Medicine and Health Sciences Commons^™

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 …

Rediscovering The Art Of Nursing For Nursing Practice, Deborah Henry

Electronic Theses and Dissertations

The art of nursing is discussed throughout nursing literature but research on the topic is lacking. The purpose of this research was to reveal experiences of the art of nursing. Nurses were asked to describe experiences about the art of nursing from their own nursing practice. This study was qualitative in nature and used a phenomenological approach to answer the research question, “What is the experience of the art of nursing in nursing practice?” The study was guided by the philosophical stance of Merleau-Ponty and the research strategies of Thomas and Pollio. Participants included nurses who had experience using the …

Relationship Of The Srss Questionnaire With Physiological And Performance Measures, Alec Perkins

Electronic Theses and Dissertations

The overall purpose of this thesis was to validate the SRSS questionnaire. This was accomplished by conducting a single investigation using eleven well-trained weightlifters with at least one year of competition experience. These weightlifters completed five testing sessions over the course of five microcycles leading up to a competition. Every testing session took place on Monday morning prior to regular training and included: hydration testing, SRSS questionnaire, blood draws followed by a standardized warm-up protocol and squat jumps (SJ) with 0kg and 20kg. While the majority of SRSS recovery and stress items did not change with changes in VL or …

Comparison Of Muscle Physiology And Performance Outcomes From Either Relative Intensity Or Repetition Maximum Training, Kevin Carroll

Electronic Theses and Dissertations

The main purpose of this dissertation was to compare performance and physiological outcomes of between a repetition maximum (RM) and a relative intensity using sets-and-repetitions (RI_SR) resistance training (RT) program in well-trained lifters. Fifteen subjects underwent RT 3 d·wk^-1 for 10-weeks in either a RM group (n=8) or RI_SR group (n=7). The RM group achieved a relative maximum each day while the RI_SR group trained based on percentages. Testing included percutaneous needle biopsies of the vastus lateralis, ultrasonography, unweighted (g to assess within and between-group alterations. RI_SR from pre-to-post yielded statistically significant increases in …

Cluster Set Loading In The Back Squat: Kinetic And Kinematic Implications, Alexander Wetmore

Electronic Theses and Dissertations

The purpose of this study was to investigate the kinetic and kinematic implications of cluster loading as a resistance training programming tactic. Cluster loading involves introducing rest during a set which may allow athletes to train at higher absolute intensities. Eleven trained males were recruited for this study. Subjects completed two testing sessions consisting of three sets of five back squats at 80% of their one repetition maximum. Cluster loading included 30s of inter-repetition rest. All testing was done on dualforce plates with four linear position transducers. Paired sample t-tests were used to determine differences between conditions with Cohen’s d …

Do Healthcare Students Endorsing Stigma Of Mental Illness Screen For Suicidal Ideation? An Evaluation Of Knowledge, Attitudes, And Behaviors, Dannel K. Petgrave

Electronic Theses and Dissertations

The stigma of mental illness endorsed by healthcare professionals has been linked to adverse outcomes. This issue underscores the need for early anti-stigma interventions in the context of professional training. The present study measured stigma change and suicide screening behaviors among medical, nursing, and pharmacy students enrolled in an interprofessional Communication Skills for Healthcare Professionals course. The Mental Health Knowledge Schedule (MAKS; Evans-Lacko et al., 2010), Opening Minds Scale for Health Care Providers (OMS-HC; Modgill, Patten, Knaak, Kassam, & Szeto, 2014), and the Marlowe-Crowne Social Desirability Scale Form C (M-C SDS Form C; Reynolds, 1982) was administered at baseline (T …

Hiv Integrase Inhibitor Pharmacogenetics And Clinical Outcomes: An Exploratory Association Study, Derek E. Murrell

Electronic Theses and Dissertations

As HIV is now primarily a chronic condition, treatment is given life-long with changes as necessitated by alterations in tolerability and efficacy. Thus, personalized medicine may be useful in the prevention of unnecessary drug exposure and avoidable side effects. Three of the four currently available HIV integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, and dolutegravir, are widely utilized antiretrovirals in the USA and exhibit variations in outcomes among subjects. To interrogate differences among subjects receiving these drugs, we investigated the association of several single nucleotide polymorphisms (SNPs) with drug exposure, clinical outcomes, and subject-reported adverse events. HIV+ adults (≥18 years …

3d-Printed Fluidic Devices And Incorporated Graphite Electrodes For Electrochemical Immunoassay Of Biomarker Proteins, Abdulhameed Alabdulwaheed

Electronic Theses and Dissertations

Biomarkers are measurable indicators of health status or disease state that can be used for diagnosis and may help guide patient treatment strategies. Enzyme-linked immunosorbent assays (ELISA) and other many clinical techniques currently used for measuring biomarker proteins lack sensitivity, demand high analysis cost, are often not well-suited for measuring multiple biomarkers in a single sample, and require long analysis times. Here, we demonstrate simple, low-cost 3D-printed flow-through devices with integrated electrodes modified with gold nanoparticles (AuNPs) for electrochemical immunoassays of S100B, a biomarker protein related to conditions like skin cancer and brain injuries. Flow-through devices are fabricated from photocurable-resin …

Effect Of Root Cause Analysis On Pre-Licensure, Senior-Level Nursing Students’ Safe Medication Administration Practices, Kristi Miller

Electronic Theses and Dissertations

Aim: The aim of this study was to examine if student nurse participation in root cause analysis has the potential to reduce harm to patients from medication errors by increasing student nurse sensitivity to signal and responder bias.

Background: Schools of nursing have traditionally relied on strategies that focus on individual characteristics and responsibility to prevent harm to patients. The modern patient safety movement encourages utilization of systems theory strategies like Root Cause Analysis (RCA). The Patient Risk Detection Theory (Despins, Scott-Cawiezell, & Rouder, 2010) supports the use of nurse training to reduce harm to patients.

Method. Descriptive and …

Fascicle Arrangement In College-Aged Athletes, Jacob Goodin

Electronic Theses and Dissertations

Purpose: To compare muscle architecture variables between sport and sex in competitive athletes, and to compare muscle architecture with performance variables in strong versus weak athletes, and good versus poor jumpers. Methods: The vastus lateralis (VL) and lateral gastrocnemius (LG) muscles of 139 collegiate athletes were collected using ultrasonography to determine muscle thickness (MT), pennation angle (PA), fascicle length (FL), and relative fascicle length (FL_rel). Absolute and relative peak power, absolute and relative isometric peak force, and jump height were measured in a subset of baseball and soccer athletes. A 5x2 factorial analysis of variance (ANOVA) was used …

Preparing For A National Weightlifting Championship: A Case Series, Spencer K. Travis

Electronic Theses and Dissertations

The purpose of this thesis was to observe psychological, physiological, and performance changes to determine when two high-level weightlifters were peaked for a major competition. We addressed this purpose by conducting a two-part case study series with one USA international level female and one USA national level male weightlifter. Both athletes were considered to be peaked on competition day. The results support our hypothesis that jumping performance would be peaked on competition day corresponding with an increased recovery and decreased stress state. However, contrary to our hypothesis, each athlete exhibited small decreases in muscle size leading into the competition relative …

The Association Between Medication Adherence In Mental Illness And Substance Use Disorder Relapse In Patients With Dual Diagnosis, Tyler Dunn

Electronic Theses and Dissertations

Objectives: The aims of the study were to (1) identify personal, social, and clinical history for patients with substance use disorder (SUD) and mental illness, (2) measure agreeance between patient self-report versus facility record history for mental illness, substance abuse, and psychotropic medication, (3) investigate the specific role of medication adherence and barriers to use for psychotropic medications upon SUD relapse, and (4) assess follow-up changes in mental illness severity and medication adherence in dual diagnosis patients enrolled in a substance abuse rehabilitation program.

Methods: The pilot study utilized a mixed methodology. Inclusion criteria included male patients at least 18 …

Designing A Calibration Set In Spectral Space For Efficient Development Of An Nir Method For Tablet Analysis, Md Anik Alam

Electronic Theses and Dissertations

Designing a calibration set is the first step in developing a spectroscopic calibration method for quantitative analysis of pharmaceutical tablets. This step is critical because successful model development depends on the suitability of the calibration data. For spectroscopic-based methods, traditional concentration based techniques for designing calibration sets are prone to have redundant information while simultaneously lacking necessary information for a successful calibration model. The traditional method also follows the same design approach for different spectroscopic techniques and different formulations, thereby lacks the optimizing capability to be technique and formulation specific.

A method for designing a calibration set in the Near …

An Ethical Framework For Organizational Resource Allocation For Patient Services In Health Care, Natalie Dick

Electronic Theses and Dissertations

Unanswered questions on how to allocate scarce resources in health care settings are often left to either bedside decision-making or, at best, the organizational policy level. Yet, there is little attention and no consensus on how organizational policy should address resource allocation in health care. An ethically sound framework is needed to guide policy development for resource allocation within health care organizations. In addition, a more comprehensive study of concepts tied to moral obligations of health care organizations is needed in terms of human rights, health disparities, and patient care quality. Until now, human rights literature has largely focused on …

Key Components For An Ethics Consultation Curriculum, Joseph Bertino

Electronic Theses and Dissertations

Due to a lack of formal credentials for clinical ethics consultants, the professionalization of clinical ethics as a normative discipline in contemporary American health care is diminished amongst other health care professionals. While medical specialties, organizational leadership positions, and other miscellaneous health care occupations possess governing bodies that posit credentials that justify these roles, clinical ethics consultants lack a standard of competence. While this gap has been temporarily reconciled by individual employer criteria, a national standard that attempts to educate and demonstrate a clinical ethicist’s abilities does not exist. Still, various attempts have been made to establish a certification program …

The Relationship Between Perceptions Of Patient Safety Culture, Nurse Advocacy, And Nurse Sensitive Patient Outcomes, Margaret Dicuccio

Electronic Theses and Dissertations

The purpose of the study was to understand relationships between and among patient safety culture, nurse reported attitude toward patient advocacy and key patient outcomes. Nurses play an integral role in patient safety, providing care through constant interaction with the patient and clinical team. Advocating for patients is part of that role; however little research existed that explored how advocacy was related to the safety culture or specific patient outcomes.

A correlational cross-sectional design was chosen for this secondary data analysis. Correlation and regression models were applied to medical/surgical unit data from seven facilities within one hospital system. Sources of …

Enhancing Quality Ethics Consultations In Pediatric Medicine, Ariel Clatty

Electronic Theses and Dissertations

Medical ethics consultations occur predominantly in the adult realm of medicine, alternatively in Pediatric Medicine there is a widespread lack of training and skilled professionals to service these requests. Most of the literature in pediatric ethics consultations revolves around mirroring adult ethics consultations. This dissertation seeks to identify and address the issues related to quality of ethics consultations in a clinical setting regarding the organizational and research settings for Pediatric Medicine, and how adopting and applying the guiding standards for ethics consultation using the Core Competencies of the American Society of Bioethics and Humanities will better assist all parties to …

Melatonin-Micronutrients Osteopenia Treatment Study (Mots): A Translational Study Assessing The Effects Of Melatonin, Strontium Citrate, Vitamin D3 And Vitamin K2 On Bone Density, Bone Turnover Markers And Health-Related Quality Of Life In Postmenopausal Osteopenic Women Following A One-Year Double-Blind Randomized Placebo-Controlled Trial And On Osteoblast-Osteoclast Co-Cultures, Sifat Maria

Electronic Theses and Dissertations

Objective: The purpose of this study was to assess if a novel combination of melatonin and three other natural bone-aiding micronutrients: strontium citrate, vitamins D₃ and K₂ (MSDK) could improve bone health by modulating the activity of osteoblasts and osteoclasts in favor of balanced bone remodeling and by improving the overall health-related quality of life in postmenopausal osteopenic women.

Methods: The Melatonin-micronutrients Osteopenia Treatment Study (MOTS) is a translational research study that used both clinical and in vitro approaches to assess the efficacy of MSDK on bone health in women and to identify potential mechanisms for its effects. …

The Effect Of A Mindfulness Intervention On The Depression Symptoms Of Mothers In Treatment For An Opioid Use Disorder, Karen Alexander

Electronic Theses and Dissertations

BACKGROUND: Mothers in treatment for an opioid use disorder experience a high prevalence of depression which may influence their relationship with their child. In the general population, mindfulness-based parenting intervention has been seen in the literature to have a clear positive effect on maternal depression. No research has been published regarding the effect of mindfulness intervention on maternal depression of women in treatment for an opioid use disorder.

OBJECTIVES: To describe the characteristics of mothers in treatment for opioid use disorder, including depression and adverse childhood experiences, and to evaluate the characteristics associated with participation in a mindfulness intervention. Lastly, …

An Ethical Framework For Communication Of Prognosis In Pediatric Critical Care Medicine, Amanda Mattone

Electronic Theses and Dissertations

The focus of this dissertation is to create an ethical framework for communication of prognosis in the pediatric critical care setting. This dissertation argues that an ethical framework for communication of prognosis in the pediatric critical care setting is necessary because ethical communication transactions lead to better care for pediatric patients in critical care by enabling surrogate decision makers to make well-informed decisions. Moreover, a lack of effective communication skills can be detrimental to the patient. The need for such a framework is revealed by research indicating that physicians often lack the necessary education and skills for effective communication transactions …

Comparison Of Two Methods Of Pediatric Triage Education, Catherine Recznik

Electronic Theses and Dissertations

Introduction. The majority of pediatric emergency patients are seen in mixed-age emergency departments and triaged by general emergency nurses. Educational methods for teaching pediatric triage education to general emergency nurses have not been well studied, and previous studies of the use of the Emergency Severity Index in children have been performed primarily in centers that are high volume for pediatrics. Methods. A repeated measures, randomized crossover study comparing two different methods of pediatric triage education was conducted. Participants were general emergency triage nurses recruited from a general emergency department that is classified as low volume for pediatrics. Each participant was …

The Logic Of Sexuation In Deleuze And Lacan, Matthew Lovett

Electronic Theses and Dissertations

In The Logic of Sexuation in Deleuze and Lacan, I argue for an account of sexual difference that responds to a tension in feminist philosophy, namely, the problem of the ontological status of the sexed body. In so doing, I turn to the work of Gilles Deleuze and Jacques Lacan. I argue that, rather than being antithetical, the two can be productively read together, in particular with regard to this very question. Ultimately basing my reading in the Deleuzian passive syntheses and dynamic geneses of Difference and Repetition and The Logic of Sense as well as in Lacan’s twentieth …

Synthesis Of Novel 5-Substituted Pyrrolo[2,3-D]Pyrimidine Antifolates As Selective And Potent Anti-Tumor Agents, Mohammad Karim

Electronic Theses and Dissertations

In last few decades many folate analogs have been discovered and several compounds are successfully being used as anticancer agents. Methotrexate (MTX), pemetrexed (PMX), raltitrexed (RTX): are a few examples of classical antifolates that are currently in clinical use. Although these compounds are widely used, all of them show dose limiting toxicity due to their non-specific transport into normal cells as well as malignant cells. Currently, clinically used classical antifolates suffer from this disadvantage because there is no way to selectively transport them into malignant cells. Currently available antifolates are transported via reduced folate career (RFC) as well as Folate …

The Core Relation Between Hospitality (Philoxenia), Dignity And Vulnerability In Orthodox Christian Bioethics: A Contribution To Global Bioethics, Rabee Toumi

Electronic Theses and Dissertations

In a pluralistic world, reaching consensus in matters of bioethics has proved to be difficult, especially with the political polarization that nurtures inimical differences. This dissertation argues that a middle ground can be identified between the plurality of value systems in contemporary bioethics based on an anthropological approach. This middle ground that reflects commonalities of the human condition can be explored in relation to the foundational principles of Orthodox Christian anthropology. To identify this middle ground the analysis discusses the core relation between hospitality, dignity, and vulnerability as a contribution to global bioethics.

In general, based on Orthodox Christian theology …