MEDICA@MUSC (Medical University of South Carolina)
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Advocating for Unrestricted Patient Access to Physical Therapy in South Carolina: Utilizing Health Services Research on Access, Quality, and Cost
Get PDFPrevention of the Oncogenic Effects of Lifestyle-Associated Advanced Glycation End-Products (AGEs) via Regular Physical Activity
Get PDFInterrelated lifestyle factors such as a sedentary habit, obesity and diets consisting of highly processed, high protein and fat containing foods, contribute to the accumulation of reactive metabolites known as advanced glycation end-products (AGEs). AGE pathogenic effects are mediated through modification of protein function, genetic fidelity, stress responses, and aberrant cellular signaling. For the first time, this study examined the effects of dietary AGE consumption on cancer progression in vivo and assessed physical activity (PA) as a potential intervention to reduce dietary AGE mediated effects. Given the links between lifestyle and AGEs, we propose that a diet high in AGEs can accelerate prostate cancer progression and severity which can be negated by regular PA. We found that chronic consumption of AGEs promotes prostate tumor growth and progression in vivo using syngeneic xenograft and spontaneous prostate cancer mouse models. Mechanistically, the stromal function of the transmembrane receptor for AGE (RAGE) was found to be a key substrate and effector of dietary-AGE tumorigenic function. Dietary AGE mediated activation of RAGE promoted a pro-tumorigenic microenvironment through the activation of cancer associated fibroblasts (CAFs) and macrophage polarization. Regular PA intervention by mice inhibited dietary-AGE induced tumor growth and progression. These results identify AGE content in food as a ubiquitous pro-tumorigenic consequence of lifestyle. They serve to focus future studies on the therapeutic potential of reducing AGEs through intervention and pharmacological strategies
Eliciting Durable Th17-mediated Memory Responses to Cancer
No full textAdoptive transfer of tumor-reactive T cells (ACT) is an effective therapy for patients with aggressive, metastatic malignancies. ACT has resulted in objective responses in 50-90% of patients, with a proportion of those responding durably for multiple years. Because T cells are expanded in culture for multiple weeks prior to infusion into the patient, this protocol drives high cost, treatment delays, and often generates sub-optimal T cells which leads to relapse. Therefore, novel approaches of generating therapeutic T cells rapidly are of clinical interest. We hypothesized that the T cell expansion process could be abbreviated by enriching CD4+ Th17 cells—a specific subset endowed with potent antitumor properties. Shortening ex vivo expansion to only four days licensed both murine and human Th17 cells to eradicate solid tumors to a greater extent than cells expanded long-term, despite compromised cell yield. We identified two novel mechanisms through which Day 4 Th17 cells ablate tumors in immunocompetent hosts. First, Day 4 Th17 cells induced multiple cytokines in the host including IL-6, IL-17, and MCP-1, and they persisted as memory cells. IL-6 was critical for therapy efficacy and for protection against tumor relapse. Mechanistically, IL-6 promoted survival of donor Th17 cells and diminished engraftment of regulatory T cells (Tregs), ultimately allowing robust infiltration of Th17 cells over Tregs into the tumor. Collectively, we highlight an underappreciated role for IL-6 in promoting durable immunity to cancer. We next hypothesized that host immune cells cooperated with infused Th17 cells to eradicate tumors. Surprisingly, host B cells, but not CD8+ T cells, were critical to Th17 immunity. While B cells were not the source of IL-6, Th17 cells promoted B cell activation and antibody secretion. B cells activated donor Th17 cells, fostered their inflammatory phenotype, and supported persistence. Our work implicates MHC-II, ICOS, IFN-γ, and IL-21 as key players in this mechanism. Overall, this dissertation reveals that therapeutic Th17 cells can be generated after a short ex vivo expansion period, and identifies a novel role for IL-6 and B cells in eliciting long-term efficacy for Th17 cell therapies. These findings have implications for harnessing effective Th17 immunity in patients
Targeted Helping in Rodents: Sex Differences and the Role of the Insula in Empathic Behavior
Get PDFEmpathy, the capacity for shared emotional valence with others, allows for cooperativity and social bonding between individuals. The evolutionary basis of the empathic behaviors observed across numerous species can be described using the Perception Action Model (PAM), in which shared affect can promote an action that eliminates the distress of both the Target and, by extension, the Observer . However, clinical studies indicate empathy is dysregulated in neuropsychiatric disorders like autism and addiction, which makes the elucidation of underlying behavioral, affective, and neurobiological variables of empathy paramount. We first introduce and validate a novel model of targeted helping, in which rats learn to aid a distressed conspecific in the absence of social reward. Next, using this model, we identify sex differences in sensory and affective signaling, including the impact of direct visualization of a distressed conspecific, and the type of ultrasonic vocalizations (USV) made between animal pairs, during the task. Further, neuronal activity in cortical and subcortical regions of interest showed distinct sex-specific patterning across time during targeted helping. Finally, we directly examined the effect of the anterior insula, a region active during perspective taking and emotional regulation hypothesized to be a critical node in the empathic brain, during empathic behavior. We not only confirmed that the anterior insula was activated during the task, but inhibition of the insula, both pharmacologically and chemogenetically, significantly attenuated helping behavior. Further, tracer studies were performed in order to elucidate critical insula-specific circuits that may modulate targeted helping. These studies, using a newly validated model of targeted helping, work to inform the underlying affective and biological variables that modulate empathic behavior in the hopes of improving the treatment outcomes and quality of life of those diagnosed with neuropsychiatric disorders
Assessing Transformation of Optimizing Ambulatory Surgery Center Services with Telehealth
Get PDFBackground: As technology advances and the ability to provide adequate and convenient surgical procedures improves; the usage of telehealth resources in an Ambulatory Surgery Center setting are evermore capable. The current environment of Ambulatory Surgery Center’s provides a baseline of support to alleviate main operating volume and to absorb more of the outpatient procedures with support from technology and telehealth. Objective: To understand how the telehealth abilities can enhance the efficiency and scope of service of Ambulatory Surgery Centers. To explore if telehealth resources can be utilized to strengthen, improve, and combine tasks that delay progress in the current model. To examine if as telehealth infuses with modern medicine, do the abilities make manual tasks obsolete given the transparent capabilities of telehealth resources. Methods: Utilizing a Value System Map (VSM) model to examine the current state of an Ambulatory Surgery Center, highlights in process delays are discussed and substituted in a later, future state model. Through displaying current vs. future state, areas of improvement are highlighted that provide areas of improvement in an Ambulatory Surgery Center setting. Results: In highlighting workflows with Ambulatory Surgery Center procedures, telehealth substitutions of current manual processes show promising improved efficiency with proper technology. Conclusion: The utilization of telehealth in place of current Ambulatory Surgery Center processes has begun due to recent pandemic of COVID-19; in which support from telehealth capabilities have supported growth in the ASC setting for more comprehensive usages when used accordingly with corresponding telehealth resources
Essential Leadership Characteristics and Critical Attributes of Strategy Implementation for Healthcare Transformation: A Systematic and Meta-Analytic Review
No full textThe uncertainty of healthcare, unrelenting cost containment pressures, market competition dynamics and increasing regulatory requirements pose significant challenges for survival for healthcare systems. The objective of this study is to determine the key leadership characteristics and attributes of strategy implementation a leader must have to survive the turbulence of healthcare. The study is designed as a qualitative study using the PRISMA model for systematic and meta-analytic review methods. Using grounded theory, the literature was coded using the Derue et al. integrated model for leadership traits and behaviors to identity key leadership characteristics. The literature was additionally coded using John Kotter’s change model to identity critical features of strategy implementation. NVivo qualitative analysis software was used to find overlaps in the literature. Search results returned 38 titles following applications of inclusion and exclusion criteria of which 1,165 references were coded. The most prevalent leadership characteristics and behaviors with a causal relationship to leadership effectiveness found in the text included: relational-oriented leadership (38%), task-oriented leadership (18%) and task competence (16%). The predominant themes of strategy implementation included: anchoring change in culture (33%), empowering action (22%) and developing a vision and strategy (20%). Leadership characteristics and features of strategy implementation overlapped most between relational-oriented leadership and anchoring change (146 references), relational-oriented leadership and empowering action (120 references), relational-oriented leadership and creating a guiding coalition (89 references), task-oriented leadership and developing a vision and strategy (71 references) and task-oriented leadership and anchoring change (69 references)
Reengineering an Allergy Group Practice in Response to COVID-19: Change Management, Quality Assessment and Financial Considerations
Get PDFTo date, few studies have provided a comprehensive set of requirements for outpatient medical practices to consider when preparing for complex external forces that impact clinic operations. The objective of this qualitative doctoral project is to establish a set of requirements for outpatient medical practices to consider when preparing for pandemic conditions. Using the backdrop of the COVID-19 pandemic, this single case study reviews how an allergy group practice responds to the variables presented during COVID-19 through change management, quality assessment and financial considerations lenses to assist other medical practices in developing pandemic preparedness programming. Findings from this case study are presented within an adapted Lewin change management framework and supported by six domains found to be requisite for an effective outpatient medical practice pandemic response: risk mitigation, operational excellence, talent considerations, clinical excellence, patient engagement and financial vitality. Annual preparedness training and response drills may assist with developing individualized criteria that supports seamless operations during uncontrollable external forces. Medical practice leaders should swiftly develop contingency plans now to better position their medical offices for a robust response during the next pandemic. Utilizing the six domains reviewed in this case study will support an individualized, effective plan to work through issues observed during a group medical practice’s COVID-19 response
Variations in ED Visits During Hurricane Irma in Florida and Potential Cost Savings Using Telehealth
Get PDFBackground: Periods of natural disasters like hurricanes can lead to traumas, worsening of existing medical conditions, travel restrictions, or healthcare systems’ inability to provide critical and timely care. A promising approach is telehealth use to provide care to remote patients in shelters or their homes. However, there is a need to better understand evacuees’ behavior and ED use during such events. Methods: We conducted a retrospective study using 2017 archival billing data in Florida during Hurricane Irma. The NYU ED algorithm was used to classify visits into emergent and non-emergent categories. Comparison groups included counties under mandatory evacuations and those with extended power outages. Comparison timelines were defined as pre-, post-, and hurricane quarters. Results: Hurricane evacuations caused more individuals to seek emergent and non-emergent care outside of their home counties during the hurricane quarter. Extended power outages caused an increase in in-county emergent and non-emergent visits after the hurricane. Telehealth could have potentially led to over $296 M in cost savings during the hurricane quarter. Discussion: Telehealth investments can be extended to meet the needs of a disaster-affected population. The availability of a robust telehealth infrastructure, appropriate planning and resource allocation, and supporting policies and regulation can make the continuity of care possible
A Small Molecule Screen to Identify a Potential Treatment for MTDPS3
Get PDFMitochondrial DNA Depletion Syndrome 3 (MTDPS3) is the most common mitochondrial DNA (mtDNA) depletion syndrome. MTDPS3 is an autosomal recessive disorder caused by a mutation in the deoxyguanosine kinase (DGUOK) gene in which a reduction in mtDNA nucleotides results in decreased levels of Adenosine Triphosphate (ATP). The DGUOK phenotypes vary; however, liver dysfunction tends to be consistent for all pediatric patients. Liver transplants can be beneficial; however, it’s only a palliative treatment at best, and the affected population rarely reaches adulthood. This thesis describes a high-throughput drug screen to identify a potential therapy for MTDPS3. MTDPS3 mutant hepatocytes derived from induced pluripotent stem cells (iPSCs) were utilized in the drug screen of the South Carolina Compound Collection (SC3) library. From the primary screen of 10,000 compounds, 63 compounds increased ATP levels at a sample number of one. The primary hits were used to perform biological replicates with the knockout cells, and six can increase ATP levels consistently. Two of the six compounds increased ATP production at eight different drug concentrations. My results show six small molecules with the therapeutic potential to treat an MTDPS3 phenotype in-vitro
Integration of Telehealth Education into the Health Care Provider Curriculum: A Review
Get PDFIntroduction: Telehealth is a rapidly expanding health care delivery modality with increasing utility in the health care community. It is imperative that telehealth education is provided during the training of health care providers to ensure the proper usage and application of this health care delivery system. A comprehensive literature review of telehealth education integrated into the curricula of physician, physician assistant, and advanced practiced registered nurse training programs has not been reported to date. Materials and Methods: An electronic literature search was performed using Scopus®, PubMed, and 17 of the 35 databases on the EBSCOHost platform. We included studies where telehealth concepts and components were integrated in the curriculum for primary care students. We extracted information pertinent to understanding the scope and sustainability of the curriculum and tabulated the results. Results: After a full-text screening of 164 articles and critically analyzing 34, eight articles were included in this review. Comparison of these articles showed no consistency in how telehealth was integrated into the various health care curricula. Content delivered usually included basic telehealth information, however, the depth and breadth of content varied significantly based on the interventions. Discussion: For the articles included in this review, there were no formal study designs regarding basic telehealth educational integration or competencies. While authors recommended conducting evaluation and determining the effectiveness of the interventions, they did not provide a clear picture as to how these efforts should be conducted. Conclusions: In addition to developing a standardized telehealth curriculum, national competencies need to be created, which will guide the development of standardized curriculum across health care training programs