Editorial: Inter-organ crosstalk during exercise in health and disease: Extracellular vesicles as new kids on the block

Within exercise physiology, the study of factors potentially mediating interorgan crosstalk during and after exercise is a fascinating field of research. As exercise activates a plethora of metabolic pathways in several tissues, organs and systems, examining the underlying biological mechanisms contributing to exercise related metabolic benefits is imperative. Since two decades, the skeletal muscle is known to secrete humoral factors into the circulation in response to exercise, originally described as “myokines” by Pedersen et al. (2003). These myokines are now well known and extensively studied in the field of exercise science (Pedersen and Febbraio, 2012). Interestingly, exercise also triggers other metabolic organs to release similar factors arising from the heart, liver, white and brown adipose tissue, and the nervous system (Chow et al., 2022). These “exerkines” (Safdar et al., 2016) have been recognized to comprise an extensive range of biologically active signalling molecules, including cytokines, lipids, metabolites and (noncoding) nucleic acids, as recently reviewed (Chow et al., 2022)

O ALUNO COM DEFICIÊNCIA DAS COMUNIDADES REMANESCENTES DE QUILOMBOS: UM ESTUDO DOS INDICADORES EDUCACIONAIS

Existe uma escassez de pesquisas na interface entre a educação especial e a educação escolar quilombola, assim, a presente pesquisa tem por objetivo discutir os indicadores educacionais sobre a escolarização do aluno com deficiência das comunidades remanescentes de quilombos no Brasil, e no estado de São Paulo, no período de 2005 a 2010.Os dados foram coletados por meio dos Microdados do Censo Escolar da Educação Básica disponibilizados pelo Instituto Nacional de Estudos e Pesquisas Educacionais Anísio Teixeira (INEP) referentes aos anos de 2005 a 2010. Os principais achados foram: aumento do número de matrículas e maior concentração de alunos com deficiências na educação regular, quando comparado as matrículas em escolas exclusivamente especializadas e classes especiais. Os resultados mostram que os alunos com deficiências estão nas escolas localizadas em áreas remanescentes de quilombos

Formação de professores para a escola inclusiva: contribuições da terapia ocupacional ao aluno com deficiência física

Este trabalho tem por objetivo analisar as contribuições da Terapia Ocupacional para a escolarização do aluno com deficiência física. A história da Terapia Ocupacional revela estreitas relações com o atendimento especializado oferecido às pessoas com deficiência física, o que abre possibilidades de contribuição. A pesquisa de campo deste estudo foi realizada em cinco escolas da Prefeitura de Campinas, os instrumentos de coleta de dados foram entrevistas com professores, diretores, inspetores de alunos, auxiliares de serviço geral e coordenadores pedagógicos, que tinham o propósito de descrever a visão desses profissionais sobre o aluno com deficiência física na escola. Os resultados mostraram a importância da partilha e do diálogo entre a Terapia Ocupacional e o cotidiano escolar, para que, assim, o aluno com deficiência física tenha garantido o seu direito à educação, não apenas de acesso, mas também de permanência e sucesso escolar

Evidence of MyomiR Regulation of the Pentose Phosphate Pathway during Mechanical Load-Induced Hypertrophy

Many of the molecular and cellular mechanisms discovered to regulate skeletal muscle hypertrophy were first identified using the rodent synergist ablation model. This model reveals the intrinsic capability and necessary pathways of skeletal muscle growth in response to mechanical overload (MOV). Reminiscent of the rapid cellular growth observed with cancer, we hypothesized that in response to MOV, skeletal muscle would undergo metabolic programming to sustain increased demands to support hypertrophy. To test this hypothesis, we analyzed the gene expression of specific metabolic pathways taken from transcriptomic microarray data of a MOV time course. We found an upregulation of genes involved in the oxidative branch of the pentose phosphate pathways (PPP) and mitochondrial branch of the folate cycle suggesting an increase in the production of NADPH. In addition, we sought to determine the potential role of skeletal muscle-enriched microRNA (myomiRs) and satellite cells in the regulation of the metabolic pathways that changed during MOV. We observed an inverse pattern in gene expression between muscle-enriched myomiR-1 and its known target gene glucose-6-phosphate dehydrogenase, G6pdx, suggesting myomiR regulation of PPP activation in response to MOV. Satellite cell fusion had a significant but modest impact on PPP gene expression. These transcriptomic findings suggest the robust muscle hypertrophy induced by MOV requires enhanced redox metabolism via PPP production of NADPH which is potentially regulated by a myomiR network

A educação especial nas escolas em áreas remanescentes de quilombos: a realidade mostrada pelos indicadores educacionais

Dados revelam que é recente a preocupação com a educação especial em quilombos. Contudo, a Fundação Cultural Palmares aponta números crescentes de regularização de terras quilombolas em todo território nacional, o que fortalece o debate sobre as escolas localizadas nessas comunidades. Neste estudo, buscou-se mapear as regiões do Brasil nas quais há escolas situadas em áreas remanescentes de quilombos, observar suas características e verificar quais delas contam com a educação especial para alunos, membros das comunidades com deficiência, altas habilidades e transtornos globais do desenvolvimento, público alvo da educação especial. Para tanto, foi realizado um trabalho com indicadores educacionais do ano de 2015. A seleção deste período justifica-se no fato de serem estes os dados mais atualizados sobre a temática em estudo.Para a leitura e tratamento estatístico dos microdados da Educação Básica, foi utilizado o software IBM SPSS, Statistical Package for the Social Sciences. Foram analisados, nos microdados do censo escolar, os dados das escolas segundo a localização diferenciada, área remanescente de quilombo no ensino regular, na educação especial e atendimento educacional especializado, um dos serviços da educação especial. Além disso, foram registrados dados específicos sobre caracterização e infraestrutura das escolas. Os resultados mostram que há alunos com deficiências nas escolas localizadas em área remanescente de quilombo tentando se escolarizar e que, em condições adversas, as escolas vêm buscando cumprir seu papel. Há escolas que oferecem o atendimento educacional especializado, contudo, ainda é uma minoria. Palavras chave: Educação Especial. Área Remanescente de Quilombo. Escola. La educación especial en las escuelas en áreas remanentes de quilombos: la realidad mostrada por los indicadores educativos ABSTRACTData reveal that the concern with special education in quilombos is recent. However, the Palmares Cultural Foundation points out increasing numbers of quilombola lands regularization throughout the national territory, which strengthens the debate about schools located in the communities. This study aimed to map the regions of Brazil where there are schools located in remaining areas of quilombos, their characteristics and which have special education for students, members of communities with disabilities, high skills and global development disorders disorders, target public special education. To do so, the study was carried out with educational indicators for the year 2015. The selection of this period is justified by the fact that these are the most up-to-date data on thesubject under study. Statistical Package for the Social Sciences was used for reading and statistical treatment of Basic Education microdata. In this paper, we present a review of the literature on the education of children and adolescents in the United States. In addition, specific data on school characterization and infrastructure were recorded. The results show that there are students with disabilities in the schools located in the remaining quilombo area trying to go to school and that in adverse conditions the schools have been trying to fulfi ll their role. There are schools that offer specialized educational services, yet it is still a minority. Keywords: Special Education. Remaining Area of Quilombo, School. La Educación especial en las escuelas en áreas remanentes de quilombos: la realidad mostrada por los indicadores educativos RESUMEN Datos revelan que es reciente la preocupación por la educación especial en quilombos. Sin embargo, la Fundación Cultural Palmares señala cifras crecientes de regularización de tierras quilombolas en todo el território nacional, lo que fortalece el debate sobre las escuelas ubicadas en esas comunidades. En este estudio, se buscó mapear las regiones de Brasil em las que hay escuelas situadas en áreas remanentes de quilombos, observar sus características y verificar cuáles de ellas cuentan con la educación especial para alumnos, miembros de las comunidades con discapacidad,altas habilidades y trastornos globales del desarrollo, público objetivo de la educación especial. Por lo tanto, se realizó un trabajo con indicadores educativos del año 2015. La selección de este período se justifica en el hecho de que estos son los datos más actualizados sobre la temática em estudio. Para la lectura y el tratamiento estadístico de los microdatos de Educación Básica, se utilizó el software IBM SPSS, Statistical Package for the Social Sciences. En los microdatos del censo escolar se analizaron los datos de las escuelas según la localización diferenciada, área remanente de quilombo en la enseñanza regular, en la educación especial y atención educativa especializada, uno de los servicios de la educación especial. Además de esto, se registraron datos específi cos sobre caracterización e infraestructura de las escuelas. Los resultados muestran que hay alumnos con discapacidades en las escuelas ubicadas en área remanente de quilombo intentando escolarizarse y que, en condiciones adversas, lãs escuelas vienen buscando cumplir su papel. Hay escuelas que ofrecen la atención educativa especializada, sin embargo, sigue siendo una minoría. Palabras clave: Educación Especial. Área Restante de Quilombo. Escuela

Does a Hypertrophying Muscle Fibre Reprogramme its Metabolism Similar to a Cancer Cell?

In 1924, Otto Warburg asked “How does the metabolism of a growing tissue differ from that of a non-growing tissue?” Currently, we know that proliferating healthy and cancer cells reprogramme their metabolism. This typically includes increased glucose uptake, glycolytic flux and lactate synthesis. A key function of this reprogramming is to channel glycolytic intermediates and other metabolites into anabolic reactions such as nucleotide-RNA/DNA synthesis, amino acid-protein synthesis and the synthesis of, for example, acetyl and methyl groups for epigenetic modification. In this review, we discuss evidence that a hypertrophying muscle similarly takes up more glucose and reprogrammes its metabolism to channel energy metabolites into anabolic pathways. We specifically discuss the functions of the cancer-associated enzymes phosphoglycerate dehydrogenase and pyruvate kinase muscle 2 in skeletal muscle. In addition, we ask whether increased glucose uptake by a hypertrophying muscle explains why muscularity is often negatively associated with type 2 diabetes mellitus and obesity

A prophylactic subcutaneous dose of the anticoagulant tinzaparin does not influence qPCR-based assessment of circulating levels of miRNA in humans

Circulating microRNAs (miRNAs) have become increasingly popular biomarker candidates in various diseases. However, heparin-based anticoagulants might affect the detection of target miRNAs in blood samples during quantitative polymerase chain reaction (qPCR)- based analysis of miRNAs involving RNA extraction, cDNA synthesis and the polymerase catalyzed reaction. Because low-molecular-weight heparins (LMWH) are widely used in routine healthcare, we aimed to investigate whether a prophylactic dose of the LMWH tinzaparin influences qPCR-based quantification of circulating miRNAs. A total of 30 subjects were included: 16 fracture patients with tinzaparin treatment and 14 non-fracture controls without anticoagulation therapy. To control for the effect of tinzaparin on miRNA analysis an identical concentration of synthetic miRNAs was added to plasma, isolated RNA and prepared complementary DNA (cDNA) from all samples in both groups. No significant difference was observed for cDNA synthesis or qPCR when comparing tinzaparin-treated patients with untreated controls. Among the tinzaparin-treated patients, plasma levels of six endogenous miRNAs (hsa-let-7i-5p, hsa-miR-30e-5p, hsa-miR-222-3p, hsa-miR-1-3p, hsamiR- 133a-3p, hsa-miR-133b) were measured before and one to six hours after a subcutaneous injection of tinzaparin 4500IU. No significant effect was observed for any of the investigated miRNAs. A prophylactic dose of 4500IU tinzaparin does not seem to affect cDNA synthesis or qRT-PCR-based quantification of circulating miRNAs

Atendimento educacional especializado: reflexões da realidade de um município paulista

The objective of this article was to analyze the Specialized Educational Care (AEE, in Portuguese) in Brazil, southeast region, state of São Paulo, specifically in a paulista municipality. Therefore, was used the laws that guide the pedagogical work within this space, official social indicators and empirical data, which was created during visits to the city, when was realized the observation in the resource room and an interview with the responsible teacher. The results indicate: increase in the number of classes that offer the AEE in Brazilian schools, in the southeast region and in the state of São Paulo; with respect to the municipality analyzed, was found that teaching the AEE is isolated from the school context and the service is directed to students with learning disabilities, although there is presence of students with other disabilities in school, in addition, the service is limited to an autonomous life activities , especially in the development of mental processes. The results showed that still there are difficulties in implementing the AEE in school that need more policies and actions based on local realities.O objetivo deste artigo foi analisar o Atendimento Educacional Especializado (AEE) no Brasil, região sudeste, estado de São Paulo, especificamente, em um município paulista. Para tanto, utilizou-se as legislações que norteiam o trabalho pedagógico dentro deste espaço, os indicadores sociais oficiais e dados empíricos construídos durante as visitas ao município, quando foi realizada a observação na sala de recursos e uma entrevista com a professora responsável pelo atendimento. Os resultados indicam: ampliação no número de turmas que oferecem o AEE nas escolas brasileiras, na região sudeste e no estado de São Paulo; com relação ao município analisado constatou-se que o trabalho docente no AEE é isolado do contexto escolar e que o serviço é direcionado para os alunos com deficiência mental, embora tenha a presença de alunos com outras deficiências na escola, além disso, o atendimento limita-se a atividades de vida autônoma, sobretudo, no desenvolvimento de processos mentais. Os achados mostram que ainda existem dificuldades na implementação do AEE na escola que carecem de ações mais diretivas e baseadas nas realidades municipais

Extracellular vesicle characteristics and micro RNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise.

In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (~25%, p \u3c 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p \u3c 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p \u3c 0.05). Interestingly, miR-486 was upregulated ~2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with C

Life-Long Reduction in MyomiR Expression Does Not Adversely Affect Skeletal Muscle Morphology

We generated an inducible, skeletal muscle-specific Dicer knockout mouse to deplete microRNAs in adult skeletal muscle. Following tamoxifen treatment, Dicer mRNA expression was significantly decreased by 87%. Wild-type (WT) and Dicer knockout (KO) mice were subjected to either synergist ablation or hind limb suspension for two weeks. There was no difference in muscle weight with hypertrophy or atrophy between WT and KO groups; however, even with the significant loss of Dicer expression, myomiR (miR-1, -133a and -206) expression was only reduced by 38% on average. We next aged WT and KO mice for ~22 months following Dicer inactivation to determine if myomiR expression would be further reduced over a prolonged timeframe and assess the effects of myomiR depletion on skeletal muscle phenotype. Skeletal muscle Dicer mRNA expression remained significantly decreased by 80% in old KO mice and sequencing of cloned Dicer mRNA revealed the complete absence of the floxed exons in KO skeletal muscle. Despite a further reduction of myomiR expression to ~50% of WT, no change was observed in muscle morphology between WT and KO groups. These results indicate the life-long reduction in myomiR levels did not adversely affect skeletal muscle phenotype and suggest the possibility that microRNA expression is uniquely regulated in skeletal muscle