In situ formation of low molecular weight organogelators for slick solidification

We have investigated the in situ formation of Low Molecular Weight Organogelator (LMWO) molecules in oil-on-water slicks through dual reactive precursor injection. This method alleviates the need for any carrier solvent or prior heating, therefore reducing the environmental impact of LMWOs, giving instantaneous gelation, even at low temperatures (−5 °C). We show minimal leaching from our gels into the water layer

[sup]1H NMR quantification of spray dried and spray freeze-dried saccharide carriers in dry powder inhaler formulations

Quantitative analysis using proton NMR (1H qNMR) has been employed in various areas such as pharmaceutical analysis (e.g., dissolution study), vaccines, natural products analysis, metabolites, and macrolide antibiotics in agriculture industry. However, it is not routinely used in the quantification of saccharides in dry powder inhaler (DPI) formulations. The aim of this study was to develop a 1H NMR method for the quantification of saccharides employed in DPI formulations. Dry powders as DPI carriers were prepared by spray drying (SD) and spray freeze drying (SFD) using three saccharides: namely D-mannitol, D-sorbitol and D-(+)-sucrose. The calibration curves constructed for all three saccharides demonstrated linearity with R2 value of 1. The 1H qNMR method produced accurate (relative error %: 0.184-3.697) and precise data with high repeatability (RSD %: 0.517-3.126) within the calibration curve concentration range. The 1H qNMR method also demonstrated significant sensitivity with low values of limit of detection (0.058 mM for D-mannitol, 0.045 mM for D-(+)-sucrose, and 0.056 mM for D-sorbitol) and limit of quantitation (0.175 mM for D-mannitol, 0.135 mM for D-(+)-sucrose, and 0.168 mM for D-sorbitol). Pulmonary deposition via impaction experiments of the three saccharides was quantified using the developed method. It was found that SFD D-mannitol (68.99%) and SFD D-(+)-sucrose (66.62%) exhibited better delivered dose (total saccharide deposition in throat and all impactor stages) than SD D-mannitol (49.03%) and SD D-(+)-sucrose (57.70%) (p< 0.05). The developed 1H qNMR methodology can be routinely used as an analytical method to assess pulmonary deposition in impaction experiments of saccharides employed as carriers in DPI formulations

New investigations into the stability of Mesna using LC-MS/MS and NMR

Both LC-MS/MS and NMR analyses confirmed the instability of Mesna and its conversion into Dimesna

Hepatitis E Virus Genotype 3 Diversity, France

We characterized 42 hepatitis E virus (HEV) genotype 3 strains from infected patients in France in 3 parts of the genome and sequenced the full-length HEV genotype 3f genome found in Europe. These strains are closely related to swine strains in Europe, which suggests zoonotic transmission of HEV in France

Domestication of different varieties in the cheese-making fungus Geotrichum candidum

Domestication is an excellent model for studying adaptation processes, involving recent adaptation and diversification, convergence following adaptation to similar conditions, as well as degeneration of unused functions. Geotrichum candidum is a fungus used for cheese making and is also found in other environments such as soil and plants. By analyzing whole-genome data from 98 strains, we found that all strains isolated from cheese formed a monophyletic clade. Within the cheese clade, we identified three genetically differentiated populations and we detected footprints of recombination and admixture. The genetic diversity in the cheese clade was similar as that in the wild clade, suggesting the lack of strong bottlenecks. Commercial starter strains were scattered across the cheese clade, thus not constituting a single clonal lineage. The cheese populations were phenotypically differentiated from other populations, with a slower growth on all media, even cheese, a prominent production of typical cheese volatiles and a lower proteolytic activity. One of the cheese clusters encompassed all soft goat cheese strains, suggesting an effect of cheese-making practices on differentiation. Another of the cheese populations seemed to represent a more advanced stage of domestication, with stronger phenotypic differentiation from the wild clade, harboring much lower genetic diversity, and phenotypes more typical of cheese fungi, with denser and fluffier colonies and a greater ability of excluding cheese spoiler fungi. Cheese populations lacked two beta lactamase-like genes present in the wild clade, involved in xenobiotic clearance, and displayed higher contents of transposable elements, likely due to relaxed selection. Our findings suggest the existence of genuine domestication in G. candidum, which led to diversification into different varieties with contrasted phenotypes. Some of the traits acquired by cheese strains indicate convergence with other, distantly related fungi used for cheese maturation

Clinical phenotype and outcome of hepatitis E virus - associated neuralgic amyotrophy

Objective: To determine the clinical phenotype and outcome in hepatitis E virus–associated neuralgic amyotrophy (HEV-NA). Methods: Cases of NA were identified in 11 centers from 7 European countries, with retrospective analysis of demographics, clinical/laboratory findings, and treatment and outcome. Cases of HEV-NA were compared with NA cases without evidence of HEV infection. Results: Fifty-seven cases of HEV-NA and 61 NA cases without HEV were studied. Fifty-six of 57 HEV-NA cases were anti-HEV IgM positive; 53/57 were IgG positive. In 38 cases, HEV RNA was recovered from the serum and in 1 from the CSF (all genotype 3). Fifty-one of 57 HEV-NA cases were anicteric; median alanine aminotransferase 259 IU/L (range 12–2,961 IU/L); in 6 cases, liver function tests were normal. HEV-NA cases were more likely to have bilateral involvement (80.0% vs 8.6%, p < 0.001), damage outside the brachial plexus (58.5% vs 10.5%, p < 0.01), including phrenic nerve and lumbosacral plexus injury (25.0% vs 3.5%, p = 0.01, and 26.4% vs 7.0%, p = 0.001), reduced reflexes (p = 0.03), sensory symptoms (p = 0.04) with more extensive damage to the brachial plexus. There was no difference in outcome between the 2 groups at 12 months. Conclusions: Patients with HEV-NA are usually anicteric and have a distinct clinical phenotype, with predominately bilateral asymmetrical involvement of, and more extensive damage to, the brachial plexus. Involvement outside the brachial plexus is more common in HEV-NA. The relationship between HEV and NA is likely to be causal, but is easily overlooked. Patients presenting with NA should be tested for HEV, irrespective of liver function test results. Prospective treatment/outcome studies of HEV-NA are warranted