Cost-effectiveness analysis of universal childhood hepatitis A vaccination in Brazil: Regional analyses according to the endemic context

Objective: To To conduct a cost-effectiveness analysis of a universal childhood hepatitis A vaccination program in Brazil. Methods: An age and time-dependent dynamic model was developed to estimate the incidence of hepatitis A for 24 years. The analysis was run separately according to the pattern of regional endemicity, one for South + Southeast (low endemicity) and one for the North + Northeast + Midwest (intermediate endemicity). The decision analysis model compared universal childhood vaccination with current program of vaccinating high risk individuals. Epidemiologic and cost estimates were based on data from a nationwide seroprevalence survey of viral hepatitis, primary data collection, National Health Information Systems and literature. The analysis was conducted from both the health system and societal perspectives. Costs are expressed in 2008 Brazilian currency (Real). Results: A universal immunization program would have a significant impact on disease epidemiology in all regions, resulting in 64% reduction in the number of cases of icteric hepatitis, 59% reduction in deaths for the disease and a 62% decrease of life years lost, in a national perspective. With a vaccine price of R$16.89 (US$7.23) per dose, vaccination against hepatitis A was a cost-saving strategy in the low and intermediate endemicity regions and in Brazil as a whole from both health system and society perspective. Results were most sensitive to the frequency of icteric hepatitis, ambulatory care and vaccine costs. Conclusions: Universal childhood vaccination program against hepatitis A could be a cost-saving strategy in all regions of Brazil. These results are useful for the Brazilian government for vaccine related decisions and for monitoring population impact if the vaccine is included in the National Immunization Program. (C) 2012 Elsevier Ltd. All rights reserved.

Capillary bioreactors based on human purine nucleoside phosphorylase: A new approach for ligands identification and characterization

The enzyme purine nucleoside phosphorylase (PNP) is a target for the discovery of new lead compounds employed on the treatment severe T-cell mediated disorders. Within this context, the development of new, direct, and reliable methods for ligands screening is an important task. This paper describes the preparation of fused silica capillaries human PNP (HsPNP) immobilized enzyme reactor (IMER). The activity of the obtained IMER is monitored on line in a multidimensional liquid chromatography system, by the quantification of the product formed throughout the enzymatic reaction. The Km value for the immobilized enzyme was about twofold higher than that measured for the enzyme in solution (255 +/- 29.2 mu M and 133 +/- 114.9 mu M, respectively). A new fourth-generation immucillin derivative (DI4G: IC50 = 40.6 +/- 0.36 nM), previously identified and characterized in HsPNP free enzyme assays, was used to validate the IMER as a screening method for HsPNP ligands. The validated method was also used for mechanistic studies with this inhibitor. This new approach is a valuable tool to PNP ligand screening, since it directly measures the hypoxanthine released by inosine phosphorolysis, thus furnishing more reliable results than those one used in a coupled enzymatic spectrophotometric assay. (C) 2011 Elsevier B.V. All rights reserved.

Reproductive biology and species geographical distribution in the Melastomataceae: a survey based on New World taxa

Apomictic plants are less dependent on pollinator services and able to occupy more diverse habitats than sexual species. However, such assumptions are based on temperate species, and comparable evaluation for species-rich Neotropical taxa is lacking. In this context, the Melastomataceae is a predominantly Neotropical angiosperm family with many apomictic species, which is common in the Campos Rupestres, endemism-rich vegetation on rocky outcrops in central Brazil. In this study, the breeding system of some Campo Rupestre Melastomataceae was evaluated, and breeding system studies for New World species were surveyed to test the hypothesis that apomixis is associated with wide distributions, whilst sexual species have more restricted areas. The breeding systems of 20 Campo Rupestre Melastomataceae were studied using hand pollinations and pollen-tube growth analysis. In addition, breeding system information was compiled for 124 New World species of Melastomataceae with either wide (1000 km) or restricted distributions. Most (80 ) of the Campo Rupestre species studied were self-compatible. Self-incompatibility in Microlicia viminalis was associated with pollen-tube arrest in the style, as described for other Melastomataceae, but most self-incompatible species analysed showed pollen-tube growth to the ovary irrespective of pollination treatment. Apomictic species showed lower pollen viability and were less frequent among the Campo Rupestre plants. Among the New World species compiled, 43 were apomictic and 77 sexual (24 self-incompatible and 53 self-compatible). Most apomictic (86 ) and self-incompatible species (71 ) presented wide distributions, whilst restricted distributions predominate only among the self-compatible ones (53 ). Self-compatibility and dependence on biotic pollination were characteristic of Campo Rupestre and narrowly distributed New World Melastomataceae species, whilst apomictics are widely distributed. This is, to a certain extent, similar to the geographical parthenogenesis pattern of temperate apomictics.

Towards a hybrid approach for adapting web graphical user interfaces to heterogeneous devices using context

Ubiquitous Computing promises seamless access to a wide range of applications and Internet based services from anywhere, at anytime, and using any device. In this scenario, new challenges for the practice of software development arise: Applications and services must keep a coherent behavior, a proper appearance, and must adapt to a plenty of contextual usage requirements and hardware aspects. Especially, due to its interactive nature, the interface content of Web applications must adapt to a large diversity of devices and contexts. In order to overcome such obstacles, this work introduces an innovative methodology for content adaptation of Web 2.0 interfaces. The basis of our work is to combine static adaption - the implementation of static Web interfaces; and dynamic adaptation - the alteration, during execution time, of static interfaces so as for adapting to different contexts of use. In hybrid fashion, our methodology benefits from the advantages of both adaptation strategies - static and dynamic. In this line, we designed and implemented UbiCon, a framework over which we tested our concepts through a case study and through a development experiment. Our results show that the hybrid methodology over UbiCon leads to broader and more accessible interfaces, and to faster and less costly software development. We believe that the UbiCon hybrid methodology can foster more efficient and accurate interface engineering in the industry and in the academy.

Mitochondrial localization and structure-based phosphate activation mechanism of Glutaminase C with implications for cancer metabolism

Glutamine is an essential nutrient for cancer cell proliferation, especially in the context of citric acid cycle anaplerosis. In this manuscript we present results that collectively demonstrate that, of the three major mammalian glutaminases identified to date, the lesser studied splice variant of the gene gls, known as Glutaminase C (GAC), is important for tumor metabolism. We show that, although levels of both the kidney-type isoforms are elevated in tumor vs. normal tissues, GAC is distinctly mitochondrial. GAC is also most responsive to the activator inorganic phosphate, the content of which is supposedly higher in mitochondria subject to hypoxia. Analysis of X-ray crystal structures of GAC in different bound states suggests a mechanism that introduces the tetramerization-induced lifting of a "gating loop" as essential for the phosphate-dependent activation process. Surprisingly, phosphate binds inside the catalytic pocket rather than at the oligomerization interface. Phosphate also mediates substrate entry by competing with glutamate. A greater tendency to oligomerize differentiates GAC from its alternatively spliced isoform and the cycling of phosphate in and out of the active site distinguishes it from the liver-type isozyme, which is known to be less dependent on this ion.

Utility Harmonic Impedance Measurement Based on Data Selection

Determination of the utility harmonic impedance based on measurements is a significant task for utility power-quality improvement and management. Compared to those well-established, accurate invasive methods, the noninvasive methods are more desirable since they work with natural variations of the loads connected to the point of common coupling (PCC), so that no intentional disturbance is needed. However, the accuracy of these methods has to be improved. In this context, this paper first points out that the critical problem of the noninvasive methods is how to select the measurements that can be used with confidence for utility harmonic impedance calculation. Then, this paper presents a new measurement technique which is based on the complex data-based least-square regression, combined with two techniques of data selection. Simulation and field test results show that the proposed noninvasive method is practical and robust so that it can be used with confidence to determine the utility harmonic impedances.

New Insights on Nontechnical Losses Characterization Through Evolutionary-Based Feature Selection

Although nontechnical losses automatic identification has been massively studied, the problem of selecting the most representative features in order to boost the identification accuracy and to characterize possible illegal consumers has not attracted much attention in this context. In this paper, we focus on this problem by reviewing three evolutionary-based techniques for feature selection, and we also introduce one of them in this context. The results demonstrated that selecting the most representative features can improve a lot of the classification accuracy of possible frauds in datasets composed by industrial and commercial profiles.

The double task of preventing malnutrition and overweight: a quasi-experimental community-based trial

Background: The Maternal-Child Pastoral is a volunteer-based community organization of the Dominican Republic that works with families to improve child survival and development. A program that promotes key practices of maternal and child care through meetings with pregnant women and home visits to promote child growth and development was designed and implemented. This study aims to evaluate the impact of the program on nutritional status indicators of children in the first two years of age. Methods: A quasi-experimental design was used, with groups paired according to a socioeconomic index, comparing eight geographical areas of intervention with eight control areas. The intervention was carried out by lay health volunteers. Mothers in the intervention areas received home visits each month and participated in a group activity held biweekly during pregnancy and monthly after birth. The primary outcomes were length and body mass index for age. Statistical analyses were based on linear and logistic regression models. Results: 196 children in the intervention group and 263 in the control group were evaluated. The intervention did not show statistically significant effects on length, but point estimates found were in the desired direction: mean difference 0.21 (95%CI −0.02; 0.44) for length-for-age Z-score and OR 0.50 (95%CI 0.22; 1.10) for stunting. Significant reductions of BMI-for-age Z-score (−0.31, 95%CI −0.49; -0.12) and of BMI-for-age > 85th percentile (0.43, 95%CI 0.23; 0.77) were observed. The intervention showed positive effects in some indicators of intermediary factors such as growth monitoring, health promotion activities, micronutrient supplementation, exclusive breastfeeding and complementary feeding. Conclusions: Despite finding effect measures pointing to effects in the desired direction related to malnutrition, we could only detect a reduction in the risk of overweight attributable to the intervention. The findings related to obesity prevention may be of interest in the context of the nutritional transition. Given the size of this study, the results are encouraging and we believe a larger study is warranted.

Potential therapeutic effects of branched-chain amino acids supplementation on resistance exercise-based muscle damage in humans

Branched-chain amino acids (BCAA) supplementation has been considered an interesting nutritional strategy to improve skeletal muscle protein turnover in several conditions. In this context, there is evidence that resistance exercise (RE)-derived biochemical markers of muscle soreness (creatine kinase (CK), aldolase, myoglobin), soreness, and functional strength may be modulated by BCAA supplementation in order to favor of muscle adaptation. However, few studies have investigated such effects in well-controlled conditions in humans. Therefore, the aim of this short report is to describe the potential therapeutic effects of BCAA supplementation on RE-based muscle damage in humans. The main point is that BCAA supplementation may decrease some biochemical markers related with muscle soreness but this does not necessarily reflect on muscle functionality.

In search of mechanisms associated with mesenchymal stem cell-based therapies for acute kidney injury

Acute kidney injury (AKI) is classically described as a rapid loss of kidney function. AKI affects more than 15% of all hospital admissions and is associated with elevated mortality rates. Although many advances have occurred, intermittent or continuous renal replacement therapies are still considered the best options for reversing mild and severe AKI syndrome. For this reason, it is essential that innovative and effective therapies, without side effects and complications, be developed to treat AKI and the end-stages of renal disease. Mesenchymal stem cell (MSC) based therapies have numerous advantages in helping to repair inflamed and damaged tissues and are being considered as a new alternative for treating kidney injuries. Numerous experimental models have shown that MSCs can act via differentiation-independent mechanisms to help renal recovery. Essentially, MSCs can secrete a pool of cytokines, growth factors and chemokines, express enzymes, interact via cell-to-cell contacts and release bioagents such as microvesicles to orchestrate renal protection. In this review, we propose seven distinct properties of MSCs which explain how renoprotection may be conferred: 1) anti-inflammatory; 2) pro-angiogenic; 3) stimulation of endogenous progenitor cells; 4) anti-apoptotic; 5) anti-fibrotic; 6) anti-oxidant; and 7) promotion of cellular reprogramming. In this context, these mechanisms, either individually or synergically, could induce renal protection and functional recovery. This review summarises the most important effects and benefits associated with MSC-based therapies in experimental renal disease models and attempts to clarify the mechanisms behind the MSC-related renoprotection. MSCs may prove to be an effective, innovative and affordable treatment for moderate and severe AKI. However, more studies need to be performed to provide a more comprehensive global understanding of MSC-related therapies and to ensure their safety for future clinical applications.