Assessing the conformational changes of pb5, the receptor-binding protein of phage T5, upon binding to its Escherichia coli receptor FhuA

Within tailed bacteriophages, interaction of the receptor-binding protein (RBP) with the target cell triggers viral DNA ejection into the host cytoplasm. In the case of phage T5, the RBP pb5 and the receptor FhuA, an outer membrane protein of Escherichia coli, have been identified. Here, we use small angle neutron scattering and electron microscopy to investigate the FhuA-pb5 complex. Specific deuteration of one of the partners allows the complete masking in small angle neutron scattering of the surfactant and unlabeled proteins when the complex is solubilized in the fluorinated surfactant F6-DigluM. Thus, individual structures within a membrane protein complex can be described. The solution structure of FhuA agrees with its crystal structure; that of pb5 shows an elongated shape. Neither displays significant conformational changes upon interaction. The mechanism of signal transduction within phage T5 thus appears different from that of phages binding cell wall saccharides, for which structural information is available

Exposure to Farm Animals and Risk of Lung Cancer in the AGRICAN Cohort.

Epidemiologic studies have found lower risks of lung cancer in farmers. However, little is known about the types of agricultural activities concerned. In the Agriculture and Cancer cohort, we assessed the relationship between animal farming and lung cancer by investigating the types of animals, tasks, and timing of exposure. Analyses included 170,834 participants from the Agriculture and Cancer (AGRICAN) cohort in France. Incident lung cancers were identified through linkage with cancer registries from enrollment (2005-2007) to 2011. A Cox model, adjusting for pack-years of cigarette smoking, was used to calculate hazard ratios and 95% confidence intervals. Lung cancer risk was inversely related to duration of exposure to cattle (≥40 years: hazard ratio = 0.60, 95% confidence interval: 0.41, 0.89; P for trend < 0.01) and to horse farming (≥20 years: hazard ratio = 0.64, 95% confidence interval: 0.35, 1.17; P for trend = 0.09), especially for adenocarcinomas, but not with poultry or pig farming. More pronounced decreased risks were reported among individuals who had cared for animals, undertaken milking, and who had been exposed to cattle in infancy. Our study provides strong evidence of an inverse association between lung cancer and cattle and horse farming. Further research is warranted to identify the etiologic protective agents and biological mechanisms

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Occupational exposures in farming and lung cancer risk

Contexte. La population agricole française, dans son ensemble, présente un plus faible risque de Cancer BronchoPulmonaire (CBP) par rapport à la population générale. Ce constat, retrouvé au niveau international, s’explique au moins en partie par un tabagisme plus faible notamment chez les plus âgés et chez les femmes ; un effet « protecteur » des endotoxines est également suspecté. Néanmoins le milieu professionnel agricole peut exposer à de nombreux cancérogènes pulmonaires avérés ou suspectés ; malgré cela, à l’exception de certains secteurs d’élevage, il n’existe que très peu de données sur les associations entre expositions ou situations de travail précises en milieu agricole et le risque de CBP. Objectifs. Le premier objectif de ce travail de thèse était d’étudier les associations, au sein de la cohorte AGRICAN (AGRIculture et CANcer), entre (1) CBP et exposition aux activités et tâches de cultures ; (2) CBP et utilisation de pesticides arsenicaux et herbicides dinitroanilines, et de mettre à profit le nombre important de sujets inclus et de cas de CBP pour réaliser ces analyses par sous-type histologique. Le deuxième objectif était d’initier un projet de métrologie de divers aérocontaminants en milieu professionnel agricole. Méthodes. Les analyses ont été menées en utilisant les données de l’étudeAGRICAN et de la matrice culture-exposition aux pesticides PESTIMAT. Nous avons utilisé un modèle de Cox, ajusté sur le sexe, le tabagisme, les élevages bovin et équin. Le projet métrologique AirExpA s’est limité à la Normandie, avec mesures personnelles des poussières totales (en temps réel), endotoxines et 38 mycotoxines (en cumulé), en élevage bovin, lors des foins et des moissons de blé/orge et pois fourrager/féverole. Résultats et discussion. Nous avons retrouvé une association inverse entre l’activité de culture de maïs et le risque de CBP, une association positive entre adénocarcinomes et viticulture, ainsi qu’entre carcinomes à petites cellules et culture de pois fourragers/féveroles. Les éléments de plausibilité d’un lien entre ces secteurs d’activité et le risque de CBP sont encore des hypothèses : la culture de maïs, par le stockage du grain, pourrait exposer aux endotoxines ; à l’inverse, la récolte de pois fourragers a été décrite comme empoussiérante, mais cet élément doit être confirmé par une caractérisation des poussières. Nous n’avons pas retrouvé d’association entre utilisation de pesticides arsenicaux, ni de dinitroanilines, et risque de CBP ; cependant les analyses stratifiées sur le sexe et le statut tabagique, montraient des associations positives chez les non-fumeurs et chez les femmes (en particulier pour les adénocarcinomes). Enfin, le projet AirExpA a permis de documenter un gradient d’exposition aux poussières et endotoxines en fonction de différentes tâches en élevage bovin, et une exposition plus modérée mais réelle, aux endotoxines, lors des activités de culture. Les analyses de mycotoxines sont toutes revenues inférieures aux limites de quantification. L’analyse des pics d’exposition, l’étude d’autres aérocontaminants et d’autres secteurs agricoles, sont des perspectives de ce projet. Conclusion. Notre travail soulève de nouvelles questions de recherche quant à des associations possibles entre certaines expositions professionnelles en milieu agricole (cultures et tâches, utilisation de certains pesticides) et risque de CBP, et contribue à une meilleure connaissance des expositions professionnelles des agriculteurs aux aérocontaminants.Background. Farmers are at lower risk of lung cancer, compared to the general population, at least partly because of a reduced rate of smoking among the elderly and women. A “protective” effect of endotoxins has also been hypothesized. Even though some of the occupational exposures occurring during farming-related activities are well-known or suspected lung carcinogens, there is scarce data in the literature, about the associations between specific occupational exposures or tasks in farming, and the risk of lung cancer. Objectives.The first aim was to analyse, in the AGRICAN cohort, the associations between lung cancer and (1) occupational exposure to various crops and related tasks; (2) arsenical pesticides and dinitroaniline herbicides use in farming. We also aimed at stratifying our analysis by histological subtypes of lung cancer. The second aim was to initiate a metrological project, to assess farmers’ occupational exposure to various airborne pollutants, in relation with the risk of lung cancer. Methods. We used the data from the French AGRIculture and CANcer cohort (AGRICAN) and from the PESTIcide MATrix project (PESTIMAT), to assess the associations between occupational farming exposures and lung cancer. A Cox model was performed, with adjustment on gender, smoking intensity, cattle and horses breeding. Our metrological project AirExpA was first launched in Normandy and focused on a few exposures – total dusts in real-time ; endotoxins and 38 mycotoxins, cumulative – in cattle breeding, wheat/barley and peas harvesting, and haymaking. Results and discussion. We reported a negative association between lung cancer and corn growing, and positive associations between (1) vineyard growing and adenocarcinoma; (2) peas growing and small cell lung cancer. Corn growing, especially grain handling, might expose to significant levels of endotoxins, thus explaining the inverse association. Peas growing, especially harvesting, is reportedly a dusty task; the AirExpA project will enable us to better characterize the dusts. We found no association between arsenicals use and lung cancer, nor with dinitroaniline herbicides use. However, stratifying on gender and smoking status showed positive associations among women and never-smokers, especially for adenocarcinomas. The AirExpA project showed dust and endotoxins exposure gradients in cattle breeding, depending on the task, and a mild but real exposure to endotoxins in various tasks in crop growing. All samples for mycotoxins were below the limit of quantification. Analysing exposure peaks, extending the project to other breedings/crops and air pollutants are among the perspectives. Conclusion. Our results raise new research questions about possible associations between occupational agricultural exposures and lung cancer, and contribute to a better knowledge and understanding of farmers’ occupational exposure to air pollutants

Herbicide exposure during occupational knapsack spraying in French gardeners and municipal workers

Context: There is a lack of data on pesticide exposure levels during spraying with a knapsack, while it could have important implications for their users’ health. Methods: We assessed levels and determinants of exposure in 24 male private landscapers/gardeners and municipal workers in France in 2011. Actual dermal exposure to glyphosate was assessed with cotton undergarments and gloves, and a cotton coverall changed between mixing and spraying to assess the contribution of each phase and body area to overall contamination. A field monitor observed the whole workshift and filled in a standardized observation grid. Results: The median actual contamination was 5,256 µg for the body, and 4,620 µg for hands. Spraying was more exposing than mixing/loading for all body parts except hands, which contributed to nearly 90% of body exposure during mixing/loading, and 30% during spraying, followed by back (14%). In the most exposed quartile, levels were close to some observations in agriculture. Conclusion: Our study provides new data on pesticide exposure levels of knapsack sprayer users; it should lead to a reinforced prevention, in order to make exposures as low as possible and lessen the risk of chronic diseases

Postharvest treatments of wild pepper ( \textitPiper spp.) in Madagascar

International audienceIntroduction. A study on postharvest treatments of wild peppers was carried out in Madagascar with the aim of describing the local practices and measuring their impacts on the quality of the products. Materials and methods. Four distinct pepper production systems (PPS) were observed, described and compared in two separate areas in East Madagascar. Major quality characteristics (piperine and essential oil) of the peppercorns were assessed in samples collected in the four systems. Results and discussion. Two main postharvest processes (dry and wet) were identified. The wet process differed from the dry one in that it involved two specific operations, blanching and sweating. The processes influenced the color of the pepper. Piperine contents were not affected by any of the pepper production systems, whereas essential oil contents were reduced by up to 27% by the wet process. After processing, piperine contents were up to eight times lower, whereas essential oil contents were up to six times higher than the specifications of the standard ISO 959-1 for black pepper ready for commercialization. Conclusion. Two main processes (dry and wet) for treatment of peppercorns in Madagascar were identified and described. The dry process, with two steps less, appeared to be easier to implement and more respectful to the product. Improving maturity control and processing according to the quality expected by the markets will be necessary to promote Malagasy peppers.Introduction. A study on postharvest treatments of wild peppers was carried out in Madagascar with the aim of describing the local practices and measuring their impacts on the quality of the products. Materials and methods. Four distinct pepper production systems (PPS) were observed, described and compared in two separate areas in East Madagascar. Major quality characteristics (piperine and essential oil) of the peppercorns were assessed in samples collected in the four systems. Results and discussion. Two main postharvest processes (dry and wet) were identified. The wet process differed from the dry one in that it involved two specific operations, blanching and sweating. The processes influenced the color of the pepper. Piperine contents were not affected by any of the pepper production systems, whereas essential oil contents were reduced by up to 27% by the wet process. After processing , piperine contents were up to eight times lower, whereas essential oil contents were up to six times higher than the specifications of the standard ISO 959-1 for black pepper ready for commercialization. Conclusion. Two main processes (dry and wet) for treatment of pep-percorns in Madagascar were identified and described. The dry process, with two steps less, appeared to be easier to implement and more respectful to the product. Improving maturity control and processing according to the quality expected by the markets will be necessary to promote Malagasy peppers. Madagascar / Piper / pepper / processing / essential oils / color Traitements post récolte du poivre sauvage (Piper spp.) à Madagascar. Résumé-Introduction. Une étude des traitements post récolte des poivres sauvages a été menée à Madagascar afin de décrire les pratiques locales et de mesurer leurs impacts sur la qualité des produits. Matériel et méthodes. Quatre systèmes de productions (PPS) ont été observés, décrits et comparés dans deux zones définies de l'est de Madagascar. Des caracté-ristiques qualitatives majeures (piperine et huile essentielle) du poivre ont été évaluées sur des échantillons collectés dans les quatre systèmes. Résultats et discussion. Deux princi-paux procédés post récolte (une voie sèche et une voie humide) ont été identifiés. La voie humide diffère de la voie sèche par deux opérations spécifiques : l'échaudage et l'étuvage. Les procédés ont montré une influence sur la couleur du poivre. Les teneurs en piperine n'ont pas été affectées par les systèmes de productions quels qu'ils soient alors que les teneurs en huile essentielle ont été réduites jusqu'à 27 % par la voie humide. En fin de procé-dés, les teneurs en piperine ont été jusqu'à huit fois plus basses et les teneurs en huile essen-tielle jusqu'à six fois plus élevées que celles spécifiées dans la norme ISO 959-1 pour le poivre noir prêt à la commercialisation. Conclusion. Deux procédés principaux (l'un « sec », l'autre « humide ») utilisés pour le traitement des poivres à Madagascar ont été identifiés et décrits. La voie sèche qui comprend deux opérations en moins, semble plus aisée à mettre en oeuvre et mieux respecter le produit que la voie humide. Le respect de la maturité du poivre sauvage lors de la cueillette ainsi que la maîtrise des procédés en fonction des produits atten-dus par les marchés seront nécessaires pour mieux valoriser les poivres malgaches. Madagascar / Piper / poivre / traitement / huile essentielle / couleu

Occupational pesticide exposure, cancer and chronic neurological disorders: A systematic review of epidemiological studies in greenspace workers

CONTEXT: The greenspace sector includes a broad range of occupations: gardeners, landscapers, municipal workers, maintenance operators of public facilities, golf-course employees and other sports facilities, horticulturists, plant and tree nursery workers etc. The health impact of occupational pesticide exposure has mainly been studied among farmers. Other professionals such as greenspace workers are also extremely exposed, presenting specific exposure features (practices, types of pesticide used). The aim of this review was to summarize epidemiological literature that examine the relationship between pesticide exposure and the risk of cancer and long-term health effects in greenspace workers. METHOD: Six main groups of greenspace workers were identified and examined through a systematic literature review based on PubMed and Scopus. The studies were then grouped according to their design, health outcomes and the type of population studied. RESULTS: Forty-four articles were selected among the 1679 identified. Fifteen studies were conducted exclusively among greenspace workers, while ten also studied these workers with other pesticide applicators. Six were cohorts from the general population in which greenspace workers were identified. Elevated risks were found in several studies for leukaemia, soft-tissue sarcoma, multiple myeloma, non-Hodgkin lymphoma and Parkinson's disease. DISCUSSION: The majority of studies used rough parameters for defining exposure such as job titles which could lead to the misclassification of exposure, with the risk of false or positive negative conclusions. Health outcomes were mainly collected through registries or death certificates, and information regarding potential confounders was often missing. CONCLUSION: The review identified only 15 studies conducted exclusively among greenspace workers. Elevated risk was found for several sites of cancer and Parkinson's diseases. Further epidemiological research is needed, conducted specifically on these workers, to better characterize this population, its exposure to pesticides and the related health effects

Description des traitements post-récolte du poivre sauvage (Piper spp.) à Madagascar

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