AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines. The mutational analysis in the eight HNSCC cell lines revealed an EGFR mutation (p.H773Y) and gene amplification in the HN13 cells. According to the growth inhibition score (GI), allitinib was the most cytotoxic drug, followed by afatinib and finally cetuximab. The higher AKT phosphorylation level was associated with resistance to anti-EGFR agents. Therefore, we further performed drug combinations with anti-AKT agent (MK2206) and AKT1 gene editing, which demonstrated afatinib and allitinib sensitivity restored. Additionally, in silico analysis of TCGA database showed that AKT1 overexpression was present in 14.7% (41/279) of HNSCC cases, and was associated with perineural invasion in advanced stage. In conclusion, allitinib presented a greater cytotoxic profile when compared to afatinib and cetuximab. AKT pathway constitutes a predictive marker of allitinib response and combination with AKT inhibitors could restore response and increase treatment success.FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT) and the Assistance Program and Incentive Research (PAIP), Barretos Cancer Hospital São Paulo, Brazil. The authors would like to acknowledge the technical support of Gabriela Lamberti in the clonogenic assays. A.L.C and R.M.R are recipients of a National Counsel of Technological and Scientific Development (CNPq) scholarship and O.C.M is recipient of a Portuguese Foundation for Science and Technology (FCT) scholarship (SFRH/BPD/108351/2015)info:eu-repo/semantics/publishedVersio

O financiamento da Atenção Básica no Brasil: um balanço de duas décadas (2000-2020)

This article analyzes the primary healthcare financing in Brazil between 2000 and 2020. We conducted an integrative review of the scientific productions available in the electronic scientific databases BVS, Scielo, and MEDLINE in December 2020. After including articles undertaken in Brazil, with free access, and excluding duplicates and non-scientific texts, ten articles were selected. Those articles were submitted to Thematic Content Analysis and organized into two categories (1) “Municipal differences in the financing of Primary Care” and (2) “Tripartite Financing of Primary Care”. The results of this review pointed out several inequalities in the financing of primary healthcare. Although federal participation in the budget has grown during the analyzed period, the transfers occurred due to incentives for the adoption of federal programs that did not reach the municipalities homogeneously. Compared to the South and Southeast, small municipalities in the North and Northeast regions had greater dependence on federal transfers. In addition, there was lower state participation in the overall financing in the North and Northeast regions. The main limitation of our review was not including studies published since 2021 analyzing the impacts of recent policies that aggravated the underfunding of primary healthcare in Brazil, which could have potentially worsened the results presented in this study and put primary healthcare quality and preservation even more at risk.Este artigo analisa o financiamento da Atenção Básica do Brasil entre 2000 e 2020 a partir de uma revisão integrativa das produções científicas disponíveis nas bases científicas eletrônicas BVS, SciELO e MEDLINE. Foram elegíveis artigos com acesso gratuito e situados no Brasil, excluindo duplicados e textos não científicos. Após aplicados os critérios de inclusão e exclusão, foram selecionados dez artigos, os quais foram submetidos à análise de conteúdo temática e organizados em duas categorias: (1) “Diferenças municipais no financiamento da Atenção Básica” e (2) “Financiamento tripartite da Atenção Básica”. Os resultados apontam para diversas desigualdades no financiamento desse nível de atenção. Apesar do crescimento da participação federal, as transferências ocorreram por incentivos à adoção de programas federais que não alcançaram os municípios homogeneamente. Houve maior dependência das transferências federais em municípios pequenos e nas regiões Norte e Nordeste, além de baixa participação estadual no financiamento. Um dos limites do estudo foi não alcançar, pelo recorte temporal, estudos analisando os impactos das atuais políticas que agravaram o desfinanciamento da Atenção Básica, que provavelmente tem piorado o contexto apresentado e colocado ainda mais em risco a qualidade e preservação dela

Qual o impacto das leis de desarmamento sobre o número de suicídios no Brasil?

Introdução. Em 2003, o Brasil introduziu uma reforma na regulamentação de armas de fogo. Objetivo. Este estudo teve como objetivo avaliar o impacto do Estatuto do Desarmamento sobre os suicídios no Brasil. Método. As taxas de suicídio antes (1990-2003) e depois da mudança na legislação (2004-2017) foram comparadas. Foi utilizado um desenho de estudo de séries temporais interrompidas com modelo linear generalizado e cálculo da tendência ao suicídio por arma de fogo, outros métodos e o total de suicídios. Resultados. Entre 1990 e 2017, foram registradas 226.407 mortes por suicídio no Brasil. Após a Lei do Desarmamento, 2004-2017, houve uma aceleração na tendência de diminuição do suicídio por arma de fogo. Foi demonstrada uma tendência de aceleração no crescimento de suicídios sem arma. Porém, no total de suicídios, não foi observada mudança significativa. Conclusão. Mais esforços são necessários para prevenir o suicídio em nível populacional do que para restringir um método letal

Identification of hereditary cancer in the general population: development and validation of a screening questionnaire for obtaining the family history of cancer

One of the challenges for Latin American countries is to include in their healthcare systems technologies that can be applied to hereditary cancer detection and management. The aim of the study is to create and validate a questionnaire to identify individuals with possible risk for hereditary cancer predisposition syndromes (HCPS), using different strategies in a Cancer Prevention Service in Brazil. The primary screening questionnaire (PSQ) was developed to identify families at-risk for HCPS. The PSQ was validated using discrimination measures, and the reproducibility was estimated through kappa coefficient. Patients with at least one affirmative answer had the pedigree drawn using three alternative interview approaches: in-person, by telephone, or letter. Validation of these approaches was done. Kappa and intraclass correlation coefficients were used to analyze data’s reproducibility considering the presence of clinical criteria for HCPS. The PSQ was applied to a convenience sample of 20,000 women of which 3121 (15.6%) answered at least one affirmative question and 1938 had their pedigrees drawn. The PSQ showed sensitivity and specificity scores of 94.4% and 75%, respectively, and a kappa of 0.64. The strategies for pedigree drawing had reproducibility coefficients of 0.976 and 0.850 for the telephone and letter approaches, respectively. Pedigree analysis allowed us to identify 465 individuals (24.0%) fulfilling at least one clinical criterion for HCPS. The PSQ fulfills its function, allowing the identification of HCPS at-risk families. The use of alternative screening methods may reduce the number of excluded at-risk individuals/families who live in locations where oncogenetic services are not established.Research supported by Barretos Cancer Hospital. EIP has a grant from FAPESP (FAPESP, SP, Brazil, #2013/24633-2). N Campacci is supported by a PhD fellowship from FAPESP (FAPESP, SP, Brazil, #2015/02444-9).info:eu-repo/semantics/publishedVersio

A simple architecture with self-assembled monolayers to build immunosensors for detecting the pancreatic cancer biomarker CA19-9

Accepted ManuscriptThe challenge of the early diagnosis of pancreatic cancer in routine clinical practice requires low-cost means of detection, and this may be achieved with immunosensors based on electrical or electrochemical principles. In this paper, we report a potentially low-cost immunosensor built with interdigitated gold electrodes coated with a self-assembled monolayer and a layer of anti-CA19-9 antibodies, which is capable of detecting the pancreatic cancer biomarker CA19-9 using electrical impedance spectroscopy. Due to specific, irreversible adsorption of CA19-9 onto its corresponding antibody, according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), the immunosensor is highly sensitive and selective. It could detect CA19-9 in commercial samples with a limit of detection of 0.68 U mL−1, in addition to distinguishing between blood serum samples from patients with different concentrations of CA19-9. Furthermore, by treating the capacitance data with information visualization methods, we were able to verify the selectivity and robustness of the immunosensor with regard to false positives, as the samples containing higher CA19-9 concentrations, including those from tumor cells, could be distinguished from those with possible interferents.CAPES, FAPESP (Grant 2013/14262-7 and 2012/15543-7), CNPq (150985/2017-7), nBioNet network and Barretos Cancer Hospital for financial supportinfo:eu-repo/semantics/publishedVersio

Estresse ocupacional em profissionais enfermeiros: revisão literária / Occupational stress in professional nurses: literary review

As diferentes e novas formas organizativas do processo de trabalho passam por alterações complexas, profundas e sofisticadas, refletindo na saúde dos trabalhadores, e alguns ambientes laborais são mais propensos para desenvolver doenças ocupacionais, sobretudo a área da saúde, e com maior potencial para o adoecimento por estresse. O estresse é caracterizado como um processo psicofisiológico gerando sintomas de irregularidades hormonais. Os enfermeiros são os mais expostos por diversos fatores, tais como, sobrecarga de trabalho, principiantes em início de carreira, as condições inadequadas para o desempenho da atividade profissional, a relação com paciente, conflitos interpessoais com outros profissionais, e óbito de pacientes, interferindo tanto na vida pessoal quanto profissional

Cardiopatia chagásica em pacientes idosos / Chagasic cardiomyopathy in elderly patients

O envelhecimento populacional é um fenômeno mundial, que passa por um percurso progressivo no decorrer da vida, resultando em distintas alterações biopsicossociais, e traz consigo maior probabilidade de morbidades relacionadas a doenças crônicas como a doença de chagas, associadas a complicações cardiovasculares. Á cardiopatia chagásica em idosos é, portanto, ainda nos dias de hoje um grave problema de saúde pública

A relação entre a terapia de reposição hormonal e o câncer de mama: revisão de literatura / The relationship between hormone replacement therapy and breast cancer: literature review

Para amenizar os efeitos da menopausa, foi desenvolvido o tratamento de Terapia de Reposição Hormonal (TRH), que apresenta riscos e benefícios. Destaca-se dentre os principais riscos, o desenvolvimento de câncer de mama conforme o tempo da terapia. A TRH em mulheres sem histórico de neoplasia mamaria ainda é controversa, sendo indicado por um período máximo de cinco anos

Immunosensor for pancreatic cancer based on electrospun nanofibers coated with carbon nanotubes or gold nanoparticles

We report the fabrication of immunosensors based on nanostructured mats of electrospun nanofibers of polyamide 6 and poly(allylamine hydrochloride) coated either with multiwalled carbon nanotubes (MWCNTs) or gold nanoparticles (AuNPs), whose three-dimensional structure was suitable for the immobilization of anti-CA19-9 antibodies to detect the pancreatic cancer biomarker CA19-9. Using impedance spectroscopy, the sensing platform was able to detect CA19-9 with a detection limit of 1.84 and 1.57 U mL-1 for the nanostructured architectures containing MWCNTs and AuNPs, respectively. The high sensitivity achieved can be attributed to the irreversible adsorption between antibodies and antigens, as confirmed with polarization-modulated infrared reflection absorption spectroscopy. The adsorption mechanism was typical Langmuir-Freundlich processes. The high sensitivity and selectivity of the immunosensors were also explored in tests with blood serum from patients with distinct concentrations of CA19-9, for which the impedance spectra data were processed with a multidimensional projection technique. The robustness of the immunosensors in dealing with patient samples without suffering interference from analytes present in biological fluids is promising for a simple, effective diagnosis of pancreatic cancer at early stages.This work was supported by FAPESP (Grant 2013/14262-7), CNPq, and CAPES (Brazil). D.S.C. also thanks FAPESP (Grant 2014/16789-5), Embrapa−Rede Agronano, and MCTI SisNano for financial support.info:eu-repo/semantics/publishedVersio

Three decades of research on Iberian wild Carnivora: trends, highlights, and future directions

1. Mammalian carnivores (Carnivora) are crucial components of landscapes, because of both their top-down effects on lower trophic level species and their sensitivity to bottom-up processes, such as limited food resources (e.g. due to climate instability). To understand their functional role in Iberian ecosystems more clearly, and to define effective plans for their management and conservation, it is crucial to sum up the available regional knowledge that can inform decision-making processes.2. We review bio-ecological research on wild Iberian carnivores over 30 years (1990–2020) and identify key knowledge gaps and priority avenues for future research. Based on a systematic review of the scientific literature, we aimed to: 1) summarise current knowledge; 2) assess species and ecoregion representativeness; 3) identify key research topics addressed and those lacking investment and 4) suggest key future research priorities.3. We examined 920 peer-reviewed articles involving wild Iberian mammalian carnivores, focusing on different bio-ecological issues. We found considerable heterogeneity in the topics and species investigated, as well as in the study areas (ecoregions) explored, with a mismatch between the research priorities identified by researchers and the knowledge gaps.4. We suggest that future research should prioritise: 1) rear-edge populations that are at the southwestern limits of the species' Eurasian range, thus being particularly sensitive to the increasing fragmentation and aridity of Iberian ecosystems, and that were less studied (e.g. brown bear Ursus arctos, stoat Mustela erminea, European mink Mustela lutreola and pine marten Martes martes); 2) less-studied topics, such as morphometry and body condition, ecophysiology, and reproductive biology, all of which provide essential information for species' management and conservation and 3) specific ecoregions for which studies on species' adaptations to environmental and anthropic contexts are lacking (e.g. northern ecoregions of Iberia, Iberian conifer forests and Northwest Iberian montane forests). Our review provides the necessary background to support future research on carnivore populations in Iberia.João Carvalho was supported by a research contract (CEECIND/01428/2018) from the Fundação para a Ciência e a Tecnologia (FCT). Nuno Santos was also supported by Fundação para a Ciência e Tecnologia (SFRH/BPD/116596/2016). Carlos Fernandes appreciates the support of cE3c through an Assistant Researcher contract (FCiência.ID contract #366) and FCT (Fundação para a Ciência e a Tecnologia) for Portuguese National Funds attributed to cE3c within the strategic project UID/BIA/00329/2020. Carlos Fernandes also thanks FPUL for a contract of Invited Assistant Professor. Pedro Monterroso was supported by UID/BIA/50027/2021 with funding from FCT/MCTES through national funds. Thanks are due to FCT/MCTES for the financial support to cE3c (UIDB/00329/2020), CHANGE (LA/P/0121/2020) and CESAM (UIDP/50017/2020 + UIDB/50017/2020+ LA/P/0094/2020), through national funds, and FEDER co-funding within the PT2020 Partnership Agreement and Compete 2020. This work was also financially supported by: i) project POCI-01-0145-FEDER-028204 (WildForests) funded by FEDER, through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI), and by national funds (OE) through FCT/MCTES; Project ref. 2022.03253.PTDC (ForCe), funded by national funds (OE) through FCT; iii) project NORTE-01-0246-FEDER-000063, supported by the Norte Portugal Regional Operational Programme (NORTE2020) under the PORTUGAL 2020 Partnership Agreement and through the European Regional Development Fund (ERDF).Peer reviewe