Synthesis of Methylene- and Alkylidenecyclopropane Derivatives

International audienceSince the methylenecyclopropane moiety is found in many biologically active natural substances, the synthesis of methylene- and alkylidenecyclopropanes remains a considerable challenge. In addition, an attractive feature is their surprising stability, accompanied by a high level of strain, conferring on them an otherwise unattainable chemical reactivity. The growing interest in the chemistry of these compounds has in its turn stimulated the development of alternative approaches to their skeleton, aimed at selectively introducing structural and chemical diversification. The three principal methods to synthesize these important compounds are based on the formation of the cyclopropane ring, the use of preformed cyclopropanes, and the use of preformed methylene- and alkylidenecyclopropanes

Recherche du coefficient de relaxation utilisé dans la méthode de Newton-Raphson pour la résolution de systèmes non-linéaires

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Method for determining relaxation factor for modified Newton-Raphson method for non-linear systems

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Preparation of both enantiomers of a synthon for novel nucleoside analogs by enzymatic desymmetrization of a meso-diol with a methylene cyclopropane skeleton

International audienceThe enzymatic desymmetrization of methylenecyclopropane diol or its corresponding diacetate derivative, generated from a [2+1] cycloaddition between dioxepin and methylchlorocarbene, is described. After screening five commercial lipases, the two enantiomers of acetic acid 2-hydroxymethyl-3-methylene-cyclopropylmethyl ester are obtained in high yields and excellent enantioselectivities by using PFL or LPP in organic solvent. The stereostructure of the desymmetrization products was established by X-ray analysis. We also reported a new example with this non racemic chiral building block where the sign of optical rotation is dramatically solvent dependent and inverted. Using these enantiopure building blocks, a synthesis of novel nucleoside analogs is also presented. (C) 2011 Elsevier Ltd. All rights reserved

Étude transversale des intentions de vaccination contre la grippe saisonnière et la COVID-19 des professionnels de santé : quels leviers pour la promotion vaccinale ?

International audienceIn France, a high vaccine coverage among healthcare workers against seasonal flu is an important public health objective, particularly in the context of the COVID-19 epidemic. We published an online questionnaire targeting all French healthcare workers investigating previous flu vaccination and intention for vaccination against the 2020-21 flu and COVID-19. The study invitation was disseminated through the GERES network during summer 2020. Among 3,556 participants, the majority worked in a hospital or nursing home setting.The results illustrate, for both vaccinations, the gradient of vaccine uptake across professional categories, higher among physicians than among nurses and weaker among nurse assistants. The results suggest that uptake could be improved by targeting promotion on healthcare workers who were occasionally vaccinated during past years and by improving access. Hypothetical acceptance of COVID-19 vaccination correlated with flu vaccination during recent years, even if performed sporadically.Une bonne couverture vaccinale des soignants contre la grippe saisonnière est un objectif de santé publique, en particulier dans le contexte de l’épidémie de Covid-19. Un questionnaire destiné aux soignants exerçant en France a été mis en ligne et diffusé par le réseau Geres durant l’été 2020. Les questions portaient sur leur statut vaccinal antigrippal antérieur et les raisons de vaccination ou non ainsi que sur leurs intentions vaccinales contre la grippe pour la période hivernale 2020-2021 et contre la Covid-19. 3 556 professionnels de santé exerçant en majorité en établissement de santé, social ou médico-social ont répondu.Les résultats reflètent, pour les deux vaccinations, le gradient professionnel d’adhésion à la vaccination, plus fort chez les médecins que chez les infirmiers et moins fort chez les aides-soignants. L’analyse révèle qu’il serait possible d’améliorer la couverture vaccinale antigrippale en ciblant les personnels vaccinés occasionnellement au cours des dernières années et en améliorant l’accès à la vaccination. L’acceptation théorique de la vaccination contre la Covid-19 apparaît corrélée à la vaccination antigrippale même pratiquée sporadiquement

Quantifying preferences around vaccination against frequent, mild disease with risk for vulnerable persons: A discrete choice experiment among French hospital health care workers

International audienceThe individual determinants of vaccine acceptance among health workers (HCWs) have been described in the literature, but there is little evidence regarding the impact of vaccine characteristics and contextual factors (e.g., incentives, communication) on vaccination intentions. We developed a single profile discrete choice experiment (DCE) to assess the impact of seven attributes on stated vaccination intention against an unnamed disease, described as frequent with rapid clinical evolution and epidemic potential (similar to influenza or pertussis). Attributes evaluated vaccine characteristics (effectiveness, security profile), inter-individual aspects (epidemic risk, controversy, potential for indirect protection, vaccine coverage) and incentives (e.g., badge, hierarchical injunction). A total of 1214 French hospital-based HCWs, recruited through professional organizations, completed the online DCE questionnaire. The relative impact of each attribute was estimated using random effects logit models on the whole sample and among specific subgroups. Overall, 52% of included HCWs were vaccinated against influenza during 2017-18 and the average vaccination acceptance rate across all scenarios was 58%. Aside from the management stance, all attributes' levels had significant impact on vaccination decisions. Poor vaccine safety had the most detrimental impact on stated acceptance (OR 0.04 for the level controversy around vaccine safety). The most motivating factor was protection of family (OR 2.41) and contribution to disease control (OR 2.34). Other motivating factors included improved vaccine effectiveness (OR 2.22), high uptake among colleagues (OR 1.89) and epidemic risk declared by health authorities (OR 1.76). Social incentives (e.g., a badge I'm vaccinated) were dissuasive (OR 0.47). Compared to HCWs previously vaccinated against influenza, unvaccinated HCWs who were favorable to vaccination in general were most sensitive towards improved vaccine effectiveness. Our study suggests that vaccine safety considerations dominate vaccine decision-making among French HCWs, while adapted communication on indirect protection and social conformism can contribute to increase vaccination acceptance

Psychometric validation of a 7C-model of antecedents of vaccine acceptance among healthcare workers, parents and adolescents in France

Support for vaccine decision-making requires a tailored approach taking into account psychological antecedents of vaccine acceptance. We aimed at validating an extended 7C-model of antecedents in three different target population groups (healthcare workers [n = 3870], parents [n = 2002] and adolescents [n = 7118]) and two vaccinations (COVID-19, HPV) in France. We performed a secondary analysis of questionnaires collecting sociodemographic characteristics, attitudes and knowledge on vaccination, and vaccine status and intention. We used standard psychometric techniques to validate a first and second order latent structure, and evaluated their association with vaccine intentionality in three levels (refusal, indecision, acceptance). In all populations, the 7C-model yielded a very good model fit (CFI and TLI > 0.90) and, in comparison with non-nested and nested 5C-models, significantly improved the model performance (Ω 2 , p < 0.05; Wald’s test, p < 0.05). The resulting vaccine readiness score was strongly associated with vaccine intentionality (acceptance vs. indecision: β HCW = 2.93, β Parents = 2.41, β Adolescents = 1.34; refusal vs. indecision: β HCW = − 1.68, β Parents = − 0.16, β Adolescents = − 0.89.). The addition of confidence in the system and social conformism among antecedents of vaccine acceptance allowed a finer understanding of the continuum moving from refusal to indecision and acceptance. To work with these antecedents in interventional research, appropriate questionnaire items should be developed for various vaccines and target populations

Is universal HBV vaccination of healthcare workers a relevant strategy in developing endemic countries? The case of a university hospital in Niger.

BACKGROUND: Exposure to hepatitis B virus (HBV) remains a serious risk to healthcare workers (HCWs) in endemic developing countries owing to the strong prevalence of HBV in the general and hospital populations, and to the high rate of occupational blood exposure. Routine HBV vaccination programs targeted to high-risk groups and especially to HCWs are generally considered as a key element of prevention strategies. However, the high rate of natural immunization among adults in such countries where most infections occur perinatally or during early childhood must be taken into account. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross sectional study in 207 personnel of 4 occupational groups (medical, paramedical, cleaning staff, and administrative) in Niamey's National Hospital, Niger, in order to assess the prevalence of HBV markers, to evaluate susceptibility to HBV infection, and to identify personnel who might benefit from vaccination. The proportion of those who declared a history of occupational blood exposure ranged from 18.9% in the administrative staff to 46.9% in paramedical staff. Only 7.2% had a history of vaccination against HBV with at least 3 injections. Ninety two percent were anti-HBc positive. When we focused on170 HCWs, only 12 (7.1%) showed no biological HBV contact. Twenty six were HBsAg positive (15,3%; 95% confidence interval: 9.9%-20.7%) of whom 8 (32%) had a viral load >2000 IU/ml. CONCLUSIONS/SIGNIFICANCE: The very small proportion of HCWs susceptible to HBV infection in our study and other studies suggests that in a global approach to prevent occupational infection by bloodborne pathogens, a universal hepatitis B vaccination of HCWs is not priority in these settings. The greatest impact on the risk will most likely be achieved by focusing efforts on primary prevention strategies to reduce occupational blood exposure. HBV screening in HCWs and treatment of those with chronic HBV infection should be however considered