Antagonism of Tetherin Restriction of HIV-1 Release by Vpu Involves Binding and Sequestration of the Restriction Factor in a Perinuclear Compartment

The Vpu accessory protein promotes HIV-1 release by counteracting Tetherin/BST-2, an interferon-regulated restriction factor, which retains virions at the cell-surface. Recent reports proposed β-TrCP-dependent proteasomal and/or endo-lysosomal degradation of Tetherin as potential mechanisms by which Vpu could down-regulate Tetherin cell-surface expression and antagonize this restriction. In all of these studies, Tetherin degradation did not, however, entirely account for Vpu anti-Tetherin activity. Here, we show that Vpu can promote HIV-1 release without detectably affecting Tetherin steady-state levels or turnover, suggesting that Tetherin degradation may not be necessary and/or sufficient for Vpu anti-Tetherin activity. Even though Vpu did not enhance Tetherin internalization from the plasma membrane (PM), it did significantly slow-down the overall transport of the protein towards the cell-surface. Accordingly, Vpu expression caused a specific removal of cell-surface Tetherin and a re-localization of the residual pool of Tetherin in a perinuclear compartment that co-stained with the TGN marker TGN46 and Vpu itself. This re-localization of Tetherin was also observed with a Vpu mutant unable to recruit β-TrCP, suggesting that this activity is taking place independently from β-TrCP-mediated trafficking and/or degradation processes. We also show that Vpu co-immunoprecipitates with Tetherin and that this interaction involves the transmembrane domains of the two proteins. Importantly, this association was found to be critical for reducing cell-surface Tetherin expression, re-localizing the restriction factor in the TGN and promoting HIV-1 release. Overall, our results suggest that association of Vpu to Tetherin affects the outward trafficking and/or recycling of the restriction factor from the TGN and as a result promotes its sequestration away from the PM where productive HIV-1 assembly takes place. This mechanism of antagonism that results in TGN trapping is likely to be augmented by β-TrCP-dependent degradation, underlining the need for complementary and perhaps synergistic strategies to effectively counteract the powerful restrictive effects of human Tetherin

Influence of the reuse of OSB and marine plywood formworks on concrete surface aesthetics

Concrete surface quality becomes more and more important because aesthetics requirements tend to spread over a wide variety of construction works. Even if it is difficult to clearly define what is beautiful or not, existing techniques maybe used to quantify aesthetic properties of concrete. As they mainly depend on formwork, the research project focuses on the reuse of two types of panels – plywood and OSB – and two types of release agents – vegetal and mineral oils. Evolution of surface properties is measured through lightness and absorption. For plywood formworks, beyond 80 reuses, a modification of surface quality is noticed; this is only 50 for OSB panels. For both types of formworks, the release oil doesn’t seem to have a major influence on formwork absorption. It is also observed that alkalis cause early degradation of the panels: release agents are not always efficient to avoid this phenomenon. Finally, if reuse doesn’t have any influence on the absorption of the plywood formworks, it is not the case for OSB formworks

Association between extremely preterm caesarean delivery and maternal depressive and anxious symptoms: a national population‐based cohort study

International audienc

Association between gestational age and severe maternal morbidity and mortality of preterm cesarean delivery: a population-based cohort study

International audienc

Active Management of the Third Stage of Labor with a Combination of Oxytocin and Misoprostol to Prevent Postpartum Hemorrhage: A Randomized Controlled Trial

International audienceOBJECTIVE: To evaluate the effectiveness and safety of misoprostol administered simultaneously with oxytocin as part of the active management of the third stage of labor. METHODS: This multicenter, double-blind, randomized, placebo-controlled trial recruited women in the first stage of labor with expected vaginal deliveries at 36-42 weeks of gestation. Exclusion criteria were multiple pregnancies, hypersensitivity to misoprostol, and cesarean delivery. Participants received routine intravenous oxytocin and were randomly allocated to receive 400 micrograms misoprostol or placebo orally immediately after delivery of the newborn. The primary outcome was postpartum hemorrhage (500 mL or greater within 2 hours of birth). Secondary outcomes included severe postpartum hemorrhage (1,000 mL or greater) and adverse maternal events such as fever, shivering, and nausea. Two groups of 1,550 women were required to demonstrate a 33% decrease of postpartum hemorrhage according to a two-tailed α at 0.05 with 80% power. An interim analysis was planned after 50% enrollment. RESULTS: Participant enrollment occurred from April 2010 to September 2013. Baseline characteristics were similar in the two groups. The study was discontinued after the planned interim analysis including 1,721 patients showed that misoprostol was not effective and was associated with significantly more adverse effects. The rate of postpartum hemorrhage was 8.4% (68/806) in the misoprostol and 8.3% (66/797) in the placebo group (P.98), and rates of severe postpartum hemorrhage were 1.8% and 2.4%, respectively (P.57). Maternal adverse events occurred significantly more frequently in the misoprostol group (for fever 30.4% in the misoprostol group compared with 6.3% in the placebo group, P<.001; for shivering 10.8% in the misoprostol group compared with 0.6% in the placebo group, P<.001). CONCLUSION: Misoprostol administered with prophylactic routine oxytocin did not reduce the rate of postpartum hemorrhage risk and increased the rate of adverse events

Influence of the reuse of OSB and marine plywood formworks on concrete surface aesthetics

peer reviewedConcrete surface quality becomes more and more important because aesthetics requirements tend to spread over a wide variety of construction works. Even if it is difficult to clearly define what is beautiful or not, existing techniques maybe used to quantify aesthetic properties of concrete. As they mainly depend on formwork, the research project focuses on the reuse of two types of panels – plywood and OSB – and two types of release agents – vegetal and mineral oils. Evolution of surface properties is measured through lightness and absorption. For plywood formworks, beyond 80 reuses, a modification of surface quality is noticed; this is only 50 for OSB panels. For both types of formworks, the release oil doesn’t seem to have a major influence on formwork absorption. It is also observed that alkalis cause early degradation of the panels: release agents are not always efficient to avoid this phenomenon. Finally, if reuse doesn’t have any influence on the absorption of the plywood formworks, it is not the case for OSB formworks

Chorionicity and neurodevelopmental outcomes at 5½ years among twins born preterm: the EPIPAGE2 cohort study

Abstract Objective To compare the neurodevelopmental outcomes of preterm twins at 5½ years by chorionicity of pregnancy. Design Prospective nationwide population‐based EPIPAGE2 (Etude Epidémiologique sur les Petits Âges Gestationnels) cohort study. Setting A total of 546 maternity units in France, between March and December 2011. Population A total of 1126 twins eligible for follow‐up at 5½ years. Methods The association of chorionicity with outcomes was analysed using multivariate regression models. Main outcome measures Survival at 5½ years with or without neurodevelopmental disabilities (comprising cerebral palsy, visual, hearing, cognitive deficiency, behavioural difficulties or developmental coordination disorders) were described and compared by chorionicity. Results Among the 1126 twins eligible for follow‐up at 5½ years, 926 (82.2%) could be evaluated: 228 monochorionic (MC) and 698 dichorionic (DC). Based on chronicity and gestational age of birth, we found no significant differences for severe neonatal morbidity. The rates of moderate/severe neurobehavioral disabilities were similar in infants from DC pregnancies versus infants from MC pregnancies (OR 1.22, 95% CI 0.65–2.28). By gestational age and without twin–twin transfusion syndrome (TTTS), no difference according to chorionicity was found for all neurodevelopmental outcome measures. Conclusions The neurodevelopmental outcomes among preterm twins at 5½ years is similar, irrespective of chorionicity

An observational study of the fresh frozen plasma: Red blood cell ratio in postpartum hemorrhage

BACKGROUND: Postpartum hemorrhage is the leading cause of maternal death worldwide. Recent data from trauma patients and patients with hemorrhagic shock have suggested that an increased fresh frozen plasma:red blood cell (FFP:RBC) ratio may be of benefit in massive bleeding. We addressed this issue in cases of severe postpartum hemorrhage. METHODS: We reviewed data from all patients diagnosed with severe postpartum hemorrhage during a 4-year period (2006-2009). Patients who were treated with sulprostone and required transfusion within 6 hours of delivery were included in the study and were divided into 2 groups according to their response to sulprostone: bleeding controlled with sulprostone alone (sulprostone group) and bleeding requiring an additional advanced interventional procedure including arterial angiographic embolization and/or surgical procedures (arterial ligation, B-Lynch suture, or hysterectomy; intervention group). The requirement or no requirement for advanced procedures constituted the primary end point of the study. Propensity scoring was used to assess the effect of a high FFP:RBC ratio on bleeding control. RESULTS: Among 12,226 deliveries during the study period, 142 (1.1%) were complicated by severe postpartum hemorrhage. Bleeding was controlled with sulprostone alone in 90 patients (63%). Advanced interventional procedures were required for 52 patients (37%). Forty-one patients were transfused with both RBCs and FFP. The FFP:RBC ratio increased over the study period (P < 0.001), from 1:1.8 at the start to 1:1.1 at the end of the study period. After propensity score modeling (inverse probability of treatment weighting), a high FFP:RBC ratio was associated with lower odds for advanced interventional procedures (odds ratio [95% confidence interval], 1.25 [1.07-1.47]; P = 0.008). There were no deaths, severe organ dysfunction, or other complications as a consequence of severe postpartum hemorrhage. CONCLUSIONS: In this retrospective study, a higher FFP:RBC ratio was associated with a lower requirement for advanced interventional procedures in the setting of postpartum hemorrhage. The benefits of transfusion using a higher FFP:RBC ratio should be confirmed by randomized-controlled trials. Copyright © 2012 International Anesthesia Research Society.SCOPUS: ar.jinfo:eu-repo/semantics/publishe