The present work aims to evaluate the manufacturing processes of free-standing graphene oxide (GO)/reduced graphene oxide(rGO)/carbon nanotube (MWCNT) papers-like and the effect on electrical conductivities after annealing treatment. The pure GO and the hybrid papers were obtained by vacuum filtration and submitted to mild thermal annealing at 400 °C under an argon atmosphere. Analyses comparing the carbon paper-like materials before and after thermal treatment were done by thermogravimetric analysis (TGA), Raman spectroscopy, scanning electron microscopy (SEM), and electrical conductivity measurements. The characterization results show the annealing process effect on the morphology of paper materials. The GO papers and the hybrid (GO/rGO/MWCNT) exhibited good free-standing structure properties. The SEM results suggest the formation of gas void due to the thermal treatment. TGA and Raman results showed the thermal reduction and restoration of the carbon sp2 network of the graphene oxide induced by thermal treatment. The thermal treatment was responsible for changing the almost insulator characteristic of free-standing pure GO paper, achieving an electrical conductivity of 752 S/m, and improving 45% of the free-standing hybrid carbon nanomaterials papers (GO/rGO/MWCNT) electrical conductivity, achieving the value of 1020 S/m.

The present study compared the effects of a footwear designed to enhance energy return (thermoplastic polyurethane, TPU) vs minimalist shoes on running economy (RE) and endurance performance. In this counterbalanced and crossover design study, 11 recreational male runners performed two submaximal constant-speed running tests and two 3-km time-trials with the two shoe models. Oxygen uptake was measured during submaximal constant-speed running tests in order to determine the RE at 12 km/h and oxygen cost of running (CTO2) at individual average speed sustained during the 3-km running time-trials wearing either of the two shoes. Our results revealed that RE was improved (2.4%) with TPU shoes compared with minimalist shoes (P=0.01). However, there was no significant difference for CTO2 (P=0.61) and running performance (P=0.52) comparing the TPU (710±60 s) and the minimalist (718±63 s) shoe models. These novel findings demonstrate that shoes with enhanced mechanical energy return (i.e. TPU) produced a lower energy cost of running at low (i.e., 12 km/h) but not at high speeds (i.e., average speed sustained during the 3-km running time-trial, ∼15 km/h), ultimately resulting in similar running performance compared to the minimalist shoe.

ABSTRACT The objective of this study was to determine the metabolizable energy, standardized ileal amino acid digestibility (SIAAD) and digestible amino acid values of wheat meal (WM), wheat gluten meal (WGM), meat bone meal (MBM) and poultry-by-product meal (PPM) in diets for broilers. In the first experiment, the total excreta collection method was used, with 180 chicks with 14 days, distributed in a completely randomized design, with 4 feeds + reference diet with 6 replicates and 6 broilers each. In the second experiment, 180 broilers from 24 to 28 days old were used, distributed in a completely randomized design, with 4 feeds + one protein free diet with 6 replicates and 6 broilers each. The AMEn values of WM, WGM, MBM and PPM were 3052, 3174, 1556 and 3200 (kcal/kg), respectively. The average SIAAD of the essential and non-essential amino acids of WM, WGM, MBM and PPM were 74.21, 97.50, 69.28 and 83.08; 76.32, 96.42, 63.93 and 77.66, respectively. The values of the main digestible limiting amino acids were 0.18, 1.42, 0.41 and 0.94 for methionine; 0.20, 1.48, 1.73 and 2.73 for lysine; 0.23, 1.67, 0.72 and 1.89 for threonine; and 0.35, 3.22, 1.38 and 2.47 for valine, respectively for the feedstuffs in study.

RESUMO A fim de avaliar o efeito de diferentes doses da rbST sobre a dinâmica folicular, a produção e a maturação in vitro de oócitos, 20 vacas Sindi, divididas em três grupos, receberam um dispositivo de progesterona intravaginal, estradiol e PGF2α, além de 2mL de solução salina (grupo controle), 250 (grupo rbST 250) ou 500mg de rbST (grupo rbST 500). Cinco dias depois, realizou-se a ovum pick up, e os complexos cumulus-oócitos (CCOs) recuperados foram selecionados, classificados e maturados in vitro. Os dados de contagem foram comparados pelo procedimento glht (General Linear Hypothesis Test), e os dados em porcentagem foram submetidos ao qui-quadrado, no programa estatístico R, onde as diferenças foram consideradas significativas quando P<0,05. Não houve diferença (P>0,05) entre os grupos quanto à quantidade de folículos e à taxa de maturação. Os grupos rbST 250 e rbST 500 foram significativamente superiores (P<0,05) ao grupo controle em relação ao número de folículos grandes (0,42±0,20 vs. 0). O grupo rbST 500 apresentou maior (P<0,05) porcentagem de oócitos viáveis (91,52%) do que os grupos controle (67,85%) e rbST 250 (53,33%). A rbST aumenta o número de folículos grandes, e 500mg de rbST aumentam a porcentagem de oócitos viáveis em vacas Sindi.

ABSTRACT In order to evaluate the effect of different doses of rbST on the follicular dynamics, production, and in vitro maturation of oocytes, 20 Sindhi cows were divided into three groups, receiving an intravaginal progesterone device, estradiol and PGF2α, and 2mL of solution saline (Control Group), 250 (rbST 250 Group) or 500mg rbST (rbST 500 Group). Five days later, the ovum pick up was performed, and the cumulus-oocyte (CCO) complexes recovered were selected, classified, and matured in vitro. The counting data were compared by the glht (General Linear Hypothesis Test) procedure, and the percentage data were submitted to Qui- square, in the statistical program R, where differences were considered significant when P< 0.05. There was no difference (P> 0.05) between the groups regarding follicle quantity and maturation rate. The rbST 250 and rbST 500 groups were significantly higher (P< 0.05) than the Control group in relation to the number of large follicles (0.42±0.20 versus 0). The rbST 500 group presented higher (P< 0.05) percentage of viable oocytes (91.52%) than the Control (67.85%) and rbST 250 (53.33%) groups. rbST increases the number of large follicles and 500mg rbST increases the percentage of viable oocytes in Sindhi cows.

Abstract Abstract: The formononetin biostimulant may be an option for reducing P fertilization once it stimulates mycelial growth of arbuscular mycorrhizal fungi and increases plant ability to take up nutrients through the roots, especially phosphorus. The objective of this study was to evaluate the effect of formononetin associated with phosphorus fertilization in maize. Field experiments were conducted in a randomized block design with a 3 × 4 factorial arrangement (0, 50 or 70, and 140 kg ha-1 P2O5; and formononetin application rates: 0, 25, 50, and 100 g ha-1), with four replications. Formononetin (100 g ha-1) increased the mycorrhizal colonization rate up to 30% in maize in the first four weeks after emergence when no P fertilizer was applied, and to 17% when 50 or 70 kg ha-1 of P2O5 were applied. The application of 50 and 100 g ha-1 of formononetin significantly increased plant height, ear height, and grain yield (22% - 76%) when no P fertilizer was applied. The use of formononetin in the field stimulates mycorrhizal colonization, has a positive effect on maize yield, and reduces the need for P fertilizer application in maize. However, this effect was evident only at low P soil contents.

RESUMO Trueperella pyogenes é uma bactéria oportunista que causa mastite, metrite e abortos esporádicos em bovinos. Este trabalho relata um caso incomum de abort em uma vaca por Trueperella pyogenes. Um feto bovino, fêmea, mestiço Brahman, com oito meses de gestação, foi encaminhado para exame anatomopatológico e exames complementares. Na necropsia, evidenciou-se grande quantidade de líquido serossanguinolento e moderada quantidade de fibrina recobrindo a pleura visceral e o saco pericárdico. Os pulmões estavam difusamente avermelhados e consolidados, com áreas firmes esbranquiçadas ao corte de não mais de 1cm. No exame histopatológico, observou-se pneumonia necrossupurativa, pleurite fibrinopurulenta e placentite purulenta. No exame microbiológico, isolou-se T. pyogenes nas amostras de fígado, pulmões, conteúdo abomasal do feto e placenta. O feto foi negativo na PCR para Neospora caninum, Toxoplasma gondii e vírus da diarreia viral bovina (BVDV). Trueperella pyogenes geralmente causa broncopneumonia supurativa com formação de abscessos, porém, no presente feto abortado, observaram-se lesões macro e microscópicas comumente descritas em casos de aborto por Brucella abortus. Este estudo constata, então, a importância dessa bactéria como causa de aborto em bovinos, com lesões semelhantes à brucelose, destacando sua relevância dentro das causas de aborto em bovinos e o potencial zoonótico pouco explorado.

ABSTRACT Trueperella pyogenes is an opportunistic bacterium associated with mastitis, metritis and occasional abortion in bovines. Here we report an uncommon case of abortion by T. pyogenes in a cow. An aborted female Brahman bovine fetus, at 8 months of gestational age was submitted for anatomopathological examination and complementary diagnostic tests. Macroscopic findings at necropsy included large amounts of free serum-blood fluid and moderate fibrin deposition covering both the visceral pleura and pericardial sack. The lungs were diffusely reddened and markedly consolidated, showing widespread smaller than 1cm, hard, white nodules. Necrosuppurative pneumonia, fibrinopurulent pleuritis, and purulent placentitis were the main histopathologic alterations observed. Trueperella pyogenes was isolated from liver, lungs, abomasa contents and placental samples. All tissue samples were PCR-negative for Neospora caninum, Toxoplasma gondii and bovine viral diarrhea virus (BVDV). Although T. pyogenes is often involved in suppurative bronchopneumonia and abscesses formation, macro and microscopic lesions in the present report were compatible with those commonly attributed to Brucella abortus fetal infections. Trueperella pyogenes is an important bovine pathogen with a neglected zoonotic potential being responsible for infections that can mimic other diseases’ typical presentations.

RESUMO Objetivou-se verificar se a utilização do modelo autorregressivo (MAR) é adequada para obtenção de parâmetros genéticos para produção de leite no dia do controle (PLDC) de bovinos leiteiros da raça Gir. Foram analisados 125.191 registros de produções diárias, nas três primeiras lactações, por meio dos modelos de repetibilidade (MREP) e MAR. No MREP, foi considerado o efeito de ambiente de curto prazo; no MAR, foi considerado, também, o efeito de ambiente de longo prazo. Os modelos foram comparados por meio do logaritmo da função de máxima verossimilhança ( − 2 log L ). A herdabilidade estimada pelo MREP foi 0,18; no caso do MAR, as estimativas para primeira, segunda e terceira lactações foram 0,32, 0,28 e 0,26, respectivamente. A estimativa de autocorrelação dos componentes de variância de longo prazo foi próxima de zero, e as de curto prazo foram de alta magnitude para primeira (0,79), segunda (0,79) e terceira (0,81) lactações. Logo, a influência do ambiente de curto prazo dentro de cada lactação não é a mesma. O valor de − 2 log L mais próximo de zero foi obtido para o MAR (-294.884,7778) em relação ao MREP (-329.266,4810). Assim, o MAR é adequado para obtenção de estimativas de parâmetros genéticos para PLDC nas três primeiras lactações de bovinos leiteiros.

ABSTRACT Aimed to verify if the autoregressive model (MAR) is adequate to obtain genetic parameters for Gyr dairy cattle milk yield on the test day in the three first lactations. Analysis was performed on 125,191 records of daily production of 9,242 cows using repeatability model (MREP) and MAR. On MREP, a long-term environment was considered, on MAR, the short-term environment was also taken into consideration. The models were compared by logarithm of the maximum likelihood function ( − 2 log L ). The heritability estimated using the MREP model was 0.18, while the heritability estimated by MAR for first, second, and third lactations were 0.32, 0.28 and 0.26, respectively. The autocorrelation estimates of the components of long-term variance were close to zero, and those of the short-term were of high magnitude for first (0.79), second (0.79) and third (0.81) lactations. Therefore, the influence of the short-term environment within each lactation is not the same. The value of − 2 log L closer to zero was obtained for MAR (-294,884.7778) in relation to MREP (-329,266.4810). Thus, MAR is suitable for obtaining genetic parameters estimates for PLDC in the first three lactations of dairy cattle.

RESUMO Objetivou-se, com este estudo, avaliar o ajuste dos modelos de Brody, Gompertz, Logístico e Von Bertalanffy aos dados de altura na cernelha de equinos Mangalarga Marchador, ponderando pelo inverso da variância, a fim de selecionar o melhor modelo e predizer sobre o crescimento e a maturidade dos animais dessa raça. Foram utilizados dados de 230 equinos dos seis aos 176 meses de idade, os quais foram divididos por sexo e em 16 classes de idade. Os modelos estudados foram comparados segundo os avaliadores de qualidade: coeficiente de determinação (R2); desvio padrão residual (DPR) e critério de informação de Akaike (AIC). A estimação dos parâmetros dos modelos foi realizada pelo método de mínimos quadrados ponderado no software R. Todos os modelos avaliados se mostraram adequados para descrever a curva de crescimento em ambos os sexos. Perante os avaliadores utilizados, o modelo Logístico foi o mais adequado para descrever as curvas de crescimento em altura na cernelha nos dois sexos da raça Mangalarga Marchador. Observou-se também um crescimento acelerado nos primeiros meses de idade. Os animais machos atingiram uma altura adulta maior, porém as fêmeas são mais precoces, pois apresentaram maior estimativa para o índice de maturidade.

ABSTRACT This work aimed to evaluate the fit of models Brody, Gompertz, Logistic and Von Bertalanffy to height at the withers of Mangalarga Marchador horses, weighed by the inverse of variance, in order to select the best model and predict growth and maturity of this breed pf animals. We used data of 230 equines from 06 to 176 months of age who were divided by sex and 16 age classes. The models were compared according to the quality assessors: coefficient of determination (R2); residual standard deviation (RSD) and Akaike information criteria (AIC). The estimation of the parameters from models was performed by the weighted least squares method in Software R. All models evaluated were suitable to describe the growth curve in both sexes. In view of the evaluators used, the logistic model was the most suitable to describe the growth curves in withers height in both sexes for the race Mangalarga Marchador. A strong growth at first age was also observed. The males reached a greater adult height, but females did so sooner, because they presented higher estimates for the maturity index.

The association between subclinical thyroid dysfunctions and autonomic modulation changes has been described by many studies with conflicting results. We aimed to analyze the association between subclinical hyperthyroidism (SCHyper), subclinical hypothyroidism (SCHypo), and heart rate variability (HRV) using the baseline from ELSA-Brasil. SCHyper and SCHypo were classified by use of medication to treat thyroid disorders, thyrotropin levels respectively above and under the reference range, and normal free thyroxine levels. For HRV, the participants underwent 10 min in supine position and the R-R intervals of the final 5 min were selected for analysis. We first used linear regression models to report crude data and then, multivariate adjustment for sociodemographic (age, sex, and race) and cardiovascular risk factors (hypertension, dyslipidemia, diabetes, smoking, body mass index, use of alcohol, and leisure physical activity) using the euthyroid group as reference. From 9270 subjects (median age, 50; interquartile range: 44–56), 8623 (93.0%) were classified as euthyroid, 136 (1.5%) as SCHyper, and 511 (5.5%) as SCHypo. Compared to euthyroid subjects, SCHyper participants presented significantly higher heart rate (68.8 vs 66.5 for euthyroidism, P=0.007) and shorter R-R intervals (871.4 vs 901.6, P=0.007). Although SCHyper was associated with lower standard deviation of NN interval (SDNN) (β: –0.070; 95% confidence interval (95%CI): –0.014 to –0.009) and low-frequency (LF) (β: –0.242, 95%CI: –0.426 to –0.058) compared to the euthyroid group, these differences lost significance after multivariate adjustment for confounders. No significant differences were found for HRV in SCHypo. No association was found between HRV and SCHyper or SCHypo compared to euthyroid subjects in this sample of apparently healthy subjects.

RESUMO Objetivou-se avaliar os desempenhos produtivo e reprodutivo de vacas F1 Holandês x Gir Minas Gerais, as quais foram mantidas em sistema de produção a pasto no verão, com suplementação de concentrado, e, no inverno, alimentadas com cana-de-açúcar, polpa de citros e concentrado. As características avaliadas foram: idade ao primeiro parto, intervalo parto-primeiro serviço, período de serviço, intervalo de partos, permanência da matriz no rebanho, produção de leite total por lactação, duração da lactação, produção média diária, produções ajustadas a 280 dias e a 305 dias de lactação, produção de leite por intervalo de partos e curvas de lactação conforme ordem de partos, época de partos e período de serviço. A função gama incompleta foi utilizada para estimação dos parâmetros das curvas de lactação. As demais características foram analisadas utilizando-se modelos lineares mistos. O rebanho apresentou ótimo desempenho (6271,56kg de leite por lactação). As fêmeas F1 Holandês x Gir são boa alternativa para a produção de leite, desde que garantidas boas condições de manejo, alimentação do rebanho e utilização de matrizes oriundas de programas de cruzamento direcionados empregando-se critérios de melhoramento genético.

ABSTRACT The objective was to evaluate the productive and reproductive performances of F1 Holstein x Gir cows in the state of Minas Gerais. The herd during the summer was managed in a pasture based production system with supplementation of concentrate according to milk production and in the winter it was fed with sugar cane, citrus pulp and concentrate. The characteristics evaluated were: age at first calving, calving to first service interval, service period, calving interval, permanence the cows in the herd, total milk production per lactation, lactation length, average milk daily, productions adjusted to 280 and to 305 days of lactation, milk production per calving interval, and lactation curves. The Incomplete Gamma function was used to estimate the parameters of lactation curves at parturition order, parturition epoch and service period. The other characteristics were analyzed using linear mixed models. The herd showed great performance (6271,56 kg of milk per lactation). F1 Holstein x Gir cows are a good alternative to milk production, as long as good conditions of handling and feeding are guaranteed, and the use of cows derived from breeding programs targeted using genetic improvement criteria.

Modifications in life-style and/or pharmacotherapies contribute to weight loss and ameliorate the metabolic profile of diet-induced obese humans and rodents. Since these strategies fail to treat hypothalamic obesity, we have assessed the possible mechanisms by which duodenal-jejunal bypass (DJB) surgery regulates hepatic lipid metabolism and the morphophysiology of pancreatic islets, in hypothalamic obese (HyO) rats. During the first 5 days of life, male Wistar rats received subcutaneous injections of monosodium glutamate (4 g/kg body weight, HyO group), or saline (CTL). At 90 days of age, HyO rats were randomly subjected to DJB (HyO DJB group) or sham surgery (HyO Sham group). HyO Sham rats were morbidly obese, insulin resistant, hypertriglyceridemic and displayed higher serum concentrations of non-esterified fatty acids (NEFA) and hepatic triglyceride (TG). These effects were associated with higher expressions of the lipogenic genes and fatty acid synthase (FASN) protein content in the liver. Furthermore, hepatic genes involved in β-oxidation and TG export were down-regulated in HyO rats. In addition, these rats exhibited hyperinsulinemia, β-cell hypersecretion, a higher percentage of islets and β-cell area/pancreas section, and enhanced nuclear content of Ki67 protein in islet-cells. At 2 months after DJB surgery, serum concentrations of TG and NEFA, but not hepatic TG accumulation and gene and protein expressions, were normalized in HyO rats. Insulin release and Ki67 positive cells were also normalized in HyO DJB islets. In conclusion, DJB decreased islet-cell proliferation, normalized insulinemia, and ameliorated insulin sensitivity and plasma lipid profile, independently of changes in hepatic metabolism.

Resumo: Com este estudo objetivou-se descrever os aspectos anatômicos e histológicos do coração do jacaré-do-pantanal (Caiman yacare), proveniente de zoocriadouro. Para tanto, estudou-se 13 exemplares da espécie, os quais foram perfundidos, conservados em solução de formaldeído a 10% e submetidos às técnicas anatômicas específicas. O coração foi separado e amostras foram colhidas e submetidas à avaliação histológica. Macroscopicamente o coração é tetracavitário, e além de dois átrios e dois ventrículos, apresenta uma estrutura denominada cone arterial, do qual emergem os vasos da base do coração. Foram identificadas duas aortas, direita e esquerda, sendo que a esquerda emerge do ventrículo direito e se comunica com o tronco sistêmico direito por meio do forame de Panizza. Histologicamente o coração possui epicárdio, miocárdio e endocárdio típicos. Concluímos que a histologia do coração, no jacaré-do-pantanal, é semelhante à de outras espécies de répteis. Contudo, anatomicamente apresenta particularidades importantes, as quais representam, possivelmente, adaptações que permitiram a perpetuação da espécie.

Abstract: The aim of this study was to describe anatomical and histological aspects of the heart of Caiman yacare from a crocodile breeding center. For this purpose, we have chosen and further studied 13 specimens which were perfused and preserved in a 10% formaldehyde solution and they were subjected to the specific anatomical techniques. The heart was separated and samples were collected and submitted to the specific histological procedures. Macroscopically, the heart is four-chambered and besides two atria and two ventricles, has a structure called arterial cone from which the large vessels of the heart emerge. Two aortas, left and right, were identified. The left aorta emerges from the right ventricle and communicates with the systemic trunk through the Foramen of Panizza. From a histological point of view, the heart is typically composed of epicardium, myocardium and endocardium. According to these observations, it is assumed that the histology of the heart of "Jacaré-do-Pantanal" is similar to other species of reptiles. However, there are some anatomic particularities, which possibly represent the adaptations allowing the perpetuation of the species.

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo das síndromes periódicas associadas à criopirina (criopirinopatias – Caps). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de quatro questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultado: Foram recuperados, e avaliados pelo título e resumo, 1.215 artigos e selecionados 42 trabalhos para sustentar as recomendações. Recomendações: 1. O diagnóstico de Caps é baseado na anamnese e nas manifestações clínicas e posteriormente confirmado por estudo genético. Pode se manifestar sob três fenótipos: FCAS (forma leve), MWS (forma intermediária) e Cinca (forma grave). Avaliações neurológica, oftalmológica, otorrinolaringológica e radiológica podem ser de grande valia na distinção entre as síndromes; 2. O diagnóstico genético com análise do gene NLRP3 deve ser conduzido nos casos suspeitos de Caps, isto é, indivíduos que apresentam, antes dos 20 anos, episódios recorrentes de inflamação expressa por urticária e febre moderada; 3. As alterações laboratoriais incluem leucocitose e elevação nos níveis séricos de proteínas inflamatórias; 4. Terapias alvo dirigidas contra a interleucina 1 levam a rápida remissão dos sintomas na maioria dos pacientes. Contudo, existem limitações importantes em relação à segurança em longo prazo. Nenhuma das três medicações anti-IL1β evita progressão das lesões ósseas.

Abstract Objective: To establish guidelines based on cientific evidences for the management of cryopyrin associated periodic syndromes. Description of the evidence collection method: The Guideline was prepared from 4 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 1215 articles were retrieved and evaluated by title and abstract; from these, 42 articles were selected to support the recommendations. Recommendations: 1. The diagnosis of CAPS is based on clinical history and clinical manifestations, and later confirmed by genetic study. CAPS may manifest itself in three phenotypes: FCAS (mild form), MWS (intermediate form) and CINCA (severe form). Neurological, ophthalmic, otorhinolaryngological and radiological assessments may be highly valuable in distinguishing between syndromes; 2. The genetic diagnosis with NLRP3 gene analysis must be conducted in suspected cases of CAPS, i.e., individuals presenting before 20 years of age, recurrent episodes of inflammation expressed by a mild fever and urticaria; 3. Laboratory abnormalities include leukocytosis and elevated serum levels of inflammatory proteins; and 4. Targeted therapies directed against interleukin-1 lead to rapid remission of symptoms in most patients. However, there are important limitations on the long-term safety. None of the three anti-IL-1β inhibitors prevents progression of bone lesions.

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo da síndrome de febre periódica, estomatite aftosa, faringite e adenite (PFAPA). Descrição do método de coleta de evidência: A Diretriz foi elaborada a partir de cinco questões clínicas que foram estruturadas por meio do Pico (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultados: Foram recuperados e avaliados pelo título e resumo 806 trabalhos e selecionados 32 artigos, para sustentar as recomendações. Recomendações: 1. O diagnóstico da PFAPA é clínico e de exclusão, deve a suspeita ser considerada em crianças que apresentam episódios febris de origem indeterminada recorrentes e periódicos ou amidalites de repetição, intercalados com períodos assintomáticos, sobretudo em crianças em bom estado geral e com desenvolvimento pondero-estatural mantido; 2. Os achados laboratoriais são inespecíficos. Não existem alterações patognomônicas nos exames complementares; 3. A evidência que sustenta a indicação do tratamento cirúrgico (tonsilectomia com ou sem adenoidectomia) é baseada em dois ensaios clínicos randomizados não cegos que incluíram pequeno número de pacientes; 4. O uso de prednisona no início do quadro febril em pacientes com PFAPA mostrou ser eficaz. Melhores evidências ainda são necessárias para apoiar seu uso na PFAPA; 5. Apesar de os resultados obtidos de estudos com inibidores de IL-1ß serem promissores, esses são limitados a poucos relatos de casos.

Abstract Objective: To establish guidelines based on scientific evidence for the management of periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome. Description of the evidence collection method: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 806 articles were retrieved and evaluated by title and abstract; from these, 32 articles were selected to support the recommendations. Recommendations: 1. PFAPA is a diagnosis of exclusion established on clinical grounds, and one must suspect of this problem in children with recurrent and periodic febrile episodes of unknown origin, or with recurrent tonsillitis interspersed with asymptomatic periods, especially in children in good general condition and with preservation of weight and height development. 2. Laboratory findings are nonspecific. Additional tests do not reveal pathognomonic changes. 3. The evidence supporting an indication for surgical treatment (tonsillectomy with or without adenoidectomy), is based on two non-blinded randomized clinical trials with small numbers of patients. 4. The use of prednisone at the onset of fever in patients with PFAPA proved to be an effective strategy. There is still need for more qualified evidence to support its use in patients with PFAPA. 5. Despite promising results obtained in studies with IL-1β inhibitors, such studies are limited to a few case reports.

Resumo Objetivo: Estabelecer diretrizes baseadas em evidências científicas para manejo da febre familiar do Mediterrâneo (FFM). Descrição do método de coleta de evidência: A diretriz foi elaborada a partir de 5 questões clínicas que foram estruturadas por meio do PICO (Paciente, Intervenção ou Indicador, Comparação e Outcome), com busca nas principais bases primárias de informação científica. Após definir os estudos potenciais para sustento das recomendações, esses foram graduados pela força da evidência e pelo grau de recomendação. Resultados: Foram recuperados, e avaliados pelo título e resumo, 10.341 trabalhos e selecionados 46 artigos para sustentar as recomendações. Recomendações: 1. O diagnóstico da FFM é baseado nas manifestações clínicas, caracterizadas por episódios febris recorrentes associados a dor abdominal, torácica ou artrite de grandes articulações; 2. A FFM é uma doença genética que apresenta traço autossômico recessivo ocasionada por mutação no gene MEFV; 3. Exames laboratoriais são inespecíficos e demonstram níveis séricos elevados de proteínas inflamatórias na fase aguda da doença, mas também, com frequência, níveis elevados mesmo entre os ataques. Níveis séricos de SAA podem ser especialmente úteis no monitoramento da eficácia do tratamento; 4. A colchicina é a terapia de escolha e demonstrou eficácia na prevenção dos episódios inflamatórios agudos e progressão para amiloidose em adultos; 5. Com base na informação disponível, o uso de medicamentos biológicos parece ser opção para pacientes com FFM que não respondem ou que são intolerantes à terapia com colchicina.

Abstract Objective: To establish guidelines based on scientific evidence for the management of familial Mediterranean fever. Description of the evidence collection method: The Guideline was prepared from 5 clinical questions that were structured through PICO (Patient, Intervention or indicator, Comparison and Outcome), to search in key primary scientific information databases. After defining the potential studies to support the recommendations, these were graduated considering their strength of evidence and grade of recommendation. Results: 10,341 articles were retrieved and evaluated by title and abstract; from these, 46 articles were selected to support the recommendations. Recommendations: 1. The diagnosis of FMF is based on clinical manifestations, characterized by recurrent febrile episodes associated with abdominal pain, chest or arthritis of large joints; 2. FMF is a genetic disease presenting an autosomal recessive trait, caused by mutation in the MEFV gene; 3. Laboratory tests are not specific, demonstrating high serum levels of inflammatory proteins in the acute phase of the disease, but also often showing high levels even between attacks. SAA serum levels may be especially useful in monitoring the effectiveness of treatment; 4. The therapy of choice is colchicine; this drug has proven effectiveness in preventing acute inflammatory episodes and progression towards amyloidosis in adults; 5. Based on the available information, the use of biological drugs appears to be an alternative for patients with FMF who do not respond or are intolerant to therapy with colchicine.