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The signaling mechanisms by which skeletal muscle electrical activity leads to changes in gene expression remain largely undefined. We have reported that myotube depolarization induces calcium signals in the cytosol and nucleus via inositol 1,4,5-trisphosphate (IP(3)) and phosphorylation of both ERK1/2 and cAMP-response element-binding protein (CREB). We now describe the calcium dependence of P-CREB and P-ERK induction and of the increases in mRNA of the early genes c-fos, c-jun, and egr-1. Increased phosphorylation and early gene activation were maintained in the absence of extracellular calcium, while the increase in intracellular calcium induced by caffeine could mimic the depolarization stimulus. Depolarization performed either in the presence of the IP(3) inhibitors 2-aminoethoxydiphenyl borate or xestospongin C or on cells loaded with BAPTA-AM, in which slow calcium signals were abolished, resulted in decreased activation of the early genes examined. Both early gene activation and CREB phosphorylation were inhibited by ERK phosphorylation blockade. These data suggest a role for calcium in the transcription-related events that follow membrane depolarization in muscle cells.

Introduction and objectives The COVID-19 outbreak has had an unclear impact on the treatment and outcomes of patients with ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess changes in STEMI management during the COVID-19 outbreak. Methods Using a multicenter, nationwide, retrospective, observational registry of consecutive patients who were managed in 75 specific STEMI care centers in Spain, we compared patient and procedural characteristics and in-hospital outcomes in 2 different cohorts with 30-day follow-up according to whether the patients had been treated before or after COVID-19. Results Suspected STEMI patients treated in STEMI networks decreased by 27.6% and patients with confirmed STEMI fell from 1305 to 1009 (22.7%). There were no differences in reperfusion strategy (> 94% treated with primary percutaneous coronary intervention in both cohorts). Patients treated with primary percutaneous coronary intervention during the COVID-19 outbreak had a longer ischemic time (233 [150-375] vs 200 [140-332] minutes, P < .001) but showed no differences in the time from first medical contact to reperfusion. In-hospital mortality was higher during COVID-19 (7.5% vs 5.1%; unadjusted OR, 1.50; 95%CI, 1.07-2.11; P < .001); this association remained after adjustment for confounders (risk-adjusted OR, 1.88; 95%CI, 1.12-3.14; P = .017). In the 2020 cohort, there was a 6.3% incidence of confirmed SARS-CoV-2 infection during hospitalization. Conclusions The number of STEMI patients treated during the current COVID-19 outbreak fell vs the previous year and there was an increase in the median time from symptom onset to reperfusion and a significant 2-fold increase in the rate of in-hospital mortality. No changes in reperfusion strategy were detected, with primary percutaneous coronary intervention performed for the vast majority of patients. The co-existence of STEMI and SARS-CoV-2 infection was relatively infrequent.

Objective-To determine the clinical features and long term prognosis of infective endocarditis in patients who were not drug addicts. Design-Prospective case series. Setting-A university hospital that is both a referral and a primary care centre. Patients-138 consecutive cases of infective endocarditis diagnosed and treated from January 1987 to March 1997. Results-Mean patient age was 44 (20) years old. 95 patients (69%) had native valve endocarditis and 43 (31%) had prosthetic valve endocarditis. Staphylococci were the causal microorganisms in 34% of cases and streptococci in 33%. Severe complications occurred in 83% of patients and 51% of patients underwent surgery during the active phase (22% was emergency surgery). Inpatient mortality was 21%. During a follow up of 56 (44) months, 10 patients (9%) needed late cardiac surgery and seven (5% of the whole series) died. Overall 10 year survival was 71%. There were no significant diVerences in survival depending on the type of treatment received during the hospital stay (medical or combined medical-surgical). Conclusions-A high early surgery rate is related to good long term results and does not increase in-hospital mortality. Medical treatment, however, also oVers favourable long term results in cases of responsive infective endocarditis where poor prognostic factors are absent. (Heart 2000;83:525-530)

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RESUMENEl presente trabajo presenta los resultados obtenidos del estudio de polimorfismos de ADN mitocondrial de muestras esqueletales de origen Kawésqar provenientes de los sitios isla Englefield, Cueva de la Cruz, isla Capitán Aracena y canal Maule; y de individuos vivos pertenecientes a la etnia Kawésqar. Los resultados obtenidos muestran una gran similitud entre las secuencias de ADN mitocondrial de los individuos vivos y las muestras antiguas. La comparación con otras secuencias publicadas para poblaciones aborígenes sudamericanas confirma los resultados y sugiere fuertemente que existe un vínculo de parentesco por vía materna entre las muestras y los Kawésqar actuales.

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In this real-life study, 32% of patients received an inappropriate dose of DOAC. Several clinical factors can identify patients at risk of this situation.