High-resolution kinetic characterization of the RIG-I-signaling pathway and the antiviral response.

RIG-I recognizes viral dsRNA and activates a cell-autonomous antiviral response. Upon stimulation, it triggers a signaling cascade leading to the production of type I and III IFNs. IFNs are secreted and signal to elicit the expression of IFN-stimulated genes, establishing an antiviral state of the cell. The topology of this pathway has been studied intensively, however, its exact dynamics are less understood. Here, we employed electroporation to synchronously activate RIG-I, enabling us to characterize cell-intrinsic innate immune signaling at a high temporal resolution. Employing IFNAR1/IFNLR-deficient cells, we could differentiate primary RIG-I signaling from secondary signaling downstream of the IFN receptors. Based on these data, we developed a comprehensive mathematical model capable of simulating signaling downstream of dsRNA recognition by RIG-I and the feedback and signal amplification by IFN. We further investigated the impact of viral antagonists on signaling dynamics. Our work provides a comprehensive insight into the signaling events that occur early upon virus infection and opens new avenues to study and disentangle the complexity of the host-virus interface.

Therapeutic approach for patients with venous thromboembolism attended in emergency departments during routine clinical practice: the EDITH study.

AIM: To analyze treatment at discharge/follow-up of patients diagnosed with venous thromboembolism (VTE) in the emergency department (ED). MATERIALS & METHODS: Ambispective study (50 Spanish centers) of consecutive patients (October-December 2014) with VTE diagnosed in ED. RESULTS: VTE was diagnosed in 775 patients (295 pulmonary embolism [PE] without deep vein thrombosis [DVT], 389 DVT without PE and 91 PE + DVT); 95.5% received anticoagulants (90.7% low-molecular-weight heparin [LMWH], 4% LMWH + vitamin K antagonists and <1% direct oral anticoagulants). Overall, 23.3% were discharged from ED and 74.5% hospitalized (98.6% with PE and 50.4% with DVT). After discharge/90/180 days, 43.6/21.0/13.5% were taking LMWH, with similar rates in nononcologic patients. CONCLUSION: There is a poor adherence to international guidelines in management of VTE patients in Spain.

Risk profile, management, and outcomes of patients with venous thromboembolism attended in Spanish Emergency Departments: The ESPHERIA registry.

The objective of this study was to determine the clinical profile of and diagnostic and therapeutic approach to patients with venous thromboembolism (VTE) in Spanish Emergency Departments (EDs). Risk factors, adherence to clinical practice guidelines, and outcomes were also evaluated.Patients with VTE diagnosed in 53 Spanish EDs were prospectively and consecutively included. Demographic data, comorbidities, risk factors for VTE, index event characteristics, hemorrhagic risk, and mortality were evaluated. Adherence to clinical practice guidelines was assessed based on clinical probability scales, requests for determination of D-dimer, use of anticoagulant treatment before confirmation of diagnosis, and assessment of bleeding and prognostic risk. Recurrence, bleeding, and death during admission and at 30, 90, and 180 days after diagnosis in the EDs were recorded.From 549,840 ED visits made over a mean period of 40 days, 905 patients were diagnosed with VTE (incidence 1.6 diagnoses per 1000 visits). The final analysis included 801 patients, of whom 49.8% had pulmonary embolism. The most frequent risk factors for VTE were age (≥70 years), obesity, and new immobility. Clinical probability, prognosis, and bleeding risk scales were recorded in only 7.6%, 7.5%, and 1% of cases, respectively. D-dimer was determined in 87.2% of patients with a high clinical probability of VTE, and treatment was initiated before confirmation in only 35.9% of these patients. In patients with pulmonary embolism, 31.3% had a low risk of VTE. Overall, 98.7% of patients with pulmonary embolism and 50.2% of patients with deep venous thrombosis were admitted. During follow-up, total bleeding was more frequent than recurrences: the rates of any bleeding event were 4.4%, 3.9%, 5.3%, and 3.5% at admission and at 30 and 90, and 180 days, respectively; the rates of VTE recurrence were 2.3%, 1.3%, 1.7%, and 0.6%, respectively. Mortality rates were 3.4%, 3.1%, 4.1%, and 2.6% during hospitalization and at 30, 90, and 180 days, respectively.VTE had a substantial impact on Spanish EDs. The clinical presentation and risk profile for the development of VTE in patients diagnosed in the EDs was similar to that recorded in previous studies. During follow-up, bleeding (overall) was more frequent than recurrences. Adherence to clinical practice guidelines could improve significantly.

[Folic acid for neural tube defects prevention: consumption and information in fertil-age women in Centro Cuyo Region]. / Acido fólico para prevenir defectos del tubo neural: consumo e información en mujeres en edad fértil de la Región Centro Cuyo.

INTRODUCTION: Neural tube defects are congenital malformations of brain and spinal cord. There is evidence that adequate amounts of folic acid supply to women before and during early pregnancy decreases the risk of having a neural tube defects affected child. Main sources of folic acid are food rich in folic acid, multivitamins with folic acid supplementation, and folic acid fortification of cereal products. OBJECTIVES: To assess folic acid consumption from food and from medication in a group of mothers. To analyze their knowledge about using folic acid to prevent neural tube defects. To evaluate association between inadequate consumption and information, level of education, and concurrence to private or public health sector. To measure the amount of folic acid in bread sold within the region. DESIGN: Observational cross-sectional study. SURVEYS: Mothers of children under 2 months of age that were assisted by 38 pediatricians in five cities in the Region, collected between November 2006 and March 2007. Amount of folic acid in bread: bread samples acquired in the same cities. RESULTS AND CONCLUSIONS: 327 surveys were collected. The average daily intake of folic acid from food was 481 Hg; 43,4% of women consume less than 400 Hg daily. Medical supplementation was suitable in 27,8% of the sample. 52,9% had appropriated knowledge about folic acid and prevention of neural tube defects. Differences were observed between mothers concurring to private or public health sector, and those who had or had not completed secondary school in relation to both supplementation and knowledge of folic acid. The media amount of folic acid in bread samples was 192,34 Hg / 100 g. All samples were manufactured with fortified flour.