Digital Commons Network^™

Mice With Infectious Colitis Exhibit Linear Growth Failure And Subsequent Catch-Up Growth Related To Systemic Inflammation And Igf-1, Mark D. Deboer, Vidhya Vijayakumar, Meiqing Gong, John L. Fowlkes, Rachel M. Smith, Fernando Ruiz-Perez, James P. Nataro

Barnstable Brown Diabetes Center Faculty Publications

In developing communities, intestinal infection is associated with poor weight gain and linear-growth failure. Prior translational animal models have focused on weight gain investigations into key contributors to linear growth failure have been lacking. We hypothesized that murine intestinal infection with Citrobacter-rodentium would induce linear-growth failure associated with systemic inflammation and suppressed serum levels of insulin-like growth factor-1 (IGF-1). We evaluated 4 groups of mice infected or sham-infected on day-of-life 28: uninfected-controls, wild-type C.-rodentium-infected, partially-attenuated C. rodentium-infected (with deletion of 3 serine protease genes involved in colonization), and pair-fed (given the amount of daily food consumed by the …

Understanding The Influence Of Stigma And Discrimination For The Functional Limitation Severity - Psychological Distress Relationship: A Stress And Coping Perspective, Robyn Lewis Brown

Sociology Faculty Publications

No abstract provided.

Acceptability Of Hiv Testing Sites Among Rural And Urban African Americans Who Use Cocaine, D. Keith Branham, Tyrone F. Borders, Katharine E. Stewart, Geoffrey M. Curran, Brenda M. Booth

Health Management and Policy Faculty Publications

African Americans (AAs) who use cocaine in the Southern region of the U.S. have a relatively high risk of HIV and need for HIV testing. Among this group, those residing in rural areas may have less favorable opinions about common HIV testing sites, which could inhibit HIV testing. We examined rural/urban variations in their acceptability of multiple HIV testing sites (private physician clinic, local health department, community health center, community HIV fair, hospital emergency department, blood plasma donation center, drug abuse treatment facility, and mobile van or community outreach worker). Results from partial proportional odds and logistic regression analyses indicate …

Nephrotoxicity During Vancomycin Therapy In Combination With Piperacillin-Tazobactam Or Cefepime, Wilbur Cliff Rutter, Jessica N. Cox, Craig A. Martin, Donna R. Burgess, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in …

Pneumocystis Infection Alters The Activation State Of Pulmonary Macrophages, Jessica M. Deckman, Cathryn J. Kurkjian, Joseph P. Mcgillis, Theodore J. Cory, Susan E. Birket, Linda M. Schutzman, Brian S. Murphy, Beth A. Garvy, David J. Feola

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Recent studies show a substantial incidence of Pneumocystis jirovecii colonization and infection in patients with chronic inflammatory lung conditions. However, little is known about the impact of Pneumocystis upon the regulation of pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages towards an alternatively activated macrophage-like phenotype. Genetically engineered mice that lack the ability to signal through IL-4 and IL-13 were used to show that Pneumocystis alternative macrophage activation is dependent upon signaling through these cytokines. To determine whether Pneumocystis-induced macrophage polarization would impact subsequent immune responses, we infected mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14 …

Radiation Induced Apoptosis Of Murine Bone Marrow Cells Is Independent Of Early Growth Response 1 (Egr1), Karine Z. Oben, Beth W. Gachuki, Sara S. Alhakeem, Mary Kathryn Mckenna, Ying Liang, Daret K. St. Clair, Vivek M. Rangnekar, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

An understanding of how each individual 5q chromosome critical deleted region (CDR) gene contributes to malignant transformation would foster the development of much needed targeted therapies for the treatment of therapy related myeloid neoplasms (t-MNs). Early Growth Response 1 (EGR1) is a key transcriptional regulator of myeloid differentiation located within the 5q chromosome CDR that has been shown to regulate HSC (hematopoietic stem cell) quiescence as well as the master regulator of apoptosis—p53. Since resistance to apoptosis is a hallmark of malignant transformation, we investigated the role of EGR1 in apoptosis of bone marrow cells; a cell population from which …

Detection Of Strongylus Vulgaris In Equine Faecal Samples By Real-Time Pcr And Larval Culture – Method Comparison And Occurrence Assessment, A. Kaspar, K. Pfister, Martin K. Nielsen, C. Silaghi, H. Fink, M. C. Scheuerle

Veterinary Science Faculty Publications

Background: Strongylus vulgaris has become a rare parasite in Germany during the past 50 years due to the practice of frequent prophylactic anthelmintic therapy. To date, the emerging development of resistance in Cyathostominae and Parascaris spp. to numerous equine anthelmintics has changed deworming management and the frequency of anthelmintic usage. In this regard, reliable detection of parasitic infections, especially of the highly pathogenic S. vulgaris is essential. In the current study, two diagnostic methods for the detection of infections with S. vulgaris were compared and information on the occurrence of this parasite in German horses was gained. For this purpose, …

Functional And Structural Studies On The Neisseria Gonorrhoeae Gmha, The First Enzyme In The Glycero-Manno-Heptose Biosynthesis Pathways, Demonstrate A Critical Role In Lipooligosaccharide Synthesis And Gonococcal Viability, Igor H. Wierzbicki, Ryszard A. Zielke, Konstantin V. Korotkov, Aleksandra E. Sikora

Molecular and Cellular Biochemistry Faculty Publications

Sedoheptulose-7-phosphate isomerase, GmhA, is the first enzyme in the biosynthesis of nucleotide-activated-glycero-manno-heptoses and an attractive, yet underexploited, target for development of broad-spectrum antibiotics. We demonstrated that GmhA homologs in Neisseria gonorrhoeae and N. meningitidis (hereafter called GmhA_GC and GmhA_NM, respectively) were interchangeable proteins essential for lipooligosaccharide (LOS) synthesis, and their depletion had adverse effects on neisserial viability. In contrast, the Escherichia coli ortholog failed to complement GmhA_GC depletion. Furthermore, we showed that GmhA_GC is a cytoplasmic enzyme with induced expression at mid-logarithmic phase, upon iron deprivation and anaerobiosis, and conserved in contemporary gonococcal …

Addendum Guidelines For The Prevention Of Peanut Allergy In The United States: Report Of The National Institute Of Allergy And Infectious Diseases–Sponsored Expert Panel, Alkis Togias, Susan F. Cooper, Maria L. Acebal, Amal Assa'ad, James R. Baker, Lisa A. Beck, Julie Block, Carol Byrd-Bredbenner, Edmond S. Chan, Lawrence F. Eichenfield, David M Fleischer, George J. Fuchs Iii, Glenn T. Furuta, Matthew J. Greenhawt, Ruchi S. Gupta, Michele Habich, Stacie M. Jones, Kari Keaton, Antonella Muraro, Marshall Plaut, Lanny J. Rosenwasser, Daniel Rotrosen, Hugh A. Sampson, Lynda C. Schneider, Scott H. Sicherer, Robert Sidbury, Jonathan Spergel, David R. Stukus, Carina Venter, Joshua A. Boyce

Pediatrics Faculty Publications

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy.

Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy …

Immune Evasion By Division Of Labor: The Trophic Life Cycle Stage Of Pneumocystis Murina Suppresses Innate Immunity To This Opportunistic, Fungal Pathogen, Heather M. Evans

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts, including AIDS patients. Pneumocystis species have a biphasic life cycle consisting of single-nucleated trophic forms and ascus-like cysts. Both stages live within the host, and, thus, must contend with threats from the host immune system. The cyst cell wall β-glucans have been shown to stimulate immune responses in lung epithelial cells, dendritic cells and alveolar macrophages. Little is known about how the trophic life forms, which do not have a fungal cell wall, interact with immune cells. In this study, the immune response to the life cycle …

Differences In Behavioral And Physiological Variables Measured With Precision Dairy Monitoring Technologies Associated With Postpartum Diseases, I Ching Tsai

Theses and Dissertations--Animal and Food Sciences

The transition period is defined as the three weeks before and three weeks after the cow calves. Transition cow diseases are considered production diseases. Precision dairy monitoring (PDM) technologies measure physiological, behavioral, and production indicators on individual animals to improve management strategies and farm performance. The objective of the first study was to assess how hypocalcemia, hyperketonemia, and metritis affected variables measured by PDM technologies. The objective of the second study was to use variables from multiple commercially available PDM to examine alert performance generated from different analyses.

Methods For Determining Time To Return To Play After Recreational Injury In Field And Court Sport Athletes, Sarah N. Morris

Theses and Dissertations--Epidemiology and Biostatistics

An observational study was used to illustrate the application of time to event analysis methods to return to play; a secondary data analysis of athlete injury data from the High School RIO^TM Injury Surveillance System (ISS) database was conducted. National Athletic Trainers’ Association (NATA)-certified athletic trainers from approximately 100 high schools in the US enroll their school in the system and complete the online “Exposure Report Form” for reportable injuries each week. New lateral ankle sprains and single-ligament knee injuries experienced by high school athletes during regularly scheduled participation in school-sanctioned sports for seven academic years (2005-2006 through 2011-2012) …

Bis(N-Amidinohydrazones) And N-(Amidino)-N'-Aryl-Bishydrazones: New Classes Of Antibacterial/Antifungal Agents, Sanjib K. Shrestha, Liliia M. Kril, Keith D. Green, Stefan Kwiatkowski, Vitaliy M. Sviripa, Justin Robert Nickell, Linda Phyliss Dwoskin, David S. Watt, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicr obial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step, resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of …

Evaluating Adherence To The Sepsis Bundle And The Effectiveness Of Best Practice Alerts, Kate M. Burnett

DNP Projects

PURPOSE: To evaluate the adherence to the CMS sepsis recommendations and sepsis bundle used by the study health system before and after the implementation of Best Practice Alerts (BPAs) and assessing the effect of these alerts on patient outcomes.

METHODS: The study was a single-center, process evaluation through a retrospective chart review within a southwest healthcare system. The sample consisted of 73 patients for the pre-implementation period (May 1, 2016-September 7, 2016) and 75 patients for the post-implementation period (September 8, 2016-April 30, 2017).

RESULTS: No major differences were found between the two groups with regard to patient age, ethnicity, …

The Effect Of A Patient And Provider Education Program On Antibiotic Overuse In Respiratory Tract Infections In A Rural Primary Care Population, Erin Chiswell

DNP Projects

Objective: In the “walk-in” portion of the Jessamine Medical and Diagnostic Center (JMC) primary care (PC) practice in Jessamine County, Kentucky, a combination patient and provider education program was implemented to assess its effects on antibiotic prescribing in respiratory tract infections (RTIs). The goal was to conduct an evaluation of the patient and provider education program at JMC, by specifically examining changes in immediate antibiotic prescribing in RTI (i.e., prescription given during visit to start taking immediately) one-year after implementation of the education program (March 1, 2015- February 28, 2016).

Methods: Utilizing a quasi-experimental pretest-posttest design, a retrospective electronic medical …

Spatio-Temporal Analysis Of Childhood Retinoblastoma And Cns Tumors In Kentucky, From 1995 Through 2014, Jennifer A. Khoury

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Objectives

Childhood cancer poses a significant public health burden, both globally and in the United States (US). The most common childhood cancers affect the brain and central nervous system (CNS). Age-adjusted childhood brain tumor (CBT) incidence rates in Kentucky are larger than in the rest of the US; these rates are also higher in Appalachian Kentucky than in the rest of the state. This study determined if high-rate clusters of either CNS tumor or retinoblastoma existed in Kentucky.

Methods

Data for this study were retrieved from the Kentucky Cancer Registry for the years 1995 through 2014. Cases were individuals between …

Implementing Medicaid Health Homes To Provide Medication Assisted Treatment To Opioid Dependent Medicaid Beneficiaries, Page M. Smith

Kentucky Law Journal

No abstract provided.

Cellular And Molecular Mechanisms Underlying Alcohol-Induced Aggressiveness Of Breast Cancer, Yongchao Wang, Mei Xu, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Breast cancer is a leading cause of morbidity and mortality in women. Both Epidemiological and experimental studies indicate a positive correlation between alcohol consumption and the risk of breast cancer. While alcohol exposure may promote the carcinogenesis or onset of breast cancer, it may as well enhance the progression and aggressiveness of existing mammary tumors. Recent progress in this line of research suggests that alcohol exposure is associated with invasive breast cancer and promotes the growth and metastasis of mammary tumors. There are multiple potential mechanisms involved in alcohol-stimulated progression and aggressiveness of breast cancer. Alcohol may increase the mobility …

Effects Of Chromium On Mouse Splenic T Lymphocytes And Effects Of Ethanol Exposure During Early Neurodevelopment On Behaviors In Mice, Lu Dai

Theses and Dissertations--Toxicology and Cancer Biology

The dissertation consists of three major projects with the focus on the immunotoxicity of chromium and the behavior disorders caused by early ETOH exposure respectively.

Hexavalent chromium [Cr(VI)] is widely used in various industrial processes and has been recognized as a carcinogen. As the first line of host defense system, the immune system can be a primary target of Cr(VI). T cell population represents a major arm of the immune system that plays a critical role in host anti-tumor immunity. Dysfunction of T cells compromises host anti-tumor immunity resulting in oncogenesis. Using mouse splenic T cells as an in vitro …

Compliance And Treatment Failure Of Hepatitis C With Direct-Acting Antivirals: A 2-Year Retrospective, Observational Study In Kentucky Medicaid Patients, Juequan Nie

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: New generation Direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C infection have been on the market for more than 3 years since late 2013. Whether these medications cure patients at the rates claimed in clinical trials is not clear. Furthermore, as compliance is known to affect treatment outcomes, DAAs compliance rate is worth studying.

Methods: We analyzed the association of social-demographic, DAA use, enrollment with Kentucky Medicaid Managed Care Organizations (MCOs) and comorbidities, and DAA compliance in 1128 Kentucky Medicaid members treated with DAAs between August 07, 2014 and August 06, 2016.

Results: Age, MCOs, liver fibrosis …

Vaccine-Preventable Disease Surveillance In Kentucky, Katherine Jay

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background: Vaccine-preventable disease (VPD) surveillance is important component to the success of vaccines. This report examines the levels of 13 of these VPDs in the state of Kentucky from 2005 to 2015.

Methods: All reported cases in the state of Kentucky for the years 2005 to 2015 of 13 vaccine-preventable diseases were obtained from the Disease Surveillance Module (DSM) and the National Electronic Disease Surveillance System (NEDSS). Where enough cases were reported, descriptive statistics were prepared. For acute hepatitis B and pertussis, more thorough analysis was performed.

Results: Rates of acute hepatitis B in Kentucky from 2005 …

Dusty Occupations And Pulmonary Obstruction In Kentucky: A Proportionate Mortality Analysis, Neil Bradford Horsley

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. Occupational exposure to vapors, gases, dusts, or fumes (VGDFs), in combination with smoking, significantly increases the risk of developing COPD. Amongst agricultural workers, exposure to pesticides has been found to cause significantly elevated rates of annual decline in lung function, ultimately leading to a clinical diagnosis of pulmonary obstruction if the period of exposure is sufficient.

Purpose

It is hypothesized that, when compared to the standard population, workers in “dusty” occupations (where VGDF workplace exposure is significant) die at significantly elevated rates from …

Hepatitis C Screening And Treatment Of Prisoners: Analysis Of Policy And Practice In Kentucky, Charity Faith Kranz

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

INTRODUCTION

The United States and the Commonwealth of Kentucky are currently overwhelmed by a triad of complex epidemics—incarceration, opioid overdose deaths secondary to substance use disorders, and hepatitis C. Research has suggested hepatitis C screening and treatment of prisoners may be a cost-effective strategy to address the hepatitis C epidemic. Since Kentucky has been particularly impacted by these interrelated health threats, further exploration of hepatitis C in Kentucky prison populations and their potential role in addressing these epidemics is warranted.

Primary Objective

The main goal of this research was to examine hepatitis C screening and treatment policy and practice within …

Precision Dairy Farming Technology Solutions For Detecting Dairy Cow Disease To Improve Dairy Cow Well-Being, Amanda Stone

Theses and Dissertations--Animal and Food Sciences

Dairy cow health is multifactorial and complex. High producing dairy cows have been described as metabolic athletes, but metabolic and infectious diseases around calving affect many cows. These diseases have drastic negative effects on dairy cow well-being, milk production, and dairy farm economics. Early disease detection could potentially improve disease management, treatment, and future prevention techniques. The first objective of this research was to evaluate the use of activity, lying behavior, reticulorumen temperature, and rumination time determined by precision dairy farming technologies to detect transition cow diseases including hypocalcemia, ketosis, and metritis. The second objective was to evaluate the ability …

Synthesis And Characterization Of Poly(Simvastatin) - Incorporated Copolymers And Blends For Bone Regeneration, Theodora Asafo-Adjei

Theses and Dissertations--Biomedical Engineering

Common biodegradable polyesters such as poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) are used as drug delivery vehicles for tissue regenerative applications. However, they are typically bioinert, with drug loading limitations. Polymerizing the active agent or precursor into its respective biodegradable polymer would control drug loading via molar ratios of drug to initiator used for synthesis. Simvastatin was chosen due to its favorable anti-inflammatory, angiogenic, and osteogenic properties. In addition, its lactone ring lends itself to ring-opening polymerization and, consequently, the synthesis of poly(simvastatin) with controlled simvastatin release.

Simvastatin was first polymerized with a 5kDa methyl-terminated poly(ethylene glycol) …

Role Of Intracellular Growth During The Gastrointestinal Stage Of Listeria Monocytogenes Infection, Grant Steven Jones

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Listeria monocytogenes is a facultative intracellular bacterium that causes foodborne disease in humans. L. monocytogenes invade the gut mucosa and then disseminate, causing systemic infections associated with high mortality rates in immunocompromised individuals. It is unknown how L. monocytogenes traffic to the mesenteric lymph nodes, which represent an important bottleneck for systemic spread. In addition, little is known about the gastrointestinal stage of infection due to the general resistance of mice to oral infection with L. monocytogenes. Our laboratory developed a novel foodborne mouse model of listeriosis utilizing a murinized strain of L. monocytogenes to investigate the gastrointestinal stage …

Novel Role Of Prostate Apoptosis Response-4 Tumor Suppressor In B-Cell Chronic Lymphocytic Leukemia, Mary Kathryn Mckenna

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Chronic Lymphocytic Leukemia (CLL) is defined by the accumulation of clonally expanded CD5+ and CD19+ B lymphocytes in blood and secondary lymphoid organs with impaired apoptotic mechanisms. CLL represents one third of all leukemia cases with an average age of 72 years at diagnosis making it the most common adult leukemia. The Eµ-Tcl1 mouse serves as an excellent model to study the development of CLL as they progress to a CLL like disease by 9-14 months of age, due to overexpression of an oncogene, T cell Leukemia 1(Tcl1), specifically in B cells through the Ig VH promoter and Eµ enhancer …

Social Determinants Of Health And Disparities In Outcomes Related To Cardiovascular Health In Vulnerable Populations, Jennifer L. Miller

Theses and Dissertations--Nursing

The purpose of this dissertation was to explore the mechanism of association between social determinants of health (SDH), particularly limited health literacy, and disparate outcomes related to cardiovascular disease in vulnerable populations. Specific aims were to 1) compare quality of life (QOL), anxiety, and depressive symptoms between genders in implantable cardioverter defibrillator (ICD) recipients; 2) examine the association between multi-morbidity burden and QOL; 3) determine whether health literacy levels independently predict CVD risk in the male prison population; 4) examine the relationship between health literacy and decisiveness regarding end of life (EOL) choices, and 5) examine SDH as predictors of …

Pneumococcal Conjugate Vaccine 13 Coverage In Children, High-Risk Adults 19-64 Years Of Age, And Adults Over 65 Years Of Age In A Commercially Insured U.S. Population, Joseph C. Vanghelof

Theses and Dissertations--Pharmacy

This thesis aimed to elucidate the demographic characteristics associated with elevated or reduced rates of pneumococcal conjugate 13 (PCV13) vaccination.

A retrospective cohort study was performed using the Truven Health MarketScan® Database. Three cohorts were created corresponding to populations for which the CDC recommends PCV13 vaccination. Cohort 1: children < 36 months of age. Cohort 2: adults 19-64 years of age with high infection risk. Cohort 3: adults > 65 years of age. Odds of having a PCV13 claim were calculated for each cohort.

For Cohort 1, 78% out of a total of 353,214 subjects had a sufficient number of PCV13 doses to meet CDC recommendations. For Cohort 2, 3.7% out of a total of 673,157 subjects had a PCV13 …

Effects Of In Utero Nicotine Exposure On Immune Cell Disposition After P. Aeruginosa Lung Infection, Nayon Kang

Theses and Dissertations--Pharmacy

Current smoking cessation guidelines recommend nicotine replacement therapy (NRT) to assist pregnant smokers to quit, but this is without strong evidence for effectiveness and safety. Nicotine, the main addictive component of tobacco, is known to exert physiological effects by binding to its receptor, the nicotinic acetylcholine receptor (nAChR). Recent studies have identified the presence of nAChRs in non-neuronal cells, and in macrophages, functional alteration upon stimulation with nicotine has been documented.

To understand the impact of in utero nicotine exposure on various immune cell disposition and function, we designed preliminary studies using an in vivo model of P. aeruginosa infection. …