Effects of comprehensive educational reforms on academic success in a diverse student body.

CONTEXT: Calls for medical curriculum reform and increased student diversity in the USA have seen mixed success: performance outcomes following curriculum revisions have been inconsistent and national matriculation of under-represented minority (URM) students has not met aspirations. Published innovations in curricula, academic support and pipeline programmes usually describe isolated interventions that fail to affect curriculum-level outcomes. METHODS: United States Medical Licensing Examination (USMLE) Step 1 performance and graduation rates were analysed for three classes of medical students before (matriculated 1995-1997, n=517) and after (matriculated 2003-2005, n=597) implementing broad-based reforms in our education system. The changes in pipeline recruitment and preparation programmes, instructional methods, assessment systems, academic support and board preparation were based on sound educational principles and best practices. RESULTS: Post-reform classes were diverse with respect to ethnicity (25.8% URM students), gender (51.8% female), and Medical College Admissions Test (MCAT) score (range 20-40; 24.1% scored ≤ 25). Mean±standard deviation MCAT scores were minimally changed (from 27.2±4.7 to 27.8±3.6). The Step 1 failure rate decreased by 69.3% and mean score increased by 14.0 points (effect size: d=0.67) overall. Improvements were greater among women (failure rate decreased by 78.9%, mean score increased by 15.6 points; d=0.76) and URM students (failure rate decreased by 76.5%, mean score increased by 14.6 points; d=0.74), especially African-American students (failure rate decreased by 93.6%, mean score increased by 20.8 points; d=1.12). Step 1 scores increased across the entire MCAT range. Four- and 5-year graduation rates increased by 7.1% and 5.8%, respectively. CONCLUSIONS: The effect sizes in these performance improvements surpassed those previously reported for isolated interventions in curriculum and student support. This success is likely to have resulted from the broad-based, mutually reinforcing nature of reforms in multiple components of the education system. The results suggest that a narrow reductionist view of educational programme reform is less likely to result in improved educational outcomes than a system perspective that addresses the coordinated functioning of multiple aspects of the academic enterprise.

Cardiac preconditioning with local laser-induced hyperthermia.

BACKGROUND: Whole body hyperthermia has been shown to be highly effective in preconditioning cardiac tissue against reperfusion injury. The current study was aimed to assess the ability of regional sublethal laser-induced hyperthermia to precondition cardiac tissue against ischemic-induced myocardial infarction. METHODS AND RESULTS: Diode laser radiation was used to locally heat (42 degrees C) the left ventricle by irradiating the epicardial surface of rat heart for 20 min. As control, another group of animals were treated with whole-body hyperthermia (WBH) for 20 min. After a 4-h recovery period, the left coronary artery was occluded for 30 min followed by 4 h of reperfusion. A significant degree of reduction in infarct size as assessed by percent of at-risk area was observed in animals that were subjected to laser-induced local hyperthermia (15.4 +/- 3.1; n = 5) versus the sham group (49.8 +/- 6.6; n = 5). The degree of cardiac protection induced by local hyperthermia was similar to the protection observed when the animals were preconditioned with WBH. Furthermore, regional laser-induced hyperthermia and WBH induced similar degree of up-regulation of heat shock protein 70 in cardiac tissue. Regional hyperthermia up-regulated heat shock protein in regions of the heart beyond that directly subjected to laser-induced heat stress. CONCLUSION: Sublethal local heating of the heart with diode laser irradiation can improve myocardial salvage and may provide a practical approach for tissue preconditioning against reperfusion injury.

Whole-body hyperthermia induces up-regulation of vascular endothelial growth factor accompanied by neovascularization in cardiac tissue.

Whole-body hyperthermia (WBH) promotes cardiac protection against ischemia/reperfusion injury, in part by up-regulation of heat shock proteins (HSP). Whether heat stress also promotes up-regulation of angiogenic factors or induces endothelial cell proliferation is unknown. We studied the effects of heat stress on up-regulation of vascular endothelial growth factor (VEGF) and growth of new blood vessels following WBH. Anesthetized rats were subjected to WBH at 42 degrees C for 15 min. The control (n=23) and heated (n=55) groups were allowed to recover for 4, 12, 24, 48, or 72 h prior to harvesting the heart for Western Blot and immunohistochemical assessment of VEGF, HSP70, and platelet endothelial cell adhesion molecular-1 (PECAM-1). A significant increase in VEGF and HSP70 expression was observed as early as 4 h post-heating. The Western Blot analysis revealed a close temporal correlation between up-regulation of HSP70 and VEGF. Maximum VEGF and HSP70 expression occurred at 12 and 24 h post-heating in the left and right ventricles, respectively. The right ventricle showed the greatest expression of both VEGF and HSP70. Immunostaining revealed that VEGF was focally increased in the endothelial cells of capillaries, small arteries, and in interstitium. At 48 and 72 h post-heating, multiple areas of extensive capillary proliferation occurred in the epicardial region of the right ventricle. These observations were verified by quantitative analysis of the density of blood vessels as determined by PECAM-1 staining. Our experiments show that sublethal heat stress can lead to upregulation of both VEGF and HSP70 in cardiac tissue and promote focal endothelial proliferation in the heart.

Sepsis-induced failure of hepatic energy metabolism.

HYPOTHESIS: Recent evidence suggests that sepsis may induce an uncoupling of oxidative phosphorylation. The purpose of this study was to quantify temporal changes in hepatic oxygen consumption and cellular energy state with increasing severity of sepsis and thus assess the interrelationship of these parameters as either primary defect or compensatory response. MAIN OUTCOME MEASURES: Pseudomonas aeruginosa was infused intravenously in eight instrumented anesthetized swine inducing a progressive severity of sepsis to shock. Eight other animals served as instrumented controls. Hepatic blood flow, oxygen use, and concentrations of ATP, ADP, AMP, NAD(+), and NADH were measured at baseline and then sequentially during the study. RESULTS: Except for an increase in heart rate, there were no temporal changes in measured values for the control animals. For swine receiving P. aeruginosa, hepatic oxygen delivery and consumption increased with early sepsis whereas there were no alterations in the concentrations of adenine nucleotides or NAD(+)/NADH within liver. Septic shock was notable for a decrease in oxygen delivery yet oxygen consumption remained elevated because of an increase in percent oxygen extraction. The hepatic concentrations of ATP and NADH decreased during septic shock. CONCLUSIONS: These findings suggest that any sepsis-induced limitation in phosphorylation may be initially compensated by an increase in oxygen use. This study also suggests that decreases in NADH availability may be a principal factor in the decompensation of sepsis to shock.

Postischemic recovery of contractile function is impaired in SOD2(+/-) but not SOD1(+/-) mouse hearts.

BACKGROUND: Reactive oxygen species (ROS) contribute to myocardial stunning. Superoxide dismutase (SOD) is a major defense mechanism against ROS. The purpose of this study was to evaluate the contributions of cytosolic (SOD1) and mitochondrial (SOD2) isoforms to protect against myocardial stunning. METHODS AND RESULTS: Isolated hearts from wild-type, heterozygous (+/-) SOD1 and SOD2 knockout mice received 30 minutes of ischemia followed by 60 minutes of reperfusion. After 60 minutes of reperfusion, the heart rate multiplied by the developed pressure (HRxDP) in the wild-type and SOD1(+/-) hearts recovered to 92 +/- 9 and 85 +/- 7 of preischemic baseline values, respectively (P=NS). In contrast, the HRxDP was significantly lower (63 +/- 7%) in the SOD2(+/-) hearts compared with the wild-type hearts. Western blot analysis and enzymatic activity of tissue lysates confirmed reduction of activities of specific SOD isoforms without compensatory increase in the other isoform in the knockout animals studied. CONCLUSIONS: Postischemic functional recovery is more sensitive to a partial deficiency of SOD2 than a partial deficiency of SOD1. Therefore, modulation of the mitochondrial SOD isoform is a critical determinant in the tolerance of the heart to oxidative stress.