MEDICA@MUSC (Medical University of South Carolina)
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Hospital Board Composition Effect on Health Equity
Get PDFGoal: As the diversity of the United States population increases, hospitals must be equipped with the appropriate tools and resources to address the unique needs of their diverse patients. The goal of this study was to examine if there is a correlation between a hospital board\u27s demographic makeup and health equity initiatives implementation. Methods: Using dataset from the American Hospital Association’s 2020 Annual Survey and the 2021 National Governance Survey, we performed a quantitative analysis of Illinois for-profit and not for profit hospitals evaluating the types of health equity initiatives implemented versus their board demographic. Hospitals were excluded if they did not complete both surveys. Using a composite score of gender and racial diversity, each hospital board was placed into a diversity category of high, medium, or low. Data was calculated using Stata/MP 17.0 software for correlation using fishers’ exact. Principle Findings: Of the 209 hospitals in Illinois, 30 (14.4%) completed both surveys and qualified for inclusion in the study. Results showcased that those hospitals with high board diversity did not have a significant difference in the implementation of health equity initiatives highlighted in the surveys compared to those with medium or low diversity. Practical Applications: As health equity policy and regulations expand, hospitals are making conscious efforts to implement tactics that address the needs of underrepresented and historically marginalized patients. Results from this study suggest that hospital boards with high diversity composition focus on streamlined health equity initiatives which will have the greatest impact on the community. However, boards with low or medium diversity composition implement a variety of initiatives which may dilute overall impact. While boards may influence the development of health equity strategies, successful implementation results from an organization’s mission and vision which define strategic alignment and individual accountability of patient outcomes across the organization
From Concepts to Clicks: Lessons from Building MUSC\u27s Bicentennial Online Exhibit Series with DCX
No full textDeveloping engaging online exhibits can be a time-consuming and tedious process, especially if designed in house and “from scratch.” Aiming to design a series of online exhibits to highlight significant moments in the history of the Medical University of South Carolina for its 2024 Bicentennial, the staff of the Waring Historical Library discovered the challenges of meeting this goal while managing the competing interests of stakeholders and while working under ever-changing timelines. In this session, Tabitha Samuel and Anna Schuldt will discuss the lessons learned from challenges they encountered in designing the first of the exhibit series, ‘“Men of Unsullied Reputation:’ The Founders of the Medical College,” the saving grace of the DCX exhibit web application, and the tricks they used to customize the user interface of DCX while maximizing the efficiency of the system
PCBP1’s Single-Stranded DNA Binding and Its Role in Transcription
No full textMetastasis, the spread of cancer cells from the tissue of origin to a secondary site(s), is the leading cause of cancer-related deaths. The molecular mechanisms underlying metastasis remain unclear. The epithelial-to-mesenchymal transition (EMT) is a transcriptionally driven phenotypic change in cell morphology, considered central to metastasis. Transcriptional dysregulation is a hallmark of cancerous cells. A single transcription factor can be activated by multiple signaling pathways. This redundancy leads to therapeutic resistance, as ultimately, genes that are downstream of therapeutic targets can still be activated by alternative pathways.
Transforming Growth Factor β (TGFβ) induces EMT by releasing cytoplasmic Polycytosine Binding Protein 1 (PCBP1) from a structurally conserved secondary structure found in the 3’UTR of pro-EMT mRNAs, the BAT (TGFβ activated translation) element, thereby allowing their translation. In addition to translational inhibition, PCBP1 regulates alternative splicing by binding to RNA secondary structures, also leading to inhibition of EMT. As PCBP1 is primarily localized to the nucleus, where key processes involve single-stranded nucleic acids prone to secondary structure formation, we began investigating PCBP1’s other potential nuclear roles.
PCBP1, an RNA and single-stranded DNA (ssDNA) binding protein, binds single-stranded polycytosine (poly(C)) tracts with high specificity. Poly(C) tracts are enriched in cancer-relevant genomic loci, and some form secondary structures: intercalated motifs (i-motifs) on the C-rich strand and G-quadruplexes (G4s) on the G-rich strand. At the start of this project, we discovered PCBP1’s binding to and potential regulation of i-motifs. As PCBP1 binding sites are enriched at gene promoters and PCBP1 knockdown results in transcriptional dysregulation, the goal of my research became to determine how and when PCBP1 binds to ssDNA to regulate transcription.
This work shows that PCBP1’s DNA binding sites are enriched at transcription start sites and that by binding to promoter regions, PCBP1 regulates transcription in addition to its previously known roles in splicing and translation. At PCBP1 target genes, PCBP1 interacts with several RNA/DNA hybrid (R-loop) associated G-quadruplex resolving helicases. Furthermore, our experiments show that PCBP1 interacts with RNA Helicase A (DHX9) to modulate transcription by regulating DHX9 accumulation and activity. PCBP1 depletion leads to defects in R-loop processing and dysregulation of transcriptional elongation of PCBP1 target genes. PCBP1’s high sequence specificity and interaction with helicases suggest that its mechanism in transcription involves guiding helicases to specific loci during transcription, thereby modulating their activity
What Are the Barriers to Midwife Service Utilization Among Low-Risk Pregnant Women in Florida?
Get PDFBackground and Need: Midwives are healthcare professionals that are educated, trained, licensed, and regulated to provide primary care; gynecologic, prenatal care; care during pregnancy, childbirth, postnatal care; and care of the normal newborn during the first 28 days of life (Florida Senate, 2021; Association of Women\u27s Health, Obstetric and Neonatal Nurses [AWHONN], 2016). The Midwives Alliance of North America also defined these professionals as providers who support labor and birth through relationships of trust and confidence with their patients (Midwives Alliance of North America [MANA], n.d.). If complications arise during pregnancy, midwives collaborate with other physicians and refer the case if necessary (AWHONN, 2016). Individualized care is one of the strengths that distinguish midwives. In the United States, there is evidence that shows the benefits of midwives in maternal care, such as promoting physiologic processes, fewer lower cesarean rates and repeats cesarean births, lower rates of health complications, lower rates of health complications, fewer repeat cesarean births and higher rates of breastfeeding (Neerland and Skalisky, 2022). Midwives have been recognized as an alternative to improve patient outcomes when working with maternity needs (Thumm et al., 2022). Ensuring the health of mothers and babies is a public health goal in the United States (Healthy People, n.d.); therefore, providing prenatal and postnatal care is essential for their wellbeing and decreases the possibilities of risks. In 2020, 209,645 infants were born in Florida (Ladapo, 2021). Florida Health reported that midwives attended 27,629 (13%) births in a hospital, versus 176,842 (84%) attended by an obstetrician, and 884 births (3%) were attended by other/unknown providers (Ladapo, 2021). In other high-income countries, midwives are 8 considered the standard of care for low-risk pregnant women. In these countries, midwives attend between 30-65% of births providing services to low-risk pregnancies, childbirth, and postpartum, compared to 9.1% in the United States (Thumm et al., 2022). Midwives\u27 utilization is lower in the United States, with only 10% of deliveries by midwives compared to 50-75% in other countries (Vedam et al., 2018). Midwifery care can benefit pregnant women with good outcomes and cost savings (MANA, n.d.). Childbirth is one of the most common reasons for hospitalization, being a high expense to the health care system (Bernecki, 2010). In Florida, the cost of a vaginal childbirth can be 14,757.28 out of pocket, and a cesarean (c-section) can cost 19,328 out of pocket. Increasing awareness among women about the midwives\u27 scope of services and better collaboration between other providers would benefit maternity services.
Problem Statement: The American Public Health Association (APHA) supports midwifery to increase maternity care options that can result in good outcomes for mothers and babies (APHA, 2014). After decades, midwifery is still undeveloped in the U.S., where the scope of practice is not understood in the healthcare field. Regulations and lack of autonomy result from physician supervision in some states affecting the midwife\u27s inclusion in women\u27s healthcare (Ollove, 2016). Public health is committed to improving individuals\u27 health and well-being, including safe pregnancies and childbirth (Health and Human Services [HHS], n.d.). Nevertheless, while there have been discussions of the benefits of midwives\u27 care, the percentage of patients seen by midwives is still low, which leads to a slow move toward change. It is unclear why low-risk pregnant women do not utilize the midwives\u27 services. Literature and anecdotal evidence indicate 9 many types of barriers, bias, lack of marketing, lack of consumer awareness, no physician backup, state mandates, and how they are perceived may all be critical factors that may prevent pregnant women from seeking midwifery services (Bernecki, 2010; Kristienne, 2020; Murphy, 2018; Thumm, 2022 and Wertman, 2020). Midwifery care still is not a routine care among women in the United States (Thumm et al., 2022).
Research Aims and Objectives: This research aims to understand women\u27s perceptions influencing their decision to utilize midwifery care. Understanding the midwife\u27s role in maternity care can be affected by misinformation (Johnson, 1998). The objectives are to get more information about how women in Florida perceive midwives and how familiar they are with this practice to determine the possible barriers that prevent them from receiving care from a midwife. In addition, findings about accessibility to a midwife\u27s office, the options given for prenatal/postnatal care, and their awareness about insurance coverage can contribute to filling some gaps to understand better why low-risk pregnant women may not select a midwife as their provider
Decellularized Heart Extracellular Matrix as a Biomimetic Substrate for Alleviating hiPSC-Cardiac Fibroblast Activation and Enhancing Isogenic Cardiac Organoids
Get PDFCardiovascular disease is the constant leading cause of death worldwide. While substantial efforts have been undertaken to improve disease outcomes, the lack of adequate human cardiac tissue models exacerbates research and development costs and clinical trial failures, hampering novel therapeutic discovery. To address this, human engineered cardiac microtissues composed of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) show potential in recapitulating hallmark qualities of natural human myocardium for novel therapeutic testing, disease modeling and cardiotoxicity screening. However, as these models are engineered in vitro, they are limited in their capacity to fully recapitulate myocardium and are vulnerable to influences often associated with in vitro techniques. To investigate the capability of engineered cardiac microtissues to model natural human myocardium, we performed an RNA-sequencing analysis of our previously established cardiac organoid model to compare their transcriptomic similarity to human myocardial samples. We identified that the inclusion of primary supporting cell types commonly found in natural myocardium, such as cardiac fibroblasts (CF), improves engineered cardiac microtissues’ recapitulation of human myocardium. Yet, it was clear that the lack of immune cells within engineered cardiac tissues prevented full recapitulation of the myocardium. However, our engineered cardiac organoid model is composed of genetically mismatched cell types and thus is incapable of predicting patient specificity for disease modeling, therapeutic discovery, and cardiotoxicity. To address this, we sought to develop an isogenic cardiac organoid model replacing the cell types found in our established model with hiPSC-derived cell types. Unfortunately, transcriptomic analysis of hiPSC-cardiac fibroblasts (hiPSC-CF) revealed their similarity to activated cardiac fibroblasts associated with numerous cardiomyopathies. We reasoned that the in vitro cell culture substrates of Matrigel and tissue culture plastic (TCP) utilized during hiPSC-CF differentiation induce their activated pathogenic phenotype. Proteomic analyses identified that Matrigel contains SPARC, a known regulator of fibroblast activation and often associated with cardiomyopathy. Further, universal TCP is known to induce the activation of fibroblasts through mechanical stimulation. We hypothesized that the activation of hiPSC-CF could be alleviated by incorporating cardiac-specific biomimetic substrates for the differentiation and expansion of hiPSC-CF. To do so, we utilized decellularized porcine heart extracellular matrix (HEM) as a TCP surface coating for hiPSC-CF differentiation and expansion. We identified that HEM reduces activated fibroblast characteristics yet does not impact hiPSC-CF differentiation. Further, we show that the alleviation in activation translates into 3D cell culture conditions and even improves cardiac organoid function in an isogenic cardiac organoid model. The results of this thesis provide an understanding of limitations and considerations in current hiPSC differentiation techniques and provide a novel solution for improving engineered cardiac tissues using biomimetic substrates
Assessment of Caregiver Burdens: A Screening Tool development for the improvement of Caregiver Health
Get PDFOpen Educational Resources (OER): A Catalyst for Health Sciences Education Innovation
No full textPoster presentation for the Disruption: Advancing Innovation in Education conference on March 17, 2023.https://medica-musc.researchcommons.org/posters/1028/thumbnail.jp
Investigating the Role of Ceramides in and Optimizing Models of Cancer-Induced Cachexia to Enhance Our Understanding of Human Disease
No full textPancreatic Ductal Adenocarcinoma (PDAC) is a deadly disease with a meager 12 percent 5-year survival rate. This is largely because PDAC is difficult to diagnose at an early stage and many patients present with both distant metastases and cancer-induced cachexia. The mouse models used to study PDAC do not sufficiently recapitulate the human phenotypes of metastasis and cachexia, making it challenging to understand the pathogenesis of this disease and develop therapeutics to treat it.
Our laboratory discovered that ceramide levels are significantly decreased in skeletal muscles of cachectic patients. Ceramides are an important component of the muscle membrane, an area of the muscle which is substantially damaged in cachectic PDAC patients but not in non-cachectic PDAC patients. We sought to understand if this loss in ceramides played a role in the initiation or development of the muscle damage and wasting that occurs in cancer cachexia.
Using our KPP genetic mouse model of cachexia and ceramide knockout mice, we investigated the effects of the regulation of ceramide levels in muscle fibers. We show that the loss of ceramides in the muscle alters the expression of MyoD, a protein along the muscle regeneration pathway but not the rate of activation of this pathway. We also developed AAV vectors to knockdown or overexpress a key ceramide synthesis enzyme to determine if the cachexia phenotype would be either exacerbated or ameliorated by its regulation. We hope to use the new models described in this thesis to test this question in the future.
We described an optimized orthotopic model of pancreatic cancer that increases the development of distant metastases and exhibits common markers of cancer-induced cachexia. This model can be utilized in our future studies to determine if the downregulation of ceramides contributes to the origin of the cachexia syndrome or if it is a consequence of the muscle wasting in this disease. We hope this model will be used by investigators to develop therapeutics to combat PDAC and that having a model that presents with both metastasis and cachexia will increase the efficacy of these treatments as they are translated to clinical trials