Medicine and Health Sciences Commons^™

Effect Of Total Body Iron On Metabolic Dysfunction Among U.S. Females In The Nhanes 2003-2010, Aged 12-49., Joseph Michael Carhart

Electronic Theses and Dissertations

Experimental and epidemiological studies have reported positive associations between iron parameters and metabolic dysfunction including: Type 2 diabetes mellitus (T2DM) (1-6), metabolic syndrome (7-15), non-alcoholic fatty liver disease (NAFLD) (16-22) and insulin resistance (23,24) with a number of studies showing that reductions in total body iron via dietary modification (e.g., reducing red meat intake) or phlebotomy lead to increases in insulin sensitivity (25), decreases in insulin resistance (26), and reductions in the prevalence of complications associated with T2DM (5, 27), metabolic syndrome (28) and NAFLD (22, 29). Moreover, the risk associated with these outcomes and total body iron differ between …

Deficiency Of Rdh10 Causes Cleft Secondary Palate In Mouse., Swetha Raja

Electronic Theses and Dissertations

The focus of this project is to understand the role of Retinoic Acid (RA) produced by RDH10-mediated metabolism of Vitamin A in palate development. For 80 years now, we have known that dietary restriction of RA/Vitamin A can cause cleft palate but we have failed to understand how RA deficiency causes cleft palate. Our gap in knowledge about how RA deficiency causes cleft palate is mainly owing to the fact that we lack a model system to study such defects. The aim of this thesis research project was to determine if conditional inactivation of the Vitamin A metabolic gene Rdh10 …

Metabolic Regulation Of Myocardial Adaptation To Exercise., Andrew Alan Gibb

Electronic Theses and Dissertations

While the benefits of exercise affect several organs, a significant adaptive response occurs within the heart. Exercise promotes cardiac growth, increases angiogenesis, and enhances cardiac function and these adaptations are associated with a cardioprotective phenotype. Additionally, extensive evidence shows that exercise dynamically regulates myocardial metabolism. This can be attributed to both changes in hormonal stimulation, increases in bioenergetic demand, and the bioavailability of circulating substrates. However, it is unclear whether these changes in metabolism contribute to physiologic cardiac growth. We reason that exercise-induced changes in metabolism are required to balance the catabolic and anabolic reactions needed for growth. Specifically, we …

The Role Of Kinases And Phosphatases In The Pathobiology Of Porphyromonas Gingivalis., Sarah Whitmore

Electronic Theses and Dissertations

Periodontal diseases result from the interplay between the dysregulation of the host inflammatory response and the actions of a dysbiotic bacterial community. These chronic inflammatory conditions affect persons on a worldwide scale. P. gingivalis is strongly implicated as a key periodontal pathogen in the more severe manifestations of periodontal diseases such as periodontitis. A core element of P. gingivalis pathogenicity is its dysregulation of innate immunity, including suppression of IL-8 production by gingival epithelial cells. The NF-κB family of related transcription factors plays a central role in regulating many important aspects of innate immune responses. NF-κB RelA/p65 homodimers regulate transcription …

Type Ix Secretion System : Characterization Of An Effector Protein And An Insight Into The Role Of C-Terminal Domain Dimeration In Outer Membrane Translocation., Lahari Koneru

Electronic Theses and Dissertations

Porphyromonas gingivalis and Tannerella forsythia are two of the primary pathogens that are associated in the etiology and progression of chronic periodontitis. In T. forsythia, KLIKK proteases are the recently identified group of proteolytic enzymes that are secreted through Type IX secretion system (T9SS). Among, these KLIKK proteases a synergistic relationship was observed between karilysin and mirolysin in invading the host complement system for the survival of the bacteria. Since, karilysin has been already characterized, in this study we propose to study about mirolysin through structural, biochemical and biological characterization. The obtained results from the experiments has shown the …

Self-Management As A Mediator Of The Relationship Between Social Support And Health Outcomes Of African American Adults With Type 2 Diabetes., Tariq N. Al-Dwaikat

Electronic Theses and Dissertations

Type 2 diabetes (T2D) is often associated with serious complications. African American adults have higher rates of diabetes-related complications than other ethnicities. Diabetes self-management reduces the risk of developing biological and psychological symptoms. Social support promotes positive behavior change and self-management that leads to improved biobehavioral and psychosocial outcomes. Few studies explored the relationship between social support dimensions and self-management behaviors, diabetes biomarkers, and psychosocial outcomes of African American adults with T2D. The purpose of this dissertation was to examine the relationships of various dimensions of social support with self-management behaviors and diabetes biomarkers and psychosocial outcomes of African American …

Evaluating Work Place Wellness In Greater Louisville's Technology Organizations : A Case Study., Andrew L. Mccart

Electronic Theses and Dissertations

Employers in the Southern Indiana and Greater Louisville region are looking for strategies to help them become a healthier workplace. Many employers see the expense of paying for an unhealthy workforce and they are looking to limit these expenses. The purpose of the study is to determine the state of workplace wellness activities in organizations in Southern Indiana and Greater Louisville. Due to the poor health statuses of Indiana and Kentucky, 39th and 45th, respectively, this study is significant for a number of stakeholders in our area. The purpose of this case study was to understand the state of health …

Moving Mountains : A Study Examining Long-Term Impacts Of Mountaintop Removal Coal Mining On Mortality In The Appalachian Region Using Geographic Information Sciences Techniques., James Howard Kent Pugh

Electronic Theses and Dissertations

Over the last hundred years, the Appalachian region has been dominated by the coal industry. It has also been and currently is one of the unhealthiest regions in the United States. Recent scholarship has examined the relationship between coal mining and health and mortality rates in the Appalachian region. The first study incorporates air quality and pollution data to examine if coal mining counties have higher levels of pollution and if this pollution contributes to mortality disadvantage. In the second study, I construct a population-based coal-exposure measure to better evaluate the relationship between coal mining and health I find that …

Role Of Human Arylamine N-Acetyltransferase 1 In Tumorigenesis And Cancer Biology., Marcus William Stepp

Electronic Theses and Dissertations

Human arylamine N-acetyltransferase 1 (NAT1) is a well-known phase II metabolic enzyme that has been associated with carcinogenesis. Its role in the biotransformation of aromatic and heterocyclic amine carcinogens has been investigated for many years, but more recent investigations focus on a possible endogenous role of human NAT1 in cancer initiation and progression. To further explore and understand possible endogenous roles for NAT1, we conducted in vitro enzymatic reactions, in vivo studies using homozygous high (rapid) or low (slow) NAT2 activity congenic F344.WKY rats, and genetically modified human breast cancer cell lines. Human NAT1 and rodent NAT2 hydrolyzed acetyl-coenzyme …

Pcb-Associated Steatohepatitis And The Role Of Nuclear Receptors., Heather Brooke Clair

Electronic Theses and Dissertations

Metabolic diseases, including fatty liver disease, hyperglycemia, and obesity, result when body systems responsible for managing allostasis (dynamic homeostasis across systems) are pressured beyond their collective compensatory reserve. Nutritional excess contributes to this state, the capacity of which is limited by genetic variation, and failure of one system will gradually lead to pathological overload in the others. Agents which act directly on the communication machinery linking these connected systems can also change the point at which allostatic load becomes allostatic overload. Environmental exposure to polychlorinated biphenyls (PCBs), a class of persistent organic pollutant, is associated with a specific form of …

Targeting The Major Regulator Of Mitosis., J. Mason Hoffman

Electronic Theses and Dissertations

Mitosis-inhibiting chemotherapeutics (e.g. taxanes) are frequently used to treat multiple cancer types. Recently, there has been much concern about the limited success of these drugs due to resistance and a lack of molecular targets. Thus, there is high demand for new drugs with diverse cellular targets. Targeting the regulators of mitosis is a promising approach. The anaphase promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle progression at multiple points. The interaction of ANAPC2 and ANAPC11, catalytic core subunits, is necessary for APC/C function. An in silico approach was used to identify compounds predicted to prevent assembly …

Mirna Expression Changes In Arsenic-Induced Skin Cancer In Vitro And In Vivo., Laila Al-Eryani

Electronic Theses and Dissertations

Arsenic is a naturally prevalent metalloid. Chronic arsenic ingestion through drinking water causes skin cancer. Arsenic-induced cancer mechanisms are not well defined. Epigenetic changes, including microRNA expression changes, might be playing a role. This dissertation investigates the impact of miRNA expression changes in arsenic-induced skin cancer. MiRNA expression was measure and compared using 3 different techniques, RTq-PCR, hybridization arrays and RNA-sequencing. MiRNAs differential expression in skin lesions was phenotype- and stage-related. Immortalized human keratinocytes (HaCaT) were transformed by chronic low arsenite exposure serving as a model for arsenic-induced skin carcinogenesis. Early changes in miRNAs and target mRNAs contribute to arsenic-induced …

The Role Of Hif-1Α In Intestinal Epithelial Barrier Function In Alcoholic Liver Disease., Tuo Shao

Electronic Theses and Dissertations

Hypoxia inducible factor 1 α (HIF1α) is an oxygen-responsive subunit. HIF-1α plays a pivotal role in many pathophysiological processes. In addition to oxygen availability, HIF-1α can be regulated by multiple other factors in response to various pathophysiological processes. Previous studies showed that hepatic HIF-1α could be beneficial or harmful in experimental alcoholic liver disease (ALD). However, the role of intestinal HIF-1α in ALD has not yet been studied. Given the critical role of the gut-liver axis in ALD, it is important to elucidate the role of intestinal epithelial HIF-1α in ALD. In the first chapter, we used wide type (WT) …

Ubqln1 : A Multi-Domain Protein With Multiple Functions., Zimple Kurlawala

Electronic Theses and Dissertations

There are 5 Ubiquilin proteins (UBQLN1-4, UBQLN-L), which are evolutionarily conserved and structurally similar. UBQLN proteins have 3 functional domains: N-terminal ubiquitin-like domain (UBL), C-terminal ubiquitin-associated domain (UBA) and STI chaperone-like regions in the middle. Alterations in UBQLN1 gene have been detected in a variety of disorders including Alzheimer’s disease, Amyotropic Lateral Sclerosis and lung cancer. UBQLN1 has been largely studied in neurodegenerative disorders in the context of protein quality control. Several studies have hypothesized that the UBA domain of UBQLN1 binds to poly-ubiquitin chains of substrate and shuttles it to the proteasome via its UBL domain for degradation. UBQLN1 …

Magnetic Field-Induced Intramolecular Cyclization As A Trigger For Nanoparticle-Based Delivery Systems., Sara Katherine Biladeau

Electronic Theses and Dissertations

Magnetic nanoparticles (MNPs) are used in a variety of applications, including as agents for magnetic resonance imaging, generation of local hyperthermia, and as platforms for drug delivery. Iron-based MNPs are often coated with a shell, such as silica or gold, to increase biocompatibility for drug delivery applications. Many MNPs used for cancer therapy rely on either an internal trigger, such as a difference in pH, or an external trigger, such as light or an alternating magnetic field (AMF), to cause release of a payload, typically a chemotherapeutic drug. Internal triggers are appealing because drug release can be targeted to a …

Stretching Adversely Modulates Locomotor Capacity Following Spinal Cord Injury Via Activation Of Nociceptive Afferents., Anastasia V. Keller

Electronic Theses and Dissertations

Spinal cord injury (SCI) is the second leading cause of paralysis in the United States, affecting around 282,000 people with 17,000 new cases each year. Initial and secondary damage to the spinal cord disrupts multiple descending pathways that modulate the function of sympathetic preganglionic neurons and central pattern generating circuitry. Resulting loss of autonomic and locomotor functions, as well as decreased levels of physical activity, lead to a myriad of complications that affect multiple organ systems and significantly reduce both quality of life and life expectancy in individuals with SCI. Spasticity and muscle contractures are two common secondary conditions that …

Exploring A Multifactorial, Clinical Model Of Thought Disorder : Application Of A Dimensional, Transdiagnostic Approach., Mara Ann Hart

Electronic Theses and Dissertations

Background: Bleuler saw thought disorder as the core defining feature of psychotic phenomena, reflective of the “splitting of the psychic functions” that occurred when, in the process of thinking, one’s ideas and feelings disconnect, becoming fragmented and competing functions. Unfortunately, interest in thought disorder as the conceptual core of psychosis was lost with rise of the modern DSM system, paralleling the shift towards a more simplistic, categorical way of defining psychiatric disorders. Aims: This study examined thought disorder from a dimensional perspective, with the aim of disentangling qualitative heterogeneity and diverse sources of influence. Analyses were based on …

Comparing Total Expenditures By Source Of Long-Term Services And Supports., Maresa R. Corder

Electronic Theses and Dissertations

This study compares total expenditures between beneficiaries enrolled in traditional Long-Term Care (LTC) and beneficiaries enrolled in Home and Community Based Services (HCBS) in a Quasi-Experimental Simple Ex Post Facto study utilizing multiple linear regression with inverted propensity score weighting. The results demonstrated, during the two years of the study period, that total expenditures were on average $14,565.03 (with a p-value oflessfor the total two years of the study, for HCBS beneficiaries when compared to their LTC counterparts. There remains today a belief that expenditures of elderly, dual beneficiaries electing to age-in-place for supported self-care expend less than that of …

Revisiting Neutrophil Responses To Toll-Like Receptor 4 : Influence Of Ligand Structures And Cellular Environments., Shuvasree Sengupta

Electronic Theses and Dissertations

Neutrophils respond to bacterial LPS through Toll-like receptor 4 (TLR4), which activates or potentiates immune defensive functions and prolongs cell survival. Activation of TLR4 signaling in neutrophils is beneficial for effective clearance of LPS-bearing Gram-negative bacteria, but may also drive aberrant inflammation if not stringently regulated. The regulatory processes by which neutrophil functions are calibrated to respond appropriately to different LPS-bearing bacteria are incompletely understood. Described here are investigations that reveal an unexpected sensitivity of TLR4 in neutrophils to small changes in LPS structure typical of various Gram-negative bacteria, including those that are dangerously virulent (Escherichia coli and Salmonella …

Mental Health And Substance Use Disorders And Treatment Receipt Among Pregnant Women In The United States, 2008-2014 : Trend Analysis, Likelihood Of Treatment Receipt, And Ethnic Disparities In Mental Health Treatment., Taghreed Nayel Salameh

Electronic Theses and Dissertations

The purposes of this dissertation were to examine trends from 2008 to 2014 in mental health and substance use disorders and treatment receipt, and explore factors associated with treatment receipt in pregnant women aged 18-44 years in the United States. A systematic review showed that illicit drug use disorder increased in pregnant women over the past decade. Despite the increase in treatment admissions for these disorders from 1992 to 2012, the overall treatment admission rate for pregnant women remained relatively stable (4%). In a trend study, compared mental health and substance use disorders and treatment receipt across Matched groups of …

Coal Ash Exposure And Asthma In Children., Jack Anthony Pfeiffer

Electronic Theses and Dissertations

This study examined the association between exposure to coal ash in the home among children aged 6-14 and asthma. Data was collected using personal modular impactors, lift tape samples, toe/finger nail samples, questionnaires, and peak flow meters. Laboratory methods used to analyze the samples included gravimetric analysis, scanning electron microscopy (SEM) / energy dispersive x-ray (EDX), and proton-induced x-ray emission (PIXE). Statistical methods used to analyze the data included the Chi Square Test of Independence, logistic regression, the Hosmer-Lemeshow Goodness of Fit test, Fisher’s Exact Test, and the Anderson-Darling Normality Test. Sample size was small, making statistical significance in calculated …

Biomechanical Testing Of An Exercise For Strengthening The Proximal Femur., Alyssa Osbourne

Electronic Theses and Dissertations

Based on the principles of cutting edge bone remodeling research, a unique therapeutic exercise device was designed specifically to improve bone quality at the most critical location of the proximal femur prone to fracture: the superior-lateral femoral neck where the fracture first initiates during a fall. The exercise/device is intended to work by inducing enough strain in the bone to stimulate the body’s natural bone remodeling mechanisms to increase bone density in the proximal femur and consequently prevent a fracture from arising if a fall to the side does occur.

In order to test the proposed exercise, experiments simulating the …

Custom Software For The 3d Printing Of Patient Specific Plate Bending Templates In Pelvic Fracture Repair., Gordon B Lents

Electronic Theses and Dissertations

The purpose of this work is to reduce the operative time and blood loss incurred during open reduction and internal fixation (ORIF) of traumatic pelvic injuries through the creation of patient specific bending templates for reconstruction plates. These templates are 3D printed in a resin capable of being sterilized and taken into the operating room so that bending may be performed by the surgeon before the patient is opened or by another team member in parallel with the surgeon.

A novel software extension was created in 3D modeling software to allow a surgeon to individually position screws on a pelvic …

Cumulative Trauma, Emotion Reactivity And Salivary Cytokine Response Following Acute Stress Among Healthy Women., Yvette Z. Szabo

Electronic Theses and Dissertations

This study furthers understanding of how trauma exposure may be connected to the development and maintenance of poor health by focusing on cytokines, tightly regulated proteins of the immune system. Cytokine responses to acute stress have been associated with the onset of poorer mental health in physically healthy women. The present study examined how two factors recently associated with cytokine reactivity –cumulative trauma and emotion reactivity– are associated with salivary cytokine reactivity among healthy women. Seventy-one women, screened to be physically and mentally healthy, completed a laboratory acute stress paradigm and self-report measures of state emotion and trauma exposure. Participants …

Attending To Systemic Racism : Advancing Public Health's Approach To Youth Violence Prevention., Billie Faith Castle

Electronic Theses and Dissertations

This dissertation examines how the field of public health addresses the impact of systemic racism on health and how that informs public health’s approach to youth violence prevention. Beginning with an overview of youth violence, it breaks down the concepts of race and racism and how they are addressed within the science. It also reviews concepts that contribute to risk and protective factors of youth violence. The dissertation is written from a Critical Race Theory approach, argues that the social environment contributes to why youth violence is pervasive in certain neighborhoods, and promotes action from a macro-level approach. Seven chapters …

Bdnf-Trkb Signaling Regulates Adult Taste Bud Innervation., Tao Tang

Electronic Theses and Dissertations

Taste receptor cells transduce stimuli transmitting information to gustatory neurons that carry it to the brain. They turn-over continuously in adulthood, and must be constantly reinnervated, making the maintenance of innervation to taste buds an active process mediated by many factors, including brain-derived neurotrophic factor (BDNF). Taste bud innervation (40%) is lost when Bdnf is removed during adulthood, but it is unclear why remaining fibers were not lost. We found that some gustatory nerve fibers remained because they lack the TrkB receptor 55% of TrkB-labeled fibers were lost and fibers without TrkB remained following adult Bdnf gene recombination. It is …

Using An Audience Response System To Calibrate Dental Faculty Assessing Student Clinical Competence., Sean A. Aiken

Electronic Theses and Dissertations

In order to best prepare students to become competent and confident practitioners in a clinical environment upon graduating dental school, it is imperative for them to receive consistent and productive feedback from the supervising faculty. Through academic engagement, and more specifically faculty calibration, it may be possible to eliminate the disconnect that sometimes exists between faculty expectations and terminology, and those of the students. In terms of definitions, academic engagement reflects faculty scholarly development activities that support integration of relevant, current theory of best practices consistent with the school's mission, expected learner outcomes, and supporting strategies.1-6, 32 The difficulty lies …

Neural Coding Of Natural And Synthetic Speech., Allison Brown

Electronic Theses and Dissertations

The present study examined whether natural and synthetic speech are differentially encoded in the auditory cortex. Auditory event-related potential (ERP) waveforms were elicited by natural and synthetic fricative-vowel stimuli (/sɑ/ and /ʃɑ/) in a passive listening paradigm in adult listeners with normal hearing. ERP response components were compared across conditions. The results indicated that peak latencies to natural speech were significantly earlier than those to synthetic speech. Natural speech also produced significant electrode hemisphere site effects, whereas synthetic speech activated left, midline, and right electrode hemisphere sites equally. Overall, the results suggest that cortical processing of natural and synthetic speech …

Treg Regulation In Periodontal Disease During Pregnancy., Aislinn Leah Hays

Electronic Theses and Dissertations

Background: Although pregnancy is prone to induce more severe periodontal inflammation and tissue damage, its mechanism remains elusive. Periodontal diseases during pregnancy are associated with adverse pregnancy outcomes including preterm birth or low birth weight. Animal models are ideal for investigating immunological mechanisms in periodontal disease. With a newly modified ligature-induced disease model, we managed to develop periodontal disease in pregnant mice and investigate the immunological mechanism of more severe symptoms during pregnancy. Hypothesis: We hypothesis that P. gingivalis infection during pregnancy will lead to a down-regulation of Treg cells, therefore causing increased inflammation and disease severity. Methods: A ligature-induced …

Exploring A Novel Nf-ĸb- Inhibiting Nanoparticle For Periodontitis Therapy., Kameswara Satya Srikanth Upadhyayula

Electronic Theses and Dissertations

Periodontitis is an infection-driven inflammatory disease characterized by gingival inflammation and bone loss. The NF-ĸB signaling pathway is pivotal in osteoclastogenesis and infection-induced pro-inflammatory responses. The use of nanoparticles as a vehicle to deliver drug increases stability, loading capacity, and facilitates transmembrane transportation. The hypothesis was that a novel nanoparticle carrying therapeutic NBD inhibitory peptides (NBD-nanoparticles) will inhibit measures of periodontal disease. In this project, we tested the nanoparticles for their ability to directly inhibit osteoclastogenesis and inflammation as an original strategy for periodontitis therapy. We also tested the capability of the nanoparticles to inhibit gingival inflammation and alveolar bone …