Everolimus-eluting stents, as compared with paclitaxel-eluting stents, resulted in reduced rates of target-lesion failure at 1 year, results that were consistent in all patients except those with diabetes, in whom the results were nonsignificantly different. (ClinicalTrials.gov number, NCT00307047.)

Taken together, these results indicate that in the conscious rabbit, the infarct-sparing effect of the late phase of ischemic PC is mediated by the activity of NOS and suggest that the specific isoform primarily responsible for this cardioprotective phenomenon is iNOS. Thus, NO appears to be a pivotal component of the pathophysiological cascade of late PC.

Brief ischemic episodes confer marked protection against myocardial stunning 1-3 d later (late preconditioning [PC] against stunning). The mechanism of this powerful protective effect is poorly understood. Although protein kinase C (PKC) has been implicated in PC against infarction, it is unknown whether it triggers late PC against stunning. In addition, the entire PKC hypothesis of ischemic PC remains controversial, possibly because the effects of PKC inhibitors on PC protection have not been correlated with their effects on PKC activity and/or translocation in vivo. Thus, conscious rabbits underwent a sequence of six 4-min coronary occlusion (O)/4-min reperfusion (R) cycles for three consecutive days (days 1, 2, and 3). In the control group (group I, n ϭ 7), the recovery of systolic wall thickening after the six O/R cycles was markedly improved on days 2 and 3 compared with day 1, indicating the development of late PC against stunning. Administration of the PKC inhibitor chelerythrine at a dose of 5 mg/kg before the first O on day 1 (group II, n ϭ 10) abrogated the late PC effect against stunning, whereas a 10-fold lower dose (0.5 mg/kg; group III, n ϭ 7) did not. Administration of 5 mg/kg of chelerythrine 10 min after the sixth reperfusion on day 1 (group IV, n ϭ 6) failed to block late PC against stunning. When rabbits were given 5 mg/kg of chelerythrine in the absence of O/R (group V, n ϭ 5), the severity of myocardial stunning 24 h later was not modified. Pretreatment with phorbol 12-myristate 13-acetate (4 g/kg) on day 1 without ischemia (group VI, n ϭ 11) induced late PC against stunning on day 2 and the magnitude of this effect was equivalent to that observed after ischemic PC. In vehicle-treated rabbits (group VIII, n ϭ 5), the six O/R cycles caused translocation of PKC isoforms ⑀ and from the cytosolic to the particulate fraction without significant changes in total PKC activity, in the subcellular distribution of total PKC activity, or in the subcellular distribution of the ␣ , ␤ 1 , ␤ 2 , ␥ , ␦ , , , , and isoforms. The higher dose of chelerythrine (5 mg/kg; group X, n ϭ 5) prevented the translocation of both PKC ⑀ and induced by ischemic PC, whereas the lower dose (0.5 mg/kg; group XI, n ϭ 5) prevented the translocation of PKC but not that of ⑀ , indicating that the activation of ⑀ is necessary for late PC to occur whereas that of is not. To our knowledge, this is the first demonstration that a PKC inhibitor actually prevents the translocation of PKC induced by ischemic PC in vivo, and that this inhibition of PKC translocation results in loss of PC protection. Taken together, the results demonstrate that the mechanism of late PC against myocardial stunning in conscious rabbits involves a PKCmediated signaling pathway, and implicate ⑀ as the specific PKC isoform responsible for the development of this cardioprotective phenomenon.

Interest in ultrasound education in medical schools has increased dramatically in recent years as reflected in a marked increase in publications on the topic and growing attendance at international meetings on ultrasound education. In 2006, the University of South Carolina School of Medicine introduced an integrated ultrasound curriculum (iUSC) across all years of medical school. That curriculum has evolved significantly over the 9 years. A review of the curriculum is presented, including curricular content, methods of delivery of the content, student assessment, and program assessment. Lessons learned in implementing and expanding an integrated ultrasound curriculum are also presented as are thoughts on future directions of undergraduate ultrasound education. Ultrasound has proven to be a valuable active learning tool that can serve as a platform for integrating the medical student curriculum across many disciplines and clinical settings. It is also well-suited for a competency-based model of medical education. Students learn ultrasound well and have embraced it as an important component of their education and future practice of medicine. An international consensus conference on ultrasound education is recommended to help define the essential elements of ultrasound education globally to ensure ultrasound is taught and ultimately practiced to its full potential. Ultrasound has the potential to fundamentally change how we teach and practice medicine to the benefit of learners and patients across the globe.Electronic supplementary materialThe online version of this article (doi:10.1186/s13089-015-0035-3) contains supplementary material, which is available to authorized users.

We tested the hypothesis that late preconditioning (PC) against myocardial infarction is triggered by the formation of nitric oxide (NO). Conscious rabbits underwent a 30-min coronary occlusion followed by 3 days of reperfusion. In group I (control group, n = 10), rabbits were not preconditioned, whereas in group II( n = 10), they were preconditioned 24 h earlier with a sequence of six 4-min occlusion/4-min reperfusion cycles. Myocardial infarct size (tetrazolium staining) was reduced by 50% by PC (28.6 ± 3.2% of the risk region in group II vs. 56.9 ± 5.9% in controls, P < 0.05). This reduction in cell death was associated with improved recovery of myocardial function [systolic thickening fraction (by sonomicrometry) at 3 days: 2.0 ± 11.0% of baseline in group II vs. −20.0 ± 2.8% in group I, P < 0.05]. Group III rabbits ( n = 11) underwent the same protocol as group II except that the rabbits received the NO synthase inhibitor N ω-nitro-l-arginine (l-NNA, 13 mg/kg) before the PC ischemia. In these animals, infarct size did not differ significantly from that observed in control rabbits, indicating thatl-NNA completely blocked the development of late PC against myocardial infarction. In group IV( n = 9), rabbits receivedl-NNA as in group III, but without the six occlusion-reperfusion cycles, and were subjected to the 30-min occlusion 24 h later. In this group, infarct size did not differ from that observed in controls, demonstrating that pretreatment withl-NNA, in itself, did not affect the extent of cell death. Taken together, these results indicate that, in the conscious rabbit, the development of late PC against myocardial infarction is triggered by the generation of NO during the PC ischemia. It is proposed that NO plays a key role in the delayed myocardial adaptation to ischemic stress.