MEDICA@MUSC (Medical University of South Carolina)
Not a member yet
1558 research outputs found
Sort by
The Impact of Patient By-pass Behavior on Rural Hospital Financial Health
Get PDFThe phenomenon of patients choosing distant, hospitals in lieu of local hospitals is known as bypass behavior. High rates of patient bypass of local hospitals mean a potential loss of revenue which could affect a hospitals financial health. My dissertation addresses the question of how patient bypass behavior impacts rural hospital financial health in three aims, using archival billing data. My dissertation expands on the existing literature in two ways 1) by evaluating the current measurement of bypass rate and 2) by evaluating the impact of bypass behavior on hospital financial indicators. The results for the patient-level and hospital-level determinates are consistent with the established literature. The exploratory analysis of the association between bypass behavior and hospital financial indicators is promising. Understanding rural patient bypass behavior and its effect on financial indicators is paramount if rural hospitals are to develop alternative responses to help them survive in the ever-evolving healthcare landscape
Accessing Calcified Teeth Using Dynamic Guidance System
Get PDFIntroduction: one of the most common challenging scenarios that a clinician faces on a regular basis is the treatment of a calcified tooth. Using CBCT to identify canals is becoming the standard of care and a tremendous help to clinicians. More recently, Dynamic guidance is becoming a popular among clinicians for dealing with challenging cases such as calcification. Objective: The aim of this study was to evaluate the accuracy of endodontic access of calcified anterior mandibular and maxillary teeth using dynamic guidance. Material and Method: 42 extracted calcified human mandibular and maxillary anterior teeth were selected. Rubber model former mold was used to mount the extracted teeth in the proper position to mimic the human jaw, and CBCT images were captured. Preoperative CBCT scans were transferred to the Dynamic Guidance system software for planning of endodontic access. To simulate a clinical scenario, the dentoforms were mounted to a manikin and placed on an operatory chair. Post-removal burs were used to gain access to the canal after calibration was completed. Once the proper depth was reached, the software prompted the operator to stop. The procedure was terminated at this point, regardless of the success of the operator to locate the canals or not. After completion, the access was evaluated by the passive placement of a #6 C file in the canal to ensure access/patency of the canal. A post-operative CBCT with and without the file in the access was taken. The teeth were then decoronated at the cementoenamel junction to remove any obstruction that would potentially deflect the file, and a file was placed in the canal and a CBCT was taken with the file. All images were assessed for access deviation and accuracy, followed by comparative statistics. Results: Of the 32 included in this study, 28 (87.5%) canals were successfully located. The angular deviation was calculated after superimposing the pre-op CBCT over the post-op CBCT by measuring the angle between the file and the natural path of the physical canal. The average angular deviation was 4.69 degrees, the average platform buccolingual deviation was 0.38 mm, the average platform mesiodistal direction was 0.23 mm, the average of non-depth deviation (deviation in any direction other than apico-coronally) was 0.99 mm, and the average of apical non-depth deviation at the apical extent of the file trajectory was 0.70 mm Conclusion: Calcified canals were located by an inexperienced operator in 87.5% of the time with an angular deviation of 4.69 degrees which confirms that dynamic guide syste
The Effect of Advanced Glycation End Products (AGEs) on Macrophages, and their Implications for Prostate Cancer Progression
Get PDFAdvanced glycation end products (AGEs) are sugar-protein adducts that may worsen cancer severity and may contribute to health disparity outcomes among prostate cancer (PCa) patients. AGEs are formed endogenously via a slow, nonenzymic reaction; however, AGEs are also formed in foods as a result of subjecting meats and sugars to high-heat conditions. AGEs are therefore prolific in the Western Pattern Diet (WPD), which has become increasingly common among industrialized nations. Previous work has identified dietary AGE as contributing to MYC-driven PCa progression, and the dependence of this process upon stromal receptor for advanced glycation end products (RAGE). This study therefore examines the changes in function and expression in macrophages -a key stromal population- in relation to this phenomenon. First, it was observed, via immunohistochemistry, that dietary AGE in a MyC-CaP xenograft model altered macrophage tumor infiltration, but not total population. Primary macrophages were isolated from wildtype and RAGE KO mice fed regular diets, and, along with RAW264.7 immortalized macrophage cell line, were subjected to BSA-AGE treatments in vitro. Evaluation of these cell populations found that AGE treatment increased MYC expression at the translational level and, to some degree, the transcriptional level. AGE treatment also increased RAGE protein expression in the immortalized RAW264.7 cells, but in all other cases remained unchanged. Macrophage polarization in response to AGE treatment was probed using qPCR, and using the markers TNF-α, IL-10, iNOS, and Arg1, it was determined that AGE treatment promoted a shift towards the classically activated M1 phenotype, which is typically characterized as being pro-inflammatory and addressing infectious disease. This relates to the nonpathogenic function of RAGE, which is a pattern recognition receptor (PRR) used for the early detection and response to local pathogens and suggests that AGEs pervert this antipathogenic process to the benefit of PCa progression
Measuring the Impact of the Affordable Care Act Medicaid Expansion on Access to Primary Care Utilizing Preventable Hospitalizations: An Interrupted Time Series
No full texthttps://medica-musc.researchcommons.org/posters/1026/thumbnail.jp
Education and Safety for Children with Autism to Prevent Elopement (E.S.C.A.P.E.) Kits
No full textPer a study published in 2019, two-thirds of patients with autism seen by the Division of Developmental-Behavioral Pediatrics (DBP) at MUSC engaged in elopement behavior, a potentially life-threatening behavior also known as wandering, that can lead to serious injury or death. E.S.C.A.P.E. kits were created by Dr. Pereira and the MUSC DBP autism research team in 2017 to help prevent elopement. Original kits included a door/window alarm, child ID kit, stop sign visual aids, ID bracelet, and printed materials with additional prevention tips. Initial survey data showed that 17 of 22 caregivers who completed surveys after receiving a kit reported decreased elopement behavior by their child since using the kit; 5 of the 17 listed elopement rates as none. Almost all caregivers found the alarm to be useful, but the other items less so. Feedback from these surveys inspired the desire to create an expanded version of E.S.C.A.P.E. kits that could include more items to offer additional layers of valuable protection against elopement behavior, as well as obtain additional data for statistical analysis since the efficacy of elopement prevention kits have not yet been reported in the literature
Altered Circadian Rhythm and Neuroinflammation in Models of ALS: A Role for NR1D1 and FABP7
No full textMost physiological processes in mammals are subjected to daily oscillations governed by a circadian system. Circadian rhythm orchestrates metabolic pathways in a time-dependent manner and loss of circadian timekeeping has been associated with cellular and system-wide alterations in metabolism, redox homeostasis, and inflammation. Nuclear Receptor subfamily 1 group D member 1 (NR1D1) is a transcription factor that participates in the molecular clock that encodes circadian rhythms and links metabolism and inflammation to circadian cycles. Fatty acid binding protein 7 (FABP7), an NR1D1 target, is a regulator of lipid metabolism, energy homeostasis, and inflammation. FABP7 can regulate fatty acid uptake, transport, and availability to nuclear receptors. In the adult brain, FABP7 is especially abundant in astrocytes that haven cytoplasmic granules originated from damaged mitochondria. Mitochondrial dysfunction and altered metabolism have been implicated in amyotrophic lateral sclerosis (ALS), either as a primary cause or as a secondary component of the pathogenic process. We investigated clock and clock-controlled genes in multiple tissues from transgenic mice expressing a mutant superoxide dismutase 1(SOD1)-linked to ALS. We identified tissue-specific changes in the relative expression as well as altered daily expression patterns of clock genes, sirtuins, metabolic enzymes, and redox regulators. We discovered NR1D1 is downregulated and FABP7 is upregulated in the spinal cord of symptomatic mutant hSOD1-expressing mice. Decreasing NR1D1 or increasing FABP7expression in primary non-transgenic astrocytes resulted in a pro-inflammatory profile and decreased neuronal survival when co-cultured with motor neurons. Moreover, astrocytes isolated from symptomatic hSOD1-expressing mice displayed endogenous up-regulation of FABP7 and silencing of FABP7 in these cultures decreased inflammatory markers and toxicity towards co-cultured motor neurons. At an organism level, our results suggest the possibility of disrupted peripheral clock synchronization in hSOD1G93A mice, while at a cellular level we demonstrate that NR1D1 and FABP7 markedly alter the biology of astrocytes and the way these cells interact with neurons. Since metabolism and redox homeostasis are intimately entangled with circadian rhythms, our data suggest that altered expression of clock genes may contribute to metabolic and redox impairment in ALS and we identify NR1D1 and FABP7 as potential therapeutic targets to prevent astrocyte-mediated motor neuron toxicity in ALS
Functional Relevance of Renal Histamine Receptors in the Kidney
No full textThe immunology of kidney disease is complex and involves factors from both the innate and the adaptive immune systems. Histamine is an important immunomodulator, as well as a regulator of allergic inflammation, gastric acid secretion, and neurotransmission. Although an increase in histamine level and expression of histamine-metabolizing enzymes have been shown in the kidney, renal pathological and physiological effects of histamine have not been clearly defined. The goal of this study was to provide insight into the physiological importance of the histamine-related pathways in the kidney, with emphasis on the collecting duct (CD), a distal part of the nephron important for the regulation of blood pressure. To address the goal of the project, we first tested histamine receptors’ (HRs) expression in the CD cells; all 4 receptors were found to be expressed in the cultured CD cells, as well as in the rat kidney. Next, we showed that histamine evokes a dose-dependent transient increase in intracellular calcium in CD cells. In addition, we observed a dose-dependent increase in cAMP in the CD cells in response to histamine. In short-circuit current studies aimed at measuring sodium reabsorption via the ENaC (epithelial sodium channel expressed in the CD), we observed an inhibition of ENaC-mediated currents by histamine. This was corroborated in immunocytochemistry and qPCR, which showed a decrease in protein and gene expression for the alpha subunit of ENaC upon histamine treatment. To test the functional importance of HRs in kidney physiology and pathophysiology, we used Dahl SS rats, an established model of salt-sensitive hypertension (SSH), which is accompanied with inflammation-driven kidney damage. Ranitidine, an inhibitor of HR2, was administered to these rats, and in vivo studies showed that blocking of this receptor affects renal electrolyte excretion, urine production and water consumption. To sum up, our data highlight the functional importance of HRs in the kidney, and suggest potential implications of histamine in inflammation-related renal diseases, such as SSH. More in-depth research is required to discern the downstream molecular pathways, and assess the role of specific receptors in renal pathophysiology
Evaluation of the Statistical Properties of Minimal Sufficient Balance as a Method for Controlling Baseline Covariate Imbalance for Sequential Clinical Trials with a Binary Endpoint
No full textWhen there is a large number of baseline covariates whose imbalance needs to be controlled in sequential randomized controlled trials, minimization is most commonly used for randomizing treatment assignments. The lack of allocation randomness associated with the minimization method has been the source of controversy. The minimal sufficient balance (MSB) method is an alternative to minimization. It prevents serious imbalance from a large number of covariates while maintaining high levels of allocation randomness. However, a formal comparison between covariate-adaptive methods of randomization has not yet been studied. Using a re-randomization of the rt-PA clinical trial dataset with 1:1 equal allocation, minimization and MSB methods are compared with respect to allocation randomness, effectiveness at balancing covariates across treatment arms, and preservation of the nominal type I error rate. Using a simulated dataset, power and bias in the estimation of treatment effect are studied for completely randomized design, stratified permuted blocks, minimization, and MSB. A novel randomization method, known as allocation ratio preserving Minimal Sufficient Balance (ARP MSB) is presented as an alternative to allocation ratio preserving biased coin minimization (ARP BCM). Using a re-randomization of the rt-PA clinical trial dataset, ARP BCM and ARP MSB are compared with respect to the allocation randomness, effectiveness at balancing covariates across treatment arms, and preservation of the nominal type I error rate in unequal allocation clinical trials. MSB and ARP MSB methods proved to have equal or superior effectiveness at controlling imbalance on a combination of continuous and categorical variables, as well as a far greater proportion of completely random treatment assignments compared to the minimization and ARP BCM methods. MSB, ARP MSB, minimization, and ARP BCM all proved to have similar properties with respect to type I error rate preservation, power, and bias in measuring treatment effects. MSB and ARP MSB, while not presented as optimal methods for controlling covariate imbalances in sequential clinical trials, provide an alternative to the minimization and ARP BCM methods. The arguments in this dissertation should be considered by those who wish to use minimization or ARP BCM for subject allocation in clinical trials
Does Psychosocial Functioning Improve with Prolonged Exposure in Veterans with PTSD? Exploring Traditional and Home-Based Telehealth Delivery Methods
Get PDFPurpose: This dissertation compendium includes an integrative literature review, an evolutionary concept analysis, and findings from a secondary data analysis. The literature review explores the effects of evidence-based interventions on psychosocial functioning in veterans with combat-related Post Traumatic Stress Disorder (PTSD). The concept analysis examines psychosocial functioning comprehensively to develop a clear understanding of this concept and its relationship to veterans with combat-related PTSD. The secondary analysis study compares the impact of Prolonged Exposure (PE) on psychosocial functioning outcomes in two groups: PTSD diagnosed, treatment seeking combat veterans who receive PE in-person compared to those receiving PE via homebased telehealth. Additional aims in that study were as follows: determine whether race, type of war conflict and service connection disability rating (SC%) moderate and whether PTSD, anxiety, and depression mediate the effect of PE on psychosocial functioning.
Problem: PTSD is linked to maladaptive or impaired psychosocial functioning, including functioning in the following domains: romantic relationships with spouse or partner, family, work, friendships, parenting, and education. Many combat veterans are unemployed, are divorced, or express dissatisfaction with their interpersonal relationships. Some research has demonstrated that treating PTSD symptoms can improve psychosocial functioning as well, yet the focus of PTSD treatment remains primarily on PTSD symptomology itself. Veterans with combat-related PTSD are being treated via telehealth modality at higher rates; however, this modality may contribute to isolation and, in turn, result in poor outcomes in functioning.
Aims: To evaluate treatment and delivery methods for improving psychosocial functioning in veterans with combat-related PTSD. We completed the following studies: first, an integrative review evaluated evidence-based therapies (EBT) and their treatment effects on psychological functioning. Second, an evolutionary concept analysis examined the phenomenon of psychosocial functioning in this population. Finally, a secondary analysis investigated whether PE was associated with improvement in psychosocial functioning, and whether the telehealth treatment modality may be an acceptable alternative to in-person treatment modality.
Design: Whittemore and Knafl’s (2005) framework informed the integrative review, while Rodger’s (2000) framework guided the evolutionary concept analysis. Using a correlational design for the secondary analysis, we investigated relationships between PE treatment delivery methods and potential reduction in psychosocial functioning symptoms. The socio-interpersonal framework of PTSD was used throughout the dissertation, guiding the conceptualization and analysis of psychosocial functioning in relation to veterans with combat-related PTSD.
Findings: The integrative review produced several important results. We found that literature in this area is limited and more research is warranted. We concluded that treating avoidance and numbing can improve functioning; furthermore, treating veterans until they no longer qualify for a PTSD diagnosis can be beneficial in functional improvement. However, the terminology and assessment tools used to assess x psychosocial functioning lacked consistency and therefore may produce confusion for treating providers.
The evolutionary concept analysis identified combat exposure as well as PTSD symptoms such as emotional numbing and withdrawal as main antecedents. Psychosocial functioning environments/domain and psychosocial functioning status were the leading attributes associated with this concept. Social support emerged as an influencing factor in alleviating PTSD symptoms, thus improving functioning. Discussion in the literature mainly focused on functioning in the romantic partnership domain, and further research is necessary to address functioning in other important domains.
The results from the secondary analysis illustrate that race, type of war conflict, and SC% did not moderate the effect of PE on psychosocial functioning. Likewise, PTSD, depression, and anxiety did not mediate the effects of PE on psychosocial functioning. However, we observed a positive correlation between depression, PTSD, and anxiety mean scores in relation to psychosocial functioning mean scores. This finding demonstrates that as depression, PTSD, and anxiety improved, so did psychosocial functioning.
The parent study’s main purpose was to investigate PTSD outcomes with a noninferiority design, the current study used a standard superiority design, therefore a conclusion of no difference between the modalities cannot be drawn at this time. The findings do provide an indication and preliminary evidence that both treatment delivery methods may be acceptable options related to psychosocial functioning outcomes. Similarly, it is too soon to formulate conclusions on the effects of PE on psychosocial functioning based on our results. Although some improvement post-treatment was xi evident, most results were not statistically significant, and mean scores mostly remained in the same functional impairment category. Nevertheless, we remain encouraged based on some promising findings that were identified. Notably, the family domain showed possible clinically significant improvement across treatment groups, and in the homebased telehealth group, the parenting domain results had a similar pattern. Moreover, the family domain in home-based telehealth group had statistically significant improvement as well.
Conclusion: Veterans with combat-related PTSD struggle in various social environments. Impairment in work, romantic partnerships, parenting, and education domains are debilitating consequences for veterans with combat-related PTSD. Although the overall results of this dissertation indicate that some evidence-based therapies (EBTs) may improve psychosocial functioning, and both modalities may be used, more research is warranted to confirm those promising preliminary findings. In conclusion, psychosocial functioning is a multidimensional concept that may affect the quality of life of veterans with combat-related PTSD, thus requiring more attention in the scientific community
Ciliogenesis and Cilia-Mediated Signaling in Cardiac Valve Development and Disease
Get PDFMitral valve prolapse (MVP) and bicuspid aortic valve (BAV) are serious heart conditions that affect a combined 3-4% of the world population. These diseases carry high risk for secondary complications including arrhythmia, blood regurgitation, and sudden cardiac death. Often, valve diseases are heritable and have complex origins that are not fully understood. The lack of knowledge about valve disease causation likely contributes to the absence of non-surgical treatment options for this patient population. Recent work by our lab and others has demonstrated a link between defects in primary cilia and the development of heart valve disease in humans. Primary cilia are singular, non-motile, microtubule-derived, signaling organelles that are ubiquitous to most cell types. In cardiac valves, they are spatially and temporally regulated, appearing primarily on interstitial cells during valvulogenesis. This dissertation presents evidence that ciliogenesis in the valves is dependent on a highly conserved octameric protein trafficking complex known as the exocyst. We demonstrate that defects in exocyst trafficking result in shorter, less prevalent cilia, the development of bicuspid aortic valves and myxomatous mitral valves in mice, and arterial stenosis in zebrafish. We also uncovered links between ciliome variants and BAV in humans through GWAS analysis. Additionally, we present findings that establish Desert Hedgehog (DHH) signaling as a necessary ciliary signaling pathway in valvulogenesis. Through morphometric analysis of murine mitral valves and biochemical in vitro studies with embryonic chicken valve cells, we describe a novel paracrine crosstalk mechanism emanating from the DHH expressing endocardium that influences the production of alpha smooth muscle actin (a-SMA) by the ciliated valve interstitial cells to promote valve remodeling. This newly generated hypothesis will guide future studies and may provide mechanistic insights of ciliopathies in other tissues. This project led to a new understanding of valve development and highlights the importance of the exocyst, primary cilia, and Desert Hedgehog signaling in valve morphogenesis. Genetic defects in any portion of this system result in faulty valve architecture and disease progression. Insights from this work will inform future discoveries into disease origins and progression and potentially lead to the identification of therapeutic targets for cardiac valve diseases