Early dietary treatment of phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, results in normal cognitive development. Although health-related quality of life (HRQoL) of PKU patients has been reported as unaffected in high-income countries, there are scarce data concerning HRQoL and adherence to treatment of PKU children and adolescents from Brazil. The present study compared HRQoL scores in core dimensions of Brazilian early-treated PKU pediatric patients with those of a reference population, and explored possible relationships between adherence to treatment and HRQoL. Early-treated PKU pediatric patient HRQoL was evaluated by self- and parent-proxy reports of the Pediatric Quality of Life Inventory (PedsQL) core scales. Adherence to treatment was evaluated by median Phe levels and percentage of results within the therapeutic target range in two periods. Means for total and core scales scores of PedsQL self- and parent proxy-reports of PKU patients were significantly lower than their respective means for controls. Adequacy of median Phe concentrations and the mean percentage of values in the target range fell substantially from the first year of life to the last year of this study. There was no significant difference in mean total and core scale scores for self- and parent proxy-reports between patients with adequate and those with inadequate median Phe concentrations. The harmful consequences for intellectual capacity caused by poor adherence to dietary treatment could explain the observed decrease in all HRQoL scales, especially in school functioning. Healthcare system and financial difficulties may also have influenced negatively all HRQoL dimensions.

Abstract Approximately 185 million people worldwide are chronically infected with hepatitis C virus (HCV). The first-wave of approved NS3 protease inhibitors (PIs) were Telaprevir and Boceprevir, which are currently discontinued. Simeprevir is a second-wave PI incorporated into the Brazilian hepatitis C treatment protocol. Drug resistance plays a key role in patients' treatment regimen. Here, we developed a simple phenotypic assay to evaluate the impact of resistance mutations in HCV NS3 protease to PIs, using a protein expression vector containing wild type NS3 protease domain and NS4A co-factor. We analyzed the impact of five resistance mutations (T54A, V36M, V158I, V170I and T54S+V170I) against Telaprevir, Boceprevir and Simeprevir. Protein purifications were performed with low cost methodology, and enzymatic inhibition assays were measured by FRET. We obtained recombinant proteases with detectable activity, and IC50 and fold change values for the evaluated PIs were determined. The variant T54A showed the highest reduction of susceptibility for the PIs, while the other four variants exhibited lower levels of reduced susceptibility. Interestingly, V170I showed 3.2-fold change for Simeprevir, a new evidence about this variant. These results emphasize the importance of enzymatic assays in phenotypic tests to determine which therapeutic regimen should be implemented.

We report novel features of the genome sequence of Leptospira interrogans serovar Copenhageni, a highly invasive spirochete. Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in mammals. Genomic sequence analysis reveals the presence of a competent transport system with 13 families of genes encoding for major transporters including a three-member component efflux system compatible with the long-term survival of this organism. The leptospiral genome contains a broad array of genes encoding regulatory system, signal transduction and methyl-accepting chemotaxis proteins, reflecting the organism's ability to respond to diverse environmental stimuli. The identification of a complete set of genes encoding the enzymes for the cobalamin biosynthetic pathway and the novel coding genes related to lipopolysaccharide biosynthesis should bring new light to the study of Leptospira physiology. Genes related to toxins, lipoproteins and several surface-exposed proteins may facilitate a better understanding of the Leptospira pathogenesis and may serve as potential candidates for vaccine.