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Abstract Background Reliable mortality data are essential for the development of public health policies. In Brazil, although there is a well-consolidated universal system for mortality data, the quality of information on causes of death (CoD) is not even among Brazilian regions, with a high proportion of ill-defined CoD. Verbal autopsy (VA) is an alternative to improve mortality data. This study aimed to evaluate the performance of an adapted and reduced version of VA in identifying the underlying causes of non-forensic deaths, in São Paulo, Brazil. This is the first time that a version of the questionnaire has been validated considering the autopsy as the gold standard. Methods The performance of a physician-certified verbal autopsy (PCVA) was evaluated considering conventional autopsy (macroscopy plus microscopy) as gold standard, based on a sample of 2060 decedents that were sent to the Post-Mortem Verification Service (SVOC-USP). All CoD, from the underlying to the immediate, were listed by both parties, and ICD-10 attributed by a senior coder. For each cause, sensitivity and chance corrected concordance (CCC) were computed considering first the underlying causes attributed by the pathologist and PCVA, and then any CoD listed in the death certificate given by PCVA. Cause specific mortality fraction accuracy (CSMF-accuracy) and chance corrected CSMF-accuracy were computed to evaluate the PCVA performance at the populational level. Results There was substantial variability of the sensitivities and CCC across the causes. Well-known chronic diseases with accurate diagnoses that had been informed by physicians to family members, such as various cancers, had sensitivities above 40% or 50%. However, PCVA was not effective in attributing Pneumonia, Cardiomyopathy and Leukemia/Lymphoma as underlying CoD. At populational level, the PCVA estimated cause specific mortality fractions (CSMF) may be considered close to the fractions pointed by the gold standard. The CSMF-accuracy was 0.81 and the chance corrected CSMF-accuracy was 0.49. Conclusions The PCVA was efficient in attributing some causes individually and proved effective in estimating the CSMF, which indicates that the method is useful to establish public health priorities.

Abstract Cerro de Pasco, Peru, has been excessively contaminated with heavy metals due to high mining activities in the region. We investigated the presence of chronic exposure to heavy metals in children living in Cerro de Pasco and its effect on health. Heavy metal concentrations were determined in hair samples collected from 78 children living in a region exposed to an open-pit mine (Paragsha region) and from other 16 children unexposed to mine activities (Carhuamayo region). Children exposed to the mine showed statistically significant higher concentration of aluminum, antimony, arsenic, cadmium, chromium, iron, lead, tin and thallium (p

© 2014 Macmillan Publishers Limited. All rights reserved.Developmental history shapes the epigenome and biological function of differentiated cells. Epigenomic patterns have been broadly attributed to the three embryonic germ layers. Here we investigate ho

Ionic gradients are found across a variety of tissues and organs. In this report, we apply the phasor representation of fluorescence lifetime imaging data to the quantitative study of ionic concentrations in tissues, overcoming technical problems of tissue thickness, concentration artifacts of ion-sensitive dyes, and calibration across inhomogeneous tissue. We used epidermis as a model system, as Ca(2+) gradients in this organ have been shown previously to control essential biologic processes of differentiation and formation of the epidermal permeability barrier. The approach described here allowed much better localization of Ca(2+) stores than those used in previous studies, and revealed that the bulk of free Ca(2+) measured in the epidermis comes from intracellular Ca(2+) stores such as the Golgi and the endoplasmic reticulum, with extracellular Ca(2+) making a relatively small contribution to the epidermal Ca(2+) gradient. Due to the high spatial resolution of two-photon microscopy, we were able to measure a marked heterogeneity in average calcium concentrations from cell to cell in the basal keratinocytes. This finding, not reported in previous studies, calls into question the long-held hypothesis that keratinocytes increase intracellular Ca(2+), cease proliferation, and differentiate passively in response to changes in extracellular Ca(2+). The experimental results obtained using this approach illustrate the power of the experimental and analytical techniques outlined in this report. Our approach can be used in mechanistic studies to address the formation, maintenance, and function of the epidermal Ca(2+) gradient, and it should be broadly applicable to the study of other tissues with ionic gradients.

Three transgenic Anopheles stephensi lines were established that strongly inhibit transmission of the mouse malaria parasite Plasmodium berghei. Fitness of the transgenic mosquitoes was assessed based on life table analysis and competition experiments between transgenic and wild-type mosquitoes. Life table analysis indicated low fitness load for the 2 single-insertion transgenic mosquito lines VD35 and VD26 and no load for the double-insertion transgenic mosquito line VD9. However, in cage experiments, where each of the 3 homozygous transgenic mosquitoes was mixed with nontransgenic mosquitoes, transgene frequency of all 3 lines decreased with time. Further experiments suggested that reduction of transgene frequency is a consequence of reduced mating success, reduced reproductive capacity, and/or insertional mutagenesis, rather than expression of the transgene itself. Thus, for transgenic mosquitoes released in the field to be effective in reducing malaria transmission, a driving mechanism will be required.

Hailey-Hailey disease (MIM16960) is a blistering skin disease caused by mutations in the Ca2+ ATPase ATP2C1. We found that the abnormal Ca2+ signaling seen in Hailey-Hailey disease keratinocytes correlates with decreased protein levels of ATP2C1. Human ATP2C1 protein approximated 115 kDa in size. The ATP2C1 is localized to the Golgi apparatus in human keratinocytes, similar to its localization in yeast and Caenorhabditis elegans. To test whether the ATP2C1 controls Golgi Ca2+ stores, we measured intraorganelle Ca2+ concentrations using specifically targeted aequorins. Whereas normal keratinocytes display Golgi Ca2+ levels comparable to other epithelial cells, Hailey-Hailey disease keratinocyte Golgi Ca2+ refill is slower, and the maximum Ca2+ concentration reached is significantly lower. These findings were replicated in vivo, because clinically normal Hailey-Hailey disease epidermis contained lower Ca2+ stores and displayed an abnormal Ca2+ gradient. In this report we localize the ATP2C1, demonstrate its physiologic relevance in mammalian cells, and measure intraorganelle Golgi Ca2+ in keratinocytes.

Rationale: Several recent studies suggest that Brazil’s Estratégia Saude de Familia (Family Health Strategy-FHS) has contributed to declines in mortality at the national and regional level. Comparatively little is known whether this approach is effective in urban populations with relatively easy access to health services. Objectives: To use detailed medical data collected as part of São Paulo’s Western Region project to examine whether the FHS program had an impact on child health in São Paulo, Brazil. Results: No associations were found between FHS and birth weight (OR 1.03, 95% CI 0.93–1.29), gestational length (OR 0.98, 95% CI 0.83–1.15) or stillbirth (OR 1.51, 95% CI 0.75–3.03). FHS eligibility was associated with a 42% reduction in the odds of child mortality (OR 0.58, 95% CI 0.34, 0.91), with largest effect sizes for the early neonatal period (OR 0.18, 95% CI 0.04–0.79). Conclusions: Community based health delivery platforms may be a highly effective way to reduce neonatal mortality in urban areas of low and middle income countries, even when access to general health services is almost universal. Keywords: Infant mortality, Estratégia saude de familia, Family health strategy, Progama de saude de familia, Brazil, Community-based programs

Among all glaucoma suspects, eyes with optic nerve head features suspicious or suggestive of early glaucoma are probably those that offer the greatest challenge for clinicians. In contrast with the robust longitudinal data published on ocular hypertension, there is no specific management guideline for these patients. Therefore, evaluating eyes with suspicious optic disc appearance and normal intraocular pressure (IOP), we sought to investigate potential differences in clinical and epidemiological characteristics to differentiate those with normal-tension glaucoma (NTG) from those with presumed large physiological optic disc cups (pLPC). In this observational case-control study, we consecutively enrolled individuals with pLPC and NTG. All eyes had vertical cup-to-disc ratio (VCDR)≥0.6 and untreated IOP

Com o objetivo de avaliar a alteração do campo visual de um trator, ocasionada pela instalação de uma cabina, foram determinadas as áreas de visibilidade nula em função da presença ou não da mesma, para cada campo visual. Os procedimentos adotados basearam-se na norma ISO 5721-1981 - Agricultural tractors - Operator's field of vision. A cabina aumentou em 34,42% a área de visibilidade nula. A relação área de projeção do trator/área total sombreada foi de 0,075 para o trator sem cabina, e 0,057 para o trator com cabina, indicando as melhores condições de visibilidade do primeiro em relação ao segundo. No que se refere aos campos visuais, a maior redução ocorreu no campo visual dos olhos e no obtido com o movimento da cabeça, em função dos suportes da cabina e da estrutura de proteção contra o capotamento. A cabina diminui o campo de visão do operador, e adequações no projeto da estrutura avaliada são necessárias para melhorar as condições de visibilidade.Aiming to evaluate the alteration of the visual field of a tractor occasioned by the installation of a cabin were determined the null visibility areas due to the presence or not of this structure, for each visual field. The procedures adopted were based on ISO 5721-1981 - Agricultural tractors - Operator's field of vision. The cabin increased in 34,42% the area of null visibility. The relationship projection area of tractor/total shadowed area was 0,075 to the tractor without a cabin, and 0,057 for the tractor with cabin, indicating the best conditions of visibility of the first in relation to the second. With respect to the visual area, the largest reduction happened in the eyes visual field and in the obtained with the head movement in function of the cabin supports and the rollover protection structure. The cabin decreases the operator’s area of vision, and adjustments in the project of the structure evaluated are necessary to improve the visibility conditions.

Reactivation of chronic chagasic patients may occur upon use of immunosuppressive drugs related to kidney or heart transplantation or when they are affected by concomitant HIV infection. This recrudescence, however, does not occur in all chagasic patients exposed to immunosuppressive agents. We therefore investigated the influence of Trypanosoma cruzi strains in the recrudescence of the parasitism in mice at the chronic phase treated with cyclophosphamide, an immunosuppressor that blocks lymphocytes DNA synthesis and therefore controls B cells response. A large variation was detected in the percentages of newly established acute phases in the groups of mice inoculated with the different strains. We suggest that reactivation of chronic T. cruzi infections is influenced by the parasite intrinsic characteristics, a phenomenon that might occur in the human disease.

This paper presents a hybrid power flow formulation unifying three-phase and single-phase (positive sequence) models. Positive sequence modeling is considered at the transmission level network and three-phase modeling is considered at the distribution level. A passive interface between these networks is proposed. The interface is based on a [pi] element that can represent transmission lines or transformers. The formulation allows both subsystems to be solved simultaneously using the classic Newton-Raphson method. The three-phase subsystem can either be represented in phase or sequence components. Tests in large-scale power systems indicate that the proposed hybrid formulation has the same robust convergence properties of the conventional all-single-phase or all-three-phase Newton-type methods. The use of the proposed formulation is motivated for studies where the focus of the analysis is in the unbalanced three-phase subsystem highly influenced by operating conditions in the single-phase-modeled subsystem. Index Terms--Distribution power flow, network equivalent, unbalanced system.

Ketoconazole an azole antifungic drug which is already in the market has also been demonstrated to be active against Trypanossoma cruzi experimental infections. In this paper we confirmed the drug effect and investigated its range of activity against different T. cruzi strains naturally resistant or susceptible to both standard drugs Nifurtimox and Benznidazole used clinically in Chagas disease. Moreover, we have shown that the association of Ketoconazole plus Lovastatin (an inhibitor of sterol synthesis), which has an antiproliferative effect against T. cruzi in vitro, failed to enhance the supressive effect of Ketoconazole displayed when administered alone to infected mice. Finally, administration in chronic chagasic patients of Ketoconazole at doses used in the treatment of deep mycosis also failed to induce cure as demonstrated by parasitological and serological tests. The strategy of identify and test drugs which are already in the market and fortuitously are active against T. cruzi has been discussed.