A novel form of human disease with a protease-sensitive prion protein and heterozygosity methionine/valine at codon 129: Case report

Background: Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare neurodegenerative disorder in humans included in the group of Transmissible Spongiform Encephalopathies or prion diseases. The vast majority of sCJD cases are molecularly classified according to the abnormal prion protein (PrPSc) conformations along with polymorphism of codon 129 of the PRNP gene. Recently, a novel human disease, termed "protease-sensitive prionopathy", has been described. This disease shows a distinct clinical and neuropathological phenotype and it is associated to an abnormal prion protein more sensitive to protease digestion. Case presentation: We report the case of a 75-year-old-man who developed a clinical course and presented pathologic lesions compatible with sporadic Creutzfeldt-Jakob disease, and biochemical findings reminiscent of "protease-sensitive prionopathy". Neuropathological examinations revealed spongiform change mainly affecting the cerebral cortex, putamen/globus pallidus and thalamus, accompanied by mild astrocytosis and microgliosis, with slight involvement of the cerebellum. Confluent vacuoles were absent. Diffuse synaptic PrP deposits in these regions were largely removed following proteinase treatment. PrP deposition, as revealed with 3F4 and 1E4 antibodies, was markedly sensitive to pre-treatment with proteinase K. Molecular analysis of PrPSc showed an abnormal prion protein more sensitive to proteinase K digestion, with a five-band pattern of 28, 24, 21, 19, and 16 kDa, and three aglycosylated isoforms of 19, 16 and 6 kDa. This PrPSc was estimated to be 80% susceptible to digestion while the pathogenic prion protein associated with classical forms of sporadic Creutzfeldt-Jakob disease were only 2% (type VV2) and 23% (type MM1) susceptible. No mutations in the PRNP gene were found and genotype for codon 129 was heterozygous methionine/valine. Conclusions: A novel form of human disease with abnormal prion protein sensitive to protease and MV at codon 129 was described. Although clinical signs were compatible with sporadic Creutzfeldt-Jakob disease, the molecular subtype with the abnormal prion protein isoforms showing enhanced protease sensitivity was reminiscent of the "protease-sensitive prionopathy". It remains to be established whether the differences found between the latter and this case are due to the polymorphism at codon 129. Different degrees of proteinase K susceptibility were easily determined with the chemical polymer detection system which could help to detect proteinase-susceptible pathologic prion protein in diseases other than the classical ones.

热处理对共沉淀法制备YAG纳米粉体性能的影响

以Al（NO3）3和Y（NO3）3为原料，采用共沉淀法制备出粒度大小为60-100nm，颗粒呈球形的纯相YAG纳米粉。研究了前驱物在不同条件下热处理对YAG纳米粉体性能的影响，并对前驱物在焙烧过程中的物相变化进行了观察。发现延长前驱物在低温下的干燥时间会导致晶粒尺寸增大，而采用在晶化温度前后分别进行保温的方法可在较低的温度获得纯相的YAG粉体。对比了焙烧温度和保温时间对产物粒度的影响，结果表明：在保证粉体晶化完全的前提下，升高焙烧温度比延长保温时间对晶粒尺寸有更显著的影响。

Synthesis and Characterization of One-Dimensional and Molecular M(tren)InAsS4 (M = Mn, Co, and Zn) Compounds with a Noncondensed AsS33- Unit

Four transition-metal-amine complexes incorporating indium thioarsenates with the general formula M(tren)InAsS4 (M=Mn, Co, and Zn) and a noncondensed AsS33- unit have been prepared and characterized. Single-crystal X-ray diffraction analyses show that compound 1 (M=Mn) crystallizes in the triclinic crystal system (space group: P (1) over bar) and consists of a one-dimensional (1D) inorganic (1)(infinity){[InAsS4](2-)} chain and [Mn(tren)](2+) groups bonded to the opposite sides of an eight-membered In2As2S4 ring along the backbone of the infinite inorganic chains. Compounds 2 (M=Mn), 3 (M=Zn), and 4 (M=Co) are isomorphous molecular compounds. They all crystallize in the monoclinic crystal system (space group: P2(1)/c). The Mn2+ cation of [Mn(tren)](2+) in 1 has a distorted octahedral environment, while the transition-metal cations of [M(tren)](2+) in the other three compounds locate in trigonal-bipyramidal environments.

Insucesso escolar: causas e consequências no contexto do Agrupamento Vertical de Ourique (período 1999/2000 a 2007/2008)

O presente estudo, de carácter quantitativo e qualitativo, assenta na temática do insucesso escolar. O mesmo foi orientado pela questão de partida que o perspectivou: “Quais as causas, consequências e dimensão do fenómeno do insucesso escolar nos alunos que iniciaram, em 1999/2000, a sua escolaridade, no concelho de Ourique? Baseados no quadro conceptual de um estudo de caso, seleccionámos uma “coorte” de alunos, que entrevistámos, com vista a inteirarmo-nos das experiências e situações reais que os conduziram a situações de insucesso escolar procurando dar resposta aos seguintes objectivos: 1) avaliar, quantitativamente, o insucesso escolar na população discente seleccionada; 2) identificar as, eventuais, causas do insucesso escolar verificado; 3) identificar as, eventuais, consequências do insucesso escolar verificado; 4) avaliar possíveis intervenções no sentido de mitigar o fenómeno do insucesso escolar. Para tal, analisámos o percurso escolar de um universo de 46 alunos, entre 1999/2000 e 2007/08, tendo verificado que 24 desses alunos vivenciaram episódios de insucesso escolar, ao longo do seu trajecto académico. Destes, entrevistámos 12 alunos, tendo essa abordagem possibilitado ir de encontro aos nossos objectivos. Através da análise e interpretação dos dados recolhidos, concluímos que: 1) a taxa de insucesso escolar é superior a 50%, na coorte de alunos que iniciaram a sua escolaridade, no ano lectivo 1999/00, no concelho de Ourique; 2) há uma forte participação dos pais e encarregados de educação nas vivências escolares dos alunos (80% do total da amostra); 3) o número médio de retenções, nos alunos com episódios de insucesso escolar, é de 1,5 retenções; 4) o 7.º ano de escolaridade é o ano em que se verifica um maior número de retenções, seguido do 4.º ano de escolaridade; 5) a maioria dos alunos (58,3%) encontra-se relativamente distante do seu meio familiar; 6) um número significativo de alunos com episódios de insucesso escolar (83,3%) referiu que recebe apoio da família; 7) a incapacidade individual foi a causa do insucesso escolar mais referida/inferida pelos entrevistados; 8) evidenciou-se que retenções precoces induzem a retenções posteriores; 9) a importância do 1.º Ciclo é relevante, quando os entrevistados indicam que a falta de apoio no 1.º Ciclo terá induzido a situações futuras de insucesso escolar. No final deste trabalho são efectuadas propostas que possam potenciar futuras investigações, nomeadamente de investigação acção, promovendo intervenção; ### Abstract: The schools failure: The causes of consequences in context the Agrupamento Vertical de Ourique The present study, of quantitative and qualitative content, is based on the thematic of the failure rate in schools. The study was oriented towards the fundamental issue which has been put in perspective: “What are the causes, consequences and dimension of the phenomena of the failure rate in schools that can be seen in the students that started in 1999/2000 their school education in the municipality of Ourique?” Based on the conceptual framework of a study case, we selected a group of students, which we interviewed, in order to know about the real experiences and situations that led them to situations of school failure, trying to give answers and to achieve the following goals: 1) to evaluate quantitatively the school failure of the selected students population; 2) to identify the eventual causes of the verified school failure; 3) to identify the eventual consequences of the verified school failure; 4) to evaluate the possible interventions in order to minimize the school failure phenomena. Therefore, we analysed the school path of an amount of 46 students between 1999/2000 and 2007/2008 and we reached the conclusion that 24 of those students experienced episodes of school failure. We interviewed 12 of those 24 and that approach permitted us to reach our goals. Through the analysis and the interpretation of the collected data we conclude that: 1) the rate of school failure is over 50% in the group of students that started their schooling in the school year 1999/2000 in the municipality of Ourique; 2) there is a strong participation of parents and tutors in the students’ school life( 80% of the sample); 3) the average number of retention in the students with episodes of school failure is 1, 5 retentions; 4) the 7th grade is the one in which we verify the highest number of retentions followed by the 4th grade ; 5) the majority of the students (53,8%) are far away from their family environment; 6) a significant number of students with episodes of school failure (83,3%) referred that they get support from their family; 7) the individual incapacity was the most referred/inferred cause of school failure by the ones who were interviewed ; 8) it became an evidence that early retentions lead to future retentions; 9) the importance of the basic education is relevant when the interviewed students show that the lack of support in the basic education should have led to future situations of school failure. At the end of this work we present some proposals that can lead to future investigation, namely of investigation/action promoting intervention.

L'Écho de Paris

1917/03/01 (Numéro 11885).

Opera omnia

UANL

A point-prevalence survey of antimicrobial utilisation within New Brunswick hospitals to focus antimicrobial stewardship efforts and decrease low-value care.

Introduction: Il est important de minimiser le gaspillage et les risques associés aux soins sans valeur. La gestion de l’utilisation des antimicrobiens vise à optimiser leur emploi et doit être adaptée au milieu et à sa population. Objectifs: Évaluer les profiles d’utilisation actuels des antimicrobiens et fixer des objectifs pour les interventions en matière de gestion des antimicrobiens. Méthode: Vingt-et-un hôpitaux du Nouveau-Brunswick offrant des soins de courte durée en médecine générale, en chirurgie et en pédiatrie ont pris part à une enquête sur la prévalence ponctuelle. Tous les patients admis aux hôpitaux participants et ayant reçu au moins un antimicrobien systémique ont été inscrits à l’étude. Les principaux critères d’évaluation étaient le profil d’utilisation, selon l’indication et l’antimicrobien prescrit, le bienfondé de l’utilisation et la durée de la prophylaxie chirurgicale. Des statistiques descriptives et un test d’indépendance 2 furent utilisés pour l’analyse de données. Résultats: L’enquête a été menée de juin à août 2012. Un total de 2244 patients ont été admis pendant la durée de l’étude et 529 (23,6%) ont reçu un antimicrobien. Au total, 691 antimicrobiens ont été prescrits, soit 587 (85%) pour le traitement et 104 (15%) pour la prophylaxie. Les antimicrobiens les plus souvent prescrits pour le traitement (n=587) étaient des classes suivantes : quinolones (25,6%), pénicillines à spectre étendu (10,2%) et métronidazole (8,5%). Les indications les plus courantes du traitement étaient la pneumonie (30%), les infections gastro-intestinales (16%) et les infections de la peau et des tissus mous (14%). Selon des critères définis au préalable, 23% (n=134) des ordonnances pour le traitement étaient inappropriées et 20% (n=120) n’avaient aucune indication de documentée. Les domaines où les ordonnances étaient inappropriées étaient les suivants : défaut de passage de la voie intraveineuse à la voie orale (n=34, 6%), mauvaise dose (n=30, 5%), traitement d’une bactériurie asymptomatique (n=24, 4%) et doublement inutile (n=22, 4%). Dans 33% (n=27) des cas, les ordonnances pour la prophylaxie chirurgicale étaient pour une période de plus de 24 heures. Conclusions: Les résultats démontrent que les efforts de gestion des antimicrobiens doivent se concentrer sur les interventions conventionnelles de gestion de l’utilisation des antimicrobiens, l’amélioration de la documentation, l’optimisation de l’utilisation des quinolones et la réduction au minimum de la durée de la prophylaxie chirurgicale.

La globalització a les aules. 'La globalización en las aulas'.

Resumen de la revista en catalán

Nuevos horizontes de las luchas afrocolombianas

En el reportaje radial “Nuevos horizontes de las luchas afrocolombianas”, las protagonistas son el Movimiento Nacional Cimarrón y Chao Racismo, dos organizaciones sociales que han trabajado por los derechos de los afrocolombianos desde diferentes puntos de vista sobre la lucha contra el racismo. De esta forma, a partir de los testimonios de sus trabajadores, voluntarios y líderes se cuenta la historia, las similitudes, las diferencias y las perspectivas sobre el contexto que viven los afrocolombianos actualmente.

Objeto de aprendizaje para la formaci??n docente orientado a desarrollar competencias para usar REA

Resumen basado en el de la publicaci??n

Combined Crystallographic and Solution Molecular Dynamics Study of Allosteric Effects in Ester and Ketone p-tert-Butylcalix[4]arene Derivatives and Their Complexes with Acetonitrile, Cd(II), and Pb(II)

We describe here a procedure to bridge the gap in the field of calixarene physicochemistry between solid-state atomic-resolution structural information and the liquid-state low-resolution thermodynamics and spectroscopic data. We use MD simulations to study the kinetics and energetics involved in the complexation of lower rim calix[4]arene derivatives (L), containing bidentate ester (1) and ketone (2) pendant groups, with acetonitrile molecule (MeCN) and Cd2+ and Pb2+ ions (M2+) in acetonitrile solution. On one hand, we found that the prior inclusion of MeCN into the calix to form a L(MeCN) adduct has only a weak effect in preorganizing the hydrophilic cavity toward metal ion binding. On the other hand, the strong ion-hydrophilic cavity interaction produces a wide open calix which enhances the binding of one MeCN molecule (allosteric effect) to stabilize the whole (M2+)1(MeCN) bifunctional complex. We reach two major conclusions: (i) the MD results for the (M2+)1(MeCN) binding are in close agreement with the ""endo"", fully encapsulated, metal complex found by X-ray diffraction and in vacuo MD calculations, and (ii) the MD structure for the more flexible 2 ligand, however, differs from the also endo solid-state molecule. In fact, it shows strong solvation effects at the calixarene lower bore by competing MeCN molecules that share the metal coordination sphere with the four C=O oxygens of an ""exo"" (M2+)2(MeCN) complex.