Digital Commons Network^™

Role Of Tnfα Antagonists And Genetic Polymorphisms In Modulating Susceptibility To Mycobacterial Infection Among Patients With Crohn's Disease, Ahmad Qasem

Electronic Theses and Dissertations

Tumor Necrosis Factor alpha antagonists (anti-TNFα) have been extensively used for Crohn's disease (CD) treatment. Even though they may control CD symptoms initially, treatment response varies among patients, which seems to depend on single nucleotide polymorphisms (SNPs) in TNFα receptors superfamily 1A and 1B (TNFRSF1A/B). Most importantly, M. tuberculosis infection has been strongly associated with these medications, but no studies have elucidated the effects of anti-TNFα on CD associated with MAP (Mycobacterium avium subspecies paratuberculosis; a possible causative agent of CD, and closely related to M. tuberculosis). Here, we investigated the effects of recombinant inflammatory cytokines and anti-TNFα therapeutics on …

Ribbeting Results: Emergent Infectious Diseases In Wetland Systems, Ariel Horner

Electronic Theses and Dissertations

North American amphibians have recently been impacted by two major emerging pathogens, the fungus Batrachochytrium dendrobatidis (Bd) and iridoviruses in the genus Ranavirus (Rv). Environmental, seasonal and host factors may play important roles in disease dynamics, but few studies incorporate these components into their analyses. Here, we investigated the role of environmental, seasonal, genetic and location effects on driving Bd and Rv infection prevalence and severity in a biodiversity hot spot, the southeastern United States. We used quantitative PCR to characterize Bd and Rv dynamics in natural populations of three amphibian species: Notophthalmus perstriatus, Hyla squirella and Pseudacris ornata and …

Determining Differential Effects Of Interleukin-2 On Innate And Adaptive Immune Cells In Lymphoid Organs And The Gastrointestinal Tract, Ayushi Singh

Electronic Theses and Dissertations

Interleukin-2 (IL-2) is a pleiotropic cytokine demonstrated to be effective in treating cancer. However, the clinical use of IL-2 can be associated with severe side effects including gastrointestinal toxicity (GT). Similar GT symptoms are observed in inflammatory diseases such as CD (CD). Interestingly mounting evidence indicates a role for IL-2 in CD, but the underlying mechanisms are unknown. Indeed, studies on the in-vivo activities of IL-2 have mostly focused on secondary lymphoid organs and immune cells associated with them. Very few studies have addressed how IL-2 signals impact populations of immune cells in the gut. Here, we aim to identify …

Modeling Disease Impact Of Vibrio-Phage Interactions, Christopher Botelho

Electronic Theses and Dissertations

Since the work of John Snow, scientists and medical professionals have understood that individuals develop cholera by means of consuming contaminated water. Despite the knowledge of cholera's route of infection, many countries have experienced and still experience endemic cholera. Cholera is caused by the Vibrio cholerae (V. cholerae) bacterium and presents with acute diarrhea and vomiting. If untreated, infected individuals may die due to dehydration. Cholera is a disease that most commonly affects countries with poor infrastructure and water sanitation. Despite efforts to control cholera in such countries, the disease persists. One such example is Haiti which has been experiencing …

Mathematical Investigation Of The Spatial Spread Of An Infectious Disease In A Heterogeneous Environment, Arielle Gaudiello

Electronic Theses and Dissertations

Outbreaks of infectious diseases can devastate a population. Researchers thus study the spread of an infection in a habitat to learn methods of control. In mathematical epidemiology, disease transmission is often assumed to adhere to the law of mass action, yet there are numerous other incidence terms existing in the literature. With recent global outbreaks and epidemics, spatial heterogeneity has been at the forefront of these epidemiological models. We formulate and analyze a model for humans in a homogeneous population with a nonlinear incidence function and demographics of birth and death. We allow for the combination of host immunity after …

Community Pharmacists And Substance Use Disorders: Attitudes, Knowledge And Practices, Deepika Rao

Electronic Theses and Dissertations

Background: Substance use disorder (SUD) is a serious health concern affecting a large proportion of the US population. Community pharmacists are well-positioned to prevent, screen, and provide appropriate treatment for SUD. Stigma towards these patients and SUD results in reduced quality of care as well as poor treatment outcomes. It is imperative that pharmacists have the appropriate knowledge of and attitude towards prevention, harm reduction and treatment to develop therapeutic relationships and improve their delivery of pharmacy services

Objective: To assess knowledge, practices (with an emphasis upon screening), stigma and general attitudes of community pharmacists towards SUD and evaluate the …

Access To Care And The Use Of Healthcare Services By Women In Rural Cameroon: A Participatory Action Research Study, Grace Tadzong-Awasum

Electronic Theses and Dissertations

Women in rural Cameroon do not access health care as timeously and as often as they should. They fail to get screened for common diseases, with the consequence that such diseases are often diagnosed at a very advanced stage. This accounts for the high morbidity and mortality rates as well as low life expectancy recorded among women. The purpose of this study was to explore and understand the health access experiences of women in rural Cameroon. Methodology: Participatory action research was used guided by a Focused ethnography in phase one. Twenty-five women aged 21-77 years were recruited through local the …

Harnessing The Anopheles Microbiome To Conditionally Express Anti-Plasmodial Effectors During The Blood Meal, Jackie Shane

Electronic Theses and Dissertations

The control of vector-borne diseases such as malaria has been an extremely important research subject for hundreds of years. Because of the complex lifecycles of the pathogens that cause these diseases, finding a comprehensive treatment or preventative strategy has proven extremely difficult. Malaria alone is responsible for almost half a million deaths annually, most of them children under 5 years old. This disease is caused by parasitic protists in the genus Plasmodium that are transmitted to humans from Anopheles sp. mosquitoes. Most preventative strategies that are in use today revolve around controlling the vectors, including bed nets, insecticides, and larval …

Probiotic Use In Trauma Patients: A Pathway To Determining The Standard Of Care To Improve Outcomes, Heather Vitko

Electronic Theses and Dissertations

The gut microbiome consists of normally non-pathogenic bacteria, viruses, and fungi. These friendly microbes serve to maintain GI barrier function and integrity, play a role in host nutrient and drug metabolism, immunomodulation, and prevent pathogenic bacteria from colonizing or causing disease. The importance of a healthy microbiome for the overall health of the host is just recently being appreciated within the medical and science communities. Disruption of the microbiome places one at greater risk for illness and infection. Patients who suffer a traumatic injury are among those at highest risk for complications associated with microbial imbalance, or dysbiosis. In addition …

The Role Of Cathelicidin In The Regulation Of Gut Microbiota And Inflammasome Activation In Alcoholic Liver Disease., Fengyuan Li

Electronic Theses and Dissertations

Alcoholic liver disease (ALD) is characterized by gut dysbiosis and hepatic and intestinal inflammation. Gut microbiota is critically maintained by antimicrobial peptides (AMPs) expressed in the epithelial and immune cells. AMPs are also identified as immune-regulators in various diseases. Previous studies demonstrated that deficiency of AMPs REG3 lectins exacerbated alcoholic steatohepatitis. LL-37 is the sole member of human cathelicidin AMP family, named CRAMP in mouse. Despite of the extensive studies in infectious diseases and in gut-microbiota-related inflammatory bowel disease, the role of LL-37/CRAMP in ALD is yet unknown. Our previous studies showed a decreased intestinal CRAMP in a mouse model …

Characterizing The Gut Microbiota During Plasmodium Infection And Antimalarial Treatment., Joshua E. Denny

Electronic Theses and Dissertations

Plasmodium, the parasitic cause of malaria, is a global pathogen, annually causing 216 million infections and 445,000 deaths. As drug resistance continues develop and no effective vaccine is available, it is critical to understand the factors underlying the severity of this disease. Plasmodium is an extra-gastrointestinal tract infection where the parasite infects red blood cells causing clinical malaria. However, recent publications have pointed to interactions between the gut microbiota and malaria. With this in mind, the role of the gut microbiota in malaria infection was studied. C57BL/6 mice from different vendors displayed differential resistance and susceptibility to severe malaria, …

Lead And Crime: An Ecological Study Between Lead Contaminated Topsoil And Violent Crime., Brian Guinn

Electronic Theses and Dissertations

Lead is a known neurotoxicant. Human exposure to lead comes primarily through environmental exposures, including remnant lead paint, lead contaminated topsoil and lead contaminated water. Prenatal and early life lead exposure has been associated with numerous neurocognitive and neuropsychiatric disorders. This dissertation presents findings from an ecological study which evaluated the geospatial association between topsoil lead content and the incidence of FBI designated violent crime in Jefferson County, Kentucky. A total of 412 topsoil samples were collected along roadways (n=300) and from Louisville Metro Parks (n=112). Jefferson County crime data was obtained from the Louisville Metro Police Department – Crime …

Is Macrolide And Beta-Lactam Combination Therapy Associated With Early Clinical Stability Or 30 Day Mortality In Hospitalized Patients With Pneumonia? An Assessment Of Confounding By Indication., Evangeline Pierce

Electronic Theses and Dissertations

Pneumonia and influenza are one of the leading causes of infectious disease-related deaths worldwide. Current guidelines for the treatment of hospitalized patients with community acquired pneumonia (CAP) include empiric antimicrobial therapy with a macrolide and a beta-lactam. There is little consensus among studies as to which antimicrobial regimen is best. The confusing results seen may very well be due to lack of assessment of confounding by indication (CBI). This analysis was a secondary analysis from Hospitalized Adults with Pneumococcal Pneumonia: Incidence Study (HAPPI). The study participants were those in HAPPI who had received either macrolide and beta-lactam combination therapy or …

Cd11b Regulation Of B Cell Receptor Signaling In Health And Systemic Lupus Erythematosus., Paul Lorenzo Dascani

Electronic Theses and Dissertations

Loss of function mutation in CD11b has been associated with incidence of systemic lupus erythematosus (SLE), a disease driven by B cell production of pathogenic autoimmune antibody. Our previous work has revealed the ability of CD11b to regulate B cell receptor (BCR) signaling and control autoimmune disease in mice. However, how CD11b regulates the immune response under normal conditions remains unknown. Through the use of a CD11b knockout model, we demonstrated that CD11b-deficient mice have an elevated antigen-specific humoral response in a Th2 type immunization. Deletion of CD11b resulted in elevated serum IgM and IgG antibody, increases in antigen-specific germinal …

Influences Of Porphyromonas Gingivalis On The Viability Of Esophageal Cancer Cells., Muddasir Mohammed

Electronic Theses and Dissertations

A recent study demonstrated an association between the Porphyromonas gingivalis (Pg)infection and the progression of ESCC (Gao et al., 2016). However, how Pg infection affects the nature of ESCC remains unknown. We examined the effects of Pg on the proliferation and chemotherapy drug-induced apoptosis of ESCC cells and elucidated the signaling molecules involved in these processes. Method: Apoptosis and cell proliferation were tested using Flow cytometry and Tetrazolium salt based proliferation assays respectively. Western Blot was utilized to detect the protein expression. CDK2 and Cyclin E were knocked down in the ESCC cells through transfection. Unpaired T-test and …

Effect Of Grape Components On Periodontal Disease., Juili Subodh Shivde

Electronic Theses and Dissertations

Background: Half of the adult American population (47 %) are victims of periodontitis, a chronic inflammatory disease which leads to destruction of the tissues supporting the tooth. Periodontitis is initiated by periodontal pathogens and caused by excessive or prolonged host mediated inflammation. Porphyromonas gingivalisis one important agent implicated in the etiopathogenesis of chronic periodontitis. Pro-inflammatory cytokines induced by periodontal pathogens can cause alveolar bone loss and periodontitis. Bone loss is caused by the imbalance of bone formation and bone resorption. Osteoclasts are major cells that cause bone resorption. Moreover, periodontal inflammation also leads to bone resorption. Grapes are rich …

Synthesis And Characterization Of Targeted Bar Encapsulated Polylactic-Co-Glycolic Acid Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Ranjith Radha Krishnan

Electronic Theses and Dissertations

Periodontal disease is one of the most prevalent infectious diseases worldwide. Between 30-50% of the global adult population suffers from periodontal disease. Some form of periodontitis is present in 46% of American adults, corresponding to annual expenditures in excess of 14 billion dollars for treatment and prevention. Current treatments for periodontal diseases involve mechanical removal of plaque, correction of risk factors, gingival surgery and/or antibiotic therapy. To our knowledge there is no effective therapeutic approach that aims to limit pathogen colonization of the oral biofilm or re-colonization after treatment. Interaction of the pathogen Porphyromonas gingivalis with oral streptococci is critical …

The Role Of Non-Neuronal Acetylcholine In Urogenital Chlamydial Infection, Jessica R. Lockhart

Electronic Theses and Dissertations

Chlamydia trachomatiscauses a bacterial sexually transmitted infection, Chlamydia, that is often chronic and casues reproductive complications in women. We hypothesized that Chlamydia infection increases local acetylcholine (ACh) production, which regulates the host’s inflammatory response to the infection. Female mice infected with C. muridarumwere sacrificed at days 3, 9, 15, and 21 post-infection, genital tract tissues harvested, and immunohistochemistry performed to enumerate ACh-producing cells. Infection increased the number of ACh-producing cells in cervical tissue at days 3,15, and 21 post-infection (pi), uterine tissue at day 3 and 9 pi, and ovarian tissue day 3, 15, and 21 pi. These …

Cannabidiol Alters The Immune Response To Porphyromonas Gingivalis In Mice., Shilpa Singh

Electronic Theses and Dissertations

Background: Porphyromonas gingivalis is an important etiologic agent of chronic periodontitis, an infectious disease defined by destruction of supporting tissues of the teeth. Marijuana is a risk factor for chronic periodontitis, although underlying mechanisms are poorly understood. As phytocannabinoids have been ascribed antiinflammatory properties, we hypothesized that cannabidiol exposure would lead to altered immune response to P. gingivalis infection facilitating bacterial persistence and, subsequently, increased alveolar bone loss in cannabidiol (CBD)-exposed mice. Methods: P. gingivalis-infected cannabinoid receptor 2 (CB2) knockout and wild type C57/Bl6 mice were exposed, or not exposed, to cannabidiol. Oral swabs from mice were used to monitor …

Social Determinants Of Health And A Grounded Mixed-Methods Approach To Explain Declining Life Expectancy In Eastern Kentucky : 1980 – 2014., William Renda

Electronic Theses and Dissertations

Trends in life expectancy for the United States from 1980-2014 suggest general improvement overall. However, eastern Kentucky stands out with a cluster of counties experiencing declining life expectancy. Given that life expectancy is an excepted indicator of overall population health, this anomaly in eastern Kentucky warrants investigation. This thesis uses a grounded mixed methods approach to explore this trend across the greater Appalachian region. Content and discourse analysis of interviews with public health and medical professionals in the study area revealed key themes perceived as being related to declining life expectancy, which informed variable selection for regression analysis. Regression models …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

Role Of Ataxia-Telangiectasia Mutated Kinase In Cardiac Autophagy And Glucose Metabolism Under Ischemic Conditions, Patsy Thrasher

Electronic Theses and Dissertations

Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase primarily located in the nucleus, is typically activated in response to DNA damage. Individuals with mutations in ATM gene develop a disease called Ataxia telangiectasia (AT). These individuals are more susceptible to ischemic heart disease and metabolic disorder. Our lab has previously shown that ATM plays a critical role in β-adrenergic receptor (β-AR) - and myocardial infarction (MI)-stimulated myocyte apoptosis and cardiac remodeling. This study tested the hypothesis that ATM plays a critical role in cardiac autophagy and glucose metabolism following MI and ischemia, respectively. Early during MI (4 hours after its onset) …

The Comparison Of Effects Of Synthetic And Natural Arachidin-3 On Rotavirus Infected Cells, Rebekah Napier-Jameson

Electronic Theses and Dissertations

Rotavirus (RV) causes severe, life-threatening diarrhea, in infants, young children and immunocompromised adults. There are several effective vaccines for young children, however they are strain specific and are not protective against many RV strains in developing countries. Therefore, it is important to investigate anti-RV therapeutic agents. Our laboratory has shown arachidin-1 (A1) and arachadin-3 (A3) significantly inhibit RV replication in two cell lines, however the molecular mechanism(s) of action are not known. A synthetic molecule of A3 (sA3) has been produced, but its’ antiviral effects have not been examined. Our hypothesis is that sA3 produces the same effects on RV-infected …

T Socio-Ecology Of Managed Honeybees (Apis Mellifera) In The Louisville Metro Area., Haileigh M. Arnold

Electronic Theses and Dissertations

Humans have a long history of the practice of beekeeping to harness the power of pollination. This managed pollinator system consists of beekeepers, honeybees, and their environment. However, recent disease, pesticide use, and land use factors honeybee threaten this relationship. In the face of such concerns it is important to examine the factors that impact and can help sustain our managed pollinator systems. In this thesis, the national and Kentucky state-level policies that affect managed pollinator systems were examined and socio-ecological factors that may contribute to honeybee hive growth and losses were assessed along an urban development gradient in Louisville, …

Malaria In The Prehistoric Caribbean : The Hunt For Hemozoin., Mallory D. Cox

Electronic Theses and Dissertations

With the increase in resistance to anti-malarials and global warming trends expanding the habitation range of the mosquito vector, research highlighting the biogeographical contexts of infected populations is critical to understanding epidemiological patterns. A bioarchaeological approach to epidemiology can shed light on previous disease patterns and aid in the prediction of future outbreaks of diseases like malaria. Currently, there is no direct evidence of malaria in the Americas prior to European contact; however, skeletal, archaeological, paleoenvironmental, historic, and ethnohistorical evidence strongly suggest the presence of Plasmodium spp. malaria in indigenous Caribbean skeletal remains held in the Yale Peabody Museum of …

Development Of Blended Polymeric Fibers To Alter The Release Of Peptide Targeting Porphyromonas Gingivalis., Sonali Suresh Sapare

Electronic Theses and Dissertations

Periodontitis is a chronic inflammatory disease that infects the tissues of the periodontium. It is estimated that 47.2% or 67.2 million American adults suffer from mild, moderate and severe periodontitis. Globally, 30-50% of the adult population is afflicted with periodontal disease, making it one of the most prevalent infectious diseases in the world. Therapeutics targeting P. gingivalis may be effective to alter periodontitis progression. However, the current treatment modalities that target critical pathogens to maintain host-biofilm homeostasis are limited, urging the development of specifically targeted therapeutics to limit P. gingivalis recolonization of the oral cavity after periodontal treatment and healing. …

Divergent Evolution Of Di-Lysine Er Retention Vs. Farnesylation Motif-Mediated Anchoring Of The Ankb Virulence Effector., John David Perpich

Electronic Theses and Dissertations

Legionella pneumophila is an aquatic organism capable of intracellular replication within a wide range of protozoan hosts and within human macrophages where it causes Legionnaires’ Disease. L. pneumophila manipulates a variety of host cell processes by translocating, into the host cell cytosol, more than 300 effector proteins via the type IVB secretion system (T4SS). The AnkB effector from the AA100/130b strain (AnkB-AA100) contains a C-terminal CaaX motif that rapidly becomes farnesylated upon translocation into the host cell and anchored to the cytosolic face of the Legionella-containing vacuole (LCV) membrane, which is essential for intracellular replication. We show that a …

An Assessment Of The Disaster Preparedness Knowledge Of Emergency Medical Services Providers In Hajj Of 2016., Ahmed Meaiwedh Al-Otaibi

Electronic Theses and Dissertations

Objectives: 1) Assess knowledge regarding disaster preparedness for mass gathering among SRC-EMS providers during the Hajj 2016 2) Explore the relationship between the demographic variables and knowledge about disaster preparedness among SRC-EMS providers during the Hajj 2016 3) Explore the sources of knowledge for SRC-EMS providers about disaster preparedness. Method: The data collection for this study was a cross-sectional survey using an online Qualtrics survey. It was convenience sample of 1650 respondents. For the analyses descriptive statistics was used, one-way ANOVA and Bonferroni correction for multiple comparisons tests, multiple regression analyses, and Pearson’s product coefficients. Results: The main findings in …

Does Spaceflight Increase The Chance Of Female Astronauts Developing Uterine Cancer?, Areej Mosa

Electronic Theses and Dissertations

One of the main questions put forth by NASA and the European Space Agency (ESA) is whether or not an organism, especially mankind, can complete an entire life cycle in space. With this in mind, it is essential to study the effect of spaceflight on reproductive tissues. Using simulated microgravity techniques and whole-body radiation we sought to determine if females subjected to a simulated spaceflight environment have increased incidences of uterine cancer. Uterine tissue from mice subjected to simulated spaceflight was analyzed using immunohistochemical staining and western blot analysis. Two pathways commonly activated in cancer were investigated. Additionally, the uterine …

Hiv-Related Knowledge, Attitudes, And Behaviors In Two Low Resource Settings, Candice Lynn Collins

Electronic Theses and Dissertations

Two Human Immunodeficiency Virus (HIV) outbreaks occurred almost simultaneously in the United States (US) (2014-2015) and in Cambodia (2015). Information is lacking on HIV-related knowledge, stigmatizing attitudes, and high-risk behaviors (KAB) among the general population, which may affect the transmission of HIV and lead to outbreaks. The current study aimed to: 1) assess KAB among the general population in a high-risk county in the US, 2) analyze KAB among the general population of Cambodia, and 3) compare KAB across samples from a high-risk county in Northeast Tennessee and a province in Cambodia. Tennessee data were collected in 2017 and Cambodian …