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In a severe accident of light water reactor (LWR), molten core material (corium) can be released into the wet cavity, and a fuel-coolant interaction (FCI) can occur. The molten jet with high speed is broken and fragmented into small debris, which may cause a steam explosion or a molten core concrete interaction (MCCI). Since the premixing stage where the jet breakup occurs has a large impact on the severe accident progression, the understanding and evaluation of the jet breakup phenomenon are highly important. Therefore, in this study, the jet breakup simulations were performed using the Smoothed Particle Hydrodynamics (SPH) method which is a particle-based Lagrangian numerical method. For the multi-fluid system, the normalized density approach and improved surface tension model (CSF) were applied to the in-house SPH code (single GPU-based SOPHIA code) to improve the calculation accuracy at the interface of fluids. The jet breakup simulations were conducted in two cases: (1) jet breakup without structures, and (2) jet breakup with structures (control rod guide tubes). The penetration depth of the jet and jet breakup length were compared with those of the reference experiments, and these SPH simulation results are qualitatively and quantitatively consistent with the experiments.

Lagrangian-based meshless CFD methods have recently been developed and are being gradually applied to various research areas. In nuclear engineering, the meshless methods are gaining attention in modeling natural disasters and severe accident phenomena, such as tsunami, molten corium behaviors, etc., because of its flexible computational domain and effective treatment of non-linear deformations. This paper introduces recent progress and on-going activities in Lagrangian-based CFD code development at Seoul National University (SNU). The code, named SOPHIA, is based on the smoothed particle hydrodynamics (SPH) method, one of the best-known meshless numerical methods, based on a Lagrangian framework that can easily handle various types of physics because of its simplicity in expressing and solving mathematical equations. The SOPHIA code currently incorporates basic conservation equations and various physical models, including fluid flow, heat transfer, turbulence, multi-phase, phase change, elastic solid, diffusion and so on. To handle multi-phase, multi-component, and multi-resolution flows simultaneously, the SOPHIA code formulates density and continuity equations based on the normalized-density form, which has been recently developed and is proposed in the current study. The SOPHIA code also adapts CUDA GPU architectures for parallelization and performance improvement. Based on the benchmark calculations, the parallelized GPU code shows much higher computational speed by two orders of magnitude compared to the single CPU code for 1.0 million particles. This paper summarizes the overall features of the SOPHIA code, including governing equations, algorithms, and parallelization methods, along with some benchmark simulations.

The Divergence-Free SPH (DFSPH) method is a recently proposed novel incompressible Smoothed Particle Hydrodynamics (SPH) method. The DFSPH method enforces incompressibility via two iterative solvers: the Divergence-Free (DF) solver and the Constant-Density (CD) solver. In this study, the DFSPH algorithm is implemented into the SOPHIA Plus framework to simulate a set of wave propagation under the same geometry and conditions of a laboratory-scale experiment. The experiments are conducted for wave propagation and interaction with a structure of scaled-down undersea topography near the Kori nuclear power plant in South Korea. This study compares the free surface propagation and the wave height with the experimental measurements for three test cases: low/medium/high frequency waves. Overall, the simulation shows good agreement with the experiment both qualitatively and quantitatively. However, according to the sensitivity study, more realistic water splashing behaviors are captured as the particle size is reduced. The predicted wave heights at three different locations are also in fairly good agreement with the experimental measurement. Slight differences are observed after the wave collides with the structure because of the low energy dissipation in the simulation. However, the differences are not significant.

Advanced modeling and analysis techniques are always essential for development of safe and reliable nuclear systems. The numerical methods in nuclear thermal-hydraulics and safety analysis are generally based on mesh-based (or grid-based) methods. These mesh-based methods have a long history and thus are very mature both mathematically and numerically. Based on their robustness and efficiency, they have been successfully applied to many applications for decades. However, the mesh-based methods suffer from difficulties in handling complex phenomena accompanied by highly non-linear deformations, which are frequently encountered in the recent nuclear safety issues related to natural disaster and severe accidents. Recent advances in Lagrangian-based CFD techniques have opened up possibilities for addressing this issue effectively. In this study, a Lagrangian-based CFD code (named as SOPHIA) has been developed based on Smoothed Particle Hydrodynamics (SPH), one of the best-known Lagrangian methods which can extensively handle various physics because of its simplicity in expressing and solving mathematical equations. The SOPHIA code incorporates basic conservation equations (mass, momentum, and energy) and various physical models including heat transfer, turbulence, multi-phase, surface tension, diffusion, etc. In addition, to handle multi-phase, multi-component, and multi-resolution flows, the code newly formulates density and continuity equations in terms of a normalized-density. One of the biggest technical challenges in the Largrangian-based CFD is its high computational cost. Therefore, the code is parallelized using multi-GPUs through multi-parallel computing techniques. Through the optimized algorithm based on these techniques, the computational performance has been improved drastically and the code obtains the capability of high resolution and large scale simulation. In order to demonstrate its applicability to nuclear safety-related issues, this study performs the simulations on three benchmark experiments related to nuclear safety: (1) water jet breakup of FCI, (2) LMR core sloshing, and (3) bubble lift force. The simulation results are compared with the experimental data both qualitatively and quantitatively, and they shows a good agreement with highly reliable visualizations.

Interrogation elicits anxiety in individuals under scrutiny regardless of their innocence, and thus, anxious responses to interrogation should be differentiated from deceptive behavior in practical lie detection settings. Despite its importance, not many empirical studies have yet been done to separate the effects of interrogation from the acts of lying or guilt state. The present fMRI study attempted to identify neural substrates of anxious responses under interrogation in either innocent or guilt contexts by developing a modified "Doubt" game. Participants in the guilt condition showed higher brain activations in the right central-executive network and bilateral basal ganglia. Regardless of the person's innocence, we observed higher activation of the salience, theory of mind and sensory-motor networks-areas associated with anxiety-related responses in the interrogative condition, compared to the waived conditions. We further explored two different types of anxious responses under interrogation-true detection anxiety in the guilty (true positive) and false detection anxiety in the innocent (false positive). Differential neural responses across these two conditions were captured at the caudate, thalamus, ventral anterior cingulate and ventromedial prefrontal cortex. We conclude that anxiety is a common neural response to interrogation, regardless of an individual's innocence, and that there are detectable differences in neural responses for true positive and false positive anxious responses under interrogation. The results of our study highlight a need to isolate complex cognitive processes involved in the deceptive acts from the emotional and regulatory responses to interrogation in lie detection schemes.

Background Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease as well as metabolic syndrome. FDG-PET is a novel imaging technique that detects vascular inflammation, which may reflect rupture-prone vulnerable atherosclerotic plaques. Methods Vascular inflammation was measured as the maximum target-to-background ratio (maxTBR), along with various cardiometabolic risk factors in 51 subjects with NAFLD, and compared with 100 age- and gender-matched subjects without NAFLD. The liver attenuation index (LAI), which was measured using computed tomography, was used as a parameter for the diagnosis of NAFLD. Results After adjusting for age and sex, both maxTBR and LAI values were associated with several cardiometabolic risk parameters. Furthermore, there was a significant inter-relationship between LAI and maxTBR values ( r = − 0.227, P = 0.005). Individuals with NAFLD had higher maxTBR values than those without NAFLD ( P = 0.026), although their carotid intima–media thickness (CIMT) values did not differ. The proportion of subjects with NAFLD showed a step-wise increment following the tertiles of maxTBR values ( P for trend = 0.015). In multiple logistic regression analysis, maxTBR tertiles were independently associated with NAFLD after adjusting for age, gender, systolic blood pressure, triglycerides, HDL-cholesterol, glucose, BUN, creatinine and homeostasis model assessment of insulin resistance (HOMA-IR) ( P = 0.030). However, their relationship was attenuated after further adjustment for waist circumference or high sensitive C-reactive protein. Conclusion Patients with NAFLD have an increased risk for vascular inflammation as measured via FDG-PET/CT even without difference in CIMT. (Clinical trials No. NCT01958411 , http://www.clinicaltrials.gov /)

Objectives: Allergic asthma generally presents with symptoms of wheezing, coughing, breathlessness, and airway inflammation. Seonpyejeongcheon-tang (SJT) consists of 12 herbs. It originated from Jeong-cheon-tang (JT), also known as Ding-chuan-tang, composed of 7 herbs, in She-sheng-zhong-miao-fang. This study aimed to evaluate the effects of local delivery of SJT via inhalable microparticles in an asthma mouse model. Methods: Microparticles containing SJT were produced by spray-drying with leucine as an excipient. SJT microparticles were evaluated with respect to their aerodynamic properties, in vitro cytotoxicity, in vivo toxicity, and therapeutic effects on ovalbumin (OVA)-induced asthma in comparison with orally-administered SJT. Results: SJT microparticles provided desirable aerodynamic properties (fine particle fraction of 48.9% +/- 6.4% and mass median aerodynamic diameter of 3.7 +/- 0.3 mu m). SJT microparticles did not show any cytotoxicity against RAW 264.7 macrophages at concentrations of 0.01 - 3 mg/mL. Inhaled SJT microparticles decreased the levels of IL-4, IL-5, IL-13, IL-17A, eotaxin and OVAIgE in bronchoalveolar lavage fluid (BALF) in mice with OVA-induced asthma. These effects were verified by histological evaluation of the levels of infiltration of inflammatory cells and collagen, destructions of alveoli and bronchioles, and hyperplasia of goblet cells in lung tissues. The effects of SJT microparticles in the asthma model were equivalent to those of orally-administered SJT extract. Conclusion: This study suggests that SJT is a promising agent for inhalation therapy for patients with asthma.

Matching-index-of-refraction (MIR) has been used for obtaining high-quality flow visualization data for the fundamental nuclear thermal-hydraulic researches. By this method, distortions of the optical measurements such as PIV and LDV have been successfully minimized using various combinations of the model materials and the working fluids. This study investigated a novel 3D printing technology for manufacturing models and an oil-based working fluid for matching the refractive indices. Transparent test samples were fabricated by various rapid prototyping methods including selective layer sintering (SLS), stereolithography (SLA), and vacuum casting. As a result, the SLA direct 3D printing was evaluated to be the most suitable for flow visualization considering manufacturability, transparency, and refractive index. In order to match the refractive indices of the 3D printing models, a working fluid was developed based on the mixture of herb essential oils, which exhibit high refractive index, high transparency, high density, low viscosity, low toxicity, and low price. The refractive index and viscosity of the working fluid range 1.453–1.555 and 2.37–6.94 cP, respectively. In order to validate the MIR method, a simple test using a twisted prism made by the SLA technique and the oil mixture (anise and light mineral oil) was conducted. The experimental results show that the MIR can be successfully achieved at the refractive index of 1.51, and the proposed MIR method is expected to be widely used for flow visualization studies and CFD validation for the nuclear thermal-hydraulic researches.

Objective Recent studies reported the presence of unique subsets of body size phenotypes that are more susceptible or more resistant to the development of obesity-associated metabolic disorders, although the underlying mechanism is not yet fully elucidated. We investigated the association between body size phenotypes and sleep duration after adjusting potential confounding factors. Materials and methods We analyzed data from the Korean National Health and Nutrition Examination Survey V (KNHANES V), a nation-wide, population-based health survey including 9077 Korean adults. The average amount of sleep per night was categorized as: ≤ 6, 7, 8, and ≥ 9 h. Body size phenotypes were classified based on body mass index (BMI) and presence of metabolic syndrome; metabolically healthy and normal weight (MHNW), metabolically abnormal but normal weight (MANW), metabolically healthy but obese (MHO), and metabolically abnormal obese (MAO). Results According to sleep duration, there were significant differences in age, gender, BMI, waist circumference, and blood pressure (all P

Recent studies have suggested that body size phenotype may contribute to atherosclerosis and cardiovascular disease. 18 F-fluorodeoxyglucose (FDG) positron emission tomography is a useful imaging technique for detecting vascular inflammation that may reflect plaque vulnerability. Therefore, we analyzed which body size phenotypes cause the increased vascular inflammation using FDG positron emission tomography. We compared 18 F-FDG uptake, measured using the blood-normalized standardized uptake value, known as the target-to-background ratio (TBR), along with various cardiometabolic risk parameters in 250 participants without a history of cardiovascular disease. Body size phenotypes were classified according to body mass index and the presence/absence of metabolic syndrome. Cardiometabolic risk factors were significantly different among the body size phenotype groups. In particular, the maximum TBR (maxTBR) values in the metabolically abnormal but normal-weight, metabolically healthy obese (MHO), and metabolically abnormal obese groups were significantly greater than those of the metabolically healthy normal-weight (MHNW) group. Components of metabolic syndrome, insulin resistance, high-sensitivity C-reactive protein, and Framingham Risk Score were associated with maxTBR value. Interestingly, although the Framingham Risk Score of the MHO group was almost similar to that of the MHNW group, maxTBR value of MHO subjects was significantly higher than that of MHNW subjects (1.38 [1.20, 1.50] vs 1.22 [1.12, 1.37], p = 0.006). In conclusion, the present study suggests that unique subsets of body size phenotype, such as MHO or metabolically abnormal but normal weight, may have distinct effects on vascular inflammation.

Social transmission of memory and its consequence on collective memory have generated enduring interdisciplinary interest because of their widespread significance in interpersonal, sociocultural, and political arenas. We tested the influence of 3 key factors-emotional salience of information, group structure, and information distribution-on mnemonic transmission, social contagion, and collective memory. Participants individually studied emotionally salient (negative or positive) and nonemotional (neutral) picture-word pairs that were completely shared, partially shared, or unshared within participant triads, and then completed 3 consecutive recalls in 1 of 3 conditions: individual-individual-individual (control), collaborative-collaborative (identical group; insular structure)-individual, and collaborative-collaborative (reconfigured group; diverse structure)-individual. Collaboration enhanced negative memories especially in insular group structure and especially for shared information, and promoted collective forgetting of positive memories. Diverse group structure reduced this negativity effect. Unequally distributed information led to social contagion that creates false memories; diverse structure propagated a greater variety of false memories whereas insular structure promoted confidence in false recognition and false collective memory. A simultaneous assessment of network structure, information distribution, and emotional valence breaks new ground to specify how network structure shapes the spread of negative memories and false memories, and the emergence of collective memory. (PsycINFO Database Record

The direct effects of dipeptidyl peptidase-IV (DPP-IV) inhibitors on endoplasmic reticulum (ER) stress-induced apoptosis and inflammation in cardiomyocytes have not been elucidated. H9c2 cell viability, which was reduced by tunicamycin, was increased after DPP-IV inhibitor gemigliptin treatment. Gemigliptin significantly decreased the tunicamycin-mediated increase in glucose regulated protein 78 (GRP78) expression and ER stress-mediated signaling molecules such as protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C-EBP homologous protein (CHOP) and inositol-requiring enzyme 1α (IRE1α)/c-Jun N-terminal kinase (JNK)-p38. Furthermore, gemigliptin effectively induced Akt phosphorylation in a dose-dependent manner. Using flow cytometry and Hoechst staining, we showed that treatment with Akt inhibitor significantly blocked the anti-apoptotic effects mediated by gemigliptin. The reduction in tunicamycin-induced GRP78 level and PERK/CHOP pathway activity by gemigliptin was reversed after treatment with Akt inhibitor. In conclusion, gemigliptin effectively inhibited ER stress-induced apoptosis and inflammation in cardiomyocytes via Akt/PERK/CHOP and IRE1α/JNK-p38 pathways, suggesting its direct protective role in cardiovascular diseases.

Background/Aims Primary aldosteronism (PA) is now widely recognized to have a higher prevalence than was once thought. In view of its increasing prevalence, we compared chronological changes in clinical manifestations of PA according to different times of diagnosis. Methods In total, 85 patients diagnosed with PA from January 1986 through March 2012 were reviewed retrospectively, based on their medical records. During two periods-1986 to 2005 and 2006 to 2012-41 and 44 patients, respectively, were diagnosed with PA. We compared the clinical and biological characteristics of PA between these periods. Results The results demonstrate an increasing trend in the prevalence of idiopathic hyperaldosteronism (IHA; p = 0.19). In the 2006 to 2012 period, patients with PA presented with higher serum potassium levels at the time of diagnosis than in the 1986 to 2005 period (p < 0.0002). Adrenal vein sampling (AVS) was performed mostly in the latter period (82.3%) and the diagnostic accuracy of adrenal computed tomography, compared with AVS, was only 56.2%. About 78.0% versus 86.3% of patients had at least one target organ damage (TOD) in the 1986 to 2005 and 2006 to 2012 periods, respectively (p = 0.39). However, patients with TOD were older and had longer durations of hypertension than patients without, in both periods. Conclusions PA is becoming more prevalent. There was an increasing tendency for IHA, and more PA patients presented with normokalemia than in the earlier period. Early and accurate diagnosis of PA with AVS and proper treatment should have substantial prognostic value.

Carrageenan (CGN) has been shown to cause inflammation through toll-like receptor 4, which may play an important role in insulin resistance and type 2 diabetes mellitus. Selenoprotein P (SeP) has recently been identified as a novel hepatokine that causes insulin resistance. Here, we report that treatment of HepG2 cells with CGN increased both CCAAT enhancer binding protein homologous protein (CHOP) and SeP expression. Pretreatment with 4-phenylbutyrate (4-PBA), an endoplasmic reticulum stress inhibitor, and PD98059, a c-Jun N-terminal kinase (JNK) inhibitor, reversed CGN-induced SeP expression. Moreover, both 4-PBA and knock-down of SeP improved CGN-induced insulin resistance. In addition, we found that adenosine monophosphate-activated protein kinase (AMPK) activators ameliorated CGN-induced insulin resistance in addition to suppressing CHOP and SeP expression. In conclusion, CGN-induced ER stress increased the expression of SeP through the JNK pathway, while AMPK activators ameliorated CGN-induced insulin resistance via SeP inhibition through the AMPK-mediated alleviation of ER stress in hepatocytes.

Collaborating with others during recall shapes both group and individual memories. Individuals contribute less when recalling in groups than when recalling alone, a phenomenon called collaborative inhibition. In contrast, collaboration improves post-collaborative individual memory by providing re-exposure to information that would have been otherwise forgotten. Collaboration also influences collective memory—the overlap in post-collaborative memory among group members. We examined the role of group configuration on such transmission of memory by varying group configuration across repeated recalls. Participants (N = 162) studied words and completed three recall sessions in one of three conditions (N = 54/condition): Individual–Individual–Individual (Control), Collaborative–Collaborative (Identical group)–Individual and Collaborative–Collaborative (Reconfigured group)–Individual. Collaborative inhibition occurred in both the Identical and Reconfigured groups during the first recall but disappeared in the Re...

OBJECTIVE To examine the effect of a combined exercise program on C1q/tumor necrosis factor-related protein (CTRP) 3 and CTRP-5 levels and novel adiponectin paralogs suggested to be links between metabolism and inflammation and to evaluate sex differences and association with cardiometabolic risk factors in humans with use of a newly developed ELISA. RESEARCH DESIGN AND METHODS This cross-sectional study explored the implications of CTRP-3 and CTRP-5 on cardiometabolic parameters in 453 nondiabetic Korean adults. In addition, we evaluated the impact of a 3-month combined exercise program on CTRP-3 and CTRP-5 levels in 76 obese women. The exercise program consisted of 45 min of aerobic exercise at an intensity of 60–75% of the age-predicted maximum heart rate (300 kcal/session) and 20 min of resistance training (100 kcal/session) five times per week. RESULTS Both CTRP-3 and CTRP-5 concentrations were significantly higher in women (P < 0.001) than in men (P = 0.030). In a multiple stepwise regression analysis, CTRP-3 levels were independently associated with age, sex, and triglyceride, LDL cholesterol, adiponectin, and retinol-binding protein 4 (RBP4) levels (R2 = 0.182). After 3 months of a combined exercise program, cardiometabolic risk factors, including components of metabolic syndrome, insulin resistance, and RBP4 levels, decreased significantly. In particular, CTRP-3 levels decreased significantly (median [interquartile range] 444.3 [373.8–535.0] to 374.4 [297.2–435.9], P < 0.001), whereas CTRP-5 levels were slightly increased (34.1 [28.6–44.3] to 38.4 [29.8–55.1], P = 0.048). CONCLUSIONS A 3-month combined exercise program significantly decreased CTRP-3 levels and modestly increased CTRP-5 levels in obese Korean women.

Objective The purpose of this study was to investigate the impact of body mass index (BMI) and the presence of metabolic syndrome (MetS) on all-cause and cardiovascular mortality in elderly Korean men and women, and especially to compare metabolically obese normal-weight (MONW) and metabolically healthy obese (MHO) subjects. Patients and methods A total of 2317 elderly people (over 60 years of age) were studied using follow-up data from the South-West Seoul (SWS) Study, a prospective cohort study. Mortality from all causes and cardiovascular disease (CVD) were evaluated according to the combination of the presence or absence of MetS and Asian-specific body mass index (BMI) criteria (BMI

SummaryObjective It has been suggested that insulin resistance, low-grade inflammation and vitamin D deficiency are associated with obesity and sarcopenia. However, their relationships with sarcopenic obesity (SO) are unclear. We evaluated the impact of homoeostasis model assessment of insulin resistance (HOMA-IR), high-sensitivity C-reactive protein (hsCRP) and 25-hydroxyvitamin D (25[OH]D) levels on SO in Korean adults. Study subject/measurements This study included 493 apparently healthy adults (180 men and 313 women) enrolled in the Korean Sarcopenic Obesity Study. Sarcopenia was defined as a skeletal muscle mass index (SMI) of 1 SD below the sex-specific mean value for a young reference group. Obesity was defined as a visceral fat area (VFA) ≥100 cm2. We classified the participants into four sarcopenia/obesity groups based on both SMI and VFA. Results The prevalence of SO was 17·8% in men and 24·9% in women. In women, the SO group had higher HOMA-IR and hsCRP levels compared with the non-SO group. In men, the 25[OH]D levels were significantly lower in the SO group than the non-SO group. Both hsCRP and HOMA-IR levels were negatively correlated with SMI and positively correlated with VFA in both men and women, whereas 25[OH]D levels were positively correlated with SMI in both men and women. Multiple binary logistic regression analysis showed that HOMA-IR and 25[OH]D levels were independently associated with SO in men, while HOMA-IR and hsCRP were significant factors predicting SO in women. Conclusion Insulin resistance, inflammation and vitamin D deficiency were associated with SO in a Korean adult population.

To evaluate vascular inflammation according to high-sensitivity C-reactive protein (hsCRP) levels in the low- (10%) and intermediate- (10%-20%) Framingham risk score (FRS) groups using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, which reflects vascular inflammation and vulnerable atherosclerotic plaque.We measured hsCRP levels and traditional cardiovascular risk factors in 142 non-diabetic subjects without history of cardiovascular disease. To assess the vascular influence of hsCRP on each FRS category, we compared carotid intima-media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), and vascular inflammation, which was represented as the target-to-background ratio (TBR) measured using FDG-PET/CT.In both low- and intermediate-FRS categories, mean TBR values in subjects with higher hsCRP levels (≥2mg/L) were significantly increased compared to those with lower hsCRP levels (2mg/L) (P=0.001, P0.001, respectively). However, baPWV and CIMT values did not significantly differ according to hsCRP levels in the same FRS categories. Mean TBR levels positively correlated with FRS, body mass index (BMI), whereas negatively correlated with HDL-cholesterol. Multiple stepwise regression analyses showed that hsCRP, LDL-cholesterol, BMI, and insulin resistance were independently associated with mean TBR values (R(2)=0.414).In both intermediate and low FRS risk groups, vascular inflammation measured using FDG-PET/CT was increased in individuals with higher hsCRP levels compared to those with lower hsCRP.

BACKGROUND Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD). METHODS We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV). RESULTS Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P

Growing evidence suggests that non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease as well as metabolic syndrome. FDG-PET is a novel imaging technique that detects vascular inflammation, which may reflect rupture-prone vulnerable atherosclerotic plaques.Vascular inflammation was measured as the maximum target-to-background ratio (maxTBR), along with various cardiometabolic risk factors in 51 subjects with NAFLD, and compared with 100 age- and gender-matched subjects without NAFLD. The liver attenuation index (LAI), which was measured using computed tomography, was used as a parameter for the diagnosis of NAFLD.After adjusting for age and sex, both maxTBR and LAI values were associated with several cardiometabolic risk parameters. Furthermore, there was a significant inter-relationship between LAI and maxTBR values (r=-0.227, P=0.005). Individuals with NAFLD had higher maxTBR values than those without NAFLD (P=0.026), although their carotid intima-media thickness (CIMT) values did not differ. The proportion of subjects with NAFLD showed a step-wise increment following the tertiles of maxTBR values (P for trend=0.015). In multiple logistic regression analysis, maxTBR tertiles were independently associated with NAFLD after adjusting for age, gender, systolic blood pressure, triglycerides, HDL-cholesterol, glucose, BUN, creatinine and homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.030). However, their relationship was attenuated after further adjustment for waist circumference or high sensitive C-reactive protein.Patients with NAFLD have an increased risk for vascular inflammation as measured via FDG-PET/CT even without difference in CIMT. (Clinical trials No. NCT01958411, http://www.clinicaltrials.gov/).

Past research has shown that emotion enhances true memory, but that emotion can either increase or decrease false memory. Two theoretical possibilities-the distinctiveness of emotional stimuli and the conceptual relatedness of emotional content-have been implicated as being responsible for influencing both true and false memory for emotional content. In the present study, we sought to identify the mechanisms that underlie these mixed findings by equating the thematic relatedness of the study materials across each type of valence used (negative, positive, or neutral). In three experiments, categorically bound stimuli (e.g., funeral, pets, and office items) were used for this purpose. When the encoding task required the processing of thematic relatedness, a significant true-memory enhancement for emotional content emerged in recognition memory, but no emotional boost to false memory (exp. 1). This pattern persisted for true memory with a longer retention interval between study and test (24 h), and false recognition was reduced for emotional items (exp. 2). Finally, better recognition memory for emotional items once again emerged when the encoding task (arousal ratings) required the processing of the emotional aspect of the study items, with no emotional boost to false recognition (EXP. 3). Together, these findings suggest that when emotional and neutral stimuli are equivalently high in thematic relatedness, emotion continues to improve true memory, but it does not override other types of grouping to increase false memory.

Recent studies have suggested that a novel adipokine, C1q/tumor necrosis factor-related protein-3 (CTRP-3), a paralog of adiponectin, may play an important role in the regulation of glucose metabolism and innate immunity. Pigment epithelium-derived factor (PEDF), a multifunctional protein with antioxidant and anti-inflammatory properties, is associated with insulin resistance and metabolic syndrome. We examined circulating CTRP-3 and PEDF concentrations in 345 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the involvement of CTRP-3 and PEDF with cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), and brachial-ankle pulse wave velocity (baPWV). CTRP-3 concentrations were significantly higher in patients with type 2 diabetes or prediabetes than the normal glucose tolerance group, whereas PEDF levels were not different. Subjects with metabolic syndrome showed significantly higher levels of both CTRP-3 and PEDF compared with subjects without metabolic syndrome. Both CTRP-3 and PEDF were significantly associated with cardiometabolic parameters, including waist-to-hip ratio, triglycerides, HDL-cholesterol, alanine aminotransferase, eGFR, hsCRP, and baPWV. In conclusion, circulating CTRP-3 concentrations were elevated in patients with glucose metabolism dysregulation. Both CTRP-3 and PEDF concentrations were increased in subjects with metabolic syndrome and associated with various cardiometabolic risk factors.

Low levels of soluble receptor for advanced glycation end-products (sRAGE) have been linked to systemic inflammation and vascular complications in patients with type 2 diabetes mellitus (T2DM).We examined the effects of exercise on sRAGE and its association with diverse cardiometabolic risk factors and indicators of atherosclerosis in patients with T2DM.Seventy-five patients with T2DM were randomized into a control group and an aerobic exercise group (60 min at moderate intensity, five times/wk for 12 wk).We evaluated sRAGE, energy expenditure, dietary energy intake, cardiorespiratory fitness, inflammatory markers, visceral fat area, pulse-wave velocity, and flow-mediated dilatation.Baseline sRAGE concentrations were independently associated with age, glycated hemoglobin, glucose, triglyceride, and high-density lipoprotein cholesterol levels (R2=0.244). After 12 wk of exercise training, the exercise group showed significantly decreased body weight, waist circumference, blood pressure, glycated hemoglobin, apolipoprotein B, and free fatty acid levels. Concurrently, cardiorespiratory fitness assessed by oxygen uptake at anaerobic threshold was improved, and body fat percentage and visceral fat area were significantly decreased in the exercise group, although pulse-wave velocity and flow-mediated dilatation were not changed. Furthermore, sRAGE levels were increased and high-sensitivity C-reactive protein levels were decreased in the exercise group but not in the control group. Percent change of sRAGE level was negatively correlated with that of high-sensitivity C-reactive protein during the study period (r=-0.27; P=0.019).Aerobic exercise increases sRAGE levels along with improvement of various cardiometabolic risk factors in patients with T2DM.

Background The receptor for advanced glycation end-products (RAGE) and its diverse ligands play a pivotal role in the development of cardiovascular disease. Soluble forms of RAGE (sRAGE), including the splice variant endogenous secretory RAGE (esRAGE), may neutralize AGE-RAGE mediated vascular damage by acting as a decoy. 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a novel imaging technique for detecting vascular inflammation. Methods We examined vascular inflammation measured using FDG-PET in 41 type 2 diabetes patients and 41 healthy control subjects in the right carotid artery. Vascular 18 F-FDG uptake was measured as the blood-normalized standardized uptake value (SUV), known as the target-to-background ratio (TBR). In addition, their relationship with carotid intima-media thickness (CIMT), estimated GFR (eGFR), and other cardiovascular risk factors was evaluated. Results Both mean and maximum TBR values were significantly higher in patients with type 2 diabetes compared to healthy subjects. After adjusting for age and gender, sRAGE levels were significantly correlated with both mean and maximum TBR values, but not with CIMT values. Multiple linear regression analysis showed that maximum TBR values were independently associated with sRAGE levels in addition to HbA1c and eGFR. Conclusions Circulating sRAGE showed significant association with TBR values measured using FDG-PET, which reflect vascular inflammation.

Aim: Adipokines have been implicated in the pathogenesis of obesity and obesity-related disorders, including atherosclerosis. Chemerin is a recently discovered adipokine which is closely correlated with various metabolic phenotypes in humans. We examined the association between circulating chemerin levels and arterial stiffness, as represented by the brachial ankle pulse wave velocity (baPWV).Methods: Fifty-eight obese and 62 non-obese individuals participated in the study. We measured the serum chemerin and high sensitivity C-reactive protein (hsCRP) levels, and the homeostasis model assessment of insulin resistance (HOMA-IR), as well as other cardiovascular risk factors. Vascular health was assessed by the baPWV and carotid intima-media thickness (IMT).Results: The serum chemerin level was significantly increased in obese individuals compared with lean controls (120.14±19.43 ng/mL vs. 106.81±23.39 ng/mL, p = 0.001). The circulating chemerin level had a significant positive correlation with the body mass index, waist circumference, HOMA-IR, and low-density lipoprotein-cholesterol, triglycerides, and hsCRP levels. The serum chemerin level was significantly associated with the baPWV (r= 0.280, p= 0.002), but not the carotid IMT (r= 0.065, p= 0.504). Multiple stepwise regression analysis showed that age (p < 0.001), waist circumference (p= 0.038), systolic blood pressure (p < 0.001), and serum fasting glucose (p= 0.003) and chemerin levels (p= 0.017) were definitive risk factors for arterial stiffness (r2=0.457).Conclusions: The circulating chemerin level was an independent risk factor for arterial stiffness even after adjusting for other cardiovascular risk factors.

OBJECTIVE: We examined the relationship between brachial-ankle pulse wave velocity (baPWV) reflecting arterial stiffness and the levels of novel hepatokines fibroblast growth factor 21 (FGF21) and fetuin-A. In addition, we evaluated the effect of a 3-month combined aerobic and resistance exercise programme on FGF21 and fetuin-A levels as well as arterial stiffness in obese women. METHODS: Forty nondiabetic, obese women (body mass index = 27·6 ± 2·4 kg/m(2) ) were included in the study and were compared before and after a 3-month exercise programme, which was composed of 45 min of aerobic exercise at an intensity of 60-75% of the age-predicted maximum heart rate (300 kcal/session) and 20 min of resistance training (100 kcal/session) five times a week. All exercise sessions were supervised by a professional exercise physiologist. RESULTS: At baseline, baPWV levels were correlated with age, body mass index (BMI), systolic blood pressure (SBP), high density lipoprotein cholesterol, fasting glucose and serum FGF21 levels. In a multiple stepwise regression analysis using baPWV as a dependent variable, baPWV levels were associated with age, BMI, SBP, FGF21 and fetuin-A levels (R(2) = 0·744). After the exercise programme, BMI, waist circumference, SBP, diastolic blood pressure and triglyceride levels were significantly decreased. Moreover, baPWV values were significantly improved (P < 0·001) along with modest decrease in FGF21 levels (P = 0·043). However, fetuin-A levels were not changed significantly (P = 0·202). CONCLUSIONS: A 3-month combined exercise programme decreases the FGF21 levels as well as arterial stiffness in obese Korean women.

The dysregulation of hepatokines may be associated with the pathogenesis of insulin resistance and type 2 diabetes. A recent study has suggested that selenoprotein P (SeP), a novel hepatokine, may play a role in the regulation of glucose metabolism and insulin sensitivity. We examined the relationship between circulating SeP levels and clinical parameters associated with insulin resistance in humans.We compared serum SeP concentrations in 100 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the relationship between SeP and cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein, and carotid intima-media thickness.Serum SeP concentrations were significantly higher in patients with type 2 diabetes or prediabetes than those with normal glucose tolerance (all P0.01) and decreased in a stepwise manner [1032.4 (495.9-2149.4) vs. 867.3 (516.3-1582.7) vs. 362.0 (252.5-694.5), P = 0.004]. In addition, overweight and obese subjects had significantly increased SeP levels compared with lean subjects (P = 0.002). Spearman's partial correlation analysis adjusted for age and gender showed a significant relationship between SeP and cardiometabolic factors including body mass index, waist circumference, systolic blood pressure, triglycerides, glucose, hemoglobin A1c, aspartate aminotransferase, and insulin resistance. Furthermore, in multiple regression analyses, SeP showed an independent association with carotid intima-media thickness as well as high-sensitivity C-reactive protein, even after adjustment for other confounding factors.Circulating SeP concentrations were elevated in patients with glucose metabolism dysregulation and were related to various cardiometabolic parameters including insulin resistance, inflammation, and atherosclerosis.

Objective Pericardial adipose tissue (PAT) is associated with adverse cardiometabolic risk factors and cardiovascular disease (CVD). However, the relative implications of PAT, abdominal visceral and subcutaneous adipose tissue on vascular inflammation have not been explored. Method and Results We compared the association of PAT, abdominal visceral fat area (VFA), and subcutaneous fat area (SFA) with vascular inflammation, represented as the target-to-background ratio (TBR), the blood-normalized standardized uptake value measured using 18F-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) in 93 men and women without diabetes or CVD. Age- and sex-adjusted correlation analysis showed that PAT, VFA, and SFA were positively associated with most cardiometabolic risk factors, including systolic blood pressure, LDL-cholesterol, triglycerides, glucose, insulin resistance and high sensitive C-reactive proteins (hsCRP), whereas they were negatively associated with HDL-cholesterol. In particular, the maximum TBR (maxTBR) values were positively correlated with PAT and VFA (r = 0.48 and r = 0.45, respectively; both P

Objectives Sarcopenia and visceral obesity have been suggested to aggravate each other, resulting in a vicious cycle. However, evidence based on prospective study is very limited. Our purpose was to investigate whether visceral fat promotes a decrease in skeletal muscle mass and vice versa. Methods We observed changes in anthropometric and body composition data during a follow-up period of 27.6±2.8 months in 379 Korean men and women (mean age 51.9±14.6 years) from the Korean Sarcopenic Obesity Study (KSOS). Appendicular lean soft tissue (ALST) mass was calculated using dual-energy X-ray absorptiometry, and visceral fat area (VFA) was measured using computed tomography at baseline and follow-up examination. Results ALST mass significantly decreased, whereas trunk and total fat mass increased in both men and women despite no significant change in weight and body mass index. In particular, women with visceral obesity at baseline had a greater decrease in ALST mass than those without visceral obesity (P = 0.001). In multiple linear regression analysis, baseline VFA was an independent negative predictor of the changes in ALST after adjusting for confounding factors including age, gender, life style and body composition parameters, insulin resistance, high sensitivity C-reactive protein and vitamin D levels (P = 0.001), whereas the association between baseline ALST mass and changes in VFA was not statistically significant (P = 0.555). Conclusions This longitudinal study showed that visceral obesity was associated with future loss of skeletal muscle mass in Korean adults. These results may provide novel insight into sarcopenic obesity in an aging society.

Recent studies have suggested that body size phenotype may contribute to atherosclerosis and cardiovascular disease. (18)F-fluorodeoxyglucose (FDG) positron emission tomography is a useful imaging technique for detecting vascular inflammation that may reflect plaque vulnerability. Therefore, we analyzed which body size phenotypes cause the increased vascular inflammation using FDG positron emission tomography. We compared (18)F-FDG uptake, measured using the blood-normalized standardized uptake value, known as the target-to-background ratio (TBR), along with various cardiometabolic risk parameters in 250 participants without a history of cardiovascular disease. Body size phenotypes were classified according to body mass index and the presence/absence of metabolic syndrome. Cardiometabolic risk factors were significantly different among the body size phenotype groups. In particular, the maximum TBR (maxTBR) values in the metabolically abnormal but normal-weight, metabolically healthy obese (MHO), and metabolically abnormal obese groups were significantly greater than those of the metabolically healthy normal-weight (MHNW) group. Components of metabolic syndrome, insulin resistance, high-sensitivity C-reactive protein, and Framingham Risk Score were associated with maxTBR value. Interestingly, although the Framingham Risk Score of the MHO group was almost similar to that of the MHNW group, maxTBR value of MHO subjects was significantly higher than that of MHNW subjects (1.38 [1.20, 1.50] vs 1.22 [1.12, 1.37], p = 0.006). In conclusion, the present study suggests that unique subsets of body size phenotype, such as MHO or metabolically abnormal but normal weight, may have distinct effects on vascular inflammation.

Irisin is an exercise-induced novel myokine that drives brown-fat-like conversion of white adipose tissue and has been suggested to be a promising target for the treatment of obesity-related metabolic disorders.To assess the association of circulating irisin concentrations with brown adipose tissue (BAT) and/or sarcopenia in humans.We examined irisin levels in 40 BAT-positive and 40 BAT-negative women detected by (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). In a separate study, we also examined 401 subjects with or without sarcopenia defined by skeletal muscle mass index (SMMI) and appendicular skeletal muscle (ASM)/height(2) using dual-energy x-ray absorptiometry.Among 6877 consecutive (18)FDG-PET scans in 4736 subjects, 146 subjects (3.1%) had positive BAT scans. The BAT-detectable group and the matched BAT-undetectable group did not differ in circulating irisin levels measured using two different ELISA kits (P = .747 and P = .160, respectively). Serum irisin levels were not different between individuals with sarcopenia and those without sarcopenia using either kit (P = .305 and P = .569, respectively). Also, serum irisin levels were not different between groups defined by ASM/height(2) using either kit (P = .352 and P = .134, respectively). Although visceral fat area and skeletal muscle mass showed significant difference according to tertiles of SMMI levels, irisin concentrations did not differ.Circulating irisin levels were not different in individuals with detectable BAT or those with sarcopenia compared with control subjects and were not correlated with SMMI.

Background C1q/TNF-related protein-3 (CTRP-3), an adiponectin paralog, and progranulin were recently identified as novel adipokines which may link obesity with glucose dysregulation and subclinical inflammation. We analyzed the relationship between CTRP-3, progranulin and coronary artery disease (CAD) in Korean men and women. Methods Circulating CTRP-3 and progranulin levels were examined in 362 Korean adults with acute coronary syndrome (ACS, n = 69), stable angina pectoris (SAP, n = 85), and control subjects (n = 208) along with various kinds of cardiometabolic risk factors. Results CTRP-3 concentrations were significantly decreased in patients with ACS or SAP compared to control subjects (P

Objective Despite recent interest in differential impact of body size phenotypes on cardiovascular outcomes and mortality, studies evaluating the association between body size phenotypes and indicators of atherosclerosis are limited. This study investigated the relationship of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis in Korean adults without cardiovascular disease. Methods A total of 1012 participants (575 men and 437 women, mean age 50.8 years), who underwent a health examination between April 2012 and May 2013 were prospectively enrolled based on inclusion and exclusion criteria. Study subjects were classified according to body mass index (BMI) and the presence/absence of metabolic syndrome. Results The prevalence of metabolically healthy normal weight (MHNW), MANW, MHO, and metabolically abnormal obese (MAO) were 54.84%, 6.42%, 22.83%, and 15.91%, respectively. Individuals with MANW had significantly higher brachial-ankle pulse wave velocity and maximal carotid intima-media thickness values than those with MHO, after adjusting for age and gender ( P = 0.026 and P = 0.018, respectively). The odds ratio (OR) of arterial stiffness and carotid atherosclerosis in the MANW group were significantly higher than in the MHNW group in unadjusted models. Furthermore, multivariable models showed that increased OR of carotid atherosclerosis in the MANW group persisted even after adjusting for confounding factors (OR = 2.98, 95% CI = [1.54, 5.73], P = 0.011). Conclusions Compared to MHNW or MHO subjects, Korean men and women with the MANW phenotype exhibited increased arterial stiffness and carotid atherosclerosis. Clinical trials no NCT01594710 .