XPlex: An Effective, Multiplex Cross-Linking Chemistry for Acidic Residues.

Cross-linking/Mass spectrometry (XLMS) is a consolidated technique for structural characterization of proteins and protein complexes. Despite its success, the cross-linking chemistry currently used is mostly based on N-hydroxysuccinimide (NHS) esters, which react primarily with lysine residues. One way to expand the current applicability of XLMS into several new areas is to increase the number of cross-links obtainable for a target protein. We introduce a multiplex chemistry (denoted XPlex) that targets Asp, Glu, Lys, and Ser residues. XPlex can generate significantly more cross-links with reactions occurring at lower temperatures and enables targeting proteins that are not possible with NHS ester-based cross-linkers. We demonstrate the effectiveness of our approach in model proteins as well as a target Lys-poor protein, SalBIII. Identification of XPlex spectra requires a search engine capable of simultaneously considering multiple cross-linkers on the same run; to achieve this, we updated the SIM-XL search algorithm with a search mode tailored toward XPlex. In summary, we present a complete chemistry/computational solution for significantly increasing the number of possible distance constraints by mass spectrometry experiments, and thus, we are convinced that XPlex poses as a real complementary approach for structural proteomics studies.

Direct Protocol for Ambient Mass Spectrometry Imaging on Agar Culture.

Herein we describe a new protocol that allows direct mass spectrometry imaging (IMS) of agar cultures. A simple sample dehydration leads to a thin solid agar, which enables the direct use of spray-based ambient mass spectrometry techniques. To demonstrate its applicability, metal scavengers siderophores were imaged directly from agar culture of S. wadayamensis, and well resolved and intense images were obtained using both desorption electrospray ionization (DESI) and easy ambient sonic-spray ionization (EASI) with well-defined selective spatial distributions for the free and the metal-bound molecules, providing clues for their roles in cellular metabolism.

Síndrome Inflamatória Multissistêmica e Covid-19 em crianças e adolescentes: aspectos epidemiológicos, Brasil, 2020-2021 / Multisystem Inflammatory Syndrome and COVID-19 in children and adolescents: epidemiological aspects, Brazil, 2020-20211

RESUMO Este estudo descreve aspectos epidemiológicos da Síndrome Inflamatória Multissistêmica Pediátrica (SIM-P) associada à Covid-19 e óbitos por Covid-19 em crianças (0-9 anos de idade) e adolescentes (10-19 anos de idade). As fontes de dados, de 2020-2021, foram os Sistemas de Vigilância Epidemiológica para SIM-P e de Informação sobre Mortalidade para Covid-19, gerenciados pelo Ministério da Saúde. Foram notificados 1.503 casos, mais frequentes em crianças (77%) do que em adolescentes (23%); e 93 óbitos por SIM-P em 26 das 27 Unidades da Federação. O maior número de casos em crianças foi notificado em São Paulo (268), contudo, a maior incidência ocorreu no Distrito Federal (7,8/100 mil habitantes). A proporção de óbitos por SIM-P foi 5,4% em crianças e 8,7% em adolescentes. No período avaliado, houve 2.329 óbitos por Covid-19 em menores de 20 anos de idade, com maior taxa em adolescentes (4,4/100 mil habitantes) do que em crianças (2,7/100 mil habitantes), com maiores taxas em Roraima. Recomenda-se intensificação da imunização contra Covid-19 nessa população, aumentando a proteção contra os efeitos negativos dessa doença e da SIM-P, que podem apresentar consequências em curto, médio e/ou longo prazo, de modo a não comprometer a inserção plena destes cidadãos na sociedade.

ABSTRACT This study describes epidemiological aspects of the Multisystemic Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 and mortality by COVID-19 in children (0-9 years old) and adolescents (10-19 years old). The data sources, for 2020-2021, were the Epidemiological Surveillance System for MIS-C and Mortality Information System for COVID-19, both managed by the Ministry of Health. There were 1,503 cases, more frequent in children (77%) than in adolescents (23%), and 93 reported deaths due to MIS-C in 26 of the 27 States of the Country. The highest number of cases in children was reported in São Paulo (268), but the highest incidence took place in the Federal District (7.8 per 100,000 inhabitants). The rate of deaths due to MIS-C was 5.4% in children and 8.7% in adolescents. There were 2,329 deaths due to COVID-19 in the population under 20 years old, with a higher rate in adolescents (4.4 per 100,000 inhabitants) than in children (2.7); the highest rate occurred in Roraima. We recommend intensifying immunization against COVID-19 in such population, increasing protection against the negative effects of COVID-19 and MIS-C, which may have short, medium and/or long-term consequences, so as not to compromise the full integration of these citizens into society.

Health collapse in Manaus: the burden of not adhering to non-pharmacological measures to reduce the transmission of Covid-19 / Colapso na saúde em Manaus: o fardo de não aderir às medidas não farmacológicas de redução da transmissão da Covid-19

ABSTRACT This article aims to compare the evolution of Covid-19 in Manaus and Fortaleza, two epicenters of the pandemic in 2020, analyzing legal measures by local governments and levels of social isolation. An algorithm was defined to calculate the Homestay Index (HSI), using data from the Google Mobility Report. We analyzed the decree's timeline, the HSI evolution, the Covid-19 incidence and the number of deaths from March/2020 to January/2021. The population of Fortaleza was exposed to more consistent measures of social distancing than that of Manaus. Longer homestay was observed from March to May 2020 and Fortaleza achieved higher and more lasting levels. As of June 2020, the HSI fell, notably in Manaus, reaching levels below zero in late December. As an aggravating factor, the government decreed broad isolation in Manaus on December 23, 2020, but after protests it was repealed on December 26, 2020. A judicial decision determined the complete closure in Manaus on January 2nd 2021, but it was too late: the SUS collapsed with an exponential increase in deaths. In Fortaleza, the demand for health services was high, but under control. We consider that only the strict application of non-pharmacological measures and mass immunization can prevent further deaths.

RESUMO Objetivou-se comparar o comportamento da Covid-19 em Manaus e Fortaleza, dois epicentros da pandemia em 2020, analisando medidas legais dos governos locais e níveis de isolamento social. Definiu-se um algoritmo para calcular o Índice de Permanência Domiciliar (IPD), com dados do Google Mobility Report. Analisaram-se a linha do tempo dos decretos, a evolução do IPD, da incidência de Covid-19 e do número de óbitos de março/2020 a janeiro/2021. A população de Fortaleza esteve exposta a medidas de distanciamento social mais consistentes que as de Manaus. Foi observado, de março a maio de 2020, uma maior permanência domiciliar, e Fortaleza atingiu níveis mais elevados e duradouros. A partir de junho, o IPD caiu, sobretudo em Manaus, atingindo níveis abaixo de zero no final de dezembro. Devido a isso, o governo decretou amplo isolamento em Manaus em 23/12/2020, mas após protestos, revogou-o em 26/12/2020. Uma decisão judicial determinava o fechamento completo em Manaus em 02/01/2021, mas foi tarde demais: o SUS entrou em colapso com aumento exponencial dos óbitos. Em Fortaleza, a demanda aos serviços de saúde estava elevada, mas sob controle. Considerou-se que somente a aplicação rigorosa de medidas não farmacológicas e imunização em massa poderiam evitar mais mortes.

Nature-inspired enzymatic cascades to build valuable compounds.

Biocatalysis currently is focusing on enzymatic and multi-enzymatic cascade processes instead of single steps imbedded into chemical pathways. Alongside this scientific revolution, this review provides an overview on multi-enzymatic cascades that are responsible for the biosynthesis of some terpenes, alkaloids and polyethers, which are important classes of natural products. Herein, we illustrate the development of studies inspired by multi- and chemo-enzymatic approaches to build the core moieties of polyethers, polypeptide alkaloids, piperidines and pyrrolidines promoted by the joint action of oxidoreductases, hydrolases, cyclases, transaminases and imine reductases.

Análise da formação pedagógica Lato Sensu em Direito Sanitário da Escola Fiocruz de Governo - Fiocruz Brasília / Analysis of the pedagogical formation Lato Sensu in Sanitary Law of the Fiocruz School of Government - Fiocruz Brasília / Análisis de la formación pedagógica Lato Sensu en Derecho Sanitario de la Escuela Fiocruz de Gobierno - Fiocruz Brasilia

Objetivo: O artigo analisou a formação pedagógica da especialização em Direito Sanitário da Escola de Governo em Saúde - Fiocruz Brasília, no período de 2006-2015. Metodologia: A pesquisa consistiu em um estudo analítico-descritivo, de caráter qualiquantitativo, baseado em pesquisa documental secundária. Foram analisados os relatórios acadêmicos e o questionário de avaliação pedagógica, realizada com os egressos. Resultados: As análises evidenciaram que houve crescimento pela procura de vagas nos processos seletivos, assim como a participação de egressos oriundos da área tanto do Direito como da Saúde. Conclusão: A implantação do curso se deu de forma exitosa, e que a especialização oferece relevantes contribuições para a qualificação de profissionais da área da saúde e demais interessadas

Objective: The study analyzed the pedagogical training of the Specialization in Sanitary Law of the School of Government in health - Brasília, in the period from 2006 to 2015. Methodology: The research consisted of an analytical-descriptive, qualitativequantitative study, based on secondary documentary research. We analyzed the academic reports and the pedagogical evaluation questionnaire, with the graduates. Results: The analyzes showed that there was growth in the search for vacancies in the selective processes, as well as the participation of graduates from both the Law and Health area. Conclusion: It was concluded that the implementation of the course was successful, and that specialization offers relevant contributions for the qualification of health professionals and others interested

Objetivo: El estudio analizó la formación pedagógica de la especialización en Derecho Sanitario de la Escuela de Gobierno en salud- Brasilia, en el período de 2006 a 2015. Metodología: La investigación consistió en un estudio analítico-descriptivo, de carácter cual-cuantitativo, basado en investigación documental secundaria. Se analizaron los informes académicos y el cuestionario de evaluación pedagógica, realizada con los egresados. Conclusión: Se concluye que la implantación del curso se dio de forma exitosa, y que la especialización ofrece relevantes contribuciones para la calificación; número de profesionales del área de la salud y demás interesadas

TOPS-MODE based QSARs derived from heterogeneous series of compounds. Applications to the design of new anti-inflammatory compounds.

A new application of TOPological Sub-structural MOlecular DEsign (TOPS-MODE) was carried out in anti-inflammatory compounds using computer-aided molecular design. Two series of compounds, one containing anti-inflammatory and the other containing nonanti-inflammatory compounds were processed by a k-means cluster analysis in order to design the training and prediction sets. A linear classification function to discriminate the anti-inflammatory from the inactive compounds was developed. The model correctly and clearly classified 88% of active and 91% of inactive compounds in the training set. More specifically, the model showed a good global classification of 90%, that is, (399 cases out of 441). While in the prediction set, they showed an overall predictability of 88% and 84% for active and inactive compounds, being the global percentage of good classification of 85%. Furthermore this paper describes a fragment analysis in order to determine the contribution of several fragments towards anti-inflammatory property, also the present of halogens in the selected fragments were analyzed. It seems that the present TOPS-MODE based QSAR is the first alternate general 'in silico' technique to experimentation in anti-inflammatory discovery.