Seroprevalence and incidence of Puumala orthohantavirus in its bank vole (Myodes glareolus) host population in northeastern France: Between-site and seasonal variability.

Given the difficulty of measuring pathogen transmission in wildlife, epidemiological studies frequently rely on cross-sectional seroprevalence. However, seropositivity indicates only exposure to a pathogen at an unknown time. By allowing to obtain repeated test results from individuals sampled multiple times over an extended period, longitudinal data help reduce this uncertainty. We used capture-mark-recapture data on bank vole (Myodes glareolus) individuals collected at four sites over ten years in northeastern France to investigate the impact of environmental variables on seroprevalence and incidence of Puumala orthohantavirus (PUUV). PUUV causes a chronic infection without apparent symptoms, that may however impair survival of its rodent host in the wild. Viral transmission between rodents may occur through direct contact or via the environment. Principal component analysis was used to deal with multicollinearity among environmental variables. Incidence and seroprevalence were investigated with either generalized estimating equations or Poisson regression models depending on the number of observations for each season. In spring, only the factor site was found to be significant for seroprevalence, while a principal component including meteorological conditions of the previous winter and the normalized difference vegetation index (NDVI) of both the previous winter and spring had a significant effect on incidence. In autumn, only the factor site was significant for incidence, while two principal components, including either the meteorological conditions of the autumn and previous spring or NDVI of the autumn significantly affected seroprevalence. We discuss these results in light of the particular demography of small mammals. We encourage other researchers to investigate the relationships between demographic parameters of wild host populations and the environment, by using both incidence and seroprevalence.

Challenges and strategies for the delivery of biologics to the cornea.

Biologics, like peptides, proteins and nucleic acids, have proven to be promising drugs for the treatment of numerous diseases. However, besides the off label use of the monoclonal antibody bevacizumab for the treatment of corneal neovascularization, to date no other biologics for corneal diseases have reached the market. Indeed, delivering biologics in the eye remains a challenge, especially at the level of the cornea. While it appears to be a rather accessible tissue for the administration of drugs, the cornea in fact presents several anatomical barriers to delivery. In addition, also intracellular delivery barriers need to be overcome to achieve a promising therapeutic outcome with biologics. This review outlines efforts that have been reported to successfully deliver biologics into the cornea. Biochemical and physical methods for achieving delivery of biologics in the cornea are discussed, with a critical view on their efficacy in overcoming corneal barriers.

A multi-technique comparison of the electronic properties of pristine and nitrogen-doped polycrystalline SnO2.

Nitrogen doped tin(iv) oxide (SnO2) materials in the form of nanometric powders have been prepared by precipitation with ammonia. Their properties have been compared with those of undoped materials obtained in a similar way using various physical techniques such as photoelectron spectroscopies (XPS and UPS), UV-Vis-NIR spectroscopy and electron paramagnetic resonance (EPR). Nitrogen doping leads to the formation of various nitrogen containing species, the more relevant of which is a nitride-type ionic species, based on the substitution of a lattice oxygen atom with a nitrogen atom. This species exists in two forms, paramagnetic (hole centre, formally N(2-)) and diamagnetic (N(3-)). The mutual ratio of the two species varies according to the oxidation state of the material. The doped solid, like most of the semiconducting oxides, tends to lose oxygen forming oxygen vacancies upon annealing under vacuum and leaving an excess of electrons in the solid. The stoichiometry of the solid can thus be markedly changed depending on the external conditions. Excess electrons are present both as itinerant electrons in the conduction band and as Sn(ii) states lying close to the valence band maximum. The presence of nitride-type centres, which are low energy states located below the top of the valence band, decreases the energy cost for the formation of oxygen vacancies by O2 release from the lattice. This particular feature of the doped system represents a severe limit to the preparation of a p-type SnO2via nitrogen doping.

Impact of fermentation on nitrogenous compounds of cocoa beans (Theobroma cacao L.) from various origins.

Tangential filtration technique was used to separate and quantify three different fractions of nitrogenous compounds depending on their molecular size, during cocoa fermentation. On every phenotype and origin analyzed, protein profile of non-fermented samples was similar. During fermentation course, proteins get degraded with a concomitant increase in amino acids content. Peptides between 3 and 10 kDa were observed at low levels. A strong correlation between amino acids and ammonia nitrogen, a fermentation marker was found. Attention was drawn on each fraction, and enabled to point out other phenomenon occurring during fermentation. The migration of some nitrogenous compounds towards the bean shell during fermentation was demonstrated. Acetone treatment of cocoa powder prior to SDS-PAGE led to losses of nitrogenous compounds. This result gives clues on the tanning phenomenon carried out by polyphenols on nitrogenous compounds, phenomenon which increases during fermentation.

Pharmacokinetics and exposure-effect relationships of capecitabine in elderly patients with breast or colorectal cancer.

PURPOSE: The aims of the present study were (1) to investigate the impact of great age on pharmacokinetics of capecitabine and its metabolites and (2) to evaluate the exposure-effect relationship of capecitabine in elderly patients. METHODS: Data collected from 20 elderly patients (75-92 years old) with breast or colorectal cancer who received oral capecitabine were analyzed. In order to study the old age effect on pharmacokinetics, data collected from two phase I studies involving 40 younger adults (<75 years old) with metastatic cancer who received oral capecitabine were added in the database. The population pharmacokinetic analysis was based on a four-compartment model describing the sequence of capecitabine and three of its metabolites. RESULTS: The absorption rate constant was found lower in the oldest patient group (≥75 years) compared with the youngest group, and the constant rate elimination of the 5-fluorouracil metabolite was found decreased over time (i.e., after 2 consecutive weeks of capecitabine administration). This time effect was not found different between the two age groups. In elderly patients, the exposure-safety analysis showed, from the second cycle of chemotherapy, significantly higher median exposures of capecitabine and its metabolites (5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine and 5-fluorouracil) in patients who experienced hand-foot syndrome compared with patients who did not. CONCLUSION: This study puts forward new arguments for the treatment of elderly cancer patients who could benefit from capecitabine chemotherapy with acceptable toxicity.

Wing geometry as a tool for discrimination of Obsoletus group (Diptera: Ceratopogonidae: Culicoides) in France.

In Europe, Culicoides chiopterus, Culicoides dewulfi, Culicoides obsoletus and Culicoides scoticus, which belongs to the subgenus Avaritia and Obsoletus group are the most proficient Bluetongue and Schmallenberg vectors. Within this group, correct identification based on morphological traits is difficult but essential to assess disease transmission risk. The development of new tools has revolutionized taxonomy (i.e. geometric morphometrics and molecular biology). Wing morphology is of primary importance to entomologists interested in systematics. Here, we report phenotypic differentiation patterns among the species above mentioned using a landmark-based geometric morphometric approach that efficiently identified C. chiopterus and C. dewulfi. Wing shape of the C. scoticus sample exhibited large specific variability. Based on landmarks and phylogenetic analyses (Maximum Parsimony), we suggest that Obsoletus group in Europe includes only C. obsoletus and C. scoticus. C. dewulfi and C. chiopterus are clearly excluded. Their shape seems closer to C. obsoletus that is why we suggest that only these two species should be grouped in the Obsoletus group. In addition, the concordance between phenetic clusters and phylogenies inferred from molecular data based on a fragment of the mtDNA COI gene and rDNA 28S suggests the existence of a strong signal in wing shape. These findings encourage us to use this powerful tool in taxonomic studies.

Near infrared spectroscopy as a new tool to determine cocoa fermentation levels through ammonia nitrogen quantification.

Fermentation is a key step in obtaining fine cocoa through the formation of potent aroma precursors. The fermentation level of cocoa beans is traditionally assessed by measuring the amount of ammonia nitrogen (NH3) using the time-consuming Conway technique. Near infrared spectroscopy (NIRS), a rapid and efficient tool, was used to analyze NH3 levels in several hundred cocoa samples at different fermentation levels from six geographical origins. Fermentation levels were expressed as the number of fermentation days and sum of temperatures. The correlation between Conway results and NIRS spectra enabled the development of a reliable and accurate NIRS calibration to determine NH3 content. We confirm that NH3 is produced during fermentation and its amount depends on the fermentation time, sum of temperatures and geographical origin. NIRS could be used by chocolate manufacturers as a routine method to sort cocoa samples according to their level of fermentation.

Morphometric and molecular characterization of the series Guyanensis (Diptera, Psychodidae, Psychodopygus) from the Ecuadorian Amazon Basin with description of a new species.

Several populations of the series Guyanensis (Diptera, Psychodidae, Psychodopygus) were collected from the Yasuní National Park in the Ecuadorian Amazon region. The specimens comprised the species Psychodopygus geniculatus, Psychodopygus luisleoni and Psychodopygus corossoniensis. Within Ps. geniculatus, we observed two populations, one with a narrow paramere and relatively short genital filaments and the other characterized by a wider coxite and longer genital filaments. A multiple approach combining morphology, morphometry and DNA sequencing of the ribosomal internal transcribed spacer 2 (ITS2) and the mitochondrial cytochrome b gene was carried out. Morphological, morphometric and molecular data strongly suggested the presence of two populations within Ps. geniculatus. The lack of intermediate forms within these populations supported the proposal of two sympatric species. This report describes Psychodopygus francoisleponti n. sp.

Quantitative proteomic analysis of cyclosporine-induced toxicity in a human kidney cell line and comparison with tacrolimus.

The calcineurin-inhibitors (CNIs) cyclosporine (CsA) and tacrolimus (TAC) remain the pillars of modern immunosuppression regimens used in solid organ transplantation. Nephrotoxicity is an adverse effect that limits their successful use. The precise molecular mechanisms underlying this nephrotoxicity remain unclear. Using SILAC together with LC-MALDI-TOF/TOF, we investigated the CNIs-induced proteomic perturbations in renal cells. Among the 495 proteins quantifiable in both forward and reverse SILAC, 69 displayed CsA-induced perturbations: proteins involved in ER-stress/protein folding, apoptosis, metabolism/transport or cytoskeleton pathways were up-regulated, while cyclophilin B as well as nuclear and RNA-processing proteins were down-regulated. Co-administration of CsA with the antioxidant N-acetylcysteine significantly decreased lipid peroxidation and also partially corrected the CsA-induced unfolded protein response. TAC toxicity profile was apparently different from that of CsA, especially without perturbation of cyclophilins A and B, up-regulation of ER-chaperones nor down-regulation of a number of nuclear proteins. These results provide a new insight and are consistent with recent data regarding the molecular mechanisms of CNIs-induced nephrotoxicity. Our findings offer new directions for future research aiming to identify specific biomarkers of CsA nephrotoxicity.

The predictive value of the maximum likelihood estimator of the number of contributors to a DNA mixture.

We propose to quantify the accuracy of a likelihood-based estimator that was recently proposed for the determination of the number of contributors to a DNA mixture, when genetic data alone is considered [H. Haned, L. Pène, J.R. Lobry, A.B. Dufour, D. Pontier, Estimating the number of contributors to forensic DNA mixtures: does maximum likelihood perform better than maximum allele count? J. Forensic Sci., in press]. Using Bayes' theorem, we derive a formula for the calculation of the predictive value (PV) of the likelihood-based estimator. The PV gives the probability that a DNA stain contains the DNAs of i people given that the maximum likelihood estimator gave an estimate of i contributors for this stain. We illustrate the PV calculations for two different types of DNA evidence: traces and body fluids. The PV varied according to the number of contributors involved in the DNA stain. Setting the maximum number of possible contributors to five, the lowest predictive values were scored for five-person mixtures with a minimum value of 0.26 for traces, but values were always above 0.94 for stains comprising one, two or three contributors, for both traces and body fluids. Values remained relatively high for four-person mixtures with a minimum value of 0.69. These findings confirm that likelihood-maximization is a powerful approach for the determination of the number of contributors to forensic DNA mixtures.

Hierarchical TiO2 photoanode for dye-sensitized solar cells.

Hierarchical or one-dimensional architectures are among the most exciting developments in material science these recent years. We present a nanostructured TiO(2) assembly combining these two concepts and resembling a forest composed of individual, high aspect-ratio, treelike nanostructures. We propose to use these structures for the photoanode in dye-sensitized solar cells, and we achieved 4.9% conversion efficiency in combination with C101 dye. We demonstrate this morphology beneficial to hamper the electron recombination and also mass transport control in the mesopores when solvent-free ionic liquid electrolyte is used.

Ag(6)Mo(2)O(7)F(3)Cl: a new silver cathode material for enhanced ICD primary lithium batteries.

As a potential cathode material for the ICD lithium battery, one advantage of Ag(6)Mo(2)O(7)F(3)Cl (SMOFC) is its enhanced gravimetric capacity of ca. 133 mAh/g above 3 V (vs Li(+)/Li) delivered by two biphasic transitions at 3.46 and 3.39 V (vs Li(+)/Li). The unique crystal structure of SMOFC enables a high silver ion conduction: sigma( perpendicular[001]) = 3.10(-2) S/cm (+/-2.10(-2) S/cm) and sigma(//[001]) = 4.10(-3) S/cm (+/-2.10(-3) S/cm) and, hence, an excellent discharge rate capability. Lithium insertion has been monitored by in situ XRD measurements with HRTEM investigations. There is a linear isotropic collapse of the structure leading to a fully amorphous structure beyond four inserted lithiums.

Discrimination of Culicoides obsoletus and Culicoides scoticus, potential bluetongue vectors, by morphometrical and mitochondrial cytochrome oxidase subunit I analysis.

Biting midges of the Culicoides obsoletus Meigen species complex (Diptera: Ceratopogonidae) are increasingly suspected as vectors of the recent emergence of bluetongue virus in Europe. Within this complex, identification of the C. obsoletus and Culicoides scoticus females is considered as difficult or sometimes not possible while the identification of males is easy, based on genitalia observation. Nolan et al. (2007) concluded that the distinction of C. obsoletus and C. scoticus females is not possible according to morphology but require molecular analyses. In 2010, the identification of biting midges is done under a stereomicroscope without specific identification within the C. obsoletus species complex. However, such a specific identification distinguishing C. obsoletus s. str. and C. scoticus s. str. is crucial to identify the European competent vectors of the virus, their relative abundances and then accurately assess the risk. We performed morphometric analyses of head, genitalia and thorax of females combined with sequencing of the cytochrome oxidase I barcode fragment of mitochondrial DNA on 88 specimens in order to have a molecular identification of our sampled species. As we knew the actual species of individuals thanks to molecular results, we explored the discriminant power of 15 morphometric variables to distinguish the females according to their species. Multivariate analyses were performed on the morphometric measurements to identify and validate a combination of variables leading to an accurate species identification. It appears that females of C. obsoletus and C. scoticus can be accurately distinguished based on only four variables: width between chitinous plates, length and width of spermathecae1 and length of spermatheca2. This approach should improve the accuracy of morphologically-based species identification.

Insights into the potentiometric response behaviour vs. Li+ of LiFePO4 thin films in aqueous medium.

The potentiometric response of PLD-made LiFePO(4) thin films versus Li(+) ions in aqueous solutions has been investigated, and a sensitivity of 54 mV dec(-1) has been observed in a Li(+) concentration range of 1-10(-4) M. Physical and electrochemical measurements of electrodes aged in aqueous medium show a slight surface oxidation with formation of heterosite-FePO(4) that we show to be responsible for the stable potential response measured. Cyclic voltamperometry measurements operated in different Li(+) concentration clearly highlight the key relation between the material lithium ion insertion/de-insertion capability and its potentiometric sensing response implying a faradaic-governed sensing mechanism. Based on such a finding, selection criteria (enlisting among others the potential of the redox couple, the nature of the insertion process) are herein underlined in the search for new sensitive materials.

Spatial and temporal patterning of bank vole demography and the epidemiology of the Puumala hantavirus in northeastern France.

Epidemiological data from bank voles, Myodes glareolus, naturally infected by the hantavirus Puumala (PUUV) were collected by a capture-mark-recapture protocol from 2000 to 2002 in the French department of Ardennes. Four monitored trapping sites were established in two forests located in two cantons (Flize and Monthermé). We captured 912 bank voles corresponding to 557 different individuals during 8820 trapping nights for an overall trapping success of 10.34%. The average PUUV seroprevalence was 22.4%. Characteristics of the system reported in North European countries are confirmed in France. PUUV seroprevalence and abundance of rodents appeared weakly linked. Adult voles were more frequently antibody-positive, but no difference between sexes was established. Anti-PUUV seropositive voles were captured and high seroprevalence was observed from both forests, without human infection reported in Flize canton during the study. One site among the four exhibited peculiar infection dynamics, where vole weight and infection risk were negatively correlated.

Study of the insertion/deinsertion mechanism of sodium into Na0.44MnO2.

Pure Na0.44MnO2 samples were prepared via a solid-state route by carefully tuning the synthesis conditions. Insertion/deinsertion of sodium into the well-crystallized particles leads to capacities as high as 140 mA.h/g. A potentiostatic intermittent titration technic, together with in situ X-ray diffraction measurements, enabled us to evidence the presence of six biphasic transitions within a potential range of 2-3.8 V (vs Na+/Na). The insertion process within the NaxMnO2 system is fully reversible over the 0.25 < x < 0.65 composition range and presents some degree of irreversibility as values of x below 0.25 are reached. Furthermore, we similarly showed that HCl treatment has a detrimental effect on these electrochemical properties because of structural and textural evolutions.

Predicting the emergence of human hantavirus disease using a combination of viral dynamics and rodent demographic patterns.

The paper proposes a model explaining the spatial variation in incidence of nephropathia epidemica in Europe. We take into account the rodent dynamic features and the replicative dynamics of the virus in animals, high in the acute phase of newly infected animals and low in the subsequent chronic phase. The model revealed that only vole populations with multi-annual fluctuations allow for simultaneously high numbers of infected rodents and high proportions of those rodents in the acute excretion phase during the culminating phase of population build-up. This leads to a brief peak in exceptionally high concentrations of virus in the environment, and thereby, to human exposure. Such a mechanism suggests that a slight ecological disturbance in animal-parasite systems could result in the emergence of human diseases. Thus, the potential risk for public health due to several zoonotic diseases may be greater than previously believed, based solely on the distribution of human cases.

A fully automated turbulent-flow liquid chromatography-tandem mass spectrometry technique for monitoring antidepressants in human serum.

Antidepressants belong to a variety of chemical and pharmacologic classes. Most require therapeutic drug monitoring, at least in certain circumstances, such as unexplained inefficacy or suspected toxicity. Several types of chromatographic methods have generally been used. This paper presents a fully automated, sensitive, and specific method for the therapeutic drug monitoring of 13 antidepressants of all classes (amoxapine, amitriptyline, citalopram, clomipramine, dothiepin, doxepin, fluoxetine, imipramine, maprotiline, mianserin, paroxetine, sertraline, trimipramine) and some of their respective active metabolites (nortriptyline, monodesmethylcitalopram, desmethylclomipramine, desipramine, norfluoxetine, desmethylmianserin, N-desmethylsertraline), based on the innovative turbulent-flow liquid chromatography (TFC) technology, coupled to tandem-mass spectrometry (MS/MS). The antidepressants were divided in two groups depending on their chromatographic properties, so that two injections would be necessary to screen all compounds (which is infrequent for therapeutic drug monitoring). Calibration curves ranged from 10 to 500 ng/mL. No significant memory effect was observed after the injection of a blank serum sample spiked at 500 ng/mL. The intra-assay and inter-assay precision CVs ranged from 0.4% to 12% and from 1% to 16%, respectively. The method was further validated by blindly analyzing Heathcontrol-Therapeutic Drugs Scheme samples (Cardiff Bioanalytical Services Ltd.) containing several antidepressants.

A study by spectroelectrochemical FTIR and density functional theory calculations of the reversible complexing ability of an electroactive tetrathiafulvalene crown.

We report on the study of the electrochemically targeted complexation/expulsion of a metal cation (Ba2+) by a crown ether tetra(thiomethyl)tetrathiafulvalene derivative (crown-TTM-TTF). Real time, in situ FTIR spectroelectrochemistry was used to obtain spectroscopic evidence of this electrochemically triggered phenomenon. Density functional theory calculations allowed the spectral information collected to be assigned. Both experimental and theoretical results clearly show that neutral crown-TTM-TTF complexes well Ba2+. Complexation is evidenced by a significant downshift of the frequency corresponding to the asymmetric stretching of the C-O-C ether groups. Concerning the cation crown-TTM-TTF, the spectroscopic signal of the complex form was difficult to identify, first because of the rather low value of the complexation constant and second because the vibration modes involving the oxygen atoms (which are the most affected by the complexation) were found by calculation to occur in the lower spectral region (<1000 cm(-1)), which is not accessible in our experimental conditions. In the case of the dication crown-TTM-TTF, it is now clear that the complex form does not exist, which means that the electrochemical formation of the dication necessarily involves the expulsion of the barium ion.