Medical University of South Carolina

About: Medical University of South Carolina is a education organization based out in Charleston, South Carolina, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 23436 authors who have published 45440 publications receiving 1769397 citations. The organization is also known as: MUSC & Medical College of the State of South Carolina.

Neuropsychological Findings in Childhood Neglect and their Relationships to Pediatric PTSD

Abstract: Although child neglect is the most prevalent form of child maltreatment, the neurocognitive effects of neglect are understudied. We examined IQ, reading, mathematics, and neurocognitive domains of fine-motor skills, language, visual-spatial, memory/learning, and attention/executive functions in two groups of nonsexually abused medically healthy neglected children, one with DSM-IV posttraumatic stress disorder (PTSD) and one without, and a demographically similar healthy nonmaltreated control group. Significantly lower IQ, reading, mathematics, and selected differences in complex visual attention, visual memory, language, verbal memory and learning, planning, problem solving, and speeded naming were seen in Neglect Groups. The Neglect with PTSD Group performed worse than controls on NEPSY Design Copying, NEPSY Tower, and Mathematics; and performed worse than controls and Neglect without PTSD on NEPSY Memory for Faces-Delayed. Negative correlations were seen between PTSD symptoms, PTSD severity, and maltreatment variables, and IQ, Academic Achievement, and neurocognitive domains. Neglected children demonstrated significantly lower neurocognitive outcomes and academic achievement than controls. Lower IQ, neurocognitive functions, and achievement may be associated with more PTSD symptoms (particularly re-experiencing symptoms), greater PTSD severity, and a greater number of maltreatment experiences. Trauma experiences may additionally contribute to subsequent neurodevelopmental risk in neglected children. (JINS, 2009, 15, 868-878.).

A phase II trial of AS1411 (a novel nucleolin-targeted DNA aptamer) in metastatic renal cell carcinoma.

Abstract: Background DNA aptamers represent a novel strategy in anti-cancer medicine. AS1411, a DNA aptamer targeting nucleolin (a protein which is overexpressed in many tumor types), was evaluated in patients with metastatic, clear-cell, renal cell carcinoma (RCC) who had failed treatment with ≥1 prior tyrosine kinase inhibitor. Methods In this phase II, single-arm study, AS1411 was administered at 40 mg/kg/day by continuous intravenous infusion on days 1–4 of a 28-day cycle, for two cycles. Primary endpoint was overall response rate; progression-free survival (PFS) and safety were secondary endpoints. Results 35 patients were enrolled and treated. One patient (2.9 %) had a response to treatment. The response was dramatic (84 % reduction in tumor burden by RECIST 1.0 criteria) and durable (patient remains free of progression 2 years after completing therapy). Whole exome sequencing of this patient’s tumor revealed missense mutations in the mTOR and FGFR2 genes which is of interest because nucleolin is known to upregulate mTOR pathway activity by enhancing AKT1 mRNA translation. No other responses were seen. Thirty-four percent of patients had an AS1411-related adverse event, all of which were mild or moderate. Conclusions AS1411 appears to have minimal activity in unselected patients with metastatic RCC. However, rare, dramatic and durable responses can be observed and toxicity is low. One patient in this study had an excellent response and was found to have FGFR2 and mTOR mutations which will be of interest in future efforts to discover and validate predictive biomarkers of response to nucleolin targeted compounds. DNA aptamers represent a novel way to target cancer cells at a molecular level and continue to be developed with a view to improving treatment and imaging in cancer medicine.

Developing Therapies for Heart Failure With Preserved Ejection Fraction: Current State and Future Directions

Abstract: The burden of heart failure with preserved ejection fraction (HFpEF) is considerable and is projected to worsen. To date, there are no approved therapies available for reducing mortality or hospitalizations for these patients. The pathophysiology of HFpEF is complex and includes alterations in cardiac structure and function, systemic and pulmonary vascular abnormalities, end-organ involvement, and comorbidities. There remain major gaps in our understanding of HFpEF pathophysiology. To facilitate a discussion of how to proceed effectively in future with development of therapies for HFpEF, a meeting was facilitated by the Food and Drug Administration and included representatives from academia, industry, and regulatory agencies. This document summarizes the proceedings from this meeting.

The relationship between ventricular electrical delay and left ventricular remodelling with cardiac resynchronization therapy

Abstract: Aims The aim of the present study was to evaluate the relationship between left ventricular (LV) electrical delay, as measured by the QLV interval, and outcomes in a prospectively designed substudy of the SMART-AV Trial. Methods and results This was a multicentre study of patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT) defibrillator implantation. In 426 subjects, QLV was measured as the interval from the onset of the QRS from the surface ECG to the first large peak of the LV electrogram. Left ventricular volumes were measured by echocardiography at baseline and after 6 months of CRT by a blinded core laboratory. Quality of life (QOL) was assessed by a standardized questionnaire. When separated by quartiles based on QLV duration, reverse remodelling response rates (>15% reduction in LV end systolic volume) increased progressively from 38.7 to 68.4% and QOL response rate (>10 points reduction) increased from 50 to 72%. Patients in the highest quartile of QLV had a 3.21-fold increase (1.58–6.50, P = 0.001) in their odds of a reverse remodelling response after correcting for QRS duration, bundle branch block type, and clinical characteristics by multivariate logistic regression analysis. Conclusion Electrical dyssynchrony, as measured by QLV, was strongly and independently associated with reverse remodelling and QOL with CRT. Acute measurements of QLV may be useful to guide LV lead placement.