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Gut Microbiome, Neuroinflammation, And Fetal Alcohol Spectrum Disorders: Insights From Rodent Models, Abdulrahman M. Busayli, Wenhua Xu, Ghaidaa A. Raffah, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorder (FASD) is a significant public health issue that affects children. It results from ethanol exposure during pregnancy, leading to considerable physical, neurodevelopmental, behavioral, and cognitive deficits. The exact mechanism is not well understood. Recently, considerable attention has been focused on the influence of gut microbiome on brain development through the gut–brain axis. Changes in the gut microbiome resulting from ethanol exposure may contribute to the pathology of FASD, potentially involving neuroinflammation. This literature review summarizes the existing research and primary animal studies on the impact of early ethanol exposure on the gut microbiome, neuroinflammation, brain development, …

Calcineurin/Nfat Inhibitors Maintain Cognition In A Preclinical Prevention Study In An Aging Canine Model Of Alzheimer Disease, Lorena Sordo, Margo F. Ubele, Kathy Boaz, Jennifer L. Mefford, Erin Dehnart Jones, Katie L. Mccarty, Hollie Y. Van Rooyen, Jeffrey R. Smiley, Stasia A. Bembenek Bailey, Jessica A. Perpich, Beverly Meacham, David K. Powell, Frederick Bresch, Jacob W. Crump, Michael J. Phelan, Jessica A. Noche, Craig E. Stark, László G. Puskás, Christopher M. Norris, Elizabeth Head

Pharmacology and Nutritional Sciences Faculty Publications

Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD. Beagles naturally develop Aβ plaques and cognitive dysfunction. We evaluated the impact of FDA-approved CN inhibitor, tacrolimus, and experimental NFAT inhibitor, Q134R, on cognitive outcomes during a three-year prevention study in 37 middle-aged beagles. While beagles treated with CN/NFAT inhibitors showed differences in the pattern …

Ceramide Homeostasis In Hepatic Lipid Droplets, Leobarda Robles-Martinez, Kylie H. Morin, Mariana Nikolova‑Karakashian

Physiology Faculty Publications

Almost all eukaryotic cells have the capacity to form lipid droplets (LDs) in conditions of excess energy. Traditionally thought to be just inert fat reservoirs, LDs have recently emerged as important metabolic regulators of cellular stress response that buffer excess free fats and protect cells from lipotoxicity. Ceramide is a bioactive lipid that accumulates in metabolic tissues during fat oversupply. Emerging evidence suggests that sphingolipids and sphingolipid-metabolizing enzymes are found in the LDs and affect LD biogenesis and functions. This article aims to summarize the evidence, delineate some plausible functions of ceramide in hepatic LD biogenesis, and illustrate some of …

Impact Of Fast Advancement And Early Fortification Of Enteral Feedings In Preterm Infants, A Retrospective, Observational Study., Enrique Gomez-Pomar, Holly Clarke, Jamie Adams

Pediatrics Faculty Publications

UNLABELLED: We aimed to evaluate the outcomes and growth of preterm infants at a Neonatal Intensive Care Unit that focuses on early initiation, fast advancement, and early fortification of enteral feeds.

METHODS: Retrospective study conducted at a community hospital level III NICU. Extensive feeding data and outcomes were collected by utilizing a NutritionIQ software application, NICUtrition®. Infants born between 26- and 34-weeks gestational age were included, whereas infants with congenital defects, deceased or with incomplete data were excluded. Frequency and descriptive statistical analysis were conducted using chi-square and Fisher's exact test. Unadjusted odds ratios were computed for categorical variables and …

Interaction Between Riluzole Treatment And Dietary Glycemic Index In The Disease Progression Of Amyotrophic Lateral Sclerosis, Ikjae Lee, Hiroshi Mitsumoto, Seonjoo Lee, Edward J. Kasarskis, Michael Rosenbaum, Pam Factor-Litvak, Jeri W. Nieves

Neurology Faculty Publications

Objective: We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).

Methods: Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (n = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates. Age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised ALS functional rating scale (ALSFRS-r) total score, and forced vital capacity, from …

Bones And Brains: The Association Between Osteoporosis And Depression, Mason Taylor

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

Introduction: Osteoporosis and depression are two public health problems that are increasing in prevalence. Previous studies have found a positive association between the two variables in women and men and women together, but there is a gap when looking at men. Therefore, it was important to investigate the odds of depression in men, women, and men and women together to make comparisons by sex.

Methods: 1,602 participants aged 65 and older were included in the study from the National Health and Nutrition Examination Survey (NHANES) 2017 – March 2020 Pre-Pandemic dataset. One unadjusted and seven adjusted models were created for …

How Sleep Disorders And Sleep Duration Impact Memory, Alexandria J. Sims

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

INTRODUCTION: Sleep duration and sleep disorders can cause changes in memory function as populations age. Previous studies have shown that disordered sleep is associated with increased risk of cognitive dysfunction and long and short sleep durations can cause memory impairment. This study studies aims to find if there is an association between sleep disorders and sleep duration and the impacts on memory.

METHODS: In this study, 3,478 participants aged 60 year and older from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 dataset were included in adjusted and unadjusted models, comparing the sleep disorders and sleep duration exposures to …

Environmental And Behavioral Determinants Of Congenital Defects: An Ecologic Study In Kentucky, Amelia G. Floyd

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

Congenital defects are a significant contributor to infant morbidity and mortality. The multifactorial etiology of such defects presents complex challenges for public health. This ecologic study investigates the association between environmental and behavioral exposures and congenital defects rates at the county level in Kentucky from 2010 to 2019. The Kentucky Department for Public Health, Office of Vital Statistics, provided all relevant defect data. County-level exposure data was collected from multiple sources.

Descriptive and geospatial analyses revealed substantial geographic variability, with notable high defect rates in northeastern Kentucky. Negative binomial regression models identified behavioral and socioeconomic factors to be the strongest …

Metabolic And Barrier Function In Response To Β-Caryophyllene In Intestinal Epithelial Cells, Hannah Scroggins

Theses and Dissertations--Animal and Food Sciences

Butyrate, a short-chain fatty acid, regulates cellular metabolism and energy status in intestinal epithelial cells. β-caryophyllene (BCP) is a plant-derived compound that may provide advantageous effects on intestinal barrier function and nutrient utilization. The goal of this thesis was to investigate the effects of BCP on butyrate utilization and metabolism in intestinal epithelial cells. Throughout this thesis, Caco-2 cells in hanging inserts in multi-well plates were used as a model for the intestinal barrier. One study was conducted to investigate the effect of BCP on butyrate utilization and barrier function in intestinal epithelial cells. A second study aimed to elucidate …

Comparison Of Sheep And Cattle Rumen Microbiological And Physiological Responses To An Abrupt Transition From A High-Forage To A High-Concentrate Diet, Katherine Purvis

Theses and Dissertations--Animal and Food Sciences

Sheep and cattle are often used interchangeably due to having the same gastrointestinal anatomy; however literature directly comparing the two species is minimal. Previous in vitro studies have pointed towards potential species differences in rumen carbohydrate utilization and acidosis susceptibility. The objective of this study was to evaluate in vivo microbiological and physiological responses of wethers and steers when abruptly transitioned from a high-forage to a high-concentrate diet. We hypothesized there are differences between species in response to abrupt dietary transition with respect to intake, rumen microbiology, and the rumen environment. Individually housed, rumen cannulated purebred Polypay wethers (n = …

Nicorandil Treatment Improves Survival And Spatial Learning In Aged Granulin Knockout Mice, Dana M. Niedowicz, Wang-Xia Wang, Paresh Prajapati, Yu Zhong, Shuling X. Fister, Colin B. Rogers, Pradoldej Sompol, David K. Powell, Indumati Patel, Christopher M. Norris, Kathryn E. Saatman, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Mutations in the human granulin (GRN) gene are associated with multiple diseases, including dementia disorders such as frontotemporal dementia (FTD) and limbic-predominant age-related TDP-43 encephalopathy (LATE). We studied a Grn knockout (Grn-KO) mouse model in order to evaluate a potential therapeutic strategy for these diseases using nicorandil, a commercially available agonist for the ABCC9/Abcc9-encoded regulatory subunit of the “K⁺ATP” channel that is well-tolerated in humans. Aged (13 months) Grn-KO and wild-type (WT) mice were treated as controls or with nicorandil (15 mg/kg/day) in drinking water for 7 months, then tested for neurobehavioral …

Disrupted Calcium Dynamics In Reactive Astrocytes Occur With End Feet–Arteriole Decoupling In An Amyloid Mouse Model Of Alzheimer’S Disease, Blaine Weiss, John C. Gant, Ruei-Lung Lin, Jenna L. Gollihue, Colin B. Rogers, Susan D. Kraner, Edmund B. Rucker, Yuriko Katsumata, Yang Jiang, Peter T. Nelson, Donna M. Wilcock, Pradoldej Sompol, Olivier Thibault, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

While cerebrovascular dysfunction and reactive astrocytosis are extensively characterized hallmarks of Alzheimer's disease (AD) and related dementias, the dynamic relationship between reactive astrocytes and cerebral vessels remains poorly understood. Here, we used jGCaMP8f and two-photon microscopy to investigate calcium signaling in multiple astrocyte subcompartments, concurrent with changes in cerebral arteriole activity, in fully awake 7- to 8-month-old male and female 5xFAD mice, a model for AD-like pathology, and wild-type (WT) littermates. In the absence of movement, spontaneous calcium transients in barrel cortex occurred more frequently in astrocyte somata, processes, and perivascular regions of 5xFAD mice. However, evoked arteriole dilations (in …

The Role Of Cooperative Extension In Community Development: A Study Of Success Stories And Leadership Practices, George Grant

Theses and Dissertations--Educational Leadership Studies

The Cooperative Extension System (CES) plays a vital role in community education and development across the United States. CES agents and specialists work directly with community members to identify needs, mobilize existing assets, and empower action. Despite the overlap in the fields of CES and community development, few studies have systematically analyzed the specific practices used by extension personnel who act as facilitators of change within communities. To address this gap in knowledge, a qualitative study was conducted using directed content analysis of CES success stories published through the University of Kentucky to identify practices used among two integral positions …

Psychological Impacts In Exercise Riders And Professional Jockeys Following Injury, Kelley M. Renner

Theses and Dissertations--Kinesiology and Health Promotion

One of the most well-known equestrian sports, horse racing, is not only a cornerstone of Kentucky’s economy, but also a vital part of its culture, with professional jockeys playing an essential role in the local communities and traditions that define the state. Despite its popularity and financial impact, mental health challenges within the sport have continually been shrouded in silence and ignored in research (Ball et al., 2007). Equally concerning is the high injury prevalence, and psychological impact of these injuries (e.g., psychological distress, depression, anxiety, loss of identity, and self-esteem (King et al., 2022; Losty et al., 2019; McConn-Palfreyman …

Exploring College Students’ Motivation For Physical Activity: Applications Of Self-Determination Theory And The Role Of Health And Wellness Education, Anne Russell Blevins

Theses and Dissertations--Kinesiology and Health Promotion

This dissertation includes three pieces of writing that aim to show the importance of physical activity for all ages but specifically college-aged students. The first piece of writing (Chapter 2) includes a teaching tip written for the Journal of Physical Education, Recreation, and Dance. Research has shown that dance was a subject of the past and many teachers did not feel comfortable teaching it. This practical piece was written to help show K-12 physical education teachers effective ways to involve students in physical activity specifically through teaching dance, mainly through using the “Teaching Dance for Understanding” model.

The second section …

Geochemical And Sedimentological Signals Of Bottom Water Oxygen Dynamics From Lake Tanganyika (Zambia), Njahi Mwangala

Theses and Dissertations--Earth and Environmental Sciences

Lake Tanganyika is a large, ancient freshwater body with exceptional biodiversity that is located in the East African Rift System. Lake Tanganyika’s size and longevity make its sedimentary record useful for understanding environmental changes that cross spatial and temporal boundaries. Lake Tanganyika is known to be susceptible to global warming given its tropical location. Over 12 million people living within Lake Tanganyika’s watershed rely on fishing for their income and nutrition. Changes to limnological function driven by climate could therefore have serious implications for human health and biodiversity conservation. This study focuses on using geochemical properties of modern lake bottom …

How To Eat Right And Why We Ask That Question, Heather N. Carpenter

Theses and Dissertations--Gender and Women's Studies

What does it mean to “eat right?” The notion is, of course, culturally, historically, nationally, politically, ethnically, and class determined. For the purposes of this project, however, I am particularly interested in changing notions of what it means to “eat right” within the post-World War II to the early new millennium American context, as such notions are represented within the prescriptions of popular culture. I turn to popular culture because this is the commons of the hegemonic call to “normalcy”—this is where we all learn to imitate, aspire, or rebel against a generic American consumer-self in conformity with the biases, …

Plastic Gerontologies: Epigenetic Clocks As Instruments Of The Profitable Medicalization Of Aging, Hans T. Purisch

Theses and Dissertations--Geography

Epigenetic clocks are algorithms that use epigenetic biomarkers of aging to calculate an organism’s ‘biological age.’ Through discursive analysis of commercially available epigenetic clock marketing materials, scientific articles, and interviews with actors in the longevity biotechnology industry, this study examines the commercialization of epigenetic clocks in the form of consumer test-kits. The study argues that longevity biotechnology companies leverage the malleable and fluid qualities of epigenetic markers of biological age to extend the domains of profitable therapies. It shows that epigenetic clock companies market the dynamic qualities of epigenetic biological age measurements to redefine health around the project of optimizing …

Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein

Theses and Dissertations--Neuroscience

Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.

After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …

Practicing Clinicians' Views Of The Life Participation Approach To Aphasia Therapy, Stephanie H. Mays

Theses and Dissertations--Communication Sciences and Disorders

The Life Participation Approach to Aphasia therapy (LPAA) aligns with a person-centered, functional approach to speech therapy. Past research has demonstrated that persons with aphasia (PWA) benefit from this approach and prefer it when compared to the traditional medical model to therapy. However, a disconnect between PWA preferences and SLP treatment approaches in therapy persists. This study aims to identify both barriers and facilitators that SLPs face when implementing LPAA. Five CCC-SLPs practicing in the state of KY with experience working with PWA were recruited as participants. Participants were placed into two focus groups, with each group meeting for 2-3 …

Zebrafish Models To Uncover Targetable Mechanisms Of Self-Renewal In T-Cell Acute Lymphoblastic Leukemia, Majd Al-Hamaly

Theses and Dissertations--Pharmacology and Nutritional Sciences

Relapsed T-cell Acute Lymphoblastic Leukemia (T-ALL) patients have dismal prognosis, with 5-year overall survival rates of 10% for adults and 36% for children. Relapse is attributed to the inability of chemotherapy agents to eliminate Leukemia Stem Cells (LSCs) that can repopulate the leukemia. Those cells exist with a unique genetic, transcriptomic, and metabolic profile compared to the rest of the leukemia and thus, finding targeted therapies toward this population of cells can result in disease eradication and elimination of relapse. However, investigating LSCs is challenging-particularly in T-ALL- for two reasons: 1) the lack of robust surface markers that define LSCs …

Assessing The Effectiveness Of A Modified Cook Together Eat Together Program On Food Resource Management Behaviors In A Rural Setting, Johanna K. Poysti

Theses and Dissertations--Nutrition and Food Systems

This study evaluated the effectiveness of a modified, hybrid Cook Together, Eat Together (CTET) program on food resource management behaviors in a rural setting. A six-week intervention combining virtual and in-person sessions aimed to improve health behaviors, food resource management skills, and self-efficacy. Although most behavioral changes were not statistically significant, participants reported increased confidence in cooking healthy meals on a budget. Positive qualitative feedback from focus group discussions indicated program feasibility and engagement. Strengths and limitations of the study were discussed as well as recommendations for future research were given.

Causes And Consequences Of Reproductive Plasticity In The Seed Beetle, Callosobruchus Maculatus, Josiah P. Ritchey

Theses and Dissertations--Entomology

Competition for resources has direct effects on traits that can influence an individual’s reproductive success in competitive mating environments. When population density is high during development, competition for resources can reduce growth and body size at maturation, influencing resources available for reproduction. In this thesis, I investigate how the developmental environment affects plasticity in male reproductive traits, as well as the consequences of male reproductive plasticity on female reproductive behavior, in the seed beetle, Callosobruchus maculatus. My results show that increasing larval density causes male beetles to emerge small and transfer small ejaculates to females. However, small males transfer …

Dinotefuran Resistance In The German Cockroach (Blattella Germanica L.), Hannah F. Blevins

Theses and Dissertations--Entomology

German cockroaches (Blattella germanica L.) are one of the most prevalent and pervasive indoor pest species in the world. Infestations can lead to many negative impacts on humans, including sensitization to allergens, increase in asthmatic symptoms, mental health declines, and potentially, the spread of diseases. While insecticides remain the most effective and affordable option for German cockroach control, resistance to many commonly used insecticide active ingredients (AIs), such as pyrethroids, has been observed globally at high levels across different populations. Given such resistance to pyrethroids, inclusion of insecticides with alternative modes of action into insecticidal treatments could potentially improve cockroach …

Bed Bugs: Health Risks And Control, Simona Principato

Theses and Dissertations--Entomology

Bed bugs are blood-feeding hemipterans strongly associated with humans. Their detection in indoor environments, such as homes, hotels, trains, and public facilities, has increased gradually over the past 20 years. The exact cause of their resurgence is still unclear, but the increase of international travel and insecticide resistance are thought to have contributed to it.

Although bed bugs are not known to transmit diseases, the EPA, CDC, and USDA have classified them as a pest of significant public health concern, mainly due to the dermatitis that they can cause. Beyond the dermatological burden of the bites, other health implications often …

The Role Of Nutrition In Managing Honey Bee Viral Pathogen, Caroline Wylie Kane

Theses and Dissertations--Entomology

This study evaluated the impact of nutritional supplements on viral infections in honey bee colonies, focusing on Lake Sinai Virus 2 (LSV2), Deformed Wing Virus A (DWVA), and Deformed Wing Virus B (DWVB). I partnered with 32 hobbyist beekeepers across Kentucky, who volunteered 138 colonies for a month-long field study. Half of the colonies received weekly commercial supplements, while the other half served as controls. Viral titers were measured before and after the supplementation period using qPCR. Supplements did not significantly reduce viral titers for any of the three viruses, suggesting that short-term supplementation may not be effective in lowering …

Gene Expression In Relation To Bone Fractures In Throughbred Racehorses, Anna M. Rauber-Ramos

Theses and Dissertations--Veterinary Science

Evidence that fractures in Thoroughbred racehorses are outcomes of chronic bone microdamage has led to extensive research into identifying horses at increased risk of fracture. This includes the use of biomarkers and messenger RNA (mRNA) as a measure of bone turnover. Previous research has found expression differences in horses with fractures compared to controls. Utilizing pre-race whole blood samples collected over an 18-month period from Thoroughbred racehorses in Southern California, RNA-sequencing was conducted on horses with bone fractures and race-matched controls to identify differences in gene expression. Focusing on third metacarpal (MC3) and proximal sesamoid bone (PSB) fractures, differentially expressed …

Engineering Novel Biomimetic Models Of Equine Host-Microbe Interactions, Lynn M. Leedhanachoke

Theses and Dissertations--Veterinary Science

One major limitation to the study of equine disease is the lack of in vitro models that accurately reflect the dynamic physiology of the horse. Thus, there is a pressing need to develop in vitro systems that recapitulate diverse equine tissue and organ microenvironments. To overcome this deficiency, we developed multiple biomimetic equine organoid systems that can be employed for a variety of investigations aimed at resolving outstanding questions in infectious disease pathogenesis, therapeutic development and drug metabolism, host defense mechanisms, immune-modulated disease, and equine developmental biology. Our innovative platform incorporates novel equine intestinal enteroid and airway organoid models derived …

Development Of A Cultivation System For Producing Pure Mycelium Materials From Distillers' Spent Grains, Keya Rani Roy

Theses and Dissertations--Biosystems and Agricultural Engineering

Stillage is a byproduct of distilleries which is rich in organic matter, minerals, and acidic components. It is commonly used as animal feed and has high potential for use as an alternative substrate for microorganisms. Filamentous fungi are saprophytes that can utilize stillage solids to grow as threadlike mycelium. The structure and composition of the filamentous mycelium has shown promise to produce pure mycelium materials (PMM), which might have many potential applications, for instance as a leather-like material or alternative protein food ingredient. Basidiomycota fungi (including true mushrooms) species are presently used in industry to produce PMM due to the …

Development Of Non-Destructive Methods For The Detection And Quantification Of Gluten Sources In Foods, Adewale Abiola Oloyede

Theses and Dissertations--Biosystems and Agricultural Engineering

Cross-contamination of food with gluten-rich grains such as wheat, barley, and rye remains a significant challenge in gluten-free food production, posing health risks to individuals with gluten-related disorders. Traditional detection methods are often time-consuming and labor-intensive, highlighting the need for rapid and reliable alternatives. This study investigates the use of hyperspectral imaging (HSI) combined with machine learning (ML) and deep learning (DL) techniques for the detection and quantification of gluten contamination in grain-based foods through three main approaches: (i) classification of gluten source contaminants in gluten-free flour, (ii) quantification of gluten content from wheat, rye, and barley flours, and …