914 resultados para Formal and informal channels
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Exposure to perinatal hypoxia results in alteration of the adult pulmonary circulation, which is linked among others to alterations in K channels in pulmonary artery (PA) smooth muscle cells. In particular, large conductance Ca-activated K (BKCa) channels protein expression and activity were increased in adult PA from mice born in hypoxia compared with controls. We evaluated long-term effects of perinatal hypoxia on the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway-mediated activation of BKCa channels, using isoproterenol, forskolin, and dibutyryl-cAMP. Whole-cell outward current was higher in pulmonary artery smooth muscle cells from mice born in hypoxia compared with controls. Spontaneous transient outward currents, representative of BKCa activity, were present in a greater proportion in pulmonary artery smooth muscle cells of mice born in hypoxia than in controls. Agonists induced a greater relaxation in PA of mice born in hypoxia compared with controls, and BKCa channels contributed more to the cAMP/PKA-mediated relaxation in case of perinatal hypoxia. In summary, perinatal hypoxia enhanced cAMP-mediated BKCa channels activation in adult murine PA, suggesting that this pathway could be a potential target for modulating adult pulmonary vascular tone after perinatal hypoxia.
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RESUME :Introduction. Les maladies cardiovasculaires représentent la première cause de mortalité dans les pays développés et l'insuffisance cardiaque (IC) est la plus fréquente. Suite à un infarctus, le coeur des patients subit un remodelage ventriculaire pouvant évoluer vers un état d'IC. L'IC se définit comme un état dans lequel le coeur n'est plus capable d'approvisionner suffisamment les organes et cet état s'accompagne souvent de troubles du rythme cardiaque. Le remodelage ventriculaire touche de nombreux gènes codant à la fois pour les voies métaboliques et pour des canaux ioniques favorisant ainsi l'apparition des arythmies responsables de la mort subite des patients atteints d'IC. Comprendre ce passage entre remodelage et IC est crucial afin de pouvoir un jour prévenir l'IC et les complications médicales qui l'accompagnent. Nous nous sommes intéressés aux canaux potassiques dépendants de l'ATP (KATP) car ces canaux ont la capacité de coupler le métabolisme de la cellule à son activité électrique. En effet, les canaux KATP s'ouvrent quand la charge énergétique (rapport ATP/ ADP) de la cellule chute. Dans les cardiomyocytes, l'ouverture des KATP induit une hyperpolarisation de la membrane cellulaire ce qui diminue indirectement la surcharge calcique et de ce fait préserve la cellule. Les canaux KATp sont formés de 4 sous-unités Kir6.x (Kir6.1 ou Kir6.2) formant le pore du canal associées à 4 sous-unités régulatrices SUR. Les propriétés électrophysiologiques ainsi que la sensibilité pharmacologique des canaux KATP dépendent de leur composition et seuls les canaux KATP formés par la sous-unité Kirô.l sont activés par le diazoxyde.Méthodes et résultats. Nous avons d'abord montré dans un modèle in vivo d'IC chez le rat adulte que les sous-unités Kir6.1 et SUR sont surexprimées dans ces conditions pathologiques. Par ailleurs, les cardiomyocytes issus des coeurs infarcis deviennent sensibles au diazoxyde reflétant la surexpression de Kir6.1. Les potentiels d'action qui sont prolongés dans l'IC et qui sont à l'origine d'arythmies majeures sont normalisés par l'ouverture des canaux KATp induite par le diazoxyde. Ainsi, l'ouverture pharmacologique des canaux KATp contribuerait à la cardio-protection. Dans une seconde partie, nous avons déterminé quels étaient les facteurs de transcription responsables de ce changement d'expression des sous-unités formant les KATP. Dans notre modèle, nous avons pu montrer que la surexpression de Kirô.l est due aux facteurs de transcription Fox03 et FoxF2 qui est aussi responsable de la surexpression des sous-unités SUR. Dans la dernière partie de ce travail, nous avons mis au point un modèle d'IC in vitro en cultivant les cardiomyocytes de rats adultes en présence d'angiotensine II (Angll) ou de TNFa. Ce modèle expérimental nous a non seulement permis de mettre en relation l'importance de L'AnglI et du TNFa sur le remodelage des canaux KATP mais aussi de développer un modèle in vitro présentant les mêmes caractéristiques que le modèle in vivo concernant le remodelage des KATP lors de l'IC. Ce dernier modèle expérimental ouvre des perspectives afin de mieux caractériser les voies de signalisation impliquées dans le remodelage des canaux KATp lors de l'IC.Conclusion. Les canaux KATp subissent un remodelage lors de l'IC et les résultats obtenus montrent le potentiel cardio-protecteur de ces canaux.ABSTRACT :Background and aim. Cardiovascular disease is the leading cause of death in developed countries and heart failure (HF) is the most common. Following myocardial infarction, the heart of the patient undergoes ventricular remodeling which may evolve toward a state of HF. HF is defined as a state in which heart is unable to supply enough blood to organs and this state is often accompanied by cardiac arrhythmias. Ventricular remodeling involves many genes coding for both metabolic enzymes and ion channels. Changes in ion channel expression can promote arrhythmias responsible for sudden death in patients with HF. A better understanding of the transition between remodeling and HF is crucial in order to prevent the complications associated to HF We were interested in ATP-dependent potassium channels (KATp) because they couple cell metabolism to electrical activity of the cell. Indeed, KATP channels open when the energy charge (ratio of ATP / ADP) of the cell collapses. In cardiomyocytes, the opening of KATP channels induces hyper- polanzation of the cell membrane which reduces calcium overload and thereby protects the cell. KATp channels are composed by 4 Kir6.x subumts (Kir6.1 or Kir6.2) forming the pore channel associated with 4 regulatory subunits SUR. The electrophysiological properties as well as pharmacological sensitivity of KATp channels depend on their composition and only KATP channels formed by Kir6.1 subunit are activated by diazoxide.Methods and results. Firstly, using an in vivo model of HF in adult rats, we showed that Kir6.1 and SUR subunits are overexpressed in HF. In addition, cardiomyocytes from post-infarction hearts became sensitive to diazoxide reflecting the overexpression of the Kir6.1 subunit. The opening of KATP by diazoxide tended to reduce the action potential duration (APD) which is extended in HF. This increase in APD is known to be a major source of arrhythmias during HF. Therefore, the opening of KATP channels by diazoxide would be cardio-protective. Secondly, we wanted to determine which transcription factors were responsible for this KATP remodeling. In our model of HF, we showed that overexpression of Kir6.1 is due to the transcription factors Fox03 and FOXF2 which is also responsible for SUR subunits overexpression. Thirdly, we developed an in vitro model of HF by cultivation of adult rat cardiomyocytes in the presence of angiotensin II (Angll) or TNFa. This model is very interesting not only because it underlines the importance of Angll and TNFa in KATp remodeling but also because this in vitro model presents the same KATP remodeling as the in vivo model of HF. These findings show that our in vitro model of HF opens up many possibilities to investigate more precisely the signaling pathways involved in remodeling of the KATP channels in HF.Conclusion. KATP channels undergo remodeling during HF and our results show the cardio¬protective potential of KATP channels in this disease.
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Astrocytes are the main neural cell type responsible for the maintenance of brain homeostasis. They form highly organized anatomical domains that are interconnected into extensive networks. These features, along with the expression of a wide array of receptors, transporters, and ion channels, ideally position them to sense and dynamically modulate neuronal activity. Astrocytes cooperate with neurons on several levels, including neurotransmitter trafficking and recycling, ion homeostasis, energy metabolism, and defense against oxidative stress. The critical dependence of neurons upon their constant support confers astrocytes with intrinsic neuroprotective properties which are discussed here. Conversely, pathogenic stimuli may disturb astrocytic function, thus compromising neuronal functionality and viability. Using neuroinflammation, Alzheimer's disease, and hepatic encephalopathy as examples, we discuss how astrocytic defense mechanisms may be overwhelmed in pathological conditions, contributing to disease progression.
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La relación educativa entraña, inevitablemente, el debate entorno de la verticalidad y del ejercicio del poder. De qué modo nos relacionamos y cómo gestionamos la comunicación entre educadores y educandos, así como entre iguales. Esa tensión se ve amplificada en la medida que incorporamos lógicas evaluativas en nuestro quehacer profesional. La siguiente comunicación describe la experiencia de la metodología de aprendizaje basada en la evaluación entre iguales aplicada a la profesionalización de los y las educadores/as sociales. Tanto a nivel escolar como en el universitario hay numerosas experiencias publicadas en relación a la metodología de evaluación entre iguales. Además, existen numerosos apartados de los “Documentos profesionalizadores” donde se justifica el hecho de que se entrenen algunas habilidades que deberían darse en la práctica profesional (como por ejemplo en la definición, en el código ético, y en el catálogo de funciones y competencias del/la educador/a social). En esta comunicación pretendemos dar a conocer la experiencia de entrenamiento de futuros educadores en aspectos que tienen una relación directa con la evaluación entre educadores/as sociales. Así pues, utilizaremos una justificación académica y metodológica de la actividad, enlazándola con los documentos profesionalizadores con un fin relacionado directamente con el ejercicio de la profesión.
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This paper studies the extent to which social networks influence the employment stability and wages of immigrants in Spain. By doing so, I consider an aspect that has not been previously addressed in the empirical literature, namely the connection between immigrants' social networks and labor market outcomes in Spain. For this purpose, I use micro-data from the National Immigrant Survey carried out in 2007. The analysis is conducted in two stages. First, the impact of social networks on the probability of keeping the first job obtained in Spain is studied through a multinomial logit regression. Second, quantile regressions are used to estimate a wage equation. The empirical results suggest that once the endogeneity problem has been accounted for, immigrants' social networks influence their labor market outcomes. On arrival, immigrants experience a mismatch in the labor market. In addition, different effects of social networks on wages by gender and wage distribution are found. While contacts on arrival and informal job access mechanisms positively influence women's wages, a wage penalty is observed for men.
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El proyecto consiste en la creación de un CRM de contact center con canal de telefonía y correo electrónico. Se ha llevado a cabo utilizando software libre. Se integra con centralita telefónica para permitir la realización de llamadas por Voip.
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Modern urban lifestyle encourages the prolongation of wakefulness, leaving less and less time for sleep. Although the exact functions of sleep remain one of the biggest mysteries in neuroscience, the society is well aware of the negative consequences of sleep loss on human physical and mental health and performance. Enhancing sleep's recuperative functions might allow shortening sleep duration while preserving the beneficial effects of sleep. During sleep, brain activity oscillates across a continuum of frequencies. Individual oscillations have been suggested to underlie distinct functions for sleep and cognition. Gaining control about individual oscillations might allow boosting their specific functions. Sleep spindles are 11 - 15 Hz oscillations characteristic for light non-rapid-eye-movement sleep (NREMS) and have been proposed to play a role in memory consolidation and sleep protection against environmental stimuli. The reticular thalamic nucleus (nRt) has been identified as the major pacemaker of spindles. Intrinsic oscillatory burst discharge in nRt neurons, arising from the interplay of low-threshold (T-type) Ca2+ channels (T channels) and small conductance type 2 (SK2) K+ channels (SK2 channels), underlies this pacemaking function. In the present work we investigated the impact of altered nRt bursting on spindle generation during sleep by studying mutant mice for SK2 channels and for CaV3.3 channels, a subtype of T channels. Using in vitro electrophysiology I showed that nRt bursting was abolished in CaV3.3 knock out (CaV3.3 KO) mice. In contrast, in SK2 channel over-expressing (SK2-OE) nRt cells, intrinsic repetitive bursting was prolonged. Compared to wildtype (WT) littermates, altered nRt burst discharge lead to weakened thalamic network oscillations in vitro in CaV3.3 KO mice, while oscillatory activity was prolonged in SK2-OE mice. Sleep electroencephalographic recordings in CaV3.3 KO and SK2-OE mice revealed that reduced or potentiated nRt bursting respectively weakened or prolonged sleep spindle activity at the NREMS - REMS transition. Furthermore, SK2-OE mice showed more consolidated NREMS and increased arousal thresholds, two correlates of good sleep quality. This thesis work suggests that CaV3.3 and SK2 channels may be targeted in order to modulate sleep spindle activity. Furthermore, it proposes a novel function for spindles in NREMS consolidation. Finally, it provides evidence that sleep quality may be improved by promoting spindle activity, thereby supporting the hypothesis that sleep quality can be enhanced by modulating oscillatory activity in the brain. Le style de vie moderne favorise la prolongation de l'éveil, laissant de moins en moins de temps pour le sommeil. Même si le rôle exact du sommeil reste un des plus grands mystères des neurosciences, la société est bien consciente des conséquences négatives que provoque un manque de sommeil, à la fois sur le plan de la santé physique et mentale ainsi qu'au niveau des performances cognitives. Augmenter les fonctions récupératrices du sommeil pourrait permettre de raccourcir la durée du sommeil tout en en conservant les effets bénéfiques. Durant le sommeil, on observe des oscillations à travers un continuum de fréquences. Il a été proposé que chaque oscillation pourrait être à l'origine de fonctions spécifiques pour le sommeil et la cognition. Pouvoir de contrôler les oscillations individuelles permettrait d'augmenter leurs fonctions respectives. Les fuseaux sont des oscillations de 11 à 15 Hz caractéristiques du sommeil à ondes lentes léger et il a été suggéré qu'elles jouent un rôle majeur pour la consolidation de la mémoire ainsi que dans la protection du sommeil contre les stimuli environnementaux. Le nucleus réticulaire du thalamus (nRt) a été identifié en tant que générateur de rythme des fuseaux. Les bouffées oscillatoires intrinsèques des neurones du nRt, provenant de l'interaction de canaux calciques à bas seuil de type T (canaux T) et de canaux potassiques à faible conductance de type 2 (canaux SK2), sont à l'origine de la fonction de générateur de rythme. Dans ce travail, j'ai étudié l'impact de la modulation de bouffées de nRT sur la génération des fuseaux pendant le sommeil en investiguant des souris génétiquement modifiées pour les canaux SK2 et les canaux CaV3.3, un sous-type de canaux T. En utilisant l'électrophysiologie in vitro j'ai démontré que les bouffées du nRT étaient abolies dans les souris knock-out du type CaV3.3 (CaV3.3 KO). D'autre part, dans les cellules nRT sur-exprimant les canaux SK2 (SK2-OE), les bouffées oscillatoires intrinsèques étaient prolongées. Par rapport aux souris wild type, les souris CaV3.3 KO ont montré un affaiblissement des oscillations thalamiques en réponse à un changement des bouffées de nRT, alors que l'activité oscillatoire était prolongée dans les souris SK2-OE. Des enregistrements EEG du sommeil dans des souris de type CaV3.3 KO et SK2-OE ont révélé qu'une réduction ou augmentation des bouffées nRT ont respectivement affaibli ou prolongé l'activité des fuseaux durant les transitions du sommeil à ondes lentes au sommeil paradoxal. De plus, les souris SK2-OE ont montré des signes de consolidation du sommeil à ondes lentes et un seuil augmenté pour le réveil, deux mesures qui corrèlent avec une bonne qualité du sommeil. Le travail de cette thèse propose que les canaux CaV3.3 et SK2 pourrait être ciblés pour moduler l'activité des fuseaux. De plus, je propose une fonction nouvelle pour les fuseaux dans la consolidation du sommeil à ondes lentes. Finalement je suggère que la qualité du sommeil peut être améliorée en promouvant l'activité des fuseaux, soutenant ainsi l'idée que la qualité du sommeil peut être améliorée en modulant l'activité oscillatoire dans le cerveau.
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O objetivo deste estudo é avaliar a percepção do adolescente obeso sobre as repercussões da obesidade em sua saúde. Baseou-se no relato de quinze adolescentes obesos, acompanhados no Ambulatório do Hospital das Clínicas da Universidade Federal de Pernambuco, no período de abril a julho de 2007. Os depoimentos, obtidos através de entrevista semi-estruturada, foram submetidos à análise de conteúdo, modalidade temática transversal. Foram identificadas quatro temáticas relacionadas com os objetivos do estudo: 1. A percepção do conceito de obesidade; 2. A obesidade afetando a auto-imagem; 3. Obesidade versus Saúde e 4. O difícil retorno à saúde. Os adolescentes perceberam a obesidade como doença, repercutindo negativamente sobre sua saúde, apresentando uma baixa auto-estima e a sensação de isolamento. Reconhecem que ser saudável é ter uma alimentação correta e praticar atividade física, sendo imprescindível o apoio formal e informal, sobrepujando as dificuldades para manter uma qualidade de vida satisfatória.
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Este estudo tem como objetivo compreender a experiência materna no cuidado ao filho dependente de tecnologia. Utilizamos a abordagem do estudo de caso etnográfico tendo como instrumentos de coleta de dados os genograma e ecomapa, entrevista aberta e observação. Os dados foram organizados em três unidades de significados: a busca pelas causas e por culpados; a alta hospitalar e as demandas para o cuidado e as redes de apoio. O estudo permitiu conhecer a experiência materna em busca por explicações, bem como os sentimentos de desconfiança, insegurança e insatisfação relacionados ao serviço de saúde. Ainda a apropriação da mãe em relação aos cuidados à criança e no que se refere à organização do ambiente domiciliar para recebê-la, a utilização das redes de apoio, destacando a carência de vínculos com familiares e vizinhos e a busca formal e informal para garantir a subsistência da criança doente e dos demais filhos.
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Aquest treball fa un estudi dels baixonets a Catalunya des de les perspectives organològica, funcional i del repertori. A partir de les informacions aportades pels instruments originals, pels tractats i per estudis especialitats, es defineixen una tipologia instrumental pròpiament hispànica, i unes funcions principalment relacionades amb la música vocal religiosa de mitjans del segle XVI a mitjans del segle XVIII. Posteriorment, es realitza un estudi de la música amb baixonet a la localitat de Canet de Mar. A partir del treball de camp al seu arxiu parroquial, es compilen vuit obres específiques per a baixonet, se'n transcriuen alguns manuscrits, i se'n defineixen els principals aspectes formals i funcionals. El cas de Canet de Mar es pot considerar com un exemple més o menys representatiu de la pràctica instrumental i del repertori específic del baixonet a Catalunya a finals del segle XVII i començaments del segle XVIII.
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The organisation of inpatient care provision has undergone significant reform in many southern European countries. Overall across Europe, public management is moving towards the introduction of more flexibility and autonomy . In this setting, the promotion of the further decentralisation of health care provision stands out as a key salient policy option in all countries that have hitherto had a traditionally centralised structure. Yet, the success of the underlying incentives that decentralised structures create relies on the institutional design at the organisational level, especially in respect of achieving efficiency and promoting policy innovation without harming the essential principle of equal access for equal need that grounds National Health Systems (NHS). This paper explores some of the specific organisational developments of decentralisation structures drawing from the Spanish experience, and particularly those in the Catalonia. This experience provides some evidence of the extent to which organisation decentralisation structures that expand levels of autonomy and flexibility lead to organisational innovation while promoting activity and efficiency. In addition to this pure managerial decentralisation process, Spain is of particular interest as a result of the specific regional NHS decentralisation that started in the early 1980 s and was completed in 2002 when all seventeen autonomous communities that make up the country had responsibility for health care services.Already there is some evidence to suggest that this process of decentralisation has been accompanied by a degree of policy innovation and informal regional cooperation. Indeed, the Spanish experience is relevant because both institutional changes took place, namely managerial decentralisation leading to higher flexibility and autonomy- alongside an increasing political decentralisation at the regional level. The coincidence of both processes could potentially explain why some organisation and policy innovation resulting from policy experimentation at the regional level might be an additional featureto take into account when examining the benefits of decentralisation.
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Nesta dissertação procura-se analisar a problemática da “Centralização versus Descentralização na Governação do Sistema Educativo de Cabo Verde: lógicas em análise” no período compreendido entre (1975 a 2006). Constata-se que Cabo Verde, depois de se tornar um país soberano e independente, assistiu a momentos de grande concentração e de grande centralização na administração do Sistema Educativo. Ao longo deste período assistiuse também a momentos de desconcentração e de ideias de descentralização que culminaram com a abertura do sistema político pluripartidário. Essa abertura abriu a possibilidade de uma nova dinâmica de transformação nos deferentes sectores da administração do sistema educacional. As mudanças políticas verificadas no país, permite-nos conhecer e desocultar as razões, as lógicas e as racionalidades que presidem a manutenção de um sistema centralizado de governação do Sistema Educativo, apesar da presença de forças políticas com diversidades ideológicas. Uma vez conhecido o historial da organização, administração e gestão do Sistema Educativo Cabo-verdiano, a partir de uma retrospectiva histórica, debruçámo-nos sobre as principais teorias que estão na base das perspectivas da centralização e descentralização, e seus conceitos associados enquanto modelo de análise teórica, para tentar perceber este aparente paradoxo. Na parte empírica, a metodologia utilizada apoia-se na abordagem qualitativa de investigação, na qual utilizámos a entrevista, a análise documental e conversas informais, que nos permitiram confirmar ou infirmar a problemática inicialmente formulada. Os dados obtidos dez entrevistados, nomeadamente os responsáveis da política educativa, os administradores do sistema, e os directores dos estabelecimentos de ensino público, levam-nos a tirar várias conclusões sobre um Sistema Educativo centralizado, com uma relativa margem de autonomia. Apesar de encontrarem algumas vantagens no modelo centralizado, a maioria dos entrevistados sublinha a relevância da opção por um modelo descentralizado de governação do Sistema Educativo.
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We provide here a detailed protocol for studying the changes in electrical surface potential of leaves. This method has been developed over the years by plant physiologists and is currently used in different variants in many laboratories. The protocol records surface potential changes to measure long-distance electrical signals induced by diverse stimuli such as leaf wounding or current injection. This technique can be used to determine signaling speeds, to measure the connectivity between different plant organs and-by exploiting mutant plants-to identify transporters and ion channels involved in electrical signaling. The approach can be combined with the analysis of mRNA expression and of metabolite concentrations to correlate electrical signaling to specific physiological events. We describe how to use this protocol on Arabidopsis, looking at the effects of leaf wounding; however, it is broadly applicable to other plants and can be used to study other aspects of plant physiology. After wound infliction, surface potential recording takes ∼20 min per plant.
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The common feature of urea cycle diseases (UCD) is a defect in ammonium elimination in liver, leading to hyperammonemia. This excess of circulating ammonium eventually reaches the central nervous system, where the main toxic effects of ammonium occur. These are reversible or irreversible, depending on the age of onset as well as the duration and the level of ammonium exposure. The brain is much more susceptible to the deleterious effects of ammonium during development than in adulthood, and surviving UCD patients may develop cortical and basal ganglia hypodensities, cortical atrophy, white matter atrophy or hypomyelination and ventricular dilatation. While for a long time, the mechanisms leading to these irreversible effects of ammonium exposure on the brain remained poorly understood, these last few years have brought new data showing in particular that ammonium exposure alters several amino acid pathways and neurotransmitter systems, cerebral energy, nitric oxide synthesis, axonal and dendritic growth, signal transduction pathways, as well as K(+) and water channels. All these effects of ammonium on CNS may eventually lead to energy deficit, oxidative stress and cell death. Recent work also proposed neuroprotective strategies, such as the use of NMDA receptor antagonists, nitric oxide inhibitors, creatine and acetyl-l-carnitine, to counteract the toxic effects of ammonium. Better understanding the pathophysiology of ammonium toxicity to the brain under UCD will allow the development of new strategies for neuroprotection.
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Los programas de aprendizaje a lo largo de la vida ( ) han ofrecido a las personas mayores una variedad de oportunidades educativas a nivel formal, no formal y informal. Dentro de esta iniciativa europea, el programa más conocido es el programa Grundtvig que está abierto a todos los programas universitarios para mayores, elevando el reto de la formación durante toda la vida a nivel europeo, y dónde los adultos adquieren herramientas en su aprendizaje, mejoran sus conocimientos y potencian sus habilidades.