428 research outputs found

    Receiving threatening or obscene messages from a partner and mental health, self-harm and suicidality: results from the Adult Psychiatric Morbidity Survey

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    PURPOSE: Threatening or obscene messaging is repeated, unwanted texts, emails, letters or cards experienced by the recipient as threatening or obscene, and causing fear, alarm or distress. It is rarely examined as an aspect of intimate partner violence. We describe the prevalence of exposure to threatening/obscene messaging from a current or ex-partner; characteristics of victims; and associations with other forms of violence and abuse, mental disorder, self-harm, and suicidality. METHODS: Cross-sectional probability-sample survey of the general population in England aged 16 + . Multivariable regression modelling tested associations between receipt of threatening/obscene messaging and current common mental disorder, past-year self-harm and suicidality. RESULTS: Threatening/obscene messages were received from a current/ex-partner by 6.6% (95%CI: 5.9-7.3) of adults who had been in a relationship; 1.7% received these in the past year. Victims were more likely to be female, under 35, single or divorced, socioeconomically disadvantaged, and to have experienced other forms of sexual and partner violence and abuse. Those who received threatening/obscene messages in the past year were more likely to experience common mental disorder (adjusted odds ratio 1.89; 1.01-3.55), self-harm (2.31; 1.00-5.33), and suicidal thoughts (2.00; 1.06-3.78). CONCLUSION: Threatening/obscene messaging commonly occurs in the context of intimate partner violence. While often occurring alongside sexual and physical violence, messaging has an additional association with mental disorder and suicidality. Routine enquiry in service settings concerning safety, including those working with people who have escaped domestic violence, should ask about ongoing contact from previous as well as current partners. This should include asking about messaging, as well as other forms of potentially technology-enabled abuse which may become increasingly common

    Gender differences in intimate partner violence and psychiatric disorders in England: results from the 2007 adult psychiatric morbidity survey

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    To assess the extent to which being a victim of intimate partner violence (IPV) is associated with psychiatric disorders in men and women. A stratified multistage random sample was used in the third English psychiatric morbidity survey. Psychiatric disorders were measured by the Clinical Interview Schedule (Revised) and screening questionnaires. IPV was measured using British Crime Survey questions. 18.7% (95% CI 17.1–20.4; n = 595 of 3197) of men had experienced some form of IPV compared with 27.8% of women (95% CI 26.2–29.4; n = 1227 of 4206; p < 0.001). IPV was associated with all disorders measured (except eating disorders in men). Physical IPV was significantly linked to psychosis and with substance and alcohol disorders in men and women, but significant associations with common mental disorders (CMDs), post-traumatic stress disorder (PTSD) and eating disorders were restricted to women. Emotional IPV was associated with CMDs in men and women. The high prevalence of experiences of partner violence, and strength of the association with every disorder assessed, suggests enquiry about partner violence is important in identifying a potential risk and maintenance factor for psychiatric disorders, and to ascertain safety, particularly in women as they are at greatest risk of being victims of violence

    Feed-Forward Microprocessing and Splicing Activities at a MicroRNA–Containing Intron

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    The majority of mammalian microRNA (miRNA) genes reside within introns of protein-encoding and non-coding genes, yet the mechanisms coordinating primary transcript processing into both mature miRNA and spliced mRNA are poorly understood. Analysis of melanoma invasion suppressor miR-211 expressed from intron 6 of melastatin revealed that microprocessing of miR-211 promotes splicing of the exon 6–exon 7 junction of melastatin by a mechanism requiring the RNase III activity of Drosha. Additionally, mutations in the 5′ splice site (5′SS), but not in the 3′SS, branch point, or polypyrimidine tract of intron 6 reduced miR-211 biogenesis and Drosha recruitment to intron 6, indicating that 5′SS recognition by the spliceosome promotes microprocessing of miR-211. Globally, knockdown of U1 splicing factors reduced intronic miRNA expression. Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs

    Common polygenic variation in coeliac disease and confirmation of ZNF335 and NIFA as disease susceptibility loci

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    Coeliac disease (CD) is a chronic immune-mediated disease triggered by the ingestion of gluten. It has an estimated prevalence of approximately 1% in European populations. Specific HLA-DQA1 and HLA-DQB1 alleles are established coeliac susceptibility genes and are required for the presentation of gliadin to the immune system resulting in damage to the intestinal mucosa. In the largest association analysis of CD to date, 39 non-HLA risk loci were identified, 13 of which were new, in a sample of 12 014 individuals with CD and 12 228 controls using the Immunochip genotyping platform. Including the HLA, this brings the total number of known CD loci to 40. We have replicated this study in an independent Irish CD case–control population of 425 CD and 453 controls using the Immunochip platform. Using a binomial sign test, we show that the direction of the effects of previously described risk alleles were highly correlated with those reported in the Irish population, (P=2.2 × 10−16). Using the Polygene Risk Score (PRS) approach, we estimated that up to 35% of the genetic variance could be explained by loci present on the Immunochip (P=9 × 10−75). When this is limited to non-HLA loci, we explain a maximum of 4.5% of the genetic variance (P=3.6 × 10−18). Finally, we performed a meta-analysis of our data with the previous reports, identifying two further loci harbouring the ZNF335 and NIFA genes which now exceed genome-wide significance, taking the total number of CD susceptibility loci to 42

    Platelet-activating factor levels of serum and gingival crevicular fluid in nonsmoking patients with periodontitis and/or coronary heart disease

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    The purpose of the present study was to investigate systemic and local levels of platelet-activating factor (PAF), a potent proinflammatory mediator implicated in cardiovascular pathophysiology in adult nonsmoking patients with periodontitis with or without coronary heart disease (CHD). Eighty-seven volunteers, 25 periodontitis patients, 19 periodontitis with CHD patients, 19 CHD patients, and 24 healthy controls were included, and periodontal conditions were assessed. Gingival crevicular fluid (GCF) and venous blood were collected, and PAF levels were measured by enzyme-linked immunosorbent assay. PAF levels in serum (303.3 ± 204 pg/ml) and in GCF (26.3 ± 6 pg/μl) of the periodontitis group with CHD, the periodontitis group (serum, 302.4 ± 241 pg/ml and GCF, 26.3 ± 8 pg/μl) and the CHD group (serum, 284.7 ± 192 pg/ml and GCF, 20.8 ± 6 pg/μl) were significantly higher than the healthy control group (serum, 65.4 ± 35 pg/ml and GCF, 7.7 ± 3 pg/μl; p < 0.05). In summary, the present study could demonstrate that in patients with periodontitis, the inflammatory mediator PAF is released into serum at least in the same range as for patients with coronary heart disease. However, no additive effects were seen when both conditions were present

    Integrative MicroRNA and Proteomic Approaches Identify Novel Osteoarthritis Genes and Their Collaborative Metabolic and Inflammatory Networks

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    BACKGROUND: Osteoarthritis is a multifactorial disease characterized by destruction of the articular cartilage due to genetic, mechanical and environmental components affecting more than 100 million individuals all over the world. Despite the high prevalence of the disease, the absence of large-scale molecular studies limits our ability to understand the molecular pathobiology of osteoathritis and identify targets for drug development. METHODOLOGY/PRINCIPAL FINDINGS: In this study we integrated genetic, bioinformatic and proteomic approaches in order to identify new genes and their collaborative networks involved in osteoarthritis pathogenesis. MicroRNA profiling of patient-derived osteoarthritic cartilage in comparison to normal cartilage, revealed a 16 microRNA osteoarthritis gene signature. Using reverse-phase protein arrays in the same tissues we detected 76 differentially expressed proteins between osteoarthritic and normal chondrocytes. Proteins such as SOX11, FGF23, KLF6, WWOX and GDF15 not implicated previously in the genesis of osteoarthritis were identified. Integration of microRNA and proteomic data with microRNA gene-target prediction algorithms, generated a potential "interactome" network consisting of 11 microRNAs and 58 proteins linked by 414 potential functional associations. Comparison of the molecular and clinical data, revealed specific microRNAs (miR-22, miR-103) and proteins (PPARA, BMP7, IL1B) to be highly correlated with Body Mass Index (BMI). Experimental validation revealed that miR-22 regulated PPARA and BMP7 expression and its inhibition blocked inflammatory and catabolic changes in osteoarthritic chondrocytes. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that obesity and inflammation are related to osteoarthritis, a metabolic disease affected by microRNA deregulation. Gene network approaches provide new insights for elucidating the complexity of diseases such as osteoarthritis. The integration of microRNA, proteomic and clinical data provides a detailed picture of how a network state is correlated with disease and furthermore leads to the development of new treatments. This strategy will help to improve the understanding of the pathogenesis of multifactorial diseases such as osteoarthritis and provide possible novel therapeutic targets
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