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Full-Text Articles in Medicine and Health Sciences

Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu Jan 2015

Structural And Biochemical Charactereization Of Lrrk2, Zhiyong Liu

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Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the most common known genetic cause of Parkinson disease (PD) , with pathogenic mutations located within each of the two catalytic cores of the protein, the GTPase and kinase domains. The most prevalent pathogenic mutation, G2019S increases kinase activity up to 5-fold, causing significant changes in the protein’s biochemical behavior. Other mutations such as R1441G and I2020T have also been demonstrated to increase LRRK2 kinase activity, however, the detailed mechanisms remains unclear. A major limitation in the field is the lack of structural information of LRRK2. This dissertation detailed …

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Spatial Analysis Of Hypertension Prevalence Using A Large Us Cohort, Matthew Loop Jan 2015

Spatial Analysis Of Hypertension Prevalence Using A Large Us Cohort, Matthew Loop

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Stroke mortality rates are highest in the Southeast US, and the cause for this "Stroke Belt" is not well understood. We investigate the spatial distribution of hypertension, an important risk factor for stroke. This investigation explores statistical issues in performing spatial analysis in a large cohort (over 30,000 participants), relating to type 1 error rate control and geocoding error. Recommendations for handling these statistical issues are made. In an applied analysis, we find that hypertension prevalence varies across the continental US, and is highest in northeast Louisiana, southeast Arkansas, west Mississippi, and east Michigan. These areas are not concordant with …

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Assessing Potential Diesel Exhaust Exposure In Truckers Resting At Truck Stops, Gumindenga Farayi Mabvuta Jan 2015

Assessing Potential Diesel Exhaust Exposure In Truckers Resting At Truck Stops, Gumindenga Farayi Mabvuta

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The nature of long haul truck driving places workers in this occupation in a peculiar setting for chronic exposure to diesel exhaust which is a known carcinogenic. These drivers endure exposure to diesel exhaust in traffic and potentially greater exposure at truck stops where they park for rest breaks as mandated by DOT regulations. This study looked at the potential exposure to diesel exhaust in long haul truck drivers resting at truck stops where up to two hundred trucks are left idling for air conditioning and other reasons. Two different trucks were used consecutively over the 21 days of sampling. …

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Some Contributions To Bayesian Regularization Methods With Applications To Genetics And Clinical Trials, Himel Mallick Jan 2015

Some Contributions To Bayesian Regularization Methods With Applications To Genetics And Clinical Trials, Himel Mallick

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Variable selection refers to the class of problems where one tries to find an optimal subset of relevant variables, which can be used to accurately predict the outcome of a certain response variable. Typically, a large number of variables are often collected; however, all but a few important variables are relevant for the prediction of the outcome, so the underlying representation is sparse. To this end, variable selection is fundamental in high-dimensional data analysis, playing a crucial role in important scientific discovery and decision-making, and has received enormous attention in the literature. Regularization method is one attractive approach that has …

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Synaptic And Neurochemical Profiles Of The Nucleus Accumbens In Postmortem Schizophrenia, Lesley Mccollum Jan 2015

Synaptic And Neurochemical Profiles Of The Nucleus Accumbens In Postmortem Schizophrenia, Lesley Mccollum

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Schizophrenia is a mental illness affecting 1% of the population worldwide. Treatment options are limited for patients, due in part to the lack of understanding of the pathophysiological mechanisms of schizophrenia. In order to improve treatment, it is vital to gain a better understanding of the underlying pathology of the disorder. One region of particular interest is the nucleus accumbens (NAcc). Part of the ventral striatum, this region is thought to play a role in schizophrenia pathology for multiple reasons: afferent input of many brain regions implicated in schizophrenia is integrated here; the dopamine and glutamate systems, both known to …

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Emergency Department Wait Time Communication Strategies And Patient Throughput Efficiency, Tom R. Mcdougal Jan 2015

Emergency Department Wait Time Communication Strategies And Patient Throughput Efficiency, Tom R. Mcdougal

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This study investigates hospital strategies used to inform patients of anticipated wait times in the Emergency Department (ED) and the association of such strategies with patient throughput efficiency. When hospitals are inefficient in ED patient throughput, conditions of overcrowding often occur. Overcrowding of the ED is a problem for many hospitals. When such conditions exist, there is evidence in the literature that it leads to lower patient satisfaction, care quality, and financial position of the hospital. Therefore, improving patient throughput efficiency is a priority for hospitals. To improve patient throughput efficiency, hospitals use a variety of strategies. This study focuses …

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A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown Jan 2015

A New Form Of Rod Photoreceptor Light Adaptation, Alex S. Mckeown

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In the first step in light perception, rod and cone photoreceptors convert photon absorption into an electrical impulse that is transmitted through the visual pathway. While the biochemistry and the signaling physiology have largely been defined in dark-adapted, isolated mammalian rods, there are still unanswered questions regarding photoreceptor light adaptation processes that involve extracellular components. In particular, the proteins of the interphotoreceptor matrix have not been considered in the studies of rod signaling and adaptation. This thesis details a new form of light adaptation, now known as adaptive potentiation (AP), in which extracellular components act on rods to transiently increase …

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Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows Jan 2015

Dna Methylation Regulates Neuronal Synaptic Scaling And Intrinsic Membrane Excitability, Jarrod P. Meadows

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Learning and memory rely on long-lasting, experience-dependent adaptations in synaptic and non-synaptic forms of neuronal plasticity. Previous evidence implicates transcriptional and epigenetic mechanisms, including DNA cytosine methylation, as critical regulators of site-specific, Hebbian alterations in synaptic efficacy such as long-term potentiation (LTP) and long-term depression (LTD). However, whether DNA methylation modulates cell-wide, non-Hebbian homeostatic adaptations like synaptic scaling and intrinsic plasticity (IP) is unclear. Whereas synaptic scaling involves bidirectional changes in postsynaptic receptor density in response to chronic alterations in neuronal activity, IP involves the activity-dependent attunement of passive and/or active membrane properties that govern action potential (AP) firing. This …

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The Impact Of Meal Timing On Cardiometabolic Syndrome Indicators In Shift Workers, Hylton Elisabeth Molzof Jan 2015

The Impact Of Meal Timing On Cardiometabolic Syndrome Indicators In Shift Workers, Hylton Elisabeth Molzof

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Shift workers exhibit a greater risk for several cardiovascular and metabolic diseases including heart disease, obesity, hypertension, and type II diabetes (Boivin, Tremblay, & James, 2007; Chen, Lin, & Hsiao, 2010; Knutsson, Jonsson, Akerstedt, & Orth-Gomer, 1986; Kroenke et al., 2007). Shift workers have been reported to consume more pro-inflammatory diets than day workers (Wirth, Burch, Shivappa, Steck, et al., 2014) and to redistribute their food intake to the night during work (Lennernas, Hambraeus, & Akerstedt, 1995; Pasqua & Moreno, 2004). Numerous studies in animal models and humans have shown that eating during the sleep or inactive period is associated …

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Nadph Oxidase-Derived Superoxide: A Potentiator Of Autoimmune Responses In Type 1 Diabetes, Lindsey E. Padgett Jan 2015

Nadph Oxidase-Derived Superoxide: A Potentiator Of Autoimmune Responses In Type 1 Diabetes, Lindsey E. Padgett

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Type 1 Diabetes (T1D) is an autoimmune disease culminating in pancreatic β-cell destruction, inducing reactive oxygen species (ROS), pro-inflammatory cytokines, and islet-infiltrating leukocutes. Macrophages, one of the first islet-infiltrating cells in T1D, secrete ROS and pro-inflammatory cytokines, which lyse pancreatic β-cells and activate diabetogenic T cells to further propagate β-cell destruction, while autoreactive CD4 T cells recruit islet-infiltrating, pro-inflammatory, M1 macrophages, and enhance CD8 T cell cytotoxicity. We previously demonstrated the importance of NADPH oxidase (NOX)-derived ROS synthesis in T1D, as Non-obese diabetic (NOD) mice lacking NOX-derived superoxide (NOD.Ncf1m1J) exhibited a delay in spontaneous and adoptive transfer of T1D. In …

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Comparison Of Three Fluoride Dentifrice Products In The Prevention Of White Spot Lesions In Orthodontic Treatment, Anna B. Palombini Jan 2015

Comparison Of Three Fluoride Dentifrice Products In The Prevention Of White Spot Lesions In Orthodontic Treatment, Anna B. Palombini

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Introduction:. During the course of orthodontic treatment, enamel decalcification is a common problem. Demineralized enamel, the precursor to caries formation, can be attributed to fixed orthodontic appliances and prolonged exposure to bacterial plaque. Progression to clinically detectable white spot lesions may occur as early as one month following the placement of orthodontic appliances. Such problems have influenced clinicians to search for a solution. Because fluoride treatment immediately upon debonding is not advocated, clinicians have proposed fluoride treatment and fluoride-releasing materials at the commencement of the therapy. The two new anti-cavity toothpastes, ClinproTM 5000 with 1.1% Sodium Fluoride and ClinproTM Tooth …

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The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues Jan 2015

The Role Of C-Reactive Protein In Acute Kidney Injury, Melissa A. Pegues

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Acute kidney injury (AKI), which manifests as an abrupt decline in renal function, occurs in ~1% of all hospitalization. Ischemia reperfusion injury (IRI), a common cause of AKI, can occur in any situation where blood flow to the kidney is significantly reduced such as hypertensive crisis, cardiovascular surgery, and inevitably during renal transplantation. Mortality from AKI is up to 80% due to incomplete knowledge of the pathogenesis of IRI and the lack of an effective therapy. It is thought that cellular damage as a result of hypoxia signals the release of proinflammatory cytokines that lead to a systemic inflammatory response. …

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Bond Of Dual Cure Resin Cements To Enamel And Dentin In Self Cure Mode, Rashmi Radhakrishnan Jan 2015

Bond Of Dual Cure Resin Cements To Enamel And Dentin In Self Cure Mode, Rashmi Radhakrishnan

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Dual cured resin cements are frequently used to cement all ceramic restorations. The increased thickness and /or opacity of restorations block light transmission. In these situations, where little or no light can be transmitted through the restorations, the polymerization of the cement is in the self-cure mode. Purpose: This study measures the bond strength and mode of failure of dual cure resin cements to enamel and dentin in a self-cure mode using e.max rods. Methods: 160 extracted human molars were ground to mid-coronal dentin (N=80) or superficial enamel (N=80) and finished to 320 grit disks. Four adhesive/cement combinations - Multilink …

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A Prospective Randomized Clinical Trial To Assess The Performance Of Microtextured Dental Implants With Or Without A Machined Collar- 1 Year Results, Elizabeth Felts Randall Jan 2015

A Prospective Randomized Clinical Trial To Assess The Performance Of Microtextured Dental Implants With Or Without A Machined Collar- 1 Year Results, Elizabeth Felts Randall

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Aim: To assess the performance of microtextured dental implants with or without a machined collar at one year after placement. Material and Methods: Fifty-eight patients received dental implant therapy to restore missing teeth in one area of the maxilla or man-dible at the UAB Department of Graduate Periodontology. Residents in the program placed microtextured implants with a microtextured collar with microgrooves (test group) and microtextured implants with a machined collar (control group). Sites were randomized to the test group or control group. Study visit protocol was followed and implants were restored by off-site dentists. Sixty-nine (69) implants were assessed at …

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Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi Jan 2015

Energy Metabolism Of Platelets During Activation, Oxidative Stress And Storage, Saranya Ravi

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The principal function of platelets is to regulate hemostasis, and dysfunction of platelet aggregation or activation can lead to either excessive thrombotic or hemorrhagic complications. It has been shown that the ability to generate ATP and exposure to oxidative stress can affect platelet thrombotic potential. While platelet metabolism has been extensively studied, the importance of substrate availability and metabolic plasticity in regulating aggregation under physiological or pathological conditions is not well understood. In this dissertation, we examined the reliance of platelets on different metabolic substrates, the importance of ATP production for aggregation in response to thrombin stimulation, metabolic stress following …

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Perceptions Of Facial Attractiveness: Outcomes Of Orthognathic Surgery, Brittany Bross Reid Jan 2015

Perceptions Of Facial Attractiveness: Outcomes Of Orthognathic Surgery, Brittany Bross Reid

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PERCEPTIONS OF FACIAL ATTRACTIVENESS: OUTCOMES OF ORTHOGNATHIC SURGERY BRITTANY REID DEPARTMENT OF ORTHODONTICS ABSTRACT Perceptions of physical attractiveness contribute to generalized assumptions that can create significant bias in social decision-making. Because these biases exist, patients often seek ways to improve facial harmony and overall appearance. Orthodontics and orthognathic surgery are treatment modalities that may be considered as a means to achieve facial balance. Orthodontists and oral surgeons must have an understanding of facial beauty and how to properly carry out techniques in order to preserve or improve facial balance. More importantly, the treatment goals of the patient and clinician(s) must …

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Patient Activation: An Examination Of The Relationship Between Care Management With Patient Activation-Customized Coaching And Patient Outcomes, Cindy L. Reistroffer Jan 2015

Patient Activation: An Examination Of The Relationship Between Care Management With Patient Activation-Customized Coaching And Patient Outcomes, Cindy L. Reistroffer

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As part of healthcare reform, patient engagement is becoming an important area of focus. Most recently, patient activation, as part of engagement, has been studied; however, interventions to improve activation are not well identified. The purpose of this dissertation was to empirically examine whether enrollment in care management with patient activation (PA)-customized coaching was associated with patient outcomes of utilization, medication adherence, and clinical outcomes. The study utilized the chronic care model framework and theoretical insights from social cognitive theory to examine the relationships among three hypotheses. Secondary data related to commercially-insured enrollees in Priority Health were used to test …

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Geographic Access To Interventional Cardiology Services In Maine, James P. Rhudy Jan 2015

Geographic Access To Interventional Cardiology Services In Maine, James P. Rhudy

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Introduction: Acute coronary syndrome is the most common cause of death in the U.S. and the world; ST segment elevated myocardial infarction is the most acute form. The preferred reperfusion therapy is immediate primary percutaneous coronary intervention at an interventional cardiology center. It is intuitive, but not known, whether delay in receipt of reperfusion therapy because of geographic distance is associated with increased coronary mortality. Even so, clinical practice guidelines recommend organizing coronary care in each community in regional systems. Hub-and-spoke has been proposed as a regionalized coronary care model. Article synthesis: The first article in this dissertation, titled Effectiveness …

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Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert Jan 2015

Glutamate And The Biology Of Malignant Glioma, Stephanie Marie Robert

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Malignant gliomas are the most prevalent primary brain tumor. They are highly aggressive and lack effective treatment options. Standard therapy includes a combination of radiation, chemotherapy, and tumor resection; however, even with aggressive treatment, median patient survival remains a dismal 12 – 14 months after diagnosis. Research has focused on understanding the unique biological mechanisms involved in glioma growth and survival in an effort to design novel therapies to treat this devastating disease. In the unique environment of the brain, gliomas have developed the ability to grow and survive at the cost of the normal surrounding brain tissue. Glutamate, the …

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Stress, Bullying, Cortisol, And Depresive Symptoms In 9th Grade Adolescents, Susan Gordon Williams Jan 2015

Stress, Bullying, Cortisol, And Depresive Symptoms In 9th Grade Adolescents, Susan Gordon Williams

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ABSTRACT Stress and bullying are known contributors to depressive symptoms in adolescents. Prevalence of depressive symptoms in adolescents is estimated to range from13% to 34% in recent studies. Ninth graders are in a transitional period developmentally,biologically, physically, and psychosocially. Few studies have examined the relationship between stress, bullying, and depressive symptoms from a biobehavioral perspective in 9th graders. The purpose of this study was to examine stress, bullying, and depressive symptoms including a biomarker of stress, salivary cortisol diurnal rhythm, to determine if there is mediation between the individual variables of stressful life events, perceivedstress, bullying, and depressive symptoms. The …

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Nonsense Suppression In A Cftr Mouse Model And Analysis Of Animo Acids Inserted At Cftr Premature Termination Codons In Mammalian Cells, Xiaojiao Xue Jan 2015

Nonsense Suppression In A Cftr Mouse Model And Analysis Of Animo Acids Inserted At Cftr Premature Termination Codons In Mammalian Cells, Xiaojiao Xue

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A nonsense mutation introduces a premature terminations codon (PTC) into an open reading frame (ORF) upstream of a normal stop codon and results in truncated protein production. In frame PTCs account for ~11% of all mutations that cause human genetic diseases. To treat PTC-associated disorders, one approach is to use drugs that facilitate the insertion of amino acids carried by near-cognate aminoacyl-tRNAs at PTCs. Aminoglycosides were shown to suppress nonsense mutations and restore full-length protein production. This process is also termed as readthrough. However, their low efficiency and their potential to induce ototoxicity and nephrotoxicity limits their long-term application for …

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Impact Of Medicare Part D Coverage Gap On Medicare Beneficiaries With Copd: Adherence, Healthcare Resource Use, And Cost, Yanni Fan Yu Jan 2015

Impact Of Medicare Part D Coverage Gap On Medicare Beneficiaries With Copd: Adherence, Healthcare Resource Use, And Cost, Yanni Fan Yu

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Medicare Part D provides prescription drug coverage for beneficiaries to support their pharmacological treatment; however, the complex deductible structure within benefit plans creates a major coverage gap and unexpected consequences. Some evidence has demonstrated reduced adherence resulting from the coverage gap; however, little research has evaluated the effect on healthcare resource use (HRU) and cost, and no studies have been conducted for beneficiaries with chronic obstructive pulmonary disease (COPD). This study examined the impact of the coverage gap on medication adherence as well as healthcare resource use and medical cost among beneficiaries with COPD. Claims data based on a 5% …

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Socs3 Deficiency In Myeloid Cells Promotes Tumor Development, Hao Yu Jan 2015

Socs3 Deficiency In Myeloid Cells Promotes Tumor Development, Hao Yu

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STAT3 signaling is a major intrinsic pathway for cancer inflammation owing to its frequent activation in malignant cells, and key role in regulating many genes crucial for inflammation in the tumor microenvironment. Persistently activated STAT3 increases tumor cell proliferation, survival, and invasion while suppressing anti-tumor immunity. Suppressor Of Cytokine Signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway, and generally function as tumor suppressors. The absence of SOCS3 in particular leads to heightened activation of the STAT3 transcription factor. In the present study, we demonstrate that genetic deletion of SOCS3 specifically in myeloid cells significantly enhances tumor growth, which …

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Functional Role Of Mepe In Tooth Mineralization: Mediation By Tgf-Beta1, Angela Gullard Jan 2015

Functional Role Of Mepe In Tooth Mineralization: Mediation By Tgf-Beta1, Angela Gullard

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Transforming growth factor-β1 (TGF-β1) is one of the most abundant cytokines of the dentin-pulp complex that regulates a broad range of biological processes related to matrix synthesis and ultimately tooth formation, including secretion and mineralization of the dentin extracellular matrix (DECM). TGF-β1 mediates odontoblast cytodifferentiation from precursor dental pulp cells, being up-regulated in odontoblasts and then incorporated into the DECM as a reservoir that can be utilized in times of mechanical, chemical, or bacterial insult. Formation of the DECM is modulated by the actions of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), which include DMP-1, DSPP, BSP, SPP1, and MEPE, with …

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Hospital-Based Skilled Nursing Facilities: Predictors Of Survival And Performance, Shivani Gupta Jan 2015

Hospital-Based Skilled Nursing Facilities: Predictors Of Survival And Performance, Shivani Gupta

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This three-paper dissertation examined the organizational and market factors predicting the response of hospital-based skilled nursing facilities (HBSNFs) to the changes in their environment such as the implementation of prospective payment system in 1998 and their role in coordination of care for patients in transition from acute care to home or a post-acute care facility. In the first study, population ecology of organizations framework was used to evaluate the organizational and market factors associated with HBSNFs’ closure after 1998. The event histories of all acute-care hospitals which had an open HBSNF in 1998 were examined across 15 years (1998-2012) to …

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Drivers Of Inter-Organizational Network Participation, Kimberly S. Davey Jan 2015

Drivers Of Inter-Organizational Network Participation, Kimberly S. Davey

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The purpose of this dissertation was to study market and organizational drivers associated with inter-organizational network participation. Inter-organizational networks are increasingly emerging across industries as a strategy for adapting to fundamental changes in competitive market environments. Specifically, this study empirically examined the association between market and organizational drivers for a sample of U.S. hospitals relative to their participation or non-participation in Medicare ACOs as a newly emergent inter-organizational network in the healthcare sector. This was a cross-sectional study of U.S. hospitals participating in Centers for Medicare and Medicaid Services (CMS) designated ACOs as of January 1, 2014 and hospitals not …

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G Protein-Coupled Inwardly-Rectifying Potassium (Girk) Chanels Mediate Entrainment Of Circadian Rhythms, Lauren Marie Hablitz Jan 2015

G Protein-Coupled Inwardly-Rectifying Potassium (Girk) Chanels Mediate Entrainment Of Circadian Rhythms, Lauren Marie Hablitz

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Circadian rhythms are 24-hour cycles in biological and behavioral processes. These cycles enable an organism to predict changes in its environment, like changes in food availability and seasonality. Although endogenously driven, these rhythms can entrain or synchronize to daily changes in the environment, allowing the animal to adapt. One way entrainment occurs is shifts in circadian phase following the presentation of nonphotic, or non-light, stimuli, such as exercise, arousal, or stress at certain times of day. The molecular mechanisms underlying nonphotic entrainment are poorly understood - specifically, how nonphotic cues alter excitability within the suprachiasmatic nucleus (SCN) of the hypothalamus, …

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The Investigation Of Quality Of Life, Perceived Disease Severity, And Adherence In Patients With The G551d Mutation Receiving Ivacaftor Therapy, Heather Young Hathorne Jan 2015

The Investigation Of Quality Of Life, Perceived Disease Severity, And Adherence In Patients With The G551d Mutation Receiving Ivacaftor Therapy, Heather Young Hathorne

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Cystic fibrosis (CF), a genetic disorder, is a chronic life threatening illness that affects 30,000 adults and children in the United States and 70,000 worldwide. Treatment for CF is complex and consuming, consisting of multiple time intensive regimens. The therapy regimen has been descried as extraordinary when compared even to therapy regimens for other chronic illnesses. Oral and nebulized medication therapy, airway clearance therapy, pancreatic enzyme replacement therapy and vitamin /nutritional supplements are all required for the multiorgan treatment regimen for CF. Daily prescribed therapy can include as many as 40-50 pills, breathing treatments lasting up to tow hours a …

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Obesity And Mortality In Us-Residing Hispanic Adults, Carrie Howell Jan 2015

Obesity And Mortality In Us-Residing Hispanic Adults, Carrie Howell

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Previous epidemiological studies observed the lack of an association between increased body mass index (BMI: kg/m2) and all-cause mortality in US-residing Hispanic adults. The purpose of this dissertation was to examine the validity of three hypothesized explanations for the absence of significant associations. Using data on Hispanic participants from the National Health and Nutrition Examination Survey (NHANES) [1988-1994 and 1999-2004] and the National Health Interview Survey (NHIS), this dissertation examined whether: (1) BMI was associated with cause-specific mortality; (2) measures of body composition was associated with all-cause mortality; and (3) the BMI-all-cause mortality association differed as a function of Hispanic …

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Infant Feeding Practices, Weight Gain, And Blood Pressure In Toddlers Born Very Preterm, Doris Rodriguez Jan 2015

Infant Feeding Practices, Weight Gain, And Blood Pressure In Toddlers Born Very Preterm, Doris Rodriguez

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Little is known about how weight gain in those born very preterm is associated with blood pressure and if cortisol, a stress biomarker, plays a mediating role. Also, the influence of infant feeding practices on weight gain has been only sporadically addressed. The purpose of this exploratory, descriptive, cross-sectional study was to examine the relationships between infant feeding practices, weight gain, and blood pressure noting any mediating effect cortisol may have between weight gain and blood pressure in 18-to-24 month old corrected age toddlers born very preterm. A convenience sample of 36 18-to-24 month old corrected age toddlers were enrolled. …

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