Suchergebnisse

The Inspectorate of Barcelona coordinates a project that FEAEC (European Forum of Educational Administrators of Catalonia) and six secondary schools are involved: Ernest Lluch, Miquel Tarradell, and La Guineueta (public schools) and Joan Pelegri, Proa, and Virolai (private schools founded by the state). This is a "Comenius Regio" Regional Development Programme 2013-2015 between Sheffield and Barcelona with reference to the theme: "Reducing Early School Leaving" (RESL). The Council of Europe establish Early School Leaving as "the percentage of young people between 18 and 24 years, at most, have passed the compulsory secondary education and not in education nor training continue". In our country, we are concerned about students who complete lower secondary education, although we cannot forget that the objectives of the Spanish and European political system success lie in universal upper secondary they can graduate. One of the products developed in the project has been the adaptation of RONI (an individual indicator of risk of dropouts) and its experimental application. ; La inspección de Barcelona coordina un proyecto en el que participan el FEAEC (Fórum Europeo de Administradores de la Educación de Cataluña) y seis centros docentes (Institutos: Ernest Lluch, La Guineueta y Miquel Tarradell y las escuelas concertadas: Joan Pelegrí, Proa i Virolai. Se trata de un Programa "Comenius regio" 2013-2015 de Desarrollo Regional entre Sheffield y Barcelona con referencia al tema: "Reducción del abandono escolar prematuro" (RESL: Reducing Early School Leaving). El Consejo de Europa establece con este concepto "el porcentaje de jóvenes entre 18 y 24 años que, como máximo, han superado la educación secundaria obligatoria y no continúan ni estudiando ni formándose". En nuestro país nos sigue preocupando que puedan graduar los alumnos que terminan la ESO, aunque no podemos olvidar que los objetivos de la política española y europea sitúan el éxito del sistema en la universalización de la secundaria postobligatoria. Uno de los ...

Altres ajuts: The authors research is supported by projects from Ministerio de Ciencia, Innovación y Universidades of Spain, CIBERNED and TERCEL funds from the Instituto de Salud Carlos III of Spain, co-funded by European Union (ERDF/ESF, "Investing in your future"). ; Peripheral nerve injuries result in the loss of the motor, sensory and autonomic functions of the denervated segments of the body. Neurons can regenerate after peripheral axotomy, but inaccuracy in reinnervation causes a permanent loss of function that impairs complete recovery. Thus, understanding how regenerating axons respond to their environment and direct their growth is essential to improve the functional outcome of patients with nerve lesions. Schwann cells (SCs) play a crucial role in the regeneration process, but little is known about their contribution to specific reinnervation. Here, we review the mechanisms by which SCs can differentially influence the regeneration of motor and sensory axons. Mature SCs express modality-specific phenotypes that have been associated with the promotion of selective regeneration. These include molecular markers, such as L2/HNK-1 carbohydrate, which is differentially expressed in motor and sensory SCs, or the neurotrophic profile after denervation, which differs remarkably between SC modalities. Other important factors include several molecules implicated in axon-SC interaction. This cell-cell communication through adhesion (e.g., polysialic acid) and inhibitory molecules (e.g., MAG) contributes to guiding growing axons to their targets. As many of these factors can be modulated, further research will allow the design of new strategies to improve functional recovery after peripheral nerve injuries.

Intraneural electrodes must be in intimate contact with nerve fibers to have a proper function, but this interface is compromised due to the foreign body reaction (FBR). The FBR is characterized by a first inflammatory phase followed by a second anti-inflammatory and fibrotic phase, which results in the formation of a tissue capsule around the implant, causing physical separation between the active sites of the electrode and the nerve fibers. We have tested systemically several anti-inflammatory drugs such as dexamethasone (subcutaneous), ibuprofen and maraviroc (oral) to reduce macrophage activation, as well as clodronate liposomes (intraperitoneal) to reduce monocyte/macrophage infiltration, and sildenafil (oral) as an antifibrotic drug to reduce collagen deposition in an FBR model with longitudinal Parylene C intraneural implants in the rat sciatic nerve. Treatment with dexamethasone, ibuprofen, or clodronate significantly reduced the inflammatory reaction in the nerve in comparison to the saline group after 2 weeks of the implant, whereas sildenafil and maraviroc had no effect on infiltration of macrophages in the nerve. However, only dexamethasone was able to significantly reduce the matrix deposition around the implant. Similar positive results were obtained with dexamethasone in the case of polyimide-based intraneural implants, another polymer substrate for the electrode. These results indicate that inflammation triggers the FBR in peripheral nerves, and that anti-inflammatory treatment with dexamethasone may have beneficial effects on lengthening intraneural interface functionality. ; Grant sponsors: European Union FPT‐ICT project NEBIAS (contract number 611687), FEDER, CERCA programme of Generalitat de Catalunya (ICN2); Grant sponsor: TERCEL; Grant number: RD12/0019/0011; Grant sponsor: CIBERNED; Grant number: CB06/05/1105 (Instituto de Salud Carlos III of Spain); Grant sponsor: Severo Ochoa programme of the Spanish Ministry of Economy, Industry and Competitiveness (MINECO; ICN2); Grant number: SEV‐2013‐0295. ; Peer reviewed

Neuroprostheses aimed to restore lost functions after a limb amputation are based on the interaction with the nervous system by means of neural interfaces. Among the different designs, intraneural electrodes implanted in peripheral nerves represent a good strategy to stimulate nerve fibers to send sensory feedback and to record nerve signals to control the prosthetic limb. However, intraneural electrodes, as any device implanted in the body, induce a foreign body reaction (FBR) that results in the tissue encapsulation of the device. The FBR causes a progressive decline of the electrode functionality over time due to the physical separation between the electrode active sites and the axons to the interface. Modulation of the inflammatory response has arisen as a good strategy to reduce the FBR and maintain electrode functionality. In this paper, transversal intraneural multi-channel electrodes (TIMEs) were implanted in the rat sciatic nerve and tested for three months to evaluate stimulation and recording capabilities under chronic administration of dexamethasone. Dexamethasone treatment significantly reduced the threshold for evoking muscle responses during the follow-up compared to saline-treated animals, without affecting the selectivity of stimulation. However, dexamethasone treatment did not improve the signal-to-noise ratio of the recorded neural signals. Dexamethasone treatment allowed to maintain more working active sites along time than saline treatment. Thus, systemic administration of dexamethasone appears as a useful treatment in chronically implanted animals with neural electrodes as it increases the number of functioning contacts of the implanted TIME and reduces the intensity needed to stimulate the nerve. ; This research was supported by the European Union FPTICT projects NEBIAS (contract number FP7-611687), EPIONE (FP7-602547), FEDER and by the European Union's Horizon 2020 Graphene Flagship Core Project 2 (grant agreement 785219) and FLAG-ERA JTC 2017 project GRAFIN, by TERCEL (RD12/0019/0011) and CIBERNED (CB06/05/1105) funds from the Instituto de Salud Carlos III of Spain, and by Fundación Ramón Areces (CIVP18A3897). The ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant SEV-2013-0295), and by the CERCA Programme/Generalitat de Catalunya. ; Peer reviewed

Altres ajuts: Instituto de Salud Carlos III of Spain, co-funded by European Union. Project number: ERDF/ESF, "Investing in your future" ; The simultaneous contribution of several etiopathogenic disturbances makes amyotrophic lateral sclerosis (ALS) a fatal and challenging disease. Here, we studied two different cell therapy protocols to protect both central and peripheral nervous system in a murine model of ALS. Since ALS begins with a distal axonopathy, in a first assay, we performed injection of bone marrow cells into two hindlimb muscles of transgenic SOD1 G93A mice. In a second study, we combined intramuscular and intraspinal injection of bone marrow cells. Fluorescence-activated cell sorting was used to assess the survival of the transplanted cells into the injected tissues. The mice were assessed from 8 to 16 weeks of age by means of locomotion and electrophysiological tests. After follow-up, the spinal cord was processed for analysis of motoneuron survival and glial cell reactivity. We found that, after intramuscular injection, bone marrow cells were able to engraft within the muscle. However, bone marrow cell intramuscular injection failed to promote a general therapeutic effect. In the second approach, we found that bone marrow cells had limited survival in the spinal cord, but this strategy significantly improved motor outcomes. Moreover, we also found that the dual cell therapy tended to preserve spinal motoneurons at late stages of the disease and to reduce microgliosis, although this did not prolong mice survival. Overall, our findings suggest that targeting more than one affected area of the motor system at once with bone marrow cell therapy results in a valuable therapeutic intervention for ALS.

Objective. It is known that multi-site interleaved stimulation generates less muscle fatigue compared to single-site synchronous stimulation. However, in the limited number of studies in which intramuscular electrodes were used, the fatigue reduction associated with interleaved stimulation could not consistently be achieved. We hypothesize that this could be due to the inability to place the intramuscular electrodes used in interleaved stimulation in locations that minimize overlap amongst the motor units activated by the electrodes. Our objective in the present study was to use independent intramuscular electrodes to compare fatigue induced by interleaved stimulation with that generated by synchronous stimulation at the same initial force and ripple. Approach. In the medial gastrocnemius muscle of an anesthetized rabbit (n = 3), ten intramuscular hook wire electrodes were inserted at different distances from the nerve entry. Overlap was measured using the refractory technique and only three electrodes were found to be highly independent. After ensuring that forces obtained by both stimulation modalities had the same ripple and magnitude, fatigue induced during interleaved stimulation across three independent distal electrodes was compared to that obtained by synchronously delivering pulses to a single proximal electrode. Main results. Contractions evoked by interleaved stimulation exhibited less fatigue than those evoked by synchronous stimulation. Twitch force recruitment curves collected from each of the ten intramuscular electrodes showed frequent intermediate plateaus and the force value at these plateaus decreased as the distance between the electrode and nerve entry increased. Significance. The results indicate that interleaved intramuscular stimulation is preferred over synchronous intramuscular stimulation when fatigue-resistant and smooth forces are desired. In addition, the results suggest that the large muscle compartments innervated by the primary intramuscular nerve branches give rise to progressively smaller independent compartments in subsequent nerve divisions. ; This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement No. 724244). AI gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. JdV and XN were supported by project GRAFIN PCI2018-093029, funded by Ministerio de Ciencia, Innovación y Universidades and European Union ERDF/ESF.

Introdução: O Transtorno do Espectro do Autismo (TEA) é um transtorno do neurodesenvolvimento. Algumas características marcantes do transtorno são as dificuldades na comunicação e na linguagem, elementos importantes para o diagnóstico precoce. Objetivo: Investigar as habilidades de comunicação de um grupo de crianças com transtorno do espectro do autismo e a relação com a faixa etária e intervenção fonoaudiológica. Método: Participaram da pesquisa, 11 crianças com TEA, entre dois e sete anos de idade, atendidas numa Clínica-Escola de Fonoaudiologia. Para a avaliação do perfil funcional da comunicação, foi utilizado o protocolo ACOTEA – Avaliação da Comunicação no Transtorno do Espectro do Autismo. Após duas sessões com jogos e brinquedos para estabelecer as situações comunicativas, os terapeutas responderam trinta e seis afirmativas, relacionadas à comunicação (expressão, compreensão e comportamento social). Além disso, foram coletados dados na anamnese sobre idade, sexo e se a criança já tinha se submetido à intervenção fonoaudiológica com comunicação ampliada e alternativa. Resultados: De acordo com os resultados, foram observados déficits nas habilidades expressivas (pragmáticas e morfossintáticas); na atenção compartilhada e em habilidades relacionadas à interação com o ambiente. Foi observado que as crianças entre cinco a sete anos apresentaram melhor desempenho na atenção compartilhada, no brincar funcional e em responderem ao nome. E as crianças que foram submetidas à intervenção com comunicação alternativa apresentaram melhora significativa na atenção compartilhada. Conclusão: Os resultados obtidos demonstram que há relação entre as habilidades comunicativas e faixa etária e que a intervenção com comunicação alternativa contribui para o desenvolvimento da atenção compartilhada.

Amyotrophic lateral sclerosis (ALS) is a lethal motor neuron disease with no cure. Currently there are only two ALS drugs approved by the FDA, both with a limited therapeutic effect. In the search for drug candidates for ALS, we studied the effect of known stem cell mobilizing agents (treatment) and antimetabolite 5-fluorouracil (5-FU) (anti-treatment) in SOD1G93A model of ALS. Surprisingly, we found that anti-cancer drug 5-FU increases lifespan, delays the disease onset and improves motor performance in ALS mice. Although we were not able to demonstrate the mechanistic basis of the beneficial 5-FU action in ALS mice, our findings suggest that 5-FU or similar drugs are possible drug candidates for the treatment of motor neuron diseases through drug repurposing. ; This work was funded by Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) from the European Union (Grants PI14/00947 and PI17/00949), Asociación Adelante de La Roda, Plataforma Afectados por la ELA, Asociación Juntos Venceremos ELA, AVPA Zaragoza (RO), TERCEL (RD12/0019/0011 and RD16/0011/0035) and CIBERNED (CB06/05/1105) funds from the Instituto de Salud Carlos III of Spain (XN), and Fondazione Roma and Agenzia Spaziale Italiana (AM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Here we used a systems biology approach and artificial intelligence to identify a neuroprotective agent for the treatment of peripheral nerve root avulsion. Based on accumulated knowledge of the neurodegenerative and neuroprotective processes that occur in motoneurons after root avulsion, we built up protein networks and converted them into mathematical models. Unbiased proteomic data from our preclinical models were used for machine learning algorithms and for restrictions to be imposed on mathematical solutions. Solutions allowed us to identify combinations of repurposed drugs as potential neuroprotective agents and we validated them in our preclinical models. The best one, NeuroHeal, neuroprotected motoneurons, exerted anti-inflammatory properties and promoted functional locomotor recovery. NeuroHeal endorsed the activation of Sirtuin 1, which was essential for its neuroprotective effect. These results support the value of network-centric approaches for drug discovery and demonstrate the efficacy of NeuroHeal as adjuvant treatment with surgical repair for nervous system trauma. ; This work was mainly supported by a grant from Fundació La Marató-TV3 (#110432, CC, AB & VP) that funded the work and contracts of TLR and MHG and partially by the Ministerio de Economía y Competitividad of Spain (#SAF 2014-59701, CC, DRG, & TLR). We are also grateful for support from CIBERNED and funding from the European Union Seventh Framework Programme for research, technological development, and demonstration (#306240, XN, FRP & CC). Part of the research leading to these results has also received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 306240. ; Peer reviewed