Human effector-memory CD8+ T cells consist of highly differentiated cells that differ in the expression of the tyrosine phosphatase isoform CD45RA, being designated as CD8+ TEM and CD8+ TEMRA cells. These highly heterogeneous and polyfunctional cells possess cytotoxic, regulatory, and suppressive features, and are capable of migrating to non-lymphoid tissues and organs, including the brain under certain conditions. Expansions of CD8+ TEM and CD8+ TEMRA cells have been described in chronic inflammatory diseases, tumors and viral infections, as well as in healthy elderly individuals, including centenarians. Over the past few decades, the role of CD8+ T cells, particularly CD8+ TEMRA cells, has been the subject of several studies in the context of aging, cognition, and neurodegeneration, where they have been generally regarded as detrimental to the central nervous system (CNS), though recent investigations have challenged this view. These highly differentiated CD8+ T cells are known to arise through TCR-dependent and TCR-independent mechanisms, such as cytokine-driven proliferation via interleukin (IL)-15. Intriguingly, chronic antigenic stimulation has been shown to drive the generation of CD8+ T cells expressing low levels of the CD8β chain, though antigen-independent mechanisms remain poorly understood. Herein, we have performed a comprehensive characterization of peripheral blood mononuclear cells (PBMC) as well as of human leukocyte antigen (HLA) molecules in a cohort of elderly volunteers differing in their cognitive status. A detailed analysis of the level of expression of CD45RA in the CD8+ TEMRA compartment revealed the presence of two distinct populations: CD8+ TEMRAlow and CD8+ TEMRAhigh cells. Notably, CD8+ TEMRAhigh cells formed a well-defined and sharply delineated population that was significantly expanded in cognitively impaired volunteers, whereas cognitively unimpaired volunteers were enriched in CD8+ TEMRAlow cells. Further analysis of CD8α and CD8β expression also identified the existence of two distinct CD8+ T cells subsets based on the expression of CD8β: CD8αβlow and CD8αβhigh T cells, with the former being more prevalent among cognitively unimpaired individuals. Moreover, stimulation with PMA and Ionomycin revealed significantly increased IFN-γ production by CD4+ T cells from cognitively impaired elderly. Noteworthy, all but one of the volunteers studied were cytomegalovirus (CMV) seropositive. Finally, a higher prevalence of the HLA-B8 serotype, which belongs to the ancestral haplotype HLA-A1, Cw7, B8, DR3, DQ2, was found among the cognitively impaired elderly. Additionally, we assessed the impact of IL-15 on the cell surface expression of CD8β using CFSE-labeled purified human naïve CD8+ T cells cultured for 12 days. IL-15 induced a robust proliferation and differentiation, resulting in a cell cycle-dependent down-modulation of CD8β from the cell surface, while CD8α expression remained stable or increased slightly. This led to the generation of CD8αβlow and CD8αβ– (i.e., CD8αα) T cells. In contrast, IL-2 and IL-7 alone were unable to replicate this effect. Determination of mRNA levels for CD8α and CD8β isoforms by qPCR revealed that IL-15 promoted a significant decrease in mRNA levels of the CD8β M-4 isoform, while increasing the levels of the M-1 and M-2 isoforms alongside with CD8α. Remarkably, analysis of the level of the tyrosine kinase Lck showed a significant increase in CD8+ T cell blasts after culture of CD8+ T cells with IL-15, when compared to CD8+ T cells at the beginning of the culture. Our findings show an association with certain CD8+ T cell subsets that is compatible with a protective role in cognition and neurodegenerative diseases by identifying novel markers that define discrete subsets of highly differentiated CD8+ T cells expanded in cognitively unimpaired elderly individuals and identify IL-15 as a factor involved in the generation of these subsets. In-depth phenotypic, functional, and transcriptomic characterization of ex vivo and in vitro obtained CD8+ T cell subset is warranted to further elucidate their unique functional properties.

Cognitive reserve (CR) is, considered to be, a mechanism that protects against significantmental decline. It is based on the concept that proxies such as education, complexityof professional occupation and cognitive stimulating activities increases one’s resistance toageor disease-related brain changes and cognition. It designates the brain’s capacity toadaptand cope with changes related to age or pathology without developing cognitive impairment. (Cheng, 2014; Stern et al., 2020; Tucker and Stern, 2011 as cited by Song, Stern &Gu, 2022). Conversely, cognitive training is the repeated and structured practice of tasks whichaimatimproving, maintaining, or restoring mental function (Valenzuela & Sachdev,2009). Variousstudies suggest that cognitive training provided later in life can be used as a protectivetool against cognitive decline. Different types of cognitive training programs have beenshowntohave large and durable effects on the cognitive functioning of older adults (Ball et al., 2002). This systematic review aims to examine the association between cognitive training andcognitive reserve and to determine if the former serves a role as a socio-behavioural proxyfor cognitive reserve. Three databases were used: Scopus, B-On and PubMed. The reviewed literature states that cognitive training is not a Socio-Behavioral proxy for cognitive reserve. Rather, it stimulates pre-existing processes that underlay cognitive reservewhich in turn modulates the efficacy of cognitive training in improving certain cognitivefunctions. However, cognitive reserve was viewed as adquired throughout one’s life; theneural dynamics which are intrinsically connected with the concept of cognitive reservethat may have been induced by a cognitive training program in older individuals were not adequately measured nor taken into account in any of the reviewed studies.

There is increasing evidence that in humans the adaptive immunological system can influence cognitive functions of the brain. We have undertaken a comprehensive immunological analysis of lymphocyte and monocyte populations as well as of HLA molecules expression in a cohort of elderly volunteers (age range, 64-101) differing in their cognitive status. Hereby, we report on the identification of a novel signature in cognitively impaired elderly characterized by: (1) elevated percentages of CD8+ T effector-memory cells expressing high levels of the CD45RA phosphate receptor (Temra hi); (2) high percentages of CD8+ T cells expressing high levels of the CD8β chain (CD8βhi); (3) augmented production of IFNγ by in vitro activated CD4+ T cells. Noteworthy, CD3+CD8+ Temra hi and CD3+CD8βhi cells were associated with impaired cognition. Cytomegalovirus seroprevalence showed that all volunteers studied but one were CMV positive. Finally, we show that some of these phenotypic and functional features are associated with an increased frequency of the HLA-B8 serotype, which belongs to the ancestral haplotype HLA-A1, Cw7, B8, DR3, DQ2, among cognitively impaired volunteers. To our knowledge, this is the first proof in humans linking the amount of cell surface CD45RA and CD8β chain expressed by CD8+ Temra cells, and the amount of IFNγ produced by in vitro activated CD4+ T cells, with impaired cognitive function in the elderly.

This scoping study synthesizes recent developments in artificial intelligence in education (AIEd), addressing knowledge structures, research priorities, learning theories, ethical considerations, and impact evaluation. A bibliometric analysis of 31 review articles (2019-2023) indexed in Scopus (Social Sciences) was conducted using VOSviewer and complementary statistical methods. The corpus is concentrated in the United Kingdom, Hong Kong, China, Germany, the United States, and Taiwan, with Asian countries accounting for 48.4%. Multidisciplinary journals attract 4.4 times more citations than education-only outlets. Findings indicate a marked rise in AIEd research, primarily led by education-affiliated scholars, yet often lacking robust pedagogical grounding and systematic impact assessment. The prevalence of small samples, limited quantitative rigor, and inconsistent contextual reporting constrain generalizability and inference. To enhance educational relevance and fairness, the field should be anchored in pedagogical frameworks and advanced through collaborative efforts that build stronger theories, methods, and practices responsive to diverse educational needs.

Introduction: Transcranial magnetic stimulation (TMS) assumes a growing role in both clinical practice and fundamental sciences. The electroencephalogram (EEG) enhances TMS applications by providing key temporal resolution, particularly evident in the study of event-related potentials (ERPs). Analysing these time-locked responses to specific stimuli may provide deeper insight into the functional role of brain regions during cognitive processing. Therefore, assessing their effectiveness as biomarkers and indicators of effect is key to advancing research in TMS. Objectives: To determine whether ERPs can serve as biomarkers and effect indicators when using TMS, evaluating the effects of rTMS and TBS on ERPs. Methods: PubMed, SCOPUS, and Web of Science were consulted until February 15th, 2024, using combinations of keywords and/or MeSH terms. The PICO-based framework inclusion criteria were: 1) =18 years old, 2) studies involving healthy or pathological brains, 3) interventions utilising rTMS and ERPs, 4) comparisons between preand post-intervention outcomes, including placebo/sham conditions, and 5) no language restrictions. Primary outcomes included ERP amplitude and latency (such as P300, MMN, N200). Results: Out of the 281 screened articles, 14 met the inclusion criteria. P300 was the most discussed ERP (9 articles), demonstrating significant latency or amplitude changes in 89% of these studies. N200 data was collected in eight studies, seven within P300 research and one independently. Among these, four reported significant changes in latency or amplitude. MMN was addressed in two studies, one reporting significant latency changes. Conclusion: The findings reinforce the potential of ERPs as effect indicators while highlighting the need for further research to validate their utility. Underrepresented ERPs, such as MMN, require deeper investigation, while ongoing P300 research should remain supported.

Purpose This study investigated the effects of a 16-week high-speed resistance training (HSRT) program on physical and cognitive function in independent older adults. Methods Seventy-nine participants were assigned to an intervention group (IG, N= 40, 68.50 ± 3.54 years) or a control group (CG, N = 39, 72.08 ± 5.89 years). The IG completed 60–70 min of supervised HSRT three times weekly for 16 weeks. All concentric actions were continuously monitored with a BEAST™ sensor. Physical function was evaluated by five tests: chair‐stand, timed up and go (TUG), seated medicine ball throw (SMBT), six-minute walk (6MWT), and handgrip strength. General cognitive function was assessed with the mini-mental state examination (MMSE). Results The intervention could induce significant improvements in favor of the IG (p < 0.001) for chair-stand ( 2 p = 0.736), TUG test ( 2 p = 0.635), SMBT ( 2 p = 0.331), 6MWT ( 2 p = 0.386), and handgrip strength test for dominant ( 2 p = 0.448) and non-dominant side( 2 p = 0.388), as well as in general cognitive function (MMSE, p = 0.001, 2 p = 0.146). Conclusions The 16-week HSRT program led to substantial enhancements in both physical and cognitive function. Inter estingly, the HSRT program, tailored to general velocity zones, proved to be a safe and motivational approach to physical exercise within this population.

A saúde cardiovascular e cerebral global são importantes para que os idosos tenham uma vida independente. Tanto o envelhecimento quanto a hipertensão estão associados à redução do desempenho cognitivo. O envelhecimento leva a uma redução da reserva fisiológica em diferentes sistemas, corroborando com um acentuado declínio no desempenho físico e cognitivo. O objetivo deste estudo foi avaliar a associação entre força máxima de preensão manual (FPM) e o desempenho cognitivo em idosos, e, num segundo momento, avaliar o envelhecimento como fator para alterações específicas no desempenho cognitivo, na força de preensão manual, função vascular e suas correlações. Idosos (n=90), com idade >60 anos, foram submetidos à avaliação do desempenho cognitivo por meio do mini exame do estado mental (MEEM), dos subtestes de Wechsler Adult Intelligence Scale 3rd Edition e dos testes Trail Making Tests A/B (TMT-A/B). A FMP foi medida usando um protocolo padronizado com um dinamômetro validado. Os participantes foram divididos em grupos de baixa (BFP) e alta força de preensão manual (AFP), de acordo com a mediana da FMP, diferente para mulheres e homens. Num segundo momento, foram subdivididos de acordo com a faixa etária: 60-69 anos (idoso-jovem), 70-79 anos (idoso) e ≥80 anos (muito idoso). Os indivíduos foram submetidos a testes cognitivos, medidas da força de preensão manual (FPM) e hemodinâmica central por tonometria de aplanação (Sphygmocor) e velocidade da onda de pulso (VOP; Complior-SP). Não foram observadas diferenças em anos de escolaridade, valores antropométricos e prevalência de hipertensão e diabetes. Embora o MEEM tenha sido semelhante entre os grupos, o subteste de fluência verbal foi menor e o TMT-B foi maior no grupo BFP. A mudança imediata na pressão arterial sistólica antes e após a preensão manual foi inversamente correlacionada com o subteste de compreensão e positivamente correlacionada com o TMT-B. As médias de idade dos grupos etários foram 65±4, 74±3 anos e 83±3 anos, respectivamente. A pressão sistólica foi semelhante, mas a diastólica foi menor no grupo muito idoso (76±9 vs 75±8 vs 68±8 mmHg, P=0,002). A VOP normalizada pela pressão foi mais alta nos grupos idoso e muito idoso (8,8±1,9 vs 10,5±2 vs 11,1±4,9 m/s, P=0,002). Na hemodinâmica central, apenas o aumento de pressão (AP; 22±10 vs 23±11 vs 35±33 mmHg, P=0,032) foi maior no grupo muito idoso. Este grupo muito idoso apresentou menor escore de compreensão e maiores escores Trail Making Tests A e B. Na regressão linear múltipla, a idade foi independentemente associada ao teste de compreensão (β=-0,27, P=0,006), FPM (β=-0,27, P=0,003), VOP-normalizada (β=0,24, P=0,008) e AP (β=0,23, P=0,008). Os idosos com BFP apresentaram déficits cognitivos específicos, relacionados à alteração imediata da pressão arterial sistólica. Medidas da força de preensão manual podem ser úteis na triagem de baixo desempenho cognitivo. Os marcadores de envelhecimento vascular na população mais idosa parecem ser cuidadosamente identificados. A VOP-normalizada e AP parecem ser indicadores mais confiáveis e testes mais específicos podem indicar declínios cognitivos mais precoces.

Além da importância do estilo de vida ativo como estratégia profilática e terapêutica de doenças físicas e mentais, estudos recentes apontam os efeitos agudos promissores do exercício físico no desempenho cognitivo de crianças e adolescentes. As funções executivas podem impactar na qualidade de vida, assim como no aprendizado, raciocínio, solução de problemas e sucesso em aspectos sociais e emocionais durante a vida. Com objetivo de investigar as relações entre funções executivas e capacidades físicas; e o efeito agudo do exercício físico nas funções executivas de crianças e adolescentes, foram desenvolvidos três estudos para essa dissertação. Estudo 1: Uma revisão sistemática e metanálise com objetivo de analisar estudos que avaliaram o efeito agudo de uma sessão de exercício físico no desempenho das funções executivas de crianças e adolescentes. Foram identificados 5.991 estudos através da busca nas bases de dados e, ao final das etapas de seleção, foram incluídos 25 estudos na metanálise. Foi identificado resultado positivo do efeito agudo do exercício físico no controle inibitório de crianças entre 5 e 17 anos de idade (SMD= 0,11; CI95%= 0,03 – 0,20; p= 0,006). Os melhores resultados foram observados após treinamentos aeróbios, com intensidade moderada e duração de 16 a 35 minutos. Estudo 2: Um estudo de corte transversal com objetivo de investigar a relação entre funções executivas, capacidades físicas e competências socioemocionais de crianças entre 8 e 12 anos de idade. Das oito variáveis de capacidades físicas incluídas na análise, sete apresentaram ao menos um resultado significativo de correlação com as funções executivas, destacando como resultado mais expressivo a relação entre controle inibitório e coordenação motora óculo-manual. Nenhum resultado significativo foi encontrado em relação às competências socioemocionais. Estudo 3: Um estudo controlado randomizado com objetivo de analisar o efeito agudo do exercício físico nas funções executivas de crianças. Foram incluídas 24 crianças entre 9 e 10 anos de idade que foram aleatoriamente alocadas no grupo controle (GC), que não realizou exercício, e no grupo exercício (GE), que realizou uma aula de Educação Física. Os testes cognitivos (Teste de Stroop e Tarefa de Dígitos) foram realizados antes e imediatamente após as sessões de cada um dos grupos. O GE foi dividido em dois subgrupos de acordo com o tempo de duração (25 e 45 minutos). A ANOVA 2-way e a comparação dos deltas (pós – pré sessão) mostraram não haver diferença significativa entre os grupos nas funções executivas investigadas. A partir do resultado dos três estudos da presente dissertação, conclui-se que o efeito agudo do exercício físico pode beneficiar temporariamente a cognição de crianças e adolescentes, além de evidenciar a provável relação positiva entre capacidades físicas e funções executivas, com destaque para a capacidade da coordenação motora óculo-manual predizer de 25 a 34% o desempenho do controle inibitório de crianças. O desenvolvimento de um programa de exercícios físicos de caráter aeróbio, com intensidade moderada e duração de 16 a 35 minutos pode favorecer o desempenho das funções executivas de crianças e adolescentes de forma aguda, assegurando maiores níveis atencionais e favorecendo, inclusive, o aprendizado.

O art. 357, §2º, do CPC/15 introduziu no ordenamento jurídico brasileiro a possibilidade de a organização do processo ser realizada por iniciativa das partes, que, no exercício de sua autonomia da vontade, poderão delimitar o objeto da cognição judicial, definindo as questões de fato, sobre as quais recairá a atividade probatória, e as questões de direito relevantes ao julgamento do mérito. Diante dessa nova fronteira de gerenciamento processual pelas partes, o presente trabalho apresenta um panorama das convenções processuais no direito brasileiro e dos principais aspectos e objetivos da organização do processo, para, então, propor a releitura do brocardo iura novit curia, o princípio dispositivo em sentido processual e a normatividade das convenções processuais como premissas para que a vontade das partes seja compreendida e respeitada na atividade cognitiva orientada pela decisão de mérito. Pretende-se, assim, traçar as diretrizes para o enfrentamento das possibilidades e dos limites das convenções processuais sobre o objeto da cognição, analisar o papel do juiz na sua homologação e conhecimento, bem como os reflexos gerados sobre terceiros não convenentes.

Background: MS is a chronic neurological, inflammatory, autoimmune, demyelinating, degenerative disease. It affects the CNS, especially young adults and middle (15-40 years). Cognitive changes are more frequent than estimated. In addittion, psychiatric disorders in MS are common and they can emerge as inaugural symptoms even without physical symptoms. MS patients are more vulnerable to psychiatric disorders, which may affect two-thirds of them. However, the findings show that it is underdiagnosed and undertreated. According to the literature, within the psychiatric disorders in MS, depression is the most prevalent, followed by anxiety and bipolar disorder. Method: We radomly evaluated 109 patients from a specialized university service in MS (Centro de Referência, Investigação e Tratamento de Esclerose Múltipla - CRIEM), in Central Brazil. They were diagnosed by experienced neurologists, according to the criteria of McDonald- 2010 and reviewed by Polman et al. - 2011, seen at CRIEM. The final sample consisted of 84 patients with MS, which were divided into two groups (BD and no-BD). Neurocognitive assessment was made by widely used instruments and researched in order to assess cognition in MS (BRB-N). For psychiatric changes, it was used BDI, BAI and screening questionnaire for BD, which was evaluated by a psychiatrist. Results: The SDMT showed statistically significant correlations with all other subtests, being the strongest correlations with PASAT3 '' PASAT2 '' and WLG. More than 60% of the sample had losses in three or four cognitive domains. As for the age groups, there were no statistically significant differences between the performance in the tests. It was possible to infer that the longer the major disease , the bigger the losses in the tests: SRT-R SRT-S, SRT-D, 10/36, SDMT, PASAT3 "and WLG. There were statistically significant differences between the groups with four to six years of diagnosis and the seven to 10 years, and this group had higher losses. We found a non-expected data in our sample, which was the finding of 14 patients with dementia. Of these, nine had symptoms consistent with the phenotype of Frontotemporal Dementia. Conclusion: Neurocognitive changes in MS have high prevalence and major impact on quality of life of patients and their families, as well as high financial costs. There was no statistically significant difference between MS patients with BD and the MS no-BD group, suggesting that cognitive changes between MS / BD overlap. Beyond depression, few studies are available in the literature on psychiatric disorders arising in MS and rather intensify the suffering of the patient. We found a prevalence of 65.5% of BD in this population, higher than the literature findings, which can be justified by a thorough assessment. No statistically significant difference between age groups, but there were differences between disease duration. In this sample, the BD group had significantly higher anxiety than no-BD group. There was presence of 14 patients with dementia, and of these, nine had symptoms consistent with the phenotype of Frontotemporal Dementia