Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death

A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown.

New concept for CTO recanalization using controlled antegrade and retrograde subintimal tracking: the CART technique

OBJECTIVES: To demonstrate the safety and feasibility of a new concept for CTO recanalization using a controlled antegrade and retrograde subintimal tracking technique (CART technique). BACKGROUND: A successful percutaneous recanalization of chronic coronary occlusions results in improved survival, as well as enhanced left ventricular function, reduction in angina, and improved exercise tolerance. However, successful recanalization of CTOs is still not optimal, and needs further improvements. METHODS: Ten patients with a CTO underwent the CART procedure. This technique combines the simultaneous use of the antegrade and retrograde approaches. A subintimal dissection is created antegradely and retrogradely, which allows the operator to limit the extension of the subintimal dissection in the CTO portion. A retrograde approach means that the occlusion site is approached in a retrograde fashion through the best collateral channel from any other patent coronary artery. RESULTS: The occlusion site was located in the RCA in 9 patients, and in the LAD in 1 patient. CTO duration varied from 7 to 84 months. Vessel recanalization was achieved in all patients. In all cases, the subintimal dissection was limited to the CTO region. No complications occurred in the collateral channel used for the retrograde approach. There were no in-hospital major adverse cardiac events. CONCLUSIONS: The CART technique is feasible, safe, and has a high success rate.

Prognosis of patients treated with cART from 36 months after initiation, according to current and previous CD4 cell count and plasma HIV-1 RNA measurements

OBJECTIVES: CD4 cell count and plasma viral load are well known predictors of AIDS and mortality in HIV-1-infected patients treated with combination antiretroviral therapy (cART). This study investigated, in patients treated for at least 3 years, the respective prognostic importance of values measured at cART initiation, and 6 and 36 months later, for AIDS and death. METHODS: Patients from 15 HIV cohorts included in the ART Cohort Collaboration, aged at least 16 years, antiretroviral-naive when they started cART and followed for at least 36 months after start of cART were eligible. RESULTS: Among 14 208 patients, the median CD4 cell counts at 0, 6 and 36 months were 210, 320 and 450 cells/microl, respectively, and 78% of patients achieved viral load less than 500 copies/ml at 6 months. In models adjusted for characteristics at cART initiation and for values at all time points, values at 36 months were the strongest predictors of subsequent rates of AIDS and death. Although CD4 cell count and viral load at cART initiation were no longer prognostic of AIDS or of death after 36 months, viral load at 6 months and change in CD4 cell count from 6 to 36 months were prognostic for rates of AIDS from 36 months. CONCLUSIONS: Although current values of CD4 cell count and HIV-1 RNA are the most important prognostic factors for subsequent AIDS and death rates in HIV-1-infected patients treated with cART, changes in CD4 cell count from 6 to 36 months and the value of 6-month HIV-1 RNA are also prognostic for AIDS.

CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling.

Altering the number of surface receptors can rapidly modulate cellular responses to extracellular signals. Some receptors, like the transferrin receptor (TfR), are constitutively internalized and recycled to the plasma membrane. Other receptors, like the epidermal growth factor receptor (EGFR), are internalized after ligand binding and then ultimately degraded in the lysosome. Routing internalized receptors to different destinations suggests that distinct molecular mechanisms may direct their movement. Here, we report that the endosome-associated protein hrs is a subunit of a protein complex containing actinin-4, BERP, and myosin V that is necessary for efficient TfR recycling but not for EGFR degradation. The hrs/actinin-4/BERP/myosin V (CART [cytoskeleton-associated recycling or transport]) complex assembles in a linear manner and interrupting binding of any member to its neighbor produces an inhibition of transferrin recycling rate. Disrupting the CART complex results in shunting receptors to a slower recycling pathway that involves the recycling endosome. The novel CART complex may provide a molecular mechanism for the actin-dependence of rapid recycling of constitutively recycled plasma membrane receptors.

Le temps des hommes doubles. Les arrangements face à l’occupation, de la Révolution française à la guerre de 1870

Le temps des hommes doubles : Louis Aragon a désigné ainsi la séparation voire l’opposition entre l’homme social et l’homme privé dans la société capitaliste. Pour les auteurs réunis ici, il s’agit plutôt de signifier qu’au temps de la souveraineté nationale en armes, dès lors que sont plus rigoureusement assignées aux soldats et aux citoyens à la fois une « identité » et une « cause » supposées dépasser leur état civil et leurs intérêts particuliers, l’occupation militaire multiplie, dans la recherche d’accommodements entre les deux camps, les tensions et les combinaisons possibles entre fonctions ou statuts publics, sociabilités et influences locales, opinions et besoins. Pour caractériser les évolutions qui ont eu lieu entre les guerres déclarées par la France à l’Autriche en 1792 et à la Prusse en 1870, le présent livre met l’accent sur trois thèmes. Il traite d’abord des enjeux politiques et administratifs de l’occupation, parmi lesquels la neutralité, son devenir en tant que concept dans les relations internationales, et le positionnement des États neutres dans des conflits où l’on s’efforce de mobiliser aussi les opinions publiques. L’attention se porte ensuite sur les armées occupantes. Quelle que soit la part d’idéologie que l’autorité politique introduit dans leurs missions, la première de ces missions est de garantir leur propre sécurité. La recherche des accommodements ou le constat de l’extrême difficulté d’en trouver sont enfin abordés du point de vue des sociétés en proie à l’occupation. Dans ces situations où le présent peut être vécu et interprété en fonction d’une mémoire individuelle et collective d’expériences antérieures, le rôle joué par les occupants ne se réduit pas à la brutalité de la soldatesque et à l’exploitation économique.

Le mitan de la vie, temps du bilan

Arrivées à l’âge mûr, de nombreuses personnes vivent une crise existentielle. Certaines divorcent ou changent de cap. D’autres redéfinissent sereinement leur identité. Chiffres et réflexion sur cette période délicate.