Ultra-sensitive and selective Hg2+ chemosensors derived from substituted 8-hydroxyquinoline analogues

International audienceNovel analogues of 8-hydroxyquinoline with phosphinate or thiophosphinate functions and styryl fluorophores in the para position to the nitrogen atom were prepared via multi-step syntheses, using phosphorylation and Wittig coupling reactions. A strong affinity between the quinoline analogues and heavy metal ions such as Pb2+, Cd2+ and Hg2+ was highlighted. The interaction of the metal ions with the nitrogen of the styrylquinoline leads to a large red shift of the absorption and emission spectra in agreement with an increase of the photoinduced charge transfer character of the styryl fluorophore. In the presence of metal ions the appearance of a green fluorescence emission is also observed upon excitation at 420 nm or 840 nm, thanks to a significant increase of the two-photon response. Under optimal conditions, a mercury concentration of 15 ppt in a partially aqueous medium can be detected using the thiophosphinate derivative without interference from other metal ions

Ruptures d'approvisionnement en médicaments anti-infectieux: causes et conséquences

International audienceAnti-infective drugs stock-outs are increasingly frequent, and this is unlikely to change. There are numerous causes for this, mostly related to parameters difficult to control: i) 60 to 80% of raw material or components are produced outside of Europe (compared to 20% 30 years ago), with subsequent loss of independence for their procurement; ii) the economic crisis drives the pharmaceutical companies to stop producing drugs of limited profitability (even among important drugs); iii) the enforcement of regulatory requirements and quality control procedures result in an increasing number of drugs being blocked during production. The therapeutic class most affected by drug stock-outs is that of anti-infective drugs, especially injectable ones, and many therapeutic dead ends have recently occurred. We provide an update on this issue, and suggest 2 major actions for improvement: i) to implement a group dedicated to anticipating drug stock-outs within the anti-infective committee in each health care center, with the objectives of organizing and coordinating the response whenever a drug stock-out is deemed at risk (i.e., contingency plans, substitution, communication to prescribers); ii) a national reflection lead by scientific societies, in collaboration with government agencies, upstream of the most problematic drug stock-outs, to elaborate and disseminate consensus guidelines for the management of these stock-outs

Introduction of SARS in France, March–April, 2003

We describe severe acute respiratory syndrome (SARS) in France. Patients meeting the World Health Organization definition of a suspected case underwent a clinical, radiologic, and biologic assessment at the closest university-affiliated infectious disease ward. Suspected cases were immediately reported to the Institut de Veille Sanitaire. Probable case-patients were isolated, their contacts quarantined at home, and were followed for 10 days after exposure. Five probable cases occurred from March through April 2003; four were confirmed as SARS coronavirus by reverse transcription–polymerase chain reaction, serologic testing, or both. The index case-patient (patient A), who had worked in the French hospital of Hanoi, Vietnam, was the most probable source of transmission for the three other confirmed cases; two had been exposed to patient A while on the Hanoi-Paris flight of March 22–23. Timely detection, isolation of probable cases, and quarantine of their contacts appear to have been effective in preventing the secondary spread of SARS in France

Autoinflammation in patients with leukocytic CBL loss-of-heterozygosity is caused by constitutive ERK-mediated monocyte activation

Patients heterozygous for germline CBL loss-of-function (LOF) variants can develop myeloid malignancy, autoinflammation, or both, if some or all of their leukocytes become homozygous for these variants through somatic loss-of-heterozygosity (LOH) via uniparental isodisomy (UPD). We observed an upregulation of the inflammatory gene expression signature in whole blood from these patients, mimicking monogenic inborn errors underlying autoinflammation. Remarkably, these patients had constitutively activated monocytes that secrete 10 to 100 times more inflammatory cytokines than those of healthy individuals and CBL LOF heterozygotes without LOH. CBL-LOH hematopoietic stem and progenitor cells (HSPC) outgrew the other cells, accounting for the persistence of peripheral monocytes homozygous for the CBL LOF variant. ERK pathway activation was required for the excessive production of cytokines by both resting and stimulated CBL LOF monocytes, as shown in monocytic cell lines. Finally, we found that about 1 in 10,000

Staphylococcus aureus infective endocarditis versus bacteremia strains: Subtle genetic differences at stake

AbstractInfective endocarditis (IE)(1) is a severe condition complicating 10–25% of Staphylococcus aureus bacteremia. Although host-related IE risk factors have been identified, the involvement of bacterial features in IE complication is still unclear. We characterized strictly defined IE and bacteremia isolates and searched for discriminant features. S. aureus isolates causing community-acquired, definite native-valve IE (n=72) and bacteremia (n=54) were collected prospectively as part of a French multicenter cohort. Phenotypic traits previously reported or hypothesized to be involved in staphylococcal IE pathogenesis were tested. In parallel, the genotypic profiles of all isolates, obtained by microarray, were analyzed by discriminant analysis of principal components (DAPC)(2). No significant difference was observed between IE and bacteremia strains, regarding either phenotypic or genotypic univariate analyses. However, the multivariate statistical tool DAPC, applied on microarray data, segregated IE and bacteremia isolates: IE isolates were correctly reassigned as such in 80.6% of the cases (C-statistic 0.83, P<0.001). The performance of this model was confirmed with an independent French collection IE and bacteremia isolates (78.8% reassignment, C-statistic 0.65, P<0.01). Finally, a simple linear discriminant function based on a subset of 8 genetic markers retained valuable performance both in study collection (86.1%, P<0.001) and in the independent validation collection (81.8%, P<0.01). We here show that community-acquired IE and bacteremia S. aureus isolates are genetically distinct based on subtle combinations of genetic markers. This finding provides the proof of concept that bacterial characteristics may contribute to the occurrence of IE in patients with S. aureus bacteremia

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation

Patients heterozygous for germline CBL loss-of-function (LOF) variants can develop myeloid malignancy, autoinflammation, or both, if some or all of their leukocytes become homozygous for these variants through somatic loss of heterozygosity (LOH) via uniparental isodisomy. We observed an upregulation of the inflammatory gene expression signature in whole blood from these patients, mimicking monogenic inborn errors underlying autoinflammation. Remarkably, these patients had constitutively activated monocytes that secreted 10 to 100 times more inflammatory cytokines than those of healthy individuals and CBL LOF heterozygotes without LOH. CBL-LOH hematopoietic stem and progenitor cells (HSPCs) outgrew the other cells, accounting for the persistence of peripheral monocytes homozygous for the CBL LOF variant. ERK pathway activation was required for the excessive production of cytokines by both resting and stimulated CBL-LOF monocytes, as shown in monocytic cell lines. Finally, we found that about 1 in 10,000 individuals in the UK Biobank were heterozygous for CBL LOF variants and that these carriers were at high risk of hematological and inflammatory conditions

La médiation culturelle: un nouveau champ de l’animation socioculturelle?

La médiation culturelle, tout comme l’animation socioculturelle, est un métier qui se professionnalise. Les organisations faîtières liées à des contextes plutôt muséaux, ont tendance à vouloir « protéger » la profession de médiatrice culturelle en établissant des critères précis : elle devrait être au bénéfice d’une formation universitaire pour pouvoir prétendre à la réalisation d’actions de médiation culturelle. Cependant, nous constatons que des animatrices socioculturelles sont engagées par des institutions culturelles afin de concevoir des actions de médiation culturelle. Ce travail de Bachelor, centré sur des actions de médiation culturelle développées dans un contexte d’exposition, cherche, d’une part, à mettre en évidence les similitudes et les divergences de ces deux métiers. Et, d’autre part, à définir si les différentes actions menées sont davantage issues du principe de démocratie ou de démocratisation culturelle. En d’autres termes, est-ce que les actions sont culturelles ou socioculturelles ? Pour ce faire, nous avons demandé à cinq animatrices socioculturelles de nous décrire des actions de médiation culturelle qu’elles ont développées. A la suite de ces entretiens, nous avons pu mettre en évidence certaines tendances. Les animatrices ont pour la plupart rencontré la médiation culturelle lors de leur formation en animation socioculturelle. De plus, les actions et les projets décrits répondent majoritairement au principe de démocratisation culturelle

Etude des immunoglobulines G anti aspergillus fumigatus dans une population d'enfants atteints de mucoviscidose

L'Aspergillose broncho-pulmonaire allergique médiée par l'Aspergillus fumigatus est une complication infectieuse évolutive de la mucoviscidose. Ses critères diagnostiques se confondent souvent avec l'évolutivité propre de la mucoviscidose. Le diagnostique difficile à établir repose donc sur un faisceau d'arguments cliniques, sérologiques, et radiologiques. Ce travail étudie chez 18 d'enfants atteints de mucoviscidose la sérologie ELISA mesurant le taux d'immunoglobulines G ( 126) spécifiques d'Aspergillus fumigatus. Le but est d'établir le rôle potentiel diagnostique et thérapeutique propre de cette sérologie. Le travail débute lors de la première sérologie positive au cours de la surveillance respiratoire de la mucoviscidose. On observe que les tous critères diagnostiques de l'aspergillose broncho-pulmonaire allergique sont rarement réunis à ce stade. L'immunoglobuline G reste un paramètre à intégrer dans un contexte évocateur ne permettant à elle seule d'établir le diagnostic. Néanmoins sa positivité reste nécessaire pour instaurer un traitement. Par ailleurs. la population a été divisée en deux groupes traités (antifongique associé ou non à une corticothérapie) ou non à partir de la première sérologie positive en lgG. On observe que chez les enfants traités, le taux d'IgG diminue significativement au terme d'un an de traitement confirmé par la réaugnientation du volume expiratoire maximal seconde prouvant l'amélioration clinique. Néanmoins, les taux d'IgG semblent se réascensionner régulièrement à distance sous traitement laissant transparaître des problèmes d'échappement (itraconazole) et d'observance thérapeutique, et de choix de molécule antifongique. Les spécifiques de l'Aspergillus fumigatus demeurent donc un paramètre indispensable au diagnostic, à l'indication et au suivi thérapeutique de l'Aspergillose bronco-pulmonaire allergique dans la mucoviscidose.ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

L’incidence des facteurs environnementaux sur le développement et la qualité de vie du jeune enfant. Projet saturnisme infantile en Région de Bruxelles-Capitale

ESP-ULB/ONE Recherche-action menée avec le soutien du Fonds Houtmaninfo:eu-repo/semantics/publishe