Development, Characterization, and In Vitro Evaluation of Resveratrol-Loaded Poly-(ε-caprolactone) Microcapsules Prepared by Ultrasonic Atomization for Intra-Articular Administration

Intra-articular administration of drugs to the joint in the treatment of joint disease has the potential to minimize the systemic bioavailability and the usual side-effects associated with oral drug administration. In this work, a drug delivery system is proposed to achieve an anti-inflammatory local effect using resveratrol (RSV). This study aims to develop microcapsules made of poly-(ε-caprolactone) (PCL) by ultrasonic atomization to preserve the antioxidant activity of RSV, to prevent its degradation and to suppress the inflammatory response in activated RAW 264.7 macrophages. An experimental design was performed to build a mathematical model that could estimate the effect of nozzle power and polymer concentration on particle size and encapsulation efficiency. RSV-loaded microcapsules showed adequate morphology, particle size, and loading efficiency properties. RSV formulations exhibited negligible cytotoxicity and an efficient amelioration of inflammatory responses, in terms of Nitric Oxide (NO), ROS (Reactive Oxygen Species), and lipid peroxidation in macrophages. Thus, RSV-loaded microcapsules merit consideration as a drug delivery system suitable for intra-articular administration in inflammatory disorders affecting the jointAcknowledgments: I.L.-G. is grateful to “Programa de axudas á etapa predoutoral da Xunta de Galicia (cofinanciadas por FSE Galicia 2014-2020), Consellería de Cultura, Educación e Ordenación Universitaria” program for doctoral fellowshipS

Overproduction and purification of protein p6 of Bacillus subtilis phage ø29

A ø29 DNA fragment containing gene 6, required for DNA replication, has been cloned in plasmid pPLc28 under the control of the PL promoter of phage lambda. A polypeptide with an electrophoretic mobility close to that of p6 was labelled with 35S methionine after heat induction. This protein, representing about 4% of the total E. coli protein after 1 h of induction, was obtained in a highly purified form. The protein was characterized as p6 by amino acid analysis and NH2 COOH-terminal sequence determination. Protein p6 has an apparent molecular weight of 23,600 suggesting that the native form of the protein is a dimer. The purified protein p6 stimulated the protein-primed initiation of ø29-coded DNA replication when added to purified proteins p2 (ø29-coded DNA polymerase) and p3 (terminal protein).Peer reviewe

Monitoring the phenolic ripening of red grapes using a multisensor system based on metal-oxide nanoparticles

Producción CientíficaThe maturity of grapes is usually monitored by means of the sugar concentration. However, the assessment of other parameters such as the phenolic content is also important because the phenolic maturity has an important impact on the organoleptic characteristics of wines. In this work, voltammetric sensors able to detect phenols in red grapes have been developed. They are based on metal oxide nanoparticles (CeO2, NiO, and TiO2,) whose excellent electrocatalytic properties toward phenols allows obtaining sensors with detection limits in the range of 10−8 M and coefficients of variation lower than 7%. An electronic tongue constructed using a combination of the nanoparticle-based sensors is capable to monitor the phenolic maturity of red grapes from véraison to maturity. Principal Component Analysis (PCA) can be successfully used to discriminate samples according to the ripeness. Regression models performed using Partial Least Squares (PLS-1) have established good correlations between voltammetric data obtained with the electrochemical sensors and the Total Polyphenolic Index, the Brix degree and the Total Acidity, with correlation coefficients close to 1 and low number of latent variables. An advantage of this system is that the electronic tongue can be used for the simultaneous assessment of these three parameters which are the main factors used to monitor the maturity of grapes. Thus the electronic tongue based on metal oxide nanoparticles can be a valuable tool to monitor ripeness. These results demonstrate the exciting possible applications of metal oxide nanoparticles in the field of electronic tongues.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (project AGL2015-67482- R)Junta de Castilla y Leon - Fondo Europeo de Desarrollo Regional (project VA011U16)Junta de Castilla y León (grant BOCYL-D-24112015-9

Evaluation is not a second phase in the pedagogical design of a sMOOC. A case study

El MOOC analizado forma parte del Proyecto Europeo ECO (UE-14-ECO-621127) financiado por la Comunidad europea dentro del programa Competitiveness and Innovation Framework Programme (CIP), coordinado por la UNED en el que han participado más de 20 universidades y empresas europeas en la creación de cursos MOOC y en la formación de “e-teachers” capaces de diseñarlos en el futuro.La evaluación en los Cursos Online Masivos Abiertos (COMA -en inglés MOOC-) es en la actualidad un elemento central de debate y por ello uno de los aspectos de mayor preocupación a la hora de proponer el diseño pedagógico de este tipo de cursos. El objetivo del artículo es doble: describir el sistema de evaluación del curso MOOC “Alfabetización Digital para colectivos en riesgo de exclusión social: Estrategias para la Intervención Socioeducativa” del Proyecto europeo ECO1 (implementado durante tres ediciones) y diagnosticar sus fortalezas y debilidades. Hemos diseñado el modelo evaluativo como una parte central y dinámica del curso, que nos permitiera conocer el perfil de nuestros participantes virtuales (evaluación inicial), tutorizar su trabajo y valorar sus resultados (evaluación de los aprendizajes) y, por último, obtener la máxima información posible de cara a aprender de este tipo de procesos formativos y tomar decisiones de mejora en cada nueva edición (evaluación orientada a la mejora). Después de describir el modelo de evaluación, presentamos y analizamos los principales datos obtenidos con las herramientas de recogida de información utilizadas (cuestionario inicial, interacciones en grupos de Facebook y otros espacios sociales, cuestionarios autoevaluativos, evaluación por pares, informantes clave y datos de la plataforma). Para finalizar, se discuten los resultados con la intención de aportar reflexiones de nuestra experiencia que puedan servir de guía a la hora de diseñar modelos de evaluación en MOOC. Nuestra tesis principal es que el modelo evaluativo es un elemento central del diseño que debe perfilarse desde el minuto uno e integrarse plenamente con el resto de los elementos del diseño pedagógico, contemplando estrategias para la evaluación inicial y formativa de los participantes y del propio proceso de enseñanza-aprendizaje y no solo relativas a la evaluación final orientada a la certificación.Evaluation in Massive Open Online Courses (MOOC) is currently a central element of debate and one of the aspects of greatest concern when planning the pedagogical design of this kind or courses. The purpose of the article is twofold. On the one hand, to describe the evaluation system implemented during three editions in the MOOC "Digital Literacy for groups at risk of social exclusion: Strategies for Socio-educational Intervention." (European Project ECO). On the other hand, we analyze the strengths and weaknesses of the assessment system described. We have designed the evaluative model as a central and dynamic part of pedagogical design, allowing us to know our virtual participants (initial evaluation), to tutor their work and to evaluate their results (assesment of learning processes) and, finally, to obtain information in order to take decisions for improvement in each new edition (evaluation oriented to improvement). First of all, we describe the evaluation model. Then we analyze the main data collected with the tools used (initial questionnaire, interactions in Facebook groups and other social spaces, self-evaluation questionnaires, peer to peer evaluation, key informants and platform data). Finally, we discuss the results obtained in order to provide reflections that can guide the design of evaluation processes in MOOC. The main thesis we defend is that the planning of the evaluative model is a central element that must be outlined from minute one and be fully integrated with the rest of elements of the pedagogical design. Evaluative model should contemplate strategies for the initial and formative assessment of the participants and of the teaching-learning process itself, and not only be based on the final assessment oriented towards certification

Memoria I Jornada Acceso Abierto a la Información sobre discapacidad en Costa Rica (29 de setiembre de 2014)

Memoria de jornadas -- Consejo Nacional de Rehabilitación y Educación Especial (CNREE). Universidad de Costa Rica. 2014. Las jornadas fueron organizadas por el CNREE y contaron la con la participación de los funcionarios de la Universidad de Costa Rica Jorge Polanco.Cortés, Saray Córdoba González, Rolando Herrera Burgos y Meilyn Garro Acón.Reúne las conferencias presentadas en la I Jornada: Acceso Abierto a la información sobre discapacidad en Costa Rica, efectuada el 29 de setiembre de 2014, por el Consejo Nacional de Rehabilitación y Educación Especial (CNREE), ente rector de discapacidad en Costa Rica. La presente memoria, aporta la reseña biográfica de las personas que participaron como conferencistas en la actividad, las conferencias dictadas y el resumen de la mayoría de las intervenciones. Los temas abordados en las exposiciones, están relacionados con áreas como: acceso abierto y su papel en la investigación, software libre, pautas para la creación de repositorios digitales, derechos de autor, acceso a la información digital y la gestión de información sobre discapacidad como un reto para Costa Rica. Esta I Jornada contó con la participación de sesenta y seis personas, quienes representaron a instituciones y universidades públicas, empresa privada, organizaciones no gubernamentales. Además asistieron estudiantes universitarios y personas con discapacidad. Al final del documento, se incorpora el resultado de una consulta dirigida a las personas participantes, de cara a la creación de un repositorio de documentos electrónicos sobre discapacidad y a mejorar la calidad de futuras jornadas de este tema. Agradecemos de manera muy especial a las y los conferencistas que participaron en esta I Jornada: Acceso Abierto a la información sobre discapacidad en Costa Rica. Muchas gracias por sus excelentes aportes y por compartir nuestra visión. Un reconocimiento para la Sra. Ivette Herrera Arias, por el trabajo de transcripción de las grabaciones de cada una de las conferencias dictadas en esta I Jornada. Finalmente, a la Unidad de Investigación e Innovación del CNREE le es muy grato comunicar que, según la MSc. Saray Córdoba González, conferencista en esta Jornada, esta es la primera actividad sobre Acceso Abierto que se efectúa fuera de la Universidad de Costa Rica.Consejo Nacional de Rehabilitación y Educación Especial (CNREE)Universidad de Costa RicaUCR::Vicerrectoría de Investigació

Comparison of Different Procedural Approaches for Left Atrial Appendage Closure: Searching for Simplicity

To assess procedural and long-term efficacy and safety of two alternative methods for appendage closure, conscious sedation with standard transoesophageal echo and procedure guided by rotational angiography. Background. Demand for appendage closure is increasing, and a reasonable time-response should be given to nonvalvular atrial fibrillation patients not suitable to receive anticoagulation. General anesthesia and the need for an anesthesiologist are limiting factors to improve procedure availability; it is time to introduce simpler approaches. Methods. Single center experience in appendage closure during 9 years, using three different procedural approaches: general anesthesia with echo guidance, conscious sedation with echo guidance, and rotational angiography guidance. Conscious sedation and rotational angiography-guided procedures were performed in the absence of an anesthesiologist. Procedural characteristics and follow-up events were recorded. Results. 260 consecutive appendage closure procedures were reviewed: 155 were performed under general anesthesia (59.6%), 71 were performed with conscious sedation (27.3%), and 34 were rotational angiography guided (13.1%). Device success rate for procedures guided by rotational angiography was significantly lower than that for general anesthesia and conscious sedation (91.2% versus 100% versus 98.6%, p � 0.001) because there was a greater need to recapture and change device size. However, final procedural success was high and without difference between approaches (98.8% versus 97.2% versus 100%, for general anesthesia, conscious sedation, and rotational angiography, respectively); with a median follow-up of 17 months (CI 95% 13–23 month) (637.9 patients-year), there was no difference among approaches for thromboembolic (1.3 versus 1.8 versus 1.8) and major bleeding events (3.2 versus 2.8 versus 1.8), respectively. Conclusions. Appendage closure performed, either with conscious sedation with echo guidance or rotational angiography guided, is feasible, with no difference in procedural success and follow-up events compared with general anesthesia and without the limitation of the need for an anesthesiologist on-site

Performance of artificial neural networks and genetical evolved artificial neural networks unfolding techniques

With the Bonner spheres spectrometer neutron spectrum is obtained through an unfolding procedure. Monte Carlo methods, Regularization, Parametrization, Least-squares, and Maximum Entropy are some of the techniques utilized for unfolding. In the last decade methods based on Artificial Intelligence Technology have been used. Approaches based on Genetic Algorithms and Artificial Neural Networks have been developed in order to overcome the drawbacks of previous techniques. Nevertheless the advantages of Artificial Neural Networks still it has some drawbacks mainly in the design process of the network, vg the optimum selection of the architectural and learning ANN parameters. In recent years the use of hybrid technologies, combining Artificial Neural Networks and Genetic Algorithms, has been utilized to. In this work, several ANN topologies were trained and tested using Artificial Neural Networks and Genetically Evolved Artificial Neural Networks in the aim to unfold neutron spectra using the count rates of a Bonner sphere spectrometer. Here, a comparative study of both procedures has been carried out

A major role of TWEAK/Fn14 axis as a therapeutic target for post-angioplasty restenosis

Background: Tumor necrosis factor-like weak inducer of apoptosis (Tnfsf12; TWEAK) and its receptor Fibroblast growth factor-inducible 14 (Tnfrsf12a; Fn14) participate in the inflammatory response associated with vascular remodeling.However, the functional effect ofTWEAK on vascular smoothmuscle cells (VSMCs) is not completely elucidated. Methods: Next generation sequencing-based methodswere performed to identify genes and pathways regulated by TWEAK in VSMCs. Flow-citometry, wound-healing scratch experiments and transwellmigration assays were used to analyze VSMCs proliferation and migration. Mouse wire injury model was done to evaluate the role of TWEAK/Fn14 during neointimal hyperplasia. Findings: TWEAK up-regulated 1611 and down-regulated 1091 genes in VSMCs. Using a gene-set enrichment method,we found a functionalmodule involved in cell proliferation defined as the minimal network connecting top TWEAK up-regulated genes. In vitro experiments in wild-type or Tnfrsf12a deficient VSMCs demonstrated that TWEAK increased cell proliferation, VSMCs motility and migration. Mechanistically, TWEAK increased cyclins (cyclinD1), cyclin-dependent kinases (CDK4, CDK6) and decreased cyclin-dependent kinase inhibitors (p15lNK4B) mRNA and protein expression. Downregulation of p15INK4B induced by TWEAK was mediated by mitogen-activated protein kinase ERK and Akt activation. Tnfrsf12a or Tnfsf12 genetic depletion and pharmacological intervention with TWEAK blocking antibody reduced neointimal formation, decreasing cell proliferation, cyclin D1 and CDK4/6 expression, and increasing p15INK4B expression compared with wild type or IgG-treated mice in wire-injured femoral arteries. Finally, immunohistochemistry in human coronary arteries with stenosis or in-stent restenosis revealed high levels of Fn14, TWEAK and PCNA in VSMCs enriched areas of the neointima as compared with healthy coronary arteries. Interpretation: Our data define a major role of TWEAK/Fn14 in the control of VSMCs proliferation and migration during neointimal hyperplasia after wire injury in mice, and identify TWEAK/Fn14 as a potential target for treating in-stent restenosis.This work was supported by Instituto de Salud Carlos III (Fondo de Investigaciones Sanitarias ISCiii/FEDER PI13/00395; PI16/01419; PI17/ 01495) and Spanish Biomedical Research Centre in Cardiovascular Disease (CIBERCV) and Metabolic Diseases and Diabetes (CIBERDEM). PM was supported by ISCIII Miguel Servet Program (CP16/00116). CGM was supported by Fundación Conchita Rábago. NMB and VE were supported by the Spanish Ministry of Economy and Competitiveness (Juan de la Cierva IJCI-2016-29630 and Ramón y Ramón Cajal Program RyC-2013-12880, respectively). JMM has been supported a postdoctoral fellowship fromthe American Diabetes Association (Grant 1-15-MI-03) and a postdoctoral fellowship fromthe American Heart Association