I want to lie about not knowing you, but my precuneus refuses to cooperate

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Sex hormones and apoptosis and immunoglobulin production in systemic lupus erythematosus

BACKGROUND: SLE is an autoimmune disease that affects predominantly female of reproductive age. Previous studies have suggested an immunomodulatory role of sex hormones in the pathogenesis of SLE. Objectives: To examine the effects of various sex hormones on apoptosis and immunoglobulin production by peripheral blood mononuclear cells (PBMCs) in SLE patients …published_or_final_versio

Relationship between autoantibody clustering and clinical subsets in SLE: cluster and association analyses in Hong Kong Chinese

OBJECTIVE: This study aims to identify the existence of, and relationship between autoantibody clusters and clinical subsets in Chinese SLE patients. METHODS: Data from 1928 SLE patients from Hong Kong were analysed. Using cluster analysis, patients were grouped by autoantibodies into clusters. The frequencies of various clinical manifestations were then compared between each cluster. Separate association analyses between individual autoantibodies and clinical manifestations as well as between clinical manifestations were also performed without any prior clustering. RESULTS: Three separate autoantibody clusters were identified, each with significantly different clinical manifestations. Cluster 1 was characterized by anti-dsDNA and the greatest prevalence of renal disorder but the lowest frequencies of other clinical manifestations. Cluster 2 was represented by the predominance of anti-Smith, anti-RNP and aPL, with greater prevalence of malar rash, oral ulcers, arthritis and serositis. Cluster 3 was characterized by anti-Ro and anti-La with greater prevalence of discoid rash, photosensitivity and haematological involvement. Individual association analysis also revealed similar findings. Patients of clusters 2 and 3 were more closely related, while cluster 1 was more distinct, associated with renal disorder only and negatively associated or not associated with other manifestations. CONCLUSION: We conclude that autoantibody clustering and clinical subsets exist in SLE patients of our locality. These clusters may be viewed as a bipolar spectrum of related autoantibody and clinical manifestations. At one end are patients with over-representation of anti-dsDNA and renal disorder, while at the other end are two distinct autoantibody clusters (anti-Sm/anti-RNP/aPL and anti-Ro/anti-La) with overlapping of other clinical manifestations.postprin

Gene-Based Meta-Analysis of Genome-Wide Association Study Data Identifies Independent Single-Nucleotide Polymorphisms in ANXA6 as Being Associated With Systemic Lupus Erythematosus in Asian Populations

Objective Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants. Methods Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing. Results More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously. Conclusion Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes. © 2015, American College of Rheumatology.postprin

Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, the detailed information for SLE association and the underlying functional mechanism(s) are still lacking. METHODS: Through meta-analysis of two genome-wide association studies (GWAS) on Chinese Han populations with a total of 1659 cases and 3398 controls matched geographically, we closely examined this region, especially on the reported single nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant association SNP with SLE using 2612 cases and 2323 controls of Asian ancestry. RESULTS: All reported SNPs in this region with different autoimmune diseases were examined in the two GWAS data and meta- analysis result, and supportive evidence of association with SLE was found (meta-analysis P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta = 2.70E-09). It showed independent effect through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand with a total of 2612 cases and 2323 controls (joint analysis of GWAS and replication result P_all = 1.31E-11, OR = 1.23). SNP rs2298428 was shown to be an eQTL for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in SLE cases. CONCLUSIONS: Association to distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms by these diseases.published_or_final_versio

Lying about the Valence of Affective Pictures: An fMRI Study

The neural correlates of lying about affective information were studied using a functional magnetic resonance imaging (fMRI) methodology. Specifically, 13 healthy right-handed Chinese men were instructed to lie about the valence, positive or negative, of pictures selected from the International Affective Picture System (IAPS) while their brain activity was scanned by a 3T Philip Achieva scanner. The key finding is that the neural activity associated with deception is valence-related. Comparing to telling the truth, deception about the valence of the affectively positive pictures was associated with activity in the inferior frontal, cingulate, inferior parietal, precuneus, and middle temporal regions. Lying about the valence of the affectively negative pictures, on the other hand, was associated with activity in the orbital and medial frontal regions. While a clear valence-related effect on deception was observed, common neural regions were also recruited for the process of deception about the valence of the affective pictures. These regions included the lateral prefrontal and inferior parietal regions. Activity in these regions has been widely reported in fMRI studies on deception using affectively-neutral stimuli. The findings of this study reveal the effect of valence on the neural activity associated with deception. Furthermore, the data also help to illustrate the complexity of the neural mechanisms underlying deception

Oral health status of Southern Chinese with systemic sclerosis

Scientific Groups Program: Seq. no. 6 - Oral Communication IV: Behavioural Science/Health Service Research/Dental Education 1: abstract no. 0040OBJECTIVES: To study oral health status and oral features of Southern Chinese with Systemic Sclerosis in Hong Kong. METHODS: Southern Chinese with Systemic Sclerosis attending the Rheumatology Clinic, Queen Mary Hospital were invited to this study. They were informed the study purposes and procedures, and were asked to sign a consent. The study comprised of a questionnaire survey and a clinical examination. In the survey, dental service attendance and oral hygiene habits were asked. Mouth opening, caries experience, periodontal and oral mucosal status were assessed during clinical examination. RESULTS: Seventy-seven people were invited and 43 joined this study. Their mean age was 54±12 year. They performed tooth-brushing daily and about one-third had regular dental visit. They all had caries experience with a mean DMFT of 11.4. Twenty-seven participants (66%) had untreated decay. No one was found to be periodontally healthy. Most of them (98%) had calculus and the majority (78%) had periodontal pockets. Oral mucosal telangiectasia was common (81%). Eighteen participants (53%) had reduced maximum mouth opening. CONCLUSIONS: Periodontal pockets and untreated decay were common amongst Southern Chinese with Systemic Sclerosis in Hong Kong. Oral mucosal telangiectasia and reduced maximum mouth opening were also common.link_to_OA_fulltextThe 22nd International Association for Dental Research (SEA Division) & 19th South East Asia Association for Dental Education, Manila, Philippines, 8-10 October 2008

Investigation of variants in estrogen receptor genes and perinatal depression

Ene-Choo Tan,1,2 Hwee-Woon Lim,1 Tze-Ern Chua,2,3 Hui-San Tan,1 Theresa MY Lee,2,3 Helen Y Chen2,3 1KK Research Centre, KK Women’s and Children’s Hospital, Singapore, Singapore; 2Paediatrics Academic Clinical Programme, SingHealth Duke-NUS Medical School, Singapore, Singapore; 3Department of Psychological Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore Objectives: Depressive symptoms are common during pregnancy and after childbirth. Estrogen levels fluctuate greatly during the course of pregnancy and may contribute to mood instability. The first aim of this case–control study was to investigate whether variants in the two estrogen receptor genes might contribute to the genetic susceptibility to pregnancy-related depression using controls that were screened for postnatal depression. The second aim was to uncover new variants in the two estrogen receptor genes. Patients and methods: Our study sample comprised 554 control subjects who had Edinburgh Postnatal Depression Scale (EPDS) scores below 7 at postnatal screening, and 159 patients with clinically diagnosed pregnancy-related depression. They were genotyped for four single-nucleotide polymorphisms (SNPs) and a dinucleotide repeat in the two genes: estrogen receptor α (ESR1) and estrogen receptor β (ESR2). Fifty-six cases with personal and/or family history of depression of psychiatric disorders were selected for resequencing of the two genes. Results: There was no statistically significant association with perinatal depression for all five variants. However, there was a trend toward higher frequencies of the genotypes associated with higher risk of depression for rs2077647 and rs4986938 in the case group. From resequencing, two novel ESR1 variants were identified from two different patients. Conclusion: Our study that used screened controls with low EPDS scores and cases with clinically diagnosed pregnancy-related depression could not replicate the association with depression for any of the SNPs for both genotype and allele frequencies. Two novel SNPs were identified and could be further investigated in a larger sample set. Keywords: childbirth, depression, hormone, single-nucleotide polymorphism, postpartu

Neural correlates of Traditional Chinese Medicine induced advantageous risk-taking decision making

This fMRI study examined the neural correlates of the observed improvement in advantageous risk-taking behavior, as measured by the number of adjusted pumps in the Balloon Analogue Risk Task (BART), following a 60-day course of a Traditional Chinese Medicine (TCM) recipe, specifically designed to regulate impulsiveness in order to modulate risk-taking behavior. The 14 participants recruited for this study were randomly assigned to the experimental and control groups and the TCM recipe (Panax, 520 mg; Astragalus membranaceous Bunge, 520 mg; Masnetitum, 840 mg; Ostrea gigas Thumb, 470 mg; Thinleaf Milkwort Root Radix Polygalae, 450 mg; and Os Draconis, 470 mg) was administered, as a diet supplement, to the seven participants in the experimental group. The neural activity of the two groups was monitored by a 3T MRI scanner, before and after the 60-day treatment. Associated with the improved advantageous risk-taking behavior seen in the experimental group, significantly stronger blood oxygenation level dependent (BOLD) responses were observed in the bilateral dorsolateral prefrontal cortex (DLPFC), left putamen, left thalamus, right insula, and right anterior cingulate cortex (ACC), regions which have previously been reported as being involved in risk-taking decision making. The effect of the TCM in improving advantageous risk-taking decision making appears to have been related to the enhanced efficiency of the cognitive affective system, the PFC-ACC-insula-striatum network, which functions to inhibit impulsiveness, to sensitize reward-related information, and to allow the opportunity, during risk estimation, to evaluate potential gains and losses. The findings of this study suggest that interventions acting on factors modulating risk-taking decision making could have a beneficial effect in terms of optimizing risk-taking behavior. © 2009 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex