Removal of Rare Earth Elements from complex mixtures by using manganese ferrite nanoparticles: Optimization through surface response methodology.

The crucial role of Rare Earth Elements (REEs) in the development of hi-tech in addition to their limited availability have urged countries to develop sustainable alternatives to their conventional primary sources (ore mining). Sorption technologies using magnetic materials such as spinel ferrite nanoparticles provide efficient removal of REEs from contaminated solutions and ease of separation through application of an external magnetic field. However, there is still limited knowledge available regarding the optimal operational conditions in which to use these materials, especially in complex aqueous mixtures with different REEs. In this study, we have used Surface Response Methodology (SRM) applied to MnFe2O4 nanosorbents to identify their ideal sorption conditions of pH (4-8), REEs concentration (1-5 µM) and sorbent mass (20-180 mg L-1) in a mixture of nine REEs in water samples of distinct salinity (NaCl: 0-30 g L-1). Our results indicated that high pH favored REEs sorption because of the material's surface charge, which promoted interactions with REEs ions at pH 6-8. Yttrium was the least removed element, but total removal was achieved for lowest REEs concentration using 151 mg L-1 of sorbent. High removals were also obtained for the concentration of 5 µM (100 % removal, except for Y and La). Salinity did not impair sorption significantly (<10 %), which was owed to the high sorbent mass used in those assays. An increase in sorbent mass and initial REEs concentration also promoted faster kinetics. The spinel type MnFe2O4 nanoparticles showed great promise in a realistic application, which is the next proposed step in this line of research.

Factors associated with oropharyngeal dysphagia in individuals with cardiovascular disease and COVID-19.

PURPOSE: Oropharyngeal dysphagia (OD) is one of the possible outcomes in patients hospitalized with COVID-19 and also in the population hospitalized for the treatment of cardiovascular disease. Thus, knowing the predictive risk factors for OD may help with referral and early intervention. This study aimed to verify the association of different factors with OD in hospitalized individuals with cardiovascular disease and COVID-19. METHODS: Cross-sectional clinical study approved by the Research Ethics Committee (4,521,771). Clinical evaluation of swallowing was carried out in 72 adult patients with cardiovascular disease and COVID-19 hospitalized from April to September 2020. Individuals under 18 years of age and without previous cardiovascular disease were excluded. The presence of general clinical and/or neurological complications, pronation, stay in the intensive care unit (ICU), orotracheal intubation (OTI), tracheostomy tube, oxygen support and age were considered as predictive risk factors for oropharyngeal dysphagia. Fisher's exact test, Mann Whitney test and logistic regression model were used for analysis. RESULTS: General clinical complications (p=0.001), pronation (p=0.003), ICU stay (p=0.043), in addition to the need for oxygen supplementation (p=0.023) and age (p= 0 .037) were statistically significant factors associated. The pronation (0.013) and age (0.038) were independently associated with dysphagia. OTI (p=0.208), tracheostomy (p=0.707) and the presence of previous cerebrovascular accidents (p=0.493) were not statistically significant. CONCLUSION: In this study, age and prone position were factors independently associated with oropharyngeal dysphagia, complications such as the need for oxygen supplementation, in addition to the need for ICU admission, were also associated factors in the population.

Deregulated immune cell recruitment orchestrated by c-MET impairs pulmonary inflammation and fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) represents the pathologic end stage of several interstitial lung diseases (ILDs) associated with high morbidity and mortality rates. However, current treatments can only delay disease progression rather than provide a cure. The role of inflammation in PF progression is well-established, but new insights into immune regulation are fundamental for developing more efficient therapies. c-MET signaling has been implicated in the migratory capacity and effector functions of immune cells. Nevertheless, the role of this signaling pathway in the context of PF-associated lung diseases remains unexplored. METHODS: To determine the influence of c-MET in immune cells in the progression of pulmonary fibrosis, we used a conditional deletion of c-Met in immune cells. To induce pulmonary fibrosis mice were administered with bleomycin (BLM) intratracheally. Over the course of 21 days, mice were assessed for weight change, and after euthanasia at different timepoints, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis. Furthermore, c-MET expression was assessed in cryobiopsy sections, bronchoalveolar lavage fluid cells samples and single cell RNA-sequencing dataset from human patients with distinct interstitial lung diseases. RESULTS: c-MET expression was induced in lung immune cells, specifically in T cells, interstitial macrophages, and neutrophils, during the inflammatory phase of BLM-induced PF mouse model. Deletion of c-Met in immune cells correlated with earlier weight recovery and improved survival of BLM-treated mice. Moreover, the deletion of c-Met in immune cells was associated with early recruitment of the immune cell populations, normally found to express c-MET, leading to a subsequent attenuation of the cytotoxic and proinflammatory environment. Consequently, the less extensive inflammatory response, possibly coupled with tissue repair, culminated in less exacerbated fibrotic lesions. Furthermore, c-MET expression was up-regulated in lung T cells from patients with fibrosing ILD, suggesting a potential involvement of c-MET in the development of fibrosing disease. CONCLUSIONS: These results highlight the critical contribution of c-MET signaling in immune cells to their enhanced uncontrolled recruitment and activation toward a proinflammatory and profibrotic phenotype, leading to the exacerbation of lung injury and consequent development of fibrosis.

A integralidade nos cuidados a uma paciente com infarto agudo do miocárdio com ações interdisciplinares / Comprehensive care for a patient with acute myocardial infarction with interdisciplinary actions

A integralidade nos cuidados a uma paciente com IAM a partir de ações interdisciplinares INTRODUÇÃO: O infarto agudo do miocárdio (IAM) é a oclusão de uma das artérias do músculo do coração, os fatores de risco podem ser tanto intrínsecos como extrínsecos, sendo o segundo associado a estressores psicossociais, que podem ter um papel relevante na ocorrência da doença, favorecendo a internação prolongada e o surgimento de complicações. MÉTODO: Atendimento multiprofissional numa enfermaria de longa permanência, contando com os atendimentos da psicologia e fonoaudiologia, que atuaram de forma Inter profissional, na conquista do cuidado integral, a partir das demandas da paciente. RELATO DE CASO: Paciente do sexo feminino, 73 anos, com diagnóstico de infarto agudo do miocárdio, realizou cateterismo e houve alterações na função renal por uso de contraste. Com a piora do quadro geral, necessitou de hemodiálise, em consequência apresentou humor deprimido, hipoatividade, diminuição na aceitação alimentar, alterações na biomecânica da deglutição e necessidade de via alternativa de alimentação. Alterações decorrentes de um funcionamento de resignação, em que a paciente abandona a si mesma, a partir de um desejo inconsciente de manter-se hospitalizada, levando a paciente a assumir uma postura de abdicação dos cuidados, recusando os cuidados em saúde. Contudo, após serem trabalhados aspectos do seu sofrimento psíquico e a ressignificação de suas questões, a paciente pôde se apropriar de seu adoecimento e atribuir valor á sua vida. Gerando uma maior aceitação das sessões fonoaudiológicas, iniciando a dieta por via oral, evoluindo a deglutição funcional, engajando nas atividades das outras áreas, o que favoreceu o reestabelecimento do seu quadro geral e o recebimento da alta hospitalar. RESULTADO: Os atendimentos compartilhados com olhar integral ao paciente promove a manifestação dos desejos, sonhos, expressão das emoções e o processo de elaboração do luto por suas perdas. A ressignificação durante a internação prolongada gerou uma nova perspectiva de vida, aceitação dos atendimentos multiprofissionais e promoção da alta hospitalar. CONCLUSÃO: O trabalho do psicólogo é fundamental na equipe multidisciplinar atuando em conjunto com as outras áreas, pois uma vez que o paciente consegue elaborar as suas demandas, abre a possibilidade das intervenções de modo assertivo favorecendo a alta hospitalar.

A atuação da equipe multiprofissional em uma paciente idosa cardiopata em cuidados paliativos no ambiente hospitalar / The performance of the multidisciplinary team in an elderly patient with heart disease undergoing palliative care in the hospital environment

Introdução: A população idosavem aumentando e consequentemente maiores riscos de doenças cardiovasculares que podem acarretar com comorbidades como a insuficiência renal. A equipe multiprofissional enfrenta o desafio de trabalhar articulada e promover da melhor forma a comunicação em um plano terapêutico de cuidados paliativos do paciente juntamente à família. Método: Atendimentos individuais com os profissionais que compõem a equipe multiprofissional de cuidados paliativos para ação de um plano terapêutico. Relato de caso: MTS de 76 anos, sexo feminino com hipertensão arterial, diabete mellitus e infarto agudo do miocárdio. No período de internação hospitalar que aguardava a clínica da hemodiálise passou por fases devido aos diagnósticos de Síndrome Coronariana Aguda, Insuficiência Cardíaca e Doença Renal Crônica Agudizada. No início a expectativa era enorme de ir para casa. A família é bem unida, apoia e tem rede de sustentação e reveza nos cuidados com a paciente. Ao ser chamada na clínica foi recusada porque estava acamada e não conseguia sentar. Assim, desse modo, ocorreu frustração e um luto da sua autonomia, independência e das atividades cotidianas que não podia realizar. A família entrou com um processo e o juiz referiu que MTS já estava sendo assistida na necessidade da hemodiálise. Ela parou de se alimentar, ficou triste e a equipe fortaleceu a rede de cuidados e trabalhou os recursos da paciente bem como sua autonomia e independência no hospital no dia a dia. Devido à fragilidade do caso, necessitou de sonda de alimentação enteral (SNE), sendo avaliada pela fonoaudiologia com diagnóstico de disfagia orofaríngea de grau moderado. Durante o processo terapêutico a paciente negava os testes com dieta oral. Através da atuação integrada com a psicologia e a assistência social, foi possível evolução no processo terapêutico, MTS a partir de então voltou a sorrir, a ficar alegre, reabilitou para deglutição funcional e aceitação das dietas. Resultado: Com o atendimento integrado notou-se a criação de um espaço seguro e efetivo da paciente para manifestar os desejos e expressar as emoções. Apesar de MTS ter ido a óbito após 06 meses, ela pôde ficar ao lado da família, realizar seus desejos e ter uma rede de suporte mais fortalecida. Conclusão: O trabalho da equipe multiprofissional é fundamental nos atendimentos de casos como este, promovendo melhor comunicação e cuidados de modo integral ao paciente dentro de um plano de cuidados paliativos.

Characterization of Azorean Plant Leaves for Sustainable Valorization and Future Advanced Applications in the Food, Cosmetic, and Pharmaceutical Industries.

The historical use of plants as sources of natural compounds has persisted over time. Increasing the intake of bioactive substances shows significant potential for promoting overall well-being and health. This study delves into the pigments, phenolic composition, and profile, along with antioxidant properties, of leaf extracts rich in bioactives from plants in the Azores region, contributing to sustainable primary food production. Analyses encompassed chlorophylls, carotenoids, total phenols, ortho-diphenols, and flavonoids, as well as antioxidant capacity assessment, polyphenolic profiling, and quantification. Psidium guajava L. and Smallanthus sonchifolius (Poepp.) H.Rob. exhibited elevated chlorophyll content, while Colocasia esculenta (L.) Schott displayed the highest carotenoid levels. Annona cherimola Mill., Eriobotrya japonica (Thunb.) Lindl, and Psidium guajava L. demonstrated pronounced total phenols, ortho-diphenols, and flavonoids. These findings align with heightened antioxidant capacity. HPLC-DAD (high-performance liquid chromatography with diode-array detection) characterization unveiled elevated hydroxycinnamic acids in E. japonica and Ipomea batatas (L.) Lam. compared to A. cherimola Mill., while C. esculenta exhibited increased flavone content. Among the quantified compounds, flavonols were the ones that predominantly demonstrated contribution to the antioxidant capacity of these leaves. This research highlights Azorean leaf plants' antioxidant potential, fostering natural product development for better health.

Metabolic regulation of the host-fungus interaction: from biological principles to therapeutic opportunities.

Fungal infections present a significant global public health concern, impacting over one billion individuals worldwide and resulting in more than 3 million deaths annually. Despite considerable progress in recent years, the management of fungal infections remains challenging. The limited development of novel diagnostic and therapeutic approaches is largely attributed to our incomplete understanding of the pathogenetic mechanisms involved in these diseases. Recent research has highlighted the pivotal role of cellular metabolism in regulating the interaction between fungi and their hosts. In response to fungal infection, immune cells undergo complex metabolic adjustments to meet the energy demands necessary for an effective immune response. A comprehensive understanding of the metabolic circuits governing antifungal immunity, combined with the integration of individual host traits, holds the potential to inform novel medical interventions for fungal infections. This review explores recent insights into the immunometabolic regulation of host-fungal interactions and the infection outcome and discusses how the metabolic repurposing of immune cell function could be exploited in innovative and personalized therapeutic approaches.

Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury that currently lacks effective clinical treatments. Evidence highlights the potential role of glycogen synthase kinase-3 (GSK-3) inhibition in mitigating severe inflammation. The inhibition of GSK-3α/ß by CHIR99021 promoted fetal lung progenitor proliferation and maturation of alveolar epithelial cells (AECs). The precise impact of CHIR99021 in lung repair and regeneration during acute lung injury (ALI) remains unexplored. This study intends to elucidate the influence of CHIR99021 on AEC behaviour during the peak of the inflammatory phase of ALI and, after its attenuation, during the repair and regeneration stage. Furthermore, a long-term evaluation was conducted post CHIR99021 treatment at a late phase of the disease. Our results disclosed the role of GSK-3α/ß inhibition in promoting AECI and AECII proliferation. Later administration of CHIR99021 during ALI progression contributed to the transdifferentiation of AECII into AECI and an AECI/AECII increase, suggesting its contribution to the renewal of the alveolar epithelial population and lung regeneration. This effect was confirmed to be maintained histologically in the long term. These findings underscore the potential of targeted therapies that modulate GSK-3α/ß inhibition, offering innovative approaches for managing acute lung diseases, mostly in later stages where no treatment is available.

Multicentric Study on the Clinical Mycology Capacity and Access to Antifungal Treatment in Portugal.

The success of the clinical management of invasive fungal diseases (IFD) is highly dependent on suitable tools for timely and accurate diagnosis for effective treatment. An in-depth analysis of the ability of European institutions to promptly and accurately diagnose IFD was previously conducted to identify limitations and aspects to improve. Here, we evaluated and discussed the specific case of Portugal, for which, to our knowledge, there are no reports describing the national mycological diagnostic capacity and access to antifungal treatment. Data from 16 Portuguese medical institutions were collected via an online electronic case report form covering different parameters, including institution profile, self-perceived IFD incidence, target patients, diagnostic methods and reagents, and available antifungals. The majority of participating institutions (69%) reported a low-very low incidence of IFD, with Candida spp. indicated as the most relevant fungal pathogen, followed by Aspergillus spp. and Cryptococcus spp. All institutions had access to culture and microscopy, whereas 94 and 88% were able to run antigen-detection assays and molecular tests, respectively. All of the institutions capable of providing antifungal therapy declared to have access to at least one antifungal. However, echinocandins were only available at 85% of the sites. Therapeutic drug monitoring (TDM) was reported to remain a very restricted practice in Portugal, being available in 19% of the institutions, with the TDM of itraconazole and posaconazole performed in only 6% of them. Importantly, several of these resources are outsourced to external entities. Except for TDM, Portugal appears to be well-prepared concerning the overall capacity to diagnose and treat IFD. Future efforts should focus on promoting the widespread availability of TDM and improved access to multiple classes of antifungals, to further improve patient outcomes.

Inflammation in Prostate Cancer: Exploring the Promising Role of Phenolic Compounds as an Innovative Therapeutic Approach.

Prostate cancer (PCa) remains a significant global health concern, being a major cause of cancer morbidity and mortality worldwide. Furthermore, profound understanding of the disease is needed. Prostate inflammation caused by external or genetic factors is a central player in prostate carcinogenesis. However, the mechanisms underlying inflammation-driven PCa remain poorly understood. This review dissects the diagnosis methods for PCa and the pathophysiological mechanisms underlying the disease, clarifying the dynamic interplay between inflammation and leukocytes in promoting tumour development and spread. It provides updates on recent advances in elucidating and treating prostate carcinogenesis, and opens new insights for the use of bioactive compounds in PCa. Polyphenols, with their noteworthy antioxidant and anti-inflammatory properties, along with their synergistic potential when combined with conventional treatments, offer promising prospects for innovative therapeutic strategies. Evidence from the use of polyphenols and polyphenol-based nanoparticles in PCa revealed their positive effects in controlling tumour growth, proliferation, and metastasis. By consolidating the diverse features of PCa research, this review aims to contribute to increased understanding of the disease and stimulate further research into the role of polyphenols and polyphenol-based nanoparticles in its management.

Pretreatment antithrombotic strategies in non-ST elevation acute coronary syndromes in contemporaneous clinical practice.

BACKGROUND: Pretreatment antithrombotic strategies in non-ST elevation acute coronary syndromes (NSTE-ACS) during hospitalization is still a matter of contention within the cardiology community. Our aim was to analyze in-hospital and one-year follow-up outcomes of patients with NSTE-ACS pretreated with dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT). METHODS: A retrospective study was carried out with NSTE-ACS patients planned to undergo an invasive strategy and were included in the Portuguese Registry of ACS between 2018-2021. A composite primary outcome (in-hospital re-infarction, stroke, heart failure, hemorrhage, death) was compared regarding antiplatelet strategy (DAPT versus SAPT). Secondary outcomes were defined as one-year all-cause mortality and one-year cardiovascular rehospitalization. RESULTS: A total of 1469 patients were included, with a mean age of 66±12 years and 73.9% were male. DAPT regime was used in 38.2% and SAPT in 61.8% of patients. NSTE myocardial infarction was the most frequent presentation (88.5%). Revascularization after 24h occurred in 44.8% patients (63% of these after 48h). Enoxaparin was the anticoagulant more frequently used (45.1%). The primary outcome was more frequently observed in the SAPT group (10.4%, p=0.033), mainly driven by more ischemic events. Time until revascularization > 48h and SAPT regime were independent predictors of the primary outcome (OR 1.66, p=0.036 and OR 2.03, p=0.008, respectively). CONCLUSION: NSTE-ACS patients pretreated with SAPT had worse in-hospital outcomes. This difference can be probably explained by a delay in time until revascularization. Pretreatment DAPT strategy and crossover between heparins is still frequently used in clinical practice.

Tumor-Infiltrating Lymphocytes and Tumor-Stroma Ratio on Early-Stage Cervix Carcinoma: Prognostic Value of Two Distinct Morphological Patterns of Microenvironment.

Background Tumor progression is influenced by the complex network of different cellular elements that make up its microenvironment. Tumor-infiltrating lymphocytes (TILs) and stroma characteristics reflect two faces of the intricate mechanisms involved in the tumor-host interaction and can be easily evaluated by routine histological examination. Their prognostic value could be demonstrated in different tumor tumor types, but they are poorly explored in cervical cancer. Methodology In this retrospective study, we analyzed the association of TILs, tumor-stroma ratio (TSR), and pattern of stromal fibroblasts with prognosis and classical clinicopathological variables. We studied 61 patients with early-stage cervical cancer. We reviewed histological type, tumor grade, Silva pattern of invasion for adenocarcinomas, tumor thickness, depth of stromal invasion, lymph vascular space invasion, and lymph node status. The median follow-up was 37.77 months (range 4.77 to 112.37 months). Results The TSR did not correlate with any clinicopathological features or disease-free and overall survival. On the other hand, the reactive pattern of stroma composed of larger fibroblasts and less collagenization was associated with the FIGO IB2 stage (p=0.04), larger tumor (p=0.03), and deeper infiltration (p=0.005). There were more recurrences in the group of reactive stroma (33.13% vs. 11.5%), although the difference did not reach statistical significance. Reactive stroma was associated with lower survival free of recurrence (p=0.05) and overall survival (p=0.009). High TILs were associated with squamous cell type (p=0.003), higher tumor grade (p=0.02), and more LVSI (p=0.02). Tumors with higher TILs presented higher free recurrence interval (p=0.06) and overall survival (p=0.03). No association was observed between stroma characteristics and TILs. Conclusions Our study suggested that although immune activation and stromal changes are important features of microenvironment remodeling during tumoral progression, they are independent, following distinct carcinogenetic pathways. Pathological assessment of stroma characteristics and TILs adds significant prognostic information and demonstrates how a simple routine laboratory assessment can generate a better understanding of biological phenomena.

Myocardial deformation analysis using cardiac magnetic resonance in apical hypertrophic cardiomyopathy: is it an useful tool to predict adverse outcomes?

Apical hypertrophic cardiomyopathy (AHCM) has a broad phenotypic spectrum and still poses many diagnostic and prognostic challenges. Our team performed a retrospective study to examine the prognostic value of myocardial deformation obtained with cardiac magnetic resonance tissue tracking (CMR-TT) analysis in predicting adverse events in AHCM patients. We included patients with AHCM referred to CMR in our department from August 2009 to October 2021. CMR-TT analysis was performed to characterize the myocardial deformation pattern. Clinical, other complementary diagnostic exams characteristics and follow-up data were analysed. Primary endpoint was the composite of all-cause hospitalizations and mortality. During the 12-year period, 51 AHCM patients were evaluated by CMR, with a median age of 64 years-old and male predominance. 56,9% had an echocardiogram suggestive of AHCM. The most frequent phenotype was "the relative form" (43,1%). CMR evaluation revealed a median maximum left ventricle thickness of 15 mm and the presence of late gadolinium enhancement in 78,4%. Applying CMR-TT analysis, median global longitudinal strain was - 14,4%, with a median global radial strain of 30,4% and global circumferential strain of -18,0%. During a median follow-up of 5,3 years, the primary endpoint occurred in 21,3% of patients, with a hospitalization rate of 17,8% and all-cause mortality rate of 6,4%. After multivariable analysis, longitudinal strain rate in apical segments was an independent predictor of the primary endpoint (p = 0,023), showing that CMR-TT analysis could be useful in predicting adverse events in AHCM patients.

Baru oil (Dipteryx alata vog.) applied in the formation of O/W nanoemulsions: A study of physical-chemical, rheological and interfacial properties.

The oil extracted from baru (Dipteryx alata Vog.) seeds is in bioactive compounds and it presents potential to be used in food and cosmetic industries. Therefore, this study aims to provide insights into the stability of baru oil-in-water (O/W) nanoemulsions. For this purpose, the effects of the ionic strength (0, 100 and 200 mM), pH (6, 7 and 8), and storage time (28 days) on the kinetic stability of these colloidal dispersions were evaluated. The nanoemulsions were characterized in terms of interfacial properties, rheology, zeta potential (ζ), average droplet diameter, polydispersity index (PDI), microstructure, and creaming index. In general, for samples, the equilibrium interfacial tension ranged from 1.21 to 3.4 mN.m-1, and the interfacial layer presented an elastic behavior with low dilatational viscoelasticity. Results show that the nanoemulsions present a Newtonian flow behavior, with a viscosity ranging from 1.99 to 2.39 mPa.s. The nanoemulsions presented an average diameter of 237-315 nm with a low polydispersity index (<0.39), and a ζ-potential ranging from 39.4 to 50.3 mV after 28 days of storage at 25 °C. The results obtained for the ζ-potential suggest strong electrostatic repulsions between the droplets, which is an indicative of relative kinetic stability. In fact, macroscopically, all the nanoemulsions were relatively stable after 28 days of storage, except the nanoemulsions added with NaCl. Nanoemulsions produced with baru oil present a great potential to be used in the food, cosmetic, and pharmaceutical industries.

Exploring the Benefits of Phycocyanin: From Spirulina Cultivation to Its Widespread Applications.

Large-scale production of microalgae and their bioactive compounds has steadily increased in response to global demand for natural compounds. Spirulina, in particular, has been used due to its high nutritional value, especially its high protein content. Promising biological functions have been associated with Spirulina extracts, mainly related to its high value added blue pigment, phycocyanin. Phycocyanin is used in several industries such as food, cosmetics, and pharmaceuticals, which increases its market value. Due to the worldwide interest and the need to replace synthetic compounds with natural ones, efforts have been made to optimize large-scale production processes and maintain phycocyanin stability, which is a highly unstable protein. The aim of this review is to update the scientific knowledge on phycocyanin applications and to describe the reported production, extraction, and purification methods, including the main physical and chemical parameters that may affect the purity, recovery, and stability of phycocyanin. By implementing different techniques such as complete cell disruption, extraction at temperatures below 45 °C and a pH of 5.5-6.0, purification through ammonium sulfate, and filtration and chromatography, both the purity and stability of phycocyanin have been significantly improved. Moreover, the use of saccharides, crosslinkers, or natural polymers as preservatives has contributed to the increased market value of phycocyanin.

Right to health and encouragement of social participation in elementary education.

OBJECTIVES: Develop and validate an ordinary meeting simulation template of the Municipal Health Council applied to students of cycle II of Elementary School. METHODS: Qualitative and descriptive research developed in two phases: construction of simulation scenario of ordinary meeting of the Municipal Health Council and validation by committee of experts who analyzed the representativeness and adequacy of the content. The scenario included the items: prebriefing, additional information about the case, scenario objectives, evaluation criteria (observers), scenario duration time, human and physical resources, instructions for the actors, context, references and debriefing. In order to be able to understand which items should be modified according to the evaluations of the experts, it was used as criterion that only items that had 80% or higher percentage of agreement between the experts for modification would be modified. RESULTS: There was agreement to modify the prebriefing in: additional information about the case (100%); learning objectives (88.8%); human and physical resources (88.8%); context (88.8%); and in the debriefing (88.8%). The prebriefing did not reach the level of agreement: evaluation criteria (66.6%), duration of the scenario (77.7%), instruction for authors (77.7%), references (77.7%), which were modified. CONCLUSIONS: With the template developed and then validated by the committee of experts, it will be possible to develop in the classroom content related to the right to health and social participation in the scope of elementary education, as well as encourage engagement in important bodies for the maintenance of democracy, justice and social equity.

Interstitial Macrophages Lead Early Stages of Bleomycin-Induced Lung Fibrosis and Induce Fibroblasts Activation.

A progressive fibrosing phenotype is critical in several lung diseases. It is irreversible and associated with early patient mortality. Growing evidence has revealed pulmonary macrophages' role as modulators of the fibrotic processes. The proportion, phenotype, and function of alveolar (AM) and interstitial macrophages (IM) at the early stages of bleomycin-induced pulmonary fibrosis have not been clearly described. In this way, our study aimed to characterize these macrophage populations and investigate the effect on fibroblast activation. C57BL/6 mice were intratracheally injected with bleomycin and were sacrificed at day 3, 5, and 7 for the performance of flow cytometry and fluorescent-activated cell sorting analysis for protein and gene expression quantification. After bleomycin administration, the proportion of IM was significantly higher than that of AM, which showed a decay during the inflammatory phase, and peaked at day 7. At day 7 of the inflammatory phase, AM started shifting their phenotype from M1-like towards M2, while IM showed a M2-like phenotype. Conditioned medium derived from IM sorted at day 7 induced fibroblast activation and differentiation in myofibroblasts in vitro. Our findings indicate that IM are the largest macrophage population at the early stages of experimental pulmonary fibrosis and are secreted mediators able to activate fibroblasts, pointing to macrophage modulation as a potential therapeutic strategy to restrain progressive fibrosing lung disorders.

Right to health and encouragement of social participation in elementary education / Derecho a la salud e incentivo a la participación social en la educación básica / Direito à saúde e o estímulo à participação social na educação básica

Objective Develop and validate an ordinary meeting simulation template of the Municipal Health Council applied to students of cycle II of Elementary School. Methods. Qualitative and descriptive research developed in two phases: construction of simulation scenario of ordinary meeting of the Municipal Health Council and validation by committee of experts who analyzed the representativeness and adequacy of the content. The scenario included the items: prebriefing, additional information about the case, scenario objectives, evaluation criteria (observers), scenario duration time, human and physical resources, instructions for the actors, context, references and debriefing. In order to be able to understand which items should be modified according to the evaluations of the experts, it was used as criterion that only items that had 80% or higher percentage of agreement between the experts for modification would be modified. Results. There was agreement to modify the prebriefing in: additional information about the case (100%); learning objectives (88.8%); human and physical resources (88.8%); context (88.8%); and in the debriefing (88.8%). The prebriefing did not reach the level of agreement: evaluation criteria (66.6%), duration of the scenario (77.7%), instruction for authors (77.7%), references (77.7%), which were modified. Conclusion. With the template developed and then validated by the committee of experts, it will be possible to develop in the classroom content related to the right to health and social participation in the scope of elementary education, as well as encourage engagement in important bodies for the maintenance of democracy, justice and social equity

Objetivo. Desarrollar y validar una plantilla de simulación de una reunión ordinaria del Consejo Municipal de Salud aplicada a estudiantes del ciclo II de Enseñanza Fundamental. Métodos. Investigación cualitativa descriptiva desarrollada en dos fases: construcción de un escenario para simular una reunión ordinaria del Consejo Municipal de Salud y validación por un comité de expertos que analizó la representatividad y adecuación del contenido. El escenario incluyó los ítems: prebriefing, información adicional sobre el caso, objetivos del escenario, criterios de evaluación (observadores), tiempo de duración del escenario, recursos humanos y físicos, instrucciones para los actores, contexto, referencias y debriefing. Para validar el escenario, se definió un nivel de acuerdo entre los expertos de mínimo 80%. Resultados. Hubo acuerdo para mejorar en el prebriefing: información adicional sobre el caso (100%); objetivos de aprendizaje (88,8%); recursos humanos y físicos (88.8%); contexto (88.8%); y en el debriefing (88.8%). En el prebriefing no alcanzó el nivel de acuerdo: criterios de evaluación (66,6%), tiempo del escenario (77.7%), instrucciones para los autores (77.7%), y las referencias (77.7%), los cuales fueron posteriormente modificados. Conclusión. Con la plantilla desarrollada y posteriormente validada por expertos será posible realizar en el aula contenidos sobre el derecho a la salud y a la Participación Social en el ámbito de la educación básica, así como fomentar el compromiso en órganos importantes para el mantenimiento de la democracia, la justicia y la equidad social.

Objetivo. Desenvolver e validar um template de simulação de reunião ordinária do Conselho Municipal de Saúde aplicado em alunos do ciclo II do Ensino Fundamental. Método. Pesquisa qualitativa e descritiva desenvolvida em duas fases: construção de cenário de simulação de reunião ordinária do Conselho Municipal de Saúde e validação por comitê de especialistas que analisaram a representatividade e adequação do conteúdo. O cenário contemplou os itens: prebriefing, informações adicionais sobre o caso, objetivos do cenário, critérios de avaliação (observadores), tempo de duração do cenário, recursos humanos e físicos, instruções para os atores, contexto, referências e debriefing. Para que fosse possível entender quais itens deveriam ser modificados de acordo com as avaliações dos especialistas, utilizou-se como critério que somente os itens que tivessem 80% ou porcentagem superior de concordância entre os especialistas para modificação é que seriam modificados. Resultados. Houve concordância para modificação em el prebriefing em: informações adicionais sobre o caso (100%); objetivos de aprendizagem (88.8%); recursos humanos e físicos (88.8%); contexto (88.8%); y em el debriefing (88.8%). Não atingiram o nível de concordância o prebriefing: critérios de avaliação (66.6%), tempo de duração do cenário (77.7%), instrução para autores (77.7%), referências (77.7%), os quais foram modificados. Conclusão. Com o template desenvolvido e despois validado pelo comitê de especialistas será possível desenvolver em sala de aula conteúdos referentes ao direito à saúde e à Participação Social no âmbito da educação básica, bem como encorajar o engajamento em órgãos importantes para manutenção da democracia, justiça e equidade social.

Challenges in Fabry disease: the combination of two individually amenable GLA variants may be nonamenable to migalastat.

Fabry disease is a rare lysosomal storage disorder caused by mutations in the GLA gene, resulting in reduced or absent α-Gal A activity. Migalastat is an oral chaperone therapy for Fabry patients with amenable GLA variants. We previously reported a case of a 60-year-old male patient with a classic phenotype of Fabry disease, presenting with two GLA variants: p.R356Q and p.G360R. Herein, we report that, although these two missense variants are individually classified as amenable to migalastat in the validated in vitro human embryonic kidney-293 cell-based assay, their combination precludes the patient to be treated with this oral chaperone. This case illustrates how therapeutic decisions may be challenging and how a good genotypic characterization of Fabry patients is critical for the selection of the correct therapeutic strategy.

Fabry disease is a rare genetic disease that is part of a group of conditions called lysosomal storage diseases. It is characterized by an abnormal accumulation of glycosphingolipids, a subclass of glycolipids which are important components of the body's cell membranes. This accumulation is caused by a reduction in, or absence of, enzyme α-Gal A activity, which normally breaks glycosphingolipids down into smaller units, avoiding their accumulation. The absence or reduction in the α-Gal A enzyme activity is caused by mutations (changes in the normal DNA sequence) in the GLA gene. Migalastat is an oral treatment for Fabry patients with GLA mutations that respond to this treatment. We report a case of a 60-year-old male patient with Fabry disease, presenting with two GLA mutations (p.R356Q and p.G360R). Although these mutations are individually amenable to migalastat, their combination and interaction in the same chromosome precludes response to this treatment. This case illustrates how therapeutic decisions for treating Fabry disease can be challenging depending on the mutations causing the disease and how genetic material is decisive for therapy selection.

The role of positive childhood experiences in the link between childhood maltreatment and affective lability in a sample of incarcerated men and women.

BACKGROUND: Individuals with a history of child maltreatment (CM) tend to show high affective lability (AL) and criminal behavior. However, positive childhood experiences (PCEs) may act as a protective factor even in the presence of child maltreatment. OBJECTIVE: The present study aimed to analyze the relationship between CM, PCEs, and AL in adulthood, identify the predictors of AL and analyze the moderating role of PCEs in the relationship between CM and AL in a sample of 424 incarcerated men (n = 343) and women (n = 81), aged between 18 and 73 years (M = 37.88). METHODS: Participants responded to an online protocol consisting of a sociodemographic questionnaire, the Childhood Trauma Questionnaire (CTQ), the Benevolent Childhood Experiences Scale (BCEs), and the Affective Lability Scale - Short Version (ALS-18). RESULTS: CM was positively associated with AL and negatively associated with PCEs, and PCEs are negatively associated with AL. Regression analyses, after controlling for age, sex, and education, confirmed the role of PCEs on AL, above and beyond CM. However, moderation analysis showed that PCEs did not moderate the relationship between CM and AL for either men or women. CONCLUSIONS: These results highlight the complexity of human development and behavior from early childhood into adulthood. Further studies are needed to better understand the role of PCEs in the relationship between ACEs and AL among inmates in order to develop more appropriate prevention and intervention programs.