Spatiotemporal regulation of signaling: focus on T cell activation and the immunological synapse

In a signaling network, not only the functions of molecules are important but when (temporal) and where (spatial) those functions are exerted and orchestrated is what defines the signaling output. To temporally and spatially modulate signaling events, cells generate specialized functional domains with variable lifetime and size that concentrate signaling molecules, enhancing their transduction potential. The plasma membrane is a key in this regulation, as it constitutes a primary signaling hub that integrates signals within and across the membrane. Here, we examine some of the mechanisms that cells exhibit to spatiotemporally regulate signal transduction, focusing on the early events of T cell activation from triggering of T cell receptor to formation and maturation of the immunological synapse

“La relación del plan de compensación de la empresa ENACAL (Empresa Nicaragüense de Acueductos y Alcantarillados) con el nivel de satisfacción de sus trabajadores, durante el año 2013, en la ciudad de Matagalpa”

Los planes de compensaciones atractivos son de mucha importancia para cualquier empresa ya que a través de una buena implementación se logra retener y atraer los mejores recursos para la organización. La compensación económica directa es la paga que cada empleado recibe en forma de dinero. Los trabajadores de la empresa ENACAL Matagalpa de acuerdo a este tipo de compensación reciben un salario por encima del mínimo establecido por la ley y bonificaciones a todo el personal de la empresa. Respecto a las compensaciones financieras indirectas reciben los permisos durante la jornada laboral, horas extras, vacaciones y afiliación al seguro social beneficio del cual goza el cien por ciento de los trabajadores. De acuerdo a las compensaciones no financieras referentes al puesto de trabajo que la empresa ENACAL otorga oportunidad de ascenso, capacitación, compensación por reconocimiento y referentes al entorno del puesto el personal cuenta con condiciones cómodas de trabajo. Actuando unidas ambas compensaciones tanto en pro de los trabajadores como de la empresa misma. El nivel de satisfacción de los trabajadores de acuerdo a las compensaciones que reciben por parte de la empresa se considera aceptable, esto debido a los diferentes beneficios y factores motivantes percibidos en su mayoría como buenos, ya que satisfacen las múltiples necesidades del personal. El análisis de relación entre las variables realizado con la prueba Chi-cuadrado de Pearson demuestra la relación que existe entre las compensaciones que otorga la empresa ENACAL y el nivel de satisfacción de sus trabajadore

Teaching based on the case method of building collective protection

One of the fundamental aspects in the adaptation of the teaching to the European higher education is changing based models of teacher education to models based on student learning. In this work we present an educational experience developed with the teaching method based on the case method, with a clearly multidisciplinary. The experience has been developed in the teaching of analysis and verification of safety rails. This is a multidisciplinary field that presents great difficulties during their teaching. The use of the case method has given good results in the competences achieved by student

Analysis of teaching experience based on teaching by the case method. Application to reinforcing wooden floors

The technique of reinforcement of wooden floors is a matter clearly multidisciplinary. The teaching of the subject using the "traditional" method, explaining the theory first and then proposing and solving problems has not been successful. This paper discusses the results of a teaching experiencie. It has been the teaching of the subject by the case method. The results are clearly superior to those obtained with the traditional methodology

Electrospinning Alginate/Polyethylene Oxide and Curcumin Composite Nanofibers

© 2020 Elsevier Ltd. All rights reserved. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/.Manufacturing a sodium alginate (SA) and polyethylene oxide (PEO) composite loaded with curcumin (CU) was accomplished in this study by using electrospinning. These composite nanofibers were crosslinked using trifluoroacetic acid (TFA) mechanically characterized along with the morphological properties of the composite nanofiber mesh. We were successful in manufacturing the composite nanofibers with a wide range of CU concentrations ranging from 10 to 40 wt%. Firstly, dissolved in a saturated water/CU solution it was added to SA/PEO blending, homogenized and electrospun. Mechanical properties were affected by both CU addition and the cross-linking process, resulting in a higher ultimate tensile stress (MPa) (from 4.3±2 to 15.1±2 at 10% CU) and Young modulus (GPa) (0.0076±0.003, 0.044±0.003 before and after TFA). CU was successfully encapsulated in the SA nanofibers and excellent mechanical properties were obtained. By using a biocompatible TFA crosslinking and the natural properties of alginate this nanofiber composite could potentially be used for filtering, environmental pollution control, food packaging and for tissue engineering.Peer reviewe

Cardiac monitoring with textile wearable Holter for atrial fibrillation detection after cryptogenic strokestroke

Informes de Evaluación de Tecnologías Sanitarias[ES] Introducción El ictus cerebral de causa indeterminada o ictus criptogénico se define como aquel infarto de tamaño medio o grande, de localización cortical o subcortical, en territorio carotídeo o vertebrobasilar, de etiología desconocida tras excluir todas las potenciales causas mediante un estudio diagnóstico completo. Se ha estimado que hasta un 40% de los ictus isquémicos son de causa desconocida. En un alto porcentaje de pacientes que han sufrido un ictus criptogénico la causa es una fibrilación auricular (FA). Se ha puesto de manifiesto que la monitorización continua del ritmo cardiaco durante periodos prolongados en personas que han sufrido un ictus criptogénico permite identificar episodios de fibrilación auricular asintomáticos que no eran previamente conocidos. La sensibilidad de los sistemas de detección de la FA varía en función de la duración y modalidad de la monitorización, con una sensibilidad más alta cuanto más se prolonga en el tiempo la monitorización. El tiempo de monitorización cardíaca que proporcionan distintos dispositivos varía entre registros ambulatorios con dispositivos portátiles no invasivos de 24 horas a 7 días, con registradores externos hasta 30 días o con monitores implantables desde varios meses a 3 años. El tiempo de monitorización está condicionado por factores técnicos y logísticos que en algunos casos impiden una monitorización prolongada. En los últimos años han surgido nuevos dispositivos portátiles, que permiten realizar electrocardiografías durante un periodo prolongado de forma no invasiva y cómoda para el paciente. Existen distintos modelos, como pueden ser parches o bandas colocadas alrededor del pecho, relojes inteligentes o relojes de pulsera que permiten registrar ECG de una sola derivación, teléfonos inteligentes o incluso ropa con sensores integrados que permiten monitorizar el ritmo cardiaco y realizar un ECG. Sin embargo, la evidencia sobre la eficacia diagnostica de estos dispositivos portátiles para la detección de la FA es aún escasa. Uno de los dispositivos textiles que permiten la monitorización cardíaca es el sistema Nuubo® desarrollado por la empresa Nuubo®. Este dispositivo está formado por un chaleco que contiene una banda textil elástica con electrodos impresos en 3D que se adapta a los movimientos del paciente y se ajusta alrededor del pecho. Junto a la banda se incluye un sistema que permite grabar, en una tarjeta microSD el ritmo cardiaco durante 30 días. El sistema Nuubo® también incluye un software que analiza los datos y genera un informe con los resultados de la monitorización cardíaca. Objetivos Determinar la efectividad y la seguridad de una estrategia de monitorización prolongada para detectar fibrilación auricular tras un ictus criptogénico mediante un chaleco de tela elástica inteligente o Textile Wearable Holter, que se adosa al cuerpo del paciente y monitoriza su actividad cardíaca. Metodología Se ha realizado una revisión sistemática de la literatura científica disponible relacionada con la eficacia, la seguridad y la eficiencia de la monitorización prolongada para detectar fibrilación auricular tras un ictus criptogénico en pacientes mayores de 18 años de edad mediante el Sistema Textile Wearable Holter Nuubo®. Dos revisores seleccionaron de forma independiente los estudios a partir de la lectura de los títulos y resúmenes localizados a través de la búsqueda de la literatura, realizaron la extracción de datos de los estudios incluidos y valoraron la calidad de los mismos mediante la aplicación de la escala de riesgo de sesgos ROBINS-I. Resultados La revisión sistemática de la literatura permitió identificar 1.452 referencias (340 en Medline, 955 en EMBASE, 157 en Cochrane Library). Tras la lectura de título y resumen se incluyeron 3 estudios para su lectura a texto completo. Finalmente se incluyó un estudio que cumplía los criterios de inclusión. El único estudio incluido es un estudio piloto realizado sobre un registro de pacientes prospectivo y multicéntrico en cuatro unidades de ictus de hospitales españoles. El estudio incluyó 174 pacientes mayores de 55 años que habían sufrido un ictus criptogénico. En el estudio se analizan dos formas de llevar el dispositivo: modelo cable con un Holter de un canal y modelo chaleco con un Holter de 3 canales. El estudio comenzó en diciembre de 2014, y en los pacientes incluidos durante los 12 primeros meses se evaluó la forma del dispositivo Nuubo® denominada cable y en los pacientes seleccionados para los 12 siguientes meses se analizó la forma denominada chaleco. Un total de 146 pacientes completaron el estudio. La tasa de FA no diagnosticada detectada con este dispositivo fue del 21,9% (32/146), con una duración media de los episodios de 469 minutos (DE: 97 minutos). La tasa de detección de FA no diagnosticada fue mayor en los pacientes con infarto cortical 24,5% (24/98) en comparación con aquellos sin infarto cortical 5,9% (2/34) (p = 0,019). Los autores también observaron un mayor porcentaje de detección de FA en aquellos pacientes con oclusión vascular mayor 31,8% (14/44) en comparación con los pacientes sin oclusión 14,1% (12/85) (p= 0,018). Se observó un incremento de la incidencia de FA detectada desde el 5,6% observada a los 3 días, al 17,5% a los 15 días y hasta el 20,9% a los 28 días. Se valoró la satisfacción del paciente evaluando el grado de comodidad con el dispositivo mediante una escala de 5 puntos, donde 5 indicaba el mayor grado de comodidad y 1 el menor. A nivel global, no se observaron diferencias significativas entre el día y la noche, con una media de 3,7 y 3,89 puntos respectivamente. Tampoco se observaron diferencias significativas entre el modelo cable y el chaleco. Respecto a la seguridad del dispositivo los autores no informaron de ninguna muerte durante el seguimiento. El estudio no recoge información sobre morbilidad cardiovascular o cerebrovascular. Los autores informaron que se produjeron un 5,6% de reacciones cutáneas reversibles que obligaron a 8 pacientes (4 en cada grupo) a abandonar la monitorización, sin diferencias estadísticamente significativas entre las dos modalidades del dispositivo analizadas. Este estudio es un estudio piloto prospectivo sin comparador con un riesgo de sesgo moderado (valorado mediante la escala ROBINS-I). Conclusiones La evidencia proporcionada por este único estudio es valorada como insuficiente para adoptar una conclusión sobre la eficacia y seguridad de este dispositivo en la detección de fibrilación auricular en pacientes que han sufrido un ictus criptogénico, así como sobre los beneficios clínicos potenciales del uso de este dispositivo en relación a otros sistemas de monitorización cardíaca a largo plazo en esta situación clínica. [EN] Introduction Cerebral stroke of undetermined cause or cryptogenic stroke is defined as an infarct of medium or large size, of cortical or subcortical location, in the carotid or vertebrobasilar territory, of unknown etiology after excluding all potential causes through a complete diagnostic study. It has been estimated that up to 40% of ischemic strokes are of unknown cause. In a high percentage of patients who have suffered a cryptogenic stroke, the cause is atrial fibrillation (AF). Continuous monitoring of heart rhythm for prolonged periods in people who have suffered a cryptogenic stroke has been shown to identify asymptomatic episodes of atrial fibrillation that were not previously known. The sensitivity of AF detection systems varies depending on the duration and modality of monitoring, with a higher sensitivity the longer the monitoring is prolonged in time. The cardiac monitoring time provided by different devices varies between ambulatory recordings with portable non-invasive devices from 24 hours to 7 days, with external recorders up to 30 days or with implantable monitors from several months to 3 years. The monitoring time is conditioned by technical and logistical factors that in some cases prevent prolonged monitoring. In recent years, new portable devices have emerged, which allow electrocardiography to be performed for a long period in a non-invasive and comfortable way for the patient. There are different models, such as patches or bands around the chest, smart watches or wristwatches that allow recording a single-lead ECG, smart phones or even clothing with integrated sensors that allow you to monitor the heart rate and perform an ECG. However, the evidence on the diagnostic efficacy of these portable devices for the detection of AF is still scarce. One of the textile devices that allow cardiac monitoring is the Nuubo® system developed by the Nuubo company. This device consists of a vest that contains an elastic textile band with 3D printed electrodes that adapts to the patient's movements and fits around the chest. A system is included together with the band to record the heart rate for 30 days on a microSD card. The Nuubo® system also includes software that analyzes the data and generates a report with the results of cardiac monitoring. Objectives To determine the effectiveness and safety of a prolonged monitoring strategy to detect atrial fibrillation after a cryptogenic stroke using a smart elastic fabric vest or Textile Wearable Holter, which is attached to the patient's body and monitors their cardiac activity. Methodology A systematic review of the available scientific literature related to the efficacy, safety and efficiency of prolonged monitoring to detect atrial fibrillation after cryptogenic stroke in patients older than 18 years of age using the Nuubo® Wearable Holter Textile System has been carried out. Two reviewers independently selected the studies by reading the titles and abstracts located through the literature search, extracted data from the included studies, and assessed their quality by applying the scale ROBINSI risk of biases. Results The systematic review of the literature allowed the identification of 1.452 references (340 in Medline, 955 in EMBASE, 157 in Cochrane Library). After reading the title and abstract, 3 studies were included for full text reading. Finally, a study was included that met the inclusion criteria. The only study included is a pilot study conducted on a prospective, multicenter patient registry in four stroke units of Spanish hospitals. The study included 174 patients older than 55 years who had suffered a cryptogenic stroke. The study analyzed two ways of wearing the device: a cable model with a one-channel Holter and a vest model with a 3-channel Holter. The study began in December 2014, and in the patients included during the first 12 months the shape of the Nuubo® device called cable was evaluated and in the patients selected for the following 12 months the shape called vest was analyzed. A total of 146 patients completed the study. The rate of undiagnosed AF detected with this device was 21.9% (32/146), with a mean duration of episodes of 469 minutes (SD: 97 minutes). The detection rate of undiagnosed AF was higher in patients with cortical infarction 24.5% (24/98) compared to those without cortical infarction 5.9% (2/34) (p = 0.019). The authors also observed a higher percentage of AF detection in those patients with major vascular occlusion 31.8% (14/44) compared to patients without occlusion 14.1% (12/85) (p = 0.018). An increase in the incidence of detected AF was observed from 5.6% observed at 3 days, to 17.5% at 15 days and up to 20.9% at 28 days. Patient satisfaction was assessed by evaluating the degree of comfort with the device using a 5-point scale, where 5 indicated the highest degree of comfort and 1 the least. Globally, no significant differences were observed between day and night, with a mean of 3.7 and 3.89 points respectively. Neither were significant differences observed between the cable model and the vest. Regarding the safety of the device, the authors did not report any deaths during follow-up. The study does not collect information on cardiovascular or cerebrovascular morbidity. The authors reported that there were 5.6% reversible skin reactions that forced 8 patients (4 in each group) to abandon monitoring, with no statistically significant differences between the two device modalities analyzed. This study is a prospective pilot study with no comparator with a moderate risk of bias (assessed using the ROBINS-I scale). Conclusions The evidence provided by this single study is considered insufficient to reach a conclusion on the efficacy and safety of this device in detecting atrial fibrillation in patients who have suffered a cryptogenic stroke, as well as on the potential clinical benefits of using this device, compared to other long term cardiac monitoring systems applicable in this clinical situation.Este documento ha sido realizado por la Agencia de Evaluación de Tecnologías Sanitarias del Instituto de Salud Carlos III en el marco de la financiación del Ministerio de Sanidad para el desarrollo de las actividades del Plan anual de Trabajo de la Red Española de Agencias de Evaluación de Tecnologías Sanitarias y Prestaciones del SNS, aprobado en el Pleno del Consejo Interterritorial del SNS del 28 de octubre de 2020 (conforme al Acuerdo del Consejo de Ministros de 9 de diciembre de 2020).1. INTRODUCCIÓN 1.1. Problema de salud 1.1.1. Epidemiología 1.1.2.Tratamiento 1.2. Descripción de la tecnología 2. OBJETIVOS 2.1. Objetivo general 2.2. Alcance 3. METODOLOGÍA 3.1. Criterios de selección de estudios 3.2. Criterios de exclusión. 3.3. Fuentes de información y estrategia de búsqueda 3.4. Proceso de selección de estudios 3.5. Evaluación crítica del riesgo de sesgo 3.6. Extracción de datos 3.7. Síntesis de los datos 4. RESULTADOS 4.1. Revisión sistemática de la literatura sobre eficacia y seguridad 4.2. Descripción y calidad de los estudios seleccionados 4.3. Eficacia y seguridad 4.4. Consideraciones de implementación 4.5. Revisión de la literatura sobre evaluación económica 5. DISCUSIÓN 6. CONCLUSIONES 7. REFERENCIAS 8. ANEXOS ANEXO 1. Estrategia de búsqueda Estrategias para la búsqueda de eficacia y seguridad Estrategias para la búsqueda de estudios económicos ANEXO 2. Referencias de estudios excluidos ANEXO 3. Valoración de riesgo de sesgos de los estudios ANEXO 4. Características de los estudiosS

Results on Proton-Irradiated 3D Pixel Sensors Interconnected to RD53A Readout ASIC

Test beam results obtained with 3D pixel sensors bump-bonded to the RD53A prototype readout ASIC are reported. Sensors from FBK (Italy) and IMB-CNM (Spain) have been tested before and after proton-irradiation to an equivalent fluence of about $1$ $\times$ $10^{16}$ $\text{n}_{\text{eq}}$ cm$^{-2}$ (1 MeV equivalent neutrons). This is the first time that one single collecting electrode fine pitch 3D sensors are irradiated up to such fluence bump-bonded to a fine pitch ASIC. The preliminary analysis of the collected data shows no degradation on the hit detection efficiencies of the tested sensors after high energy proton irradiation, demonstrating the excellent radiation tolerance of the 3D pixel sensors. Thus, they will be excellent candidates for the extreme radiation environment at the innermost layers of the HL-LHC experiments.Comment: Conference Proceedings of VCI2019, 15th Vienna Conference of Instrumentation, February 18-22, 2019, Vienna, Austria. arXiv admin note: text overlap with arXiv:1903.0196

T-cell epitopes of the major peach allergen, Pru p 3: Identification and differential T-cell response of peach-allergic and non-allergic subjects

Lipid transfer proteins (LTPs), particularly peach Pru p 3, are the most relevant plant food allergens in the South of Europe, and, therefore, their allergic properties have been extensively studied. However, neither T-cell epitopes nor their effect on the patients’ T-cell response has been investigated in any member of the LTP panallergen family. The objective of the present study was to map the major T-cell epitopes of Pru p 3, as well as to evaluate their induced T-cell response in peach-allergic versus control subjects. Thus, peripheral blood mononuclear cells (PBMCs) from 18 peach-allergic patients and Pru p 3-specific T-cell lines (TCLs) from 9 of them were cultured with Pru p 3 and with a panel of 17 derived peptides (10-mer overlapping in 5 amino acids representing the full sequence of Pru p 3). Proliferation in 5-day assays was carried out via tritiated-thymidine incorporation, while IL4 and IFNγ production was assessed via sandwich enzyme-linked immunosorbent tests (ELISA) of TCL culture supernatants. The results were compared to those obtained from 10 non-peach allergic control volunteers. Two consecutive peptides showed the highest activation capacity. About 74% of PBMCs and TCLs recognized them, forming a single T-epitope: Pru p 365–80. Additionally, other specific T-cell epitopes were observed. Pru p 325–35 was detected by more than 60% of TCLs from peach-allergic patients, and Pru p 345–55 only activated PBMCs from control subjects. Interestingly, TCLs from patients were associated with a Th2-type, whereas control TCLs presented a Th1-type cytokine response. The major immunogenic T-cell epitope identified in Pru p 3, Pru p 365–80, is a good candidate to develop new vaccines for hypersensitivity reactions associated with LTP allergens from Rosaceae fruits

Factors affecting the relationship between psychological status and quality of life in COPD patients

<p>Abstract</p> <p>Background</p> <p>This study aims to (i) evaluate the association between anxiety and depressive symptoms and health-related quality of life (HRQoL); and (ii) identify the effect modifiers of this relationship in patients with chronic obstructive pulmonary disease (COPD).</p> <p>Methods</p> <p>A total of 337 clinically stable COPD patients answered the St. George's Respiratory Questionnaire (SGRQ) (assessing HRQoL) and the Hospital Anxiety and Depression Scale (HADS). Socio-demographic information, lung function, and other clinical data were collected.</p> <p>Results</p> <p>Most patients (93%) were male; they had a mean (SD) age of 68 (9) years and mild to very severe COPD (post-bronchodilator FEV₁52 (16)% predicted). Multivariate analyses showed that anxiety, depression, or both conditions were associated with poor HRQoL (for all SGRQ domains). The association between anxiety and total HRQoL score was 6.7 points higher (indicating a worse HRQoL) in current workers than in retired individuals. Estimates for patients with "both anxiety and depression" were 5.8 points lower in stage I-II than in stage III-IV COPD, and 10.2 points higher in patients with other comorbidities than in those with only COPD.</p> <p>Conclusions</p> <p>This study shows a significant association between anxiety, depression, or both conditions and impaired HRQoL. Clinically relevant factors affecting the magnitude of this association include work status, COPD severity, and the presence of comorbidities.</p

Lung ultrasound as a translational approach for non-invasive assessment of heart failure with reduced or preserved ejection fraction in mice

Aims: Heart failure (HF) has become an epidemic and constitutes a major medical, social, and economic problem worldwide. Despite advances in medical treatment, HF prognosis remains poor. The development of efficient therapies is hampered by the lack of appropriate animal models in which HF can be reliably determined, particularly in mice. The development of HF in mice is often assumed based on the presence of cardiac dysfunction, but HF itself is seldom proved. Lung ultrasound (LUS) has become a helpful tool for lung congestion assessment in patients at all stages of HF. We aimed to apply this non-invasive imaging tool to evaluate HF in mouse models of both systolic and diastolic dysfunction. Methods and results: We used LUS to study HF in a mouse model of systolic dysfunction, dilated cardiomyopathy, and in a mouse model of diastolic dysfunction, diabetic cardiomyopathy. LUS proved to be a reliable and reproducible tool to detect pulmonary congestion in mice. The combination of LUS and echocardiography allowed discriminating those mice that develop HF from those that do not, even in the presence of evident cardiac dysfunction. The study showed that LUS can be used to identify the onset of HF decompensation and to evaluate the efficacy of therapies for this syndrome. Conclusions: This novel approach in mouse models of cardiac disease enables for the first time to adequately diagnose HF non-invasively in mice with preserved or reduced ejection fraction, and will pave the way to a better understanding of HF and to the development of new therapeutic approaches.This study was supported by grants from the Spanish Ministerio de Economia y Competitividad (SAF2015-65722-R), Comunidad Autonoma de Madrid (2010-BMD2321, FIBROTEAM Consortium), European Union's FP7 (CardioNeT-ITN-289600, CardioNext-ITN-608027) and the Spanish Instituto de Salud Carlos III (CPII14/00027 to E.L-P, RD12/0042/0054 to B.I. and RD12/0042/066 to P.G.-P. and E.L-P). This work was also supported by the Plan Estatal de I+D+I 2013-2016 - European Regional Development Fund (FEDER) "A way of making Europe", Spain. The CNIC is supported by the Ministry of Economy, Industry and Competitiveness (MINECO) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).S