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.

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.

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.

General Beliefs About Illicit Drug Use and Stigma: Perspective of People Who Use Illicit Drugs.

People who use illicit drugs are continuously subjected to harsh stigmatization from society. This study explores the perspectives of people who use illicit drugs, specifically their general beliefs about illicit drug use and related stigma. A convergent parallel mixed methods design was used, combining quantitative and qualitative methods. The participants were recruited in a Psychosocial Care Centre (CAPSad) of a municipality in the state of Sao Paulo in Brazil. Findings revealed that illicit drug use can cause individual, family, professional and social difficulties, including problems with the law. The participants indicated they felt victimized by illicit drugs and their use, but also shared prejudicial and discriminatory views, highlighting self-stigmatizing perspectives. There is a need to develop intervention studies with a psychosocial approach on the use of illicit drugs, valuing the person's participation in the treatment, covering biomedical approaches, having in mind the social impact of illicit drugs and their use.

Synthesis of Vitamin B3 through a Heterogeneous Photocatalytic Approach Using Metal-Free Carbon Nitride-Based Catalysts.

Vitamin B3 (nicotinic acid, VB3) was synthesized through the photocatalytic oxidation of 3-pyridinemethanol (3PM) under visible-light-emitting diode (LED) irradiation using metal-free graphitic carbon nitride (GCN) - based materials. A bulk (GCN) material was prepared by a simple thermal treatment using dicyandiamide as the precursor. A post-thermal treatment under static air and nitrogen flow was employed to obtain the GCN-T and GCN-T-N materials, respectively. The conditions adopted during the post-treatment revealed differences in the resulting materials' morphological, electronic, and optical properties. The post-treated photocatalysts revealed an enhanced efficiency in the oxidation of 3PM into VB3, with the GCN-T-N photocatalyst being the best-performing material. The defective surface, reduced crystallinity, and superior photoabsorption of GCN-T-N account for this material's improved performance in the production of VB3. Nevertheless, the presence of nitrogen vacancies in the carbon nitride structure and, consequently, the creation of mid-gap states also accounts to its highly oxidative ability. The immobilization of GCN-T-N in sodium alginate hydrogel was revealed as a promising strategy to produce VB3, avoiding the need for the photocatalyst separation step. Concerning the mechanism of synthesis of VB3 through the photocatalytic oxidation of 3PM, it was possible to identify the presence of 3-pyridinecarboxaldehyde (3PC) as the intermediary product.

Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression.

BACKGROUND: We compared transcranial direct-current stimulation (tDCS) with a selective serotonin-reuptake inhibitor for the treatment of depression. METHODS: In a single-center, double-blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram. RESULTS: A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, -2.3 points; 95% confidence interval [CI], -4.3 to -0.4; P=0.69) was lower than the noninferiority margin of -2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups. CONCLUSIONS: In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT-TDCS ClinicalTrials.gov number, NCT01894815 .).

Clinical implications of using non-invasive haemoglobin monitoring for red blood cell transfusion decision in hip arthroplasty.

INTRODUCTION: The decision to transfuse red blood cells requires accurate haemoglobin concentration values. In this study, we evaluated if continuous non-invasive haemoglobin (SpHb) measurement could substitute laboratory determined haemoglobin (LabHb) in patients undergoing elective hip replacement. As secondary objective, we analyzed the trend of the difference between techniques. MATERIALS/METHODS: LabHb measurements were done using an automated analyser and SpHb measurements were acquired using Radical-7®. In randomly selected patients undergoing hip replacement, whenever blood was collected for LabHb, concomitant SpHb was recorded. Correlation, bias and accuracy of SpHb were calculated in comparison with LabHb. RESULTS: 108 paired measurements were obtained from 43 patients. The Pearson R of the correlation between SpHb and LabHb was 0.7 (p < 0.001). Bland-Altman test revealed a bias of 1 ± 1.4 g dL-1, meaning Lab Hb was recurrently higher than SpHb. Limits of agreement were [-1.7; 3.8]. Considering RBC transfusion threshold of 8 g dL-1, we found that in two situations transfusion decision would differ based on the measurement considered. Trending ability of SpHb study showed a significant difference between preoperative and postoperative LabHb-SpHb. DISCUSSION: There was a good correlation between SpHb and LabHb, while bias and limits of agreement were higher than those in literature. There was a limited trending ability of SpHb during the perioperative period. Despite this, using SpHb instead of LabHb for decision making regarding transfusion would only change the decision in 1.9 % of our cases. Our findings suggest that this device could be used as a reference but cannot replace venous puncture as gold standard.

Alignment and contribution of nursing doctoral programs to achieve the sustainable development goals.

BACKGROUND: Different social segments from several regions of the world face challenges in order to achieve the sustainable development goals (SDGs). Nursing represents the greatest number of health workforce in the globe, dealing with these challenges in different paths, among them the training of human resources. In this context, the goal of this study was to compare the relationship between the objectives and research areas underlying nursing doctoral programs in Latin America and the SDGs. METHOD: Documental research comparing data of all Latin American nursing doctoral programs and the SDGs, conducted between January and March 2020. RESULTS: From the total of 56 existing programs in Latin America, this study analyzed 52 of them, representing 92.8% of the total. Most nursing doctoral programs have contributed to SDG 3, in addition to goals 1, 2, 4, 5, 6, 8, 9, 10, 12 and 16. The SDGs 11, 13, 14, 15 and 17 were not related to any of the analyzed programs. Data reveal that the training of nursing PhDs is essential to fulfilling these goals. Results also indicate a need of programs to remain committed to relationships that enhance nursing skills to cope with the current challenges in terms of global health, such as investments for the reduction of social and gender inequities. CONCLUSION: The doctoral training of nurses in Latin America needs to be better aligned with the sustainable development goals (SDGs), since there is a high concentration in SDG 3. We believe that nursing will bring a greater contribution to the movement to protect planetary health as the principles governing nursing practices are better aligned with international health demands and agendas.

p.G360R Is a Pathogenic GLA Gene Mutation Responsible for a Classic Phenotype of Fabry Disease.

The authors report the case of a classic phenotype of Fabry disease in a 60-year-old male patient presenting with left ventricular hypertrophy and stroke. Genetic analysis revealed 2 GLA-gene variants, i.e., p.R356Q and p.G360R. This clinical case highlights that the finding of 2 or more GLA gene variants in a Fabry patient should lead to a careful evaluation in order to determine their exact role in the condition. This case also provides the first clinical evidence that the p.G360R mutation is pathogenic and responsible for a classic phenotype of Fabry disease. The clinical improvement following the initiation of enzyme replacement therapy reinforces the importance of Fabry disease awareness and diagnosis in patients exhibiting red flags, such as left ventricular hypertrophy and stroke.

Therapeutic comparison between treatments for Vulvar Lichen Sclerosus: study protocol of a randomized prospective and controlled trial.

BACKGROUND: Vulvar lichen sclerosus (VLS) is a lymphocyte-mediated disease of unknown etiology that can cause intense itching as well stenosis, hindering the evacuation and urination. It can also limit the sex life due to severe local pruritus, pain and dyspareunia (pain during sexual intercourse). The standard treatment for this disease is the use of topical corticosteroids to reduce the clinical symptoms and to try to increase disease-free intervals. Photodynamic therapy (PDT), a treatment that associates a light radiation with a photosensitizing agent and photobiomodulation (PBM) are therapies that can promote effective immunomodulatory responses at the application site by means of photophysical and photochemical phenomena from the molecular to the systemic level, which promote their use in chronic dermatoses. The aim is to compare the effects of PDT, PBM, and topical corticosteroid in VLS evaluating clinical, histological, immunohistochemical and spectroscopic responses. METHODS: The study is prospective, randomized and controlled, in a population of 60 women with histological diagnoses of VLS. There will be 3 treatments groups: PDT, PBM and topical corticosteroid (control group), where will be allocated by randomization 20 patients in each one. The clinical course will be monitored by measuring local temperature, itching, atrophy, and the area of the lesion. Histologically, the slides will be classified and will have the ordering of collagen fibers quantified. Immunohistochemical analysis will be done using the markers IFN-γ, TGF-ß, CD4, CD8, IL-1, p53 and Ki-67. Finally, the spectroscopic evaluation will be done by reflectance. Descriptive and inferential statistical analyses will be conducted to compare the groups and make associations between different responses. The study is an open-label for patients with active symptomatic disease with a period of 1 year follow-up to determine the rate of recurrence in each groups. DISCUSSION: The immunological effects of PDT and PBM are described by several authors in inflammatory skin diseases, stimulating the production and organization of the associated collagen. Thus, it is reasonable to determine the efficacy and safety of these new treatments in VLS, in comparison to the control group, analyzing the recurrence time, the impact on the optical properties of the skin, and the benefit to patients. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02416531 .

Interviews of Children in a Portuguese Special Judicial Procedure.

Since 2007, alleged victims of child sexual abuse in Portugal have provided evidence in a mandatory "Declarações para Memória Futura" (DMF; English transl. 'Statement for future use') proceeding. In order to protect children from having to testify in court, interviews conducted at the DMF can be used later as trial evidence because the hearings are conducted by judges. The present study examined 137 interviews with 3- to 17-year-olds conducted in several Portuguese criminal courts. Detailed examination of interview transcripts showed that 69% of all questions asked were option-posing questions, 16% were directive questions, 11% were suggestive questions, and only 3% were open-ended prompts. The vast majority of details provided by children were thus obtained using the risky recognition-based prompts (i.e., option posing and suggestive questions) associated with the risks of contaminating and limiting children's informativeness, both potential threats to the credibility of their testimony. There is an urgent need to address this issue and consider the implementation of a scientifically validated structured interview protocol in Portugal. Copyright © 2017 John Wiley & Sons, Ltd.

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.

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.

[Effectiveness of cleaning or disinfecting the urinary meatus before urinary catheterization: a systematic review]. / Eficácia da limpeza ou desinfeção do meato urinário antes da cateterização urinária: revisão sistemática.

The urinary tract infections associated with catheterization are very common in hospital and home care contexts. Currently there are several recommendations for its prevention, however, when approaching the kind of solute used in the urinary meatus prior to catheterization doubts continue to persist. Thus this study aimed at determining the effectiveness of cleaning the urinary meatus with water or saline comparing to its sterilization through a systematic review and meta-analysis. In order to do so, the principles proposed by the Cochrane Handbook were followed, a critical analysis was conducted by two researchers and the statistical analysis was performed with the use of STATA 11.1. We concluded that the cleaning or disinfection of the urinary canal prior to bladder catheterization is not statistically significant (OR=1.07, CI 95%=0.68-1.68, p=0.779) and that there is some evidence that the use of water/saline reduces rates of UTI (urinary tract infection).

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.

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.

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.

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.

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.

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.