Abstract Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance ( P <5 × 10 −8 ), rs1116357 near CCDC85A , rs147538848 in FAM60A , rs1575972 near DMRTA1 , rs9309245 near ASB3 , rs67156297 near ATP8B2 , rs7107784 near MIR4686 and rs67839313 near INAFM2 . Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P <0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.
Abstract Background and Aim The aim of this study is to elucidate the natural history of pancreatic cystic lesions (PCLs), including branch duct‐type intraductal papillary mucinous neoplasm (BD‐IPMN), via midterm follow‐up analysis of a multicenter prospective observational study (NSPINAL study). Methods From July 2011 to October 2016, 881 patients with PCLs were enrolled in NSPINAL study, and 664 patients with > 12 months of follow up were analyzed. Every patient was asymptomatic, and endoscopic ultrasound was performed at the initial diagnosis to exclude high‐risk individuals. Follow up included endoscopic ultrasound, computed tomography, or magnetic resonance imaging at least once a year. Serial morphological changes and the pancreatic cancer (PC) incidence, including malignant progression of PCLs, were evaluated. Results The 664 patients (358 men) were followed for a median of 33.5 months (interquartile range 29). The cyst and main pancreatic duct sizes were 16.6 ± 9.3 and 2.3 ± 1.0 mm, respectively. Morphologically, 518 cases were multilocular, 137 were unilocular, and 9 had a honeycomb pattern; 269 cases involved multifocal lesions. Ninety‐six patients (14.5%) showed worsening progression on imaging. There were two resectable and four unresectable cases of pancreatic ductal adenocarcinoma and three cases of malignant BD‐IPMN. The 3‐year risk of developing PC was 1.2%. The standardized incidence ratio for PC among PCLs was 10.0 (95% confidence interval 3.5–16.5), and the standardized incidence ratio among BD‐IPMN was 16.6 (95% confidence interval 5.1–28.1). Multivariate analysis showed that development of symptoms and worsening progression were significant predictors of PC. Conclusions Malignant progression of PCLs, including PC development, is not uncommon. Patients with PCLs should be carefully monitored to detect pancreatic ductal adenocarcinoma at early stages.
The application of carbon nanotubes (CNTs) as biomaterials is of wide interest and studies examining their application in medicine have had considerable significance. Biological safety is the most important factor when considering the clinical application of CNTs as biomaterials and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority; however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs; instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.
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