Digital Commons Network^™

The Differential Proteomic Response To Ischemic Stroke In Appalachian Subjects Treated With Mechanical Thrombectomy, Christopher J. Mclouth, Benton Maglinger, Jacqueline A. Frank, Kristin J. Hazelwood, Jordan P. Harp, Will Cranford, Shivani Pahwa, David Dornbos Iii, Amanda L. Trout, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Neurology Faculty Publications

Introduction The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. Methods There were 81 subjects that met inclusion criteria for this …

Screening Incarcerated Women For Opioid Use Disorder, Michele Staton, Martha Tillson, Mary M. Levi, Matthew Webster, Carrie B. Oser, Carl Leukefeld

Behavioral Science Faculty Publications

The overall aim of the present study is to examine the utility of the DSM OUD Checklist and the NM-ASSIST screening tools to identify symptoms consistent with OUD among incarcerated women in county jails. This study contributes to the existing literature because research on screening and assessment approaches for incarcerated women has been limited. The focus of the current study is to describe the screening procedures and study recruitment for a larger parent study focused on increasing treatment linkages. Study findings indicate a positive correlation between indicators of OUD using the two screening tools, as well as a high degree …

Abnormalities In Pharyngeal Arch-Derived Structures In Satb2-Associated Syndrome, Yuri A. Zarate, Katherine Bosanko, Nada Derar, Jennifer L. Fish

Pediatrics Faculty Publications

SATB2-associated syndrome (SAS, glass syndrome, OMIM#612313) is a neurodevelopmental autosomal dominant disorder with frequent craniofacial abnormalities including palatal and dental anomalies. To assess the role of Satb2 in craniofacial development, we analyzed mutant mice at different stages of development. Here, we show that Satb2 is broadly expressed in early embryonic mouse development including the mesenchyme of the second and third arches. Satb2-/- mutant mice exhibit microglossia, a shortened lower jaw, smaller trigeminal ganglia, and larger thyroids. We correlate these findings with the detailed clinical phenotype of four individuals with SAS and remarkable craniofacial phenotypes with one requiring mandibular distraction in …

Astrocytic Mitochondrial Transfer To Brain Endothelial Cells And Pericytes In Vivo Increases With Aging, Gopal V. Velmurugan, Hemendra J. Vekaria, Samir P. Patel, Patrick G. Sullivan, W. Brad Hubbard

Neurology Faculty Publications

Intercellular mitochondrial transfer (IMT) is an intriguing biological phenomenon where mitochondria are transferred between different cells and notably, cell types. IMT is physiological, occurring in normal conditions, but also is utilized to deliver healthy mitochondria to cells in distress. Transferred mitochondria can be integrated to improve cellular metabolism, and mitochondrial function. Research on the mitochondrial transfer axis between astrocytes and brain capillaries in vivo is limited by the cellular heterogeneity of the neurovascular unit. To this end, we developed an inducible mouse model that expresses mitochondrial Dendra2 only in astrocytes and then isolated brain capillaries to remove all intact astrocytes. …

Detecting Cognitive Decline In High-Functioning Older Adults: The Relationship Between Subjective Cognitive Concerns, Frequency Of High Neuropsychological Test Scores, And The Frontoparietal Control Network, Justin E. Karr, Jonathan G. Hakun, Daniel B. Elbich, Cristina N. Pinheiro, Frederick A. Schmitt

Neurology Faculty Publications

Objective: Neuropsychologists have difficulty detecting cognitive decline in high-functioning older adults because greater neurological change must occur before cognitive performances are low enough to indicate decline or impairment. For high-functioning older adults, early neurological changes may correspond with subjective cognitive concerns and an absence of high scores. This study compared high- functioning older adults with and without subjective cognitive concerns, hypothesizing those with cognitive concerns would have fewer high scores on neuropsychological testing and lower frontoparietal network volume, thickness, and connectivity.

Method: Participants had high estimated premorbid functioning (e.g., estimated intelligence ≥75th percentile or college-educated) and were divided based on …

Using Digital Pathology To Analyze The Murine Cerebrovasculature, Dana M. Niedowicz, Jenna L. Gollihue, Erica M. Weekman, Panhavuth Phe, Donna M. Wilcock, Christopher M. Norris, Peter T. Nelson

Neurology Faculty Publications

Research on the cerebrovasculature may provide insights into brain health and disease. Immunohistochemical staining is one way to visualize blood vessels, and digital pathology has the potential to revolutionize the measurement of blood vessel parameters. These tools provide opportunities for translational mouse model research. However, mouse brain tissue presents a formidable set of technical challenges, including potentially high background staining and crossreactivity of endogenous IgG. Formalin-fixed paraffin-embedded (FFPE) and fixed frozen sections, both of which are widely used, may require different methods. In this study, we optimized blood vessel staining in mouse brain tissue, testing both FFPE and frozen fixed …

Estrogen’S Sex-Specific Effects On Ischemic Cell Death And Estrogen Receptor Mrna Expression In Rat Cortical Organotypic Explants, Amanda L. Trout, Christopher J. Mclouth, Jenna Westberry, Tomoko Sengoku, Melinda E. Wilson

Neurology Faculty Publications

Estrogens, such as the biologically active 17-β estradiol (E2), regulate not only reproductive behaviors in adults, but also influence neurodevelopment and neuroprotection in both females and males. E2, contingent upon the timing and concentration of the therapy, is neuroprotective in female and male rodent models of stroke. In Vivo studies suggest that E2 may partially mediate this neuroprotection, particularly in the cortex, via ERα. In Vitro studies, utilizing a chemically induced ischemic injury in cortical explants from both sexes, suggest that ERα or ERβ signaling is needed to mediate the E2 protection. Since we know that the timing and concentration …

Changes In Primary Care Availability In Appalachia, Whitney Beckett

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

The Affordable Care Act (ACA) was a groundbreaking moment in the United States healthcare system. It affected many different aspects of the system, including access to primary care professionals. Primary care professionals provide a key role in American’s health, especially when it comes to preventative care. With one-third of Americans experiencing barriers to such access, a solution is desperately needed to increase said access. These barriers are especially profound in low-income, underserved areas such as the Appalachian regions of Georgia, Kentucky, Tennessee, and West Virginia. The ACA attempted to increase access via Medicaid expansion; however, not all States expanded their …

Empirical Insights Into Survivorship Care: A Cross-Sectional Study Of Coc Accredited Hospitals In Kentucky, Amanda M. Beckett

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

ABSTRACT

Background:

Cancer survivorship care programs play a vital role in supporting cancer survivors and improving their quality of life. Understanding the landscape of survivorship and the potential barriers is key to optimizing care delivery.

Methods:

The primary purpose of this cross-sectional study was to explore existing cancer survivorship care programs offered by Commission on Cancer (CoC) accredited hospitals in Kentucky. Data from the Markey Cancer Affiliate Network (MCCAN) from 2022 through 2023 was analyzed. Variables included hospital characteristics such as rural code, types of survivorship services offered, and reported barriers to these services.

Results:

Analysis of n=19 CoC facilities …

Environmental Justice In West Louisville, Ky, Ashley Wright

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

It is evident that West Louisville and Rubbertown are experiencing environmental exposures and related health impacts. It is important for environmental justice (EJ) areas like West Louisville and Rubbertown to gain increased awareness, due to EJ areas commonly being overlooked and forgotten about because of unjust treatment and lack of involvement. Furthermore, all of the data used for this project was publicly accessible. Community residents and the general public can access these data sources to identify which facilities are emitting toxins, as well as specific hazardous substances that are being released, the location of hazardous sites, cleanup status, and more. …

Improving Black Maternal Outcomes In Christian County, Ky: A Social Marketing Approach To Perinatal Provider Change, Ariel A. Arthur

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

Compared to other states in the country, Kentucky has historically poor population health outcomes. While the statewide maternal mortality rate is 16.1 per 100,000 live births, this statistic belies the stark racial disparities that exist. In 2018, the pregnancy-related death rate for Black women was 40.2 per 100,000 live births compared to 13.1 for White women. This pattern is persistent even after controlling for socioeconomic status, prenatal care, and other protective factors. Research shows that institutional and interpersonal racism when receiving obstetric care contributes to poor childbirth and postpartum outcomes for Black women. Additionally, geography and rural status may compound …

Implementation Of A Postpartum Depression Program In A Rural Kentucky County, Abby Cecil

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

This paper aims to describe the process of implementing a Postpartum Depression (PPD) prevention program in low-income women residing in rural communities. The paper describes the process of recruiting women in this population, where and how the program will be integrated into an existing clinic, and how the program will be sustained. PPD is a significant global public health problem that can be prevented and treated. The ROSE program (Reach Out, Stay Strong, Essentials for new mothers) is a series of classes that provide informational and social support to prevent PPD. This evidence-based program has been previously successful in reducing …

Increasing Hpv Vaccination In Two Appalachian Counties, Autumn Rice

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

In response to the Funding Opportunity Announcement (FOA), the evidence-based Making Effective HPV Vaccine Recommendations training program will be implemented in the Southeast Kentucky AHEC region over the course of three years. The implementation of the Making Effective HPV Vaccine Recommendations program has three specific aims:

Aim 1: Effectively implement and deliver the Making Effective HPV Vaccine Recommendations program to immunization providers in the Southeast Kentucky AHEC region

Aim 2: Increase provider self-efficacy for making strong recommendations for HPV routinely

Aim 3: Increase the number of recommendations for the HPV vaccine among adolescents of Bell and Harlan Counties in Kentucky …

Child Language And Happiness Behaviors: Evaluating The Effects Of Caregiver Coaching, Ashlen Grubbs

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Caregivers of young children who have or are at risk for disabilities may struggle supporting their child’s language development. This study used a tailored rapid coaching intervention to teach a caregiver different naturalistic language interventions that can be used with their child during play. Evidence-based naturalistic skills for increasing child communication were chosen to teach the caregiver based on baseline levels of skills. The purpose of this study was to evaluate the effectiveness of a tailored RCI (training and coaching) with caregivers of children with developmental disabilities. Like other studies, this study involved evaluating child-level communication but extended child measures …

Supporting Children’S Eating Behavior In A Preschool Classroom, Olajumoke Leshi

Theses and Dissertations--Early Childhood, Special Education, and Counselor Education

Food selectivity, commonly observed in young children, has a significant effect on their health outcomes, and this poses a major challenge for parents and caregivers. This proposed study aims to investigate the effectiveness of a teaching package comprising prompting, shaping, and reinforcement strategies in enhancing exploratory eating behaviors among preschool children displaying food selectivity in a classroom setting. The study seeks to answer the research question: does the delivery of a teaching package consisting of prompting, shaping, and reinforcement result in an increase in exploratory eating behaviors (touch, smell, taste) by young children displaying food selectivity? This study will use …

The Impacts Of Gut-Supporting Feed Additives On The Growth Performance, Gut Health, Blood Chemistry, And Immune Status Of Broiler Chickens Exposed To Different Stressors, Richard A. Adefioye

Theses and Dissertations--Animal and Food Sciences

Three experiments were conducted to examine the effects of different feed additives in mitigating stress in broiler chickens. Experiment 1 used 504-day-old male by-product Cobb breeder chicks with 8 treatments replicated 9 times with 7 birds per replicate cage, structured as a 2x4 factorial arrangement of treatments. All birds were on the experimental diets for 20 days. There were 2 levels of lipopolysaccharide (LPS) challenge [no challenge vs. LPS challenge at 1 mg/kg BW) and 4 types of feed additives [no additive, 0.05% PostB, 0.1% PostB, and 0.1% Tynagen^TM]. In experiment 2, 672-day-old male by-product Cobb breeder chicks …

Exploring Elementary Teachers’ Self-Efficacy And Propensity For Teaching Stem, Ashley Wilkirson

Theses and Dissertations--Science, Technology, Engineering, and Mathematics (STEM) Education

The following research is conducted in the interest in exploring self-efficacy (or the lack of) in pre- and in-service elementary school teachers when it comes to teaching STEM. In order to explore the issue of self-efficacy for STEM in elementary schools, it comes to defining what STEM education is and what self-efficacy is. These definitions guide research collected in building these future and current teachers’ self-efficacy, with factors ranging from resources available, pre-service training, professional development, content area knowledge, pedagogical knowledge, perceptions of teaching STEM, and opportunities to collaborate with other teachers were listed as some of the reasons. These …

Exploring Teachers’ Views Of The Nature Of Science And Their Beliefs And Understanding About Viruses And Covid-19: A Multiple Case Study Of Three Secondary Science Teachers At A Rural High School In The Southeastern United States, Jeffrey Chalfant

Theses and Dissertations--Science, Technology, Engineering, and Mathematics (STEM) Education

Over the past several decades, science education reforms have called for students to develop appropriate views of the nature of science and have a comprehensive understanding of subject matter. Additionally, education research has demonstrated that teachers must have appropriate views of the nature of science and strong content knowledge as necessary conditions for appropriate instruction on the nature of science. However, research has consistently shown that teachers hold naïve or inadequate views of the nature of science. This is problematic as teachers are tasked with teaching science to students that is aligned with current education standards. Therefore, teachers need to …

Effects Of Unilateral Lower Limb Suspension On Quadriceps’ Structure And Contractile Function, Eve N. Elmore

Theses and Dissertations--Kinesiology and Health Promotion

BACKGROUND: Muscle unloading such as bed rest or space flight decreases strength and cross-sectional area concomitant with a slow-to-fast fiber type shift, of anti-gravitational muscles such as the quadriceps. Diffusion tensor imaging (DTI) quantifies tissue anisotropic properties such as Fractional Anisotropy, Mean Diffusivity, Axial Diffusivity, and Radial Diffusivity, as well as muscle volume, fascicle length, and physiological cross-sectional area, and has recently been adapted to assess skeletal muscle structure. In skeletal muscle, anisotropic properties correlate with muscle fiber type and contractile function and may be responsive to unloading-induced atrophy.

PURPOSE: To assess the changes in quadriceps’ size, anisotropy, and contractile …

Developing An Immunomodulatory Strategy Using Biophysical Cues To Modulate Macrophage Phenotype For Fracture Healing And Bone Regeneration, Harshini Suresh Kumar

Theses and Dissertations--Biomedical Engineering

Chronic inflammation is a major cause of the pathogenesis of musculoskeletal diseases such as fragility, fracture, and nonunion. Studies have shown that modulating the immune phenotype of macrophages from proinflammatory to pro-healing can heal recalcitrant bone defects. Current therapeutic strategies predominantly apply biochemical cues, which often lack target specificity, and controlling their release kinetics in vivo is challenging spatially and temporally. We have developed a magnetic iron-oxide nanocomplexes (MNC)-based therapy for resolving chronic inflammation in the context of promoting fracture healing. Here, we show that MNC internalized macrophages, when coupled with an external magnetic field, can exert an intracellular magnetic …

Relating Temperature, Sleep, And Pathology In Mouse Models Of Alzheimer's Disease, Jun Wang

Theses and Dissertations--Biomedical Engineering

It is well established that sleep plays an important role in Alzheimer’s disease (AD) pathology. There is growing evidence that sleep issues may accelerate AD pathology by interrupting the physiological clearance of amyloid‐β (Aβ) from the brain, which mainly occurs in normal sleep. As the over-accumulation of amyloid‐β (Aβ) is believed to lead the cascade effect that eventually causes neurodegeneration in AD patients, development of therapeutic strategies for improving sleep quality may help slow disease progression. It is well documented that the composition and dynamics of sleep are sensitive to changes in ambient temperature. We therefore developed a sleep enhancement …

Development Of Iron Oxide Nanozyme For Cancer Therapy, Zhongchao Yi

Theses and Dissertations--Biomedical Engineering

Cancer therapies that leverage reactive oxygen species (ROS) have shown potential for cancer inhibition due to their ability to induce oxidative stress in tumor cells. Iron oxide nanoparticles (IONPs) have garnered significant attention as a promising platform for ROS-dependent disease treatment, owing to their remarkable biocompatibility and Fenton catalytic activity. However, the low catalytic activity of IONPs has been a major hurdle in their clinical translation. To overcome this challenge, IONPs of different compositions are examined for their Fenton reaction under pharmacologically relevant conditions in this work. The results show that wüstite (Fe_1-xO) nanoparticles exhibit higher catalytic activity …

Language Models For Rare Disease Information Extraction: Empirical Insights And Model Comparisons, Shashank Gupta

Theses and Dissertations--Computer Science

End-to-end relation extraction (E2ERE) is a crucial task in natural language processing (NLP) that involves identifying and classifying semantic relationships between entities in text. This thesis compares three paradigms for end-to-end relation extraction (E2ERE) in biomedicine, focusing on rare diseases with discontinuous and nested entities. We evaluate Named Entity Recognition (NER) to Relation Extraction (RE) pipelines, sequence-to-sequence models, and generative pre-trained transformer (GPT) models using the RareDis information extraction dataset. Our findings indicate that pipeline models are the most effective, followed closely by sequence-to-sequence models. GPT models, despite having eight times as many parameters, perform worse than sequence-to-sequence models and …

The Aesthetics Of Environmental Risk In Paolo Bacigalupi’S The Windup Girl And The Water Knife, David Schwartz

Theses and Dissertations--English

Any work of environmentally oriented fiction that seeks to represent the wide-reaching effects of climate change is faced with the problem of scale. These texts must render visible change which is at once ubiquitous and microscopic, along with the cascade of side-effects generated in the wake of rising temperature, rising sea levels, and winnowing biodiversity. In short order, these texts must fully imagine what it means to live within the modern global risk society. Borrowing this sociological model from the late Ulrich Beck, I analyze the literary work of Paolo Bacigalupi, one of the foremost authors in the growing genre …

Functional Analyses Of The Polycomb-Group Genes In Sea Lamprey Embryos Undergoing Programmed Dna Loss, Cody Saraceno

Theses and Dissertations--Biology

During early embryonic development, the sea lamprey (Petromyzon marinus) undergoes programmatic elimination of DNA from somatic progenitor cells in a process termed programmed genome rearrangement (PGR). Eliminated DNA eventually becomes condensed into micronuclei, which are then physically degraded and permanently lost from the cell. Previous studies indicated that many of the genes eliminated during PGR have mammalian homologs that are bound by polycomb repressive complex (PRC) in embryonic stem cells. To test whether PRC components play a role in the faithful elimination of germline-specific sequences, we used a combination of CRISPR/Cas9 and lightsheet microscopy to investigate the impact …

Effects Of Neonatal Estradiol Treatment On Regulating Sexual Differentiation Of Daily Rhythms Underlying Diet-Induced Obesity In Female Mice, Samuel Nwadialo

Theses and Dissertations--Biology

Sex differences of the brain and behavior often require the combination of organizational and activational effects of sex hormones. The activational effects of estrogens in adult female mice protect daily eating and activity rhythms from disruption by high-fat diet feeding and inhibit diet-induced obesity. However, male mice have disrupted eating rhythms when fed high-fat diet and this causes obesity. Treatment of adult male mice with estradiol does not protect rhythms from disruption by high-fat diet, as it does in females. In this study, we sought to determine whether the organizational effects of estradiol masculinize the daily eating and activity rhythms …

Investigations Across Biology And Education: Exploring The Gut Microbiome Of Freshwater Mussels And Understanding Undergraduate Biology Student Motivation, Mary Foley

Theses and Dissertations--Biology

A PhD aims to make a unique contribution to the current body of knowledge while developing as an independent researcher and critical thinker. This dissertation covers a wide range of topics, from microbiome analysis to biology education. Although there is no broad overarching research theme, all the chapters are connected by the process of scientific inquiry and by their contribution to the completion of a PhD.

Chapter One serves as a comprehensive literature review, delving into the standard methods of measuring the health of at-risk species. It describes direct measures of health (e.g., birth and death rates) crucial for predicting …

Estrogen Signaling Regulates The Sex Difference In Resynchronization To Abrupt Shifts Of The Light-Dark Cycle In A Mouse Model Of Jet Lag, Maria Venegas

Theses and Dissertations--Biology

The circadian system coordinates 24-hour cycles of internal biological processes with the environmental light-dark cycle. Abrupt shifts in the timing of the light-dark cycle misalign internal circadian clocks with the environment and cause jet lag until resynchronization occurs. The objective of this study was to investigate the mechanisms underlying sex differences in jet lag in mice. Female mice resynchronized faster than male mice to 6-hour advances and delays of the light-dark cycle, which mimicked eastward and westward travel, respectively. Circulating estradiol was necessary for rapid resynchronization in female mice since ovariectomized females resynchronized slower than mice treated with estradiol. We …

All Eyes On The Spiny Mouse: An Investigation Into Acomys Dimidiatus As A Model For Retinal Biology And Regeneration, Jessica D. Bills

Theses and Dissertations--Biology

The retina is a complex tissue with six types of neurons, supported by an intrinsic glia cell, that work in concert to input a visual stimulus and relay a visual message to the brain. Efficient communication between neurons is vital to this process and each neuron plays a significant role in vision. When retinal neurons degenerate, that visual signal is lost. Degenerative eye diseases affect the neurons of the retina in millions of people world-wide and can ultimately lead to blindness. While treatments are evolving, most are designed to prevent further damage; the field has yet to piece together how …

High Resolution Sedimentary Investigations Of Extant Lakes In North America, John Dilworth

Theses and Dissertations--Earth and Environmental Sciences

Investigation of past lake environments forms the discipline of paleolimnology. Paleolimnological studies seek to evaluate geophysical, geochemical, and ecological proxies and indicators contained within lake sediment archives. Using these potential stores of high-resolution environmental information, questions regarding climate, biological, and geochemical changes experienced by a lake and its watershed can be investigated. This dissertation research utilized lake sediment records from two lakes within North America to study different aspects of environmental change. This dissertation consists of three separate studies presented in three chapters.

Chapter Two presents a retrospective environmental assessment of Jackson Lake, Wyoming to investigate the impacts of dam …