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International audience; During the dispensing process of medical orders (MOs), community pharmacists (CPs) can manage drug-related problems (DRPs) by performing pharmacist interventions (PIs). There is little evidence that the PI rate is higher with MOs from hospitals (MOHs) than ambulatory (MOAs) settings, and their impact on the patient and community pharmacy is unknown. The primary objective of this study was to compare the MOH and MOA PI rates. The secondary objective was to describe PIs and their clinical and organizational impacts on patient and community pharmacy workflow. A total of 120 CPs participated in a prospective study. Each CP included 10 MOH and 10 MOA between January and June 2020. DRP and PI description and clinical and organizational impacts between MOH and MOA were assessed and compared. We analyzed 2325 MOs. PIs were significantly more frequent in MOH than in MOA (9.7% versus 4.7%; p < 0.001). The most reported PI was the difficulty of contacting hospital prescribers (n = 45; 52.2%). MOHs were associated with a longer dispensing process time and a greater impact on patient pathway and community pharmacy workflow than MOAs. Lack of communication between hospital and primary care settings partly explains the results. Implementation of clinical pharmacy activities at patient discharge could alleviate these impacts.

International audience; To limit functional surgical failure and reduce the rate of revision surgery in case of surgical ossicular chain reconstruction, a piezoelectric device was developed for assessment of ossicular chain vibrations during the middle ear surgery. The device resembled a pen and consisted of a reusable main body and a disposable sensitive head including piezoelectric polymer sensor. Almost all of components of the device were made of polymer for light weight and for acoustic impedance matching to the middle ear system. Several frequencies can be analyzed simultaneously and several measures can be taken by time. The results showed that the device can record normal and reconstructed ossicular chain vibration in response to an acoustic stimulation, with similar results to those achieved by laser Doppler vibrometer. This light, handheld and low-cost device allows fast, easy and safe assessments of normal ossicular chain mobility and ossicular chain reconstruction efficiency. Primary pre-clinical trial showed very promising performance of the device that could be used to qualitatively control ossiculoplasty during real-time surgical procedure. Clinical assessments will be done to further evaluate the real-life performance of the device.

Histoire de la garnison américaine de Verdun de 1951 à 1967.

International audience; Numerous studies have led to a better understanding of the mechanisms of action of viruses in systemic infections for the development of prevention strategies and very promising antiviral therapies. Viruses still remain one of the main causes of human diseases, mainly because the development of new vaccines is usually challenging and drug resistance has become an increasing concern in recent decades. Therefore, the development of potential antiviral agents remains crucial and is an unmet clinical need. One abundant source of potential therapeutic molecules are plants: they biosynthesize a myriad of compounds, including peptides which can have antimicrobial activity. Our objective is to summarize the literature on peptides with antiviral properties derived from plants and to identify key features of these peptides and their application in systemic viral infections. This literature review highlights studies including clinical trials which demonstrated that plant cyclotides have the ability to inhibit the growth of viruses causing human diseases, defensin-like peptides possess anti-HIV-1 activity, and lipid transfer proteins and some lectins exhibit a varied antimicrobial profile. To conclude, plant peptides remain interesting to explore in the context of emerging and re-emerging infectious diseases.

Ce travail décrit quelques exemples de forëts domaniales concédées à l'armée américaine entre 1950 et 1967, et des difficultés que ces dévolutions ont engendrées avec l'administration des Eaux et Forëts. Le conflit provient des déboisements dont l'ampleur dépasse ce qui avait été envisagé ou promis.; Ce travail décrit quelques exemples de forëts domaniales concédées à l'armée américaine entre 1950 et 1967, et des difficultés que ces dévolutions ont engendrées avec l'administration des Eaux et Forëts. Le conflit provient des déboisements dont l'ampleur dépasse ce qui avait été envisagé ou promis.

International audience

To promote the nutritional and pharmacological values of four sea cucumber species (Holothuria poli, H. tubulosa, H. arguinensis, and H. sanctori), harvested from the Algerian coast, we aimed to study their proximate composition, fatty acid profile and angiotensin-converting enzyme (ACE) inhibitory activity. Their phospholipids were also used to elaborate nanoliposomes and to encapsulate peptides obtained from the same source. After the physico-chemical characterization of nanoliposomes and peptides, in vitro analyses were realized. The four holothurian species showed a high amount of protein (49.26–69.34%), and an impressive lipid profile of 27 fatty acids, mainly composed of polar fatty acids (91.16–93.85%), with a high polyunsaturated fatty acids (PUFA) content (50.90–71.80%), particularly eicosapentaenoic acid (EPA) (5.07–8.76%) and docosahexaenoic acid (DHA) (4.86–7.25%). A high phospholipids amount was also found (55.20–69.85%), mainly composed of phosphatidylcholine (PC) (51.48–58.56%). Their peptide fractions exhibited a high ACE inhibitory activity (IC50 0.30 to 0.51 mg/mL). The results also showed that the nanoliposomes do not induce cytotoxicity and cell death in human MSCs and no perturbation of proliferation for all the times and the tested concentrations, as well as the combined nanoliposomes and hydrolysates (HTS) at a concentration of 0.1 mg/mL. All four sea cucumbers show potential as a new source for omega-3, omega-6, and bioactive peptides.

L’huile essentielle de Lavande aspic est couramment employee en therapeutique aromatique. A l’inverse de celle de Lavande officinale, avec laquelle elle est souvent confondue par les neophytes, elle a fait l’objet de peu d’etudes scientifiques. Sa composition tres variee est a l’origine de ses nombreuses et tres interessantes indications. Sa toxicite potentielle doit etre prise en compte.

National audience; Les nanobjets (NOb), structures libres possédant au moins une dimension d'échelle nanométrique (inférieure à 100 nm), ont de plus en plus d'applications et sont donc de plus en plus présents dans la vie quotidienne et en milieu professionnel. Leur petite taille leur confère des propriétés différentes de celles de mêmes composés de taille micrométrique ou supérieures et, souvent, une toxicité supérieure. Cette dernière est étudiée au laboratoire avec des modèles soit de cultures cellulaires soit d'animaux de laboratoire. Les études, nombreuses, utilisent des protocoles expérimentaux très divers. Elles sont indispensables pour comprendre les mécanismes de toxicité des NOb. Ceux-ci déclenchent dans les cellules des mécanismes pro-inflammatoires, des altérations du métabolisme, ainsi que des morts cellulaires. L'administration de NOb à l'animal se traduit par des réactions inflammatoires mais également des disséminations dans l'organisme et, après une administration locale, ils se retrouvent dans différents tissus. Ces deux modèles ne miment qu'imparfaitement les conditions d'exposition humaine. Les doses administrées sont souvent importantes et correspondent le plus souvent à des expositions aiguës. Cependant, malgré leurs imperfections, ces études peuvent servir d'alerte pour prévenir ou limiter l'utilisation de tel ou tel NOb.

International audience; Audibility in noise is hearing impaired people essential problem. Hearing aids manufacturers, in recent years, improved signal processing options such as adaptive microphone directivity and noise reduction. The most recent hearing aids use of the source localization to distinguish the useful signals (speech) from those caused by the nuisance (noise). Once localized, the noises are attenuated to let the speech out. The objective of this study is to investigate this speech intelligibility options effectiveness using the Signal-to-Noise Ratio (SNR), for different types of masking noise, different sound levels and different speech signal directions. The auditory simulation platform of the Faculty of Pharmacy audiology training center of the University of Lorraine has been used to reproduce the free-field vocal audiometry conditions and to analyze the output signals of the hearing aids placed on the ears of an artificial head. The output SNR of hearing aids is estimated using the Hagerman and Olofsson method (2004). The SNR frequency variation for the different tested noise types and speech signal directions allows us to discuss algorithmic strategies. Finally, listening to the analyzed signals makes it possible to compare the measured objective numerical values with our subjective intelligibility and listening comfort feeling.

International audience; L’huile essentielle de Géranium rosat, Pelargonium asperum, est parfois appelée “l’HE dela peau” en raison de ses propriétés anti-inflammatoires, antiseptiques, astringentes etrégénérantes cutanées. Elle est aussi utilisée comme antimycosique et contre les insectespiqueurs chez l’homme et l’animal.

International audience

International audience; L’huile essentielle de Ravintsara, immunostimulante, puissamment antivirale et antiinfectieuse,se révèle très utile en cas d’affections virales d’ordre respiratoire et digestive.Elle est produite à Madagascar par distillation des feuilles d’une Lauracée, Cinnamomumcamphora, appelée aussi faux camphrier.

International audience; Despite great histological and molecular heterogeneity, the clinical management of highgrade ovarian carcinomas remains unspecialized. As a major subgroup, high-grade serous ovarian carcinomas (HGSOCs) require novel therapies. In addition to utilizing conventional histological prognostic markers and performing oncogenetic investigations, the molecular diagnostic method of next generation sequencing (NGS) was performed to identify ‘druggable’ targets that could provide access to innovative therapy. The present study was performed in 45 HGSOC patients (mean age, 59.1 years; range, 2587 years) with histologically proven HGSOC. Breast cancer 1/2 (BRCA1/2) germline mutations were screened in 17 patients with a familial or personal history of cancer, which was justified by oncogenetic investigations. Tumor protein 53 (P53) and phosphatase and tensin homolog (PTEN) expression were assessed in formalinfixed paraffinembedded tissues using immunohistochemistry. Somatic mutations of Kirsten rat sarcoma viral oncogene homolog, neuroblastoma RAS viral oncogene homolog (NRAS), BRaf protooncogene, serine/threonine kinase, phosphatidylinositol4,5bisphosphate 3kinase catalytic subunit α (PIK3CA) and MET protooncogene, receptor tyrosine kinase (MET) were screened using NGS on DNA extracts from frozen tumor specimens obtained at diagnosis. With a median followup of 38 months (range, 6-93 months), 20 patients are alive, 10 patients are diseasefree and 14 patients progressed within 6 months following platinumbased therapy. P53 overexpression was detected in 67% of patients and PTEN loss was detected in 38% of the patients. The overexpression of mutant P53 was found to be associated with a longer progressionfree and overall survival. In total, 2 NRAS (exon 3), 3 PIK3CA (exon 5 and 10) and 5 MET mutations (exons 14 and 18) were detected. In HGSOCs, in addition to P53 and PTEN alterations, somatic genetic abnormalities can be detected using NGS and provide molecular rationale for targeted therapies, potentially offering novel therapeutic opportunities to patients.

Angiogenesis is a critical parameter to consider for the development of tissue-engineered bone substitutes. The challenge is to promote sufficient vascularization in the bone substitute to prevent cell death and to allow its efficient integration. The capacity of nacre extract to restore the osteogenic activity of osteoarthritis osteoblasts has already been demonstrated. However, their angiogenic potential on endothelial progenitor cells (EPCs) was not yet explored. Therefore, the current study aimed at investigating if nacreous molecules affect EPC behavior. The gene and protein expression levels of endothelial cell (EC)-specific markers were determined in EPCs cultivated in presence of a nacre extract (ethanol soluble matrix [ESM] at two concentrations: 100 μg/mL and 200 μg/mL (respectively abbreviated ESM100 and ESM200)). Cell functionality was explored by proangiogenic factors production and in vitro tube formation assay. ESM200 increased the expression of some EC-specific genes. The in vitro tube formation assay demonstrated that ESM200 stimulated tubulogenesis affecting angiogenic parameters. We demonstrated that a stimulation with 200 μg/mL of ESM increased angiogenesis key elements. This in vitro study strongly highlights the proangiogenic effect of ESM. Due to its osteogenic properties, previously demonstrated, ESM could constitute the key element to develop an ideal prevascularized bone substitute. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

International audience; Les plantes carnivores sont des végétaux insolites qui ont toujours intrigué les scientifiques.Leur principal emploi en thérapeutique concerne l’homéopathie, mais depuis plusieursannées, de nouvelles approches commencent à émerger.

Sickle cell anemia is an autosomal recessive hemoglobinopathy affecting the production of hemoglobin involved in the functioning of red blood cells. This disease is characterized by the presence of sickle cells wich have a low affinity for oxygen. This red blood cells alteration will, among other things, affect the oxygenation of organs, cause severe vaso-occlusive crises during intense and prolonged physical activity and will lead to premature death of patients. To date, no universal treatment exists to these patients.Gene therapy is currently a major issue to treat sickle cell disease. Appeared in the second half of the 20th century, following the discovery of the structure of DNA, this new therapy has already conduced to the development of new treatments (immunotherapies, recombinant vaccines, growth hormones, etc.). To be able to treat patients with sickle cell anemia, gene therapy must attack the cause of the disease by modifying the cell genome.To treat patients with sickle cell anemia, various clinical gene therapy protocols are tested. In these protocols, medical staff extracts the stem cells from the patient, to correct them (by adding a gene) before to reimplant them. This gene may be the beta chain of hemoglobin A (which is mutated in these patients), or another hemoglobin chain (gamma chain) or a gene coding for a molecule which will ultimately regulate hemoglobin production (inhibition of BCL11A). The first results obtained during these trials allowed the healing of a patient, which gave hope. However, gene therapy must prove is efficiency on a large and long-term basis to be considered as the therapy in sickle cell disease.; La drépanocytose est une hémoglobinopathie, autosomique récessive touchant la production de l’hémoglobine impliquée dans le fonctionnement des hématies. Cette maladie est caractérisée par la présence d’hématies falciformes possédant une faible affinité pour l’oxygène. Cette altération des hématies va entre autres impacter l’oxygénation des organes et provoquer des crises vaso-occlusives sévères en cas d’activité physique intense et prolongée et va conduire à une mort prématurée des patients. À ce jour, aucun traitement universel n’est proposé à ces patients.La thérapie génique représente, à l’heure actuelle, un enjeu majeur dans la prise en charge des patients. Apparu dans la seconde moitié du XXème siècle, suite à la découverte de la structure de l’ADN, cette nouvelle thérapie a déjà permis la mise sur le marché de nouveaux traitements (immunothérapies, vaccins recombinants, hormones de croissance…). Pour pouvoir traiter efficacement les patients atteints de drépanocytose, la thérapie génique doit s’attaquer à l’essence même de la maladie en modifiant le génome cellulaire.Afin de prendre en charge le plus efficacement possible les patients atteints de drépanocytose, le personnel soignant teste actuellement différents protocoles cliniques de thérapie génique. Ces protocoles visent à extraire les cellules souches du patient porteur de la maladie, de les corriger (par ajout de gène) et de les réimplanter aux patients. Ce gène peut être celui de la chaine bêta de l’hémoglobine A (qui est muté chez ces patients), celui d’une autre chaine de l’hémoglobine (chaine gamma) ou un gène codant pour une molécule qui in fine permettra de réguler la production d’hémoglobine (inhibition de BCL11A). Les premiers résultats obtenus lors de ces essais ont permis la guérison d’un patient, ce qui a redonné espoir aux malades. Néanmoins, la thérapie génique doit encore faire ses preuves à grande échelle et sur le long terme avant d’être réellement considérée comme une thérapie efficace.

Sickle cell anemia is an autosomal recessive hemoglobinopathy affecting the production of hemoglobin involved in the functioning of red blood cells. This disease is characterized by the presence of sickle cells wich have a low affinity for oxygen. This red blood cells alteration will, among other things, affect the oxygenation of organs, cause severe vaso-occlusive crises during intense and prolonged physical activity and will lead to premature death of patients. To date, no universal treatment exists to these patients.Gene therapy is currently a major issue to treat sickle cell disease. Appeared in the second half of the 20th century, following the discovery of the structure of DNA, this new therapy has already conduced to the development of new treatments (immunotherapies, recombinant vaccines, growth hormones, etc.). To be able to treat patients with sickle cell anemia, gene therapy must attack the cause of the disease by modifying the cell genome.To treat patients with sickle cell anemia, various clinical gene therapy protocols are tested. In these protocols, medical staff extracts the stem cells from the patient, to correct them (by adding a gene) before to reimplant them. This gene may be the beta chain of hemoglobin A (which is mutated in these patients), or another hemoglobin chain (gamma chain) or a gene coding for a molecule which will ultimately regulate hemoglobin production (inhibition of BCL11A). The first results obtained during these trials allowed the healing of a patient, which gave hope. However, gene therapy must prove is efficiency on a large and long-term basis to be considered as the therapy in sickle cell disease.; La drépanocytose est une hémoglobinopathie, autosomique récessive touchant la production de l’hémoglobine impliquée dans le fonctionnement des hématies. Cette maladie est caractérisée par la présence d’hématies falciformes possédant une faible affinité pour l’oxygène. Cette altération des hématies va entre autres impacter l’oxygénation des organes et provoquer des crises vaso-occlusives sévères en cas d’activité physique intense et prolongée et va conduire à une mort prématurée des patients. À ce jour, aucun traitement universel n’est proposé à ces patients.La thérapie génique représente, à l’heure actuelle, un enjeu majeur dans la prise en charge des patients. Apparu dans la seconde moitié du XXème siècle, suite à la découverte de la structure de l’ADN, cette nouvelle thérapie a déjà permis la mise sur le marché de nouveaux traitements (immunothérapies, vaccins recombinants, hormones de croissance…). Pour pouvoir traiter efficacement les patients atteints de drépanocytose, la thérapie génique doit s’attaquer à l’essence même de la maladie en modifiant le génome cellulaire.Afin de prendre en charge le plus efficacement possible les patients atteints de drépanocytose, le personnel soignant teste actuellement différents protocoles cliniques de thérapie génique. Ces protocoles visent à extraire les cellules souches du patient porteur de la maladie, de les corriger (par ajout de gène) et de les réimplanter aux patients. Ce gène peut être celui de la chaine bêta de l’hémoglobine A (qui est muté chez ces patients), celui d’une autre chaine de l’hémoglobine (chaine gamma) ou un gène codant pour une molécule qui in fine permettra de réguler la production d’hémoglobine (inhibition de BCL11A). Les premiers résultats obtenus lors de ces essais ont permis la guérison d’un patient, ce qui a redonné espoir aux malades. Néanmoins, la thérapie génique doit encore faire ses preuves à grande échelle et sur le long terme avant d’être réellement considérée comme une thérapie efficace.

International audience; L’huile essentielle (HE) de Corymbia citriodora est parfois appelée “l’HE du sportif” en raisonde ses propriétés antalgiques et myorelaxantes. C’est également une HE de choix pourlutter contre l’inflammation, les douleurs, les parasites et les champignons.

International audience; The development of chemotherapy using conventional anticancer drugs has been hindered due to several drawbacks related to their poor water solubility and poor pharmacokinetics, leading to severe adverse side effects and multidrug resistance in patients. Nanocarriers were developed to palliate these problems by improving drug delivery, opening the era of nanomedicine in oncology. Liposomes have been by far the most used nanovectors for drug delivery, with liposomal doxorubicin receiving US FDA approval as early as 1995. Antibody drug conjugates and promising drug delivery systems based on a natural polymer, such as albumin, or a synthetic polymer, are currently undergoing advanced clinical trials or have received approval for clinical applications. However, despite attractive results being obtained in preclinical studies, many well-designed nanodrugs fell short of expectations when tested in patients, evidencing the gap between nanoparticle design and their clinical translation. The aim of this review is to evaluate the extent of nanotherapeutics used in oncology by providing an insight into the most successful concepts. The reasons that prevent nanodrugs from expanding to clinic are discussed, and the efforts that must be taken to take full advantage of the great potential of nanomedicine are highlighted.

International audience; Influenza A virus (IAV) circulate among the bird population and infection of domestic animals are common and due to several sub-types. Before 1997, human infections by avian strains were considered as mild. The epizootic that occurred in 1997, due to an IAV(H5N1), was accompanied by severe human infections and deaths. From 2003 on, a panzootic due to the same sub-type has had as consequence to increase the surveillance of avian infections and the establishment of protective measures at an international level. Thus, the epizootic that began in November 2015 in South-West France has brought the government to implement strict administrative measures and this episode ended in August 2016 although a late unique episode was observed in March 2017. Three different sub-types were in cause and 81 farms in 8 departments were concerned. The consequences were important for the flocks and the local economy. The farms had to renew completely their flock with animals of certified origin. The strains were not pathogenic for humans. Epizootics of avian influenza occur regularly in all the countries all over the world and the surveillance of raised poultry must be pursued.; Les Influenza A virus (IAV) circulent au sein de l’avifaune et l’infection des oiseaux d’élevage est fréquente et due à de nombreux sous-types. Jusqu’en 1997, les infections humaines par des souches aviaires étaient considérées comme bénignes. La survenue en 1997 d’une épizootie à IAV(H5N1) accompagnée d’infections humaines graves et de décès puis à partir de 2003 le déclenchement d’une panzootie par ce même sous-type, a entraîné une surveillance accrue des infections aviaires et la mise en place de mesures de protection au niveau mondial. Dans ce contexte, l’épizootie qui s’est déclarée dans le Sud-Ouest de la France en novembre 2015 a amené la mise en place de mesures administratives strictes et l’épisode s’est terminé en août 2016 avec, cependant, un épisode tardif en mars 2017. Au total 82 foyers dans 8 départements ont été comptabilisés. Ils ont eu des conséquences économiques importantes et le cheptel aviaire dans les départements touchés a été entièrement renouvelé. Ces souches, pathogènes pour la volaille, ne l’étaient pas pour l’Homme. Cependant des épizooties d’influenza aviaires surviennent régulièrement dans tous les pays et la surveillance des élevages de volaille ne doit pas être relâchée.

microRNAs (miRNAs) are a group of small non-coding RNA molecules known to regulate target genes at the post-transcriptional level. miRNAs are implicated in the regulation of multiple pathophysiological processes including dyslipidemia, a major risk factor for atherosclerosis. Emerging evidence suggests that miRNAs act as a novel class of epigenetic regulators of high-density lipoproteins cholesterol (HDL-C) from synthesis to clearance contributing remarkably to the pathogenesis of atherosclerosis. Accumulating studies have revealed that miRNAs such as miR-33, miR-27, miR-144, miR-758 and miR-20 are involved in the post-transcriptional control of ABCA1, ABCG1 and SCARB1 genes regulatory network of the reverse cholesterol transport (RCT). These miRNAs have been shown to be central players in the impairment of RCT pathway leading to the development of atherosclerosis. In this article, we present most recent understanding of involvement of relevant miRNAs in different steps of HDL metabolism and RCT pathway. We also discuss some of the actual limitations to the promise of these miRNAs and perspectives on their translation to clinical settings.

Objectives To determine whether call center dispatchers wearing headsets are subject to auditory fatigue at the end of a work shift. Material and methods Data was gathered at times when call centers were busiest. All call operators wore a headset for up to 12 h. Acoustic environment and noise exposure under the headset were continuously recorded during the entire work shift. Variations in auditory parameters were assessed using pure-tone air-conduction audiometry and an objective test based on distortion product otoacoustic emissions - contralateral suppression of distortion product otoacoustic emission (DPOAE) amplitudes (EchoScan test). Thirty-nine operators and 16 controls, all volunteers, were selected from 3 call centers (sales, assistance, and emergency) where all cognitive tasks were accomplished by phone and on computers. Results No acoustic shock was detected during the investigation. The highest normalized noise exposure (daily noise exposure level - LEX,8 h) measured was 75.5 dBA. No significant variation in auditory performances was detected with either pure-tone air-conduction audiometry or the EchoScan test. Nevertheless, dispatchers expressed a feeling of tiredness. Conclusions For an equivalent diffuse field noise exposure, the use of a headset does not seem to worsen auditory fatigue for call center operators. The dispatcher's fatigue was probably due to the duration of the work shift or to the tasks they performed rather than to the noise exposure under a headset. Int J Occup Med Environ Health 2018;31(2):217-226.

Influenza A virus (IAV) circulate among the bird population and infection of domestic animals are common and due to several sub-types. Before 1997, human infections by avian strains were considered as mild. The epizootic that occurred in 1997, due to an IAV(H5N1), was accompanied by severe human infections and deaths. From 2003 on, a panzootic due to the same sub-type has had as consequence to increase the surveillance of avian infections and the establishment of protective measures at an international level. Thus, the epizootic that began in November 2015 in South-West France has brought the government to implement strict administrative measures and this episode ended in August 2016 although a late unique episode was observed in March 2017. Three different sub-types were in cause and 81 farms in 8 departments were concerned. The consequences were important for the flocks and the local economy. The farms had to renew completely their flock with animals of certified origin. The strains were not pathogenic for humans. Epizootics of avian influenza occur regularly in all the countries all over the world and the surveillance of raised poultry must be pursued., Les Influenza A virus (IAV) circulent au sein de l’avifaune et l’infection des oiseaux d’élevage est fréquente et due à de nombreux sous-types. Jusqu’en 1997, les infections humaines par des souches aviaires étaient considérées comme bénignes. La survenue en 1997 d’une épizootie à IAV(H5N1) accompagnée d’infections humaines graves et de décès puis à partir de 2003 le déclenchement d’une panzootie par ce même sous-type, a entraîné une surveillance accrue des infections aviaires et la mise en place de mesures de protection au niveau mondial. Dans ce contexte, l’épizootie qui s’est déclarée dans le Sud-Ouest de la France en novembre 2015 a amené la mise en place de mesures administratives strictes et l’épisode s’est terminé en août 2016 avec, cependant, un épisode tardif en mars 2017. Au total 82 foyers dans 8 départements ont été comptabilisés. Ils ont eu des conséquences économiques importantes et le cheptel aviaire dans les départements touchés a été entièrement renouvelé. Ces souches, pathogènes pour la volaille, ne l’étaient pas pour l’Homme. Cependant des épizooties d’influenza aviaires surviennent régulièrement dans tous les pays et la surveillance des élevages de volaille ne doit pas être relâchée.

International audience

To evaluate knowledge and behaviours concerning antibiotics and bacterial resistance in the French population, and to identify the socio-demographic factors associated with a high level of such knowledge and appropriate behaviours.A survey of the general population was conducted in 2015 in northeast France. The 44-item standardized questionnaire used comprised three parts, focusing on the assessment of knowledge, behaviours, and the collection of main socio-demographic characteristics of respondents (gender, age, having children, education level, and profession). The association of these characteristics with the level of knowledge about antibiotics, and with related behaviours, as well as the association between knowledge and behaviours was identified in a bivariate analysis (Chi-2 tests) and a multivariate analysis when necessary (logistic regression).The 200 respondents had quite a good level of knowledge about antibiotics for several points: the lack of effectiveness of antibiotics for colds (75.5%), the risk of inefficacy of antibiotics when misused (93%), and the effects of overconsumption on bacterial resistance (92%). Conversely, the effects of different doses and treatment durations on resistance were less well known. Inappropriate behaviours were frequent, especially non-adherence to dosing schedules and to treatment duration (35.5%), and self-medication practices (18%). Female gender, older age, and having children were independently associated with a good level of knowledge. A low level of education and older age were associated with appropriate behaviours.No association was found between knowledge and behaviours, highlighting the relevance of national public information campaigns to limit the misuse of antibiotics.

Background Allogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB). Methods Fourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment. Results One patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease. Conclusions Adoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered). Electronic supplementary material The online version of this article (doi:10.1186/s13045-017-0469-0) contains supplementary material, which is available to authorized users.

Selected paper from the 6th China–France International Symposium “Stem Cells and Regenerative Medicine” and the first meeting of the France–China International CNRS Network (GDRI) CeSMeR, Nancy, 10–13 July 2016; International audience; Mesenchymal stem cells (MSCs) are a common tool in regenerative medicine. The nanoscale extracellular vesicles (nEVs) secreted by these cells were recently brought up to light thanks to their therapeutic potential. In this study, we assessed the in vitro behaviour of human umbilical vein endothelial cells (HUVECs) exposed to nEVs derived from human umbilical cord mesenchymal stem cells (hUC-MSCs). Nanoscale extracellular vesicles were isolated and characterized by NanoSight® and flow cytometry. HUVECs were stimulated with various concentrations of nEVs. To assess nEV interactions with HUVECs, confocal microscopy and angiogenesis assay were performed. The use of nEVs derived from hUC-MSCs was able to produce positive outcomes on HUVECs by acting on their angiogenic potential.

International audience; Wharton's jelly mesenchymal stem cells (WJ-MSCs) are widely used in tissue engineering. In vascular engineering, the ability to obtain a vessel replacement with contractile smooth muscle cells (SMC) is a key factor. In this work, we demonstrated that WJ-MSCs differentiate towards a SMC phenotype with various stimulations in vitro and that the modification of redox state could be involved. WJ-MSCs were isolated from umbilical cords. After their expansion, the cells were stimulated with ascorbic acid (AA, 300 μM) or transforming growth factor (TGF)-β1 (1 to 5 ng/mL). SMC markers were analyzed by Western blot. Modification of redox state was evaluated by reactive oxygen species (ROS) production and glutathione (GSH) content measurements. TGF-β1 or AA-stimulated WJ-MSCs express early and intermediate SMC markers. TGF-β1 (5 ng/mL) modifies the redox state by a ROS production and a GSH content drop, while AA has no effect. This work showed that TGF-β1 and AA are effective SMC phenotype inducers to differentiate WJ-MSCs.

International audience; Background Antibiotic-resistant bacteria are a major public health problem throughout the world. In 2006, in accordance with the national guidelines for antibiotic use, the CHRU of Nancy created an operational multidisciplinary antibiotic team at one of its sites. In 2011, a cluster-controlled trial showed that the operational multidisciplinary antibiotic team (the intervention) had a favourable short-term effect on antibiotic use and costs. Objective Our objective was to determine whether these effects continued over the medium to long term (that is, 2–7 years after creation of the operational multidisciplinary antibiotic team, 2009–2014). Setting The 1800-bed University Hospital of Nancy (France). Method The effect in the medium to long term is measured according to the same criteria and assessed by the same methods as the first study. A cluster controlled trial was performed on the period 2009–2014. The intervention group comprised 11 medical and surgical wards in settings where the operational multidisciplinary antibiotic team was implemented and the control group comprised 6 wards without this operational team. Main outcome measure Consumption of antibiotics overall and by therapeutic class (in defined daily doses per 1000 patient-days) and costs savings (in €). Results The reduction in antibiotic use and costs continued, but at a lower rate than in the short term (11% between 2009 and 2014 compared with 33% between 2007 and 2009) at the site of the intervention. The principal decreases concerned fluoroquinolones and glycopeptides. At the site without an operational multidisciplinary antibiotic team (the control group), total antibiotic use remained stable. Between 2009 and 2014, costs fell 10.5% in the intervention group and 5.7% in the control group. Conclusion This study shows that it is possible to maintain the effectiveness over time of such an intervention and demonstrates its role in defining a hospital’s antibiotic policy.

Many clinical trials report mesenchymal stem/stromal cells (MSCs) efficacy in various indications. Therefore, standardization of MSC production becomes necessary. MSC properties are impacted by tissue origin, especially if they are from extraembryonic tissue or adult sources. For this reason, we evaluated the impact of MSC tissue origin on production. Methods: Three productions of MSC from Wharton’s Jelly (WJ) or from bone marrow (BM) were performed according to good manufacturing practice. The identity (phenotype, differentiation, and clonogenic capacities), safety (karyotype, telomerase activity, sterility, and donor qualification), and functionality (viability, mixed lymphocyte reaction) of each cell batch were analyzed. Results: Slight differences between MSC sources were observed for phenotype, telomerase activity, and clonogenic capacities. Conclusion: Both sources have made it possible to quickly and easily obtain clinical grade MSC. However, as availability of the source is thought to be essential, WJ seems more advantageous than BM.

International audience; Mesenchymal stem cells (MSCs) are widely used in cell therapy and tissue engineering thanks to their self-renewal, their multipotency, and their immunomodulatory properties that make them an attractive tool for regenerative medicine. A large part of MSCs positive effects is due to their secretion products which participate in creating a favorable microenvironment and closely relate these cells to other cell types. Extracellular vesicles (EVs) belong to cellular secretions. They are produced by cells continuously or after stimulation (e.g., calcium flux, cellular stress) and act in tissue homeostasis and intercellular communication. The understanding of the role of EVs is growing, more particularly their impact on cell migration, differentiation, or immunomodulation. EVs derived from MSCs show these interesting properties that may be considered in therapeutics, although they can have adverse effects by facilitating cancer propagation. Moreover, MSC behavior may also be influenced (proliferation, differentiation) by EVs derived from other donor cells. The aim of this mini review is to summarize the two-way communication between MSCs and other cell types, and how they can affect each other with their microenvironment through EVs. On the one hand, the manuscript presents the influence of MSC-derived EVs on diverse recipient cells and on the other hand, the effects of EVs derived from various donor cells on MSCs. The discrepancies between cancer cells and MSCs communication according to the sources of MSCs but also the tumor origins are also mentioned.

International audience; Background According to new recommendations for the management of acute decompensated heart failure (ADHF) in 2015, intravenous vasodilator therapy might be given as an early therapy when systolic blood pressure is normal to high (≥110 mmHg). Only 29% of patients with ADHF are treated with vasodilators without medical contraindication. Objective To evaluate the effect of the systematic use of ISDN on ADHF without contraindication especially on rehospitalization rate. Settings The 600-bed hospital (Centre Hospitalier de l’Ouest Vosgien, Neufchâteau, France). Methods This is a retrospective study with data analysed from medical records. Patients with ADHF episodes and hospitalization in the cardiology department or intensive care unit (ICU) between November 2013 and December 2015 were included resulting in 199 hospitalizations in the analysis (37 were treated by ISDN, and 162 were not). Main outcome measure Effects of ISDN on 180-day hospital readmission for ADHF or acute myocardial infarction (AMI), in-hospital mortality, length of stay, number of ICU admissions, and ICU length of stay. Results Patients who received ISDN required more ICU admissions than the other patients (54.1 vs 33.3%, p = 0.02). Nevertheless 180-day hospital readmission was lower for patients who were receiving ISDN (8.1 vs 22.8%, p = 0.04). ISDN did not influence other clinical outcomes tested. Conclusion ISDN may minimize or prevent the consequences of altered haemodynamics. Lower rehospitalization rate with ISDN was seen in this study.

International audience; We describe herein the first reported case of a drug–drug interaction between dasatinib and esomeprazole in a patient with Philadelphia-positive acute lymphoblastic leukemia leading to a decrease in dasatinib oral absorption.

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International audience; Background: Oral absorption of low-molecular-weight heparin (LMWH) is limited by its molecular size and negative charge. It has been shown previously that orally administered polymeric nano- or microparticles containing encapsulated LMWH have led to gastrointestinal absorption of heparin in rabbits.Method: Based on these investigations, pellets containing two LMWHs, enoxaparin (MW 4500 Da) or bemiparin (MW 3600 Da), and EudragitRS30D (ERS), were prepared using extrusion/ spheronization technique. Uncoated or coated (ERS) pellets were evaluated in vitro and in vivo on rabbits.Results: Enoxaparin pellets showed fast in vitro release in phosphate buffer (pH 7.4) and prolonged in vivo drug absorption after a single oral dose of 600 anti-Xa IU/ kg of body weight, leading to relative bioavailabilities ranging from 9.7 +/- 1.9% to 12.8 +/- 2.7% and anti-Xa activity over the curative dose. Bemiparin included in matrix pellets of ERS and coated with ERS exhibited in vitro prolonged release up to 4 hours and in vivo anti-Xa activity below the therapeutic minimum value of 0.1 IU/mL.Conclusion: This study presents LMWH in a pellet dosage form, which compared to nano- or microparticles, may offer a more convenient and industrializable way of manufacture leading to an easier scale-up process.

International audience; The better knowledge of the mechanisms of nuclear incidents and lessons learned from accidents in the recent past to improve the effectiveness of measures taken following a nuclear accident exposure to fallout of radioactive iodine isotopes. Thus, immediate, passive measures, such as containment, and stopping consumption of contaminated products are paramount. The earliest possible administration of stable iodine as potassium iodide (KI) reduces significantly (up to 90% if taken at the same time of the accident) thyroid radioactive contamination. These tablets should be given in priority to children and pregnant women. The side effects are minor. KI is not recommended for persons aged over 60 years, or for adults suffering from cardiovascular disorders.

Vascular endothelial growth factor (VEGF) is an angiogenic and neurotrophic factor, secreted by endothelial cells, known to impact various physiological and disease processes from cancer to cardiovascular disease and to be pharmacologically modifiable. We sought to identify novel loci associated with circulating VEGF levels through a genome-wide association meta-analysis combining data from European-ancestry individuals and using a dense variant map from 1000 genomes imputation panel. Six discovery cohorts including 13,312 samples were analyzed, followed by in-silico and de-novo replication studies including an additional 2,800 individuals. A total of 10 genome-wide significant variants were identified at 7 loci. Four were novel loci (5q14.3, 10q21.3, 16q24.2 and 18q22.3) and the leading variants at these loci were rs114694170 (MEF2C, P = 6.79x10-13), rs74506613 (JMJD1C, P = 1.17x10-19), rs4782371 (ZFPM1, P = 1.59x10-9) and rs2639990 (ZADH2, P = 1.72x10-8), respectively. We also identified two new independent variants (rs34528081, VEGFA, P = 1.52x10-18; rs7043199, VLDLR-AS1, P = 5.12x10-14) at the 3 previously identified loci and strengthened the evidence for the four previously identified SNPs (rs6921438, LOC100132354, P = 7.39x10-1467; rs1740073, C6orf223, P = 2.34x10-17; rs6993770, ZFPM2, P = 2.44x10-60; rs2375981, KCNV2, P = 1.48x10-100). These variants collectively explained up to 52% of the VEGF phenotypic variance. We explored biological links between genes in the associated loci using Ingenuity Pathway Analysis that emphasized their roles in embryonic development and function. Gene set enrichment analysis identified the ERK5 pathway as enriched in genes containing VEGF associated variants. eQTL analysis showed, in three of the identified regions, variants acting as both cis and trans eQTLs for multiple genes. Most of these genes, as well as some of those in the associated loci, were involved in platelet biogenesis and functionality, suggesting the importance of this process in regulation of VEGF levels. This work also provided new insights into the involvement of genes implicated in various angiogenesis related pathologies in determining circulating VEGF levels. The understanding of the molecular mechanisms by which the identified genes affect circulating VEGF levels could be important in the development of novel VEGF-related therapies for such diseases., Author Summary Vascular Endothelial Growth Factor (VEGF) is a protein with a fundamental role in development of vascular system. The protein, produced by many types of cells, is released in the blood. High levels of VEGF have been observed in different pathological conditions especially in cancer, cardiovascular, and inflammatory diseases. Therefore, identifying the genetic factors influencing VEGF levels is important for predicting and treating such pathologies. The number of genetic variants associated with VEGF levels has been limited. To identify new loci, we have performed a Genome Wide Association Study meta-analysis on a sample of more than 16,000 individuals from 10 cohorts, using a high-density genetic map. This analysis revealed 10 variants associated with VEGF circulating levels, 6 of these being novel associations. The 10 variants cumulatively explain more than 50% of the variability of VEGF serum levels. Our analyses have identified genes known to be involved in angiogenesis related diseases and genes implicated in platelet metabolism, suggesting the importance of links between this process and VEGF regulation. Overall, these data have improved our understanding of the genetic variation underlying circulating VEGF levels. This in turn could guide our response to the challenge posed by various VEGF-related pathologies.

Chitosan thin films, elaborated by solvent casting, were functionalized by incorporating nanoliposomes based on natural vegetable (soy based) and marine (salmon derived) lecithin. The marine lecithin used in this study contains a higher percentage of polyunsaturated fatty acids (PUFAs) and polar lipids compared with vegetal lecithin. The physical-chemistry properties of the obtained films were characterized by water contact angle (WCA), Fourier Transform InfraRed spectroscopy (FT-IR), water uptake test, and Torsional Harmonic Atomic Force Microscopy analysis (TH-AFM). The surface wettability, swelling ratio, roughness and local stiffness of the thin films can be modified and controlled by adding nanoliposomes. The WCA decreased with the increase of the amount of nanoliposomes. Equilibrium water uptakes of about 170% were achieved in 24 h for the different formulations. The FT-IR results showed the existence of chemical interactions between chitosan and nanoliposomes. The surface topography of the films were identical in terms of asymmetry and amplitude distribution of roughness measurements but showed a significant increase of asperity height when incorporating soya nanoliposomes. This variation is accompanied with a decrease in the average of surface rigidity and of adhesive force value, resulting in a heterogeneous surface. The behaviour of human mesenchymal stem cells (hMSCs) cultured on the films was investigated. Results showed that the films favor cell proliferation when the concentration of soya and salmon nanoliposomes is below 2 mg mL(-1) and 4 mg mL(-1), respectively. The highest cell proliferation of hMSCs culture was observed when the concentration of salmon nanoliposomes was 1 mg mL(-1). This work provides evidence that nanoliposome-functionalized chitosan thin films could offer adequate cyto-friendly cell culture supports for hMSCs, and may potentially be used as suitable scaffolds for tissue engineering applications.

Introduction Paracetamol, the highest over-the-counter (OTC) selling drug in France, has become the first cause of acute hepatic failure [1] . Patient's knowledge of paracetamol has to date only been assessed in hospitalized patients. We aimed to assess good use and knowledge of paracetamol in patients in a realistic setting of self-medication in our region. Methods We conducted a prospective observational study in randomly selected community pharmacies of Metz (France) agglomeration. Patients coming to buy OTC paracetamol for themselves or their family had to answer to an anonymous auto-questionnaire. After being asked about gender, age, weight, parenthood and chronic disease, the patient had to answer to 14 items about paracetamol indications, recommended maximal dose per intake and maximal daily dose, delay between 2 doses, consequences of overdosage and alcohol intake, and the need to adapt dosage to the body weight. The patient also had to identify drugs containing paracetamol among 6 usual drugs; and finally to tell how he gets information and circumstances that can lead him to stop self-medication and visit his general practitioner. Responses were individually and concomitantly analyzed through 3 scores: good use (5 points; good user if > 3), overdosage (4 points; positive if ≤ 3) and knowledge (9 points; good knowledge if > 6). Univariate and multivariate analysis were performed with SAS, version 9.3 (SAS Institute, Cary, NC). Results Twenty-four community pharmacies participated and 302 individual questionnaires were collected. Most of patients (84.4%) could be considered as “good users”. Independent factors of good use were a good knowledge of paracetamol (OR = 5.3; p Conclusion Patients should be better informed about hepatotoxicity of paracetamol to warrant a better safety of its consumption by self-medication. Pharmacists and physicians have to remind patients the risk factors of unintentional overdose and liver toxicity and not hesitate to check if the patient may be at risk for overdosage. Package leaflets should also to be more informative.

National audience; Les parois qui délimitent les locaux industriels présentent souvent un relief à l'origine de la diffusion acoustique des rayons sonores se propageant. Des logiciels prévisionnels d'acoustique permettant de tracer des cartographies du champ acoustique dans des lieux de travail utilisent les caractéristiques acoustiques comme l'absorption ou la diffusion acoustique de ces parois. Dans ce travail, nous avons validé un nouveau système de mesure pour déterminer le coefficient de diffusion in situ des parois verticales. La technique de mesure développée à l'origine dans des conditions de champ libre a été adaptée pour éviter les problèmes d'échos parasites venant de la réverbération et des sources bruyantes présentes sur le site. Pour cela, une antenne acoustique multipolaire et une source impulsive permettant respectivement le filtrage spatial et la séparation des échos parasites ont été utilisées dans un premier banc d'essai pour l'étude des mécanismes de diffusion des parois horizontales (posée au sol). Le nouveau dispositif développé a été validé en étudiant la reproductibilité des résultats sur site, amélioré par une meilleure synchronisation des échos réfléchis dans le processus de moyennage utilisé dans la technique de mesure. L'implantation d'une plus grande antenne multipolaire a permis également d'obtenir une meilleure précision des résultats en basses fréquences. Des mesures du coefficient de diffusion d'une paroi verticale à relief périodique possédant des cavités rectangulaires ont été effectuées pour plusieurs angles d'incidence dans un milieu bruyant et réverbérant. Ces mesures ont finalement permis de tracer des cartographies du coefficient diffusion acoustique selon les directions XY et ainsi d'apprécier les mécanismes de diffusion très variable d'une structure diffusante selon le point de mesure. Ces cartographies pourront être comparées avec des calculs effectués grâce à un modèle précédemment développé.

International audience; Standard methods for detecting enteroviruses in environmental samples require cell culture, which is time consuming and expensive. The reverse transcription-polymerase chain reaction (RT-PCR) is a rapid, sensitive method for detecting enteroviruses in water. However, environmental samples often contain substances that inhibit PCR amplification of target RNA. Hence the virus must be concentrated by procedures that do not interfere with amplification. This study shows that virus concentration by adsorption onto glass powder or glass wool supports is suitable for detecting viral genomes in treated wastewater by RT semi-nested PCR. No enterovirus genome was detected directly in 25 samples of treated wastewater by RT semi-nested PCR. However, samples concentrated by adsorption onto glass wool or glass powder showed that 48% (glass powder) and 56% (glass wool) contained virus. Secondary concentration by organic flocculation was unsuitable for detecting virus concentrated on glass wool (20% positive samples), but it helped to increase the detection of the genome after concentration on glass powder (72% positive samples).

International audience; We attempted to prepare a subcutaneous pharmaceutical form of warfarin based on a suspension or poly(ε-caprolactone) microparticles to improve patient adherence. The warfarin suspension had a mean particle size of 20.0 μm and in vitro release close to 100% in 72 h. Microparticle size and encapsulation efficiencies ranged from 54.0 to 80.0 μm and 37.0 to 47.0%, respectively. After 72 h, warfarin microparticles exhibited in vitro drug release ranging from 62.0 to 80.0%. Warfarin subcutaneous dosage forms were administered to rabbits. Plasma concentration of warfarin was determined and biological activity was measured by prothrombin time monitoring. The observed relative bioavailabilities calculated from plasma concentrations and prothrombin times were 54.2 and 92.1%, and 61.8 and 61.4% for suspension and microparticles, respectively.

Sir, We read with great interest the study of Michie et al (2010) evaluating capecitabine-induced hypertriglyceridaemia (CIHT). The authors suggest that it should be classified as a common adverse effect and we fully agree with their recommendation for targeted screening in patients with diabetes or pre-existing hyperlipidaemia. Here we report an additional case of severe CIHT in a patient with pre-existing hyperlipidaemia to focus attention on possible mechanisms. A 50-year-old woman with a history of breast cancer, treated by surgery and hyperlipidaemia stabilised with pravastatin, was diagnosed in January 2009 with a progression of her breast cancer. Before receiving carboplatin, TAXOL (Bristol Myers Squibb, France) and bevacizumab, cholesterolaemia level was 6.68 mmol l−1 (2.59 g l−1) and triglyceridemia level was 2.51 mmol l−1 (2.20 g l−1) (Figure 1). During the 6-month treatment, a transient increase in triglycerides was observed and pravastatin was replaced by rosuvastatin. In July 2009, bevacizumab alone was administered once a week as maintenance treatment. In August 2009, because of secondary gastric and ganglion infiltration, carboplatin and taxol were stopped and the patient received a combination of capecitabine and bevacizumab. Nine cycles of this treatment were scheduled. After six cycles, in December 2009, highly raised triglycerides (26.77 mmol l−1 (23.48 g l−1)) and slightly raised cholesterol levels (8.75 mmol l−1 (3.39 g l−1)) were observed, without any clinical sign of pancreatitis. At no time had the patient reported alcohol consumption or dietary changes and no weight gain was observed. The replacement of rosuvastatin by fenofibrate was followed 1 week later by a significant decrease in her triglyceride level to 6.26 mmol l−1 (5.49 g l−1). However, 1 month later, the triglycerides level again increased to 11.33 g l−1 (9.94 mmol l−1). Owing to both side effects and progression of her cancer, capecitabine and bevacizumab were stopped and replaced by fulvestrant (FASLODEX; Astrazeneca, Cheshire, UK). A return to baseline triglyceridaemia values (3.27 mmol l−1 (2.87 g l−1)) was observed within 2 months. Figure 1 Clinical course of triglyceride (▪) and cholesterol (▴) levels in patients, expressed in mmol l−1. Our case fulfils the criteria for a probable case of CIHT. Concomitant bevacizumab was not suspected because the increase in triglycerides during first-line chemotherapy resolved spontaneously, whereas treatment with rosuvastatin was unchanged. We would like to propose two ways to improve our understanding of CIHT: A defect of lipoprotein lipase (LPL) is linked with an accumulation of chylomicrons and/or of very low-density lipoprotein (VLDL). Kurt et al (2006) suggest that CIHT may appear more readily in individuals with hereditary LPL deficiency. It is worth noting that LPL defect also occurs in the case of an increase in its inhibitor (apolipoprotein CIII) and/or a decrease in its activator (apolipoprotein CII). As far as we know, the link between capecitabine and apolipoprotein CII/CIII levels has never been explored. We suggest that laboratory test of patient should include measure of LPL activity as well as of apolipoprotein CII/CIII levels. As a triple prodrug, capecitabine is designed to be sequentially activated to 5-FU: capecitabine is hydrolysed in the liver to 5′-deoxy-5-fluorocytidine, which is then converted into 5′-deoxy-5-fluorouridine (5′-dFUR) and subsequently into 5-FU by thymidine phosphorylase. Many cases of severe hypertriglyceridaemia were described with capecitabine, but to the best of our knowledge only one study has dealt with the influence of 5-FU on serum and it did not report any changes in triglyceride level in human (Stathopoulos et al, 1995). Recently, a case of recurrent grade-4 hypertriglyceridaemia in a patient treated with capecitabine and tegafur/uracil was reported (Yildiz et al, 2010). This observation of hypertriglyceridaemia with another prodrug of 5-FU suggest that capecitabine and tegafur might share a mechanism responsible for hypertriglyceridaemia. Tegafur is bioactivated in 5-FU by thymidine phosphorylase in a single step. Considering that this enzyme is also responsible for the phosphorylation of 5′-DFUR in 5-FU, we suggest that thymidine phosphorylase could have a role in the generation of hypertriglyceridaemia. Thymidine kinase and thymidine phosphorylase compete for thymidine, and catalyse opposing synthetic and catabolic reactions implicated in proliferation and angiogenesis, respectively (Brockenbrough et al, 2009). As a modification of the expression and activity of thymidine kinase as well as a strong increase in the secretory phospholipase-A2 was observed in resistant colon cancer cells (Temmink et al, 2010), a link between thymidine metabolic pathways and phospholipids metabolism that may at least partially explain CIHT. A lipid survey should be mandatory before initiation of capecitabine or other 5-FU prodrugs. Patients with dyslipidaemia should be closely monitored and further studied.

International audience; The aim of this work is to predict sound pressure in front of wall facings based on periodic sound scattering surface profiles. The method involves investigating plane wave reflections randomly incident upon an uneven surface. The waveguide approach is well suited to the geometries usually encountered in industrial workplaces. This method simplifies the profile geometry by using elementary rectangular volumes. The acoustic field in the profile interstices can then be expressed as the superposition of waveguide modes. In past work, walls considered are of infinite dimensions and are subjected to a periodic surface profile in only one direction. We therefore generalise this approach by extending its applicability to ''double-periodic'' wall facings. Free-field measurements have been taken and the observed agreement between numerical and experimental results supports the validity of the waveguide method.

International audience; Nanoparticles (prepared from a mixture of polyester and a polycationic polymer) loaded with insulin were prepared by a double emulsion method followed by evaporation solvent. Low molecular weight heparin (LMWH) was bound by electrostatic interactions onto the surface of the particles to confer Stealth properties. These nanoparticles were characterized in vitro (mean diameter, zeta potential, encapsulation efficiency, and release kinetics) and compared with conventional (without LMWH) and unloaded nanoparticles. The pharmacokinetics of insulin were studied after intravenous injection into diabetic rats in the form of Stealth or conventional nanoparticles or as a solution. Stealth nanoparticles allowed an increase in the elimination half-life of insulin, showing that the hydrophilic layer of LMWH was able to limit recognition by the mononuclear phagocytosis system in vivo. However, complement activation studies (CH50) did not reveal significant difference between Stealth and conventional nanoparticles.

Button batteries (BB) are frequently swallowed and must be removed immediately as, if they remain in the esophagus, they can cause severe damage with fatal prognosis. To better understand the molecular mechanism of esophagus damage, we performed a study aimed to analyze heat production, pH variation, electrical work and metal release from BB incubated in cell culture media. Cytotoxicity and apoptosis induced in a human monocytes cell line (U937) was also investigated.Calculated transferred heat was around 244 J with a maximal increase of temperature of 7.26 K/g medium whose pH, reflecting medium electrolysis, was 12.2 after about 2 h incubation. Release of metals also occurred. Only 49.7 ± 1.9% of U937 monocytes remained viable after 90 min of incubation in DMEM containing BB. Those results suggest that BB discharge induce cytotoxicity and tissue injury probably due to multiple combinations of at least thermic, caustic and toxic phenomena. As maximal effects occurred in less than 2 h, they prompt for fast removal of battery from esophagus. Keywords: Button battery, Electrolysis, Calorimetry, Heat transfer, Metal ions, pH, Cytotoxicity, Apoptosis

Aims and background The transcription factor NF-κB is implicated in the expression of genes involved in cell proliferation, apoptosis and metastasis. In melanoma, high constitutive levels of NF-κB activation are usually observed. NF-κB is regulated by oxidation/reduction (redox) processes, and the occurrence of constitutive oxidative stress in melanoma cells has been documented. Recent studies of our laboratories showed that the membrane-bound gamma-glutamyl transferase (GGT) enzyme activity – expressed by a number of malignancies, including melanoma – can act as a basal source of superoxide, hydrogen peroxide and other prooxidants. Methods In the present study we utilized the 2/60 clone of Me665/2 human metastatic melanoma, which displays high levels of GGT activity, in order to verify if the presence of this enzyme - through the promotion of redox processes - may influence the activation status of NF-κB. The latter was evaluated by determining the nuclear translocation of the p65 subunit (by immunoblot), the DNA binding of NF-kB (by elec-trophoretic mobility shift assay) and its transcriptional activity (by gene transactivation studies). Results Me665/2/60 cells displayed a basal production of hydrogen peroxide. Stimulation of GGT activity by its substrates glutathione and glycyl-glycine caused additional production of hydrogen peroxide, up to levels approx. double the basal levels. Nuclear translocation of the NF-κB p65 subunit, DNA-binding and gene transactivation were thus investigated in Me665/2/60 cells whose GGT activity was modulated by means of substrates or inhibitors. Stimulation of GGT activity resulted in increased nuclear translocation of p65, while on the other hand NF-κB DNA binding and gene transactivation were paradoxically decreased. NF-κB DNA binding could be restored by treating cell lysates with the thiol-re-ducing agent dithiothreitol (DTT). Treatment of cells with exogenous hydrogen peroxide did not affect NF-κB activation status. Conclusions Altogether, the data obtained indicate that GGT activity may impair the redox status of thiols that is critical for NF-κB DNA binding and gene transactivation, through the production of prooxidant species allegedly distinct from hydrogen peroxide. GGT activity therefore appears to be an additional factor in modulation of NF-κB transcriptional activity in melanoma, capable of hindering NF-κB DNA binding even in conditions where continuous oxidative stress would favor NF-κB nuclear translocation.

In this study, three types of treated wastewater were tested for infectious enteroviruses, the enterovirus genome, somatic coliphages, and Bacteroides fragilis phages. The aim of this work was to determine whether the presence of the two types of bacteriophages or of the enterovirus genome was a good indicator of infectious enterovirus contamination. The enterovirus genome was detected by reverse transcription-polymerase chain reaction. Infectious enteroviruses were quantified by cell culturing (BGM cells), and the bacteriophages were quantified by plaque formation on the host bacterium ( Escherichia coli or B. fragilis ) in agar medium. Forty-eight samples of treated wastewater were analyzed. Sixteen samples had been subjected to a secondary treatment for 8 to 12 h (A), 16 had been subjected to a secondary treatment for 30 h (B1), and 16 had been subjected to both secondary and tertiary treatments (B2). The mean concentrations of somatic coliphages were 4.9 × 10 4 PFU · liter −1 for treatment line A, 9.8 × 10 3 PFU · liter −1 for B1, and 1.4 × 10 3 PFU · liter −1 for B2, with all the samples testing positive (100%). The mean concentrations of B. fragilis phages were 1.7 × 10 3 PFU · liter −1 for A (100% positive samples), 17 to 24 PFU · liter −1 for B1 (44% positive samples), and 0.8 to 13 PFU · liter −1 for B2 (6% positive samples). The mean concentrations of infectious enteroviruses were 4 most probable number of cytopathogenic units (MPNCU) · liter −1 for A (31% positive samples) and −1 for B1 and B2 (0% positive samples). The percentages of samples testing positive for the enterovirus genome were 100% for A, 56% for B1, and 19% for B2. The percentages of samples testing positive for the enterovirus genome were significantly higher than those for infectious enteroviruses. This finding may have been due to the presence of noninfectious enteroviruses or to the presence of infectious enteroviruses that do not multiply in BGM cell cultures. However, under our experimental conditions, nondetection of the genome implies the absence of infectious viruses. There was a significant correlation between the concentration of somatic coliphages or B. fragilis phages and the presence of infectious enteroviruses or the presence of the enterovirus genome. However, the somatic coliphage concentration did not lead to fluctuations in the infectious enterovirus concentration, whereas the B. fragilis phage concentration did.