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We compared endogenous ω-3 PUFA production to supplementation for improving obesity-related metabolic dysfunction. Fat-1 transgenic mice, who endogenously convert exogenous ω-6 to ω-3 PUFA, and wild-type littermates were fed a high-fat diet and a daily dose of either ω-3 or ω-6 PUFA-rich oil for 12 wk. The endogenous ω-3 PUFA production improved glucose intolerance and insulin resistance but not hepatic steatosis. Conversely, ω-3 PUFA supplementation fully prevented hepatic steatosis but failed to improve insulin resistance. Both models increased hepatic levels of ω-3 PUFA-containing 2-monoacylglycerol and N-acylethanolamine congeners, and reduced levels of ω-6 PUFA-derived endocannabinoids with ω-3 PUFA supplementation being more efficacious. Reduced hepatic lipid accumulation associated with the endocannabinoidome metabolites EPEA and DHEA, which was causally demonstrated by lower lipid accumulation in oleic acid-treated hepatic cells treated with these metabolites. While both models induced a significant fecal enrichment of the beneficial Allobaculum genus, mice supplemented with ω-3 PUFA displayed additional changes in the gut microbiota functions with a significant reduction of fecal levels of the proinflammatory molecules lipopolysaccharide and flagellin. Multiple-factor analysis identify that the metabolic improvements induced by ω-3 PUFAs were accompanied by a reduced production of the proinflammatory cytokine TNFα, and that ω-3 PUFA supplementation had a stronger effect on improving the hepatic fatty acid profile than endogenous ω-3 PUFA. While endogenous ω-3 PUFA production preferably improves glucose tolerance and insulin resistance, ω-3 PUFA intake appears to be required to elicit selective changes in hepatic endocannabinoidome signaling that are essential to alleviate high-fat diet-induced hepatic steatosis. [ABSTRACT FROM AUTHOR]

Dietary micronutrients act at the intestinal level, thereby influencing microbial communities, the host endocannabinoidome, and immune and anti-oxidative response. Selenium (Se) is a trace element with several health benefits. Indeed, Se plays an important role in the regulation of enzymes with antioxidative and anti-inflammatory activity as well as indicators of the level of oxidative stress, which, together with chronic low-grade inflammation, is associated to obesity. To understand how Se variations affect diet-related metabolic health, we fed female and male mice for 28 days with Se-depleted or Se-enriched diets combined with low-and high-fat/sucrose diets. We quantified the plasma and intestinal endocannabinoidome, profiled the gut microbiota, and measured intestinal gene expression related to the immune and the antioxidant responses in the intestinal microenvironment. Overall, we show that intestinal segmentspecific microbiota alterations occur following high-fat or low-fat diets enriched or depleted in Se, concomitantly with modifications of circulating endocannabinoidome mediators and changes in cytokine and antioxidant enzyme expression. Specifically, Se enrichment was associated with increased circulating plasma levels of 2-docosahexaenoyl-glycerol (2-DHG), a mediator with putative beneficial actions on metabolism and inflammation. Others eCBome mediators also responded to the diets. Concomitantly, changes in gut microbiota were observed in Se-enriched diets following a high-fat diet, including an increase in the relative abundance of Peptostreptococcaceae and Lactobacillaceae. With respect to the intestinal immune response and anti-oxidative gene expression, we observed a decrease in the expression of proinflammatory genes Il1b and Tnfa in high-fat Seenriched diets in caecum, while in ileum an increase in the expression levels of the antioxidant gene Gpx4 was observed following Se depletion. The sex of the animal influenced the response to the diet of both the gut microbiota and endocannabinoid mediators. These results identify Se as a regulator of the gut microbiome and endocannabinoidome in conjunction with high-fat diet, and might be relevant to the development of new nutritional strategies to improve metabolic health and chronic low-grade inflammation associated to metabolic disorders. [ABSTRACT FROM AUTHOR]

Abstract Background Elderly patients admitted to Geriatric Assessment Units (GAU) typically have complex health problems that require multi-professional care. Considering the scope of human and technological resources solicited during hospitalization, as well as the many risks and discomforts incurred by the patient, it is important to ensure the communication of pertinent information for quality follow-up care in the community setting. Conventional discharge summaries do not adequately incorporate the elements specific to an aging clientele. Objective To develop a discharge summary adapted to the frail elderly patient (D-SAFE) in order to communicate relevant information from hospital to community services. Methods The items to be included in the D-SAFE have been determined by means of a modified Delphi method through consultation with clinical experts from GAUs (11 physicians and 5 pharmacists) and the community (10 physicians and 5 pharmacists). The consensus analysis and the level of agreement among the experts were reached using a modified version of the RAND®/University of California at Los Angeles appropriateness method. Results A consensus was reached after two rounds of consultation for all the items evaluated, where none was judged «inappropriate». Among the items proposed, four were judged to be « uncertain » and were eliminated from the final D-SAFE, which was divided into two sections: the medical discharge summary (22 main items) and the discharge prescription (14 main items). Conclusions The D-SAFE was developed as a more comprehensive tool specifically designed for GAU inpatients. Additional research to validate its acceptability and practical impact on the continuity of care is needed before it can be recommended for use on a broader scale.

The amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)-linked RNA-binding protein called FUS (fused in sarcoma) has been implicated in several aspects of RNAregulation, includingmRNA translation. Themechanismby which FUS affects the translation of polyribosomes has not been established. Here we show that FUS can associate with stalled polyribosomes and that this association is sensitive tomTOR (mammalian target of rapamycin) kinase activity. Specifically, we show that FUS association with polyribosomes is increased by Torin1 treatment or when cells are cultured in nutrient-deficient media, but not when cells are treated with rapamycin, the allosteric inhibitor of mTORC1.Moreover, we report that FUS is necessary for efficient stalling of translation because deficient cells are refractory to the inhibition of mTOR-dependent signaling by Torin1. We also show that ALS-linked FUS mutants R521G and P525L associate abundantly with polyribosomes and decrease global protein synthesis. Importantly, the inhibitory effect on translation by FUS is impaired by mutations that reduce its RNA-binding affinity. These findings demonstrate that FUS is an important RNAbinding protein that mediates translational repression through mTOR-dependent signaling and that ALS-linked FUS mutants can cause a toxic gain of function in the cytoplasm by repressing the translation ofmRNAat polyribosomes. [ABSTRACT FROM AUTHOR]

Background: Elderly patients admitted to Geriatric Assessment Units (GAU) typically have complex health problems that require multi-professional care. Considering the scope of human and technological resources solicited during hospitalization, as well as the many risks and discomforts incurred by the patient, it is important to ensure the communication of pertinent information for quality follow-up care in the community setting. Conventional discharge summaries do not adequately incorporate the elements specific to an aging clientele. Objective: To develop a discharge summary adapted to the frail elderly patient (D-SAFE) in order to communicate relevant information from hospital to community services. Methods: The items to be included in the D-SAFE have been determined by means of a modified Delphi method through consultation with clinical experts from GAUs (11 physicians and 5 pharmacists) and the community (10 physicians and 5 pharmacists). The consensus analysis and the level of agreement among the experts were reached using a modified version of the RAND®/University of California at Los Angeles appropriateness method. Results: A consensus was reached after two rounds of consultation for all the items evaluated, where none was judged «inappropriate». Among the items proposed, four were judged to be « uncertain » and were eliminated from the final D-SAFE, which was divided into two sections: the medical discharge summary (22 main items) and the discharge prescription (14 main items). Conclusions: The D-SAFE was developed as a more comprehensive tool specifically designed for GAU inpatients. Additional research to validate its acceptability and practical impact on the continuity of care is needed before it can be recommended for use on a broader scale. [ABSTRACT FROM AUTHOR]

The structural change of La9.33−2 x(SiO4)6O2−3 x with increasing x value was investigated by means of laboratory X-ray powder diffraction (Cu Kα1). Crystal structures of the three types of specimens with x=0, 0.06, and 0.085 were refined by the Rietveld method, with the anisotropic displacement ( U) parameters being assigned for all atoms. Each crystal structure was composed of three types of polyhedra: La1O9, La2O7, and SiO4. With increasing x value, the occupancies ( g) of both La1 and La2 sites decreased steadily. The La vacancies were charge balanced by the deficiency of the mobile O atoms that were not covalently bonded to Si atoms. The polyhedral volume of La2O7 decreased steadily about 0.7% with a decrease of the g(La2) value from 0.995 to 0.982. On the other hand, the polyhedral volume of La1O9 showed an increase of about 1.0% with a decrease of the g(La1) value from 0.841 to 0.818. The marked difference in deformation behavior of the two types of polyhedra could be attributable to the distinction in site occupancies between La1 [ g(La1)<0.85] and La2 [ g(La2)>0.98]. For the mobile O atoms, the displacement magnitudes, being evaluated from the U parameters, decreased steadily with increasing x value. The positional disordering of these atoms might be related to their mobilities at high temperatures. [ABSTRACT FROM AUTHOR]

Abstract: Lanthanum silicate oxyapatites of structural formula La9.33+x (SiO4)6O2+1.5x (0< x <0.27) are currently investigated for their high ionic conductivity. We have studied the synthesis of pure apatite powders, especially La9.33(SiO4)6O2 and La9.56(SiO4)6O2.34, by solid state reactions. We have finalized a synthesis process which limits the formation of the often encountered secondary phases La2SiO5 and La2Si2O7 by using an appropriate thermal treatment of the starting mixture. Lanthanum oxyapatite powders were synthesized at a temperature much lower (1200°C) than that used in the conventional powder solid-state synthesis routes (T >1600°C). X-ray diffraction, scanning electron microscopy and specific surface area measurements were used to analyze the structural and microstructural changes of the as prepared powders heated at different temperatures. Electrical characterization of pure sintered materials was conducted and showed that the incorporation of extra oxide ions, corresponding to the La9.56(SiO4)6O2.34 composition, enhanced the ionic conductivity by one order of magnitude when comparing to that of the La9.33(SiO4)6O2 sample. [Copyright &y& Elsevier]