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BACKGROUND: The association of soluble suppression of tumorigenesis-2 (sST2) levels with prognosis in pulmonary embolism (PE) is unknown. OBJECTIVE: This study aimed to investigate the relationship between sST2 levels in patients with acute PE and 6-month mortality and recurrent hospitalizations. METHODS: This prospective study included 100 patients with acute PE. Patients were classified into two groups according to 6-month mortality and the presence of recurrent Cardiovascular-Related hospitalizations. Two groups were compared. A p-value of 0.05 was considered statistically significant. RESULTS: Soluble ST2 levels were significantly higher in the group with mortality and recurrent hospitalizations. (138.6 ng/mL (56.7-236.8) vs. 38 ng/mL (26.3-75.4); p<0.001) The best cut-off threshold for sST2 levels in the prediction of a composite outcome of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization was found to be >89.9 with a specificity of 90.6% and a sensitivity of 65.2%, according to the receiver operating characteristic curve (area under the curve = 0.798; 95% CI, 0.705-0.891; p <0.0001). After adjusting for confounding factors that were either statistically significant in the univariate analysis or for the variables correlated with the sST2 levels, sST2 level (OR = 1.019, 95% CI: 1.009-1.028, p 0.001) and C-reactive protein (CRP ) (OR = 1.010, 95% CI: 1.001-1.021, p = 0.046) continued to be significant predictors of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in the multiple logistic regression model via backward stepwise method. CONCLUSION: Soluble ST2 level seems to be a biomarker to predict 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in patients with acute PE.

FUNDAMENTO: A associação de supressão solúvel da tumorigênese-2 (sST2) com prognóstico em embolia pulmonar (EP) é desconhecida. OBJETIVO: Este estudo teve como objetivo investigar a relação entre os níveis de sST2 em pacientes com EP aguda e mortalidade em 6 meses e hospitalizações recorrentes. MÉTODOS: Este estudo prospectivo incluiu 100 pacientes com EP aguda. Os pacientes foram classificados em dois grupos de acordo com a mortalidade em 6 meses e a presença de hospitalizações recorrentes relacionadas a doenças cardiovasculares. Dois grupos foram comparados. Um valor de p de 0,05 foi considerado estatisticamente significativo. RESULTADOS: Os níveis de ST2 solúvel foram significativamente maiores no grupo com mortalidade e internações recorrentes. (138,6 ng/mL (56,7-236,8) vs. 38 ng/mL (26,3-75,4); p<0,001) O melhor limite de corte para níveis de sST2 na previsão de um desfecho composto de mortalidade em 6 meses e/ou a hospitalização recorrente relacionada a doenças cardiovasculares foi >89,9, com especificidade de 90,6% e sensibilidade de 65,2%, de acordo com a curva Receiver Operating Characteristic (área sob a curva = 0,798; IC 95%, 0,705­0,891; p <0,0001). Após ajuste para fatores de confusão que foram estatisticamente significativos na análise univariada ou para as variáveis correlacionadas com os níveis de sST2, nível de sST2 (OR = 1,019, IC 95%: 1,009-1,028, p 0,001) e proteína C reativa (PCR). (OR = 1,010, IC 95%: 1,001-1,021, p = 0,046) continuaram a ser preditores significativos de mortalidade em 6 meses e/ou hospitalização recorrente relacionada a doenças cardiovasculares no modelo de regressão logística múltipla através do método backward stepwise. CONCLUSÕES: O nível de ST2 solúvel parece ser um biomarcador para prever mortalidade em 6 meses e/ou hospitalização recorrente relacionada a doenças cardiovasculares em pacientes com EP aguda.

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BACKGROUND: Acinetobacter baumannii international clone II (IC2) is a widespread pandemic clone, however, it is rarely described in South America. The present study reported an outbreak caused by XDR IC2 strains in a clinical setting in Rio de Janeiro in 2022. METHODS: Molecular epidemiology analysis was conducted with MLST to determine the clonal relationship and to assign a sequence type. The antimicrobial resistance profile of A. baumannii strains was assessed by the disk-diffusion method and MIC determination, and the presence of antibiotic resistance genes was determined by PCR and Sanger sequencing. The whole genome of one representative strain (AB91) was sequenced to prospect its resistome and virulome. RESULTS: The MLST revealed that all strains belonged to the ST2 (Pasteur scheme) that corresponded to the pandemic IC2 lineage. They presented the XDR phenotype, which was compatible with their resistome composed of several acquired resistance genes and altered housekeeping genes. Additionally, an expressive virulome was revealed in AB91 genome. Genomic comparison with the unique other available IC2 genome from Brazil revealed that outbreaks occurring during (São Paulo - 2020/2021) and after (Rio de Janeiro - 2022) COVID-19 pandemics were caused by the same IC2 lineage. CONCLUSIONS: This study suggests that the presence of a huge arsenal of resistance and virulence genes may have contributed to the persistence and the successful establishment of IC2 in Brazilian clinical settings during and after the COVID-19 pandemics in response to a series of events, such as the antibiotic overused during that period.

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OBJECTIVES: Among the high-risk clones of Acinetobacter baumannii, called international clones (ICs), IC2 represents the main lineage causing outbreaks worldwide. Despite the successful global spread of IC2, the occurrence of IC2 is rarely reported in Latin America. Here, we aimed to evaluate the susceptibility and genetic relatedness of isolates from a nosocomial outbreak in Rio de Janeiro/Brazil (2022) and perform genomic epidemiology analyses of the available genomes of A. baumannii. METHODS: Sixteen strains of A. baumannii were subjected to antimicrobial susceptibility tests and genome sequencing. These genomes were compared phylogenetically with other IC2 genomes from the NCBI database, and virulence and antibiotic resistance genes were searched. RESULTS: The 16 strains represented carbapenem-resistant A. baumannii (CRAB) with an extensively drug-resistant profile. In silico analysis established the relationship between the Brazilian CRAB genomes and IC2/ST2 genomes in the world. The Brazilian strains belonged to three sub-lineages, associated with genomes from countries in Europe, North America, and Asia. These sub-lineages presented three distinct capsules, KL7, KL9, and KL56. The Brazilian strains were characterised by the co-presence of blaOXA-23 and blaOXA-66, in addition to the genes APH(6), APH(3"), ANT(3"), AAC(6'), armA, and the efflux pumps adeABC and adeIJK. A large set of virulence genes was also identified: adeFGH/efflux pump; the siderophores barAB, basABCDFGHIJ, and bauBCDEF; lpxABCDLM/capsule; tssABCDEFGIKLM/T6SS; and pgaABCD/biofilm. CONCLUSION: Widespread extensively drug-resistant CRAB IC2/ST2 is currently causing outbreaks in clinical settings in southeastern Brazil. This is due to at least three sub-lineages characterised by an enormous apparatus of virulence and resistance to antibiotics, both intrinsic and mobile.

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Third molar extraction surgery is a frequentprocedure in dentistry. Like any surgical procedure, it may lead to inflammatory responses, and postoperative pain is one of its main complications. Furthermore, temporomandibular disorder (TMD) is a collective termfor several clinicalproblems involving orofacial structures. Patients withparafunction are more sensitive to mechanical stimuli such as pressure during surgical procedures. Aim: To analyze postoperative pain in patients with and without bruxism subjected to third molar extraction surgery. Materials and Method: This was an observational study including four groups with a 1:1:1:! allocation ratio, conducted following ethical approval. Patients classified as ASA I with an indication for lower third molar extraction were recruited. Bruxism was self-reported. Two surgical techniques were used: one with only forceps and levers (ST1) and another with osteotomy and odontosection (ST2). Results: Four groups (bruxism and surgical techniques) were enrolled, each with a convenience sample (n=34). Postoperative pain levels were higher in patients with than without bruxism (p<0.05). The comparison between surgical techniques showed significantly higher pain levels only on the seventh day for ST2 groups (p<0.05). Oral mucosaflap incisions did not cause significantly higher persistence and pain levels. Conclusions: Bruxism, osteotomy, and odontosection may have increased postoperative pain levels, whereas performing an oral mucosa flap did not cause significant differences. Nevertheless, these preliminary data should be interpreted carefully. Randomized controlled trials are required to reinforce the findings of this study.

A cirurgia de extragao de terceiros molares é um procedimento frequente na odontologia. Como em qualquer procedimento cirúrgico, pode levar a respostas inflamatorias. A dor pós-operatória é uma das principais complicagoes após a cirurgia de extragao de terceiros molares. Além disso, disfungao temporomandibular (DTM) é um termo coletivo para vários problemas clínicos envolvendo estruturas orofaciais. Pacientes com parafungao sao mais sensíveis a estímulos mecánicos como pressao durante procedimentos cirúrgicos. Objetivo: Analisar a dor pós-operatória em pacientes com e sem bruxismo submetidos á cirurgia de extragao de terceiros molares. Material e Método: Um estudo observacional incluindo quatro grupos com uma proporgao de alocagao de 1:1:1:1 foi realizado após aprovagao ética. Foram recrutados pacientes classificados como ASA I com indicagao de exodontia de terceiros molares inferiores. O bruxismo foi autorreferido e foram realizadas duas técnicas cirúrgicas: uma com apenas fórceps e alavancas (ST1) e outra com osteotomia e odontosecgao (ST2). Resultados: Foram incluidos quatro grupos (bruxismo e técnicas cirúrgicas), cada um com uma amostra de conveniencia (n=34). Os níveis de dor pós-operatória foram maiores em pacientes com bruxismo (p<0,05). A comparagao entre as técnicas cirúrgicas mostrou níveis de dor significativamente maiores apenas no sétimo diapara os grupos ST2 (p<0,05). Incisoes de retalhos de mucosa oral nao mostraram níveis de dor significativamente maiores. Conclusoes: Bruxismo, osteotomia e odontosecgaopodem aumentar os níveis de dor pós-operatória, enquanto a realizagao de retalho de mucosa oral nao apresenta diferengas significativas. No entanto, a interpretagao cuidadosa desses dados preliminares é recomendada, e ensaios clínicos randomizados sao necessários para fortalecer os achados deste estudo.

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Schistosoma mansoni eggs retained in host tissues induce innate cytokine release, contributing to the induction of Type-2 immune responses and granuloma formation, important to restrain cytotoxic antigens, but leading to fibrosis. Interleukin(IL)-33 participates in experimental models of inflammation and chemically induced fibrosis, but its role in S. mansoni-induced fibrosis is still unknown. To explore the role of the IL-33/suppressor of the tumorigenicity 2 (ST2) pathway, serum and liver cytokine levels, liver histopathology, and collagen deposition were comparatively evaluated in S. mansoni-infected wild-type (WT) and IL-33-receptor knockout (ST2-/-) BALB/c mice. Our data show similar egg counts and hydroxyproline in the livers of infected WT and ST2-/- mice; however, the extracellular matrix in ST2-/- granulomas was loose and disorganised. Pro-fibrotic cytokines, such as IL-13 and IL-17, and the tissue-repairing IL-22 were significantly lower in ST2-/- mice, especially in chronic schistosomiasis. ST2-/- mice also showed decreased α-smooth muscle actin (α-SMA) expression in granuloma cells, in addition to reduced Col III and Col VI mRNA levels and reticular fibres. Therefore, IL-33/ST2 signalling is essential for tissue repairing and myofibroblast activation during S. mansoni infection. Its disruption results in inappropriate granuloma organisation, partly due to the reduced type III and VI collagen and reticular fibre formation.

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The Interleukin (IL)-33 is important in several inflammatory diseases and its cellular receptor is the Interleukin 1 receptor-like 1 (IL1RL1), also called suppression of tumorigenicity 2 ligand (ST2L). This study investigated associations between single nucleotide variants (SNVs) in the IL33 gene and in the IL1RL1 (ST2) gene with periodontitis. Additionally, aimed to determine the role of Aggregatibacter actinomycetemcomitans (Aa) relative amount in the subgingival biofilm in these associations. A cross-sectional study was carried out with 506 individuals that answered a structured questionnaire used to collect their health status, socioeconomic-demographic, and behavioral characteristics. Periodontal examination was performed to determine the presence and severity of periodontitis, and subgingival biofilm samples were collected to quantify the relative amount of Aa by real time polymerase chain reaction. Human genomic DNA was extracted from whole blood cells and SNV genotyping was performed. Logistic regression estimated the association measurements, odds ratio (OR), and 95% confidence interval (95%CI), between the IL33 and ST2 genes with periodontitis, and subgroup analyses assessed the relative amount of Aa in these associations. 23% of individuals had periodontitis. Adjusted measurements showed a statistically significant inverse association between two SNVs of the ST2; rs148548829 (C allele) and rs10206753 (G allele). These two alleles together with a third SNV, the rs11693204 (A allele), were inversely associated with moderate periodontitis. One SNV of the IL33 gene also showed a statistically significant inverse association with moderate periodontitis. Nine SNVs of the ST2 gene were inversely associated with the relative amount of Aa. In the high Aa subgroup, there was a direct association between 11 SNVs of the ST2 gene and moderate periodontitis and two SNVs of the ST2 gene and severe periodontitis, and eight SNVs of the ST2 gene and periodontitis. These exploratory findings of genetic variants in IL-33/ST2 axis support the concept that the different tissue responses among individuals with periodontitis may be modulated by the host's genetics, influencing the physiopathology of the disease.

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When discovered in the early 2000s, interleukin-33 (IL-33) was characterized as a potent driver of type 2 immunity and implicated in parasite clearance, as well as asthma, allergy, and lung fibrosis. Yet research in other models has since revealed that IL-33 is a highly pleiotropic molecule with diverse functions. These activities are supported by elusive release mechanisms and diverse expression of the IL-33 receptor, STimulation 2 (ST2), on both immune and stromal cells. Interestingly, IL-33 also supports type 1 immune responses during viral and tumor immunity and after allogeneic hematopoietic stem cell transplantation. Yet the IL-33-ST2 axis is also critical to the establishment of systemic homeostasis and tissue repair and regeneration. Despite these recent findings, the mechanisms by which IL-33 governs the balance between immunity and homeostasis or can support both effective repair and pathogenic fibrosis are poorly understood. As such, ongoing research is trying to understand the potential reparative and regulatory versus pro-inflammatory and pro-fibrotic roles for IL-33 in transplantation. This review provides an overview of the emerging regenerative role of IL-33 in organ homeostasis and tissue repair as it relates to transplantation immunology. It also outlines the known impacts of IL-33 in commonly transplanted solid organs and covers the envisioned roles for IL-33 in ischemia-reperfusion injury, rejection, and tolerance. Finally, we give a comprehensive summary of its effects on different cell populations involved in these processes, including ST2 + regulatory T cells, innate lymphoid cell type 2, as well as significant myeloid cell populations.

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Salmonella Heidelberg is a clinically-important serovar linked to food-borne illness, and commonly isolated from poultry products. Since 1962, Salmonella Heidelberg has been widely reported from poultry production systems in several countries, including Brazil. The emergence of multidrug-resistant (MDR) Salmonella Heidelberg strains in food animals underscores a significant food safety hazard. In our study, we performed antimicrobial susceptibility testing (AST) and Whole-genome sequencing (WGS) to identify the antimicrobial resistance (AMR) genes, pathogenicity mechanisms and virulence factors (VF) in Salmonella Heidelberg E2 strain recovered from a chicken carcass in Southern Brazil. Salmonella Heidelberg strain belonged to ST15 and showed to be susceptible to colistin (MIC ≤2 µg/mL) and multidrug-resistant to amoxicillin-clavulanic acid, gentamicin, ampicillin, cefaclor, cefazolin, ceftiofur, nalidixic acid, azithromycin, erythromycin, doxycycline, tetracycline and sulfonamide. We identified AMR genes mediating resistance to aminoglycosides (aac(6')-Iaa, aac(3)-VIa, aph(3')-Ia, aadA, 16S rrsD), ß-lactams (blaCTX-M-2), quinolones (parC), macrolides (acrB), tetracyclines (tet(A)), fosfomycin (fosA7) and sulfonamide (sul1). Interestingly, the mutation in parC T255S has never been reported among Salmonella Heidelberg strains. To our knowledge, this is the first report of a Salmonella enterica strain harbouring 16S rrsD 471G > A, acrB F28L and acrB L40P chromosomal point mutations. Three plasmid replicon types, ST2-IncHI2, ST2-IncHI2A and IncX1 were identified. Nine Salmonella Pathogenicity Islands and 98 virulence genes encoding virulence factors were identified associated with cell adhesion, invasion, intracellular survival and resistance to antimicrobial peptides. Although Salmonella Heidelberg E2 strain likely originated from poultry, cross-contamination during meat processing cannot be excluded. This study adds to our understanding of Salmonella Heidelberg transmission along the food-chain and informs ongoing regulatory discussions on Salmonella Heidelberg in poultry.

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Type 2 Innate lymphoid cells (ILC2s) are tissue-resident immune cells activated by epithelial-derived alarmins upon tissue damage. They regulate immunity against helminth parasites and allergies by expressing type 2 immune response cytokines including IL-9, known to be critical for inducing and potentiating the immune response in such context. Although ILC2s are reported to be the main source of IL-9 in mice during N. brasiliensis infection, the mechanisms that regulate the expression of IL-9 in these cells are yet to be described. Recent studies have shown that in addition to cytokines, multiple molecules can differentially modulate the functions of ILC2s in various contexts both in vitro and in vivo. Among these stimuli are lipid mediators and neuropeptides, which activate the PKA pathway and have been associated with the regulation of type 2 immune cytokines. In this work we found that ILC2s in mice infected with N. brasiliensis can be classified into different groups based on the expression of IL-9 and ST2. These distinct populations were distributed in the lung and the small intestine. Through the development of an in vitro culture system, we sought to determine the stimuli that regulate the expression of these markers in ILC2s. We identified the alarmin IL-33 as being a key player for increased IL-9 expression. Additionally, we found the PKA pathway to be a dual regulator of ILC2 cells, working synergistically with IL-33 to enhance IL-9 production and capable of modulating proliferation and the expression of ILC2 markers. These data provide further evidence of a high heterogeneity between ILC2 subsets in a context dependent manner and calls for careful consideration when choosing the markers to identify these cells in vivo. Distinguishing ILC2 subsets and dissecting their mechanisms of activation is critical for a deeper understanding of the biology of these cells, allowing their manipulation for therapeutic purposes.

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BACKGROUND: Obesity is a chronic complex disease with great prevalence for children all over the world. Characterized for low-grade inflammation associated with several comorbidities such as resistance and type 2 diabetes mellitus (T2DM). OBJECTIVES: To investigate whether genetic variants in IL10, IL1RL1, IL1B, IRF4, TNF, IL6, and IL33 genes are associated with being overweight in children. METHODS: We performed the genotyping of 1004 children using Illumina 2.5 Human Omni bead chip, and association analysis on the genetic variants and the overweight through logistic regression adjusted for sex, age and components principal. RESULTS: Of the seven genes analyzed, 16 SNVs significantly associated. Eleven variants in IL1RL1, two in IL1B and one in IRF4 genes increased overweight risk and two SNVs in IL1RL1 were associated with protection against overweight. The rs2287047-A was negatively associated (OR: 0.66, CI95%: 0.19-0.45) and had a reduced IL1RL1 expression in whole blood (p 0.033) in silico eQTL. The rs12203592-T, in IRF4, was positively associated with being overweight, and led to an increased gene expression in whole blood (p < 0.001) and adipose tissue (p < 0.001). CONCLUSION: These results suggest that genetic variants in inflammatory genes may play an important role in the development of overweight in children.

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