Search

BackgroundsThe prognostic implication of weight loss after discharge from acute heart failure (AHF) remains unclear. We sought to investigate the association of weight loss between discharge and 6-month visit with subsequent clinical outcomes in patients with AHF.MethodsWe analyzed 686 patients with AHF in the prospective longitudinal follow-up study derived from the Kyoto Congestive Heart Failure registry, and divided them into 2 groups based on the weight loss at 6-month index visit. We defined the weight loss as ≥ 5% decrease in body weight from discharge to 6-month index visit.ResultsThere were 90 patients (13.1%) with a weight loss at 6-month visit. Patients in the weight loss group compared with those in the no weight loss group had higher body weight at discharge and lower body weight at 6-mont visit. Patients in the weight loss group had a lower systolic blood pressure, higher brain-type natriuretic peptide, lower serum albumin, lower hemoglobin, higher prevalence of heart failure with reduced ejection fraction at 6-month visit, and a lower prescription rate of inhibitors of renin-angiotensin system than those in the no weight loss group. The cumulative 6-month incidence of all-cause death was significantly higher in the weight loss group than in the no weight loss group (14.2% and 4.3%, log-rank PConclusionBody weight loss of ≥5% at 6-month visit after discharge was associated with subsequent all-cause death in patients with AHF.

Introduction Current pandemic prompted a surge in the television (TV) news watching. However, its influence is poorly understood. In Japan, wide show, a major genre of soft news TV programs, broadcasted COVID-19 for long hours, and was pointed out that it broadcasted COVID-19 sensationally, arousing fear and anxiety, and that it criticized individuals gathering in closed places. Thus, wide show may promote preventive behaviors but also produce fear or anxiety and aggressiveness towards others not engaging in preventive behaviors. We examined this issue using large-scale nationwide data. Methods We analyzed the cross-sectional data of 25,482 individuals from the Japan COVID-19 and Society Internet Survey conducted in 2020. Participants reported the type of COVID-19 information sources including TV news and wide show, and their trustworthiness. We calculated multivariable-adjusted prevalence ratios (PRs) of engaging in recommended preventive behaviors strictly (defined as always engaging in hand washing, mask wearing, and attempting to keep physical distancing) and alerting others not engaging in preventive behaviors, respectively. Results About 72.4% of the participants obtained information from TV news with reliance, while corresponding values were 50.3% for wide show. Overall, 32.8% engaged in recommended preventive behaviors strictly, and 9.6% alerted others. Watching wide show both with and without reliance were significantly associated with alerting others (adjusted PRs: 1.48 and 1.34, respectively) but not associated with preventive behaviors. Watching TV news was neither associated with strict preventive behaviors nor alerting others. Conclusion Watching TV news and wide show was not associated with strict preventive behaviors; watching wide show was associated with only alerting others. Although causality is unclear, actions may be needed for TV stations broadcasting wide show to understand own influences on society in a timely manner amid the health emergencies.

PurposeTo analyze the cause of prolonged recovery from general anesthesia with remimazolam.MethodsWe studied 65 patients under general anesthesia with remimazolam. According to time to extubation, patients were divided into short period (SP) (n = 34, < 15 min) and long period (LP) (n = 31, ≥ 15 min) groups. Variables affecting time to extubation such as age, sex, height, body weight, body mass index (BMI), plasma albumin concentration, ASA class, duration of surgery, and total duration of general anesthesia, and total dose of remimazolam were compared between SP and LP groups. At the end of remimazolam infusion and upon extubation, predictive remimazolam concentrations were calculated using pharmacokinetic/pharmacodynamic three compartment modeling.ResultsLP group showed significantly higher BMI, older age, and lower plasma albumin concentration compared with those of SP group. Logistic regression analysis showed that the probability of time to extubation of ≥ 15 min was higher in patients with BMI greater than 22.0 kg/m2 (AUC 0.668, 95% CI 0.533‒0.803), ages older than 79.0 years (AUC 0.662, 95% CI 0.526‒0.798), and plasma albumin concentrations lower than 3.60 g/dl (AUC 0.720, 95% CI 0.593‒0.847). LP group showed significantly lower predicted remimazolam concentration than SP group upon extubation despite no difference in concentration between both groups at the end of infusion. Pharmacological analysis estimates that LP group is more sensitive to remimazolam than SP group through amplified responses.ConclusionsLower remimazolam doses should be considered for the overweight patients, elderly, and those with lower plasma albumin concentration.

The gas emanating from human skin is known to vary depending on one's physical condition and diet. Thus, skin gas has been gaining substantial scholarly attention as an effective noninvasive biomarker for understanding different physical conditions. This study focuses on the relationship between psychological stress and skin gas, which has remained unclear to date. It has been deduced that when participants were subjected to interviews confirmed as stressful by physiological indicators, their skin emitted an odor similar to stir-fried leeks containing allyl mercaptan and dimethyl trisulfide. This characteristic, recognizable odor appeared reproducibly during the stress-inducing situations. Furthermore, the study deduced that individuals who perceive this stress odor experience subjective tension, confusion, and fatigue (Profile of Mood States scale). Thus, the study findings indicate the possibility of human nonverbal communication through odor, which could enhance our understanding of human interaction.

BackgroundThis study aimed to investigate the association between changes in brain natriuretic peptide (BNP) from discharge to 6-month visit and subsequent clinical outcomes in patients with acute heart failure (AHF).MethodsAmong 1246 patients enrolled in the prospective longitudinal follow-up study nested from the Kyoto Congestive Heart Failure registry, this study population included 446 patients with available paired BNP data at discharge and 6-month index visit. This study population was classified into 3 groups by percent change in BNP from discharge to 6-month visit; the low tertile (≤-44%, N = 149), the middle tertile (>-44% and ≤22%, N = 149) and the high tertile (>22%, N = 148).FindingsThe cumulative 180-day incidence after the index visit of the primary outcome measure (a composite endpoint of all-cause death or hospitalization for HF) was significantly higher in the high and middle tertiles than in the low tertile (26.8% and 14.4% versus 6.9%, log-rank PConclusionsPercent change in BNP was associated with a subsequent risk for a composite of all-cause death and hospitalization for HF after adjustment of the absolute BNP values, suggesting that observing the change in BNP levels, in addition to absolute BNP levels themselves, helps us to manage patient with HF.

ObjectiveThe complex link between nutritional status, protein and lipid synthesis, and immunity plays an important prognostic role in patients with heart failure. However, the association between appetite loss at discharge and long-term outcome remains unclear.MethodsThe Kyoto Congestive Heart Failure registry is a prospective cohort study that enrolled consecutive patients hospitalized for acute decompensated heart failure (ADHF) in Japan. We assessed 3528 patients alive at discharge, and for whom appetite and follow-up data were available. We compared one-year clinical outcomes in patients with and without appetite loss at discharge.ResultsIn the multivariable logistic regression analysis using 19 clinical and laboratory factors with P value < 0.1 by univariate analysis, BMI < 22 kg/m2 (odds ratio (OR): 1.57, 95% confidence interval (CI): 1.11-2.24, P = 0.01), CRP >1.0mg/dL (OR: 1.49, 95%CI: 1.04-2.14, P = 0.03), and presence of edema at discharge (OR: 4.30, 95%CI: 2.99-6.22, PConclusionsLoss of appetite at discharge was associated with worse 1-year mortality in patients with ADHF. Appetite is a simple, reliable, and useful subjective marker for risk stratification of patients with ADHF.

Duchenne muscular dystrophy (DMD) is an intractable genetic muscular disorder characterized by the loss of DYSTROPHIN. The restoration of DYSTROPHIN is expected to be a curative therapy for DMD. Because muscle stem cells (MuSCs) can regenerate damaged myofibers with full-length DYSTROPHIN in vivo, their transplantation is being explored as such a therapy. As for the transplanted cells, primary satellite cells have been considered, but donor shortage limits their clinical application. We previously developed a protocol that differentiates induced pluripotent stem cells (iPSCs) to MuSCs (iMuSCs). To ameliorate the respiratory function of DMD patients, cell transplantation to the diaphragm is necessary but difficult, because the diaphragm is thin and rapidly moves. In the present study, we explored the transplantation of iMuSCs into the diaphragm. First, we show direct cell injection into the diaphragm of mouse was feasible. Then, to enhance the engraftment of the transplanted cells in a rapidly moving diaphragm, we mixed polymer solutions of hyaluronic acid, alginate and gelatin to the cell suspension, finding a solution of 20% dissolved hyaluronic acid and 80% dissolved gelatin improved the engraftment. Thus, we established a method for cell transplantation into mouse diaphragm and show that an injectable hyaluronic acid-gelatin solution enables the engraftment of iMuSCs in the diaphragm.

PurposeDrug-eluting stents (DESs) play an important role in endovascular therapy (EVT) for femoropopliteal (FP) lesions. Cilostazol improves patency after bare-metal nitinol stent (BNS) implantation for femoropopliteal lesions. This study aimed to establish whether cilostazol is effective in improving the patency of DESs and determine whether BNS or DESs with or without cilostazol are more effective in improving the 12-month patency after EVT for FP lesions.Materials and methodsIn this prospective, open-label, multicenter study, 85 patients with symptomatic peripheral artery disease due to de novo FP lesions were enrolled and treated with DESs with cilostazol from eight cardiovascular centers between April 2018 and May 2019. They were compared with 255 patients from the DEBATE SFA study, in which patients were randomly assigned to the BNS, BNS with cilostazol, or DES groups. The primary endpoint was the 12-month patency rate using duplex ultrasound (peak systolic velocity ratio < 2.5). This study was approved by the ethics committee of each hospital.ResultsThe 12-month patency rates for the BNS, BNS with cilostazol, DES, and DES with cilostazol groups were 77.6%, 93.1%, 82.8%, and 94.2%, respectively (p = 0.007). The 12-month patency rate was higher in the DES with cilostazol group than in the DES group (p = 0.044). In small vessels, the DES with cilostazol group had a higher patency rate than the DES group (100.0% vs. 83.4%, p = 0.023).ConclusionsDES with cilostazol showed better patency than DES alone. Cilostazol improved patency after EVT with DES in FP lesions and small vessels.Clinical trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry (no. UMIN 000032473).

Direct measurements of gross primary productivity (GPP) in the water column are essential, but can be spatially and temporally restrictive. Fast repetition rate fluorometry (FRRf) is a bio-optical technique based on chlorophyll a (Chl-a) fluorescence that can estimate the electron transport rate (ETRPSII) at photosystem II (PSII) of phytoplankton in real time. However, the derivation of phytoplankton GPP in carbon units from ETRPSII remains challenging because the electron requirement for carbon fixation (Фe,C), which is mechanistically 4 mol e- mol C-1 or above, can vary depending on multiple factors. In addition, FRRf studies are limited in freshwater lakes where phosphorus limitation and cyanobacterial blooms are common. The goal of the present study is to construct a robust Фe,C model for freshwater ecosystems using simultaneous measurements of ETRPSII by FRRf with multi-excitation wavelengths coupled with a traditional carbon fixation rate by the 13C method. The study was conducted in oligotrophic and mesotrophic parts of Lake Biwa from July 2018 to May 2019. The combination of excitation light at 444, 512 and 633 nm correctly estimated ETRPSII of cyanobacteria. The apparent range of Фe,C in the phytoplankton community was 1.1-31.0 mol e- mol C-1 during the study period. A generalised linear model showed that the best fit including 12 physicochemical and biological factors explained 67% of the variance in Фe,C. Among all factors, water temperature was the most significant, while photosynthetically active radiation intensity was not. This study quantifies the in situ FRRf method in a freshwater ecosystem, discusses core issues in the methodology to calculate Фe,C, and assesses the applicability of the method for lake GPP prediction.

BackgroundPortopulmonary hypertension (PoPH) is a subtype of the pulmonary arterial hypertension (PAH) associated with portal hypertension. There is a dissociation between the proportion of PoPH in PAH and that of PoPH in patients with liver cirrhosis, suggesting PoPH underdiagnosis and an incomplete understanding of this entity in the clinical setting. Specifically, real-world data in Japan is largely unknown as compared with in Europe and the United States. The present study aims to elucidate the prevalence and etiology of PoPH in Japanese patients with chronic liver disease.Methods and designIn this prospective, single-center, observational investigation of PoPH patients with chronic liver disease, a targeted 2,500 Japanese adult patients regularly visiting Shinshu University Hospital in Matsumoto, Japan, for chronic liver disease will complete a standardized questionnaire on the presence of PoPH symptoms. If the respondent has signs of possible PoPH, ultrasound echocardiography (UCG) will be performed as a primary screening. In the case that UCG findings indicate pulmonary hypertension, the patient will be referred to a cardiologist for further evaluation, whereby a definitive diagnosis PoPH can be made. PoPH prevalence and etiology will be investigated at the time of diagnosis. Afterwards, patients with PoPH will be followed for five years for determination of survival rate.DiscussionThis study will reveal the prevalence, etiology, and 5-year survival rate of PoPH in Japanese patients with chronic liver disease.Trial registrationThis study is being performed at Shinshu University following registration as UMIN 000042287 on October 29, 2020.

The present study identified the active radical species in acidic sodium chlorite and investigated the feasibility of quantifying these species with the diethylphenylenediamine (DPD) method. Electron spin resonance (ESR) spectroscopy was used to identify the active species generated in solutions containing sodium chlorite (NaClO2). The ESR signal was directly observed in an acidified sodium chlorite (ASC) aqueous solution at room temperature. This ESR signal was very long-lived, indicating that the radical was thermodynamically stable. The ESR parameters of this signal did not coincide with previously reported values of the chlorine radical (Cl●) or chlorine dioxide radical (O = Cl●-O and O = Cl-O●). We refer to this signal as being from the chloroperoxyl radical (Cl-O-O●). Quantum chemical calculations revealed that the optimal structure of the chloroperoxyl radical is much more thermodynamically stable than that of the chlorine dioxide radical. The UV-visible spectrum of the chloroperoxyl radical showed maximum absorbance at 354 nm. This absorbance had a linear relationship with the chloroperoxyl radical ESR signal intensity. Quantifying the free chlorine concentration by the DPD method also revealed a linear relationship with the maximum absorbance at 354 nm, which in turn showed a linear relationship with the chloroperoxyl radical ESR signal intensity. These linear relationships suggest that the DPD method can quantify chloroperoxyl radicals, which this study considers to be the active species in ASC aqueous solution.

BackgroundAdmission systolic blood pressure has emerged as a predictor of postdischarge outcomes of patients with acute decompensated heart failure; however, its validity in varied clinical conditions of this patient subset is unclear. The aim of this study was to further explore the prognostic value of admission systolic blood pressure in patients with acute decompensated heart failure.MethodsThe Kyoto Congestive Heart Failure (KCHF) registry is a prospective, observational, multicenter cohort study enrolling consecutive patients with acute decompensated heart failure from 19 participating hospitals in Japan. Clinical characteristics at baseline and prognosis were examined by the following value range of admission systolic blood pressure: ResultsWe analyzed 3564 patients discharged alive out of 3804 patients hospitalized for acute decompensated heart failure. In the entire cohort, lower admission systolic blood pressure was associated with poor outcomes (1-year cumulative incidence of all-cause death: ConclusionsAdmission systolic blood pressure is useful for postdischarge risk stratification in patients with acute decompensated heart failure. Its magnitude of the effect as a prognostic predictor may differ across clinical conditions of patients.

Baroreflex dysfunction is partly implicated in hypertension and one responsible region is the dorsal medulla oblongata including the nucleus tractus solitarius (NTS). NTS neurons receive and project glutamatergic inputs to subsequently regulate blood pressure, while G-protein-coupled metabotropic glutamate receptors (mGluRs) play a modulatory role for glutamatergic transmission in baroreflex pathways. Stimulating group II mGluR subtype 2 and 3 (mGluR2/3) in the brainstem can decrease blood pressure and sympathetic nervous activity. Here, we hypothesized that the chronic stimulation of mGluR2/3 in the dorsal medulla oblongata can alleviate hypertensive development via the modulation of autonomic nervous activity in young, spontaneously hypertensive rats (SHRs). Compared with that in the sham control group, chronic LY379268 application (mGluR2/3 agonist; 0.40 μg/day) to the dorsal medulla oblongata for 6 weeks reduced the progression of hypertension in 6-week-old SHRs as indicated by the 40 mmHg reduction in systolic blood pressure and promoted their parasympathetic nervous activity as evidenced by the heart rate variability. No differences in blood catecholamine levels or any echocardiographic indices were found between the two groups. The improvement of reflex bradycardia, a baroreflex function, appeared after chronic LY379268 application. The mRNA expression level of mGluR2, but not mGluR3, in the dorsal medulla oblongata was substantially reduced in SHRs compared to that of the control strain. In conclusion, mGluR2/3 signaling might be responsible for hypertension development in SHRs, and modulating mGluR2/3 expression/stimulation in the dorsal brainstem could be a novel therapeutic strategy for hypertension via increasing the parasympathetic activity.

[This corrects the article DOI: 10.1371/journal.pone.0230190.].

A 23-amino acid peptide named obestatin is derived from the ghrelin gene. The aim of the experiment was to study the effects of enteral obestatin administration for a 6-day period on intestinal contractility in piglets fed milk formula. Pigs were treated with 0.9% NaCl (group C) or varying doses of obestatin: 2 μg/kg body weight (BW) (group O2), 10 μg/kg BW (O10) or 15 μg/kg BW (O15) every 8 hours via a stomach tube. Blood was sampled for assessment of obestatin concentration. Duodenal and middle jejunum whole-thickness preparations were studied in an organ bath for isometric recording under electric field stimulation (EFS) and increasing doses of acetylcholine (ACh), and in the presence of atropine and tetrodotoxin (TTX). Additionally, the measurement of intestinal muscularis layer and the immunodetection of Muscarinic Acetylcholine Receptors (M1 and M2) were performed. In comparison to C animals, the obestatin concentration in blood plasma was significantly increased in groups O10 and O15. In both studied intestinal segments, significant increases in the frequency and amplitude of spontaneous contractions were observed in O15 and C groups. In the duodenum and middle jejunum significant differences in responsiveness to EFS (0.5, 5 and 50 Hz) were observed between the groups. The addition of 10-4 M ACh to the duodenum significantly increased the responsiveness in tissues. In contrast, in the middle jejunum a significant increase in the amplitude of contraction was observed after the addition of 10-9 and 10-6 M ACh (groups O15 and O10, respectively). Pretreatment with atropine and TTX resulted in a significant decrease in the responsiveness of the intestinal preparations from all groups, in both studied segments. The increased contractility was not dependent on the expression of muscarinic receptors. Results indicate the importance of enteral obestatin administration in the regulation of intestinal contractility in neonatal piglets.

Aortic dissection (AD) is a major cause of acute aortic syndrome with high mortality due to the destruction of aortic walls. Although recent studies indicate the critical role of inflammation in the disease mechanism of AD, it is unclear how inflammatory response is initiated. Here, we demonstrate that myocardin-related transcription factor A (MRTF-A), a signal transducer of humoral and mechanical stress, plays an important role in pathogenesis of AD in a mouse model. A mouse model of AD was created by continuous infusion of angiotensin II (AngII) that induced MRTF-A expression and caused AD in 4 days. Systemic deletion of Mrtfa gene resulted in a marked suppression of AD development. Transcriptome and gene annotation enrichment analyses revealed that AngII infusion for 1 day caused pro-inflammatory and pro-apoptotic responses before AD development, which were suppressed by Mrtfa deletion. AngII infusion for 1 day induced pro-inflammatory response, as demonstrated by expressions of Il6, Tnf, and Ccl2, and apoptosis of aortic wall cells, as detected by TUNEL staining, in an MRTF-A-dependent manner. Pharmacological inhibition of MRTF-A by CCG-203971 during AngII infusion partially suppressed AD phenotype, indicating that acute suppression of MRTF-A is effective in preventing the aortic wall destruction. These results indicate that MRTF-A transduces the stress of AngII challenge to the pro-inflammatory and pro-apoptotic responses, ultimately leading to AD development. Intervening this pathway may represent a potential therapeutic strategy.

The objective of this study was to determine the radiocesium transfer rates of pigs fed haylage contaminated with low levels of cesium at different growth stages. We measured the body weight of juvenile and adult pigs during the treatment period to confirm their health status. We also performed pig blood hematologic and biochemical analyses at both growth stages. To our knowledge, this is the first study to report pig radiocesium transfer coefficient rates after 1 month of chronic oral treatment, which is the period assumed to be required for body equilibrium under a diet of radiocesium-contaminated food. The results showed higher radiocesium retention rates in the kidneys, liver, spleen, genitals, psoas major, bladder, thyroid, and urine than in the blood and bone (tibia and femur) of pigs at both growth stages. The radiocesium retention levels were generally higher in juvenile pigs than in adult pigs, with the highest transfer coefficient ratio in the kidneys (16.2%).

ObjectiveThis observational study aimed to examine the prognostic association of angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blockers (ARB) in different left ventricular ejection fraction (LVEF) categories.MethodsIn 3717 patients enrolled in the KCHF Registry, a multicentre registry including consecutive patients hospitalized for acute heart failure (HF), we assessed patient characteristics and association between ACE-I/ARB and clinical outcomes according to LVEF. In the three LVEF categories (reduced LVEF [HFrEF], mid-range LVEF [HFmrEF] and preserved LVEF [HFpEF]), we compared the patients with ACE-I/ARB as discharge medication and those without, and assessed their 1-year clinical outcomes. We defined the primary outcome measure as a composite of all-cause death and HF hospitalization.ResultsThe 1-year cumulative incidences of the primary outcome measure were 36.3% in HFrEF, 30.1% in HFmrEF and 33.8% in HFpEF (log-rank P = 0.07). The adjusted risks of the ACE-I/ARB group relative to the no ACE-I/ARB group for the primary outcome measure were significantly lower in HFrEF and HFmrEF (HR 0.66 [95%CI 0.54-0.79], PConclusionsACE-I/ARB for patients who were hospitalized for acute HF was associated with significantly lower risk for a composite of all-cause death and HF hospitalization in HFrEF and HFmrEF, but not in HFpEF. ACE-I/ARB might be a potential treatment option in HFmrEF as in HFrEF.

BackgroundThe composite Model for End-Stage Liver Disease Excluding International Normalized Ratio Score (MELD-XI) is a novel tool to evaluate cardio-renal and cardio-hepatic interactions in patients with advanced heart failure (HF). However, its prognostic ability remains unclear in elderly HF patients.Methods and resultsFrom July 2014 to July 2018, patients hospitalized for HF were prospectively recruited at 16 centers. Clinical features, laboratory findings, and echocardiography results were assessed prior to discharge. Cardiovascular (CV) death and HF re-hospitalization were recorded. Of the 676 patients enrolled, 264 (39.1%) experienced CV events throughout a 1-year median follow-up period. Patients with high MELD-XI were predominantly male and had a higher prevalence of NYHA III/IV, history of HF admission, hyperuricemia, ventricular tachycardia, anemia, and ischemic heart disease. In Kaplan-Meyer analysis, patients with higher MELD-XI (≥11) scores showed a worse prognosis than did those with lower (ConclusionsCardio-renal and cardio-hepatic interactions predicted CV events in aged HF patients.

Autonomic nervous function evaluated by heart rate variability (HRV) and blood characteristics were compared between Holstein Friesian cows that developed postpartum fever (PF; n = 5) and clinically healthy (CH; n = 6) puerperal cows in this case-control study. A cow was defined as having PF when its rectal temperature rose to ≥39.5°C between 1 and 3 days postpartum. We recorded electrocardiograms during this period using a Holter-type electrocardiograph and applied power spectral analysis of HRV. Comparisons between the groups were analyzed by t test or Mann-Whitney U test, and the relationship between rectal temperature and each parameter was analyzed using multiple regression analysis. Heart rate was higher in PF cows than in CH cows (Mean ± SE, 103.3 ± 2.7 vs. 91.5 ± 1.7 bpm). This result suggested that PF cows had a relatively dominant sympathetic nervous function. Total (44,472 ± 2,301 vs. 55,373 ± 1,997 ms) and low frequency power (24.5 ± 3.8 vs. 39.9 ± 5.3 ms) were lower in PF cows than in CH cows. These findings were possibly caused by a reduction in autonomic nervous function. The total white blood cell count (54.3 ± 5.1 vs. 84.5 ± 6.4 ×102/μL) and the serum magnesium (2.1 ± 0.1 vs. 2.4 ± 0.1 mg/dL) and iron (81.5 ± 8.0 vs. 134.4 ± 9.1 μg/dL) concentrations were lower and the serum amyloid A concentration (277 ± 33 vs. 149 ± 21 μg/mL) was higher in PF cows than in CH cows. These results imply that more inflammation was present in PF cows than in CH cows. Multiple regression analysis showed that both of low frequency power and concentration of serum iron were associated with rectal temperature. We found differences in changes in hematologic results, biochemical findings, and HRV patterns between PF cows and CH cows.

ObjectivesTo investigate the association between a healthy lifestyle index (HLI) (i.e., a composite score comprising multiple lifestyle factors) and hypertension among community adults living in Sri Lanka.MethodsThe present study used baseline information of a cluster randomized controlled trial among 456 adults aged 27-65 years in a semi-urban community in Colombo, Sri Lanka. The HLI was constructed by summing a number of low-risk lifestyle factors: low body mass index, sufficient physical activity, non-smoking, low alcohol consumption, and sufficient fruit and vegetable consumption. Hypertension was defined as systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or the use of antihypertensive medication. A logistic regression model was used to investigate the association between the HLI (low: 0-2; middle: 3; high: 4-5) and hypertension.ResultsA total of 178 (39%) participants were hypertensive. Compared with the low HLI group, multivariate-adjusted odds ratios (95% confidence intervals) of hypertension were 0.72 (0.44-1.19) and 0.28 (0.15-0.54) for the middle and high HLI groups, respectively (p-trend ConclusionsThe present study provides essential evidence on an inverse association between adherence to healthy lifestyles and hypertension.

BackgroundDespite the prognostic importance of hypoalbuminemia, the prognostic implication of a change in albumin levels has not been fully investigated during hospitalization in patients with acute decompensated heart failure (ADHF).MethodsUsing the data from the Kyoto Congestive Heart Failure registry on 3160 patients who were discharged alive for acute heart failure hospitalization and in whom the change in albumin levels was calculated at discharge, we evaluated the association with an increase in serum albumin levels from admission to discharge and clinical outcomes by a multivariable Cox hazard model. The primary outcome measure was a composite of all-cause death or hospitalization for heart failure.FindingsPatients with increased albumin levels (N = 1083, 34.3%) were younger and less often had smaller body mass index and renal dysfunction than those with no increase in albumin levels (N = 2077, 65.7%). Median follow-up was 475 days with a 96% 1-year follow-up rate. Relative to the group with no increase in albumin levels, the lower risk of the increased albumin group remained significant for the primary outcome measure (hazard ratio: 0.78, 95% confidence interval: 0.69-0.90: P = 0.0004) after adjusting for confounders including baseline albumin levels. When stratified by the quartiles of baseline albumin levels, the favorable effect of increased albumin was more pronounced in the lower quartiles of albumin levels, but without a significant interaction effect (interaction P = 0.49).ConclusionsIndependent of baseline albumin levels, an increase in albumin during index hospitalization was associated with a lower 1-year risk for a composite of all-cause death and hospitalization in patients with acute heart failure.

The first outbreak in Japan of GES-5 carbapenemase-producing Pseudomonas aeruginosa occurred in a long-term care facility in 2014. To assess the spread of GES-5 producing P. aeruginosa clinical isolates in medical settings in Japan, 1,476 carbapenem-resistant P. aeruginosa isolates obtained from 2012 to 2016 were characterized. Of these 1,476 isolates, 104 (7.0%) harbored blaGES-5. Southern blotting revealed that the blaGES-5 was located on the chromosome. The isolation rates of these GES-5 producers increased significantly every year, from 2.0% (6 of 295) in 2012 to 2.8% (8 of 283) in 2013 to 5.3% (16 of 303) in 2014 to 9.7% (29 of 300) in 2015 to 15.3% (45 of 295) in 2016. Of the 104 GES-5 producers, 102 belonged to clonal complex (CC) 235, including 99 belonging to ST235 and three belonging to ST2233). Whole genome sequence analysis revealed that CC235 P. aeruginosa harboring blaGES-5 spread in a clonal manner. These results indicate that these GES-5 producing CC235 P. aeruginosa clinical isolates have spread in medical settings throughout Japan.

[This corrects the article DOI: 10.1371/journal.pone.0142779.].

This study investigated the effect of enteral administration of obestatin on the development of small intestine, as well as oxidative stress markers and trancriptomic profile of gastrointestinal genes. Suckling rats were assigned to 3 groups treated with: C-saline solution; OL-obestatin (125 nmol/kg BW); OH-obestatin (250 nmol/kg BW) administered twice daily, from the 14th to the 21st day of life. Enteral administration of obestatin in both studied doses had no effect neither on the body weight of animals nor the BMI calculated in the day of euthanasia. Compared to the control group (C), treatment with obestatin resulted in significant changes in the histometry of the small intestinal wall as well as intestinal epithelial cell remodeling. The observed changes and their possible implications for intestinal development were dependent on the dosage of peptide. The enteral administration of high dose (OH) of obestatin significantly decreased its expression in the stomach and increased markers of oxidative stress. The gene profile revealed MAPK3 (mitogen-activated protein kinase-3) as the key regulator gene for obestatin action in the gastrointestinal track. In conclusion, we have showed that enteral administration of obestatin influences the gut mucosa remodeling. It is also suggested that the administration of high dose (OH) has inhibitory effect on the intestinal maturation of suckling rats.

Although oxygen therapy rapidly improves arterial oxygen saturation in idiopathic pulmonary arterial hypertension, the effects of chronic administration of oxygen are unknown. The purpose of the present study was to investigate the effects of chronic oxygen therapy on the histological changes and survival rate in rats with idiopathic pulmonary arterial hypertension. Idiopathic pulmonary arterial hypertension was induced by monocrotaline injection. The rats were then randomly assigned to receive or not receive oxygen therapy (O2 group and non-O2 group, respectively). The rats in the O2 group were exposed to a high (90%) oxygen environment from day 17 following injection of monocrotaline, when hypoxemia was first observed. The pulmonary arteriole walls were significantly thicker in monocrotaline-injected rats than in saline-injected rats as vehicle on day 19 and were significantly thicker in the rats that received oxygen therapy than in the rats that did not. Right ventricular inflammations were significantly higher in monocrotaline-injected rats than in saline-injected rats on day 19 and were significantly higher in the rats that received oxygen therapy than in the rats that did not. By day 20 after injection of monocrotaline, the survival rate was significantly lower in the rats that received oxygen therapy than in those that did not. Superoxide dismutase activity in the lungs was higher in monocrotaline-injected rats than in saline-injected rats on day 19 after monocrotaline injection and was also higher in the saline-injected rats that received oxygen therapy than in the saline-injected rats that did not. No interaction was detected between monocrotaline injection and oxygen therapy. These results suggest that chronic oxygen therapy worsens the histological changes and survival rate in idiopathic pulmonary arterial hypertension. The fact that degradation of the histological changes and survival rate was accompanied by increase in superoxide dismutase activity suggests that antioxidant capacity may contribute to the degradation.

We have previously investigated the physiological role of C-type natriuretic peptide (CNP) on endochondral bone growth, mainly with mutant mouse models deficient in CNP, and reported that CNP is indispensable for physiological endochondral bone growth in mice. However, the survival rate of CNP knockout (KO) mice fell to as low as about 70% until 10 weeks after birth, and we could not sufficiently analyze the phenotype at the adult stage. Herein, we generated CNP KO rats by using zinc-finger nuclease-mediated genome editing technology. We established two lines of mutant rats completely deficient in CNP (CNP KO rats) that exhibited a phenotype identical to that observed in mice deficient in CNP, namely, a short stature with severely impaired endochondral bone growth. Histological analysis revealed that the width of the growth plate, especially that of the hypertrophic chondrocyte layer, was markedly lower and the proliferation of growth plate chondrocytes tended to be reduced in CNP KO rats. Notably, CNP KO rats did not have malocclusions and survived for over one year after birth. At 33 weeks of age, CNP KO rats persisted significantly shorter than wild-type rats, with closed growth plates of the femur in all samples, which were not observed in wild-type rats. Histologically, CNP deficiency affected only bones among all body tissues studied. Thus, CNP KO rats survive over one year, and exhibit a deficit in endochondral bone growth and growth retardation throughout life.

BACKGROUND:The blood pressure (BP) variability (BPV) is a predictor of cardiovascular disease, independently of the BP itself. In addition, visceral fat accumulation can trigger atherosclerotic disease through various mechanisms. METHODS AND RESULTS:We examined the association between fat accumulation and day-to-day BPV in 61 adult hypertensive patients. Visceral fat area (VFA) was measured using the dual bioelectrical impedance analysis method. Participants were divided into three groups based on VFA. The standard deviation (SD) in home systolic BP (SBP) for 7 consecutive days was significantly lower in the high VFA tertile (low VFA, 8.40±4.15 mmHg; intermediate VFA, 8.47±2.80 mmHg; and high VFA, 5.84±2.37 mmHg, p of One-way ANOVA = 0.017, p for trend = 0.0126). A similar association was observed between the coefficient of variance (CV) of home SBP and the VFA tertile. Multiple-regression analysis adjusted for age, sex, antihypertensive drug, diabetes, habitual drinking, and SBP level also showed a significant association between the VFA tertile and the SD or CV of home SBP. The adjusted coefficient of regression for the SD of home SBP was -3.28 (95%CI: -5.60 to -0.97, p = 0.008) and the CV of home SBP was -2.51 (95%CI: -4.31 to -0.71, p = 0.008) for the highest VFA tertile as compared to the lowest VFA tertile. CONCLUSIONS:These results show for the first time negative correlation between VFA and day-to-day BPV. The degree of obesity should be taken into account when evaluating the value of BPV.

Sanitation of environmental surfaces with chlorine based-disinfectants is a principal measure to control outbreaks of norovirus or Clostridium difficile. The microbicidal activity of chlorine-based disinfectants depends on the free available chlorine (FAC), but their oxidative potential is rapidly eliminated by organic matter. In this study, the microbicidal activities of weakly acidified chlorous acid water (WACAW) and sodium hypochlorite solution (NaClO) against feline calcivirus (FCV) and C. difficile spores were compared in protein-rich conditions. WACAW inactivated FCV and C. difficile spores better than NaClO under all experimental conditions used in this study. WACAW above 100 ppm FAC decreased FCV >4 log10 within 30 sec in the presence of 0.5% each of bovine serum albumin (BSA), polypeptone or meat extract. Even in the presence of 5% BSA, WACAW at 600 ppm FAC reduced FCV >4 log10 within 30 sec. Polypeptone inhibited the virucidal activity of WACAW against FCV more so than BSA or meat extract. WACAW at 200 ppm FAC decreased C. difficile spores >3 log10 within 1 min in the presence of 0.5% polypeptone. The microbicidal activity of NaClO was extensively diminished in the presence of organic matter. WACAW recovered its FAC to the initial level after partial neutralization by sodium thiosulfate, while no restoration of the FAC was observed in NaClO. These results indicate that WACAW is relatively stable under organic matter-rich conditions and therefore may be useful for treating environmental surfaces contaminated by human excretions.

We have performed open cell transmission electron microscopy experiments through pure water vapor in the saturation pressure regime (>0.6 kPa), in a modern microscope capable of sub-Å resolution. We have systematically studied achievable pressure levels, stability and gas purity, effective thickness of the water vapor column and associated electron scattering processes, and the effect of gas pressure on electron optical resolution and image contrast. For example, for 1.3 kPa pure water vapor and 300kV electrons, we report pressure stability of ± 20 Pa over tens of minutes, effective thickness of 0.57 inelastic mean free paths, lattice resolution of 0.14 nm on a reference Au specimen, and no significant degradation in contrast or stability of a biological specimen (M13 virus, with 6 nm body diameter). We have also done some brief experiments to confirm feasibility of loading specimens into an in situ water vapor ambient without exposure to intermediate desiccating conditions. Finally, we have also checked if water experiments had any discernible impact on the microscope performance, and report pertinent vacuum and electron optical data, for reference purposes.

The ankle-brachial index (ABI) is a marker of generalized atherosclerosis and is predictive of future cardiovascular events. However, few studies have assessed its relation to long-term future cardiovascular events, especially in patients with borderline ABI. We therefore evaluated the relationship between long-term future cardiovascular events and ABI.In the IMPACT-ABI study, a single-center, retrospective cohort study, we enrolled 3131 consecutive patients (67 ± 13 years; 82% male) hospitalized for cardiovascular disease and measured ABI between January 2005 and December 2012. After excluding patients with an ABI > 1.4, the remaining 3056 patients were categorized as having low ABI (≤ 0.9), borderline ABI (0.91-0.99), or normal ABI (1.00-1.40). The primary endpoint was MACE (cardiovascular death, myocardial infarction [MI] and stroke). The secondary endpoints were cardiovascular death, MI, stroke, admission due to heart failure, and major bleeding.During a 4.8-year mean follow-up period, the incidences of MACE (low vs. borderline vs. normal: 32.9% vs. 25.0% vs. 14.6%, P

Reduced ankle-brachial index (ABI) is a predictor of cardiovascular events. However, the significance of high ABI remains poorly understood. This study aimed to assess the characteristics and outcomes of patients with high ABI.The IMPACT-ABI study was a retrospective cohort study that enrolled and examined ABI in 3,131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 2,419 patients were identified and stratified into two groups: high ABI (> 1.4; 2.6%) and normal ABI (1.0-1.4; 97.3%). The primary endpoint was the cumulative incidence of major adverse cardiovascular events (MACE), including cardiovascular-associated death, myocardial infarction, and stroke.Compared with the normal ABI group, patients in the high ABI group showed significantly lower body mass index (BMI) and hemoglobin level, but had higher incidence of chronic kidney disease and hemodialysis. Multivariate logistic regression analysis revealed that hemodialysis was the strongest predictor of high ABI (odds ratio, 6.18; 95% confidence interval (CI), 3.05-12.52; P < 0.001). During the follow-up (median, 4.7 years), 172 cases of MACE occurred. Cumulative MACE incidence in patients with high ABI was significantly increased compared to that in those with normal ABI (32.5% vs. 14.5%; P = 0.005). In traditional cardiovascular risk factors-adjusted multivariate Cox proportional hazard analysis, high ABI was an independent predictor of MACE (hazard ratio, 2.07; 95% CI, 1.02-4.20; P = 0.044).Lower BMI, chronic kidney disease, and hemodialysis are more frequent in patients with high ABI. Hemodialysis is the strongest predictor of high ABI. High ABI is a parameter that independently predicts MACE.

The effect of the Fukushima Daiichi Nuclear Power Plant (FNPP) accident on humans and the environment is a global concern. We performed biochemical analyses of plasma from 49 Japanese Black cattle that were euthanized in the ex-evacuation zone set within a 20-km radius of FNPP. Among radionuclides attributable to the FNPP accident, germanium gamma-ray spectrometry detected photopeaks only from 134Cs and 137Cs (radiocesium) commonly in the organs and in soil examined. Radioactivity concentration of radiocesium was the highest in skeletal muscles. Assuming that the animal body was composed of only skeletal muscles, the median of internal dose rate from radiocesium was 12.5 μGy/day (ranging from 1.6 to 33.9 μGy/day). The median of external dose rate calculating from the place the cattle were caught was 18.8 μGy/day (6.0-133.4 μGy/day). The median of internal and external (total) dose rate of the individual cattle was 26.9 μGy/day (9.1-155.1 μGy/day). Plasma levels of malondialdehyde and superoxide dismutase activity were positively and glutathione peroxidase activity was negatively correlated with internal dose rate. Plasma alanine transaminase activity and percent activity of lactate dehydrogenase (LDH)-2, LDH-3 and LDH-4 were positively and LDH-1 was negatively correlated with both internal and total dose rate. These suggest that chronic exposure to low-dose rate of ionizing radiation induces slight stress resulting in modified plasma protein and enzyme levels.

The control of blood glucose levels, blood pressure (BP), and low-density lipoprotein cholesterol (LDL-C) levels reduces the risk of diabetes complications; however, data are scarce on control status of these factors among workers with diabetes. The present study aimed to estimate the prevalence of participants with diabetes who meet glycated hemoglobin (HbA1c), BP, and LDL-C recommendations, and to investigate correlates of poor glycemic control in a large working population in Japan.The Japan Epidemiology Collaboration on Occupational Health (J-ECOH) Study is an ongoing cohort investigation, consisting mainly of employees in large manufacturing companies. We conducted a cross-sectional analysis of 3,070 employees with diabetes (2,854 men and 216 women) aged 20-69 years who attended periodic health examinations. BP was measured and recorded using different company protocols. Risk factor targets were defined using both American Diabetes Association (ADA) guidelines (HbA1c < 7.0%, BP < 140/90 mmHg, and LDL-C < 100 mg/dL) and Japan Diabetes Society (JDS) guidelines (HbA1c < 7.0%, BP < 130/80 mmHg, and LDL-C < 120 mg/dL). Logistic regression models were used to explore correlates of poor glycemic control (defined as HbA1c ≥ 8.0%).The percentages of participants who met ADA (and JDS) targets were 44.9% (44.9%) for HbA1c, 76.6% (36.3%) for BP, 27.1% (56.2%) for LDL-C, and 11.2% (10.8%) for simultaneous control of all three risk factors. Younger age, obesity, smoking, and uncontrolled dyslipidemia were associated with poor glycemic control. The adjusted odds ratio of poor glycemic control was 0.58 (95% confidence interval, 0.46-0.73) for participants with treated but uncontrolled hypertension, and 0.47 (0.33-0.66) for participants with treated and controlled hypertension, as compared with participants without hypertension. There was no significant difference in HbA1c levels between participants with treated but uncontrolled hypertension and those with treated and controlled hypertension.Data from a large working population, predominantly composed of men, suggest that achievement of HbA1c, BP, and LDL-C targets was less than optimal, especially in younger participants. Uncontrolled dyslipidemia was associated with poor glycemic control. Participants not receiving antihypertensive treatment had higher HbA1c levels.

Phase changes in Bacteroides fragilis, a member of the human colonic microbiota, mediate variations in a vast array of cell surface molecules, such as capsular polysaccharides and outer membrane proteins through DNA inversion. The results of the present study show that outer membrane vesicle (OMV) formation in this anaerobe is also controlled by DNA inversions at two distantly localized promoters, IVp-I and IVp-II that are associated with extracellular polysaccharide biosynthesis and the expression of outer membrane proteins. These promoter inversions are mediated by a single tyrosine recombinase encoded by BF2766 (orthologous to tsr19 in strain NCTC9343) in B. fragilis YCH46, which is located near IVp-I. A series of BF2766 mutants were constructed in which the two promoters were locked in different configurations (IVp-I/IVp-II = ON/ON, OFF/OFF, ON/OFF or OFF/ON). ON/ON B. fragilis mutants exhibited hypervesiculating, whereas the other mutants formed only a trace amount of OMVs. The hypervesiculating ON/ON mutants showed higher resistance to treatment with bile, LL-37, and human β-defensin 2. Incubation of wild-type cells with 5% bile increased the population of cells with the ON/ON genotype. These results indicate that B. fragilis regulates the formation of OMVs through DNA inversions at two distantly related promoter regions in response to membrane stress, although the mechanism underlying the interplay between the two regions controlled by the invertible promoters remains unknown.

Gfi1 plays an important role in the development and maintenance of many hematopoietic linage cells. However, the impact of Gfi1-deficiency on the iNKT cell differentiation remains unclear. We herein demonstrate a critical role of Gfi1 in regulating the development of iNKT cell subsets. In the thymus of T cell-specific Gfi1-deficient mice, iNKT cells normally developed up to stage 2, while the number of stage 3 NK1.1pos iNKT cells was significantly reduced. Furthermore, CD4pos iNKT cells were selectively reduced in the peripheral organs of T cell-specific Gfi1-deficient mice. The α-GalCer-dependent production of IFN-γand Th2 cytokines, but not IL-17A, was severely reduced in T cell-specific Gfi1-deficient mice. In addition, a reduction of the α-GalCer-induced anti-tumor activity was observed in Gfi1-deficient mice. These findings demonstrate the important role of Gfi1 in regulating the development and function of NKT1- and NKT2-type iNKT cell subsets.

The aim of this study was to evaluate the efficacy of daclatasvir plus asunaprevir therapy in patients infected with hepatitis C virus and determine its relevance to resistant variants.A total of 629 consecutive patients infected with hepatitis C virus genotype 1 were assessed. Daclatasvir (60 mg/day) plus asunaprevir (200 mg/day) was given for 24 weeks. The virological responses and resistance-associated substitutions of hepatitis C virus mutants were examined by the direct sequence and cycleave methods were evaluated.Overall, 89.4% (555/621) of patients exhibited a sustained virological response (SVR). The SVR rates in the patients with wild type, mixed, and mutant type Y93 by direct sequencing were 92.5% (520/562), 70.3% (26/37), and 42.9% (9/21), respectively. The SVR rates in the patients with 100%, 90%, 80%-30%, and 20%-0% Y93 wild by the cycleave method were 93.4% (456/488), 88.2%(30/34), 56.0%(14/25), and 36.8%(7/19), respectively. In contrast, the SVR rates for the wild type and mixed/mutant type L31 by direct sequencing were 90.2% (534/592) and 72.4% (21/29), respectively. In the multivariate analyses, the wild type Y93, no history of simeprevir therapy, the wild type L31, and low HCV RNA level were independent factors of SVR.NS5A resistance-associated substitutions, especially Y93H, were major factors predicting the SVR. Although direct sequencing can predict the SVR rate, the cycleave method is considered to be more useful for predicting the SVR when used in combination.

BACKGROUND:Hypertension often occurs after tracheal intubation using a Macintosh laryngoscope and may lead to rare but serious complications. The Macintosh laryngoscope may increase the incidence of hypertension because it requires forced alignment of the oral and pharyngeal axes in order to view the glottis. In contrast, the McGRATH MAC video laryngoscope does not require this manipulation. The objective of this study was to evaluate the incidence of hypertension after tracheal intubation using a McGRATH laryngoscope compared with a Macintosh laryngoscope. METHODS:Data of 360 consecutive patients who underwent general anesthesia with tracheal intubation by Macintosh laryngoscope or McGRATH video laryngoscope were obtained retrospectively. A total of 16 variables including patient characteristics, anesthetic drug used, and intubation techniques were extracted as potential factors affecting the incidence of hypertension after intubation. The incidence of hypertension after tracheal intubation was defined as an increase in systolic blood pressure (SBP) >20% of values immediately before intubation. Propensity scoring with inverse probability weighting was used to calculate the odds ratio for the incidence of hypertension after intubation with a McGRATH video laryngoscope as the primary outcome. The mean difference in SBP change between the two laryngoscopes was also calculated. RESULTS:A McGRATH laryngoscope was used in 68 of 360 patients (18%). The numbers of patients who increase in systolic blood pressure of more than 20% was 189 patients (53%). The odds ratio for the use of a McGRATH laryngoscope was 0.43 (95% confidence interval (CI), 0.19-0.96; P = 0.04). The mean difference in SBP change between the two laryngoscopes was -8.6 mmHg (95% CI, -17.4 to 0.2; P = 0.06). CONCLUSIONS:The use of a McGRATH laryngoscope may reduce the incidence of hypertension after tracheal intubation compared to the Macintosh laryngoscope.

[This corrects the article DOI: 10.1371/journal.pone.0155069.].

To examine the association of smoking status, smoking intensity, and smoking cessation with the risk of type 2 diabetes (T2D) using a large database.The present study included 53,930 Japanese employees, aged 15 to 83 years, who received health check-up and did not have diabetes at baseline. Diabetes was defined as fasting plasma glucose ≥126 mg/dl, random plasma glucose ≥200 mg/dl, HbA1c ≥6.5% (≥48 mmol/mol), or receiving medication for diabetes. Cox proportional-hazards regression models were used to investigate the association between smoking and the risk of diabetes.During 3.9 years of median follow-up, 2,441 (4.5%) individuals developed T2D. The multivariable-adjusted hazard ratios (95% CI) for diabetes were 1 (reference), 1.16 (1.04 to 1.30) and 1.34 (1.22 to 1.48) for never smokers, former smokers, and current smokers, respectively. Diabetes risk increased with increasing numbers of cigarette consumption among current smokers (P for trend

Risk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population.Participants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008-2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG) ≥ 126 mg/dl, random plasma glucose ≥ 200 mg/dl, glycated hemoglobin (HbA1c) ≥ 6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort.The area under the curve (AUC) for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703-0.731). In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883-0.902). When the risk scores were applied to the validation cohort, AUCs (95% CI) for the non-invasive and invasive model were 0.734 (0.715-0.753) and 0.882 (0.868-0.895), respectively. Participants with a non-invasive score of ≥ 15 and invasive score of ≥ 19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years.The simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c.