siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a primary regulator of transferrin uptake

A survey of 1,804 human dicer-generated signaling siRNAs using automated quantitative imaging identified the phosphatidylinositol-3,4,5-trisphosphate-mTOR signaling pathway as a primary regulator of iron-transferrin uptake

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Comment fonctionne un récepteur couplé aux protéines G ? Le cas des récepteurs métabotropiques du glutamate et du GABA

Trois à six pour cent des gènes d’un organisme codent pour des récepteurs couplés aux protéines G, ce qui en fait la plus grande famille de protéines membranaires répertoriée à ce jour. L’analyse structurale du fonctionnement d’une classe particulière de récepteurs couplés aux protéines G, ceux de la classe III, qui regroupe notamment les récepteurs métabotropiques des deux principaux neurotransmetteurs (le glutamate et l’acide γ-aminobutyrique ou GABA), a révélé un mécanisme mettant en jeu des dimères de récepteurs. Cette observation n’est pas sans rappeler le mécanisme d’activation d’autres types de récepteurs membranaires tels que, par exemple, les récepteurs à activité tyrosine kinase de l’insuline. Ce mécanisme pourrait également s’appliquer à d’autres récepteurs couplés aux protéines G, et ouvrir de nouvelles voies d’action pharmacologique visant la régulation de ces récepteurs qui sont déjà la cible de près de la moitié des médicaments existants, quels que soient les domaines thérapeutiques considérés

Oligomérisation et activation des récepteurs couplés aux protéines G (ce que révèle l'étude du récepteur GABAb)

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Modification du transfert de trois métaux lourds (Zn, Pb et Cd) dans un sol issu d'un dépot fluvio-glaciaire carbonate par l'introduction de geotextiles

Les géotextiles sont des géomatériaux fibreux de plus en plus utilisés au sein des bassins d'infiltration d'eaux pluviales, sans faire l'objet d'un questionnement particulier par rapport à leur influence sur le devenir des contaminants transportés par ces eaux. Cette étude vise à caractériser, à l'aide de colonnes de laboratoire, la modification du transfert simultané de trois métaux lourds (Zn, Pb et Cd) induite par l'introduction de géotextiless dans un sol saturé et soumis à un écoulement unidirectionnel et permanent. Ce sol est issu d'un dépôt fluvio-glaciaire carbonaté qui sert de support à plusieurs bassins d'infiltration de l'Est lyonnais (France). Cette modification a été caractérisée pour différentes conditions hydriques de mise en place (géotextiles mis en place secs ou saturés) et pour deux vitesses d'écoulement, pour un géotextile aiguilleté. La rétention des métaux a ensuite été optimisée par le choix du type de géotextile (aiguilleté, thermolié) et par le nombre de géotextiles introduits. L'écoulement a été caractérisé au niveau de son homogénité à l'aide de traçages. Des essais colonnes complémentaires spécifiques ont été réalisés pouur l'observation au microscope électronique à balayage du sol et des géotextiles après contamination. Les résultats mettent en évidence que les géotextiles introduits secs induisent une augmentation de la rétention des métaux, différant selon le type de géotextiles (aiguilleté ou thermolié). S'ils n'induisent aucune rétention particulière en leur sein, ils favorisent la rétention des métaux dans le sol avoisinant. L'augmentation de la rétention résulte d'un meilleur contact entre la solution métallique et les particules solides réactives du sol (carbonates) du fait d'une homogénéisation de l'écoulement au voisinage des géotextiles. Les géotextiles régulent la rétention des métaux dans le sol en modifiant l'écoulement.Geotextiles are fibrous materials that are more and more employed for the design of infiltration basins. And yet, their influence on the transfer of contaminants carried by stormwater has not been fully investigated. This study, based on leaching experiments, was aimed at characterising the modification of the transfer of three heavy metals (Zn, Pb and Cd), due to the introduction of geotextiles in a saturated soil under steady state and unidirectional flow. The soil was collected in a carbonated fluvio-glacial deposit on which several infiltration basins were constructed in the Eastern region of Lyon (France). This modification was characterised in different installation hydric conditions (the geotextiles were put either wet or dry) and at two flow-rates. The retention of heavy metals was then optimised thanks to the kind of geotextiles (needle-punched or heat-bonded) and the number of geotextiles put in the soil. The flow was characterised by tracer experiments. Specific leaching experiments were monitored for the observation of the soil and the geotextiles after contamination with a scanning electron microscope. The results show that the geotextiles which were dry when placed triggered an increase in the retention of the heavy metals and that this increase depended on the kind of geotextiles (needle-punched or heat-bonded). While there was no specific retention inside geotextiles, they increased the retention in the neighbouring soil. This increase was due to a better contact between the metallic solution and the reactive particles of the soil (carbonates) thanks to a local homogenisation of flow in the neighbouring of geotextiles. The geotextiles ruled the retention of heavy metals in soil by modifying the flow.VILLEURBANNE-DOC'INSA LYON (692662301) / SudocSudocFranceCanadaFRC

Modifications hydrodynamiques du comportement des métaux lourds dans un sol hétérogène présentant une contamination résiduelle en NAPL (étude sur la contamination mixte des sols)

La contamination mixte des sols par les dérivés organiques pétroliers et les métaux lourds est une situation répandue et problématique dans les zones urbaines et industrialisées. Toutefois, aucun travail ne s'était penché, à ce jour, sur le rôle joué au sein de ce type de contamination par les interactions entre les métaux lourds et les liquides organiques non miscibles (NAPL). Les objectifs de la présente étude ont été de 1) vérifier la présence d'une influence des NAPL résiduels sur le transfert métallique dans les sols, 2) déterminer la nature de cette influence et 3) caractériser les mécanismes qui la déterminent. Les travaux entrepris ont permis d'identifier et de mesurer à l'échelle du laboratoire, à l'aide de colonnes de sol, les mécanismes d'interaction NAPL-métaux dans les sols. Un premier volet expérimental a servi à identifier la nature des interactions NAPL-métaux et à proposer leurs mécanismes sous-jacents. Un second volet expérimental a permis de quantifier les mécanismes d'influence du NAPL résiduel sur l'écoulement aqueux par modélisation mathématique. Les résultats de modélisation de l'écoulement aqueux ont ensuite été utilisés afin d'analyser les modifications du transfert des métaux lourds. Les résultats ont montré que les NAPL résiduels peuvent modifier le transfert des métaux lourds en altérant les conditions hydrodynamiques au sein du sol. La présence de NAPL résiduel a accentué l'hétérogénéité du réseau poreux en déconnectant les chenaux préférentiels et les micropores. Ceci a eu pour résultat de confiner la phase aqueuse au sein des chenaux préférentiels. En conséquence, ceci a modifié la capacité du sol à atténuer le flux métallique infiltrant. Les résultats ont aussi souligné le rôle de certains paramètres importants sur l'impact des NAPL résiduels sur le transfert des métaux lourds, notamment la viscosité du NAPL, les conditions hydriques initiales du sol et de la vitesse d'écoulement aqueux.Mixed soil contamination by petroleum hydrocarbons and heavy metals is a common occurrence in urban and industrial localities. However, there is no reported study on the impact of interactions between heavy metals and non-aqueous phase liquids (NAPL) on contaminant mobility. The objectives of this study were to 1) verify the possibility of an influence of residual NAPL on heavy metal transfer in mixed contaminated soils, 2) determine the nature of this influence, and 3) characterize the mechanisms underlying this influence. Experimental work at the laboratory scale using soil columns was used to identify and measure the interaction mechanisms between NAPL and heavy metals in soils. A first experimental phase was used to identify the nature of the NAPL-heavy metal interactions and to propose their possible mechanisms. A second experimental phase was used to quantify, using mathematical modeling, the mechanisms controlling the influence of residual NAPL on water flow. The modeling results were then used to analyze the modifications of heavy metal transfer. Results have shown that residual NAPLs can modify heavy metal transfer by changing the hydrodynamic regime in the soil. Residual NAPL increased the heterogeneity of the void network by decreasing the connectivity between preferential channels and micropores. This confined the infiltrating water to the preferential channels, which in turn modified the soil's capacity to attenuate the heavy metal flux. Results have also outlined the role of important parameters on the impact of residual NAPLs on heavy metal transfer, such as NAPL viscosity, initial soil water saturation and water flow velocity.VILLEURBANNE-DOC'INSA LYON (692662301) / SudocSudocFranceCanadaFRC