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Articles 158521 - 158550 of 325135

Full-Text Articles in Medicine and Health Sciences

Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood Jan 2020

Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood

All ETDs from UAB

Alpha-synuclein (αsyn) is the key component of proteinaceous aggregates termed Lewy Bodies (LBs) that pathologically define a group of disorders known as synucleinopathies, including Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn is thought to misfold and spread throughout the brain in a prion-like fashion. Transmission of αsyn necessitates the release of misfolded αsyn from one cell and the uptake of that αsyn by another, in which it templates the misfolding of endogenous αsyn. Identifying regulators of this process is essential to understanding how αsyn propagates and furthers disease progression. In this study, we investigated Rab27 and 14-3-3θ …

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Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk Jan 2020

Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk

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Alzheimer’s disease (AD) is the leading neurodegenerative disorder that affects an astonishing 5.8 million Americans, a number projected to reach 14 million by the year 2050. While only about 1% of all AD cases are caused by mutations in APP, PSEN1, and PSEN2, the cause of sporadic AD remains unknown. Variations in several risk genes have been proposed to contribute to the development of sporadic AD cases. Since, currently, there are no disease-modifying therapies for families affected by AD and multiple anti-amyloid-beta therapies failed in clinical trials, determining how these risk genes contribute to the development of AD is crucial …

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The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman Jan 2020

The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman

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Differentiation of pre-osteoblasts is critical to controlling in-vivo development and growth of bone. Recent studies highlight the importance of epigenetic regulation in directing osteoblast commitment and function. Here we show that the microRNA-23a cluster (miR-23a, 27a, and 24-2) controls bone mass in-vivo through a previously unknown epigenetic mechanism. MiR-23a cluster knockdown increased the intensity of Alkaline Phosphatase staining in MC3T3-E1 cells. Additionally, it upregulated mRNA expression of osteogenic marker genes such as Runx2 and Osteocalcin. Micro-CT analysis of 2-month and 6-month femurs showed that trabecular bone volume and trabecular number significantly increased in miR-23aClZIP mice as compared to controls. Histological …

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Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen Jan 2020

Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen

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GENE–ENVIRONMENT INTERACTION IN PARKINSON DISEASE: THE GUT MICROBIOME ZACHARY D. WALLEN GENETICS, GENOMICS, AND BIOINFORMATICS ABSTRACTParkinson disease (PD) is a progressive neurodegenerative disease with no cure. Majority of cases are idiopathic, and the cause is unknown. Studies have been conducted in human and animals to identify PD risk factors, resulting in a list of genetic and environmental factors that modestly increases risk of PD. Still, no individual risk factor fully explains the cause of PD, and neither has the combination of these factors. Additional avenues of research are being investigated to find potential triggers of PD, and factors that might …

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T Cells In Synucleinopathies, Gregory Paul Williams Jan 2020

T Cells In Synucleinopathies, Gregory Paul Williams

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Synucleinopathies, which include Parkinson disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA), are a collection of neurodegenerative diseases that are in major part defined by the presence of alpha-synuclein (α-syn) rich protein aggregates in the brain. Increasing evidence has highlighted a neuroinflammatory phenotype also associated with these synucleinopathies. This neuroinflammatory phenotype includes the activation of central nervous system (CNS) microglia, increased pro-inflammatory cytokines, and the infiltration of peripheral T cells into the CNS. We sought to further explore the T cell responses associated with PD and MSA. Using two preclinical mouse models of PD and MSA, …

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Race, Type Ii Diabetes Mellitus And Vertebral Fragility Fractures: A Cross-Sectional Analysis From Nhanes, Yuchen At Xiao Jan 2020

Race, Type Ii Diabetes Mellitus And Vertebral Fragility Fractures: A Cross-Sectional Analysis From Nhanes, Yuchen At Xiao

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IntroductionThis study examined the association between race and bone health, and if T2DM modifies this association in a diverse sample of adults. Methods We conducted a cross-sectional study using the 2013-2014 National Health and Nutrition Examine Survey (NHANES) data. Bone health outcomes included lumbar spine BMD (lowered BMD based on T-scores <-1), and vertebral deformities, assessed via vertebral fracture assessment (VFA), including presence, number of deformities, and severity ratio of deformities. T2DM status and other demographic, lifestyle, and health characteristics were self-reported via questionnaire data. To assess if T2DM modifies the association between race and bone health outcomes, we conducted stratified analyses using logistic regression for dichotomous outcomes, Poison regression for count outcomes, and linear regression for continuous outcomes. Results Non-Hispanic (NH) Blacks have significantly less odds of being lowered BMD and osteoporosis comparing to NH-Whites in the crude model and significantly less odds of having vertebral deformities comparing to NH-White in both crude and adjusted model for non-diabetic participants. Such differences are not observed in diabetic groups. Participants in Other race group have significantly more odds of being lowered BMD comparing to NH-Whites in the adjusted model for both diabetic and non-diabetic groups. And have significantly more odds of having vertebral deformities in the diabetic group, crude and adjusted, yet the differences are not significant in non-diabetic groups. Similar results were seen in the number of deformities and total bone loss ratio. The potential modification effect of T2DM was not significant in these models. Conclusions In our national evaluation, bone health differs not only by race and ethnic group but also by T2DM status. The protective vertebral fragility effects observed among NH-Blacks was no longer present among those with diabetes. Likewise, among participants in other racial and ethnic groups, T2DM seemed to magnify the association of worse vertebral fragility. Such trends indicate a potential modifying effect of participants’ T2DM status and should be noted clinically, yet more studies are required for more precise results.

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The Role Of The Viral Envelope Protein Gpul132 In Assembly Compartment Formation And Virion Production: Intracellular Lipids And/Or Cholesterol, Hui Wu Jan 2020

The Role Of The Viral Envelope Protein Gpul132 In Assembly Compartment Formation And Virion Production: Intracellular Lipids And/Or Cholesterol, Hui Wu

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Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects over 50% of the world’s population. HCMV infection is asymptomatic in healthy individuals, however can cause severe morbidity and mortality in individuals with compromised innate or adaptive immunity. As a complex virus that has been known for about 70 years, we are still in search of vaccines or effective treatments against it. HCMV genome encodes over 175 open reading frames with the function of majority proteins remains to be defined. A unique feature of HCMV among herpesvirus is the reorganization of cellular secretory pathway and membranes to form assembly compartment (AC). …

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Co-Factors In Fgf Signaling, Christopher Yanucil Jan 2020

Co-Factors In Fgf Signaling, Christopher Yanucil

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The fibroblast growth factor (FGF) family consists of a group of proteins whose diverse biological functions are mediated by receptor tyrosine kinases, termed FGF receptors (FGFR) 1-4. While paracrine FGFs require heparin sulfate as a co-factor for FGFR bind-ing and signaling, it has been assumed that endocrine FGFs, such as FGF23, do not bind heparin but instead require klotho, a family of transmembrane proteins, as a co-receptor on specific target cells. FGF23 acts as bone-derived hormone that targets tubular epitheli-al cells in the kidney via FGFR1 and α-klotho to reduce renal phosphate uptake. In chron-ic kidney disease (CKD), the kidney …

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Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue Jan 2020

Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue

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With rapidly increasing novel discoveries of associations between genomic data and complex disease phenotypes, the translation of those associations into knowledge and the identification of critical molecular mechanisms are essential to guild clinical decisions such as the diagnosis of symptomatic individuals, the prediction of disease risk, reproductive genetic counseling, and determining pharmacogenetic profiles for treatment. To decipher the genome of complex diseases, gene-centric analyses focus on detecting molecular mechanisms lead by driver genetics variants, abnormally expressed genes and high-abundance proteins through gene module construction. Additionally, the gene module construction approaches implement systems biology analysis to reveal the causative co-expressed gene …

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Exploring The Mechanism Of Cleavage And Secretion Of The Major Sperm Protein (Msp) Domain Of The Vapb/Vpr-1 Protein, Hala Zein-Sabatto Jan 2020

Exploring The Mechanism Of Cleavage And Secretion Of The Major Sperm Protein (Msp) Domain Of The Vapb/Vpr-1 Protein, Hala Zein-Sabatto

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VAPB is one of three mammalian VAP proteins. It is a type-II ER transmembrane protein whose N-terminal major sperm protein domain (MSPd) is cleaved and secreted. Since the MSPd faces the cytosol, rather than the ER lumen, how it is cleaved and secreted is not yet known. In humans, P56S is a substitution mutation within the VAPB protein that segregates with cases of familial Amyotrophic Lateral Sclerosis (ALS) and prevents the secretion of VAPB MSPd. The work described in this thesis uses C. elegans to study how the N-terminal MSPd of VAPB is proteolytically processed, secreted, and regulated. C. elegans …

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Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang Jan 2020

Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang

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Many physiological processes, including blood pressure (BP) regulation, follow specific rhythms tied to a 24-h cycle. This is largely because circadian genes operate in virtually every cell type in the body. In healthy individuals, BP during nighttime is 10-20% lower compared to daytime, a phenomenon known as “nocturnal dipping”. It is acknowledged that the dipping of BP is essential in maintaining normal cardiovascular and renal function. However, it remains unclear as to what factors contribute to nocturnal dipping. The purpose of this dissertation is to elucidate mechanisms underlying the circadian rhythm of BP. Bmal1 is one of the core circadian …

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Development Of Natural Language Processing Algorithm For Dental Charting, Yi-Fan Zhang Jan 2020

Development Of Natural Language Processing Algorithm For Dental Charting, Yi-Fan Zhang

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Purpose: The purpose was to develop a natural language processing algorithm, which will input data from oral examination transcripts to a structured database. Methods: Four case vignettes were produced for primary, mixed, and permanent dentition patients with varying degree of soft tissue pathology, caries, existing restorations and occlusion relationships. After calibration, dental students were instructed to perform simulated oral examinations based on the case vignettes, using natural language as they would to an assistant who was charting the case. The investigator transcribed the audio recordings of the simulated oral exams. Twenty simulated oral examinations were collected to develop a natural …

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Toward The Mechanism Underlying Latanoprost- And Benzalkonium Chloride-Induced Meibomian Gland Dysfunction In Patients Treated For Glaucoma, Jillian Ziemanski Jan 2020

Toward The Mechanism Underlying Latanoprost- And Benzalkonium Chloride-Induced Meibomian Gland Dysfunction In Patients Treated For Glaucoma, Jillian Ziemanski

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Once thought to be no more than a vexing eye condition, ocular surface disease (OSD) is now being viewed as a differentiating factor between sight and no sight. In the setting of glaucoma, OSD can interfere with treatment success, potentially allowing the visually devastating pathology of glaucoma to plow onward with little restraint. Compounding the clinical challenge is the growing awareness that glaucoma-associated OSD appears to be iatrogenically induced by topical ophthalmic medications. Daily, topical instillation of preserved prostaglandin analogs (PGAs), the most common first-line treatment for glaucoma, has been linked to a variety of OSD subtypes, including meibomian gland …

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Dietary Nitrate And The Oral Microbiome In Obesity, Health And Exercise, Christian E. Behrens Jan 2020

Dietary Nitrate And The Oral Microbiome In Obesity, Health And Exercise, Christian E. Behrens

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Obesity ranks among the top growing health concerns worldwide. The prevalence of obesity at all life stages continues to rise with nearly 40% of adults and 35% of children/adolescents being affected. Equally troublesome is the increased risk for a number of comorbidities associated with obesity including cardiovascular disease, stroke, type 2 diabetes mellitus, and certain types of cancer. The successful treatment of obesity, particularly long-term, continues to prove challenging and is often met with limited success. This highlights the importance of continued investigation into alternative strategies that may reduce the incidence and severity of obesity and associated pathophysiologies. Regular physical …

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Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea Jan 2020

Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea

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The Ldb1:Isl1 LIM transcriptional complex is critical for endocrine pancreas development as well as b-cell terminal differentiation. These complexes have been shown to interact with various proteins to elicit transcriptional regulation in other tissues, yet few interactors have been identified in b-cells. Therefore, the objective of this dissertation was to identify interactors of Ldb1 and Isl1 and assess their contributions to endocrine pancreas development and function. Using a reversible crosslink immunoprecipitation (ReCLIP) and mass spectrometry (MS) strategy to isolate endogenous Ldb1 and/or Isl1 interacting protiens, SSBP3, Rnf20, and Rnf40 (E3 ubiquitin ligases) coregulators were identified. SSBP3 was found to interact …

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Transcriptional, Translational, And Enzymatic Metabolic Regulation By L-2 Hyroxyglutarate, Garrett Brinkley Jan 2020

Transcriptional, Translational, And Enzymatic Metabolic Regulation By L-2 Hyroxyglutarate, Garrett Brinkley

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Recent studies have identified elevated levels of a small metabolite, L-2 Hydroxyglutare (L-2HG), which curiously has no known metabolic roles. Renal tumors, hypoxia as well as larval development, specifically in Drosophila, all have been identified to have high levels of L-2HG. These broad categories suggest L-2HG has a physiological role. This work uncovers the impact of elevated levels of L-2HG in altering normal kidney and renal tumors. With structural similarity to α-Ketoglutarate (αKG), L-2HG acts as a competitive inhibitor to enzymes that utilize αKG as substrates or co-factors. L-2HG is known to be metabolized by L-2HG dehydrogenase (L2HGDH). Loss of …

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Epigenetic Regulation In Cancer And Development, Theodore Busby Jan 2020

Epigenetic Regulation In Cancer And Development, Theodore Busby

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Feedback loops between cellular cues and changes in gene expression mediate the interactions between a multitude of regulatory events that promote development and cancer. Vesicular trafficking is an important process in carrying out signaling events by transporting receptors and ligands to and from the cell surface. GBF1 and BIG1 are large guanine-exchange factors (GEFs) that activate GTPase mediated shuttling of cargo through the Golgi apparatus. This dissertation demonstrates that GBF1 localizes to the cytoplasmic membrane in glioblastoma multiform cells to maintain cell shape and promote migration. Reports have shown that BIG1translocates to the nucleus is hepatocyte carcinoma cell lines in …

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Restless Legs Syndrome And Multiple Sclerosis: The Possible Role Of Physical Activity For Managing Symptoms, Katie Cederberg Jan 2020

Restless Legs Syndrome And Multiple Sclerosis: The Possible Role Of Physical Activity For Managing Symptoms, Katie Cederberg

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Restless legs syndrome (RLS) is an idiopathic neurological disorder characterized by unpleasant sensations in the legs that affects 26% of persons with multiple sclerosis (MS). The current pharmacological treatments for RLS are associated with a number of side effects, including the worsening of symptoms (i.e., augmentation). Physical activity represents a promising, behavioral approach for managing symptoms of RLS in MS. To date, physical activity has demonstrated tremendous benefits for managing many consequences of MS, but there is no evidence on its efficacy for managing RLS in MS. This dissertation described the current literature regarding physical activity and RLS in adults …

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Abnormalities In The Akt-Mtor Signaling Pathway In The Dorsolateral Prefrontal Cortex In Schizophrenia, Radhika Chadha Jan 2020

Abnormalities In The Akt-Mtor Signaling Pathway In The Dorsolateral Prefrontal Cortex In Schizophrenia, Radhika Chadha

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Schizophrenia (SZ) is a complex and heterogeneous mental illness in which myriad changes across multiple neurotransmitter systems (dopamine, serotonin, GABA, glutamate, and others) have been reported. Numerous regulatory mechanisms have been explored in SZ research and rather than being a disorder of one specific neurotransmitter pathway, SZ may instead be a disturbance of intracellular signaling processes that underlie the regulation of these systems. The AKT-mTOR signaling cascade plays an important role in core cellular processes of cell growth, metabolism and survival and is one such potential candidate. Abnormalities in AKT expression and activity have been consistently implicated in SZ pathophysiology …

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Understanding Adolescent Sexual Health Through Exploration Of Their Perceptions, Behaviors, And Beliefs, Jessica L. Corcoran Jan 2020

Understanding Adolescent Sexual Health Through Exploration Of Their Perceptions, Behaviors, And Beliefs, Jessica L. Corcoran

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Adolescents in the United States disproportionately experience adverse sexual health outcomes compared to adolescents in other developed countries. The purpose of this dissertation is to provide an in-depth examination of adolescent sexual health through the generation of three manuscripts. The first manuscript will provide an integrative review of adolescents’ perceptions of sexual health education programs. The second manuscript will illuminate the five-year trends in adolescent chlamydia rates by region, race, and sex. The third manuscript will provide a qualitative analysis from interviews with African American adolescent females in the southern U.S. Manuscript one reviewed studies from 2008 to 2019. The …

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Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo Jan 2020

Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo

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Genomic enhancers are cis-regulatory elements in the DNA that exhibit spatial and temporal control over intricate gene expression programs shaping fate and function of heterogeneous cell populations in the developing and adult brain. In addition to their role in cellular development and maintenance, enhancer activity drives transcriptional changes in response to stimulation. Active enhancers are subject to bidirectional transcription that yields non-coding enhancer RNAs (eR-NAs). However, the functional role of eRNAs in transcriptional regulation remains controversial. Therefore, we used primary neuronal cultures to investigate en-hancers and eRNAs in the rat genome. We identified and verified enhancer-gene pairs, characterized their response …

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Disparities In End-Of-Life Care In Children Dying Of Cancer In Alabama: A Cross Sectional Study, Elizabeth Statham Davis Jan 2020

Disparities In End-Of-Life Care In Children Dying Of Cancer In Alabama: A Cross Sectional Study, Elizabeth Statham Davis

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Regional studies show that children dying of cancer receive medically intense end-of-life care but there is limited information about end-of-life care in the Deep South and limited information about hospice and palliative care involvement at EOL. We conducted a retrospective electronic medical record review of children (0-x years) that died of cancer between 2010-20199 who received cancer directed therapy at Children’s of Alabama. We collected patient clinical and sociodemographics factors, including sex, race, and area deprivation index, cancer diagnosis and treatment, palliative care and hospice involvement, location of death, and medical care in the last 30d of life, including chemotherapy …

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Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis Jan 2020

Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis

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Circadian rhythms are biological processes that cycle every ~24 hours and have allowed life to adapt for optimal function across the day. These rhythms are present in all tissues in the body and are coordinated to the light/dark cycle by the suprachiasmatic nucleus (SCN) in the hypothalamus. Along with active-rest cycles, cognitive performance fluctuates across the course of the day, peaking during the active phase. In addition to the light cycle, food and meal timing can provide signaling cues to extra-SCN tissues. Food access only during the inactive phase results in weight gain and memory impairment. High fat diet protocols …

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Obesity-Induced Immune Dysfunction: Implications For Anti- Tumor Immunity And Immunotherapeutic Efficacy, Justin Tyler Gibson Jan 2020

Obesity-Induced Immune Dysfunction: Implications For Anti- Tumor Immunity And Immunotherapeutic Efficacy, Justin Tyler Gibson

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In the US, nearly 40% of adults have obesity. Further, obesity is known toincrease the risk for development, recurrence, and mortality associated with multiple types of cancer. However, despite such high prevalence, the impact of excess body weight on anti-tumor immunity and response to immunotherapeutics remains poorly and incompletely understood. In order to address these deficiencies, we have utilized multiple approaches to study obesity-associated perturbations in the immunogenetic, soluble protein, and cellular profiles of mice bearing mammary tumors and treatment naive human subjects with clear cell renal cell carcinoma (ccRCC). In a pre-clinical murine model of breast cancer, we find …

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Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould Jan 2020

Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould

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Vesicular stomatitis virus (VSV) is a member of the order Mononegavirales, which is comprised of viruses with genomes of non-segmented negative sense RNA. Many fundamental insights into the molecular biology of mononegaviruses were first made in VSV, such as the unique viral RNA synthesis template comprised of the nucleocapsid (N) protein and genomic RNA and the distinctive large (L) protein which contributes all enzymatic activities of RNA synthesis and transcript maturation. The L protein performs its enzymatic functions in concert with the phosphoprotein (P), a flexible, charged, and phosphorylated cofactor. The goal of the research presented in this dissertation was …

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Mechanisms Of Virtual Reality To Improve Walking And Reaching Behavior In Individuals With Chronic Low Back Pain, Rebecca Hennessy Jan 2020

Mechanisms Of Virtual Reality To Improve Walking And Reaching Behavior In Individuals With Chronic Low Back Pain, Rebecca Hennessy

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Chronic low back pain (cLBP), low back pain persisting longer than three to six months, is a prevalent condition that can greatly interfere with movement quality. Specifically, cLBP can result in slower walking speeds and negatively affect reaching movements. Virtual reality (VR) encompasses a variety of technologies which may potentially improve therapeutic interventions for individuals with cLBP by presenting users with fun, distracting, and engaging challenges that align with their rehabilitative goals. While VR systems have become more accessible to everyday users, there is limited research which specifically examines VR mechanisms to improve walking and reaching quality. This dissertation presents …

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Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong Jan 2020

Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong

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IL-23 promotes autoimmune disease, including Th17 CD4 T-cell development and autoantibody (autoAb) production. Here, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19−/−) mouse leads to a shift of the follicular T-helper cell program from Tfh-IL-17 to Tfh-IFN-ɣ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19−/− mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that while Ifngr1, Il21r and Il4r genes exhibited a synchronized expression …

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Characterization Of Intraocular Pressure Fluctuations, Intracranial Pressure And Translaminar Pressure Measured With Wireless Telemetry In Nonhuman Primates, Jessica Violet Jasien Jan 2020

Characterization Of Intraocular Pressure Fluctuations, Intracranial Pressure And Translaminar Pressure Measured With Wireless Telemetry In Nonhuman Primates, Jessica Violet Jasien

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Glaucoma is the second leading cause of blindness and third leading cause of visual impairment worldwide; 180 million people suffer from a glaucomatous visual disability. Glaucoma is an ocular neurodegenerative disease with several risk factors. The major identified risk factors of glaucoma are intraocular pressure (IOP), age, race, central cornea thickness, family history, and low diastolic blood pressure. The lowering of IOP is the only modifiable risk factor for the disease. However, we know little about the true character of IOP. Periodic IOP measurements are obtained every few months or at the discretion of the clinician during office hours and …

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Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly Jan 2020

Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly

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Parkinson’s disease (PD) is an age-related, progressive, movement disorder pathologically characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of proteinaceous aggregates, termed Lewy bodies, that are largely comprised of αSynuclein (αSyn). Missense mutations in the leucine-rich repeat kinase (LRRK2) gene are the most common genetic cause of PD and lead to gain-of-function increases in kinase activity. The G2019S-LRRK2 mutation is the most frequent mutation and elevates kinase activity by ~2-3 fold. Genetic and biochemical evidence suggest elevated LRRK2 kinase activity plays a pathogenic role in the development of PD, implicating LRRK2 …

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The Effect Of Gi Patients' Health Literacy Levels On Gi Patients' Health Outcomes, Dae Hyun Kim Jan 2020

The Effect Of Gi Patients' Health Literacy Levels On Gi Patients' Health Outcomes, Dae Hyun Kim

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The paper in this dissertation provide empirical evidence on the effect of GI patients’ health literacy levels on GI patients’ health outcomes. The findings of this study contribute to existing body of literature on health literacy and health outcomes. Furthermore, the findings also offer both theoretical and practical implications to physicians, healthcare administrators, and policymakers. Overall, the results of this study show that GI patients’ health literacy levels are negatively associated with GI patients’ health outcomes (hospital length of stay, readmission, and complication). However, partial support was shown for different types of GI surgeries accentuating the negative association between GI …

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