Hypertension is one of the primary modifiable risk factors for morbidity and mortality worldwide, being a major risk factor for coronary artery disease, stroke, and kidney failure. Furthermore, it is highly prevalent, affecting more than one-third of the global population. Blood pressure measurement is a MANDATORY procedure in any medical care setting and is carried out by various healthcare professionals. However, it is still commonly performed without the necessary technical care. Since the diagnosis relies on blood pressure measurement, it is clear how important it is to handle the techniques, methods, and equipment used in its execution with care. It should be emphasized that once the diagnosis is made, all short-term, medium-term, and long-term investigations and treatments are based on the results of blood pressure measurement. Therefore, improper techniques and/or equipment can lead to incorrect diagnoses, either underestimating or overestimating values, resulting in inappropriate actions and significant health and economic losses for individuals and nations. Once the correct diagnosis is made, as knowledge of the importance of proper treatment advances, with the adoption of more detailed normal values and careful treatment objectives towards achieving stricter blood pressure goals, the importance of precision in blood pressure measurement is also reinforced. Blood pressure measurement (described below) is usually performed using the traditional method, the so-called casual or office measurement. Over time, alternatives have been added to it, through the use of semi-automatic or automatic devices by the patients themselves, in waiting rooms or outside the office, in their own homes, or in public spaces. A step further was taken with the use of semi-automatic devices equipped with memory that allow sequential measurements outside the office (ABPM; or HBPM) and other automatic devices that allow programmed measurements over longer periods (HBPM). Some aspects of blood pressure measurement can interfere with obtaining reliable results and, consequently, cause harm in decision-making. These include the importance of using average values, the variation in blood pressure during the day, and short-term variability. These aspects have encouraged the performance of a greater number of measurements in various situations, and different guidelines have advocated the use of equipment that promotes these actions. Devices that perform HBPM or ABPM, which, in addition to allowing greater precision, when used together, detect white coat hypertension (WCH), masked hypertension (MH), sleep blood pressure alterations, and resistant hypertension (RHT) (defined in Chapter 2 of this guideline), are gaining more and more importance. Taking these details into account, we must emphasize that information related to diagnosis, classification, and goal setting is still based on office blood pressure measurement, and for this reason, all attention must be given to the proper execution of this procedure.

La hipertensión arterial (HTA) es uno de los principales factores de riesgo modificables para la morbilidad y mortalidad en todo el mundo, siendo uno de los mayores factores de riesgo para la enfermedad de las arterias coronarias, el accidente cerebrovascular (ACV) y la insuficiencia renal. Además, es altamente prevalente y afecta a más de un tercio de la población mundial. La medición de la presión arterial (PA) es un procedimiento OBLIGATORIO en cualquier atención médica o realizado por diferentes profesionales de la salud. Sin embargo, todavía se realiza comúnmente sin los cuidados técnicos necesarios. Dado que el diagnóstico se basa en la medición de la PA, es claro el cuidado que debe haber con las técnicas, los métodos y los equipos utilizados en su realización. Debemos enfatizar que una vez realizado el diagnóstico, todas las investigaciones y tratamientos a corto, mediano y largo plazo se basan en los resultados de la medición de la PA. Por lo tanto, las técnicas y/o equipos inadecuados pueden llevar a diagnósticos incorrectos, subestimando o sobreestimando valores y resultando en conductas inadecuadas y pérdidas significativas para la salud y la economía de las personas y las naciones. Una vez realizado el diagnóstico correcto, a medida que avanza el conocimiento sobre la importancia del tratamiento adecuado, con la adopción de valores de normalidad más detallados y objetivos de tratamiento más cuidadosos hacia metas de PA más estrictas, también se refuerza la importancia de la precisión en la medición de la PA. La medición de la PA (descrita a continuación) generalmente se realiza mediante el método tradicional, la llamada medición casual o de consultorio. Con el tiempo, se han agregado alternativas a través del uso de dispositivos semiautomáticos o automáticos por parte del propio paciente, en salas de espera o fuera del consultorio, en su propia residencia o en espacios públicos. Se dio un paso más con el uso de dispositivos semiautomáticos equipados con memoria que permiten mediciones secuenciales fuera del consultorio (AMPA; o MRPA) y otros automáticos que permiten mediciones programadas durante períodos más largos (MAPA). Algunos aspectos en la medición de la PA pueden interferir en la obtención de resultados confiables y, en consecuencia, causar daños en las decisiones a tomar. Estos incluyen la importancia de usar valores promedio, la variación de la PA durante el día y la variabilidad a corto plazo. Estos aspectos han alentado la realización de un mayor número de mediciones en diversas situaciones, y diferentes pautas han abogado por el uso de equipos que promuevan estas acciones. Los dispositivos que realizan MRPA o MAPA, que además de permitir una mayor precisión, cuando se usan juntos, detectan la hipertensión de bata blanca (HBB), la hipertensión enmascarada (HM), las alteraciones de la PA durante el sueño y la hipertensión resistente (HR) (definida en el Capítulo 2 de esta guía), están ganando cada vez más importancia. Teniendo en cuenta estos detalles, debemos enfatizar que la información relacionada con el diagnóstico, la clasificación y el establecimiento de objetivos todavía se basa en la medición de la presión arterial en el consultorio, y por esta razón, se debe prestar toda la atención a la ejecución adecuada de este procedimiento.

A hipertensão arterial (HA) é um dos principais fatores de risco modificáveis para morbidade e mortalidade em todo o mundo, sendo um dos maiores fatores de risco para doença arterial coronária, acidente vascular cerebral (AVC) e insuficiência renal. Além disso, é altamente prevalente e atinge mais de um terço da população mundial. A medida da PA é procedimento OBRIGATÓRIO em qualquer atendimento médico ou realizado por diferentes profissionais de saúde. Contudo, ainda é comumente realizada sem os cuidados técnicos necessários. Como o diagnóstico se baseia na medida da PA, fica claro o cuidado que deve haver com as técnicas, os métodos e os equipamentos utilizados na sua realização. Deve-se reforçar que, feito o diagnóstico, toda a investigação e os tratamentos de curto, médio e longo prazos são feitos com base nos resultados da medida da PA. Assim, técnicas e/ou equipamentos inadequados podem levar a diagnósticos incorretos, tanto subestimando quanto superestimando valores e levando a condutas inadequadas e grandes prejuízos à saúde e à economia das pessoas e das nações. Uma vez feito o diagnóstico correto, na medida em que avança o conhecimento da importância do tratamento adequado, com a adoção de valores de normalidade mais detalhados e com objetivos de tratamento mais cuidadosos no sentido do alcance de metas de PA mais rigorosas, fica também reforçada a importância da precisão na medida da PA. A medida da PA (descrita a seguir) é habitualmente feita pelo método tradicional, a assim chamada medida casual ou de consultório. Ao longo do tempo, foram agregadas alternativas a ela, mediante o uso de equipamentos semiautomáticos ou automáticos pelo próprio paciente, nas salas de espera ou fora do consultório, em sua própria residência ou em espaços públicos. Um passo adiante foi dado com o uso de equipamentos semiautomáticos providos de memória que permitem medidas sequenciais fora do consultório (AMPA; ou MRPA) e outros automáticos que permitem medidas programadas por períodos mais prolongados (MAPA). Alguns aspectos na medida da PA podem interferir na obtenção de resultados fidedignos e, consequentemente, causar prejuízo nas condutas a serem tomadas. Entre eles, estão: a importância de serem utilizados valores médios, a variação da PA durante o dia e a variabilidade a curto prazo. Esses aspectos têm estimulado a realização de maior número de medidas em diversas situações, e as diferentes diretrizes têm preconizado o uso de equipamentos que favoreçam essas ações. Ganham cada vez mais espaço os equipamentos que realizam MRPA ou MAPA, que, além de permitirem maior precisão, se empregados em conjunto, detectam a HA do avental branco (HAB), HA mascarada (HM), alterações da PA no sono e HA resistente (HAR) (definidos no Capítulo 2 desta diretriz). Resguardados esses detalhes, devemos ressaltar que as informações relacionadas a diagnóstico, classificação e estabelecimento de metas ainda são baseadas na medida da PA de consultório e, por esse motivo, toda a atenção deve ser dada à realização desse procedimento.

Abstract Background: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID 19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID 19 hospitalizations in patients with RA. Methods: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID 19 were compared to 220 patients who tested negative for COVID 19 (control group). All patient data were collected from the Research Electronic Data Capture database. Results: The participants were predominantly female (90.6%) with a mean age of 53 ±12 years. Of the patients with COVID 19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR =4.61, 95% CI 1.06–20.02. P < 0.001) and current use of glucocorticoids (OR =20.66, 95% CI 3.09–138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR =0.26; 95% CI 0.10–0.67, P < 0.005). Conclusion: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID 19 in patients with RA. Trial registration: Brazilian Registry of Clinical Trials RBR 33YTQC.

Abstract Background: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. Methods: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. Results: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren’s syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). Conclusion: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

It is herein described the synthesis of a series of thirty novel 1,2,3-triazole-1,4 disubstituted compounds inspired on the known SRPKs inhibitor N-(2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl)isonicotinamide (SRPIN340) and biological evaluation of them against human glioblastoma multiforme cell line U87MG. Starting with 1-fluoro-2 nitro-4-(trifluoromethyl)benzene (1), the substances were prepared via a five-step synthetic route. The crucial step corresponded to the copper-catalyzed cycloaddition reaction between trifluoromethyl phenyl azides and different alkynes. In general, the compounds were obtained with good yields and they were characterized utilizing spectroscopic (IR and NMR) and spectrometric (HRMS) techniques. The evaluation of the synthesized compounds at three different treatment time (24 h, 48 h, and 72 h) and concentrations (50, 100, and 150 µmol L-1) revealed that five derivatives were capable of reducing cell viability by 50% after 72 h of treatment at the highest concentration. On the contrary, three derivatives significantly increased cell viability being this effect more pronounced after 48 h of treatment. In this regard, it stands out the compound 2-((1-(2-morpholino-5-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)isoindoline-1,3-dione (7) which increased cell viability in approximately 300% after 48 h of treatment at 100 µmol L-1. The substances that increased cell viaiblity present as common structural features the presence of a saturated nitrogen-containing six-membered ring and carbonylated fragments.

BACKGROUND During routine Coronavirus disease 2019 (COVID-19) diagnosis, an unusually high viral load was detected by reverse transcription real-time polymerase chain reaction (RT-qPCR) in a nasopharyngeal swab sample collected from a patient with respiratory and neurological symptoms who rapidly succumbed to the disease. Therefore we sought to characterise the infection. OBJECTIVES We aimed to determine and characterise the etiological agent responsible for the poor outcome. METHODS Classical virological methods, such as plaque assay and plaque reduction neutralisation test combined with amplicon-based sequencing, as well as a viral metagenomic approach, were performed to characterise the etiological agents of the infection. FINDINGS Plaque assay revealed two distinct plaque phenotypes, suggesting either the presence of two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains or a productive coinfection of two different species of virus. Amplicon-based sequencing did not support the presence of any SARS-CoV-2 genetic variants that would explain the high viral load and suggested the presence of a single SARS-CoV-2 strain. Nonetheless, the viral metagenomic analysis revealed that Coronaviridae and Herpesviridae were the predominant virus families within the sample. This finding was confirmed by a plaque reduction neutralisation test and PCR. MAIN CONCLUSIONS We characterised a productive coinfection of SARS-CoV-2 and Herpes simplex virus 1 (HSV-1) in a patient with severe symptoms that succumbed to the disease. Although we cannot establish the causal relationship between the coinfection and the severity of the clinical case, this work serves as a warning for future studies focused on the interplay between SARS-CoV-2 and HSV-1 coinfection and COVID-19 severity.

Despite the difficulties of integrating every student, every teacher and every school in the digital revolution of the 21st century, there are new tendencies in education using digital technology that are trying to change the everyday life in schools. The Flipped Classroom is one of them. This is a blended learning model that reverses the traditional teaching learning model, putting the student in focus, using digital technology (or not) to learn the contents for homework, usually in small videos, and spend the class time in the application of resources, usually in motivating activities. Following this path, this paper is the result of a case study that we performed in the school year of2015/2016, with about 80 students, with average ages of 13, in the classroom of History. To complete this experience, we planned an inverted History class, pursuing the main ideas of this methodology, using apps installed in the students' personal mobile phones and asking students to develop some activities during the class and after the end of class time. The outcome of this case study aims to be a contribution to the idea that Flipped Classroom can be an innovative strategy that reinforces the dialogues between Historical Education and the use of ICT, as well as an original and well-succeeded methodology in History teaching.

Resumo OBJETIVO Avaliar a qualidade de vida entre idosos que trabalham e não trabalham. MÉTODO Trata-se de um estudo descritivo, de corte transversal e abordagem quantitativa com 113 idosos, no período de junho a setembro de 2014, em um grupo de convivência no município de Cajazeiras - PB, utilizando-se os questionários sociodemográficos, o WHOQOL-BREF e WHOQOL-OLD. Os dados foram analisados mediante estatística descritiva e testes T de Student e Mann-Whitney. RESULTADOS A partir da análise observou-se que os idosos que trabalham apresentaram maiores escores médios na maioria dos domínios do WHOQOL-BREF e facetas do WHOQOL-OLD, evidenciando-se o domínio Psicológico (70,0) e a faceta Habilidades Sensoriais (72,5). O domínio físico apresentou diferença estatisticamente significante (p=0,046) entre os dois grupos. CONCLUSÃO O estudo demonstrou que o trabalho é um fator importante para a qualidade de vida do idoso.

Abstract OBJECTIVE To assess the quality of life of working and non-working elderly people. METHOD Descriptive study with cross-sectional cohort and quantitative approach, with 113 elderly subjects, conducted from June to September 2014, in a peer group in the city of Cajazeiras-PB, using the WHOQOL-BREF and WHOQOL-OLD sociodemographic questionnaires. Data were analyzed through descriptive statistics and Mann-Whitney and Student’s t-tests. RESULTS The working elderly people had higher mean scores in most WHOQOL-BREF domains and WHOQOL-OLD facets, with emphasis to the Psychological domain (70.0) and the Sensory abilities facet (72.5). A statistically significant difference (p=0.046) was found between the two groups in the physical domain. CONCLUSION The study demonstrated that work is an important factor for the quality of life of elderly individuals.

Resumen OBJETIVO Evaluar la calidad de vida entre ancianos que trabajan y que no trabajan. MÉTODO Se trata de un estudio descriptivo, con corte transversal y planteamiento cuantitativo, con 113 ancianos, durante el período comprendido entre junio y septiembre de 2014, en un grupo de convivencia en la ciudad de Cajazeiras-PB, utilizando los cuestionarios sociodemográficos WHOQOL-BREF y WHOQOL-OLD. Los datos fueron analizados por medio de estadística descriptiva y de las pruebas t-Student y Mann-Whitney. RESULTADOS A partir del análisis, se notó que los ancianos que trabajan presentaron mayores puntuaciones promedio en la mayoría de los dominios del WHOQOL-BREF y facetas del WHOQOL-OLD, haciendo hincapié en el dominio Psicológico (70,0) y en la faceta Capacidades sensoriales (72,5). El dominio Físico mostró diferencia estadísticamente significativa (p=0,046) entre los dos grupos. CONCLUSIÓN El estudio demostró que el trabajo es un factor importante para la calidad de vida del anciano.

Abstract OBJECTIVE To assess the quality of life of working and non-working elderly people. METHOD Descriptive study with cross-sectional cohort and quantitative approach, with 113 elderly subjects, conducted from June to September 2014, in a peer group in the city of Cajazeiras-PB, using the WHOQOL-BREF and WHOQOL-OLD sociodemographic questionnaires. Data were analyzed through descriptive statistics and Mann-Whitney and Student’s t-tests. RESULTS The working elderly people had higher mean scores in most WHOQOL-BREF domains and WHOQOL-OLD facets, with emphasis to the Psychological domain (70.0) and the Sensory abilities facet (72.5). A statistically significant difference (p=0.046) was found between the two groups in the physical domain. CONCLUSION The study demonstrated that work is an important factor for the quality of life of elderly individuals.

Resumen OBJETIVO Evaluar la calidad de vida entre ancianos que trabajan y que no trabajan. MÉTODO Se trata de un estudio descriptivo, con corte transversal y planteamiento cuantitativo, con 113 ancianos, durante el período comprendido entre junio y septiembre de 2014, en un grupo de convivencia en la ciudad de Cajazeiras-PB, utilizando los cuestionarios sociodemográficos WHOQOL-BREF y WHOQOL-OLD. Los datos fueron analizados por medio de estadística descriptiva y de las pruebas t-Student y Mann-Whitney. RESULTADOS A partir del análisis, se notó que los ancianos que trabajan presentaron mayores puntuaciones promedio en la mayoría de los dominios del WHOQOL-BREF y facetas del WHOQOL-OLD, haciendo hincapié en el dominio Psicológico (70,0) y en la faceta Capacidades sensoriales (72,5). El dominio Físico mostró diferencia estadísticamente significativa (p=0,046) entre los dos grupos. CONCLUSIÓN El estudio demostró que el trabajo es un factor importante para la calidad de vida del anciano.

Resumo OBJETIVO Avaliar a qualidade de vida entre idosos que trabalham e não trabalham. MÉTODO Trata-se de um estudo descritivo, de corte transversal e abordagem quantitativa com 113 idosos, no período de junho a setembro de 2014, em um grupo de convivência no município de Cajazeiras - PB, utilizando-se os questionários sociodemográficos, o WHOQOL-BREF e WHOQOL-OLD. Os dados foram analisados mediante estatística descritiva e testes T de Student e Mann-Whitney. RESULTADOS A partir da análise observou-se que os idosos que trabalham apresentaram maiores escores médios na maioria dos domínios do WHOQOL-BREF e facetas do WHOQOL-OLD, evidenciando-se o domínio Psicológico (70,0) e a faceta Habilidades Sensoriais (72,5). O domínio físico apresentou diferença estatisticamente significante (p=0,046) entre os dois grupos. CONCLUSÃO O estudo demonstrou que o trabalho é um fator importante para a qualidade de vida do idoso.

Resumo Este artigo avalia, através de charges publicadas na revista O Malho entre 1902 e 1910, a percepção dos caricaturistas e/ou editores desse periódico acerca dos processos políticos republicanos - a prática eleitoral, a classe política e suas instituições - e de como tal interpretação era divulgada. As publicações revelam a dinâmica eleitoral e os resultados dos pleitos, tradicionalmente criticados como excludentes, previsíveis e fraudulentos. Tais manifestações tornaram-se objeto de pesquisas recentes e vêm demonstrando que as eleições eram mais competitivas do que aparentavam. Buscamos relacionar a visão política da Revista O Malho aos trabalhos historiográficos atuais que abordam e revisitam a interpretação dos pleitos eleitorais.

Abstract This article uses the cartoons published in O Malho magazine between 1902 and 1910 to assess the perception of cartoonists and/or publishers of this periodical on the political republican processes-the electoral practice, the political class and its institutions-and how such interpretation was published. The publications reveal the electoral dynamic and the results of the elections, traditionally criticized as exclusive, predictable and fraudulent. Such facts became object of recent researches, and have been showing that the elections were more competitive than they seemed to be. We attempted to relate the political view of O Malho magazine to the present historiographic works approaching and revisiting the interpretation of the elections.

Resumo O presente estudo valoriza o projeto pedagógico como quadro de ação para os indivíduos na organização escolar. É, justamente, a essa luz que se analisa a forma como o espaço escolar é interpretado pelos utilizadores (nomeadamente, docentes), em um contexto muito específico: a Escola da Ponte (Portugal). Em um quadro de insucesso generalizado da experiência das escolas de área aberta em Portugal, aquilo que se procura demonstrar é que, no caso da Escola da Ponte, o êxito da experiência assentou no caráter inovador do projeto pedagógico (pondo em causa o DNA da organização pedagógica das escolas – a classe). A nossa interpretação, baseada no conceito de espaço como construção social, sustenta que foi, sobretudo, a consistência do projeto pedagógico e a interação entre atores e objetos da ação que determinaram a forma como o espaço foi sendo organizado; muito mais do que se tratar de um processo de indução resultante de o edifício ser de área aberta. A recolha empírica constituiu a base para conhecer o modo de apropriação do espaço pelo projeto pedagógico. Nessa ordem de ideias, foi enviado (por correio eletrônico) um inquérito através de um questionário a docentes que lecionaram na referida escola entre meados da década de 1970 e o ano de 2012. O arco cronológico tem a seguinte justificação: tratou-se do lapso de tempo que decorreu entre o início do projeto pedagógico e a transferência de instalações para um novo edifício.

Abstract The present study values the pedagogical project as a frame of action for individuals in the school organization. Indeed, it is according to this perspective that interpretations of the school space by its users (teachers in particular) are analyzed in a very specific context – Escola da Ponte –.Within the scope of widespread failure of the open-plan school experience in Portugal, the aim of this study is to highlight how the successful experience of Escola da Ponte was born out of the innovative nature of the pedagogical project (questioning the “DNA” of the pedagogical organization of schools – the class). Our interpretation is based on the concept of space as a social construction. Above all, it sustains that it was the consistency of the pedagogical project and the interaction between actors and objects of action that determined how the space was organized rather than the induction process of an open-plan school building. The empirical collection served to ascertain how the space was appropriated by the pedagogical project. A survey was sent by e-mail to the teachers who taught at this school between the mid-1970s and 2012. The chronological gap is due to the lapse of time between the beginning of the pedagogical project and the transfer of facilities to a new building.

Resumo Objetivos Avaliar incidência de tuberculose e triagem para tuberculose latente em brasileiros com artrite reumatoide em uso de agentes biológicos na prática clinica. Pacientes e métodos Estudo de coorte com dados do Registro Brasileiro de Monitoração de Terapias Biológicas (BiobadaBrasil), de 01/2009 a 05/2013, abrangeu 1.552 tratamentos, 415 somente com drogas modificadoras do curso da doença (MMCDs) sintéticas, 942 MMCDs sintéticas em associação com anti-TNF (etanercepte, infliximabe, adalimumabe) e 195 MMCDs sintéticas em associação com outros biológicos (abatacepte, rituximabe e tocilizumabe). Avaliaram-se ocorrência de tuberculose, tempo de exposição às drogas e triagem para TB. Análise estatística: teste t não pareado e teste de Fisher bicaudal; p < 0,05. Resultados O tempo de exposição dos controles foi de 981 pacientes-ano, do grupo de anti-TNF foi de 1.744 pacientes-ano (adalimumabe = 676, infliximabe = 547 e etanercepte = 521 pacientes-ano) e o de outros biológicos de 336 pacientes-ano. A incidência de TB foi de 1,01/1.000 pacientes-ano nos controles e de 2,87 pacientes-ano nos usuários de anti-TNF (adalimumabe = 4,43/1.000 pacientes-ano; etanercepte = 1,92/1.000 pacientes-ano e infliximabe = 1,82/1.000 pacientes-ano). Não houve casos de tuberculose no grupo de outros biológicos. O tempo médio de exposição até a ocorrência de tuberculose foi de 27(11) meses para o grupo anti-TNF. Conclusões A incidência de tuberculose foi maior nos usuários de MMCDs sintéticas e anti-TNF do que nos usuários de MMCDs sintéticas e de MMCDs sintéticas e biológicos não anti-TNF, e também mais tardia, sugerindo infecção durante o tratamento, e não falha na triagem.

Abstract Objectives To assess the incidence of tuberculosis and to screen for latent tuberculosis infection among Brazilians with rheumatoid arthritis using biologics in clinical practice. Patients and methods This cohort study used data from the Brazilian Registry of Biological Therapies in Rheumatic Diseases (Registro Brasileiro de Monitoração de Terapias Biológicas - BiobadaBrasil), from 01/2009 to 05/2013, encompassing 1552 treatments, including 415 with only synthetic disease-modifying anti-rheumatic drugs, 942 synthetic DMARDs combined with anti-tumor necrosis factor (etanercept, infliximab, adalimumab) and 195 synthetic DMARDs combined with other biologics (abatacept, rituximab and tocilizumab). The occurrence of tuberculosis and the drug exposure time were assessed, and screening for tuberculosis was performed. Statistical analysis: Unpaired t-test and Fisher's two-tailed test; p < 0.05. Results The exposure times were 981 patient-years in the controls, 1744 patient-years in the anti-TNF group (adalimumab = 676, infliximab = 547 and etanercept = 521 patient-years) and 336 patient-years in the other biologics group. The incidence rates of tuberculosis were 1.01/1000 patient-years in the controls and 2.87 patient-years among anti-TNF users (adalimumab = 4.43/1000 patient-years; etanercept = 1.92/1000 patient-years and infliximab = 1.82/1000 patient-years). No cases of tuberculosis occurred in the other biologics group. The mean drug exposure time until the occurrence of tuberculosis was 27(11) months for the anti-TNF group. Conclusions The incidence of tuberculosis was higher among users of synthetic DMARDs and anti-TNF than among users of synthetic DMARDs and synthetic DMARDs and non-anti-TNF biologics and also occurred later, suggesting infection during treatment and no screening failure.

Resumo A febre chikungunya tem se tornado um importante problema de saúde pública nos países onde ocorrem as epidemias, visto que metade dos casos evolui com artrite crônica, persistente e incapacitante. Os dados na literatura sobre terapêuticas específicas nas diversas fases da artropatia ocasionada pela infecção pelo vírus chikungunya (CHIKV) são limitados, não existem estudos randomizados de qualidade que avaliem a eficácia das diferentes terapias. Há algumas poucas publicações sobre o tratamento das manifestações musculoesqueléticas da febre chikungunya, porém com importantes limitações metodológicas. Os dados atualmente disponíveis não permitem conclusões favoráveis ou contrárias a terapêuticas específicas, bem como uma adequada avaliação quanto à superioridade entre as diferentes medicações empregadas. O objetivo deste trabalho foi elaborar recomendações para o tratamento da febre chikungunya no Brasil. Foi feita uma revisão da literatura com seleção de artigos baseados em evidência, nas bases de dados Medline, SciELO, PubMed e Embase e de resumos de anais de congressos, além da opinião dos especialistas para dar apoio às decisões tomadas para definir as recomendações. Para a definição do grau de concordância foi feita uma metodologia Delphi, em duas reuniões presenciais e várias rodadas de votação on line. Este artigo refere-se à parte 2 das Recomendações da Sociedade Brasileira de Reumatologia para Diagnóstico e Tratamento da Febre Chikungunya, que trata especificamente do tratamento.

Abstract Chikungunya fever has become an important public health problem in countries where epidemics occur because half of the cases progress to chronic, persistent and debilitating arthritis. Literature data on specific therapies at the various phases of arthropathy caused by chikungunya virus (CHIKV) infection are limited, lacking quality randomized trials assessing the efficacies of different therapies. There are a few studies on the treatment of musculoskeletal manifestations of chikungunya fever, but these studies have important methodological limitations. The data currently available preclude conclusions favorable or contrary to specific therapies, or an adequate comparison between the different drugs used. The objective of this study was to develop recommendations for the treatment of chikungunya fever in Brazil. A literature review was performed via evidence-based selection of articles in the databases Medline, SciELO, PubMed and Embase and conference proceedings abstracts, in addition to expert opinions to support decision-making in defining recommendations. The Delphi method was used to define the degrees of agreement in 2 face-to-face meetings and several online voting rounds. This study is part 2 of the Recommendations of the Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia - SBR) for the Diagnosis and Treatment of chikungunya fever and specifically addresses treatment.

Resumo A febre chikungunya tem se tornado um importante problema de saúde pública nos países onde ocorrem as epidemias. Até 2013, as Américas haviam registrado apenas casos importados quando, em outubro desse mesmo ano, foram notificados os primeiros casos na Ilha de Saint Martin, no Caribe. No Brasil, os primeiros relatos autóctones foram confirmados em setembro de 2014 e até a semana epidemiológica 37 de 2016 já haviam sido registrados 236.287 casos prováveis de infecção pelo chikungunya vírus (CHIKV), 116.523 confirmados sorologicamente. As mudanças ambientais causadas pelo homem, o crescimento urbano desordenado e o número cada vez maior de viagens internacionais têm sido apontados como os fatores responsáveis pela reemergência de epidemias em grande escala. Caracterizada clinicamente por febre e dor articular na fase aguda, em cerca de metade dos casos existe evolução para a fase crônica (além de três meses), com dor persistente e incapacitante. O objetivo deste trabalho foi elaborar recomendações para diagnóstico e tratamento da febre chikungunya no Brasil. Para isso, foi feita revisão da literatura nas bases de dados Medline, SciELO e PubMed, para dar apoio às decisões tomadas para definir as recomendações. Para a definição do grau de concordância foi feita uma metodologia Delphi, em duas reuniões presenciais e várias rodadas de votação on line. Foram geradas 25 recomendações, divididas em três grupos temáticos: (1) diagnóstico clínico, laboratorial e por imagem; (2) situações especiais e (3) tratamento. Na primeira parte estão os dois primeiros temas e o tratamento na segunda.

Abstract Chikungunya fever has become a relevant public health problem in countries where epidemics occur. Until 2013, only imported cases occurred in the Americas, but in October of that year, the first cases were reported in Saint Marin island in the Caribbean. The first autochthonous cases were confirmed in Brazil in September 2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection with Chikungunya virus had been registered, 116,523 of which had serological confirmation. Environmental changes caused by humans, disorderly urban growth and an ever-increasing number of international travelers were described as the factors responsible for the emergence of large-scale epidemics. Clinically characterized by fever and joint pain in the acute stage, approximately half of patients progress to the chronic stage (beyond 3 months), which is accompanied by persistent and disabling pain. The aim of the present study was to formulate recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A literature review was performed in the MEDLINE, SciELO and PubMed databases to ground the decisions for recommendations. The degree of concordance among experts was established through the Delphi method, involving 2 in-person meetings and several online voting rounds. In total, 25 recommendations were formulated and divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis; (2) special situations; and (3) treatment. The first 2 themes are presented in part 1, and treatment is presented in part 2.

The monoterpenoid 1,8-cineole is obtained from the leaves of Eucalyptus globulus and it has important biological activities. It is a cheap natural substrate because it is a by-product of the Eucalyptuscultivation for wood and pulp production. In this study, it was evaluated the potential of three filamentous fungi in the biotransformation of 1,8-cineole. The study was divided in two steps: first, reactions were carried out with 1,8-cineole at 1 g/L for 24 h; afterwards, reactions were carried out with substrate at 5 g/L for 5 days. The substrate was hydroxylated into 2-exo-hydroxy-1,8-cineole and 3-exo-hydroxy-1,8-cineole by fungi Mucor ramannianus and Aspergillus niger with high stereoselectivity. Trichoderma harzianum was also tested but no transformation was detected. M. ramannianus led to higher than 99% of conversion within 24 h with a starting high substrate concentration (1 g/L). When substrate was added at 5 g/L, only M. ramannianuswas able to catalyze the reaction, but the conversion level was 21.7% after 5 days. Both products have defined stereochemistry and could be used as chiral synthons. Furthermore, biological activity has been described for 3-exo-hydroxy-1,8-cineol. To the best of our knowledge, this is the first report on the use of M. ramannianus in this reaction.

O gênero Cleome encontra-se distribuído em áreas tropicais e subtropicais do mundo. Cleome dendroides é uma espécie endêmica de Mata Atlântica do estado do Rio de Janeiro, enquanto C. rosea é uma espécie nativa que ocorre principalmente em restingas, ambos ecossistemas que sofrem constante impacto antrópico. Cleome spinosa é frequentemente encontrada em áreas urbanas. Muitas espécies de Cleome têm sido utilizadas na medicina tradicional, como C. spinosa. No presente trabalho, avaliou-se a influência do substrato, da temperatura e da luz sobre a germinação in vivo das três espécies, bem como determinaram-se as condições para germinação in vitro e as etapas do desenvolvimento pós-seminal. Observaram-se que apenas sementes de C. spinosa apresentam dormência fisiológica, a qual é superada utilizando-se temperaturas alternadas. O substrato influenciou significativamente a germinação de C. rosea e as sementes de C. dendroides apresentaram alta porcentagem de germinação nas diferentes condições avaliadas. As etapas do desenvolvimento pós-seminal sob condições in vivo e in vitro foram definidas. Observou-se que o desenvolvimento sob condições in vitro foi mais acelerado que in vivo. Uma eficiente metodologia para germinação in vitro foi estabelecida para C. dendroides e C. spinosa, fornecendo material juvenil em condições assépticas para futuros experimentos de cultura de tecidos vegetais.

The genus Cleome is widely distributed in drier areas of the tropics and subtropics. Cleome dendroides and C. rosea are Brazilian native species that occur mainly in Atlantic Forest and sandy coastal plains, respectively ecosystems negatively affected by human impacts. Cleome spinosa is frequently found in urban areas. Many Cleome species have been used in traditional medicine, as C. spinosa. In the present work, was investigated C. dendroides, C. rosea and C. spinosa germinative behavior under in vivo conditions, as well as was established suitable conditions to in vitro germination and seedling development. The in vivo germination was performed evaluating the influence of temperature, substrate and light. It was observed that only C. spinosa seeds presents physiological dormancy, which was overcome by using alternate temperatures. The substrate influenced significantly the germination of C. rosea and the seeds of C. dendroides showed the highest germination percentages in the different conditions evaluated. The post-seminal development stages under in vivo and in vitro conditions were defined. It was observed that the development was faster under in vitro than in vivo conditions. An effective methodology for in vitro germination, enabling the providing of material to experiment on plant tissue culture was established to C. dendroides and C. spinosa.