Evaluation of the Influence of Geodimensional and Histological Parameters on the Need for Margin Widening in Breast Lesions Marked With Magnetic Seeds.

Objective: Breast cancer is an important topic worldwide, posing morbidity and mortality to women. Considerable efforts have been put in the early recognition of malignancy through different screening methods, such as mammography and ultrasound. The precise localization of infraclinical malignant lesions is key in surgical management and magnetic seeds gather particular interest for this purpose. As with other systems, a need for reintervention may be needed to obtain adequate surgical margins. This work evaluated the relation between the need for surgical reintervention in order to obtain negative margins and geodimensional and histological parameters. The main objective was the identification of parameters significantly associated with reintervention for margin widening. Materials and Methods: A retrospective analysis of 198 patients from a single centre was performed. The association between pre-defined geodimensional and histological parameters and the need for margin widening in infraclinical lesions marked with magnetic seed was evaluated. Results: Results showed that reintervention to widen margins was significantly higher in patients with ductal carcinoma in situ (DCIS) in the pre-operative biopsy when compared with invasive carcinoma (p = 0.03) in the bivariate analysis. No statistically significant differences were observed between the need for reintervention and lesion size (p = 0.197), breast quadrant location (p = 0.626) and distance of skin to lesion (p = 0.356). Conclusion: This work suggests that a more invasive margin clearance in lesions with a pre-operative DCIS diagnosis might obviate the need for reintervention to obtain negative margins. On the other hand, it is not necessary to be surgically more invasive in larger lesions, deeply located or that are present in a certain quadrant, since there are no significant differences regarding the need for reintervention.

MITIG.RA: study protocol of a tailored psychological intervention for managing fatigue in rheumatoid arthritis randomized controlled trial.

BACKGROUND: Despite remarkable medical advances in the treatment of rheumatoid arthritis (RA), a subset of patients fails to achieve complete clinical remission, as the Patient Global Assessment (PGA) of disease activity remains above 1, even after the inflammatory process is brought under control. This so-called state of 'PGA-near-remission' negatively impacts individuals' functioning and potentiates inadequate care. Fatigue is a distressing and disabling symptom frequently reported by patients in PGA-near-remission, and its management remains challenging. While classic cognitive-behavioural interventions show some benefits in managing fatigue, there is potential for improvement. Recently, contextual-cognitive behavioural therapies (CCBT), like mindfulness, acceptance, and compassion-based interventions, have shown promising results in fatigue-associated disorders and their determinants. This study primarily aims to examine the efficacy of the Compassion and Mindfulness Intervention for RA (MITIG.RA), a novel intervention combining different components of CCBT, compared to treatment-as-usual (TAU) in the management of RA-associated fatigue. Secondary aims involve exploring whether MITIG.RA produces changes in the perceived impact of disease, satisfaction with disease status, levels of depression, and emotion-regulation skills. METHODS: This is a single center, two-arm parallel randomized controlled trial. Patients will be screened for eligibility and willingness to participate and will be assessed and randomized to the experimental (MITIG.RA + TAU) or control condition (TAU) using computer randomization. MITIG.RA will be delivered by a certified psychologist and comprises eight sessions of 2 h, followed by two booster sessions. Outcomes will be assessed through validated self-report measures, including fatigue (primary outcome), perceived impact of disease, depressive symptoms, mindfulness, self-compassion, safety, and satisfaction (secondary outcomes). Assessment will take place at baseline, post-intervention, before the first and second booster sessions (weeks 12 and 20, respectively), and at 32 and 44 weeks after the interventions' beginning. DISCUSSION: We expect MITIG.RA to be effective in reducing levels of RA-associated fatigue. Secondarily, we hypothesize that the experimental group will show improvements in the overall perceived impact of disease, emotional distress, and emotion regulation skills. Our findings will contribute to determine the benefits of combining CCBT approaches for managing fatigue and associated distress in RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT05389189. Registered on May 25, 2022.

Patient-Reported Outcomes and Experiences Assessment in Women with Breast Cancer: Portuguese Case Study.

In 2020, female breast cancer was the most commonly diagnosed cancer worldwide, representing the type of cancer with the highest incidence among women and the second most common cause of cancer death among women in all OECD countries. The conventional measures addressing the burden of breast cancer by measuring mortality, incidence, and survival do not entirely reflect the quality of life and patients experience when receiving breast cancer care. The main objective of this study is to capture patient-reported outcomes and experiences in women with breast cancer in Portugal using methods developed for international benchmarking purposes, such as the OECD Patient-reported Indicators Surveys. The study included 378 women with breast cancer, with the age distribution being 19.8% aged 15 to 49 years and 80.2% aged 50 years and over. The data collection procedure and analysis followed the "OECD Breast Cancer Patient Reported Outcomes Working Group" protocol, allowing subsequent comparability with data from other OECD member countries. Most women were satisfied with the treatment outcome regarding the shape of their lumpectomy breast when wearing a bra (96.1%) and with the equal size of both breasts (78.3%). Findings on the WHO QOL-BREF showed that women manifest a lower score in well-being when compared with the general population or populations living with chronic diseases. This study shows the feasibility of implementing and using patient-reported metrics (PROM and PREM) in breast cancer services in Portugal. Measuring PROMs and PREMs from Portuguese women receiving breast cancer care provides insightful evidence into the quality and value of cancer care.

A comprehensive approach to identify challenges for clinical reasoning development in undergraduate dental students and their potential solutions.

INTRODUCTION: Clinical reasoning is a core competence in health professions that impacts the ability to solve patients' health problems. Due to its relevance, it is necessary to identify difficulties arising from different sources that affect clinical reasoning development in students. The aim of this study was to explore a comprehensive approach to identify challenges for clinical reasoning development in undergraduate dental students and their potential solutions. METHODS: Mixed methods were used in four stages: (1) students and clinical teachers focus groups to identify challenges to clinical reasoning development; (2) literature review to explore potential solutions for these challenges; (3) Delphi technique for teacher consensus on pertinence and feasibility of solutions (1-5 scale); and (4) teachers' self-perception of their ability to implement the solutions. RESULTS: Three categories and seven subcategories of challenges were identified: (I) educational context factors influencing the clinical reasoning process; (II) teacher's role in clinical reasoning development; and (III) student factors influencing the clinical reasoning process. From 134 publications identified, 53 were selected for review, resulting in 10 potential solutions. Through two Delphi rounds, teachers rated the potential solutions very highly in terms of relevance (4.50-4.85) and feasibility (3.50-4.29). Finally, a prioritisation ranking of these solutions was generated using their scores for relevance, feasibility, and teachers' self-perception of their ability to implement them. CONCLUSIONS: The present comprehensive approach identified challenges for clinical reasoning development in dental students and their potential solutions, perceived as relevant and feasible by teachers, requiring further research and follow-up actions to address them.

IL-1ß is not critical to chronic heart dysfunction in mice with Chagas disease.

Long after Trypanosoma cruzi infection, 40% of individuals develop a progressive chronic chagasic cardiomyopathy (CCC), with systolic dysfunction and arrhythmias. Since we previously showed IL-1ß mediates the development of systolic dysfunction and cardiac arrhythmias in diabetes mellitus and cardiorenal syndrome, and IL-1ß remains elevated in Chagas disease patients, here we tested the role of IL-1ß in CCC using a mouse model. Mice deficient in IL-1R expression (Il-1r-/- ) survived acute T. cruzi infection with greater parasitemia than controls but did not lose weight as wild-type (WT) did. At the chronic stage, WT presented prolonged ventricular repolarization intervals (QJ), while Il-1r-/- presented intervals like noninfected controls. Infected Il-1r-/- and WT did not differ in stroke volume (SV), the incidence of cardiac arrhythmias on electrocardiography (EKG), whole heart action potential duration (APD), or the incidence of triggered activity after S1-S2 protocol, which is a measure of susceptibility to cardiac arrhythmias. We also treated chronically infected WT mice with an IL-1R antagonist, anakinra. Treatment shortened the QJ interval but did not improve the SV or the incidence of cardiac arrhythmias on EKG. Anakinra failed to reduce triggered activity following the electrical extra-stimulation protocol. In conclusion, the absence of functional IL-1ß/IL-1R signaling did not prevent or reverse the decrease of SV or the incidence of cardiac arrhythmias induced by chronic T. cruzi infection, implying this is not a critical mechanism in generating or maintaining CCC. Since similar cardiac abnormalities were previously credited to IL-1ß signaling, ruling out this mechanism is important to discourage further attempts of IL-1ß blockade as a therapeutical measure.

The Role of the Immune System on the Cardiac Complications Observed in SARS-CoV-2

Abstract An acute respiratory syndrome caused by SARS-CoV2 was declared a pandemic by the World Health Organization. Current data in the world and in Brazil show that approximately 40% of patients who died have some type of cardiac comorbidity. There are also robust reports showing an increase in IL-6 / IL-1B / TNF-alpha and the presence of lymphopenia in patients with COVID-19. Our team and others have shown that increased cytokines are the link between arrhythmias/Left ventricular dysfunction and the immune system in different diseases. In addition, it has been well demonstrated that lymphopenia can not only be a good marker, but also a factor that causes heart failure. Thus, the present review focused on the role of the immune system upon the cardiac alterations observed in the SARS-CoV2 infection. Additionally, it was well described that SARS-CoV-2 is able to infect cardiac cells. Therefore, here it will be reviewed in deep.

Chloroquine inhibits pro-inflammatory effects of heme on macrophages and invivo.

BACKGROUND: Chloroquine has been used successfully to treat Malaria, including by chloroquine-resistant Plasmodium sp., indicating that it has effects on disease itself. Since heme has inflammatory effects and contributes to the pathogenesis of hemolytic diseases, we hypothesize that the anti-inflammatory effect of chloroquine is partially due to its inhibitory effect on heme-induced macrophage activation and on inflammatory tissue damage. METHODS: Bone marrow derived macrophages (BMDMs) were incubated with chloroquine before stimulation with heme, in different conditions, to evaluate cytokines secretion, ROS production, mitogen activated protein kinases (MAPK) or spleen tyrosine kinase (Syk) activation, alone or combined with LPS. The effects of chloroquine upon heme inflammation were also evaluated in vivo, through simultaneous i.p. injection of LPS and heme, intratracheal instillation of Poly-IC followed by heme injection, and in a rhabdomyolysis model. RESULTS: Chloroquine inhibited TNF secretion, mitochondrial ROS production, MAPK, and Syk activation induced by heme. Inhibition of TNF production could be mimicked by zinc ionophore quercetin, but not by primaquine, a chloroquine analog with low affinity for heme. IL-6 and IL-1ß secretions induced by heme in the presence of PRRs agonists were inhibited by chloroquine, but not by calcium chelator BAPTA or inhibitor of endosomal acidification concamycin B. Chloroquine also protected mice from heme inflammatory effects in vivo, inhibiting lethal synergism with PRR agonists, lung pathology caused by heme injection after intratracheal instillation of Poly-IC, and delaying death after rhabdomyolisis. CONCLUSION: Our data indicate that chloroquine might be used as a supportive therapy to control heme-induced deleterious inflammation in different hemolytic diseases.

Mitochondrial Reactive Oxygen Species Participate in Signaling Triggered by Heme in Macrophages and upon Hemolysis.

Hemolysis causes an increase of intravascular heme, oxidative damage, and inflammation in which macrophages play a critical role. In these cells, heme can act as a prototypical damage-associated molecular pattern, inducing TLR4-dependent cytokine production through the MyD88 pathway, independently of TRIF. Heme promotes reactive oxygen species (ROS) generation independently of TLR4. ROS and TNF production contribute to heme-induced necroptosis and inflammasome activation; however, the role of ROS in proinflammatory signaling and cytokine production remains unknown. In this study, we demonstrate that heme activates at least three signaling pathways that contribute to a robust MAPK phosphorylation and cytokine expression in mouse macrophages. Although heme did not induce a detectable Myddosome formation, the TLR4/MyD88 axis was important for phosphorylation of p38 and secretion of cytokines. ROS generation and spleen tyrosine kinase (Syk) activation induced by heme were critical for most proinflammatory signaling pathways, as the antioxidant N-acetyl-l-cysteine and a Syk inhibitor differentially blocked heme-induced ROS, MAPK phosphorylation, and cytokine production in macrophages. Early generated mitochondrial ROS induced by heme was Syk dependent, selectively promoted the phosphorylation of ERK1/2 without affecting JNK or p38, and contributed to CXCL1 and TNF production. Finally, lethality caused by sterile hemolysis in mice required TLR4, TNFR1, and mitochondrial ROS, supporting the rationale to target these pathways to mitigate tissue damage of hemolytic disorders.

[Dental recommendations in the COVID-19 pandemic: A narrative review]. / Recomendaciones odontológicas en la pandemia COVID-19: revisión narrativa.

INTRODUCTION: COVID-19 is a world public health problem due to its morbidity and mortality, especially in at-risk groups. The dental environment has a high risk of viral transmission; accordingly, this study aimed to identify recommendations based on the best available evidence for dental care during this pandemic. METHODS: We performed a search for scientific evidence published since 2002 to March 23th 2020 in electronic databases (MEDLINE/PubMed, EMBASE, Cochrane, and Epistemonikos) and the web pages of the American Dental Association, Centers for Disease Control and Prevention Oral Health, the Ministry of Health in Chile and scientific societies. RESULTS: We included nine published studies. The recommendations were the following: unrestricted use of personal protection elements, use of extraoral radiographic techniques, use of mouth rinses with 1% hydrogen peroxide or 0.2% iodine povidone, a four-hand technique with ongoing aspiration and the use of absorbable sutures. Furthermore, there is a consensus that non-urgent treatments should be postponed during periods of community transmission. CONCLUSIONS: Dental practitioners are exposed to a high risk of cross-infection, meaning they must implement recommendations based on the best available evidence to preserve the health of team members and the population they are caring for.

INTRODUCCIÓN: La enfermedad por coronavirus-19 (COVID-19) es un problema mundial de salud pública debido a su morbimortalidad, especialmente en grupos de riesgo. El entorno odontológico tiene un alto riesgo de transmisión viral, por ello el objetivo de este estudio fue identificar recomendaciones para la atención odontológica durante esta pandemia. MÉTODOS: Se realizó una búsqueda de evidencia científica publicada desde 2002 hasta el 23 de marzo de 2020 en bases de datos electrónicas (MEDLINE/PubMed, EMBASE, Cochrane y Epistemonikos) y en las páginas electrónicas de la Asociación Dental Americana, de Centers for Disease Control and Prevention Oral Health, del Ministerio de Salud de Chile y de sociedades científicas. RESULTADOS: Se incluyeron nueve artículos publicados, en los cuales se recomienda el uso irrestricto de elementos de protección personal, preferir técnicas radiográficas extraorales, uso de enjuagues bucales con peróxido de hidrógeno al 1% o povidona yodada al 0,2%, técnica a cuatro manos con aspiración constante y uso de suturas reabsorbibles. Además, existe consenso respecto a que durante los periodos de transmisión comunitaria se deben posponer los tratamientos odontológicos no urgentes. CONCLUSIONES: Debido al alto riesgo de infección cruzada que presentan los equipos odontológicos, deben implementarse recomendaciones basadas en la mejor evidencia disponible, con el fin de preservar la salud de los miembros del equipo y de la población a su cuidado.

Heme oxygenase-1 in protozoan infections: A tale of resistance and disease tolerance.

Heme oxygenase (HO-1) mediates the enzymatic cleavage of heme, a molecule with proinflammatory and prooxidant properties. HO-1 activity deeply impacts host capacity to tolerate infection through reduction of tissue damage or affecting resistance, the ability of the host to control pathogen loads. In this Review, we will discuss the contribution of HO-1 in different and complex protozoan infections, such as malaria, leishmaniasis, Chagas disease, and toxoplasmosis. The complexity of these infections and the pleiotropic effects of HO-1 constitute an interesting area of study and an opportunity for drug development.

Abdominal Actinomycosis misdiagnosed as liposarcoma

Actinomycosis is an uncommon, endogenous, and chronic infection with varied and nonspecific clinical features such as abdominal, pelvic or cervical masses, ulcerative lesions, abscesses, draining fistula, fibrosis, and constitutional symptoms. The disease ensues when the bacteria disrupt the mucosal barrier, invade, and spread throughout interfascial planes. Currently, the diagnosis of actinomycosis is challenging because of its very low frequency and depending on the clinical presentation it may masquerade malignancies. Therapy consists initially in intravenous penicillin, followed by an oral regimen that may be extended until a year of treatment. A timely diagnosis is crucial to avoid extensive therapeutic attempt as surgery. However, a biopsy or drainage of abscesses and fistula's tract may be required not only as a diagnostic procedure as part of the therapy. We report the case of a 72-year-old woman with an abdominal mass initially misdiagnosed as a liposarcoma. A second biopsy of a skin lesion of the abdominal wall made the diagnosis of actinomycosis, avoiding a major surgical procedure. The patient was treated with a long-term course of antibiotics with favorable outcome. Liposarcoma was ruled out after the patient's full recovery with antibiotics and the misdiagnosis was credit to the overconfidence on the immunohistochemical positivity to MDM2.

Abdominal Actinomycosis misdiagnosed as liposarcoma.

Actinomycosis is an uncommon, endogenous, and chronic infection with varied and nonspecific clinical features such as abdominal, pelvic or cervical masses, ulcerative lesions, abscesses, draining fistula, fibrosis, and constitutional symptoms. The disease ensues when the bacteria disrupt the mucosal barrier, invade, and spread throughout interfascial planes. Currently, the diagnosis of actinomycosis is challenging because of its very low frequency and depending on the clinical presentation it may masquerade malignancies. Therapy consists initially in intravenous penicillin, followed by an oral regimen that may be extended until a year of treatment. A timely diagnosis is crucial to avoid extensive therapeutic attempt as surgery. However, a biopsy or drainage of abscesses and fistula's tract may be required not only as a diagnostic procedure as part of the therapy. We report the case of a 72-year-old woman with an abdominal mass initially misdiagnosed as a liposarcoma. A second biopsy of a skin lesion of the abdominal wall made the diagnosis of actinomycosis, avoiding a major surgical procedure. The patient was treated with a long-term course of antibiotics with favorable outcome. Liposarcoma was ruled out after the patient's full recovery with antibiotics and the misdiagnosis was credit to the overconfidence on the immunohistochemical positivity to MDM2.

The Role of MIF on Eosinophil Biology and Eosinophilic Inflammation.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine that participates in innate and adaptive immune responses. MIF contributes to the resistance against infection agents, but also to the cellular and tissue damage in infectious, autoimmune, and allergic diseases. In the past years, several studies demonstrated a critical role for MIF in the pathogenesis of type-2-mediated inflammation, including allergy and helminth infection. Atopic patients have increased MIF amounts in affected tissues, mainly produced by immune cells such as macrophages, Th2 cells, and eosinophils. Increased MIF mRNA and protein are found in activated Th2 cells, while eosinophils stock pre-formed MIF protein and secrete high amounts of MIF upon stimulation. In mouse models of allergic asthma, the lack of MIF causes an almost complete abrogation of the cardinal signs of the disease including mucus secretion, eosinophilic inflammation, and airway hyper-responsiveness. Additionally, blocking the expression of MIF in animal models leads to significant reduction of pathological signs of eosinophilic inflammation such as rhinitis, atopic dermatitis, eosinophilic esophagitis and helminth infection. A number of studies indicate that MIF is important in the effector phase of type-2 immune responses, while its contribution to Th2 differentiation and IgE production is not consensual. MIF has been found to intervene in different aspects of eosinophil physiology including differentiation, survival, activation, and migration. CD4+ T cells and eosinophils express CD74 and CXCR4, receptors able to signal upon MIF binding. Blockage of these receptors with neutralizing antibodies or small molecule antagonists also succeeds in reducing the signals of inflammation in experimental allergic models. Together, these studies demonstrate an important contribution of MIF on eosinophil biology and in the pathogenesis of allergic diseases and helminth infection.

Recomendaciones odontológicas en la pandemia COVID-19: revisión narrativa / Dental recommendations in the COVID-19 pandemic: a narrative review

INTRODUCCIÓN: La enfermedad por coronavirus-19 (COVID-19) es un problema mundial de salud pública debido a su morbimortalidad, especialmente en grupos de riesgo. El entorno odontológico tiene un alto riesgo de transmisión viral, por ello el objetivo de este estudio fue identificar recomendaciones para la atención odontológica durante esta pandemia. MÉTODOS: Se realizó una búsqueda de evidencia científica publicada desde 2002 hasta el 23 de marzo de 2020 en bases de datos electrónicas (MEDLINE/PubMed, EMBASE, Cochrane y Epistemonikos) y en las páginas electrónicas de la Asociación Dental Americana, de Centers for Disease Control and Prevention Oral Health, del Ministerio de Salud de Chile y de sociedades científicas. RESULTADOS: Se incluyeron nueve artículos publicados, en los cuales se recomienda el uso irrestricto de elementos de protección personal, preferir técnicas radiográficas extraorales, uso de enjuagues bucales con peróxido de hidrógeno al 1% o povidona yodada al 0,2%, técnica a cuatro manos con aspiración constante y uso de suturas reabsorbibles. Además, existe consenso respecto a que durante los periodos de transmisión comunitaria se deben posponer los tratamientos odontológicos no urgentes. CONCLUSIONES: Debido al alto riesgo de infección cruzada que presentan los equipos odontológicos, deben implementarse recomendaciones basadas en la mejor evidencia disponible, con el fin de preservar la salud de los miembros del equipo y de la población a su cuidado.

INTRODUCTION: COVID-19 is a world public health problem due to its morbidity and mortality, especially in at-risk groups. The dental environment has a high risk of viral transmission; accordingly, this study aimed to identify recommendations based on the best available evidence for dental care during this pandemic. METHODS: We performed a search for scientific evidence published since 2002 to March 23th 2020 in electronic databases (MEDLINE/PubMed, EMBASE, Cochrane, and Epistemonikos) and the web pages of the American Dental Association, Centers for Disease Control and Prevention Oral Health, the Ministry of Health in Chile and scientific societies. RESULTS: We included nine published studies. The recommendations were the following: unrestricted use of personal protection elements, use of extraoral radiographic techniques, use of mouth rinses with 1% hydrogen peroxide or 0.2% iodine povidone, a four-hand technique with ongoing aspiration and the use of absorbable sutures. Furthermore, there is a consensus that non-urgent treatments should be postponed during periods of community transmission. CONCLUSIONS: Dental practitioners are exposed to a high risk of cross-infection, meaning they must implement recommendations based on the best available evidence to preserve the health of team members and the population they are caring for.

The Paradoxical Leishmanicidal Effects of Superoxide Dismutase (SOD)-Mimetic Tempol in Leishmania braziliensis Infection in vitro.

Leishmaniasis is an infectious disease caused by protozoans of the genus Leishmania. The macrophage is the resident cell in which the parasite replicates and it is important to identify new compounds that can aid in parasite elimination since the drugs used to treat leishmaniasis are toxic and present side effects. We have previously shown that treatment of Leishmania braziliensis-infected macrophages with DETC (Diethyldithiocarbamate) induces parasite killing, in vivo. Thus, the objective of this study was to further evaluate the effect of oxidants and antioxidants in L. braziliensis-infected macrophages, following treatment with either oxidizing Hydrogen Peroxide, Menadione, DETC, or antioxidant [NAC (N-Acetyl-Cyteine), Apocynin, and Tempol] compounds. We determined the percentage of infected macrophages and number of amastigotes. Promastigote survival was also evaluated. Both DETC (SOD-inhibitor) and Tempol (SOD-mimetic) decreased the percentage of infected cells and parasite load. Hydrogen peroxide did not interfere with parasite burden, while superoxide-generator Menadione had a reducing effect. On the other hand, NAC (GSH-replenisher) and Apocynin (NADPH-oxidase inhibitor) increased parasite burden. Tempol surfaces as an interesting candidate for the chemotherapy of CL with an IC50 of 0.66 ± 0.08 mM and selectivity index of 151. While it remains obscure how a SOD-mimetic may induce leishmanicidal effects, we suggest the possibility of developing Tempol-based topical applications for the treatment of cutaneous leishmaniasis caused by L. braziliensis.

Cardiac arrhythmias after renal I/R depend on IL-1ß.

AIMS: Cardiac arrhythmias are one of the most important remote complications after kidney injury. Renal ischemia reperfusion (I/R) is a major cause of acute renal injury predisposing to several remote dysfunctions, including cardiac electrical disturbance. Since IL-1ß production dependent on NLRP3 represents a link between tissue malfunctioning and cardiac arrhythmias, here we tested the hypothesis that longer ventricular repolarization and arrhythmias after renal I/R depend on this innate immunity sensor. METHODS AND RESULTS: Nlrp3-/- and Casp1-/- mice reacted to renal I/R with no increase in plasma IL-1ß, different from WT (wild-type) I/R. A prolonged QJ interval and an increased susceptibility to ventricular arrhythmias were found after I/R compared to Sham controls in wild-type mice at 15 days post-perfusion, but not in Nlrp3-/- or CASP1-/- I/R, indicating that the absence of NLRP3 or CASP1 totally prevented longer QJ interval after renal I/R. In contrast with WT mice, we found no renal atrophy and no renal dysfunction in Nlrp3-/- and Casp1-/- mice after renal I/R. Depletion of macrophages in vivo after I/R and a day before IL-1ß peak (at 7 days post-perfusion) totally prevented prolongation of QJ interval, suggesting that macrophages might participate as sensors of tissue injury. Moreover, treatment of I/R-WT mice with IL-1r antagonist (IL-1ra) from 8 to 15 days post perfusion did not interfere with renal function, but reversed QJ prolongation, prevented the increase in susceptibility to ventricular arrhythmias and rescued a close to normal duration and amplitude of calcium transient. CONCLUSION: Taken together, these results corroborate the hypothesis that IL-1ß is produced after sensing renal injury through NRLP3-CASP1, and IL-1ß on its turn triggers longer ventricular repolarization and increase susceptibility to cardiac arrhythmias. Still, they offer a therapeutic approach to treat cardiac arrhythmias that arise after renal I/R.

Toll-Like Receptor 4 and NLRP3 Caspase 1- Interleukin-1ß-Axis are Not Involved in Colon Ascendens Stent Peritonitis-Associated Heart Disease.

Hemodynamic collapse and myocardial dysfunction are among the major causes of death in severe sepsis. The purpose of this study was to assess the role played by toll-like receptor 4 and by the NLRP3 inflammasome in the cardiac dysfunction that occurs after high-grade polymicrobial sepsis. We performed the colon ascendens stent peritonitis (CASP) surgery in Tlr4, Nlrp3, and caspase-1 mice. We also assessed for the first time the electrical heart function in the colon ascendens stent peritonitis (CASP) model. The QJ interval was increased in wild-type C57BL/6J mice after CASP when compared with sham controls, a result paralleled by an increase in the cardiac action potential (AP) duration (APD). The decreases in ejection fraction (EF), left ventricle end diastolic volume, stroke volume, and cardiac output found after CASP were similar among all groups of mice. Similar heart response was found when Nlrp3 mice were submitted to high-grade cecal ligation and puncture. Despite developing cardiac dysfunction similar to wild types after CASP, Nlrp3 mice had reduced circulating levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α. Our results demonstrate that the genetic ablation of Tlr4, Nlrp3, and caspase-1 does not prevent the cardiac dysfunction, despite preventing the increase in pro-inflammatory cytokines, indicating that these are not feasible targets to therapy in high-grade sepsis.

Diálogos com adolescentes sobre direitos sexuais na escola pública: intervenções educativas emancipatórias! / Dialogues with adolescents on sexual rights in public school: emancipatory educational interventions / Diálogos con adolescentes sobre derechos sexuales en la escuela pública: intervenciones educativas emancipatorias!

Este estudo busca compreender significados e saberes de adolescentes sobre direitos sexuais para subsidiar intervenções educativas emancipatórias nas escolas. Desenvolveu-se pesquisa de abordagem qualitativa, foram realizadas entrevistas individuais com 29 adolescentes de 15 a 18 anos, alunos do ensino médio de escola pública e utilizou-se análise de conteúdo para interpretação das informações em profundidade. A pesquisa revelou que há falhas e omissões entre o que se estabelece nas leis e sua efetivação no cotidiano dos adolescentes, com violações aos seus direitos sexuais, tais como poucas informações qualificadas sobre sexualidade, a falta da educação em sexualidade nas escolas para todos os alunos, além de serviços de saúde específicos que atendam às suas necessidades, o que afeta a saúde sexual. Intervenções educativas emancipatórias que considerem conhecimentos científicos e os saberes de adolescentes e o pleno exercício da cidadania sexual podem reduzir vulnerabilidades relacionadas à saúde sexual e gerar transformações na realidade.

This study aims to understand the meanings and knowledge of adolescents about sexual rights to subsidize educational emancipatory interventions in schools. Qualitative approach research was developed, individual interviews were conducted with 29 adolescents aged 15 to 18, high school students from public schools, and content analysis was used to interpret the information in depth. The research revealed that there are flaws and omissions between what is established in the laws and their effectiveness in the daily life of adolescents, with violations of their sexual rights, such as few qualified information about sexuality, lack of sexuality education in schools for all students, besides Of specific health services that meet their needs, which affects sexual health. Emancipatory educational interventions that consider scientific knowledge and the knowledge of adolescents with the full exercise of sexual citizenship can reduce vulnerabilities related to sexual health and generate transformations in reality.

Este estudio busca comprender significados y saberes de adolescentes sobre derechos sexuales para subsidiar intervenciones educativas emancipatorias en las escuelas. Se desarrolló investigación de abordaje cualitativo, se realizaron entrevistas individuales con 29 adolescentes de 15 a 18 años, estudiantes de la Enseñanza Media de escuela pública, se utilizó análisis de contenido para interpretación de las informaciones en profundidad. La investigación reveló que hay fallas y omisiones entre lo que se establece en las leyes y su efectividad en el cotidiano de los adolescentes, con violaciones a sus derechos sexuales, tales como pocas informaciones calificadas sobre sexualidad, falta educación en sexualidad en las escuelas para todos los alumnos, además de servicios de salud específicos que atiendan a sus necesidades, lo que afecta la salud sexual. Las intervenciones educativas emancipatorias que consideren conocimientos científicos y los saberes de adolescentes con el pleno ejercicio de la ciudadanía sexual pueden reducir vulnerabilidades relacionadas con la salud sexual y generar transformaciones en la realidad.