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BackgroundKawasaki disease (KD) is the leading cause of acquired heart disease in children. The major challenge in KD diagnosis is that it shares clinical signs with other childhood febrile control (FC) subjects. We sought to determine if our algorithmic approach applied to a Taiwan cohort.MethodsA single center (Chang Gung Memorial Hospital in Taiwan) cohort of patients suspected with acute KD were prospectively enrolled by local KD specialists for KD analysis. Our previously single-center developed computer-based two-step algorithm was further tested by a five-center validation in US. This first blinded multi-center trial validated our approach, with sufficient sensitivity and positive predictive value, to identify most patients with KD diagnosed at centers across the US. This study involved 418 KDs and 259 FCs from the Chang Gung Memorial Hospital in Taiwan.FindingsOur diagnostic algorithm retained sensitivity (379 of 418; 90.7%), specificity (223 of 259; 86.1%), PPV (379 of 409; 92.7%), and NPV (223 of 247; 90.3%) comparable to previous US 2016 single center and US 2020 fiver center results. Only 4.7% (15 of 418) of KD and 2.3% (6 of 259) of FC patients were identified as indeterminate. The algorithm identified 18 of 50 (36%) KD patients who presented 2 or 3 principal criteria. Of 418 KD patients, 157 were infants younger than one year and 89.2% (140 of 157) were classified correctly. Of the 44 patients with KD who had coronary artery abnormalities, our diagnostic algorithm correctly identified 43 (97.7%) including all patients with dilated coronary artery but one who found to resolve in 8 weeks.InterpretationThis work demonstrates the applicability of our algorithmic approach and diagnostic portability in Taiwan.

Background: Argonautes (AGOs) are a type of protein that degrade specific messenger RNAs, consequently reducing the expression of a specific gene. These proteins consist of small, single-stranded RNA or DNA and may provide a route for detecting and silencing complementary mobile genetic elements. In this research, we investigated which AGO(s) were involved in Kawasaki disease (KD). Methods and Materials: We obtained mRNA-level gene expression profiles from leukocyte samples that had previously been gathered in another study and uploaded to the NCBI GEO database. The Human Transcriptome Array (HTA 2.0) analysis included 50 children with KD prior to IVIG (KD1), 18 children with KD three weeks post-IVIG (KD3), 18 non-febrile controls (HC), and 18 febrile controls (FC), which were arranged in the quoted publications for all materials and methods in order to collect data. We used the default value of the commercialized microarray tool Partek to perform an analysis of variance and determine any significant fold changes (KD1, KD3, HC, and FC individually). Results: The data revealed that the AGO2 and AGO4 genes displayed significant within-group differences with p = 0.034 and 0.007, respectively. In AGO2, significant differences were observed between KD1 vs. HC + FC with p = 0.034. KD1 appears higher than the other specimens in AGO4, with significant differences between KD1 and HC (p = 0.033), KD1 and FC (p = 0.033), KD1 and KD3 (p = 0.013), and KD1 and HC + FC (p = 0.007). We observed no substantial differences in AGO1 or AGO3 (p > 0.05). There were no significant differences between AGO(s) and coronary artery lesions or intravenous immunoglobulin resistance. (p > 0.05) Conclusion: Endothelial cell inflammation and injury, two basic pathological mechanisms, are thought to be involved in coronary endothelial dysfunction in KD. AGO2 and AGO4 are likely to participate in the endothelial dysfunction of children with KD, with AGO4 potentially playing a key role, while AGO1 and AGO3 appear not to participate. [ABSTRACT FROM AUTHOR]

Introduction: Currently the diagnosis of Kawasaki disease is still heavily reliant on clinical criteria which may be subject to interpretation or mimic other common febrile diseases of childhood. Biomarkers that can aid in the accurate and timely diagnosis of KD are of great clinical utility. Areas covered: A literature search of PubMed was performed using the key words: Kawasaki disease, diagnosis, biomarkers, proteomics and transcriptomics. In this article we review biomarkers that are widely clinically available including NT-ProBNP and ferritin. We also include promising novel biomarkers that have been identified through newer transcriptomic and proteomic techniques. Expert opinion: While the identification of biomarkers that can accurately assist in diagnosing patients with KD is a promising field of research, more still remains to be done to in order to validate new biomarkers in larger cohorts, and to set standardized cutoff values for potential biomarkers that are currently clinically available. Further research is needed before KD biomarkers that are consistent, readily available, and cost-effective can be a clinical reality. [ABSTRACT FROM AUTHOR]

We conducted a 12-week randomized double-blind placebo-controlled clinical trial to investigate the potential impact of Bifidobacterium bifidum (Bf-688) supplementation on attention-deficit/hyperactivity disorder (ADHD). Children with ADHD who were already receiving a stable dose of methylphenidate (MPH) treatment were enrolled and were randomly assigned to two groups: one receiving add-on Bf-688 (daily bacterial count of 5 × 109 CFUs) (n = 51) and the other receiving a placebo (n = 51). All participants underwent assessments using Conners' Continuous Performance Test (CPT) and Conners' Continuous Auditory Test of Attention (CATA). Additionally, fecal samples were collected at the beginning of the trial (week 0) and at the endpoint (week 12). Remarkably, the group receiving Bf-688 supplementation, but not the placebo group, exhibited significant improvements in omission errors in CPT as well as Hit reaction time in both CPT and CATA. Gut microbiome analysis revealed a significant increase in the Firmicutes to Bacteroidetes ratio (F/B ratio) only in the Bf-688 group. Furthermore, we identified significant negative correlations between N-Glycan biosynthesis and Hit reaction time in both CPT and CATA. Our results demonstrate that the probiotic Bf-688 supplement can enhance neuropsychological performance in children with ADHD, possibly by altering the composition of the gut microbiota, ultimately leading to reduced N-Glycan biosynthesis. [ABSTRACT FROM AUTHOR]

Background: Kawasaki disease (KD) is a syndrome primarily affecting young children, typically under the age of five, and is characterized by the development of acute vasculitis. Through extensive research conducted on both murine and human subjects, it has been demonstrated that heightened levels of reactive oxygen species (ROS) play a pivotal role in the development of KD, especial coronary artery lesions (CALs). Hydrogen gas exhibits potent antioxidant properties that effectively regulate ROS production and the inflammatory response. Methods: We used Lactobacillus casei cell wall extract (LCWE)-induced vasculitis in mice as an animal model of KD and treated the mice with hydrogen gas inhalation. Results: We observed significant dilatation and higher Z scores in the left coronary artery (LCA) in D21 and D28 in mice after LCWE treatment compared to the control group (p < 0.001) and a significant resolution of LCA diameters (p < 0.01) and Z scores (p < 0.01) after treatment with inhaled hydrogen gas. We further demonstrated that serum IL-6 expression was higher in mice after LCWE treatment (p < 0.01) and IL-6 significantly decreased after inhaled hydrogen gas therapy (p < 0.001). Conclusion: According to our literature review, this is the first report where hydrogen gas inhalation has been demonstrated to be effective for the treatment of coronary artery dilatation in a KD murine model. [ABSTRACT FROM AUTHOR]

The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31)). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.