Introduction
Blood‐based biomarkers are the next challenge for Alzheimer's disease (AD) diagnosis and prognosis.
Methods
Mild cognitive impairment (MCI) participants (N = 485) of the BALTAZAR study, ...a large‐scale longitudinal multicenter cohort, were followed‐up for 3 years. A total of 165 of them converted to dementia (95% AD). Associations of conversion and plasma amyloid beta (Aβ)1‐42, Aβ1‐40, Aβ1‐42/Aβ1‐40 ratio were analyzed with logistic and Cox models.
Results
Converters to dementia had lower level of plasma Aβ1‐42 (37.1 pg/mL 12.5 vs. 39.2 11.1 , P value = .03) and lower Aβ1‐42/Aβ1‐40 ratio than non‐converters (0.148 0.125 vs. 0.154 0.076, P value = .02). MCI participants in the highest quartile of Aβ1‐42/Aβ1‐40 ratio (>0.169) had a significant lower risk of conversion (hazard ratio adjusted for age, sex, education, apolipoprotein E ε4, hippocampus atrophy = 0.52 (95% confidence interval 0.31–0.86, P value = .01).
Discussion
In this large cohort of MCI subjects we identified a threshold for plasma Aβ1‐42/Aβ1‐40 ratio that may detect patients with a low risk of conversion to dementia within 3 years.
To better understand the origin of animal cell types, body plans, and other morphological features, further biological knowledge and understanding are needed from non-bilaterian phyla, namely, ...Placozoa, Ctenophora, and Porifera. This chapter describes recent cell staining approaches that have been developed in three phylogenetically distinct sponge species-the homoscleromorph Oscarella lobularis, and the demosponges Amphimedon queenslandica and Lycopodina hypogea-to enable analyses of cell death, proliferation, and migration. These methods allow for a more detailed understanding of cellular behaviors and fates, and morphogenetic processes in poriferans, building on current knowledge of sponge cell biology that relies chiefly on classical (static) histological observations.
On s'habitue - presque - à tout, même à la violence ! On s'exaspère de tout, parfois des livres sur la violence ! On se proclame expert en tout, surtout quand il s'agit de dénoncer la violence ! On ...se veut cynique en tout, plus spécialement quand on administre la violence ! On se fatigue de tout, surtout des pratiques et représentations de la violence. Celle-ci est un défi à l'intelligence, à l'éthique et au sens de la responsabilité. Les formes de violence des histoires postcoloniales et leur perpétuation nous poussent à les (re)lire et à y traquer les confusions, les manipulations et les maquillages. Affectant l'histoire et la géographie, le physique et le mental, les individus et les communautés, les États et les sociétés civiles, le sacré et le profane, le local et le global, les contemporains et leurs aïeux, les violences nous récitent non seulement le chapelet de la construction de l'absurdité de l'existence postcoloniale, mais aussi l'injustifiable permanence de l'injustice. La violence révèle le fonds bestial qui sommeille en nous, chaque fois que, ivres de notre puissance ou de notre échec, nous mettons nos intelligences et nos responsabilités en veilleuse.
We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for ...gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk~and rare variants in SORL1, TREM2, and ABCA7. No exome-wide significant signal was obtained in the LOAD sample, and significance of the order of 10$^{-6}$ was observed in the whole AD group for TREM2. Our study confirms previous gene-level results for TREM2, SORL1, and ABCA7 and provides a~clearer insight into the classes of rare variants involved. Despite different effect sizes and~varying~cumulative minor allele frequencies, the rare protein-truncating and missense-predicted~damaging variants in TREM2, SORL1, and ABCA7 contribute similarly to the heritability of EOAD and explain between 1.1% and 1.5% of EOAD heritability each, compared with 9.12% for APOE $\varepsilon$4.
Cocaine-induced sensitization induces long-term neuroplastic changes in the striatum. Among these, extracellular signal-regulated kinase (ERK) is a fundamental component in striatal gene and ...epigenetic regulation and plays an important role in reward processes. As previous studies suggested that the chemokine CCL2 enhanced striatal dopamine release and as its cognate CCR2 receptor was located in brain structures implicated in cocaine reward, we tested the hypothesis that CCR2/CCL2 could be involved in cocaine-induced behavioral response. We used CCR2 knockout mice (CCR2
−/−
) and studied two crucial steps in cocaine sensitization: locomotor activity in sensitized mice and ERK activation in the striatum. We show that locomotor sensitization is significantly reduced in CCR2
−/−
mice as well as the dopamine transporter regulation and the cocaine-induced p-ERK striatal activation. Taken together, our results suggest that CCR2 receptor is involved in cocaine sensitization.
Rituximab, a monoclonal antibody now widely used to treat autoimmune diseases, has been reported to be effective against refractory Wegener's granulomatosis and its ophthalmic involvement. Herein, we ...report on 2 patients with refractory Wegener's granulomatosis and scleritis in whom cystoid macular oedema occurred several weeks after rituximab infusions. Notably, scleritis had already resolved when macular oedema was diagnosed. One patient's macular oedema was successfully treated with a subtenon injection of triamcinolone but recurred soon after she received a second cycle of rituximab as maintenance therapy. To our knowledge, to date no ophthalmic side effect has been reported after rituximab administration. The short time between each rituximab infusion and the onset of cystoid macular oedema strongly suggests a causal link.
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