Putative Secondary Structure at 5'UTR as a Potential Antiviral Target against SARS-CoV-2.

SARS-CoV-2 is an enveloped positive-sense single-stranded RNA coronavirus that causes COVID-19, of which the current outbreak has resulted in a high number of cases and fatalities throughout the world, even vaccine doses are being administered. The aim of this work was to scan the SARS-CoV-2 genome in search for therapeutic targets. We found a sequence in the 5'UTR (NC\_045512:74-130), consisting of a typical heptamer next to a structured region that may cause ribosomal frameshifting. The potential biological value of this region is relevant through its low similarity with other viruses, including coronaviruses related to SARS-CoV, and its high sequence conservation within multiple SARS-CoV-2 isolates. We have predicted the secondary structure of the region by means of different bioinformatic tools. We have suggested a most probable secondary structure to proceed with a 3D reconstruction of the structured segment. Finally, we carried out virtual docking on the 3D structure to look for a binding site and then for drug ligands from a database of lead compounds. Several molecules that could be probably administered as oral drugs show promising binding affinity within the structured region, and so it could be possible interfere its potential regulatory role.

Low recurrence of syncope in patients with inducible sustained ventricular tachyarrhythmias treated with an implantable cardioverter-defibrillator.

AIMS: To determine the effectiveness of the implantable cardioverter defibrillator (ICD) in preventing recurrence of syncope in patients with structural heart disease, previously unexplained syncope and inducible ventricular arrhythmias. METHODS: Thirty-eight patients with syncope, structural heart disease and inducible arrhythmias had an ICD implanted. All ICDs delivered antitachycardia pacing and shocks of adjusted energy. Detection and therapy were programmed according to uniform criteria. RESULTS: The mean age of the patients was 63+/-11 years and most of them were male (36/38). After a mean follow-up of 28+/-15 (4-61) months, six patients died and one underwent heart transplantation. Syncope recurred in three patients, but in none of them was it caused by an arrhythmic event. In 18 patients, 113 episodes of ventricular tachycardia/ventricular fibrillation were detected and appropriately treated by the ICD. The mean time from implant until first appropriate therapy was 18+/-14 months. The actuarial probability of receiving appropriate therapy was 20% and 42% at 12 and 24 months, respectively. CONCLUSIONS: In patients with unexplained syncope, structural heart disease and inducible arrhythmias, ICD prevents syncope associated with arrhythmic events. Frequent effective use of antitachycardia pacing and shocks of adjusted energy seem essential to this aim.

[How and when to use cardioversion in atrial fibrillation at the beginning of the year 2000]. / Cuándo y cómo cardiovertir la fibrilación auricular al inicio del año 2000.

The high incidence and associated complications are causing atrial fibrillation to emerge as a disease of uncertain prognosis, rather than an acceptable alternative to sinus rhythm. There is accumulated evidence of an electrical and anatomical remodelling in atrial fibrillation that facilitates the onset and maintenance of this arrhythmia, and the capacity for these changes may be reversed if sinus rhythm is restored. The development of new drugs that decrease the incidence of recurrences and the advent of internal cardioversion, which has proven to be very effective when traditional methods have failed, have widened the indications and increased the number of patients who may benefit from this technique. These advances pave the way for the development of an implantable atrial cardioverter, which would allow an early treatment of atrial fibrillation and, therefore, lessen the deleterious effects brought on by this rhythm disorder.

[Unstable angina in the elderly: clinical, profile, management and mortality at three months. The PEPA Registry Data]. / Angina inestable en el anciano: perfil clínico, manejo y mortalidad a los tres meses. Datos del registro PEPA.

INTRODUCTION AND OBJECTIVES: Few reports in the literature have studied the characteristics and management of unstable angina in the elderly in Spain. The aim of this study was to analyze the clinical characteristics and the use of diagnostic and therapeutic resources in patients > or = 70 years of age. PATIENTS AND METHODS: A total of 1,551 patients > or = 70 years of age were included out of 4,115 included in the PEPA registry with a follow up of 90 days. These patients were compared with 2,564 < 70 years. RESULTS: In comparison, the elderly (76 +/- 5 years) versus the younger group (58 +/- 8.5 years) included a higher proportion of women (43 vs 27%), diabetics (30 vs 23%)and hypertensive patients (60 vs 49%) with a lower proportion (p < 0.001) of hypercholesterolemia (33 vs 43%), smoking (40 vs 60%) or family history (9 vs 17%). A previous history of angina (49 vs 35%) or infarction (38 vs31%) and comorbidity was found to be significantly more frequent in the elderly, with a worse previous functional class (NYHA > 2 out of 34 vs 15%). The elderly were treated with fewer invasive procedures (25 vs 44%) or catheterization (26 vs 36%) and they were more frequently controlled with medical treatment (86 vs 83%) although with a lower use of beta blockers (45 vs 53%). The mortality at 3 months was greater in the elderly (7.4 vs 3.0%;p < 0.005) with age being an independent predictor of bad prognosis. Cox multivariate analysis showed the age, ST segment depression, diabetes and heart failure on admission to be predictors of bad prognosis in the elderly. CONCLUSIONS: A different pattern is observed in cardiovascular risk factors with a more unfavorable clinical profile in elderly patients with unstable angina. The management of these patients is less aggressive and the mortality is greater. Diabetes, heart failure and ST segment depression on admission are independent predictors of bad prognosis in elderly patients.

[The prognostic value of dobutamine echocardiography after an uncomplicated acute myocardial infarct]. / Valor pronóstico de la ecocardiografía con dobutamina después de un infarto agudo de miocardio no complicado.

BACKGROUND AND PURPOSE: The identification of patients at risk for future events after an infarction is mandatory. The aim of this study was to assess the prognostic value of dobutamine stress echocardiography after an uncomplicated myocardial infarction. METHODS: One hundred and twenty five patients (mean age 65 +/- 11 years, males 82%) underwent dobutamine-echo within ten days after an uncomplicated myocardial infarction. Four myocardial responses were identified: a) negative; b) sustained improvement of myocardial contractility; c) initial improvement followed by worsening, and d) worsening at a distance or in the infarcted zone. RESULTS: Mean follow-up was 7.4 +/- 4.6 months. An adverse outcome occurred in 47 patients: non cardiac death in 3, cardiac death in 6, myocardial infarction in 5, angina in 21, congestive heart failure in 2, and in 10 patients revascularization. Cox regression analysis showed that worsening of contractility was the best predictor for adverse events (p < 0.0001, relative risk 2.8; 95% confidence interval: 1.7-4.5). Non-smoking and previous angina were also predictors of adverse events (p = 0.003 and p = 0.04, respectively). Similar results were obtained after excluding the revascularized patients. CONCLUSIONS: Sustained improvement of contractility in the infarcted region is not a predictor of adverse events. Asynergy at a distance or in the infarcted region during dobutamine echocardiography within ten days after an uncomplicated myocardial infarction predicts adverse cardiac events during follow-up. Therefore, dobutamine echocardiography could be used for risk stratification after acute myocardial infarction.

[Prognostic implications of early discharge from the coronary unit in patients with acute myocardial infarction]. / Implicaciones pronósticas del alta precoz de la unidad coronaria en pacientes con infarto agudo de miocardio.

INTRODUCTION AND OBJECTIVES: The high demand for health care has obliged Coronary Units to hasten the discharge of patients in less serious condition and this might be an influence on their prognosis. Our objective have been: a) to analyse the characteristics and the evolution (death or readmission) during the first month of patients with myocardial infarction and very early discharge from the Coronary Unit (stay of 2 days or less), and b) to assess the profile of very low risk group patients for complications who could be discharged early from the Coronary Unit. PATIENTS AND METHODS: A study of 978 consecutive patients who had been admitted for acute myocardial, in faration were divided into two groups according to their length of stay in the Coronary Unit (A < or = 2 and B > 2 days). Their baseline characteristics, course of stay and vital status at month, were compared. A subgroup of patients at low risk was studied and complications that might have arisen from their early discharge from the Coronary Unit were assessed. RESULTS: Seventy-three patients (7.5%) died within the first two days. Of the remaining 905, the stay was 2 days or less for 336 patients (group A); and longer than 2 days for 569 (group B). Group A had a higher frequency of dyslipemia, Killip class I on admission, uncomplicated myocardial infarction in the Coronary Unit and the use of beta-blockers and had less frequency of diabetes, Q wave myocardial infarction, anterior infarction or the use of fibrinolytics. In the first month after discharge from the Coronary Unit, 10 patients from group A and 18 patients from group B died, the rate of death or readmission into the Coronary Unit within 30 days was similar between both groups (group A = 13% and group B = 13%). A multiple regression showed that Killip class on admission (p < 0.001) and an uncomplicated course (p < 0.001) were independently related with the length of stay in the coronary unit. A subset of 378 low risk patients (Killip I on admission, uncomplicated course in the ICU and age < 71 years) had no mortality at 30 days and their readmission rate in the first month was 4%. In this subgroup, those patients whose stay was equal to or less than two days were more frequently readmitted in the first week. (group A = 9/197 [5%] and group B = 1/181 ([0.5%]; p = 0.034). CONCLUSION: Selected patients with myocardial infarction can be discharged very early from the Coronary Unit with a low risk of death. A readmission rate following discharge of some 5% must be allowed for these patients.

[The effect of a reduction in plasma cholesterol on the evolution of coronary disease]. / Influencia de la reducción del colesterol plasmático en la evolución de la enfermedad coronaria.

Elevated serum cholesterol level has a causal role in the genesis of coronary atherosclerosis and causes plaque activation because it leads to plaque rupture, increases thrombus formation and adversely influences the function of endothelial cells. In patients with evidence of coronary heart disease (angina pectoris, previous myocardial infarction or previous coronary revascularization) the overall effect of cholesterol reduction therapy on the progression of lesions is modest. Nevertheless, the results of secondary prevention trials provide evidence that a reduction in the level of cholesterol leads to a significant decrease in the rate of cardiovascular events, in the rate of new procedures of revascularization by means of coronary surgery or angioplasty, in the coronary-heart-disease-mortality and in the non-coronary-heart-disease mortality. These effects probably mean some benefit on function, vulnerability and thrombogenicity of the plaque. In patients with previous revascularization procedures interest of secondary prevention by means of cholesterol lowering must be special, because in them the probability of long-term success should be optimized for the maximum patient benefit and the best use of health-care resources.