OBJECTIVES: To investigate the expression levels of surface markers of activation (CD38 and HLA-DR), inhibition (PD-1, TIGIT and CD57) and co-stimulation (CD28 and CD127) on CD4+ T cells of children/adolescents with vertical HIV infection (HI patients) and HIV-uninfected (HU) controls vaccinated with the meningococcal C conjugate vaccine (MCC). METHODS: HI patients (n=12), aged 8-17 years, were immunized with two MCC injections, while HU controls (n=9), aged 5.3-10.7 years, received a single MCC dose (as per national recommendation at the time of this study, a single MCC vaccine dose should be given for healthy children and youth aged 1-18 years). The HI patients were categorized according to the combined antiretroviral therapy (cART) treatment. Blood samples were obtained before vaccination, after priming, and after the administration of a booster dose of vaccine to determine the serum bactericidal antibody (SBA) titers and the expression levels of surface markers on CD4+ T cells by flow cytometry. The levels of serum cytokines, IL-4 and CXCL-13 were also measured using Luminex kits. RESULTS: The co-expression of the TIGIT-HLA-DR-CD38 molecules increased in the CD4+ T cells of HI patients/no-cART who also showed a lower frequency of CD127+CD28+ CD4+ T cells than HI patients/cART and HU group subjects. There were significant negative correlations between the frequency of exhausted CD4+ T cells and the SBA response. IL-4 levels were higher in HI patients/cART and positively correlated with SBA titers but negatively associated with the expression of exhaustion markers. Moreover, the CXCL-13 levels were positively correlated with the exhausted CD4+ T cells. CONCLUSION: The results of our study suggest that the co-expression of exhaustion markers and/or loss of co-stimulatory molecules influence the SBA response in HI patients.

Resumo Uma nova espécie de Characidium é descrita dos riachos tributários do rio Tocantins, bacia do rio Tocantins, localizados na vertente sul da Chapada dos Veadeiros, a aproximadamente 1.200 metros de altitude, Goiás, Brasil. A nova espécie pode ser diagnosticada pela combinação não usual de dois caracteres apomórficos presentes em clados distintos de Characidium, a presença do istmo sem escama em conjunto com uma única série de dentes no dentário. Adicionalmente, a nova espécie tem um padrão de coloração único de barras verticais desconectadas na região dorsal, formando sete a nove manchas quadradas ao longo do lado do corpo, e pela presença de uma mancha em forma de sela na base da nadadeira dorsal. Osteologicamente, ela pode ser diagnosticada por possuir o primeiro e segundo radiais da nadadeira anal fusionados e em contato com o terceiro espinho hemal, que é ramificado. A espécie nova também possui uma variação peculiar e pouco usual no número de raios das nadadeiras entre os congêneres.

Abstract A new species of Characidium is described from the tributaries of the rio Tocantinzinho, rio Tocantins basin, located in the southern portion of the Chapada dos Veadeiros, at about 1,200 meters of elevation, Goiás, Brazil. The new species can be diagnosed by an unusual combination of two apomorphic features present in distinct clades of Characidium, the presence of a scaleless isthmus in allied to with a single row of dentary teeth. Additionally, the new species has a unique color pattern of inconspicuous vertical bars disconnected from the dorsal midline, forming seven to nine square blotches along body sides, and the presence of a dark saddle-shaped mark at the dorsal-fin base. Osteologically, it can be diagnosed by having the first and second anal-fin proximal radials fused and contacting the third hemal spine, which is branched. The new species also has a peculiar, unusual variation of fin-ray counts among its congeners.

The semi-synthesis of 11 isatin derivatives was achieved through bimolecular nucleophilic substitution and click chemistry. Seven new compounds were obtained. All chemical structures were determined by infrared spectroscopy (IR), nuclear magnetic resonance spectrometry (NMR) and high-resolution mass spectrometry (HRMS) data. These derivatives were evaluated for their anti-GSK-3b activity and all isatin derivatives (N-alkyl and 1,2,3-triazolic) exhibited strong inhibitory activity, with 2b and 4h exhibiting remarkable potency. In addition, docking studies were performed with 2b and 2e models to unravel the molecular mechanism underlying the polar interactions on the GSK-3b ATP-binding site.

Three molecular hybrids containing 1,4-naphthoquinones, 1,3,5-triazines, morpholine and 7-chloroquinoline, which have recognized contributions to the biological activity of many drugs, were synthesized in yields ranging from 43-84%. All hybrids were obtained in three steps starting from readily available reactants: lawsone, cyanuric chloride, morpholine and 4,7-dichloroquinoline. A previous docking study was carried out to identify the binding energy and pharmacophore conformation of the promising anticancer compounds with PI3Kγ (phosphoinositide 3-kinase) and AMPK (5’ AMP-activated protein kinase). The cancer activity in human metastatic melanoma cells (SKMEL-103) were performed, and the synthetized compounds presented half maximal inhibitory concentration (IC50) values around 25 µM. The expressions of PI3K and AMPK were also determined using western blotting technique, and all molecular hybrids negatively modulated both targets.

Abstract Objective: To evaluate autoimmune hepatitis (AIH) in a multicenter cohort of childhood-onset systemic lupus erythematosus (cSLE) patients. Methods: This retrospective multicenter study included 847 patients with cSLE, performed in 10 Pediatric Rheumatology services of São Paulo state, Brazil. AIH was defined according to the International Autoimmune Hepatitis Group criteria (IAHGC). The statistical analysis was performed using the Bonferroni's correction (p < 0.0033). Results: AIH in cSLE patients confirmed by biopsy was observed in 7/847 (0.8%) and all were diagnosed during adolescence. The majority occurred before or at cSLE diagnosis [5/7 (71%)]. Antinuclear antibodies were a universal finding, 43% had concomitantly anti-smooth muscle antibodies and all were seronegative for anti-liver kidney microsomal antibodies. All patients with follow-up ≥18 months (4/7) had complete response to therapy according to IAHGC. None had severe hepatic manifestations such as hepatic failure, portal hypertension and cirrhosis at presentation or follow-up. Further comparison of 7 cSLE patients with AIH and 28 without this complication with same disease duration [0 (0–8.5) vs. 0.12 (0–8.5) years, p = 0.06] revealed that the frequency of hepatomegaly was significantly higher in cSLE patients in the former group (71% vs. 11%, p = 0.003) with a similar median SLEDAI-2 K score [6 (0–26) vs. 7 (0–41), p = 0.755]. No differences were evidenced regarding constitutional involvement, splenomegaly, serositis, musculoskeletal, neuropsychiatric and renal involvements, and treatments in cSLE patients with and without AIH (p > 0.0033). Conclusions: Overlap of AIH and cSLE was rarely observed in this large multicenter study and hepatomegaly was the distinctive clinical feature of these patients. AIH occurred during adolescence, mainly at the first years of lupus and it was associated with mild liver manifestations.

Kinetic models of solid thermal decomposition are traditionally used for individual fit of isothermal experimental data. However, this methodology presents unacceptable errors in some regions of the data. To solve this problem, a neural network was adopted in this work. The implemented algorithm uses the rate constants as predetermined weights between the input and intermediate layer and kinetic models as activation functions of neurons in the hidden layer. The contribution of each model in the overall fit of experimental data is calculated as the weights between the intermediate and output layer. In this way, the phenomenon is better described as a sum of kinetic processes. Two rigid polyurethane foam samples: loaded with Al2O3 and no inorganic filler were used in this work. The R3 and D2 models described the thermal decomposition kinetic process for all temperatures for both foams with smaller residual error. However, the network, combining the kinetic models, presented residual errors on average 102 times lower compared to these individual models. The determined activation energy is 12.44 kJ mol-1 higher for the loaded foam. This result corroborates the use of this material as flame retardant, even with the presence of a small amount of charge in its structure.

ABSTRACT Soil pollution by heavy metals has increased worldwide and the search for plants that can be used to remediate polluted areas is an interesting alternative. The aim of this study was to evaluate the tolerance of tropical grasses to Ni and its availability for the Mehlich 1, DTPA, and USEPA 3051 and 3052 extraction methods in Ni-contaminated Oxisol. Megathyrsus maximus (Jacq.) B.K. Simon & S.W.L. Jacobs ‘Aruana’ and ‘Tanzania’, Urochloa brizantha (Hochst. ex A. Rich.) R.D. Webster ‘Xaraés’ and ‘Marandu’, and Urochloa decumbens (Stapf) R.D. Webster ‘Basilisk’ were grown for 90 d in a Typic Hapludox (Oxisol) after adding 20, 40, and 120 mg Ni kg-1 to the soil. Tropical grasses showed a positive response to the application of Ni doses. The order of decreasing tolerance of tropical grasses to Ni in the soil was: ‘Basilisk’ > ‘Xaraés’ > ‘Marandu’ > ‘Aruana’ > ‘Tanzania’ based on the critical toxicity dose. Nickel concentration and accumulation increased with increasing soil Ni doses in all the tropical grasses. Mehlich 1, DTPA, USEPA 3051, and USEPA 3052 Ni extraction methods in the soil are efficient to diagnose Ni availability in tropical grasses.

Objetivo: Compilar o conhecimento existente sobre a síndrome de Tourette (ST), tiques e patologias associadas.Metodologia: Foi realizada uma revisão sistemática da literatura usando os níveis 5S (sistemas, sumários, sinopses, sínteses e estudos) de organização de evidência de pesquisa em saúde, com base no modelo proposto por Haynes. Os termos de busca foram Tourette, tiques e comorbidades, completados por pesquisa por referência cruzada. Os artigos fornecidos pelos editores e aqueles a serem processados para publicação em 31 de julho de 2013 também foram incluídos.Resultados: De todos os artigos encontrados durante a pesquisa, 64 foram selecionados porque analisavam a epidemiologia, as características clínicas e a etiopatogenia da ST. A ST define-se como um distúrbio hipercinético do movimento, e pelo menos 90% dos pacientes apresentam comorbidades neuropsiquiátricas, das quais as mais comuns são a perturbação de déficit de atenção com hiperatividade e a perturbação obsessivo- -compulsiva. Esta síndrome é clinicamente heterogênea e tem sido relacionada com a disfunção dos circuitos córtico-estriado- -tálamo-corticais envolvendo vários neurotransmissores. Apesar de sua etiologia genética ter sido amplamente estudada, outros fatores podem ser importantes para entender esta síndrome e as perturbações relacionadas.Conclusões: A ST resulta de uma perturbação do desenvolvimento neurológico causado pelo impacto de fatores de estresse num substrato biológico vulnerável durante os períodos críticos do desenvolvimento neurológico. O estudo da ST e das suas comorbidades poderá contribuir, em diferentes níveis, para o entendimento de várias perturbações neuropsiquiátricas com relevância clínica e terapêutica.

Objective: To compile data on Tourette's syndrome (TS), tics and associated disorders.Methods: A systematic review of the literature was conducted using the 5S levels of organization of healthcare research evidence (systems, summaries, synopses, syntheses, studies), based on the model described by Haynes. The search keywords were Tourette, tics and comorbidity, which were cross-referenced. Studies provided by publishers and articles being processed on July 31, 2013, were also included.Results: Of all studies retrieved during the search, 64 were selected because they analyzed the epidemiology, clinical features and etiopathogenesis of TS and its comorbidities. TS is classified as a hyperkinetic movement disorder, and at least 90% of the patients have neuropsychiatric comorbidities, of which attention deficit hyperactivity and obsessive-compulsive disorders are the most common. The syndrome is clinically heterogeneous and has been associated with a dysfunction of cortico-striatal-thalamic-cortical circuits involving various neurotransmitters. Although its genetic etiology has been widely studied, other factors may be important to understand this syndrome and its associated disorders.Conclusions: TS is a neurodevelopmental disorder that results from the impact of stress factors on a vulnerable biological substrate during the critical periods of neurodevelopment. The study of TS and its comorbidities may contribute, at different levels, to the understanding of several neuropsychiatric disorders of clinical and therapeutic relevance.