Medicine and Health Sciences Commons^™

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

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

Electronic Theses and Dissertations

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

Distributing Data And Analysis Software Containers For Better Data Sharing In Clinical Research, William A. Mattingly Phd, Stephen Furmanek, Christopher M. Sinclair, Timothy L. Wiemken Phd

The University of Louisville Journal of Respiratory Infections

Introduction: Data sharing in clinical research is critical for increasing knowledge discovery. Data and software tools should be FAIR: Findable, Accessible, Inter-operable and Re-usable. Many bottlenecks exist in the process of a clinical investigator using shared data including data acquisition and statistical analysis. The objective of this project is to develop a structure for sharing data and providing rapid automated statistical analysis through creation of a pre-packaged, open-source software container.

Methods: We use the open source software container technologies VirtualBox and Vagrant to create a template for sharing clinical data and analysis scripts as a single container. We use …

Streptococcus Pneumoniae Antigen, Missing Opportunities Of A Promising Point Of Care Diagnostic Test, Magdelina Słomka, Ruby Gupta, Baltej Singh, Venkatesh Gondhi, Siddartha Bhandary, Ekezie Francis, Jose Bordon

The University of Louisville Journal of Respiratory Infections

Background: The etiologic diagnosis of community acquired pneumonia (CAP) and community-acquired meningitis (CAM) are still far from optimal accuracy and turnaround time. The most common bacterial pathogen identified in both CAP and CAM is Streptococcus pneumoniae.

Methods: We reviewed the literature on S. pneumoniae antigen to highlight opportunities to optimize its use as a point of care diagnostic test to maximize quality of patient care, antimicrobial stewardship outcomes and cost saving. A PubMed search was performed using key words “S. pneumoniae antigen; rapid diagnostic tests for S. pneumoniae”. We selected articles in English and sorted into randomized …

Most Common Statistical Methodologies In Recent Clinical Studies Of Community-Acquired Pneumonia, Stephen Furmanek, Connor L. English, Thomas Chandler, Timothy L. Wiemken Phd

The University of Louisville Journal of Respiratory Infections

Background: Training new individuals in pneumonia research is imperative to produce a new generation of clinical investigators with the expertise necessary to fill gaps in knowledge. Clinical investigators are often intimidated by their unfamiliarity with statistics. The objective of this study is to define the most common statistical methodologies in recent clinical studies of CAP to inform teaching approaches in the field.

Methods: Articles met inclusion criteria if they were clinical research with an emphasis on incidence, epidemiology, or patient outcomes, searchable via PubMed or Google Scholar, published within the timeframe of January 1st 2012 to August 1st 2017, …

Rationale And Methods Of The Study Protocol: Streptococcus Pneumoniae Serotypes In Adults 18 Years And Older With Radiographically-Confirmed Community-Acquired Pneumonia (Cap), Ronika Alexander, Paula Peyrani, Julio A. Ramirez, Wesley H. Self Md, Mph, Carlos Grijalva, Francis Counselman, Gregory A. Volturo, Heidi Kabler, Luis Ostrosky-Zeichner, Richard Wunderink, Robert L. Sherwin, Senen Pena, Thomas File, Timothy L. Wiemken, Sharon Gray, Michael Pride, Kimbal D. Ford, Qin Jiang, Raul Isturiz

The University of Louisville Journal of Respiratory Infections

This study was an active, prospective surveillance study of adults 18 years and older hospitalized with community-acquired pneumonia (CAP) due to Streptococcus pneumoniae conducted at 21 hospitals in ten cities across the United States. This report describes the surveillance methodology applied between October 7, 2013 and September 30, 2016, including the identification and description of surveillance areas and populations at-risk for CAP hospitalization for estimation of incidence rates for selected study sites.

Pneumonia Pathogenesis And The Lung Microbiome: Back To The Drawing Board, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Level Of Recall Bias Regarding Pneumococcal Vaccination History Among Adults Hospitalized With Community-Acquired Pneumonia: Results From The University Of Louisville Pneumonia Study, Sarah Van Heiden, Ruth Carrico, Timothy L. Wiemken, Ronika Alexander, John M. Mclaughlin, Qin Jiang, Paula Peyrani, William A. Mattingly, Stephen P. Furmanek, Connor L. English, Senen Pena, Raul Isturiz, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Background: Recall bias is likely to occur in vaccine effectiveness studies using self-reported vaccination history. The validity of patient-reported vaccination status for adults is not well defined. The objective of this study was to evaluate the validity of self-reported pneumococcal vaccination history among patients hospitalized with community-acquired pneumonia (CAP).

Methods: Prospective ancillary study of a population-based observational study of hospitalized patients with CAP in the city of Louisville. To be included in the analysis, patients had to (i) be reached by phone 30-days after discharge from the hospital and (ii) report that they remembered whether or not they received a …

Preliminary Evaluation Of An Lyta Pcr Assay For Detection Of Streptococcus Pneumoniae In Urine Specimens From Hospitalized Patients With Community-Acquired Pneumonia, Subathra Marimuthu, James T. Summersgill, Kuldeep Ghosh, Leslie A Wolf

The University of Louisville Journal of Respiratory Infections

Community acquired pneumonia (CAP) due to Streptococcus pneumoniae still occurs in at risk populations, despite the availability of effective vaccines. Laboratory confirmation of S. pneumoniae remains challenging in cases of CAP despite advances in blood culture techniques and the availability of nucleic acid amplification tests such as PCR-based methods. Urine specimens are an attractive sample type because they are non-invasive compared to bronchial washes or whole blood specimens for patients with CAP. While urine specimens have been used successfully in antigen detection assays, they have not been extensively evaluated for PCR-based assays. In this preliminary study, we evaluated the potential …

Antimicrobial Stewardship In Hospitalized Patients With Respiratory Infections: Ten-Year Experience From The Robley Rex Louisville Va Medical Center, Leslie A. Beavin, Forest W. Arnold, Paula Peyrani, Anupama Raghuram, David Newman, Ronald Smith, Carmen Sciortino, Stephen P. Furmanek, Ruth M. Carrico, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Rationale: Antibiotic stewardship has been defined as coordinated interventions designed to improve and measure the appropriate use of antibiotic agents. Respiratory infections are the most common infectious reason for hospitalization in the United States. Therefore, one could extrapolate that respiratory infections are then also the most common reason for hospital antibiotic use and possess the highest potential for hospital antibiotic misuse. The primary objective of this article was to evaluate the role of antimicrobial stewardship on improving antibiotic use for respiratory infections in hospitalized patients on intravenous (IV) antibiotics at the Robley Rex Louisville VAMC over a 10-year period.

Methods: …

One-Year Mortality In Patients With Community-Acquired Pneumonia, Paula Peyrani, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

Pneumonia remains a common cause of morbidity and mortality in the US. Although, communityacquired pneumonia (CAP) has traditionally been considered an acute process, more recently, data have emerged showing that patients surviving an episode of CAP are at increased risk of death long after hospital discharged. In this descriptive review, we examine the current knowledge of long-term mortality and propose a hypothesis explaining the pathogenesis of long-term mortality in patients with CAP.

Using Steroids In Patients With Community-Acquired Pneumonia At The University Of Louisville Hospital: Who, What, And When, Rodrigo Cavallazzi, Julio A. Ramirez

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Lung Cytokines And Systemic Inflammation In Patients With Copd, Alessandra Morello Gearhart, Rodrigo Cavallazzi, Paula Peyrani, Timothy L. Wiemken, Stephen P. Furmanek, Andrea Reyes-Vega, Umair Gauhar, Hiram Rivas-Perez, Jesse Roman, Julio A. Ramirez, Rafael Fernandez-Botran

The University of Louisville Journal of Respiratory Infections

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by lung and systemic inflammation. The role of cytokines in local and systemic inflammation in COPD is not well understood. This study aimed to compare plasma and bronchoalveolar lavage (BAL) fluid cytokine levels in COPD and non-COPD subjects with the intent of better understand their potential roles in driving local and systemic inflammation.

Methods: This cross-sectional study analyzed data from 65 subjects: 31 with COPD confirmed by spirometry and 34 non-COPD controls. All subjects underwent spirometry, plasma sample collection, and bronchoscopy/BAL. Levels of 21 inflammatory cytokines were measured in the plasma (systemic …

Lung Cytokines And Systemic Inflammation In Patients With Copd., Alessandra Morello Gearhart, Rodrigo Cavallazzi, Paula Peyrani, Timothy L. Wiemken, Stephen P. Furmanek, Andrea Reyes-Vega, Umair Gauhar, Hiram Rivas-Perez, Jesse Roman, Julio A. Ramirez, Rafael Fernandez-Botran

Faculty Scholarship

Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by lung and systemic inflammation. The role of cytokines in local and systemic inflammation in COPD is not well understood. This study aimed to compare plasma and bronchoalveolar lavage (BAL) fluid cytokine levels in COPD and non-COPD subjects with the intent of better understand their potential roles in driving local and systemic inflammation.

Methods: This cross-sectional study analyzed data from 65 subjects: 31 with COPD confirmed by spirometry and 34 non-COPD controls. All subjects underwent spirometry, plasma sample collection, and bronchoscopy/BAL. Levels of 21 inflammatory cytokines were measured in the plasma (systemic …

Gender Differences In Virologic Response After Antiretroviral Therapy In Treatment-Naïve Hiv-Infected Individuals: Results From The 550 Clinic Hiv Cohort Study., Andrea Reyes-Vega, Alejandra Loban, Kavitha Srinivasan, Stephen P. Furmanek, Conner English, Mary Bishop, Cathy Spencer, Daniel Truelove, Julio A. Ramirez, Anupama Raghuram, Paula Peyrani

Faculty Scholarship

Background

Controversy still exists regarding gender differences in virologic response between treatment-na•ve HIV-infected individuals. The objective of this study was to evaluate gender difference in virologic and immunologic response to antiretroviral therapy in treatment-na•ve HIV-infected individuals. Methods

This was a retrospective, observational study of treatment-na•ve HIV-infected individuals managed at the 550 clinic who started antiretroviral therapy (ART) between January 1st, 2010 and December 31, 2015. Patients with available viral load and CD4 counts before and one year after initiating ART were included in this study. Virologic suppression was defined as < 48 HIV-1 RNA copies/mL, and mmunologic recovery was defined as a CD4 count increase of at least 150 cells/mm3. Dichotomous variables were reported in number and percentages and analyzed using Chi-squared tests and Fisher’s exact (whichever was appropriate). Continuous variables were reported as median and interquartile range (IQR) and analyzed using Wilcox rank-sum tests. Multivariate analyses performed were logistic regressions with adjustment for other covariates. P value <0.05 was considered statistically significant. R version 3.3.2 was used for the statistical analysis. Results

A total of 70 women and 90 men were included …

A New Journal And New Opportunities, Ruth M. Carrico

Journal of Refugee & Global Health

No abstract provided.

Health Profiles Of Newly Arriving Refugees In Kentucky, 2016: Data From The University Of Louisville Global Health Program, Ruth M. Carrico, Timothy L. Wiemken, Rahel Bosson, William A. Mattingly, Rebecca Ford, Sarah Van Heiden, Stanley Kotey, Julio A. Ramirez

Journal of Refugee & Global Health

Objectives: Refugees resettling in the United States bring with them a number of health conditions, the majority chronic. These health conditions may impact their ability to be successful with disease self-management and employment, and acculturate and thrive in their new communities. Knowledge of health conditions present in individual refugee populations can be of benefit to healthcare providers in the community and public health. The objective of this manuscript is to describe the state of health among refugees newly arriving in the US and resettling in Kentucky during 2016.

Methods: Using data from the domestic health screens, immunization clinics, and the …

Evaluating Mental Health In Cuban Refugees: The Role Of The Refugee Health Screener-15, Rahel Bosson, Victoria A. Schlaudt, Monnica T. Williams, Ruth M. Carrico, Adriana Peña, Julio A. Ramirez, Jonathan Kanter

Journal of Refugee & Global Health

The Refugee Health Screener-15 (RHS-15) is widely used in refugee populations, but the psychometric properties and clinical utility have not been evaluated in Cuban refugees and entrants. The current study explored results from the Spanish version of the RHS-15 in a sample of 53 Cuban entrants and refugees, and of these, 17.6% screened positive for a mental health concern. Analyses suggested that a positive screening was significantly related to symptoms of anxiety, depression, and posttraumatic stress disorder; however, it was not associated with demographic variables such as gender, mode of transport, or the number of countries through which a refugee …

Refugee-Centered Medical Home:A New Approach To Care At The University Of Louisville Global Health Center, Rahel Bosson, Ruth M. Carrico, Anupama Raghuram, Paula Peyrani, William A. Mattingly, Rebecca Ford, Stephen P. Furmanek, Julio A. Ramirez

Journal of Refugee & Global Health

Refugees arrive to the United States with a full spectrum of health conditions, many of which involve intense case management requiring significant financial investments and use of healthcare resources. Kentucky receives more than 3,000 new refugees each year and ranked 10th in the nation for numbers of new arrivals resettled during 2015. These refugees arrive from diverse countries representing different cultures and speaking different languages. In addition, they arrive with diverse health conditions and medical needs. The aims of this paper are to share experiences from the University of Louisville Global Health Center regarding conceptualization, implementation and evaluation of a …

Subjective Well-Being And Hiv Prevention: A Cross-Country Descriptive Study Using Multiple Indicator Cluster Survey Data, Janine Foggia, Anne Sebert Kuhlmann

Journal of Refugee & Global Health

Subjective well-being (SWB) is positively associated with improved health outcomes and, in particular, preventative behaviors. Yet, the relationship between SWB and HIV prevention is not well understood, especially in the context of developing countries. Furthermore, young females experience a high burden of HIV as well as sociodemographic factors which influence SWB. Therefore, this descriptive study sought to describe the global landscape of three constructs of SWB - happiness, life satisfaction, and life perception - and the following HIV prevention variables: comprehensive HIV knowledge, HIV testing, and condom use among young adult females aged 15-24 years. Descriptive statistics of Multiple Indicator …

Use Of Emergency Department For Care Access By Refugees Resettling In Kentucky, 2015: Findings From The University Of Louisville Global Health Center, Ruth M. Carrico, Carmen Mitchell, Dawn Balcom, Linda Goss, Anna Persaud, Karen Mutsch, Timothy L. Wiemken, Rahel Bosson, Julio A. Ramirez

Journal of Refugee & Global Health

Background: Kentucky is one of the largest rural resettlement areas for refugees in the US welcoming more than 3,000 refugees and other entrants during 2015. Refugees arrive with a number of chronic health conditions that require ongoing management in a healthcare system where they lack knowledge and ability to navigate. This may encourage them to seek care that is easy to access but episodic and fragmented. The objective of this study was to determine the frequency and reasons for accessing care via a local emergency department by resettling refugees during their first twelve months of resettlement.

Methods: Using data from …