Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Caractérisation de gènes de ß-glucisidase et d'UDP-glycosyltransférase potentiellement impliqués dans la lignification chez arabidopsis thaliana

Les lignines sont des hétéropolymères complexes formés par la polymérisation de sous-unités dérivées des monolignols. Du fait de leur noyau phénolique, les monolignols sont des composés toxiques pour la cellule et ils ne peuvent donc être stockés par celle-ci sous leur forme libre. Il a été suggéré que leur forme glucosylée pourrait être impliquée dans leur stockage et/ou leur transport. Les gènes UGT72E1, UGT72E2 et UGT72E3 codent pour des UDP-glycosyltransférases acceptant préférentiellement les monolignols comme substrats in vitro. Bien qu exprimés au niveau de la tige, ces trois gènes ne sont pas impliqués dans la lignification. Cependant, la répression de l expression de ces gènes mène à une dérégulation du métabolisme des phénylpropanoïdes. De même, le gène UGT72D1, phylogénétiquement proche des gènes UGT72E1, UGT72E2 et UGT72E3 n est pas impliqué dans la lignification et semble avoir un rôle proche de celui de l UGT72E3 in planta. Les gènes BGLU45, BGLU46 et BGLU47 codent pour des b-glucosidases proches d une b-glucosidase de pin spécifique de la coniférine (monolignol glycosylé). BGLU47 n est pas impliquée dans le métabolisme des phénylpropanoïdes. En revanche la répression de l expression des gènes BGLU45 et BGLU46 est responsable d une forte augmentation de la coniférine au niveau des tiges et des racines exposées à la lumière ainsi qu à une dérégulation de la voie de biosynthèse des phénylpropanoïdes. Bien qu ayant confirmé la présence de monolignols glycosylés dans les tiges d Arabidopsis, les travaux réalisés durant cette thèse n ont pas permis d établir une relation claire entre ceux-ci et le processus de lignification.Lignins are complex heteropolymers formed by the polymerization of sub-units derived from three monolignols. Due to the presence of their phenolic rings, monolignols are toxic compounds for cells, and they cannot be stored under their free form in the cytosol. It has been suggested that their glucosylated form could be involved in their storage and/or their transport. The UGT72E1, UGT72E2 and UGT72E3 genes code for UDP-glycosyltransferases specific for monolignols in vitro. Even if these three genes are expressed at the stem level, they are not involved in lignification. However, the repression of expression of these genes is responsible for a deregulation of the global phenylpropanoid pathway. In the same way, the UGT72D1 gene which is close to the UGT72E1, UGT72E2 and UGT72E3 genes is not involved in the lignification process and seems to have a similar role than UGT72E3 in planta. BGLU45, BGLU46 and BGLU47 code for b-glucosidases close to a pinus b-glucosidase specific for coniferin (a monolignol glucoside). BGLU47 is not involved in the phenylpropanoid metabolism. However, the repression of expression of BGLU45 and BGLU46 is responsible for an important increase of coniferin and of a deregulation of the global phenylpropanoid pathway in the stems and in light-grown roots of Arabidopsis. This work has allowed to confirm the presence of monolignol glucosides in Arabidopsis stems in normal growth conditions but hasn t allowed to confirm that these glucosides are involved in the lignification process.ORSAY-PARIS 11-BU Sciences (914712101) / SudocSudocFranceF

Dream recall frequency is associated with attention rather than with working memory abilities

International audienceSeveral factors influencing dream recall frequency (DRF) have been identified, but some remain poorly understood. One way to study DRF is to compare cognitive processes in low and high dream recallers (LR and HR). According to the arousal-retrieval model, long-term memory encoding of a dream requires wakefulness while its multisensory short-term memory is still alive. Previous studies showed contradictory results concerning short-term memory differences between LR and HR. It has also been found that extreme dream recall frequencies are associated with different electrophysiological traits related to attentional processes. However, to date, there is no evidence for attentional differences between LR and HR at the behavioural level. To further investigate attention and working memory in HR and LR, we used a newly-developed challenging paradigm, called MEMAT: it allows to study selective attention and working memory interaction, during memory encoding of non-verbal auditory stimuli. We manipulated the difficulties of the distractor to ignore and of the memory task. The performance of the two groups were not differentially impacted by working memory load. However, HR were slower and less accurate in presence of hard, rather than easy, toignore distractor, while LR were much less impacted by the distractor difficulty. Therefore, we show behavioural evidence towards less resistance to hard-to-ignore distractors in HR. Using a challenging task, we show for the first time attentional differences between HR and LR at the behavioural level. The impact of auditory attention and working memory on dream recall is discussed

Micro and nanotechnology evolution towards vertical Silicon nanowires for ultra-sensitive gas detection

International audienceMost commercial sensors, using metal oxide as sensitive layer, exhibit sensitivity in the ppm range with low selectivity. A part of our previous work is focused on developing new gas sensor array in a small chip based on microhotplates with four silicon membranes and various nanoscaled sensing materials on top deposited by inkjet printing. Moreover, to enhance significantly their performances, these layers operate at various temperatures in pulsed operating mode which drastically increases the possibility to discriminate mixtures of gases thank to appropriate data analysis. The main drawbacks of these structures concern the complexity of the process, the limit of detection above ppm and the power consumption as well. The one-dimensional nanostructures, such as nanowires (NWs) [1] or the nanotubes [2] are very promising for new generations of sensors with very low power consumption needed and potential sub-ppm detection. This is due to their very high form factor (surface / volume ratio), but also by the ability to be functionalized. The silicon NWs, popularized by Lieber [3], are particularly attractive due to their high sensitivity, biocompatibility and diversity of possible applications (gas [4] chemicals [5] biological [6] sensors). There are two main approaches to structure NWs: a "bottom-up" approach (rising) and "top-down" (down) [7]. The first method involves the growth of NWs by synthesis from elementary constituents by chemical reaction (polymerization) or physico-chemical assembly (crystal growth). The main limitation of this approach is the integration of NWs obtained in devices, due to difficulties in positioning the one hand, and to contact them electrically on the other hand. In the case of the "top-down" approach, the nanowire is formed by masking and then etching of bulk material. The key point of this method is the solution of nano-masking patterns, which often requires expensive equipment (electron beam lithography). NWs based gas sensors have already been discussed in the literature and various materials have been studied, such as SnO2 [8], CuO [9], Si [10] and InAs [11]. Whenever in a configuration known as "resistor", which consists in measuring the variation of electrical resistance of NW induced by variation of surround atmosphere. Currently, the best performance for a gas sensor based on silicon NWs (without any functionalization), from the viewpoint of the detection NH3 and NO2 was obtained by using horizontal NWs with a diameter of 130 nm [10]. The detection limit is closed to 0.5 ppm, and the sensitivity around 27%. The InAs NWs also demonstrate good sensitivity to NO2 (at 115 ppb), but with a relatively long response time (10 min) [11]. The objective of our present studies is to develop a new generation of highly sensitive gas sensors based on nanostructuring silicon as vertical nanowires well controlled with reproducible manner by a "top-down" approach. These nanowires are electrically contacted by a metallic suspended bridge. Thus a large surface NWs is available, and can react with the surrounding gas. This approach allows networks of NWs defined by optical photolithography. The number, diameter, spacing and position of NWs are perfectly controlled and thus we obtain reproducible devices. The sensors were then electrically characterized and mounted to be tested under different gas atmospheres (CO, NH3 and NO2). The first best results showed a strong sensitivity to low concentration of NO2 (30% at 50 ppb) with very low limit of detection (few ppb) and low sensitivity to both other gases

Le rôle émergeant de l'acétylation des protéines non-nucléaires

Lysine acetylation is a post-translational modification that critically regulates gene transcription by targeting histones as well as a variety of transcription factors in the nucleus. More recent reports have also demonstrated that numerous proteins located outside the nucleus are also acetylated and that this modification has profound consequences on their functions. This review describes the latest findings on the substrates acetylated outside the nucleus and on the acetylases and deacetylates that catalyse these modifications. Protein acetylation is emerging as a major mechanism by which key proteins are regulated in many physiological processes such as migration, metabolism and aging as well as in pathological circumstances such as cancer and neurodegenerative disorders

Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study.

OBJECTIVE:The study aimed to evaluate if the rate of tissue factor pathway inhibitor during pregnancy and following delivery could be a predictive factor for placenta-mediated adverse pregnancy outcomes in high-risk women. METHODS:This was a prospective multicentre cohort study of 200 patients at a high risk of occurrence or recurrence of placenta-mediated adverse pregnancy outcomes conducted between June 2008 and October 2010. Measurements of tissue factor pathway inhibitor resistance (normalized ratio) and tissue factor pathway inhibitor activity were performed for the last 72 patients at 20, 24, 28, 32, and 36 weeks of gestation and during the postpartum period. RESULTS:Overall, 15 patients presented a placenta-mediated adverse pregnancy outcome. There was no difference in normalized tissue factor pathway inhibitor ratios between patients with and without placenta-mediated adverse pregnancy outcomes during pregnancy and in the post-partum period. Patients with placenta-mediated adverse pregnancy outcomes had tissue factor pathway inhibitor activity rates that were significantly higher than those in patients without at as early as 24 weeks of gestation. The same results were observed following delivery. CONCLUSION:Among high-risk women, the tissue factor pathway inhibitor activity of patients with gestational vascular complications is higher than that in other patients. Hence, these markers could augment a screening strategy that includes an analysis of angiogenic factors as well as clinical and ultrasound imaging with Doppler measurement of the uterine arteries

Impact of the absence of stem-specific β-glucosidases on lignin and monolignols

Monolignol glucosides are thought to be implicated in the lignin biosynthesis pathway as storage and/or transportation forms of cinnamyl alcohols between the cytosol and the lignifying cell walls. The hydrolysis of these monolignol glucosides would involve beta-glucosidase activities. In Arabidopsis (Arabidopsis thaliana), in vitro studies have shown the affinity of beta-GLUCOSIDASE45 (BGLU45) and BGLU46 for monolignol glucosides. BGLU45 and BGLU46 genes are expressed in stems. Immunolocalization experiments showed that BGLU45 and BGLU46 proteins are mainly located in the interfascicular fibers and in the protoxylem, respectively. Knockout mutants for BGLU45 or BGLU46 do not have a lignin-deficient phenotype. Coniferin and syringin could be detected by ultra-performance liquid chromatography-mass spectrometry in Arabidopsis stems. Stems from BGLU45 and BGLU46 mutant lines displayed a significant increase in coniferin content without any change in coniferyl alcohol, whereas no change in syringin content was observed. Other glucosylated compounds of the phenylpropanoid pathway were also deregulated in these mutants, but to a lower extent. By contrast, BGLU47, which is closely related to BGLU45 and BGLU46, is not implicated in either the general phenylpropanoid pathway or in the lignification of stems and roots. These results confirm that the major in vivo substrate of BGLU45 and BGLU46 is coniferin and suggest that monolignol glucosides are the storage form of monolignols in Arabidopsis, but not the direct precursors of lignin

Correction: Tissue factor pathway inhibitor for prediction of placenta-mediated adverse pregnancy outcomes in high-risk women: AngioPred study.

[This corrects the article DOI: 10.1371/journal.pone.0173596.]