Now showing items 1-20 of 1262

    • Protecting the Hidden Victims: Increasing Family Bonding Throughout Incarceration

      Rinberger, Taylor
      Final report of a Service Scholars project to provide family-friendly visitation areas in correctional facilities.
    • Middle to Middle: Middle Georgia Students Engaging in Middle Eastern Studies

      Zgonc, Maddie
      Proposal and final report of a Service Scholars project to engage Middle Georgia students in Middle Eastern studies.
    • Sexual Health Education Series

      Bobo, Madeline
      Proposal and final report of a Service Scholars project to conduct sexual education workshops with Mercer University incoming freshmen
    • ABLE Mercer

      Wright, Johna
      Final report of a Service Scholars project establishing a peer mentoring program among first-year college students.
    • Operation Lighthouse

      Guta, Elliza
      Proposal and final report of a Service Scholars project to prevent dating violence in the Macon community.
    • Designing and Implementing A STEAM Education Mercer on Mission

      Darragh, William
      Final report of a Service Scholars project to teach computer science in underserved communities in middle Georgia and South Africa.
    • A PHENOMENOLOGICAL INVESTIGATION OF HIGH SCHOOL COUNSELORS’ EXPERIENCE AND KNOWLEDGE IN ADVISING STUDENT-ATHLETES ON THE NCAA COLLEGE TRANSITION PROCESS

      Howard, Leah; College of Professional Advancement
      This phenomenological investigation examined the experiences and knowledge of high school counselors in advising student-athletes on the NCAA college transition process. The study sought to gain a deeper understanding of the challenges, successes, and experiences of school counselors in supporting student-athletes during a critical transition period. School counselors often receive insufficient training in this area, resulting in a lack of adequate support for student-athletes to navigate the college transition process effectively and maximize their opportunities for postsecondary education (Paramo-Garfio, 2017; Vaughn & Smith, 2018). The research was conducted using interviews to capture the lived experiences and perspectives of nine Georgia high school counselors. The research examined school counselors’ roles and their facilitation of advising student-athletes on the NCAA college transition process. The findings of this study may contribute to the existing literature and provide insights for improving support services and training programs for high school counselors working with student-athletes (Stahlke and Cranmore 2021). The study concludes with recommendations for a comprehensive and collaborative approach to facilitating a successful college transition for student-athletes.
    • Use of Simulation in U.S. Physical Therapist Programs: A Multiple Case Study

      Ross, Sarah; Tift College of Education
      This study explored how U.S. Doctor of Physical Therapy (DPT) programs integrate and implement simulation-based learning into their curricula. While recent research takes a broad view of how physical therapy (PT) programs are using simulation, this research sought an in-depth understanding by exploring the questions about (1) how are programs integrating simulation into curricula, (2) how are programs designing and implementing simulation, (3) what are barriers or challenges to simulation use, and (4) how are programs using simulation for interprofessional education. This exploration spans across three manuscripts. The first manuscript is a systematic literature review, which examines current published research regarding how PT programs use simulation. The review of the literature showed that many programs use simulation to replicate the acute care setting, to address interprofessional education, and to assess clinical decision-making skills. The second and third manuscripts are qualitative case studies that examine in-depth how three different PT programs use simulation in their curricula. The empirical research part of this dissertation was a multiple case study design. Three DPT programs were selected for their diversity from volunteers who responded to a national call for participants. Three one-on-one semi-structured interviews were conducted via Zoom with all three participants. Artifacts were also gathered to enrich the interview discussions and enhance data analysis, such as plans of study, simulation planning documents, debriefing guides, case information, and assessment rubrics. Utilizing Saldaña’s Themeing the Data approach for data analysis of the interview revealed a consensus on important aspects of curricular integration, planning and executing effective simulations, and challenges with conducting simulations. Additionally, Interprofessional Education Collaborative Core Competencies underscored interprofessional simulations. Finally, participants agreed that collaboration of participating programs and intentional integration in the design and planning phases of simulations are necessary to accomplish effective learning events. The findings from this study serve to further understanding of how PT programs use simulation, to identifying existing gaps in following best practices, and to continuing the push towards developing standards of best practice and assessment specifically for simulation use in PT education.
    • STEM PERSISTENCE AND THE DOUBLE BIND: INSTITUTIONAL FACTORS THAT CONTRIBUTE TO STEM SUCCESS

      Jenkins, Tynetta; Tift College of Education
      This study investigated the complex relationship between women’s attributes, collegiate experiences, and STEM cultural ideology, all of which significantly impact STEM persistence. This study specifically addressed the disparities between Black and White women pursuing undergraduate STEM degrees across diverse institutions in the United States. Furthermore, it explored how institution type and collegiate experiences influenced STEM persistence among women pursuing STEM undergraduate degrees. Multiple methods were used to collect and analyze the data. Results of statistical analyses revealed significant differences in collegiate interpersonal relationships, institutional influences, and STEM cultural ideology experienced by Black women and White women, echoing the prevailing trends in existing research. Further, significant differences in collegiate interpersonal relationships and institutional influences were observed between public and private institutions, with no significant differences between universities and four-year institutions or between historically Black colleges and universities and their non-historically Black counterparts. Finally, the results of statistical analyses for the sample revealed that STEM cultural ideology was the only predictor that influenced STEM persistence, while race/ethnicity, women’s attributes, interpersonal relationships, and institutional influences did not. These findings challenge much of the available literature and suggest that STEM persistence may be influenced by additional factors not accounted for in this study. As such, further research is necessary to gain a comprehensive understanding of the contributors to STEM persistence for Black and White women in STEM undergraduate programs of study.
    • Novel Pain-Free Immunization of a Combination Microparticulate Vaccine for COVID-19 and Influenza

      Vijayanand, Sharon Christina Pearline; College of Pharmacy
      Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Influenza are contagious respiratory viruses that can only be effectively prevented by vaccination. Both COVID-19 and Influenza have previously caused Pandemics that have significantly affected the well-being of people globally. Although there are several approved vaccines for both diseases, the limitations and shortcomings of these vaccines are why there is constant research for developing a better vaccine. The current vaccines are primarily painful and non-patient-friendly intramuscular injections, resulting in vaccine hesitancy in children and older adults. IM injections also require trained healthcare professionals for vaccine administration, contributing to the workforce's burden. There is also a requirement to store these vaccines in a cold temperature setting to preserve the life of these biologicals. However, such conditions pose an issue during the transportation and distribution of these vaccines worldwide. Developing and underdeveloped countries are affected by such limitations in storage and distribution. All these factors lead to declining vaccination rates and an increase in the frequency of the emerging mutant strains. Considering all these factors, we tested an inactivated microparticulate vaccine for COVID-19 and a combination microparticulate vaccine for COVID-19 and Influenza. Utilizing a microparticle matrix to encapsulate the vaccine antigen protects the antigen from degradation. Additionally, particle-based vaccines are being investigated for stability at various temperatures, including room temperature. The vaccine was tested via different non-invasive routes such as transdermal using microneedles, buccal using oral dissolving films, and intranasal route to minimize or eliminate pain during vaccination. First, the microparticle vaccines were prepared, characterized, and assessed in vitro for their immunogenicity, cytotoxicity, autophagy, and antigen presentation. Next, the inactivated SARS-CoV-2 vaccine and the inactivated combination SARS-CoV-2-Influenza vaccine were tested in vivo in a preclinical mouse model and evaluated for immunogenicity and efficacy upon administration to mice. The study's results are summarized in this dissertation and clearly show that non-invasive vaccination strategies can induce effective immune responses in mice. A microparticle vaccine approach can solve multiple problems in vaccine development, distribution, storage, and administration when combined with a non-invasive vaccination strategy. However, like every vaccine, novel vaccination strategies warrant further investigation.
    • Astrocytic Influences in the Auditory Brainstem in Fragile X Syndrome

      Warner, Katharine D; School of Medicine
      Fragile X Syndrome is one of the leading genetic causes of autism spectrum disorder. Fragile X Syndrome is associated with auditory hypersensitivity and childhood audiogenic frontal-temporal lobe seizures, which may be the result of abnormalities in the auditory nuclei found in the brainstem. The purpose of this research is to expand on preliminary findings that dysfunction in the auditory brainstem contributes to sound sensitivity and subsequently to frontal-temporal lobe seizures. To test the role of the LSO, VCN, and MNTB we examined the astrocyte function in these areas by extracting the auditory brainstem from Fmr1 KO mice and wild type mice. We then co-cultured these astrocytes with neurons from either mouse genotype to determine differences in the neuronal size, morphology, and synaptogenic factors. Our research examined the levels of SPARC, hevin, and thrombospondin-1, which are synaptic proteins found in the synapses in the auditory brainstem. Our results showed that Fmr1 KO astrocytes altered the size of WT neurons to a size comparable to a standard Fmr1 KO neuron, and Fmr1 KO astrocytes secreted significantly less SPARC than WT astrocytes. Overall, abnormal astrocyte function among Fmr1 KO mice was found to cause morphological changes in auditory brainstem neurons and differences in the amount of the SPARC found in the auditory brainstem between wild type and Fmr1 KO mice.
    • WHAT DOES MIDDLE SCHOOL TEACH? THE CURRICULUM OF BEING/BECOMING MIDDLE SCHOOL TEACHERS

      Warren, Erica Adela; Tift College of Education
      This post-critical ethnographic study explored the curriculum of being/becoming a middle school teacher that 5 emergency-certified new-to-teaching teachers experienced through the quotidian interactions of their first fully in-person school year. The curriculum of being/becoming teachers is increasingly important as the percentage of teachers entering the profession through alternative and emergency certification pathways increases each year and school and district leaders inherit more of the responsibility to prepare and develop these teachers. The purpose of this study is to describe how participants developed a sense of students, content, and contexts through the curriculum of being/becoming teachers. Additionally, this study describes how the instructional coach/researcher co-developed and evolved a new teacher community of practice (NTCOP) that pushed participants toward becoming more sensitive, humane, and empathetic curriculum makers. Three questions guided this inquiry: (1) What are some of the core teachings in the curriculum of being/becoming teachers at this school site as evidenced by policies, practices, and relationships between teachers and students in place during their inaugural school year?; (2) In what ways does engagement in a learning group aimed at intervening in the curriculum of being/becoming teachers interact with new-to-teaching teachers' understanding of who they become, what they know, and how they interact with students and as middle school teachers?; and (3) What questions do new-to-teaching teachers’ experiences grappling with the curriculum of being/becoming teachers and emerging teacher identity raise about the ways districts and schools provide support? In middle schools, where nearly a third of adolescents experience academic and social challenges due to developmental and cultural mismatches between teachers and students, this study’s findings suggest that the curriculum of being/becoming teachers reinforced these mismatches in three ways: school and district leaders assigned teaching tasks as a mechanism of control, middle school policies and practices reinscribed deficit narratives about adolescents, and administrators and colleagues cultivated a hostile environment for new-teacher learning. The NTCOP provided a counter-space for participants to disrupt deficit narratives and to discuss and affirm placemaking practices. However, the participants did not adopt active advocacy stances toward adolescents despite the researcher’s efforts.
    • CEREBROVASCULAR COMPLICATIONS OF SARS-CoV-2 IN TYPE-2 DIABETES

      Burnett, Faith; School of Medicine
      Diabetics are more vulnerable to SARS-CoV-2 cerebrovascular complications, including brain fog, cognitive impairment, and strokes. This study aims to identify the molecular mechanisms of SARS-CoV-2-induced cerebrovascular dysfunction in diabetics. We hypothesize that SARS-CoV-2 exacerbates diabetes-induced cerebral oxidative stress and inflammation via activation of the destructive arm of the renin-angiotensin system (RAAS) and toll-like receptor (TLR) signaling. Methods: SARS-CoV-2 spike protein interacts with human ACE2 receptors but not murine Ace2. Therefore, type-two diabetes was induced in humanized ACE2 (hACE2) transgenic knock-in mice using low-dose streptozotocin followed by eight weeks of a high-fat diet. Recombinant SARS-CoV-2 spike protein was injected intravenously in control and diabetic mice. Cognitive functions were tested using Y-maze and Barnes maze. Cerebral blood flow was measured using laser speckle imaging. RAAS system and TLR signaling were assessed using RT-PCR and western blot analysis. The cerebrovascular architecture was measured using immunohistochemistry. Human brain microvascular endothelial cells were treated with hyperglycemia (25 mM glucose) to mimic diabetic conditions. Results: Spike protein exacerbated diabetes-induced cerebrovascular oxidative stress and inflammation as detected by increased (NOX1, NOX5) and (Il-6, Il-1β, and TNF-α) gene expression, respectively. Spike protein enhanced the destructive RAAS arm (angiotensin ll and AT1R) at the expense of the RAAS protective arm (ACE2 and AT2R) gene expression (P<0.05). In parallel, spike-protein exacerbated TLR signaling in diabetes as indicated by the increase in TLR-8 receptor and its ligands (HMGB1 and S100) and downstream adaptor proteins (MyD88, TRAF6, and NF-κB) expression (P<0.05). Spike-protein increased cerebrovascular rarefaction and decreased blood flow and cognitive functions in diabetes compared to control (P<0.05). Conclusion: SAR-CoV-2 spike protein intensified RAAS and TLR signaling in diabetes, increasing cerebrovascular damage and cognitive dysfunction. Targeting RAAS and TLR singling are possible therapeutic strategies to protect against SAR-COV-2-induced cerebrovascular dysfunction in diabetes.
    • Deciphering The Effect of Xenobiotic Exposure on The Immunobiology of Human Mesenchymal Stem Cells & Their Interaction with Dendritic Cells

      Uwazie, Crystal Chidinma; School of Medicine
      Mesenchymal Stromal Cells (MSCs) are nonhematopoietic multipotent stem cells that possess a myriad of immunomodulatory and regenerative functions and thus maintain immune physiology and tissue homeostasis in the body. MSCs primarily carry out these functions through intercellular immune interactions involving paracrine secretion of secretory factors such as cytokine, chemokines, and growth factors. Previous study has extensively shown that MSCs display immunosuppressive properties on immune cells of lymphoid lineage; however, MSC’s interactions with cells of myeloid lineage such as dendritic cells require further research. Furthermore, given the central role of dendritic cells in immunity as antigen-presenting cells and the bridge between the innate and adaptive immune systems, it is important to understand how disruptions in the interactions between MSCs and dendritic cells can have implications on immune physiology. This project seeks to address this lack of knowledge by 1) identifying the interactions between human bone marrow derived MSCs and two circulating dendritic cells subtypes (plasmacytoid and myeloid) and by 2) defining the functionality of human bone marrow derived MSCs upon exposure to atrazine. MSC and dendritic cell interactions were investigated by conducting MSC and peripheral blood mononuclear cell (PBMCs) co-cultures under TLR7 or TLR4 stimulation. The presence of MSCs and TLR7 stimulation showed no effects on the function of the plasmacytoid dendritic cell subset. Contrarily, the presence of MSCs and TLR7 stimulation led to a decrease in maturation in the myeloid dendritic cell subset, as measured by CD83 expression using flow cytometry. Interestingly, MSCs present in a co-culture and TLR4 stimulation led to an increase in maturation in the myeloid dendritic cell subset. Secretome analysis of stimulated MSCs using multiplex assays suggests that secretory factors may be the reason for the results seen. Disruptions to MSC immune interactions were investigated by exposing MSCs to the xenobiotic herbicide atrazine at a range of dosages and for various durations of time. Cells were analyzed using an assay matrix comprising of MTT assays, flow cytometry, and multiplex assays. Atrazine was shown to affect MSC metabolic viability, size and granularity in a dose and time dependent manner. Atrazine exposure also modulates certain immunomodulatory and angiogenic secretory factors. Furthermore, atrazine exposure attenuates MSC responsiveness to exogenous cues, namely IFNγ. These results provide the context necessary in understanding how xenobiotic disruptions from atrazine exposure can affect immune interactions between MSCs and circulating dendritic cells.
    • Application of Recurrent Neural Networks for Pharmacokinetic Modeling and Simulation

      Khusial, Richard Darien; College of Pharmacy
      Pharmacometrics and the utilization of population pharmacokinetics play an integral role in model informed drug discovery and development (MIDD). Recently, there has been a growth in the application of deep learning approaches to aid in areas within MIDD. In this work, we aim to explore the potential of deep learning approaches towards drug concentration prediction and simulation. A total of 1,527 olanzapine drug concentrations sparsely sampled from 523 individuals along with eleven patient-specific covariates provided by the CATIE studies were used in model development, validation, and simulation. LSTM and LSTM-ANN with multiple inputs were investigated towards olanzapine drug concentration predictions. The LSTM-ANN model captured the relationships within a pharmacokinetic dataset and generated olanzapine drug concentration predictions with a lower RMSE than the LSTM model. Bayesian optimization was implemented to tune the hyperparameters of the LSTM-ANN model. The LSTM-ANN model had a RMSE of 29.566 in the validation set. A population pharmacokinetic model using NONMEM model was constructed as a reference to compare the performance of the LSTM-ANN model. The RMSE of the NONMEM model was 31.129. Permutation importance revealed age, sex and smoking were highly influential covariates in the LSTM-ANN model. The LSTM-ANN model showed potential in drug concentration prediction as it performed comparably to the NONMEM model. Future studies investigating clinical studies with varying sample sizes and sampling strategies are required to further examine the potential of a LSTM-ANN model towards drug concentration prediction. For olanzapine drug concentration simulations, three RNN cells within an RNN-ANN model with multiple inputs were studied. The GRU-ANN model resulted in the optimal RNN-ANN model with the lowest RMSE in the simulation data. Bayesian optimization was implemented to optimize the hyperparameters of the GRU-ANN model. The optimized GRU-ANN model resulted in a simulation RMSE of 24.844. Visual inspection revealed the simulated olanzapine drug concentrations were lower than their respected observed olanzapine drug concentrations. Exploratory data analysis revealed the underperformance may have been a result of dosing levels between the CATIE studies having little overlap. A comprehensive clinical trial study is required to fully explore the potential of a GRU-ANN model towards drug concentration simulations.
    • COUNSELING EDUCATION’S THEORY ON COUNSELING INDVIDUALS WITH SEVERE MENTAL ILLNESS

      Cespedes, Hanna Watson; College of Professional Advancement
      Severe mental illness (SMI) impacts one out of five individuals in the United States (CDC, 2022) and counselors provide over 60% of care to these individuals (ACA, 2014). The field of counseling focuses on building a working relationship with clients through emphasizing strengths, wellness, and empowerment (ACA, 2014); yet little is known on how counseling education utilizes these concepts with individuals diagnosed with SMI. Furthermore, there is a lack of research on how this topic is approached within counseling education training programs. This study utilized the constructivist grounded theory model to identify how the field of counseling education theorizes counseling individuals with SMI. The results from this study reveal an intricate model of how counselor educators and counselors in training approach this topic within academic spaces. The significance of the present study offers unique intervention opportunities for these same training programs and for the field of counseling education.
    • Metallothionein Protects Against Hg-Induced Nephrotoxicity in Models of Reduced Renal Mass

      Caroland, Anasalea Julius Violett; School of Medicine
      Metallothioneins are low-molecular-weight proteins that are rich in sulfhydryl groups. Consequently, they bind readily to metal ions such as mercury (Hg). Hg is a critical environmental toxicant to which humans are exposed regularly. Individuals with renal insufficiencies, such as those with chronic kidney disease (CKD), may be more susceptible to the effects of Hg, and exposure to Hg enhances the progression of the disease. We hypothesized that metallothionein (MT) acts as an endogenous antioxidant that can reduce the nephrotoxic effects of heavy metals. The effect of MT is significant in patients with reduced renal function, such as those with CKD. To test our hypothesis, we used male and female Wistar rats that underwent uninephrectomy or were sham controls. Animals were allowed to recover for three weeks and were then injected intraperitoneally (i.p.) with saline or zinc (Zn), followed by intravenous (i.v.) injection with HgCl2 (0.5 or 1.25 µmol kg-1). Rats were euthanized 24 h after the Hg injection, and a kidney and liver were harvested. One-half of one kidney was placed in fixative for histological analyses; the remaining renal tissue was frozen immediately in liquid nitrogen for future studies. qPCR and Western blotting confirmed that injecting rats with zinc enhanced the expression of mRNA encoding MT. Expression of mRNA encoding superoxide dismutase and glutamate-cysteine ligase was also measured in the kidney using qPCR to show that MT reduced oxidative stress in these organs. Histological analyses of kidney sections showed significant renal injury in animals injected with saline and exposed to 1.25 µmol HgCl2. Interestingly, renal in corresponding animals injected with zinc demonstrated less nephrotoxicity, suggesting that increased expression of MT protects against Hg-induced nephrotoxicity. Enhanced expression of MT may slow the progression of renal disease in individuals with CKD living in areas contaminated with heavy metals.
    • EFFECT OF THE IMMUNE STRESS RESPONSE ON HYALURONIC ACID METABOLISM IN THE BRAIN UNDER CHRONIC STRESS CONDITIONS

      Weehunt, Timothy; School of Medicine
      Hyaluronic acid (HA) is a glycosaminoglycan present in the extracellular matrix of the brain that has been shown to exhibit a wide range of cell signaling functions based on differing molecular weights metabolized by cells. For my thesis, I evaluated how HA metabolism of the brain is altered by and involved in the immune stress response under conditions of chronic stress in the presence of latent viral infection. Characterization of how HA is involved in the stress response has become an ever-increasing area of research associated with anxiety, depression, and even suicide. However, little has been revealed as to how HA metabolism is affected by stress and whether these changes are associated with pathological manifestation. Our murine model of chronic stress included four main groups with an additional baseline (N=6) control collected prior to experimentation. The remaining mice were divided in half comprising virally infected and non-virally infected groups. Virally infected mice were intranasally inoculated with murine herpes virus (MHV4) strain 68. The infected and non-infected mice groups were further divided into two more groups where animals were subjected to a 30-day period of chronic unpredictable mild stressors (CUMS model). The 4 groups in the study were designated Non-stressed/Non-Viral (S-V-; N=7), Stressed/Non-Viral (S+V-; N=8), Non-stressed/Viral (S-V+; N=8), and Stressed/Viral (S+V+; N=8). Following the 30-day period of stress the mice were sacrificed and key organs/tissues (brain, spleen, and blood plasma) were collected. During the stress period, animal weights were measured at regular intervals along with performing marble tests to gauge how the stressors were affecting behavioral reactivity of the mice. Statistically significant differences in food consumption and mice weights based on the presence of stress and viral infection were found. As well, lymphocyte subset distribution, systemic cytokine, and corticosterone levels were altered significantly enough to suggest active immune stress response in the animals. Gene expression of all hyaluronic acid synthase isoforms (HAS) were affected with the most changes (16-fold increase) in HAS-3, which produces pro-inflammatory low molecular weight HA (LMW-HA). An increased presence of LMW-HA could lead to an increased inflammatory state in the brain and contribute to psychological pathologies.
    • CELLULAR EFFECTS OF MERCURY EXPOSURE IN PROXIMAL TUBULAR CELLS

      Lotwala, Purva; School of Medicine
      Mercury (Hg) is a lethal and persistent contaminant that does not decompose readily in the environment. Hg, as a pollutant, is distributed globally because of its volatile nature and its ability to convert between chemical forms. Humans are exposed to various forms of Hg by ingestion, inhalation, and dermal absorption. Inorganic forms of Hg accumulate readily in the kidney and can cause significant cellular injury. The purpose of this study was to test the hypothesis that Hg has detrimental effects on cellular components and processes such as protein folding, calcium homeostasis, mitochondrial activity, and junctional complexes. To test our hypothesis, cultured proximal tubular cells (TH1 cells) were exposed to different concentrations of mercuric chloride (HgCl2), and various assays were performed to assess different cellular parameters. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was utilized to identify the specific concentrations of Hg that lead to decreases in cellular viability. Quantitative Polymerase Chain Reaction (qPCR) was used to analyze the mRNA expression of B-cell lymphoma 2 (Bcl-2) and caspase 9 to determine if Hg induces apoptosis in exposed cells. Alterations in cell permeability were detected by measuring the passage of various dextran (4kD, 10kD, and 20kD) across a cell monolayer and immunocytochemistry was used to visualize changes in occludin. In addition, the ability of two antioxidant compounds, α-lipoic acid, and oxo thiazolidine-4-carboxylic acid (OTC), to prevent Hg-induced cellular alterations was also measured. The findings from this study indicate that exposure to inorganic forms of Hg has significant effects on numerous intracellular processes, which leads to cell intoxication and death. Although additional studies are necessary for a complete understanding of the effects of Hg on cellular processes, the current data are an important start to this process.
    • Chronic Stress and the Immune Response's Impact on Ghrelin and its Role in the Development of Cardiovascular Disease.

      Chastain, Ronnie; School of Medicine
      The purpose of this study was to investigate how the chronic ‘stress of life’ and stress- induced changes in immune reactivity plays a role in the development of cardio-vascular disorders with an emphasis on the appetite hormone, ghrelin. Ghrelin is pertinent as it has been found to be an anti-inflammatory and cardio-protective peptide hormone. Chronic stress more often affects poorer and medically underserved communities which consists of about three- fourths of Georgia’s counties. Additionally, the state ranks fifteenth in death rates due to cardio-vascular disease in the U.S. This study could provide further insight as to how poorer and stressed-out Georgians’ health are significantly affected by the stress in their lives. In our murine model of chronic stress, we infected a group of mice with murine herpes virus (MHV) 4 Strain 68, as viruses have been implicated in cardiovascular related diseases. Half of infected and half of the uninfected animals were subjected to different stressors for 30-day period. Data analysis was performed with Jamovi v2.3 (The jamovi project http://www.jamovi.org) and SigmaPlot (Systat Software, Inc., CA) statistical software. One- and Two-Way ANOVA and ANOVA on Ranks followed by the post-hoc t-test were used to determine statistical significance in observed changes. Throughout the study the mice and their food were weighed at regular intervals to track how the stress and/or viral infection affected their food consumption and weight. After the month of stress, the mice were sacrificed, and key organs (heart, brain, spleen, and stomach) were collected to evaluate tissue-specific expression of genes of interest. Additionally, blood was drawn to characterize the systemic distribution of leukocytes via flow cytometry. Plasma was separated from the blood for analysis of systemic levels for markers of the endocrine (cortisol) and immune (cytokine) responses. Post-stress challenge statistically significant differences in leukocyte subset distribution were observed between the non-infected and infected animals. Additionally, a significant decrease in overall food intake throughout the stress period between the stressed and non-stressed groups based on viral infections as well as the viral and non-virally infected groups based on stress. Differences in gene expression for genes encoding Atrial Natriuretic Peptide, Brain Natriuretic Peptide, Vascular Endothelial Growth Factor Alpha, and Endothelial Nitric Oxide Synthase along with both Ghrelin and its receptor, Growth Hormone Secretagogue Receptor within the heart. Changes in gene expression were also observed for the Growth Hormone Secretagogue Receptor within the brain in addition to changes in Ghrelin mRNA levels in both the brain and stomach. Altered plasma levels of cytokines were observed in groups subjected to stress and/or viral challenges in comparison to control group. Collected data suggests chronic stress in the setting of the immune stress response negatively impacts the heart and decreases Ghrelin expression in the heart.