MEDICA@MUSC (Medical University of South Carolina)
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    1558 research outputs found

    Targeting STAT3 in Medulloblastoma Propagating Cells to Treat SHH-Driven Medulloblastoma

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    Brain cancer is the leading cause of cancer-related death in pediatric patients, and medulloblastoma is the most common one. The subset of medulloblastoma specifically addressed in this research is driven by over activation of the SONIC HEDGEHOG (SHH) pathway. Recurrence of disease and metastases are significant problems within medulloblastoma and can decrease 5-year survival rates from 80% to 18%. Therapy-resistance is hypothesized to be a strong driver of these outcomes. There is a population of cells within the tumor, referred to as Medulloblastoma Propagating Cells (MPCs), that have been implicated as drivers of tumor recurrence and metastases. These cells have stem-like properties and are molecularly unique from the more differentiated transit-amplifying tumor cells, marked by a heighted expression of SOX2. They also are un-responsive to the normal SHH targeted therapy, Vismodegib. My data revealed Signal Transducer and Activator of Transcription 3 (STAT3) signaling as an over-activated pathway within these cells versus SOX2 negative cells via co-localization assays and transcriptomics analysis. Pharmacological and molecular genetics approaches to inhibit STAT3 signaling in MPC enriched cultures resulted in a significant decrease of ex vivo tumor propagation (self-renewal assays), and cell viability (MTT assays). The STAT3 inhibitor used in these experiments was Stattic. If my hypothesis was correct and MPCs were driving therapy-resistance and STAT3 was driving the MPCs, it stands to reason that inhibiting STATA3 should re-sensitize these tumors to the original therapy, Vismodegib. A series of cell viability and self-renewal assays using single agent Vismodegib and Stattic, as well as a combination therapy, revealed a synergistic relationship between the two compounds resulting in significantly decreased survival of the cells and ability to renew, suggesting a lack of stemness. Significant in vivo studies need to be conducted to confirm that this synergistic effect seen results in destruction of the entire tumor and bearable toxicity. However, these studies did conclude STAT3 inhibition, both genetically and pharmacologically, reduces MPCs viability and stem-ness. Additionally, pharmacological inhibition of STAT3 by Stattic resulted in re-sensitivity of previously resistant MPCs to Vismodegib

    Reconnecting with Library Users: Providing Remote Library Services During a Library Renovation

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    This poster was presented at the Medical Library Association Annual meeting in New Orleans, Louisiana May 6, 2022https://medica-musc.researchcommons.org/posters/1014/thumbnail.jp

    Telehealth: Reaching Out to Patients and Providers

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    The integration of telehealth modalities into clinical, research and education systems is an evolving area of health informatics. While many of these technology concepts are not novel, their applications in today’s healthcare ecosystem provide the opportunity for the development of high-quality, secure interactions to better support patients, caregivers and their providers. Important regulatory, professional and legislative guidelines have been established to guide the development of technologies and practices across various practice settings, geographic areas and patient populations. This chapter explores telehealth applications and innovations related to service development specific to the integration of telehealth into health informatics systems and in partnership with broader healthcare teams.https://medica-musc.researchcommons.org/faculty-books/1002/thumbnail.jp

    Genetic Variation Within Nicotine Addiction Pathways in Relation to Smoking Cessation and Smoking Relapse Throughout Adulthood: A Longitudinal Study of Female Registered Nurses

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    Cigarette smoking is a leading cause of premature death and preventable illness; more than 480,000 deaths annually in the U.S. are attributable to smoking. Of the more than 34 million U.S. adult smokers, more than half make a quit attempt each year but more than 90% will relapse within 6 months. Twin studies show that smoking cessation is more than 50% heritable, thus genetics plays a significant role in cessation. However, the understanding of genetic susceptibility to cessation failure is still in its nascent stages. Genetic studies of smoking cessation have typically used short-term follow-up or cross-sectional design, study design characteristics that cannot account for multiple quit attempts and relapse episodes over time, a phenomenon common in smokers. Additionally, prior genetic studies have often excluded light smokers even though light smokers comprise 15% of U.S. adult smokers, and few studies have examined genetic associations specifically among women. These factors limit the understanding of genetic susceptibility in smoking cessation because mechanisms of addiction may vary between light and heavy smokers as well as between men and women. To overcome these limitations, we used existing high-quality genetic and phenotype data available in the Nurses’ Health Study (NHS) and NHS 2, two large all-female cohorts with up to 38 years of longitudinal measurement of cigarette smoking for nearly 13,000 former/current smokers. We conducted a systematic review of the current evidence of genetic associations with smoking cessation focusing on genetic variation within biological pathways influencing nicotine addiction to inform two complementary methods of single nucleotide polymorphism (SNP) selection: 1) a candidate SNP approach, and 2) a candidate gene approach selecting thorough coverage of SNPs within genes that influence mechanisms of nicotine addiction. We examined the selected SNPs associations with 1) the likelihood of smoking cessation throughout adulthood and 2) the likelihood of relapse during adulthood and the proportion of follow-up in relapse. Using this approach, SNPs were observed to be associated with smoking cessation throughout female adulthood. Several SNP associations provided evidence to suggest that the associations may differ between light versus moderate to heavy smokers. Furthermore, SNPs were observed to be associated with the likelihood of sustained abstinence after successful cessation and, among women who relapsed, with the proportion of follow-up in relapse. The findings also revealed that some SNP associations with proportion of follow-up in relapse were stronger in women who quit smoking post-menopause. This research advanced understanding of the role of genetics of persistent smoking throughout adulthood, specifically in women. The evidence holds relevance for guiding precision medicine approaches to smoking cessation and indicate the need for intervention approaches to long-term cessation management and relapse prevention

    Optimization of Mental Health Appointment Mix: Telemental Health and In-person Appointment Model Maximizing Revenue and Mitigating No-shows

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    Mental Health care leaders are challenged with meeting revenue requirements while incorporating telemental health (TMH) to increase access. The objective of this project was to create a model to optimize revenue based on variables derived from the literature, notably no-shows, reimbursement, salary cost, and appointment type. The model was tested through sensitivity analysis. The order of sensitivity to net revenue based on a 10% variable increase was reimbursement rate (19% increase), appointment volume (10% increase), cost (8.5% decrease), and no-shows (1% decrease). 3 scenarios were run for large (10 providers), mid-sized (4 providers), and single provider facilities. In-person vs telemental health appointment mix for each scenario was set at 80%/20%, 50%/50%, and 20%/80%. Reimbursement rate for TMH was set at 70%, 80%, 90% and 100% (parity) of in-person recovery. Results showed 100% TMH reimbursement was the only scenario increased TMH appointments increased revenue. 90% reimbursement had minimal revenue loss with increased TMH (2-3%) and 70% or 80% had significant losses (9%-30%). Parity is vital to TMH revenue impact and adoption

    Using Adult Learning Characteristics and the Humanities to Teach Undergraduate Healthcare Students about Social Determinants of Health: Data and Lessons Learned from Photography Essays

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    Social determinants of health (SDOH) refer to the factors that influence one\u27s quality of life and various health outcomes like morbidity, mortality, life expectancy, healthcare expenditures, and much more (Artiga & Hinton, 2018). These factors may also be viewed as predictors of various health outcomes and include factors like access to healthcare, education, socio-economic status, and physical conditions such as living environments (Baverstock et al., 2018). Healthcare leaders are recognizing the growing significance of SDOH impact on health and health equity. Educators in medicine are using classroom space to teach about SDOH and their effect (Doobay-Persaud et al., 2019; Klein et al., 2011; Martinez et al., 2015; Sharma et al., 2018; Witten & Maskarinec, 2015); however, not much is seen in the literature for allied healthcare professionals (Brown et al., 2021). Authors employed several lenses to teach SDOH to allied healthcare professionals who are also students in an online Bachelor of Science Healthcare Studies program at a large academic medical center in the southeastern United States: (1) characteristics of adult learning, (2) aspects of a transparency framework, and (3) fundamentals of the humanities.https://medica-musc.researchcommons.org/posters/1021/thumbnail.jp

    The Effect of Robot-Assisted Haptic Guidance on Time Osteotomy Volume, and Bevel Angle in Endodontic Microsurgery

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    The Yomi (Neocis, Miami, FL, USA) is a novel robotic technology that utilizes haptic guidance for implant surgery. No research has been done on robot guided applications for endodontic microsurgery (EMS). The current study was an in vitro study examining how the use of robot guidance would affect the time, osteotomy volume, as well as bevel angle during endodontic microsurgery. The study aimed to compare those variables between a robot guided approach, a second-year endodontic resident freehand, and an experienced endodontist with over fifteen years of experience. Forty-five extracted mandibular molars and premolars were mounted in stone/pumice casts. Endodontic microsurgery was performed by robot guidance, the endodontic resident, as well as experienced endodontist. The results were analyzed by ANOVA tests for significance. When compared to the second-year endodontic resident, robot guidance performed better in all categories. The use of robot guidance had a significantly smaller bevel angle and time when compared to the freehand technique by the two operators. The study shows that robot guidance can be used in endodontic microsurgery to increase time efficiency as well as improve the osteotomy volume and bevel angle

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