ABSTRACT The Scientists of Tomorrow/ Cientistas do Amanhã project is an immersive science training program developed by the Program of Post-Graduation in Health Sciences at Hospital Israelita Albert Einstein. This program was conducted in partnership with Volunteering and Escola Municipal de Ensino Fundamental Professor Paulo Freire in Paraisópolis, São Paulo, Brazil. The Scientists of Tomorrow Program comprised a short training period conducted in May 2022 involving 37 students, and a long training period from August to December 2022, which included 15 students. It aimed to popularize science through practical activities; transfer knowledge to young students; sensitize and guide them to pursue academic-scientific careers; reduce stereotypes about scientific work and scientists; and help students understand the social, political, and ethical roles of science within society. All activities were led by postgraduate students and professors from our postgraduate program, physicians, nurses, physiotherapists, biomedicals, and veterinarians from Hospital Israelita Albert Einstein, as well as medical students from Faculdade Israelita de Ciências da Saúde Albert Einstein . Activities in the short training included lectures on cinema and science, strategies to combat fake news, non-violent communication, innovation, design-thinking framework, and developing a scientific project. During the long training period, discussions were focused on nanotechnology, animal research, big data, bioinformatics, meditation, blood and bone marrow donation, telemedicine, sex and sexually-transmitted infections, rehabilitation, career opportunities, and scientific integrity. In addition, practical activities were further expanded using optical and confocal microscopy, cytometry, and basic concepts regarding the structure and function of living cells. The program also included the launching of the open-air outreach Education E-natureza activity, which turned students into ambassadors of nature. In conclusion, the Scientists of Tomorrow Program was innovative and enabled young students to learn that science is a collective activity that can enhance public health.

ABSTRACT Objective We performed a systematic review of the literature and meta-analysis on the efficacy and safety of hydroxychloroquine to treat COVID-19 patients. Methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and LILACS (January 2019 to March 2021) for patients aged 18 years or older, who had COVID-19 and were treated with hydroxychloroquine versus placebo or standard of care. We also searched the WHO Clinical Trials Registry for ongoing and recently completed studies, and the reference lists of selected articles and reviews for possible relevant studies, with no restrictions regarding language or publication status. Random-effects models were used to obtain pooled mean differences of treatment effect on mortality, and serious adverse effects between hydroxychloroquine and the Control Group (standard of care or placebo); heterogeneity was assessed using the I2 and the Cochran´s Q statistic. Results Nine studies met the inclusion criteria and were included in the meta-analysis. There was no significant difference in mortality rate between patients treated with hydroxychloroquine compared to standard of care or placebo (16.7% versus 18.5%; pooled risk ratio 1.09; 95% confidence interval: 0.99-1.19). Also, the rate of serious adverse effects was similar between both Groups, Hydroxychloroquine and Control (3.7% versus 2.9%; pooled risk ratio 1.22; 95% confidence interval: 0.76-1.96). Conclusion Hydroxychloroquine is not efficacious in reducing mortality of COVID-19 patients. Prospero database registration (www.crd.york.ac.uk/prospero) under number CRD42020197070.

RESUMO Linfócitos T auxiliares foliculares são uma subpopulação de linfócitos T CD4+ identificada inicialmente nos centros germinativos dos folículos dos órgãos linfoides secundários. Sua função primordial é auxiliar os linfócitos B na produção de anticorpos. A mudança de classe e de afinidade dos anticorpos, a diferenciação das células B e a geração de memória dependem da cooperação entre os linfócitos T auxiliares foliculares e as células B. No sangue, recebem o nome de linfócitos T auxiliares circulantes. Considera-se que possuem especificidades semelhantes às desenvolvidas nos órgãos linfoides secundários. O fenótipo dos linfócitos T auxiliares humanos é dado pela expressão conjunta dos marcadores CXCR5, Bcl-6, CD40L, PD-1 e ICOS. Nos folículos, linfócitos T auxiliares sintetizam a interleucina 21 como citocina predominante. No sangue, são descritas várias subpopulações de linfócitos T auxiliares circulantes com expressões variadas dos marcadores clássicos de linfócitos T auxiliares, além de poderem agregar outros, como CXCR3 e CCR6. Existe um enorme interesse no estudo de linfócitos T auxiliares e linfócitos T auxiliares circulantes, para a avaliação de eficácia de vacinação. São também investigados como possíveis marcadores de atividade em muitas doenças e potenciais intervenções terapêuticas. Esta breve revisão descreve aspectos da imunobiologia e da quantificação de linfócitos T auxiliares humanos e linfócitos T auxiliares circulantes, além de apresentar alguns achados relacionados em lúpus eritematoso sistêmico, artrite reumatoide, infecção por HIV e vacinação.

ABSTRACT Follicular helper T lymphocytes are a subpopulation of CD4+ T lymphocytes initially identified in germinal centers of follicles found in secondary lymphoid organs. The primary function of follicular helper T lymphocytes is to help B lymphocytes’ antibody production. Changing of antibody class and affinity, B cell differentiation and memory generation depend on cooperation between follicular helper T lymphocytes and B cells. In blood, follicular helper T lymphocytes are called circulating follicular helper T lymphocytes. They are considered to have specificities similar to those developed in the secondary lymphoid organs. The phenotype of human follicular helper T lymphocytes is given by simultaneous expression of the markers CXCR5, Bcl-6, CD40L, PD-1, and ICOS. In germinal centers, follicular helper T lymphocytes synthesize interleukin 21 as predominant cytokine. In blood, subpopulations of circulating follicular helper T lymphocytes can be recognized, with different expressions of the classical follicular helper T lymphocytes markers and, in addition, can express other markers such as CXCR3 and CCR6. Presently, there is great interest in follicular helper T lymphocytes and circulating follicular helper T lymphocytes in vaccination studies as indicators of immunization efficacy. In addition, follicular helper T lymphocytes are investigated as possible markers of activity in many diseases and potential therapeutic intervention. This short review describes aspects of immunobiology and quantification of follicular helper T lymphocytes and circulating follicular helper T lymphocytes, and presents a few examples of related findings in systemic lupus erythematosus, rheumatoid arthritis, HIV infection and vaccination.

RESUMO Objetivo Descrever as características epidemiológicas e clínicas de pacientes com infecção confirmada pelo SARS-CoV-2, diagnosticados e tratados no Hospital Israelita Albert Einstein, que admitiu os primeiros pacientes com essa condição no Brasil. Métodos Neste estudo retrospectivo, de centro único, incluímos todos os casos com confirmação laboratorial de COVID-19 no Hospital Israelita Albert Einstein, em São Paulo (SP) de fevereiro a março de 2020. Foram analisados dados demográficos, clínicos, laboratoriais e radiológicos. Resultados Foram incluídos 510 pacientes com diagnóstico confirmado de COVID-19. A maioria dos pacientes era do sexo masculino (56,9%), com média de idade de 40 anos. Foi relatada história de contato próximo com um caso positivo/suspeito por 61,1% dos pacientes, e 34,4% tinham história de viagens internacionais recentes. Os sintomas mais comuns foram febre (67,5%), congestão nasal (42,4%), tosse (41,6%) e mialgia/artralgia (36,3%). A tomografia computadorizada de tórax foi realizada em 78 (15,3%) pacientes, e 93,6% deles apresentaram resultados anormais. A hospitalização foi necessária para 72 (14%) pacientes, e 20 (27,8%) foram admitidos na Unidade de Terapia Intensiva. Quanto ao tratamento clínico, os medicamentos mais utilizados foram antibióticos intravenosos (84,7%), cloroquina (45,8%) e oseltamivir (31,9%). A ventilação mecânica invasiva foi necessária em 65% dos pacientes na Unidade de Terapia Intensiva. O tempo médio de internação foi 9 dias para todos os pacientes (22 e 7 dias para pacientes que necessitaram ou não de cuidados intensivos, respectivamente). Apenas um (1,38%) paciente morreu durante o acompanhamento. Conclusão Estes resultados podem ser relevantes para o Brasil e outros países com características semelhantes, que começaram a lidar com essa pandemia.

ABSTRACT Objective This study describes epidemiological and clinical features of patients with confirmed infection by SARS-CoV-2 diagnosed and treated at Hospital Israelita Albert Einstein , which admitted the first patients with this condition in Brazil. Methods In this retrospective, single-center study, we included all laboratory confirmed COVID-19 cases at Hospital Israelita Albert Einstein , São Paulo, Brazil, from February until March 2020. Demographic, clinical, laboratory and radiological data were analyzed. Results A total of 510 patients with a confirmed diagnosis of COVID-19 were included in this study. Most patients were male (56.9%) with a mean age of 40 years. A history of a close contact with a positive/suspected case was reported by 61.1% of patients and 34.4% had a history of recent international travel. The most common symptoms upon presentation were fever (67.5%), nasal congestion (42.4%), cough (41.6%) and myalgia/arthralgia (36.3%). Chest computed tomography was performed in 78 (15.3%) patients, and 93.6% of those showed abnormal results. Hospitalization was required for 72 (14%) patients and 20 (27.8%) were admitted to the Intensive Care Unit. Regarding clinical treatment, the most often used medicines were intravenous antibiotics (84.7%), chloroquine (45.8%) and oseltamivir (31.9%). Invasive mechanical ventilation was required by 65% of Intensive Care Unit patients. The mean length of stay was 9 days for all patients (22 and 7 days for patients requiring or not intensive care, respectively). Only one patient (1.38%) died during follow-up. Conclusion These results may be relevant for Brazil and other countries with similar characteristics, which are starting to deal with this pandemic.

RESUMO Relatamos o caso de uma paciente com dermatite atópica grave, que mostrou boa resposta ao dupilumabe. Ela já tinha usado dois agentes imunossupressores, a ciclosporina A e o micofenolato de mofetila, para o tratamento da dermatite atópica, sem obter o controle adequado da doença. Ela também vinha fazendo uso de todas as medidas de controle para casos graves da doença: cuidados com o banho, controle ambiental, corticosteroides potentes tópicos e emolientes. Apresentava prurido e lesões cutâneas constantes, infeções de pele frequentes e qualidade de vida ruim. Passou a apresentar depressão devido à sua doença. Recentemente, o dupilumabe, um agente biológico novo, foi aprovado para o tratamento de dermatite atópica moderada a severa em muitos países, incluindo o Brasil. Dupilumabe é um anticorpo monoclonal cujo alvo é a cadeia alfa comum aos receptores da interleucina (IL) 4 e IL-13, duas citocinas envolvidas no perfil de resposta imune Th2, que promove inflamação atópica. De modo pioneiro no Brasil, a paciente iniciou o tratamento, com dose de ataque de 600mg por via subcutânea de dupilumabe e 300mg também por via subcutânea a cada 2 semanas. Até o momento deste relato, ela realizou quatro aplicações, apresentando grande melhora da doença e da qualidade de vida. Não houve efeitos adversos, nem no local da injeção e nem de outro tipo. A paciente e sua família estão muito satisfeitas, e os médicos que a tratam avaliam que a terapia está sendo bem-sucedida. Este relato de caso subsidia o uso de dupilumabe no tratamento da dermatite atópica grave refratária ao uso de imunossupressores.

ABSTRACT Case report of a patient with severe atopic dermatitis who showed a good response to dupilumab. She had already used two immunosuppressive agents, cyclosporine A and mycophenolate mofetil, for the treatment of atopic dermatitis with no proper control of the disease. She had also been taking all measures to control severe cases of the disease: bath and environmental controls, topical potent corticosteroids and emollients. She presented constant pruritus and skin lesions, frequent skin infections e poor quality of life. She also developed depression due to her disease. Recently, dupilumab, a new biological agent, was approved for the treatment of moderate/severe atopic dermatitis in many countries, including Brazil. Dupilumab is a monoclonal antibody with a common alpha chain of interleukin (IL) 4 and IL-13 receptors, two cytokines involved in the Th2 profile immune response that promote atopic inflammation. In a pioneer way in Brazil, the patient initiated the treatment with an attack dose of 600mg subcutaneous of dupilumab and 300mg subcutaneous every other week. Up to now, she has taken four applications, presenting a great improvement of the disease and her quality of life. There were no adverse effects, nor in the injection site nor of other kind. Patient and her family are very satisfied, and the medical team evaluates that the treatment is being well succeed. The case report described here subsidizes the use of dupilumab in the treatment of severe atopic dermatitis refractory to use of immunosuppressive agents.

RESUMO Objetivo: Analisar o uso do PCR em tempo real (qPCR) na detecção do DNA do T. gondii no sangue periférico e no humor aquoso de pacientes com lesões de retinocoroidite focal, ativa por toxoplasmose. Métodos: Cinquenta e cinco pacientes com uveite infecciosa foram incluídos neste estudo. Os pacientes foram atendidos entre 2009 a 2013, no Departamento de Oftalmologia e Ciências Visuais da Universidade Federal de São Paulo. Quarenta e três pacientes tiveram o diagnóstico de lesões de retinocoroidite focal, ativa por toxoplasmose e, os outros 12 tiveram o diagnóstico de uveíte infecciosa não toxoplásmica e, por isso foram usados como grupo controle. A técnica de qPCR foi utilizada na detecção de DNA do T. gondii em amostras de sangue periférico e humor aquoso. Resultados: O qPCR foi positivo para o DNA do T. gondii em 37,21% (16/43) das amostras de humor aquoso, 2,33% (1/43) nas amostras de sangue periférico e, 16,27% (7/43) em ambas amostras simultaneamente. Conclusão: O qPCR foi capaz de detectar o DNA do T. gondii em pacientes com lesões de retinocoroidite focal, ativa por Toxoplasmose, no sangue bem como, no humor aquoso, podendo ajudar no diagnostico.

ABSTRACT Purpose: To evaluate the ability of real-time quantitative PCR (qPCR) for detectingToxoplasma gondii DNA in the peripheral blood and aqueous humor of patients with toxoplasmic active focal necrotizing retinochoroiditis. Methods: Fifty-five patients with infectious uveitis seen from 2009 to 2013 at the Department of Ophthalmology and Visual Sciences of the Federal University of São Paulo were enrolled in this study. Forty-three patients had toxoplasmic active focal necrotizing retinochoroiditis, and the remaining 12 had non-toxoplasmic infectious uveitis and served as controls. qPCR analysis forT. gondii DNA was performed on the patients' peripheral blood and aqueous humor samples. Results: The qPCR was positive for T. gondii DNA in 37.21% (16/43) of the aqueous humor samples and 2.33% (1/43) of the peripheral blood samples; further, 16.27% (7/43) of the patients had positive results in both their blood and aqueous humor samples. Conclusion: qPCR was able to detect T. gondii DNA in patients with toxoplasmic active focal necrotizing retinochoroiditis in the blood as well as the aqueous humor and can help with the diagnosis of the disease.

A segunda parte desta revisão trata das moléculas e processos envolvidos no processamento e apresentação dos fragmentos antigênicos ao receptor de célula-T. Apesar de variar a natureza do antígeno apresentado, a classe mais significativa é a das proteínas, as quais são processadas dentro da célula para enfim serem reconhecidas na forma de peptídeos, o que confere um grau extraordinário de precisão a essa forma de resposta imune. A eficiência e a precisão desse sistema se devem também à miríade de mecanismos envolvidos no processamento de proteínas e produção de peptídeos, além da captura e reciclagem de fontes alternativas de antígenos com o objetivo de gerar ainda maior diversidade na apresentação à célula-T.

The second part of this review deals with the molecules and processes involved in the processing and presentation of the antigenic fragments to the T-cell receptor. Though the nature of the antigens presented varies, the most significant class of antigens is proteins, processed within the cell to be then recognized in the form of peptides, a mechanism that confers an extraordinary degree of precision to this mode of immune response. The efficiency and accuracy of this system is also the result of the myriad of mechanisms involved in the processing of proteins and production of peptides, in addition to the capture and recycling of alternative sources aiming to generate further diversity in the presentation to T-cells.

O cenário no qual ocorre a resposta imune é o da necessidade de fazer frente a uma vasta gama de antígenos diferentes, de fontes patogênicas e não patogênicas. Quando as primeiras barreiras contra infecção e a defesa inata falham, a resposta imune adaptativa entra em campo, para efetuar o reconhecimento dos antígenos, utilizando, para esse fim, moléculas extremamente variáveis, que são as imunoglobulinas e os receptores de células-T. Estes últimos reconhecem o antígeno, exposto na superfície das células como peptídeo apresentado pelas moléculas HLA. A primeira parte desta revisão detalha o papel central dessas moléculas, estabelecendo a conexão que existe entre a estrutura e a função de apresentação de antígenos.

The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function.

Objetivo A participação de médicos em programas de Educação Médica Continuada pode ser influenciada por inúmeros fatores. Para avaliar os fatores associados ao cumprimento dos requisitos para Educação Médica Continuada em um hospital privado, investigamos se a atividade médica, medida por volume de internações e procedimentos, esteve relacionada à obtenção de 40 créditos (40 horas-aula) em um ciclo do programa de 12 meses. Métodos Em um programa exclusivo e não obrigatório de Educação Médica Continuada, coletamos o número de admissões e de procedimentos realizados por médico. Analisamos dados como tempo de formado, idade e sexo. Resultados Foram analisados dados de 3.809 médicos credenciados e autônomos. A análise univariada mostrou que os requisitos de Educação Médica Continuada eram mais preenchidos por médicos do sexo masculino (odds ratio de 1,251; p=0,009) e que eles apresentavam números de internações mais significativos (odds ratio de 1,022; p<0,001). A análise multivariada mostrou que idade e número de admissões estiveram associados ao cumprimento das metas estabelecidas. Cada admissão aumentou a chance de atingir a meta em 0,4%. Entre os que realizaram procedimentos cirúrgicos, a análise multivariada mostrou que médicos do sexo masculino eram 1,3 vez mais propensos a atingir a meta estabelecida que seus pares do sexo feminino. Cada procedimento cirúrgico realizado elevou a chance de atingir a meta em 1,4%. Conclusão O número de admissões e de procedimentos cirúrgicos realizados por médicos em nosso hospital foi associado à probabilidade de alcançar a meta de Educação Médica Continuada. Estes achados lançaram uma nova luz sobre o nosso programa de Educação Médica Continuada.

Objective Physician participation in Continuing Medical Education programs may be influenced by a number of factors. To evaluate the factors associated with compliance with the Continuing Medical Education requirements at a private hospital, we investigated whether physicians’ activity, measured by volumes of admissions and procedures, was associated with obtaining 40 Continuing Medical Education credits (40 hours of activities) in a 12-month cycle. Methods In an exclusive and non-mandatory Continuing Medical Education program, we collected physicians’ numbers of hospital admissions and numbers of surgical procedures performed. We also analyzed data on physicians’ time since graduation, age, and gender. Results A total of 3,809 credentialed, free-standing, private practice physicians were evaluated. Univariate analysis showed that the Continuing Medical Education requirements were more likely to be achieved by male physicians (odds ratio 1.251; p=0.009) and who had a higher number of hospital admissions (odds ratio 1.022; p<0.001). Multivariate analysis showed that age and number of hospital admissions were associated with achievement of the Continuing Medical Education requirements. Each hospital admission increased the chance of achieving the requirements by 0.4%. Among physicians who performed surgical procedures, multivariate analysis showed that male physicians were 1.3 time more likely to achieve the Continuing Medical Education requirements than female physicians. Each surgical procedure performed increased the chance of achieving the requirements by 1.4%. Conclusion The numbers of admissions and number of surgical procedures performed by physicians at our hospital were associated with the likelihood of meeting the Continuing Medical Education requirements. These findings help to shed new light on our Continuing Medical Education program.

Introdução: A saliva exerce influência primordial na homeostase do sistema digestório, pelos seus componentes inorgânicos e pelos fatores de crescimento. Indivíduos com sindrome de Sjögren (SS) apresentam maior incidência da doença do refluxo gastroesofágico (DRGE) e do refluxo laringofaríngeo (RLF). Concentrações salivares diminuídas do fator transformador de crescimento alfa (TGF-α) foram observadas em doentes dispépticos, porém não há estudos em populações com SS e RLF. Objetivo: Comparar concentrações salivares do TGF-α; de indivíduos com SS e RLF a de controles saudáveis. Método: Trata-se de um estudo prospectivo controlado. Doze pacientes com SS e RLF e 11 indivíduos controles saudáveis tiveram amostras salivares espontâneas e estimuladas coletadas para estabelecer concentração de TGF-α. Resultados: A concentração salivar de TGF-α; foi estatisticamente maior no grupo estudo para ambas amostras. Este aumento foi confirmado nos sete indivíduos do grupo estudo que não apresentavam esofagite erosiva quando comparados ao grupo controle, porém não houve diferença estatística da concentração de TGF-α; entre pacientes do grupo estudo que apresentava mesofagite erosiva em comparação ao grupo controle. Conclusão: A concentração salivar de TGF-α; foi estatisticamente maior no grupo de indivíduos com SS e RLF, sem esofagite erosiva.

Introduction: Saliva plays a key role in the homeostasis of the digestive tract, through its inorganic components and its protein growth factors. Sjögren's syndrome patients have a higher prevalence of gastroesophageal reflux disease and laryngopharyngeal reflux. Decreased salivary transforming growth factor alpha levels were observed in dyspeptic patients, but there have been no studies in patients with Sjögren's syndrome and laryngopharyngeal reflux. Objective: To compare the salivary transforming growth factor alpha levels of patients with Sjögren's syndrome and laryngopharyngeal reflux to those of healthy controls. Methods: This is a prospective controlled study. Twelve patients with Sjögren's syndrome and laryngopharyngeal reflux and 11 controls were prospectively evaluated. Spontaneous and stimulated saliva samples were obtained to establish salivary transforming growth factor alpha concentrations. Results: The salivary transforming growth factor alpha levels of patients were significantly higher than those of healthy controls. Five patients with laryngopharyngeal reflux also had erosive esophagitis; their salivary transforming growth factor alpha levels were comparable to controls. Conclusion: Salivary transforming growth factor alpha level was significantly higher in patients with Sjögren's syndrome and laryngopharyngeal reflux when compared to the control group.

OBJETIVO: Implementar um programa de gestão da pesquisa científica em um hospital geral aplicando as ferramentas de gestão empresarial Lean Seis Sigma e PMBOK no gerenciamento de projetos nessa área. MÉTODOS: Foi utilizada a metodologia Lean Seis Sigma para melhoria do processo de gestão da pesquisa científica institucional por meio de ferramenta específica (DMAIC) para identificação, implementação e posterior análise das soluções encontradas, tendo como base as boas práticas descritas no PMBOK. RESULTADOS: São apresentadas as soluções implementadas na Sociedade Beneficente Israelita Brasileira Albert Einstein para o gerenciamento dos projetos de pesquisa institucionais. As soluções foram categorizadas em quatro instâncias: pessoas, processos, sistema e cultura organizacional. Uma análise preliminar das soluções implementadas mostra que essas são, total ou parcialmente, aderentes às preconizadas no Guia PMBOK. CONCLUSÃO: Neste estudo de caso post facto, verificou-se que as soluções implementadas a partir do projeto Lean Seis Sigma e baseadas no PMBOK permitiram a melhoria de processo da gestão da pesquisa científica institucional, constituindo um modelo que pretende contribuir com a busca de soluções inovadoras na gestão da pesquisa pelas diferentes instituições com atividade científica no Brasil.

OBJECTIVE: Introduce a program for the management of scientific research in a General Hospital employing the business management tools Lean Six Sigma and PMBOK for project management in this area. METHODS: The Lean Six Sigma methodology was used to improve the management of the institution's scientific research through a specific tool (DMAIC) for identification, implementation and posterior analysis based on PMBOK practices of the solutions found. RESULTS: We present our solutions for the management of institutional research projects at the Sociedade Beneficente Israelita Brasileira Albert Einstein. The solutions were classified into four headings: people, processes, systems and organizational culture. A preliminary analysis of these solutions showed them to be completely or partially compliant to the processes described in the PMBOK Guide. CONCLUSION: In this post facto study, we verified that the solutions drawn from a project using Lean Six Sigma methodology and based on PMBOK enabled the improvement of our processes dealing with the management of scientific research carried out in the institution and constitutes a model to contribute to the search of innovative science management solutions by other institutions dealing with scientific research in Brazil.