FTY720 induces apoptosis in B16F10-NEX2 murine melanoma cells, limits metastatic development in vivo, and modulates the immune system

OBJECTIVE: Available chemotherapy presents poor control over the development of metastatic melanoma. FTY720 is a compound already approved by the Food and Drug Administration for the treatment of patients with multiple sclerosis. It has also been observed that FTY720 inhibits tumor growth in vivo (experimental models) and in vitro (animal and human tumor cells). The aim of this study was to evaluate the effects of FTY720 on a metastatic melanoma model and in tumor cell lines. METHODS: We analyzed FTY720 efficacy in vivo in a syngeneic murine metastatic melanoma model, in which we injected tumor cells intravenously into C57BL/6 mice and then treated the mice orally with the compound for 7 days. We also treated mice and human tumor cell lines with FTY720 in vitro, and cell viability and death pathways were analyzed. RESULTS: FTY720 treatment limited metastatic melanoma growth in vivo and promoted a dose-dependent decrease in the viability of murine and human tumor cells in vitro. Melanoma cells treated with FTY720 exhibited characteristics of programmed cell death, reactive oxygen species generation, and increased β-catenin expression. In addition, FTY720 treatment resulted in an immunomodulatory effect in vivo by decreasing the percentage of Foxp3+ cells, without interfering with CD8+ T cells or lymphocyte-producing interferon-gamma. CONCLUSION: Further studies are needed using FTY720 as a monotherapy or in combined therapy, as different types of cancer cells would require a variety of signaling pathways to be extinguished.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Conselho Nacional de Pesquisa e Desenvolvimento (CNPq)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina (EPM-UNIFESP) Departamento de Microbiologia, Imunologia e ParasitologiaUNIFESP, EPM, (EPM-UNIFESP) Depto. de Microbiologia, Imunologia e Parasitologia2008/51256-7SciEL

O PAPEL DO AGENTE COMUNITÁRIO DE SAÚDE FRENTE AO DESAFIO DA NOVA POLÍTICA NACIONAL DE ATENÇÃO BÁSICA

Este ensaio propõe-se a discorrer sobre o papel do Agente Comunitário de Saúde (ACS) à luz do novo texto da Política Nacional de Atenção Básica (PNAB). Partindo da atuação específica desse profissional, o artigo busca contribuir com reflexões acerca do modelo de atenção à saúde que poderá se consolidar a partir dessas transformações. O ACS é essencial na implementação do Sistema Único de Saúde (SUS) por fortalecer a integração entre os serviços de Atenção Básica à Saúde e a comunidade. É personagem protagonista na efetivação de uma prática que considere o conceito ampliado de saúde. Seu trabalho tem como principal objetivo contribuir para a qualidade de vida das pessoas e da comunidade, atuando desde a identificação dos fatores que interferem na saúde, promoção da saúde e prevenção de doenças, exercendo inclusive a função de estimular e organizar as reivindicações da comunidade. As mudanças no texto da PNAB devem ser acompanhadas com atenção, uma vez que o ACS enquanto profissional da equipe da Estratégia Saúde da Família, é um agente promotor de saúde que dialoga com as pessoas em seus territórios e que atua nas desigualdades em saúde

Artisanal cheese of Minas Gerais, not all are AMC: a brief review

The artisanal Minas cheese (AMC) is a product widely produced and consumed throughout the state of Minas Gerais, with the regions of Araxá, Campo das Vertentes, Canastra, Cerrado, Ibitipoca, Serra do Salitre, Serro, Triângulo considered as the eight traditional regions of artisanal Minas cheese. With the publication of the Law 23,157, of December 18, 2018, related to the production and sale of artisanal cheeses in Minas Gerais, other artisanal cheese varieties could also be recognized and regularized, in addition to the AMC. Among the varieties of artisanal cheeses of Minas Gerais (ACM), which are not AMC, are: artisanal cheese from Alagoa, artisanal Mantiqueira de Minas cheese, Cabacinha cheese, artisanal cheese from Vale do Suaçuí, artisanal cheese from Serra Geral, and also the artisanal processed cheese, known as requeijão Moreno. While the AMC must follow a standard manufacturing technology in all regions where it is produced, other artisanal cheeses made in Minas Gerais have some particularities, such as heating and cooking the curd, melting, or stretching, among other steps that are not allowed in the AMC. In short, artisanal cheeses of Minas Gerais include artisanal Minas cheeses (AMC) and artisanal cheeses that have specific manufacturing technology only for their variety. The artisanal cheeses of Minas Gerais are part of history and culture of the state, however they have not yet been extensively studied, so there are not many scientific publications about their characteristics and how these cheeses are made. In this context, this review aimed to study the literature to elucidate the main characteristics of artisanal cheeses of Minas Gerais that do not fit the AMC classification, as well as their production regions and manufacturing technologies

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Extraction of the Muon Signals Recorded with the Surface Detector of the Pierre Auger Observatory Using Recurrent Neural Networks

We present a method based on the use of Recurrent Neural Networks to extract the muon component from the time traces registered with water-Cherenkov detector (WCD) stations of the Surface Detector of the Pierre Auger Observatory. The design of the WCDs does not allow to separate the contribution of muons to the time traces obtained from the WCDs from those of photons, electrons and positrons for all events. Separating the muon and electromagnetic components is crucial for the determination of the nature of the primary cosmic rays and properties of the hadronic interactions at ultra-high energies. We trained a neural network to extract the muon and the electromagnetic components from the WCD traces using a large set of simulated air showers, with around 450 000 simulated events. For training and evaluating the performance of the neural network, simulated events with energies between 1018.5, eV and 1020 eV and zenith angles below 60 degrees were used. We also study the performance of this method on experimental data of the Pierre Auger Observatory and show that our predicted muon lateral distributions agree with the parameterizations obtained by the AGASA collaboration