MEDICA@MUSC (Medical University of South Carolina)
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Healthcare System Resilience and Chronic Disease Care Management During Extreme Heat Events in New York City: A Mixed-Methods Study of Emergency Department Utilization and Preparedness Frameworks
No full textHealthcare systems, particularly in urban centers like New York City (NYC), are at severe risk due to the increasing frequency and intensity of climate-related events, which are being driven by climate change. In NYC, extreme heat events (EHE) are defined as two or more days with a heat index (HI) of or higher, or one or more days reaching . These events exacerbate health inequities, disproportionately affecting vulnerable populations, such as older adults and individuals with chronic illnesses (PwCD). The primary objective of this mixed-methods study is to investigate the impact of EHE on healthcare utilization, primarily emergency department (ED) utilization from 2019-2022, among Medicare populations in NYC and control counties in New York State. It will further assess chronic disease care management in heat action plans (HAP) and examine preparedness strategies through qualitative research with the German Red Cross in Dhaka, Bangladesh. Ultimately, this study aims to be an impetus for a toolbox for public health, healthcare systems, and government agencies in NYC, to make healthcare systems more ready and able to respond
PCBP1 as a Tumor Suppressor: Enhancing cGAS-STING-Mediated Innate Immunity in Breast Cancer
No full textNucleic acid sensing pathways are key mediators of innate immune surveillance and antitumor defense. Among these, the cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway plays a central role by detecting cytosolic double-stranded DNA (dsDNA) and inducing the production of type I interferons (IFNs) and interferon-stimulated genes (ISGs), thereby promoting immune cell recruitment and tumor immunogenicity.
This dissertation investigates the role of a nucleic acid binding protein, Poly(rC) Binding Protein 1 (PCBP1), as a tumor suppressor that activates the cGAS-STING pathway and impairs breast cancer development. Previous studies have shown that PCBP1 is downregulated in several cancer types and metastatic lesions. Here, we show that high PCBP1 expression is associated with improved survival in breast cancer patients. Using a transgenic mouse model of mammary tumorigenesis with conditional PCBP1 knockout in mammary epithelial cells, animals expressing PCBP1 exhibited significantly reduced tumor burden, together with increased type I IFN signaling and chemokine expression associated with enhanced cytotoxic T cell infiltration compared to knockout animals.
Mechanistically, PCBP1 functions as a nucleic acid co-sensor that binds DNA containing single-stranded poly-cytosine tracts through its KH domains, thereby increasing cGAS affinity for these DNA substrates without altering its intrinsic catalytic activity. This interaction enhances 2′3′-cyclic GMP–AMP (2’3’-cGAMP) synthesis and downstream STING activation, leading to amplified IFN and ISG responses in both mouse and human mammary epithelial cells. Importantly, mutation of PCBP1’s conserved GXXG loops within its KH domains abolished nucleic acid binding and cGAS activation, confirming the structural basis of its co-sensing function.
On a clinical level, reduced PCBP1 expression may contribute to poor responsiveness to immune checkpoint blockade due to diminished tumor immunogenicity. Therapeutic approaches aiming at stabilizing PCBP1 or combining STING agonists with immune checkpoint inhibitors may therefore enhance antitumor immunity in PCBP1-deficient cancers
Comprehensive Analysis of High-Dimensional, Longitudinal Multi-Modal Molecular and Electronic Health Record Data
Get PDFHealthcare is poised to comprise over a third of the market for big data by 2032, making it the dominant sector in this field (Insights 2024). This growth is driven by the increasing volume and variety of data sources, including electronic health records, payer records, research studies, personal health devices, and smartphones. The integration of such data holds transformative potential, enabling earlier disease diagnosis through biomarker identification, advancing preventive care by pinpointing risk factors, and enhancing hospital quality standards, among other benefits. Despite these promising applications, significant challenges arise in processing and analyzing high-dimensional biomedical data. This dissertation focuses on utilizing high-dimensional diffusion drift methods to address these challenges, with an emphasis on data derived from research studies and electronic health records. By developing and applying these advanced analytical approaches, this work aims to uncover actionable insights, demonstrate the utility of high-dimensional methods in handling complex healthcare datasets, and contribute to innovative applications in improving healthcare outcomes.
This initial segment establishes a robust framework for analyzing high- dimensional data, with a primary focus on univariate and multivariate analytical methods. This framework is applied to evaluate the multi-omic profiles of patient-derived samples in relation to three distinct diseases: lupus, oral mucositis, and Fanconi anemia (Chapters 2 - 4). Particular emphasis is placed on the utility of distance-based multivariate analyses for characterizing disease states within high-dimensional datasets.
Succeeding sections of this study detail the derivation of key estimates under the MD3F framework, accompanied by a simulation study to evaluate the type I error rate and statistical power characteristics of the proposed approach (Chapter 5). Subsequently, we apply this method to three distinct microbiome datasets and one electronic health record dataset (Chapter 6). The findings from these applications demonstrate the utility of MD3F in elucidating multivariate trajectories within high-dimensional patient data and capturing variability between patient groups or at the individual level. Overall, our results indicate MD3F as a robust framework for analyzing high-dimensional longitudinal datasets; however, further refinement and characterization are needed to enhance its applicability to biological contexts in future studies.
The following portion of this study explores the development of UNAFIED-8, a logistic regression model designed to predict a 2-year risk score for atrial fibrillation. The results demonstrate the model effectiveness of atrial fibrillation risk prediction and exhibits generalizability by utilizing readily available electronic health record data. These findings highlight the potential of electronic health record data to support and enhance clinical care.
Concluding chapters discern future directions for this work, emphasizing the translational implications for the studies discussed herein and their potential to drive innovative healthcare outcomes. By identifying key avenues for further research, these chapters aim to highlight how the methodologies and findings can be adapted and implemented to improve clinical decision-making, patient outcomes, and overall healthcare delivery
The Use of Equine-Assisted Services to Develop Life Skills and Improve Educational Outcomes in Young Adults with Disabilities
Get PDFYoung individuals with disabilities often face significant challenges in acquiring essential life skills, primarily those with cognitive impairments. This often limits their ability to live independently and fully participate in daily activities. Without progress in developing these skills, individuals may struggle with tasks such as Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs). Equine-assisted services (EAS), as defined by The Journal of Alternative and Complementary Medicine, is recommended as an optimal unifying term to refer to multiple services in which professionals incorporate horses and other equines to benefit people (Wood et al., 2021).
A doctoral capstone project was conducted in collaboration with Charleston Area Therapeutic Riding (CATR) to evaluate the use of EAS in developing life skills and its impact on educational outcomes for young adults with disabilities.
Educators of participants completed surveys at multiple intervals (pre, midterm, post, and weekly) to track progress. Results showed that 100% of students demonstrated improvement in both life skills and educational outcomes, according to the educators’ reports. In addition, a quality improvement project was developed to provide CATR with resources to advocate for the program\u27s expansion, allowing for more students with disabilities the opportunity to benefit from EAS.
Sources:
Wood, W., Alm, K., Benjamin, J., Thomas, L., Anderson, D., Pohl, L., & Kane, M. (2021). Optimal terminology for services in the United States that incorporate horses to benefit people: A consensus document. The Journal of Alternative and Complementary Medicine, 27(1), 88–95. https://doi.org/10.1089/acm.2020.041
Home Activity Resources in Senior Activity Centers
No full textDue to the growing population of older adults in both our local community and in the world, the need for promotion of healthy aging is essential. The literature shows that community support and resources are critical to aging in place, which helps maintain independence as older adults age. A doctoral capstone project was conducted to address the need for support and resource to increase the quality of life of senior citizens attending community day centers. The project goals were to design and implement educational resources that increase older adult’s overall level of activity physically, cognitively, and socially. Through a mixed methods approach, data was collected to evaluate the effectiveness of the educational resources after implementation at the senior center. The outcomes of the data collection showed an increase of activity levels in all participants, along with an increase in confidence to engage in physical activity at home. Continued development of educational resources and support at senior centers can further promote healthy aging of older adults
Enhancing Mental Health Awareness and Sustainability: A Playbook and Needs Assessment Approach
No full textThe purpose of this capstone project was to promote greater awareness and education regarding mental health resources within a local non-profit organization dedicated to supporting individuals\u27 mental health through recreation, education, and community-building. The project aimed to enhance the visibility and understanding of available mental health services, while also assessing the effectiveness of current initiatives and improving the sustainability of these programs.
To achieve these goals, a comprehensive playbook was designed to serve as an educational tool for the community, which included findings from a needs assessment of existing mental health initiatives. A multifaceted approach was used, incorporating one-on-one interviews, surveys, and online research to gather data on both current program effectiveness and potential areas for improvement.
Throughout this project, I emphasized the unique perspective that occupational therapy (OT) can offer in mental health care. OT\u27s role-based, activity-focused approach encourages individuals to find purpose and meaning in their lives, ultimately improving mental health outcomes. Techniques such as activity analysis, stress management, and motivational interviewing are just a few of the tools OTs can utilize in mental health treatment. While OT has traditionally been rooted in mental health, its contributions in this field have often been overlooked. This project aimed to demonstrate that OT remains an essential discipline in improving mental health practices. The outcome of the project was a well-rounded, sustainable plan for advancing mental health awareness, demonstrating OT’s role in this care
We Are All Made of Star-Stuff: Targeting Astrocytic Calcium to Prevent Alcohol-Induced Changes in Orbitofrontal Cortex Excitability, Synaptic Dynamics, and Behavior
No full textApproximately 28.9 million people aged 12 and older meet the diagnostic criteria for alcohol use disorder (AUD), characterized by compulsive and frequent alcohol consumption often to avoid negative effects associated with withdrawal. The orbitofrontal cortex (OFC), critical for goal-directed behavior, is disrupted in individuals with AUD. However, the role of specific cell types, such as astrocytes, in regulating alcohol-induced changes in the OFC remains unknown. Previous studies show that acute ethanol inhibits firing of OFC neurons while chronic intermittent ethanol (CIE) exposure increases firing accompanied by enhanced ethanol drinking. The acute ethanol inhibition of OFC neuronal firing is mediated by inhibitory glycine receptors and is reduced by expressing a plasma membrane calcium exporter (PMCA) in OFC astrocytes.
The studies in this dissertation examined the effects of astrocyte PMCA on CIE-induced increases in OFC excitability, the physical interaction between astrocytes and neurons, and alcohol drinking. Adult male and female C57Bl/6J mice were infused in the OFC with an astrocyte specific LCK-GFP or PMCA virus. Separate cohorts of mice underwent 4 weeks of CIE exposure or CIE accompanied with drinking followed by an analysis of OFC neuronal spiking, astrocyte-neuron interaction, and limited access homecage alcohol drinking. A final cohort underwent CIE exposure followed by behavioral testing.
The results suggest that there are sex-dependent differences in how OFC astrocytes and neurons interact and respond to chronic ethanol. For example, CIE increased neuronal firing in male and female LCK-GFP mice compared to Air controls. Interestingly, while PMCA itself increased firing in male Air mice, PMCA reduced CIE-mediated hyperexcitability in females. Similar to spiking, both PMCA and CIE increased the number of GluA1 synapses within the vicinity of astrocytes in males. However, in females, CIE only increased the number of puncta in the PMCA group. CIE did not affect colocalization of astrocytes and GluA1 puncta in male or female controls, but it was elevated in PMCA males. Lastly, CIE exposure increased alcohol consumption in male but not female mice and this was prevented by expressing PMCA in OFC astrocytes. These findings reveal important sex-dependent interactions between OFC astrocyte PMCA and CIE exposure
Predictors of Early Withdrawal in Alzheimer\u27s Disease Clinical Trials: The Role of Demographics in Retention
No full textRetention in Alzheimer’s disease clinical trials is a critical challenge, with participant withdrawal impacting statistical power, data integrity, and generalizability. Underrepresented racial and ethnic groups (URGs) face disproportionately high dropout rates, necessitating a deeper understanding of withdrawal predictors. This retrospective cohort study analyzed demographic and site-related factors influencing withdrawal in ADNI1, ADNI2, and ADNI-GO trials using publicly available data from the Laboratory of Neuro Imaging (LONI) database. After data cleaning, the final dataset included 3,008 participants, with 1,324 withdrawn and 1,684 retained. Logistic regression identified younger age (p \u3c .001, OR = 0.977), retired status (p = .005, OR = 1.309), race (p = .003, OR = 0.784), and site number (p \u3c .001, OR = 1.004) as significant predictors of withdrawal, while gender, marital status, handedness, primary language, and education level were non-significant. These findings suggest that targeted retention strategies for younger and retired participants, culturally tailored engagement for URGs, and site-specific monitoring could improve retention and enhance the diversity and generalizability of Alzheimer’s disease research
A Comparative, Quantitative Analysis of Birth Outcomes Among Women with Intellectual or Developmental Disabilities
Get PDFWomen who are pregnant or planning to give birth deserve equitable resources, respect, and assurances to ensure a healthy and safe pregnancy, including women of childbearing age who are diagnosed with intellectual or developmental disabilities (IDD). These women are more likely to experience negative perinatal, delivery, and postpartum health outcomes (Tarasoff et al., 2020). Healthcare providers, clinicians, and the family and friends of those with IDD must understand the impact and implications of the prenatal and postpartum journey for this group of women. This comparative research examined 2021 birth outcomes of women in the United States with IDD compared to those without, as well as their demographics, birth complications, length of stay, and discharge disposition. The birthrates among women with IDD have increased over time, despite increased risks to birth outcomes. This research included an analysis of more than 114,000+ women with IDD, accounting for 16.5% of the 2021 NIS HCUP dataset. Births by women with IDD showed disparities across a multitude of variables including median household income, sterilization, geographic location (e.g. metro, rural), and race
Empowering Families in a Pediatric Intensive Care Unit
Get PDFIn the U.S., it is estimated that at least 239,000 children were admitted to the intensive care unit (ICU) in the year 2019 (Killeen et al., 2023). Post Intensive Care Syndrome (PICS) describes the adverse impacts that patients suffer from after the ICU, and children are especially vulnerable in the critical period of growing and developing (Smith & Rahman, 2023). The Sleep, Play, Heal (SPH) program is a pediatric ICU liberation movement at a local children’s hospital aimed to decrease PICS and improve outcomes for children and families. Through team interviews, the need for educational resources to maintain a continuum of quality care and increase preparedness when leaving the PICU, was revealed. The purpose of this capstone was to further understand and collaborate to address the needs of the SPH program. Our aims were to enhance consistent interdisciplinary care by increasing awareness and knowledge of the importance of the SPH program, leading to better recovery outcomes for children and their families in and after the PICU. This capstone project supported the SPH program by development of educational materials for both staff and families, including a comprehensive PowerPoint and discharge packet. These materials were reviewed by SPH team members and distributed to interprofessional staff. Nine professionals provided feedback via surveys, while four families participated in interviews to share their perspectives. Data were analyzed using descriptive statistics and thematic analysis. Results showed positive responses, with 100% of staff agreeing or strongly agreeing that the resources improved their understanding of the SPH program and they were likely to use them in practice. Families expressed a desire for more information on PICS and the SPH program, validating the need for resource development. Suggestions for improvement were continuously integrated throughout the 14-week implementation period. This project highlights the importance of comprehensive educational resources in enhancing awareness and confidence among PICU staff and families to support better outcomes for pediatric ICU survivors.
References:
Killien, E. Y., Keller, M. R., Watson, R. S., & Hartman, M. E. (2023). Epidemiology of intensive care admissions for children in the US from 2001 to 2019. JAMA Pediatrics, 177(5), 506-515. 10.1001/jamapediatrics.2023.0184
Smith, S., & Rahman, O. (2023). Postintensive care syndrome. StatPearls (). StatPearls Publishin