Metabolomics reveals biomarkers in human urine and plasma to predict cytochrome P450 2D6 (CYP2D6) activity.

Individualized assessment of cytochrome P450 2D6 (CYP2D6) activity is usually performed through phenotyping following administration of a probe drug to measure the enzyme's activity. To avoid any iatrogenic harm (allergic drug reaction, dosing error) related to the probe drug, the development of non-burdensome tools for real-time phenotyping of CYP2D6 could significantly contribute to precision medicine. This study focuses on the identification of markers of the CYP2D6 enzyme in human biofluids using an LC-high-resolution mass spectrometry-based metabolomic approach. Plasma and urine samples from healthy volunteers were analysed before and after intake of a daily dose of paroxetine 20 mg over 7 days. CYP2D6 genotyping and phenotyping, using single oral dose of dextromethorphan 5 mg, were also performed in all participants. We report four metabolites of solanidine and two unknown compounds as possible novel CYP2D6 markers. Mean relative intensities of these features were significantly reduced during the inhibition session compared with the control session (n = 37). Semi-quantitative analysis showed that the largest decrease (-85%) was observed for the ion m/z 432.3108 normalized to solanidine (m/z 398.3417). Mean relative intensities of these ions were significantly higher in the CYP2D6 normal-ultrarapid metabolizer group (n = 37) compared with the poor metabolizer group (n = 6). Solanidine intensity was more than 15 times higher in CYP2D6-deficient individuals compared with other volunteers. The applied untargeted metabolomic strategy identified potential novel markers capable of semi-quantitatively predicting CYP2D6 activity, a promising discovery for personalized medicine

Using smart meters to estimate low voltage losses

Losses on low voltage networks are often substantial. For example, in the UK they have been estimated as being 4% of the energy supplied by low voltage networks. However, the breakdown of the losses to individual conductors and their split over time are poorly understood as generally only the peak demands and average loads over several months have been recorded. The introduction of domestic smart meters has the potential to change this. How domestic smart meter readings can be used to estimate the actual losses is analysed. In particular, the accuracy of using 30 minute readings compared with 1 minute readings, and how this accuracy could be improved, were investigated. This was achieved by assigning the data recorded by 100 smart meters with a time resolution of 1 minute to three test networks. Smart meter data from three sources were used in the investigation. It was found that 30 minute resolution data underestimated the losses by between 9% and 24%. By fitting an appropriate model to the data, it was possible to reduce the inaccuracy by approximately 50%. Having a smart meter time resolution of 10 minutes rather than 30 gave little improvement to the accuracy

Environmental isolation of black yeast-like fungi involved in human infection

The present study focuses on potential agents of chromoblastomycosis and other endemic diseases in the state of Paraná, Southern Brazil. Using a highly selective protocol for chaetothyrialean black yeasts and relatives, environmental samples from the living area of symptomatic patients were analysed. Additional strains were isolated from creosote-treated wood and hydrocarbon-polluted environments, as such polluted sites have been supposed to enhance black yeast prevalence. Isolates showed morphologies compatible with the traditional etiological agents of chromoblastomycosis, e.g. Fonsecaea pedrosoi and Phialophora verrucosa, and of agents of subcutaneous or systemic infections like Cladophialophora bantiana and Exophiala jeanselmei. Some agents of mild disease were indeed encountered. However, molecular analysis proved that most environmental strains differed from known etiologic agents of pronounced disease syndromes: they belonged to the same order, but mostly were undescribed species. Agents of chromoblastomycosis and systemic disease thus far are prevalent on the human host. The hydrocarbon-polluted environments yielded yet another spectrum of chaetothyrialean fungi. These observations are of great relevance because they allow us to distinguish between categories of opportunists, indicating possible differences in pathogenicity and virulence

Recomendações Para O Tratamento Da Crise Migranosa - Um Consenso Brasileiro

In this article, a group of experts in headache management of the Brazilian Headache Society developed through a consensus strategic measurements to treat a migraine attack in both the child and the adult. Particular emphasis was laid on the treatment of migraine in women, including at pregnancy, lactation and perimenstrual period. © 2016, Associacao Arquivos de Neuro-Psiquiatria. All rights reserved.74326227

Human toxocariasis: contribution by Brazilian researchers

In the present paper the main aspects of the natural history of human infection by Toxocara larvae that occasionally result in the occurrence of visceral and/or ocular larva migrans syndrome were reviewed. The contribution by Brazilian researchers was emphasized, especially the staff of the Tropical Medicine Institute of São Paulo (IMT)

Níveis de proteína bruta para juvenis de pirarucu

The objective of this work was to verify the effect of four protein levels on pirarucu, Arapaima gigas, growth performance. One hundred and twenty pirarucu juveniles, with an average weight of 120.6±3.5 g, were stocked into 12 floating cages with 1 m3 (ten fish per cage), in a complete randomized design with four treatments (32.7%, 39.3%, 43.4% and 48.6% crude protein), in three replicates each. After 45 days, results showed that diet with highest protein level (48.6%) produced a better weight gain, specific growth rate, and differentiated body composition. Feed conversion and protein efficiency ratios did not show any differences among treatments. The dietary protein level required to produce maximum growth is 48.6%