Welsh Newman (smellcotton39)
The therapeutic landscape of thrombotic thrombocytopenic purpura (TTP) is rapidly changing with the recent availability of new targeted therapies. This progressive shift from empiricism to pathophysiology-based treatments reflects an intensive interaction between the continuous findings in the field of basic science and an efficient collaborative clinical research and represents a convincing example of the strength of translational medicine. Despite the rarity of TTP, national and international efforts could circumvent this limitation and shed light on the epidemiology, clinical presentation, prognosis, and long-term outcome of this disease. Importantly, they also provided high-quality results and practice changing studies for the benefit of patients. We report here the most recent therapeutic findings that allowed progressively improving the prognostic of TTP, both at the acute phase and through long-term outcome.Many surgeons have modified the technique to reduce bleeding from anastomosis line since Bentall and De Bono introduced aortic root replacement using a composite graft. We present a new composite, butterfly wing-shaped, valve graft fixated using hand-made double sewing cuff. The "wings of a butterfly" technique is a method of reinforcement suturing between an added sewing cuff and residual aortic wall at the proximal stump and helps to reduce bleeding after the modified Bentall's procedure.Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (P less then 1.0 × 10-4) in an independent case-control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stages 1 and 2) using meta-analysis, the associations of two loci reached a genome-wide significance level rs12630354 near STT3B on chromosome 3, P = 1.62 × 10-9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11-1.23, and rs140508424 within PALM2 on chromosome 9, P = 4.19 × 10-8, OR = 1.61, 95% CI 1.36-1.91. However, the association of these two loci was not replicated in Korean, European or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (P = 2.17 × 10-6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.Posttranslational modification of a protein with glycosylphosphatidylinositol (GPI) is a conserved mechanism exists in all eukaryotes. Thus far, >150 human GPI-anchored proteins have been discovered and ~30 enzymes have been reported to be involved in the biosynthesis and maturation of mammalian GPI. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) catalyzes the very first step of GPI anchor biosynthesis. Patients carrying a mutation of the PIGA gene usually suffer from inherited glycosylphosphatidylinositol deficiency (IGD) with intractable epilepsy and intellectual developmental disorder. We generated three mouse models with PIGA deficits specifically in telencephalon excitatory neurons (Ex-M-cko), inhibitory neurons (In-M-cko) or thalamic neurons (Th-H-cko), respectively. Both Ex-M-cko and In-M-cko mice showed impaired long-term fear memory and were more susceptible to kainic acid-indu
