport Rock Climbers, Grace Antoinette Macdonald

UNLV Theses, Dissertations, Professional Papers, and Capstones

Background: Rock climbing has been increasing in popularity both recreationally and competitively. Indoor sport rock climbing is a type of climbing where the climber ascends a wall using artificial rocks (hand and foot holds) and is attached to a safety rope. Despite this increase in popularity of the sport, the physiological responses to sport climbing as an exercise to specific muscle groups are not well defined in literature. Purpose: The purpose of this study was to quantify the change in handgrip strength over a 30-minute bout of continuous climbing, specifically in intermediate sport climbers. An additional aim of this study …

Development Of An Evidence-Based Nursing Leadership Fellowship Program Guide, Jennie Noren

UNLV Theses, Dissertations, Professional Papers, and Capstones

Faced with an increasing demand for nurse leaders with competencies in effective inter-professional communication, change management, conflict resolution, business and financial acumen, and the ability to lead both within and across systems, the current practice of promoting the highest skilled clinicians into leadership positions is not effective. Leadership skills which have been demonstrated in the literature to generate successful and impactful leaders must be provided through immersive educational experiences in an efficient and effective manner to produce leaders who can promote the transformation of healthcare at all levels with confidence. This DNP Project has created a guide for an evidence-based …

Electronic Health Record Instruction In First-Semester Nursing Students: A Comparative Study, Angela Ruckdeschel

UNLV Theses, Dissertations, Professional Papers, and Capstones

The use of health information technology has been shown to have positive effects on patient outcomes and provider efficiency. New nurses make more than half of the 7 million life-threatening medication errors that occur each year, and electronic health records (EHRs) have been shown to significantly reduce these errors. Nurses now are expected to enter practice with a solid foundation in health information technology and the use of the EHR. Unfortunately, the vast majority of nursing schools do not specifically train their students in effective EHR utilization. Academic EHRs (AEHRs) are software packages with learning features that can be incorporated …

Efficacy Of Combined 5-Fluorouracil And Photodynamic Therapy In Glioma Spheroids, Karanjit Singh

UNLV Theses, Dissertations, Professional Papers, and Capstones

Standard treatment regimens consisting of surgery, radiation and chemotherapy have proven ineffective for the treatment of high-grade gliomas such as glioblastoma multiforme (GBM). An effective cure requires elimination of nests of tumor cells that have migrated from the resection margin and infiltrated normal brain. A number of localized therapies, including light-based approaches such as photodynamic therapy (PDT) and photochemical internalization (PCI) are currently under investigation for the management of GBM patients.

Several studies have demonstrated a high degree of synergy between PDT and bleomycin, via the PCI mechanism, in a variety of in vitro and in vivo models, including glioma …

Rna Binding Proteins Co-Localize With Small Tau Inclusions In Tauopathy, Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz De Rocha, Cheng Zhang, Wai Haung Yu, John Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies demonstrated …