Medicine and Health Sciences Commons^™

The Influence Of Apoe Genotype On Lipid Droplet Dynamics, Cassi Friday

Theses and Dissertations--Physiology

Excess lipid droplet (LD) accumulation is associated with several pathological states, including neurodegenerative disorders such as Alzheimer’s disease (AD). However, the mechanism(s) by which changes in LD composition and dynamics may contribute to the pathophysiology of AD remains unclear. Apolipoprotein E (ApoE) is a droplet-related protein with a common variant (ApoE4) that confers the largest increase in genetic risk for late-onset AD. Interestingly, ApoE4 is associated with both increased neuroinflammation and excess LD accumulation. This dissertation work seeks to quantitatively profile the lipid and protein composition of LDs between the ‘neutral’ ApoE3 and ‘risk’ ApoE4 isoforms, in order to gain …

Effects Of Traumatic Brain Injury On The Intestinal Tract And Gut Microbiome, Anthony Desana

Theses and Dissertations--Physiology

Traumatic brain injury (TBI) initiates not only complex neurovascular and glial changes within the brain but also pathophysiological responses that extend beyond the central nervous system. The peripheral response to TBI has become an intensive area of research, as these systemic perturbations can induce dysfunction in multiple organ systems. As there are no approved therapeutics for TBI, it is imperative that we investigate the peripheral response to TBI to identify targets for future intervention. Of particular interest is the gastrointestinal (GI) system. Even in the absence of polytrauma, brain-injured individuals are at increased risk of suffering from GI-related morbidity and …

Clinical And Biological Factors Determine Spinal Cord Injury Outcomes: Liquor To Lipids, Ethan Glaser

Theses and Dissertations--Physiology

Spinal cord injuries (SCI) are debilitating and life altering events that can lead to permanent motor and sensory loss. SCI outcomes are impacted by both clinical factors such as blood alcohol content (BAC) at the time of injury as well as biological factors like the lipid-rich myelin debris that accumulates in the injury site. Both clinical and biological factors contribute to SCI recovery, impacting neuroinflammation, locomotor recovery, and histopathology. The purpose of the studies described here is to investigate the role of acute alcohol intoxication and intracellular lipid processing pathways on SCI outcomes in a rodent model.

An elevated BAC …

Improving Radiotherapy Workflow: Evaluation And Implementation Of Deep Learning Auto-Segmentation In A Multi-User Environment, And Development Of Automatic Contour Quality Assurance System, Jingwei Duan

Theses and Dissertations--Radiation Medicine

Radiotherapy is a frequently used therapeutic modality for cancer patients. Accurately contouring of tumors and organs at risk (OARs) is critical for developing optimal treatment plans in radiotherapy, especially after the implementation of Intensity-modulated radiation therapy (IMRT) and Stereotactic Body Radiation Therapy (SBRT). The manual contouring process is time-consuming and suffers from inter-observer variations. However, manual contouring is often hindered by laborious clinical duties, leading to reduced effectiveness, and increased segmentation errors due to fatigue. Additionally, online adaptive radiation therapy(ART), which has been shown to benefit patient outcomes, places higher demands on contouring and quality assurance (QA) speed.

Recently, deep …

Dosimetric And Clinical Investigation Into Dose Variations Of The Target And Organs At Risk In High Dose Rate Gynecological Brachytherapy, Brien Washington

Theses and Dissertations--Radiation Medicine

The technological advancements in brachytherapy have allowed for increased precision and better-quality treatments. This is apparent in treating GYN cancers of the uterine cervix. Lengthy low dose rate (LDR) treatments, implant systems, and two-dimensional (2D) image-guided treatments have been replaced by quicker high dose rate (HDR) treatments and adaptive treatment planning with three-dimensional (3D) imaging modalities. However, this increased precision can result in reduced dosimetric accuracy. Implant systems were designed to conform to the prescribed dose, and 2D plans were only concerned with dose to two organs at risk (OAR) parameters. Now, planners must consider added OAR position data and …

Development Of A Community-Based Plan For An Effective Behavioral Intervention To Reduce Childhood Obesity In A Rural Appalachian Community, Jennifer Stacy Wells

Theses and Dissertations--Nutrition and Food Systems

Rural children experience increased rates of obesity and reduced access to specialized weight management facilities, which makes receiving the recommended frequency of care difficult. Clinical-community partnerships, recommended by the American Academy of Pediatrics (AAP) to expand access, have been shown to be a feasible strategy of care delivery. Examination of literature and stakeholder interviews were used to inform the development of a collaborative pediatric weight management program in a rural, Appalachian community. Screening articles as well as intervention articles were reviewed. Outcomes of screening articles reviewed included BMI measures (3), screening practices (7), and referral practices (4). Common outcomes of …

Examining The Utility Of A Kentucky Fcs Cooperative Extension Curriculum On Community Members’ Healthy And Sustainable Diet-Related Behaviors, Catharine Pickford

Theses and Dissertations--Nutrition and Food Systems

Experts recommend individuals adopt healthy and sustainable dietary behaviors to improve human and environmental health. The objective of this study was to pilot a sustainable eating Family and Consumer Sciences (FCS) Cooperative Extension curriculum and evaluate the effectiveness of the lesson series by measuring participants’ changes in knowledge, perceptions, and intentions towards healthy and sustainable dietary behaviors as well as overall satisfaction with lessons. A five-lesson sustainable eating curriculum was developed with topics focused on: reducing food waste; eating more seasonal, local plant-based foods; varying protein sources; maintaining energy balance; and consuming fewer highly processed and packaged foods. To assess …

Assessing 4-H And Its Circle Of Courage In A Psychiatric Residential Treatment Facility: A Case Study, Elizabeth Steering

Theses and Dissertations--Family Sciences

This 4-H case study takes place in a psychiatric residential treatment facility (PRTF) in Kentucky. The PRTF provides clinical services to youth that are not able to be safely maintained in their homes due to having demonstrated unsafe or harmful behaviors. Youth admitted to the PRTF stay for an average of three to six months while they receive intensive therapeutic and psychiatric care as well as medical treatment and public schooling. The current case study incorporates programming from 4-H, which is the youth development program of the Cooperative Extension System (CES) and the National Institute of Food and Agriculture (NIFA), …

Exploring The Distinction Between Support And Enabling In Families With Substance Use Disorder, Krystal N. King

Theses and Dissertations--Family Sciences

Substance use disorders (SUD) are a pervasive public health problem facing families in the United States. Although families are frequently urged to support loved ones who have SUD and cautioned against enabling them, there is a dearth of literature that distinguishes between supporting and enabling. Through qualitative interviews, this phenomenological study examined the experiences of eight parents with adult children with SUD who were currently in recovery. Five themes emerged from the data including: (a) living in despair, (b) addiction and recovery knowledge, (c) support group philosophy, (d) coping with addiction, and (e) differentiation. The results from this study suggest …

Effects Of High-Speed Training On Messenger Rna Expression In Two-Year-Old Thoroughbred Racehorses, Mackenzie Grace Johnson

Theses and Dissertations--Veterinary Science

Accumulating high-speed exercise has been identified as a significant risk factor for catastrophic injuries in racing Thoroughbreds. Injuries, regardless of severity, are a main cause of withdrawal from the racing industry, raising animal welfare concerns and resulting in significant economic losses. While most of the current literature focuses on catastrophic injuries incurred during racing rather than training, the present study aims to help fill this gap as well as discuss the associated risk factors. The evaluation of messenger RNA (mRNA) expression changes provides an efficient and straightforward approach to identifying horses at risk for catastrophic injury. While alternative injury risk …

Equine Fecal Microbiota Response To Short Term Antibiotic Administration, Jordan Lacey Parker

Theses and Dissertations--Veterinary Science

Though generally regarded as safe, research continues to demonstrate negative side effects of antibiotic administration on the gastrointestinal (GIT) microbiota across species. In horses, antibiotic associated diarrhea (AAD) is a life-threatening side effect linked to the GIT microbiota. This study tested the hypothesis that short term antibiotic administration to healthy horses would negatively impact the fecal microbiota as measured by their ability to digest nutrients and produce short chain fatty acids (SCFAs). Twenty-four horses were assigned to one of four treatments: control (CO); potassium penicillin/gentamicin sulfate (KPG); ceftiofur crystalline free acid (EX); trimethoprim/sulfamethoxazole (SMZ); and treated for 4 days. Fecal …

The Effect Of Land-Cover/Land-Use And Habitat Fragmentation On Spatial Patterns Of Lyme Disease In The Eastern United States, Maria Elizabeth Topmiller

Theses and Dissertations--Forestry and Natural Resources

Lyme disease has been of national concern for the past few decades. As our understanding of the role of landscape structure in epidemiology expands, it is essential to apply the principles of landscape ecology to the research of vector-borne and zoonotic disease. This study examined the strength of the relationship between land-cover class, degree of habitat fragmentation and county-level Lyme disease cases. Forest, agricultural, and urban land cover types were the categories of interest, while percent cover, edge density, and patch density were the landscape metric used to measure habitat amount and fragmentation. The general linear trends were modelled with …

Surveillance For Ticks And Tick-Borne Pathogens In Kentucky, Anna Rosalee Pasternak

Theses and Dissertations--Entomology

Tick-borne diseases are an emerging threat to human and animal health. In Kentucky, tick-borne disease surveillance has identified rising incidences of spotted fever rickettsiosis, ehrlichiosis, and Lyme disease. Since these diseases occur through the bites of infected ticks, effective prevention efforts are reliant upon knowing where the risk of exposure to tick bites exists. Historical data on tick distribution in Kentucky is variable, with very little reported on a statewide scale, leaving vector control workers, public health personnel, physicians, veterinarians, and others to rely on outdated, intermittent, or out-of-state information. In my dissertation, I surveyed ticks and select tick-borne pathogens …

Trauma-Informed Care: A Collaborative Strategy To Address Hiv-Infection Rates Among Black Gay And Bisexual Men, Willie T. Boddie Jr.

DSW Capstone Projects

The Human Immunodeficiency Virus and Acquired Immune Deficiency Syndrome (HIV/AIDS) continues to be an epidemic among gay and bisexual men or men who have sex with men (MSMs). For Black MSMs, the HIV infection rate is disproportionate compared to the number of Black or African American citizens in the U.S. Black MSMs have the highest HIV infection rate in the U.S. This Capstone Project seeks to explore the possible impact of trauma experiences among this group and determine how providing trauma-informed care, along with the standard HIV education and awareness can be used to effectively reduce this disparity and ultimately …

Use Of A Nurse-Led Daily Goals Checklist To Improve Multidisciplinary Rounds In The Icu, Marissa Riley

DNP Projects

Research has shown a multidisciplinary rounding approach can improve patient care outcomes in the intensive care unit (ICU). Due to the complexity and wide range of the healthcare team, many patient details and treatment goals may be overlooked during daily patient rounds without a daily goals checklist to help ensure collaboration and communication of the multidisciplinary team. A nurse led daily goals checklist could be useful for framing nurse-provider conversations to promote comprehensive communication and collaboration. The purpose of this project was to improve adherence to a nurse-led daily goals checklist to improve communication and collaboration between the nurses and …

The Impact Of Flooding Events In Kentucky Counties On Preventable Asthma Hospitalizations, Mckaylee Copher

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

Objective: Given the frequency and intensity of flooding, along with the disparities in respiratory illnesses in Kentucky, this study aims to determine if there is an association between flooding and asthma is crucial to the health of the state population.

Methods: Preventable asthma hospitalizations in adults aged 18-39 were obtained from the Kentucky Cabinet of Health and Family Services, Health and Facility Services Data and included the count of admissions of an ICD-9 diagnosis of asthma, as determined by hospital discharge data. FEMA disaster declarations were used to identify 69 counties that had floods during the period of 2008-2015. A …

Sociodemographic Factors Related To Late-Stage Lung Cancer Diagnosis In Kentucky, Kaylee Stickler

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

Lung cancer is the leading cause of cancer mortality in the United States, and the state of Kentucky has a significant burden of lung cancer morbidity and mortality. The aim of this study is to examine the sociodemographic factors associated with late-stage lung cancer diagnosis in Kentucky. The present study is a retrospective, population-based cohort study that utilizes data from the Kentucky Cancer Registry to examine the associations between late-stage lung cancer diagnosis and sociodemographic factors. Descriptive, bivariate, and multivariable analyses were conducted to estimate the significance of these associations. Significant relationships between the variables of sex, age, Appalachian status, …

Nonoperative Management Of Shoulder Instability, Margie K. Olds, Timothy L. Uhl

Physical Therapy Faculty Publications

Non-operative management following a shoulder dislocation or subluxation remains a challenging and complex task. Accurate diagnosis of the condition, and shared decision-making regarding operative and non-operative management, as well as timing of return to play is required. This clinical concept paper introduces a shoulder instability framework that addresses these fundamental clinical dilemmas. Valid clinical prognostic tools which can predict recurrent shoulder instability are reviewed. The process of shared decision-making within the realm of shoulder instability is also presented. Finally, a framework for progressive rehabilitation that addresses deficits in motor control, strength, and endurance in scapula and shoulder musculature is presented …

Prediction Of Mortality And Major Adverse Kidney Events In Critically Ill Patients With Acute Kidney Injury, Javier A. Neyra, Victor M. Ortiz-Soriano, Lucas J. Liu, Taylor D. Smith, Xilong Li, Donglu Xie, Beverly Adams-Huet, Orson W. Moe, Robert D. Toto, Jin Chen

Markey Cancer Center Faculty Publications

Rationale & Objective: Risk prediction tools for assisting acute kidney injury (AKI) management have focused on AKI onset but have infrequently addressed kidney recovery. We developed clinical models for risk stratification of mortality and major adverse kidney events (MAKE) in critically ill patients with incident AKI.

Study Design: Multicenter cohort study.

Setting & Participants: 9,587 adult patients admitted to heterogeneous intensive care units (ICUs; March 2009 to February 2017) who experienced AKI within the first 3 days of their ICU stays.

Predictors: Multimodal clinical data consisting of 71 features collected in the first 3 days of ICU stay.

Outcomes: (1) …

Machine Learning Framework For Real-World Electronic Health Records Regarding Missingness, Interpretability, And Fairness, Jing Lucas Liu

Theses and Dissertations--Computer Science

Machine learning (ML) and deep learning (DL) techniques have shown promising results in healthcare applications using Electronic Health Records (EHRs) data. However, their adoption in real-world healthcare settings is hindered by three major challenges. Firstly, real-world EHR data typically contains numerous missing values. Secondly, traditional ML/DL models are typically considered black-boxes, whereas interpretability is required for real-world healthcare applications. Finally, differences in data distributions may lead to unfairness and performance disparities, particularly in subpopulations.

This dissertation proposes methods to address missing data, interpretability, and fairness issues. The first work proposes an ensemble prediction framework for EHR data with large missing …

Can Testing The Environment For Severe Acute Respiratory Coronavirus Virus 2 (Sars-Cov-2) Be A Signal For Coronavirus Disease 2019 (Covid-19) Cases Among Nursing Home Staff?, Gabrielle M. Gussin, Raveena D. Singh, Izabela Coimbra Ibraim, Raheeb Saavedra, Thomas T. Tjoa, Micaila Curtis, Kristine P. Nguyen, Ilhem Messaoudi, Susan S. Huang

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Prior to widespread COVID-19 vaccination, nursing homes were required to perform comprehensive weekly testing of staff. After the vaccine became available, testing became symptom-based for vaccinated staff despite continued waves of different severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variants. Nursing homes need pragmatic, affordable strategies to identify SARS-CoV-2–positive staff because financial and job-related pressures drive reluctance to disclose mild symptoms. We sought to determine whether positive environmental samples for SARS-CoV-2 could serve as trigger for comprehensive staff testing in lieu of weekly testing of all staff.

Correlates Of Sars-Cov-2 Anti-Rbd Igg Antibody Titers Among Persons Experiencing Homelessness In Los Angeles, Adeline Nyamathi, Sanghyuk S. Shin, Brianna M. Doratt, Alexandria Jones-Patten, Benissa Salem, Lillian Gelberg, Darlene Lee, Dana Garfin, Kartik Yadav, Alicia H. Chang, Kathryn White, Nicholas Arce, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Objectives: People experiencing homelessness (PEH) have been especially impacted by the COVID-19 pandemic, likely due to increased vulnerabilities stemming from chronic diseases, substance use, and mental health conditions.

Design: A case–control study to assess the presence of antibodies against SARS-CoV-2 among PEH and associations with key variables.

Sample: A convenience sample of 97 PEH in Skid Row, Los Angeles.

Measurements: A structured questionnaire assessing socio-demographic, mental health, drug and alcohol use, health care access, pandemic stress, and other COVID-19-specific questions.

Results: We found high anti-receptor binding domain (RBD) IgG titers among five of 15 PEH who reported no prior COVID-19 …

Maternal Obesity Blunts Antimicrobial Responses In Fetal Monocytes, Suhas Sureshchandra, Brianna M. Doratt, Norma Mendza, Oleg Varlamov, Monica Rincon, Nicole E. Marshall, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Maternal pre-pregnancy (pregravid) obesity is associated with adverse outcomes for both mother and offspring. Amongst the complications for the offspring is increased susceptibility and severity of neonatal infections necessitating admission to the intensive care unit, notably bacterial sepsis and enterocolitis. Previous studies have reported aberrant responses to LPS and polyclonal stimulation by umbilical cord blood monocytes that were mediated by alterations in the epigenome. In this study, we show that pregravid obesity dysregulates umbilical cord blood monocyte responses to bacterial and viral pathogens. Specifically, interferon-stimulated gene expression and inflammatory responses to respiratory syncytial virus (RSV) and E. coli were significantly …

Sars-Cov-2 Infection And Seroconversion Rates In Healthcare Providers Prior To Covid-19 Vaccine Rollout, Sanghyuk S. Shin, Miriam Bender, Delphine C. Malherbe, Hannah Vasquez, Brianna M. Doratt, Ilhem Messaoudi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Objective: A 6-month longitudinal surveillance study of asymptomatic healthcare providers (HCP) was carried out at a large urban academic medical center in the United States to assess whether their job occupation with higher exposure risks to SARS-CoV-2 would equate with higher risk of contracting COVID-19 at the beginning of the pandemic before COVID-19 vaccines were available.

Methods: A longitudinal cohort study design was used to collect and analyze immunological and virological monitoring data and self-report survey assessments of personal protective equipment (PPE) availability, adherence to infection control guidelines, and time spent on COVID-19 wards.

Results: Among 289 eligible participants, SARS-CoV-2 …

Single-Dose Vsv-Based Vaccine Protects Cynomolgus Macaques From Disease After Taï Forest Virus Infection, Paige Fletcher, Kyle L. O'Donnell, Brianna M. Doratt, Delphine C. Malherbe, Chad S. Clancy, Joseph F. Rhoderick, Friederike Feldmann, Patrick W. Hanley, Thomas G. Ksiazek, Thomas W. Geisbert, Ilhem Messaoudi, Andrea Marzi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Taï Forest virus (TAFV) is a lesser-known ebolavirus that causes lethal infections in chimpanzees and is responsible for a single human case. Limited research has been done on this human pathogen; however, with the recent emergence of filoviruses in West Africa, further investigation and countermeasure development against this virus is warranted. We developed a vesicular stomatitis virus (VSV)-based vaccine expressing the TAFV glycoprotein as the viral antigen and assessed it for protective efficacy in nonhuman primates (NHPs). Following a single high-dose vaccination, NHPs developed antigen-specific binding and neutralizing antibodies as well as modest T cell responses. Importantly, all vaccinated NHPs …

Transcriptional Profiling Of Immune Responses In Nhps After Low-Dose, Vsv-Based Vaccination Against Marburg Virus, Cecilia A. Prator, Brianna M. Doratt, Kyle L. O'Donnell, Justin Lack, Amanda N. Pinski, Stacy M. Ricklefs, Craig A. Martens, Ilhem Messaoudi, Andrea Marzi

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Infection with Marburg virus (MARV), the causative agent of Marburg virus disease (MVD), results in haemorrhagic disease and high case fatality rates (>40%) in humans. Despite its public health relevance, there are no licensed vaccines or therapeutics to prevent or treat MVD. A vesicular stomatitis virus (VSV)-based vaccine expressing the MARV glycoprotein (VSV-MARV) is currently in clinical development. Previously, a single 10 million PFU dose of VSV-MARV administered 1–5 weeks before lethal MARV challenge conferred uniform protection in nonhuman primates (NHPs), demonstrating fast-acting potential. Additionally, our group recently demonstrated that even a low dose VSV-MARV (1000 PFU) protected NHPs …

Lifetime Interpersonal Violence Or Abuse And Diabetes Rates By Sex And Race, Maureen Sanderson, Mekeila Cook, L. Lauren Brown, Veronica Mallett, Ann L. Coker

Obstetrics and Gynecology Faculty Publications

Introduction: Lifetime exposure to interpersonal violence or abuse has been associated with several chronic diseases, including adult-onset diabetes, yet this pattern has not been confirmed by sex and race within a large cohort.\Methods: Data from the Southern Community Cohort Study collected between 2002−2009 and 2012−2015 were used to explore the relationship between lifetime interpersonal violence or abuse and diabetes (N=25,251). Prospective analyses of lower-income people living in the southeastern U.S. were conducted in 2022 to examine the risk of adult-onset diabetes associated with lifetime interpersonal violence or abuse by sex and race. Lifetime interpersonal violence or abuse was defined as …

Cd47 Antisense Oligonucleotide Treatment Attenuates Obesity And Its-Associated Metabolic Dysfunction, Taesik Gwag, Dong Li, Eric Ma, Zhenheng Guo, Ying Liang, Shuxia Wang

Saha Cardiovascular Research Center Faculty Publications

Previous study from our lab has revealed a new role of CD47 in regulating adipose tissue function, energy homeostasis and the development of obesity and metabolic disease in CD47 deficient mice. In this study, the therapeutic potential of an antisense oligonucleotide (ASO) targeting to CD47 in obesity and its‑associated complications was determined in two obese mouse models (diet induced and genetic models). In diet induced obesity, male C57BL6 mice were fed with high fat (HF) diet to induce obesity and then treated with CD47ASO or control ASO for 8 weeks. In genetic obese mouse model, male six‑week old ob/ob mice …

Platelet Glycogenolysis Is Important For Energy Production And Function, Kanakanagavalli Shravani Prakhya, Hemendra J. Vekaria, Daniёlle M. Coenen, Linda Omali, Joshua Lykins, Smita Joshi, Hammodah Rawhi Hammodah Alfar, Qing Jun Wang, Patrick G. Sullivan, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Although the presence of glycogen in platelets was established in the 1960s, its importance to specific functions (i.e., activation, secretion, aggregation, and clot contraction) remains unclear. Patients with glycogen storage disease often present with increased bleeding and glycogen phosphorylase (GP) inhibitors, when used as treatments for diabetes, induce bleeding in preclinical studies suggesting some role for this form of glucose in hemostasis. In the present work, we examined how glycogen mobilization affects platelet function using GP inhibitors (CP316819 and CP91149) and a battery of ex vivo assays. Blocking GP activity increased glycogen levels in resting and thrombin-activated platelets and inhibited …

The Complementary Roles Of Vamp-2, -3, And -7 In Platelet Secretion And Function, Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N. Smith, Harry Chanzu, Ming Zhang, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/ VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α …