Escola Francesc d’Albranca: un repte de futur

Aquest treball mostra alguns dels mètodes d’ensenyament que es duen a terme al CP Francesc d’Albranca des Migjorn Gran (Menorca) a partir de la convicció que l’ensenyament ha de tenir a veure amb els interessos i les necessitats dels !llets i !lletes. Aquesta manera de treballar ens permet una dinàmica oberta i "exible i també facilita molt el treball autònom de l’alumnat i l’atenció a la diversitat per part dels mestres.El presente trabajo muestra algunos de los métodos de enseñanza que se llevan a la práctica en el Colegio Público Francesc d’albranca des Migjorn Gran (isla de Menorca) a partir de la convicción de que la enseñanza tiene que ver con los intereses y con las necesidades de los niños y niñas... esta manera de trabajar nos permite una dinámica abierta, "exible... y también facilita el trabajo autónomo del alumnado, y la atención a la diversidad por parte de maestros y maestras

Practical application of the ATOM study: Treatment efficacy of antihypertensive drugs in monotherapy or combination (ATOM metaanalysis according to PRISMA statement); tables for the use of antihypertensive drugs in monotherapy or combination

Background: The response to antihypertensive drugs is predictable. The absence of precise prescription recommendations to treat arterial hypertension (HT) lead to use drugs unable to reduce blood pressure (BP) to target values. We published ATOM study, in which we found significant differences in the ability to reduce BP between the different drugs. The objective of the study was to determine the expected decrease in blood pressure with the use of commercialized doses of the drugs commonly used in the treatment of HT in clinical practice, to avoid the use of drugs or combinations that even with the best response, are unable to obtain the necessary BP decrease to reach the goal. Methods: The analysis was based on the results of the ATOM study. To convert the mean doses of the different drugs and combinations in commercialized doses, the conclusions of the study by Law et al have been applied. Results: Based on the results, two tables were drawn, one for systolic BP and the other for diastolic BP, where the doses of the different drugs and combinations are classified according to the BP decrease that can be expected from them. In order to favor the use of the tables in clinical practice, the different drugs have been grouped in intervals of 10 millimeters of mercury (mmHg) for the decrease of the systolic BP and of 5 mmHg for the diastolic BP. Conclusions: Recommendations for the use of antihypertensive treatments should not be limited to pharmacological families. They should also consider differences between drugs or specific combinations. From the data of the ATOM study we have implemented tables that express the effect of the drugs commonly used in clinical practice and that should allow the clinicians to choose with care the treatment to use

L'afectació del llenguatge en la malaltia d'Alzheimer

En el deteriorament de les capacitats cognitives de la malaltia de l'Alzheimer (MA) destaquen, a més del trastorn amnèsic progressiu, les pèrdues de l'àrea del llenguatge. Tot i que en el procés d'envelliment normal el llenguatge és una de les funcions cognitives que queden afectades més tard, en la MA el trastorn lingüístic pot presentar-se com un dels primers símptomes. Aquestes dificultats transcorren des d'alteracions en tasques de denominació fins a la pèrdua total de llenguatge en els casos més avançats. L'article revisa de manera divulgativa alguns dels casos de persones lletrades que han sofert la malaltia i com aquesta situació ha afectat el seu treball. Així mateix, l'article resumeix algunes de les troballes empíriques més importants que descriuen l'afectació del llenguatge en les persones que pateixen aquesta malaltia

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

Neural cultures derived from Huntington's disease (HD) patient-derived induced pluripotent stem cells were used for 'omics' analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. These data suggest that mutant huntingtin impairs neurodevelopmental pathways that could disrupt synaptic homeostasis and increase vulnerability to the pathologic consequence of expanded polyglutamine repeats over time

Lack of Helios during neural development induces adult schizophrenia-like behaviors associated with aberrant levels of the TRIF-recruiter protein WDFY1

The role of the WDFY1 protein has been studied as a TLR3/4 scaffold/recruiting protein in the immune system and in different oncogenic conditions. However, its function in brain remains poorly understood. We have found that in mice devoid of Helios (He−/− mice), a transcription factor specifically expressed during the development of the immune cells and the central nervous system, there is a permanent and sustained increase of Wdfy1 gene expression in the striatum and hippocampus. Interestingly, we observed that WDFY1 protein levels were also increased in the hippocampus and dorsolateral prefrontal cortex of schizophrenic patients, but not in the hippocampus of Alzheimer's disease patients with an associated psychotic disorder. Accordingly, young He−/− mice displayed several schizophrenic-like behaviors related to dysfunctions in the striatum and hippocampus. These changes were associated with an increase in spine density in medium spiny neurons (MSNs) and with a decrease in the number and size of PSD-95-positive clusters in the stratum radiatum of the CA1. Moreover, these alterations in structural synaptic plasticity were associated with a strong reduction of neuronal NF-κB in the pyramidal layer of the CA1 in He−/− mice. Altogether, our data indicate that alterations involving the molecular axis Helios-WDFY1 in neurons during the development of core brain regions could be relevant for the pathophysiology of neuropsychiatric disorders such as schizophrenia

The neolithic necropolis of Feixa del Moro (Juberri, Andorra): review and new data

[EN] The data presented in this paper resume all the available information on the Feixa del Moro site, correcting old mistakes and bias, updating the 1980s archaeological registers and presenting new analyses as well. Our aim is to ensure that Feixa del Moro remains a reference site for the Pyrenean and Western Mediterranean Neolithic. At the same time, we wish to encourage other researchers to undertake new analyses and to embrace new perspectives in order to improve our understanding of Neolithic societies.[FR] Le travail que nous présentons ici rassemble toutes les données disponibles sur la Feixa del Moro jusqu’à aujourd’hui, expose les confusions détectées dans les sources, actualise les registres archéologiques obtenus dans les années 1980 et présente les résultats des nouvelles analyses effectuées. Grâce à cette démarche nous souhaitons que ce site continue d’être une référence pour le Néolithique dans les Pyrénées et la Méditerranée occidentale. Nous souhaitons également attirer l’attention d’autres chercheurs afin qu’ils continuent d’analyser et d’apporter de nouveaux éléments et de nouvelles approches pour mieux comprendre les sociétés néolithiques.Peer Reviewe

Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

Here we unravel the mechanism of action of Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons that express dopamine 2 receptor (D2R) and enkephalin (ENK). To exert this effect He is expressed in neural progenitor cells (NPCs) retaining them into the G1/G0 phase of the cell cycle. Thus, the lack of He produces an increase of S-phase entry and S-phase length of NPCs which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ) that end up dying at postnatal stages. Therefore, He-/- mice show a reduction in the number of Dorso-Medial Striatal MSNs in the adulthood that produces deficits in motor skills acquisition. In addition, overexpression of He in NPCs induce DARPP32 phenotype when transplanted in mouse striatum.Present findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development

Community-acquired methicillin-resistant Staphylococcus aureus: what do we need to know?

AbstractCommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has become a matter of concern worldwide, in particular in the USA. For the analysis of emergence and spread, clear definitions based on epidemiological origin are needed for discrimination between CA-MRSA, healthcare-associated community MRSA, and healthcare-associated MRSA (HA-MRSA). Although its role in pathogenesis is currently under debate, the capability for Panton–Valentine leukocidin formation is associated with the majority of CA-MRSA isolates from North America and from Europe. Most CA-MRSA isolates are attributed to clonal lineages different from HA-MRSA; there are, however, clonal lineages from which both HA-MRSA and CA-MRSA have been reported (e.g. ST1, ST5, ST8, and ST22); CA-MRSA ST8 (USA300), which is most frequent in the USA, has meanwhile been reported from Europe. CA-MRSA ST80 is widely disseminated in Europe; because of its pronounced oxacillin heteroresistance phenotype, cefoxitin-based assays are advisable for reliable detection. So far, CA-MRSA infections seem to be much less frequent in Europe than in the USA, where patients with particular predispositions and low social status are at especial risk

Large Genomic Imbalances in Brugada Syndrome

Purpose Brugada syndrome (BrS) is a form of cardiac arrhythmia which may lead to sudden cardiac death. The recommended genetic testing (direct sequencing of SCN5A) uncovers disease-causing SNVs and/or indels in ~20% of cases. Limited information exists about the frequency of copy number variants (CNVs) in SCN5A in BrS patients, and the role of CNVs in BrS-minor genes is a completely unexplored field. Methods 220 BrS patients with negative genetic results were studied to detect CNVs in SCN5A. 63 cases were also screened for CNVs in BrS-minor genes. Studies were performed by Multiplex ligation-dependent probe amplification or Next-Generation Sequencing (NGS). Results The detection rate for CNVs in SCN5A was 0.45% (1/220). The detected imbalance consisted of a duplication from exon 15 to exon 28, and could potentially explain the BrS phenotype. No CNVs were found in BrS-minor genes. Conclusion CNVs in current BrS-related genes are uncommon among BrS patients. However, as these rearrangements may underlie a portion of cases and they undergo unnoticed by traditional sequencing, an appealing alternative to conventional studies in these patients could be targeted NGS, including in a single experiment the study of SNVs, indels and CNVs in all the known BrS-related genes

Helios modulates the maturation of a CA1 neuronal subpopulation required for spatial memory formation

Currently, molecular, electrophysiological and structural studies delineate several neural subtypes in the hippocampus. However, the precise developmental mechanisms that lead to this diversity are still unknown. Here we show that alterations in a concrete hippocampal neuronal subpopulation during development specifically affect hippocampal-dependent spatial memory. We observed that the genetic deletion of the transcription factor Helios in mice, which is specifically expressed in developing hippocampal calbindin-positive CA1 pyramidal neurons (CB-CA1-PNs), induces adult alterations affecting spatial memory. In the same mice, CA3-CA1 synaptic plasticity and spine density and morphology in adult CB-CA1-PNs were severely compromised. RNAseq experiments in developing hippocampus identified an aberrant increase on the Visinin-like protein 1 (VSNL1) expression in the hippocampi devoid of Helios. This aberrant increase on VSNL1 levels was localized in the CB-CA1-PNs. Normalization of VSNL1 levels in CB-CA1-PNs devoid of Helios rescued their spine loss in vitro. Our study identifies a novel and specific developmental molecular pathway involved in the maturation and function of a CA1 pyramidal neuronal subtype