Clinical standards for diagnosis, treatment and prevention of post-COVID-19 lung disease

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice' care for the diagnosis, treatment and prevention of post-COVID-19 lung disease.METHODS: A panel of international experts representing scientific societies, associations and groups active in post-COVID-19 lung disease was identified; 45 completed a Delphi process. A 5-point Likert scale indicated level of agreement with the draft standards. The final version was approved by consensus (with 100% agreement).RESULTS: Four clinical standards were agreed for patients with a previous history of COVID-19: Standard 1, Patients with sequelae not explained by an alternative diagnosis should be evaluated for possible post-COVID-19 lung disease; Standard 2, Patients with lung function impairment, reduced exercise tolerance, reduced quality of life (QoL) or other relevant signs or ongoing symptoms ≥4 weeks after the onset of first symptoms should be evaluated for treatment and pulmonary rehabilitation (PR); Standard 3, The PR programme should be based on feasibility, effectiveness and cost-effectiveness criteria, organised according to local health services and tailored to an individual patient's needs; and Standard 4, Each patient undergoing and completing PR should be evaluated to determine its effectiveness and have access to a counselling/health education session.CONCLUSION: This is the first consensus-based set of clinical standards for the diagnosis, treatment and prevention of post-COVID-19 lung disease. Our aim is to improve patient care and QoL by guiding clinicians, programme managers and public health officers in planning and implementing a PR programme to manage post-COVID-19 lung disease.CONTEXTE : L’objectif de ces normes cliniques est de fournir des conseils sur les « meilleures pratiques » en matière de diagnostic, de traitement et de prévention des maladies pulmonaires post-COVID-19. MÉTHODES : Un groupe d’experts internationaux représentant des sociétés scientifiques, des associations et des groupes actifs dans le domaine des maladies pulmonaires post-COVID-19 a été constitué ; 45 d’entre eux ont participé à un processus Delphi. Une échelle de Likert en 5 points a permis d’indiquer le niveau d’accord avec les projets de normes. La version finale a été approuvée par consensus (100% d’accord). RÉSULTATS : Quatre normes cliniques ont été approuvées pour les patients ayant des antécédents de COVID-19 : Norme 1, les patients présentant des séquelles non expliquées par un autre diagnostic doivent être évalués en vue d’une éventuelle maladie pulmonaire post-COVID-19 ; Norme 2, les patients présentant une altération de la fonction pulmonaire, une diminution de la tolérance à l’effort, une réduction de la qualité de vie (QoL) ou d’autres signes pertinents ou des symptômes persistants, quatre semaines ou plus après l’apparition des premiers symptômes, doivent être évalués en vue d’un traitement et d’une réadaptation pulmonaire (PR, de l’anglais ‘pulmonaire rehabilitation’) ; Norme 3, le programme de PR doit être basé sur des critères de faisabilité, d’efficacité et de rentabilité, organisé en fonction des services de santé locaux et adapté aux besoins individuels des patients ; et Norme 4, chaque patient qui suit et termine un programme de PR doit être évalué pour déterminer son efficacité et avoir accès à une session de conseil/éducation à la santé. CONCLUSION : Il s’agit du premier ensemble consensuel de normes cliniques pour le diagnostic, le traitement et la prévention des maladies pulmonaires post-COVID-19. Notre objectif est d’améliorer les soins et la qualité de vie des patients en guidant les cliniciens, les responsables de programmes et les responsables de la santé publique dans la planification et la mise en œuvre d’un programme de relations publiques pour la prise en charge des maladies pulmonaires post-COVID-19

RG108 increases NANOG and OCT4 in bone marrow-derived mesenchymal cells through global changes in DNA modifications and epigenetic activation. RG108 increases NANOG and OCT4 through epigenetic activation.

Human bone marrow-derived mesenchymal stem cells (hBMSCs) are important for tissue regeneration but their epigenetic regulation is not well understood. Here we investigate the ability of a non-nucleoside DNA methylation inhibitor, RG108 to induce epigenetic changes at both global and gene-specific levels in order to enhance mesenchymal cell markers, in hBMSCs. hBMSCs were treated with complete culture medium, 50 μM RG108 and DMSO for three days and subjected to viability and apoptosis assays, global and gene-specific methylation/hydroxymethylation, transcript levels' analysis of epigenetic machinery enzymes and multipotency markers, protein activities of DNMTs and TETs, immunofluorescence staining and western blot analysis for NANOG and OCT4 and flow cytometry for CD105. The RG108, when used at 50 μM, did not affect the viability, apoptosis and proliferation rates of hBMSCs or hydroxymethylation global levels while leading to 75% decrease in DNMTs activity and 42% loss of global DNA methylation levels. In addition, DNMT1 was significantly downregulated while TET1 was upregulated, potentially contributing to the substantial loss of methylation observed. Most importantly, the mesenchymal cell markers CD105, NANOG and OCT4 were upregulated being NANOG and OCT4 epigenetically modulated by RG108, at their gene promoters. We propose that RG108 could be used for epigenetic modulation, promoting epigenetic activation of NANOG and OCT4, without affecting the viability of hBMSCs. DMSO can be considered a modulator of epigenetic machinery enzymes, although with milder effect compared to RG108

Steer performance on deferred pastures of Brachiaria brizantha and Brachiaria decumbens

ABSTRACT The objective of this study was to compare structural, morphological and bromatological characteristics of forage as well as performance of Caracu beef cattle (200 ± 9 kg of initial body weight) supplemented with a multi-mineral mixture (0.25% of body weight) on deferred pastures of , digestibilidade in vitro da matéria orgânica (57,7 vs 53, 9 ± 0,4%), os menores teores de fibra em detergente neutro (69,2 vs 72,7 ± 0,4%

Inclusão x formação de professor

Uma nova perspectiva surge no sistema educacional: a inclusão, que contempla a construção de uma sociedade não excludente em que a diversidade é respeitada. Na declaração de Salamanca (1884), “inclusão e participação são essenciais à dignidade humana e ao gozo e exercício dos direitos humanos. No campo da educação, tal se reflete no desenvolvimento de estratégias que procuram proporcionar uma equalização genuína de oportunidades”. Assim sendo, é importante que haja ressignificação da formação de professores para o desenvolvimento de culturas, políticas e práticas de inclusão. O presente trabalho teve como objetivo investigar as deficiências na capacitação dos profissionais de educação com relação à orientação inclusiva para os alunos com necessidades educacionais especiais. A pesquisa evidenciou-se por meio de uma abordagem qualitativa, onde os sujeitos não são concebidos como seres passivos e sim como sujeitos históricos possuidores de constituição subjetiva construída a partir da inserção em determinado contexto social e segundo suas singularidades. Conforme Lüdke e André (1986) a “pesquisa qualitativa supõe o contato direto e prolongado do pesquisador com o ambiente e a situação que está sendo investigada, via de regra através do trabalho intensivo de campo”. A pesquisa realizou-se em uma escola pública de ensino fundamental do Distrito Federal. Essa escola é de ensino regular com turmas de inclusão. Os sujeitos da pesquisa foram: professor regente, diretor, coordenador pedagógico e aluno. Foram aplicados os seguintes instrumentos: análise documental, observação participante e entrevistas semi-estruturadas. Os resultados foram organizados em três categorias de análise: inclusão, mediação e formação de professores. Nesta escola, a inclusão não acontece, pois não há recursos físicos, administrativos e pedagógicos necessários para atender os alunos com necessidades educacionais especiais. A mediação é evidenciada, pois professores e alunos produzem conhecimento em interação, num diálogo coletivo que oportuniza uma aprendizagem significativa. A escola não se reconhece como espaço de formação para professores, as coordenações coletivas não favorecem estudos que gerem movimentos de busca e de renovação por novas teorias e novas práticas. As categorias apontam pontos positivos e negativos, sendo que na escola pesquisada, os pontos negativos sobressaem-se sobre os positivos. A análise dos resultados remete à conclusão de que há um longo caminho a ser percorrido, pois a inclusão ainda encontra-se em processo de construção e a deficiência na formação dos professores dificulta e até mesmo, inviabiliza esse processo. Entretanto a mediação se efetiva num processo dinâmico e coletivo que se dá na interação professor-aluno-meio

Indole-Containing Pyrazino[2,1-b]quinazoline-3,6-diones Active against Plasmodium and Trypanosomatids

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00589.Malaria, leishmaniasis, and sleeping sickness are potentially fatal diseases that represent a real health risk for more than 3,5 billion people. New antiparasitic compounds are urgent leading to a constant search for novel scaffolds. Herein, pyrazino[2,1-b]quinazoline-3,6-diones containing indole alkaloids were explored for their antiparasitic potential against Plasmodium falciparum, Trypanosoma brucei, and Leishmania infantum. The synthetic libraries furnished promising hit compounds that are species specific (7, 12) or with broad antiparasitic activity (8). Structure-activity relationships were more evident for Plasmodium with anti-isomers (1S,4R) possessing excellent antimalarial activity, while the presence of a substituent on the anthranilic acid moiety had a negative effect on the activity. Hit compounds against malaria did not inhibit β-hematin, and in silico studies predicted these molecules as possible inhibitors for prolyl-tRNA synthetase both from Plasmodium and Leishmania. These results disclosed a potential new chemotype for further optimization toward novel and affordable antiparasitic drugs.publishersversionpublishe

what is the evidence?

Background: This study's aims are to assess the current evidence presented in the literature regarding the potential risks of COVID-19 infection among pregnant women and consequent fetal transmission. Methods: a systematic literature review assessing papers published in the most comprehensive databases in the field of health intended to answer the question, "What are the effects of COVID-19 infection during pregnancy, and what is the neonatal prognosis?" Results: 49 papers published in 2020 were eligible, presenting low levels of evidence. A total of 755 pregnant women and 598 infants were assessed; more than half of pregnant women had C-sections (379/65%). Only 493 (82%) infants were tested for SARS-CoV-2, nine (2%) of whom tested positive. There is, however, no evidence of vertical transmission based on what has been assessed so far, considering there are knowledge gaps concerning the care provided during and after delivery, as well as a lack of suitable biological samples for testing SARS-CoV-2. Conclusions: We cannot rule out potential worsening of the clinical conditions of pregnant women infected with SARS-CoV-2, whether the infection is associated with comorbidities or not, due to the occurrence of respiratory disorders, cardiac rhythm disturbances, and acid-base imbalance, among others. We recommend relentless monitoring of all pregnant women in addition to testing them before delivery or the first contact with newborns.publishersversionpublishe

Different Assay Conditions for Detecting the Production and Release of Heat-Labile and Heat-Stable Toxins in Enterotoxigenic Escherichia coli Isolates

Enterotoxigenic Escherichia coli (ETEC) produce heat-labile (LT) and/or heat-stable enterotoxins (ST). Despite that, the mechanism of action of both toxins are well known, there is great controversy in the literature concerning the in vitro production and release of LT and, for ST, no major concerns have been discussed. Furthermore, the majority of published papers describe the use of only one or a few ETEC isolates to define the production and release of these toxins, which hinders the detection of ETEC by phenotypic approaches. Thus, the present study was undertaken to obtain a better understanding of ST and LT toxin production and release under laboratory conditions. Accordingly, a collection of 90 LT-, ST-, and ST/LT-producing ETEC isolates was used to determine a protocol for toxin production and release aimed at ETEC detection. for this, we used previously raised anti-LT antibodies and the anti-ST monoclonal and polyclonal antibodies described herein. the presence of bile salts and the use of certain antibiotics improved ETEC toxin production/release. Triton X-100, as chemical treatment, proved to be an alternative method for toxin release. Consequently, a common protocol that can increase the production and release of LT and ST toxins could facilitate and enhance the sensitivity of diagnostic tests for ETEC using the raised and described antibodies in the present work.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Butantan Inst, Bacteriol Lab, BR-05503900 São Paulo, BrazilSão Paulo Trop Med Inst, Seroepidemiol & Immunol Lab, BR-05403000 São Paulo, BrazilFleury Med & Hlth, BR-04344903 São Paulo, BrazilButantan Inst, Immunopathol Lab, BR-05503900 São Paulo, BrazilButantan Inst, Immunochem Lab, BR-05503900 São Paulo, BrazilAdolfo Lutz Inst, Bacteriol Sect, BR-01246000 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol, BR-04923062 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol, BR-04923062 São Paulo, SP, BrazilWeb of Scienc

PRODH Polymorphisms, Cortical Volumes and Thickness in Schizophrenia

Schizophrenia is a neurodevelopmental disorder with high heritability. Several lines of evidence indicate that the PRODH gene may be related to the disorder. Therefore, our study investigates the effects of 12 polymorphisms of PRODH on schizophrenia and its phenotypes. To further evaluate the roles of the associated variants in the disorder, we have conducted magnetic resonance imaging (MRI) scans to assess cortical volumes and thicknesses. A total of 192 patients were evaluated using the Structured Clinical Interview for DSM-IV (SCID), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale, Global Assessment of Functioning (GAF) and Clinical Global Impression (CGI) instruments. the study included 179 controls paired by age and gender. the samples were genotyped using the real-time polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP)-PCR and Sanger sequencing methods. A sample of 138 patients and 34 healthy controls underwent MRI scans. One polymorphism was associated with schizophrenia (rs2904552), with the G-allele more frequent in patients than in controls. This polymorphism is likely functional, as predicted by PolyPhen and SIFT, but it was not associated with brain morphology in our study. in summary, we report a functional PRODH variant associated with schizophrenia that may have a neurochemical impact, altering brain function, but is not responsible for the cortical reductions found in the disorder.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo UNIFESP, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psiquiatria, São Paulo, BrazilFac Med ABC FMABC, Dept Ginecol & Obstet, Disciplina Genet & Reprod Humana, São Paulo, BrazilFed Univ Para, Lab Genet Humana & Med, BR-66059 Belem, Para, BrazilUniv Fed ABC, Ctr Math Computat & Cognit, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Disciplina Genet, Dept Morfol & Genet, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, LiNC, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psiquiatria, São Paulo, BrazilFAPESP: 2011/50740-5FAPESP: 2007/58736-1Web of Scienc

Immature Dengue Virus Is Infectious in Human Immature Dendritic Cells via Interaction with the Receptor Molecule DC-SIGN

BACKGROUND: Dengue Virus (DENV) is the most common mosquito-borne viral infection worldwide. Important target cells during DENV infection are macrophages, monocytes, and immature dendritic cells (imDCs). DENV-infected cells are known to secrete a large number of partially immature and fully immature particles alongside mature virions. Fully immature DENV particles are considered non-infectious, but antibodies have been shown to rescue their infectious properties. This suggests that immature DENV particles only contribute to the viral load observed in patients with a heterologous DENV re-infection. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we re-evaluated the infectious properties of fully immature particles in absence and presence of anti-DENV human serum. We show that immature DENV is infectious in cells expressing DC-SIGN. Furthermore, we demonstrate that immature dendritic cells, in contrast to macrophage-like cells, do not support antibody-dependent enhancement of immature DENV. CONCLUSIONS/SIGNIFICANCE: Our data shows that immature DENV can infect imDCs through interaction with DC-SIGN, suggesting that immature and partially immature DENV particles may contribute to dengue pathogenesis during primary infection. Furthermore, since antibodies do not further stimulate DENV infectivity on imDCs we propose that macrophages/monocytes rather than imDCs contribute to the increased viral load observed during severe heterotypic DENV re-infections