RESUMO
[This corrects the article DOI: 10.3389/fpsyg.2023.1194294.].
RESUMO
Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity. Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level. Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1, and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels. Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.
Assuntos
Artrite Juvenil , Perfilação da Expressão Gênica , Inflamação , Monócitos , Transcriptoma , Adulto , Criança , Feminino , Humanos , Anticorpos Antiproteína Citrulinada , Artrite Juvenil/classificação , Artrite Juvenil/genética , Artrite Juvenil/imunologia , Artrite Juvenil/patologia , Estudos de Casos e Controles , Doença Crônica , Análise por Conglomerados , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Mediadores da Inflamação/imunologia , Interferon gama/imunologia , Monócitos/imunologia , Monócitos/metabolismo , Fenótipo , Medicina de Precisão , Pré-Menopausa , Ligação Proteica , Mapas de Interação de Proteínas , Fator Reumatoide , Análise de Sequência de RNA , Transcriptoma/genética , Fator de Necrose Tumoral alfa/imunologia , Aprendizado de Máquina não SupervisionadoRESUMO
Modern insects have inhabited the earth for hundreds of millions of years, and part of their successful adaptation lies in their many reproductive strategies. Insect reproduction is linked to a high metabolic rate that provides viable eggs in a relatively short time. In this context, an accurate interplay between the endocrine system and the nutrients synthetized and metabolized is essential to produce healthy offspring. Lipids guarantee the metabolic energy needed for egg formation and represent the main energy source consumed during embryogenesis. Lipids availability is tightly regulated by a complex network of endocrine signals primarily controlled by the central nervous system (CNS) and associated endocrine glands, the corpora allata (CA) and corpora cardiaca (CC). This endocrine axis provides hormones and neuropeptides that significatively affect tissues closely involved in successful reproduction: the fat body, which is the metabolic center supplying the lipid resources and energy demanded in egg formation, and the ovaries, where the developing oocytes recruit lipids that will be used for optimal embryogenesis. The post-genomic era and the availability of modern experimental approaches have advanced our understanding of many processes involved in lipid homeostasis; therefore, it is crucial to integrate the findings of recent years into the knowledge already acquired in the last decades. The present chapter is devoted to reviewing major recent contributions made in elucidating the impact of the CNS/CA/CC-fat body-ovary axis on lipid metabolism in the context of insect reproduction, highlighting areas of fruitful research.
RESUMO
BACKGROUND: Juvenile idiopathic arthritis (JIA) comprises a whole spectrum of chronic arthritis starting before 16 years of age. The study aims to explore the clinical and demographic descriptors, treatment, and disease progression of enthesitis-related arthritis (ERA) in comparison with juvenile-onset spondyloarthritis (SpA). METHODS: Cross-sectional analysis of consecutive patients in two dedicated clinics, with a single visit and retrospective case-notes review. Arthritis, enthesitis and sacroiliitis were evaluated by scoring disease activity and damage. Continuous variables were reported by median, interquartile range; categorical variables were reported by the frequency comparison of the two groups. RESULTS: Thirty-three cases were included, being 23 (69.7%) with ERA. The median age at diagnosis was 12.5 y (SpA) vs. 9 y (ERA) (p < 0.01); the time from symptom onset to diagnosis was 5.5 y (SpA) vs. 1.5 y (ERA) (p < 0.03). In both groups, the predominant presentation was a single joint or < 5 lower limb joints and asymmetric involvement, with a high frequency of enthesitis. There was a higher frequency of mid-tarsal and ankle synovitis in the ERA group and hip involvement in those with SpA. The comparison of the frequency of spine symptoms at presentation, 30% SpA vs. 21.7% ERA (p = 0.7), was not significant, and radiographic progression to spinal involvement occurred in 43.5% of ERA patients. The median time for spinal progression and age at onset was 2.2 and 12 y for ERA, and 4 and 16.5 y for SpA, respectively. Activity and damage scores were not significantly different between the groups. Treatment comparison resulted in 91.3% of ERA and 100% SpA being treated, predominantly with NSAIDs in both groups, followed by DMARDs and biologics, with a higher frequency of biologics in SpA. CONCLUSION: The main differences were the late diagnoses of SpA, and the hip and spine involvement, with higher frequency of biologic treatment in juvenile-onset SpA compared to ERA.
Assuntos
Antirreumáticos , Artrite Juvenil , Progressão da Doença , Espondilartrite , Humanos , Estudos Transversais , Artrite Juvenil/complicações , Artrite Juvenil/tratamento farmacológico , Artrite Juvenil/diagnóstico , Criança , Adolescente , Feminino , Masculino , Estudos Retrospectivos , Espondilartrite/complicações , Espondilartrite/tratamento farmacológico , Espondilartrite/diagnóstico , Antirreumáticos/uso terapêutico , Entesopatia/etiologia , Entesopatia/diagnóstico por imagem , Sacroileíte/diagnóstico por imagem , Idade de Início , AdultoRESUMO
Background: Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement. Methods: Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels. Results: Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls. Conclusion: This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.
Assuntos
Dermatomiosite , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Anticorpos Antinucleares , Apoptose , Proteína X Associada a bcl-2 , Caspase 3 , Dermatomiosite/complicações , Células Matadoras Naturais , Receptores Tipo I de Fatores de Necrose TumoralRESUMO
The care of adolescents in reclusion has been a field of work for occupational therapists in different parts of the world. The objective of this study was to describe and analyze Brazilian occupational therapists' practices with adolescents in reclusion. Research conducted in Brazil, identifying 56 professionals, invited to answer a questionnaire (n = 43); participate in discussion groups (n = 9); and interview (n = 4). Professionals reported different visions that guide their practices, including the identification of individual skills and the profession's possibilities for social action. Occupational therapists have specificities to work in these institutions, highlighting the possibilities of acting with a focus on social change. Practices in occupational therapy can lead to social change if focused on social issues. Social occupational therapy offers theoretical and methodological elements that inform the profession. Reflections on the practice carried out, according to a critical perspective, enable a performance in occupational therapy that intends social change.
OBJECTIVE: The objective was to describe and analyze the practice of occupational therapists in custodial units of the Brazilian juvenile justice system. METHODOLOGY: Mapping and identification of occupational therapists in institutions of juvenile incarceration; questionnaire; workshops; semi-structured interviews; and synthesis meeting. RESULTS AND DISCUSSION: Forty-three professionals with diverse practices participated in this study. The collected data in the different stages of the research were analyzed based on social occupational therapy. CONCLUSION: Occupational therapy practices can lead to social change if focused on social issues. Social occupational therapy offers theoretical and methodological elements for that.
Occupational Therapy and Imprisoned Adolescents: An Analysis of Professional PracticesIntroduction: In Brazil, the number of adolescents convicted of infractions is increasing. Judicial sanctions may be imposed on this population, including imprisonment. There are occupational therapists working with these adolescents, but their practices are little recorded and debated.
RESUMO
In 2007, Mexico implemented a strategy to combat drug trafficking through military intervention, after which a significant increase in homicides, mainly among young men, was observed and linked to structural problems as well as organized crime, especially the recruitment of youth, with adolescents being particularly vulnerable. Through a systematic review of the literature from 2013 to 2022, we have compiled the reported factors influencing the recruitment of adolescents by organized crime in Mexico and conducted a metasynthesis of the data according to the multiple levels that affect adolescents: individual, family, community, cultural, and social. This research has shown that many of the factors reported are interrelated and need to be studied holistically. In addition, many of the factors are common to other forms of juvenile delinquency, but the main difference is the presence of organized crime itself in the community and culture.
RESUMO
Hemophagocytic lymphohistiocytosis (HLH) is a rare genetic hyperinflammatory syndrome that occurs early in life. Macrophage activation syndrome (MAS) usually refers to a secondary form of HLH associated with autoimmunity, although there are other causes of secondary HLH, such as infections and malignancy. In this article, we reviewed the concepts, epidemiology, clinical and laboratory features, diagnosis, differential diagnosis, prognosis, and treatment of HLH and MAS. We also reviewed the presence of MAS in the most common autoimmune diseases that affect children. Both are severe diseases that require prompt diagnosis and treatment to avoid morbidity and mortality.
Assuntos
Doenças Autoimunes , Linfo-Histiocitose Hemofagocítica , Síndrome de Ativação Macrofágica , Criança , Humanos , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/etiologia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/complicações , Doenças Autoimunes/complicações , Diagnóstico DiferencialRESUMO
OBJECTIVES: To understand the burden associated with pediatric chronic pain (CP) on the health care system compared with other costly chronic diseases prior to subspecialty care. STUDY DESIGN: In this retrospective cohort study, we assessed all-cause health care utilization and direct health care costs associated with pediatric CP (n = 91) compared with juvenile arthritis (n = 135), inflammatory bowel disease (n = 90), type 1 diabetes (n = 475) or type 2 diabetes (n = 289), anxiety (n = 7193), and controls (n = 273) 2 and 5 years prior to patients entering subspecialty care in Manitoba, Canada. Linked data from physician encounters, emergency department visits, hospitalizations, and prescriptions were extracted from administrative databases. Differences in health care utilization and direct health care costs associated with CP vs the other conditions were tested using negative binomial and zero-inflated negative binomial regression models, respectively. RESULTS: After adjustment for age at diagnosis, sex, location of residence, and socioeconomic status, CP continued to be associated with the highest number of consulted physicians and subspecialists and the highest number of physician billings compared with all other conditions (P < .01, respectively). CP was significantly associated with higher physician costs than juvenile arthritis, inflammatory bowel disease, type 1 diabetes, type 2 diabetes, or controls (P < .01, respectively); anxiety was associated with the highest physician and prescription costs among all cohorts (P < .01, respectively). CONCLUSION: Compared with chronic inflammatory and endocrinologic conditions, pediatric CP and anxiety were associated with substantial burden on the health care system prior to subspecialty care, suggesting a need to assess gaps and resources in the management of CP and mental health conditions in the primary care setting.
Assuntos
Dor Crônica , Custos de Cuidados de Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Criança , Masculino , Feminino , Estudos Retrospectivos , Custos de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Dor Crônica/economia , Dor Crônica/terapia , Pré-Escolar , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/economia , Estudos de Coortes , Doença Crônica , Manitoba , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/economia , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/economia , Artrite Juvenil/economia , Artrite Juvenil/terapia , Ansiedade/epidemiologiaRESUMO
Microplastics, considered emerging environmental contaminants resulting from plastic degradation, are discovered in diverse aquatic ecosystems and can be unintentionally ingested by fish. Therefore, it is essential to characterize their interaction with other contaminants, such as agrochemicals, in aquatic environments. This study aimed to assess histological, enzymatic, and genotoxic biomarkers in juvenile pacú (Piaractus mesopotamicus) exposed to polyethylene (PE) microplastic particles and the herbicide atrazine, individually or combined, for 15 days. Four treatments were used: a negative control (CON), PE in the fish diet (0.1% w/w, FPE), atrazine through water (100 µg L-1, ATZ), and the mixture (ATZ+FPE). Results confirmed histological alterations in gills (edema and lamellar fusion) and liver (necrotic areas and congestion) of fish exposed to ATZ and ATZ+FPE. The number of goblet cells increased in the posterior intestine of fish under ATZ+FPE compared to CON and FPE. Enzyme activities (CAT, GST, AChE, and BChE) significantly increased in ATZ+FPE compared to CON. However, no genotoxic effect was demonstrated. These findings provide insights into the complex impacts of simultaneous exposure to atrazine and microplastics, emphasizing the need for continued research to guide effective environmental management strategies against these contaminants that represent a risk to aquatic organisms.