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Partindo da concepção de multiletramento engajado como praxiologia pedagógica proposta por Liberali (2022) em relação com a pedagogia dos multiletramentos (NLG, 1996; 2021) e a obra de Paulo Freire (1987), este artigo pretende apresentar esta nova abordagem como como possibilidade para a justiça curricular (PONCE, 2019; PONCE; ARAÚJO, 2019). Neste sentido, analisa as ações realizadas pelo Grupo de Estudos Linguagens em Contexto Escolar (Grupo LACE), da Pontifícia Universidade Católica de São Paulo (PUC-SP), apresentando a estrutura utilizada para a artesania das práticas do grupo, que parte do brincar (LIBERALI; MAZUCHELLI; MODESTO-SARRA, 2021) com atividades sociais para promover a desencapsulação curricular (LIBERALI, 2015; BENTO; LIBERALI, 2021) e a busca pelo bem viver. Ademais, propõe uma discussão sobre o como o brincar, nessas práticas, atua como exercício exotópico, permitindo aos participantes a objetivação das situações de opressão vivenciadas, bem como o retorno crítico a essa mesma realidade com o objetivo de transformá-la. Por fim, demonstra como as características e as ações do multiletramento engajado cumprem as dimensões da justiça curricular.

A educação financeira tem como função principal gerar conhecimento para entender as funcionalidades do recurso monetário de forma crítica e analítica, visando obter perspectivas mais ampla da situação financeira, bem como possibilitando melhor qualidade de vida aos indivíduos. Neste contexto, o presente artigo tem como questão norteadora: como a educação financeira pode auxiliar na formação dos discentes? Desta forma, tem-se como objetivo relatar a educação financeira como uma ferramenta que auxilia na formação dos discentes e sugerir algumas práticas que podem ser utilizadas pelos docentes. Para isso, realizou-se uma pesquisa de natureza qualitativa, de método descritivo e meios bibliográficos. Como resultados, verificou-se que a educação financeira promove uma melhor qualidade de vida aos discentes, diminuindo as preocupações com dívidas através de noções do gerenciamento responsável da vida financeira. Constatou-se, também, que ela promove uma melhor compreensão, entendimento e possibilidade de lidar de forma estratégica e inteligente com os seus recursos monetários.

Doxorubicin (DOX) and mitoxantrone (MTX) are classical chemotherapeutic agents used in cancer that induce similar clinical cardiotoxic effects, although it is not clear if they share similar underlying molecular mechanisms. We aimed to assess the effects of DOX and MTX on the cardiac remodeling, focusing mainly on metabolism and autophagy. Adult male CD-1 mice received pharmacologically relevant cumulative doses of DOX (18 mg/kg) and MTX (6 mg/kg). Both DOX and MTX disturbed cardiac metabolism, decreasing glycolysis, and increasing the dependency on fatty acids (FA) oxidation, namely, through decreased AMP-activated protein kinase (AMPK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) content and decreased free carnitine (C0) and increased acetylcarnitine (C2) concentration. Additionally, DOX heavily influenced glycolysis, oxidative metabolism, and amino acids turnover by exclusively decreasing phosphofructokinase (PFKM) and electron transfer flavoprotein-ubiquinone oxidoreductase (ETFDH) content, and the concentration of several amino acids. Conversely, both drugs downregulated autophagy given by the decreased content of autophagy protein 5 (ATG5) and microtubule-associated protein light chain 3 (LC3B), with MTX having also an impact on Beclin1. These results emphasize that DOX and MTX modulate cardiac remodeling differently, despite their clinical similarities, which is of paramount importance for future treatments.

Background: The chemotherapeutic agent doxorubicin (DOX) has been widely used in the treatment of solid tumors and hematological malignancies [1]. However, serious adverse side effects have emerged in patients treated with this drug, notably cardiotoxicity [2]. Moreover, aging is a risk factor for the development of cardiovascular diseases in cancer treated patients [3]. Objective: We herein aimed to evaluate the molecular effects of DOX on the cardiac muscle of old CD-1 mice. Methods: Old CD-1 male mice (19 months) were administered with a pharmacologically relevant cumulative dose of 9 mg/kg DOX (DOX group) or saline (CTRL group), distributed intraperitoneally for three weeks (biweekly). The experiments were performed with the approval of the national competent authorities (DGAV, reference nº 0421/000/000/2016). Animal welfare was monitored daily. Two months after the last drug or saline administration, mice were sacrificed for collection of blood and heart. Results: Serum glucose concentration was decreased after DOX administration, but no other differences were seen in serum markers evaluated. Regarding the heart, DOX increased the activity of citrate synthase (CS), suggesting increased mitochondrial density. Moreover, the content of peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) was decreased after DOX, pointing to decreased mitochondrial biogenesis. In parallel, the content of Beclin1 and microtubule-associated protein light chain 3 (LC3B) was decreased in DOX group, highlighting lower activation of autophagy. In addition, the content of mast/stem cell growth factor receptor Kit (SCFR) was increased after DOX, pointing to activation of cardiac regeneration. Conclusions: This work showed that even a low cumulative dose of DOX affects the cardiac muscle in multiple pathways requiring further studies to find new molecular mechanisms as to clinically address the cardiotoxicity induced by this anticancer agent., Scientific Letters, Vol. 1 No. Sup 1 (2023)

Mitoxantrone (MTX) is a topoisomerase II inhibitor used to treat a wide range of tumors and multiple sclerosis but associated with potential neurotoxic effects mediated by hitherto poorly understood mechanisms. In adult male CD-1 mice, the underlying neurotoxic pathways of a clinically relevant cumulative dose of 6 mg/kg MTX was evaluated after biweekly administration for 3 weeks and sacrifice 1 week after the last administration was undertaken. Oxidative stress, neuronal damage, apoptosis, and autophagy were analyzed in whole brain, while coronal brain sections were used for a closer look in the hippocampal formation (HF) and the prefrontal cortex (PFC), as these areas have been signaled out as the most affected in 'chemobrain'. In the whole brain, MTX-induced redox imbalance shown as increased endothelial nitric oxide synthase and reduced manganese superoxide dismutase expression, as well as a tendency to a decrease in glutathione levels. MTX also caused diminished ATP synthase β expression, increased autophagic protein LC3 II and tended to decrease p62 expression. Postsynaptic density protein 95 expression decreased in the whole brain, while hyperphosphorylation of Tau was seen in PFC. A reduction in volume was observed in the dentate gyrus (DG) and CA1 region of the HF, while GFAP-ir astrocytes increased in all regions of the HF except in the DG. Apoptotic marker Bax increased in the PFC and in the CA3 region, whereas p53 decreased in all brain areas evaluated. MTX causes damage in the brain of adult CD-1 mice in a clinically relevant cumulative dose in areas involved in memory and cognition.

Este artigo apresenta uma reflexão teórico-epistemológica acerca da escrita acadêmica como processo dialógico, com foco em práticas colaborativas em ambientes virtuais. Partindo dos conceitos de dialogia e de exotopia (BAKHTIN, 2003; 2006; 2016), bem como das atividades epilinguísticos e da compreensão da escrita como processo (GERALDI, 1997; GARCEZ, 1998; 2004), objetiva-se delinear um esboço do ciclo responsivo/colaborativo da escrita. Foram analisados textos elaborados por alunos de Letras da Universidade Federal de Goiás através do Google Docs. Essa observação permitiu verificar que as ferramentas da plataforma on-line permitiram o exercício contínuo do excedente de visão e de atividades epilinguísticas, não apenas ao final da redação, mas durante todo o processo de produção textual.

INTRODUÇÃO: A dor pós-APB é incapacitante e desafiadora. A compreensão de como a dor se inicia e as características que a compõem são aspectos fundamentais para sucesso nos tratamentos clínicos e cirúrgicos. MÉTODOS: Nosso objetivo foi avaliar as características clínicas dos doentes com APB sem dor e com dor, também os subgrupos do grupo dor: dor mista e dor neuropática. Todos os doentes foram avaliados por questionários de dor, sensação fantasma, humor, qualidade de vida e incapacidade física. Avaliação da plasticidade cortical foi realizada através de excitabilidade cortical e área cortical do M1. RESULTADOS: Do total de 56 doentes estudados, a dor estava presente em 43 doentes, sendo que 24 apresentavam dor mista (dor nociceptiva em outra região além da dor no membro desaferentado) e 19 com dor neuropática (dor somente no membro desaferentado). Cinquenta e oito porcento apresentavam lesão à direita e maior tendência a dor que pode ter relação com plasticidade cortical mal adaptativa. Os doentes referiam que o sofrimento com a dor é pior do que a plegia. Entre todos os doentes, 77% apresentaram dor do membro fantasma e 75% sensação fantasma, com características distintas dos doentes com amputação. A intensidade da dor é maior da região distal para proximal do membro desaferentado e a dor cervical e na escapular têm intensidade maior que nas regiões do membro desaferentado. A interferência funcional da dor, no BPI, tem tendência a ser pior nos grupos dor mista que no dor neuropática (p = 0,076). O escore geral do NPSI é maior no grupo com dor mista (p = 0,036) e a dimensão dor evocada que tem o maior impacto (p = 0,007). O DN4 foi maior no grupo dor mista (p = 0,008), mas tem sensibilidade prejudicada nos doentes com APB. McGill Breve não apresenta diferença entre os subgrupos. Os doentes com dor não apresentam catastrofização, mas apresentam ansiedade no HADS e maior incapacidade para trabalhos bimanuais e de força no Quickdash e o impacto na qualidade de vida, SF-12, é maior no aspecto físico (p < 0,001) que no psíquico. Identificamos diferenças na plasticidade cortical ao avaliar a excitabilidade cortical entre os lados ipsilateral x contralateral e trapézio x contralateral do grupo com dor, do grupo sem dor e dos subgrupos. A área do córtex motor ipsilateral e contralateral também tem diferença entre os grupos e subgrupos. CONCLUSÃO: Os doentes com dor pós-APB apresentam dor nociceptiva, neuropática que apresentam mesma intensidade de dor, mas impactam de forma diferente a vida dos doentes. As sensações fantasmas se apresentam de forma distinta e a ausência de motricidade pode ser um ponto que contribui para a plasticidade cortical mal adaptativa INTRODUCTION: Post-APB pain is disabling and challenging. Understanding its mechanisms and characteristics is key to achieve success in clinical and surgical treatments. METHODS: Our objective was to evaluate the clinical characteristics of patients with APB without pain and with pain, also the subgroups of the group with pain, mixed pain, and neuropathic pain. All patients were evaluated by questionnaires on pain, phantom sensation, mood, quality of life and physical disability. Evaluation of cortical plasticity was performed through cortical excitability and cortical area of M1. RESULTS: Of the 56 patients studied, pain was present in 43 patients, 24 of whom had mixed pain (nociceptive pain in a region other than pain in the disaffected limb) and 19 had neuropathic pain (pain only in the disaffected limb). Fifty eight percent have a lesion on the right and are more prone to pain, which may be related to maladaptive cortical plasticity. Patients with lesion on the left had more roots affected. Patients report that suffering with pain is worse than having a plegic limb. Among all patients, 77% have phantom limb pain and 75% phantom sensation, which have different characteristics from patients with amputation. Pain intensity is greater from distal to proximal and pain in the cervical and scapular regions have greater intensity than in the disaffected limb regions, with a possible contribution to cortical plasticity. The functional interference of pain in BPI tends to be worse in the mixed pain groups than in the neuropathic pain groups (p = 0.076). The overall NPSI score is higher in the mixed pain group (p = 0.036) and the evoked pain dimension has the greatest impact (p = 0.007). The DN4 was higher in the mixed pain group (p = 0.008), but it has impaired sensitivity in patients with APB. McGill Brief shows no difference between the subgroups. Patients with pain do not present catastrophizing, but they present anxiety in HADS and greater incapacity for bimanual and strength work in Quickdash and the impact on quality of life, SF12, is greater in the physical aspect (p < 0.001) than in the psychological one. We identified differences in cortical plasticity when assessing cortical excitability between the ipsilateral vs. contralateral and trapezius vs. contralateral sides of the pain group, the pain-free group, and the subgroups. The area of the ipsilateral and contralateral motor cortex also differs between groups and subgroups. CONCLUSION: Patients with post-APB pain present nociceptive, neuropathic pain that present the same pain intensity, but impact patients\' lives differently. Phantom sensations present themselves differently and the absence of motor skills may be a point that contributes to maladaptive cortical plasticity

Doxorubicin (DOX) is an anthracycline used to treat a wide range of tumours. Despite its effectiveness, it is associated to a long range of adverse effects of which cognitive deficits stand out. The present study aimed to assess the neurologic adverse outcome pathways of two clinically relevant cumulative doses of DOX. Adult male CD-1 mice received biweekly intraperitoneal administrations for 3 weeks until reaching cumulative doses of 9 mg/kg (DOX9) or 18 mg/kg (DOX18). Animals were euthanized one week after the last administration, and biomarkers of oxidative stress and brain metabolism were evaluated in the whole brain. Coronal sections of fixed brains were used for specific determinations on the prefrontal cortex (PFC) and hippocampal formation (HF). In the whole brain, DOX18 tended to disrupt the antioxidant defences, affecting glutathione levels and manganese superoxide dismutase (MnSOD) expression. Considering the regional analysis, DOX18 increased the volume of all brain areas evaluated, while GFAP-immunoreactive astrocytes decreased in the dentate gyrus (DG) and increased in the CA3 region of HF both in a dose-dependent manner. Concerning apoptosis pathway, whereas Bax increased in the DOX9 group, it decreased in the DOX18 group, but only in the latter group, Bcl-2 levels also decreased. While p53 only increased in the CA3 region of the DOX9 group, AIF increased in the PFC and DG of DOX18. Finally, phosphorylation of Tau decreased with the highest DOX dose in DG and CA3, while TNF-α levels increased in CA1 of DOX18. Our results indicate new pathways not yet described that could be responsible for the cognitive impairments observed in treated patients.

Mitoxantrone (MTX) is an antineoplastic agent used to treat advanced breast cancer, prostate cancer, acute leukemia, lymphoma and multiple sclerosis. Although it is known to cause cumulative dose-related cardiotoxicity, the underlying mechanisms are still poorly understood. This study aims to compare the cardiotoxicity of MTX and its' pharmacologically active metabolite naphthoquinoxaline (NAPHT) in an in vitro cardiac model, human-differentiated AC16 cells, and determine the role of metabolism in the cardiotoxic effects. Concentration-dependent cytotoxicity was observed after MTX exposure, affecting mitochondrial function and lysosome uptake. On the other hand, the metabolite NAPHT only caused concentration-dependent cytotoxicity in the MTT reduction assay. When assessing the effect of different inhibitors/inducers of metabolism, it was observed that metyrapone (a cytochrome P450 inhibitor) and phenobarbital (a cytochrome P450 inducer) slightly increased MTX cytotoxicity, while 1-aminobenzotriazole (a suicide cytochrome P450 inhibitor) decreased fairly the MTX-triggered cytotoxicity in differentiated AC16 cells. When focusing in autophagy, the mTOR inhibitor rapamycin and the autophagy inhibitor 3-methyladenine exacerbated the cytotoxicity caused by MTX and NAPHT, while the autophagy blocker, chloroquine, partially reduced the cytotoxicity of MTX. In addition, we observed a decrease in p62, beclin-1, and ATG5 levels and an increase in LC3-II levels in MTX-incubated cells. In conclusion, in our in vitro model, neither metabolism nor exogenously given NAPHT are major contributors to MTX toxicity as seen by the residual influence of metabolism modulators used on the observed cytotoxicity and by NAPHT's low cytotoxicity profile. Conversely, autophagy is involved in MTX-induced cytotoxicity and MTX seems to act as an autophagy inducer, possibly through p62/LC3-II involvement.

The control of Parkinson's disease (PD) is challenged by the motor and non-motor fluctuations as well as dyskinesias associated with levodopa long-term therapy. As such, pharmacological alternatives to reduce the reliance on this drug are needed. Melanostatin (MIF-1), a positive allosteric modulator (PAM) of D2 receptors (D2R), is being explored as a novel pharmacological approach focused on D2R potentiation. In this work, 3-furoic acid (3-Fu) was successfully employed as an l-proline (Pro) surrogate, affording two potent MIF-1 analogues, methyl 3-furoyl-l-leucylglycinate (4a) and 3-furoyl-l-leucylglycinamide (6a). In this series, the C-terminal carboxamide moiety was found crucial to enhancing the potency and toxicological profile, yet it is not considered a requisite for the PAM activity. Conformational analysis excludes 4a from adopting the claimed type II β-turn. The discovery and validation of 6a as a lead compound open a new avenue for the development of a novel class of anti-Parkinson therapeutics targeting the D2R.