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Hepatic glucose metabolism serves dual purposes: maintaining glucose homeostasis and converting glucose into energy sources; however, the underlying mechanisms are unclear. We quantitatively measured liver metabolites, gene expression, and phosphorylated insulin signaling molecules in mice orally administered varying doses of glucose, and constructed a transomic network. Rapid phosphorylation of insulin signaling molecules in response to glucose intake was observed, in contrast to the more gradual changes in gene expression. Glycolytic and gluconeogenic metabolites and expression of genes involved in glucose metabolism including glucose-6-phosphate, G6pc, and Pck1, demonstrated high glucose dose sensitivity. Whereas, glucokinase expression and glycogen accumulation showed low glucose dose sensitivity. During the early phase after glucose intake, metabolic flux was geared towards glucose homeostasis regardless of the glucose dose but shifted towards energy conversion during the late phase at higher glucose doses. Our research provides a comprehensive view of time- and dose-dependent selective glucose metabolism. [ABSTRACT FROM AUTHOR]

We have performed a lab-based hypergravity cultivation experiment using a centrifuge equipped with a lighting system and examined long-term effects of hypergravity on the development of the main axis of the Arabidopsis (Arabidopsis thaliana (L.) Heynh.) primary inflorescence, which comprises the rachis and peduncle, collectively referred to as the main stem for simplicity. Plants grown under 1 × g (gravitational acceleration on Earth) conditions for 20–23 days and having the first visible flower bud were exposed to hypergravity at 8 × g for 10 days. We analyzed the effect of prolonged hypergravity conditions on growth, lignin deposition, and tissue anatomy of the main stem. As a result, the length of the main stem decreased and cross-sectional area, dry mass per unit length, cell number, and lignin content of the main stem significantly increased under hypergravity. Lignin content in the rosette leaves also increased when they were exposed to hypergravity during their development. Except for interfascicular fibers, cross-sectional areas of the tissues composing the internode significantly increased under hypergravity in most types of the tissues in the basal part than the apical part of the main stem, indicating that the effect of hypergravity is more pronounced in the basal part than the apical part. The number of cells in the fascicular cambium and xylem significantly increased under hypergravity both in the apical and basal internodes of the main stem, indicating a possibility that hypergravity stimulates procambium activity to produce xylem element more than phloem element. The main stem was suggested to be strengthened through changes in its morphological characteristics as well as lignin deposition under prolonged hypergravity conditions. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) bleeding control is critical in elderly patients with atrial fibrillation (AF) receiving oral anticoagulants (OAC). This subgroup analysis aimed to clarify the actual state and significance of GI bleeding in elderly non-valvular AF (NVAF) patients. We evaluated the incidence and risk factors of GI bleeding during the 2-year follow-up and examined the GI bleeding impact on mortality. Of the 32,275 patients in the ANAFIE Registry, 1139 patients (3.5%) experienced GI bleeding (incidence rate, 1.92 events per 100 person-years; mean follow-up, 1.88 years); 339 upper and 760 lower GI bleeding events occurred. GI bleeding risk factors included age ≥ 85 years, body mass index ≥ 25.0 kg/m2, prior major bleeding, hyperuricaemia, heart failure, P-glycoprotein inhibitor use, GI disease, and polypharmacy (≥ 5 drugs). No significant differences in GI bleeding risk were found between direct OAC (DOAC) vs warfarin users (adjusted hazard ratios [95% confidence interval], 1.01 [0.88–1.15]). The 1-year post-GI bleeding mortality rate was numerically higher in patients with upper (19.6%) than lower GI bleeding (8.9%). In elderly Japanese NVAF patients, this large-scale study found no significant difference in GI bleeding risk between DOAC vs. warfarin users or 1-year mortality after upper or lower GI bleeding. [ABSTRACT FROM AUTHOR]

Recently, a once-daily dose of edoxaban (15-mg) has been approved for stroke prevention in non-valvular atrial fibrillation (NVAF) patients aged ≥ 80 years, in whom standard oral anticoagulants are not recommended because of high bleeding risk (HBR), based on the ELDERCARE-AF trial. However, information regarding the characteristics and clinical outcomes among such patients is limited. Thus, this study aimed to clarify the characteristics and event rates in elderly patients with NVAF and HBR defined by the ELDERCARE-AF criteria. Of the 7406 NVAF outpatients included in the J-RHYTHM Registry, 60 patients with creatinine clearance (CrCl) < 15 mL/min were excluded. The remaining 7346 patients (age, 69.7 ± 9.9 years; men, 70.9%; warfarin use, 78.7%) were divided into three groups: Group 1, aged < 80 years (n = 6165); Group 2, aged ≥ 80 years without HBR (n = 584); and Group 3, aged ≥ 80 years with HBR (at least one of the followings; CrCl, 15–30 mL/min, history of bleeding, body weight ≤ 45 kg, and antiplatelet use) (n = 597, eligible for 15-mg edoxaban). Patients in Group 3 had a higher prevalence of comorbidities, and therefore, both higher thromboembolic and bleeding risk scores than in the other groups. During the 2-year follow-up period, the incidence rates (per 100 person-years) of thromboembolism in Groups 1, 2, and 3 were 0.7, 1.5, and 2.1 (P < 0.001), major hemorrhage, 0.8, 1.2, and 2.0 (P < 0.001), and all-cause death, 0.8, 2.6, and 4.6 (P < 0.001), respectively. Adjusted hazard ratios of Group 3 were 1.64 (95% confidence interval 0.89–3.04, P = 0.116) for thromboembolism, 1.53 (0.85–2.72, P = 0.154) for major hemorrhage, and 1.84 (1.19–2.85, P = 0.006) for all-cause death compared with Group 1. The NVAF Patients aged ≥ 80 years with HBR defined by the ELDERCARE-AF criteria were certainly at a higher adverse event risk, especially for all-cause death. Clinical trial registration: The J-RHYTHM Registry is registered in the University Hospital Medicine Information Network (UMIN) Clinical Trials Registry (unique identifier: UMIN000001569) http://www.umin.ac.jp/ctr/. [ABSTRACT FROM AUTHOR]

Real-world data on coronary events (CE) in elderly patients with atrial fibrillation (AF) are lacking in the direct oral anticoagulant era. This prespecified sub-analysis of the ANAFIE Registry, a prospective observational study in > 30,000 Japanese patients aged ≥ 75 years with non-valvular AF (NVAF), investigated CE incidence and risk factors. The incidence and risk factors for new-onset CE (a composite of myocardial infarction [MI] and cardiac intervention for coronary heart diseases other than MI), MI, and cardiac intervention for coronary heart diseases other than MI during the 2-year follow-up were assessed. Bleeding events in CE patients were also examined. Among 32,275 patients, the incidence rate per 100 patient-years was 0.48 (95% confidence interval (CI): 0.42–0.53) for CE during the 2-year follow-up, 0.20 (0.16–0.23) for MI, and 0.29 (0.25–0.33) for cardiac intervention for coronary heart diseases other than MI; that of stroke/systemic embolism was 1.62 (1.52–1.73). Patients with CE (n = 287) likely had lower creatinine clearance (CrCL) and higher CHADS2 and HAS-BLED scores than patients without CE (n = 31,988). Significant risk factors associated with new-onset CE were male sex, systolic blood pressure of ≥ 130 mmHg, diabetes mellitus (glycated hemoglobin ≥ 6.0%), CE history, antiplatelet agent use, and CrCL < 50 mL/min. Major bleeding incidence was significantly higher in patients with new-onset CE vs without CE (odds ratio [95% CI], 3.35 [2.06–5.43]). In elderly patients with NVAF, CE incidence was lower than stroke/systemic embolism incidence. New-onset CE (vs no CE) was associated with a higher incidence of major bleeding. Trial registration: UMIN000024006. [ABSTRACT FROM AUTHOR]

Continuing previous studies by one of us (HI), a polar decomposition and a functional calculus for an unbounded Tomita’s observable are studied. For both problems we distinguish two different cases dictated by commutation properties. [ABSTRACT FROM AUTHOR]

Tin dioxide-modified Pt electrodes with different coverages ( θ SnO 2 ) were prepared by potentiostatically depositing tin on a Pt electrode in 0.1 M H2SO4 solutions containing various concentrations of SnCl2, followed by oxidizing in air. The θ SnO 2 was controlled by the SnCl2 concentration. The CO-stripping voltammogram of the Pt/SnO2 electrode with θ SnO 2 = 0.61 (Pt/SnO2(0.61)) exhibited two peaks, a prepeak due to the oxidation of adsorbed CO at Pt sites adjacent to SnO2 and a main peak due to that at Pt sites far from SnO2. In the kinetic analysis of both peaks using CO-stripping voltammograms at various sweep rates, the rate-determining steps for the prepeak and main peak were the coupling of adsorbed CO on Pt with OH on SnO2 surface by bifunctional effect and the dissociatively adsorption reaction of water to adsorbed OH on Pt, similar to the Pt electrode, respectively. In the linear sweep voltammograms of Pt/SnO2 electrodes in a (0.1 M HClO4 + 1 M ethanol) solution, the current for ethanol oxidation reaction (EOR) was the highest for θ SnO 2 = 0.61. The analysis of EOR products at different potentials for the Pt/SnO2(0.61) electrode by in situ infrared reflectance-absorption spectroscopy exhibited the Pt/SnO2(0.61) electrode facilitated acetic acid production. Moreover, rhodium was electrochemically deposited on the Pt sites adjacent to SnO2 using the limited CO-stripping technique. The area-controlled Rh deposition did not change the rate-determining steps of both peaks, but it not only enhanced EOR activity, but also decreased acetic acid selectivity and increased CO2 selectivity. [ABSTRACT FROM AUTHOR]

The present study assessed the impact of regime shifts on the ecosystems that support fisheries in the coastal area of Kyoto Prefecture, the Sea of Japan. Ecopath models were constructed during cold (1985) and warm (2013) regime periods, when the fishery structures were different. Both models evaluated by pre-balance diagnostics were reliably constructed. Multiple ecosystem indicator values were compared between the two periods to assess changes in the ecosystem structure and the impact of fisheries on the ecosystem. The major change in catches in the coastal area of Kyoto Prefecture between 1985 and 2013 was that the Japanese sardine drastically declined and Spanish mackerel increased. The primary production requirements of fisheries (%PPR) were higher in 1985, reflecting the greater impact of sardine. The mean trophic level of catch and system omnivory index suggested that stability of trophic network increased after the sharp decline in sardine biomass. The %PPR, the loss of secondary production due to fisheries exploitation and probability analysis of fishery sustainability suggested that the fishery structure in 2013, which was dominated by set nets, contributed to a more sustainable fishery than the structure in 1985, when fishery was dominated by purse seines and set nets. [ABSTRACT FROM AUTHOR]

Intermetallic or substitutional solid-solution PdZn alloy nanoparticle (NP)-loaded carbon black (i-PdZn/C, s-PdZn/C) was prepared by reducing equimolar palladium acetate and zinc acetate in ethanol dispersion of carbon black with sodium tetrahydroborate with and without the following heat-treatment in an autoclave. The Pd 3d and Zn 2p core-level spectra exhibited that the binding energy of Pd and Zn for i-PdZn/C shifted positively and negatively compared to that for metallic Pd and Zn sheets, respectively, suggesting a strong electronic interaction between Pd and Zn. In contrast, for s-PdZn/C, the binding energy for Pd shifted positively, but only a peak for ZnO was observed. In 1 M KOH aqueous solution at 20 ºC, the Zn content of s-PdZn/C was almost zero in 30 min, while i-PdZn/C held the Zn component of 75% at 20 ºC and 70% at 60 ºC after 30 min, indicating that i-PdZn/C was much more tolerant to alkaline medium than s-PdZn/C. Consequently, s-PdZn NPs were changed to porous Pd NPs, whereas i-PdZn NPs were changed to core–shell NPs whose surface was porous Pd. In the (1 M KOH + 1 M ethanol) aqueous solution at 20 ºC, i-PdZn/C and s-PdZn/C significantly enhanced the activity for ethanol oxidation reaction (EOR) compared to Pd NP-loaded carbon black (Pd/C). In the potentiostatic electrolysis at 0.7 V for 10,000 s, the deterioration of i-PdZn/C was effectively delayed compared to Pd/C and s-PdZn/C due to the electronic effect of the intermetallic PdZn core. [ABSTRACT FROM AUTHOR]

Metabolic regulation in skeletal muscle is essential for blood glucose homeostasis. Obesity causes insulin resistance in skeletal muscle, leading to hyperglycemia and type 2 diabetes. In this study, we performed multiomic analysis of the skeletal muscle of wild-type (WT) and leptin-deficient obese (ob/ob) mice, and constructed regulatory transomic networks for metabolism after oral glucose administration. Our network revealed that metabolic regulation by glucose-responsive metabolites had a major effect on WT mice, especially carbohydrate metabolic pathways. By contrast, in ob/ob mice, much of the metabolic regulation by glucose-responsive metabolites was lost and metabolic regulation by glucose-responsive genes was largely increased, especially in carbohydrate and lipid metabolic pathways. We present some characteristic metabolic regulatory pathways found in central carbon, branched amino acids, and ketone body metabolism. Our transomic analysis will provide insights into how skeletal muscle responds to changes in blood glucose and how it fails to respond in obesity. [ABSTRACT FROM AUTHOR]

Oral glucose ingestion induces systemic changes of many blood metabolites related not only to glucose, but also other metabolites such as amino acids and lipids through many blood hormones. However, the detailed temporal changes in the concentrations of comprehensive metabolites and hormones over a long time by oral glucose ingestion are uncharacterized. We measured 83 metabolites and 7 hormones in 20 healthy human subjects in response to glucose ingestion. We characterized temporal patterns of blood molecules by four features: (i) the decomposability into "amplitude" and "rate" components, (ii) the similarity of temporal patterns among individuals, (iii) the relation of molecules over time among individuals, and (iv) the similarity of temporal patterns among molecules. Glucose and glucose metabolism-related hormones indicated a rapid increase, and citrulline and lipids, which indicated a rapid decrease, returned to fasting levels faster than amino acids. Compared to glucose metabolism-related molecules and lipids, amino acids showed similar temporal patterns among individuals. The four features of temporal patterns of blood molecules by oral glucose ingestion characterize the differences among individuals and among molecules. [ABSTRACT FROM AUTHOR]

The EXPAND Study demonstrated the effectiveness and safety of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) in routine clinical practice in Japan. This sub-analysis was conducted to reveal the effectiveness and safety of rivaroxaban in Japanese NVAF patients according to baseline creatinine clearance (CrCl) levels and rivaroxaban doses in the EXPAND Study. We examined 6806 patients whose baseline CrCl data were available and classified them into 2 groups: normal renal function group with CrCl ≥ 50 mL/min (n = 5326, 78%) and renal dysfunction group with CrCl < 50 mL/min (n = 1480, 22%). In the normal renal function group, 1609 (30%) received 10 mg/day (under-dose), while in the renal dysfunction group, 108 (7%) received 15 mg/day (over-dose). In the normal renal function group, under-dose of rivaroxaban was associated with higher all-cause mortality, while in the renal dysfunction group, over-dose was associated with higher incidence of major bleeding. In contrast, the incidence of stroke or systemic embolism was not different between the 2 groups regardless of the dose of rivaroxaban. In the propensity score matched analysis to adjust the difference in characteristics according to doses of rivaroxaban, the incidences of clinical outcomes were comparable between the 2 dose groups in both renal function groups. These results indicate that the dose of rivaroxaban should be reduced depending on the renal function, considering the balance between risks of bleeding and ischemia. [ABSTRACT FROM AUTHOR]

Background and Objectives: Beraprost sodium (BPS), an orally administrable prostaglandin I2 derivative, is used for the treatment of chronic arterial occlusion and pulmonary arterial hypertension and has potential efficacy in nephropathy. Beraprost sustained release (beraprost SR) is an oral sustained-release formulation of BPS. To confirm the dose rationale reported in a multi-regional study of nephropathy patients in Asia, this open-label study evaluated ethnic differences in the pharmacokinetic profiles of BPS and its active diastereomer (BPS-314d) after beraprost SR administration among healthy Japanese, Chinese, and Korean adult males. Methods: Twelve healthy subjects in each ethnic group were enrolled. Subjects received a single oral dose of 120 μg beraprost SR under fasting conditions. Results: The geometric mean ratio (90% confidence interval) of the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve from time 0 to time of the last quantifiable concentration (AUClast) of BPS was 1.12 (0.85–1.48) and 1.40 (1.05–1.86) in Chinese, and 1.18 (0.90–1.55) and 1.18 (0.89–1.58) in Korean compared to Japanese subjects. These differences were not clinically relevant. Similarly, differences in the Cmax and AUClast of BPS-314d were also small among the ethnic groups. Urinary excretion of BPS and BPS-314d was limited in all ethnic groups. Together, these findings indicate that the pharmacokinetics of beraprost SR are not affected by ethnic background. Conclusions: There were no clinically meaningful ethnic differences in the pharmacokinetics of BPS and BPS-314d following beraprost SR administration among Japanese, Chinese and Korean populations. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Impacts of regime shift on the fishery ecosystem in the coastal area of Kyoto prefecture, Sea of Japan, assessed using the Ecopath model." The article was originally published without open access, but the author later decided to make it an open access publication. The copyright of the article has been changed to © The Author(s) 2024, and it is now distributed under the terms of the Creative Commons Attribution 4.0 International License. The original article has been corrected. Springer Nature, the publisher, remains neutral regarding jurisdictional claims and institutional affiliations. [Extracted from the article]

Background: Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates. Methods: The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls. Clinical data at the time of and 5 years before HCC diagnosis were collected. Results: The mean patient age at HCC diagnosis was approximately 73 years, and 80% of the patients were male. The proportion of patients with insulin use increased, whereas the body mass index (BMI), proportion of patients with fatty liver, fasting glucose levels, and hemoglobin A1c (HbA1c) levels decreased significantly in 5 years. In the cohort study, 18 patients developed HCC during the mean follow-up period of 4.7 years with an annual incidence of 0.11%. Multivariate logistic regression analyses showed that the FIB-4 index was an outstanding predictor of HCC development along with male sex, presence of hypertension, lower HbA1c and albumin levels, and higher BMI and gamma-glutamyl transpeptidase levels. Receiver-operating characteristic analyses showed that a FIB-4 cut-off value of 3.61 could help identify high-risk patients, with a corresponding annual HCC incidence rate of 1.1%. Conclusion: A simple calculation of the FIB-4 index in diabetes clinics can be the first step toward surveillance of HCC with a non-viral etiology. [ABSTRACT FROM AUTHOR]

Accumulating evidence demonstrates that not only sustained elevation of blood glucose levels but also the glucose fluctuation represents key determinants for diabetic complications and mortality. Current closed-loop insulin therapy option is limited to the use of electronics-based systems, although it poses some technical issues with high cost. Here we demonstrate an electronics-free, synthetic boronate gel-based insulin-diffusion-control device technology that can cope with glucose fluctuations and potentially address the electronics-derived issues. The gel was combined with hemodialysis hollow fibers and scaled suitable for rats, serving as a subcutaneously implantable, insulin-diffusion-active site in a manner dependent on the subcutaneous glucose. Continuous glucose monitoring tests revealed that our device not only normalizes average glucose level of rats, but also markedly ameliorates the fluctuations over timescale of a day without inducing hypoglycemia. With inherent stability, diffusion-dependent scalability, and week-long & acute glucose-responsiveness, our technology may offer a low-cost alternative to current electronics-based approaches. Here, the authors develop an in vivo insulin delivery system which consists of a glucose responsive gel combined with hemodialysis hollow fibers. This system is electronics-free, temperature independent, and can stably sustain acute glucose-responsiveness in rats. [ABSTRACT FROM AUTHOR]

In the original publication of the article, the Figure 2b and the Tables 2 and 3 were published incorrectly. The corrected figure and tables are provided below. [ABSTRACT FROM AUTHOR]

For Japanese patients with non-valvular atrial fibrillation (NVAF), the risk of stroke and major bleeding events was assessed by using the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The risk factors for embolism and major bleeding under DOAC may be different from current reports. We analyzed the data set of the EXPAND Study to determine the risk factors for events among Japanese NVAF patients in the era of direct oral anticoagulant. Using the data of EXPAND Study, the validity for predictability of the CHADS2, CHA2DS2-VASc, and HAS-BLED scores was identified using the receiver operating characteristic curve analysis. Multivariate analysis was performed with the Cox proportional hazard model to determine the independent risk factors for stroke/systemic embolism and major bleeding among NVAF patients receiving rivaroxaban. Explanatory variables were selected based on the univariate analysis. A total of 7141 patients (mean age 71.6 ± 9.4 years, women 32.3%, and rivaroxaban 15 mg per day 56.5%) were included. Incidence rates of stroke/systemic embolism and major bleeding were 1.0%/year and 1.2%/year, respectively. The multivariate analysis revealed that only history of stroke was associated with stroke/systemic embolism (hazard ratio 3.4, 95% confidence interval 2.5-4.7, p < 0.0001). By contrast, age (1.7, 1.1–2.6, p = 0.0263), creatinine clearance (CrCl) 30–49 mL/min (1.6, 1.2-2.2, p = 0.0011), liver dysfunction (1.7, 1.1–2.8, p = 0.0320), history/disposition of bleeding (1.8, 1.0–3.0, p = 0.0348), and concomitant use of antiplatelet agents (1.6, 1.2–2.3, p = 0.0030) were associated with major bleeding. This sub-analysis showed that some components of the HAS-BLED score were independently associated with major bleeding in Japanese NVAF patients receiving anticoagulation therapy by rivaroxaban. Additionally, CrCl value of 30–49 mL/min was an independent predictor of major bleeding in patients receiving rivaroxaban. [ABSTRACT FROM AUTHOR]

The EXPAND Study examined the real-world efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism (SE) in Japanese patients with non-valvular atrial fibrillation (NVAF). In this sub-analysis, we compared the differences in efficacy and safety between patients with and those without history of stroke or transient ischemic attack (TIA). This multicenter, prospective, non-interventional, observational, cohort study was conducted at 684 medical centers in Japan. A total of 7141 NVAF patients aged ≥ 20 years [mean age 71.6 ± 9.4 (SD) years] who were being or planned to be treated with rivaroxaban (10 mg/day, 43.5%; 15 mg/day, 56.5%) were followed for a mean period of 897.1 ± 206.8 days with a high follow-up rate (99.7%). The primary prevention group comprised patients without history of ischemic stroke or TIA (n = 5546, 77.7%), and the secondary prevention group comprised those with history of ischemic stroke or TIA (n = 1595, 22.3%). In the primary and secondary prevention groups, the incidence rate of stroke or SE (primary efficacy endpoint) was 0.7 and 2.2%/year, respectively (P < 0.001), and the incidence rate of major bleeding (primary safety endpoint) was 1.2 and 1.5%/year, respectively (P = 0.132). For major bleeding events, the incidence rate of intracranial bleeding was 0.4 and 0.8%/year (P = 0.002) in the primary and secondary prevention groups, respectively. This sub-analysis of the EXPAND Study showed that the Japan-specific dosages of rivaroxaban were effective and safe in Japanese NVAF patients with and those without ischemic stroke or TIA in routine clinical practice. [ABSTRACT FROM AUTHOR]

A narrow and calcified sinotubular junction (STJ) represents a risk for ascending aortic dissection after balloon-expandable transcatheter aortic valve implantation (TAVI). The aim of this study was to assess computed tomography (CT)-based aortic root morphology in patients with aortic stenosis (AS), and to evaluate the feasibility of a two-step inflation technique that we devised for TAVI using the SAPIEN 3 in patients with a narrow and calcified STJ. We retrospectively analyzed the STJ diameter (STJD) as well the as aortic annulus diameter (AAD) and STJ calcification using CT imaging in 412 patients undergoing TAVI. We defined a “narrow STJ” as a minimum STJD that was smaller than the diameter corresponding to a 10% oversized annulus area, and a “calcified STJ” as an STJ calcification angle > 90°. A “narrow and calcified STJ” was identified in 54 patients (13.1%) of patients. Among them, we performed TAVI using the two-step inflation technique with SAPIEN 3 in 20 patients and compared with 11 patients that underwent the conventional inflation procedure. Two-step inflation was successfully performed without ascending aortic dissection in all 20 patients. The effective orifice area index at discharge in these 20 patients was similar to that in 11 patients who underwent the conventional inflation procedure for a “narrow and calcified STJ” [1.40 (1.20-1.51) vs. 1.33 (1.18-1.41) cm2/m2, p = 0.23]. Although further assessment is required, the two-step inflation technique with the SAPIEN 3 is feasible for a narrow and calcified STJ. [ABSTRACT FROM AUTHOR]

To elucidate involvement of age-related impairments of right ventricular (RV) distensibility in the elderly congestive heart failure (CHF), we examined the prevalence of less-distensible right ventricle in patients with preserved left ventricular ejection fraction (LVEF) over a wide range of ages. In 893 patients aged from 40 to 102 years, we simultaneously recorded electrocardiogram, phonocardiogram, and jugular venous pulse wave. Using signal-processing techniques, the prominent ‘Y’ descent of jugular pulse waveform was detected as a hemodynamic sign of a less-distensible right ventricle. Prevalence of less-distensible right ventricle and elevated RV systolic pressure increased along with aging from the 50s to the 90s in an exponential fashion from 3.3 and 12% up to 33 and 61%, respectively (p < 0.001 for each). This age-dependent deterioration of ventricular distensibility was not observed for the left ventricle. Higher age and higher RV systolic pressure were independently associated with less-distensible right ventricle (Odds ratio, 1.05 per 1 year, p = 0.003; and 1.03 per 1 mmHg, p = 0.026, respectively). The elderly CHF was associated with high prevalence of the less-distensible right ventricle and higher RV systolic pressure, both of which were independent risk factors for CHF (Odds ratio, 5.27, p = 0.001, and 1.08 per 1 mmHg, p < 0.001, respectively). In elderly patients with preserved LVEF, the combination of a less-distensible right ventricle and a high RV systolic pressure seems to be related to developing CHF. The less-distensible right ventricle and elevated RV systolic pressure are closely associated with CHF with preserved LVEF in the elderly patients. [ABSTRACT FROM AUTHOR]

Vasovagal syncope (VVS) is known to have a benign prognosis and be associated with enhanced contraction and activation of the left ventricular (LV) mechanoreceptors. However, a little is known about VVS in patients with LV dysfunction. The present study aimed to investigate the prevalence and prognosis of VVS in patients with LV dysfunction. We enrolled 368 patients with unexplained syncope. In 7 of these patients, LV ejection fraction was lower than 40%. The results of a head-up tilt test (HUT) and the recurrence of syncope were compared between these 7 patients with LV dysfunction and the remaining patients. Positive HUT was obtained in the 6 patients (86%) with LV dysfunction; this rate tended to be higher as compared with normal cardiac function (192/361, 53%, P = 0.069). In patients with LV dysfunction, response in HUT was mostly vasodepressor type (62%); however, most of HUT responses were mixed type in patients with normal LV function (67%). Among patients with positive HUT, the recurrent rate of syncope after HUT was higher in those with LV dysfunction than in those with normal LV function (67 vs. 21%, P = 0.008). VVS in patients with LV dysfunction may be refractory to treatment and could be associated with poor prognosis. [ABSTRACT FROM AUTHOR]

We used the modified Bönnemann method to prepare PtxRu (x = 1, 3, and 4) alloy-loaded carbon black (PtxRu/C) catalysts. And we performed galvanostatic electrolysis with the gas diffusion electrodes (GDEs) including PtxRu/C in the catalyst layer to evaluate hydrogenation activity of toluene (TL) and analyze hydrogenation product qualitatively and quantitatively. From X-ray diffraction patterns and X-ray photoelectron spectra, it was found that Pt was alloyed with Ru. In the activation, the surface Ru atoms of each alloy partially dissolved, and the surface area of Pt increased. The Pt3Ru/C-loaded GDE had highest specific surface area after initial activation. In addition, the Pt3Ru/C-loaded GDE after initial activation exhibited the highest apparent current densities for the TL hydrogenation over the whole potential in this study, suggesting that the Pt3Ru/C-loaded GDE exhibited the highest hydrogenation activity. Gas chromatograph/mass spectrometric measurements showed the sole hydrogenation product of TL at the Pt3Ru/C-loaded GDE was methylcyclohexane (MCH). The total production amount of MCH increased with the reaction time. After the galvanostatic electrolysis for 2 h, the production of hydrogen was confirmed by gas chromatography. Then, MCH production and the faradaic efficiency for hydrogen evolution were 84.6 and 7.1%, respectively, so the total faradaic efficiency is 91.7%.ᅟ [ABSTRACT FROM AUTHOR]

Background: Easier to perform than the conventional procedure, mini-tracheostomy (MT) is widely used in the operating room or intensive care unit to remove sputum or other obstructions of the upper airway. This option, however, does carry the risk of various complications, including malposition, disposition, bleeding, and subcutaneous emphysema. Here, we report a case of endotracheal tube obstruction due to a massive clot resulting from late bleeding around the insertion site of an MT tube. This necessitated removal of the endotracheal tube together with the clot followed tube re-introduction. Case presentation: The patient was an 85-year-old man in whom an MT tube had been inserted 6 days earlier following aortic replacement surgery. On re-admittance to our intensive care unit, large amounts of hemosputum and clotting were observed around the insertion site of the tube. The MT tube was subsequently removed and tracheal intubation performed. Ventilation via the endotracheal tube proved impossible, however, and cardiac arrest ensued. Fiberoptic bronchoscopy revealed that the endotracheal tube was completely obstructed by a massive clot. Therefore, we immediately pushed the clot toward the right main bronchus to secure ventilation via the left lung. After many attempts to remove the massive clot, including suction and grasping with basket forceps, it was successfully dislodged by replacing the endotracheal tube with a new one while maintaining oxygenation by one-lung ventilation. Any small fragments of the clot that still remained were then removed by suction under fiberoptic bronchoscopy. Conclusions: Here, we report a case of endotracheal tube obstruction due to a clot derived from very late (6 days) bleeding after insertion of an MT tube. The patient was successfully rescued by replacing the clot-bearing endotracheal tube with a new one. This experience suggests that the intensive care physician should be aware of the potential risk of clot retention in endotracheal tubes after the elapse of several days. [ABSTRACT FROM AUTHOR]

KCNE1 encodes a modulator of KCNQ1 and KCNH2 channels. Although KCNE1(G38S), a single-nucleotide polymorphism (SNP) causing a G38S substitution in KCNE1, is found frequently, whether and how this SNP causes long QT syndrome (LQTS) remains unclear. We evaluated rate-dependent repolarization dynamics using Holter electrocardiogram (ECG) to assess the pathogenicity of KCNE1(G38S). Forty-five patients exhibiting long QT intervals, as assessed by their baseline ECGs, and 16 control subjects were enrolled. KCNE1(G38S) carriers were identified using genome sequencing. LQTS patients were classified into LQT1 or LQT2 using genetic analysis or epinephrine test. QT-RR relations were determined using 24-h Holter ECG recordings. Among the 15 patients (33.3 %) with KCNE1(G38S), four patients without any mutations or amino acid changes in other major cardiac ion channels were categorized as KCNE1(G38S) carriers. In the QT-RR regression lines, the QT-RR slope was greater in the KCNE1(G38S) carriers and the LQT2 patients (0.215 ± 0.021 and 0.207 ± 0.032, respectively) than in the LQT1 patients (0.163 ± 0.014, P < 0.05) and the control subjects (0.135 ± 0.025, P < 0.001). The calculated QT intervals at an RR interval of 1200 ms were longer in the KCNE1(G38S) carriers and LQT1 and LQT2 patients than in the control subjects. Patients with KCNE1(G38S) had a rate-dependent repolarization abnormality similar to patients with LQT2 and, therefore, may have a potential risk to develop lethal arrhythmias. [ABSTRACT FROM AUTHOR]

Effects of an angiotensin II receptor blocker, irbesartan (IRB), on the development of atrial fibrosis and atrial fibrillation (AF) were assessed in a canine model of atrial tachycardia remodeling (ATR) with left ventricular dysfunction, together with its possible association with involvement of p53. Atrial tachypacing (400 bpm for 4 weeks) was used to induce ATR in beagles treated with placebo (ATR-dogs, n = 6) or irbesartan (IRB-dogs, n = 5). Non-paced sham dogs served as control (Control-dogs, n = 4). ATR- and IRB-dogs developed tachycardia-induced left ventricular dysfunction. Atrial effective refractory period (AERP) shortened (83 ± 5 ms, p < 0.05), inter-atrial conduction time prolonged (72 ± 2 ms, p < 0.05), and AF duration increased (29 ± 5 s, p < 0.05 vs. baseline) after 4 weeks in ATR-dogs. ATR-dogs also had a larger area of atrial fibrous tissue (5.2 ± 0.5 %, p < 0.05 vs. Control). All these changes, except for AERP, were attenuated in IRB-dogs (92 ± 3 ms, 56 ± 3 ms, 9 ± 5 s, and 2.5 ± 0.7 %, respectively; p < 0.05 vs. ATR for each). In ATR-dogs, p53 expression in the left atrium decreased by 42 % compared with Control-dogs ( p < 0.05); however, it was highly expressed in IRB-dogs (+89 % vs. ATR). Transforming growth factor (TGF)-β1 expression was enhanced in ATR-dogs ( p < 0.05 vs. Control) but reduced in IRB-dogs ( p < 0.05 vs. ATR). Irbesartan suppresses atrial fibrosis and AF development in a canine ATR model with left ventricular dysfunction in association with p53. [ABSTRACT FROM AUTHOR]

Cardiac hypertrophy and fibrosis in heart failure with preserved ejection fraction are associated with a pro-inflammatory state and reduced NO bioavailability. Effects on myocardial structural and molecular alterations were compared between Waon therapy (WT; repeated dry sauna therapy) and statin in hypertensive rats. Seven-week-old Dahl salt-sensitive rats were assigned to 4 groups: low-salt (LS) diet, high-salt (HS) diet, HS diet with oral fluvastatin (FL; 10 mg/kg/day for 4 weeks) starting from the age of 9 weeks, and HS diet with WT treatment in a far-infrared dry sauna (39 °C for 15 min followed by 34 °C for 20 min once daily for 4 weeks). HS rats developed left ventricular (LV) hypertrophy with preserved LV systolic function. WT reduced LV wall thickness and myocyte cross-sectional area along with decreased levels of myocardial ANP and BNP mRNA expression compared with HS rats. Reduction in LV fibrosis and increase in capillary density in WT animals were accompanied by reductions in myocardial levels of TGF-β1, MMP2, p22 and gp91 mRNA expression, and increases in myocardial levels of VEGF and HSP90 mRNA and phosphorylated eNOS protein. These effects were comparable between WT and FL animals. WT improves structural and molecular alterations in salt-induced hypertensive rats similarly to fluvastatin. [ABSTRACT FROM AUTHOR]

Various humoral factors are involved in the regulation of energy and glucose metabolism mediated by the interaction between the central nervous system and peripheral tissues. Insulin, which strictly regulates glucose metabolism in the liver, skeletal muscles, and adipose tissue, also plays a role in brain-mediated regulation of energy and glucose metabolism. Through the hypothalamus, insulin regulates not only diet intake and postprandial thermogenesis, but also glucose metabolism in the liver and skeletal muscles. Insulin exerts its action on the liver via the vagus nerve by activating phosphoinositide-3-kinase and K channels in the hypothalamic neurons. Central insulin action enhances the secretion of interleukin-6 from hepatic Kupffer cells and activates the transcription factor signal transducer and activator of transcription 3 (STAT3), which suppresses the expression of gluconeogenic enzyme genes in hepatocytes and thereby reducies hepatic glucose production. Brain-mediated suppression of hepatic glucose production also arises from an increase in the plasma histidine level. Histidine is converted to histamine in the hypothalamus, which activates hepatic STAT3 and thereby suppresses the expression of gluconeogenic enzyme genes via hypothalamic histamine H1 receptors. In obesity and type 2 diabetes, suppression of hepatic glucose production by central insulin action is impaired, potentially increasing hepatic glucose production. However, further studies are needed to elucidate the molecular mechanisms underlying the interaction between the central nervous system and peripheral tissues. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy is associated with increased oxidative stress and vascular endothelial dysfunction, which lead to coronary microangiopathy. We tested whether statin-induced redox imbalance improvements could ameliorate diabetic cardiomyopathy and improve coronary microvasculature in streptozotocin-induced diabetes mellitus (DM). Fluvastatin (10 mg/kg/day) or vehicle was orally administered for 12 weeks to rats with or without DM. Myocardial oxidative stress was assessed by NADPH (nicotinamide adenine dinucleotide phosphate) oxidase subunit p22 and gp91 mRNA expression, and myocardial 8-iso-prostaglandin F (PGF) levels. Myocardial vascular densities were assessed using anti-CD31 and anti-α-smooth muscle actin (SMA) antibodies. Fluvastatin did not affect blood pressure or plasma cholesterol, but attenuated increased left ventricular (LV) minimum pressure and ameliorated LV systolic dysfunction in DM rats in comparison with vehicle (LV d P/d t, 8.9 ± 1.8 vs 5.4 ± 1.0 × 10 mmHg/s, P < 0.05). Myocardial oxidative stress increased in DM, but fluvastatin significantly reduced p22 and gp91 mRNA expression and myocardial PGF levels. Fluvastatin enhanced myocardial endothelial nitric oxide synthase (eNOS) protein levels and increased eNOS, vascular endothelial growth factor, and hypoxia-inducible factor-1α mRNA expression. CD31-positive cell densities were lower in DM rats than in non-DM rats (28.4 ± 13.2 vs 48.6 ± 4.3/field, P < 0.05) and fluvastatin restored the number (57.8 ± 18.3/field), although there were no significant differences in SMA-positive cell densities between groups. Fluvastatin did not affect cardiac function, oxidative stress, or vessel densities in non-DM rats. These results suggest that beneficial effects of fluvastatin on diabetic cardiomyopathy might result, at least in part, from improving coronary microvasculature through reduction in myocardial oxidative stress and upregulation of angiogenic factor. [ABSTRACT FROM AUTHOR]

Introduction: Results from the multicenter trial (J-Land study) of landiolol versus digoxin in atrial fibrillation (AF) and atrial flutter (AFL) patients with left ventricular (LV) dysfunction revealed that landiolol was more effective for controlling rapid HR than digoxin. The subgroup analysis for patient characteristics was conducted to evaluate the impact on the efficacy and safety of landiolol compared with digoxin. Methods: Two hundred patients with AF/AFL, heart rate (HR) ≥ 120 beats/min, and LV ejection fraction (LVEF) 25-50% were randomized to receive either landiolol ( n = 93) or digoxin ( n = 107). Successful HR control was defined as ≥20% reduction in HR together with HR < 110 beats/min at 2 h after starting intravenous administration of landiolol or digoxin. The subgroup analysis for patient characteristics was to evaluate the impact on the effectiveness of landiolol in AF/AFL patients complicated with LV dysfunction. Results: The efficacy in patients with NYHA class III/NYHA class IV was 52.3%/35.3% in landiolol, and 13.8%/9.1% in digoxin ( p < 0.001 and p = 0.172), lower LVEF (25-35%)/higher LVEF (35-50%) was 45.7%/51.1% in landiolol, and 14.0%/12.7% in digoxin ( p < 0.001 and p < 0.001), CKD stage 1 (90 < eGFR)/CKD stage 2 (60 ≤ eGFR < 90)/CKD stage 3 (30 ≤ eGFR < 60)/CKD stage 4 (15 ≤ eGFR < 30) was 66.7%/59.1%/39.6%/66.7% in landiolol, and 0%/13.8%/17.0%/0% in digoxin ( p = 0.003, p < 0.001, p = 0.015 and p = 0.040). Conclusions: This subgroup analysis indicated that landiolol was more useful, regardless of patient characteristics, as compared with digoxin in AF/AFL patients complicated with LV dysfunction. Particularly, in patients with impaired renal function, landiolol should be preferred for the purpose of acute rate control of AF/AFL tachycardia. [ABSTRACT FROM AUTHOR]

Present study aimed to investigate the impact of anti-inflammatory cytokines provoked by the hemoglobin scavenger receptor, CD163, on left ventricular (LV) functional recovery after successful reperfusion in patients with acute myocardial infarction (AMI). Intraplaque hemorrhage accelerates plaque destabilization. Extracellular hemoglobin is cleared by CD163, a macrophage scavenger receptor. This process provokes secretion of anti-inflammatory atheroprotective cytokine, interleukin (IL)-10. In 40 patients with the first AMI, coronary atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI), stained with antibodies to CD163 and IL-10. LV function was determined by echocardiography before PCI and 6 months after PCI. %CD163 was defined as ratio of CD163 (+)-cells to whole cells. %IL-10 was expressed as the ratio of positively stained areas per total tissue. Patients were divided into two groups depending on the amount of CD163 (+)-cells: CD163 > 10 % (CD, n = 20) and CD163 ≤ 10 % (CD, n = 20). CD group had significantly higher %IL-10. Final thrombolysis in myocardial infarction (TIMI) flow grade was significantly lower in CD group. In subgroups with the final TIMI-3 flow (CD-Reflow, n = 15 and CD-Reflow, n = 20), the time to reperfusion, infarct size, LV dimensions and fractional shortening (%FS) before PCI were similar. Significant correlation was observed between %IL10 and changes in LV dimensions (diastole, r = −0.49, P = 0.01; systole, r = −0.65, P < 0.01) or %FS ( r = 0.51, P < 0.01) at 6 months after PCI. Plaque with CD163(+)-macrophages could impair distal flow after primary PCI. However, CD163(+)-macrophages enhance the anti-inflammatory cytokine expression that aids in ventricular functional recovery if distal flow can be achieved by successful reperfusion. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to identify prognostic genes by integrated microarray analysis between comparative genomic hybridization and gene expression with laser microdissection in non-small cell lung cancer (NSCLC). Methods: Integrated microarray analysis in 11 lung adenocarcinomas was performed, and several genes were identified. Among them, neural precursor cell-expressed developmentally down-regulated 4-like ( NEDD4L) was chosen for further characterization. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was used to explore the clinicopathological significance of NEDD4L expression in 84 NSCLC patients. Results: 18q was more frequently lost in advanced lung cancer. Therefore, we selected the NEDD4L gene, located on chromosome18q, for which reduced expression was significantly correlated with copy number loss. NEDD4L mRNA expression in paired tumor/normal samples from 79 cases of lung cancer was evaluated using real-time PCR analysis. NEDD4L mRNA expression was significantly lower in tumor tissues than in normal lung tissues ( p < 0.0001). Clinicopathological factors, such as excessive smoking history, histological grade (moderately and poorly), T stage (T2–4), lymph node metastasis, and pathological stage (stage II–IV), were significantly associated with low NEDD4L expression ( p < 0.05). In the low expression group, prognoses were significantly poorer than in the high expression group ( p < 0.05). Conclusions: Low NEDD4L expression may be a marker of prognosis. This is the first report to describe NEDD4L expression in NSCLC. NEDD4L may be considered a key gene in the progression of NSCLC, and its expression is likely affected by genomic alterations. [ABSTRACT FROM AUTHOR]

To improve kinetics for hydrogen absorption of Mg and hydrogen desorption of MgH2, ternary composites were prepared from MgH2, Ni and Si or Ni2Si by a mechanochemical technique. The X-ray diffraction spectra of the resultant ternary composites after the initial hydrogen desorption treatment at 400 °C in vacuum suggested that in all composites the nanocrystalline Mg2Ni would be formed in the intergrain region between Mg and Ni components, while in the MgH2-Ni-Si composite the nanocrystalline Mg2Si would also be formed in the intergrain region between Mg and Si components. However, Ni2Si did not form any alloys with Mg. The hydrogen absorption rate at 250 °C for the MgH2-Ni-Ni2Si composite was comparable to that for the MgH2-Ni and MgH2-Ni-Si composites, while the hydrogen desorption rate at 250 °C decreased in the order of MgH2-Ni > MgH2-Ni-Ni2Si > MgH2-Ni-Si. In contrast, the hydrogen desorption rate at 220 °C for the MgH2-Ni-Ni2Si composite was faster than that for the MgH2-Ni composite, suggesting that Ni2Si was a key material in the improvement of hydrogen desorbability at lower temperatures. Moreover, the most plausible reaction model and the rate-determining process for hydrogen absorption and desorption at 250 °C were determined. [ABSTRACT FROM AUTHOR]

Background: The oncogenic single nucleotide polymorphism rs6983267, located on 8q24.21, may affect copy number aberrations and/or expression profiles in colorectal cancer (CRC). We investigated the role of this single nucleotide polymorphism in the clinical outcome of CRC. Methods: Array comparative genomic hybridization (aCGH) and oligomicroarrays were performed on cancer cells from 157 primary CRC tissues. Expression profiles were analyzed by means of extraction expression module (EEM) analyses. Mutations in TP53, KRAS, and BRAF and microsatellite instability were also examined in 107 of the 157 cases. Results: aCGH analysis revealed two clusters; more frequent genomic copy number alteration (CNA) was observed in the 89 cases in cluster B than in the 18 cases in cluster A. The average CNA was higher in samples containing the major allele (GT/TT) of rs6983267 than in those containing the minor allele (GG). Additionally, MYC expression was the highest in samples containing the GG allele ( n = 18), followed by the GT and TT alleles ( n = 41 and 48, respectively). EEM analysis revealed dominant up-regulation of MYC in samples containing the minor allele. Moreover, the presence of the minor allele in a MYC-positive, CNA-negative context predicted a poorer prognosis than the presence of the major allele in a MYC-negative, CNA-positive context in CRC. Conclusions: The presence of the minor allele of rs6983267 at 8q24.21 worsened the prognosis of CRC through up-regulation of MYC transcription. Furthermore, progression of CRC may require global CNA in the presence of the major allele and with lack of MYC transcription. [ABSTRACT FROM AUTHOR]

Various mechanisms are involved in detoxification of heavy metals such as lead (Pb) in plant cells. Most of the Pb taken up by plants accumulates in their roots. However, the detailed properties of Pb complexes in roots remain unclear. We have investigated the properties of Pb deposits in root cell walls of radish ( Raphanus sativus L.) seedlings grown on glass beads bed containing Pb pellets, which are the source of Pb-contamination in shooting range soils. Pb deposits were tightly bound to cell walls. Cell wall fragments containing about 50,000 ppm Pb were prepared from the roots. After extracting Pb from the cell wall fragments using HCl, Pb ions were recombined with the Pb-extracted cell wall fragments in a solution containing Pb acetate. When the cell wall fragments were treated with pectinase (E.C. 3.2.1.15) and were chemically modified with 1-ethyl-3-dimethylamino-propylcarboimide, the Pb-rebinding ability of the treated cell wall fragments decreased. When acid-treated cell wall fragments were incubated in a solution containing Pb and excess amounts of a chelating agent, Pb recombined with the cell wall fragments were measured to estimate the affinity between Pb and the cell wall fragments. Our data show that Pb binds to carboxyl groups of cell walls. The source of the carboxyl groups is suggested to be pectic compounds. A stability constant of the Pb-cell wall complex was estimated to be about 10. The role of root cell walls in the mechanism underlying heavy metal tolerance was discussed. [ABSTRACT FROM AUTHOR]

Au nanoparticle-loaded carbon black (Au/CB) was prepared simply by bubbling CO as a reducing agent in a KAuCl aqueous solution containing polyvinyl alcohol as a stabilizer and then mixing Ketjen black as carbon black. X-ray diffraction spectra and transmission electron micrographs exhibited that the Au nanoparticles loaded on CB had the mean size of 3.3 nm which was scarcely increased even by the heat-treatment at 400 °C. For the Au/CB heat-treated at 400 °C (Au/CB-HT400), the modification of the Au nanoparticles with a Pt monolayer shell was performed by underpotential deposition of Cu and the following galvanic displacement with Pt. Cyclic voltammograms of Au-Pt/CB-HT400 and Au-Pt/CB-HT400 electrodes, which mean a Pt monolayer shell was deposited once and twice on Au/CB-HT400, indicated that 73 % and 97 % of the Au core nanoparticle surface were covered with the Pt shell, respectively. Koutecky-Levich plots made from hydrodynamic voltammograms of the Au-Pt/CB-HT400 ( x = 1, 2) electrodes exhibited that oxygen reduction reaction at both electrodes proceeded in four-electron mechanism like commercial Pt/CB. The mass activity at 0.9 V vs. RHE for Au-Pt/CB-HT400 and Au-Pt/CB-HT400 was ca. 5.1 and 4.4 times as high as that for the commercial Pt/CB, respectively. Moreover, in durability tests in which the square-wave potential cycling between 0.6 and 1.0 V vs. RHE was repeated 10 times, both catalysts were equivalent or superior to the commercial Pt/CB. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) oncogenesis was considered to be determined by interactions between genetic and environmental factors. Specific interacting factors that influence CRC morbidity have yet to be fully investigated. Methods: A multi-institutional collaborative study with 1511 CRC patients and 2098 control subjects was used to compare the odds ratios for the occurrence of polymorphisms at 11 known single nucleotide polymorphisms (SNPs). TaqMan PCR and questionnaires were used to evaluate the effects of environmental exposures. Results: Variants of rs6983267 on 8q24 were the most significant markers of risk for CRC (odds ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.0015). Non-insulin-dependent diabetes mellitus (DM), a higher body mass index at age 20, and meat consumption were environmental risk factors, whereas a tuna-rich diet and vitamin intake were protective factors. The cohort of rs6983267 SNP major (T) allele at 8q24 and DM had a 1.66-fold higher risk ratio than the cohort of major allele patients without DM. Conclusions: We confirmed that interactions between the genetic background and environmental factors are associated with increased risk for CRC. There is a robust risk of the minor G allele at the 8q24 rs6983267 SNP; however, a major T allele SNP could more clearly reveal a correlation with CRC specifically when DM is present. [ABSTRACT FROM AUTHOR]

During fasting, induction of hepatic gluconeogenesis is crucial to ensure proper energy homeostasis. Such induction is dysregulated in type 2 diabetes, resulting in the development of fasting hyperglycemia. Hormonal and nutrient regulation of metabolic adaptation during fasting is mediated predominantly by the transcriptional coactivator peroxisome proliferative activated receptor ? coactivator 1? (PGC-1?) in concert with various other transcriptional regulators. Although CITED2 (CBP- and p300-interacting transactivator with glutamic acid- and aspartic acid-rich COOH-terminal domain 2) interacts with many of these molecules, the role of this protein in the regulation of hepatic gluconeogenesis was previously unknown. Here we show that CITED2 is required for the regulation of hepatic gluconeogenesis through PGC-1?. The abundance of CITED2 was increased in the livers of mice by fasting and in cultured hepatocytes by glucagon-cAMP-protein kinase A (PKA) signaling, and the amount of CITED2 in liver was higher in mice with type 2 diabetes than in non-diabetic mice. CITED2 inhibited the acetylation of PGC-1? by blocking its interaction with the acetyltransferase general control of amino acid synthesis 5-like 2 (GCN5). The consequent downregulation of PGC-1? acetylation resulted in an increase in its transcriptional coactivation activity and an increased expression of gluconeogenic genes. The interaction of CITED2 with GCN5 was disrupted by insulin in a manner that was dependent on phosphoinositide 3-kinase (PI3K)-thymoma viral proto-oncogene (Akt) signaling. Our results show that CITED2 functions as a transducer of glucagon and insulin signaling in the regulation of PGC-1? activity that is associated with the transcriptional control of gluconeogenesis and that this function is mediated through the modulation of GCN5-dependent PGC-1? acetylation. We also found that loss of hepatic CITED2 function suppresses gluconeogenesis in diabetic mice, suggesting it as a therapeutic target for hyperglycemia. [ABSTRACT FROM AUTHOR]

Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci ( DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height ( P < 0.05), including five novel loci. Of these, two nsSNPs ( TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study ( n = 1,000) and five ( ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis ( n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits. [ABSTRACT FROM AUTHOR]

Conductive non-woven fabric sheets coated with polypyrrole nanoparticles and having resistivity from 1.5 × 10 to 3.0 Ω cm were prepared by immersing non-woven fabric sheets in solutions containing various concentrations of oxidizing agent and dopant and then exposing the sheets to pyrrole vapor. A stack of ten treated sheets could absorb more than 95% of electromagnetic waves in the frequency range of 75-110 GHz and more than 99% in the range of 85-105 GHz, irrespective of the resistivity of the sheet. This absorption was achieved even though the thickness of the stack was less than 10 mm. Furthermore, a conductive non-woven fabric sheet with resistivity of 7.5 Ω cm and thickness of only 0.5 mm could absorb about 90% of electromagnetic waves in the range of 75-110 GHz. These results clearly demonstrate that the stacked conductive non-woven fabric sheets prepared in this study are a new material that effectively absorbs electromagnetic waves with extremely high frequencies in the millimeter band. [ABSTRACT FROM AUTHOR]

To understand the regulatory mechanisms involved in tissue development by light, the kinetics of regulation of Casparian strip (CS) development in garden pea stems was studied. We found that short-term irradiation with white light delayed the development of the CS and used this delay to assess the quantitative effect of light on CS development. We examined the effect of the duration and fluence rates of white light treatment on CS development and observed a significant relationship between fluence and the delay in CS development indicating that the Bunsen-Roscoe law of reciprocity holds for this response. The effect of white light irradiation was not inhibited in the presence of a photosynthetic inhibitor, DCMU, or a carotenoid biosynthesis inhibitor, Norflurazon, indicating that the delay in CS development by light is a photomorphogenetic response rather than a subsidiary effect mediated by photosynthetic activity. An action spectrum for the response displayed a major peak in the blue-light region, suggesting a dominant role for blue-light receptors. A minor peak in the red-light region also suggested the possible involvement of phytochromes. Although phytochromes are known to contribute to blue-light responses, phytochrome-deficient mutants showed a normal delay of CS development in response to blue light, indicating that the response is not mediated by phytochrome and suggesting a role for one or more specific blue-light receptors. [ABSTRACT FROM AUTHOR]