Major depression favors the expansion of Th17-like cells and decrease the proportion of CD39+Treg cell subsets in response to myelin antigen in multiple sclerosis patients.

BACKGROUND: Mood disorders have been associated with risk of clinical relapses in multiple sclerosis (MS), a demyelinating disease mediated by myelin-specific T cells. OBJECTIVES: We aimed to investigate the impact of major depressive disorder (MDD) and cytokine profile of T-cells in relapsing remitting MS patients. METHODS: For our study, plasma and PBMC were obtained from 60 MS patients (30 with lifetime MDD) in remission phase. The PBMC cultures were stimulated with anti-CD3/anti-CD28 beads or myelin basic protein (MBP), and effector and regulatory T cell phenotypes were determined by flow cytometry. The cytokine levels, both in the plasma or in the supernatants collected from PBMC cultures, were quantified by Luminex. In some experiments, the effect of serotonin (5-HT) was investigated. RESULTS: Here, higher Th17-related cytokine levels in response to anti-CD3/anti-CD28 and MBP were quantified in the plasma and PBMC cultures of the MS/MDD group in comparison with MS patients. Further, elevated frequency of CD4+ and CD8+ T cells capable of producing IL-17, IL-22 and GM-CSF was observed in depressed patients. Interestingly, the percentage of myelin-specific IFN-γ+IL-17+ and IFN-γ+GM-CSF+ CD4+ T cells directly correlated with neurological disabilities. In contrast, the occurrence of MDD reduced the proportion of MBP-specific CD39+Tregs subsets. Notably, the severity of both neurological disorder and depressive symptoms inversely correlated with these Tregs. Finally, the addition of 5-HT downregulated the release of Th17-related cytokines in response to anti-CD3/anti-CD28 and myelin antigen. CONCLUSIONS: In summary, our findings suggested that recurrent major depression, by favoring imbalances of effector Th17 and Treg cell subsets, contributes to MS severity.

Elevated proportion of TLR2- and TLR4-expressing Th17-like cells and activated memory B cells was associated with clinical activity of cerebral cavernous malformations.

BACKGROUND: Recent evidences have suggested the involvement of toll-like receptor (TLR)-4 in the pathogenesis of cerebral cavernous malformations (CCM). Elevated frequency of TLR+T-cells has been associated with neurological inflammatory disorders. As T-cells and B-cells are found in CCM lesions, the objective of the present study was to evaluate the cytokine profile of T-cells expressing TLR2 and TLR4, as well as B-cell subsets, in asymptomatic (CCMAsympt) and symptomatic (CCMSympt) patients. METHODS: For our study, the cytokine profile from TLR2+ and TLR4+ T-cell and B-cell subsets in CCMAsympt and CCMSympt patients was investigated using flow cytometry and ELISA. T-cells were stimulated in vitro with anti-CD3/anti-CD28 beads or TLR2 (Pam3C) and TLR4 (LPS) ligands. RESULTS: CCMSymptc patients presented a higher frequency of TLR4+(CD4+ and CD8+) T-cells and greater density of TLR4 expression on these cells. With regard to the cytokine profile, the percentage of TLR2+ and TLR4+ Th17 cells was higher in CCMSympt patients. In addition, an elevated proportion of TLR4+ Tc-1 cells, as well as Tc-17 and Th17.1 cells expressing TLR2 and TLR4, was observed in the symptomatic patients. By contrast, the percentage of TLR4+ IL-10+CD4+ T cells was higher in the CCMAsympt group. Both Pam3C and LPS were more able to elevate the frequency of IL-6+CD4+T cells and Th17.1 cells in CCMSympt cell cultures. Furthermore, in comparison with asymptomatic patients, purified T-cells from the CCMSympt group released higher levels of Th17-related cytokines in response to Pam3C and, mainly, LPS, as well as after activation via TCR/CD28. Concerning the B-cell subsets, a higher frequency of memory and memory activated B-cells was observed in CCMSympt patients. CONCLUSIONS: Our findings reveal an increase in circulating Th17/Tc-17 cell subsets expressing functional TLR2 and, mainly, TLR4 molecules, associated with an increase in memory B-cell subsets in CCM patients with clinical activity of the disease.

Canadian and Brazilian Percentile Ranks for the Alberta Infant Motor Scale.

Aim: To verify if there is a difference between the percentile ranks for Brazilian infants compared with norms for Canadian infants on the Alberta Infant Motor Scale (AIMS). Method: A cross-sectional study in which 322 Brazilian infants, 2 to 15 months old, were administered the AIMS. Percentile ranks were calculated using norms for Canadian infants and norms from two studies of Brazilian infants. The Friedman test compared the AIMS percentile ranks for the entire sample. For reliability analysis, the interclass correlation coefficient (ICC) was used. Bland Altman's analysis was applied to compare percentile ranks. Results: Of the 322 evaluations analyzed, there were significant differences (p<.001) between the three percentile ranks compared. The Canadian norms presented the lowest average rating. There was good reliability between the percentile ranks (ICC > 0.75) but low agreement (Bland Altman; p<.001). Conclusion: There are differences between the Brazilian and Canadian percentile ranks and between the Brazilian percentile ranks of 2014 and 2016, and these differences may influence identification of motor development.

Major Depressive Disorder Enhances Th2 and Th17 Cytokines in Patients Suffering from Allergic Rhinitis and Asthma.

INTRODUCTION: Major depressive disorder (MDD) can impact the severity of allergic rhinitis (AR) and asthma (AA). Here, we evaluated the cytokine production by T-cells from AR and AA patients with or without MDD. The effect of serotonin on the in vitro T-cell response was also evaluated. METHODS: The cytokines produced by activated T-cells were measured by Luminex and flow cytometry. In some cell cultures, serotonin was added. RESULTS: MDD not only enhanced the production of Th2- and Th17-related cytokines, but also, the levels of interleukin (IL)-5 and IL-17 were directly correlated with the severity of depression and anxiety symptoms. As compared with AR, the levels of IL-17 were higher and the release of IL-10 was lower in activated T-cell cultures from AA patients, mainly those with MDD. In AA/MDD patients, the severity of anxiety symptoms and lung disease was directly correlated with Th17-like and hybrid Th2/Th17 cells, but inversely correlated with IL-10-secreting CD4+ T-cells. Finally, the addition of serotonin reduced the production of Th2- and Th17-related cytokines, but elevated IL-10 secretion in cell cultures from both AR and AA patients. CONCLUSIONS: Our findings suggest that not only the occurrence of MDD but also the severity of anxiety symptoms, may adversely affect the outcome of allergic reactions by favoring the production of cytokines implicated in the pathogenesis of AR and AA, a phenomenon that was attenuated by serotonin.

TLR-2 and TLR-4 agonists favor expansion of CD4+ T cell subsets implicated in the severity of neuromyelitis optica spectrum disorders.

BACKGROUND: High frequency of circulating Th17 cell subsets expressing TLR2, TLR4 and TLR9 was observed in Neuromyelitis optica spectrum disorder (NMOSD) patients, a severe humoral autoimmune disease of the central nervous system. Our objective was to evaluate the direct effects of different TLR ligands on CD4+ T-cells form those patients. METHODS: CD4+ T-cell cultures from NMOSD and healthy individuals were stimulated with different TLR ligands and the cell proliferation and cytokine profile was analyzed by [3H] TdR up take and ELISA/ cytometry, respectively. The plasma levels of CD14 were determined by ELISA. RESULTS: Here, Pam3C (TLR2) and LPS (TLR4) induced significant cell proliferation and IL-6, IL-17 and IL-21 production by CD4+ T-cells from NMOSD. Additionally, while both TLR ligands were more potent in favoring the expansion of TFH-like cells, Pam3C reduced the frequency of IL-10-secreting FoxP3+and FoxP3- CD4+ T-cells. With regard to disease severity, the levels of IL-6, IL-17 and IL-21 produced by CD4+ T-cells, as well as the frequency of TFH-like cells, in response to TLR2 and TLR4 agonists were positively correlated with neurological disabilities and the occurrence of new acute relapses during follow up. Finally, circulating levels of CD14, an indirect marker of microbial translocation, were positively correlated with IL-6, IL-17 and IL-21 release by Pam3C- and LPS-activated CD4+ T-cells. CONCLUSIONS: In summary, our data suggest that microbial antigens may affect NMOSD outcomes by favoring an imbalance between Th17 and TFH-like cells and regulatory T cell subsets.

[Mass gatherings, [corrected] disasters and public health]. / Eventos de massa, desastres e Saúde Pública.

Brazil has hosted mass event (ME) and participants are exposed to health risks. The scope of this paper is to systematize the main relationships between ME and the occurrence of disasters of interest to Public Health. Three methodological strategies were used: systematic search and review of the literature on ME; systematization of the main information on ME; and selection and systematization of the references located for the theme of disaster in the search for key words, title or abstract. 28 references for ME were selected, mostly scientific papers, literature reviews, publications in 2012 and sports events. The main subjects addressed were surveillance systems and planning of ME. There was little analytical information about ME, as well as the importance of non-communicable events for the occurrence of disasters with emphasis on those related to crowds. It is important to consider the risk of disasters when planning ME to increase response time. Strategic areas such as medical emergencies, surveillance of communicable diseases and vectors, food and health service security, environmental health and laboratories should be considered. The importance of analytical research and registration of experience acquired in ME should be stressed for disaster risk reduction.

Eventos de massa, desastres e Saúde Pública / Mass events, disasters and public health

O Brasil tem sediado eventos de massa (EM) e seus participantes estão sujeitos a riscos à saúde. Objetivou-se sistematizar as principais relações, de interesse da Saúde Pública, entre eventos de massa e ocorrência de desastres. Foram realizadas três estratégias metodológicas: revisão da literatura de EM, com busca sistemática, sistematização das principais informações sobre EM e seleção e sistematização das Referências que tratavam do tema desastre em suas palavras-chave, título ou Resumo. Foram selecionadas 28 Referências sobre EM, a maioria artigo científico, revisão de literatura, de 2012 e de natureza esportiva. Os principais assuntos abordados foram sistemas de vigilância e planejamento dos EM. Evidenciou-se a pouca informação analítica sobre os EM, bem como a importância de eventos não transmissíveis para a ocorrência de desastres, com destaque aos relacionados à multidão. O risco de desastres deve ser considerado no planejamento dos EM, para aumentar a capacidade de resposta considerando áreas estratégicas como: emergência médica, vigilância de doenças transmissíveis e vetores, segurança alimentar e dos serviços de saúde, saúde ambiental e laboratório. Ressalta-se a importância de pesquisas analíticas e de registro das experiências relacionadas aos EM, para a redução de risco de desastres.

Brazil has hosted mass event (ME) and participants are exposed to health risks. The scope of this paper is to systematize the main relationships between ME and the occurrence of disasters of interest to Public Health. Three methodological strategies were used: systematic search and review of the literature on ME; systematization of the main information on ME; and selection and systematization of the references located for the theme of disaster in the search for key words, title or abstract. 28 references for ME were selected, mostly scientific papers, literature reviews, publications in 2012 and sports events. The main subjects addressed were surveillance systems and planning of ME. There was little analytical information about ME, as well as the importance of non-communicable events for the occurrence of disasters with emphasis on those related to crowds. It is important to consider the risk of disasters when planning ME to increase response time. Strategic areas such as medical emergencies, surveillance of communicable diseases and vectors, food and health service security, environmental health and laboratories should be considered. The importance of analytical research and registration of experience acquired in ME should be stressed for disaster risk reduction.

Micromorfologia do esmalte decíduo intacto ou desgastado em função do agente condicionador / Micromorphology of grounded or ungrounded primary enamel in function of the etchant

O objetivo deste estudo foi observar, ao microscópio eletrônico de varredura (MEV), a micromorfologia do esmalte de dentes decíduos intacto ou desgastado após condicionamento com ácido fosfórico a 37% ou com sistemas adesivos autocondicionantes de uma ou duas etapas. Foram selecionados 15 dentes decíduos, que foram divididos em três grupos, com 5 dentes em cada, de acordo com o agente condicionador e dentre eles, sub-divididos mantendo-se a superfície do esmalte intacta ou desgastada. G1: ácido fosfórico a 37% (Condicionador Dental Gel - Dentsply). G1A: esmalte intacto. G1B: esmalte desgastado. G2: condicionamento com primer do sistema adesivo autocondicionante de duas etapas (Adhese - Ivoclar Vivadent). G2A: esmalte intacto. G2B: esmalte desgastado. G3: condicionamento com sistema adesivo autocondicionante de etapa única (Xeno III – Dentsply). G3A: esmalte intacto. G3B: esmalte desgastado. Após os tratamentos propostos, todas as amostras foram desidratadas, montadas em bases metálicas e observadas ao MEV quanto ao padrão de condicionamento ácido. As amostras do G1A revelaram um padrão não homogêneo de condicionamento (áreas de esmalte condicionado e outras não condicionadas). No G1B foi observado um padrão homogêneo de condicionamento, prevalecendo o padrão Tipo 2 de Silverstone et al.(1975). As amostras dos G2A e G2B não revelaram um padrão homogêneo de condicionamento, tanto no esmalte íntegro como no desgastado. Concluiu-se que o uso do ácido fosfórico parece ser mais favorável para a formação de uma superfície micro retentiva, notadamente no esmalte desgastado. O uso de sistemas adesivos autocondicionantes, tanto no esmalte intacto como no desgastado não propiciou a formação de uma superfície do esmalte micro retentiva.

The aim of this study was to examinate under scanning electron microscopy (SEM) the micromorphology of grounded and ungrounded primary enamel after conditioning with 37% phosphoric acid, single or two-step self etching adhesive systems. Fiftheen primary teeth were selected and divided into three groups (n=5), according to the etchant and then sub-divided maintaining the enamel surface ungrounded or grounded. G1: 37% phosphoric acid (Condicionador Dental Gel – Dentsply). G1A: ungrounded enamel. G1B; grounded enamel. G2: etching with primer of a two-step adhesive system Adhese (Ivoclar – Vivadent). G2A: ungrounded enamel. G2B: grounded enamel.G3: etching with a single-step adhesive system (Xeno III – Dentsply). G3A: ungrounded enamel. G3B: grounded enamel. After enamel etching, all the samples were dehydrated, mounted on metal stubs and observed by SEM for etching pattern. G1A samples showed a non-uniform pattern of enamel etching (with etched and unetched areas). In G1B samples it was observed an uniform Type 2 etching pattern, according Silverstone et al. (1975). G2A and G2B samples did not reveal an uniform etching pattern, for both grounded and ungrounded enamel. It was concluded that the use of phosphoric acid seems to be more suitable to create a micro retentive surface, specially when enamel surface was grounded. Use of a self etching adhesive system on grounded or ungrounded primary enamel did not propitiate the formation of a microretentive enamel pattern.