Critical evaluation of migration studies of silver nanoparticles present in food packaging: a systematic review.

The large use of silver nanoparticles (AgNPs) has provided safety concerns due to the risks of exposure to this nanomaterial caused by the possibility of transfer of the AgNP from the polymer to the food. The gap in scientific knowledge regarding AgNP's migration capacity has been high in the number of publications. This article critically analyzes AgNP migration studies in food packaging, showing which parameters should be followed to ensure reliability in the results found. A systematic review (SR) of the literature was performed in the electronic databases PubMed, SCOPUS, SciELO, LILACS/BVS, and Embase and in the gray literature, without date restrictions, until August 21, 2017, to identify studies who evaluated the migration of AgNP in food packaging. Among the 26 articles that have been part of this SR, only 2 (M3 and M5) showed no migration evidence; however, these results are questionable, because all studies present conflicting, contradictory, or questionable results. From this RS, it was not possible to assure that the AgNPs present in food packages tend to migrate to the food matrix, since some methodological inconsistences were identified in all studies evaluated, demonstrating the need for standardization of methodological guidelines for the new migration studies.

Applicability of the Monocyte Activation Test (MAT) in the quality control of the 17DD yellow fever vaccine.

The need for alternatives to animal use in pyrogen testing has been driven by the Three Rs concept. This has resulted in the inclusion of the monocyte activation test (MAT) in the European Pharmacopoeia, 2010. However, some technical and regulatory obstacles must be overcome to ensure the effective implementation of the MAT by the industry, especially for the testing of biological products. The yellow fever (YF) vaccine (17DD-YFV) was chosen for evaluation in this study, in view of: a) the 2016-2018 outbreak of YF in Brazil; b) the increase in demand for 17DD-YFV doses; c) the complex production process with live attenuated virus; d) the presence of possible test interference factors, such as residual process components (e.g. ovalbumin); and e) the need for the investigation of other pyrogens that are not detectable by the methods prescribed in the YF vaccine monograph. The product-specific testing was carried out by using cryopreserved and fresh whole blood, and IL-6 and IL-1ß levels were used as the marker readouts. After assessing the applicability of the MAT on a 1:10 dilution of 17DD-YFV, endotoxin and non-endotoxin pyrogens were quantified in spiked batches, by using the lipopolysaccharide and lipoteichoic acid standards, respectively. The quantitative analysis demonstrated the correlation between the MAT and the Limulus amoebocyte lysate (LAL) assays, with respect to the limits of endotoxin recovery in spiked batches and the detection of no pyrogenic contamination in commercial batches of 17DD-YFV. The data demonstrated the applicability of the MAT for 17DD-YFV pyrogen testing, and as an alternative method that can contribute to biological quality control studies.

[Profile and career path of graduates from the Oswaldo Cruz Foundation master's and doctoral courses (2013-2020)]. / Perfil e percurso profissional de egressos dos cursos de mestrado e doutorado da Fundação Oswaldo Cruz (2013-2020).

This study aims to analyze the profile of graduates and identify factors associated with positive performance regarding training and professional insertion among those who have completed face-to-face master's and doctoral courses at the Oswaldo Cruz Foundation (Brazil). A total of 2,462 graduates participated in the study (1,402 master's and 1,060 doctoral graduates), who answered a digital questionnaire containing questions about individual characteristics and professional insertion before entering the course and after completion. A measure on "positive post-course performance" was created. The results show that Master's graduates with a positive impact from the course tend to be men; to have a specialization degree before entering the course; to have paid employment after finishing the course in the areas of research, education, assistance, and management; and to be civil servants. In the Doctorate, the following profile is evident: graduates with paid employment after finishing the course in the areas of research or education; hired under a single legal regime or temporary contract as a legal entity; and with a scientific publication or patent. Evaluating/monitoring graduates must be established as an important public educational policy, incorporated into the institutional self-evaluation process, which makes it possible to review directions and priorities in the institution's educational and pedagogical agenda.

O objetivo do estudo é analisar o perfil de egressos e identificar fatores associados ao desempenho positivo relativo à trajetória de formação e de inserção profissional entre aqueles que concluíram cursos presenciais de mestrado e doutorado acadêmico da Fundação Oswaldo Cruz (Brasil). Participaram do estudo 2.462 egressos (1.402 de mestrado e 1.060 de doutorado) que responderam um questionário digital, contendo questões sobre perfil do egresso e inserção profissional antes do ingresso no curso e após a conclusão. Foi criada uma medida sobre "desempenho positivo pós-curso". Os resultados revelam que egressos de mestrado com impacto positivo do curso tendem a ser homens; ter especialização antes de ingressar no curso; ter emprego remunerado após o término do curso nas áreas de pesquisa, educação, assistência e gestão; e ser servidor público. No doutorado o seguinte perfil é evidenciado: egressos com emprego remunerado após o término do curso nas áreas de pesquisa ou educação; contratados por Regime Jurídico Único ou contrato temporário de pessoa jurídica; e com publicação científica ou patente. A avaliação/acompanhamento de egressos deve se instaurar como uma importante política pública educacional, incorporada no processo de autoavaliação institucional, o que possibilita rever rumos e prioridades na agenda educacional e pedagógica da instituição.

El objetivo del estudio es analizar el perfil de egresados e identificar factores asociados al desempeño positivo relacionado a la trayectoria de formación e inserción profesional entre aquellos que concluyeron cursos presenciales de maestría y doctorado académico de la Fundación Oswaldo Cruz (Brasil). Participaron del estudio 2.462 egresados (1.402 de maestría y 1.060 de doctorado) que contestaron el cuestionario de manera digital, con preguntas sobre el perfil del egresado y la inserción profesional antes del ingreso al curso y tras su conclusión. Se creó una medida sobre "desempeño positivo tras el curso". Los resultados muestran que los egresados de la maestría con un impacto positivo del curso tienden a ser hombres; tener especialización antes de ingresar al curso; tener trabajo remunerado tras concluir el curso en las áreas de investigación, educación, asistencia y gestión; y ser funcionario público. Se evidencia el siguiente perfil en el doctorado: egresados con trabajo remunerado tras el término del curso en las áreas de investigación o educación; contratados bajo un régimen jurídico único o un contrato temporal de persona jurídica; y con publicación científica o patente. La evaluación/seguimiento de egresados se debe establecer como una importante política pública educativa, incorporada en el proceso de autoevaluación institucional, lo que permite revisar direcciones y prioridades en la agenda educativa y pedagógica de la institución.

Professional trajectory and the impact of education on Fiocruz specialization graduates. / Trajetória profissional e impacto da formação em egressos da Especialização da Fiocruz.

This work aimed to analyze graduates' profiles, education's effects, and the professional trajectory of those who completed lato sensu courses at Fiocruz. A total of 1,620 graduates participated in 79 courses completed in the 2013-2020 period. A questionnaire was applied before the course and after its completion. A description of the absolute and relative frequency of the variables was realized. A binary logistic regression model was developed to identify variables associated with the positive impact of the course. The odds ratio and its 95% confidence interval were the measures used. Among graduates with a positive impact from the course, those with black/brown skin color are 40% more likely to have a positive impact from the course than those with white skin color; those who have other academic education before the course are 1.5 times more likely than those who have no previous education; those who changed their professional activity as a result of the course are 3.3 more likely than those who were not working; those who reported that the course was closely related to their professional activity were 5.7 more likely than those who reported that the course had poor or no relationship. Every one-year increase since graduation increased the likelihood of the course's positive impact by 14%.

O objetivo da pesquisa foi analisar o perfil dos egressos, os efeitos da formação e a trajetória profissional dos que concluíram cursos presenciais de Especialização da Fiocruz. Participaram 1.620 egressos de 79 cursos concluídos entre 2013 e 2020. Foi aplicado questionário antes do ingresso e após o término do curso. Foi realizada descrição da frequência absoluta e relativa das variáveis e desenvolvido modelo de regressão logística binária para identificar variáveis associadas ao impacto positivo do curso. A razão de chance e seu intervalo de confiança de 95% foram as medidas utilizadas. Entre os egressos com impacto positivo do curso concluído: aqueles com cor de pele preta ou parda têm cerca de 40% mais chance de ter impacto positivo do curso do que os de cor de pele branca; os que têm outra formação acadêmica antes do curso têm 1,5 vez mais chance do que os que não têm outra formação anterior, aqueles que mudaram a atividade profissional em função do curso têm 3,3 mais chance do que os que não estavam trabalhando, os que informaram que o curso estava muito relacionado à atividade profissional têm 5,7 mais chance do que os que relataram que o curso teve pouca ou nenhuma relação; e cada acréscimo de 1 ano no tempo de formado aumenta em 14% a chance do impacto positivo do curso.

Epidemiology of enteric virus infections in children living in the Amazon region.

OBJECTIVES: To verify the frequency of viruses causing acute gastroenteritis (AGE) in association with the histo-blood group antigen (HBGA) and Rotarix™ vaccination coverage in children from the Amazon region. DESIGN: Fecal and saliva samples were collected from children with AGE (n = 485) and acute respiratory infection (ARI) (n = 249) clinical symptoms. Rotavirus A (RVA), norovirus, human adenovirus (HAdV), and sapovirus (SaV) were verified in feces by molecular detection. Saliva samples were used for HBGA phenotyping/FUT3 genotyping. Blood group types, clinical aspects and Rotarix™ RVA vaccination data were recorded. RESULTS: Norovirus remained the most prevalently detected cause of AGE (38%, 184/485 and ARI 21.3%, 53/249). High HAdV frequencies were observed in AGE children (28.6%, 139/485) and ARI children (37.3%, 93/249). RVA was the third most prevalent virus causing AGE (22.7%, 110/485 and ARI 19.3%, 48/249) and a low RV1 coverage (61%, 448/734) was verified. The SaV frequencies were lower (7.2%, 35/485 for AGE and 6.8%, 17/249 for ARI). Secretor children were HBGA susceptible to HAdV infection (OR 1.5, 95% CI 1.0-2.3; P = 0.04) but not to RVA, norovirus or SaV infection. CONCLUSIONS: Norovirus could be considered the main etiological agent of AGE. No association was verified for HBGA susceptibility to RVA, norovirus and SaV. Secretor children showed a slight susceptibility to HAdV infection and the Le (a-b-) heterogeneous SNPs on the FUT3 gene.

Postnatal development and fertility of offspring from mice exposed to triphenyltin (fentin) hydroxide during pregnancy and lactation.

Fentin or triphenylthin (TPT) is an organotin compound (OTC) widely used as an agricultural fungicide and miticide. It is well known that TPT exerts adverse effects on the reproductive and immune systems and may disrupt the endocrine system, raising concerns regarding the risks posed by exposure to this metal on environmental and human health. In this study the effects of maternal exposure to TPT at doses of control (0), 1.875, 3.75, or 7.5 mg/kg body weight/d, po, were examined during gestation and lactation on offspring growth, organ weights, and fertility. Except for a significant liver enlargement at the highest dose, TPT produced no maternal toxicity. Increased neonatal mortality (death of 3 entire litters from a total of 18 treated litters) was noted at 7.5 mg/kg. Pup body weight at birth was significantly reduced at all dose levels, but no marked weight loss was found on postnatal day (PND) 5 and thereafter. Offspring maturation (ear unfolding, incisor eruption, vagina opening, and testes descent) and fertility in adulthood were not significantly affected by maternal exposure to TPT. In conclusion, data provided by this study indicate that maternal treatment with TPT during pregnancy and lactation delayed prenatal growth but did not impair postnatal development and fertility in exposed offspring in adulthood.

Antenatal exposure to antidepressant drugs and the risk of neurodevelopmental and psychiatric disorders: a systematic review.

This study investigated whether antenatal exposure to antidepressants (ADs) increases the risks of autism spectrum disorders (ASD), attention deficit/hyperactivity disorders (ADHD), schizophrenia and other mental illnesses, and cognitive and developmental deficits in infants or preschool children. PubMed, EMBASE, BIREME/BVS databases were searched to identify studies examining associations of ADs in pregnancy with neurodevelopmental and psychiatric disorders. Twenty studies addressed ASD and/or ADHD risks while 30 focused on developmental and cognitive deficits in infants or preschool children. Most studies detected no association of antenatal AD with ASD after adjustment of risk ratios for maternal depression or psychiatric disorders. Some studies showed that maternal depression, regardless of whether it is treated or untreated, increased ASD risks. Seven out of 8 studies found no increase in ADHD risk associated with antenatal exposure to selective serotonin reuptake inhibitors, the most commonly used AD. No consistent evidence was found linking AD in pregnancy to neurocognitive developmental deficits in infants or preschool children. A residual confounding by indication (depression severity) remained in almost all studies. This systematic review found no consistent evidence suggesting that ADs in pregnancy increase risks of ASD, ADHD, and neurocognitive development deficits. Some studies, however, found evidence that maternal depression increases ASD risks.

Human Bocavirus genotypes 1 and 2 detected in younger Amazonian children with acute gastroenteritis or respiratory infections, respectively.

OBJECTIVES: This study aimed to verify the frequency, genotypes, and etiological role of Human Bocavirus (HBoV) in younger Amazonian children with either acute gastroenteritis (AGE) or respiratory infections (ARI). The influence of Rotarix™ vaccination and co-infection status was also investigated. DESIGN: HBoV quantitative polymerase chain reaction (qPCR) testing was done on both fecal and saliva (1468 samples) from 734 children < 5 months old living in the Amazon (Brazil, Guyana, and Venezuela). High and median HBoV viral load samples were used for extraction, nested PCR amplification, and sequencing for genotyping. HBoV mRNA detection was done by reverse transcription following DNA amplification. RESULTS: The overall HBoV frequencies were 14.2% (69/485; AGE) and 14.1% (35/249; ARI) (p = 0.83). HBoV exclusively infected 4.5% (22/485; AGE) and 4% (10/249) of the Amazonian children (Odds ratios 1.13, 95% confidence interval= 2.42-0.52). HBoV 1 was mainly detected in feces and saliva from AGE children; and HBoV2, from ARI children. HBoV mRNA was detected only in feces. The Rotarix™ vaccination status did not affect the HBoV frequencies. CONCLUSIONS: We suggest that, after entry into the air/oral pathways, HBoV1 continues infecting toward the intestinal tract causing AGE. HBoV2 can be a causative agent of AGE and ARI in younger Amazonian children.

Perfil e percurso profissional de egressos dos cursos de mestrado e doutorado da Fundação Oswaldo Cruz (2013-2020) / Profile and career path of graduates from the Oswaldo Cruz Foundation master's and doctoral courses (2013-2020) / Perfil y trayectoria profesional de egresados de los cursos de maestría y doctorado de la Fundación Oswaldo Cruz (2013-2020)

Resumo: O objetivo do estudo é analisar o perfil de egressos e identificar fatores associados ao desempenho positivo relativo à trajetória de formação e de inserção profissional entre aqueles que concluíram cursos presenciais de mestrado e doutorado acadêmico da Fundação Oswaldo Cruz (Brasil). Participaram do estudo 2.462 egressos (1.402 de mestrado e 1.060 de doutorado) que responderam um questionário digital, contendo questões sobre perfil do egresso e inserção profissional antes do ingresso no curso e após a conclusão. Foi criada uma medida sobre "desempenho positivo pós-curso". Os resultados revelam que egressos de mestrado com impacto positivo do curso tendem a ser homens; ter especialização antes de ingressar no curso; ter emprego remunerado após o término do curso nas áreas de pesquisa, educação, assistência e gestão; e ser servidor público. No doutorado o seguinte perfil é evidenciado: egressos com emprego remunerado após o término do curso nas áreas de pesquisa ou educação; contratados por Regime Jurídico Único ou contrato temporário de pessoa jurídica; e com publicação científica ou patente. A avaliação/acompanhamento de egressos deve se instaurar como uma importante política pública educacional, incorporada no processo de autoavaliação institucional, o que possibilita rever rumos e prioridades na agenda educacional e pedagógica da instituição.

Abstract: This study aims to analyze the profile of graduates and identify factors associated with positive performance regarding training and professional insertion among those who have completed face-to-face master's and doctoral courses at the Oswaldo Cruz Foundation (Brazil). A total of 2,462 graduates participated in the study (1,402 master's and 1,060 doctoral graduates), who answered a digital questionnaire containing questions about individual characteristics and professional insertion before entering the course and after completion. A measure on "positive post-course performance" was created. The results show that Master's graduates with a positive impact from the course tend to be men; to have a specialization degree before entering the course; to have paid employment after finishing the course in the areas of research, education, assistance, and management; and to be civil servants. In the Doctorate, the following profile is evident: graduates with paid employment after finishing the course in the areas of research or education; hired under a single legal regime or temporary contract as a legal entity; and with a scientific publication or patent. Evaluating/monitoring graduates must be established as an important public educational policy, incorporated into the institutional self-evaluation process, which makes it possible to review directions and priorities in the institution's educational and pedagogical agenda.

Resumen: El objetivo del estudio es analizar el perfil de egresados e identificar factores asociados al desempeño positivo relacionado a la trayectoria de formación e inserción profesional entre aquellos que concluyeron cursos presenciales de maestría y doctorado académico de la Fundación Oswaldo Cruz (Brasil). Participaron del estudio 2.462 egresados (1.402 de maestría y 1.060 de doctorado) que contestaron el cuestionario de manera digital, con preguntas sobre el perfil del egresado y la inserción profesional antes del ingreso al curso y tras su conclusión. Se creó una medida sobre "desempeño positivo tras el curso". Los resultados muestran que los egresados de la maestría con un impacto positivo del curso tienden a ser hombres; tener especialización antes de ingresar al curso; tener trabajo remunerado tras concluir el curso en las áreas de investigación, educación, asistencia y gestión; y ser funcionario público. Se evidencia el siguiente perfil en el doctorado: egresados con trabajo remunerado tras el término del curso en las áreas de investigación o educación; contratados bajo un régimen jurídico único o un contrato temporal de persona jurídica; y con publicación científica o patente. La evaluación/seguimiento de egresados se debe establecer como una importante política pública educativa, incorporada en el proceso de autoevaluación institucional, lo que permite revisar direcciones y prioridades en la agenda educativa y pedagógica de la institución.

Trajetória profissional e impacto da formação em egressos da Especialização da Fiocruz / Professional trajectory and the impact of education on Fiocruz specialization graduates

Resumo O objetivo da pesquisa foi analisar o perfil dos egressos, os efeitos da formação e a trajetória profissional dos que concluíram cursos presenciais de Especialização da Fiocruz. Participaram 1.620 egressos de 79 cursos concluídos entre 2013 e 2020. Foi aplicado questionário antes do ingresso e após o término do curso. Foi realizada descrição da frequência absoluta e relativa das variáveis e desenvolvido modelo de regressão logística binária para identificar variáveis associadas ao impacto positivo do curso. A razão de chance e seu intervalo de confiança de 95% foram as medidas utilizadas. Entre os egressos com impacto positivo do curso concluído: aqueles com cor de pele preta ou parda têm cerca de 40% mais chance de ter impacto positivo do curso do que os de cor de pele branca; os que têm outra formação acadêmica antes do curso têm 1,5 vez mais chance do que os que não têm outra formação anterior, aqueles que mudaram a atividade profissional em função do curso têm 3,3 mais chance do que os que não estavam trabalhando, os que informaram que o curso estava muito relacionado à atividade profissional têm 5,7 mais chance do que os que relataram que o curso teve pouca ou nenhuma relação; e cada acréscimo de 1 ano no tempo de formado aumenta em 14% a chance do impacto positivo do curso.

Abstract This work aimed to analyze graduates' profiles, education's effects, and the professional trajectory of those who completed lato sensu courses at Fiocruz. A total of 1,620 graduates participated in 79 courses completed in the 2013-2020 period. A questionnaire was applied before the course and after its completion. A description of the absolute and relative frequency of the variables was realized. A binary logistic regression model was developed to identify variables associated with the positive impact of the course. The odds ratio and its 95% confidence interval were the measures used. Among graduates with a positive impact from the course, those with black/brown skin color are 40% more likely to have a positive impact from the course than those with white skin color; those who have other academic education before the course are 1.5 times more likely than those who have no previous education; those who changed their professional activity as a result of the course are 3.3 more likely than those who were not working; those who reported that the course was closely related to their professional activity were 5.7 more likely than those who reported that the course had poor or no relationship. Every one-year increase since graduation increased the likelihood of the course's positive impact by 14%.

Métodos alternativos para determinação da potência de veneno e antiveneno botrópico: aplicações e perspectivas para o controle da qualidade / Alternative methods for potency evaluation for Bothrops venom and antivenom: applications and perspectives for quality control

Introdução: Acidentes com animais peçonhentos são classificados como doenças tropicais negligenciadas e são atualmente a mais frequente causa de intoxicação em humanos no Brasil. O único tratamento disponível é a rápida administração de antivenenos específicos e de qualidade garantida. Para assegurar a eficácia e a segurança desses produtos, são realizados ensaios de determinação da potência in vivo para veneno e antiveneno, desde as etapas de produção até sua liberação final. Apesar dos diversos estudos sobre métodos   alternativos ao ensaio murino, nenhum método foi efetivamente validado. Objetivo: Compilar os métodos alternativos desenvolvidos para os antivenenos botrópicos, avaliando sua disponibilidade, perspectivas e aplicações em laboratórios de produção e controle da qualidade. Método: Foi realizada uma busca nas bases PubMed, BVS e Scopus entre novembro de 2021 e junho de 2022. Foram identificados 89 trabalhos, dos quais 31 foram selecionados de acordo com os critérios de elegibilidade. Resultados: Nos métodos alternativos identificados, observamos a preferência de 42,80% dos estudos por metodologias que utilizem linhagens celulares como método alternativo aos ensaios murinos, sendo que a maioria destes trabalhos 58,30% optou pela linhagem celular Vero. Conclusões: Pela diversidade das toxinas encontradas em cada gênero de serpentes, entende-se que é de extrema importância que o ensaio de potência dos antivenenos tenha como base a avaliação e a quantificação precisa da inibição da atividade biológica dos venenos. Ensaios de citotoxicidade são amplamente utilizados e têm acumulado evidências de sua adequação como importante ferramenta alternativa ao ensaio murino para o controle da qualidade de veneno e antiveneno antibotrópico.

Introduction: Accidents with venomous animals are classified as neglected tropical diseases and are currently the most frequent cause of intoxication in humans in Brazil. The only available treatment is the rapid administration of specific, quality-assured antivenoms. To ensure the efficacy and safety of these products, in vivo potency determination tests for venom and antivenom are performed during the production stages, until final release. Despite several studies on alternative methods to the murine assay, no method has been effectively validated. Objective: To compile alternative methods developed for Bothrops antivenoms, assessing the availability of the methods and the prospects and applications in Bothrops venom and antivenom production and quality control laboratories. Method: A search was conducted in PubMed, BVS, and Scopus databases between November 2021 and June 2022. 89 articles were identified, of which 31 were selected according to the eligibility criteria. Results: We observed in the alternative methods identified a preference of 42.80% of the studies for methodologies that use cell lines as an alternative method to the murine assays, and most of these works (58.30%) opted for a VERO cell line. Conclusions: Due to the diversity of toxins found in each genus of snakes, it is understood that the potency assay for antivenoms should be based on the evaluation and precise quantification of the inhibition of biological activity of venoms. Cytotoxicity assays are widely used and have been accumulating evidence of their suitability as an important alternative tool to the murine assay for quality control for Bothrops venom and antivenom.

On the safety and effectiveness of COVID-19 vaccines, certainties and uncertainties / Sobre a segurança e efetividade das vacinas para COVID-19, certezas e incertezas

Introduction: The COVID-19 vaccines in use (inactivaded virus, encapsulated m-RNA, non-replicating adenovirus-vectored DNA) were clinically tested in randomized placebo- controlled phase-3 studies. Objective: To address certainties and uncertainties about safety and effectiveness of COVID-19 vaccines that were approved for use in various countries.Method: The evidence provided by clinical studies on the efficacy and safety of COVID-19 vaccines was critically appraised. Results: COVID-19 vaccines proved to be efficacious and safe in clinical trials. Adverse events were mostly those of minor severity commonly noted with other vaccines such as injection site pain, mild flu-like symptoms, headache and asthenia. Although being very rare, anaphylaxis-like reactions were noted with mRNA vaccines. Uncertainties regarding vaccine effectiveness refer mainly to the (long-term) duration of immunity provided by vaccination, the degree of protection conferred to elderly people, and how effective vaccines are against emerging SARS-CoV-2 variants. There are few uncertainties about vaccine safety including the absence of clinical trial data in pregnant women (and the impact on the unborn child), children and adolescents. Conclusions: Notwithstanding the knowledge gaps about effectiveness and safety of COVID-19 vaccines (to be further addressed by observational studies), there is overwhelming evidence that public health benefits of vaccination by far outweigh any foreseeable risk.

Introdução: As vacinas contra COVID-19 (vírus inativado, m-RNA encapsulado, vetor adenovírus não replicante) foram testadas em ensaios clínicos randomizados (fase-3) controlados com placebo. Objetivo: Abordar as certezas e incertezas sobre segurança e efetividade das vacinas para COVID-19 já aprovadas para uso em vários países. Método: A evidência clínica de eficácia e segurança das vacinas contra COVID-19 foram examinadas criticamente. Resultados: As vacinas (COVID-19) mostraram ser eficazes e seguras nos ensaios clínicos. Os eventos adversos foram predominantemente os de menor gravidade comumente observados com outras vacinas, tais como dor no local da injeção, sintomas gripais leves, cefaleia e fraqueza. Embora sejam raras, reações do tipo anafilático foram registradas com vacinas mRNA. As incertezas sobre efetividade referem-se à duração da imunidade conferida pela vacina, o grau de proteção de idosos, e a efetividade das vacinas contra as novas variantes do SARS-CoV-2. As incertezas sobre segurança são poucas e incluem a ausência de estudos clínicos em grávidas (e sobre o bebê no útero), em crianças e adolescentes. Conclusões: Não obstante as poucas lacunas acerca da efetividade e segurança das vacinas contra COVID-19 (a serem abordadas por estudos observacionais), os previsíveis benefícios da vacinação para a saúde pública excedem de longe quaisquer riscos antecipáveis.

Applicability of the Monocyte Activation Test (MAT) for hyperimmune sera in the routine of the quality control laboratory: Comparison with the Rabbit Pyrogen Test (RPT).

Pyrogen tests are safety assays performed during the routine quality control of injectable products required by regulatory agencies. Currently, there are three available testing possibilities: 1) the Rabbit Pyrogen Test (RPT); 2) the Bacterial Endotoxin Test (BET); and 3) test systems using human whole-blood or monocytes, termed Monocyte Activation Test (MAT). Although BET is often considered as a replacement for the animal test, it is unable to detect pyrogens other than endotoxin. MAT is based on the human fever reaction and thus, most closely reflects the human response. The aim of this study was to conduct a parallel comparison of the RPT and MAT for hyperimmune sera (HS) batches analyzed during the routine of a quality control laboratory. MAT was performed in the same 43 batches of HS previously tested using RPT. The results showed that MAT presented 100% sensitivity and approximately 85% specificity as compared to RPT, i.e., no false-negative results were obtained. Few suspicious samples, which were negative in the RPT after retesting, provided divergent positive results suggesting a lower limit of detection of MAT. MAT is thus able to detect contaminants in biological products such as HS batches.

Antenatal exposure to antidepressant drugs and the risk of neurodevelopmental and psychiatric disorders: a systematic review / Exposição intrauterina a antidepressivos e risco de transtornos de neurodesenvolvimento e psiquiátricos: uma revisão sistemática / Exposición prenatal a medicamentos antidepresivos y riesgo de trastornos psiquiátricos y en el desarrollo neurológico: una revisión sistemática

Abstract: This study investigated whether antenatal exposure to antidepressants (ADs) increases the risks of autism spectrum disorders (ASD), attention deficit/hyperactivity disorders (ADHD), schizophrenia and other mental illnesses, and cognitive and developmental deficits in infants or preschool children. PubMed, EMBASE, BIREME/BVS databases were searched to identify studies examining associations of ADs in pregnancy with neurodevelopmental and psychiatric disorders. Twenty studies addressed ASD and/or ADHD risks while 30 focused on developmental and cognitive deficits in infants or preschool children. Most studies detected no association of antenatal AD with ASD after adjustment of risk ratios for maternal depression or psychiatric disorders. Some studies showed that maternal depression, regardless of whether it is treated or untreated, increased ASD risks. Seven out of 8 studies found no increase in ADHD risk associated with antenatal exposure to selective serotonin reuptake inhibitors, the most commonly used AD. No consistent evidence was found linking AD in pregnancy to neurocognitive developmental deficits in infants or preschool children. A residual confounding by indication (depression severity) remained in almost all studies. This systematic review found no consistent evidence suggesting that ADs in pregnancy increase risks of ASD, ADHD, and neurocognitive development deficits. Some studies, however, found evidence that maternal depression increases ASD risks.

Resumo: O estudo teve como objetivo investigar se a exposição intrauterina a antidepressivos (ADs) aumenta o risco de transtornos do espectro autista (TEA), transtorno de déficit de atenção e hiperatividade (TDAH), esquizofrenia e outros transtornos mentais e déficits cognitivos e de desenvolvimento em lactentes e pré-escolares. Foram realizadas buscas nas bases PubMed, EMBASE e BIREME/BVS para identificar estudos sobre associações entre o uso de ADs durante a gestação e transtornos de neurodesenvolvimento e psiquiátricos. Vinte estudos trataram de riscos de TEA e/ou TDAH, enquanto 30 focaram em déficits cognitivos e de desenvolvimento em lactentes ou pré-escolares. A maioria dos estudos não detectou associação entre AD na gestação e TEA, depois de ajustar as razões de risco para depressão ou outros transtornos psiquiátricos maternos. Alguns estudos mostraram que a depressão materna, quer tratada ou não, aumenta o risco de TEA. Sete entre oito estudos não detectaram aumento de risco de TDAH associado à exposição intrauterina a inibidores seletivos da recaptação da serotonina, o AD mais comumente utilizado. Não foram encontradas evidências consistentes entre o uso de AD na gestação e déficits de desenvolvimento neurocognitivo em lactentes ou pré-escolares. Em quase todos os estudos, permaneceu um confundimento residual por indicação (gravidade da depressão). A revisão sistemática não encontrou evidências consistentes de que os ADs na gestação aumentassem o risco de TEA, TDAH ou déficits de desenvolvimento neurocognitivo. Entretanto, alguns estudos evidenciaram que a depressão materna aumenta o risco de TEA.

Resumen: Este estudio investigó si la exposición prenatal a antidepresivos (ADs) incrementa los riesgos de trastornos del espectro autista (TEA), trastornos de déficit de atención/hiperactividad (TDAH), esquizofrenia, así como otras enfermedades mentales, cognitivas, y déficits en el desarrollo de niños de primaria o preescolares. Se consultaron las bases de datos PubMed, EMBASE, BIREME/BVS para identificar estudios de asociaciones de ADs durante el embarazo con trastornos de desarrollo neurológico y psiquiátricos. Veinte estudios estaban centrados en riesgos de TEA y/o TDAH, mientras que 30 se centraron en déficits de desarrollo y cognitivos en niños de primaria o preescolares. La mayor parte de los estudios no detectaron asociación de AD, durante la etapa prenatal, con TDA tras el ajuste de las ratios de riesgo para depresión materna o trastornos psiquiátricos. Algunos estudios mostraron que la depresión materna, independientemente de si es tratada o no, incrementó los riesgos de TEA. Siete de los 8 estudios no encontraron un incremento en el riesgo de TDAH, asociado con la exposición prenatal a inhibidores selectivos de la recaptación de serotonina, el antidepresivo más usado habitualmente durante el período prenatal. No se encontraron evidencias consistentes relacionando AD durante el embarazo y déficits en el desarrollo neurocognitivo de niños de primaria o preescolares. En casi todos los estudios hubo una desviación residual señalada como gravedad de la depresión. Esta revisión sistemática no halló evidencias consistentes, sugiriendo que el consumo de ADs durante el embarazo incremente el riesgo de TEA, TDAH, y déficits en el desarrollo neurocognitivo. Algunos estudios, no obstante, encontraron evidencias de que la depresión materna incrementa riesgos de TEA.

[Pesticide use and poisoning among farmers from the county of Paty do Alferes, Rio de Janeiro, Brazil]. / Intoxicações e uso de pesticidas por agricultores do Município de Paty do Alferes, Rio de Janeiro, Brasil.

This survey is part of a more comprehensive study on the health consequences of pesticide exposure. In the county (municipality) of Paty do Alferes, Rio de Janeiro State, Brazil, 55 agricultural workers were interviewed on the use of pesticides, use of personal protective equipment, data on health status, and symptoms related to pesticide exposure, disposal of agrochemical containers, and technical assistance. The most widely used pesticides were insecticides such as abamectin, organophosphate compounds, and pyrethroids, and fungicides such as mancozeb, chlorothalonil, and copper products. As a rule, pesticides are handled carelessly, and 92% of workers involved in the mixing, loading, and spraying of insecticides and fungicides used no protective clothing or equipment whatsoever. Some 62% of workers reported at least one illness associated with mixing or spraying pesticides. The most frequently reported symptoms were headache, nausea, vomiting, dizziness, skin irritation, and blurred vision, and 21% of affected workers required medical care. In more than half (51%) of the cases, workers reported using organophosphate insecticides from toxicological class I when they felt sick.

Serum levels of organochlorine pesticides and polychlorinated biphenyls among inhabitants of Greater Metropolitan Rio de Janeiro, Brazil.

Levels of persistent organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were determined in the blood serum of people living and working in the urban area of greater Rio de Janeiro city. Blood samples from 33 volunteers (16 males, 17 females, 19-63 years old) were taken in January 1999. OCP residues (op'DDT, pp'DDT, pp'DDD, pp'DDE, Aldrin, Dieldrin, Endrin, Heptachlor, Heptachlor-epoxide, alpha-, beta- and gamma-Hexachlorocyclo-hexane, Hexachlorobenzene) and PCBs (congeners: 28, 52, 101, 138, 153, 180) were extracted with n-hexane and analyzed by gas chromatography with electron capture detection. Except for pp'DDE (detection limit = 1.4 microg/L) no other OCP residue was found in the samples. No PCB congener (detection limit = 2.0 microg/L) was detected either. pp'DDE was found in 17 out of 33 samples in concentrations that ranged from 1.4 to 8.4 microg/L of serum or, on a fat basis, from 0.200 to 3.452 microg/g of serum lipids. Percentage of positive samples (%) and levels of pp'DDE (range of positive samples) increased from the youngest to the oldest group (< or = 29 yrs: 10%, 0.278 microg/g; 30-39 yrs: 60%, 0.200-0.765 microg/g; > or = 40 yrs: 77%, 0.257-3.452 microg/g).

Adverse events and technical complaints related to central venous catheters marketed in Brazil.

AIM: The objective of this study was to critically analyze data of the National Notification System for Adverse Events and Technical Complaints (Notivisa) related to central venous catheters, through an evaluation of the description of notifications recorded between 2006 and 2009. METHODS: NOTIFICATIONS WERE CATEGORIZED AND EVALUATED TO: (i) determine the number of adverse events and technical complaints, (ii) verify compliance with the classification criteria defined by the legislation, (iii) reclassify notifications, when necessary, in order for them to fit in with the legal definitions, (iv) verify registered companies in Brazil, (v) quantify the notifications according to the registered company and product lot, and (vi) identify the country of original of the notified product. Microsoft Excel((r)) 2010 was used to categorize and systematize the data. RESULTS: Some conceptual errors and incomplete records were found. Altogether, 228 notifications of technical complaints and 119 of adverse events were identified. Some notifications on guidewires and broken catheters were reported which led to the necessity of duplicating some medical procedures and to the occurrence of lesions/lacerations of vessels and tissue injury. Forty-seven percent of companies presented at least one notification in Notivisa and in all, 38 product lots had more than one notification. CONCLUSION: These data support a necessity for cooperation between all entities of the National Health Surveillance System to check compliance of this type of product and to properly report adverse events and technical complaints. It is also important to incorporate minimum standards for the management of technologies in health services, including in the acquisition of products and training of staff.

Ensaio do linfonodo local murino (LLNA) na diferenciação entre a dermatite de contato alérgica e de contato irritante: um estudo da expressão de marcadores de superfície de linfócitos T / Local Lymph node assay in the differentiation between an allergic contact dermatitis and irritation: study of the expression of T lymphocyte surface markers

Introdução: O ensaio do linfonodo local murino (LLNA) foi desenvolvido como uma alternativa aos testes de Buhler e Maximização. O teste é utilizado com o objetivo de identificar substâncias capazes de induzir dermatite de contato e tem como desfecho a quantificação celular nos linfonodos auriculares. Embora recomendado por agências internacionais envolvidas no desenvolvimento de metodologias alternativas, o LLNA ainda necessita de aprimoramento. Objetivo: O objetivo do trabalho foi estudar possíveis diferenças nos padrões de subpopulações linfocitárias entre camundongos tratados com substâncias irritantes e dermosensibilizantes. Método: Os animais foram tratados com os sensibilizantes dinitroclorobenzeno (DNCB) e parafenilenidiamina (PPD), os irritantes lauril sulfato de sódio (LSS) e tritonX-100 (TX-100), por três dias consecutivos no dorso de ambas as orelhas. As subpopulações foram analisadas por citometria de fluxo e possíveis alterações histopatológicas nas orelhas dos animais foram também analisadas. Resultados: Foram observadas diferenças nas células CD4+CD25+ e CD4+CD69+, assim como na proliferação dessas subpopulações. Nenhuma diferença foi vista nos estudos histopatológicos das orelhas dos animais quando tratados com dermosensibilizantes ou irritantes. Conclusões: A fenotipagem de linfócitos T pode ser considerada útil no desenvolvimento de possíveis protocolos de ensaios que visem a diferenciação entre substâncias dermosensibilizantes e irritantes. Além disso, os resultados obtidos podem vir a contribuir com o aumento do conhecimento nesta área e auxiliar na busca por um ensaio in vitro correlato.

Introduction: The Local Lymph Node Assay (LLNA) was developed as an alternative to Buhler and Maximization assays. It is applied to discriminate substances that are able to induce contact dermatitis and the endpoint is cell quantification in mice auricular lymph nodes. Although recommended by international agencies involved in the development of alternative methodologies, LLNA still needs to be improved. Objective: In this context, the goal of this study was to investigate possible differences in lymphocyte subpopulation patterns among mice treated with irritants and dermosensitizers. Method: Animals were treated with sensitizers dinitrochlorobenzene (DNCB) and paraphenylenediamine (PPD) and irritants sodium lauryl sulfate (SLS) and tritonX-100 (TX-100) for 3 days, using dorsum area of both ears. The percentage of different lymphocyte subpopulations were analyzed by flow cytometry. Ears of animals were also evaluated for possible pathological alterations. Results: Differences were observed in CD4+ CD25+ and CD4+ CD69+ cells, as well as in the proliferation of these subpopulations. The histopathological analysis of the ears showed no difference between the treatment with either dermosensitizers or irritants. Conclusions: T lymphocyte phenotyping might still be a useful tool in the development of an assay to differentiate between dermosensitizers and irritants. Moreover, these results may contribute to improving knowledge on this field and helping in the search of a correlate in vitro assay.

Métodos alternativos para a detecção de pirogênios em produtos e ambientes sujeitos a Vigilância Sanitária: avanços e perspectivas no Brasil a partir do reconhecimento internacional do Teste de Ativação de Monócitos / Alternative methods for the detection of pyrogens in products and environment subject to public health surveillance: advances and perspectives in Brazil based on the international recognition of the Monocyte Activation Test

Introduction: The detection of pyrogens is essential for the quality control of injectable products. The Rabbit Pyrogen Test remains widely used, despite the existence of alternative methods such as the Monocyte Activation Test (MAT). Objective: To review the use of alternative methods for pyrogen testing, pointing out advances and perspectives from the recognition of MAT by the European pharmacopoeia and its acceptance for regulatory purposes in Brazil. Method: A search was performed on the PubMed and BVS databases, with further classification, categorization by topic and critical analysis of the results. Results: Twenty-four papers were identified, addressing topics such as applications of MAT, its validation and comparisons with in vivo tests. MAT presented better results when compared to other tests, both in the evaluation of biological products and in the detection of non-endotoxin pyrogens. Limitations to diffusion include difficulties in obtaining whole human blood as a source of monocytes, for which several alternatives have been proposed. Conclusions: MAT is a promising method, with application in safety evaluation of new technologies. Its application in Brazil depends on a national implementation policy, which might include greater integration between BraCVAM, Concea and RENAMA in search for its recognition for regulatory purposes.

Introdução: A detecção de pirogênios é imprescindível no controle da qualidade de produtos injetáveis. O Teste de Pirogênio em coelhos ainda tem larga aplicação, apesar da existência de métodos alternativos como o Teste de Ativação de Monócitos (MAT). Objetivo: Revisar o uso dos métodos alternativos no teste de pirogênio, apontando avanços e perspectivas a partir do reconhecimento do MAT pela Farmacopeia Europeia e sua aceitação para fins regulatórios no Brasil. Método: Uma busca foi realizada nas bases PubMed e BVS, com posterior classificação, categorização por assuntos e análise crítica dos resultados. Resultados: Foram identificados 24 trabalhos, abordando temas como as aplicações do MAT, sua validação e comparação com testes in vivo. O MAT apresentou melhores resultados quando comparado a outros testes, tanto na avaliação de produtos biológicos como na detecção de pirogênios não-endotoxinas. Limitações para sua difusão incluem a dificuldade de obtenção de sangue total humano como fonte de monócitos, para o qual diversas alternativas têm sido propostas. Conclusões: O MAT se mostra um método promissor, com aplicação na avaliação da segurança de novas tecnologias. Sua aplicação no Brasil depende de uma política nacional de implantação, que inclua maior Integração entre BraCVAM, Concea e RENAMA na busca por seu reconhecimento para fins regulatórios.