New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

EPOXY POLYMERS : New materials and innovations

International audienc

Thermosetting Polymers

International audienceThermosetting polymers (also called thermosets) are a family of plastics characterized by the fact that they are formed starting from a liquid solution that irreversibly leads to a solid material during a heating step. This chapter focuses on some aspects of the chemistry of epoxy polymers because it provides examples of both step-growth and chain-growth polymerizations employed in the synthesis of polymer networks. The chapter explains structural transformations such as gelation, vitrification, that take place during network formation. Then, it talks about rules for processing thermosetting polymers. Processing techniques for thermosetting polymers are described in what follows in relation to the most extended applications

Nanostructured epoxies based on the self-assembly of block copolymers: a new miscible block that can be tailored to different epoxy formulations

International audienceNanostructured thermosets may be obtained by the self-assembly of amphiphilic block copolymers (BCP) in a reactive solvent and fixation of the resulting morphologies by the cross-linking reaction. Nanostructuration requires the presence of a block that remains miscible in the thermosetting polymer during polymerization. The selection of the miscible block depends on the particular system, and in some cases (e.g., for epoxy-amine network based on diglycidyl ether of bisphenol A, DGEBA, and 4,4'-diaminodiphenyl sulfone, DDS) it is very difficult to find such a block. In this paper it is shown that random copolymers of methyl methacrylate (MMA) and N,N-dimethylacrylamide (DMA) containing different molar fractions of DMA can be used as a miscible block for the nanostructuration of epoxies, a fact that is particularly illustrated for a DGEBA-DDS epoxy network. The miscibility of the random copolymer during formation of the epoxy network was first analyzed determining cloud-point conversions as a function of the molar fraction of DMA in the copolymer. A thermodynamic model of the phase separation was performed using the Flory-Huggins model and taking the polydispersities of both polymers into account. A single expression of the interaction parameter based on the theory of random copolymers provided a reasonable fitting of the experimental cloud-point curves. The significant increase in the miscibility produced by using small DMA molar fractions in the copolymer was explained by the high negative value of the binary interaction energy between DMA and the epoxy-amine solvent, associated with the positive value of the interaction energy between DMA and MMA units. Block copolymers with poly-(n-butyl acrylate) as the immiscible block and the random copolymer P(MMA-co-DMA) as the miscible block were used for the nanostructuration of DGEBA-DDS networks. The necessary molar fraction of DMA in the miscible block to stabilize a dispersion of nanosize domains depended on the fraction of the immiscible block in the BCP

Miscibility of blends of poly(methyl methacrylate) and oligodiols based on a bisphenol A nucleus and ethylene oxide or propylene oxide branches

International audienceCloud-point curves of blends of poly(methyl methacrylate) (PMMA) with a series of oligodiols based on a bisphenol A nucleus and short branches of poly(ethylene oxide) or poly(propylene oxide) (BPA-EO or BPA-PO), and with PEO and PPO oligomers, were obtained using a light transmission device. Experimental results were fitted with the Flory-Huggins model using an interaction parameter depending on both temperature and composition. For PMMA/PEO and PMMA/PPO blends, the miscibility increased when increasing the size of the diol, due to the significant decrease in the entropic and enthalpic terms contributing to the interaction parameter. This reflected the decrease in the self-association of solvent molecules and in the contribution of terminal OH groups to the mismatching of solubility parameters. For PMMA/BPA-EO blends, a decrease of the entropic contribution to the interaction parameter when increasing the size of the oligodiol was also found. However, the effect was counterbalanced by the opposite contribution of combinatorial terms leading to cloud-point curves located in approximately the same temperature range. For PMMA/BPA-PO blends, the interaction parameter exhibited a very low value. In this case, the effect of solvent size was much more important on combinatorial terms than on the interaction parameter, leading to an increase in miscibility when decreasing the oligodiol size. For short BPA-PO oligodiols no phase separation was observed. The entropic contribution of the interaction parameter exhibited an inverse relationship with the size of the oligodiols, independent of the nature of the chains bearing the hydroxyls and the type of OH groups (primary or secondary). This indicates that the degree of self-association of solvent molecules through their OH terminal groups, was mainly determined by their relative sizes

Thermodynamic analysis of the reaction-induced phase separation of random copolymers of methyl methacrylate and N,N-dimethylacrylamide in a polythiourethane network

Communication par affich

Monofunctional epoxy-POSS dispersed in epoxy-amine networks: effect of a pre-reaction on the morphology and crystallinity of POSS domains

International audienceSeveral studies have recently reported the use of monofunctional octahedral oligomeric silsesquioxanes (monofunctional POSS) to modify polymer networks. In most of these studies the final material is depicted as a network with pendent POSS units randomly dispersed in the structure. The aim of this paper is to show that this representation is generally not correct due to the occurrence of a polymerization-induced phase separation (PIPS) process. In this sense, monofunctional POSS are not different from different types of rubbers, thermoplastics, or liquid crystals used to modify polymer networks. Although some authors have noticed the occurrence of PIPS in particular systems, a comparative study of the effect of the chemical structure of POSS and its prereaction with one of the monomers on the morphologies generated has not been previously reported. Glycidyloxypropylheptaisobutyl POSS (iBu-GlyPOSS) and glycidyloxypropyl-heptaphenyl POSS (Ph-GlyPOSS) were used to modify an epoxy network based on diglycidyl ether of bisphenol A (DGEBA) and 4,4'-methylenebis(2,6-diethylaniline) (MDEA). POSS was introduced in the formulation either nonreacted or prereacted with MDEA (molar ratio POSS/MDEA: 1/10). While both nonreacted and prereacted iBu-GlyPOSS were soluble in the epoxy-amine precursors at the polymerization temperature (135 °C), only prereacted Ph-GlyPOSS could be dissolved in epoxy-amine precursors. For every case a polymerization-induced phase separation took place. For the nonreacted iBu-GlyPOSS this process led to a dispersion of spherical particles with sizes in the range of the micrometers that crystallized upon cooling. Both prereacted POSS led to different types of amorphous biphasic structures. Therefore, the nature of the organic inert group and the prereaction of a monofunctional POSS can be used to control the morphologies generated in the POSS-modified polymer network