A single dose of angiotensin-(1-7) resolves eosinophilic inflammation and protects the lungs from a secondary inflammatory challenge.

OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge. METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed. RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation. CONCLUSION: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.

Therapeutic treatment with phosphodiesterase-4 inhibitors alleviates kidney injury and renal fibrosis by increasing MMP-9 in a doxorubicin-induced nephrotoxicity mouse model.

Nephrotic syndrome (NS) is associated with kidney dysfunction and is an important cause of morbidity and mortality in industrialized countries. Here, we evaluated the effects of the phosphodiesterase-4 (PDE-4) inhibitors rolipram and roflumilast on a doxorubicin-induced NS model. Early-stage rolipram treatment preserved glomerular filtration barrier function, as indicated by reduced serum protein and albumin loss and the prevention of hypercholesterolemia. These effects were associated with reduced glomerular and tubular lesions and abrogated renal cell apoptosis. In addition, rolipram treatment reduced inflammation, which was characterized by a decrease in macrophage accumulation and reduced levels of CCL2 and TNF in the kidneys. Rolipram also reduced renal fibrosis, which was associated with decreased α-smooth muscle actin (α-SMA) area and increased metalloproteinase 9 (MMP9) activity in renal tissue. Late-stage rolipram or roflumilast treatment preserved glomerular filtration barrier function, as characterized by reduced serum albumin loss, decreased proteinuria, and the prevention of hypercholesterolemia. Importantly, only roflumilast treatment was associated with a reduction in glomerular and tubular lesions at this time point. In addition, both rolipram and roflumilast reduced renal tissue fibrosis and MMP9 activity in renal tissue.

Factors Associated With the Limitation at Work Because of the Voice: Study With Teachers of Basic Education In Brazil.

INTRODUCTION: The voice disorder can cause limitations at work, as it affects the communication and the performance of the teaching function. OBJECTIVE: To analyze the limitation at work because of the voice and to examine possible associations with sociodemographic characteristics, life and health habits and work conditions among Basic Education teachers in Brazil. METHODS: Cross-sectional epidemiological study, with a representative sample, carried out between October 2015 and March 2016, with 6,324 teachers working in Basic Education in Brazil. Data collection was carried out through the application of a questionnaire via telephone with questions regarding health and working conditions. The "limitation at work because of the voice" was considered a dependent variable, whose response options were a scale with four Likert items that varied from frequently to never. The independent variables were grouped in blocks for ordinal logistic regression analysis with hierarchical entry. The magnitude of the association was assessed by the Odds Ratio (OR) with the respective confidence intervals (95% CI). RESULTS: One third of Brazilian teachers (32.7%) reported some frequency of limitation at work (sometimes; rarely, frequently) because of the voice at some moment in the month before the survey and, of these, 5% declared high frequency. The factors that increased the chance of a greater frequency of limitation at work because of the voice were: being female (OR = 1.32; 95% CI = 1.15-1.51); teaching for elementary school (OR = 1.35; 95% CI = 1.02-1.78); use anxiolytic or antidepressant medications (OR = 1.46; 95% CI = 1.20-1.78); losing sleep due to concerns (OR = 1.69; CI = 95% = 1.46-1.95); high noise at school (OR = 2.09; 95% CI = 1.78-2.46); agitated environment by students' indiscipline (OR = 1.37; 95% CI =1.15-1.63); high demands at work (OR = 1.18; 95% CI = 1.02-1.36); not having social support (OR = 1.19; 95% CI = 1.04-1.38); having suffered verbal violence by the students (OR = 1.43; 95% CI = 1.23-1.67). On the other hand, the practice of regular physical activity (OR = 0.86; 95% CI = 0.75-1.00) and the fact of having enough time to complete work tasks (OR = 0.71; 95% CI = 0,62-0.82) decreased the chance of a higher frequency of limitation at work due to vocal problems. The perception that the work limits the teaching performance because of the voice was more frequent among teachers in the North (OR=1.41; 95% CI = 1.17-1.71) and Northeast (OR=1.46; 95% CI = 1.22-1.76) compared to the Southeast region. CONCLUSION: Factors associated with an increase in the chance of higher frequency of reporting work limitations due to the voice: being female, lack of physical activity, losing sleep due to concern, using anxiolytic or antidepressant medication, school location in the North and Northeast, teaching for the elementary school stage, high noise at school and psychosocial aspects of work organization. The Brazilian educational sector needs public policies that take into account regional inequalities and the health and work conditions of teachers.

Psychosocial factors at work and teachers' illness: a systematic review.

The aim of the present study is to analyze scientific evidence about associations between psychosocial factors at work and teachers' illness. A systematic literature review based on the PRISMA statement was conducted. Biblioteca Virtual em Saúde, Medical Literature Analysis and Retrievel System Online, Cumulative Index of Nursing and Allied Health Literature, Scopus, Web of Science, PsycINFO, and Excerpta Medica Database databases were searched. Articles in Portuguese, English and Spanish, published in the past 11 years, were of interest. In total, 861 articles were identified, but only 15 of them met all the eligibility criteria and were included in the review. Eleven articles (73.3%) used validated instruments to assess psychosocial factors, and the Job Content Questionnaire was the most cited one. Low social support, heavy workload, high job demands, and low job control were the most commonly investigated factors and showed statistically significant associations with teachers' illness.

O objetivo do presente estudo é analisar as evidências científicas sobre as associações entre os fatores psicossociais do trabalho e o adoecimento de professores. Desenvolveu-se uma revisão sistemática da literatura de acordo com a declaração PRISMA, nos bancos de dados Portal Biblioteca Virtual em Saúde, Medical Literature Analysis and Retrieval System Online, Cumulative Index of Nursing and Allied Health Literature, Scopus, Web of Science, PsycINFO e Excerpta Medica Database, em idioma português, inglês e espanhol e publicados nos últimos 10 anos. Foram identificados 861 estudos, dos quais 15 preencheram os critérios de seleção e foram incluídos na revisão. Onze estudos (73,3%) utilizaram instrumentos validados para avaliação dos fatores psicossociais, sendo o Job Content Questionnaire o mais citado. Os resultados indicam que o baixo apoio social, carga elevada de trabalho, alta demanda e baixo controle sobre o trabalho foram os fatores mais investigados e com presença de significância estatística quanto a associação com o adoecimento de professores.

Resolution of Inflammation in Acute Graft-Versus-Host-Disease: Advances and Perspectives.

Inflammation is an essential reaction of the immune system to infections and sterile tissue injury. However, uncontrolled or unresolved inflammation can cause tissue damage and contribute to the pathogenesis of various inflammatory diseases. Resolution of inflammation is driven by endogenous molecules, known as pro-resolving mediators, that contribute to dampening inflammatory responses, promoting the resolution of inflammation and the recovery of tissue homeostasis. These mediators have been shown to be useful to decrease inflammatory responses and tissue damage in various models of inflammatory diseases. Graft-versus-host disease (GVHD) is a major unwanted reaction following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is characterized by an exacerbated inflammatory response provoked by antigen disparities between transplant recipient and donor. There is no fully effective treatment or prophylaxis for GVHD. This review explores the effects of several pro-resolving mediators and discusses their potential use as novel therapies in the context of GVHD.

PAF signaling plays a role in obesity-induced adipose tissue remodeling.

BACKGROUND/OBJECTIVES: Platelet-activating factor receptor (PAFR) activation controls adipose tissue (AT) expansion in animal models. Our objective was twofold: (i) to check whether PAFR signaling is involved in human obesity and (ii) investigate the PAF pathway role in hematopoietic or non-hematopoietic cells to control adipocyte size. MATERIALS/SUBJECTS AND METHODS: Clinical parameters and adipose tissue gene expression were evaluated in subjects with obesity. Bone marrow (BM) transplantation from wild-type (WT) or PAFR-/- mice was performed to obtain chimeric PAFR-deficient mice predominantly in hematopoietic or non-hematopoietic-derived cells. A high carbohydrate diet (HC) was used to induce AT remodeling and evaluate in which cell compartment PAFR signaling modulates it. Also, 3T3-L1 cells were treated with PAF to evaluate fat accumulation and the expression of genes related to it. RESULTS: PAFR expression in omental AT from humans with obesity was negatively correlated to different corpulence parameters and more expressed in the stromal vascular fraction than adipocytes. Total PAFR-/- increased adiposity compared with WT independent of diet-induced obesity. Differently, WT mice receiving PAFR-/--BM exhibited similar adiposity gain as WT chimeras. PAFR-/- mice receiving WT-BM showed comparable augmentation in adiposity as total PAFR-/- mice, demonstrating that PAFR signaling modulates adipose tissue expansion through non-hematopoietic cells. Indeed, the PAF treatment in 3T3-L1 adipocytes reduced fat accumulation and expression of adipogenic genes. CONCLUSIONS: Therefore, decreased PAFR signaling may favor an AT accumulation in humans and animal models. Importantly, PAFR signaling, mainly in non-hematopoietic cells, especially in adipocytes, appears to play a significant role in regulating diet-induced AT expansion.

Endogenous opioid and cannabinoid systems modulate the muscle pain: A pharmacological study into the peripheral site.

The participation of the peripheral opioid and cannabinoid endogenous systems in modulating muscle pain and inflammation has not been fully explored. Thus, the aim of this study was to investigate the involvement of these endogenous systems during muscular-tissue hyperalgesia induced by inflammation. Hyperalgesia was induced by carrageenan injection into the tibialis anterior muscles of male Wistar rats. We padronized an available Randal-Sellito test adaptation to evaluate nociceptive behavior elicited by mechanical insult in muscles. Western blot analysis was performed to evaluate the expression levels of opioid and cannabinoid receptors in the dorsal root ganglia. The non-selective opioid peptide receptor antagonist (naloxone) and the selective mu opioid receptor MOP (clocinnamox) and kappa opioid receptor KOP (nor-binaltorphimine) antagonists were able to intensify carrageenan-induced muscular hyperalgesia. On the other hand, the selective delta opioid receptor (DOP) antagonist (naltrindole) did not present any effect on nociceptive behavior. Moreover, the selective inhibitor of aminopeptidases (Bestatin) provoked considerable dose-dependent analgesia when intramuscularly injected into the hyperalgesic muscle. The CB1 receptor antagonist (AM251), but not the CB2 receptor antagonist (AM630), intensified muscle hyperalgesia. All irreversible inhibitors of anandamide hydrolase (MAFP), the inhibitor for monoacylglycerol lipase (JZL184) and the anandamide reuptake inhibitor (VDM11) decreased carrageenan-induced hyperalgesia in muscular tissue. Lastly, MOP, KOP and CB1 expression levels in DRG were baseline even after muscular injection with carrageenan. The endogenous opioid and cannabinoid systems participate in peripheral muscle pain control through the activation of MOP, KOP and CB1 receptors.

Cannabidiol Enhances Intestinal Cannabinoid Receptor Type 2 Receptor Expression and Activation Increasing Regulatory T Cells and Reduces Murine Acute Graft-versus-Host Disease without Interfering with the Graft-versus-Leukemia Response.

Cannabidiol (CBD) is a highly lipidic phytocannabinoid with remarkable anti-inflammatory effects. The aim of this study was to evaluate CBD's effects and mechanisms of action in the treatment of mice subjected to acute graft-versus-host disease (aGVHD). aGVHD was induced by the transplantation of bone marrow cells and splenocytes from C57BL-6j to Balb-c mice. The recipient mice were treated daily with CBD, and the treatment reduced mouse mortality by decreasing inflammation and injury and promoting immune regulation in the jejunum, ileum, and liver. Analysis of the jejunum and ileum showed that CBD treatment reduced the levels of C-C motif chemokine ligand (CCL) 2, CCL3, CCL5, tumor necrosis factor α, and interferon γ (IFNγ). CCL3 and IFNγ levels were also decreased in the liver. Mechanistically, CBD also increased the number of cannabinoid receptor type 2 (CB2) receptors on CD4+ and forkhead box P3+ cells in the intestine, which may explain the reduction in proinflammatory cytokines and chemokines. Antagonists of the CB2 receptor reduced the survival rates of CBD-treated mice, suggesting the participation of this receptor in the effects of CBD. Furthermore, treatment with CBD did not interfere with the graft-versus-leukemia response. CBD treatment appears to protect aGVHD mice by anti-inflammatory and immunomodulatory effects partially mediated by CB2 receptor interaction. Altogether, our study suggests that CBD represents an interesting approach in the treatment of aGVHD, with potential therapeutic applications in patients undergoing bone marrow transplantation. SIGNIFICANCE STATEMENT: This study provides for the first time a mechanism by which cannabidiol, a phytocannabinoid with no psychoactive effect, induces immunomodulation in the graft-versus-host disease. Enhancing intestinal cannabinoid receptor type 2 (CB2) receptor expression on CD4+ and forkhead box P3+ cells and increasing the number of these regulatory cells, cannabidiol decreases proinflammatory cytokines and increases graft-versus-host disease mice survival. This effect is dependent of CB2 receptor activation. Besides, cannabidiol did not interfere with graft-versus-leukemia response, a central response to avoid primary disease relapse.

Effect of Physical Training on Exercise-Induced Inflammation and Performance in Mice.

Acute exercise increases the amount of circulating inflammatory cells and cytokines to maintain physiological homeostasis. However, it remains unclear how physical training regulates exercise-induced inflammation and performance. Here, we demonstrate that acute high intensity exercise promotes an inflammatory profile characterized by increased blood IL-6 levels, neutrophil migratory capacity, and leukocyte recruitment to skeletal muscle vessels. Moreover, we found that physical training amplified leukocyte-endothelial cell interaction induced by acute exercise in skeletal muscle vessels and diminished exercise-induced inflammation in skeletal muscle tissue. Furthermore, we verified that disruption of the gp-91 subunit of NADPH-oxidase inhibited exercise-induced leukocyte recruitment on skeletal muscle after training with enhanced exercise time until fatigue. In conclusion, the training was related to physical improvement and immune adaptations. Moreover, reactive oxygen species (ROS) could be related to mechanisms to limit aerobic performance and its absence decreases the inflammatory response elicited by exercise after training.

Factors associated with perception of loud occupational noise by school teachers in basic education in Brazil. / Fatores associados à percepção de ruído ocupacional intenso pelos professores da educação básica no Brasil.

OBJECTIVE: To determine the prevalence of the perception of loud noise in basic education schools in Brazil and the associated factors. METHODS: A cross-sectional study with a representative national sample of teachers. The data collection was conducted with 6,510 teachers from October 2015 to March 2016. All teachers answered a telephone questionnaire with questions related to health and working conditions. The measure of association was prevalence ratio, estimated using Poisson regression. RESULTS: The prevalence of reported loud occupational noise was 33.0%. There was a positive association in the outcome of classroom disturbance reports (PR = 3.41; 95%CI 3.07 - 3.75), feeling of working under high-pressure levels (PR = 1.33; 95%CI 1.22-1.45), having suffered verbal abuse from students (PR = 1.21; 95%CI 1.11-1.31), teaching in different teaching modalities (PR = 1.21; 95%CI 1.02-1.42), more than 30 active teachers in the school (PR = 1.28; 95%CI 1.07-1.54). The teachers who reported a pleasant school environment (PR = 0.81; 95%CI 0.75-0.87), along with the teachers who worked in rural areas (PR = 0.84; 95%CI 0.75-0.95), experienced less noise at work. CONCLUSION: The prevalence of loud noise perception in Brazilian schools reached high levels and showed statistical significance with the characteristics of schools and teacher's work environment. These results demonstrate the need for developing public policies that take into consideration the reduction of noise levels in schools.

OBJETIVO: Estimar a prevalência e os fatores associados à percepção de ruído intenso nas escolas da educação básica no Brasil. MÉTODOS: Estudo transversal com amostra nacional representativa dos professores. A coleta de dados foi realizada com 6.510 professores, de outubro de 2015 a março de 2016. Todos os professores responderam a um questionário via telefone com perguntas referentes à saúde e às condições de trabalho. A medida de associação foi a razão de prevalência (RP), estimada com a regressão de Poisson. RESULTADOS: A prevalência de ruído ocupacional intenso referido foi de 33,0%. Houve associação positiva ao desfecho os relatos de agitação em sala de aula (RP = 3,41; IC95% 3,07 - 3,75), percepção de trabalhar sob alto nível de exigência (RP = 1,33; IC95% 1,22 - 1,45), ter sofrido violência verbal praticada pelos alunos (RP = 1,21; IC95% 1,11 - 1,31), lecionar para diferentes modalidades de ensino (RP = 1,21; IC95% 1,02 - 1,42) e a escola contar com número de professores atuantes superior a 30 (RP = 1,28; IC95% 1,07 - 1,54). Os professores que relataram um ambiente agradável na escola (RP = 0,81; IC95% 0,75 - 0,87), assim como os que atuavam na área censitária rural (RP = 0,84; IC95% 0,75 - 0,95), perceberam menor ruído no trabalho. CONCLUSÃO: A prevalência de percepção de ruído intenso nas escolas brasileiras foi elevada e apresentou significância estatística com as características da escola e do trabalho de professores da educação básica. Esses achados demonstram a necessidade de planejamento de políticas públicas que considerem a redução dos níveis de ruído no ambiente escolar.

Condições de saúde vocal e do trabalho dos professores brasileiros: EDUCATEL, 2015-2016 / Condições de saúde vocal e do trabalho dos professores brasileiros: EDUCATEL, 2015-2016

Introdução: A Educação se articula a diferentes dimensões e espaços da vida e está entrelaçada às dinâmicas econômica, social, cultural e política da sociedade. Os professores são responsáveis pelo preparo do cidadão e, portanto, é reconhecida a importância que ocupam. No entanto, a precarização das condições de trabalho a que estão expostos podem influenciar a atuação profissional e explicar a presença de morbidades entre os docentes com impacto direto na saúde vocal. Objetivos: 1) Estimar a prevalência e os fatores associados à percepção de ruído intenso nas escolas da Educação Básica no Brasil. 2) Analisar a limitação no trabalho por causa da voz e a associação com características individuais e do trabalho entre os professores da Educação Básica no Brasil. Métodos: Estudo epidemiológico de corte transversal de base populacional, realizado entre outubro de 2015 a março de 2016 com 6.510 professores. Os procedimentos de amostragem utilizados visaram obter amostra probabilística do universo de professores da Educação Básica em escala nacional. A coleta dos dados aconteceu via telefone por meio de um questionário com 54 questões sobre condições do trabalho, saúde e estilo de vida. Os desfechos de interesse foram: ruído intenso no trabalho (desfecho 1) e limitação no trabalho por causa da voz (desfecho 2). Para a análise dos dados foram realizadas análises descritiva e de associação, por meio da regressão de Poisson (objetivo 1) e regressão logística ordinal (objetivo 2) a fim de se investigar a associação das variáveis respostas elegíveis com as variáveis explicativas para cada modelo elaborado. O nível de significância adotado foi de 5%. Resultados: A maioria dos professores brasileiros era do sexo feminino (80,3%), com idade média de 40,3±10,6 anos, se autodeclarou branco (50,8%) e tinha filhos (66,5%). Ao analisar o ruído como desfecho de interesse verificou-se alta prevalência de percepção de ruído intenso nas escolas brasileiras (33%). Houve associação positiva ao desfecho os relatos de agitação em sala de aula (RP=3,41; IC95%=3,07-3,75); percepção de trabalhar sob alto nível de exigência (RP=1,33; IC95%=1,22-1,45); ter sofrido violência verbal pelos alunos (RP=1,21; IC95%=1,11=1,31); lecionar para diferentes modalidades de ensino (RP=1,21; IC95%=1,02-1,42) e a escola contar com número de professores atuantes superior a trinta (RP=1,28; IC95%=1,07-1,54). Os professores que relataram um ambiente agradável na escola (RP=0,81; IC95%=0,75-0,87), assim como os que atuavam na área censitária rural (RP=0,84; IC95%=0,75-0,95) perceberam menor ruído no trabalho. Para o desfecho relacionado à limitação no trabalho por problemas na voz, um terço dos professores brasileiros relatou perceber esta limitação com alguma frequência e, destes, 5% declararam que esta limitação ocorreu frequentemente. Os fatores que aumentaram a chance de maior frequência de limitação no trabalho por causa da voz foram: ser do sexo feminino (OR=1,32; IC95%=1,15-1,51); lecionar para o ensino fundamental (OR=1,35; IC95%=1,02-1,78); usar medicamentos ansiolíticos ou antidepressivos (OR=1,46; IC95%=1,20-1,78); perder o sono por preocupações (OR=1,69; IC=95%=1,46-1,95); ruído elevado na escola (OR=2,09; IC95%=1,78-2,46); ambiente agitado por indisciplina dos alunos (OR=1,37; IC95%=1,15-1,63); alta exigência no trabalho (OR=1,18; IC95%=1,02-1,36); não possuir apoio social (OR= 1,19; IC95%=1,04-1,38); ter sofrido violência verbal pelos alunos (OR=1,43; IC95%=1,23-1,67). Em contrapartida a prática de atividade física regular (OR=0,86; IC95%=0,75-1,00) e o fato de ter tempo suficiente para cumprir as tarefas do trabalho (OR=0,71; IC95%=0,62-0,82) diminuiu a chance de maior frequência de limitação no trabalho por problemas vocais. A percepção que o trabalho limita a atuação docente por causa da voz foi mais frequente entre os professores das regiões Norte (OR=1,41; IC95%=1,17-1,71) e Nordeste (OR=1,46; IC95%=1,22-1,76) comparado à região Sudeste. Conclusão: Este estudo de caráter nacional avaliou o comprometimento da saúde vocal e das condições de trabalho dos professores brasileiros. Houve elevada prevalência de limitação no trabalho por problemas na voz, assim como relato de ruído intenso nas escolas. Constatou-se ainda que a localização da escola, assim como aspectos ambientais e organizacionais do trabalho estão associados à percepção de limitação no trabalho por problemas vocais e ruído intenso no contexto escolar.

Introduction: Education is linked to different dimensions and spaces of life and is intertwined with the economic, social, cultural and political dynamics of society. Teachers are responsible for citizen preparation and therefore their importance is recognized. However, the precariousness of working conditions to which they are exposed may influence their professional performance and explain the presence of morbidities among teachers with direct impact on vocal health. Objectives: 1) To determine the prevalence of the perception of loud noise in basic education schools in Brazil and the associated factors. 2) Analyze the limitation at work because of the voice and the association with individual and work characteristics among Basic Education teachers in Brazil. Methods: A population-based cross-sectional epidemiological study conducted from October 2015 to March 2016 with 6,510 teachers. The sampling procedures used aimed to obtain a probabilistic sample of the universe of basic education teachers on a national scale. Data collection took place via telephone through a questionnaire with 54 questions about working conditions, health and lifestyle. Outcomes of interest were: loud noise at work (outcome 1) and limitation at work because of voice (outcome 2). For data analysis, descriptive and association analyzes were performed using Poisson regression (objective 1) and ordinal logistic regression (objective 2) in order to investigate the association of the eligible response variables with the explanatory variables for each model elaborated. The adopted significance level was 5%. Results: Most Brazilian teachers were female (80.3%), with a mean age of 40.3 ± 10.6 years, self-declared white (50.8%) and had children (66.5%). Analyzing noise as an outcome of interest showed a high prevalence of perception of intense noise in Brazilian schools (33%). There was a positive association with the outcome of reports of classroom agitation (PR = 3.41; 95% CI = 3.07- 3.75); perception of working under high demands (PR = 1.33; 95% CI = 1.22-1.45); have suffered verbal violence by students (PR = 1.21; 95% CI = 1.11 = 1.31); teach for different teaching modalities (PR = 1.21; 95% CI = 1.02-1.42) and the school has more than 30 active teachers (PR = 1.28; 95% CI = 1.07- 1.54). Teachers who reported a pleasant environment at school (PR = 0.81; 95% CI = 0.75-0.87), as well as those working in the rural census area (PR = 0.84; 95% CI = 0.75) -0.95) noticed less noise at work. For the outcome related to limitation at work due to voice problems, one third of Brazilian teachers reported noticing this limitation with some frequency, and of these, 5% stated that this limitation occurred frequently. The factors that increased the chance of higher frequency of limitation at work due to voice were: being female (OR = 1.32, 95% CI = 1.15-1.51); teach for elementary school (OR = 1.35, 95% CI = 1.02-1.78); use anxiolytic or antidepressant medications (OR = 1.46, 95% CI = 1.20- 1.78); losing sleep due to worries (OR = 1.69, CI = 95% = 1.46-1.95); high noise at school (OR = 2.09, 95% CI = 1.78-2.46); hectic environment for students' indiscipline (OR = 1.37, 95% CI = 1.15-1.63); high demands at work (OR = 1.18, 95% CI = 1.02-1.36); lacking social support (OR = 1.19, 95% CI = 1.04-1.38); have suffered verbal violence by students (OR = 1.43, 95% CI = 1.23-1.67). In contrast, the practice of regular physical activity (OR = 0.86, 95% CI = 0.75-1.00) and having sufficient time to perform work tasks (OR = 0.71, 95% CI = 0 , 62-0,82) decreased the chance of a higher frequency of limitation at work due to vocal problems. The perception that work limits teaching performance because of voice was more frequent among teachers in the North (OR = 1.41, 95% CI = 1.17-1.71) and Northeast (OR = 1.46, CI95 regions). % = 1,22-1,76) compared to the Southeast region. Conclusion: This national study evaluated the impairment of vocal health and working conditions of Brazilian teachers. There was a high prevalence of work limitation due to voice problems, as well as reports of loud noise in schools. It was also found that the location of the school, as well as environmental and organizational aspects of work are associated with the perception of limitation at work due to vocal problems and loud noise in the school context.

Treatment with Apocynin Limits the Development of Acute Graft-versus-Host Disease in Mice.

Graft-versus-host disease (GVHD) is the most serious complication limiting the clinical utility of allogeneic hematopoietic stem cell transplantation (HSCT), in which lymphocytes of donors (graft) are activated in response to the host antigen. This disease is associated with increased inflammatory response through the release of inflammatory mediators such as cytokines, chemokines, and reactive oxygen species (ROS). In this study, we have evaluated the role of ROS in GVHD pathogenesis by treatment of recipient mice with apocynin (apo), an inhibitor of intracellular translocation of cytosolic components of NADPH oxidase complex. The pharmacological blockade of NADPH oxidase resulted in prolonged survival and reduced GVHD clinical score. This reduction in GVHD was associated with reduced levels of ROS and TBARS in target organs of GVHD in apocynin-treated mice at the onset of the mortality phase. These results correlated with reduced intestinal and liver injuries and decreased levels of proinflammatory cytokines and chemokines. Mechanistically, pharmacological blockade of the NADPH oxidase was associated with inhibition of recruitment and accumulation of leukocytes in the target organs. Additionally, the chimerism remained unaffected after treatment with apocynin. Our study demonstrates that ROS plays an important role in mediating GVHD, suggesting that strategies aimed at blocking ROS production may be useful as an adjuvant therapy in patients subjected to bone marrow transplantation.

ROCK Inhibition Drives Resolution of Acute Inflammation by Enhancing Neutrophil Apoptosis.

Uncontrolled inflammation leads to tissue damage and it is central for the development of chronic inflammatory diseases and autoimmunity. An acute inflammatory response is finely regulated by the action of anti-inflammatory and pro-resolutive mediators, culminating in the resolution of inflammation and restoration of homeostasis. There are few studies investigating intracellular signaling pathways associated with the resolution of inflammation. Here, we investigate the role of Rho-associated kinase (ROCK), a serine/threonine kinase, in a model of self-resolving neutrophilic inflammatory. We show that ROCK activity, evaluated by P-MYPT-1 kinetics, was higher during the peak of lipopolysaccharide-induced neutrophil influx in the pleural cavity of mice. ROCK inhibition by treatment with Y-27632 decreased the accumulation of neutrophils in the pleural cavity and was associated with an increase in apoptotic events and efferocytosis, as evaluated by an in vivo assay. In a model of gout, treatment with Y-27632 reduced neutrophil accumulation, IL-1ß levels and hypernociception in the joint. These were associated with reduced MYPT and IκBα phosphorylation levels and increased apoptosis. Finally, inhibition of ROCK activity also induced apoptosis in human neutrophils and destabilized cytoskeleton, extending the observed effects to human cells. Taken together, these data show that inhibition of the ROCK pathway might represent a potential therapeutic target for neutrophilic inflammatory diseases.

Quality of life of children with poor school performance: association with hearing abilities and behavioral issues.

The aim of the present study was to investigate the quality of life of children with poor school performance and its association with behavioral aspects and hearing abilities. METHODS: This cross-sectional observational study, developed in a town in the state of Minas Gerais, Brazil, investigated a random sample of public school children, aged 7-12 years old, who performed poorly in school and received specialized educational assistance. The study comprised two stages: 1) collection of data from parents on their children's health, educational, and socioeconomic profile, and from the Strengths and Difficulties Questionnaire; 2) administration of a quality of life evaluation scale to the schoolchildren. For the assessment of auditory function, transient otoacoustic emissions were used and auditory processing was tested. The following tests were used: verbal sequential memory, nonverbal sequential memory, sound localization, dichotic digits, duration pattern test (flute) and random gap detection. The collected data were analyzed using Excel and STATA 11.0 software. Quality of life was considered the response variable. The explanatory variables were grouped for univariate and multivariate logistic regression analysis with the level of significance set at 5%. RESULTS: A statistically significant association was found between impaired quality of life, altered pro-social behavior, and the absence of parental complaints about the children's written language development. CONCLUSIONS: Quality of life is impaired in children with poor school performance. The lack of parental complaints about written language and changes in social behavior increased the likelihood of a child having a poor quality of life.

Inhibition of the sphingosine-1-phosphate pathway promotes the resolution of neutrophilic inflammation.

Sphingosine-1-phosphate (S1P) is an important sphingolipid derived from plasma membrane and has a known role in productive phase of inflammation, but its role in neutrophil survival and resolution phase of inflammation is unknown. Here, we investigated the effects of inhibition of S1P receptors and the blockade of S1P synthesis in BALB/c mice and human neutrophils. S1P and S1PR1-3 receptors expression were increased in cells from the pleural cavity stimulated with LPS. Using different antagonists of S1PRs and inhibitors of different steps of the metabolic pathway of S1P production, we show that S1P and its receptors are involved in regulating neutrophil survival and resolution of inflammation in the pleural cavity. Given the role of the S1P-S1PR axis in resolution of inflammation, we sought to identify whether blockade at different levels of the sphingosine-1-phosphate synthesis pathway could affect neutrophil survival in vitro. Inhibitors of the S1P pathway were also able to induce human neutrophil apoptosis. In addition, blockade of S1P synthesis or its receptor facilitated the efferocytosis of apoptotic neutrophil. Taken together, our data demonstrate a fundamental role for S1P in regulating the outcome of inflammatory responses, and position S1P-S1PR axis as a potential target for treatment of neutrophilic inflammation.

Quality of life of children with poor school performance: association with hearing abilities and behavioral issues / Qualidade de vida de crianças com mau desempenho escolar: associação com as habilidades auditivas e aspectos comportamentais

ABSTRACT The aim of the present study was to investigate the quality of life of children with poor school performance and its association with behavioral aspects and hearing abilities. Methods: This cross-sectional observational study, developed in a town in the state of Minas Gerais, Brazil, investigated a random sample of public school children, aged 7-12 years old, who performed poorly in school and received specialized educational assistance. The study comprised two stages: 1) collection of data from parents on their children's health, educational, and socioeconomic profile, and from the Strengths and Difficulties Questionnaire; 2) administration of a quality of life evaluation scale to the schoolchildren. For the assessment of auditory function, transient otoacoustic emissions were used and auditory processing was tested. The following tests were used: verbal sequential memory, nonverbal sequential memory, sound localization, dichotic digits, duration pattern test (flute) and random gap detection. The collected data were analyzed using Excel and STATA 11.0 software. Quality of life was considered the response variable. The explanatory variables were grouped for univariate and multivariate logistic regression analysis with the level of significance set at 5%. Results: A statistically significant association was found between impaired quality of life, altered pro-social behavior, and the absence of parental complaints about the children's written language development. Conclusions: Quality of life is impaired in children with poor school performance. The lack of parental complaints about written language and changes in social behavior increased the likelihood of a child having a poor quality of life.

RESUMO Investigar a qualidade de vida de crianças de 7 a 12 anos de idade com mau desempenho escolar e a associação com as características comportamentais e habilidades auditivas. Métodos: Estudo observacional transversal realizado com crianças de 7 a 12 anos de idade, com mau desempenho escolar das escolas públicas municipais de uma cidade do interior de Minas Gerais, Brasil, participantes de atendimentos educacionais especializados. Etapas: 1) coleta de informações com os pais sobre a saúde, perfil escolar e socioeconômico e preenchimento do Strengths and Difficulties Questionnaire; 2) etapa com as crianças para aplicação da Escala de Avaliação da Qualidade de Vida. Para a avaliação da função auditiva foram utilizadas as Emissões Otoacústicas Transientes e a avaliação do processamento auditivo, sendo os testes aplicados: teste de memória de sons verbais em sequência, teste de memória de sons não verbais em sequência, localização sonora, teste dicótico de dígitos, teste de padrão de duração (flauta) e Random Gap Detection. Os dados coletados foram analisados por meio dos programas Excel e STATA 11.0. Foi considerada como variável resposta a qualidade de vida e as variáveis explicativas foram agrupadas para análise de regressão logística uni e multivariada, considerando o nível de significância de 5%. Resultados: Foi encontrada associação estatística entre qualidade de vida prejudicada, comportamento pró-social alterado e ausência de queixa parental de linguagem escrita. Conclusão: A qualidade de vida está comprometida nas crianças com mau desempenho escolar. A ausência de queixa sobre o desenvolvimento da linguagem escrita e comportamento pró-social alterado aumentaram a chance de a criança apresentar qualidade de vida prejudicada.

Tempo de amamentação e sinais de respiração oral em crianças com mau desempenho escolar / Breastfeeding duration and sings of mouth breathing in children with poor school performance / Tiempo de lactancia materna y signos de respiración bucal en niños con rendimiento escolar malo

Introdução: A amamentação é fator de proteção para doenças respiratórias, além de contribuir para o desenvolvimento intelectual das crianças. Objetivo: Analisar a relação do tempo de amamentação com sinais de respiração oral em crianças com mau desempenho escolar. Métodos: Estudo transversal, realizado com 82 crianças de 7 a 12 anos de idade, com mau desempenho escolar, recrutadas nas escolas públicas de uma cidade do interior de Minas Gerais. Os pais responderam a um questionário contendo os seguintes temas: tempo de amamentação em meses, sexo da criança, escolaridade materna e sinais de respiração oral. Para a análise estatística foi empregado o teste Qui-quadrado de Pearson e Teste Exato de Fisher, considerando o nível de significância de 5%. Resultados: Do total das crianças estudadas, 61 (74%) receberam amamentação por mais de seis meses, 60 (73%) eram do sexo masculino, 47 (56%) das mães eram analfabetas ou tinham o ensino fundamental incompleto. Os sinais de respiração oral estavam presentes em 57 (70%) dos escolares. Houve associação entre o tempo de amamentação e o relato de queixas de obstrução nasal esporadicamente, dificuldade ou demora ao engolir o alimento e dormir de boca aberta. Conclusão: As crianças que foram amamentadas por tempo inferior a seis meses apresentaram maior número combinado de sinais de respiração oral. Houve associação estatisticamente significante entre os sinais de respiração oral e o tempo de amamentação. O rastreamento de crianças que precisam ser encaminhadas para avaliação multiprofissional do modo respiratório pode ser realizado por meio das informações sobre tempo de amamentação e sinais de respiração oral combinados.

Introduction: Breastfeeding is a protective factor for respiratory diseases, as well as contributing to the intellectual development of children. Objective: To analyze the relationship of breastfeeding time with signs of oral breathing in children with poor school performance. Methods: A cross-sectional study was carried out with 82 children aged 7 to 12 years old with poor school performance, recruited from public schools in a city in the interior of Minas Gerais. The parents answered a questionnaire containing the following topics: breastfeeding time in months, gender of the child, maternal schooling and signs of oral breathing. For the statistical analysis, Pearson's Chi-square test and Fisher's exact test were used, considering a significance level of 5%. Results: Of the total number of children studied, 61 (74%) received breastfeeding for more than six months, 60 (73%) were male, 47 (56%) of the mothers were illiterate or had incomplete elementary education. Signs of oral breathing were present in 57 (70%) of schoolchildren. There was an association between the time of breastfeeding and the report of complaints of nasal obstruction sporadically, difficulty or delay when swallowing food and sleeping with open mouth. Conclusion: Children who were breastfed for less than six months had a greater combined number of signs of oral breathing. There was a statistically significant association between the signs of oral breathing and the time of breastfeeding. Screening of children who need to be referred for multiprofessional evaluation of the respiratory mode can be performed through information on breastfeeding time and combined mouth breathing signals.

Introducción: La lactancia materna es un factor de protección para las enfermedades respiratorias, además de contribuir al desarrollo intelectual de los niños. Objetivo: Analizar la relación del tiempo de lactancia con signos de respiración oral en niños con mal desempeño escolar. Métodos: Estudio transversal, realizado con 82 niños de 7 a 12 años de edad, con mal desempeño escolar, reclutados en las escuelas públicas de una ciudad del interior de Minas Gerais. Los padres respondieron a un cuestionario que contenía los siguientes temas: tiempo de lactancia en meses, sexo del niño, escolaridad materna y signos de respiración oral. Para el análisis estadístico se empleó la prueba Chi-cuadrado de Pearson y la prueba exacta de Fisher, considerando el nivel de significancia del 5% .Resultados: Del total de los niños estudiados, 61 (74%) recibieron amamantación superior a seis meses, 60 (73%) eran del sexo masculino, 47 (56%) de las madres eran analfabetas o tenían la enseñanza fundamental incompleta. Los signos de respiración oral estaban presentes en 57 (70%) de los escolares. Se observó asociación entre el tiempo de lactancia y el relato de quejas de obstrucción nasal esporádicamente, dificultad o demora al tragar el alimento y dormir de boca abierta. Conclusión: Los niños que fueron amamantados por tiempo inferior a seis meses presentaron mayor número combinado de signos de respiración oral. Se observó asociación estadísticamente significativa entre los signos de respiración oral y el tiempo de lactancia. El seguimiento de niños que necesitan ser encaminados para evaluación multiprofesional del modo respiratorio puede ser realizado por medio de las informaciones sobre tiempo de lactancia y señales de respiración oral combinadas.

Sensory Ganglia-Specific TNF Expression Is Associated With Persistent Nociception After Resolution of Inflammation.

Joint pain is a distressing symptom of arthritis, and it is frequently persistent even after treatments which reduce local inflammation. Continuous production of algogenic factors activate/sensitize nociceptors in the joint structures and contribute to persistent pain, a challenging and difficult condition to treat. TNF is a crucial cytokine for the pathogenesis of several rheumatic diseases, and its inhibition is a mainstay of treatment to control joint symptoms, including pain. Here, we sought to investigate the inflammatory changes and the role of TNF in dorsal root ganglia (DRG) during persistent hypernociception after the resolution of acute joint inflammation. Using a model of antigen-induced arthritis, the peak of joint inflammation occurred 12-24 h after local antigen injection and was characterized by an intense influx of neutrophils, pro-inflammatory cytokine production, and joint damage. We found that inflammatory parameters in the joint returned to basal levels between 6 and 8 days after antigen-challenge, characterizing the resolving phase of joint inflammation. Mechanical hyperalgesia was persistent up to 14 days after joint insult. The persistent nociception was associated with the inflammatory status of DRG after cessation of acute joint inflammation. The late state of neuroinflammation in the ipsilateral side was evidenced by gene expression of TNF, TNFR2, IL-6, IL-1ß, CXCL2, COX2, and iNOS in lumbar DRG (L3-L5) and leukocyte adhesion in the lumbar intumescent vessels between days 6 and 8. Moreover, there were signs of resident macrophage activation in DRG, as evidenced by an increase in Iba1-positive cells. Intrathecal or systemic injection of etanercept, an agent clinically utilized for TNF neutralization, at day 7 post arthritis induction, alleviated the persistent joint hyperalgesia by specific action in DRG. Our data suggest that neuroinflammation in DRG after the resolution of acute joint inflammation drives continuous neural sensitization resulting in persistent joint nociception in a TNF-dependent mechanism.

Qualidade de vida e autopercepção de saúde de crianças com mau desempenho escolar / Quality of life and health self-perception in children with poor school performance

RESUMO Objetivo: Verificar a associação entre qualidade de vida e autopercepção de saúde em crianças com mau desempenho escolar, considerando fatores sociodemográficos. Métodos: Estudo observacional analítico transversal com 99 crianças de 7 a 12 anos, participantes dos Atendimentos Educacionais Especializados. Os responsáveis responderam a questões sobre aspectos sociodemográficos. Para a avaliar a qualidade de vida e os domínios propostos (autonomia, funções, lazer e família) as crianças responderam ao Autoquestionnarie Qualité de Vie Enfant Imagé (AUQEI) e a uma questão referente à autopercepção de saúde. A análise de dados foi realizada por meio da regressão linear múltipla, considerando nível de significância de 5%. Resultados: Das crianças avaliadas, 69 (69,7%) eram do sexo masculino, com média de idade de 8,7±1,5. Do total, 27% delas autoavaliaram a saúde como ruim/muito ruim e 36,4% referiram ter qualidade de vida prejudicada. Quanto aos domínios avaliados pelo AUQEI, houve significância estatística dos domínios família e idade, autonomia e classificação econômica, lazer e funções em relação à autopercepção de saúde. Conclusões: A qualidade de vida de crianças com mau desempenho escolar está associada à autopercepção de saúde e a características sociodemográficas.

ABSTRACT Objective: To examine the association between quality of life and health self-perception of children with poor school performance, considering sociodemographic factors. Methods: An analytical, observational, cross-sectional study was conducted with 99 children aged 7 to 12 years receiving specialized educational assistance. Parents and legal guardians answered questions concerning the sociodemographic profile. For an assessment of the quality of life and proposed domains (autonomy, functioning, leisure, and family), the children completed the Autoquestionnarie Qualité de Vie Enfant Imagé (AUQEI) and answered a question concerning their self-perceived health. Data were analyzed using multiple linear regression, considering a 5% significance level. Results: Among the evaluated children, 69 (69.7%) male participants with mean age of 8.7±1.5, 27% self-assessed their health status as poor/very poor, and 36.4% of the children reported having impaired quality of life. As for the domains assessed by AUQEI, there was statistical significance in the associations between family with age, autonomy with economic classification, and leisure and functioning with self-perceived health. Conclusions: The quality of life of children with academic underachievement is associated with their health self-perception and sociodemographic characteristics.

QUALITY OF LIFE AND HEALTH SELF-PERCEPTION IN CHILDREN WITH POOR SCHOOL PERFORMANCE. / QUALIDADE DE VIDA E AUTOPERCEPÇÃO DE SAÚDE DE CRIANÇAS COM MAU DESEMPENHO ESCOLAR.

OBJECTIVE: To examine the association between quality of life and health self-perception of children with poor school performance, considering sociodemographic factors. METHODS: An analytical, observational, cross-sectional study was conducted with 99 children aged 7 to 12 years receiving specialized educational assistance. Parents and legal guardians answered questions concerning the sociodemographic profile. For an assessment of the quality of life and proposed domains (autonomy, functioning, leisure, and family), the children completed the Autoquestionnarie Qualité de Vie Enfant Imagé (AUQEI) and answered a question concerning their self-perceived health. Data were analyzed using multiple linear regression, considering a 5% significance level. RESULTS: Among the evaluated children, 69 (69.7%) male participants with mean age of 8.7±1.5, 27% self-assessed their health status as poor/very poor, and 36.4% of the children reported having impaired quality of life. As for the domains assessed by AUQEI, there was statistical significance in the associations between family with age, autonomy with economic classification, and leisure and functioning with self-perceived health. CONCLUSIONS: The quality of life of children with academic underachievement is associated with their health self-perception and sociodemographic characteristics.

OBJETIVO: Verificar a associação entre qualidade de vida e autopercepção de saúde em crianças com mau desempenho escolar, considerando fatores sociodemográficos. MÉTODOS: Estudo observacional analítico transversal com 99 crianças de 7 a 12 anos, participantes dos Atendimentos Educacionais Especializados. Os responsáveis responderam a questões sobre aspectos sociodemográficos. Para a avaliar a qualidade de vida e os domínios propostos (autonomia, funções, lazer e família) as crianças responderam ao Autoquestionnarie Qualité de Vie Enfant Imagé (AUQEI) e a uma questão referente à autopercepção de saúde. A análise de dados foi realizada por meio da regressão linear múltipla, considerando nível de significância de 5%. RESULTADOS: Das crianças avaliadas, 69 (69,7%) eram do sexo masculino, com média de idade de 8,7±1,5. Do total, 27% delas autoavaliaram a saúde como ruim/muito ruim e 36,4% referiram ter qualidade de vida prejudicada. Quanto aos domínios avaliados pelo AUQEI, houve significância estatística dos domínios família e idade, autonomia e classificação econômica, lazer e funções em relação à autopercepção de saúde. CONCLUSÕES: A qualidade de vida de crianças com mau desempenho escolar está associada à autopercepção de saúde e a características sociodemográficas.