Medicine and Health Sciences Commons^™

Anabolic Properties Of The Progestin Altrenogest And Its Regulation As An Environmental Substance In Horse Racing – Review And Analysis, Andreas F. Lehner, Levent Dirikolu, Sarah Jacob, Kimberly Brewer, Abelardo Morales Briceñoe, Robert Holland, George Maylin, Clara Fenger, Thomas Tobin

Maxwell H. Gluck Equine Research Center Faculty Publications

Altrenogest is a progestogen substance used in equine medicine for the synchronization of ovulation during the spring breeding season and the control of estrus in mares. It accomplishes its actions by down-regulation of endometrial progesterone receptors and repression of estrogen receptor transcriptional activation. However, various groups have also measured androgen receptor binding activity for altrenogest in vitro; these findings combined with androgenic and anabolic properties roughly 1/20 in potency of testosterone and its structural similarity to the anabolic steroid trenbolone have created concerns among racing authorities of altrenogest’s potential abilities to alter the outcome of equine athletic performance, even though …

Development Of An Artificial Intelligence Powered Software For Automated Analysis Of Skeletal Muscle Ultrasonography, Zoe Calulo Rivera, Felipe González-Seguel, Arimitsu Horikawa-Strakovsky, Catherine Granger, Aarti Sarwal, Sanjay Dhar, George Ntoumenopoulos, Jin Chen, V. K. Cody Bumgardner, Selina M. Parry, Kirby P. Mayer, Yuan Wen

Center for Muscle Biology Faculty Publications

Muscle ultrasound has high utility in clinical practice and research; however, the main challenges are the training and time required for manual analysis to achieve objective quantification of muscle size and quality. We aimed to develop and validate a software tool powered by artificial intelligence (AI) by measuring its consistency and comparability of expert manual analysis quantifying lower limb muscle ultrasound images. Quadriceps complex (QC) and tibialis anterior (TA) muscle images of healthy, intensive care unit, and/or lung cancer participants were captured with portable devices. Manual analyses of muscle size and quality were performed by experienced physiotherapists taking approximately 24 …

The Effect Of Fructose Metabolism On Hepatic De Novo Lipogenesis And Adipose Tissue Insulin Resistance, Taghreed Ibrahim Fadhul

Theses and Dissertations--Nutritional Sciences

There is a worldwide epidemic of obesity and metabolic dysfunction. The root cause of obesity is driven by a positive energy balance, which is a consequence of increased caloric intake and decreased energy expenditure. Energy intake is the more dominant force, as increasing energy expenditure is a time-consuming and labor-intensive process. The caloric surplus can be mainly accounted for by increased consumption of high-fat and high-sugar diets. While the risks associated with fat consumption are well-documented, the impact of sugar intake is less understood.

Fructose is a simple sugar widely consumed in modern diets. Its intake has been associated with …

Antibiotic Alternatives And Next-Generation Therapeutics For Salmonella Control: A One Health Approach To Combating Antimicrobial Resistance, Mohamed Saleh, Ashutosh Verma, Khaled A. Shaaban, Yosra A. Helmy

Veterinary Science Faculty Publications

The growing prevalence of antimicrobial resistance has significantly compromised the efficacy of conventional antibiotic-based interventions in controlling Salmonella infections across human and veterinary settings. This growing challenge necessitates a strategic rethinking of pathogen control, prompting the integration of next-generation therapeutics capable of disrupting Salmonella pathogenesis through novel, antibiotic-sparing mechanisms. In this context, a diverse array of emerging alternatives, including bacteriophages, antimicrobial peptides, probiotics, prebiotics, short-chain fatty acids, nanoparticles, and host-directed immunomodulators, have gained prominence as a promising frontier in non-antibiotic therapeutics. These modalities offer targeted approaches to inhibit Salmonella colonization, virulence expression, and persistence, while minimizing collateral damage to the …

Community-Engaged Approach To Improve Food Access And Consumption Of Fruits And Vegetables In A Rural Appalachian Community, Courtney Luecking, Makenzie Barr, Dawn Brewer, Kathryn M. Cardarelli

Dietetics and Human Nutrition Faculty Publications

Background/Objectives: Community–academic partnerships offer unique opportunities to leverage expertise and resources to modify structural factors that address community priorities. However, few in-depth examples of successful partnerships in rural communities to improve food security are available. This manuscript describes the process of building a partnership to reduce food insecurity in a rural Kentucky community.

Methods: The research team worked with Cooperative Extension to form a community advisory board (CAB) representative of diverse sectors of the community who had interest in food security, agriculture, and/or nutrition. The CAB convened regularly, in-person or virtually, to review community assessment information and identify, select, and …

Crystal Structures And Low-Affinity Complex Formation Of Halogenase Ctcp And Fad Reductase Ctcq From The Chlortetracycline Biosynthetic Pathway, Caixia Hou, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Publications

Enzymatic halogenation in natural products has been intensely investigated due to its potential utility as a tool to improve pharmacological and pharmaceutical properties of drug leads. Chlortetracycline (CTC), the first tetracycline (TC) antibiotic discovered nearly eight decades ago, contains a chlorine group. This chlorine is installed enzymatically by the flavin adenine dinucleotide (FAD)-dependent halogenase CtcP. CtcP and the FAD reductase CtcQ, which is also encoded in the CTC biosynthetic gene cluster, function as a two-component system. Structural information on CtcP and CtcQ has been lacking. In this study, we determined crystal structures of CtcP from Kitasatospora aureofaciens in a complex …

Borreliosis And Doxycycline Treatment Disrupt Gut Microbiota And Immune Responses In Nonhuman Primates, Ethan G. Napier, Isaac R. Cinco, Sheridan B. Wagner, Ethan V. Stuart, Qi Qiao, Joshua Taylor, Brian Stevenson, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi (Bb) is the spirochete that causes Lyme disease (LD). Transmission to humans occurs via bites of infected Ixodes spp. ticks. Doxycycline is often used to treat LD patients, which is sometimes delayed due to current diagnostic challenges. Recently, several lines of evidence show dysbiosis of the gut microbiome in LD patients, which may be a host factor contributing to pathogenesis and symp tomology but is still an understudied area in the field. To address this knowledge gap, we longitudinally compared the immune response and gut microbial composi tion of Japanese macaques after intradermal infection with Bb strain 297 …

Aluminum In Beverages And Foods: A Comprehensive Compilation Of Regulations; Concentrations In Raw, Prepared, And Stored Beverages And Foods; And Intake, Robert Yokel

Pharmaceutical Sciences Faculty Publications

The history and controversy concerning aluminum use in beverage and food preparation and storage are reviewed. This review on aluminum in drinking water, foods, and beverages updates and exceeds prior reviews. Country and international organization regulations that permit incorporation of aluminum containing food additives, their use limit, and purposes are presented. The aluminum concentration in beverages and foods consumed worldwide was gleaned from approximately 2100 sources available to the author. The approximately 17700 values are compiled in 175 tables by beverage or food category that include the analytical method used, sample source, and reference. The tables are posted on the …

A Cocaine Hydrolase Engineered From Human Butyrylcholinesterase As A Medical Countermeasure For Aldicarb Poisoning, Johnathan E. Lesaint, Nellore Bhanu Chandar, Annet Kyomuhangi, Huimei Wei, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

Aldicarb is known to be the most toxic carbamate pesticide and could be used easily by terrorists to cause a mass casualty incident. It is highly desired to discover a medical countermeasure for aldicarb poisoning. Based on structural insights from molecular modeling and in vitro experimental validation, CocH3-Fc(M3), a potent cocaine hydrolase engineered from human butyrylcholinesterase (BChE), has a ~4-fold improved binding affinity with aldicarb compared to wild-type human acetylcholinesterase (AChE) and BChE and a 9-28-fold improved bimolecular rate constant for the carbamylation with aldicarb compared to AChE. CocH3-Fc(M3) also has significant catalytic activity for aldicarb hydrolysis and, hence, is …

Development Of A Ghrelin Deacylase To Attenuate Drug Reward And Associated Effects Of Methamphetamine, Madeline J. Stewart, Huimei Wei, Nellore Bhanu Chandar, Fang Zheng, Chang-Guo Zhan

Pharmaceutical Sciences Faculty Publications

All addictive substances directly or indirectly interact with the dopamine reward system to alter the brain’s dopamine receptor activities. It is essential for a truly effective addiction medication to attenuate substance reward and normalize the brain’s physiological functions. Conventional pharmacological intervention approaches to the treatment of substance addiction usually aim to develop and deliver a potential therapeutic agent to the brain to directly block or decrease actions of the substance or its therapeutic target in the brain. However, it is a grand challenge to attenuate the substance reward without affecting the normal physiological functions of brain receptors or transporters. Here, …

Effects Of Biased Analogues Of The Kappa Opioid Receptor Agonist, U50,488, In Preclinical Models Of Pain And Side Effects, Ross Van De Wetering, Loan Y. Vu, Lindsay D. Kornberger, Dan Luo, Brittany Scouller, Sheein Hong, Kelly F. Paton, Thomas E. Prisinzano, Bronwyn M. Kivell

Pharmaceutical Sciences Faculty Publications

Kappa opioid receptor (KOR) agonists have well-established antinociceptive effects. However, many KOR agonists have negative side effects, which limit their therapeutic potential. Some researchers have suggested that the development of biased agonists that preferentially stimulate KOR G-protein pathways over β-arrestin pathways may yield drugs with fewer adverse side effects. This was investigated in the current study. We describe the synthesis and characterization of three U50,488 analogues, 1, 2, and 3. We evaluated the acute and chronic antinociceptive effects of these compounds in mice using the warm-water tail flick assay and in a paclitaxel-induced neuropathic pain model. Side …

Effects Of Fentanyl-Adulterated Methamphetamine On Circulating Ghrelin In Rats, Huimei Wei, Elise C. Maul, Shawn Park, Kaniz Fatema, Daniel J. Peter, Chang-Guo Zhan, Fang Zheng

Pharmaceutical Sciences Faculty Publications

The appetite hormone ghrelin influences biological processes that are responsible for substance use disorder, which is related to alcohol and most abused drugs including cocaine, methamphetamine, nicotine, etc. In general, upregulation of the ghrelin system enhances drug cravings and substance use. Studies reported in the literature consistently demonstrated that the ghrelin system is associated with stimulants. However, research on opioids in combination with methamphetamine has not been reported. In this study, we examined the relationship of circulating ghrelin with the polydrug use of fentanyl and methamphetamine in male Sprague-Dawley rats, demonstrating for the first time that concurrent use of fentanyl …

Effects Of Fentanyl-Laced Cocaine On Circulating Ghrelin, Insulin, And Glucose Levels In Rats, Huimei Wei, Elise C. Maul, Annet Kyomuhangi, Shawn Park, Maddilynn L. Mutchler, Chang-Guo Zhan, Fang Zheng

Pharmaceutical Sciences Faculty Publications

Opioid mixed with cocaine has been increasingly implicated in overdose deaths, including both intentional co-use of opioid and cocaine and fentanyl-adulterated drug supply. As ghrelin plays an important role in drug reward and can also influence insulin, this study aimed to assess responses of the circulating ghrelin, insulin, and glucose levels to the combined use of fentanyl and cocaine (a polydrug) in rats by performing combined animal behavioral experiments and biochemical analysis. The experimental data consistently revealed that the fentanyl and cocaine co-use can significantly elevate both the acyl-ghrelin and desacyl-ghrelin levels and significantly decrease the insulin level without significant …

Fluorescence-Guided Resection Of Gl261 Red-Fluc And Trp-Mcherry-Fluc Mouse Glioblastoma Tumors, Louis T. Rodgers, Bryan J. Maloney, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Background: Most preclinical studies on glioblastoma (GBM) fail to provide translational utility in the clinic. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) improves tumor resection, disease prognosis, and, thus, patient outcomes. Given the critical role of surgery in managing recurrent GBM, it is essential to incorporate surgical elements into preclinical models to accurately reflect clinical scenarios and enhance translational success. However, existing protocols for 5-ALA-guided resection in preclinical models are limited and often lack clinical relevance.

Methods: To address this gap, we developed a novel protocol for the 5-ALA-guided resection in two mouse GBM models: TRP-mCherry-FLuc and GL261 Red-FLuc.

Results: The …

Development Of Zafirlukast Analogues For Improved Antithrombotic Activity Through Thiol Isomerase Inhibition, Justine A. Keovilay, Kaitlind C. Howard, Kirk A. Taylor, Sabeeya Khan, Sienna E. Wurl, Melanie K. Szahaj, Tanya Sage, Nishad Thamban Chandrika, Caixia Hou, Oleg V. Tsodikov, Jonathan M. Gibbins, Sylvie Garneau-Tsodikova, Daniel R. Kennedy

Pharmaceutical Sciences Faculty Publications

Background:   Thiol isomerases play essential and nonredundant roles in platelet activation, aggregation, and thrombus formation. Thiol isomerase inhibitors have the potential to overcome the 2 major drawbacks of current antithrombotic therapies, as they target both arterial and venous thrombosis without enhancing bleeding risks. Recently, a Food and Drug Administration–approved drug, zafirlukast (ZAF), was shown to be a promising pan-thiol isomerase inhibitor. The objective of this study is to develop analogues of ZAF with optimized thiol isomerase inhibition and antithrombotic activity.   Methods:   Thirty-five ZAF analogues were tested in an insulin turbidometric assay for thiol isomerase inhibition. Analogues were tested for platelet …

Functional And Structural Studies On The Esperamicin Thioesterase And Progress Toward Understanding Enediyne Core Biosynthesis, Erome D. Hankore, Mitchell D. Miller, Abigael J. Kosgei, Weijun Xu, Kemin Tan, Michael Endres, Minakshi Bhardwaj, Grazyna Joachimiak, Andrzej Joachimiak, George N. Phillips Jr., Jon S. Thorson, Steven G. Van Lanen

Pharmaceutical Sciences Faculty Publications

Enediynes are among the most potent antitumor and antibacterial natural products. Studies on their biosynthetic pathways have identified a shared, linear polyene precursor generated from an iterative type I polyketide synthase (PKSE) as the source of the enediyne warhead. A key step is the release of this polyene from the PKSE by a discrete thioesterase (TE). Here, we used X-ray crystallography, site-directed mutagenesis, and heterologous coexpression of PKSEs and TEs to elucidate how enediyne TEs mediate the production of the polyene. We solved the structure of wild-type EspE7 from esperamicin producer Actinomodura verrucosospora. The substrate binding pocket was also …

Association Between Lifetime Interpersonal Violence And Post– Covid-19 Condition Among Women In Kentucky, 2020-2022, Ayşe Güler, Heather M. Bush, Katie Schill, Nurlan Kussainov, Ann L. Coker

Biostatistics Faculty Publications

Objective: The COVID-19 pandemic increased the risk of interpersonal violence. We investigated the association between lifetime interpersonal violence experience and risk of post–COVID-19 condition (the persistence of symptoms of COVID-19 and severity of health problems associated with COVID-19 that last a few weeks, months, or years) among women with lifetime interpersonal violence experience.   Methods: Women participants aged ≥18 years in Kentucky’s Wellness, Health & You—COVID-19 study completed online quantitative surveys about the impacts of the pandemic, developing COVID-19, and symptoms of post–COVID-19 condition. We conducted cross-sectional analyses estimating rate ratios of developing COVID-19 and symptoms of post–COVID-19 condition during the …

Development And Clinical Validation Of The Sensor-E Exoskeleton For Objective Hand Function Assessment In Stroke Rehabilitation, Madison Bates

Theses and Dissertations--Biomedical Engineering

Hand function is often impaired following neurological trauma or in conditions such as stroke, limiting independence and the ability to perform activities of daily living (ADLs). Current clinical assessments rely heavily on subjective rating scales that lack the resolution to detect subtle changes in motor performance, which can limit access to rehabilitation. Recent advances in wearable technologies highlight the potential for hand-worn devices to provide objective, real-time measures of hand function. However, most systems focus solely on kinematics and rarely capture both movement and exerted force. Moreover, integration into rehabilitation frameworks and brain-computer interface (BCI) protocols remains limited. To address …

Examining The Relationship Between Cognitive Auditory Processing And Sex Hormones, Trey A. Cline

Theses and Dissertations--Gerontology

Estrogen and progesterone have demonstrated modulatory effects on central auditory nervous system (CANS) function. Post-menopausal females often present to audiology clinics with complaints of difficulty hearing in background noise. However, these individuals often have normal peripheral hearing sensitivity on standard audiometry. Previous studies using the auditory brainstem response (ABR) in post-menopausal females demonstrated longer response latencies compared to their premenopausal counterparts, suggesting that sound does not transmit through the CANS as efficiently. However, to date, the available literature focused on sex hormones and the CANS relies mainly on objective measures, predominantly the ABR. The ABR reflects physiologic function through the …

High-Resolution Geospatial Database: National Criteria-Air-Pollutant Concentrations In The Contiguous U.S., 2016–2020, Tianjun Lu, Sun-Young Kim, Julian D. Marshall

Epidemiology and Environmental Health Faculty Publications

Concentration estimates for ambient air pollution are used widely in fields such as environmental epidemiology, health impact assessment, urban planning, environmental equity and sustainability. This study builds on previous efforts by developing an updated high-resolution geospatial database of population-weighted annual-average concentrations for six criteria air pollutants (PM_2.5, PM₁₀, CO, NO₂, SO₂, O₃) across the contiguous U.S. during a five-year period (2016–2020). We developed Land Use Regression (LUR) models within a partial-least-squares–universal kriging framework by incorporating several land use, geospatial and satellite–based predictor variables. The LUR models were validated using conventional …

Evaluating Impact Of Stress First Aid Programs In A Primary Care Setting, Ryan Marler

DNP Projects

Background: Prolonged stress in healthcare workers (HCWs) can lead to burnout and absenteeism. High stress also negatively impacts work productivity and healthcare quality. The Stress First Aid (SFA) program aims to improve recovery from stress among HCWs. Chronic stress is evident in primary care clinics, where absenteeism and burnout symptoms have increased.

Purpose: This project aimed to evaluate the SFA program's effectiveness in reducing burnout and absenteeism and improving healthcare workers (HCW) knowledge of stress and available resources at University of Kentucky Healthcare (UKHC).

Methods: A quasi-experimental quality improvement project included pre- and post-education surveys, an SFA education session, and …

Regulation Of Human Dna Mismatch Repair, Breanna Knicely

Theses and Dissertations--Toxicology and Cancer Biology

The DNA mismatch repair (MMR) pathway identifies and corrects misincorporations that arise during DNA replication. MMR is a pathway that is critical for maintaining genomic stability. Mutations within the MMR pathway, both germline and somatic, lead to the development of cancer. There are a variety of mechanisms that regulate the MMR pathway including protein-protein interactions, DNA damage response, and post-translational modifications. In this study, we aim to dive deeper into each of these mechanisms to obtain novel information regarding the mechanisms and regulation of human DNA MMR. In this study we generated hExo1 constructs mutating Exo1’s interactions with MSH2 and …

Body Mass Index, Sleep, And Food Insecurity Predict Prevalence Of Anxiety And Depression In College Students, Makenzie Barr-Porter, Amelia Sullivan, Jade Mcnamara

Dietetics and Human Nutrition Faculty Publications

This study aimed to assess the relationship between mental health, health behaviors, and food security in young adults in a university environment. Young adults (N = 536) at two United States universities completed a survey assessing health behaviors and characteristics. Logistic regression determined the odds of anxiety and/or depression based on gender identity, body mass index (BMI), food security status (FSS), and sleep restfulness. Over one-third of students were food insecure (36.7%), and almost all reported anxiety (57%) and/or depression (39.1%). Students who identified as female, reported very low FSS, poor sleep, and had higher BMI were at greater odds …

A Program Evaluation Case Study, Madelyne G. Culbertson

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

This case study presents a program evaluation of a physical activity intervention implemented in Bourbon County, Kentucky, guided by the Centers for Disease Control and Prevention’s Framework for Program Evaluation in Public Health.

A Case Study In Program Evaluation, Alexis Strottman

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

This paper presents a comprehensive evaluation plan for the Bourbon County Physical Activity Improvement Program, as prompted in the University of Kentucky's 2025 MPH-Health Management and Policy Capstone Case Study. The case study outlines a program developed in response to high obesity and inactivity rates in Bourbon County, Kentucky. Utilizing the CDC's 6-step program evaluation framework, the plan outlines engagement of a diverse group of stakeholders to assess the program's effectiveness in increasing physical activity among residents. The evaluation focuses on both process and outcome measures, examining the implementation of exercise facilities, community events, and an app designed to track …

A Case Study In Program Evaluation: Evaluation Of A Program Designed To Increase Activity Levels In Bourbon County Residents, Brooke M. Woodburn

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

This paper provides recommendations to eliminate possible barriers in a program developed to reduce inactive levels across Bourbon County.

Increasing Hpv Vaccination Adherence In Floyd County, Ky: Give Teens Vaccines, Taylor M. Stumbo

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

Cervical cancer remains a pressing public health issue, particularly in underserved and rural areas where access to preventive care is limited. This capstone addresses the urgent need to increase human papillomavirus (HPV) vaccination adherence in Floyd County, Kentucky—part of the central Appalachian region that experiences disproportionately high cervical cancer incidence and mortality. Despite the proven effectiveness of HPV vaccines in preventing the virus strains most responsible for cervical cancer, uptake in this region remains below national targets due to socioeconomic barriers, limited healthcare access, and lack of awareness. Give Teens Vaccines is a two component intervention leveraging existing healthcare systems …

A Case Study In Program Evaluation Evaluation Of A Physical Inactivity Program In Bourbon County, Kentucky, Carine N. Malekera

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

This paper evaluates a physical activity program by the Bourbon County Health Department aimed at increasing physical activity among local residents. Using the CDC’s Framework for Program Evaluation, the study includes both process and outcome evaluations to assess program implementation and impact on health outcomes. Key findings indicate success in urban areas but challenges in rural regions due to limited access to resources. Recommendations include improving access to exercise opportunities in rural areas and offering virtual classes. This evaluation emphasizes the importance of continuous assessment for effective public health interventions.

A Case Study In Program Evaluation, Kaitlyn E. Lee

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

This capstone project evaluates a fictious online MRSA education program developed by the Lexington-Fayette County Health Department and Fayette County Public Schools after a suspected outbreak among student athletes. Using the CDC’s 6-Step Framework for Program Evaluation, the project focuses on how stakeholders were engaged, how the program was described and mapped, how the evaluation questions were developed, what evidence was collected, and how conclusions were formed. The goal of the evaluation is to understand whether the program’s structure, delivery, and implementation support clear infection-control education for the different school personnel who use it. This project emphasizes the overall evaluation …

The Role Of Self-Efficacy In Rehabilitation And Recovery From Ankle Sprains, Bridget M. Walsh

Theses and Dissertations--Rehabilitation Sciences

Ankle sprains are among the most common musculoskeletal injuries in the United States. Approximately 2 million ankle sprains occur annually, with an estimated 46% of affected individuals experiencing residual symptoms and developing chronic ankle instability (CAI). In addition to physical impairments, individuals with CAI may exhibit lower physical and psychological health-related quality of life (HRQL). HRQL integrates the physical, psychological, and social domains of a person’s health and is influenced by their experiences, expectations, and perceptions.

Injury-related fear is a common psychological impairment in individuals with CAI and has been associated with decreased physical function, reduced physical activity, and greater …