The AMPA receptor positive allosteric modulator S 47445 rescues in vivo CA3-CA1 long-term potentiation and structural synaptic changes in old mice

Positive allosteric modulators of cc-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are small molecules that decrease deactivation of AMPARs via an allosteric site. These molecules keep the receptor in an active state. Interestingly, this type of modulator has been proposed for treating cognitive decline in ageing, dementias, and Alzheimer's disease (AD). S 47445 (8-cyclopropyl-3[2-(3-fluorophenyflethy1]-7,8-dihydro-3H-[1,3]oxazino[6,5-g][1,2,3]benzotriazine-4,9-dione) is a novel AMPAR positive allosteric modulator (AMPA-PAM). Here, the mechanisms by which S 47445 could improve synaptic strength and connectivity were studied and compared between young and old mice. A single oral administration of S 47445 at 10 mg/kg significantly increased long-term potentiation (LTP) in CA3-CA1 hippocampal synapses in alert young mice in comparison to control mice. Moreover, chronic treatment with S 47445 at 10 mg/kg in old alert animals significantly counteracted the deficit of LTP due to age. Accordingly, chronic treatment with S 47445 at 10 mg/kg seems to preserve synaptic cytoarchitecture in old mice as compared with young control mice. It was shown that the significant decreases in number and size of pre-synaptic buttons stained for VGlutl, and post-synaptic dendritic spines stained for spinophilin, observed in old mice were significantly prevented after chronic treatment with 10 mg/kg of S 47445. Altogether, by its different effects on LTP, VGlutl-positive particles, and spinophilin, S 47445 is able to modulate both the structure and function of hippocampal excitatory synapses known to be involved in learning and memory processes. These results open a new window for the treatment of specific age-dependent cognitive decline and dementias such as AD. (C) 2017 The Authors. Published by Elsevier Ltd

Chronic Stress Modulates Interneuronal Plasticity: Effects on PSA-NCAM and Perineuronal Nets in Cortical and Extracortical Regions

Chronic stress has an important impact on the adult brain. However, most of the knowledge on its effects is focused on principal neurons and less on inhibitory neurons. Consequently, recent reports have begun to describe stress-induced alterations in the structure, connectivity and neurochemistry of interneurons. Some of these changes appear to be mediated by certain molecules particularly associated to interneurons, such as the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) and components of the perineuronal nets (PNN), specialized regions of the extracellular matrix. These plasticity-related molecules modulate interneuronal structure and connectivity, particularly of parvalbumin expressing basket interneurons, both during development and adult life. These inhibitory neurons are specially affected after chronic stress and in some stress-related disorders, in which the expression of PSA-NCAM and certain components of PNN are also altered. For these reasons we have decided to study PSA-NCAM, PNN and parvalbumin expressing interneurons after 10 days of chronic restraint stress, a time point in which its behavioral consequences are starting to appear. We have focused initially on the medial prefrontal cortex (mPFC), basolateral amygdala (BLA) and hippocampus, regions affected by stress and stress-related psychiatric diseases, but we have also explored the habenula and the thalamic reticular nucleus (TRN) due to the important presence of PNN and their relationship with certain disorders. PSA-NCAM expression was increased by stress in the stratum lacunosum-moleculare of CA1. Increases in parvalbumin immunoreactive cells were detected in the mPFC and the BLA, but were not accompanied by increases in the number of parvalbumin expressing perisomatic puncta on the somata of principal neurons. The number of PNN was also increased in the mPFC and the habenula, although habenular PNN were not associated to parvalbumin cells. Increased expression of parvalbumin and components of PNN were also detected in the TRN after chronic restraint stress, revealing for the first time substantial effects on this region. Our study shows that, even a short chronic stress protocol, can induce consistent changes in interneuronal plasticity-related molecules in cortical and extracortical regions, which may represent initial responses of inhibitory circuits to counteract the effects of this aversive experience

Red de coordinación de la implantación del primer curso del grado en Tecnologías de la Información para la Salud

En este trabajo se ha intentado recoger las acciones que se han llevado a cabo en la coordinación de la implantación del primer curso del nuevo grado de Tecnologías de la Información para la Salud, grado con un marcado carácter multidisciplinar que condiciona la enseñanza de los contenidos. Entre estas acciones se han revisado las guías de cada asignatura participante en la red y se han realizado reuniones de seguimiento de la implantación de las asignaturas para detectar fortalezas y debilidades en el proceso docente. También se ha contado con la opinión de alumnos bien a través de encuestas bien directamente en conversaciones con los representantes del alumnado. Pretendemos que las conclusiones obtenidas tras el análisis de resultados se puedan aplicar el curso que viene y, de esta forma, avanzar en la implantación de la titulación con calidad y, especialmente, con el objetivo de formar egresados que satisfagan las necesidades de la sociedad

Clinical and pathological characteristics of peripheral T-cell lymphomas in a Spanish population: a retrospective study

We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P 15% of cells were positive in anaplastic lymphoma kinase-positive and -negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub-classification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors.This study was sponsored by Takeda

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Neurodiversidad y perspectiva de género en la: Alta Sensibilidad

Proyecto financiado por las ayudas para la Innovación educativa por parte del Vicerrectorado de Formación Permanente, Transformación Docente y Empleo, para el curso 2023-2024.El presente proyecto se centra en acercar el conocimiento sobre la sensibilidad de procesamiento sensorial (SPS) desde la perspectiva de género como parte de la neurodiversidad que existe en la sociedad y en el aula. La mirada del proyecto se centra en las fortalezas de este rasgo, permitiendo el autoconocimiento del mismo (la expresión del rasgo SPS en el futuro docente) y ayuda a la comprensión y a la práctica de medidas para el cuidado de la salud mental-educación para la salud (regulación del estrés y educación emocional). Las prácticas de estas pautas servirán para todo el alumnado exprese o no la SPS, teniendo en cuenta que, además, la profesión docente es una de las que más agotamiento por estrés presenta. Adicionalmente se analizará en el futuro docente la posible presencia del rasgo de SPS desde la perspectiva de género. Con esta experiencia educativa o situación de aprendizaje, el alumnado aprenderá sobre la neurodiversidad a través de un ejemplo práctico, mediante las pautas diseñadas para la inclusión que recomienda el DUA. Proyecto financiado por las ayudas para la Innovación educativa por parte del Vicerrectorado de Formación Permanente, Transformación Docente y Empleo, para el curso 2023-2024, proyecto UV-SFPIE_PIEE-27368643 - Salut i Benestar4 - Educació de Qualitat5 - Igualtat de Gèner

Impact of chronic transcranial random noise stimulation (tRNS) on GABAergic and glutamatergic activity markers in the prefrontal cortex of juvenile mice

Transcranial random noise stimulation (tRNS), a non-invasive neuromodulatory technique capable of altering cortical activity, has been proposed to improve the signal-to-noise ratio at the neuronal level and the sensitivity of the neurons following an inverted U-function. The aim of this study was to examine the effects of tRNS on vGLUT1 and GAD 65–67 and its safety in terms of pathological changes. For that, juvenile mice were randomly distributed in three different groups: “tRNS 1 ×” receiving tRNS at the density current used in humans (0.3 A/m2, 20 min), “tRNS 100 ×” receiving tRNS at two orders of magnitude higher (30.0 A/m2, 20 min) and “sham” (0.3 A/m2, 15 s). Nine tRNS sessions during 5 weeks were administered to the prefrontal cortex of awake animals. No detectable tissue macroscopic lesions were observed after tRNS sessions. Post-stimulation immunohistochemical analysis of GAD 65–67 and vGLUT1 immunoreactivity showed reduced GAD 65–67 immunoreactivity levels in the region directly beneath the electrode for tRNS 1 × group with no significant effects in the tRNS 100 × nor sham group. The observed results suggest an excitatory effect associated with a decrease in GABA levels in absence of major histopathological alterations providing a novel mechanistic explanation for tRNS effects. © 2021 Elsevier B.V

The GABAergic septohippocampal pathway is directly involved in internal processes related to operant reward learning

We studied the role of γ-aminobutyric acid (GABA)ergic septohippocampal projections in medial septum (MS) self-stimulation of behaving mice. Self-stimulation was evoked in wild-type (WT) mice using instrumental conditioning procedures and in J20 mutant mice, a type of mouse with a significant deficit in GABAergic septohippocampal projections. J20 mice showed a significant modification in hippocampal activities, including a different response for input/ output curves and the paired-pulse test, a larger long-term potentiation (LTP), and a delayed acquisition and lower performance in the MS self-stimulation task. LTP evoked at the CA3-CA1 synapse further decreased self-stimulation performance in J20, but not in WT, mice. MS self-stimulation evoked a decrease in the amplitude of field excitatory postsynaptic potentials (fEPSPs) at the CA3-CA1 synapse in WT, but not in J20, mice. This self-stimulation-dependent decrease in the amplitude of fEPSPs was also observed in the presence of another positive reinforcer (food collected during an operant task) and was canceled by the local administration of an antibody-inhibiting glutamate decarboxylase 65 (GAD65). LTP evoked in the GAD65Ab-treated group was also larger than in controls. The hippocampus has a different susceptibility to septal GABAergic inputs depending on ongoing cognitive processes, and the GABAergic septohippocampal pathway is involved in consummatory processes related to operant rewards. © The Author 2013.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Cuadernos de pedagogía

Tras la muerte de Ángel Rivière se ofrecen diez testimonios de personas de su entorno, tales como su hija Lucía o su hermano Vicente Rivière, compañeros del departamento, de profesión y dos alumnas de la universidad donde impartía docencia. Estos diez testimonios rinden homenaje al quehacer profesional y científico de este psicólogo y valoran sus características humanas y personales.CataluñaES