MEDICA@MUSC (Medical University of South Carolina)
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Creating Mental Health Resources for Veterans and Caregivers at the Charleston Fisher House
Get PDFThe Charleston Fisher House (FHC) provides free lodging, food, and transportation to the Veterans Administration (VA) hospital for veterans and families receiving care at a VA or associated hospital (Friends of Fisher House Charleston, 2024). Stays range from 1 night to several months, based on the veteran’s medical needs. Being away from home and caring for a sick loved one can cause stress and decrease the caregiver’s effectiveness in aiding the loved one and for self-care (Adelman et al., 2014). Occupational Therapy (OT) holistically addresses the person, including their mental health. A capstone project was implemented to improve mental health in the caregivers and veterans at the FHC to increase their quality of life by reducing stress.
Surveys were given to guests at check-in with questions relating to mental health and any services they requested. 46% reported feeling stressed, 40% reported feeling anxious, and 31% reported feeling overwhelmed at least some of the time. Based on this indicated need, a quality improvement project was conducted to provide mental health resources to the guests staying at the FHC. Handouts on symptoms of anxiety, depression, and PTSD were created with holistic ways to help: time management, sleep hygiene, stress management, affirmations, mantras, and mindfulness. Three classes were taught using handouts as the basis for the class, with 100% of attendees agreed that the class was helpful and 88% of attendees reported they will use the information most days or daily. 88% of attendees reported that a brief mindfulness activity was helpful to their mood. Other mindfulness activities were implemented at the site, with all guests agreeing that they helped them relax.
Sources:
Adelman, R. D., Tmanova, L. L., Delgado, D., Dion, S., & Lachs, M. S. (2014). Caregiver Burden: A Clinical Review. JAMA : The Journal of the American Medical Association, 311(10), 1052-1060. 10.1001/jama.2014.304
Friends of Fisher House Charleston. (2022). Friends of Fisher House Charleston. Retrieved 15 August 2022, from https://friendsoffisherhousecharleston.org
The Development of Intervention Toolkits for Non-Specialized Personnel and Families of Children with Autism Spectrum Disorder in La Paz, Bolivia
Get PDFINTRODUCTION: There has been an increase in the understanding of autism-spectrum disorder (ASD) and corresponding occupational therapy (OT) interventions; however, much of this has yet to be implemented in several resource-limited countries, including Bolivia. Parent-mediated interventions (PMIs) are being heralded as a promising approach to address this gap. Through the creation of toolkits for non-specialized personnel (e.g., parents, teachers), the purpose of this quality improvement (QI) project is to enhance the occupational engagement and quality of life for children with ASD and their families in La Paz, Bolivia. METHODS: Pre-surveys were administered to parents of children with ASD at the sites to determine beneficial topics for the toolkits. Post-toolkit development, a self-report questionnaire was administered to healthcare professionals who reviewed and will distribute the toolkits to nonspecialized personnel. These surveys consisted of a variety of question types to acquire data, which was analyzed using both quantitative and qualitative methods. RESULTS: The findings indicate that the toolkits were found to be helpful, and the healthcare providers plan to share them with other non-specialized personnel. Qualitatively, there were reports of the toolkits being useful and easy to replicate; however, concerns were presented for ease of mass dissemination and comprehensibility for parents. CONCLUSION: This toolkit intervention for non-specialized personnel is viewed as a helpful and effective option among healthcare providers in Bolivia for reducing the gaps surrounding access to clinic-based services. The QI project supports the targeted goal for this population, and the sustainability allows for the continuation of this project
Next Generation Human Cardiac Organoids: Modeling Inflammatory Diseases and Engineering Their Protection in vivo
No full textIn the context of excessive inflammation, cardiovascular complications such as arrhythmias, functional deficits, vascular dysfunction and fibrosis have all been reported. However, characterizing these pathologies has remained challenging given the complex interplay of cytokines, immune cells, and the affected tissue. Given the immune system’s known roles in remodeling post ischemic injury, preclinical efforts have been directed towards minimizing excessive fibrosis and immune cell infiltration. To facilitate the healing process and spare the myocardium from pathological remodeling and functional decline, cellular transplantation therapies have been employed, with the intent to either replace damaged cardiomyocytes, or provide a continued source of healing factors to the affected area. However, the inability to produce universally transplantable organoids capable of avoiding immune rejection has limited advances in engineering approaches aimed at regenerating damaged human myocardium.
Animal models and 2D cultures of human cells have been employed to study the effects of cytokines, immune cells, and infectious insults on the heart, but their translational impact has been limited due to interspecies differences, cell-cell communication, and the significance of three-dimensional tissue organization. To this end, our lab has developed human cardiac organoids for disease modeling and regenerative medicine. Given their ability to recapitulate key hallmarks of myocardial infarctions and drug induced cardiotoxicity and the intrinsic inflammatory properties of the cell types composing the organoids, we hypothesized these human cardiac organoids would provide a suitable platform to model myocardial inflammation. We further hypothesized the vasculature in our cardiac organoids could be leveraged to engineer a vascularized cardiac microtissue. In doing so, the vascular network would address current limitations such as nutrient accessibility and enable the incorporation of immune cells. Finally, we hypothesized that engineering T cells, or the organoid graft to abrogate the host immune response would prolong organoid survival time to increase their therapeutic benefit. In the enclosed dissertation, we illustrate these human cardiac organoids have the potential to model inflammatory conditions such as the acute cardiac injuries induced by COVID-19 Cytokine Storm, to be engineered into a perfusable microtissue, and show that multiple immune engineering approaches have the potential to augment cellular transplantation therapies in the context of cardiac regeneration post myocardial infarction
The Role of SOX9 in Epicardial-Mediated Cardiovascular Development and Valve Homeostasis
Get PDFCongenital heart defects (CHDs) are the most common birth defects in humans, affecting as many as 1% of live births, thereby representing a major public health burden. These defects arise when signaling pathways and mechanical forces guiding heart development are disrupted, either by genetic mutations, aneuploidies, environmental influences, or any combination of these factors. The vast majority of CHDs have undetermined etiologies. Understanding the molecular and cellular mechanisms of normal heart development is critical for unraveling the origins of CHDs and for developing more effective diagnostics and interventional treatments for those affected by cardiovascular diseases of developmental origin.
The epicardium is a single-cell layer of progenitor cells lining the outside of the heart. Epicardial-derived cells (EPDCs) play important roles in the proper development and homeostasis of the atrioventricular (AV) valves, myocardium, and coronary vasculature. This thesis describes a novel role for the transcription factor SOX9 in regulating the contribution of EPDCs to the developing heart. We utilize transgenic lineage-tracing mouse models, high-resolution immunofluorescence analyses, bulk, and single-cell RNA-sequencing (scRNA- seq) to understand the morphological, cellular, and molecular changes associated with epicardial-specific deletion of Sox9. These studies demonstrate that loss of Sox9 results in a marked impairment in the invasion of EPDCs into both the AV valves and the ventricular myocardium. This impaired invasion results in pathogenic changes to the mitral valve reminiscent of myxomatous mitral valve disease (MVD) in humans. Reduced EPDC invasion due to loss of Sox9 also delays the development of the myocardium and the coronary vascular plexus. Sequencing experiments identified Cd109 as a novel gene associated with myxomatous valve pathogenesis in this model. Overall, these studies support an important role for Sox9 in the regulation of epicardial invasion critical for proper heart development and AV valve homeostasis. We also identify Cd109, a gene never previously described in the context of heart development or disease, as a novel player in various cardiovascular developmental events. These insights contribute to a better understanding of etiologies of cardiovascular diseases with developmental origins
Stress, Coping, and Health-Related Quality of Life in Parents of Children with Congenital Heart Disease
No full textThe primary objective of this study was to describe and test the role of coping processes in perceived stress and health related quality of life (HRQoL) in parents of children with congenital heart disease (CHD) and determine the influence of sociodemographic factors on these variables. We used a multi-methods design, guided by the Transactional Model of Stress and Coping, to examine the relationships among coping strategies, perceived stress, HRQoL, and sociodemographic factors in parents of children with CHD and to explore parent perceptions and experiences with stress and coping. Participants were recruited through convenience sampling by in-person efforts at Boston Children’s Hospital and advertising on social media support groups. Surveys were administered to parents of children with CHD through REDCap to examine the relationships among perceived stress, coping strategies, HRQoL, and sociodemographic factors using advanced statistical methods including mediation and moderation analysis. Purposeful sampling was utilized to identify a subset of participants interested in completing semi-structured interviews to explore parent perceptions of CHD-related stressors, past and current coping strategies, barriers and facilitators of effective coping, and preferences for future interventions. This study addresses a gap in the literature regarding barriers and facilitators of effective coping and the role of different coping strategies in the relationship between stress and HRQoL for parents of children with CHD. The result is a comprehensive description of stress, coping, a HRQoL in parents of children with CHD with implications for future research, clinical intervention, and policy development
Development of a Novel Array-Based Capture Method for Bulk and Single-Cell Multi-Omic MALDI-MSI Analysis
No full textMass Spectrometry Imaging (MSI) is a powerful technique that enables the analysis of a wide variety of analytes from diverse samples such as tissue sections and spotted serum. This versatility fosters the development of innovative techniques, offering valuable tools for both research and clinical diagnostics. Our laboratory had initially developed a method for the MALDI-MSI glycan analysis of specific proteins following antibody capture. We hypothesized that we could also develop a MSI-compatible capture method for the affinity-based immobilization of cells, facilitating MALDI-MSI analysis. The initial version of this method successfully captured thousands of cells within a spotted antibody region via antibody-epitope interactions. This approach enabled rapid N-glycan imaging of the captured cells, with a particular emphasis on immune cells. Alternative methods for cellular N-glycan profiling are primarily catered towards homogenous samples, making the analysis of heterogenous samples such as PBMCs difficult for large scale and comprehensive N-glycan profiling. We successfully captured and profiled N-glycans from helper T cells, cytotoxic T cells and B cells from 30 cryopreserved PBMC samples, revealing a distinct N-glycan profile amongst the different cell types. MALDI-MSI is a soft ionization technique that preserves sample integrity during laser ablation. This allows for multiple rounds of imaging and analyte investigation to occur. We demonstrated that from captured cells, we could profile a range of molecules including lipids, N-glycans, glycogen, and tryptic peptides providing a comprehensive dataset from the same immobilized cells. We further hypothesized that our cell capture approach could be adapted for single-cell applications by reducing the capture spot size to enable the capture of individual cells. By integrating micro contact printing with polydimethylsiloxane (PDMS) stamps, we achieved capture spot diameters of 30-40 µm, suitable for single-cell capture. We developed an AI-based application, SoloCell, to facilitate the automated selection of captured single cells within the array. This method successfully captured thousands of single cells in a grid format, allowing for the rapid lipid and N-glycan profiling from the same cell at a rate of 6 cells per second. Overall, the workflow described in this thesis exhibits a sensitive, versatile and high throughput technique for bulk and single cell profiling
Waring Library Society Newsletter, Spring 2024
Get PDFThe Spring 2024 issue of the Waring Library Society Newsletter is available now. In this issue, Waring Library Society President Dr. Robert Ball gives his first remarks as WLS President for the newsletter; JoAnn Zeise discusses Louis R. Agassiz’s time at the Medical College in 1849; Tabitha Samuel announces the new additions to MEDICA@MUSC; and Kathryn Glorioso provides insight into one MUSC lab intersection with history and Francis Peyre Porcher.https://medica-musc.researchcommons.org/wls-newsletters/1008/thumbnail.jp
Complement Propagates Visual System Pathology After Traumatic Brain Injury
No full textBackground: Traumatic brain injury is associated with the development of visual system disorders, including deficits in visual acuity. Visual deficits can present with delay and worsen over time, suggesting that ongoing neuroinflammatory changes contribute to their development and progression. Complement activation is strongly associated with the neuroinflammatory response after TBI and has been shown to contribute to neuronal and synaptic loss. However, the contributions of complement activation after TBI to vision loss remains unclear.
Methods: We employed an open skull controlled cortical impact model of traumatic brain injury in adult male mice to study how TBI affects vision. Animals were treated with a single i.v. dose of complement inhibitor CR2-Crry or saline. Acute neuroinflammatory changes were assessed in the dorsal LGN at 3 days after injury. Behavioral and visual function tests were performed in another cohort of animals, and neuroinflammatory and histopathological changes were assessed at 49 days after injury.
Results: C3 was deposited on retinogeniculate synapses in both the ipsilateral and contralateral dorsal lateral geniculate nuclei (dLGN) within 3 days after TBI, and was reduced in CR2-Crry treated animals. Microglia exhibited quantifiable morphological changes in both the ipsilateral and contralateral dLGN, with a more amoeboid phenotype after TBI in vehicle vs. CR2-Crry treated animals. Microglia in vehicle treated animals also had a greater internalized VGLUT2+ synaptic volume after TBI compared to CR2-Crry treated animals, reminiscent of aberrant phagocytosis seen in perilesional areas of the brain after TBI and stroke. There were no changes in the thickness of the retina. These pathologies were accompanied by reduced visual acuity in both the ipsilateral and contralateral eyes at 10 and 35 days after TBI; vision was absent in the majority of contralateral eyes in both groups of animals, but complement inhibition preserved visual acuity in the ipsilateral eye.
Conclusion: Traumatic brain injury induces complement activation within the dorsal lateral geniculate nucleus and promotes synaptic internalization and microglial activation. Inhibition of the complement system with an injury site-targeted complement inhibitor is sufficient to preserve visual acuity in the ipsilateral eye, reduce complement activation and microglial morphological changes, and preserve synaptic count within the dorsal LGN. Altogether, these data suggest that complement plays a role in the development of visual deficits after TBI, and that inhibition of complement acutely after TBI has therapeutic potential for ameliorating visual and other deficits
Exploring the Interaction Between Klebsiella pneumoniae and Clostridioides difficile at the Mucosal Interface
Get PDFThe gut microbiota plays a major role in human diseases. The impact of these microbes on human health comes not only from individual microbes but also from their interactions with each other. A prime example of this is Clostridioides difficile, an intestinal pathobiont that causes severe gastrointestinal illness. C. difficile works cooperatively with other gut bacteria, including Klebsiella pneumoniae. We hypothesized that K. pneumoniae would work synergistically with C. difficile and promote its pathogenesis. We screened over 40 K. pneumoniae strains to assess their interaction with the intestinal mucus layer, a key colonization site for C. difficile. In our screening, we observed that 10% of our clinical isolates exhibited distinct virulence phenotypes when grown on antibiotic selective agar, showing divergent antibiotic responses, biofilm production and motility. We found that all our K. pneumoniae strains had robust adhesion to mucus and flagellated strains of K. pneumoniae chemotaxed towards mucus and individual sugars found in the mucin glycans. We performed computational analysis to examine the mucin glycan degrading capacity of K. pneumoniae and found that it harbored galactosidases and N-acetyl-hexosaminidases. We also found that K. pneumoniae consumed free galactose and N-acetyl-hexosamines and had low level growth with intact mucus. In a larger analysis of gut pathobionts and pathogens, we found that the majority of these microbes did not possess extensive mucin-glycan associated glycosyl hydrolases; suggesting that mucus degradation by most pathobionts is limited. When we grew K. pneumoniae and C. difficile together, we observed both bacteria in co-cultures. We also observed that the presence of K. pneumoniae or its metabolites enhanced the intrinsic green autofluorescence of C. difficile; allowing us to separate the bacteria by flow cytometry. We also found that K. pneumoniae and C. difficile could grow together aerobically, as K. pneumoniae quenched oxygen and supported C. difficile growth in aerobic culture. We observed a similar phenomenon when the bacteria were grown together in bioreactors. Mice that were co-inoculated with C. difficile and K. pneumoniae showed increased gut inflammation and damage. These findings highlight the complexity of microbial interactions in the gut and how they affect human health