Dépression et niveau de fardeau chez les aidants familiaux des sujets déments en Tunisie

Introduction: La démence peut retentir lourdement sur les aidants familiaux du patient. Les objectifs de notre étude étaient de déterminer le niveau de fardeau et de la dépression chez les aidants familiaux de sujets déments, et d’identifier les facteurs associés à un niveau de fardeau élevé. Méthodes: Il s’agissait d’une enquête auprès de 65 aidants tunisiens. Les niveaux de fardeau et de la dépression ont été évalués par, respectivement, l’inventaire de Zarit et l’échelle de Beck. Résultats: Le taux des aidants qui avaient un niveau de fardeau élevé était de 52,3 %. Une dépression modérée ou sévère a été relevée chez 46,2 %. Un niveau de fardeau élevé était corrélé, du côté de l’aidant, avec le niveau socioéconomique moyen à élevé, la cohabitation avec le patient, le fait d’être son conjoint, la réduction des activités quotidiennes et la sévérité de la dépression, et, du côté du dément, avec l’agressivité. Conclusion: Les facteurs corrélés à un niveau de fardeau élevé orientent vers les cibles d’intervention et sont susceptibles d’être améliorés par la prise en charge, ce qui contribuerait à alléger la détresse des aidants

Oral Probiotic Control Skin Inflammation by Acting on Both Effector and Regulatory T Cells

Probiotics are believed to alleviate allergic and inflammatory skin disorders, but their impact on pathogenic effector T cells remains poorly documented. Here we show that oral treatment with the probiotic bacteria L. casei (DN-114 001) alone alleviates antigen-specific skin inflammation mediated by either protein-specific CD4+ T cells or hapten-specific CD8+ T cells. In the model of CD8+ T cell-mediated skin inflammation, which reproduces allergic contact dermatitis in human, inhibition of skin inflammation by L. casei is not due to impaired priming of hapten-specific IFNγ-producing cytolytic CD8+ effector T cells. Alternatively, L. casei treatment reduces the recruitment of CD8+ effector T cells into the skin during the elicitation (i.e. symptomatic) phase of CHS. Inhibition of skin inflammation by L. casei requires MHC class II-restricted CD4+ T cells but not CD1d-restricted NK-T cells. L casei treatment enhanced the frequency of FoxP3+ Treg in the skin and increased the production of IL-10 by CD4+CD25+ regulatory T cells in skin draining lymph nodes of hapten-sensitized mice. These data demonstrate that orally administered L. casei (DN-114 001) efficiently alleviate T cell-mediated skin inflammation without causing immune suppression, via mechanisms that include control of CD8+ effector T cells and involve regulatory CD4+ T cells. L. casei (DN-114 001) may thus represent a probiotic of potential interest for immunomodulation of T cell-mediated allergic skin diseases in human

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

Palladium-Catalysed C–F Alumination of Fluorobenzenes: Mechanistic Diversity and Origin of Selectivity

A palladium pre-catalyst, [Pd(PCy3)2] is reported for the efficient and selective C–F alumination of fluorobenzenes with the aluminium(I) reagent [{(ArNCMe)2CH}Al] (1, Ar = 2,6-di-iso-propylphenyl). The catalytic protocol results in the transformation of sp2 C–F bonds to sp2 C–Al bonds and provides a route into reactive organoaluminium complexes (2a-h) from fluorocarbons. The catalyst is highly active. Reactions proceed within 5 minutes at 25 ºC (and at appreciable rates at even –50 ºC) and the scope includes low-fluorine-content substrates such as fluorobenzene, difluorobenzenes and trifluorobenzenes. The reaction proceeds with complete chemoselectivity (C–F vs C–H) and high regioselectivities ( >90% for C–F bonds adjacent to the most acidic C–H sites). The heterometallic complex [Pd(PCy3)(1)2] was shown to be catalytically competent. Catalytic C–F alumination proceeds with a KIE of 1.1–1.3. DFT calculations have been used to model potential mechanisms for C–F bond activation. These calculations suggest that two competing mechanisms may be in operation. Pathway 1 involves a ligand-assisted oxidative addition to [Pd(1)2] and leads directly to the product. Pathway 2 involves a stepwise C–H to C–F functionalisation mechanism in which the C–H bond is broken and reformed along the reaction coordinate, allowing it to act as a directing group for the adjacent C–F site. This second mechanism explains the experimentally observed regioselectivity. Experimental support for this C–H activation playing a key role in C–F alumination was obtained by employing [{(MesNCMe)2CH}AlH2] (3, Mes = 2,4,6-trimethylphenyl) as a reagent in place of 1. In this instance, the kinetic C–H alumination intermediate could be isolated. Under catalytic conditions this intermediate converts to the thermodynamic C–F alumination product

Topical Ivermectin 10~mg/g and Oral Doxycycline 40~mg Modified-Release: Current Evidence on the Complementary Use of Anti-Inflammatory Rosacea Treatments

International audienceRosacea is a common, chronic inflammatory skin disease that can present with a variety of signs and symptoms. The potentially simultaneous occurrence of different signs and symptoms is due to different underlying inflammatory pathways, emphasizing the need for complementary treatment approaches. Topical ivermectin cream (10~mg/g) and systemic, oral anti-inflammatory doxycycline (40 mg modified-release) are both approved for the treatment of papulopustular rosacea (PPR). Whether or not a combined therapeutic approach may be more beneficial than monotherapy for patients with PPR remains to be tested. Here, we summarize underlying inflammatory pathways implicated in rosacea and clarify the impact of these two agents on selective pathways during inflammation, due to specific characteristics of their individual mechanisms of action (MoA). Based on the complementary MoA of doxycycline modified-release and ivermectin, a scientific rationale for a combined therapy targeting inflammatory lesions in rosacea is given. We propose that topical ivermectin cream is a promising new candidate as first-line treatment to target the inflammatory lesions of rosacea, which can be used in combination with systemic doxycycline modified-release to provide an optimal treatment approach considering all inflammatory pathways involved in PPR. Funding Galderma

Alumination of Aryl Methyl Ethers: Switching Between Sp2 and Sp3 C–O Bond Functionalisation with Pd-Catalysis

The reaction of [{(ArNCMe)2CH}Al] (Ar = 2,6-di-iso-propylphenyl, 1) with aryl methyl ethers proceeded with alumination of the sp3 C–O bond by a presumed SN2 pathway. The selectivity of this reaction could be switched by inclusion of a catalyst. In the presence of [Pd(PCy3)2], chemoselective sp2 C–O bond functionalisation was observed. Kinetic isotope experiments and DFT calculations support a catalytic pathway involving the ligand-assisted oxidative addition of the sp2 C–O bond to a Pd---Al intermetallic complex. The net result of both non-catalysed and catalytic pathways is the generation of polar organoaluminium complexes from aryl methyl ethers with complete atom-efficiency. Switches in selectivity yield isomeric products from a single starting material. The methodology (and mechanistic insight) holds promise as a means to functionalise aromatic molecules derived from lignin depolymerisation and we demonstrate an application to a derivative of vanillin

Catalyst Control of Selectivity in the C–O Bond Alumination of Biomass Derived Furans

Non-catalysed and catalysed reactions of aluminium reagents with furans, dihydrofurans and dihydropyrans were investigated and lead to the ring-expanded products due to the formal insertion of the aluminium reagent into a C–O bond of the heterocycle. Specifically, the reaction of [{(ArNCMe)2CH}Al] (Ar = 2,6-di-iso-propylphenyl, 1) with furan, 2-methylfuran, 2,3-dimethylfuran and 2-methoxyfuran proceeded between 25 and 80 ºC leading to ring-expanded and dearomatised products due to the net transformation of a sp2 C–O bond into a sp2 C–Al bond. The kinetics of the reaction of 1 with furan were found to be 1st order with respect to 1 with activation parameters ΔH‡ = +19.7 (± 2.7) kcal mol-1, ΔS‡ = –18.8 (± 7.8) cal K-1 mol-1 and ΔG‡298 K = +25.3 (± 0.5) kcal mol-1 and a KIE of 1.0 ± 0.1. DFT calculations support a stepwise mechanism involving an initial (4+1) cycloaddition of 1 with furan to form a bicyclic intermediate that rearranges by an a-migration. The selectivity of ring-expansion is influenced by factors that weaken the sp2 C–O bond through population of the s*-orbital. Inclusion of [Pd(PCy3)2] as a catalyst in these reactions results in expansion of the substrate scope to include 2,3-dihydrofurans and 3,4-dihydropyrans but also improves the selectivity. Under catalysed conditions, the C–O bond that breaks is that adjacent to C–H bond. The aluminium(III) dihydride reagent [{(MesNCMe)2CH}AlH2] (Mes = 2,4,6-trimethylphenyl, 2) can also be used under catalytic conditions to effect a dehydrogenative ring-expansion of furans. Further mechanistic analysis of the Pd-catalysed reaction of 1 with furan shows that C–O bond functionalisation occurs via an initial C–H bond alumination. Kinetic products can be isolated that are derived from installation of the aluminium reagent at the 2-position of the heterocycle. C–H alumination proceeds with a strong primary KIE of 4.8 ± 0.3 consistent with a turnover limiting step involving oxidative addition of the C–H bond to a palladium catalyst. Isomerisation of the kinetic C–H aluminated product to the thermodynamic C–O ring expansion product is an intramolecular process that is again catalysed by [Pd(PCy3)2]. DFT calculations suggest that the key C–O bond breaking step involves attack of an aluminium based metalloligand on the 2-palladated heterocycle. The new methodology has been applied to the upgrading of molecules derived from furfuraldehyde, an important platform chemical from biomass

Quantifying critical N dilution curves across G × E × M effects for potato using a partially-pooled Bayesian hierarchical method

Multiple critical N dilution curves [CNDCs] have been previously developed for potato; however, attempts to directly compare differences in CNDCs across genotype [G], environment [E], and management [M] interactions have been confounded by non-uniform statistical methods, biased experimental data, and lack of proper quantification of uncertainty in the critical N concentration [%Nc]. This study implements a partially-pooled Bayesian hierarchical method to develop CNDCs for previously published and newly reported experimental data, systematically evaluates the difference in %Nc [∆%Nc] across G × E × M effects, and directly compare CNDCs from the Bayesian framework to CNDCs from conventional statistical methods. The partially-pooled Bayesian hierarchical method implemented in this study has the advantage of being less susceptible to inferential bias at the level of individual G × E × M interactions compared to alternative statistical methods that result from insufficient quantity and quality of experimental datasets (e.g., unbalanced distribution of N limiting and non-N limiting observations). This method also allows for a direct statistical comparison of differences in %Nc across levels of the G × E × M interactions. Where found to be significant, ∆%Nc was hypothesized to be related to variation in the timing of tuber initiation (e.g., maturity class) and the relative rate of tuber bulking (e.g., planting density) across G x E × M interactions. In addition to using the median value for %Nc (i.e., CNDC), the lower and upper boundary values for the credible region (i.e., CNDClo and CNDCup) derived using the Bayesian framework should be used in calculation of N nutrition index (and other calculations) to account for uncertainty in %Nc. Overall, this study provides additional evidence that%Nc is dependent upon G × E × M interactions; therefore, evaluation of crop N status or N use efficiency must account for variation in %Nc across G × E × M interactions.EEA BalcarceFil: Bohman, Brian J. University of Minnesota. Department of Soil, Water, and Climate; Estados Unidos.Fil: Culshaw-Maurer, Michael J. University of Arizona. CyVerse; Estados Unidos.Fil: Abdallah, Feriel Ben. Walloon Agricultural Research Centre. Productions in Agriculture Department, Crop Production Unit, Bélgica.Fil: Giletto, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina. Unidad Integrada Balcarce. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Bélanger, Gilles. Science and Technology Branch, Agriculture and Agri-Food Canada; Canadá.Fil: Fernández, Fabián G. University of Minnesota. Department of Soil, Water, and Climate; Estados Unidos.Fil: Miao, Yuxin. University of Minnesota. Department of Soil, Water, and Climate; Estados Unidos.Fil: Mulla, David J. University of Minnesota. Department of Soil, Water, and Climate; Estados Unidos.Fil: Rosen, Carl J. University of Minnesota. Department of Soil, Water, and Climate; Estados Unidos