Intra-articular corticosteroid utilization and characterizations of use in juvenile idiopathic arthritis within the PR-COIN registry.

Objective: Intra-articular corticosteroid injections (IACI) have been shown to be effective at improving arthritis across juvenile idiopathic arthritis (JIA) categories. The American College of Rheumatology (ACR) recommends IACI use as primary and adjunctive therapy for JIA patients. However, there remains minimal data describing actual IACI use in North America. The objective of this study was to describe and to evaluate IACI use in JIA, utilizing the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry. Methods: Study participants from 13 sites were enrolled in the PR-COIN registry from 2011 to 2015. Demographic and clinical variables were summarized and Chi-squared and t-tests were used to evaluate differences between participants who did or did not receive IACI. Multiple logistic regression models were used to evaluate characteristics associated with IACI treatment. Results: Our study included 3,241 participants, the majority of whom were white (85%), female (71%) and had oligoarticular JIA (39%). IACI was administered at least once in 23% of participants, the majority of whom had oligoarticular disease (52.5%), but overall use in oligoarticular participants was low at 30.8%. IACI use varied significantly between treatment centers and use was associated with oligoarticular disease, ANA positivity, and use of other systemic medications. Conclusion: This study demonstrates that participants with JIA enrolled in the PR-COIN registry between 2011 and 2015 with persistent oligoarticular disease, ANA positivity, and use of other systemic medications were more likely to receive IACI. However, IACI use was lower than expected for oligoarticular participants.

Altered effective connectivity of the default mode network in juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is associated with brain dysconnectivity in the default mode network (DMN). Most previous studies of patients with JME have assessed static functional connectivity in terms of the temporal correlation of signal intensity among different brain regions. However, more recent studies have shown that the directionality of brain information flow has a more significant regional impact on patients' brains than previously assumed in the present study. Here, we introduced an empirical approach incorporating independent component analysis (ICA) and spectral dynamic causal modeling (spDCM) analysis to study the variation in effective connectivity in DMN in JME patients. We began by collecting resting-state functional magnetic resonance imaging (rs-fMRI) data from 37 patients and 37 matched controls. Then, we selected 8 key nodes within the DMN using ICA; finally, the key nodes were analyzed for effective connectivity using spDCM to explore the information flow and detect patient abnormalities. This study found that compared with normal subjects, patients with JME showed significant changes in the effective connectivity among the precuneus, hippocampus, and lingual gyrus (p < 0.05 with false discovery rate (FDR) correction) with most of the effective connections being strengthened. In addition, previous studies have found that the self-connection of normal subjects' nodes showed strong inhibition, but the self-connection inhibition of the anterior cingulate cortex and lingual gyrus of the patient was decreased in this experiment (p < 0.05 with FDR correction); as the activity in these areas decreased, the nodes connected to them all appeared abnormal. We believe that the changes in the effective connectivity of nodes within the DMN are accompanied by changes in information transmission that lead to changes in brain function and impaired cognitive and executive function in patients with JME. Overall, our findings extended the dysconnectivity hypothesis in JME from static to dynamic causal and demonstrated that aberrant effective connectivity may underlie abnormal brain function in JME patients at early phase of illness, contributing to the understanding of the pathogenesis of JME. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09994-4.

The epigenetic determinants for systemic juvenile idiopathic arthritis phenotyping and treatment response.

BACKGROUND: Determining the role of epigenetics in systemic juvenile idiopathic arthritis (SJIA) provides an opportunity to explore previously unrecognized disease pathways and new therapeutic targets. AIM: We aimed to identify the clinical significance of microRNAs (miRNA-26a, miRNA-223) in SJIA. MATERIALS AND METHODS: This cross-sectional study was conducted on a group of children with SJIA attending to pediatric rheumatology clinic, at Mansoura University Children's Hospital (MUCH) from December 2021 to November 2022. Patient demographics, and clinical, and laboratory data were collected with the measurement of microRNAs by quantitative real-time PCR. The Mann-Whitney, Kruskal-Wallis, and Spearman correlation tests were used for variable comparison and correlations, besides the receiver operating characteristic (ROC) curve for microRNAs disease activity and treatment non-response discrimination. RESULTS: Forty patients were included in the study. On comparison of miRNA-26a, and miRNA-223 levels to the clinical, assessment measures, and laboratory features, miRNA-26a was statistically higher in cases with systemic manifestations versus those without. Similarly, it was higher in children who did not fulfill the Wallace criteria for inactive disease and the American College of Rheumatology (ACR) 70 criteria for treatment response. Meanwhile, miRNA-223 was not statistically different between cases regarding the studied parameters. The best cut-off value for systemic juvenile arthritis disease activity score-10 (sJADAS-10) and the ability of miRNA-26a, and miRNA-223 to discriminate disease activity and treatment non-response were determined by the (ROC) curve. CONCLUSION: The significant association of miRNA-26a with SJIA features points out that this molecule may be preferentially assessed in SJIA disease activity and treatment non-response discrimination.

Causal association of juvenile idiopathic arthritis or JIA-associated uveitis and gut microbiota: a bidirectional two-sample Mendelian randomisation study.

Background: The gut microbiota significantly influences the onset and progression of juvenile idiopathic arthritis (JIA) and associated uveitis (JIAU); however, the causality remains unclear. This study aims to establish a causal link between gut microbiota and JIA or JIAU. Methods: Using publicly available genome-wide association studies (GAWS) summary data, we conducted a two-sample Mendelian randomisation (MR) analysis employing various methods, namely inverse variance weighted (IVW), simple mode, weighted mode, weighted median and MR-Egger regression methods, to assess the causal association between JIA or JIAU and gut microbiota. Sensitivity analyses, including Cochrane's Q test, MR-Egger intercept test, leave-one-out analysis and MR-PRESSO, were performed to evaluate the robustness of the MR results. Subsequently, reverse MR analysis was conducted to determine causality between gene-predicted gut microbiota abundance and JIA or JIAU. Results: The MR analysis revealed a causal association between gut microbiota abundance variations and JIA or JIAU risk. Specifically, the increased abundance of genus Ruminococcaceae UCG013 (OR: 0.055, 95%CI: 0.006-0.103, p = 0.026) and genus Ruminococcaceae UCG003 (ß: 0.06, 95%CI: 0.003-0.117, p = 0.041) correlated with an increased risk of JIA, while genus Lachnospiraceae UCG001 (OR: 0.833, 95%CI: 0.699~0.993, p = 0.042) was associated with a reduced risk of JIA, among others. Sensitivity analysis confirmed MR analysis robustness. Conclusions: This study provides substantial evidence supporting a causal association between genetically predicted gut microbiota and JIA or JIAU. It highlights the significant role of intestinal flora in JIA or JIAU development, suggesting their potential as novel biomarkers for diagnosis and prevention. These findings offer valuable insights to mitigate the impact of JIA or JIAU.

Assessing disparities through missing race and ethnicity data: results from a juvenile arthritis registry.

Introduction: Ensuring high-quality race and ethnicity data within the electronic health record (EHR) and across linked systems, such as patient registries, is necessary to achieving the goal of inclusion of racial and ethnic minorities in scientific research and detecting disparities associated with race and ethnicity. The project goal was to improve race and ethnicity data completion within the Pediatric Rheumatology Care Outcomes Improvement Network and assess impact of improved data completion on conclusions drawn from the registry. Methods: This is a mixed-methods quality improvement study that consisted of five parts, as follows: (1) Identifying baseline missing race and ethnicity data, (2) Surveying current collection and entry, (3) Completing data through audit and feedback cycles, (4) Assessing the impact on outcome measures, and (5) Conducting participant interviews and thematic analysis. Results: Across six participating centers, 29% of the patients were missing data on race and 31% were missing data on ethnicity. Of patients missing data, most patients were missing both race and ethnicity. Rates of missingness varied by data entry method (electronic vs. manual). Recovered data had a higher percentage of patients with Other race or Hispanic/Latino ethnicity compared with patients with non-missing race and ethnicity data at baseline. Black patients had a significantly higher odds ratio of having a clinical juvenile arthritis disease activity score (cJADAS10) of ≥5 at first follow-up compared with White patients. There was no significant change in odds ratio of cJADAS10 ≥5 for race and ethnicity after data completion. Patients missing race and ethnicity were more likely to be missing cJADAS values, which may affect the ability to detect changes in odds ratio of cJADAS ≥5 after completion. Conclusions: About one-third of the patients in a pediatric rheumatology registry were missing race and ethnicity data. After three audit and feedback cycles, centers decreased missing data by 94%, primarily via data recovery from the EHR. In this sample, completion of missing data did not change the findings related to differential outcomes by race. Recovered data were not uniformly distributed compared with those with non-missing race and ethnicity data at baseline, suggesting that differences in outcomes after completing race and ethnicity data may be seen with larger sample sizes.

WRKY75 regulates anthocyanin accumulation in juvenile citrus tissues.

The anthocyanin accumulation in juvenile tissues can enhance the ornamental value, attract pollinators, and help improve abiotic stress. Although transcriptional regulation studies of anthocyanin have been relatively extensive, there are few reports on the mechanism of anthocyanin accumulation in young tissues. This study reveals that many juvenile citrus tissues (flowers, leaves, and pericarp) undergo transient accumulation of anthocyanins, exhibiting a red coloration. Using weighted gene co-expression network analysis (WGCNA) identified CitWRKY75 as a candidate gene. After detecting the expression levels of CitWRKY75 in various citrus juvenile tissues, the expression trend of CitWRKY75 was highly consistent with the red exhibiting and fading. Overexpression of CitWRKY75 in tobacco significantly increased the anthocyanin content. LUC and yeast one-hybrid assay demonstrated that CitWRKY75 could bind to the promoter of CitRuby1(encoding the key transcription factor promoting anthocyanin accumulation) and promote its expression. Finally, comparing the expression levels of CitWRKY75 and CitRuby1 in the late development stage of blood orange found that CitWRKY75 was not the main regulatory factor for anthocyanin accumulation in the later stage. This study used reverse genetics to identify a transcription factor, CitWRKY75, upstream of CitRuby1, which promotes anthocyanin accumulation in citrus juvenile tissues. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01490-9.

Lipases are differentially regulated by hormones to maintain free fatty acid homeostasis for insect brain development.

BACKGROUND: Free fatty acids (FFAs) play vital roles as energy sources and substrates in organisms; however, the molecular mechanism regulating the homeostasis of FFA levels in various circumstances, such as feeding and nonfeeding stages, is not fully clarified. Holometabolous insects digest dietary triglycerides (TAGs) during larval feeding stages and degrade stored TAGs in the fat body during metamorphosis after feeding cessation, which presents a suitable model for this study. RESULTS: This study reported that two lipases are differentially regulated by hormones to maintain the homeostasis of FFA levels during the feeding and nonfeeding stages using the lepidopteran insect cotton bollworm Helicoverpa armigera as a model. Lipase member H-A-like (Lha-like), related to human pancreatic lipase (PTL), was abundantly expressed in the midgut during the feeding stage, while the monoacylglycerol lipase ABHD12-like (Abhd12-like), related to human monoacylglycerol lipase (MGL), was abundantly expressed in the fat body during the nonfeeding stage. Lha-like was upregulated by juvenile hormone (JH) via the JH intracellular receptor methoprene-tolerant 1 (MET1), and Abhd12-like was upregulated by 20-hydroxyecdysone (20E) via forkhead box O (FOXO) transcription factor. Knockdown of Lha-like decreased FFA levels in the hemolymph and reduced TAG levels in the fat body. Moreover, lipid droplets (LDs) were small, the brain morphology was abnormal, the size of the brain was small, and the larvae showed the phenotype of delayed pupation, small pupae, and delayed tissue remodeling. Knockdown of Abhd12-like decreased FFA levels in the hemolymph; however, TAG levels increased in the fat body, and LDs remained large. The development of the brain was arrested at the larval stage, and the larvae showed a delayed pupation phenotype and delayed tissue remodeling. CONCLUSIONS: The differential regulation of lipases expression by different hormones determines FFAs homeostasis and different TAG levels in the fat body during the feeding larval growth and nonfeeding stages of metamorphosis in the insect. The homeostasis of FFAs supports insect growth, brain development, and metamorphosis.

Maternal exposure to low-dose bisphenol A and its potential neurotoxic impact on male pups: A histological, immunohistochemical, and ultrastructural study.

BACKGROUND: Bisphenol A (BPA) is a widely used chemical with a harmful effect on animal and human. The neonatal and juvenile period is a highly risky neurodevelopmental period. AIM: This study aimed to determine how male albino rat pups' cerebral cortex was altered by low doses of BPA given to mothers and the role of the oxidative stress. METHODS: Thirty pregnant rats were randomly split into three equal groups, negative control, and positive control: received 1 cc of corn oil once a day through gastric tube and BPA treated: a dose of 200 µg/kg/day (dissolved in 1 cc corn oil). The male rat pups of each group were sacrificed at 1 week, 3 weeks and 6 weeks. The cerebra were then separated from the brain for histological and biochemical studies. RESULTS: Rats administered BPA had raised levels of lipid peroxidation marker (MDA), lower levels of enzymatic antioxidants (SOD and CAT) with decreased body, cerebral weights, and decreased levels of non-enzymatic antioxidant defense (GSH). Histo-pathologically, shrunken pyramidal cells with congested blood vessels appeared. GFAP displayed increased number of positive immune-reactive astrocytes with high statistically significant increase in the area % in BPA treated group when compared to the control groups, on contrary to MBP. Semi-thin and ultra-thin BPA-sections revealed degenerative changes in myelinated axons with tiny nucleus and broken nuclear membranes. Lysosomes, dilated endoplasmic reticulum cisternae with noticeable increase in unmyelinated nerve fibers were also observed. CONCLUSION: The structure of the developing cerebral cortex is negatively impacted by BPA due to oxidative stress.

Association of IL-17A and IL-10 Polymorphisms with Juvenile Idiopathic Arthritis in Finnish Children.

To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11-3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08-1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06-2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06-3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited.

Non-chemical stresses do not strongly induce male offspring in Daphnia magna ascertained using the short-term juvenile hormone activity screening assay.

Juvenile hormone (JH), together with ecdysone, regulates molting, metamorphosis, growth, and reproduction in arthropods. The effects of its analogs used as insecticides on nontarget species are of concern. Since JH and JH analogs (JHAs) induce male offspring in daphnids, which generally reproduce by parthenogenesis, short-term JH activity screening assay (JHASA) using the male offspring ratio as an endpoint has been developed as a detection method for JHA. However, the production of male offspring is also induced by environmental stresses such as temperature, short-day length, overcrowding, and food limitation. Thus, it is vital to prevent non-chemical stresses from inducing male offspring during the test to detect chemicals with potential JH activity accurately. Therefore, we investigated the effects of temperature (low and high), hardness, high density with low feeding, and day length on male production utilizing JHASA. Male offspring were not strongly induced by any stresses in JHASA, although the male ratios of 4-12% were observed in the preculture under high density (≥70 daphnid/L) and constant darkness. The Clone A strain was relatively more sensitive to high density and day length compared with the strain from National Institute for Environmental Studies (NIES). The selection of strains that rarely produce males under non-chemical stresses and finding the culturing conditions for each strain appropriate for not-inducing male offspring are recommended to control and prevent male offspring induction during JHASA.

Current evidence for janus kinase inhibitors in adult and juvenile dermatomyositis and key comparisons.

INTRODUCTION: Adult dermatomyositis (DM) and juvenile dermatomyositis (JDM) are rare autoimmune diseases with characteristic skin rashes, weakness, and other systemic features. Upregulated interferon signaling has been consistently described in both adult and juvenile DM which makes janus kinase inhibitors (jakinibs) an attractive therapeutic agent that has a targeted mechanism of action. AREAS COVERED: Herein is a review of the growing literature of jakinib use in adult and juvenile DM, including reports on specific disease features and safety of jakinibs in this population and a comparison between adult and juvenile DM. We performed a literature review using PubMed including all English-language publications before 1 February 2024 and abstracts from key recent rheumatology conferences. EXPERT OPINION: Jakinibs are an exciting and promising treatment in both adult and juvenile DM. Current Phase 2 and 3 randomized placebo-controlled trials of jakinibs in both adult and JDM will provide significant insights into the efficacy of this class of medication as a potentially more mechanistically targeted treatment of both skin and muscle disease. In fact, these results will likely inform the treatment paradigm of dermatomyositis in that it may even be considered as first or second line. The next five years in the therapeutic landscape of both juvenile and adult DM is an exciting time for both patients and medical providers.

Corrigendum: The transition of Chilean adolescents from the child welfare system to the adolescent justice system: a continuation or an accumulation of adverse factors?

[This corrects the article DOI: 10.3389/fpsyg.2023.1194294.].

Sublethal effects of nitenpyram on the development of silkworm.

The utilization of nitenpyram for aphid and whitefly control may induce environmental contamination and negative repercussions on non-target organisms. Formerly, we found that nitenpyram would pollute the peripheral and sub-peripheral areas of the adjacent mulberry orchard. Under acute toxicity conditions, nitenpyram induced oxidative damage in silkworms, affected biological metabolism, synthesis, immunity, and signal transduction. Considering the impact of nitenpyram mist drift on mulberry leaves, we investigated the effects of low concentrations of nitenpyram on silkworms. The results showed that silkworms exposed to 0.17 mg/L, 0.35 mg/L and 0.70 mg/L of nitenpyram (1/40 LC50, 1/20 LC50 and 1/10 LC50) showed obvious poisoning symptoms. The cocoon weight and cocoon shell weight decreased gradually with increases in the concentration, and these decreases prolonged the growth and development time of silkworms and induced the detoxification enzymes carboxylesterase (CarE) and glutathione-S-transferase (GST) to cope with the stress damage caused by nitenpyram. Exposure to low concentrations of nitenpyram downregulates genes involved in the drug metabolism-other enzymes and peroxisome pathway in silkworms. Additionally, through injection of miRNA mimics and inhibitors, we discovered that detoxifying enzyme pathway genes are influenced by bmo-miR-3382-3P, bmo-miR-3213-5P and bmo-miR-133, regulating the immune response of silkworms. This study provides an overall view of the toxicity and detoxification metabolism of nitenpyram in silkworm, and provides a reference for environmental assessment.

Contextual determinants of family-driven care implementation in juvenile justice settings.

INTRODUCTION: Engaging families in behavioral health services is a high priority for juvenile justice (JJ) systems and family advocacy groups. Family-driven care (FDC) enhances family engagement and decision-making power in youth behavioral health services, ultimately, improving youth and family mental health and substance abuse outcomes. Despite the benefits, there is limited guidance on how to integrate FDC into behavioral health care within the JJ system. Therefore, the goal of this study is to understand factors that promoted adoption of FDC the JJ context. METHODS: JJ staff and leadership across the state of Georgia participated in surveys and interviews to understand contextual implementation determinants related to the adoption of FDC. Between November 2021- July 2022, 140 JJ staff participated in the survey from 61 unique JJ organizations. In addition, 16 staff participated in follow-up key informant interviews to explain quantitative findings. RESULTS: Based on a mixed methods analysis, JJ agencies were more likely to implement FDC if they had the following characteristics: (1) presence of site leaders that were strongly committed to family engagement, (2) a shared understanding that family engagement was a top priority, (3) staff training related to family engagement, (4) external partnerships with organizations that serve families, (5) a workplace culture that was supportive of innovation, and (6) presence of family engagement programs that were easier (or more feasible) for staff to implement. DISCUSSION: This mixed methods study underscores the importance of strengthening these 6 inner and outer setting implementation determinants when preparing to integrate FDC into JJ systems. Findings are used to promote the adoption and delivery of this high priority intervention in a state-level JJ system.

Uncovering the hidden socioeconomic impact of juvenile idiopathic arthritis and paving the way for other rare childhood diseases: an international, cross-disciplinary, patient-centered approach (PAVE Consortium).

BACKGROUND: Juvenile idiopathic arthritis (JIA) refers to a heterogeneous group of rheumatic conditions in children. Novel drugs have greatly improved disease outcomes; however, outcomes are impacted by limited awareness of the importance of early diagnosis and adequate treatment, and by differences in access across health systems. As a result, patients with JIA continue to be at risk for short- and long-term morbidity, as well as impacts on virtually all aspects of life of the child and family. MAIN BODY: Literature on the socioeconomic burden of JIA is largely focused on healthcare costs, and the impact of JIA on patients, families, and communities is not well understood. High quality evidence on the impact of JIA is needed to ensure that patients are receiving necessary support, timely diagnostics, and adequate treatment, and to inform decision making and resource allocation. This commentary introduces the European Joint Programme on Rare Diseases: Producing an Arthritis Value Framework with Economic Evidence: Paving the Way for Rare Childhood Diseases (PAVE) project, which will co-develop a patient-informed value framework to measure the impact of JIA on individuals and on society. With a patient-centered approach, fundamental to PAVE is the involvement of three patient advocacy organizations from Canada, Israel, and Europe, as active research partners co-designing all project phases and ensuring robust patient and family engagement. The framework will build on the findings of projects from six countries: Canada, Germany, Switzerland, Spain, Israel, and Belgium, exploring costs, outcomes (health, well-being), and unmet needs (uveitis, mental health, equity). CONCLUSION: This unique international collaboration will combine evidence on costs (from family to societal), outcomes (clinical, patient and family outcomes), and unmet needs, to co-design and build a framework with patients and families to capture the full impact of JIA. The framework will support the development of high-quality evidence, encompassing economic and clinical considerations, unmet needs, and patient perspectives, to inform equitable resource allocation, health system planning, and quality of care better aligned with the needs of children with JIA, their families, and communities. Knowledge gained from this novel approach may pave the way forward to be applied more broadly to other rare childhood diseases.

A child with recurrent headache, fever and diffuse meningeal enhancement on MRI.

Juvenile neurolupus presents primarily with neuropsychiatric manifestations which may also be the initial presentation. Such primary neuropsychiatric SLE (NPSLE) events are a consequence either of microvasculopathy and thrombosis, or of autoantibodies and inflammatory mediators. Diagnosis of NPSLE requires the exclusion of other causes, and clinical assessment directs the selection of appropriate investigations. These investigations include measurement of autoantibodies, analysis of cerebrospinal fluid, electrophysiological studies, neuropsychological assessment and neuroimaging to evaluate brain structure and function. In our patient, the disease presented with chronic headache initially diagnosed as migraine, followed by fever and paraparesis. Fundoscopy showed retinal haemorrhages. Investigations revealed anaemia, neutrophilic leucocytosis, thrombocytopenia and raised inflammatory markers (ESR 119 mm/h CRP 58 mg/L) and high globulin. MRI brain showed diffuse meningeal enhancement resembling meningitis but CSF analysis was normal. ANA and dsDNA were positive with low C3, C4. All diffuse meningeal enhancements may not be meningitis and one needs to corroborate all the clinical, biochemical and imaging analyses to come to a diagnosis.

Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis.

BACKGROUND: Juvenile dermatomyositis (JDM) is a systemic vasculopathy associated with metabolic derangements and possible increased risk for premature atherosclerosis. Oxidation of low-density lipoprotein (LDL) in the endothelium is an early step in atherosclerotic plaque formation. It is not known if oxidized LDL is altered in children with untreated JDM. The deposition of oxidized LDL in the vasculature of muscle biopsies (MBx) from patients with untreated JDM and pediatric controls was assessed. FINDINGS: Frozen tissue sections of MRI-directed MBx from 20 female children with untreated JDM and 5 female controls were stained with DAPI and fluorescently labeled antibodies against von Willebrand factor (vWF) and LDL oxidized by copper (oxLDL). Blood vessels were identified by positive vWF staining, and total fluorescence of oxLDL within the vessel walls was measured. Children with untreated JDM had increased deposition of oxLDL in the walls of muscle vasculature compared to healthy children (difference in means ± SEM = 19.86 ± 8.195, p = 0.03). Within the JDM cohort, there was a trend towards increased oxLDL deposition with longer duration of untreated disease (r = 0.43, p = 0.06). There was no significant correlation found between oxLDL deposition and markers of acute JDM disease activity including disease activity scores or muscle enzymes. CONCLUSIONS: This study found increased deposition of oxLDL within blood vessels of children with untreated JDM supporting the concern that these children are at increased risk for premature atherosclerosis from chronic exposure to vascular oxLDL. This study highlights the importance of early diagnosis and treatment initiation to ameliorate cardiovascular damage.

Prevalence of Juvenile-Onset and Pediatric Huntington's Disease and Their Availability and Ability to Participate in Trials: A Dutch Population and Enroll-HD Observational Study.

Background: Juvenile-onset Huntington's disease (JHD) represents 1-5% of Huntington's disease (HD) patients, with onset before the age of 21. Pediatric HD (PHD) relates to a proportion of JHD patients that is still under 18 years of age. So far, both populations have been excluded from interventional trials. Objective: Describe the prevalence and incidence of JHD and PHD in the Netherlands and explore their ability to participate in interventional trials. Methods: The prevalence and incidence of PHD and JHD patients in the Netherlands were analyzed. In addition, we explored proportions of JHD patients diagnosed at pediatric versus adult age, their diagnostic delay, and functional and modelled (CAP100) disease stage in JHD and adult-onset HD patients at diagnosis. Results: The prevalence of JHD and PHD relative to the total manifest HD population in January 2024 was between 0.84-1.25% and 0.09-0.14% respectively. The mean incidence of JHD patients being diagnosed was between 0.85-1.28 per 1000 patient years and of PHD 0.14 per 1.000.000 under-aged person years. 55% of JHD cases received a clinical diagnosis on adult age. At diagnosis, the majority of JHD patients was functionally compromised and adolescent-onset JHD patients were significantly less independent compared to adult-onset HD patients. Conclusions: In the Netherlands, the epidemiology of JHD and PHD is lower than previously suggested. More than half of JHD cases are not eligible for trials in the PHD population. Furthermore, higher functional dependency in JHD patients influences their ability to participate in trials. Lastly, certain UHDRS functional assessments and the CAP100 score do not seem appropriate for this particular group.

Real-life data of etanercept efficacy and safety in juvenile idiopathic arthritis: a 24-month retrospective study at a single center.

OBJECTIVE: The aim of this study was to assess the efficacy and safety of etanercept (ETA) use in juvenile idiopathic arthritis (JIA). METHODS: The 24-month data of patients with JIA on etanercept in a single center were evaluated retrospectively. Response to treatment was assessed according to 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and JIA-American College of Rheumatology (ACR) improvement criteria. Safety assessments were based on adverse event (AE) reports. RESULTS: The study included 152 patients with JIA. The mean age at diagnosis of JIA was 8.5 ± 4.4 years, and treatment with ETA started at a mean age of 11.1 ± 4.4 years. The mean duration of ETA use was 16 ± 11.1 months. The mean JADAS10 score at baseline was 18.5 ± 5.9. By the third month, it had reduced to 8.6 ± 6.6 and by the sixth month to 5.7 ± 6. By the twelfth month, the JADAS10 score was 4.9 ± 6.7, and by the twenty-fourth month, it had worsened to 7.3 ± 7.8. ACR50 response was achieved in 79.6% of patients at 3 months, 67.1% at 6 months, 79.3% at twelfth months, 70.7% at the twenty-fourth month. During ETA treatment, 10 patients required hospitalization for serious infections. CONCLUSION: Etanercept is a safe and effective option for patients with JIA. However, variations in response between JIA subtypes highlight the need for individualized treatment strategies.

Modified viscotrabeculotomy versus modified trabeculotomy in late-onset primary congenital, juvenile, and secondary open-angle glaucoma.

PURPOSE: To compare modified viscotrabeculotomy (VCO-Tbo) to modified trabeculotomy (Tbo) in late-onset primary congenital, juvenile open-angle, steroid-induced, and pigmentary glaucoma. METHODS: Patients were randomly assigned to VCO-Tbo and Tbo groups in this study. Intraocular pressure (IOP), antiglaucoma medications, and success/failure rates were assessed. A linear mixed model was used to compare the change trend at different follow-up times. Survival time was evaluated using the Kaplan-Meier graph and Log-Rank test. RESULTS: The mean IOP at 1, 3, and 12 months in the VCO-Tbo group was 14.1 ± 3.1, 15.9 ± 3 and 17 ± 3.1 mmHg, respectively. The mean IOP at the same time points in the Tbo group was 15.9 ± 3.3, 17.6 ± 3.5 and 18.4 ± 3.2 mmHg (P = 0.051, 0.058, 0.088, respectively). The VCO-Tbo group had significantly lower IOP after six months (16.5 ± 4.1 mmHg vs. 18.7 ± 3.8 mmHg; p = 0.031) and by the last visit (16.8 ± 2.1 mmHg vs. 18.8 ± 2 mmHg; p = 0.013). The reduction in the number of medications was significant in both groups compared to baseline (P < 0.001), but there was no significant difference between groups (P = 0.450). The complete and qualified success rate was 43.9% and 34.1% in the VCO-Tbo group and 46.8% and 10.6% in the Tbo group at the final follow-up (p = 0.040, and 0.039, respectively). CONCLUSION: Both procedures are effective in IOP and medication reduction. The survival time and efficacy of modified trabeculotomy can be augmented by injecting cohesive viscoelastic in the Schlemm's canal.