Construction of a [15]Annulenone-[15]annulenyl Ion Cycle

Previously, we have reported the synthesis of furanoid [15]annulenones and their protonated species. With the benefits of FT NMR spectroscopy, some of experiments have now been reinvestigated. The annulenone may undergo dynamic conformational changes to provide an interesting cycle, which can be driven by protonation- deprotonation sequence

Copy number alterations in urothelial carcinomas: their clinicopathological significance and correlation with DNA methylation alterations

The aim of this study was to clarify the genetic backgrounds underlying the clinicopathological characteristics of urothelial carcinomas (UCs). Array comparative genomic hybridization analysis using a 244K oligonucleotide array was performed on 49 samples of UC tissue. Losses of 2q33.3–q37.3, 4p15.2–q13.1 and 5q13.3–q35.3 and gains of 7p11.2–q11.23 and 20q13.12–q13.2 were correlated with higher histological grade, and gain of 7p21.2–p21.12 was correlated with deeper invasion. Losses of 6q14.1–q27 and 17p13.3–q11.1 and gains of 19q13.12–q13.2 and 20q13.12–q13.33 were correlated with lymph vessel involvement. Loss of 16p12.2–p12.1 and gain of 3q26.32–q29 were correlated with vascular involvement. Losses of 5q14.1–q23.1, 6q14.1–q27, 8p22–p21.3, 11q13.5–q14.1 and 15q11.2–q22.2 and gains of 7p11.2–q11.22 and 19q13.12–q13.2 were correlated with the development of aggressive non-papillary UCs. Losses of 1p32.2–p31.3, 10q11.23–q21.1 and 15q21.3 were correlated with tumor recurrence. Unsupervised hierarchical clustering analysis based on copy number alterations clustered UCs into three subclasses: copy number alterations associated with genome-wide DNA hypomethylation, regional DNA hypermethylation on C-type CpG islands and genome-wide DNA hypo- and hypermethylation were accumulated in clusters A, B1 and B2, respectively. Tumor-related genes that may encode therapeutic targets and/or indicators useful for the diagnosis and prognostication of UCs should be explored in the above regions. Both genetic and epigenetic events appear to accumulate during urothelial carcinogenesis, reflecting the clinicopathological diversity of UCs

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Oceanographic Data of the 16th Japanese Antarctic Research Expedition 1974-1975

This is a report of the results of oceanographic observation carried out on board FUJI during the mission of the 16th Japanese Antarctic Research Expedition in 1974-1975

ダイ16ジ ナンキョク チイキ カンソクタイ カイヨウ ブモン ホウコク

第16次南極地域観測において,定常観測(1974-1975)として,海上保安庁水路部の担当した表面観測,バシサーモグラフ(BT)観測,温度-塩分-深度記録計(STD)による観測,および各層観測の結果を報告する.This is a report of the results of oceanographic observation carried out on board FUJI during the mission of the 16th Japanese Antarctic Research Expedition in 1974-1975