First report of eprinomectin-resistant isolates of Haemonchus contortus in 5 dairy sheep farms from the Pyrénées Atlantiques département in France.

Infection of sheep by gastrointestinal nematodes (GIN) in pastoral systems such as those found in the South Western area of France, the Pyrénées Atlantiques, is one of the main reasons for economic loss and degradation of their welfare. In the present study, the efficacy of eprinomectin (EPN) was monitored on farms from this area following suspicion of lack of anthelmintic efficacy. Suspicions were raised by veterinarians, based on clinical signs ranging from milk and body condition loss, to anaemia, and mortality. Resistance was evaluated according to the World Association for the Advancement for Veterinary Parasitology (WAAVP) guidelines using fecal egg count reduction tests reinforced by individual analysis of drug concentration in the serum of all treated ewes by high-performance liquid chromatography (HPLC). EPN was administered by subcutaneous (SC) and topical (T) route according to manufacturer's requirements, as well as by the oral route (O) with the topical solution according to off-labelled practices in the field. For the first time in France, the presence of resistant isolates of Haemonchus contortus to EPN was observed in 5 dairy sheep farms. The HPLC dosages showed exposure of worms to concentrations compatible with anthelmintic activity for animals treated by the SC and O routes. By contrast, they showed under exposure to the drug of most individuals treated by the T route. EPN is the only null milk withdrawal anthelmintic molecule currently available. The presence of resistant isolates of the pathogenic H. contortus to EPN in this important dairy region requires an urgent change in grazing, and sometimes production, systems.

[Allergic respiratory diseases related to mould in the home]. / Pathologies allergiques respiratoires liées aux moisissures de l'habitat.

Exposure to mould is a potential risk factor for asthma in both adults and children. In adult, the relation between exposure, sensitization and symptoms has been demonstrated in severe asthmatics sensitized to Alternaria. For children, exposure to mould in childhood is a risk factor for asthma in both atopic and non-atopic individuals. Exposure or sensitization to moulds are a risk factor for severe asthma and/or exacerbations in children. There appears to be a causal relationship between exposure and asthma. This link seems less significant in adults. However, in adults mould sensitive asthma seems to determine a phenotype of severe asthma associated with more marked obstructive lung disease. Moulds can stimulate either innate or the acquired immunity. They are responsible for a marked Th2 inflammation leading to more severe asthma. Besides the immunological mechanisms, toxic mechanisms can also intervene. It is therefore not correct to reduce the effect of moulds, particularly in respiratory symptoms, to only allergic mechanisms.

[Vocal cord dyskinesia and/or asthma]. / Dyskinésie des cordes vocales et/ou asthme.

INTRODUCTION: Vocal cord dyskinesia or vocal cord dysfunction (VCD) is characterized by intermittent abnormal adduction of the vocal cords leading to airflow limitation at the level of the larynx, in the absence of local organic disease. It may occur in isolation or in association with asthma. The pathophysiology is complex and poorly understood. Wheeze, stridor or apparent upper airway obstruction are the most common symptoms. It occurs in a wide age range, more commonly in women, and diagnosis is often delayed and leads to unnecessary treatments (intubation, tracheostomy and high dose steroids). METHODS: A retrospective study of 15 cases of VCD (8 cases of isolated VCD and 7 cases of VCD with associated asthma) describing the main clinical features and the diagnosis strategy. RESULTS: Apparent upper airway obstruction, with or without associated asthma, requires an ear nose and throat examination with laryngoscopy to confirm the paradoxical adduction of the vocal cords during an acute episode of dyspnoea or during a provocation test with triggers like exercise or exposure to irritants, and for the purpose of differential diagnosis. CONCLUSIONS: VCD remains under-appreciated and misdiagnosed, often by mimicking asthma with which it can be associated. A delayed diagnosis by emergency specialists, pulmonologists and ear nose and throat surgeons leads to unnecessary treatments and morbidity before specific therapy can be given.

3-month prognostic impact of severe acute renal failure under veno-venous ECMO support: Importance of time of onset.

PURPOSE: Veno-venous ECMO is increasingly used for the management of refractory ARDS. In this context, acute kidney injury (AKI) is a major and frequent complication, often associated with poor outcome. We aimed to identify characteristics associated with severe renal failure (Kidney Disease Improving Global Outcome (KDIGO) 3) and its impact on 3-month outcome. METHODS: Between May 2009 and April 2016, 60 adult patients requiring VV-ECMO in our University Hospital were prospectively included. RESULTS: AKI occurrence was frequent (75%; n=45), 51% of patients (n=31) developed KDIGO 3 - predominantly prior to ECMO insertion - and renal replacement therapy was required in 43% (n=26) of cases. KDIGO 3 was associated with a lower mechanical ventilation weaning rate (24% vs 68% for patients with no AKI or other stages of AKI; p<0.001) and a higher 90-day mortality rate (72% vs 32%, p=0.002). Multivariate logistic regression suggested that KDIGO 3 occurrence prior to ECMO insertion, as well as PaCO2>57mmHg and mSOFA>12 were independent risks factors for 90-day mortality. CONCLUSION: KDIGO 3 AKI occurrence is correlated with the severity of patients' clinical condition prior to ECMO insertion and is negatively associated with 90-day survival.

Inhibition of OCT2, MATE1 and MATE2-K as a possible mechanism of drug interaction between pazopanib and cisplatin.

We hypothesized that pazopanib is an inhibitor of cisplatin renal transporters OCT2, MATE1 and MATE2-K based on previous studies demonstrating an interaction between tyrosine kinase inhibitors and these transporters. Because several combinations of targeted therapies and cytotoxics are currently in development for cancer treatment, such an interaction is worth investigating. Experiments on HEK293 cells stably transfected to express OCT2, MATE1, MATE2-K or an empty vector (EV) were conducted. The inhibitory effect of pazopanib on these transporters was measured using the uptake of fluorescent substrate ASP+ and cisplatin in the different cell lines. The effect of pazopanib on cisplatin-induced cytotoxicity was also evaluated. A decrease of ASP+ uptake was observed in OCT2-HEK, MATE1-HEK and MATE2K-HEK cell lines after addition of pazopanib at increasing concentrations. Pazopanib inhibited cisplatin specific uptake in OCT2-HEK, MATE1-HEK and MATE2K-HEK lines. Cytotoxicity experiments showed that co-incubation of cisplatin with pazopanib multiplied up to 2.7, 2.4 and 1.6 times the EC50 values of cisplatin in OCT2-HEK, MATE1-HEK and MATE2K-HEK cell lines respectively, reaching about the same values as in EV-HEK cells. To conclude, pazopanib inhibits OCT2, MATE1 and MATE2-K, which are involved in cisplatin secretion into urine. The combination of these two drugs may lead to an interaction and increase the cisplatin-induced systemic toxicity. Given the wide variability of plasma pazopanib concentrations observed in vivo, the interaction may occur in a clinical setting, particularly in overexposed patients. The existence of a drug-drug interaction should be investigated when pazopanib is associated with a substrate of these transporters.

Genotyping of a family with a novel deleterious DPYD mutation supports the pretherapeutic screening of DPD deficiency with dihydrouracil/uracil ratio.

Despite the growing evidence that dihydropyrimidine dehydrogenase deficiency (DPD, encoded by the DPYD gene) confers a higher risk of developing severe toxicity, most patients are not screened for DPD deficiency before fluoropyrimidine treatment. We report here the genetic and phenotypic analyses of DPD in a family related to a patient who died after a first cycle of 5-fluorouracil and in 15 additional retrospective patients having a partial DPD deficiency (as measured by plasma dihydrouracil/uracil ratio). The patient with lethal toxicity was found to be a compound heterozygote for two DPYD mutations: a novel 8-bp duplication (c.168_175dupGAATAATT, p.Phe59Ter) and c.1679T>G (Ile560Ser). The patient's dihydrouracil/uracil ratio indicates complete DPD deficiency. The novel mutation was found in two members of the patient's family. Deleterious DPYD mutations were identified in 9 out of the 15 patients. The relationship between genotype and dihydrouracil/uracil values in the 22 patients of the present study was significant (P = 0.01).

Relative impact of mate versus pollinator availability on pollen limitation and outcrossing rates in a mass-flowering species.

Plant mating systems are driven by several pre-pollination factors, including pollinator availability, mate availability and reproductive traits. We investigated the relative contributions of these factors to pollination and to realized outcrossing rates in the patchily distributed mass-flowering shrub Rhododendron ferrugineum. We jointly monitored pollen limitation (comparing seed set from intact and pollen-supplemented flowers), reproductive traits (herkogamy, flower size and autofertility) and mating patterns (progeny array analysis) in 28 natural patches varying in the level of pollinator availability (flower visitation rates) and of mate availability (patch floral display estimated as the total number of inflorescences per patch). Our results showed that patch floral display was the strongest determinant of pollination and of the realized outcrossing rates in this mass-flowering species. We found an increase in pollen limitation and in outcrossing rates with increasing patch floral display. Reproductive traits were not significantly related to patch floral display, while autofertility was negatively correlated to outcrossing rates. These findings suggest that mate limitation, arising from high flower visitation rates in small plant patches, resulted in low pollen limitation and high selfing rates, while pollinator limitation, arising from low flower visitation rates in large plant patches, resulted in higher pollen limitation and outcrossing rates. Pollinator-mediated selfing and geitonogamy likely alleviates pollen limitation in the case of reduced mate availability, while reduced pollinator availability (intraspecific competition for pollinator services) may result in the maintenance of high outcrossing rates despite reduced seed production.

Ionizing radiations sustain glioblastoma cell dedifferentiation to a stem-like phenotype through survivin: possible involvement in radioresistance.

Glioblastomas (GBM) are some bad prognosis brain tumors despite a conventional treatment associating surgical resection and subsequent radio-chemotherapy. Among these heterogeneous tumors, a subpopulation of chemo- and radioresistant GBM stem-like cells appears to be involved in the systematic GBM recurrence. Moreover, recent studies showed that differentiated tumor cells may have the ability to dedifferentiate and acquire a stem-like phenotype, a phenomenon also called plasticity, in response to microenvironment stresses such as hypoxia. We hypothesized that GBM cells could be subjected to a similar dedifferentiation process after ionizing radiations (IRs), then supporting the GBM rapid recurrence after radiotherapy. In the present study we demonstrated that subtoxic IR exposure of differentiated GBM cells isolated from patient resections potentiated the long-term reacquisition of stem-associated properties such as the ability to generate primary and secondary neurospheres, the expression of stemness markers and an increased tumorigenicity. We also identified during this process an upregulation of the anti-apoptotic protein survivin and we showed that its specific downregulation led to the blockade of the IR-induced plasticity. Altogether, these results demonstrated that irradiation could regulate GBM cell dedifferentiation via a survivin-dependent pathway. Targeting the mechanisms associated with IR-induced plasticity will likely contribute to the development of some innovating pharmacological strategies for an improved radiosensitization of these aggressive brain cancers.

Massive floral display affects insect visits but not pollinator-mediated pollen transfer in Rhododendron ferrugineum.

Fragmentation of natural vegetation creates one of the largest threats to plant-pollinator interactions. Although fragmentation impacts on plant populations have been explored in many, mainly herbaceous, species, the response of wild mass-flowering species is poorly known. Here, we studied 28 heathland patches dominated by the mass-flowering shrub Rhododendron ferrugineum, each presenting different R. ferrugineum floral display sizes (total inflorescence number per patch) and patch isolation (median distance to the three nearest patches). We assessed the impacts of these two factors on (i) heathland patch visitor assemblage (considering R. ferrugineum versus surrounding community) and (ii) R. ferrugineum flower visitation rate and pollen transfer limitation (comparing seed set from emasculated to pollen-supplemented flowers). We found that diversity and abundance of bees visiting R. ferrugineum in heathland patches significantly decreased with decreasing R. ferrugineum floral display, while overall visitor density per patch and flower visitation rate increased. Moreover, a decrease in massive floral display and increase in patch isolation resulted in reduced visitor density in the surrounding community. Even in patches with few individuals, we found disproportionate visitor abundance in R. ferrugineum compared to the surrounding community. Finally, pollen transfer limitation in R. ferrugineum was neither affected by visitation rate nor by patch attributes. By disproportionally attracting pollinators from co-flowering species, and probably promoting geitonogamous pollen transfer, the mass-flowering trait appears adequate to compensate, in terms of conspecific pollen transfer, for the decrease in visitor diversity and abundance and in mate availability, which usually result from population fragmentation.

First evidence of increased plasma serotonin levels in Tako-Tsubo cardiomyopathy.

BACKGROUND: There is no data about the serotonergic activity during the acute phase of Tako-Tsubo Cardiomyopathy (TTC). The objective of our study was to investigate evidence of serotonin release from patients with TTC in comparison with patients with ST elevation myocardial infarction (STEMI) and healthy control subjects (HCS). METHODS AND RESULTS: Plasma serotonin levels in 14 consecutive patients with TTC were compared with those in 14 patients with STEMI and 14 HCS. Plasma serotonin levels at admission were markedly higher in patients with TTC and STEMI as compared to HCS (3.9 ± 4.6, P = 0.02 versus control; 5.7 ± 5.6, P = 0.001 versus control; and 1 ± 0.4 ng/mL, resp.). There was no difference in serotonin levels between patients with TTC and those with STEMI (P = 0.33). CONCLUSION: This finding suggests that serotonin could participate to the pathophysiology of TTC.

[Evolution of food supply (apart from school catering) between 2004/2005 and 2009/2010 in middle- and high-schools of Aquitaine, France]. / Évolution de l'offre alimentaire hors restauration scolaire entre 2004-2005 et 2009-2010 dans les établissements du second degré d'Aquitaine.

BACKGROUND: The aim of this study was to assess the evolution of food supply (apart from school catering) between school years 2004/2005 and 2009/2010, in middle- and high-schools from the Aquitaine region (southwest France), in order to evaluate the impact of actions conducted within the framework and the program Nutrition, Prevention and Health of children and adolescents in Aquitaine (southwest France). METHODS: Two surveys were carried out among all middle- and high-schools of the Aquitaine region in 2004/2005 (n=536) and 2009/2010 (n=539) within the framework of a regional multidisciplinary public health program "Nutrition, prevention and health of children and teenagers in Aquitaine". For both 2004/2005 and 2009/2010, data were collected using the same questionnaire and dealt with school characteristics and modalities of food supply (apart from school catering). RESULTS: Response rate was 84.1% in 2004/2005 and 79.6% in 2009/2010. The proportion of schools offering food to pupils (apart from school catering) significantly decreased in 5 years (from 80.1% to 50.1%, P<0.001). Between 2004/2005 and 2009/2010, we observed a stabilization in the proportion of schools offering free food (from 19.7 to 17%, P=0.3), a significant decrease of those selling food (from 62.8 to 37.1, P<0.001), offering vending machines (from 43.5 to 7.2, P<0.001) and a significant increase of those offering water supply (from 8.2 to 44%, P<0.001). The composition of each modality of food supply (apart from school catering) has also been improved: less sweet and fat food, more bread and fruits. CONCLUSION: This study shows an overall improvement of food supply apart from school catering (food sale, free food and vending machines) in middle- and high-schools from the Aquitaine region (southwest France) between 2004/2005 and 2009/2010. This improvement is related to the proportion of schools offering food (quantitative improvement), as well as to the composition of food supply (qualitative improvement). These results show an improvement of food supply (apart from school catering), suggesting that actions implemented in the framework of the program "Nutrition, prevention and health of children and adolescents in Aquitaine" may have led to these improvements.

Epidemiology and evolution of antibiotic resistance of Haemophilus influenzae in children 5 years of age or less in France, 2001-2008: a retrospective database analysis.

Trends in the evolution of antimicrobial resistance and mechanisms of resistance of Haemophilus influenzae to ß-lactam antibiotics in France were assessed through a retrospective database review. The antimicrobial resistance of 2,206 H. influenzae strains from children aged ≤5 years was studied between 2001 and 2008. Strains were isolated from blood or cerebrospinal fluid (n = 170), bronchial secretions (n = 188), middle ear fluid, and nasopharynx or conjunctiva (n = 1,848). A proportion of 95.1 % (n = 2,097) were non-typeable H. influenzae (NTHi). ß-lactamase production was identified in 27.5 % of NTHi isolates (all TEM-1), while ß-lactamase-negative ampicillin resistance and ß-lactamase-negative amoxicillin-clavulanate resistance among NTHi was 16.9 and 6.4 %, respectively. Over time, a statistically significant decrease in ß-lactamase-producing strain prevalence (p < 0.0001) and a statistically significant increase in ß-lactamase-negative ampicillin-resistant (BLNAR) strains (p < 0.0001) were observed in NTHi isolates from 2001 to 2008. The largest changes coincided with a campaign to reduce antibiotic use in France. An increasing diversity of amino acid substitution patterns was observed, with the emergence of group III/'III-like' patterns linked to high-level resistance. In France, amino acid substitution patterns are increasingly diverse, and strains with high-level antibiotic resistance are emerging. This study highlights the complexity of resistance dynamics within a given country. These results have implications on antibiotic guidelines and illustrate the importance of continued surveillance.

The P2-Na(2/3)Co(2/3)Mn(1/3)O2 phase: structure, physical properties and electrochemical behavior as positive electrode in sodium battery.

Manganese substituted sodium cobaltate, Na(2/3)Co(2/3)Mn(1/3)O(2), with a layered hexagonal structure (P2-type) was obtained by a co-precipitation method followed by a heat treatment at 950 °C. Powder X-ray diffraction analysis revealed that the phase is pure in the absence of long-range ordering of Co and Mn ions in the slab or Na(+) and vacancy in the interslab space. The oxidation states of the transition metal ions were studied by magnetic susceptibility measurements, electron paramagnetic resonance (ESR) and (23)Na magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy. The charge compensation is achieved by the stabilization of low-spin Co(3+) and Mn(4+) ions. The capability of Na(2/3)Co(2/3)Mn(1/3)O(2) to intercalate and deintercalate Na(+) reversibly was tested in electrochemical sodium cells. It appears that the P2 structure is maintained during cycling, the cell parameter evolution versus the sodium amount is given. From the features of the cycling curve the formation of an ordered phase for the Na(0.5)Co(2/3)Mn(1/3)O(2) composition is expected.

(Li/Ag)CoO2: a new intergrowth cobalt oxide composed of rock salt and delafossite layers.

A new ordered (Li/Ag)CoO(2) layered compound with an unusual oxygen packing combining rock salt and delafossite layers is obtained during the (Li(+), Na(+))/Ag(+) ionic exchange from the OP4-(Li/Na)CoO(2) precursor. This compound is actually an intermediate step to the final D4-AgCoO(2) delafossite and can be isolated thanks to the kinetics difference between the Li(+)/Ag(+) and Na(+)/Ag(+) exchange processes. It crystallizes in the P6(3)/mmc space group with cell parameters a(hex.) = 2.848(3) Å and c(hex.) = 21.607(7) Å. The details of the structure as well as its thermal stability and transport properties are presented and discussed.

Reactivity of (1→3)-ß-d-glucan assay in bacterial bloodstream infections.

To diagnose invasive fungal infections, the detection of (1 → 3)-ß-d-glucan in serum has shown variable specificity, depending on the targeted population. Several circumstances for false-positive results of beta-glucan tests have been identified, among which are severe bacterial infections. In this study, we measured (1 → 3)-ß-d-glucan by the Fungitell test in the serum of 62 patients (one serum sample tested per patient) for whom invasive fungal infection was not suspected: 19 control subjects and 43 patients with bacteraemia. The test was interpretable for 58 sera: all 19 control subjects had negative beta-glucan test; among the 39 bacteraemic patients, we report 16 false-positive results. For the 22 patients undergoing bacteraemia due to Gram-negative bacilli, we observed 13 false-positive results (59%). Among the 17 patients with bloodstream infection involving Gram-positive cocci, three false-positive tests were recorded, but none in the eight cases of Streptococcus pneumoniae bacteraemia. Statistical analysis showed that beta-glucan levels were significantly higher in patients with Gram-negative bacilli bloodstream infection in comparison to those with bacteraemia due to Gram-positive cocci. These results were independent from other previously described causes for false-positive beta-glucan tests. These data might help physicians to interpret positive beta-glucan detection when an invasive fungal infection is suspected, especially for patients with bacterial infections.

First experimental evidence of a new D4-AgCoO2 delafossite stacking.

A new polytype of AgCoO(2) delafossite has been prepared from the ordered OP4-(Li/Na)CoO(2) layered compound using ion-exchange reaction in molten salts. As expected from the structural model assuming a topotactic process, the lamellar structure of this new polytype is an alternate combination of the already known 2H and 3R delafossite polytypes. It crystallizes in the P6(3)/mmc space group with cell parameters a(hex.) = 2.871(1) Å and c(hex.) = 24.448(1) Å. Thermal stability, morphology characterization, and electrical properties are reported here and compared with those of the 2H and 3R AgCoO(2) polytypes.

Reinvestigation of the OP4-(Li/Na)CoO2-layered system and first evidence of the (Li/Na/Na)CoO2 phase with OPP9 oxygen stacking.

The composition and synthesis conditions of the (Li/Na)CoO(2) phase with an ordered 1:1 Li/Na stacking alternating with CoO(2) slabs were determined from a careful study of the P2-Na(∼0.7)CoO(2)-O3-LiCoO(2) system. An in situ X-ray diffraction (XRD) thermal study emphasizes the metastable character of this phase that can be stabilized only by very fast quenching. Its composition, (Li(0.42)Na(0.37))CoO(2), is significantly different from the ideally expected one, (Li(0.50)Na(0.35))CoO(2), and its structure, confirmed by Rietveld refinement of the XRD pattern, presents an ideal alternate ordering of lithium, cobalt, and sodium layers within OP4-type oxygen packing. The presence of vacancies in both alkali-ion layers was confirmed by electrochemical intercalation of lithium and sodium. For the first time, a new type of layered oxide exhibiting OPP9-type oxygen packing was evidenced. Between the CoO(2) slabs, alkali ions are intercalated in the following order: Li(octa)-Na(prism)-Na(prism). This material crystallizes in the R3m space group with a(hex) = 2.828 Šand c(hex) = 46.85 Šcell parameters.

Electrochemical investigation of the P2­NaxCoO2 phase diagram.

Sodium layered oxides NaxCoO2 form one of the most fascinating low-dimensional and strongly correlated systems; in particular P2­NaxCoO2 exhibits various single-phase domains with different Na+/vacancy patterns depending on the sodium concentration. Here we used sodium batteries to clearly depict the P2­NaxCoO2 phase diagram for x≥0.50. By coupling the electrochemical process with an in situ X-ray diffraction experiment, we identified the succession of single-phase or two-phase domains appearing on sodium intercalation with a rather good accuracy compared with previous studies. We reported new single-phase domains and we underlined the thermal instability of some ordered phases from an electrochemical study at various temperatures. As each phase is characterized by the position of its Fermi level versus the Na+/Na couple, we showed that the synthesis of each material, even in large amounts, can be carried out electrochemically. The physical properties of the as-prepared Na1/2CoO2 and Na2/3CoO2 ordered phases were characterized and compared. Electrochemical processes are confirmed to be an accurate route to precisely investigate in a continuous way such a complex system and provide a new way to synthesize materials with a very narrow existence range.