MEDICA@MUSC (Medical University of South Carolina)
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Rapid Displacement of BRD4 from Chromatin by the DNA-PK Inhibitor NU7441
No full textDNA is continually assaulted by various intrinsic and extrinsic agents. To safeguard genome integrity, cells utilize a complex signaling network called the DNA damage response (DDR). The Bromodomain and Extraterminal (BET) protein BRD4 is a chromatin reader that regulates transcription of numerous oncogenes and DNA repair genes by recruiting transcription factors and protein complexes. However, recent studies have revealed a more direct role for BRD4 in the DDR. BRD4 contains two bromodomains that interact with acetylated histones, serving as a scaffold to coordinate transcription and DNA repair by recruiting multiple protein complexes to chromatin, including P-TEFb, SWI/SNF, Rad51, and the MRN complex. We have now shown that the DDR plays an important role in regulating BRD4 function by controlling its interaction with chromatin.
The DNA-dependent protein kinase (DNA-PK) is a signaling kinase that helps to activate the DDR. Using the DNA-PK inhibitor NU7441, I have revealed a novel mechanism of action for the drug that involves BRD4. The overall goal of my thesis is to unravel the mechanism underlying rapid displacement of BRD4 from chromatin by NU7441. Investigating how NU7441 rapidly displaces BRD4 from chromatin sheds light on its off-target effects, as well as that of other related DNA-PK inhibitors. Additionally, by elucidating the interplay between DNA-PK inhibition and BRD4 binding to chromatin, this thesis not only enriches our understanding of how the DDR regulates chromatin biology, but also lays the groundwork for innovative therapeutic strategies targeting BRD4 in cancer therapy
Increasing Occupational Therapy Student Confidence with Cultural Humility in Clinical Practice Through Meaningful Resources
Get PDFAn Assessment of the Impact of Patient Characteristics on Pediatric ECMO Outcome in the United States
Get PDFBackground. Extracorporeal membrane oxygenation (ECMO) is a critical life support mechanism in the intensive care of children with cardiopulmonary dysfunction. In this study, we aim to identify factors that impact ECMO outcome in pediatric population in the United States.
Methods. We conducted a retrospective cohort study of all ECMO admissions in the United States in years 2016, 2017 and 2019 using the National Inpatient sample (NIS) of the Healthcare Cost and Utilization Project (HCUP). The 2019 data was assessed to identify associations with the addition of ECMO type (VA vs VV).
Results. ECMO mortality rate was found to be 36.6%. Only pediatric chronic complex conditions (CCC) score and VA ECMO indication were associated with ECMO mortality. Age group, hospital region and CCC score were predictors of length of stay (LOS) for ECMO hospitalization. Hospital region and CCC score were predictors of total charges for ECMO hospitalization.
Conclusion. Age group, hospital region, VA ECMO type, and CCC score are predictors of ECMO outcome. Race, median household income and insurance type were not associated with ECMO outcome
Pediatric Sensorineural Hearing Loss: Improving Services for Children At-Risk for Future Developmental Delays
Get PDFHiding in Plain Sight: Medical Theses, Slavery, and Reparative Archival Practices
Get PDFDespite the prevalence of the use and abuse of enslaved individuals in the pursuit of medical education at the Medical College of South Carolina during the pre-Civil War era, evidence of the institution\u27s involvement with slavery is scarce in the discoverable archival resources at the Waring Historical Library. The Waring Historical Library Inaugural Theses Project aims to identify and bring these hidden narratives into focus through reparative description work. Key outcomes include enhancing the outdated index, transferring it to a LibGuide format, and improving descriptions, subject headings, and transcripts within catalog records. The project emphasizes how interdisciplinary cooperation between archivists and historians can shape reparative description work to benefit researchers and expedite project workflows
Prelimbic Neuronal Ensembles in Natural Reward Seeking
No full textExternal cues can become powerful motivators of behavior when paired with rewarding stimuli, such as natural rewards or drugs of abuse, as is the case in individuals with substance use disorder (SUD). The dorsomedial prefrontal cortex (dmPFC) has been implicated as a neural substrate which encodes cue-reward associations and has been shown to exert top-down control over both natural and drug reward seeking. We and others have shown that activity within the dmPFC is heterogeneous during reward seeking, with some neurons displaying excitatory responses to reward-predictive cues, and others showing inhibitory responses to the same cues. Furthermore, this response heterogeneity cannot be fully explained by the genetic identity or projection targets of the neurons in question. To investigate this, we train mice to perform a head-fixed Pavlovian sucrose seeking task while monitoring dmPFC activity via in vivo two-photon calcium imaging. Using this approach, we identify five non-overlapping dmPFC neuronal ensembles that develop unique cue- and reward-related activity as a function of learning. We find that these ensemble-specific activity patterns are stable after learning occurs, and that each ensemble differentially encodes task-related stimuli and conditioned behavioral responses. To directly probe the function of these ensembles, we utilize two-photon holographic optogenetics to manipulate the activity of these ensembles during sucrose seeking and disrupt conditioned licking responses. Further analysis of dmPFC activity reveals that network dynamics are perturbed following holographic stimulation. Altogether, these findings reveal that functional neuronal ensembles in the dmPFC stably encode learned cue-reward associations and the following behavioral response. Targeted manipulation of dmPFC ensembles is sufficient to disrupt conditioned behavior both during and immediately after stimulation, perhaps by temporarily biasing ensemble output. Future studies that characterize the circuit connectivity, gene expression, and behavioral function of each neuronal ensemble, defined based on in vivo activity dynamics, are essential for understanding the dmPFC circuit contributions to reward-motivated behavior
Unforeseen Consequences of Visual Literacy: Alternative Mechanisms for Creating a More Inclusive Environment
Get PDFAcknowledging the commendable efforts of colleagues in articulating significant concepts and theoretical approaches to enhance visual literacy within the LIS field, this work critically examines the Visual Literacy (VL) Framework. The analysis calls for a more inclusive representation of diverse experiences, particularly those of individuals with disabilities. Drawing inspiration from the conceptualization of critique as care, the study emphasizes a collaborative approach to integrate social justice, equity, and inclusion principles better into LIS work. While recognizing the VL Framework\u27s value as a starting point, the study identifies gaps related to universal accessibility and challenges in the language used. The chapter emphasizes the need for practical guidance on implementing the VL Framework components in real-time. The chapter delves into the language used in discussing visual literacy, highlighting its potential perpetuation of exclusion. In the context of visual literacy pedagogy, the study poses reflective questions to promote inclusivity in higher education settings. Ethical considerations regarding material interactions and institutional access are also explored.https://medica-musc.researchcommons.org/faculty-books/1004/thumbnail.jp
Implementation of Psychiatric Collaborative Care Management in Rural Primary Care Practices
Get PDFBehavioral health (BH) disorders are highly prevalent in the United States and especially concerning in rural communities which disproportionately lack access to BH services. While models for integrating BH into primary care, such as psychiatric collaborative care management (CoCM), have shown promise in mitigating the BH crisis, implementation in rural communities has proved challenging. This dissertation examines implementation of CoCM nationally and in rural settings through three distinct aims. First, a claims-based retrospective cohort study was used to determine whether commercially insured patients receiving CoCM had lower acute BH care utilization and cost as compared to similar patients not receiving CoCM. Second, a mixed-methods systematic review was conducted to describe barriers and facilitators to rural implementation of CoCM. Finally, implementation science evaluation was applied to a telehealth-enabled CoCM pilot conducted at four rural primary care sites to determine optimal adaptations to the model and characterize barriers and facilitators to implementation. While each aim was distinct in terms of methods and results, the challenge of implementing CoCM was common across study findings. However, results also showed that successful implementation of CoCM in rural communities is feasible, especially when tailored to these contexts and aided by external supports
Addressing the Physical Demands of Caregiving or Children with Disabilities in Nicaragua: A Quality Improvement Collaboration with FNE International
Get PDFMany caregivers of children with disabilities experience chronic pain and related symptoms of cumulative physical trauma. This type of phenomenon is particularly prevalent in developing, low-income countries where environmental accommodations may not be as accessible. A quality improvement program, was conducted as a doctoral capstone project to create resources addressing the physical needs of caregivers of children with disabilities in Nicaragua. Program participants included teachers at a school for children with disabilities and special needs in Nicaragua. The primary project deliverable consisted of conducting an in-person workshop to train the teachers with evidence-based methods for preventing chronic pain and other symptoms of cumulative physical trauma with a focus on protective ergonomics. Program evaluation included a mixed methods design with pre and post intervention focus groups of teachers and school administrators. A post intervention survey was also conducted assessing teachers’ knowledge of content in their native language and with visual imagery to provide clarity. Results included reduction in teachers’ self-reported pain at least one week later as well as increased knowledge and self-efficacy in preventing chronic pain as a caregiver of children with disabilities. Additional video and written resources were developed and made publicly accessible online in Spanish, serving as supplementary educational and support resources for teachers and parents of children with disabilities. These were shared with the teachers incorporating feedback from the focus group and provided to similar schools in Central America via an app Juntos Podemos. This global health project demonstrates promising approaches to address the needs of caregivers for children with disabilities across borders in developing countries through collaborative communication and leveraging technology. Future programs should include increased opportunities for parent engagement in preventative training, further expansion of online and sustainable resources, and ongoing collaboration with in-country community partners to support caregivers of children with disabilities in developing countries
An Analysis of Inpatient and Outpatient Radiofrequency Cardiac Ablation: Quality Outcomes and Reimbursement
No full textBackground
Radiofrequency ablation for the treatment of atrial fibrillation currently stands as the first line therapy for the condition. The therapy is a costly means of managing the disease, with both inpatient and outpatient coding options in the hospital. A major determinant ablation readiness and status of the patient still remains in the physician’s discretion, and outcomes may not be aligned with the status of patient at the time of the ablation. Shifting these patients to an outpatient ablation status may create significant savings if the outcomes are equivalent.
Results
A total of 87 new onset AF patients were sampled and monitored post ablation. Recurrence rates for markedly higher for those in the inpatient setting (14.2%) over the course of a year versus the inpatient cohort (8.2%). Similar findings were observed in readmission rates, whereas the inpatient cohort reflected a higher incident of readmission post ablation within the course of a year versus that of the inpatient cohort (14.2% vs. 2.6%).
Conclusion
Although there is a need for an inpatient billing paradigm, stabilizing a new onset AF patient and shifting them to the outpatient setting can and create significant savings to Medicare while still maintaining the same quality of care