Downregulation of mTOR Signaling Increases Stem Cell Population Telomere Length during Starvation of Immortal Planarians

Reduction of caloric intake delays and prevents age-associated diseases and extends the life span in many organisms. It may be that these benefits are due to positive effects of caloric restriction on stem cell function. We use the planarian model Schmidtea mediterranea, an immortal animal that adapts to long periods of starvation by shrinking in size, to investigate the effects of starvation on telomere length. We show that the longest telomeres are a general signature of planarian adult stem cells. We also observe that starvation leads to an enrichment of stem cells with the longest telomeres and that this enrichment is dependent on mTOR signaling. We propose that one important effect of starvation for the rejuvenation of the adult stem cell pool is through increasing the median telomere length in somatic stem cells. Such a mechanism has broad implications for how dietary effects on aging are mediated at the whole-organism level.C.G.-E. was funded by a Contrato de Investigadores Miguel Servet (CP12/03214) and by the FLI. The FLI is a member of the Leibniz Association and is financially supported by the Federal Government of Germany and the State of Thuringia. O.G.-G. was funded by an LGSA scholarship. R.P. and B.F.-V. were funded by a grant (PI17-01401) from Fondo de Investigaciones Sanitarias (Instituto de Salud Carlos III, Spain) and FEDER funds. I.F. was funded by grants from Ministerio de Ciencia, Innovación y Universidades (SAF2016-80406-R), Comunidad de Madrid (S2017/BMD-3875), and the Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (RD12/0042/0045). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). A.A.A. was funded by grants from the BBSRC (BB/K007564/1) and MRC (MR/M000133/1), and S.S. by a University of Oxford Clarendon Fund Scholarship.S

El desarrollo postembrionario del Sistema Nervioso Central de Macrostomum lignano (Platyhelminthes, Rhabditophora)

Los Platyhelminthes, comúnmente llamados gusanos planos, es un filo de animales que comprende especies de vida libre (como turbelarios o planarias) y parásitos de gran importancia en medicina o veterinaria (duelas, tenias o monogéneos). En investigación, el microturbalario marino Macrostomum lignano (Platyhelminthes, Rhabditophora) es un modelo emergente de laboratorio de fácil cultivo y manejo, de genoma secuenciado y múltiples herramientas moleculares al alcance para su estudio. Se trata de un organismo bilateral basal con un verdadero Sistema Nervioso Central, el cual consiste en un cerebro compartimentado y dos cordones nerviosos principales laterales. Aquí, se presentan por primera vez los tipos celulares, la ultraestructura y los modelos tridimensionales de las células que forman parte del complejo glandular frontal de la especie. Esto es, el conjunto de receptores sensoriales que conectan anteriormente con el cerebro y las glándulas que lo atraviesan. Se reportan dos nuevas células glandulares; un modelo 3D de su fotorreceptor ciliado; la localización de los cuerpos celulares de los receptores sensoriales en el córtex cerebral; y el lugar donde se establece su límite superior. Se describe también la ultraestructura de las neuronas del córtex cerebral; sus sinapsis; el crecimiento del cerebro; y los procesos de neurogénesis que tienen lugar durante el desarrollo postembrionario a partir de células madre llamadas neoblastos

Assessment of two complementary influenza surveillance systems : Sentinel primary care influenza-like illness versus severe hospitalized laboratory-confirmed influenza using the moving epidemic method

Monitoring seasonal influenza epidemics is the corner stone to epidemiological surveillance of acute respiratory virus infections worldwide. This work aims to compare two sentinel surveillance systems within the Daily Acute Respiratory Infection Information System of Catalonia (PIDIRAC), the primary care ILI and Influenza confirmed samples from primary care (PIDIRAC-ILI and PIDIRAC-FLU) and the severe hospitalized laboratory confirmed influenza system (SHLCI), in regard to how they behave in the forecasting of epidemic onset and severity allowing for healthcare preparedness. Epidemiological study carried out during seven influenza seasons (2010-2017) in Catalonia, with data from influenza sentinel surveillance of primary care physicians reporting ILI along with laboratory confirmation of influenza from systematic sampling of ILI cases and 12 hospitals that provided data on severe hospitalized cases with laboratory-confirmed influenza (SHLCI-FLU). Epidemic thresholds for ILI and SHLCI-FLU (overall) as well as influenza A (SHLCI-FLUA) and influenza B (SHLCI-FLUB) incidence rates were assessed by the Moving Epidemics Method. Epidemic thresholds for primary care sentinel surveillance influenza-like illness (PIDIRAC-ILI) incidence rates ranged from 83.65 to 503.92 per 100.000 h. Paired incidence rate curves for SHLCI-FLU/PIDIRAC-ILI and SHLCI-FLUA/PIDIRAC-FLUA showed best correlation index' (0.805 and 0.724 respectively). Assessing delay in reaching epidemic level, PIDIRAC-ILI source forecasts an average of 1.6 weeks before the rest of sources paired. Differences are higher when SHLCI cases are paired to PIDIRAC-ILI and PIDIRAC-FLUB although statistical significance was observed only for SHLCI-FLU/PIDIRAC-ILI (p-value Wilcoxon test = 0.039). The combined ILI and confirmed influenza from primary care along with the severe hospitalized laboratory confirmed influenza data from PIDIRAC sentinel surveillance system provides timely and accurate syndromic and virological surveillance of influenza from the community level to hospitalization of severe cases

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective

Role of age and comorbidities in mortality of patients with infective endocarditis.

The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups: A total of 3120 patients with IE (1327  There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in th

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes