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This is an up-to-date review on external environmental factors for adult-onset idiopathic inflammatory myopathies (IIMs). Environmental factors with suggestive evidence including ultraviolet radiation, smoking, infectious agents (viruses in particular), pollutants, medications (ie, statin) and vitamin D deficiency are discussed. We also discuss the potential implications of environmental factors in IIM development, identify current challenges, and provide insight into future investigations.

Familial associations can be indicators of shared genetic susceptibility between two diseases. Previous data on familial autoimmunity in patients with idiopathic inflammatory myopathies (IIM) are scarce and inconsistent.To investigate which autoimmune diseases (ADs) may share genetic susceptibility with IIM, we examined the familial associations between IIM and different ADs.In this Swedish population-based family study, we assembled 7615 first-degree relatives (FDRs) of 1620 patients with IIM and 37,309 relatives of 7797 matched individuals without IIM. Via register linkages, we ascertained rheumatoid arthritis, other rheumatic inflammatory diseases (RIDs), multiple sclerosis, inflammatory bowel diseases (IBD), type 1 diabetes mellitus, autoimmune thyroid diseases (AITD), coeliac disease (CeD) and myasthenia gravis among the FDRs. We estimated the familial association between IIM and each AD using conditional logistic regression and performed subgroup analyses by kinship.Patients with IIM had significantly higher odds of having ≥1 FDR affected by other RIDs (adjusted odds ratio [aOR] = 1.40, 95% confidence interval [CI] 1.11-1.78) and greater odds of having ≥2 FDRs affected by CeD (aOR = 3.57, 95% CI 1.28-9.92) compared to the individuals without IIM. In the analyses of any FDR pairs, we observed familial associations for other RIDs (aOR = 1.34, 95% CI 1.14-1.56), IBD (aOR = 1.20, 95% CI 1.02-1.41), AITD (aOR = 1.10, 95% CI 1.02-1.19) and CeD (aOR = 1.37, 95% CI 1.08-1.74) while associations for other ADs were not statistically significant.The observed familial associations may suggest that IIM shares genetic susceptibility with various ADs, information that may be useful for clinical counselling and guiding future genetic studies of IIM.

ObjectivesThe magnitude of the genetic contribution to idiopathic inflammatory myopathies (IIMs) is unknown. In this project, we aimed to investigate the familial aggregation and heritability of IIM.MethodsThis is a family-based study using nationwide healthcare register data in Sweden. We matched each patient with IIM to individuals without IIM, identified their first-degree relatives and determined the IIM status among all first-degree relatives. We estimated the adjusted ORs (aORs) of familial aggregation of IIM using conditional logistic regression. In addition, we used tetrachoric correlation to estimate the heritability of IIM.ResultsWe included 7615 first-degree relatives of 1620 patients with IIM diagnosed between 1997 and 2016 and 37 309 first-degree relatives of 7797 individuals without IIM. Compared with individuals without IIM, patients with IIM were more likely to have ≥1 first-degree relative affected by IIM (aOR=4.32, 95% CI 2.00 to 9.34). Furthermore, the aOR of familial aggregation of IIM in full siblings was 2.53 (95% CI 1.62 to 3.96). The heritability of IIM was 22% (95% CI 12% to 31%) among any first-degree relatives and 24% (95% CI 12% to 37%) among full siblings.ConclusionsIIM has a familial component with a risk of aggregation among first-degree relatives and a heritability of about 20%. This information is of importance for future aetiological studies and in clinical counselling.

Objectives To examine pregnancy outcomes among births to women with idiopathic inflammatory myopathy (IIM) in relation to time of IIM diagnosis using population-based data. Methods This study used Swedish nationwide registers to identify all singleton births that occurred between 1973 and 2016 among women diagnosed with IIM between 1998 and 2016 and among women unexposed to IIM. We classified births according to the IIM status of the mother at time of delivery: post-IIM (n = 68), 1–3 years pre-IIM (n = 23), >3 years pre-IIM (n = 710) and unexposed to IIM (n = 4101). Multivariate regression models were used to estimate relative risks of adverse pregnancy outcomes in post-IIM births and pre-IIM births separately, in comparison with their non-IIM comparators. Results We found that post-IIM births had increased risks of caesarean section [adjusted relative risk (aRR) = 1.98; 95% CI: 1.08, 3.64], preterm birth (aRR = 3.35; 95% CI: 1.28, 8.73) and low birth weight (aRR = 5.69; 95% CI: 1.84, 17.55) compared with non-IIM comparators. We also noticed higher frequencies of caesarean section and instrumental delivery in 1–3 years pre-IIM births than in the non-IIM comparators. Conclusion Women who gave birth after IIM diagnosis had higher risks of caesarean section, preterm birth and low birth weight. These results further underline the importance of special care and close monitoring of women with IIM. Higher frequencies of caesarean section and instrumental delivery in pre-IIM births highlight the need for future research on the influence of subclinical features of IIM on pregnancy outcomes.

Objective To examine the association between idiopathic inflammatory myopathy (IIM) and cancer before and after IIM diagnosis. Methods We used prospectively collected nationwide register data to design a case-control study to investigate the occurrence of cancer before IIM, and a cohort study to investigate the occurrence of cancer after IIM. Patients diagnosed with IIM between 2002 and 2016 in Sweden, were compared to the general population. The association between cancer and IIM was estimated before and after IIM diagnosis via logistic regression and Cox regression models, respectively. Results We included 1419 patients with IIM and 7045 individuals from the general population. The overall odds of cancer before IIM diagnosis were increased in IIM compared to the general population, adjusted odds ratio (AOR) 1.5, 95% confidence interval (CI) 1.3–1.8. This association was also noted after IIM diagnosis, adjusted hazard ratio (AHR) 1.7 (95% CI 1.4–2.0), or one additional cancer in every 125 IIM patients per year. Colorectal (AOR 2.1), lung (AOR 5.4) and ovarian (AOR 7.0) cancers were associated with IIM before diagnosis. Oropharyngeal (AHR 9.1) and cervical (AHR 3.8) cancers, malignant melanoma (AHR 3.2) and non-melanoma skin cancer (AHR 3.1) were associated with IIM after diagnosis. Adenocarcinomas were associated with dermatomyositis before diagnosis and squamous cell cancers after IIM diagnosis. Lymphatic hematopoietic cancers were associated with IIM both before and after diagnosis. Conclusions The cancer types that occur before IIM diagnosis differ from the ones that occur after diagnosis. This may have an impact on screening decisions for IIM.

Background Prevalence figures of major depressive disorder (MDD) in children and adolescents across various epidemiological studies have been inconclusive. This is a systematic review and meta-analysis of the pooled prevalence of MDD and its associated factors in children and adolescents in China. Method A systematic review and literature search were conducted covering PubMed, PsycINFO, EMBASE and Chinese databases (China National Knowledge Internet, WANFANG Data and SinoMed) to identify studies reporting the prevalence of MDD in children and adolescents in China. The pooled prevalence estimates and associated factors were examined using the Comprehensive Meta-Analysis program, Version 2. Results Fourteen studies involving 82,592 subjects were included in this meta-analysis. The pooled point prevalence of MDD in Chinese children and adolescents was 1.3% (95% CI: 0.8%–2.0%). Subgroup and meta-regression analyses revealed that diagnostic criteria, age, year of survey and study quality were significantly associated with the prevalence of MDD. Conclusions The point prevalence of MDD in children and adolescents in China is similar to worldwide figures. Further national epidemiological studies with the view of developing effective intervention strategies should be considered.

Objective.To examine the reproductive pattern of women with idiopathic inflammatory myopathy (IIM) compared to the general population.Methods.Population-based, nationwide registers were used to identify offspring of women with IIM and comparators.Results.Women with IIM in general had similar reproductive patterns as the comparators, whereas in those diagnosed between 26 and 45 years of age, there was an overall trend for fewer children as well as a higher proportion of nulliparity and a lower fertility rate in women with dermatomyositis than their comparators.Conclusion.Reproductive attention should be paid to patients with IIM diagnosed during the childbearing period.

Depressive symptoms are common in children and adolescents. The prevalence of depressive symptoms in children and adolescents in China vary significantly across studies. A meta-analysis of the prevalence of depressive symptoms in children and adolescents in China was conducted. Literature search was performed in both English (PubMed, PsycINFO and EMBASE) and Chinese (China National Knowledge Internet, WANFANG Data and SinoMed) databases. Random-effects model was used to synthesize the prevalence of depressive symptoms. Eighteen studies covering 29,626 participants were identified and analyzed. All these studies used the same measurement to identify depressive symptoms. The reported point prevalence of depressive symptoms ranged between 4% and 41% in the studies; the pooled prevalence of depressive symptoms was 19.85% (95% confidence interval: 14.75%-24.96%). In the subgroup analyses the prevalence of depressive symptoms was significantly associated with the region where the study was conducted: 17.8% in eastern, 23.7% in central, 22.7% in western, and 14.5% in northeast regions of China (P 0.001). Considering the adverse impact of depressive symptoms on health outcomes, regular screening and effective interventions should be implemented in this population.

Inactivation of the p53 transcription factor by mutation or other mechanisms is a frequent event in tumorigenesis. One of the major endogenous negative regulators of p53 in humans is hDM2, a ubiquitin E3 ligase that binds to p53 causing proteasomal p53 degradation. In this work, a library of organometallic iridium(III) compounds were synthesized and evaluated for their ability to disrupt the p53/hDM2 protein-protein interaction. The novel cyclometallated iridium(III) compound 1 [Ir(eppy)2(dcphen)](PF6) (where eppy = 2-(4-ethylphenyl)pyridine and dcphen = 4, 7-dichloro-1, 10-phenanthroline) blocked the interaction of p53/hDM2 in human amelanotic melanoma cells. Finally, 1 exhibited anti-proliferative activity and induced apoptosis in cancer cell lines consistent with inhibition of the p53/hDM2 interaction. Compound 1 represents the first reported organometallic p53/hDM2 protein-protein interaction inhibitor.

STAT3 modulates the transcription of a wide variety of regulatory genes involved in cell proliferation, differentiation, migration, apoptosis, and other critical cellular functions. Constitutive activation of STAT3 has been detected in a wide spectrum of human malignancies. A pharmacophore model constructed from a training set of STAT3 inhibitors binding to the SH2 domain was used to screen an in-house database of compounds, from which azepine 1 emerged as a top candidate. Compound 1 inhibited STAT3 DNA-binding activity in vitro and attenuated STAT3-directed transcription in cellulo with comparable potency to the well-known STAT3 inhibitor S3I-201. A fluorescence polarization assay revealed that compound 1 targeted the SH2 domain of STAT3. Furthermore, compound 1 inhibited STAT3 phosphorylation in cells without affecting the total expression of STAT3. This study also validates the use of pharmacophore modeling to identify inhibitors of protein–protein interactions. ASTAR (Agency for Sci., Tech. and Research, S’pore)