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Chronic hyperglycemia increases the carbon flux through the hexosamine pathway, allowing the accumulation of UDP-GlcNAc. UDP-GlcNAc is the sugar donor for the enzyme-mediated protein glycosylation event known as OGlcNAcylation. This posttranslational modification targets several transcription factors implicated in glucose toxicity, insulin resistance, and diabetes. Vitamin D plays an important role in glucose homeostasis and insulin secretion through transcriptional mechanisms mediated by its receptor (VDR). Vitamin D deficiency has been associated with higher susceptibility to bacterial diseases in diabetic patients. However, it has not been explored whether VDR is subject to OGlcNAcylation or whether high glucose affects its transcriptional or biological activities. The aim of this study was to evaluate the effect of hyperglycemia on VDR OGlcNAcylation and its effects on vitamin D-mediated transcription. We predicted potential OGlcNAcylation sites using free software. Our results showed that hyperglycemia (30 mM) induces the OGlcNAcylation of VDR in THP1 cells and in human macrophages derived from monocytes (MDM). This condition did not hamper the vitamin D-dependent activation of LL-37 gene expression, and even did not impair the macrophage bactericidal activity. Our study provides new insight into vitamin D receptor posttranslational modification that may have relevance on the physiological responses of long-term hyperglycemia. [ABSTRACT FROM AUTHOR]

Aim To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene ( IL10) have been consistently associated with Behçet's disease ( BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility. Methods To identify IL10 low-frequency variants, a discovery group of 50 Portuguese BD patients were Sanger-sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD- and/or Portuguese-specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian). Results Rare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non-coding variants in five heterozygous cases. ss836185595, located in the IL10 3′ untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset. Conclusion This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non-coding variants and statistical tests which incorporate these predictions. [ABSTRACT FROM AUTHOR]

Introduction. This study aimed to assess the genetic determinants of poor outcome in Portuguese patients with juvenile idiopathic arthritis (JIA). Methods. Our study was conducted in Reuma.pt, the Rheumatic Diseases Portuguese Register, which includes patients with JIA. We collected prospectively patient and disease characteristics and a blood sample for DNA analysis. Poor prognosis was defined as CHAQ/HAQ >0.75 at the last visit and/or the treatment with biological therapy. A selected panel of single nucleotide polymorphisms (SNPs) associated with susceptibility was studied to verify if there was association with poor prognosis. Results. Of the 812 patients with JIA registered in Reuma.pt, 267 had a blood sample and registered information used to define “poor prognosis.” In univariate analysis,we found significant associationswith poor prognosis for alleleAof TNFA1P3/20 rs6920220, allele Gof TRAF1/C5 rs3761847, and alleleGof PTPN2 rs7234029. Inmultivariate models, the associationswith TRAF1/C5 (1.96 [1.17–3.3]) remained significant at the 5% level, while TNFA1P3/20 and PTPN2 were no longer significant. Nevertheless, none of associations found was significant after the Bonferroni correction was applied. Conclusion. Our study does not confirmthe association between a panel of selected SNP and poor prognosis in Portuguese patients with JIA. [ABSTRACT FROM AUTHOR]

Objective Our aims were to evaluate the correlation between Juvenile Arthritis Disease Activity Score 27-joint reduced count (JADAS27) with erythrocyte sedimentation rate (ESR) and JADAS27 with C-reactive protein (CRP) scores and to test the agreement of both scores on classifying each disease activity state. We also aimed at verifying the correlation of the 2 scores across juvenile idiopathic arthritis (JIA) categories and to check the correlation between JADAS27-ESR and clinical JADAS27 (JADAS27 without ESR). Methods A nationwide cohort of patients with JIA registered in the Portuguese Register, Reuma.pt, was studied. JADAS27-CRP was adapted by replacing ESR with CRP level as the inflammatory marker. JADAS27-CRP was calculated similarly to JADAS27-ESR as the simple linear sum of its 4 components. Pearson's correlations and K statistics were used in the analyses. Results A total of 358 children had full data to calculate JADAS27; 65.4% were female and the mean ± SD disease duration was 11.8 ± 9.1 years. The correlation coefficient between JADAS27-ESR and JADAS27-CRP was 0.967 ( P < 0.0001), although the correlation coefficient between ESR and CRP level was 0.335 ( P < 0.0001). The strong correlation between JADAS27-ESR and JADAS27-CRP was maintained when compared within each JIA category. The agreement between JADAS27-ESR and JADAS27-CRP across the 4 activity states was very good, showing 91.1% of the observations in agreement; K = 0.867 (95% confidence interval 0.824-0.91). The correlation between JADAS27 with ESR and JADAS27 without ESR was high (r = 0.97, P < 0.0001). Conclusion JADAS27 based on CRP level correlated closely with JADAS27-ESR across all disease activity states and JIA categories, indicating that both measures can be used in clinical practice. Moreover, the correlation of JADAS27 with and without ESR was also high, suggesting that this tool might be useful even in the absence of laboratorial measures. [ABSTRACT FROM AUTHOR]

The case of a 13-year-old Caucasian girl with a 1-year history of a linear plaque on her thigh is reported. Histopathologic examination of the incisional biopsy tissue established the diagnosis of lupus erythematosus panniculitis. Six months later she developed the clinical and laboratory criteria for the diagnosis of systemic lupus erythematosus ( SLE). She was treated with azathioprine and oral prednisolone, with a favorable clinical outcome. Our case illustrates a child with linear lupus erythematosus profundus as an initial manifestation of SLE. To our knowledge, only eight other cases of linear lupus erythematosus profundus have been reported in the literature, five in children. In contrast to our patient, none of those cases progressed to SLE during the reported follow-up period. The authors report this case to illustrate an unusual superimposed segmental manifestation of an inflammatory polygenic disorder. [ABSTRACT FROM AUTHOR]

A 12-month-old girl presented with an asymptomatic, pearly nodule on the left nipple that had been present from birth and was currently 3 mm in diameter and growing. Assuming the diagnosis of congenital primary milium of the nipple, we took a 'wait and see' approach. After 3 months, the pearl disappeared without any scarring. [ABSTRACT FROM AUTHOR]

A question related to midline perineal lesion in a newborn girl is presented.