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Despite the strong decrease in antimicrobial use in the French poultry and pig sectors over the last decade, room for improvement remains. A participatory approach was set up in France, involving representatives of veterinarians, the pig and poultry industries, technical institutes, the French Ministry of Agriculture, and researchers, to further improve how antimicrobials are used on farms. By successively defining a shared, long-term vision of future antimicrobial use on farms, identifying lock-in mechanisms impeding this future vision from being realized, and articulating practical questions on how to move in the desired direction, the group rapidly reached a consensus. The results highlight the need for consensual standardized monitoring tools that would allow farmers and veterinarians to jointly monitor the health, welfare, antimicrobial resistance, and antimicrobial use on farms. Other results relate to better communication and training for citizens regarding animal health, animal welfare, and proper antimicrobial use; some benefits but also counterproductive effects of antibiotic-free labels that imperil animal health and welfare; the economic competitiveness of farms on international markets; and the economic sustainability of farm animal veterinary practices. These results call for a concerted way to produce tools for farmers and veterinarians and the broader involvement of other food sector actors.

Following the first French national action plan EcoAntibio (2012-2016) which has two main goals; 25% reduction of antibiotic (AB) use in veterinary medicine in 5 years, and a reduction of the use of critical antibiotics (fluoroquinolones and cephalosporin), several French broiler companies started to communicate on their antibiotic reduction schemes. In the scope of the ROADMAP project, six interviews were conducted within the broiler sector including 3 producers’ organizations (PO), 1 PO president (poultry farmer), 1 hatchery and 1 retailer. The purpose of these interviews was to understand how the aforementioned private standards work and what their roles are in the reduction of antimicrobial (AM) use. You can download the article in Spanish version here:https://www.roadmap-h2020.eu/uploads/1/2/6/1/126119012/final_antibiotic_reduction_schemes_in_the_french_poultry_es_fv_1.pdf

From November 2015 to July 2017, two successive episodes of H5 highly pathogenic avian influenza viruses (HP AIVs) infections occurred on poultry farms in France, mostly in domestic ducks raised for foie gras production in southwestern France. During the two epizootics, epidemiological investigations were carried out on infected farms and control and biosafety measures were implemented in association with surveillance in order to stop the spread of the viruses. Effluents are known to be an important factor in environmental dissemination of viruses, and suitable effluent management is needed to help prevent the spread of epizootics to other farms or pathogen persistence at the farm level. The present study was therefore designed to assess how long infectious A/H5 HP AIVs can persist in naturally or experimentally contaminated fecal slurry samples from ducks, with or without sanitization by lime treatment., Infections by A/H5 and A/H7 avian influenza viruses (AIVs) can cause acute disease and are therefore notifiable in poultry and wild birds. During winter 2015-2016, several cases of infection caused by highly pathogenic (HP) AIVs belonging to the A/H5N1, A/H5N2, and A/H5N9 subtypes were detected in southwestern France. Throughout winter 2016-2017, several cases of infections caused mainly by A/H5N8 HP AIV (A/goose/GD/1/1996, clade 2.3.4.4) were detected across Europe. On both occasions, the viruses were widely detected on palmiped farms in France. This study was designed to evaluate the persistence of A/H5 HP AIV in slurry from various duck productions. This was achieved (i) in the laboratory setting by artificially spiking four AIV-free slurry samples with known amounts of A/H5N9 HP AIV and monitoring virus infectivity, with or without lime treatment to achieve pH 10 or pH 12, and (ii) by sampling slurry tanks on five naturally A/H5N8 HP-contaminated farms. Experimental results in artificially spiked slurry suggested virus survival for 4 weeks in slurry from Muscovy or Pekin duck breeders and for 2 weeks in slurry from ducks for foie gras production during the assisted-feeding period, without lime treatment. Persistence of infectious A/H5N9 HP AIV in all slurry samples after lime treatment at pH 10 or pH 12 was less than 1 week. The A/H5N8 HP AIV persisted in naturally contaminated untreated slurry for 7 weeks. The results obtained provide experimental support for the 60-day storage period without treatment or the 7-day interval after lime treatment defined in French regulations for slurry sanitization. IMPORTANCE From November 2015 to July 2017, two successive episodes of H5 highly pathogenic avian influenza viruses (HP AIVs) infections occurred on poultry farms in France, mostly in domestic ducks raised for foie gras production in southwestern France. During the two epizootics, epidemiological investigations were carried out on infected farms and control and biosafety measures were implemented in association with surveillance in order to stop the spread of the viruses. Effluents are known to be an important factor in environmental dissemination of viruses, and suitable effluent management is needed to help prevent the spread of epizootics to other farms or pathogen persistence at the farm level. The present study was therefore designed to assess how long infectious A/H5 HP AIVs can persist in naturally or experimentally contaminated fecal slurry samples from ducks, with or without sanitization by lime treatment.

International audience; The application of manure may result in contamination of the environment with antimicrobials, antimicrobial-resistant bacteria, resistance genes and plasmids. The aim of this study was to investigate the impact of the administration of colistin and of manure management on (i) the presence of colistin-resistant Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and (ii) the prevalence of various antimicrobial resistance genes in feces and in composted or stored manure. One flock of chickens was treated with colistin at the recommended dosage and a second flock was kept as an untreated control. Samples of feces, litter and stored or composted manure from both flocks were collected for isolation and determination of the colistin-susceptibility of E. coli, K. pneumoniae and P. aeruginosa and quantification of genes coding for resistance to different antimicrobials. The persistence of plasmids in stored or composted manure from colistin-treated broilers was also evaluated by plasmid capturing experiments. Results revealed that colistin administration to chickens had no apparent impact on the antimicrobial resistance of the dominant Enterobacteriaceae and P. aeruginosa populations in the chicken gut. Composting stimulated an apparently limited decrease in genes coding for resistance to different antimicrobial families. Importantly, it was shown that even after six weeks of composting or storage, plasmids carrying antimicrobial resistance genes could still be transferred to a recipient E. coli. In conclusion, composting is insufficient to completely eliminate the risk of spreading antimicrobial resistance through chicken manure.

National audience

Objectives/Hypothesis Delta aminolevulinic acid (ALA)–induced protoporphyrin IX (PpIX) is a fluorescent sensitizer that permits detection and treatment of squamous cell carcinoma of the oral cavity. An exogenously induced decrease in tissue pH was evaluated for its effect in enhancing cellular uptake of ALA and facilitating its transformation into PpIX. Study Design Mice grafted with HT29 colonic cancers had been given glucose and amiloride to modify the pH of tissues. Influence of pH changes has been evaluated on ALA-induced PPIX fluorescence by optic fiber spectrofluorimetry as well as on tumor growth. Methods Results: The pH in HT 29 tumor decreased from 7.1 to 6.67 (P

Photodynamic therapy (PDT) with Photofrin ® has already been authorized for certain applications in Japan, the USA and France, and powerful second-generation sensitizers such as meta -(tetrahydroxyphenyl) chlorin ( m -THPC) are now being considered for approval. Although sensitizers are likely to localize within the cytoplasm or the plasma membrane, nuclear membrane can be damaged at an early stage of photodynamic reaction, resulting in DNA lesions. Thus, it is of critical importance to assess the safety of m -THPC-PDT, which would be used mainly against early well-differentiated cancers. In this context, m -THPC toxicity and phototoxicity were studied by a colorimetric MTT assay on C6 cells to determine the LD 50 (2.5 μg/ml m -THPC for 10 J/cm 2 irradiation and 1 μg/ml for 25 J/cm 2 irradiation) and PDT doses inducing around 25% cell death. Single-cell electrophoresis (a Comet assay with Tail Moment calculation) was used to evaluate DNA damage and repair in murine glioblastoma C6 cells after LD 25 or higher doses for assays of PDT. These results were correlated with m -THPC nuclear distribution by confocal microspectrofluorimetry. m -THPC failed to induce significant changes in the Tail Moment of C6 cells in the absence of light, whereas m -THPC-PDT induced DNA damage immediately after irradiation. The Tail Moment increase was not linear (curve slope being 43 for 0–1 μg/ml m -THPC and 117 for 1–3 μg/ml), but the mean value increased with the light dose (0, 10 or 25 J/cm 2 ) and incubation time (every hour from 1 to 4 h) for an incubation with m -THPC 1 μg/ml. However, cultured murine glioblastoma cells were capable of significant DNA repair after 4 h, and no residual DNA damage was evident after 24-h post-treatment incubation at 37°C. An increase in the light dose appeared to be less genotoxic than an increase in the m -THPC dose for similar toxicities. Our results indicate that m -THPC PDT appears to be a safe treatment since DNA repair seemed to not be impaired and DNA damage occurred only with lethal PDT doses. However, the Comet assay cannot give us the certainty that no mutation, photoadducts or oxidative damage have been developed so this point would be verified with another mutagenicity assay.

Le changement climatique amplifie les risques pesant sur les ressources hydriques et les capacités agricoles au sud de la Méditerranée. Cet article analyse la portée méthodologique du concept de « commerce d'eau virtuelle » en quantifiant le contenu en eau des importations céréalières des pays d'Afrique du Nord. Il montre aussi sa pertinence en tant qu'outil stratégique, susceptible de structurer les politiques d'adaptation à la rareté croissante de l'eau. Le remodelage sectoriel de l'allocation des ressources que permettrait l'importation des produits intensifs en eau pourrait être une mesure holistique d'adaptation à la rareté mais dont l'opportunité reste tributaire de la configuration des accords commerciaux.

Le changement climatique fait peser de nombreux risques d'impacts en Chine. Les ressources en eau dans les plaines du nord pourraient être particulièrement affectées. Si les équilibres sont déjà souvent rompus dans cette région, le réchauffement attendu jouera un rôle d'accélérateur de dynamiques existantes d'aggravation des déficits hydriques. Dans le contexte de compétition intersectorielle pour l'allocation de l'eau qui se dessine, la production céréalière du nord de la Chine apparaît comme un secteur particulièrement vulnérable. La diminution attendue des rendements des principales cultures pose alors la question des stratégies d'adaptation qui pourraient être adoptées. Mise en place de manière anticipée, une politique de l'eau axée de manière structurelle sur la rareté de la ressource permettrait de réduire ces risques tout en répondant à des défis déjà sensibles. Les impacts résiduels pourraient cependant rester conséquents. L'ouverture commerciale et les possibilités d'importer de l'eau sous forme de produits agricoles ouvrent de nouvelles perspectives pour une utilisation plus efficace des ressources hydriques,à mettre en balance avec le principe d'autosuffisance alimentaire.

Le changement climatique fait peser des risques élevés pour l'agriculture méditerranéenne, qui pourrait voir ses rendements diminuer fortement, en liaison avec lararéfaction des ressources hydriques. L'adaptation anticipative des systèmes agricoles à ces changements apparaît ainsi comme un enjeu majeur pour cette région pour le 21e siècle.

Photodynamic therapy induces the production of reactive oxygen species (ROS) within tissues exposed to laser light after administration of a sensitizer. In the context of continuing clinical and commercial development of chemicals with sensitizing properties, a minimally invasive assay is needed to determine the tissue kinetics of fluorescent or non-fluorescent photoreactive drugs. The level of ROS was determined ex vivo from 1 mm 3 biopsy samples using 2′-7′ dichlorofluorescin diacetate (DCFH-DA), a fluorescent probe which was converted into highly fluorescent dichlorofluorescein (DCF) in the presence of ROS. This assay was tested on meta(tetrahydroxyphenyl)chlorin ( m -THPC, FOSCAN ® ), a powerful and fluorescent sensitizer, and bacteriochlorophyll derivative WST09 (TOOKAD ® ), a near-infrared absorbing sensitizer that is only slightly fluorescent. In conjunction with the ROS assay, the tissue accumulation of m -THPC was determined on biopsy samples using an optic fibre spectrofluorometer (OFS). DCF fluorescence was proportional to the level of oxidation induced by horseradish peroxidase used as a control and to the concentration (range: 0–5 μg ml −1 ) of both selected photosensitizers irradiated in a tube together with DCFH. Regardless of the organ studied, an excellent correlation was found between fluorescence measurement by OFS and ROS determination for m -THPC. m -THPC (2 mg kg −1 iv) accumulation in tumour tissues was best after 48 h, and the best signal was obtained in liver. With non-fluorescent WST09 (2 mg kg −1 ), ROS determination showed the best tumour uptake 48 h after injection, with a tumour/muscle ratio of 5.4. The ROS assay appears to be feasible for determining sensitizer concentration in regular grip biopsy tissue samples.

Photodynamic therapy (PDT) induces cell-membrane damage and alterations in cancer-cell adhesiveness, an important parameter in cancer metastasis. These alterations result from cell sensitivity to photosensitizers and the distribution of photosensitizers in cells. The efficacy of photosensitizers depends on their close proximity to targets and thus on their pharmacokinetics at the cellular level. We studied the cellular distribution of photosensitizers with a confocal microspectrofluorimeter by analysing the fluorescence emitted by benzoporphyrin derivative-monoacid ring A (BPD-MA) and Photofrin relative to their cell sensitivity. Two cancer cell lines of colonic origin, but with different metastatic properties, were used: PROb (progressive) and REGb (regressive). For BPD-MA (1.75 microg/ml), maximal fluorescence intensity (8,300 cts) was reached after 2 h for PROb and after 1 h (4,900 cts) for REGb. For Photofrin (10 microg/ml), maximal fluorescence intensity (467 cts) was reached after 5 h for PROb and after 3 h (404 cts) for REGb. Intracellular studies revealed stronger cytoplasmic than nuclear fluorescence for both BPD and Photofrin. Both of the sensitizers induced a dose-dependent phototoxicity; LD50 with BPD-MA was 93.3 ng/ml for PROb and 71.1 ng/ml for REGb, under an irradiation of 10 J/cm2. With Photofrin, LD50 was 1,270 ng/ml for PROb and 1,200 ng/ml for REGb under an irradiation of 25 J/cm2. The photosensitizer effect within PROb and REGb cancer cells was assessed by incorporation kinetics and toxicity-phototoxicity tests. The intracellular concentration of the photosensitive agent was one important factor in the effectiveness of PDT, but not the only one contributing to the photodynamic effect. In conclusion, this study showed that there was a clear difference between sensitizer uptake and phototoxicity, even in cancer cells of the same origin. This could induce cell-killing heterogeneity in clinics.

L’auteure de ce livre a souhaite nous montrer les incidences identitaires du vetement de travail sur le sujet. Pour ce faire, Ginette Francequin a recueilli pendant plus de trois annees des entretiens aupres de diverses populations de travail: pompiers, infirmieres, avocats, bouchers, gendarmes (artisans, cadres, ouvriers...). Une des impressions maitresse qui se degage de cette redaction et de ces temoignages illustrerait la these «qu’un vetement de travail serait porteur de changement ident...

Synthesis of delta-aminolevulinic acid (ALA) derivatives is a promising way to improve the therapeutic properties of ALA, particularly cell uptake or homogeneity of protoporphyrin IX (PpIX) synthesis. The fluorescence emission kinetics and phototoxic properties of ALA-n-pentyl ester (E1) and R,S-ALA-2-(hydroxymethyl) tetrahydrofuranyl ester (E2) were compared with those of ALA and assessed on C6 glioma cells. ALA (100 micrograms/mL), E1 and E2 (10 micrograms/mL) induced similar PpIX-fluorescence kinetics (maximum between 5 and 7 h incubation), fluorescence being limited to the cytoplasm. The 50% lethal dose occurred after 6 h with 45, 4 and 8 micrograms/mL of ALA, E1 and E2, respectively. ALA, E1 and E2 induced no dark toxicity when drugs were removed after 5 min of incubation. However, light (25 J/cm2) applied 6 h after 5 min incubation with 168 micrograms/mL of each compound induced 85% survival with ALA, 27% with E1 and 41% with E2. Increasing the incubation time with ALA, E1 and E2 before washing increased the phototoxicity, but E1 and E2 remained more efficient than ALA, regardless of incubation time. ALA-esters were more efficient than ALA in inducing phototoxicity after short incubation times, probably through an increase of the amount of PpIX synthesized by C6 cells.