Establishment and molecular characterization of HCB-541, a novel and aggressive human cutaneous squamous cell carcinoma cell line.

Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer that can result in significant morbidity, although it is usually well-managed and rarely metastasizes. However, the lack of commercially available cSCC cell lines hinders our understanding of this disease. This study aims to establish and characterize a new metastatic cSCC cell line derived from a Brazilian patient. A tumor biopsy was taken from a metastatic cSCC patient, immortalized, and named HCB-541 after several passages. The cytokeratin expression profile, karyotypic alterations, mutational analysis, mRNA and protein differential expression, tumorigenic capacity in xenograft models, and drug sensitivity were analyzed. The HCB-541 cell line showed a doubling time between 20 and 30 h and high tumorigenic capacity in the xenograft mouse model. The HCB-541 cell line showed hypodiploid and hypotetraploidy populations. We found pathogenic mutations in TP53 p.(Arg248Leu), HRAS (Gln61His) and TERT promoter (C228T) and high-level microsatellite instability (MSI-H) in both tumor and cell line. We observed 37 cancer-related genes differentially expressed when compared with HACAT control cells. The HCB-541 cells exhibited high phosphorylated levels of EGFR, AXL, Tie, FGFR, and ROR2, and high sensitivity to cisplatin, carboplatin, and EGFR inhibitors. Our study successfully established HCB-541, a new cSCC cell line that could be useful as a valuable biological model for understanding the biology and therapy of metastatic skin cancer.

Predictors of serious infections in rheumatoid arthritis-a prospective Brazilian cohort.

BACKGROUND: Infections increase mortality and morbidity and often limit immunosuppressive treatment in rheumatoid arthritis patients. OBJECTIVE: To analyze the occurrence of serious infections and the associated factors in a cohort of rheumatoid arthritis patients under real-life conditions. METHODS: We analyzed data from the REAL, a prospective observational study, that evaluated Brazilian RA patients, with clinical and laboratory data collected over a year. Univariate and multivariate analyses were performed from the adjustment of the logistic regression model Generalized Estimating Equations (GEE), with the primary outcome being the occurrence of serious infection, defined as need for hospitalization or use of intravenous antibiotics for its treatment. RESULTS: 841 patients were included with an average follow-up time of 11.2 months (SD 2.4). Eighty-nine serious infections occurred, corresponding to 13 infections per 100 patient-years. Pulmonary fibrosis, chronic kidney disease (CKD) and central nervous system disease increased the chances of serious infection by 3.2 times (95% CI: 1.5-6.9), 3.6 times (95% CI: 1.2-10.4) and 2.4 times (95% CI: 1.2-5.0), respectively. The use of corticosteroids in moderate doses increased the chances by 5.4 times (95% CI: 2.3-12.4), and for each increase of 1 unit in the health assessment questionnaire (HAQ), the chance increased 60% (95% CI: 20-120%). CONCLUSION: The use of corticosteroids at moderate doses increased the risk of serious infection in RA patients. Reduced functionality assessed by the HAQ and comorbidities were other important factors associated with serious infection in this cohort.

Genetic parameters for visual scores, growth and carcass traits in Nellore Cattle.

Growth and carcass traits are essential selection criteria for beef cattle breeding programs. However, it is necessary to combine these measurements with body composition traits to meet the demand of the consumer market. This study aimed to estimate the genetic parameters for visual scores, growth (pre and post-weaning weights), and carcass (rib eye area (REA), back and rump fat thickness) traits in Nellore cattle using Bayesian inference. Data from 12,060 animals belonging to the HoRa Hofig Ramos herd were used. Morphological traits were evaluated by the MERCOS methodology. The heritability estimates obtained ranged from low to high magnitude, from 0.15 to 0.28 for visual scores, 0.13 to 0.44 for growth, and from 0.42 to 0.46 for carcass traits. Genetic correlations between visual scores and growth traits were generally of moderate to high magnitudes, however, visual scores showed low correlations with carcass traits, except between sacral bone and structure and REA. Selection for visual score traits can lead to favorable responses in body weight and vice versa, but the same is not true for carcass traits. Morphological categorical traits can be used as complementary tools that add value to selection.

Consumo de substâncias psicoativas entre estudantes de medicina antes e depois do ingresso no curso / Use of psychoactive substances among medicine students before and after admission to course

Introdução: Substâncias psicoativas são capazes de alterar a consciência, o humor ou o pensamento de um indivíduo, resultando em mudanças fisiológicas ou de comportamento. Objetivo: Este estudo avaliou se houve diferença no consumo de 13 substâncias psicoativas por estudantes de medicina, de uma faculdade privada do interior paulista, antes e depois do ingresso no curso. Método: Um questionário estruturado e impresso foi apresentado a ingressantes no curso de medicina, em abril de 2019, e, novamente, em dezembro, ao final do primeiro ano da graduação. Resultados: Na análise dos dados, foi realizado o Teste de Wilcoxon, com o emprego do programa estatístico JASP. No total, 90 estudantes participaram do estudo. Dentre as 13 substâncias consideradas, apenas para o álcool foram encontradas evidências estatísticas que indicaram ter ocorrido um aumento significativo no consumo após o ingresso no curso (W = 1308,00, p < 0,001). Conclusão: A continuidade dos estudos sobre o uso de substâncias lícitas e ilícitas entre os estudantes da instituição de ensino considerada será fundamental para garantir um monitoramento contínuo. Desse modo, a instituição poderá identificar usos abusivos e implementar políticas de prevenção, garantindo o bem-estar de seus alunos

Introduction: Psychoactive substances are capable of altering an individual's consciousness, mood or thinking, resulting in physiological or behavioral changes. Objective: This study assessed whether there was a difference in the consumption of 13 psychoactive substances by medical students at a private college in the interior of São Paulo, before and after enrolling in the course. Method: A structured, printed questionnaire was presented to new medicine students in April 2019, and again in December, at the end of the first year of graduation. Results: In data analysis, the Wilcoxon Test was performed, using the JASP statistical program. In total, 90 students participated in the study. Among the 13 substances considered, only for alcohol was statistical evidence found that indicated that there had been a significant increase in consumption after enrolling in the course (W = 1308.00, p < 0.001). Conclusion: Continuing studies on the use of legal and illicit substances among students at the educational institution considered will be essential to ensure continuous monitoring. In this way, the institution will be able to identify abusive uses and implement prevention policies, ensuring the well-being of its students

Introducción: Las sustancias psicoactivas son capaces de alterar la conciencia, el estado de ánimo o el pensamiento de un individuo, resultando en cambios fisiológicos o de comportamiento. Objetivo: Este estudio evaluó si existía diferencia en el consumo de 13 sustancias psicoactivas por estudiantes de medicina de una facultad privada del interior de São Paulo, antes y después de matricularse en el curso. Método: Se presentó un cuestionario impreso estructurado a los nuevos estudiantes de medicina en abril de 2019, y nuevamente en diciembre, al final del primer año de graduación. Resultados: En el análisis de los datos se realizó la Prueba de Wilcoxon, utilizando el programa estadístico JASP. En total, 90 estudiantes participaron en el estudio. Entre las 13 sustancias consideradas, sólo para el alcohol se encontró evidencia estadística que indicaba que había habido un aumento significativo en el consumo después de la inscripción al curso (W = 1308,00, p < 0,001). Conclusión: Continuar con los estudios sobre el uso de sustancias legales e ilícitas entre los estudiantes de la institución educativa considerada será fundamental para garantizar un seguimiento continuo. De esta manera, la institución podrá identificar usos abusivos e implementar políticas de prevención, asegurando el bienestar de sus estudiantes

Progesterone Device Use Improves Ovum Pick-Up Efficiency in Acyclic Donors.

The aim of this study was to evaluate follicular dynamics and ovum pick-up (OPU) efficacy in untreated mares or mares treated with an intravaginal progesterone (P4) device during seasonal anestrus (acyclic) and during the breeding season (cyclic). Six mares (mean age = 5 years), were recruited into an ovum pick-up scheme that was performed every 14 days with and without the P4 device, during the acyclic and cyclic phases. Aspirations amounted to seven procedures with or without the P4 device during each phase. Five ultrasound assessments were performed at each interval between the OPUs. Data on follicular number and diameter as well as the numbers of recovered and the percentage of recovered oocytes were also collected. The number of follicles from mares in the acyclic phase was higher (P < .005) regardless of the treatment. However, the follicular diameter was smaller for the P4 group (P < .005) from the 2nd to the 5th evaluation post-OPU procedure. The percentage of oocytes recovered during the acyclic phase was higher for mares treated with the P4 device (P < .005). The P4 device resulted in follicles with smaller diameters and facilitated OPU efficacy.

Exploring microplastic contamination in Guiana dolphins (Sotalia guianensis): Insights into plastic pollution in the southwestern tropical Atlantic.

Marine mammals are considered sentinel species and may act as indicators of ocean health. Plastic residues are widely distributed in the oceans and are recognised as hazardous contaminants, and once ingested can cause several adverse effects on wildlife. This study aimed to identify and characterise plastic ingestion in the Guiana dolphins (Sotalia guianensis) from the Southwestern Tropical Atlantic by evaluating the stomach contents of stranded individuals through KOH digestion and identification of subsample of particles by LDIR Chemical Imaging System. Most of the individuals were contaminated, and the most common polymers identified were PU, PET and EVA. Microplastics were more prevalent than larger plastic particles (meso- and macroplastics). Smaller particles were detected during the rainy seasons. Moreover, there was a positive correlation between the stomach content mass and the number of microplastics, suggesting contamination through trophic transfer.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort.

INTRODUCTION: Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. OBJECTIVE: To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. METHOD: Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whitney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). RESULTS: 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. CONCLUSIONS: ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Methyl gallate nanomicelles impairs neutrophil accumulated in zymosan-induced arthritis.

Arthritis is a chronic disease that affects, approximately, 1 % of the total global population. It is characterized by chronic inflammation, accompanied in most of the cases of motor disability and sever pain. The main therapies available have high risk of failure and advanced treatments are scarce and highly cost. In this scenario, search for effective, safe and low-cost treatments is quite desirable. Methyl gallate (MG) is a plant-derived phenolic compound described to present remarkable anti-inflammatory effect in experimental models of arthritis. Thus, in this study we formulated nanomicelles of MG using Pluronic (F-127) as matrix and evaluated in vivo the pharmacokinetic, biodistribution and its effect in the mice model of zymosan-induced arthritis. The nanomicelles were formed with a size 126 nm. The biodistribution showed a ubiquitous tissue deposition with a renal excretion. The pharmacokinetics showed elimination half-life of 1.72 h and a clearance of 0.006 L/h. The oral pretreatment with nanomicelles containing MG (3.5 or 7 mg/kg) demonstrated a reduction in total leukocytes, neutrophils, and mononuclear cells from the inflammation site. The data supports the use of methyl gallate nanomicelles as an alternative drug for arthritis. DATA AVAILABILITY: All the data of this study are transparent.

Genetic association between feed efficiency, growth, scrotal circumference, and carcass traits in Guzerat cattle.

The objective of this study was to estimate the genetic parameters for feed efficiency-related traits and their genetic correlations with growth, male fertility, and carcass traits using multi-trait analysis in Guzerat cattle. Further, it aimed to predict the direct and correlated responses for feed efficiency traits when selection was applied for growth, male fertility, and carcass traits. The evaluated traits were adjusted weight at 120 (W120), 210 (W210), 365 (W365), and 450 days of age (W450), adjusted scrotal circumference at 365 days of age (SC365) and at 450 days of age (SC450), scrotal circumference, ribeye area (REA), backfat thickness (BFT), rump fat thickness (RFT), residual feed intake (RFI), and dry matter intake (DMI). The genetic parameters were obtained by the restricted maximum likelihood method (REML), using an animal model in multi-trait analyses. The heritability estimates for W120, W210, W365, W450, SC365, and SC450 varied from low to high (0.17 to 0.39). The carcass traits, REA, BFT, and RFT, displayed low to moderate heritability estimates, 0.27, 0.10, and 0.31, respectively. The heritability estimates for RFI (0.15) and DMI (0.23) were low and moderate, respectively. The RFI showed low genetic correlations with growth traits, ranging from - 0.07 to 0.22, from 0.03 to 0.05 for scrotal circumference, and from - 0.35 to 0.16 for carcass, except for DMI, which ranged from 0.42 to 0.46. The RFI and DMI presented enough additive genetic variability to be used as selection criteria in Guzerat breed genetic improvement program. Additionally, the response to selection for RFI would be higher when selection is performed directly for this trait. The selection for residual feed intake would not promote unfavorable correlated responses for scrotal circumference, carcass (yield and finish), and growth traits. Therefore, the selection for more efficient animals would not compromise the productive, reproductive, and carcass performance, contributing to reduce the production costs, increasing the profitability and sustainability of beef cattle production in tropical areas.

Primary Effusion Lymphoma: A Rare and Challenging Diagnosis for Recurrent Pleural Effusion.

Primary Effusion Lymphoma is an extremely rare and aggressive subtype of B-cell lymphoma, accounting for only <1% of all cases of this neoplasm. It has a unique clinical presentation because it has a predilection for appearing in body cavities, such as the pleural space, pericardium and peritoneum. It mainly affects immunocompromised individuals and may also affect individuals in the Mediterranean region and in areas endemic for human herpesvirus 8 (HHV-8). Herein, we report the case of an 83-year-old immunocompetent male complaining of coughing, fever and progressive dyspnea for 3 days. His past medical history revealed a recurrent pleural effusion for the last three years, as well as losing weight and malaise. A subsequent investigation revealed a PEL diagnosis of the pleura.

Plant-microbiome crosstalk and disease development.

Plants harbor a complex immune system to fight off invaders and prevent diseases. For decades, the interactions between plants and pathogens have been investigated primarily through the lens of binary interactions, largely neglecting the diversity of microbes that naturally inhabit plant tissues. Recent research, however, demonstrates that resident microbes are more than mere spectators. Instead, the plant microbiome extends host immune function and influences the outcome of a pathogen infection. Both plants and the interacting microbes produce a large diversity of metabolites that form an intricate chemical network of nutrients, signals, and antimicrobial molecules. In this review, we discuss the involvement of the plant microbiome in disease development, focusing on the biochemical conversation that occurs between plants and their associated microbiota before, during and after infection. We also highlight outstanding questions and possible directions for future research.

Morte encefálica: conhecimento dos fisioterapeutas a respeito dos conceitos e protocolo em um hospital de urgências / Brain death: knowledge of physiotherapists about the concepts and protocol in an emergency hospital

INTRODUÇÃO: A morte encefálica (ME) é caracterizada pela presença de coma aperceptivo e ausência de reflexos de tronco encefálico. O sucesso no processo de doação de órgãos é complexo e depende do envolvimento ativo dos profissionais no processo de busca ativa e notificação de potenciais doadores (PD). O fisioterapeuta lida diretamente com o paciente crítico e, dentre outras funções, gerencia a ventilação mecânica, sendo fundamental no processo de manutenção do PD. OBJETIVO: Avaliar o conhecimento dos fisioterapeutas sobre os conceitos e protocolo de ME em um hospital de urgências. METODOLOGIA: Estudo transversal, analítico, realizado por meio de perguntas sociodemográficas e um questionário constituído por nove questões objetivas, elaborado com base na resolução nº 2.173/2017 do CFM. RESULTADOS: Participaram do estudo 27 fisioterapeutas que obtiveram uma pontuação média de 4,74 (DP ± 1,65) no questionário. As perguntas com maiores índices de erros foram as que indagaram sobre o tempo mínimo para abertura do protocolo de ME (92,6%) e a manutenção do suporte de vida em não doador (66,7%). CONCLUSÃO: Os fisioterapeutas avaliados demonstraram possuir conhecimento limitado acerca dos conceitos e protocolo de ME diante do número limítrofe de acertos. Além disso, a maioria dos profissionais referiu não ter recebido nenhum tipo de capacitação, podendo configurar um dos determinantes para o baixo desempenho no questionário.

INTRODUCTION: Brain death (BD) is characterized by the presence of apperceptive coma and the absence of brainstem reflexes. The success o the organ donation process is complex and depends on the active involvement of professionals in the process of active search and notification of potential donors (PD). The physiotherapist deals directly with the critical patient and, among other functions, manages mechanical ventilation, being essential in the process of maintaining the PD. OBJECTIVE: To assess the knowledge of physiotherapists regarding the concepts and protocol of BD in an emergency hospital. METHODOLOGY: Cross-sectional, analytical study carried out using sociodemographic questions and a questionnaire consisting of nine objective questions, prepared based on CFM Resolution No. 2,173/2017. RESULTS: The study included 27 physiotherapists who obtained an average score of 4.74 (SD ± 1.65) in the questionnaire. The questions with the highest error rates were those that asked about the minimum time to open the BD protocol (92.6%) and maintenance of life support in non-donor (66.7%). CONCLUSION: The physical therapists evaluated showed limited knowledge about BD concepts and protocol in view of the borderline number of correct answers. In addition, most professionals did not receive any type of training, which could be one of the determinants of low performance in the questionnaire.

[How much does a specialized medical consultation cost for families of pediatric patients in the Brazilian Unified National Health System?] / Quanto custa uma consulta médica especializada para as famílias de pacientes pediátricos no Sistema Único de Saúde?

In this study, we investigated the costs of transportation for each outpatient consultation in patients referred to specialized surgical evaluation in a tertiary hospital in Rio de Janeiro, Brazil. Descriptive study with guardians of pediatric patients scheduled for pediatric surgery, questioning transportation cost, and opportunity costs (loss of remuneration, food, payment of caregivers for other children, expenses for other companions). About half patients were aged up to five years; about two thirds had diseases of simple and definitive surgical resolution; and 181 families (89.17%) presented monthly family income up to BRL 1,999.00. The proportion of families that benefited from free transportation ranged from 4.26% to 15.56% for patients living up to 100 km away from the hospital (45.83% for patients living more than 100 km away from the institution). A total of 176 (87.13%) guardians reported expenses buying food, 12 (5.94%) paid caregivers to the other children on the day of the consultation, and 80 (39.6%) reported loss of remuneration for the working day. Among the high complexity cases, 9.33% of the mothers have given up their regular paid employment. Transportation expenses for a pediatric surgery consultation at a reference hospital in Rio de Janeiro cost about 4.42% of the current minimum wage, spending around 217.32 minutes of displacement/consultation. Expenses with food and loss of remuneration due to absence at work also entail significant financial charges or loss of remuneration for the patient at each consultation.

Nesta pesquisa, estudamos os custos de transporte por consulta ambulatorial em pacientes referenciados para avaliação cirúrgica especializada em um hospital terciário no Rio de Janeiro, Brasil. Trata-se de um estudo descritivo com responsáveis por pacientes pediátricos agendados para consulta de cirurgia pediátrica, questionando fatores ligados ao custo de transporte e de oportunidade (perda de remuneração, alimentação, pagamento de cuidadores para outros filhos, despesas para outros acompanhantes). Aproximadamente metade dos pacientes tinham até 5 anos de idade, cerca de 2/3 apresentavam doenças de resolutividade cirúrgica simples e definitiva e 181 famílias (89,17%) contavam com renda familiar mensal de até R$ 1.999,00. A proporção de famílias beneficiadas por transporte gratuito variou entre 4,26-15,56% para pacientes morando até 100km de distância do hospital (45,83% para pacientes com residência a mais de 100km da instituição). Dos responsáveis, 176 (87,13%) relataram despesas para alimentação, 12 (5,94%) pagavam cuidadores para os outros filhos no dia da consulta e 80 (39,6%) referiram perda do pagamento do dia de trabalho. Dos casos de alta complexidade, 9,33% das mães entrevistadas abriram mão de exercer atividade remunerada regular. As despesas com transporte para uma consulta em cirurgia pediátrica em um hospital de referência do Rio de Janeiro custam em média 4,42% do salário mínimo vigente, com uma média de 217,32 minutos de deslocamento por consulta. Despesas com alimentação e perda de remuneração pela ausência no trabalho também implicam encargos financeiros ou perda de remuneração significativos para o paciente em cada consulta.

En esta investigación se estudiaron los costes de transporte por visita ambulatoria en pacientes remitidos para evaluación quirúrgica especializada en un hospital de atención terciaria en Río de Janeiro, Brasil. Es un estudio descriptivo con responsables de pacientes pediátricos programados para consulta de cirugía pediátrica, en el que se cuestionaron factores relacionados con el coste del transporte y los costes de oportunidad (pérdida de remuneración, alimentación, pago de cuidadores de otros niños, gastos de otros cuidadores). Aproximadamente la mitad de los pacientes tenían hasta 5 años de edad; cerca de 2/3 presentaban enfermedades de resolución quirúrgica simple y definitiva, 181 familias (89,17%) con renta familiar mensual de hasta BRL 1.999,00. La proporción de familias que se benefician de transporte gratuito varía entre el 4,26% y el 15,56% para los pacientes que viven hasta a 100 km del hospital (45,83% para los pacientes que viven a más de 100 km de la institución). Ciento setenta y seis (87,13%) cuidadores declaran gastos de alimentación, 12 (5,94%) pagan a los cuidadores de sus otros hijos en el día de la consulta y 80 (39,6%) declaran pérdida de salario por la jornada laboral. De los casos de alta complejidad, el 9,33% de las madres entrevistadas habían abandonado su actividad remunerada habitual. Los gastos de transporte para una consulta de cirugía pediátrica en un hospital de referencia de Río de Janeiro cuestan de media el 4,42% del salario mínimo vigente, con una media de 217,32 minutos de tiempo de viaje/consulta. Los gastos de alimentación y la pérdida de salario por ausencia en el trabajo también implican una importante carga económica o pérdida de salario para el paciente en cada cita.

Short-Finned Pilot Whale Strandings Associated with Pilot Whale Morbillivirus, Brazil.

Cetacean morbillivirus (CeMV) causes illness and death in cetaceans worldwide; the CeMV strains circulating in the Southern Hemisphere are poorly known. We detected a pilot whale CeMV strain in 3 short-finned pilot whales (Globicephala macrorhynchus) stranded in Brazil during July-October 2020. Our results confirm this virus circulates in this species.

P2Y2-P2X7 receptors cross-talk in primed mesenteric endothelial cells upregulates NF-κB signaling favoring mononuclear cell adhesion in schistosomiasis.

Schistosomiasis is an intravascular infectious disease that impacts over 200 million people globally. In its chronic stage, it leads to mesenteric inflammation with significant involvement of monocytes/macrophages. Endothelial cells lining the vessel lumens play a crucial role, and mount of evidence links this disease to a downregulation of endoprotective cell signaling favoring a primed and proinflammatory endothelial cell phenotype and therefore the loss of immunovascular homeostasis. One hallmark of infectious and inflammatory conditions is the release of nucleotides into the extracellular milieu, which, in turn, act as innate messengers, activating purinergic receptors and triggering cell-to-cell communication. ATP influences the progression of various diseases through P2X and P2Y purinergic receptor subtypes. Among these receptors, P2Y2 (P2Y2R) and P2X7 (P2X7R) receptors stand out, known for their roles in inflammation. However, their specific role in schistosomiasis has remained largely unexplored. Therefore, we hypothesized that endothelial P2Y2R and P2X7R could contribute to monocyte adhesion to mesenteric endothelial cells in schistosomiasis. Using a preclinical murine model of schistosomiasis associated with endothelial dysfunction and age-matched control mice, we showed that endothelial P2Y2R and P2X7R activation increased monocyte adhesion to cultured primary endothelial cells in both groups. However, a distinct upregulation of endothelial P2Y2R-driven canonical Ca2+ signaling was observed in the infected group, amplifying adhesion. In the control group, the coactivation of endothelial P2Y2R and P2X7R did not alter the maximal monocyte adhesion induced by each receptor individually. However, in the infected group, this coactivation induced a distinct upregulation of P2Y2R-P2X7R-driven canonical signaling, IL-1ß release, and VCAM-1 expression, with underlying mechanisms involving inflammasome and NF-κB signaling. Therefore, current data suggest that schistosomiasis alters endothelial cell P2Y2R/P2X7R signaling during inflammation. These discoveries advance our understanding of schistosomiasis. This intricate interplay, driven by PAMP-triggered endothelial P2Y2R/P2X7R cross-talk, emerges as a potential key player in the mesenteric inflammation during schistosomiasis.

Extra-articular manifestations of rheumatoid arthritis remain a major challenge: data from a large, multi-centric cohort

Abstract Introduction Although Rheumatoid Arthritis (RA) extra-articular manifestations (ExtRA) occurrence has been decreasing over time, they are still a major mortality risk factor for patients. Objective To determine the prevalence of ExtRA in a large cohort, and its association with demographic and clinical variables. Method Cross-sectional and observational study, based on a multi-centric database from a prospective cohort, in which 11 public rheumatology centres enrolled RA patients (1987 ARA or 2010 ACR-EULAR). Data collection began in 08-2015, using a single online electronic medical record. Continuous variables were compared using Mann-Whit-ney U-test, and Fisher's exact test or chi-square test, as appropriate, were used for categorical variables. The level of significance was set at 5% (p < 0.05). Results 1115 patients were included: 89% women, age [mean ± SD] 58.2 ± 11.5 years, disease duration 14.5 ± 12.2 years, positive Rheumatoid Factor (RF, n = 1108) in 77%, positive anti-cyclic citrullinated peptide (ACPA, n = 477) in 78%. Regarding ExtRA, 334 occurrences were registered in 261 patients, resulting in an overall prevalence of 23.4% in the cohort. The comparison among ExtRA and Non-ExtRA groups shows significant higher age (p < 0.001), disease duration (p < 0.001), RF high titers (p = 0.018), Clinical Disease Activity index (CDAI) (p < 0.001), Disease Activity Index 28 (DAS 28) (p < 0.001), and Health Assessment Questionnaire (HAQ) (p < 0.001) in ExtRA group. Treatment with Azathioprine (p = 0.002), Etanercept (p = 0.049) Glucocorticoids (GC) ('p = 0.002), and non-steroidal anti-inflammatory drugs (NSAIDs) (p < 0.001) were more frequent in ExtRA group. Conclusions ExtRA manifestations still show an expressive occurrence that should not be underestimated. Our findings reinforce that long-term seropositive disease, associated with significant disability and persistent inflammatory activity are the key factors related to ExtRA development.

Muito além do trauma: uma investigação sobre o papel das reações peritraumáticas sobre o transtorno de estresse pós-traumático / Beyond the trauma: an investigation of the role of peritraumatic reactions on posttraumatic stress disorder

O Transtorno de Estresse Pós-Traumático (TEPT) é uma condição debilitante que impacta significativamente a qualidade de vida dos seus portadores. Dentre vários fatores de risco para o TEPT, as reações peritraumáticas (RP), como a imobilidade tônica peritraumática (ITP), dissociação (DP) e reações físicas de pânico (RFP), estão entre as mais investigadas. No entanto, a maioria dos estudos avaliou essas RP separadamente, e o elo entre elas e o TEPT ainda não foi bem compreendido. Portanto, essa tese teve como objetivos: (i) estimar simultaneamente o efeito das três RP sobre o TEPT utilizando um instrumento validado; e (ii) avaliar se há efeito indireto da ITP sobre o TEPT mediado pelo sentimento de culpa/vergonha. Utilizamos modelagem de equações estruturais para analisar dados de 3211 participantes do Rio de Janeiro e de São Paulo. Tratamos as RP como variáveis latentes, selecionando desconfundidores específicos para cada reação. Nossas exposições foram as RP, sendo TEPT o desfecho. Calculamos odds ratios e intervalos de confiança de 95%. Utilizamos o Bayesian Information Criterion para comparar o ajuste de modelos não aninhados. Quando analisadas separadamente, todas as RP alcançaram significância estatística. No entanto, apenas DP (ORDP=1,8; IC95%:1,3-2,4) e RFP (ORRFP=2,5; IC95%:1,8-3,4) permaneceram estatisticamente significativas quando incluímos as três reações em um modelo com seus respectivos desconfundidores e correlações entre elas. Os resultados sugeriram um possível efeito da ITP sobre o TEPT (ORITP=1,4; IC95%:1,0-1,9). As interações entre as RP não foram estatisticamente significativas. Ao investigarmos o sentimento de culpa/vergonha como mediador entre ITP e TEPT, o efeito indireto alcançou apenas significância estatística limítrofe (ORITP(TNIE)=1,1; IC95%:1,0-1,2). Os efeitos direto (ORITP(PNDE)=1,3; IC95%: 0,8-1,8) e total (ORITP(TE)=1,4; IC95%:0,9-1,9) para ITP perderam significância quando todas as RP, seus desconfundidores e correlações entre elas fizeram parte do mesmo modelo. As demais RP, no entanto, permaneceram estatisticamente significativas (ORDP=1,7; IC95%:1,3-2,3 e ORRFP=2,5; IC95%:1,8-3,4). Nossos resultados mostraram que a DP e as RFP aumentaram o risco de TEPT mesmo quando consideradas em conjunto. A ITP pode ter efeito sobre o risco de TEPT, mas esse achado deve ser interpretado com cautela devido a significância limítrofe dessa RP em nosso modelo final. Também não identificamos uma mediação significativa entre ITP e TEPT pelos sentimentos de culpa/vergonha. Contudo, a significância limítrofe encontrada para o efeito indireto demanda investigações adicionais. Nossos achados reforçam a ideia de que as reações peritraumáticas devem ser analisadas e compreendidas como ocorrências simultâneas. Também seria oportuno que estudos envolvendo culpa/vergonha, ITP e TEPT focalizassem traumas caracterizados por aprisionamento e impossibilidade de escapar, dado que estas experiências são apontadas como mais susceptíveis para desencadear a ITP. (AU)

Posttraumatic stress disorder (PTSD) is a debilitating condition that greatly impacts quality of life. Among several PTSD risk factors, peritraumatic reactions (PR) such as peritraumatic tonic immobility (PTI), dissociation (PD) and physical panic reactions (PPR) are some of the most investigated. However, several studies have assessed these PR separately, and the pathway connecting them to PTSD is not well understood. Therefore, this thesis aimed to: (i) simultaneously estimate the effect of the three PR on PTSD using a validated instrument; and (ii) assess if there is an indirect effect of PTI on PTSD mediated by feelings of guilt/shame. We used structural equation modelling to analyse data from 3211 participants from Rio de Janeiro and São Paulo. We treated the PR as latent variables and selected specific confounders for each reaction. Our exposures were the PR, and PTSD was the outcome. We calculated odds ratios and 95% confidence intervals for each analysis. We also employed the Bayesian Information Criterion to compare the goodness of fit between non-nested models. Separately, all PR achieved statistically significant results. However, only PD (ORPD=1.8; 95%CI:1.3-2.4) and PPR (ORPPR=2.5; 95%CI:1.8-3.4) remained statistically significant when all three were included in a model with their respective confounders and correlations among all PR. Our findings suggested a possible effect of PTI on PTSD (ORPTI=1.4; 95%CI:1.0-1.9). Interactions between the PR were not statistically significant. When we investigated feelings of guilt/shame as the mediator between PTI and PTSD, the indirect effect achieved a borderline statistical significance (ORPTI(TNIE)=1.1; 95%CI:1.0-1.2). Direct (ORPTI(PNDE)=1.3; 95%CI:0.8-1.8) and total (ORPTI(TE)=1.4; 95%CI:0.9-1.9) effects lost their significance when all PR, their confounders and correlations were included in the same model. The other PR remained statistically significant (ORPD=1.7; 95%CI:1.3-2.3 and ORPPR=2.5; 95%CI:1.8-3.4). Our findings showed PD and PPR to increase the risk of PTSD even when considered in tandem. PTI could have an effect on PTSD, but this must be considered cautiously, as this PR only reached borderline significance in our final model. Feelings of guilt/shame did not significantly mediate PTI's effect on PTSD. However, a borderline statistical significance in the indirect effects warrants further investigation. Our findings reinforce the hypothesis that peritraumatic reactions should be analysed and understood as simultaneous occurrences, not as separate entities. It would also be appropriate for studies concerning guilt/shame, PTI and PTSD to focus on traumas characterized by imprisonment and feelings of inescapability, given that these experiences are allegedly more likely to trigger PTI. (AU)

Promoting adequate and healthy food in early childhood education: a systematic review / Promoção da alimentação adequada e saudável na educação infantil: uma revisão sistemática

Abstract Objectives: to identify and describe the characteristics of studies that address the promotion of adequate and healthy food in early childhood education units and their repercussions on the school community. Methods: the search and selection were performed according to the PRISMA recommendations in the Medline databases via OVID, EMBASE and LILACS. Data extraction took placeusing a table developed by the authors. The evaluation of the quality of the evidence of the studies was carried out through the risk of bias using an adapted scale. Result: twelve articles that met the eligibility criteria were selected. All studies were applied in public or private educational institutions with a median of 236 participants. In the analysis of food and nutrition education activities, the most adopted with preschoolers were playful; with the parents it was the meetings and counseling; and with the professionals it was the training. The methodological qualification of the studies was considered low, which may be related to their limitations included in this review, mainly due to the types of designs adopted, the time and lack of continuity of interventions and sample size. Conclusion: food and nutrition education activities seem to be a promising strategy in knowledge, adoption of healthy eating practices and transmission of values in the school community.

Resumo Objetivos: identificar e descrever as características de estudos que abordam a promoção da alimentação adequada e saudável em unidades de educação infantil e suas repercussões na comunidade escolar. Métodos: a busca e seleção foram realizadas segundo as recomendações do PRISMA nas bases de dados Medline via OVID, EMBASE e LILACS. A extração de dados ocorreu utilizando uma tabela elaborada pelas autoras. A avaliação da qualidade das evidências dos estudos foi realizada por meio do risco de viés utilizando uma escala adaptada. Resultados: foram selecionados 12 artigos que atenderam aos critérios de elegibilidade. Todos os estudos foram aplicados em instituições de ensino públicas ou privadas com uma mediana de 236 participantes. Na análise das atividades de educação alimentar e nutricional, as mais adotadas com os pré-escolares foram as lúdicas; com os pais foram as reuniões e aconselhamentos; e com os profissionais foram as capacitações. A qualificação metodológica dos estudos foi considerada baixa, podendo estar relacionada às limitações dos próprios estudos incluídos nesta revisão, principalmente pelos tipos de desenhos adotados, o tempo e a falta de continuidade das intervenções e tamanho amostrai. Conclusão: atividades de educação alimentar e nutricional parecem ser uma estratégia promissora na disseminação do conhecimento, adoção de práticas alimentares saudáveis e transmissão de valores na comunidade escolar.

Quanto custa uma consulta médica especializada para as famílias de pacientes pediátricos no Sistema Único de Saúde? / How much does a specialized medical consultation cost for families of pediatric patients in the Brazilian Unified National Health System? / ¿Cuánto cuesta una consulta médica especializada para las familias de pacientes pediátricos en el Sistema Único de Salud brasileño?

Nesta pesquisa, estudamos os custos de transporte por consulta ambulatorial em pacientes referenciados para avaliação cirúrgica especializada em um hospital terciário no Rio de Janeiro, Brasil. Trata-se de um estudo descritivo com responsáveis por pacientes pediátricos agendados para consulta de cirurgia pediátrica, questionando fatores ligados ao custo de transporte e de oportunidade (perda de remuneração, alimentação, pagamento de cuidadores para outros filhos, despesas para outros acompanhantes). Aproximadamente metade dos pacientes tinham até 5 anos de idade, cerca de 2/3 apresentavam doenças de resolutividade cirúrgica simples e definitiva e 181 famílias (89,17%) contavam com renda familiar mensal de até R$ 1.999,00. A proporção de famílias beneficiadas por transporte gratuito variou entre 4,26-15,56% para pacientes morando até 100km de distância do hospital (45,83% para pacientes com residência a mais de 100km da instituição). Dos responsáveis, 176 (87,13%) relataram despesas para alimentação, 12 (5,94%) pagavam cuidadores para os outros filhos no dia da consulta e 80 (39,6%) referiram perda do pagamento do dia de trabalho. Dos casos de alta complexidade, 9,33% das mães entrevistadas abriram mão de exercer atividade remunerada regular. As despesas com transporte para uma consulta em cirurgia pediátrica em um hospital de referência do Rio de Janeiro custam em média 4,42% do salário mínimo vigente, com uma média de 217,32 minutos de deslocamento por consulta. Despesas com alimentação e perda de remuneração pela ausência no trabalho também implicam encargos financeiros ou perda de remuneração significativos para o paciente em cada consulta.

In this study, we investigated the costs of transportation for each outpatient consultation in patients referred to specialized surgical evaluation in a tertiary hospital in Rio de Janeiro, Brazil. Descriptive study with guardians of pediatric patients scheduled for pediatric surgery, questioning transportation cost, and opportunity costs (loss of remuneration, food, payment of caregivers for other children, expenses for other companions). About half patients were aged up to five years; about two thirds had diseases of simple and definitive surgical resolution; and 181 families (89.17%) presented monthly family income up to BRL 1,999.00. The proportion of families that benefited from free transportation ranged from 4.26% to 15.56% for patients living up to 100 km away from the hospital (45.83% for patients living more than 100 km away from the institution). A total of 176 (87.13%) guardians reported expenses buying food, 12 (5.94%) paid caregivers to the other children on the day of the consultation, and 80 (39.6%) reported loss of remuneration for the working day. Among the high complexity cases, 9.33% of the mothers have given up their regular paid employment. Transportation expenses for a pediatric surgery consultation at a reference hospital in Rio de Janeiro cost about 4.42% of the current minimum wage, spending around 217.32 minutes of displacement/consultation. Expenses with food and loss of remuneration due to absence at work also entail significant financial charges or loss of remuneration for the patient at each consultation.

En esta investigación se estudiaron los costes de transporte por visita ambulatoria en pacientes remitidos para evaluación quirúrgica especializada en un hospital de atención terciaria en Río de Janeiro, Brasil. Es un estudio descriptivo con responsables de pacientes pediátricos programados para consulta de cirugía pediátrica, en el que se cuestionaron factores relacionados con el coste del transporte y los costes de oportunidad (pérdida de remuneración, alimentación, pago de cuidadores de otros niños, gastos de otros cuidadores). Aproximadamente la mitad de los pacientes tenían hasta 5 años de edad; cerca de 2/3 presentaban enfermedades de resolución quirúrgica simple y definitiva, 181 familias (89,17%) con renta familiar mensual de hasta BRL 1.999,00. La proporción de familias que se benefician de transporte gratuito varía entre el 4,26% y el 15,56% para los pacientes que viven hasta a 100 km del hospital (45,83% para los pacientes que viven a más de 100 km de la institución). Ciento setenta y seis (87,13%) cuidadores declaran gastos de alimentación, 12 (5,94%) pagan a los cuidadores de sus otros hijos en el día de la consulta y 80 (39,6%) declaran pérdida de salario por la jornada laboral. De los casos de alta complejidad, el 9,33% de las madres entrevistadas habían abandonado su actividad remunerada habitual. Los gastos de transporte para una consulta de cirugía pediátrica en un hospital de referencia de Río de Janeiro cuestan de media el 4,42% del salario mínimo vigente, con una media de 217,32 minutos de tiempo de viaje/consulta. Los gastos de alimentación y la pérdida de salario por ausencia en el trabajo también implican una importante carga económica o pérdida de salario para el paciente en cada cita.

Avaliação do crescimento de crianças escolares / Assessing schoolchildren's growth / Evaluación del crecimiento de los niños em edad escolar

Objetivo: avaliar o crescimento de crianças do ensino fundamental matriculadas em uma escola pública no município de Macaé, Rio de Janeiro. Método: estudo transversal de abordagem quantitativa. Participaram da pesquisa 217 escolares com idades entre seis e 14 anos. A análise de dados foi feita pelo software RStudio® e o Teste de Exato de Fisher foi utilizado, considerando índice de confiança de 95%. Protocolo de pesquisa aprovado pelo Comitê de Ética em Pesquisa. Resultado: no turno matutino, identificou-se que o segundo ano apresentou uma maior proporção de crianças com peso adequado para idade (90,48%). No turno vespertino, a maior proporção de crianças com IMC adequado para idade está no primeiro ano (83,33%). Na relação IMC/idade, identificou-se diferença estatística significativa entre os alunos do quinto ano manhã/tarde (p-valor=0,0278). Conclusão: os resultados apontam a necessidade de uma orientação/educação alimentar e em saúde para as crianças e suas famílias, a fim de obter um crescimento mais adequado para a idade.

Objective: to evaluate the growth of lower secondary school children at a public school in the town of Macaé, Rio de Janeiro. Method: in this quantitative, cross-sectional study of 217 schoolchildren between six and 14 years old, the data were analyzed using RStudio® software and Fisher's Exact Test was used, to a 95% confidence level. The research protocol was approved by the research ethics committee. Result: in the morning shift, the second year was found to have the highest proportion (90.48%) of children with weight appropriate to their age. In the afternoon shift, the highest proportion of children with BMI appropriate to their age was found in the first year (83.33%). A statistically significant difference in the relationship BMI-to-age was found between morning and afternoon fifth-year students (p-value of 0.0278). Conclusion: the results point to the need for nutritional and health guidance and education for children and their families, in order to foster growth more appropriate to their age.

Objetivo: evaluar el crecimiento de niños en edad escolar matriculados en una escuela pública de la ciudad de Macaé, Rio de Janeiro. Método: estudio transversal con enfoque cuantitativo. Participaron en la investigación un total de 217 niños con edades comprendidas entre seis y 14 años. El análisis de los datos se realizó mediante el software RStudio® y se utilizó la Prueba Exacta de Fisher, considerando un nivel de confianza del 95%. El protocolo de investigación fue aprobado por el Comité de Ética en Investigación. Resultado: en el turno de la mañana se encontró que el segundo año tuvo mayor proporción de niños con peso adecuado para su edad (90,48%). En el turno de la tarde, la mayor proporción de niños con un IMC adecuado para su edad se encuentra en el primer año (83,33%). En la relación entre el IMC y la edad, se identificó una diferencia estadísticamente significativa entre los estudiantes de quinto año de la mañana/tarde (P-valor de 0,0278). Conclusión: los resultados apuntan hacia la necesidad de orientación/educación nutricional y en salud a niños y familias, para obtener un crecimiento más adecuado respecto a su edad.