Phosphorylation of Eukaryotic Initiation Factor 4G1 (eIF4G1) at Ser1147 Is Specific for eIF4G1 Bound to eIF4E in Delayed Neuronal Death after Ischemia

Ischemic strokes are caused by a reduction in cerebral blood flow and both the ischemic period and subsequent reperfusion induce brain injury, with different tissue damage depending on the severity of the ischemic insult, its duration, and the particular areas of the brain affected. In those areas vulnerable to cerebral ischemia, the inhibition of protein translation is an essential process of the cellular response leading to delayed neuronal death. In particular, translation initiation is ratelimiting for protein synthesis and the eukaryotic initiation factor (eIF) 4F complex is indispensable for cap-dependent protein translation. In the eIF4F complex, eIF4G is a scaffolding protein that provides docking sites for the assembly of eIF4A and eIF4E, binding to the cap structure of the mRNA and stabilizing all proteins of the complex. The eIF4F complex constituents, eIF4A, eIF4E, and eIF4G, participate in translation regulation by their phosphorylation at specific sites under cellular stress conditions, modulating the activity of the cap-binding complex and protein translation. This work investigates the phosphorylation of eIF4G1 involved in the eIF4E/eIF4G1 association complex, and their regulation in ischemia-reperfusion (IR) as a stress-inducing condition. IR was induced in an animal model of transient cerebral ischemia and the results were studied in the resistant cortical region and in the vulnerable hippocampal CA1 region. The presented data demonstrate the phosphorylation of eIF4G1 at Ser1147, Ser1185, and Ser1231 in both brain regions and in control and ischemic conditions, being the phosphorylation of eIF4G1 at Ser1147 the only one found in the eIF4E/eIF4G association complex from the cap-containing matrix (m7GTP-Sepharose). In addition, our work reveals the specific modulation of the phosphorylation of eIF4G1 at Ser1147 in the vulnerable region, with increased levels and colocalization with eIF4E in response to IR. These findings contribute to elucidate the molecular mechanism of protein translation regulation that underlies in the balance of cell survival/death during pathophysiological stress, such as cerebral ischemia

A rare challenge: A patient with progressive fibrodysplasia ossificans and acute ischemic stroke treated with mechanical thrombectomy.

Summary: Fibrodysplasia ossificans progressiva (FOP) is a rare, disabling genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification. Here, we briefly describe the case of a 56-year-old male with known FOP and acute ischemic stroke that underwent mechanical thrombectomy with conscious sedation. Treating physicians should be aware of special medical considerations to prevent flare-ups and inflammation that result from any tissue injuries in this disease. Mechanical thrombectomy is a challenging scenario because general anesthesia and injections should be avoided in these patients. The treatment is still preventive and supportive, but this is the first report of the procedure in a patient with FOP

Patent Foramen Ovale Closure in patients with Cryptogenic Stroke: a way with negative and positive results

Approximately 40% of patients with cryptogenic stroke have a Permeable Foramen Oval, which is present in 20-25% of the healthy population. Controversy and doubt whether this structure should be closed when paradoxical embolism is suspected has been proposed to reduce the risk of recurrence. Some publications (trials CLOSURE I, RESPECT 2013 or PC TRIAL) discouraged it, based on the results obtained. New evidence published at the end of 2017 (CLOSE, REDUCE and RESPECT 2017 trials) changes the way of evidence to reopen the debate and delimit which patients the procedure should be considered since there is sufficient evidence to reduce the risk of recurrence in some selected patient

El cierre del Foramen Oval Permeable en pacientes con ictus isquémico de origen criptogénico: un camino de resultados negativos y positivos

Approximately 40% of patients with cryptogenic stroke have a Permeable Foramen Oval, which is present in 20-25% of the healthy population. Controversy and doubt whether this structure should be closed when paradoxical embolism is suspected has been proposed to reduce the risk of recurrence. Some publications (trials CLOSURE I, RESPECT 2013 or PC TRIAL) discouraged it, based on the results obtained. New evidence published at the end of 2017 (CLOSE, REDUCE and RESPECT 2017 trials) changes the way of evidence to reopen the debate and delimit which patients the procedure should be considered since there is sufficient evidence to reduce the risk of recurrence in some selected patientsAproximadamente un 40% de los pacientes con ictus criptogénico presentan una comunicación auricular cardíaca, el Foramen Oval Permeable, que está presente en 20-25% de población sana. La controversia y duda de si conviene cerrar esta estructura cuando se sospecha la embolia paradójica, se ha planteado para reducir el riesgo de recurrencia. Algunas publicaciones (ensayos clínicos CLOSURE I, RESPECT 2013 o PC TRIAL) lo desaconsejaban inicialmente, basados en los resultados obtenidos. Nueva evidencia publicada a finales de 2017 (ensayos CLOSE, REDUCE y RESPECT 2017) cambian el camino de la evidencia para reabrir el debate y acotar a qué pacientes habría que considerar el procedimiento puesto que hay datos suficientes para poder reducir el riesgo de recurrencia en algunos pacientes seleccionados

Dimensiones de la aurícula izquierda en pacientes con ictus isquémico criptogénico como método para predecir el desarrollo de fibrilación auricular.

Objective: To determine whether the left atrial size can predict the development of atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS).Methods: Patients with ischemic stroke were included prospectively (January 2015-July 2015) when ESUS was suspected. Clinical and cardiac imaging data were recorded. Patients with cardiac failure were excluded.Results: a total of 55 patients were included. Medium age was 71 years. The proportion of patients who developed AF during the follow-up (1 year) was 23, 63%. 10 % of patients did not have any vascular risk factor. Basal ECG was normal in 98% of cases. The left atrial size volume was 36, 08 ml in patients who developed AF and 27, 14 ml in patients who did not.Conclusions: In patients with ESUS, left atrial size dimensions do not predict the occurrence of AF.Objetivos. Determinar si el grado de dilatación de aurícula izquierda (AI) nos permitirían predecir la existencia de fibrilación auricular (FA) subyacente en pacientes con ictus embólico de origen indeterminado.Material y métodos. Se incluyeron de manera prospectiva pacientes que acudieron como Código Ictus a nuestro centro (Enero 2015-Julio 2015), con sospecha etiológica de embolia sin arritmia documentada. Se documentaron datos clínicos y de imagen cardíaca.Resultados. Un total de 55 pacientes fueron incluidos en el estudio. La edad media fue de 71 años. El porcentaje de pacientes que desarrollaron FA durante el seguimiento (1 año) fue del 23,63%. Un 10% de los pacientes no presentaban ningún factor de riesgovascular clásico. El ECG basal fue normal en el 98%. El volumen medio de AI en ETT ajustado por superficie corporal fue de 36,08 ml en pacientes que desarrollaron FA y de 27,14 ml en aquellos que no la desarrollaron.Conclusiones. En pacientes con ictus isquémico con sospecha mecanismo embólico las dimensiones de la aurícula izquierda no predicen el desarrollo de FA a medio plaz

Left atrial size in patients with cryptogenic stroke as a predictor of occurrence of atrial fibrillation

Objective: To determine whether the left atrial size can predict the development of atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS). Methods: Patients with ischemic stroke were included prospectively (January 2015-July 2015) when ESUS was suspected. Clinical and cardiac imaging data were recorded. Patients with cardiac failure were excluded. Results: a total of 55 patients were included. Medium age was 71 years. The proportion of patients who developed AF during the follow-up (1 year) was 23, 63%. 10 % of patients did not have any vascular risk factor. Basal ECG was normal in 98% of cases. The left atrial size volume was 36, 08 ml in patients who developed AF and 27, 14 ml in patients who did not. Conclusions: In patients with ESUS, left atrial size dimensions do not predict the occurrence of AF

Las referencias bibliográficas en la nutrición

A small group of editors of general medical journals met informally in Vancouver, British Columbia, in 1978 to establish guidelines for the format of manuscripts submitted to their journals. The group became known as the Vancouver Group. Its requirements for manuscripts, including formats for bibliographic references developed by the USA National Library of Medicine, were first published in 1979. The Vancouver Group expanded and evolved into the International Committee of Medical Journal Editors (ICMJE), which meets annually. The ICMJE gradually has broadened its concerns to include ethical principles related to publication in biomedical journals. The total content of the Uniform Requirements for Manuscripts Submitted to Biomedical Journals may be reproduced for educational, not-for-profit purposes without regard for copyright; the committee encourages distribution of the material

Quality of Chronic Anticoagulation Control in Patients with Intracranial Haemorrhage due to Vitamin K Antagonists

Introduction. Patients treated with vitamin K antagonists (VKA) are at increased risk of intracranial haemorrhage (ICH). The purpose of our study was to determine the quality of previous anticoagulation control in patients with VKA-associated ICH. Materials and Methods. We prospectively assessed every consecutive patient admitted to our stroke unit with VKA-associated ICH between 2013 and 2016. Demographic, clinical, and radiological variables, as well as consecutive international normalized ratios (INR) during 7 previous months, were extracted. Time in therapeutic range (TTR), time over range (TOR), time below range (TBR), and percentage of INR within range (PINRR) were calculated. Results and Discussion. The study population comprised 53 patients. Mean age was 79 years; 42% were women. Forty-eight patients had atrial fibrillation (AF) and 5 mechanical prosthetic valves. Therapeutic or infratherapeutic INR on arrival was detected in 64.4% of patients (95% CI 2.7 to 3.2). TTR was 67.8% (95% CI: 60.2 to 75.6 %) and PINRR was 75% (95% CI: 49.9-100). TOR was 17.2% (95% CI: 10.4 to 23.9% ) and TBR was 17% (95% CI: 10.6 to 23.9%). Conclusion. VKA-associated ICH happens usually in the context of good chronic anticoagulation control. Newer risk assessment methods are required