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Item Embargo UNDERSTANDING THE ROLE OF RAB10 IN NEURONAL RESILIENCE(East Carolina University, 2023-12-08) Bunner, Wyatt P; Szatmari, Erzsebet M; Physical TherapyNeuroresilience refers to the remarkable capacity of the brain to maintain its normal functioning and safeguard against cognitive decline even in the face of stress or trauma. The exploration of genes and pathways that play a role in mediating neuroresilience has garnered significant attention in recent years with the small GTPase known as Rab10 emerging as one of significant note. Functioning as a "resilience factor," a rare variant of Rab10 that has reduced activity has been found to confer resilience against Alzheimer's disease (AD). The primary objectives of this dissertation were to shed new light on the intricate functions of Rab10 and to contribute to the identification of novel biomarkers for neuroresilience, as well as therapeutic targets for the treatment of neurodegenerative disorders. Nanostring nCounter platform was utilized for the analysis of 880 genes involved in neurodegeneration. This showed that Rab10+/− mice have increased activation of pathways associated with neuronal metabolism, structural integrity, neurotransmission, and neuroplasticity compared with their Rab10+/+ littermates. Lower activation was observed for pathways involved in neuroinflammation and aging. We identified and validated several differentially expressed genes (DEGs), including Stx2, Stx1b, Vegfa, and Lrrc25 (downregulated) and Prkaa2, Syt4, and Grin2d (upregulated). Behavioral testing showed that Rab10+/− mice perform better in a hippocampal-dependent spatial task (object in place test), while their performance in a classical conditioning task (trace eyeblink classical conditioning, TECC) was significantly impaired. We also identified different central and peripheral immune targets that Rab10 may help grant to combat neurodegeneration. Of note, basal microglia activation is significantly less in Rab10+/−. Peripheral immune profiling of Rab10+/− mice showed reduced Natural Killer cells and a different phenotype distribution of CD8+ and CD4+ positive T-cells. Finally, Rab10 may provide a neuroprotective role via its ability to lower the production of inflammatory cytokines such as interleukin-1β, tumor necrosis factor-alpha, and interferon gamma. Further work is needed to evaluate whether any of these changes mediates the behavioral phenotypes and the resilience that Rab10 confers. We conclude that Rab10+/− mice described here can be a valuable tool to study the mechanisms of resilience in AD model mice and to identify novel therapeutical targets to prevent cognitive decline associated with normal and pathologic aging.Item Embargo PSYCHOLOGICAL IMPACT OF PROSTHETIC JOINT INFECTIONS FOLLOWING TOTAL HIP AND KNEE REPLACEMENT(East Carolina University, 2023-12-06) Harding, Maggie; Bolin, Linda P; NursingBackground. Prosthetic Joint Infection (PJI) is a devastating complication of total joint arthroplasty (TJA) with a relative survival rate worse than that of prostate cancer, melanoma, and breast cancer. This study explores the psychological impact of PJI of the hip and knee. Methods. Two separate studies were conducted - a qualitative study, using descriptive phenomenology, and a quantitative cross-sectional descriptive correlational study. Results. Participants reported substantial impact on independence, identity, and relationships. Functional limitations were associated with negative illness impact, anxiety, depression, and decision regret. Social support was an important moderator for negative illness impact, anxiety, and depression. Resilient coping was common, and linked to lower negative illness impact, lower intolerance of uncertainty, and lower depression scores. Poor surgical outcomes, including amputation and death, were common. Conclusion. The significant psychological impact of PJI may be moderated by stage of life. As in previous studies, loss of independence and identity, pain, burden, and emotional responses are impactful experiences in PJI, with social support playing a major role. Additionally, this study supports that decision regret is not as common as previously thought among those with PJI.Item Embargo A Multi-Compartmental Investigation of Bcl-2 Associated Athanogene 3 (BAG3) in Peripheral Artery Disease(East Carolina University, 2023-12-13) Terwilliger, Zoe Simone; McClung, Joseph M; PhysiologyPeripheral artery disease (PAD) is caused by an atherosclerotic blockage to a vessel that restricts blood flow to the lower extremity. Chronic limb threatening ischemia (CLTI) is the most severe manifestation of PAD, and is associated with gangrenous lesions, necrosis, high rates of limb loss, reduced quality of life, and mortality. Despite PAD affecting more than 230 million people worldwide, minimal improvements in patient outcomes have been made over the last two decades (1–4). Therapeutics and endovascular procedures aimed at restoring blood flow have been largely unsuccessful at improving limb outcomes (5–11), particularly in Black patients with CLTI who experience rates of amputation as high as 37% compared with their White counterparts (12). Limb muscle from patients with CLTI exhibit severe myopathy and unique bioenergetic signatures indicative of an inherent or associated muscle response to ischemia (8,13–15). This reinforces the necessity for development of targeted adjuvant therapies to supplement vascular interventions and promote whole tissue regeneration. The aims of this dissertation were to characterize the transcriptomic profile of Black and White patients with CLTI and to determine the role of Bcl-2 associated athanogene 3 (BAG3) in pre-clinical limb ischemia via a multi-compartmental interrogation. This dissertation incorporates previous clinical data on the described racial disparities in PAD manifestation and clinical outcomes and the documented pathologic role of BAG3 mutants that are correlative or causative of striated muscle pathology. The overarching hypotheses of these studies were that: 1) Limb tissue from Black and White patients with CLTI would exhibit distinct transcriptomic profiles from each other and from age/sex/race matched control tissues, and 2, 3) BAG3 is required for cooperative regeneration in both the vascular and skeletal muscle compartments of the ischemic limb and that deletion of BAG3 in either compartment would augment ischemic degeneration of the vasculature and skeletal muscle. Our results reveal a unique transcriptomic profile in the limb tissue of patients with CLTI with significant alterations in genes associated with bioenergetics. We also observed distinct transcriptomic signatures in Black patients with CLTI when compared with race/age matched healthy controls and White patients with CLTI. Preclinically, deletion of BAG3 from the vasculature yielded negligible differences in tissue repair/regeneration, while deletion of BAG3 from skeletal muscle resulted in an enhanced myopathy and a significant delay in blood flow recovery.Item Embargo MODULATING MMP-9 SUBSTRATE PREFERENCE TO REDUCE INFLAMMATION POST-MI(East Carolina University, 2023-12-08) Cakir, Sirin Nazan; de Castro Brás, Lisandra E; PhysiologyWorldwide, the prevalence of cardiovascular disease (CVD) is escalating, with myocardial infarction (MI) significantly contributing to the heightened rates of morbidity and mortality. Notably, one in every four MI patients progress to heart failure (HF). Following an MI, the left ventricle (LV) undergoes extensive alterations in both its structure and function, a phenomenon referred to as LV remodeling. The inflammatory response triggered by MI can exacerbate ventricular remodeling, culminating in chamber dilation, progressive dysfunction, and an elevated risk of HF. The extracellular matrix (ECM) plays a crucial role in post-MI wound healing, with proteolytically-released ECM fragments, known as matricryptins, exhibiting significant biological activity. In this dissertation, we conducted an extensive examination of the roles of a cardiac collagen matricryptin in the acute inflammatory response that follows infarction, placing a specific emphasis on how this matricryptins alters remodeling of the ECM. Previous work from our lab showed this matricryptin, p1159, significantly reduces long-term cardiac remodeling post-MI. Our objective was to determine whether p1159 beneficial effects stem from alterations to the acute inflammatory response, identifying it as a viable anti-inflammatory strategy for the treatment of cardiac remodeling. Additionally, this approach aimed to determine if exogenous delivery of p1159, as a competitive substrate of matrix metalloproteinase (MMP)-9, is sufficient to mitigate MMP-9 proteolysis of cardiac ECM post-MI. Since MMP-9 directly correlates with mortality and morbidity in MI patients, identification of a novel modulator of MMP-9 proteolytic activity could lead to a new therapeutic strategy aimed at mitigating cardiac dysfunction. In the first study presented in this thesis, we explored the impact of the collagen-derived matricryptin p1159 on the initiation, progression, and resolution of inflammation following MI, aiming to identify potential therapeutic targets to mitigate adverse LV remodeling. Utilizing a rodent model of MI, we meticulously measured various inflammatory markers, assessed the infiltration, numbers, and phenotype of leukocytes, and quantified both systemic and local levels of inflammatory cytokines and chemokines from day 3 (D3) and day 5 (D5) post-MI in both adult males and females. These time points are known for presenting peak levels of neutrophils and macrophages, respectively, post-MI in rodents. Our study showed that while matricryptin p1159 treatment does not change the number of infiltrating leukocytes into the LV post-MI, it altered both neutrophil and macrophage phenotype by reducing expression of pro-inflammatory molecules. Surprisingly, our study did not reveal sex-dependent differences. In the second study of this thesis, we aimed to understand how alterations in the substrate profile of matrix metalloproteinase-9 (MMP-9). Utilizing Terminal Amine Isotopic Labeling of Substrates (TAILS) proteomics, we compared and quantified the peptidome in mice treated with either control vehicle or the matricryptin p1159. Through this study, we sought to address three pivotal questions: 1) Is p1159 a competitive substrate of MMP-9 in vivo? By modulating MMP-9 proteolytic capacity, as opposed to inhibiting the enzyme, can we effectively reduce adverse LV remodeling post-MI?; 3) What are the molecular and cellular consequences of reducing MMP-9 activity on myocardial substrates in the immediate post-MI response? Here, we demonstrate p1159 treatment significantly reduced formation of naturally cleaved peptides, particularly at D3 post-MI, suggesting that p1159 presence decreases proteolysis of endogenous substrates. Specifically, p1159 treated LVs presented reduced formation of known MMP-9 products, showing that p1159 can act as a competitive substrate of MMP-9 in vivo. Our study opens a new research avenue for the MMP world and offers a novel approach to modulate proteases’ capacity without inhibition to preserve their beneficial roles. Furthermore, this research demonstrated how omics approaches can be applied to fundamental research questions, providing insights that can be later translated into clinical settings.Item Embargo Identification of galectin-1 as a marker for claudin-low breast cancer and implications for tumor progression(East Carolina University, 2024-01-04) Balestrieri, Kassondra; Verbanac, Kathryn; Biomedical ScienceTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. Patients with TNBC have a high rate of metastasis and mortality due to the lack of targeted therapies and resistance to chemotherapy. This research aimed to develop reliable models of metastatic TNBC to investigate targetable proteins and pathways. The 2225L and T11 murine tumor lines, which are highly analogous to human basal-like and claudin-low TNBC subtypes, were serial passaged heterotopically and orthotopically in syngeneic mice to generate lines that would consistently metastasize to the lung. Immunochemical and transcriptomic methods were used to define the immune microenvironment of the primary and metastatic tumors and to compare tumors with variable metastatic potential. Both resulting 2225LM and T11 tumor lines displayed an immunosuppressive tumor microenvironment characterized by high myeloid-to-lymphocyte ratio (CD11b+:CD3+) and elevated expression of protumor cytokines compared to control tissues. Subsequent analysis of T11 primary and metastatic claudin-low breast tumors employed a discovery-based proteomic approach that detected significant differential galectin-1 expression compared to normal control tissues. Label-free quantitation, Western immunoblot, and ELISA confirmed galectin-1 identity and elevated expression in primary and metastatic tumors compared to normal control tissues. Mass spectrometry spatial mapping and immunohistochemistry revealed high localization of galectin-1 in T11 metastatic lung foci. Transcriptomic analysis of mouse and human breast cancer subtypes showed significant and differential galectin-1 expression in claudin- low primary tumors compared to other breast cancer subtypes. Galectin-1 is an N-acetyllactosamine (LacNAc)-binding protein that promotes anti-inflammatory actions and has a wide range of reported intracellular and extracellular activities, but its role in breast cancer has not been well studied. We next evaluated galectin-1 effects on CD11b+ myeloid cells, based on their high proportion in T11 tumors, using in vitro, ex vivo, and in vivo models. The CD11b+ murine macrophage cell line RAW 264.7 was susceptible to galectin-1-induced apoptosis in vitro in a dose-dependent, carbohydrate-specific manner. However, ex vivo assays with murine CD11b+ peritoneal exudate cells showed no effect on apoptosis. In vivo systemic administration of galectin-1 allosteric inhibitor OTX008 in T11-tumor-bearing mice slowed tumor growth but did not affect the percentage of infiltrating myeloid populations. Fluorescence microscopy evaluation of overall tumor apoptosis and CD3+ and CD11b+ cell apoptosis in primary tumors at sacrifice showed no statistical difference between the OTX008 treatment and the vehicle control groups. These findings suggest that galectin-1 does not affect CD3+ or CD11b+ immune cell infiltration or apoptosis in claudin-low primary tumors. Larger in vivo studies and analysis of different drug regimens, smaller tumors and metastatic models are indicated. Future studies focusing on alternative actions of galectin-1 in claudin-low breast cancer, including its potential effects on tumor proliferation and angiogenesis, should be conducted to explore its viability as a therapeutic target.Item Embargo STUDENT TRAJECTORIES RELATED TO READING AND ATTENTION SKILLS: IS THERE EVIDENCE OF THE MATTHEW EFFECT?(East Carolina University, 2024-01-04) Gonzales, Christine Rivera; Walcott, Christy; PsychologyResearch on reading is widespread given its predictive nature for adult outcomes pertaining to success, such as high school graduation, college entrance, health literacy, employment status and wages earned. Research focusing on attention problems is also widespread, as attention has been found to be an integral part of the learning process. Previous research demonstrates that problems in reading and attention, individually, are associated with negative outcomes, and the prognosis for children who possess deficits in both areas is significantly worse. However, the relationship between reading and attention is complex and a myriad of studies have come to numerous conclusions regarding the relationship between reading and attention, depending both on the type of data and statistical analysis used for the study. Expanding on a previous study (Gonzales, 2019) which examined the unique growth trajectories regarding both attention and reading performance of students throughout elementary school, this study used data from the Early Childhood Longitudinal Study (ECLS: K-2011), an updated and improved nationally, representative database containing both reading and attention measures for students from kindergarten through fifth grade. Consistent with previous research, initial reading scores were significantly predicted by SES, with scores being higher for those students from higher SES backgrounds. Similarly, girls had higher initial reading scores than boys. The findings indicated five unique growth trajectories with respect to reading and attention skills over the course of elementary school. These results remained consistent even after controlling for students’ gender and SES. Reading performance for all groups improved over the course of elementary school. Attention, as rated by teachers, was much more variable with one group improving over time, another declining over time, and the other groups remaining relatively stable over the course of elementary school. There was a group that struggled both with reading and attentional skills throughout the course of elementary school, even though they were not the lowest rated class in regard to attention by the spring of fourth grade. Specifics regarding each of the five trajectories as well as implications for research and practice are discussed.Item Embargo The importance of land use on public health. Case studies from the Rivanna River Watershed.(East Carolina University, 2023-12-11) Potter, Emily Jane; Kearney, Gregory; Public HealthIntroduction: Safe and reliable water is vital to sustaining the environment and human health. However, factors including an expanding population, aging infrastructure, climate change, emerging contaminants, nonpoint source pollutants, and outdated regulations pose serious threats to water qualiry and public health. The overall purpose of this research was to examine the land use patterns and potential risk factors impacting the Rivanna River Watershed surrounding Charlottesville, Virginia, with respect to water quality and public health. The ecological model was selected as the overarching framework for examining three case studies. The primary research aims for each case study were to, i) examine statistical associations between deforestation and urban development on the drinking water treatment process in the Rivanna River Watershed; ii) assess the relationship between increased chemical use in public drinking water and associated economic costs, and iii) investigate disparities and equitable communication of recreational water impairment among different populations. Methods: Secondary data for this project were obtained from multiple governmental sources including the U.S. Environmental Protection Agency, U.S. Geological Survey, Virginia Department of Health, and Rivanna Service Authority. Linear regression and correlation analysis were used to identify relationships between land use, water quality, and public health. Results: The decrease of forested land cover and the increase of impervious surface have negative impact on watershed health and surface water quality, increasing the risk of negative health outcomes. Raw water turbidity levels increased 13.59%, requiring increased treatment chemical use ranging from 7.59% to 107.87%. Rising treatment costs of 33% per MG of water treated resulted in a 20.28% increase in wholesale water rates, and 14-32% increases in customer water utility rates. Despite increasing numbers of biologically impaired waters, recreational use of the James and Rivanna Rivers increased, indicating ineffective water quality communication. Conclusion: An integrated view of water resource management involving collaboration between land owners, public health and land managers to increase source water protection can promote equitable access to safe water.Item Embargo NITROGEN AND BACTERIA TREATMENT EFFICIENCY OF ONSITE WASTEWATER SYSTEMS IN THE PIEDMONT OF NORTH CAROLINA(East Carolina University, 2023-12-01) Jernigan, Jordan; Humphrey, Charles; Iverson, Guy; Public HealthOnsite wastewater treatment systems (OWTSs) are commonly used in rural areas for wastewater disposal. These systems can contribute elevated concentrations of nutrients and bacteria into water resources, resulting in potential impairment. Drinking water wells are often permitted on the same lot as OWTSs, where access to public water supply is limited. Groundwater, drinking water wells, and recreational waters containing excess nutrients and bacteria pose harmful effects on both environmental and public health. More specifically, exposure to nitrate via drinking water can lead to human health effects, such as methemoglobinemia, cancers, and pregnancy complications, and environmental health effects, such as eutrophication, algal blooms, and fish kills in surface waters. E. coli in drinking water and body contact exposure during recreational activities can lead to gastrointestinal illnesses, and in severe cases, death. The goal of this study was to evaluate OWTS treatment efficiency of nitrogen and E. coli from wastewater to groundwater in conventional- and alternative-style OWTS within an impaired watershed, Falls Lake Watershed, North Carolina, USA. Specific objectives included: 1) quantifying nitrogen and E. coli concentrations in wastewater, groundwater, and sand filter effluent; 2) determining treatment efficiencies of nitrogen and E. coli in different OWTSs; 3) assessing mechanisms of nitrogen and E. coli concentration reductions in subsoil beneath the drainfields and in a sand filter system; and 4) providing management strategies to help reduce nitrogen and E. coli inputs into impaired watersheds. Five volunteered sites (Sites 100 – 500) with conventional- or alternative-style OWTSs were evaluated during this study. The original system age across all sites ranged from 49 – 53 years. Replacement systems were installed at Sites 200, 400, and 500 with age since replacement ranging from 2 – 14 years. There were three conventional-style OWTSs (e.g., gravel and chamber) and two alternative-style OWTSs (e.g., bed and single-pass sand filter). Wastewater samples were collected from septic tanks at each site and a drainfield port at Site 400. Groundwater monitoring piezometers were installed beneath the drainfields at Sites 100 – 400. Additional piezometers were installed downgradient from the OWTSs at Sites 100 and 200. The OWTS at Site 500 was a single-pass sand filter where effluent was collected from a surface discharge pipe. Physicochemical properties (e.g., pH, dissolved oxygen, specific conductance, temperature, oxidation-reduction potential) of wastewater, groundwater, and sand filter effluent were measured in the field. Collected samples were analyzed for nitrogen species, E. coli, and chloride concentrations. Nitrate isotope analysis of groundwater was also carried out. Soil samples were collected from beneath the drainfield and analyzed for physicochemical properties (e.g., pH, effective cation exchange capacity, and sand/silt/clay percentages). The duration of the study was from September 2020 – June 2021. Sampling occurred 4 – 6 times at each site and at least once during each season. Specific sampling dates included September 21, 2020; November 17, 2020; January 14, 2021; March 10, 2021; April 19, 2021; and June 29, 2021. Sampling did occur during the coronavirus disease 2019 (COVID-19) pandemic, which resulted in more people working from home leading to the potential of greater residential water use and wastewater generation. Findings from this study show that OWTSs were influencing nitrogen and E. coli concentrations in groundwater and sand filter effluent. Treatment efficiency of nitrogen from wastewater to groundwater beneath the drainfields and downgradient ranged from 86 – 89%, which performed better than the sand filter OWTS (79%). The difference in mean nitrogen concentration reductions from wastewater (~ 77 mg·L-1) to groundwater and sand filter effluent (~ 11 mg·L-1) was statistically significant (p < 0.01). While groundwater beneath OWTS drainfields is typically not used for drinking water, findings from this study show average nitrogen concentration in groundwater exceeds the United States Environmental Protection Agency drinking water standard of 10 mg·L-1. Elevated nitrogen concentrations in groundwater can pose concerns for nearby surface waters during recharge and from surface discharging OWTSs, or if contamination occurs in drinking water wells. E. coli treatment efficiency from wastewater (median: 1,579,500 MPN·100 mL-1) to groundwater and sand filter effluent (median: 7 MPN·100 mL-1) was > 99% and differences in median E. coli concentrations were found to be statistically significant (p < 0.05). Any amount of E. coli in groundwater poses risks for environmental and public health due to potential exposure through drinking water contamination and/or during recreational activities. OWTSs across all sites were influencing nitrogen and E. coli concentrations in groundwater. While limited research has been conducted in the Piedmont of North Carolina regarding OWTS contributions of nitrogen and E. coli into impaired watersheds, this study suggests the need for additional research to assess how aging systems may be influencing water quality. There should be more economically affordable options for repairs of malfunctioning OWTS or cost-share programs to help cover the costs.Item Embargo Addressing Rising Hospital Acquired Infections (HAIs) Using Novel Nanotechnology: Implications for Public Health Protection(East Carolina University, 2023-12-11) Ubah, Chukwudi S; Pokhrel, Lok R; Public HealthGlobally rising antibiotic-resistant (AR) and multi-drug resistant (MDR) bacterial infections are of public health concern due to lower efficacy of current antibiotic therapy. Specifically, Hospital Acquired Infections (HAIs) or nosocomial Infections pose a significant threat to public health, with an alarming rise in cases attributed to pathogens like Escherichia coli and Pseudomonas aeruginosa. These infections not only lead to increased morbidity and mortality rates but also impose substantial economic burdens on healthcare systems worldwide. Given the persistent challenge of antibiotic resistance, there is an urgent need for innovative and sustainable solutions to curb the prevalence of HAIs. E. coli causes surgical wound infections, bloodstream infections, sepsis, and urinary tract infections, among others. P. aeruginosa causes cystic fibrosis, meningitis, septicemia, endophthalmitis. This study explores the application of novel amino-functionalized silver nanoparticles (NH2–AgNP) and nanotechnology as a promising strategy to combat the proliferation of E. coli and P. aeruginosa in healthcare settings, thereby reducing the burden of HAIs and antibiotic resistance. Utilizing the unique physicochemical properties of NH2–AgNP, including their high surface-to-volume ratio and inherent antimicrobial activity, this research investigates their efficacy in inhibiting the growth and spread of these multidrug-resistant pathogens. Herein, we tested the antibacterial efficacy, mode of action (MoA), and safety of novel amino-functionalized silver nanoparticles (NH2–AgNP) against two AR E. coli strains (i.e., ampicillin-resistant, and kanamycin-resistant E. coli), including a susceptible strain of E. coli DH5α and P. aeruginosa. Complementary toxicity bioassays were performed, and results were confirmed using dynamic light scattering (DLS) and transmission electron microscopy (TEM). Our results showed that ampicillin and kanamycin did not inhibit growth in both AR E. coli strains with doses up to 160 µg/mL tested, and up to 20 µg/mL for P. aeruginosa. Treatment with ≥1 µg/mL NH2–AgNP significantly inhibited the growth of all three E. coli strains, and at ≥10 µg/mL inhibited the growth of P. aeruginosa, suggesting a broad-spectrum bactericidal activity of NH2–AgNP. The DLS analyses showed significant cell leakage and cell debris formation over time with NH2–AgNP treatment for all bacterial strains tested and this was confirmed by TEM. Further combined treatment of NH2–AgNPs with ampicillin or kanamycin showed antagonistic effects, suggesting that combination treatment is less effective than NH2–AgNP alone treatment. Based on these findings, we propose two MoA for NH2–AgNP: (i) electrostatic interactions, followed by (ii) cell wall damage. Furthermore, in vitro safety assessment revealed that NH2–AgNP was noncytotoxic and antioxidative to primary human lung epithelial cells. These findings suggest that NH2–AgNP may serve as an effective and safer bactericidal therapy as an alternative to current antibiotics and could help combat rising HAI associated with AR/MDRO, thereby protecting global public health. This dissertation advances the field of public health by proposing an alternative antibacterial agent to address global public health challenges. The implications of this research for public health protection are multifaceted. Firstly, the successful integration of NH2–AgNP in hospital environments could significantly reduce the incidence of HAIs, thereby enhancing patient safety and healthcare outcomes. Secondly, the development of targeted nanotechnology-based antibacterial agent, NH2–AgNPs, may support combating antibiotic-resistant pathogens, providing a sustainable alternative to conventional antimicrobial agents. Thirdly, this research contributes to the growing body of knowledge on the applications of nanomedicine in the field of healthcare, paving the way for the development of novel and effective strategies for infectious disease control. Overall, this study underscores the critical role of interdisciplinary research in addressing the global challenge of HAIs and emphasizes the potential of nanotechnology as a transformative tool for promoting public health and mitigating the impact of pathogenic bacterial diseases in the healthcare setting. Further clinical studies are needed to determine the efficacy and safety of NH2–AgNP in patients with nosocomial infections, and other possible medical applications of NH2–AgNP could be explored such as its use in diagnostics and medical device and implant coating.Item Embargo HUMAN HEALTH EFFECTS OF LEAD IN THE ENVIRONMENT: A MULTI-SOURCE APPROACH OF ELEVATED LEAD EXPOSURE AMONG AT-RISK POPULATIONS IN PITT COUNTY, NORTH CAROLINA, USA(East Carolina University, 2023-12-05) Abioro, Elizabeth May; Pokhrel , Lok R; Public HealthDespite lead (Pb) in public drinking water has been studied extensively, Pb in homes has received less attention. Elevated Pb level in homes is a growing public health concern as Pb exposure in children is known to cause a multitude of health outcomes, including impaired brain function, behavioral disorders, reduced attention span, memory loss, lower IQ, antisocial behavior, and mood disorders. Most of the homes with higher Pb levels are considered low-income, older, or outdated apartment buildings, where at-risk populations (low-income, minority populations that rely on government assistance to assist with daily needs) typically live and may be unaware of Pb exposure risks. Using secondary data from multiple databases, this ecological study was aimed to: (1) identify potential environmental sources of Pb in different areas of homes in Pitt County, North Carolina, and (2) explore the association between children blood lead level (BLL) and age, gender, race, and sampled years (2018, 2019, 2020) using General Linear Model (GLM). Further, the distribution of minority populations, education level, Pb in homes, and age of homes were mapped using ArcGIS and EPA EJScreen for the United States to determine potential trend. Our GLM results showed a significant positive association between BLL and age of the child (p=0.022); however, there were no significant racial or gender differences in BLL (p>0.05), and that sampled years (2018, 2019, 2020) did not differ significantly in BLL (p>0.05). On average, White children had higher average BLL compared to Black or Other races; while White females, Black males and Other males had higher average BLL compared to their opposite gender. ArcGIS and/or EJScreen mapping showed a general clustering of minority populations and low-income status with the distribution of homes with Pb-based paint in the United States. Within homes, windowsill had more than an order of magnitude higher Pb level (691.8 µg/ft2) compared to other areas (common entry, bedroom, kitchen, and dust) sampled in North Carolina, suggesting windowsill as a prominent source of children Pb exposure in homes. In Pitt County, Greenville had the highest number of homes with elevated Pb compared to other major cities. Overall, children between the age of 1 year 3 month and 3 year 6 month showed a pattern of elevated BLL, while around the 2 yr. age group, the W population had a BLL over the current CDC threshold (3.5 µg/dL) and almost reaching the previous CDC threshold (5 µg /dL), underscoring the need to protect White children that may be disproportionately exposed to Pb in homes. The lack of specific federal and state laws and/or policies around the need to testing all children for BLL calls for an immediate action to implement mandatory testing for children BLL regardless of race or housing conditions. Only then more children could be protected from Pb exposure and health risks.Item Embargo ANALYSIS OF COMMUNITY HEALTH WORKER’S SELF-DEFINED ATTITUDE, BEHAVIOR, AND EXPERIENCE REGARDING INTERPROFESSIONAL COLLABORATION(East Carolina University, 2023-11-30) Schenall, Alice J; Cummings, Doyle; Public HealthEvidence suggests that the role of community health workers (CHWs) continues to evolve in support of the demand to address social determinants of health, prevention, cost, and population health. The aim of this mixed-methods study was to characterize the difference in CHWs’ perceived ability to work on interprofessional teams in a clinical setting based on their years of experience in the field (>5 years). The study measured attitudes, experiences, and behaviors regarding interprofessional roles, using a validated and published instrument (n=131). Qualitative data, using an open-ended question, examined the CHW’s experience navigating power structures, cultural barriers, and hierarchy (n=80). Boundary Spanning Leadership (BSL), a conceptual framework, was piloted as an intervention to support augmenting the current skills of CHWs in a small subsample. The BSL training focused on interprofessional communication, one of four competencies in the interprofessional collaborative domain. Results indicated that participants with five or more years of experience as CHWs were more likely to report stronger (positive) behaviors in interprofessional collaboration. The results indicated that there was no significant difference between the attitudes of the CHWs of those with less than 5 years’ experience (M = 12.44, SD = 3.07) and those with five or more years of experience (M = 11.36, SD = 3.1), p = 0.06. Those CHWs with less than 5 years of experience (M = 16.46, SD = 4.30) had significantly higher mean values for behavior (less positive behaviors) toward interprofessional collaboration regarding the healthcare team than their counterparts with five or more years of experience (M = 13.98, SD = 4.06), t(120) = 3,134, p = 0.002. Modest but non-significant differences in these parameters were noted by age (older vs. younger), race (Black/Hispanic vs. White), and geography (urban vs. rural). The results of the pilot study indicated that there was no significant difference between the attitudes or behaviors at pre-training (Pre-training Attitude = M = 13.000, SD = 2.582 and Behavior =M = 15.846, SD = 3.716)) and post training (Post-training Attitude = M = 12.46, SD = 2.57 and Behavior = M = 15.462, SD = 5.85, t(12) = .65, p = .528 and t(12) = .26, p = .80). Findings from this study inform hiring, training, onboarding, and evaluating CHW performance.Item Embargo FEEDING KNOWLEDGE AND FEEDING CONFIDENCE OF PROFESSIONAL GROUPS IN EASTERN NORTH CAROLINA WHO ARE INVOLVED IN PROVIDING PRENATAL CARE VISITS FOR PARENTS HAVING A BABY DIAGNOSED WITH CLEFT LIP WITH OR WITHOUT CLEFT PALATE(East Carolina University, 2023-11-29) Tahmasebifard, Neda; Perry, Jamie; Communic Science & DisordersObjective: This study aimed to evaluate the feeding knowledge and feeding confidence of different professional groups in eastern North Carolina who provided prenatal care visits (PNVs) for parents having a baby diagnosed with cleft lip with or without cleft palate (CL ± P). Methods: The study sample consisted of three obstetricians and gynecologists (OBGYN), two maternal fetal medicine (MFM) specialists, two nurses, two lactation consultants, and one genetic consultant in eastern North Carolina who provided PNVs for parents having a baby diagnosed with CL ± P. Descriptive statistics were used to evaluate feeding knowledge and feeding confidence of these professionals. Results: Differences in the feeding knowledge scores and feeding confidence levels were found among professionals working in eastern North Carolina who provided PNVs for parents having a baby diagnosed with CL ± P. Specifically, two nurses and one of the lactation consultants had the highest knowledge scores related to the feeding of infants with CL ± P. One of the MFMs, two nurses, and two lactation consultants had the highest confidence levels related to the feeding of infants with CL ± P. All participants who received training related to the feeding of infants with CL ± P, had the greatest confidence levels and higher feeding knowledge scores. Conclusion: Results from the present study highlight the need for methods to improve knowledge and confidence related to feeding among those who provide PNVs to families having a baby diagnosed with CL ± P.Item Embargo Investigating the genetic basis of aposematic coloration in poison frogs(East Carolina University, 2023-11-29) Rubio, Andrew Otto; Summers, Kyle; BiologyAposematic organisms rely on their conspicuous appearance to signal that they are defended and unpalatable. Such phenotypes are strongly tied to survival and reproduction. Aposematic colors and patterns are highly variable; however, the genetic, biochemical and physiological mechanisms producing this conspicuous coloration have not yet been elucidated. Here, I attempt to 1) identify genes and gene networks potentially affecting color variation in two color morphs of Ranitomeya imitator: the orange-banded Sauce and the red-headed Varadero morphs, 2) identify the overall effects of dietary carotenoids on pigmentation and gene expression on R. imitator frogs, and 4) identity genes associated with color development that are under positive selection in poison frogs (Amphibia: Anura: Dendrobatidae). My results show that key genes may be playing vital roles in producing bright aposematic coloration. In addition, we found that genes related to lipid storage were up-regulated in the tissue of Ranitomeya imitator froglets that were fed a carotenoid enriched diet. Lastly, we found key genes related to color formation to be under positive selection when testing transcriptome data from a set of poison frog species in the family Dendrobatidae. These three chapters will allow us to make some preliminary inferences concerning the relevance of our results to important general issues in ecology and evolution. For instance, results from this dissertation could help identify expression levels of a wide variety of different genes that are involved in determining differences in color pattern between different mimetic morphs of R. imitator, and between this mimic and its model species. In addition, results from this dissertation can pave the way for future studies to test hypotheses of mechanisms of color morph maintenance in populations and investigate the evolution of color pattern across aposematic vertebrates in a phylogenetic context.Item Embargo SPATIAL AND PLANAR DYSREGULATION OF RHOGTPASES IN HUMAN AND ALZHEIMER’S DISEASE MOUSE MODEL(East Carolina University, 2023-11-27) Nik Akhtar, Shayan; Lu, Qun; Anatomy and Cell BiologyRho proteins belong to the Ras superfamily of small GTPases. In humans, the Rho family of GTPases contains 20 members out of which the most studied Rho proteins are RhoA, Rac1, and Cdc42. Rho signaling is known to regulate actin cytoskeleton dynamics in neuronal cells which are important for growth cone dynamics, axongenesis, neuronal polarity, synaptic plasticity, and neuronal survival. Rho GTPases are considered molecular switches due to their dual state of activation and inactivation. Briefly, in the inactive state, the GTPase is bound to Guanosine-5’- diphosphate (GDP) and in the active state, the GTPase is bound to Guanosine-5’-Triphosphate (GTP). The active and inactive forms of GTPase are controlled by three main types of proteins: Guanine nucleotide exchange factors (GEF), GTPase activating proteins (GAP), and Guanine nucleotide- dissociation inhibitors (GDI). GEFs promote inactive to active Rho GTPase. GAPs promote active to inactive Rho GTPase. The GDI does not allow the GDP to dissociate from the GTPase resulting in an inactive form of GTPase.A vast number of studies have implicated Rho-GTPases dysregulation in promoting neurodegenerative diseases such as Alzheimer’s disease (AD). RhoA GTPase and ROCK1, its downstream effector protein, increased in AD brains compared to non-AD brains. In Tg2575 AD mouse model, RhoA levels are reduced in the synaptic terminal while they were elevated in dystrophic neurites. Treatment of cultured neurons with beta-amyloid (Aβ) increased RhoA activity which leads to dendritic spine loss. Rac1 expression was shown to decrease in AD cortex compared to control. In 3xTg-AD mouse model, Rac1 levels were shown to be decreased by 7 months. Inhibition of Rac1 resulted in reduced expression of Amyloid Precursor Protein (APP) via decreasing the level of APP mRNA. Cdc42 was increased in frontal cortex in patients suffering from Frontotemporal dementia (FTLD) compared to control. Cdc42 conditional knockout mice demonstrated impaired synaptic plasticity. Cdc42 knockout neurons lead to abnormal axonal morphology. Aside from the studies mentioned there are numerous other studies highlighting the importance of Rho GTPase signaling homeostasis in neurodegeneration. Despite their importance it has been a challenge to elucidate the exact nature of dysregulation of Rho GTPases in AD. This can be attributed to several factors such as the model of choice, the specific region of the brain, as well as the different states of Rho GTPases, which is the focus of this study, such as expression vs activity. We hypothesize that there are different regional expressions of Rho-GTPases and their activation and inactivation states in the brain.In this study we have demonstrated that there is a regional and spatial dependent change in expression and activity for both RhoA and Rac/Cdc42 activity. We demonstrated that Rho GTPase activity changes in the different subregions of the hippocampus, such as CA3, CA2, CA1 and dentate gyrus, and cortex. We also demonstrated that there is a dynamic nuclear to cytoplasmic redistribution of both Rho and Rac/Cdc42 proteins in a plane dependent manner. In human brain sample Rho GTPases are also differentially expressed in the cortex and cytoplasm. Overall, we demonstrated that Rho GTPases are differentially dysregulated in both human AD brain samples and in 3xTg-AD mouse model.Modulation of Cdc42 through small molecules such as ZCL278, ZCL279 and ZCL367 in 3xTg AD mice showed an improvement in mental status as well as burrowing behavior. ZCL278 reduced tau in 3xTg-AD mice compared to nontreated 3xTg-AD mice. Knowing the potential of small molecules to modulate protein-protein interaction, they can be potentially used to target specific regions of the brain along the rostral to caudal dimensions to perturb a unique protein-protein interaction.Item Embargo Age-Related Diagnostic Considerations and Neurocognitive Impairment Implications for Insomnia Disorder(East Carolina University, 2023-12-01) Gencarelli, Amy Marie; Everhart, Daniel E; PsychologyInsomnia affects 10-30% of the U.S. population and can be found across varying stages of life. While it has previously been shown that the addition of quantitative indices would be helpful for distinguishing between sleep disturbances and insomnia, it begs the question if quantity-derived thresholds vary throughout the lifespan. One of the major current diagnostic systems utilized in the U.S. (the DSM-5) acknowledges quantitative indices being useful in identifying cases of insomnia and that daytime impairment is necessary for a diagnosis of insomnia. This study aims to see how these two factors, may vary by age, sex, and/or race as well as if standardized objective neurocognitive measures can better assess for daytime impairment than self-report.Item Embargo Adapt & Overcome: Hypoxia Resistance is a Novel Phenotype of the Flexor Digitorum Brevis Skeletal Muscle(East Carolina University, 2023-11-30) Minchew, Everett C.; Spangenburg, Espen E; PhysiologySkeletal muscle comprises the largest mammalian organ system by mass that enables movement, respiration, and thermogenesis. Each of these processes requires the presence of molecular oxygen (O2). Inadequate O2 bioavailability (i.e., hypoxia) is detrimental to muscle contractile function and morphology, and in chronic cases can result in muscle wasting. Importantly, modern therapeutics and surgical approaches have proven largely ineffective to rescue skeletal muscle from hypoxic damage. Such a gap in the field is attributed predominantly to the fact that known skeletal muscles are highly susceptible to hypoxic insults. Thus, current knowledge of specific cellular properties that promote hypoxia resistance is sparse. However, our lab has identified a murine skeletal muscle that retains physiological function in the complete absence of O2. Using models of in vivo hindlimb ischemia and ex vivo muscle hypoxia exposure, we observed the preservation of force production and plasma membrane stability in the flexor digitorum brevis (FDB). In contrast, the extensor digitorum longus (EDL) and soleus muscles suffered functional decline and structural damage following the same hypoxic insults. A critical aspect of hypoxia resistance in the FDB is the ability to sustain energetic charge. Hypoxia decreases the mass action ratio of adenosine triphosphate ([ATP]) to adenosine diphosphate ([ADP]), which determines the capacity of a cell to perform work. However, the [ATP]/[ADP] ratio is maintained by the hypoxic FDB. Contrary to the EDL and soleus, we found that the FDB does not depend upon the mitochondria but requires glycolysis to function during hypoxia. Furthermore, the hypoxic FDB preserves stability of the plasma membrane whereas hypoxia causes membrane damage in the EDL and soleus. Following an unbiased, discovery-based interrogation of muscle proteomes, we identified significantly higher expression of multiple protein targets in the FDB as compared to the EDL and soleus that related to our findings. Due to the loss of force output in the FDB with inhibition of glycolysis, we selected the transmembrane glucose transporter GLUT1 as our first target. Loss- and gain-of-function experiments surrounding GLUT1 were employed to further characterize the FDB phenotype. Skeletal muscle-specific deletion of GLUT1 accelerated the loss of force output in the FDB during hypoxia exposure. Thus, to test the sufficiency of GLUT1 to attenuate hypoxia-induced damage in other skeletal muscles, we utilized an adeno-associated virus (AAV) to overexpress GLUT1 in the EDL. During these experiments we also manipulated concentrations of glucose and the oxidized form of ascorbic acid as these are the primary substrates that are transported by GLUT1. However, all conditions failed to prevent the loss of force production of the EDL during hypoxia exposure. Collectively, our results demonstrate that GLUT1 is necessary for the FDB phenotype, but insufficient to rescue other skeletal muscles from functional decline in a hypoxic environment. Due to the preservation of structural integrity in the FDB during hypoxia, we selected the membrane repair protein Annexin A2 and the extracellular matrix protein Col5a1 as our second and third targets, respectively. In separate sets of experiments, FDBs lacking Annexin A2 and Col5a1 did not demonstrate increased susceptibility to hypoxic damage as compared to control muscles. Importantly, however, using the same experimental approach that revealed the FDB’s ability to resist hypoxia, we have observed that the phenotype is adapted over time as opposed to an innate feature of the muscle. Hypoxic FDBs from young mice (4 weeks) exhibit a loss of force output and structural integrity in a manner that is similar to the hypoxic EDL. Following our observation of this apparent adaptation, we employed a proteomic analysis of FDBs from adult and young mice to further characterize differences between age groups. We subsequently integrated this data with our initial discovery-based proteomics analysis of the FDB, EDL, and soleus with the goal of improving the precision of our future target selection. Collectively, the data suggest that the FDB’s ability to survive hypoxia may be conferred by protection against structural damage via stabilization of the dystrophin-glycoprotein protein complex (DGC), which links the muscle plasma membrane to the extracellular matrix. In turn, structural protection likely promotes the maintenance of physiological function in the hypoxic FDB. Defining the FDB’s unique ability to resist hypoxic damage remains of critical importance for the muscle biology field to develop novel therapeutic approaches that promote the survival of skeletal muscle during times of limited O2 availability.Item Embargo A UNIQUE MITOCHONDRIAL BIOENERGETIC PATHWAY UNDERLIES ACUTE MYELOID LEUKEMIA SURVIVAL AND CHEMORESISTANCE(East Carolina University, 2023-12-01) Hagen, James T; Fisher-Wellman, Kelsey H; PhysiologyIn his early research on cancer cell metabolism, Otto Warburg made the hypothesis that the respiration of cancer cells has become damaged. The insult to cancer cell respiration, Warburg proposed, was either 1) a decrease in oxygen consumption, or 2) with undiminished oxygen consumption, the coupling of respiration and ATP synthesis has become broken. Herein, using multiple models of acute myeloid leukemia (AML) (i.e., chemosensitive and chemoresistant), we present evidence that supports the early hypothesis of Otto Warburg. Specifically, we discovered that 1) AML mitochondria present with defects in respiration that are masked by increases in mitochondrial content and 2) under basal conditions, AML mitochondria consume, rather than synthesize, ATP. The ATP consumption of AML cells confers a survival advantage and poises AML cells to participate in a futile cycle that mimics an alternating current circuit model. In chapter I, we provide a background on acute myeloid leukemia bioenergetics that establishes the groundwork for the research outlined in this dissertation. Specifically, our previous research discovered that relative to normal blood cells, AML cells are characterized by two important mitochondrial phenotypes: 1) AML cells present with deficiencies in oxidative phosphorylation (i.e., OxPhos) that are more pronounced in the context of chemoresistant disease; and, 2) AML import extramitochondrial ATP into the mitochondrial matrix space where it inhibits respiratory flux. In Chapter II, we discovered that, universally, the AML mitochondrion presents with 1) reductions in respiratory flux, driven by intrinsic lesions in the electron transport system, that were associated with 2) a utilization of ATP synthase as an F1-ATPase proton pump to sustain the mitochondrial membrane potential. Sustaining polarization across the inner mitochondrial membrane via F1-ATPase activity conferred chemoresistance to AML. Importantly however, chemoresistant AML were re-sensitized to chemotherapy when F1-ATPase mediated polarization was disrupted using mitochondrial-targeted lipophilic small molecules. In Chapter III, we discovered that reactivation of AML OxPhos induces BAX-independent cytotoxicity that, based on unpublished data in Chapter IV, appears to involve cytotoxic ROS production. Collectively, this dissertation proposes a unique model of AML mitochondrial bioenergetics where ATP consumption, rather than ATP synthesis, supports AML survival and confers resistance to chemotherapy. Furthermore, this dissertation presents a novel AML-specific mitochondrial pathway that can be selectively targeted by 1) disrupting F1-ATPase mediated polarization of the mitochondrial membrane, or 2) reactivating AML OxPhos.Item Embargo IMPLEMENTATION OF A PARENT-LED COMBINED GROWTH-MINDSET AND HOME LITERACY INTERVENTION: A PILOT STUDY(East Carolina University, 2023-11-30) Robinson, Sam; Walcott, Christy M; College of Arts and ScienceThis pilot study examined the implementation feasibility and preliminary effectiveness of a combined growth-mindset and literacy intervention delivered in the home by parents and guardians. The study was completed in two parts: Pilot Study 1 was completed with one parent. Feedback was gathered and the program was modified accordingly for Pilot Study 2. During the second study, an additional 9 elementary school students and their parents/guardians participated. Parents administered reading interventions from the PASTEL (Parents and Schools Together to Enhance Learning) guidebook and mindset interventions from PERTS (Project for Education Research that Scales). Prior to implementation, parents attended two group meetings during which they were provided materials and coached on how to use them. Qualitative data gathered from parents found that all parents reported intervention materials to be easy to use, fun for their children, and to require a reasonable time commitment. Additionally, pre- and post-test data assessed parent and child mindset, parent and child self-efficacy, child academic motivation, and child reading ability. A statistically significant increase occurred across all child-reported psychosocial outcomes, but no other significant pre-post changes occurred. Limitations and further directions are discussed in detail.Item Open Access Feasibility and Acceptability of a Values-Based Telehealth Intervention to Promote Adherence in Cardiopulmonary Rehabilitation Patients(East Carolina University, 2023-12-07) Midgette, Emily P; Whited, Matthew C; PsychologyBackground: Current research indicates an ongoing need to identify interventions to promote Cardiopulmonary Rehabilitation (CVPR) participation, as participation in CVPR remains low despite positive effects on health outcomes. Values-based interventions, such as Behavioral Activation and Acceptance & Commitment Therapy (ACT), have been shown to be effective for improving the quality of life of patients with a variety of chronic illnesses including cardiovascular disease. We hypothesized that a values-based intervention may be helpful to promote CVPR participation through reduced avoidance and exploration of intrinsically motivating factors that improve patients’ willingness to engage in potentially unpleasant activities (e.g., physical activity) that are important for managing their diagnoses. The COVID-19 pandemic also provided the opportunity for more widespread implementation of telehealth interventions to increase access to psychosocial support, especially for marginalized patient populations who experience a high number of attendance barriers. Purpose: The purpose of this study was to assess the feasibility and acceptability of a novel telehealth intervention that is informed by ACT principles and focused on improving adherence to CVPR. Methods: Participants in this single-armed study could choose to participate in a 5-session ACT-informed telehealth intervention via live virtual meetings (at home) or self-guided pre-recorded videos (at home or onsite) featuring the same content. Feasibility was assessed by the number of participants enrolled (goal of 50), sessions attended, Ecological Momentary Assessment (EMA) response rates (measuring mood, experiential avoidance, values congruence), and rates of post-completion assessment. Acceptability was assessed through a qualitative interview following the five-week intervention period. Results: Feasibility of the study was hindered by low participation. Forty-four participants were consented and 21 did post-completion questionnaires. Only 8 participants attended > of the 5 live sessions. Twenty participants requested pre-recorded videos, and though exact numbers of views could not be determined due to our distribution method, only 6 reported watching > 1 videos. Participants often reported difficulty with the virtual meetings and EMA technology, despite staff demonstrating its use and a prior study’s success with the same EMA program. Also, participants anecdotally reported exhaustion with virtual meetings across multiple settings. Fourteen participants dropped out of the study due to illness/hospitalization or time conflicts. Five participants completed the qualitative follow-up interview. Qualitative responses generally indicated a high acceptability of the intervention, though this small group included mostly those with high engagement; those who dropped out may feel differently. Discussion: Overall, our results indicate that major changes are needed to increase feasibility and better measure acceptability of this intervention. Participants provided helpful feedback regarding their preferences, challenges encountered, and suggestions for improvement that will be helpful for future repetitions of this research. The results especially highlight the potential benefits of developing a self-guided version that is modified to improve accessibility to the technology required to participate in the intervention.Item Open Access Comparing Clinical Judgment Competency Between Accelerated and Traditional Bachelor of Science in Nursing Students during High-fidelity Simulation(East Carolina University, 2023-12-01) Martin, Jeanne; Gantt, Laura; NursingABSTRACT Background: Evidence suggests that competency in clinical judgment may be lacking in new graduate nurses. Graduates from accelerated baccalaureate nursing (ABSN) programs have even less time to develop clinical judgment competency. Various simulation modalities, including high-fidelity manikin and virtual reality, have been used to develop clinical judgment in pre-licensure students. However, the outcomes of these simulation modalities on clinical judgment in accelerated and traditional baccalaureate nursing students (TBSN) is not well understood. Method: Using Tanner’s Clinical Judgment Model as the theoretical framework, a quasi-experimental design compared clinical judgment competency between two interventions groups using a manikin with TBSN participants and virtual simulation with ABSN participants. Results: ABSN participants had statistically significant higher noticing, interpreting, and overall clinical judgment competency scores that the TBSN group. Conclusion: Findings from this study indicate accelerated nursing programs are effective in developing clinical judgment competency. However, results may have been affected by the simulation modality used in the TBSN group. Future research should include comparison studies aimed at examining the effect of these modalities with students in both traditional and accelerated programs.