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Background The Japanese quail (Coturnix japonica) is an important poultry species owing to their high economic efficiency and biological advantages. The genetic diversity of farm quail populations has rarely been studied. Objectives This study aimed to assess the genetic diversity of farm quail populations and their genetic relationships, which could provide important information for designing breeding programmes to maintain egg and/or meat production efficiency. Methods Molecular phylogenetic and STRUCTURE analyses were conducted for seven farm populations and six laboratory lines using 50 microsatellite markers previously developed by us. Results The genetic diversity within each farm population was relatively high despite long‐term breeding within closed colonies. However, the genetic variation between populations was absent. Twenty highly polymorphic markers, selected based on Ne, He and FST values, enabled the construction of reliable phylogenetic trees and STRUCTURE plots. Conclusions In the farm populations analysed in the present study, gene flow between genetically distant populations is needed to restore genetic diversity between farm populations, which could exploit heterosis and decrease the risk of inbreeding depression. Our findings demonstrate that these markers are useful for examining the genetic structure of farm quail populations., We conducted genetic monitoring for six farm populations in Aichi prefecture, Japan, and five laboratory lines, whose breeding histories are well recorded, using 48 microsatellite markers. We estimated the genetic diversity of the farm populations and their genetic relationships by molecular phylogenetic and STRUCTURE analyses, which provided important information to obtain suitable genetically distinct candidates for cross‐mating to restore genetic diversity among populations.

Diabetic kidney disease (DKD) is a key determinant of morbidity and mortality in patients with type 1 diabetes (T1D). Identifying factors associated with early glomerular filtration rate (GFR) decline in T1D is important in prevention or early intervention for DKD. This study investigated whether phosphate metabolism, including fibroblast growth factor 23 (FGF23) is associated with the kidney function of patients with T1D. We randomly recruited 118 patients with T1D with a normal or mildly impaired kidney function [chronic kidney disease (CKD) stages of G1/G2, A1/A2], and measured their serum FGF23 levels. Serum FGF23 was significantly negatively associated with the estimated GFR (eGFR) (r = -0.292, P = 0.0016), but not urinary albumin creatinine ratio (UACR), and positively associated with serum phosphate (Pi; r = 0.273, P = 0.0027). Serum FGF23 increased with decreasing eGFR quartiles (P for linear trend = 0.0371), while FGF23 was modestly higher in the higher quartiles of UACR (not statistically significant). The multiple linear regression analysis also showed a significant inverse association between FGF23 and eGFR (Model 1: β = -0.149, P = 0.0429; Model 2: β = -0.141, P = 0.0370). The association remained significant after adjustment for Pi. We identified that FGF23 was inversely associated with the eGFR in T1D patients with a normal or mildly impaired kidney function.

Daily glucose profile (DGP) involves various factors contributing to diabetic complications: diet, physical activity, insulin dose, social context and stressors. We aimed to identify specific DGPs susceptive to microvascular complication in T1D, exploring endpoint-oriented CGM metrics. First, cluster analysis with 5,584 pooled DGPs from 102 T1D subjects detected 4 major clusters characterized as aligned control (A), biphasic dysglycemia (B), continuous nocturnal hyperglycemia (C) and dyscontrol (D) (Figure 1). The presence of neuropathy and nephropathy was significantly associated with the increase of cluster B (+76%, p=0.002) and C (+69%, p=0.002), respectively. Next, we determined metric ∫B/∫C as the integration of loge (glucose excursions from 70-180 mg/dL):0-12am/:0-6am to represent cluster B/C. To evaluate ∫B/∫C, the retrospective study investigated 18,457 DGPs from 231 adults with T1D (steroid users and available DGPs New CGM metrics ∫B/∫C derived from vulnerable DGP clusters may support risk assessment and early intervention for diabetic complications. Disclosure Y. Maeda: Research Support; Self; Abbott, Arkray, Inc. Speaker's Bureau; Self; Abbott, Arkray, Inc., Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Terumo Medical Corporation. M. Morita: None. A. Tamura: None. K. Takasu: None. Y. Kurogi: None. I. Nimura: Speaker's Bureau; Self; Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Taisho Pharmaceutical Co., Ltd. R. Yoshioka: None. M. Minami: Speaker's Bureau; Self; Abbott, Eli Lilly and Company, Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Sanofi, Terumo Medical Corporation. Funding Kondou Kinen Medical Foundation

IntroductionType 1 diabetes (T1D) is associated with higher fracture risk. However, few studies have investigated the relationship between severe hypoglycemia and fracture risk in patients with T1D, and the results are controversial. Besides, none has investigated the risk factors for fracture in Asian patients with T1D. The aim of the present study was to investigate the prevalence of bone fracture and its relationship between severe hypoglycemia and other risk factors in Japanese patients with T1D.Research design and methodsThe single-center cross-sectional study enrolled 388 Japanese patients with T1D (mean age, 45.2 years; women, 60.4%; mean duration of diabetes, 16.6 years) between October 2019 and April 2020. The occurrence and circumstances of any fracture after the diagnosis of T1D were identified using a self-administered questionnaire. The main outcomes were any anatomic site of fracture and fall-related fracture. Severe hypoglycemia was defined as an episode of hypoglycemia that required the assistance of others to achieve recovery.ResultsA total of 92 fractures occurred in 64 patients, and 59 fractures (64%) were fall-related. Only one participant experienced fracture within the 10 years following their diagnosis of diabetes. In logistic regression analysis, the multivariate-adjusted ORs (95% CIs) of a history of severe hypoglycemia were 2.11 (1.11 to 4.09) for any fracture and 1.91 (0.93 to 4.02) for fall-related fracture. Fourteen of 18 participants with multiple episodes of any type of fracture had a history of severe hypoglycemia (pConclusionsWe have shown that a history of severe hypoglycemia is significantly associated with a higher risk of bone fracture in Japanese patients with T1D.

The contribution of caspases to hepatic ischemia/reperfusion (I/R)-induced apoptosis has not been completely understood yet. Several studies have demonstrated increased caspase activity during I/R and the protective effect of caspase inhibitors against I/R injuries. However, reports with opposing results also exist. Herein, we examined the contribution of caspases to the I/R-induced hepatic apoptosis in rats using caspase inhibitors and specific substrates of caspases. Hepatic I/R was induced via a 2-h occlusion of the portal vein and the hepatic artery, without conducting bile duct occlusion. DNA laddering and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL)-positive cells were increased at 3 h after reperfusion. Pretreatment with caspase inhibitors (Z-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp-cmk) 2 or 10 mg/kg intravenously (i.v.), 20 mg/kg intraperitoneally (i.p.), Z-Val-Ala-Asp(OMe)-fluoromethylketone (Z-VAD-fmk) 3 mg/kg i.v.) failed to reduce apoptosis induced by I/R. Interestingly, apoptosis induced by the portal triad (hepatic artery, portal vein, and bile duct) occlusion/reperfusion could be marginally attenuated using Z-Asp-cmk (2 mg/kg i.v.). The cleavage activity for Ac-DEVD-α-(4-methylcoumaryl-7-amide) (MCA), a caspase-3/7/8/9 substrate, was significantly increased by I/R. Conversely, the cleavage activities for Ac-DNLD-MCA and MCA-VDQVDGW[K-DNP]-NH2, specific substrates for caspase-3 and -7 respectively, were decreased by I/R. Protein expression of the cellular inhibitor of apoptosis protein 2 (c-IAP2), an endogenous caspase inhibitor, was increased by ischemia. Nuclear translocation of the apoptosis-inducing factor (AIF), an initiator protein of caspase-independent apoptosis, was also increased during I/R. These results suggest that caspases are inhibited by c-IAP2 induced during ischemia and that AIF may be involved in initiation of apoptosis induced by hepatic I/R without bile duct occlusion.

Owing to their narrow therapeutic range, most antiarrhythmic agents require Therapeutic Drug Monitoring (TDM). Though TDM is an effective tool for adjusting the individual dosage to the optimum level, no study has shown that TDM is useful for dose adjustment in the case of cibenzoline. The aim of this study was thus to evaluate the usefulness of TDM in cibenzoline therapy.In the National Cardiovascular Center, TDM was introduced for cibenzoline in 1998. This resulted in reductions in mean serum concentrations and mean doses, and very few adverse effects have been reported. Thanks to dosage adjustment based on TDM, there was a decrease in the proportion of patients having serum concentrations of above 400 ng/mL from 2000 onwards. These results suggest that TDM is an effective tool for preventing cibenzoline toxicity and that it helps to ensure that cibenzoline is administered properly.

Unsubstituted and trimethyl-4,8-diphosphathiophenetriptycenes (4 and 3d) were synthesized by reduction of the corresponding phosphine oxides (8a and 8b) with trichlorosilane which were prepared by the reaction of trilithium salts, derived from tri-3-thienylphosphine oxides (7a and 7b), with P(OPh)3. The reaction of 3d with W(CO)5(THF) gave a 1:2 complex 12 in high yield.