Attention deficit hyperactivity disorder symptoms and cannabis use after 1 year among students of the i-Share cohort

ADHD; Cannabis; StudentsTDAH; Canabis; EstudiantesTDAH; Cànnabis; EstudiantsBackground Cannabis use in university students is associated with academic achievement failure and health issues. The objective of the study was to evaluate the association between attention deficit hyperactivity disorder (ADHD) symptoms and cannabis use after 1 year among students according to previous cannabis use. Methods Students in France were recruited from February 2013 to July 2020 in the i-Share cohort. 4,270 participants were included (2,135 who never used cannabis at inclusion and 2,135 who did). The Adult ADHD Self-Report Scale (ASRS) was used to assess ADHD symptoms at inclusion. Cannabis use frequency was evaluated 1 year after inclusion. Multinomial regressions were conducted to assess the association between inclusion ADHD symptoms and cannabis use after 1 year. Results Increase in ASRS scores was linked with a greater probability to use cannabis after 1 year and to have a higher cannabis use frequency (once a year—once a month adjusted odds ratio [OR]: 1.24 (1.15–1.34), more than once a month adjusted OR: 1.43 (1.27–1.61)). Among participants who never used cannabis at inclusion, this association disappeared (once a year—once a month adjusted OR: 1.15 (0.95–1.39), more than once a month adjusted OR: 1.16 (0.67–2)) but remained in participants who ever used cannabis at inclusion (once a year—once a month adjusted OR: 1.17 (1.06–1.29), more than once a month adjusted OR: 1.35 (1.18–1.55)). Conclusions High levels of ADHD symptoms in students could lead to continued cannabis use rather than new initiations.The preparation and initiation of the i-Share project was funded by the program ‘Invest for future’ (reference ANR-10-COHO-05). The i-Share Project is currently supported by an unrestricted grant from the Nouvelle-Aquitaine Regional Council (Conseil Régional Nouvelle-Aquitaine) (grant number: 4370420) and by the Bordeaux ‘Initiatives d’excellence’ (IdEx) program of the University of Bordeaux (ANR-10-IDEX-03-02). It has also received grants from the Nouvelle-Aquitaine Regional Health Agency (Agence Régionale de Santé Nouvelle-Aquitaine, grant N°6066R-8 R-8), Public Health France (Santé Publique France, grant number: 19DPPP023–0), the National Cancer Institute (Insitut national du cancer, grant number: INCa_11502), and the Medical Research Foundation (Fondation pour la recherche)

038 Major bleeding still predicts death with a radial invasive strategy in NSTE-ACS: an analysis from theABOARD Study

AimWe sought to determine the incidence and type of major bleeding in moderate-to-high risk acute coronary syndromes (ACS) treated with intense antiplatelet therapy and systematic invasive strategy using predominantly the radial approach. We also examined whether these bleedings has an impact on mortality after multivariable adjustment.MethodsIn the multicenter randomized ABOARD study, 352 patients with acute coronary syndromes without ST-segment elevation were randomized for a “primary PCI” strategy or a strategy of intervention deferred to the next working day. No difference was observed in clinical outcomes between the two groups. Major bleeding complications (STEEPLE definitions) were correlated to 1 month mortality.ResultsPatients were treated by intense antiplatelet therapy: with a mean 660mg (±268) loading of clopidogrel and 111mg (±40) maintenance dose while 99% of the PCI patients receive abciximab the radial approach was predominant (84%).During the first 30 days major bleeding complications occurred in 19 patients (5.4%) with transfusion in 16 patients (4.5%). Occurrence of major bleeding did not differ between immediate and delayed intervention. The most frequent overt bleeding complications were from the gastrointestinal tract. The composite of GI bleeding and occult bleeding (loss of Hb of >3g/dL) represented n = 11 (57.9%) of all major bleeding complications. Major bleeding was associated with a significantly higher peak of creatinine during hospitalization 170.16 μmol/L ± 169.34 vs. 97.05 μmol/L ± 56.96 (p = 0.005) and a higher mortality rate 26.3% vs. 0.6%. After adjustment for all baseline characteristics, major bleeding was independently associated with an impressive increased hazard of death during the first 30 days (Odd ratio 75.7; 95% CI, 11.3 to 505.3; p<0.0001).ConclusionIn a population of radial catheterization for NSTEACS, GI bleeding is the most frequent bleeding complication. Despite the reduction of access site bleeding, major bleeding still remains a major independent predictor of mortality

Oxidative protein folding in bacteria

Ten years ago it was thought that disulphide bond formation in prokaryotes occurred spontaneously. Now two pathways involved in disulphide bond formation have been well characterized, the oxidative pathway, which is responsible for the formation of disulphides, and the isomerization pathway, which shuffles incorrectly formed disulphides. Disulphide bonds are donated directly to unfolded polypeptides by the DsbA protein; DsbA is reoxidized by DsbB. DsbB generates disulphides de novo from oxidized quinones. These quinones are reoxidized by the electron transport chain, showing that disulphide bond formation is actually driven by electron transport. Disulphide isomerization requires that incorrect disulphides be attacked using a reduced catalyst, followed by the redonation of the disulphide, allowing alternative disulphide pairing. Two isomerases exist in Escherichia coli , DsbC and DsbG. The membrane protein DsbD maintains these disulphide isomerases in their reduced and thereby active form. DsbD is kept reduced by cytosolic thioredoxin in an NADPH-dependent reaction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75150/1/j.1365-2958.2002.02851.x.pd

2019 ESC/EAS guidelines for the management of dyslipidaemias : Lipid modification to reduce cardiovascular risk

Correction: Volume: 292 Pages: 160-162 DOI: 10.1016/j.atherosclerosis.2019.11.020 Published: JAN 2020Peer reviewe

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60&nbsp;years old

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Fine-Tuning of the Cpx Envelope Stress Response Is Required for Cell Wall Homeostasis in Escherichia coli

The envelope of Gram-negative bacteria is an essential compartment that constitutes a protective and permeability barrier between the cell and its environment. The envelope also hosts the cell wall, a mesh-like structure made of peptidoglycan (PG) that determines cell shape and provides osmotic protection. Since the PG must grow and divide in a cell-cycle-synchronized manner, its synthesis and remodeling are tightly regulated. Here, we discovered that PG homeostasis is intimately linked to the levels of activation of the Cpx system, an envelope stress response system traditionally viewed as being involved in protein quality control in the envelope. We first show that Cpx is activated when PG integrity is challenged and that this activation provides protection to cells exposed to antibiotics inhibiting PG synthesis. By rerouting the outer membrane lipoprotein NlpE, a known Cpx activator, to a different envelope subcompartment, we managed to manipulate Cpx activation levels. We found that Cpx overactivation leads to aberrant cellular morphologies, to an increased sensitivity to β-lactams, and to dramatic division and growth defects, consistent with a loss of PG homeostasis. Remarkably, these phenotypes were largely abrogated by the deletion of ldtD, a Cpx-induced gene involved in noncanonical PG cross-linkage, suggesting that this transpeptidase is an important link between PG homeostasis and the Cpx system. Altogether our data show that fine-tuning of an envelope quality control system constitutes an important layer of regulation of the highly organized cell wall structure

Reconception des systèmes de production forestiers : distinguer intensification écologique et imitation de la nature

Le concept de « sylviculture proche de la nature » a joué un rôle important au cours des 30 dernières années, fournissant une doctrine et un mouvement à une volonté de changement dans les pratiques de gestion. Il a bénéficié, au moins pour la France, d'une conjonction efficace entre une contestation de l'ordre sylvicole établi dans l’après-guerre et une fidélité à plusieurs principes traditionnels - et fortement identitaires - de l’école sylvicole française depuis le début du 19ème siècle (notamment le mot d’ordre « imiter la nature, hâter son œuvre » de Lorentz et Parade). Même si ce n’était pas une motivation à l’émergence du mouvement, la convergence avec la faiblesse des industries du bois françaises et la montée générale des préoccupations environnementales de la société, stimulée pour la forêt par la crise des pluies acides, a donné au mouvement une forte influence dans la formation des idées sylvicoles.Aujourd’hui, la génération qui a porté cet agenda de sylviculture proche de la nature dispose du maximum de leviers professionnels et institutionnels pour mettre en œuvre ses idées : on peut le mesurer, en particulier, dans sa capacité à imposer un vocabulaire, une interprétation des phénomènes et traduire ses priorités en normes de gestion durable (voir le contenu des standards de certification). Ces idées constituent, dans une large partie de l’Europe, une nouvelle forme d’orthodoxie.Néanmoins, plusieurs aspects structurants du contexte actuel (changements globaux, pression sur l’usage des sols, émergence de la bioéconomie, intensification écologique) rendent problématiques, voire contre-productifs ou risqués certains des principes et modalités d’action de la sylviculture proche de la nature. La confiance exagérée dans le potentiel des forêts à évoluer de manière satisfaisante sous les nouvelles pressions et dans la capacité des sylviculteurs à satisfaire les attentes socio-économiques uniquement en pilotant la dynamique de la végétation naturelle, cette confiance conduit à restreindre le champ des options possibles, à sous-investir certaines compétences et à négliger des opportunités.La communication vise, à travers quelques exemples (gestion des ressources génétiques, recours à la plantation, fertilisation, révolutions courtes, planification), d’une part à distinguer intensification écologique de la gestion forestière et imitation de la nature ; d’autre part à définir une intensification écologique permettant de répondre aux défis actuel