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Walison Nunes da Silva,1 Pedro Augusto Carvalho Costa,1 Sérgio Ricardo Aluotto Scalzo Júnior,1 Heloísa AS Ferreira,1 Pedro Henrique Dias Moura Prazeres,2 Caroline Leonel Vasconcelos Campos,3 Marco Túllio Rodrigues Alves,1 Natália Jordana Alves da Silva,1 Ana Luiza de Castro Santos,1 Lays Cordeiro Guimarães,1 Maria Eduarda Chen Ferris,1 Ajay Thatte,4 Alex Hamilton,4 Kelly Alves Bicalho,5 Anderson Oliveira Lobo,6 Helton da Costa Santiago,3 Lucíola da Silva Barcelos,1 Maria Marta Figueiredo,7 Mauro Martins Teixeira,3 Vivian Vasconcelos Costa,8 Michael J Mitchell,4 Frédéric Frézard,1 Pedro Pires Goulart Guimaraes1 1Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil; 2Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil; 3Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil; 4Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA; 5Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG, Brazil; 6Department of Materials Engineering, Federal University of Piauí, Teresina, PI, Brazil; 7State University of Minas Gerais, Divinopolis, MG, Brazil; 8Department of Morphology, Federal University of Minas Gerais, Belo Horizonte, MG, BrazilCorrespondence: Pedro Pires Goulart Guimaraes, Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil, Email ppiresgo@reitoria.ufmg.brIntroduction: Immunotherapy has revolutionized cancer treatment by harnessing the immune system to enhance antitumor responses while minimizing off-target effects. Among the promising cancer-specific therapies, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted significant attention.Methods: Here, we developed an ionizable lipid nanoparticle (LNP) platform to deliver TRAIL mRNA (LNP-TRAIL) directly to the tumor microenvironment (TME) to induce tumor cell death. Our LNP-TRAIL was formulated via microfluidic mixing and the induction of tumor cell death was assessed in vitro. Next, we investigated the ability of LNP-TRAIL to inhibit colon cancer progression in vivo in combination with a TME normalization approach using Losartan (Los) or angiotensin 1– 7 (Ang(1– 7)) to reduce vascular compression and deposition of extracellular matrix in mice.Results: Our results demonstrated that LNP-TRAIL induced tumor cell death in vitro and effectively inhibited colon cancer progression in vivo, particularly when combined with TME normalization induced by treatment Los or Ang(1– 7). In addition, potent tumor cell death as well as enhanced apoptosis and necrosis was found in the tumor tissue of a group treated with LNP-TRAIL combined with TME normalization.Discussion: Together, our data demonstrate the potential of the LNP to deliver TRAIL mRNA to the TME and to induce tumor cell death, especially when combined with TME normalization. Therefore, these findings provide important insights for the development of novel therapeutic strategies for the immunotherapy of solid tumors.Keywords: immunotherapy, TRAIL, mRNA, lipid nanoparticle, losartan, angiotensin (1– 7)

Pulmonary arterial hypertension (PAH) is a form of precapillary pulmonary hypertension caused by a complex process of endothelial dysfunction and vascular remodeling. If left untreated, this progressive disease presents with symptoms of incapacitating fatigue causing marked loss of quality of life, eventually culminating in right ventricular failure and death. Patient management is complex and based on accurate diagnosis, risk stratification, and treatment initiation, with close monitoring of response and disease progression. Understanding the underlying pathophysiology has enabled the development of multiple drugs directed at different targets in the pathological chain. Vasodilator therapy has been the mainstay approach for the last few years, significantly improving quality of life, functional status, and survival. Recent advances in therapies targeting dysfunctional pathways beyond endothelial dysfunction may address the fundamental processes underlying the disease, raising the prospect of increasingly effective options for this high-risk group of patients with a historically poor prognosis. Resumo: A hipertensão arterial pulmonar (HAP) é um tipo de hipertensão pulmonar pré-capilar causada por um processo complexo de disfunção endotelial e remodelação vascular desfavorável. A história natural desta doença progressiva inclui sintomatologia de insuficiência cardíaca e perda de qualidade de vida, culminando em falência ventricular direita e morte. A gestão dos doentes é complexa, baseando-se num diagnóstico preciso, estratificação de risco e início de terapêutica adequada, sendo essencial a monitoração apertada da resposta e progressão da doença.A compreensão da fisiopatologia subjacente permitiu o desenvolvimento de múltiplos fármacos dirigidos a diferentes alvos na cadeia patológica. A terapêutica vasodilatadora destaca-se como a abordagem de base nas últimas décadas, tendo permitido melhoria significativa da qualidade de vida, estado funcional e sobrevida dos doentes. Os avanços terapêuticos recentes, com o advento da utilização de fármacos dirigido aos mecanismos subjacentes à doença, trazem a promessa de opções terapêuticas cada vez mais eficazes para este grupo de doentes de alto risco, com um prognóstico historicamente reservado.

RESUMO O estudo objetivou obter evidências baseadas na estrutura interna da Escala de Percepção de Suporte Social no Trabalho (EPSST) para o contexto da segurança pública. Participaram do estudo 9.591 agentes da segurança pública de diferentes corporações de todas as unidades federativas do Brasil. A maioria dos participantes (83,7%) era do sexo masculino (f=8.029), com idade média de 40 anos (DP=7,69) e tempo médio de serviço na instituição de 14 anos (DP=8,14). Realizou-se análises fatoriais para verificar a estrutura fatorial da escala e estimou-se a consistência interna. Os resultados apontaram para uma estrutura de três fatores (suporte social informacional; suporte social emocional; suporte social instrumental ou material), itens com cargas fatoriais acima de 0,30, índices de ajustes adequados e estimativas de precisão com valores satisfatórios para todos os fatores (entre 0,73 e 0,94). Conclui-se que a EPSST apresenta qualidades psicométricas adequadas para o contexto de segurança pública.

Abstract Background Seed conditioning with bioinputs (biopriming) offers a promising and sustainable alternative to mitigate the adverse effects of salt stress on soybeans. This study aims to evaluate the potential of isolated or combined biopriming using microalgae and different microorganisms in alleviating salinity-induced stress in soybeans in early-stage. Methods Seeds were subjected to five biopriming treatments: Parachlorella sp. microalgae culture, Bacillus subtilis, Trichoderma harzianum, Parachlorella sp. + B. subtilis, and Parachlorella sp. + T. harzianum, along with a control group without biopriming. Subsequently, the seeds were exposed to two conditions: (i) control (0.0 MPa), and (ii) salinity induced by NaCl (-0.8 MPa). Germination, photochemical indicators, and seedling performance were assessed. Results Salinity impaired root protrusion and seed physiology, resulting in a high percentage of abnormal seedlings, thus creating a stressful condition. However, biopriming alleviated the negative effects of salinity, particularly with T. harzianum, Parachlorella sp. + B. subtilis, and Parachlorella sp. + T. harzianum, which led to high germination rates and normal seedlings. All biopriming treatments, especially the combined ones, reduced the suppression of non-photochemical quenching, thereby enhancing the maximum yield of photosystem II. Seedlings under salt stress without biopriming exhibited short lengths and low fresh and dry mass, whereas those bioprimed with Parachlorella sp. + B. subtilis and Parachlorella sp. + T. harzianum showed significantly higher values. Conclusion Seed biopriming, especially with Parachlorella sp. microalgae culture combined with B. subtilis or T. harzianum, effectively alleviates the stressful effects of salinity on germination and early-stage growth seedling of soybeans.

Abstract Resting tremor (RT) is a Parkinson’s disease (PD) symptom with an unclear relationship to the dopaminergic system. We analysed data from 432 subjects from the Parkinson’s Progression Markers Initiative, 57 additional PD patients and controls and 86 subjects referred for dopamine transporter single-photon emission computed tomography (DaT-SPECT). Caudate binding ratio (CBR), but not putamen binding ratio, was higher in RT patients. Furthermore, higher baseline CBR was linked to RT development. In the smaller cohorts, a 4–6 Hz oscillation-based metric from inertial sensors correlated with RT amplitude, distinguished controls from patients with reduced DaT binding and correlated with CBR in the latter group. In silico modelling uncovered that higher CBR in RT patients explained correlations between RT and DaT-SPECT found in several datasets, supporting a spurious origin for ipsilateral correlations between CBR and RT. These results suggest that caudate dopaminergic terminals integrity is a feature of RT with potential pathophysiological implications.

OBJECTIVE: To identify the factors related to difficulty sleeping in adults and older people registered on the Family Health Strategy at Primary Care Health Centers. METHODS: This is a cross-sectional, quantitative study conducted in the town of Três Lagoas (MS, Brazil), with 300 people of both sexes, aged 45 years and over, registered on the town's Family Health Strategy. Data were collected using a structured questionnaire containing questions on sociodemographics, health, and social support networks. The dependent variable difficulty sleeping was assessed using the question: "Do you have difficulty sleeping?" Data were analyzed with binomial logistic regression. RESULTS: The prevalence of difficulty sleeping was 43% (95% confidence interval [95%CI] 37 – 49). According to the adjusted analyses, the following variables were associated with the outcome: female sex (Odds Ratio = 2.08; 95%CI 1.21 – 3.60); number of medications per day (Odds Ratio = 1.18; 95%CI 1.05 – 1.33); self-report of visual impairment (Odds Ratio = 3.56; 95%CI 1.54 – 8.25); self-report of hearing loss (Odds Ratio = 2.28; 95%CI 1.18 – 4.41); and social isolation (Odds Ratio = 2.01; 95%CI 1.14 – 3.54). CONCLUSIONS: Identification of the principal factors related to complaints of insomnia is of relevance to support planning of care and of public policies, targeting improved sleep quality in people going through the aging process and beyond.

Este artigo oferece uma visão atual sobre o alinhamento estratégico da comunicação organizacional nas instituições da Rede Federal de Educação Profissional, Científica e Tecnológica (RFEPCT). O estudo explora a importância de uma comunicação clara, transparente e inclusiva como um pilar estratégico essencial para o sucesso e a eficácia institucional. Através de uma abordagem exploratória baseada em revisão bibliográfica, a pesquisa examina como a comunicação se integra ao planejamento estratégico nas instituições, com foco na referida área hoje existente na rede federal de ensino. A análise evidencia que a falta de uma comunicação eficaz pode comprometer o alcance dos objetivos institucionais, resultar em processos ineficazes e prejudicar a imagem institucional. Conclui-se que a integração estratégica da comunicação e a profissionalização das ferramentas comunicativas são cruciais para garantir a transparência, fortalecer a reputação e apoiar a gestão estratégica das instituições da RFEPCT.

Uma alternativa para minimizar os efeitos da indução de resistência aos herbicidas é a rotação de ingredientes ativos. Entre os herbicidas amplamente utilizados, destacam-se os inibidores das enzimas acetolactato sintase (ALS) e da protoporfirinogênio oxidase (PROTOX). No entanto, a utilização destes pode causar uma série de danos ao metabolismo fotossintético da soja e comprometer o desenvolvimento da cultura, tendo como alternativa para mitigar os efeitos a aplicação de bioestimulante derivado da alga Ascophyllum nodsosum. Portanto, objetivou-se com o presente estudo verificar o potencial de um bioestimulante derivado de A. nodosum em mitigar danos ao processo fotossintético de plantas de soja tratadas com herbicidas em casa de vegetação e pós-emergência. Para isto, foi instalado um experimento em casa de vegetação com nove tratamentos, em arranjo fatorial com 3 aplicações de herbicidas (sem herbicida; Cloransulan; Lactofen) X 3 aplicações de biostimulante (sem aplicação; 3 dias após a aplicação dos herbicidas (DAA); 6 DAA). Foram realizadas avaliações de trocas gasosas, índices de clorofilas e fluorescência da clorofila a. Por meio dos resultados obtidos foi possível concluir que aos 2 dias após a aplicação dos bioestimulantes, os herbicidas não proporcionaram inibição das trocas gasosas das plantas de soja. Por outro lado, aos 10 DAA dos herbicidas foi possível constatar que o cloransulam e lactofen alterou os parâmetros da fluorescência da clorofila a, porém não foi constatado efeito protetor do bioestimulante. Embora não tenha efeito isolado do bioestimulante nos parâmetros da fluorescência, sua aplicação aos 3 DAA dos herbicidas proporcionou incrementos na taxa fotossintética, condutância estomática e na eficiência da carboxilação das plantas de soja. É possível concluir que o bioestimulante tem potencial de uso na cultura da soja com o propósito de mitigar os efeitos da aplicação de herbicidas seletivos.

O presente artigo tem como proposta discutir/refletir sobre alguns aspectos relativos às pedagogias de povos culturalmente distinto – Manoki/Iranxe, Mӱky, Apyãwa/Tapirapé e A’uwẽ/Xavante - a partir de uma ótica simétrica e de equidade dos diferentes saberes socioeducativos. Saberes e conhecimentos esses que nos explicita essa peculiaridade que cada povo possui na condução do processo socioeducativo de suas crianças. Nesse contexto, buscamos ainda mostrar a necessidade de ampliar o espectro epistemológico dos saberes e conhecimentos o que, consequentemente, nos obriga a considerar e respeitar outros modos de produzir sentidos, saberes e conhecimentos, ou seja, reconhecer/respeitar a diversidade de concepções e de identidades culturais nesse processo de produção do conhecimento. Ao discutir as diferentes pedagogias na perspectiva dos Etnosaberes, reconhecemos nelas um importante modo de se viver a experiência do encontro das diferentes formas de conceber, produzir, sistematizar e difundir saberes e conhecimentos em espaços distintos.

ABSTRACT Objective: To analyze the relationship between structural empowerment and sociodemographic and professional factors of nurses at a reference hospital providing emergency care. Method: Analytical, cross-sectional study, with 124 nurses from an emergency hospital, applying the questionnaires: sociodemographic and professional data and the Conditions of Effectiveness at Work II (CET-II) questionnaire. The Spearman or Kruskal Wallis statistical tests were used and the significance level was updated to 5% for the study's statistical analyses. Results: Structural empowerment was moderate among nurses and “opportunity” presented greater mean among the dimensions. Although the correlations were weak, support was the dimension that showed the greatest results with the other variables. It is more noticeable when: shorter training time; greater age and; longer time at the institution. There was no difference between the dimensions of the instrument and the qualitative variables of the study, except between Opportunity and the surgical hospitalization unit and the total score of the instrument and the burns unit, compared with the other units of the hospital. Conclusion: The structural empowerment of nurses in the hospital was moderate and influenced by variables such as: age, time since graduation, time at the institution and with differences between sectors.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a high transmissibility profile which favors the accumulation of mutations along its genome, providing the emergence of new variants. In this context, haplotype studies have allowed mapping specific regions and combining approaches and tracking phylogenetic changes. During the COVID-19 pandemic, it was notorious that home environments favored the circulation of SARS-CoV-2, in this study we evaluated 1,407 individuals positive for SARS-CoV-2, in which we located 53 families in the period from June 2021 to February 2023. The epidemiological data were collected in E-SUS notifica and SIVEP-gripe. Then, the genetic material was extracted using the commercial kit and the viral load was evaluated and the viral genomes were sequenced using the Illumina MiSeq methodology. In addition, the circulation of 3 variants and their respective subvariants was detected. The delta variant represented the highest number of cases with 45%, the Omicron variant 43% and the lowest number with 11% of cases the Gamma variants. There were cases of families infected by different subvariants, thus showing different sources of infection. The haplotype network showed a distribution divided into 6 large clusters that were established according to the genetic characteristics observed by the algorithm and 224 Parsimony informative sites were found. In addition, 92% of subjects were symptomatic and 8% asymptomatic. The secondary attack rate of this study was 8.32%. Therefore, we can infer that the home environment favors the spread of SARS-CoV-2, so it is of paramount importance to carry out genomic surveillance in specific groups such as intradomiciliary ones.