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Developing Novel And Effective Treatments For Pancreatic Ductal Adenocarcinoma, Aubrey Miller Jan 2018

Developing Novel And Effective Treatments For Pancreatic Ductal Adenocarcinoma, Aubrey Miller

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Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor with a 5-year survival rate of 8%. Over 80% of patients are diagnosed with locally advanced or metastatic disease and undergo systemic chemotherapy with gemcitabine. Virtually all patients develop gemcitabine-resistant disease and median survival for these patients is ~6 months. Thus, identification of novel molecular targets and pre-clinical evaluation of therapeutics is essential to improving patient outcome. The bromodomain and extraterminal domain (BET) proteins are important regulators of transcription and have recently become a potentially effective target to treat PDAC. We have shown that the BET inhibitor JQ1 suppressed PDAC tumor …


Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner Jan 2018

Novel Insights Into Neurofibromin Function And Human Neurofibromatosis Type 1 Mutations Using Genetically Engineered Mouse Models, Ashley Nicole Turner

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Loss of NF1 in different developmental and cellular contexts leads to unique physiological outcomes due to loss of neurofibromin function, including embryonic lethality, sporadic cancers, and the genetic disorder NF1. Neurofibromin acts as a tumor suppressor by modulation of RAS signaling, with other functions of this multi-domain protein being less clear. Even within the monogenic disorder of NF1, the clinical heterogeneity and mutational spectrum are immense, revealing the complexity underlying this disorder. There is a huge urgency and need for NF1 therapeutic treatments, and the same urgency to develop in vivo models to better understand NF1 that can be utilized …


Molecular Characterization Of The Rare Cftr Mutation P67l As A Model For Genotype-Specific Drug Development And Personalized Medicine In Cystic Fibrosis, Carleen Mae Pomperada Sabusap Jan 2018

Molecular Characterization Of The Rare Cftr Mutation P67l As A Model For Genotype-Specific Drug Development And Personalized Medicine In Cystic Fibrosis, Carleen Mae Pomperada Sabusap

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The traditional CFTR functional defect subcategories (i.e. protein misfolding, gating, conductance, etc.) are sometimes inadequate for determining patients most likely to benefit from emerging modulator treatment. We employ the P67L variant as emblematic of ways a thorough biochemical analysis of a rare CF defect can guide new therapeutic approaches, help predict drug response, and facilitate clinical precision. Historically, P67L has been designated a class IV conductance abnormality (i.e., malformed ion pore). In contrast, our studies demonstrate P67L disrupts CFTR protein maturation, prompts misfolding, causes gating defects, and exhibits wild-type like conductance. We show that P67L CFTR is robustly rescued by …


A Mixed Methods Study Evaluating A Pediatric To Adult Care Transition Program For Sickle Cell Disease, Ardie Vanessa Pack-Mabien Jan 2018

A Mixed Methods Study Evaluating A Pediatric To Adult Care Transition Program For Sickle Cell Disease, Ardie Vanessa Pack-Mabien

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A MIXED METHODS STUDY EVALUATING A PEDIATRIC TO ADULT CARE TRANSITION PROGRAM FOR SICKLE CELL DISEASE ARDIE VANESSA PACK-MABIEN SCHOOL OF NURSING ABSTRACT Sickle cell disease is a potentially life-threatening hereditary hematological disorder. Transition from pediatric to adult care is a challenging process for many adolescents and young adults with sickle cell disease. These challenges involve the adolescent, young adult, family caregiver, health care provider, and health care system. To address the challenges, a limited number of sickle cell centers have developed transition programs to facilitate the transition process. However, research on transition programs is sparse. To address this gap, …


The Oxidative Tyrosine Modification, O,O’-Dityrosine, In Lung Disease, Morgan Locy Jan 2018

The Oxidative Tyrosine Modification, O,O’-Dityrosine, In Lung Disease, Morgan Locy

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The oxidative tyrosine modification, o,o′-dityrosine, has been identified in various pathologic conditions associated with oxidative stress in mammalian systems, and demonstrated to be important in physiologic processes in invertebrate organisms. The formation of o,o’-dityrosine is catalyzed by a heme peroxidase (hPx) in the presence of hydrogen peroxide (H2O2). The understanding of this stable, covalent tyrosine modifica-tion in lung biology is limited. Oxidative stress has been implicated in the pathogenesis of various lung diseases, including interstitial lung disease (ILD) and cystic fibrosis (CF). We observed that the oxidative protein modification, o,o’-dityrosine, was markedly ele-vated in the circulating plasma of ILD patients …


Financial Distress – Causes And Consequences: An Examination Of The Nursing Home Industry, Justin Caleb Lord Jan 2018

Financial Distress – Causes And Consequences: An Examination Of The Nursing Home Industry, Justin Caleb Lord

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Nursing homes operate in a tumultuous and changing environment and are under increasing financial pressure, risk of closure, and financial distress. The issue of financial distress has been explored tangentially within the nursing home industry. This study is the first to validate the Altman Z-Score, a financial distress prediction model, within the nursing home context. The Altman Z-Score model uses multiple discriminate analysis (MDA) to examine multiple financial ratios (liquidity, efficiency, profitability and net worth) simultaneously to predict the likelihood of a firm’s financial distress. After calculating the Z-Score, clustering was used to classify the observations into three groups, distressed, …


Hiv Disclosure, Retention In Hiv Care, And Viral Load Suppression : A Study Among New To Hiv Care Patients, Riddhi Modi Jan 2018

Hiv Disclosure, Retention In Hiv Care, And Viral Load Suppression : A Study Among New To Hiv Care Patients, Riddhi Modi

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HIV remains a major ongoing public health problem globally and in the United States (US). Despite the advances in the antiretroviral therapy (ART), new HIV cases continue to occur. Hence, understanding the factors that influence patient’s decision to HIV treatment and prevention is of paramount. HIV disclosure, an important modifiable behavior, is a barrier to linkage and engagement in HIV care. Thus far, studies examining HIV disclosure and its impact on HIV related outcomes, retention in care (RIC) and viral load (VL) suppression among HIV patients newly initiating care are scant. While these studies provide insights on risk factors of …


Bone Marrow Transplantation In A Mouse Model Of Cooley’S Anemia, Jonathan Russell Lockhart Jan 2018

Bone Marrow Transplantation In A Mouse Model Of Cooley’S Anemia, Jonathan Russell Lockhart

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β-thalassemia is a group of inherited blood disorders that result in defects in β-globin chain production. Cooley’s anemia (CA), or β-thalassemia major, is the most severe form of the disease and occurs when an individual has mutations in both copies of the adult β-globin gene. Patients with CA fail to make adult hemoglobin, have ineffective erythropoiesis, suffer from severe anemia, and are transfusion dependent for life. Currently, allogeneic bone marrow transplantation (BMT) is the only cure; however, few patients have suitable donors for this procedure that carries a significant risk of morbidity and mortality. To develop new and safer alternatives …


Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb Jan 2018

Nf-Κb And Methyl-Lysine Signaling In The Epigenetic Regulation Of Memory, William Mitchell Webb

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Epigenetic mechanisms such as DNA methylation and histone methylation are critical regulators of gene transcription during memory consolidation and retrieval. However, the means by which these mechanisms are themselves initiated and directed to specific gene regions, and the extent to which these marks coordinate control of gene expression, remain poorly understood. In this dissertation, we explore the role of methyl-lysine signaling in the epigenetic regulation of gene expression in two contexts. First, we investigated the role of histone H3 lysine 4 tri-methylation (H3K4me3) and DNA 5-hydroxymethylation (5hmC) during memory retrieval, finding that these marks increased globally and at CpG-enriched coding …


Pharmacological Inhibition Of Thioredoxin-Interacting Protein To Protect Against Diabetes, Lance Thielen Jan 2018

Pharmacological Inhibition Of Thioredoxin-Interacting Protein To Protect Against Diabetes, Lance Thielen

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The loss of functional beta cell mass represents a major factor in the pathogenesis of type 1 and type 2 diabetes. Inadequate production of insulin, a glucose-lowering hormone, and elevated glucagon production, a gluconeogenic hormone, contribute to impaired glycemic control and hyperglycemia. This promotes a vicious cycle involving glucotoxicity and additional beta cell dysfunction. Currently there are no therapies that halt this process; however, thioredoxin-interacting protein (TXNIP) has recently emerged as a promising therapeutic target. TXNIP was found to be the top glucose-induced gene in a human pancreatic islet microarray, is increased in mouse models of diabetes and diabetic human …


Psychological Well-Being And Smoking Cessation, Christopher Thorne Jan 2018

Psychological Well-Being And Smoking Cessation, Christopher Thorne

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Introduction: The substantial death toll from smoking combined with the low success rates of current treatment approaches warrants further investigation into mechanisms that promote cessation. While the role of negative affect has been studied extensively in relationship to smoking cessation, the role of psychological well-being (PWB; e.g., life satisfaction, optimism, positive affect, purpose in life, resilience) has received little attention. Treatment outcomes might improve with a better understanding of PWB’s role in smoking cessation. Methods: Relationships between smoking and PWB were examined in three studies. First, using panel data from the biennial, longitudinal Health and Retirement Study, I developed separate …


Susceptibility To Late-Onset Sepsis Is Controlled By The Neonatal Microbiome And Intestinal Immune System, Jeffrey Robert Singer Jan 2018

Susceptibility To Late-Onset Sepsis Is Controlled By The Neonatal Microbiome And Intestinal Immune System, Jeffrey Robert Singer

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When mammals leave the womb, they encounter a world teeming with microbial life. Their intestinal tract, which will ultimately harbor an ecosystem of trillions of bacteria, must progress through a process called ecological succession. Late-onset sepsis (LOS) commonly occurs in preterm infants when pioneer members of the intestinal microbiome cause systemic infections. Both antibiotics and probiotics are used as prophylaxis for LOS, but mechanisms underlying susceptibility to the disease remain unclear. This is in large part due to a lack of animal models that mimic the relevant pathophysiology of LOS. This study begins with the development of a novel model …


Pathological Changes In Hippocampal Synaptic Transmission And Neuronal Function During Early Disease In The Novel Tgf344-Ad Rat Model, Lindsey Allyson Smith Jan 2018

Pathological Changes In Hippocampal Synaptic Transmission And Neuronal Function During Early Disease In The Novel Tgf344-Ad Rat Model, Lindsey Allyson Smith

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Alzheimer’s disease (AD) is the leading cause of dementia in those 65 years and older and the 6th leading cause of death in the United Sates. Current treatments only target symptoms of the disease and cannot slow or halt disease progression. The novel and comprehensive TgF344-AD rodent model may bridge the translational gap previous animal models have failed to traverse by providing the platform to probe pre-lesion synapse dysfunction, which is thought to result primarily from increased levels of toxic soluble amyloid beta and hyperphosphorylated tau. The most recently developed model, the TgF344-AD rat was created in 2013 by insertion …


The Influence Of Perceived Stress And Sleep Disturbance On Fatigue And Blood Pressure As Mediated By Cortisol In Children With Sickle Cell Disease, Heather Carol Soistmann Jan 2018

The Influence Of Perceived Stress And Sleep Disturbance On Fatigue And Blood Pressure As Mediated By Cortisol In Children With Sickle Cell Disease, Heather Carol Soistmann

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ABSTRACT Introduction: Life expectancy is improving for those with sickle cell disease (SCD); however, with this improvement come increasing risks for long-term health complications. Early identification of health concerns could lead to improved long-term health outcomes. Two health concerns in school-age children with SCD are fatigue and blood pressure (BP). Previous research with other populations indicates perceived stress and sleep disturbance may influence outcomes of fatigue and BP. Further, cortisol, a stress hormone, may mediate the proposed relationships. Therefore, the purpose of the study was to determine effect sizes of relationships between fatigue, BP, perceived stress, and sleep disturbance in …


The Role Of Pim Kinases In Hepatoblastoma Tumorigenicity, Stem Cell-Like Cancer Cell Maintenance, And Chemoresistance, Laura Lee Stafman Jan 2018

The Role Of Pim Kinases In Hepatoblastoma Tumorigenicity, Stem Cell-Like Cancer Cell Maintenance, And Chemoresistance, Laura Lee Stafman

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Hepatoblastoma is the most common primary liver malignancy in children. Despite increasing incidence, treatment has not changed significantly in the past 20 years, making the need for novel therapeutics imperative. Proviral Integration site for Moloney murine leukemia virus (PIM) kinases are a family of serine/threonine kinases that have been implicated in multiple other cancer types including the adult liver cancer, hepatocellular carcinoma. Emerging evidence has begun to elucidate a role for PIM kinases in stem-cell like cancer cells (SCLCCs). This subpopulation of cells is thought tobe responsible for tumor maintenance, recurrence, metastasis, and chemoresistance. Chemoresistance is a significant barrier to …


Protein O-Glcnacylation In Hippocampal Hyperexcitability & Gabaergic Neurotransmission, Luke Thomas Stewart Jan 2018

Protein O-Glcnacylation In Hippocampal Hyperexcitability & Gabaergic Neurotransmission, Luke Thomas Stewart

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Plasticity at central synapses is a vital component of neuronal function and an intensively studied phenomenon thought to underlie learning and memory processes in brain structures including the hippocampus and cerebral cortex. A principle mechanism at work during long-term plasticity is the rapid and heavily regulated post-translational modification of synaptic proteins such as phosphorylation and ubiquitination. A comparatively understudied modification is ‘O-GlcNAcylation’, a distinct form of monoglycosylation with rapid intracellular signaling capacity as opposed to the structural and extracellular signaling roles of O- and N-linked polysaccharide chains on conventionally glycosylated proteins. O-GlcNAcylated proteins are found in every cell type/tissue system …


The Role Of Glycosylation Initiation By Galnac-Ts In Iga Nephropathy, Tyler Stewart Jan 2018

The Role Of Glycosylation Initiation By Galnac-Ts In Iga Nephropathy, Tyler Stewart

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The autoimmune disease IgA nephropathy (IgAN) is a common cause of primary glo-merulonephritis, often resulting in end-stage renal disease. IgAN patients have elevated serum levels of immunoglobulin A1 (IgA1) with autoantigenic galactose-deficient (gd) O-glycans. The gd-O-glycans occur at specific sites within IgA1 hinge-region. We hy-pothesized that GalNAc-Ts play a role in the formation of gd-IgA1, due to their role in determining glycosylation sites and densities. To better understand how GalNAc-Ts may change O-glycans of IgA1 in IgAN we characterized the complex glycosylation mecha-nism involved in mucin-type O-glycan synthesis of IgA1 hinge-region. In the first section of this work, we explore …


Membrane Capacitance Derived From Bioimpedance Spectroscopy Is Associated With Insulin Resistance In Relatively Healthy U.S. Women, But Not Men, Valene Garr Barry Jan 2018

Membrane Capacitance Derived From Bioimpedance Spectroscopy Is Associated With Insulin Resistance In Relatively Healthy U.S. Women, But Not Men, Valene Garr Barry

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Current screening methods have failed to detect more than 50% of the 120 million U.S. adults with insulin resistance and/or metabolic syndrome, conditions that substantially increase one’s risk for cardiometabolic disease (CMD).1 Evidence exists that metabolic health is associated with cell membrane composition, which is reflected in the electrical properties of the body cell mass. The objective of this study was to determine whether bioimpedance spectroscopy can identify insulin resistance and/or metabolic syndrome by evaluating membrane capacitance (CM). We hypothesized that CM would be higher in individuals with insulin resistance and/or metabolic syndrome when compared to healthy individuals. This cross-sectional …


Endodontic Post Retention With Resin Cements (Ilumi Fiber Post), Faimeena Farheen Jan 2018

Endodontic Post Retention With Resin Cements (Ilumi Fiber Post), Faimeena Farheen

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Objectives: Loss of post retention is the leading cause in the cemented post. There is no good method of bonding a fiber post in a post space with resin cements because adhesive cementation into a prepared post space is difficult- due to an inability to place, dry and light cure the adhesive and the cement. A new post system (iLumi) that transmits light to the apex of the post has recently been developed. We want to know if this system will improve post retention in each section (coronal, middle and apical) of the prepared post space and if this curing …


Simulation Of Correlated Variables, Mixture Distributions, And Repeated Measures And Comparison Of Pharmacogenetic Prediction With Machine Learning Methods, Allison Cynthia Fialkowski Jan 2018

Simulation Of Correlated Variables, Mixture Distributions, And Repeated Measures And Comparison Of Pharmacogenetic Prediction With Machine Learning Methods, Allison Cynthia Fialkowski

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Pharmacogenetics aims to improve individualized medicine by combining genetic information with clinical data when assigning drug treatments. Different diseases are often associated with different factors, each with its own distributional characteristics. For rare or complex diseases, these characteristics may not be well understood and standard analysis methods may not be appropriate. In psychiatric disorders, for example, multiple drug treatments need to be compared across small sample sizes with heterogeneous patient populations, making implementation of standard methods difficult. Simulating data that mirrors clinical data is important because it allows investigators to determine which method is best suited for data from their …


Novel Mediators Of The Blood Pressure Response To Acute Psychosocial Stress In Health And Disease, Brandon Fox Jan 2018

Novel Mediators Of The Blood Pressure Response To Acute Psychosocial Stress In Health And Disease, Brandon Fox

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Psychosocial stress occurs in response to threatening or uncertainty-provoking stimuli and triggers a complex physiological reaction that facilitates survival and adaptation. In the cardiovascular system, acute psychosocial stress elicits a rapid increase in blood pressure, and importantly, cumulative exposure to psychosocial stress is a risk factor for cardiovascular disease. The present studies examined the impact of psychosocial stress on the cardiovascular system in both health and disease. Circulating endothelin-1 (ET-1) levels are induced by psychosocial stress. We hypothesized that endothelium-derived ET-1 contributes to the pressor response to stress via activation of the endothelin A (ETA) receptor. Vascular endothelium-specific ET-1 knockout …


Elevated Blood Lead Levels, Cancer Incidence, And All-Cause Mortality In Adults, Sherri L. Davidson Jan 2018

Elevated Blood Lead Levels, Cancer Incidence, And All-Cause Mortality In Adults, Sherri L. Davidson

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Epidemiologic studies have indicated an association between lead exposure and cancer. Although lead exposure has declined in recent decades, from removal of lead in gasoline and paint, lead exposure remains a health concern from environmental and occupational sources including aging water systems. In a retrospective cohort study, Adult Blood Lead Epidemiology and Surveillance (ABLES) records in Alabama were linked to cancer incidence data in the Alabama Statewide Cancer Registry and mortality data from the Alabama Center for Health Statistics, using a probabilistic linkage program. Blood lead level (BLL) measurements were used to categorize exposure levels. Odds ratios approximated relative risks. …


Examining The Relationship Between Operational And Clinical Performances Of Federally Qualified Community Health Centers, Ganisher K. Davlyatov Jan 2018

Examining The Relationship Between Operational And Clinical Performances Of Federally Qualified Community Health Centers, Ganisher K. Davlyatov

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This dissertation studied the role of Health Information Technology (HIT) adoption on clinical performance; the effects of clinical performance on chief executive officer (CEO) compensation; and the association between CHC’s financial and clinical performances in Community Health Centers (CHC). Data from the Uniform Data System (UDS) and the Internal Revenue System (IRS) 990 Forms were extracted for the period 2011-2016. Generalized estimating equations models with state and year fixed effects were performed. To test the relationship between the age and extent of HIT adoption and clinical performance, Resource-Based View of the Firm constructs were used. The age of HIT adoption …


Effects Of Dietary R,S-1,3 Butanediol Diacetoacetate On Components Of Energy Balance, Rachel A H Davis Jan 2018

Effects Of Dietary R,S-1,3 Butanediol Diacetoacetate On Components Of Energy Balance, Rachel A H Davis

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Ketogenic diet (KD) has been used to attenuate the decline in energy expenditure occurring from calorie restriction-induced weight loss, but long-term adherence can be difficult due to the strict nature of the diet. The growing body of evidence supporting KD-treatment of neurologic and metabolic diseases, as well as obesity, has prompted interest in the ability to increase circulating ketones via exogenous delivery. Ketone esters (KE) can raise blood ketone concentrations similarly to fasting and appear to reduce food intake acutely, but studies assessing effects on energy balance are limited and provide a potentially promising direction for weight control. Previous investigations …


Functional Analysis Of Cdc45 In The Replication Fork And In Response To Replicative Stress, Amanda Debrot Jan 2018

Functional Analysis Of Cdc45 In The Replication Fork And In Response To Replicative Stress, Amanda Debrot

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DNA replication is a highly conserved and tightly regulated process, with a variety of factors acting to ensure faithful duplication and stability of chromosomal DNA. During replication, positive supercoils form ahead of the advancing replication fork. DNA topoisomerase 1 (Top1) acts to prevent DNA damage by relieving the torsional strain created by these supercoils. The camptothecin (CPT) class of chemotherapeutics target Top1, creating a long-lived DNA-Top1-CPT covalent complex, which leads to S-phase specific DNA lesions and cellular death. Our lab previously performed a genetic screen to isolate mutant proteins that enhance cell sensitivity to Top1-mediated DNA damage. One of the …


The Association Between Designation As Leader In Lgbt Healthcare Equality And Hospitals' Patient Experience Scores, Rita Dileo Jan 2018

The Association Between Designation As Leader In Lgbt Healthcare Equality And Hospitals' Patient Experience Scores, Rita Dileo

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ABSTRACT There are an increasing number of LGBT individuals who openly acknowledge their sexuality and are visibly part of society. Unfortunately, a stigma remains among this group and a fear of discrimination that prevents many individuals from seeking healthcare. This is a long-standing issue and further challenged by lack of culturally competent LGBT healthcare providers. Using a conceptual framework based on the Resource Dependence and Resource-Based theories, the association between designation as a 2016 Leader in LGBT Healthcare Equality and patient experience scores are evaluated. Regression analyses were performed to assess the association between market factors, organizational characteristics, HCAHPS survey …


The Effect Of Mitochondrial-Derived Ros On Calcium Handling And Cardiac Function In Heart, Kah Yong Goh Jan 2018

The Effect Of Mitochondrial-Derived Ros On Calcium Handling And Cardiac Function In Heart, Kah Yong Goh

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Mitochondria are abundantly present in metabolic active organs such as the heart. The presence of mitochondria are crucial to provide energy in the form of ATP, regulate calcium handling, facilitate cell fate, and are involved in metabolic modulation. In the process of generating ATP through oxidative phosphorylation, mitochondria produce reactive oxygen species (ROS) as a side product. In the heart, mitochondria is a major source of ROS. Under normal conditions, ROS are kept at a physiologically relevant and healthy level. Unfortunately, excessive ROS levels during pathological states, such as pressure overload heart failure, appears as a threat to the whole …


African American Caregivers’ Decision To Use Hospice Services For A Loved One: A Grounded Theory Study, Paula M. Gordon Jan 2018

African American Caregivers’ Decision To Use Hospice Services For A Loved One: A Grounded Theory Study, Paula M. Gordon

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This qualitative grounded theory study explored the process of decision making for African American family caregivers in the southeastern United States, as they make hospice decisions for their loved ones, Although hospice use in the United States has grown over the last decade, a disparity continues to exist between African American and Caucasian populations. African Americans represent a small percentage of hospice users in the United States, despite research that has found that patients who use hospice experience improved symptom control, fewer unmet needs, and better end of life care. Research has identified many reasons for this disparity; however, little …


Interactions Between Posture And Locomotion In Nonimpaired And Poststroke Walking, Sarah Anne Graham Jan 2018

Interactions Between Posture And Locomotion In Nonimpaired And Poststroke Walking, Sarah Anne Graham

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Background: Inappropriate paretic-limb force generation is a hallmark of impaired walking function poststroke. In addition to weakness, the paretic limb misdirects foot forces during stance, which may be due to inappropriate postural influence over weakened locomotor control. Purpose: Investigate neural control interactions between posture and locomotor functions by manipulating postural influence during walking of nonimpaired and individuals poststroke. I present four studies investigating measures associated with locomotor function and foot-force direction under varying postural demands during walking. Methods: Study 1 compared comfortable walking speed (CWS) outcomes following two body-weight-support (BWS) training protocols for N=29 participants with chronic (≥5 months) poststroke …


Risk Factors Associated With Multiple Myeloma, Stephen Gragg Jan 2018

Risk Factors Associated With Multiple Myeloma, Stephen Gragg

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Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cells accumulate in the bone marrow, leading to the formation of lytic bone lesions, hypercalcemia, anemia, renal insufficiency, and immunosuppression. It develops from a pre-malignant condition known as monoclonal gammopathy of undetermined significance (MGUS), which is prevalent in up to 3% of White populations over the age of 50 years, and twice that in Black populations. Although much progress has been made toward understanding the large scale genomic aberrations that facilitate the formation of MGUS clones and the various copy-number variations and mutations that trigger the development of MM, …