Administration of intravenous iron formulations induces complement activation in-vivo

Background: Intravenous (IV) iron is widely used to treat anemia in chronic kidney disease patients. Previously, iron formulations were shown to induce immune activation in-vitro. The current study aimed to investigate the effect of IV iron on complement activation in-vivo, and whether this subsequently induces inflammation and/or oxidative stress. Methods: Two distinct patient groups were included: 51 non-dialysis and 32 dialysis patients. The non-dialysis group received iron sucrose or ferric carboxymaltose, based on physicians’ choice. Plasma samples were collected prior to and 1 h after completion of IV iron infusion. The dialysis group received iron sucrose exclusively. Plasma samples were collected at the start and end of two consecutive hemodialysis sessions, one with and one without IV iron. Finally, plasma levels of MBL, C1q, properdin, factor D, sC5b-9, MPO, PTX3 were assessed by ELISA. Results: In the non-dialysis group, sC5b-9 levels significantly increased after IV iron by 32%, while levels of factor D and MBL significantly dropped. Subgroup analysis demonstrated that iron sucrose induced complement activation whereas ferric carboxymaltose did not. In the dialysis group, levels of sC5b-9 significantly increased by 46% during the dialysis session with IV iron, while factor D levels significantly fell. Furthermore, the relative decrease in factor D by IV iron correlated significantly with the relative increase in sC5b-9 by IV iron. MPO levels rose significantly during the dialysis session with IV iron, but not in the session without iron. Moreover, the relative increase in MPO and sC5b-9 by IV iron correlated significantly. PTX3 levels were not affected by IV iron. Conclusions: Iron sucrose but not ferric carboxymaltose, results in complement activation possibly via the lectin and alternative pathway partially mediating oxidative stress but not inflammation.Conflict of Interest Statement: CG received speaking fees and research funding from Vifor Pharma

O AMOR INCONDICIONAL NO CONTO “A CAOLHA”, DE JÚLIA LOPES DE ALMEIDA

A Caolha, conto escrito por Júlia Lopes de Almeida, reforça o estereótipo de mãe, no qual o amor incondicional está presente. Nesse sentido, propõe-se a análise dos mecanismos empregados pela autora, a fim de desafiar os paradigmas ainda hoje impostos à maternidade. Pautando-nos na crítica feminista, define-se como objetivo geral analisar a contestação dos paradigmas maternos, empreendida no conto em questão, e como objetivos específicos: a) compreender o relacionamento entre os personagens a Caolha e Antonico, e o amor incondicional daquela pelo filho; b) identificar as estratégias empregadas por Júlia Lopes, a fim de mostrar o quanto a mãe foge aos padrões da sociedade da época, uma vez que, além de ser mulher, cria seu filho sozinha, sofrendo diversas humilhações por parte de uma sociedade conservadora; e c) verificar até que ponto a maternidade pode ser considerada uma imposição e não um instinto. Para o cumprimento dos objetivos, será realizada a análise do enredo do conto, buscando-se elencar os elementos que representem o universo materno através da problematização da maternidade, tendo como referência o livro Um amor conquistado: o mito do amor materno, de Elisabeth Badinter, o qual possibilitará entendermos o amor incondicional da Caolha para com seu filho. Da mesma forma propomos analisar a situação da mulher presente na sociedade contemporânea conforme vista nos estudos de Adriana Piscitelli, assim como o preconceito sofrido por ela ao ter que criar seu filho sozinha.PALAVRAS-CHAVE: A Caolha. Maternidade. Amor incondicional.DOI: https://doi.org/10.47295/mgren.v7i1.153

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

Avaliação de desempenho: discutindo a tecnologia para o planejamento e gestão de recursos humanos em saúde

Este ensaio apresenta o produto de reflexões e análises a partir do exame de opções conceituais inerentes às metodologias de avaliação de desempenho (AD) de profissionais e sua possibilidade de aplicação na área da saúde. Estabelece uma discussão conceitual para a área, articulando e integrando conhecimentos de campos distintos - o da saúde e o da administração pública. Promove a intersecção entre a gestão do trabalho em saúde no setor público e as técnicas da administração de pessoal. Pretende gerar novas análises e estudos que possibilitem uma releitura das práticas administrativas para avaliação de desempenho utilizadas nas organizações, adaptá-las para atender às especificidades do setor saúde

Positive solutions for nonlinear singular elliptic equations of p-Laplacian type with dependence on the gradient

In this paper, we study a nonlinear Dirichlet problem of p-Laplacian type with combined effects of nonlinear singular and convection terms. An existence theorem for positive solutions is established as well as the compactness of solution set. Our approach is based on Leray-Schauder alternative principle, method of sub-supersolution, nonlinear regularity, truncation techniques, and set-valued analysis

Sensitivity Analysis for Not-at-Random Missing Data in Trial-Based Cost-Effectiveness Analysis : A Tutorial

Cost-effectiveness analyses (CEA) of randomised controlled trials are a key source of information for health care decision makers. Missing data are, however, a common issue that can seriously undermine their validity. A major concern is that the chance of data being missing may be directly linked to the unobserved value itself [missing not at random (MNAR)]. For example, patients with poorer health may be less likely to complete quality-of-life questionnaires. However, the extent to which this occurs cannot be ascertained from the data at hand. Guidelines recommend conducting sensitivity analyses to assess the robustness of conclusions to plausible MNAR assumptions, but this is rarely done in practice, possibly because of a lack of practical guidance. This tutorial aims to address this by presenting an accessible framework and practical guidance for conducting sensitivity analysis for MNAR data in trial-based CEA. We review some of the methods for conducting sensitivity analysis, but focus on one particularly accessible approach, where the data are multiply-imputed and then modified to reflect plausible MNAR scenarios. We illustrate the implementation of this approach on a weight-loss trial, providing the software code. We then explore further issues around its use in practice

Reductions in the Prevalence and Incidence of Geohelminth Infections following a City-wide Sanitation Program in a Brazilian Urban Centre

In the city of Salvador, a large urban centre in Northeast Brazil, a city-wide sanitation intervention started in 1997, aiming to improve the sewerage coverage of households from 26% to 80%. Our aim was to study the impact of the intervention on the prevalence and incidence of geohelminths in the school-aged population. The longitudinal study comprised two cohorts: from the beginning of 1997 to 1998, where data was collected before the intervention, and at the end of 2003 to 2004, after the intervention. Copro-parasitological examinations were carried out on every individual from both cohorts, at the start and nine months later. Demographic, socio-economic, and environmental data were collected using semi-structured questionnaires. The variables utilized to demonstrate the effects of intervention, when utilized together in a multivariate model, accounted for a 100% observed reduction in the prevalence ratio (PR) and incidence ratio (IR). As well as proving that the variables associated with the effect of the program intervention were mediators in this reduction, the reduction in the PR and IR between these periods demonstrated that modifications to the urban environment, particularly those associated with sanitary sewage systems, affected the health of the population, significantly reducing the prevalence of geohelminths