Identification of Two Eosinophil Subsets in Induced Sputum from Patients with Allergic Asthma According to CD15 and CD66b Expression

Allergic asthma; Eosinophil subsets; Induced sputumAsma alérgica; Subconjuntos de eosinófilos; Esputo inducidoAsma al·lèrgica; Subconjunts d'eosinòfils; Esput induïtTwo subsets of eosinophils have been described: resident eosinophils with homeostatic functions (rEOS) in healthy subjects and in patients with nonallergic eosinophilic asthma, and inflammatory eosinophils (iEOS) in blood and lung samples from patients with allergic asthma. We explored if it would be possible to identify different subsets of eosinophils using flow cytometry and the gating strategy applied to induced sputum. We conducted an observational cross-sectional single-center study of 62 patients with persistent allergic asthma. Inflammatory cells from induced sputum samples were counted by light microscopy and flow cytometry, and cytokine levels in the supernatant were determined. Two subsets of eosinophils were defined that we call E1 (CD66b-high and CD15-high) and E2 (CD66b-low and CD15-low). Of the 62 patients, 24 were eosinophilic, 18 mixed, 10 paucigranulocytic, and 10 neutrophilic. E1 predominated over E2 in the eosinophilic and mixed patients (20.86% vs. 6.27% and 14.42% vs. 4.31%, respectively), while E1 and E2 were similar for neutrophilic and paucigranulocytic patients. E1 correlated with IL-5, fractional exhaled nitric oxide, and blood eosinophils. While eosinophil subsets have been identified for asthma in blood, we have shown that they can also be identified in induced sputum.This research was supported by the Spanish Allergy and Clinical Immunology Society (SEAIC) by means of a grant awarded in the call of 2017 (reference 17/06) and a BRN—Fundació Pla i Armengol grant in the call of 2018. The funds provided contributed to the acquisition of the material necessary to carry out the study, but the collaborating entities had no role in the analysis or interpretation of the results

Characteristics of Induced-Sputum Inflammatory Phenotypes in Adults with Asthma : Predictors of Bronchial Eosinophilia

The objectives of this study were, for patients attending a specialist asthma clinic at a tertiary care hospital, to determine, from sputum induction (SI), proportions of bronchial inflammatory phenotypes, demographic, clinical and functional characteristics of each phenotype, and the most accessible non-invasive inflammatory marker that best discriminates between phenotypes. Included were 96 patients with asthma, attending a specialist asthma clinic at a tertiary care hospital, who underwent testing as follows: SI, spirometry, fractional exhaled nitric oxide (FeNO), blood eosinophilia, total immunoglobulin E (IgE), and a skin prick test. SI phenotypes were 46.9% eosinophilic, 33.3% paucigranulocytic, 15.6% neutrophilic, and 4.2% mixed. No significantly different clinical or functional characteristics were observed between the phenotypes. A positive correlation was observed between SI eosinophilia and both emergency visits in the last 12 months (p = 0.041; r = 0.214) and FeNO values (p = 0.000; r = 0.368). Blood eosinophilia correlated with SI eosinophilia (p = 0.001; r = 0.362) and was the best predictor of bronchial eosinophilia, followed by FeNO, and total blood IgE (area under the receiver operating characteristic curve (AUC-ROC) 72%, 65%, and 53%, respectively), although precision was only fair. In consultations for severe asthma, the most frequent phenotype was eosinophilic. Peripheral blood eosinophilia is a reliable marker for discriminating between different bronchial inflammatory phenotypes, is useful in enabling doctors to select a suitable biologic treatment and so prevent asthma exacerbation, and is a better predictor of bronchial eosinophilia than FeNO and IgE values

Biotecnologia a serviço do homem: ponderações acerca da manipulação genética na perspectiva da ética da responsabilidade, de Hans Jonas

As possibilidades advindas dos avanços tecnocientíficos são consideradas fórmulas de medição para o desenvolvimento de sociedades modernas. Na mesma linha, segue a manipulação genética, uma vez que cria – ainda que desconhecido seu alcance – mecanismos de melhoramento de organismos com o fim de alcançar o aprimoramento da vida, saúde e reprodução humana. Contudo, pode em certos casos, dar lugar para problemas sociais que ameaçam diretamente as liberdades individuais e dignidade dos indivíduos, sobretudo quando unicamente voltada aos interesses mercadológicos que suscitam a coisificação humana. Nesse parâmetro, o presente artigo, por intermédio do método dedutivo e revisão bibliográfica, indaga em que medida a ética da responsabilidade, de Hans Jonas, problematiza o ideal mercadológico e controlador, mantendo um prognóstico de felicidade social, com escopo de demonstrar que o princípio da responsabilidade, fundamentado na ética intergeracional, visa concretizar uma fórmula de equiparação temporal, onde o futuro faça parte do presente, tornando-se imprescindível a adoção de estratégias de mitigação dos riscos biotecnológicos. Com efeito, torna-se necessário o debate, ainda que, em um primeiro momento, hipotético, acerca da prevalência da ética da responsabilidade sobre a manipulação genética, sendo uma possível forma de se prever consequências danosas às futuras gerações.Palavras-chave: Manipulação genética; ética da responsabilidade; Hans Jonas

Editorial dossiê “Bioética, Meio Ambiente e Saúde Global: perspectivas científicas, epistêmicas e sociais”

O dossiê “Bioética, Meio Ambiente e Saúde Global: perspectivas científicas, epistêmicas e sociais”, publicado na Revista Humanidades & Tecnologia (FINOM), elege a Bioética, especialmente com enfoque ambiental, enquanto disciplina que reúne perspectivas de diversas áreas do conhecimento (como a medicina, biologia, química, antropologia, sociologia, filosofia, direito, entre outras), pela interdisciplinaridade, permitindo avaliar os fenômenos relacionados a vida em sentido amplo, suscitando reflexões sobre a ética animal e ambiental, sociedade tecnocientífica e sustentabilidade, justiça climática e socioambiental, cidadania ecológica, entre tantos outros recortes e perspectivas possíveis

Aprimoramento humano entre riscos e benefícios: considerações éticas e jurídicas a partir da distopia “Divergente”

Resumo: Desde épocas mais remotas, o ser humano sempre buscou a evolução, seja no meio ou em si próprio, e as formas pelas quais ela poderia se realizar. Com os constantes avanços da ciência e tecnologia, a partir do século XX, foi possível realizar grandes descobertas da natureza humana, sobretudo no âmbito da genética, e com elas implementar mudanças na forma de viver, além de possibilitar práticas de manipulação genética, como forma de alcançar o aprimoramento humano. Com base nessas premissas, o presente artigo tem por objetivo geral analisar as repercussões infligidas à humanidade em virtude da manipulação genética, a partir de uma visão distópica e transumanista, com base na trilogia “Divergente”, de Veronica Roth. O estudo está amparado no método dedutivo e em revisão bibliográfica e documental. Nessa perspectiva, é possível constatar a maneira pela qual a literatura contemporânea, principalmente do gênero de ficção científica, aborda a dicotomia entre os benefícios e malefícios da ciência e tecnologia, notadamente quando utilizadas sem o devido controle e fiscalização estatal. Tal análise proporciona um interessante pano de fundo para debates éticos e jurídicos acerca dos avanços e limites das novas tecnologias na sociedade. Trata-se do observar o modo pelo qual o ordenamento jurídico pátrio incorporou os avanços científicos e tecnológicos e decidiu por legislar sobre as técnicas de manipulação e engenharia genética humana e outras, ressaltando a permanente necessidade de imposição de limites e fiscalização aos assuntos biotecnológicos, com o fim de evitar a violação aos direitos humanos e garantias fundamentais.Palavras-chave: Manipulação genética; aprimoramento humano; trilogia divergente

The Effect of ACTN3 and VDR Polymorphisms on Skeletal Muscle Performance in Axial Spondyloarthropathies

Funding Information: This study was supported by the funding through project MyoSpA, from iNOVA4 health. PM was supported by the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre (BRC). Publisher Copyright: © Copyright © 2021 Pimenta, Mateus, Rodrigues-Manica, Pinheiro-Torres, Neto, Domingues, Lage Crespo, Sardoo, Machado, Branco, Silva and Pimentel-Santos.PBackground: Spondyloarthritis (SpA) are the most common group of chronic inflammatory rheumatic diseases affecting about 1.5% of the adult Caucasian population. Low back pain is the most common symptom. The aetiopathogenesis of SpA is multifactorial, with well-known genetic and environmental contributions. Furthermore, muscle properties might also be involved in the pathophysiological process and these could be modulated by the genetic background. Alpha-actinin-3 (ACTN3) and Vitamin D receptor (VDR) genes are well-known genes related with muscle performance. Our aim was to analyze four SNPs of these genes and to evaluate their influence in axial SpA (axSpA) susceptibility, phenotype and muscle properties. Methods: We performed a pilot study based on case-control approach involving 56 participants: 28 axSpA patients and 28 healthy controls matched by age, gender and levels of physical activity. Clinical, epidemiological and muscle characterization data—muscle physical properties (stiffness, tone, and elasticity), strength, mass, and performance, were collected. Two different muscles were considered for analysis, the Multifidus and Gastrocnemius. Four SNPs of ACTN3 (rs1815739) and VDR (rs2228570, rs731236, and rs7975232), were selected, analyzed and correlated with clinical, epidemiological and muscle characterization data. Results: In total, 51 individuals (27 axSpA patients and 24 matched controls) were eligible for further genetic analysis, 66.7% being male and with a mean age of 36 years. Muscle physical properties, muscle strength and muscle mass were similar in both groups; however, axSpA patients showed a decrease in muscle performance. None of the studied SNPs were associated with disease susceptibility/phenotype, muscle physical properties, muscle strength or muscle mass. However, ACTN3 rs1815739 and VDR rs2228570 were shown to be associated with muscle performance. Conclusion: Our results suggest an association between ACTN3 and VDR polymorphisms and muscle performance in axSpA.publishersversionpublishe

Asthma with bronchial hypersecretion : expression of mucins and toll-like receptors in sputum and blood

1) Define the clinical and inflammatory phenotype of asthma with bronchial hypersecretion of mucus. 2) Compare the type of mucin present in induced sputum (IS) of patients with and without bronchial hypersecretion. 3) Determine the expression of TLRs in IS and blood of asthmatics with and without bronchial hypersecretion. Cross-sectional study which included 43 non-smoking asthmatic patients without bronchiectasis, 19 with bronchiectasis, and 24 without bronchial hypersecretion. All patients underwent the following: IS, spirometry, fractional exhaled nitric oxide, prick test, total immunoglobulin E (IgE), and blood albumin. Analysis of mucins was determined by ELISA and expression of TLR2 and TLR4 by flow cytometry. The level of asthma control was determined by the Asthma Control Test (ACT) questionnaire and quality of life was assessed by the reduced version of the Asthma Quality of Life Questionnaire (mini-AQLQ). Asthmatics with bronchial hypersecretion were significantly older (62.6 years vs 48.5 years; p =0.02); had greater severity (persistent severe asthma 94.7% vs 29.2%; p =0.000); a higher proportion of nasal polyposis (36.8% vs 8.3%; p =0.022); less control of asthma (73.7% vs 8.3%; p =0,000); a higher proportion of asthma with negative prick test (68.4% vs 16.6%; p =0.001), and lower levels of IgE (113.4 IU/mL vs 448 IU/mL; p =0.007), compared with asthmatics without bronchial hypersecretion. Significant differences were observed neither in the expression of TLRs 2 and 4 in inflammatory cells of IS or peripheral blood, nor in the expression of mucins between both groups. Asthma patients with bronchial hypersecretion have more severe and uncontrolled disease, with poor quality of life as well as a non-allergic inflammatory phenotype. Within the mechanisms involving these differences, it does not appear that mucins and TLRs play an important role

Phenotypic diversity of circulating tumour cells in patients with metastatic castration‐resistant prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/1/bju13631_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/2/bju13631.pd