Medicine and Health Sciences Commons^™

Equine Influenza Virus And Vaccines, Fatai S. Oladunni, Saheed Oluwasina Oseni, Luis Martinez-Sobrido, Thomas M. Chambers

Veterinary Science Faculty Publications

Equine influenza virus (EIV) is a constantly evolving viral pathogen that is responsible for yearly outbreaks of respiratory disease in horses termed equine influenza (EI). There is currently no evidence of circulation of the original H7N7 strain of EIV worldwide; however, the EIV H3N8 strain, which was first isolated in the early 1960s, remains a major threat to most of the world’s horse populations. It can also infect dogs. The ability of EIV to constantly accumulate mutations in its antibody-binding sites enables it to evade host protective immunity, making it a successful viral pathogen. Clinical and virological protection against EIV …

Human Apobec3 Variations And Viral Infection, Shiva Sadeghpour, Saeideh Khodaee, Mostafa Rahnama, Hamzeh Rahimi, Diako Ebrahimi

Plant Pathology Faculty Publications

Human APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) enzymes are capable of inhibiting a wide range of endogenous and exogenous viruses using deaminase and deaminase-independent mechanisms. These enzymes are essential components of our innate immune system, as evidenced by (a) their strong positive selection and expansion in primates, (b) the evolution of viral counter-defense mechanisms, such as proteasomal degradation mediated by HIV Vif, and (c) hypermutation and inactivation of a large number of integrated HIV-1 proviruses. Numerous APOBEC3 single nucleotide polymorphisms, haplotypes, and splice variants have been identified in humans. Several of these variants have been reported to be associated …

Identification Of A Ruminant Origin Group B Rotavirus Associated With Diarrhea Outbreaks In Foals, Tirth Uprety, Chithra C. Sreenivasan, Ben M. Hause, Ganwu Li, Solomon O. Odemuyiwa, Stephan Locke, Jocelynn Morgan, Li Zeng, William F. Gilsenan, Nathan Slovis, Laurie Metcalfe, Craig N. Carter, Peter J. Timoney, David W. Horohov, Dan Wang, Erdal Erol, Emma Adam, Feng Li

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine rotavirus group A (ERVA) is one of the most common causes of foal diarrhea. Starting in February 2021, there was an increase in the frequency of severe watery to hemorrhagic diarrhea cases in neonatal foals in Central Kentucky. Diagnostic investigation of fecal samples failed to detect evidence of diarrhea-causing pathogens including ERVA. Based on Illumina-based metagenomic sequencing, we identified a novel equine rotavirus group B (ERVB) in fecal specimens from the affected foals in the absence of any other known enteric pathogens. Interestingly, the protein sequence of all 11 segments had greater than 96% identity with group B …

Concurrent Covid-19 Infection In Children With Acute Appendicitis: A Report Of Three Cases, Maximo J. Acevedo, Dylan Steffey, Johanne E. Dillon, James T. Lee, David J. Worhunsky

Radiology Faculty Publications

Literature describing patients with concomitant COVID-19 infection with acute appendicitis in pediatric patients is growing, and understanding the clinical picture of such patients is relevant in their treatment. We report 3 male children who were surgically treated for acute appendicitis and had concomitant SARS-CoV-2 infection. Our first patient was a 12-year-old male who presented with symptoms indicative of appendicitis but no respiratory symptoms associated with COVID-19 (eg cough, shortness of breath). Laboratory evaluation revealed leukopenia and an elevated C-reactive protein; imaging was consistent with acute appendicitis and an acute pulmonary viral infection. Though he lacked diffuse peritonitis on physical examination …

Effect Of Clinical Isolate Or Cleavage Site Mutations In The Sars-Cov-2 Spike Protein On Protein Stability, Cleavage, And Cell-Cell Fusion, Chelsea T. Barrett, Hadley E. Neal, Kearstin Edmonds, Carole L. Moncman, Rachel Thompson, Jean M. Branttie, Kerri Beth Boggs, Cheng-Yu Wu, Daisy W. Leung, Rebecca E. Dutch

Molecular and Cellular Biochemistry Faculty Publications

The trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2-infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. A furin cleavage site at the border between the S1 and S2 subunits (S1/S2) has …

An Inactivated Bacterium (Paraprobiotic) Expressing Bacillus Thuringiensis Cry5b As A Therapeutic For Ascaris And Parascaris Spp. Infections In Large Animals, Joseph F. Urban, Martin K. Nielsen, David Gazzola, Yue Xie, Ethiopia Beshah, Yan Hu, Hanchen Li, Florentina Rus, Kelly Flanagan, Austin Draper, Sridhar Vakalapudi, Robert W. Li, Gary R. Ostroff, Raffi V. Aroian

Maxwell H. Gluck Equine Research Center Faculty Publications

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus …

Piglet Immunization With A Spike Subunit Vaccine Enhances Disease By Porcine Epidemic Diarrhea Virus, Jieshi Yu, Chithra Sreenivasan, Tirth Uprety, Rongyuan Gao, Chen Huang, Ella J. Lee, Steven Lawson, Julie Nelson, Jane Christopher-Hennings, Radhey S. Kaushik, Eric Nelson, Diego G. Diel, Ben M. Hause, Feng Li, Dan Wang

Maxwell H. Gluck Equine Research Center Faculty Publications

Immunization with an insect cell lysate/baculovirus mixture containing recombinant porcine epidemic diarrhea virus (PEDV) spike protein induced high levels of neutralizing antibodies in both mice and piglets. However, immunization of piglets with this vaccine resulted in enhancement of disease symptoms and virus replication in vaccine recipients exposed to PEDV challenge. Thus, these observations demonstrate a previously unrecognized challenge of PEDV vaccine research, which has important implications for coronavirus vaccine development.

Therapeutic Development Of Group B Streptococcus Meningitis By Targeting A Host Cell Signaling Network Involving Egfr, Ningyu Zhu, Chengxian Zhang, Atish Prakash, Zheng Hou, Wei Liu, Weifeng She, Andrew J. Morris, Kwang Sik Kim

Gill Heart & Vascular Institute Faculty Publications

Group B Streptococcus (GBS) remains the most common Gram‐positive bacterium causing neonatal meningitis and GBS meningitis continues to be an important cause of mortality and morbidity. In this study, we showed that GBS penetration into the brain occurred initially in the meningeal and cortex capillaries, and exploits a defined host cell signaling network comprised of S1P₂, EGFR, and CysLT1. GBS exploitation of such network in penetration of the blood–brain barrier was demonstrated by targeting S1P₂, EGFR, and CysLT1 using pharmacological inhibition, gene knockout and knockdown cells, and gene knockout animals, as well as interrogation of the …

Characterizing The Physiology And Genetics Of Contact Dependent Growth Inhibiton Systems In Burkholderia Species, Alice Elizabeth Oates

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

Contact-dependent growth inhibition (CDI) systems mediate interbacterial competition. The genes encoding these systems are widespread among Gram-negative bacteria, including Burkholderia pathogens. CDI systems of Burkholderia species are composed of two-partner secretion pathway proteins and function to deliver the toxic C-terminus of a polymorphic surface-exposed exoprotein BcpA (Burkholderia CDI protein A) to the cytoplasm of neighboring recipient bacteria upon cell-cell contact. Specific outer and inner membrane proteins facilitate BcpA translocation both out of the donor bacterium and into the recipient cell cytoplasm. Most Burkholderia species-specific CDI translocation factors in recipient cells are unknown. BcpA intoxication functions as a mechanism by …

Factors Associated With Lifestyle Modification For Type 2 Diabetes Self-Management And Prevention, Leigh Anne Koonmen

Theses and Dissertations--Nursing

Diabetes is the seventh leading cause of death in the United States, affecting roughly 13% of U.S. adults aged 18 years or older. Type 2 diabetes accounts for 90-95% of all diabetes cases and is characterized by the progressive development of insulin resistance leading to sustained elevated blood glucose levels. Management of type 2 diabetes includes risk-reduction strategies and continuous medical care to prevent the development of complications.

Lifestyle is a major contributing factor to morbidity and mortality rates in the United States. Preventative health behaviors, such as engaging in physical activity, maintaining a healthy weight, and following a healthy …

Effects Of Season And Nutrition On Insulinemic Responses In Insulin Dysregulated Horses, Erica Lyn Macon

Theses and Dissertations--Veterinary Science

Insulin dysregulation (ID) is the main risk factor for the development of hyperinsulinemia-associated laminitis (HAL). ID in the equid has been extensively researched; however, recommendations for diagnosing and managing ID horses have originated from work completed in other models, such as the ID pony and healthy horse. Therefore, our overall objective was to improve current diagnostic tools and nutritional management strategies by investigating the effect of season, the fed and fasted state on the oral sugar test (OST) and dietary nutrient content on insulinemic responses in the ID horse. To address this, four main objectives with three specific aims were …

Pre-Clinical Advancements In Biomarkers, Tools, And Therapeutics For A Metabolic Neurodegenerative Disease, Zoë Simmons

Theses and Dissertations--Molecular and Cellular Biochemistry

Glycogen is the storage form of glucose and a highly important substrate for cellular metabolism. Characterization of the enzymes and mechanisms of glycogen metabolism began over 70 years ago and over the last 20 years, a previously unknown protein called laforin has emerged as an important contributor to glycogen metabolism homeostasis. Multiple labs demonstrated that laforin is a glycogen phosphatase and mutations in the gene encoding laforin cause the formation of aberrant glycogen-like aggregates called Lafora bodies (LBs). LBs are cytoplasmic, water-insoluble aggregates that drive neurodegeneration and early death in Lafora disease (LD) patients. The direct relationship between mutated laforin, …

Human Regulatory T Cells Control Inflammation From Effector T Cells In Prediabetes, Rui Liu

Theses and Dissertations--Pharmacy

Type 2 diabetes (T2D) is a chronic low-grade inflammatory disease. A T cell cytokine profile (Th17) from PBMCs can distinguish obese T2D from obese non-diabetes subjects. Individual T cell subsets interact with each other and the diverse subsets jointly determine overall inflammation. Cellular metabolism drives cytokine production of CD4⁺ T cells, and therefore contributes to inflammation in T2D. However, specific changes in metabolism and function of CD4⁺ T cells during the progression from lean healthy to obese and diabetic stages in people have not been clarified.

We hypothesize that human regulatory T cells (Treg) impact metabolism of effector …

Characterization Of Spontaneous Preeclampsia In The African Green Monkey (Chlorocebus Aethiops Sabaeus), Chelsea Christina Weaver

Theses and Dissertations--Biology

Hypertensive pregnancy disorders are a major contribution to maternal and neonatal mortality worldwide. Two of these disorders, preeclampsia and chronic hypertension in pregnancy, affect up to 10% of all pregnancies. These hypertensive disorders of pregnancy are associated with long-term, postnatal risk factors for both mother and offspring. Despite numerous recent advances in preeclampsia research, the underlying mechanisms are still not understood. This could be due to lack of a spontaneous animal model. This dissertation presents the African Green Monkey (AGM; Chlorocebus aethiops sabaeus) as the first known spontaneous animal model of preeclampsia and a highly translational model of chronic …

Therapeutic Drug Monitoring Of Beta-Lactam Antibiotics In Critically Ill Patients With Sepsis, Melissa Thompson Bastin

Theses and Dissertations--Clinical and Translational Science

Sepsis is a devastating diagnosis affecting over 750,000 patients a year, accounting for approximately 10% of all hospital admissions, costs more than $50,000 per patient, and exceeds $17 billion annual spending. The mortality rate for sepsis remains unacceptably high: one out of every three patients diagnosed with sepsis dies. Sepsis physiology induces physiologic changes to drug pharmacokinetic (PK) parameters that alter the ability to achieve the goal pharmacodynamic (PD) target for beta-lactams of >4-fold unbound concentration above the minimum inhibitory concentration for 100% of the dosing interval (100% fT >4x MIC). Sepsis treatment such as volume resuscitation and vasopressor …

Epigenetic States Regulate Tumor Aggressiveness And Response To Targeted Therapies In Lung Adenocarcinoma, Fan Chen

Theses and Dissertations--Toxicology and Cancer Biology

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide, 85% of which are lung adenocarcinomas (LUAD). Although molecular studies of NSCLC identified targetable mutations of some oncogenes including BRAF, EGFR and ALK, no targeted therapies exist for most cases. Cancer epigenetics is the study of epigenetic modifications, including histone modifications, that control gene expression in cancer. Recent advances have revealed numerous epigenetic abnormalities in human cancers, and targeting epigenetic regulators could be effective at reversing dysregulated epigenetic programs or driving sensitivity to other targeted therapies.

Inhibitors of the histone methyltransferase EZH2 have recently been approved as …

Promotion Of Most Forms Through Education About Importance Of Advance Care Planning In Seriously Ill Patients, Nidhi More

DNP Projects

Abstract

Purpose: To establish the importance of early Advance Care Planning (ACP) and improve the utilization of Medical Orders for Scope of Treatment (MOST) forms in seriously ill patients by educating providers and nurses to identify patients who meet specified criteria. The goals of this intervention are reduction of readmissions and better quality of life for this patient population.

Methods: A quasi-experimental design was used for evaluation of an Educational intervention to promote MOST forms, Advance Directives (AD) and Palliative Care (PC) consults. A retrospective and prospective chart review was conducted to determine the number of patients who met criteria …

Evaluating The Effect Of An Electronic Health Record Patient Portal On The Management Of Hypertension, Ashley Hall

DNP Projects

Background: Hypertension is the leading cause of cardiovascular disease and affects individuals globally, nationally, and locally. Consequences of uncontrolled hypertension include atherosclerosis, heart failure, stroke, and renal disease. The electronic health portal is a patient-specific, interactive tool that has been shown to promote adherence to provider recommendations and improve chronic disease management.

Purpose: The purpose of this project was to determine the effects of education via an electronic healthcare portal on the blood pressure management of adults at a primary care clinic in a small town in Kentucky.

Methods: This study was a one-group pre/post intervention designed to evaluate provider …

Identification Of Infant Feeding Practices In Eastern Kentucky And Southern West Virginia That Correlate With High Weight-For-Length, Havilah R. Adkins

DNP Projects

Background: Approximately 20% of children in the United States are obese. West Virginia and Kentucky rank in the top 10 for obesity rates in children as young as 2-4 years old. Obesity increases the risk for numerous short-term health problems and impacts long-term health, development, quality of life, and life expectancy. Research indicates that obesogenic behaviors can be addressed prior to the development of obesity or significant health problems to prevent, rather than treat. Interventions targeting caregivers of infants younger than 2-years can promote early development of healthy feeding habits that persist through the developmental stages of nutrition. Before a …

An Assessment Of The Carrier State And A Novel Marker Of Leptospira And Abortion In Central Kentucky Horses, Gloria Louise Gellin

Theses and Dissertations--Veterinary Science

Leptospirosis is a reemerging zoonotic infection of worldwide importance and affects all mammals. The bacterium is transmitted to animals and humans by urine, fetal membranes and body fluids. Leptospira shedding in the urine contaminates both soil and water, exposing both humans and animals to the bacterium. Leptospirosis in horses can cause abortion and is one of the etiologies of equine recurrent uveitis which can lead to blindness. Equine leptospiral abortion in Central Kentucky is primarily caused by serovar Pomona, with occasional cases attributed to serovar Grippotyphosa. There are a few reports in the literature attributing abortion to serovar Bratislava in …

Predicting Tomorrow: Optimizing The Early Detection Of Disease And Disease Recovery In Dairy Calves Using Precision Technologies, Melissa Cantor

Theses and Dissertations--Animal and Food Sciences

The leading causes of morbidity and mortality in preweaned dairy calves are diarrhea and bovine respiratory disease complex (BRD). The delayed detection of these diseases in calves can also delay intervention and disease recovery. The overarching objective of this dissertation was to follow a cohort of calves daily for the first 90 days of life for naturally occurring clinical BRD bouts and diarrheal bouts. The objective answered if feeding behaviors and activity levels were different in at-risk calves during BRD development and BRD recovery from an antimicrobial intervention. Furthermore, the potential of colostrum replacer as a feeding intervention strategy to …

Dietary Assessments And Their Association With Psychological Factors, Inflammation, And Cardiovascular Health Outcomes, Junghee Kang

Theses and Dissertations--Nursing

Cardiovascular diseases (CVDs), a group of disorders of the heart and blood vessels, are the leading cause of death worldwide, causing one-third of deaths each year. Diet is one of the most important behavioral risk factors for CVD. The effects of behavioral risk factors, such as diet, may lead to increased blood pressure, increased blood glucose, raised blood lipids, and overweight and obesity. Inflammation contributes to the development of CVD and can be influenced by diet. Dietary assessment indices can measure diet quality from an individual's dietary intake by scoring food and nutrient intakes. However, the mediation effects of diet …

The Gestation Of Health: Environmental Insults, Behavioral Interventions, And Protective Mechanisms, Brittany Breon Rice

Theses and Dissertations--Pharmacology and Nutritional Sciences

Diabetes remains a leading cause of death nationwide despite pharmacological advances. Recent etiological investigations of the disease detail the role of perinatal exposure to environmental contaminants, such as polychlorinated biphenyls (PCBs), in enhancing disease susceptibility. Polychlorinated biphenyl 126, a coplanar PCB, elicits its toxic effects through the aryl-hydrocarbon receptor and the disruption of endocrine signaling. The goal of this dissertation was to focus on delineating the differences in the developmental windows of diabetes susceptibility respective to the timing of PCB126 exposure and to understand the influence of maternal exercise and nuclear-factor erythroid-2-related factor 2 (Nrf2) expression in combating the negative …

Abc Transporters In Glioblastoma: Anticancer Drug Transport And Transporter Regulation At The Blood-Brain Barrier, Julia A. Schulz

Theses and Dissertations--Pharmacy

Glioblastoma is one of the deadliest cancers, with a median survival of only one year. Even after aggressive treatment consisting of surgical resection, radiation, and chemotherapy, most glioblastoma patients suffer from tumor recurrence within 6-9 months. One reason for treatment failure of anticancer drugs is the blood-brain barrier that protects the brain by impeding xenobiotic uptake from the blood. To this end, efflux transporters at the human blood-brain barrier, such as P-glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2), prevent many compounds, including anticancer drugs, from entering the brain. Thus far, approaches to deliver anticancer drugs across the blood-brain barrier …

Identification And Characterization Of Epitope Specific Immune Responses In Humans And Mice, David Henson

Theses and Dissertations--Pharmacy

Cardiovascular disease (CVD) is a major cause of morbidity and mortality around the world causing approximately 14% of total disease burden. A major factor in the progression to major CVD within patients is immune activation, which led to the study of various immune products as potential biomarkers for the prediction of cardiovascular events, including antigen-specific antibodies and immune complexes. One focus of this biomarker research is IgG autoantibodies targeting apolipoprotein A-I (ApoA-I), and several studies of these antibodies have found an association with increased CVD events. Based on the encouraging results from these studies and previous research which has identified …

Rad Modulation Of The L-Type Calcium Channel Confers Systolic Advantage In The Heart, Brooke Mildred Ahern

Theses and Dissertations--Physiology

Heart failure is a major public health problem and a leading cause of mortality. This clinical condition affects populations of all ages, and is the result of various cardiomyopathies. Almost half of these patients suffer specifically from heart failure with reduced ejection fraction; these hearts have decreased performance due to a failure of the heart to contract with sufficient force to meet demand. While there are therapies available to increase contractility, none of these enhance contraction without also further promoting pathological signaling and remodeling.

Under normal physiological conditions, the body elevates cardiac output through the fight-or-flight response. This response activates …

The Role Of Microtubule-Associated Protein Tau In Neuronal Excitability And Epileptogenesis, Ryan A. Cloyd

Theses and Dissertations--Physiology

Tauopathies, including Alzheimer’s disease (AD), are devastating diseases with an immense burden on society which is predicted to increase in coming decades. In addition to progressive loss of memory and cognitive function, patients with tauopathies have a 6-10 fold increase in lifetime risk for seizures, and many are diagnosed with epilepsy. The presence of epileptiform activity on electroencephalogram (EEG) recordings from patients with AD predicts faster cognitive decline compared to patients without abnormal EEG readings. Electrophysiological measurements in murine models of AD have identified neuronal hyperexcitability. Furthermore, reducing tau phosphorylation or expression confers seizure resistance in animal epilepsy models. Although …

Impact Of Smoking And Hpv Status On Cervical Cancer Survival In Women Living In Kentucky, 2004-2005 And 2014-2015, Brittany M. Mckinley

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

BACKGROUND/ OBJECTIVE: Cervical cancer is the fourth most commonly occurring malignancy in women worldwide, with an estimated 530,000 new cases and 270,000 new deaths each year (Small et al, 2017). While the incidence of cervical cancer has decreased by approximately 1.9% per year between 2007 and 2011, the death rate has remained stable (Bernard et al, 2014). Studies have shown that nearly all cervical cancer cases are associated with the Human Papilloma Virus (HPV). Many studies support the association of smoking with increased risk of invasive cervical cancer in women with high-risk HPV (Castle et al, 2002; Fang et al, …

Methenamine Prophylaxis For Recurrent Urinary Tract Infections In A Tertiary Referral Center, Cameron A. Wade

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

Purpose: Methenamine hippurate (MH) is a urinary antiseptic, indicated for prophylaxis of recurrent urinary tract infections (UTIs) but with only few and limited studies regarding its efficacy. To help address this knowledge gap we reviewed our experience with MH for UTI prophylaxis, focusing on women with recurrent uncomplicated UTIs.

Materials and Methods: The University of Kentucky electronic health record was queried to identify adults who were prescribed MH from the Urology clinic between January 2013 and January 2019. Charts were reviewed to assess patient-reported UTI frequency, demographics and relevant health factors. Treatment success was defined as 0-1 UTI in 6 …

Maternal Proximity To Mountaintop Removal Mining And Birth Defects In Appalachian Kentucky, 1997-2003, Daniel B. Cooper

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

Background: Extraction of coal through mountaintop removal mining (MTR) alters many dimensions of the landscape, and explosive blasts, exposed rock, and coal washing have the potential to pollute air and water with substances known to increase risk of developmental and birth anomalies. Previous research suggests that infants born to mothers living in MTR coal mining counties have higher prevalence of most types of birth defects.

Objectives: This study seeks to examine further the relationship between MTR activity and birth defects by employing individual level exposure estimation through precise satellite data of MTR activity in the Appalachian region and maternal residence …