Spinal nerve involvement in early Guillain-Barré syndrome: The Haymaker and Kernohan's legacy

Pathological studies of early Guillain-Barré syndrome (GBS), defined as of 10 days of disease onset, are scanty making it difficult to interpret the physiopathology of clinical and electrophysiological features. In 1949, Webb Haymaker and James Kernohan reported 50 clinico-pathological studies of fatal GBS cases, 32 of them having died between days 2 and 10 after onset. They established that the brunt of initial lesions, consisting of endoneurial oedema interpreted as degenerative, relied on spinal nerves. That this oedema was inflammatory was soon thereafter recognized. Two decades later, however, the pathogenic role of endoneurial oedema was disputed. In experimental allergic neuritis, considered an animal model of GBS, the initial lesion appearing on day 4 post-inoculation is marked inflammatory oedema in the sciatic nerve and lumbosacral nerve roots. Additional detailed clinico-pathological studies corroborated that the appearance of epi-perineurium at the subarachnoid angle, where anterior and posterior roots join to form the spinal nerve, is a pathological hotspot in early GBS, there developing inflammatory oedema, incipient demyelination and endoneurial ischemic zones with axonal degeneration. Furthermore, nerve ultrasonography has demonstrated predominant spinal nerve changes in early GBS, either demyelinating or axonal. Other outstanding Haymaker and Kernohan's contributions were to clarify the complex nosology of the syndrome bringing under the same rubric Landry's paralysis, acute febrile polyneuritis and GBS, and critically analyzing GBS exclusion criteria by then prevailing. It is concluded that the authors' legacy remains as relevant as ever

Moldeo de cilindros de laminación

Se trata de los procedimientos seguidos en la fabricación y moldeo de cilindros de laminació

Fabricación de Fundición Nodular

Se trata de una monografía sobre aspectos prácticos de la fabricación de piezas moldeadas de fundición con grafito esferoidal, prestando mayor atención a los métodos de elaboración del nodular, especialmente en lo que concierne a los métodos de nodulización. Este trabajo no pretende ser original; simplemente se intenta hacer una revisión de la tecnología existente a fin de que sea de interés para todos los fundidores involucrados en esta parcela de la fundición

Molde a terraja de una hélice

Estudio del molde a terraja de una hélice de barc

Neuroprotective Effect of Bexarotene in the SOD1(G93A) Mouse Model of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and muscle atrophy related to the loss of upper and lower motor neurons (MNs) without a curative treatment. There is experimental evidence suggesting that retinoids may be involved in ALS pathogenesis. Bexarotene (Bxt) is a retinoid-X receptor agonist used in the treatment of cutaneous lymphoma with a favorable safety profile whose effects have been recently investigated in other neurodegenerative diseases. In this study, we analyze the potential therapeutic effect of Bxt in the SOD1(G93A) mouse model of ALS. Mice were treated with Bxt or vehicle five times per week from day 60 onward. Survival, weight, and neuromuscular function studies together with histological and biochemical analyses were performed. Bxt significantly delayed motor function deterioration, ameliorated the loss of body weight, and extended mice survival up to 30% of the symptomatic period. Histological analyses of the lumbosacral spinal cord revealed that Bxt markedly delayed the early motor-neuron degeneration occurring at presymptomatic stages in ALS-transgenic mice. Bxt treatment contributed to preserve the MN homeostasis in the SOD1(G93A) mice. Particularly, it reduced the neuronal loss and the chromatolytic response, induced nucleolar hypertrophy, decreased the formation of ubiquitylated inclusions, and modulated the lysosomal response. As an agonist of the retinoic-X receptor (RXR) pathway, Bxt notably increased the nuclear expression of the RXRα throughout transcriptionally active euchromatin domains. Bxt also contributed to protect the MN environment by reducing reactive astrogliosis and preserving perisomatic synapsis. Overall, these neuroprotective effects suggest that treatment with Bxt could be useful in ALS, particularly in those cases related to SOD1 mutations

Fabricación de acero inoxidable

Descripción de los procesos utilizados en la fabricación de acero inoxidabl

Connective Intelligence for Childhood Mathematics Education

La construcción de un cerebro conectivo comienza en las edades más tempranas del desarrollo humano. Sin embargo, el conocimiento que ya se tiene sobre los cerebros individual y colectivo apenas se ha incorporado en el desarrollo del pensamiento matemático en Educación Infantil, donde comienzan a gestarse elementos clave para tomar decisiones, resolver problemas de la vida cotidiana, tratar con datos y comprender el entorno. Desde esta perspectiva la presente investigación marca como objetivo general analizar el proceso de enseñanza-aprendizaje de las matemáticas en Educación Infantil a partir del conexionismo, considerando como objetivos específicos, por un lado, determinar las características de una práctica matemática que promueva las conexiones y, por otro lado, identificar los distintos tipos de conexiones matemáticas para fomentar la inteligencia conectiva. La investigación se lleva a cabo a lo largo de dos años consecutivos bajo un paradigma interpretativo con un enfoque metodológico basado en el uso combinado de Investigación-Acción y Teoría Fundamentada. Los resultados han permitido concretar un prototipo de actividad o conjunto de actividades que, en forma de secuencia didáctica, promueve tres tipos de conexiones matemáticas para desarrollar la inteligencia conectiva en Educación Infantil: conceptuales, que producen nexos entre contenidos matemáticos diversos; docentes, que vinculan diversos conceptos matemáticos a través de una metodología activa y de vivenciar las experiencias matemáticas con otras materias; y prácticas, que relacionan las matemáticas con el entornoThe construction of a connective brain begins at the earliest ages of human development. However, knowledge about individual and collective brains provided so far by research has been rarely incorporated into Maths in Early Childhood classrooms. In spite of that, it is obvious that it is at these ages when the learning of mathematics acts as a nuclear element for decision – making, problem –solving, data– processing and the understanding of the world. From that perspective, this research aims to analyse the mathematics teaching-learning process at early ages based on connectionism, with the specific objectives being, on the one hand, to determine the features of mathematics practices which promote connections and, on the other hand, to identify different types of mathematics connections to enhance connective intelligence. The research was carried out over two consecutive academic years under an interpretative paradigm with a methodological approach combining Action Research and Grounded Theory. The results obtained allow the characterization of a prototype of a didactic sequence that promotes three types of mathematics connections for the development of connective intelligence in young children: conceptual, giving rise to links between mathematics concepts; teaching, linking mathematics concepts through an active methodology, and practical ones connecting maths with the environmen

Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis

Introducción: La esclerosis lateral amiotrófica (ELA) es la enfermedad degenerativa de las motoneuronas más frecuente. Aunque un peque?no porcentaje de los casos de ELA tienen un origen familiar y son secundarios a mutaciones en genes concretos, a la gran mayoría de ellos se les presupone un origen multifactorial, sin que su patogenia haya sido completamente aclarada. No obstante, en los últimos a?nos varios estudios han aumentado el conocimiento sobre la patogenia de la enfermedad, planteando la cuestión de si se trata de una proteinopatía, una ribonucleinopatía, una axonopatía o una enfermedad del microambiente neuronal. Desarrollo: En el presente artículo revisamos los trabajos publicados tanto en pacientes como en modelos animales de ELA y discutimos la implicación de los principales procesos celulares que parecen contribuir a su patogenia (procesamiento génico, metabolismo de proteínas, estrés oxidativo, transporte axonal y relación con el microambiente neuronal). Conclusiones: Aunque la patogenia de la ELA dista de estar aclarada, los estudios recientes apuntan a la idea de que hay unos desencadenantes iniciales que varían de unos sujetos a otros,y unas vías finales de degeneración de las motoneuronas que están implicadas en la mayor parte de los casos de enfermedad.Introduction: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Although a small proportion of ALS cases are familial in origin and linked to mutations in specific genes, most cases are sporadic and have a multifactorial aetiology. Some recent studies have increased our knowledge of ALS pathogenesis and raised the question of whether this disorder is a proteinopathy, a ribonucleopathy, an axonopathy, or a disease related to the neuronal microenvironment. Development: This article presents a review of ALS pathogenesis. To this end, we have reviewed published articles describing either ALS patients or ALS animal models and we discuss how the main cellular pathways (gene processing, protein metabolism, oxidative stress, axonal transport, relationship with neuronal microenvironment) may be involved in motor neurons degeneration. Conclusions: ALS pathogenesis has not been fully elucidated. Recent studies suggest that although initial triggers may differ among patients, the final motor neurons degeneration mechanisms are similar in most patients once the disease is fully established

A novel pathway of TEF regulation mediated by microRNA-125b contributes to the control of actin distribution and cell shape in fibroblasts

Background: Thyrotroph embryonic factor (TEF), a member of the PAR bZIP family of transcriptional regulators, has been involved in neurotransmitter homeostasis, amino acid metabolism, and regulation of apoptotic proteins. In spite of its relevance, nothing is known about the regulation of TEF. Principal findings: p53-dependent genotoxic agents have been shown to be much more harmful for PAR bZIP-deficient mice as compared to wild type animals. Here we demonstrate that TEF expression is controlled by p53 through upregulation of microRNA-125b, as determined by both regulating the activity of p53 and transfecting cells with microRNA-125b precursors. We also describe a novel role for TEF in controlling actin distribution and cell shape in mouse fibroblasts. Lack of TEF is accompanied by dramatic increase of cell area and decrease of elongation (bipolarity) and dispersion (multipolarity). Staining of actin cytoskeleton also showed that TEF (-/-) cells are characterized by appearance of circumferential actin bundles and disappearance of straight fibers. Interestingly, transfection of TEF (-/-) fibroblasts with TEF induced a wild type-like phenotype. Consistent with our previous findings, transfection of wild type fibroblasts with miR-125b promoted a TEF (-/-)-like phenotype, and a similar but weaker effect was observed following exogenous expression of p53. Conclusions/significance: These findings provide the first evidence of TEF regulation, through a miR-125b-mediated pathway, and describes a novel role of TEF in the maintenance of cell shape in fibroblasts