In addition, the ESBL-producing E. coli identified showed genetic characteristics related to those reported from humans.BACKGROUND Men's perpetration of intimate partner violence (IPV) limits gains in health and wellbeing for populations globally. Largely informal, rapidly expanding peri-urban settlements, with limited basic services such as electricity, have high prevalence rates of IPV. Evidence on how to reduce men's perpetration, change social norms and patriarchal attitudes within these settings is limited. Our cluster randomised controlled trial aimed to determine the effectiveness of the Sonke CHANGE intervention in reducing use of sexual and/or physical IPV and severity of perpetration by men aged 18-40 years over 2 years. METHODOLOGY The theory-based intervention delivered activities to bolster community action, including door-to-door discussions, workshops, drawing on the CHANGE curriculum, and deploying community action teams over 18 months. In 2016 and 2018, we collected data from a cohort of men, recruited from 18 clusters; nine were randomised to receive the intervention, while the nine control clusters received s between arms for sexual IPV was 0.01 (95% CI - 0.04 to 0.06), while severe IPV followed a similar pattern (Diff = 0.01; 95% CI - 0.05 to 0.07). A secondary analysis using LCA suggests that among the men living in intervention communities, there was a greater reduction in IPV among less violent and more law abiding men than among more highly violent men, although the differences did not reach statistical significance. CONCLUSION The intervention, when implemented in a peri-urban settlement, had limited effect in reducing IPV perpetrated by male residents. Further analysis showed it was unable to transform entrenched gender attitudes and use of IPV by those men who use the most violence, but the intervention showed promise for men who use violence less. TRIAL REGISTRATION ClinicalTrials.gov, NCT02823288. Registered on 30 June 2016.BACKGROUND Systemic lupus erythematosus (SLE) is an autoimmune inflammatory rheumatic disease. SLE susceptibility is affected by multiple genetic elements, environmental factors, and their interactions. We aimed in this study to statistically and functionally characterize a gene-gene interaction (epistasis) recently documented to affect SLE risk. METHODS Two single-nucleotide polymorphisms, rs2230926 in TNFAIP3 (A20) gene and rs131654 in UBE2L3 (UBCH7) gene, were genotyped in all 3525 Korean participants, and their SLE risk association and epistasis were statistically analyzed by calculating odds ratio (OR), 95% confidence interval (CI), and P values in genotype comparisons between 1318 SLE patients and 2207 healthy controls. https://www.selleckchem.com/products/sto-609.html Furthermore, their effects on gene functions were assessed by comparatively examining separate and combined effects of TNFAIP3 and UBE2L3 knockdowns on NF-κB transcription factor activity in human cells. RESULTS SLE susceptibility is associated with TNFAIP3 rs2230926 (OR = 1.9, 95% CI 1.observed in SLE risk, as being evident in comparison of genotype distributions between SLE patients and controls. Additionally, the synergistic gene-gene interaction is functionally validated, as TNFAIP3 reduction and UBE2L3 augment exert synergism in activation of NF-κB and subsequent induction of inflammatory cytokines. Accordingly, SLE inflammation and risk could be synergistically alleviated by TNFAIP3 upregulation and UBE2L3 downregulation.BACKGROUND Systemic lupus erythematosus (SLE) is a complex multi-system disease, characterized by both autoimmune and autoinflammatory clinical and laboratory features. The role of type I interferon (IFN) in SLE has been demonstrated from the 2000s, by gene expression analyses showing significant over-expression of genes related to type I IFN signalling pathway (IFN signature). However, several studies questioned the role of measuring the intensity of IFN signature (IFN score) to chase SLE activity. We would assess if the IFN signature can help the clinical and therapeutic stratification of patients with pediatric SLE. METHODS We measured the IFN score in peripheral whole blood from a series of subjects with childhood-onset SLE and correlated the results with clinical and laboratory parameters. RESULTS Thirty-one subjects were included in the study, among which the 87% displayed a positive IFN score. The only significant relation was found for high IFN score in subjects with normocomplementemia. No correlation was observed between IFN score and SLEDAI-2K, BILAG-2004 and SLICC. Patients with high IFN score and normal complement levels also presented lower anti-dsDNA antibodies. CONCLUSIONS The integration between IFN signature analysis and complement levels may easily distinguish two groups of subjects, in which the autoimmune or autoinflammatory component of the disease seems to be prevalent.BACKGROUND Vacuolar H+-ATPase (V-ATPase) is a highly conserved protein complex which hydrolyzes ATP and pumps protons to acidify vacuolar vesicles. Beyond its role in pH maintenance, the involvement of V-ATPase in endocytosis is well documented in mammals and plants but is less clear in Trypanosoma brucei. METHODS In this study, the subcellular localization of V-ATPase subunit B (TbVAB) of T. brucei was assessed via in situ N-terminal YFP-tagging and immunofluorescence assays. Transgenic bloodstream forms (BSF) of T. brucei were generated which comprised either a V-ATPase subunit B (TbVAB) conditional knockout or a V-ATPase subunit A (TbVAA) knockdown. Acridine orange and BCECF-AM were employed to assess the roles of V-ATPase in the pH regulation of BSF T. brucei. The endocytic activities of three markers were also characterized by flow cytometry analyses. Furthermore, trypanosomes were counted from trypanolysis treatment groups (either containing 1% or 5% NHS) and endocytosed trypanosome lytic factor (TLF) w in BSF of T. brucei. Besides vacuolar alkalinization, the dysregulation of endocytosis in TbVAB depleted T. brucei is considered to contribute to the reduced sensitivity to lysis by normal human serum.BACKGROUND Clonorchiasis is endemic in East and Southeast Asian countries. For a preventive strategy against infectious diseases, vaccination is the most effective. Here, we evaluated the molecular characteristics and immune responses of CsAg17 protein from Clonorchis sinensis, and investigated its protective effects against C. sinensis challenge. METHODS A cDNA clone encoding CsAg17 protein and containing a secretory signal peptide at the N-terminus was retrieved from the C. sinensis transcriptome bank. Recombinant CsAg17 B-cell epitope protein and cDNA vaccines were produced and their immune responses were evaluated in FVB mice. The proportional changes of CD3+/CD4+ and CD3+/CD8+ T cells were detected by flow cytometry, and immune effectors were measured by ELISA. RESULTS The CsAg17 mRNA was transcribed at a higher level in C. sinensis adults than in metacercariae. The CsAg17 protein was distributed in the sperms, oral and ventral suckers, and mesenchymal tissues of C. sinensis adults. In mice challenged with C.