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Direct oral anticoagulants (DOACs) have been used to prevent cardiogenic embolism in patients with atrial fibrillation (AF). No evidence has been established for the follow-up renal function evaluation intervals. We hypothesized that a proposed follow-up interval of renal function can be estimated by patient's baseline characteristics including creatinine clearance (CCr).We conducted a single-center retrospective study at Kindai University Hospital from May 2011 to December 2017. Patients were screened and they were enrolled if baseline CCr of ≥50 mL/min. To provide a periodical synchronization for measurements of CCr in all patients, these were evaluated at four different time points (approximately at 3, 6, 9, and 12 months). Primary endpoint was defined as a CCr value of50 mL/min during the follow-up period. We analyzed associations between the cumulative risk for renal endpoint and baseline characteristics by the Kaplan-Meier method and the Cox proportional hazards model.Renal endpoint was associated with age (95% CI: 0.07 to 0.21, p0.01), body weight (95% CI: -0.09 to -0.01, p0.01), CCr (95% CI: -0.18 to -0.07, p0.01), and CHA2DS2-VASc score (95% CI: 0.14 to 0.63, p0.01). Combining baseline CCr of60 mL/min and other risk factors, acceptable intervals for 5% risk levels were 78 days (age ≥75 years old), 100 days (CHA2DS2-VASc score of4 points), and 90 days (body weight60kg), respectively. Under conditions of baseline CCr of60 mL/min, age ≥75 years old, CHA2DS2-VASc score of4 points, or body weight60 kg, an increased risk of renal endpoints is 4.85, 3.29, 1.24, 2.44 fold, respectively.We propose a risk-stratified follow-up interval for renal evaluation in patients with AF and DOACs therapy according to a combination of baseline CCr and other risk factors.

Highlights • We created a new algorism to detect a left atrial appendage (LAA) thrombus on CT. • We measured HU density at one proximal (ostium) and seven distal sites of LAA. • A distal/proximal ratio and a standard deviation of HU density were analyzed by ROC. • Combination of the two parameters demonstrated a high accuracy for LAA thrombus., Background Transesophageal echocardiography (TEE) is currently the gold standard technique for diagnosing left atrial appendage (LAA) thrombi. Cardiac computed tomography (CT) has been expected to become an alternative method to TEE; however, a reliable quantitative evaluation method has not been established. Methods and results We enrolled 177 patients with persistent atrial fibrillation who underwent both cardiac CT and TEE before catheter ablation. The patients were classified into two groups according to the TEE results: the thrombus group (13 patients) and non-thrombus group (164 patients). The Hounsfield unit (HU) density at the proximal LAA (LAAp) and distal LAA (LAAd) was measured on cardiac CT images. The LAAd/LAAp HU ratio and standard deviation of HU density (HU-SD) at the LAAd were evaluated. We created an algorithm by decision tree analysis to predict LAA thrombus formation using the HU ratio and HU-SD. Definite absence of LAA thrombus (Category-I) was diagnosed for 139 patients by combining the first and second branching of the decision tree (Category-Ia: HU ratio of ≥0.26, Category-Ib: HU ratio of

Implantable cardioverter-defibrillator and cardiac resynchronization therapy using a defibrillator (ICD/CRT-D) are established means of reducing mortality due to ventricular arrhythmia. Although atrial fibrillation/flutter (AF) is the most common cardiac arrhythmia in patients with heart disease, the impact of AF on the prognosis of patients with ICD/CRT-D remains controversial.We analyzed data from the Nippon Storm Study, a prospective observational study of 1570 patients that was conducted at 48 Japanese ICD centers. We allocated 1549 participants to AF and non-AF groups, compared their clinical data at the time of enrollment, and monitored the incidences of mortality, hospitalization, and appropriate and inappropriate ICD/CRT-D therapy during a median 28 months. When the AF (n = 257, 16.6%) and non-AF-(n = 1292, 83.4%) groups were compared, the AF group was older (67.7 vs. 61.4 years; p0.0001), and had lower left ventricular ejection fraction (38.0 ± 17.0% vs. 43.5 ± 18.9%; p0.0001). During follow up, mortality was significantly higher in the AF than the non-AF group (p0.0001). In multivariate analysis, AF was significantly associated with all-cause mortality [p = 0.013; hazard ratio (HR)=1.62]. Inappropriate ICD/CRT-D therapy occurred in 40/257 patients (15.6%) and AF was associated with a higher prevalence of inappropriate ICD/CRT-D therapy (p0.0001; HR=2.25).The presence of AF at ICD/CRT-D implantation carries subsequent independent risks of 1.62-fold for death and 2.25-fold for inappropriate therapy.

Caffeine is a methylxanthine derived from plant foods such as coffee beans and tea leaves, and has multiple biological activities against physiological response and several diseases. Although there are some reports about the direct effect of caffeine against anti-lipid accumulation in vitro, the effect of caffeine on lipid accumulation in adipocytes through stimulating intestinal epithelial cells is unknown. Since direct treatment with caffeine to 3T3-L1 cells did not affect lipid accumulation, we determined whether caffeine-stimulated intestinal epithelial Caco-2 cells influence the lipid accumulation in 3T3-L1 adipocytes. Caco-2 cells were cultured on a transwell insert with or without caffeine for 24 h. Subsequently, the basolateral component of the Caco-2 cell culture on the transwell was collected and termed caffeine-conditioning medium (CCM). When 3T3-L1 adipocytes were incubated with CCM, CCM decreased lipid accumulation and suppressed gene expression of proliferator activated receptor (PPAR) γ and CCAAT/enhancer binding protein (C/EBP) α in 3T3-L1 adipocytes. Furthermore, CCM decreased the expression of C/EBPβ and C/EBPδ at the protein level, but not at the mRNA level. We observed that a proteasome inhibitor, MG132, inhibited CCM-caused down-expression of C/EBPβ and C/EBPδ proteins, and that CCM promoted the ubiquitination level of C/EBPβ and C/EBPδ proteins. Protein microarray analysis showed caffeine suppresses the secretion of inflammatory cytokines, interleukin-8 and plasminogen activator inhibitor-1 from Caco-2 cells. These results suggest that caffeine indirectly suppresses lipid accumulation in 3T3-L1 adipocytes through decreasing secretion of inflammatory cytokines from Caco-2 cells.

Glucose uptake ability into L6 skeletal muscle cell was examined with eleven kinds of ring fission metabolites of (-)-epigallocatechin gallate (EGCG) produced by intestinal bacteria. The metabolites 5-(3,5-dihydroxyphenyl)-γ-valerolactone (EGC-M5), 4-hydroxy-5-(3,4,5-trihydroxyphenyl)valeric acid (EGC-M6), 5-(3,4,5-trihydroxyphenyl)-γ-valerolactone (EGC-M7) and 5-(3-hydroxyphenyl)valeric acid (EGC-M11) have been found to promote uptake of glucose into L6 myotubes significantly. EGC-M5, which is one of the major ring fission metabolites of EGCG, was also found to have a promotive effect on glucose transporter 4 (GLUT4) translocation accompanied by phosphorylation of AMP-activated protein kinase (AMPK) signaling pathway in skeletal muscle both in vivo and in vitro. Furthermore, the effect of oral single dosage of EGC-M5 on glucose tolerance test with ICR mice was examined and significant suppression of hyperglycemia was observed. These data suggested that EGC-M5 has an antidiabetic effect in vivo.

Our previous report demonstrated that epigallocatechin gallate (EGCg) promotes translocation of glucose transporter 4 (GLUT4) in skeletal muscle. In this study, we investigated the molecular mechanism of GLUT4 translocation by EGCg at the physiological concentration range. In L6 cells, EGCg induced phosphorylation of phosphatidylinositide 3′-kinase (PI3K) and downstream protein kinase C (PKC) λ/ξ without affecting the phosphorylation of insulin receptor and Akt. EGCg-induced GLUT4 translocation was suppressed by RNA interference-mediated knockdown of PI3K and treatment with PKC inhibitor Go6983. Moreover, EGCg increased Rac1 activity and actin remodelling as downstream events of PKCλ/ξ. These results indicate that EGCg induced GLUT4 translocation through a PI3K-dependent pathway, but its mode of action differed from that of insulin. EGCg also induced GLUT4 translocation through a 5′-adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway. 67 kDa laminin receptor, which is a target molecule of EGCg, was not involved in EGCg-induced glucose uptake in L6 cells. The oral administration of EGCg suppressed postprandial hyperglycaemia accompanied by GLUT4 translocation through both PI3K- and AMPK-dependent pathways, and promoted glycogen accumulation in skeletal muscle of ICR mice. EGCg promotes GLUT4 translocation through both PI3K- and AMPK-dependent pathways and glycogen accumulation in skeletal muscle.

Donor–π–acceptor (D–π–A) type pyridinium dye bearing an iodide ion as the counter anion that has been newly synthesized showed specific solvatochromism, leading to large bathochromic shift of absorption band in halogenated solvents: the bathochromic shifts of the D–π–A type pyridinium dye in halogenated solvents are larger than those of the non-halogenated solvents of low ɛr values. Investigation of absorption spectral measurement, 1H NMR measurements, and semi-empirical molecular calculations (AM1 and INDO/S using the SCRF Onsager Model) revealed that the intramolecular charge transfer (ICT) characteristics of the D–π–A type pyridinium dye became stronger in the halogenated solvents. On the basis of the experimental results and the theoretical calculations, the influences of halogenated solvent on the large bathochromic shift of D–π–A type pyridinium dye are discussed. ©2012 Elsevier Science. All rights reserved.

We have newly designed and synthesized unsymmetrical carbazole-type D–π–A fluorescent dyes. The dyes show a bathochromic shift-type mechanofluorochromism (MFC): grinding of as-recrystallized dyes induces a bathochromic shift of fluorescent color and the fluorescent color is recovered by heating or exposure to solvent vapor. In order to clarify the MFC mechanism for the carbazole-type D–π–A fluorescent dyes, time-resolved fluorescence spectroscopy, X-ray powder diffractometry, single-crystal X-ray structural analysis, IR spectroscopy, and differential scanning calorimetry are performed before and after grinding of the solids. On the basis of experimental results and semi-empirical molecular orbital calculations (AM1 and INDO/S), we have revealed that the MFC is attributed to a reversible switching between crystalline and amorphous states with changes of intermolecular hydrogen bonding and π–π interaction.

A new-type of donor-acceptor π-conjugated (D-π-A) fluorescent dyes NI3-NI8 with a pyridine ring as electron-withdrawing-injecting anchoring group have been developed and their photovoltaic performances in dye-sensitized solar cells (DSSCs) are investigated. The short-circuit photocurrent densities and solar energy-to-electricity conversion yields of DSSCs based on NI3-NI8 are greater than those for the conventional D-π-A dye sensitizers NI1 and NI2 with a carboxyl group as the electron-withdrawing anchoring group. The IR spectra of NI3-NI8 adsorbed on TiO(2) indicate the formation of coordinate bonds between the pyridine ring of dyes NI3-NI8 and the Lewis acid sites (exposed Ti(n+) cations) of the TiO(2) surface. This work demonstrates that the pyridine rings of D-π-A dye sensitizers that form a coordinate bond with the Lewis acid site of a TiO(2) surface are promising candidates as not only electron-withdrawing anchoring group but also electron-injecting group, rather than the carboxyl groups of the conventional D-π-A dye sensitizers that form an ester linkage with the Brønsted acid sites of the TiO(2) surface.

An anthracene-amino acid system with two carboxyl groups has been designed and synthesized as a new class of fluorescence PET (photo-induced electron transfer) sensor for detection of water in organic solvents. An enhancement in fluorescence is observed with increasing water content in 1,4-dioxane, THF, acetonitrile and ethanol, which is attributable to the suppression of PET by the intramolecular proton transfer of the carboxyl proton to the amino group. The detection limit and quantitation limit are, respectively, 0.1 and 0.3 wt% for 1,4-dioxane, 0.4 and 1.2 wt% for THF, 0.1 and 0.3 wt% for acetonitrile and 0.1 and 0.3 wt% for ethanol.

A series of benzofuro[2,3-c]oxazolo[4,5-a]carbazole-type fluorescent dyes OH1, OH2, OH4, OH7, and OH17 with carboxyl groups on different positions of a chromophore skeleton are synthesized and applied to dye-sensitized solar cells (DSSCs) as a new class of donor-π-acceptor (D-π-A) photosensitizers. In the dye OH1, a carboxyl group acts as not only the anchoring group for attachment on TiO2 surface but also the electron acceptor. For OH2, OH4, and OH7, on the other hand, a carboxyl group is an anchoring group, but the electron acceptor is not a carboxyl group but a cyano group. The dye OH17 has two carboxyl groups, which are located at the same positions as those of OH1 and OH7. The absorption and fluorescence spectra and cyclic voltammograms of these fluorescent dyes resemble very well, showing a negligible influence of the position of carboxyl group on photophysical and electrochemical properties of these dyes. When these dyes are used in DSSCs, however, their photovoltaic performances differ considerably. In order to elucidate the difference in the DSSC performance among the five dyes, kinetics of the electron injection from the conduction band of TiO2 to dye cation and to I3− ions in solution were studied by employing the transient absorption spectroscopy and the transient photovoltage technique, respectively. It is found that the charge recombination rate for OH2 is similar to that of OH1 and is much slower than those of OH4 and OH17, consistent with the high short-circuit photocurrent densities for OH1 and OH2. On the basis of the MO calculations (AM1 and INDO/S) and the charge recombination kinetics, the differences of the photovoltaic performances among the five dyes are discussed from the viewpoint of configuration of the dyes adsorbed on TiO2 surface, and a new molecular design for D-π-A dye sensitizers based on a control of molecular orientation and arrangement of dye adsorbed on TiO2 surface is proposed.

New-type donor–acceptor π-conjugated (D–π–A) fluorescent dyes OH11, OH14, and OH15 with pyridine, 4-phenylpyridine, and quinoline rings, respectively, as electron-accepting groups have been develop...

Anthracene–boronic acid ester as a new class of fluorescence PET sensors for detection of a trace amount of water in organic solvents has been designed and developed.

A new class of fluorescence sensor for detection of water in organic solvents based on photo-induced electron transfer (PET) of anthracene coupled with an amino acid has been designed and developed.