MEDICA@MUSC (Medical University of South Carolina)
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Appendix 1: College of Medicine Departmental Synoptic Histories
No full textThis is a multi-contributor compilation of the histories of all the academic departments in the College of Medicine. It was edited by Philippa Newfield, MD, and J.G. Reves, MD. Each department in the College of Medicine has a history and the histories are told primarily by the chairs of the departments.https://medica-musc.researchcommons.org/faculty-books/1005/thumbnail.jp
Individual Differences in Cannabis Use Disorder with Implications for Endocannabinoid Modulation in Therapeutics Development
Get PDFCannabis use disorder (CUD) is increasingly prevalent in the United States, but there is no effective pharmacological means to treat it. The endocannabinoid (eCB) system has emerged as a candidate therapeutic target demonstrating some evidence of efficacy in treating CUD. However, clinical trials evaluating eCB-modulating therapeutics have historically undervalued individual differences that could contribute to variation in treatment outcome (e.g. sex, comorbid psychiatric illness). To address this gap in the literature, the present set of studies (a) compared plasma eCB tone in groups underrepresented in treatment trials for CUD (females, individuals with comorbid major depressive disorder; MDD/CUD) with males or otherwise healthy people with CUD, (b) examined group differences in behavioral predictors of relapse (withdrawal symptoms, stress response), and (c) related plasma eCB tone to these behavioral predictors. We found that, as hypothesized, women or individuals with MDD/CUD self-reported more severe cannabis withdrawal symptoms compared to men or individuals with CUD alone, respectively. Self-reported withdrawal was moderately positively associated with eCB tone across studies, with the strongest associations observed in women with CUD. In MDD/CUD, however, self-reported withdrawal appeared largely uncoupled from objective withdrawal measures and abstinence from cannabis. With respect to stress, MDD/CUD was associated with a prolonged stress response relative to CUD alone, suggesting individuals with MDD/CUD may be at a greater risk for stress-induced relapse. Individuals with MDD/CUD also presented differently from those with CUD alone in stress-associated eCB levels, raising questions as to the mechanistic role of peripheral eCBs in stress responding. Taken together, these studies demonstrate that exploration into individual differences in the eCB system, particularly in the periphery, is still in its infancy. The utility of eCB-modulating pharmacotherapeutics likely differs significantly across subpopulations of people with CUD. Greater mechanistic understanding of the eCB system across subpopulations is warranted
Assessing the Types of Juvenile Detention Medical Issues: A Focus on Florida
Get PDFThe justice system for young people in the United States has been a source of worry as more people acknowledge the possible adverse outcomes of involvement in the justice system during adolescence. Involvement with law enforcement can lead to various difficulties for young people, such as heightened susceptibility to psychological problems, interruptions in their education, and reduced prospects for achievement in the future. Hence, it is crucial to understand the interplays between the health care for juveniles referred by courts or law enforcement for hospital care to identify opportunities for process and outcome improvements. The interaction between juveniles and the criminal justice system has garnered noteworthy consideration in contemporary times owing to its impact on the welfare and growth of young people. Documenting the trends of juvenile admittance and release between medical care and law enforcement is vital in creating efficient policies and interventions to meet their requirements and diminish their engagement in the legal system. This study aims to provide statistics regarding adolescents taken into custody by law enforcement who required hospital care in Florida. The analysis will concentrate on the instances where these youths, ages 10-18, were brought to the emergency department or admitted to a hospital in 2018
Enhancing Adoptive T Cell Therapy: Unveiling the Cell Autonomous Role of Stat5 in T Cell Engraftment
No full textIn the past four decades, immunotherapies have revolutionized cancer treatment, offering new hope for patients with various malignancies. Among these groundbreaking therapies is adoptive T cell therapy (ACT), which involves enriching and expanding autologous tumor-reactive T cells for reinfusion into the patient, capitalizing on the potent ability of T cells to target tumors. This powerful approach can induce complete durable responses in subsets of patients. However, several aspects of adoptive T cell therapy can be improved warranting further development in the context of recent technological advances. A nearly ubiquitous practice in T cell adoptive transfer protocols is lymphodepleting pre-conditioning, which often leads to clinically significant side effects that limit utility and adoption of ACT. Specifically, lymphodepleting regimens used clinically lead to pan-cytopenia, immune suppression, and reactive myelopoiesis potentially undermining the therapeutic index of ACT. To address these challenges, we embarked on studies aimed at investigating the mechanisms underlying effective engraftment in ACT, hypothesizing that such mechanisms might be cell autonomous and not reliant on the host\u27s lymphodepleted immune status. Leveraging mouse models, we focused on exploring the role of Stat5 signaling during T cell adoptive transfer. Remarkably, through transient expression of a constitutively active mutamer of Stat5 during the adoptive transfer process, we successfully obviated the need for lymphodepletion prior to transfer. Functional assays revealed minimal differences in the function and phenotype of engrafted T cells compared to those transferred after conventional lymphodepletion. Moreover, bypassing lymphodepletion reduced peripheral IL-6 spikes and signatures of suppressive myeloid cells typically associated with poor clinical responses. Our findings shed light on a cell-autonomous mechanism mediated by transient Stat5 signaling during engraftment, which has lasting effects on T cell function. Thus, this dissertation provides compelling evidence that the efficacy of adoptive T cell therapy can be substantially improved by eliminating lymphodepleting protocols entirely and replacing them with mRNA transfection of T cells with transcripts encoding active Stat5. This paradigm shift holds promise for advancing the field of ACT and improving outcomes for patients
Life-Skills and Transition Training in Special Education: Evidence-Based and Stakeholder Driven
Get PDFIdentification and Characterization of Novel, Small Molecule Inhibitors of Spermine Oxidase
Get PDFThe major intracellular polyamines spermine and spermidine are abundant endogenous compounds that are essential for cellular growth and development. Dysregulation of polyamine metabolism has been implicated as a key mechanism of injury across multiple forms of clinically challenging pathologies. Of the enzymes within the polyamine pathway, the catabolic enzyme spermine oxidase (SMOX) is of particular interest as it is subject to induction in response to infection, neuronal excitotoxicity, ischemia, and oxidative stress. In addition to the loss of radical scavenging capabilities associated with spermine depletion, catabolism of spermine by SMOX results in the production of toxic byproducts, including H2O2 and acrolein, a highly toxic aldehyde with the ability to form adducts with DNA and inactivate vital cellular proteins. Catabolism of spermine by SMOX has been identified as the most significant endogenous source of acrolein, highlighting the importance of this enzyme in acrolein-mediated cellular damage. Despite extensive evidence implicating SMOX as a key enzyme contributing to secondary injury associated with multiple pathologic states, the lack of potent and selective inhibitors has significantly impeded investigation of SMOX as a therapeutic target. In this study, we used a virtual and physical screening approach to identify and characterize a series of compounds with inhibitory activity against SMOX. Hit compounds underwent enzymatic characterization for potency, selectivity, and mechanism of inhibition. In addition, select compounds were assessed for the ability to alter cellular response. In this work we describe the identification of two unique structural scaffolds demonstrating selective inhibition of SMOX, representing the most potent competitive SMOX inhibitors reported to date. The majority of structural derivates that were characterized in this work maintained inhibitory activity for SMOX, despite minor structural variations, indicating the discovery of a fundamentally novel pharmacophore with the ability to tolerate further chemical modification in the development of targeted therapies suitable for in vivo studies and ultimately, to aid in the development of compounds suitable for clinical evaluation
Healthcare Key Performance Indicators; A DHA Study in Perception and Importance by Clinical and Non-Clinical Healthcare Professionals at a Large Healthcare System
Get PDFHealthcare systems in the United States are unique structures where compassion for the care of others meets the science of medicine. It is a business, but it is a business with passionate professionals who care about the health of its customers, or patients. While most businesses have one structured financial system, health care contains finance for both the business and the patient.
KPIs or Key Performance Indicators, reported by finance are usually created for revenue driven initiatives with little contact and communication with the clinical teams. KPIs are a prominent driver utilized by health systems and reimbursement agencies to measure efficiency and cost (hfma.org, 2023). They indicate the state of important measurements within the hospital (hfma.org, 2023). They measure the health of the facility through a series of patient-related and financial related targets (hfma.org, 2023). KPIs are considered best practice and are recognized at a national level (hfma.org, 2023). It is unclear which KPIs are perceived as most important to an organization, and if there is a difference between clinical leaders and financial leaders. The goal of this study is to review what is perceived as the most important KPIs and why by both clinical and financial leadership in a health organization.
A small nominal group survey study was performed, and the survey was sent to clinical physician and nurse leaders and non-clinical financial leaders who reviewed and selected KPIs that are the most important. Participants were asked their rankings and reasoning for those rankings. Participants were asked to choose their top 5 most important, then to rank the top 5 in level of importance with 5 being the most important.
The results indicate that the most important KPIs to both revenue cycle and operational leaders are similar and hold high values within the organization as they are directly related to revenue. Although treating patients is the most important aspect for all healthcare leaders, understanding the bottom line is a large contributor to an organization’s success. The participant group understands the metrics needed to maintain quality of care, employment, and critical ancillary needs for the hospital. The study results indicate the understanding of KPIs is equal among revenue cycle and operational leaders
Neural Correlates of Socially Rewarding Memories in Posttraumatic Stress Disorder
Get PDFSignificance. Memory disturbances for emotional content are central to PTSD, yet most research focuses on trauma memories. Recent evidence suggests that enhancing access to positive memories could improve mood, affect regulation, self-esteem, and integration of trauma memories. However, the neurocognitive mechanisms underlying positive memory encoding in PTSD are poorly understood. No study has examined memory for positive social items in PTSD, which is important because PTSD entails social withdrawal and reduced accessibility to positive memory. Additionally, positive memories embedded in a social context have enhanced subjective value and strengthening their accessibility may confer greater benefits to wellbeing compared to non-social positive memories. Approach. Adults with PTSD (N=14) and trauma-resilient control individuals (TRC, N=18) completed a social reward task during functional magnetic resonance imaging. In this task, participants received evaluations according to whether unfamiliar peers “expected to like” the participant if they met in real life. Evaluations received were either favorable or neutral (i.e., no rating). Post-scanning, participants completed an episodic memory exercise wherein they indicated who had rated them favorably or did not rate them at all. Contrasts between successfully encoded social conditions were examined at the voxel-level with psychophysiological interaction using the bilateral amygdala (AMY) as seeds and hippocampi (HIP) as primary ROIs. Post-hoc general linear models (GLMs) were conducted to probe moderation by diagnosis and symptom severity. Recognition performance was similarly assessed using GLMs considering diagnosis, valence, diagnosis x valence, and sex as a covariate. Findings. No recognition performance differences emerged between PTSD and TRC groups, and AMY-HIP connectivity differences were limited to the neutral condition. Whereas functional uncoupling occurred during neutral memory encoding for TRCs, AMY-HIP co-activation was observed in PTSD. Symptom severity did not explain variability in AMY-HIP connectivity within the PTSD sample. Conclusions. Although positive memories may have distinct phenomenological characteristics in PTSD samples, quantitative indices of performance for rewarding social memories are similar between PTSD and TRC individuals. Notwithstanding, individuals with PTSD may inappropriately activate emotional memory networks in neutral contexts, suggesting an overgeneralization of emotional processing. Thus, this study provides evidence of dysfunctional emotional memory processing in non-trauma, neutral situations within PTSD samples
Mental Fatigue and Self-Care in Informal Oncology Caregivers: A Descriptive Mixed Methods Study
Get PDFPurpose:
This dissertation study aimed to enhance understanding of informal caregiver wellbeing by exploring the presence of mental fatigue, the relationships among mental fatigue, self-care, and informal oncology caregiver quality of life (QOL), and determining whether differences exist in self-care engagement and QOL between caregivers who report high and low levels mental fatigue.
Problem:
Healthcare is becoming increasingly reliant on informal caregivers for the management and care of individuals with serious illnesses such as cancer. Previous research has shown that informal caregivers routinely experience many negative effects as a result of providing care including decreased mental health and QOL and increased mental fatigue. Due to the impact of mental fatigue on cognitive functioning, many caregivers rely on self-care activities to manage its effects however caregivers also report that mental fatigue interferes with their ability to engage in self-care. An inability to properly cope and recover from mental fatigue pose a direct threat to patient health outcomes and safety.
Aims:
Aim 1: Determine the prevalence of mental fatigue among a sample (N=204) of informal caregivers of individuals receiving cancer treatment in an outpatient oncology treatment center measured with the Mental Fatigue Scale (MFS).
Aim 2: Examine the relationship between mental fatigue, self-care, and caregiver quality of life in informal oncology caregivers measured with the MFS, Clinical Mindful Self-Care Scale (MSCS-C), and Caregiver Quality of Life Index-Cancer (CQOL-C).
Aim 3: Expand the understanding of mental fatigue’s impact on self-care and QOL through individual interviews of informal oncology caregivers with high (N=15) and low (N=15) levels of mental fatigue.
Exploratory Aim: Explore informal caregiver perceptions of caregiving, measured with the Appraisal of Caregiving Scale (ACS), and caregiver appraisal’s relationship to mental fatigue, self-care, and QOL.
Design:
This dissertation used a cross-sectional, convergent parallel, mixed methods design, guided by the Transactional Theory of Stress and Coping (TTSC).
Findings:
There were 66.8% participants who scored in the high mental fatigue group. T-tests revealed lower QOL and self-care engagement and higher threat appraisal in caregivers with high mental fatigue compared to those with low mental fatigue. MANOVA revealed a significant association of mental fatigue with self-care and QOL combined and multiple significant correlations were noted among mental fatigue, self-care, QOL, and appraisal of threat, stress and benefit. Four inductive themes (and subthemes) were identified among interviewed caregivers including: 1) caregiver perception of the experience (positive and negative), 2) lack of boundaries (identity, goals, and relationships), 3) resources (used and requested), and 4) self-care while caregiving (physical, mental, emotional, and other). Integration of quantitative and qualitative data revealed a previously unidentified, probable relationship between mental fatigue and reappraisal that impacts the caregiving experience.
Conclusions:
Mental fatigue is prevalent among informal oncology caregivers with the potential to negatively affect patient care and outcomes. We hypothesize that mental fatigue is both affected by and affects the reappraisal process and coping mechanisms used by caregivers. Longitudinal studies are needed to test for cause-effect relationships among mental-fatigue, self-care, and QOL but the associations noted in the results highlight specific areas to target when developing interventions to address caregiver stress and burden. Specifically, healthcare providers should focus their efforts on creating and providing effective caregiver resources while emphasizing the importance of maintaining boundaries and engaging in appropriate self-care activities
A Comparative Analysis of Births for Women Aged 20-25 Vs. 35-39: An Examination of Longitudinal Trends of Volume and Outcomes
Get PDFMaternal health impacts the well-being of society as it is commonly viewed as an indicator of public health welfare. Childbirth at an advanced maternal age (AMA) increases the likelihood of less favorable birth outcomes. As births to AMA women have increased over time, it is important to understand the impact age has on birth methods and birth outcomes. This research examined the proportion of births to women aged 20-25 years in comparison to AMA women aged 35-39 years in North Carolina from 2002-2017. The proportions of births to AMA women have increased over time despite increased risk and birth outcomes. An examination of longitudinal trends over 16 years showed more births to women aged 20-25 years, accounting for 73.6% of total births between the 2 age groups. AMA women showed a higher rate of cesarean sections, stillbirths, and longer length of stay following childbirth