Molecular detection of EGFRvIII-positive cells in the peripheral blood of breast cancer patients

The aim of this study is to evaluate epidermal growth factor receptor variant III, EGFRvIII, a cancer specific mutant, as a possible marker for the diagnosis of breast cancer occult systemic disease. EGFRvIII mRNA was identified by an RT-nested PCR with a high sensitivity. In 102 women studied, the mutant was detected in the peripheral blood of 30% of 33 low risk, early stage patients, in 56% of 18 patients selected for neoadjuvant chemotherapy, in 63.6% of 11 patients with disseminated disease and 0% of 40 control women. In low risk, early stage patients, the presence of one or more tumour characteristics predicting recurrence such as the absence of oestrogen receptors and the presence of ERBB2 or histologic grades G2/G3 was significantly associated with EFGRvIII detection (p < 0.05). EGFRvIII mRNA has characteristics to be a useful marker for the diagnosis of occult systemic disease in breast cancer. Follow-up studies will evaluate its clinical value as a decision criterion for systemic therapy.http://www.sciencedirect.com/science/article/B6T68-4KV2RH2-1/1/8d7f06700e09e0cb34c8a3861e1b0ba

Analysis of the Characteristics and Cytotoxicity of Titanium Dioxide Nanomaterials Following Simulated In Vitro Digestion

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Several metallic nanomaterials (NMs), such as titanium dioxide nanomaterials (TiO2), present beneficial properties with a broad range of innovative applications. The human population is exposed to TiO2, particularly by ingestion, due to its increasing use as a food additive and inclusion in dietary supplements and food packaging materials. Whether this oral exposure may lead to adverse local or systemic outcomes has been the subject of research, but studies have generated contradictory results, reflecting differences in the physicochemical properties of the TiO2 studied, effects of the surrounding matrix, and modifications during digestion. This work aimed to investigate the toxic effects of three different TiO2 NMs (NM-103, NM-103 and NM-105) on the gastrointestinal tract cells, Caco-2 and HT29-MTX-E12, after the use of the standardized static INFOGEST 2.0 in vitro digestion method to mimic human digestion of TiO2, contributing to hazard assessment. The results show that, for one of the digested TiO2 NMs studied (NM-105), a more pronounced toxicity occurs after exposure of HT29-MTX-E12 intestinal cells, as compared to undigested NM, concomitantly with subtle changes in characteristics of the NM. Thus, the inclusion of the digestion simulation in the safety evaluation of ingested NMs through in vitro bioassays can better integrate the modifications that NMs suffer in the organism. It is expected that such an approach will reduce uncertainties in the hazard assessment of ingested NMs for human health.This research was funded by the Portuguese Foundation for Science and Technology FCT/MCTES through national funds (PIDDAC), PTDC/SAU-PUB/29481/2017 and co-funded by UIDB/00009/2020 (Centre for Toxicogenomics and Human Health—ToxOmics, FCT), iMed.ULisboa (Pest-UID/DTP/04138/2019) and CESAM (UIDP/50017/2020+UIDB/50017/2020), through national funds.info:eu-repo/semantics/publishedVersio

Investigation of potential respiratory adverse effects of micro/nanofibrillated cellulose and cellulose nanocrystals using human lung cell lines.

Abstract publicado em: Environ Mol Mutagen. 2022 Aug;63(Suppl 1):72-73. (Abstracts from the 13th International Conference on Environmental Mutagens and 53rd Annual Meeting of the Environmental Mutagenesis and Genomics Society). https://onlinelibrary.wiley.com/toc/10982280/2022/63/S1Micro/nanofibrillated (CMF/CNF) and nanocrystalline (CNC) celluloses are innovative materials with enormous potential for industrial and biomedical applications. Their expanding production/application urges the investigation of their safety for human health. This study aimed at investigating the potential respiratory outcomes of two CMF/CNF and one CNC produced from bleached Eucalyptus globulus kraft pulp using human alveolar epithelial (A549) cells grown in monoculture or co-cultured with THP-1 monocyte-derived macrophages, by assessing their cellular uptake, cytotoxic, immunotoxic, genotoxic, and epigenetic effects. The nanocelluloses were characterized for their physicochemical properties: CMF displays a low percentage of nanofibrils while CNF comprises 100% fibrils with a diameter (D) circa 11 nm; CNC consists of nanorods with D of 4-5 nm and aspect ratio around 42. TEM analysis evidenced that CMF and CNF were internalised into A549 cells whereas CNC were not. Neither cytotoxicity (colorimetric and clonogenic assays) nor ROS induction was observed for any of the nanocelluloses. CMF caused chromosomal alterations (in vitro micronucleus assay) in A549 cells while negative results were obtained in co-culture and for the other micro/nanocelluloses in mono- or co-culture. Results in progress of DNA damage and gene mutation analyses will complement mutagenesis assessment. Additionally, potential inflammatory and epigenetic effects are being evaluated. These results contribute to the weight of evidence of nanocelluloses biological effects and knowledge of the underlying molecular mechanisms. Such information will drive the synthesis of the safest nanocelluloses,thus minimising potential negative impacts of their use on human and environmental health.FCT/MCTES through nacional funds (PTDC/SAU-PUB/32587/2017; UIDP/00009/2020; UIDB/00009/2020; 020.07168.BD)info:eu-repo/semantics/publishedVersio

Attitudes of nurses towards families: validation of the scale Families' Importance in Nursing Care - Nurses Attitudes

The attitudes of nurses towards families determine the care process. With this study, we aimed to obtain an instrument that would allow us to learn about this variable. Hence, our purpose was to perform the cross-cultural adaptation and evaluate the psychometric features of the Portuguese version of the instrument Families' Importance in Nursing Care - Nurses Attitudes (FINC-NA), which aims to evaluate the attitudes of nurses towards the importance of involving the patient's family in the nursing care. The method recommended by the literature was followed. The sample consisted of 136 nurses working in primary health care. The results obtained in the reliability tests showed good internal consistency (Cronbach's Alpha=0.87). The psychometric study permits us to state that the Portuguese version of the FINC-NA, which in Portuguese is referred to as A importância das famílias nos cuidados de enfermagem - atitudes dos enfermeiros (IFCE-AE), is a reliable and valid tool.As atitudes que os enfermeiros adotam em relação à família condicionam o processo de cuidar. Nosso propósito com este estudo foi nesse sentido: dispor de um instrumento que nos permitisse conhecer esta variável. Assim, nossa proposta foi efetuar a adaptação transcultural e avaliar as propriedades psicométricas da versão portuguesa do instrumento Families' Importance in Nursing Care - Nurses Attitudes (FINC-NA), que visa avaliar as atitudes dos enfermeiros acerca da importância de envolver a família nos cuidados de enfermagem. Foi seguido o método preconizado pela literatura. A amostra foi constituída por 136 enfermeiros dos Cuidados de Saúde Primários. Os resultados obtidos nos testes de confiabilidade revelam uma boa consistência interna para o total dos itens (Alpha de Cronbach = 0,87). O estudo psicométrico permite-nos afirmar que a versão em português da FINC-NA, que denominamos A importância das famílias nos cuidados de enfermagem - atitudes dos enfermeiros (IFCE-AE), é um instrumento fidedigno e válido.Las actitudes adoptadas por enfermeros en relación a la familia condicionan el proceso de cuidar. En tal sentido, nos propusimos con este estudio, disponer de un instrumento que nos permita conocer esta variable. Así, nos propusimos efectuar la adaptación transcultural y evaluar las propiedades psicométricas de la versión portuguesa del instrumento Families Importance in Nursing Care - Nurses Attitudes (FINC-NA), que apunta a evaluar actitudes de enfermeros acerca de involucrar a la familia en los cuidados de enfermería. Se siguió el método sugerido por la literatura. Muestra constituida por 136 Enfermeros de Atención Primaria de Salud. Los resultados obtenidos en pruebas de fiabilidad revelan buena consistencia interna para el total de ítems (Alpha de Cronbach=0,87). El estudio psicométrico nos permite afirmar que la versión en Portugués del FINC-NA, que denominamos La importancia de las familias en el cuidado de enfermería - actitudes de los enfermeros (IFCE-AE) es un instrumento fidedigno y válido

Genotoxicity biomarkers in workers exposed to hexavalent chromium: a study under the European Human Biomonitoring Initiative

No âmbito da Iniciativa Europeia em Biomonitorização Humana (HBM4EU) realizou-se um estudo ocupacional, envolvendo trabalhadores com potencial exposição a crómio hexavalente [Cr( VI)], um reconhecido agente carcinogénico. No presente estudo são apresentados os resultados de biomarcadores de genotoxicidade, incluindo a análise de lesão no DNA e de alterações cromossómicas em células sanguíneas. O estudo foi realizado em vários Países Europeus e abrangeu trabalhadores de diversos setores industriais e atividades, bem como um grupo de controlo constituído por trabalhadores administrativos das mesmas empresas (controlo interno) e de outras não relacionadas com produção/aplicação de Cr( VI) (controlo externo). Os resultados mostraram níveis de alterações cromossómicas (ensaio do micronúcleo) e de lesão no DNA (ensaio do cometa) significativamente aumentados nos trabalhadores expostos comparativamente aos controlos externos ( p=0,03; p<0,001, respetivamente). Estes resultados sugerem que mesmo um baixo nível de exposição ao Cr( VI) representa um risco acrescido para a saúde dos trabalhadores e, principalmente, para os que realizam cromagem em banho. O grupo controlo interno apresentou níveis médios de lesões no DNA e nos cromossomas comparáveis aos do grupo exposto, salientando a relevância de se considerarem também em risco. O uso de biomarcadores de efeito demonstrou ser crucial para a deteção precoce de efeitos biológicos decorrentes de baixos níveis de exposição ao Cr( VI), contribuindo para a identificação de subgrupos em maior risco. O presente estudo vem apoiar a necessidade de uma reavaliação do limite de exposição ocupacional a Cr( VI), bem como da implementação de medidas de gestão de risco conducentes a uma melhor proteção da saúde dos trabalhadores.An occupational study was carried out within the scope of the European Initiative on Human Biomonitoring (HBM4EU), involving workers with potential exposure to hexavalent chromium [Cr(VI)], a recognized carcinogenic agent. In the present study, the results of biomarkers of genotoxicity are presented, including the analysis of DNA damage and chromosomal alterations in blood cells. The study was carried out in several countries and included workers from different industrial sectors and activities, as well as a control group including administrative workers from the same companies (internal control) and from others not related to the production/application of Cr(VI) (external control). Results showed significantly increased levels of chromosomal alterations (micronucleus assay) and DNA damage (comet assay) in exposed workers compared to external controls (p=0.03; p<0.001, respectively). These results suggest that even a low level of exposure to Cr(VI) represents an increased risk for the health of workers and, mainly, for those who per form chromium bath plating. The internal control group displayed DNA and chromosomal damage levels comparable to those of the exposed group, highlighting the impor tance of also being considered as potentially at risk. The use of ef fect biomarkers proved to be crucial for the early detection of biological ef fects resulting from low levels of exposure to Cr(VI), contributing to the identification of subgroups at a higher risk. The present study suppor ts the need for a reassessment of the occupational exposure limit to Cr(VI), as well as the implementation of risk management measures leading to a better protection of workers' health.Este projeto recebeu financiamento do programa de investigação e inovação Horizonte 2020 da União Europeia sob o acordo de subvenção n.º 733032 e recebeu cofinanciamento das organizações dos autores.info:eu-repo/semantics/publishedVersio

Características químicas de um latossolo adubado com uréia e cloreto de potássio em ambiente protegido

A produção de vegetais mais sadios e de boa qualidade e o fornecimento contínuo no mercado são fatores que têm determinado a adoção do sistema de cultivo protegido por um número maior de produtores. Porém, devido ao pouco conhecimento sobre o manejo do solo nessas condições, tem-se aplicado altas doses de fertilizantes, ocasionando problemas de salinidade e desequilíbrio nutricional. O objetivo desse trabalho foi avaliar os efeitos da aplicação da uréia e do cloreto de potássio nas características químicas de um LATOSSOLO VERMELHO Destrófico, principalmente nos índices de acidez e saturação em potássio. O N e o K foram aplicados em cobertura, nas doses equivalentes de 13,3 e 39,9 g m-2 de N e 5,5 e 16,6 g m-2 de K, em esquema fatorial (2x2+1), com tratamento adicional, sem a aplicação dos nutrientes. Cultivou-se pimentão, cultivar Mayata, em condições de ambiente protegido, durante 34 semanas. Após o pegamento das mudas, foi aplicado 1/6 dos nutrientes a cada dez dias. Ao final do ciclo, as formas de N nítrico e N amoniacal representaram melhor as doses do nutriente aplicados ao solo e não houve acidificação. As raízes tiveram significativo crescimento após a aplicação de N, enquanto que o aumento da dose de K, aplicado como KCl, prejudicou o crescimento radicular, provavelmente associado à alta concentração de K no solo e possíveis efeitos salinos, correspondendo a mais de 5,0 mmol c dm-3 e mais que 5,3% de saturação do K no complexo de troca, na camada superficial do solo

Regional differences in clinical care among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group

Background\ud To determine the characteristics of clinical care offered to type 1 diabetic patients across the four distinct regions of Brazil, with geographic and contrasting socioeconomic differences. Glycemic control, prevalence of cardiovascular risk factors, screening for chronic complications and the frequency that the recommended treatment goals were met using the American Diabetes Association guidelines were evaluated.\ud \ud Methods\ud This was a cross-sectional, multicenter study conducted from December 2008 to December 2010 in 28 secondary and tertiary care public clinics in 20 Brazilian cities in north/northeast, mid-west, southeast and south regions. The data were obtained from 3,591 patients (56.0% females and 57.1% Caucasians) aged 21.2 ± 11.7 years with a disease duration of 9.6 ± 8.1 years (<1 to 50 years).\ud \ud Results\ud Overall, 18.4% patients had HbA1c levels <7.0%, and 47.5% patients had HbA1c levels ≥ 9%. HbA1c levels were associated with lower economic status, female gender, age and the daily frequency of self-blood glucose monitoring (SBGM) but not with insulin regimen and geographic region. Hypertension was more frequent in the mid-west (32%) and north/northeast (25%) than in the southeast (19%) and south (17%) regions (p<0.001). More patients from the southeast region achieved LDL cholesterol goals and were treated with statins (p<0.001). Fewer patients from the north/northeast and mid-west regions were screened for retinopathy and nephropathy, compared with patients from the south and southeast. Patients from the south/southeast regions had more intensive insulin regimens than patients from the north/northeast and mid-west regions (p<0.001). The most common insulin therapy combination was intermediate-acting with regular human insulin, mainly in the north/northeast region (p<0.001). The combination of insulin glargine with lispro and glulisine was more frequently used in the mid-west region (p<0.001). Patients from the north/northeast region were younger, non-Caucasian, from lower economic status, used less continuous subcutaneous insulin infusion, performed less SBGM and were less overweight/obese (p<0.001).\ud \ud Conclusions\ud A majority of patients, mainly in the north/northeast and mid-west regions, did not meet metabolic control goals and were not screened for diabetes-related chronic complications. These results should guide governmental health policy decisions, specific to each geographic region, to improve diabetes care and decrease the negative impact diabetes has on the public health system.We thank Mrs. Karianne Aroeira Davidson, Mrs. Anna Maria Ferreira, Mrs. Elisangela Santos and Sandro Sperandei for their technical assistance.This work was supported by grants from Farmanguinhos/Fundação Oswaldo Cruz/National Health Ministry, the Brazilian Diabetes Society, Fundação do Amparo à Pesquisa do Estado do Rio de Janeiro, and Conselho Nacional de Desenvolvimento Científico e Tecnológico do Brasil