Factores que influyen en los procesos administrativos del Centro Escolar Colonia Santa Leonor, Centro Escolar Tránsito Cienfuegos y Centro Escolar Presbítero Rafael Paz Fuentes del Municipio de Santa Ana Departamento de Santa Ana,año 2018

La presente investigación tiene como propósito el estudio de los factores que influyen en los procesos administrativos de los Centros Escolares Colonia Santa Leonor, Transito Cienfuegos y Presbítero Rafael Paz Fuentes, además, como estos afectan a la comunidad educativa en la realización de las funciones, proyectos y diferentes actividades que se deberían llevar acabo, para el desarrollo integral del estudiantad

SARS-CoV-2 infection in a pediatrics STAT1 GOF patient under Ruxolitinib therapy-a matter of balance?

Recently, 94 inborn errors of immunity (IEI) patients suffering from COVID-19 have been described, overall demonstrating a mild phenotype [1] although more severe disease manifestations have been suggested for patients with alterations in the interferon (IFN) signaling pathway, including auto-antibodies against type I IFN [2]. Patients with STAT1 GOF mutations show a complex and often severe phenotype, combining an increased susceptibility of fungal, (myco-) bacterial and viral infections as well as autoimmune and autoinflammatory manifestations [3]. Characteristically, in response to type I and type II IFN stimulation, these patients show STAT1 hyperphosphorylation [3, 4]. Whether in the context of SARS-CoV-2 infection, the hyperactivation of the IFN-JAK1/2-STAT1 pathway would be protective (antiviral effect) or deleterious (hyperinflammation) is unclear. Ruxolitinib (a selective JAK1/2 inhibitor) has been successfully used in STAT1 GOF patients controlling many disease manifestations [5] and also resulted in improved pulmonary function and faster recovery from lymphopenia in previously healthy individuals suffering from severe COVID-19 [6].This work was supported by the Instituto de Salud Carlos III, Madrid (Spain) [Sara Borrell, CD20/00124 to P.B.L, Juan Rodés JR18/00042 to P.O, FIS PI19/01471 to O.N] and the Consejería de Salud, Junta Andalucía [SA0051/2020 to O.N]. A.G-V was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprograma Miguel Servet (CP19/00159).Peer reviewe

Ampicillin Plus Ceftriaxone Combined Therapy for Enterococcus faecalis Infective Endocarditis in OPAT

Cardiovascular Infectious Study Group of the Andalusian Society of Infectious Diseases.Ampicillin plus ceftriaxone (AC) is a well-recognized inpatient regimen for Enterococcus faecalis infective endocarditis (IE). In this regimen, ceftriaxone is usually administered 2 g every 2 h (AC12). The administration of AC in outpatient parenteral antibiotic treatment (OPAT) programs is challenging because multiple daily doses are required. AC regimens useful for OPAT programs include once-daily high-dose administration of ceftriaxone (AC24) or AC co-diluted and jointly administered in bolus every 4 h (ACjoined). In this retrospective analysis of prospectively collected cases, we aimed to assess the clinical effectivity and safety of three AC regimens for the treatment of E. faecalis IE. Fifty-nine patients were treated with AC combinations (AC12 n = 32, AC24 n = 17, and ACjoined n = 10). Six relapses occurred in the whole cohort: five (29.4%) treated with AC24 regimen and one (10.0%) with ACjoined. Patients were cured in 30 (93.3%), 16 (94.1%), and eight (80.0%) cases in the AC12, AC24 and ACjoined groups, respectively. Unplanned readmission occurred in eight (25.0%), six (35.3%), and two (20.0%) patients in the AC12, AC24 and ACjoined groups, respectively. The outcome of patients with E. faecalis IE treated with AC in OPAT programs relies on an optimization of the delivery of the combination. AC24 exhibit an unexpected rate of failures, however, ACjoined might be an effective alternative which clinical results should corroborate in further studies.The authors received no financial support for the research, authorship, and/or publication of this article. GVA was supported by the Instituto de Salud Carlos III, cofinanced by the European Development Regional Fund (“A way to achieve Europe”), Subprograma Miguel Servet (grant CP19/00159). HHL was supported by the Instituto de Salud Carlos III, Subprograma Rio Hortega (grant CM19/00152)

PDA-Based Glyconanomicelles for Hepatocellular Carcinoma Cells Active Targeting Via Mannose and Asialoglycoprotein Receptors

Hepatocellular carcinoma (HCC) is the sixth most common neoplasia and the fourth most common cause of cancer-related mortality worldwide. Sorafenib is the first-line molecular therapy for patients in an advanced stage of HCC. However, the recommended clinical dose of Sorafenib is associated with several complications, which derive from its lack of cell specificity and its very low water solubility. To circumvent these drawbacks, in the present study we developed two sugar-coated polydiacetylene-based nanomicelles-Sorafenib carriers targeting mannose and asialoglycoprotein receptors (MR and ASGPR, respectively). The strategies allowed the inducement of apoptosis and reduction of cell proliferation at a nanomolar, instead of micromolar, range in liver cancer cells. The study showed that, contrary to literature data, Sorafenib included into the pMicMan (Man = mannose) vector (targeting MR) is more efficient than pMicGal (Gal = galactose) (targeting ASGPR). Indeed, pMicMan increased the endosomal incorporation with an increased intracellular Sorafenib concentration that induced apoptosis and reduced cell proliferation at a low concentration range (10-20 nM).Financial support was provided by the Spanish Ministry of Economy and Competitiveness (CTQ2016-78580-C2-1-R to N.K.) and the Institute of Health Carlos III (ISCIII) (PI13/00021, PI16/00090, and PI19/01266 to J.M.) both cofinanced by the European Regional Development Fund (ERDF) from FEDER and the European Social Fund (ESF), as well by the Andalusian Ministry of Economy, Science and Innovation (P07-FQM-2774 to N.K., CV20-04221 to N.K. P20_00882 to N.K. and CTS-6264 to J.M.), the PAIDI Program from the Andalusian Government (FQM-313 to N.K., CV20-04221 to N.K., P20_00882 to N.K., P20_00882 to N.K., and CTS-0664 to J.M.), the Andalusian Ministry of Health (PI-00025-2013, and PI-0198-2016 to J.M.), and the CSIC (CSIC–COV19-047). We thank the Biomedical Research Network Center for Liver and Digestive Diseases founded by the ISCIII and cofinanced by FEDER “A way to achieve Europe” and ERDF for their financial support. The COST action CA-18132 “Functional Glyconanomaterials for the Development of Diagnostic and Targeted Therapeutic Probe” is also acknowledged. E.R.B., C.C.A., and P. de la C.-O. were supported by FPU predoctoral fellowship (FPU15/04267, FPU17/00190, and FPU17/00026) from Spanish Ministry of Education, Culture and Sports. E.N.-V. was supported by the predoctoral i-PFIS IIS-enterprise contract in science and technologies in health (IFI18/00014) from ISCiii.Peer reviewe

Experiencias de Innovación docente en los Estudios Jurídicos: una visión práctica

Esta publicación se enmarca dentro de las actividades del Grupo de Investigación de la Universidad de Extremadura Fiscalitas & Iuris.Este trabajo surge con el objetivo principal de dar visibilidad y publicidad a las nuevas técnicas docentes en el seno de la Facultad de Derecho de la UEx. Como se sabe, se ha producido un innegable y significativo avance en el uso de nuevas técnicas docentes y también de las TICs aplicadas a la docencia en la Facultad de Derecho, no obstante, aún es necesario profundizar en el uso de las mismas y extenderlas entre todos los miembros del claustro de profesores, y fundamentalmente entre aquellos que llevan más años ejerciendo la docencia a través de la colaboración y la coordinación con los profesores noveles, que son quienes principalmente se sirven en mayor medida de tales instrumentos docentes. De otra parte, también era necesario que los docentes más experimentados pudieran encontrar un foro en el que transmitir y compartir con los noveles cuales son las técnicas e instrumentos docentes que ellos han venido utilizando durante el ejercicio de su magisterio, de modo que, en el marco de una relación sinalagmática, se produjera una interacción entre uno u otro grupo de docentes, a fin de fomentar el necesario debate y el intercambio de experiencias e instrumentos docentes, y en su caso el desarrollo y perfeccionamiento de los mismos; algo que hemos pretendido realizar con este trabajo, y que en buena medida hemos logrado. Las finalidades y objetivos concretos que perseguíamos, en atención a la situación expuesta eran fundamentalmente tres: • En primer lugar, la implementación de un proyecto de innovación docente integrado por una diversidad de actividades coordinadas, cada uno de ellas bajo la directa coordinación de un profesor o profesora de la UEx, aplicado a una o varias asignaturas impartidas en la Facultad de Derecho. • En segundo lugar, el establecimiento en la Facultad de Derecho de un foro de coordinación e intercambio de buenas prácticas docentes sobre la base de cada uno de las actividades coordinadas, en el que pudieran participar profesores noveles y veteranos. Para ello se desarrolló espacio virtual de innovación docente en estudios jurídicos, a través del Campus Virtual de la UEx, en el que los Profesores noveles y veteranos pudieron y puede compartir recursos e informaciones sobre prácticas de innovación. • Y, en tercer lugar, la difusión y consolidación de instrumentos de innovación docente directamente aplicadas a la docencia de los estudios jurídicos, mediante la transferencia de los resultados y la publicación de los mismos; a fin de que esta transferencia sirva de base a futuras profundizaciones en el campo de la innovación docente en los estudios jurídicos.Proyecto “Desarrollo, profundización e intercambio de buenas prácticas de innovación docente en la Facultad de Derecho” (UEx 2015-2016

Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes

Background: Coronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness. Methods: We used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays. Results: Increased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 µM; p<0.001) as an early criterion to accurately classify patients with critical outcomes. Conclusion: Our findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.This work has been developed in the framework of the COVIDOMICS’ project supported by Direcció General de Recerca i Innovació en Salut (DGRIS), Departament de Salut, Generalitat de Catalunya (PoC-6-17 and PoC1-5). The research was also funded by the Programa de Suport als Grups de Recerca AGAUR (2017SGR948), the SPANISH AIDS Research Network [RD16/0025/0006]-ISCIII-FEDER (Spain) and the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas-ISCIII [CB21/13/00020], Madrid, Spain. LR is supported by the Instituto de Salud Carlos III (ISCIII) under grant agreement “CD20/00105” through the program “Contratos Sara Borrell”. FV is supported by grants from the Programa de Intensificación de Investigadores (INT20/00031)-ISCIII and by “Premi a la Trajectòria Investigadora dels Hospitals de l’ICS 2018”. AR is supported by a grant from IISPV through the project “2019/IISPV/05” (Boosting Young Talent), by GeSIDA through the “III Premio para Jóvenes Investigadores 2019” and by the Instituto de Salud Carlos III (ISCIII) under grant agreement “CP19/00146” through the Miguel Servet Program. This study was also supported by grants SAF2015–65019-R and RTI2018–093919-B-100 (to SF-V.) funded by MCIN/AEI and by “ERFD A way of making Europe”; PI19/01337 to FV, PI20/00095 to VC.-M, PI20/00326 to AR and PI20/00338 to JV funded by ISCIII, cofinanced by the European Regional Development Fund (ERDF), and from Fundación Bancaria Caixa d’Estalvis i Pensions de Barcelona (HR20-00051 to SF-V). The Spanish Biomedical Research Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) (CB07708/0012) is an initiative of the Instituto de Salud Carlos III. SF-V acknowledges support from the Miguel Servet tenure-track program (CP10/00438 and CPII16/00008) from the Fondo de Investigación Sanitaria, cofinanced by the ERDF. VC-M acknowledges support from the Ramón y Cajal program (RYC2019-026490-I) from the Spanish Ministry of Science and Innovation, cofinanced by the ERDF. The work was also supported by Consejeria de Salud y Familia (COVID-0005-2020), Consejeria de Transformacion Economica, Industria, Conocimiento y Universidades Junta de Andalucia (CV20-85418to ER-M) and Instituto de Salud Carlos III (ISCIII) under grant agreement CP19/00159 to AGV “a way to make Europe”. ER-M was supported by the Spanish Research Council (CSIC). The funders have no roles in study design, data collection, data analysis, interpretation or the writing of this research.Peer reviewe

Migration and activation marker expressing in monocytes subset in mild and several/critical patients (S/C)

S2 Fig. Migration and activation marker expressing in monocytes subset in mild and several/critical patients (S/C).Peer reviewe

S1 Fig - Clinical, laboratory data and inflammatory biomarkers at baseline as early discharge predictors in hospitalized SARS-CoV-2 infected patients

A, Predictive models for hospital discharge during the first week in mild patients. B, Predictive models for worsening of clinical status during the first week in patients who were admitted mildly ill. AUC, area under the curve.Peer reviewe

Activation, homing and maturation marker expression in different monocyte subsets

Data are expressed by percentage and interquartile range. Medians fluorescence intensitive (MFI) were calculated in those markets that have a high rate of expression.Peer reviewe

Baseline characteristics of the mild patients who were discharged and worsened during the first week

Quantitative variables are expressing as number (percentage) or median (interquartile range). Pa value for differences between patients who were or not discharged. Pb value for differences between patients who who did and did not get wore. SpO2, peripheral capillary oxygen saturation; CRP, C-reactive protein; LDH, Lactate dehydrogenase; NLR, neutrophil/lymphocyte ratio.Peer reviewe