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Articles 781 - 810 of 2525

Full-Text Articles in Medicine and Health Sciences

The Role Of Astrocytes In The Development Of Central Chemosensitivity, Kelsey Patterson Jan 2018

The Role Of Astrocytes In The Development Of Central Chemosensitivity, Kelsey Patterson

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In the two decades since MECP2 was identified as the causative gene in the majority of Rett Syndrome (RTT) cases, transgenic mouse models have played a critical role in our understanding of this X-linked neurodevelopmental disease. However, their exclusive use presents a limitation in translating findings from animal models to the clinic. Here, we characterized growth, anatomical, behavioral, and motor deficits in a novel zinc-finger nuclease murine RTT model from birth through adulthood. Male rats lacking the transcriptional regulatory protein, MeCP2 (Mecp2ZFN/y), are noticeably symptomatic as early as postnatal day (P) 21 and die prematurely, while females lacking one copy …

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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 …

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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 …

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Morphological And Functional Characterization Of A Murine Garp2-Specific Knockout, Delores Stacks Jan 2018

Morphological And Functional Characterization Of A Murine Garp2-Specific Knockout, Delores Stacks

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GARP2, found exclusively in retinal rod photoreceptors, has been proposed to function as a structural protein, a calcium binding protein, and a modulator of the phosphodiesterase regulating visual phototransduction cascade kinetics. GARP2 is a splice variant of the Cngb1 gene which also encodes the β-subunit of the phototransduction cyclic nucleotide-gated cation channel and another glutamic acid-rich protein, GARP1. Mutations of the β-subunit and, recently discovered regions shared with the GARP en-coding regions of Cngb1cause retinitis pigmentosa (RP), while overexpression of GARP2 in the absence of the β-subunit accelerates the observed Cngb1-mediated retinal degeneration in mouse β-subunit knockout disease models. In …

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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 …

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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 …

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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 …

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The Effects Of Body Size, Growth, And History Of Diabetes On Glioma Risk, Rebecca Barnhill Little Jan 2018

The Effects Of Body Size, Growth, And History Of Diabetes On Glioma Risk, Rebecca Barnhill Little

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Many dietary exposures have weak or null associations with glioma risk. As nutrition can affect growth rate in adolescence, body size throughout the lifespan, and the propensity for Type 2 diabetes, the goal of this project was to examine the relationships between these surrogates of nutritional states and the risk of glioma. The aims of this project were to examine the associations between glioma risk and 1) self-reported body measures; 2) age when full height was attained; 3) and a history of diabetes. To investigate the first aim, 1,111 glioma cases and 1,096 community controls completed a structured interview to …

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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 …

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Applying Polytomous Rasch Analysis To Validate Parenting Related Scales, Lei Huang Jan 2018

Applying Polytomous Rasch Analysis To Validate Parenting Related Scales, Lei Huang

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This study applies Rasch analysis to validate two scales in the Parenting for the First-time project: Beck Depression Inventory (BDI-II) and Parenting Stress Index (PSI). The main purpose of this study is to evaluate quality of the two scales by using Rasch analysis to examine the unidimensionality, reliability, fit statistics, group and time invariance, and optimal response categories. Meanwhile, this study also compares the results of Rasch model and Classical Test Theory (CTT) to assess the advantages of Rasch analysis. Result: Both Rach analysis and CTT show the evidence of unidimensionality of BDI-II in the three administrative periods: Prenatal, 6 …

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Characterization Of Membrane Associated Mucins In Ocular Surface Disease, Anna Ablamowicz Jan 2018

Characterization Of Membrane Associated Mucins In Ocular Surface Disease, Anna Ablamowicz

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Mucins on the ocular surface are found in the tear film and are attached to corneal and conjunctival epithelial cells on the eye. The bulbar conjunctiva of the ocular surface can be divided into four anatomical regions: temporal, superior, nasal, and inferior. The palpebral conjunctiva is the epithelial layer of the inner surfaces of the upper and lower eyelids. In the tears, mucins provide lubrication of the ocular surface through formation of a hydrophilic gel. The primary mucin in the tear film is MUC5AC which is secreted by goblet cells that are located in varying densities within the bulbar conjunctiva. …

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Effects Of Medicare Reimbursement Policies On The Quality Of Hospital Care, Monica Aswani Jan 2018

Effects Of Medicare Reimbursement Policies On The Quality Of Hospital Care, Monica Aswani

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This dissertation is composed of two papers related to the role of social risk factors in the Hospital Readmissions Reduction Program (HRRP). As value-based initiatives like the HRRP become more commonplace, there is growing need to understand the relationship between performance in these programs and social risk factors, such as race and poverty, which are not incorporated in the program’s risk adjustment methodology. To address this gap in the literature, this dissertation specifically focuses on three areas: 1) how hospital and community factors are related to average HRRP penalties, taking the context of geography into account, 2) how hospital and …

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Parental Decision-Making In Use Of Complementary And Alternative Medicine, Meka B. Astin Jan 2018

Parental Decision-Making In Use Of Complementary And Alternative Medicine, Meka B. Astin

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One health care trend is the growing public interest in, and use of, complementary and alternative medicine (CAM). Research in the United States suggests that significant numbers of children are involved in various forms of alternative medicine. The purpose of this dissertation is to assess the predictors of parental decision-making of CAM use for their child using five categories of CAM therapies: alternative medical systems, biologically- based, mind-body, manipulative, and a separate and distinct category to include all CAM medical systems. Andersen’s health care Utilization Model (HUM), which holds that health service use is a function of predisposing, enabling, needs …

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A Study To Examine The Relationship Between Hospital Mergers And Patient Experience, Timothy William Attebery Jan 2018

A Study To Examine The Relationship Between Hospital Mergers And Patient Experience, Timothy William Attebery

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Since 2009, the United States has experienced another wave of hospital mergers. Consequently, health systems are getting larger and increasing their market concentration. How patients benefit from hospital consolidation remains an open issue for policy-makers, economists, health care executives, community leaders, politicians, government agencies, and others. One measure of healthcare consolidation’s impact, and its potential benefit/detriment, is how mergers affect patient experience, which, since 2007, has been measured by the standardized HCAHPS instrument. Hundreds of studies conducted over the past 50 years have found mergers trigger an internal, socially-disruptive effect in the first 12 to 24 months following the event …

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The Impact Of The Cd11b 77his And 1146ser Variants On Mac-1 Activity And Functions, Justin Timothy Avery Jan 2018

The Impact Of The Cd11b 77his And 1146ser Variants On Mac-1 Activity And Functions, Justin Timothy Avery

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Mac-1 (CD11b/CD18, ITGAM/ITGB2, CR3) is a member of the β2 integrin family. While primarily expressed on myeloid lineage cells such as monocyte/macrophages, neutrophils, and dendritic cells, Mac-1 is also found on natural killer cells and some B cells and T cell populations. Mac-1 has over 50 ligands, many of which are critical for adhesion, signaling, and the promotion of immune functions like phagocytosis. Genome-wide association studies (GWAS) have linked several SNPs in ITGAM, the gene which codes for CD11b, with the autoimmune disease systemic lupus erythematosus (SLE). rs1143679 results in an arginine to histidine change at amino acid position 77 …

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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 …

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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 …

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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 …

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Effects Of Medicaid Expansion On The Financial Performance Of Rural Hospitals, Keith Darryl Brady Jan 2018

Effects Of Medicaid Expansion On The Financial Performance Of Rural Hospitals, Keith Darryl Brady

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EFFECTS OF MEDICAID EXPANSION ON THE FINANCIAL PERFORMANCE OF RURAL HOSPITALS KEITH BRADY DOCTOR OF SCIENCE IN HEALTH SERVICES ADMINISTRATION ABSTRACT The purpose of this research was to examine the effects of Medicaid expansion on the financial performance of rural hospitals. The analysis compares Medicaid revenue, uncompensated care cost and operating margins between rural hospitals in states that expanded Medicaid and rural hospitals in states that did not expand Medicaid. Strategic Management Theory was used to develop a theoretical framework to address three primary hypotheses. Secondary data from the Medicare Cost Report (MCR), the Agency for Healthcare Research and Quality …

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An Analysis Of The Association Between An Established Chief Experience Officer Position And Hospital Patient Experience Scores Within Three States, William Robert Breen Jan 2018

An Analysis Of The Association Between An Established Chief Experience Officer Position And Hospital Patient Experience Scores Within Three States, William Robert Breen

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Few industries operate with as much capacity to personally satisfy or disappoint, as does the U.S healthcare industry. Healthcare outcomes sought by society include wellness, safety, healing, and, ultimately, experiences. While healthcare involves complex relationships between patients, families, providers, payers, and regulators, the use of management theory can be insightful in studying and explaining the motivations and strategic decisions of healthcare managers. The healthcare industry is currently reacting to multiple stakeholders demanding improvements to the patient experience. New ways to measure patient experiences in healthcare are emerging. Some healthcare organizations are implementing new management structures, i.e., the role of Chief …

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The Evolving Landscape Of Mechanical Circulatory Support In The United States: Observations From National Registries, Ryan Segler Cantor Jan 2018

The Evolving Landscape Of Mechanical Circulatory Support In The United States: Observations From National Registries, Ryan Segler Cantor

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Mechanical circulatory support (MCS) is a rapidly evolving field. This dissertation describes trends in patient selection, device utilization, and outcomes for adult and pediatric patients receiving MCS in the United States by examining data from two national registries. Trends in adult MCS device recipients and their support outcomes were evaluated using data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), a national registry collecting detailed information for patients implanted with Food and Drug Administration (FDA)-approved durable MCS devices. Between June 2006 and December 2016, INTERMACS enrolled more than 19,000 patients. During this time, the widespread use of devices …

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Mechanistic Connections Between Metabolic And Differentiation Programs In T Cells, Danielle Alexandria Chisolm Jan 2018

Mechanistic Connections Between Metabolic And Differentiation Programs In T Cells, Danielle Alexandria Chisolm

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Cellular metabolism is closely coupled to differentiation gene programs in many developmental systems. In part, this is due to a similar complement of transcription factors playing dual roles in regulating both the gene expression programs associated with specific metabolic pathways and the differentiation gene program of the cell. In T cells, T cell receptor- (TCR) and IL-2-sensitive transcription factors coordinate the programming of metabolic states with the effector and memory gene programs. Currently, our understanding of the mechanisms by which metabolic states contribute to the regulation of T cell differentiation gene programs is unclear. Metabolites are directly involved in epigenetic …

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Adiposity And Health In Zoo African And Asian Elephants, Daniella Chusyd Jan 2018

Adiposity And Health In Zoo African And Asian Elephants, Daniella Chusyd

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African (Loxodonta africana) and Asian (Elephas maximus) elephant populations are rapidly declining due to poaching, and habitat fragmentation and loss. Due to the precarious situation elephants are facing worldwide, captive elephant populations are being viewed as an insurance policy against extinction. Unfortunately, captive elephant populations are not self-sustaining, in part because of reproductive and health issues. One hypothesis for the observed reproductive and health issues is zoo elephants are obese. The current method of assessing obesity in elephants is based on a qualitative visual tool, the body condition score, which does not quantify fat mass. The purpose of this dissertation …

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A Randomized Trial To Evaluate The Effect Of Allograft Bone Particle Size On Histomorphometric And Clinical Outcomes Following Ridge Augmentation Procedures, Hussein Basma Jan 2018

A Randomized Trial To Evaluate The Effect Of Allograft Bone Particle Size On Histomorphometric And Clinical Outcomes Following Ridge Augmentation Procedures, Hussein Basma

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Ridge deficiency is an unfortunate obstacle that obviates the placement of dental implants or results in placing them at an angle that compromises the prosthetic restoration. An ideal volume is essential for implant placement in an optimal three-dimensional position. Several methods for augmenting the alveolar ridge in preparation for implant placement have been described. Autogenous bone grafts, considered to be the “gold standard”, are associated with significant morbidity and require a second surgical site. Guided bone regeneration (GBR), is an alternative technique that use bone-substitute materials as adjuncts to or replacements for autografts in bone augmentation procedures to overcome the …

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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 …

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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 …

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Constraint-Induced Movement Therapy To Improve Gait And Mobility Of People With Chronic Stroke: A Mixed Methods Study, Sarah Monteiro Dos Anjos Jan 2018

Constraint-Induced Movement Therapy To Improve Gait And Mobility Of People With Chronic Stroke: A Mixed Methods Study, Sarah Monteiro Dos Anjos

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Walking impairment after stroke impacts on participation and quality of life. Different techniques have been developed in the last decades to overcome walking difficulties after stroke, however, few have been shown to be efficacious. Constraint-induced Movement Therapy (CIMT) is a family of techniques that has been reported as one the most effective intervention for improving functional use and motor skills of a more-affected upper extremity (UE). The intervention protocol includes: 1) intensive supervised training; 2) use of shaping as a strategy for the motor training, 3) a group of behavioral strategies called the transfer package, and 4) procedures to increase …

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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 …

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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 …

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The Primary Cilium Regulates Interstitial Immune Cells During Renal Cystogenesis, Cheng Song Jan 2018

The Primary Cilium Regulates Interstitial Immune Cells During Renal Cystogenesis, Cheng Song

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Renal cysts are a pathological condition that can lead to end-stage renal failure and death. The mechanisms that underlie renal cyst development are under active investigation, and emerging evidence has revealed defects in a number of proteins required for cilia assembly or signaling, such as intraflagellar transport (IFT) proteins and the polycystins. Characterization of mice harboring conditional IFT mutations suggests that the rate of cyst formation is dependent upon the timing of cilia loss. Induction of cilia loss in juvenile mice results in rapid cyst development, while induction of cilia loss in adult mice leads to a slower progressing form …

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