Neural Correlates of Analogical Reasoning on Syntactic Patterns.

Analogical reasoning is central to thought and learning. However, previous neuroscience studies have focused mainly on neural substrates for visuospatial and semantic analogies. There has not yet been research on the neural correlates of analogical reasoning on syntactic patterns generated by the syntactic rules, a key feature of human language faculty. The present investigation took an initial step to address this paucity. Twenty-four participants, whose brain activity was monitored by fMRI, engaged in first-order and second-order relational judgments of syntactic patterns as well as simple and complex working memory tasks. After scanning, participants rated the difficulty of each step during analogical reasoning; these ratings were related to signal intensities in activated regions of interest using Spearman correlation analyses. After prior research, differences in activation levels during second-order and first-order relational judgments were taken as evidence of analogical reasoning. These analyses showed that analogical reasoning on syntactic patterns recruited brain regions consistent with those supporting visuospatial and semantic analogies, including the anterior and posterior parts of the left middle frontal gyrus, anatomically corresponding to the left rostrolateral pFC and the left dorsolateral pFC. The correlation results further revealed that the posterior middle frontal gyrus might be involved in analogical access and mapping with syntactic patterns. Our study is the first to investigate the process of analogical reasoning on syntactic patterns at the neurobiological level and provide evidence of the specific functional roles of related regions during subprocesses of analogical reasoning.

GPR56 Promotes Diabetic Kidney Disease Through eNOS Regulation in Glomerular Endothelial Cells.

Although glomerular endothelial dysfunction is well recognized as contributing to the pathogenesis of diabetic kidney disease (DKD), the molecular pathways contributing to DKD pathogenesis in glomerular endothelial cells (GECs) are only partially understood. To uncover pathways that are differentially regulated in early DKD that may contribute to disease pathogenesis, we recently conducted a transcriptomic analysis of isolated GECs from diabetic NOS3-null mice. The analysis identified several potential mediators of early DKD pathogenesis, one of which encoded an adhesion G protein-coupled receptor-56 (GPR56), also known as ADGRG1. Enhanced glomerular expression of GPR56 was observed in human diabetic kidneys, which was negatively associated with kidney function. Using cultured mouse GECs, we observed that GPR56 expression was induced with exposure to advanced glycation end products, as well as in high-glucose conditions, and its overexpression resulted in decreased phosphorylation and expression of endothelial nitric oxide synthase (eNOS). This effect on eNOS by GPR56 was mediated by coupling of Gα12/13-RhoA pathway activation and Gαi-mediated cAMP/PKA pathway inhibition. The loss of GPR56 in mice led to a significant reduction in diabetes-induced albuminuria and glomerular injury, which was associated with reduced oxidative stress and restoration of eNOS expression in GECs. These findings suggest that GPR56 promotes DKD progression mediated, in part, through enhancing glomerular endothelial injury and dysfunction.

Effect of ultra-high pressure on the relationship between endogenous proteases and protein degradation of Yesso scallop (Mizuhopecten yessoensis) adductor muscle during iced storage.

This study aimed to explore the effect of ultra-high pressure (UHP) treatment (100-500 MPa, 5 min, 15 ± 1 â„ƒ) on the relationship between endogenous proteases and protein degradation of Yesso scallop (Mizuhopecten yessoensis) adductor muscle during iced storage for 28 days. Our findings showed that the UHP treatment kept the water holding capacity stable, increased the hardness and decreased the springiness of scallop adductor muscle during iced storage. 400 and 500 MPa UHP treatments caused protein denaturation and oxidation significantly, decreased protein degradation rate and inhibited the activities of endogenous proteases. According to the correlation analysis, the activities of cathepsin B, D, H, L, calpain and serine protease were positively correlated with TCA-soluble peptides. The activities of endogenous proteases were significantly correlated with protein degradation. Therefore, the effect of UHP on endogenous protease caused the protein degradation rate to slow down and prevented the texture deterioration in scallops.

Neutrophil Extracellular Traps Induce Glomerular Endothelial Cell Dysfunction and Pyroptosis in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease. Neutrophil extracellular traps (NETs) are a network structure composed of loose chromatin and embedded with multiple proteins. Here, we observed increased NETs deposition in the glomeruli of DKD patients and diabetic mice (streptozotocin-induced or db/db mice). After NETs were degraded with DNase I, diabetic mice exhibited attenuated glomerulopathy and glomerular endothelial cells (GECs) injury. We also observed alleviated glomerulopathy and GECs injury in peptidylarginine deiminase 4-knockout mice with streptozotocin-induced diabetes. In vitro, NETs-induced GECs pyroptosis was characterized by pore formation in the cell membrane, dysregulation of multiple genes involved in cell membrane function, and increased expression of pyroptosis-related proteins. Strengthening the GECs surface charge by oleylamine significantly inhibited NETs-induced GECs pyroptosis. These findings suggest that the GECs charge-related pyroptosis is involved in DKD progression, which is promoted by NETs.

Effect of Glomerular Filtration Rate by Different Equations on Prediction Models for End-Stage Renal Disease in Diabetes.

Background and Objectives: The study aimed to evaluate the performance of a predictive model using the kidney failure risk equation (KFRE) for end-stage renal disease (ESRD) in diabetes and to investigate the impact of glomerular filtration rate (GFR) as estimated by different equations on the performance of the KFRE model in diabetes. Design Setting Participants and Measurements: A total of 18,928 individuals with diabetes without ESRD history from the UK Biobank, a prospective cohort study initiated in 2006-2010, were included in this study. Modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI) or revised Lund-Malmö (r-LM) were used to estimate GFR in the KFRE model. Cox proportional risk regression was used to determine the correlation coefficients between each variable and ESRD risk in each model. Harrell's C-index and net reclassification improvement (NRI) index were used to evaluate the differentiation of the models. Analysis was repeated in subgroups based on albuminuria and hemoglobin A1C (HbA1c) levels. Results: Overall, 132 of the 18,928 patients developed ESRD after a median follow-up of 12 years. The Harrell's C-index based on GFR estimated by CKD-EPI, MDRD, and r-LM was 0.914 (95% CI = 0.8812-0.9459), 0.908 (95% CI = 0.8727-0.9423), and 0.917 (95% CI = 0.8837-0.9496), respectively. Subgroup analysis revealed that in diabetic patients with macroalbuminuria, the KFRE model based on GFR estimated by r-LM (KFRE-eGFRr-LM) had better differentiation compared to the KFRE model based on GFR estimated by CKD-EPI (KFRE-eGFRCKD-EPI) with a KFRE-eGFRr-LM C-index of 0.846 (95% CI = 0.797-0.894, p = 0.025), while the KFRE model based on GFR estimated by MDRD (KFRE-eGFRMDRD) showed no significant difference compared to the KFRE-eGFRCKD-EPI (KFRE-eGFRMDRD C-index of 0.837, 95% CI = 0.785-0.889, p = 0.765). Subgroup analysis of poor glycemic control (HbA1c >8.5%) demonstrated the same trend. Compared to KFRE-eGFRCKD-EPI (C-index = 0.925, 95% CI = 0.874-0.976), KFRE-eGFRr-LM had a C-index of 0.935 (95% CI = 0.888-0.982, p = 0.071), and KFRE-eGFRMDRD had a C-index of 0.925 (95% CI = 0.874-0.976, p = 0.498). Conclusions: In adults with diabetes, the r-LM equation performs better than the CKD-EPI and MDRD equations in the KFRE model for predicting ESRD, especially for those with macroalbuminuria and poor glycemic control (HbA1c >8.5%).

Protection by Hosta ventricosa polysaccharides against oxidative damage induced by t-BHP in HepG2 cells via the JNK/Nrf2 pathway.

Hosta ventricosa is a plant that can be used for medicine and diet. It has been proven to have anti-inflammatory, antibacterial and antitumor activities, and one of its main constituents is polysaccharides. However, studies on polysaccharides of Hosta ventricosa are limited, and their physiological activities have not been clarified. Therefore, isolation, purification and characterization of Hosta ventricosa root polysaccharides (HVRPp-1) were performed in this research. Furthermore, the effect of HVRPp-1 on tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in HepG2 cells was investigated in vitro. The results showed that HVRPp-1 is a nonhomogeneous polysaccharide that could protect HepG2 cells from oxidative damage through the C-Jun N-terminal kinase (JNK)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. In conclusion, this research proved the antioxidant mechanism of HVRPp-1 for the first time, providing a reliable theoretical basis for basic research on Hosta ventricosa polysaccharides and the possibility of their application in functional foods.

Kidney single-cell transcriptome profile reveals distinct response of proximal tubule cells to SGLT2i and ARB treatment in diabetic mice.

Angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been used as the standard therapy for patients with diabetic kidney disease (DKD). However, how these two drugs possess additive renoprotective effects remains unclear. Here, we conducted single-cell RNA sequencing to profile the kidney cell transcriptome of db/db mice treated with vehicle, ARBs, SGLT2i, or ARBs plus SGLT2i, using db/m mice as control. We identified 10 distinct clusters of kidney cells with predominant proximal tubular (PT) cells. We found that ARBs had more anti-inflammatory and anti-fibrotic effects, while SGLT2i affected more mitochondrial function in PT. We also identified a new PT subcluster, was increased in DKD, but reversed by the treatments. This new subcluster was also confirmed by immunostaining of mouse and human kidneys with DKD. Together, our study reveals kidney cell-specific gene signatures in response to ARBs and SGLT2i and identifies a new PT subcluster, which provides new insight into the pathogenesis of DKD.

Relationship Between the TyG Index and Diabetic Kidney Disease in Patients with Type-2 Diabetes Mellitus.

BACKGROUND: Diabetic kidney disease (DKD) lacks a simple and relatively accurate predictor. The Triglyceride-Glucose (TyG) Index is a proxy of insulin resistance, but the association between the TyG Index and DKD is less certain. We investigated if the TyG Index can predict DKD onset effectively. MATERIALS AND METHODS: Cross-sectional and longitudinal analyses were undertaken. In total, 1432 type-2 diabetes mellitus (T2DM) patients were included in the cross-sectional analysis. The TyG Index (calculated by ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]) was split into three tertiles. Associations of the TyG Index with microalbuminuria and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 were calculated. Longitudinally, 424 patients without DKD at baseline were followed up for 21 (range, 12-24) months. The main outcome was DKD prevalence as defined with eGFR <60 mL/min/1.73 m2 or continuously increased urinary microalbuminuria: creatinine ratio (>30 mg/mL) over 3 months. Cox regression was used to analyze the association between the TyG Index at baseline and DKD. Receiver operating characteristics curve (ROC) analysis was used to assess the sensitivity and specificity of the TyG Index in predicting DKD. RESULTS: In cross-sectional analysis, patients with a higher TyG Index had a higher risk of microalbuminuria (OR = 2.342, 95% CI = 1.744-3.144, p < 0.001), and eGFR <60 mL/min/1.73 m2 (1.696, 95% CI =1.096-2.625, p = 0.018). Longitudinally, 94 of 424 participants developed DKD. After confounder adjustment, patients in the high tertile of the TyG Index at baseline had a greater risk to developing DKD than those in the low tertile (HR = 1.727, 95% CI = 1.042-2.863, p = 0.034). The area under the ROC curve was 0.69 (0.63-0.76). CONCLUSION: The TyG Index is a potential predictor for DKD in T2DM patients. CLINICAL TRIAL: Clinical Trials identification number = NCT03692884.

Age-Related Changes in Body Composition and Bone Mineral Density and Their Relationship with the Duration of Diabetes and Glycaemic Control in Type 2 Diabetes.

PURPOSE: To investigate age-related changes in body composition (BC) and bone mineral density (BMD) in type 2 diabetes (T2D) and analyse whether diabetes duration or glycaemic control affects these factors. PATIENTS AND METHODS: We enrolled 1474 hospitalized T2D patients (817 males and 657 females; 45-85 years). BC and BMD were assessed by dual-energy X-ray absorptiometry (DEXA). Patients were stratified into age groups: 45-54, 55-64, 65-74, and ≥75 years. Continuous variables were compared using t-tests or one-way analysis of variance (ANOVA), and categorical variables were compared using chi-square tests. Effects of age, diabetes duration, and haemoglobin A1C (HbA1c) on BC and BMD were assessed with multiple linear regression models. RESULTS: In T2D, in females, changes in fat mass index (FMI) were positively correlated with age, while changes in lean mass index (LMI) were unrelated to age. Changes in FMI or LMI in males were unrelated to age. For regional BC distribution, changes in visceral adipose tissue (VAT) were positively correlated with age for both males and females, while changes in appendage lean mass (ALM) were negatively correlated with age. For BMD, changes in total BMD (TBMD) in males were not correlated with age, while changes in lumbar spine BMD (LBMD) were positively correlated with age, and femoral neck BMD (FNBMD) was negatively correlated with age. Changes in BMD in all parts of females were negatively correlated with age. In addition, changes in BC and BMD were unrelated to diabetes duration, and HbA1c was mainly associated with decreases in lean mass but had little effect on other BC and BMD parameters. CONCLUSION: In T2D, changes in BC and BMD were associated with age but not diabetes duration. A higher HbA1c is associated with lower lean mass.

Early-Onset Type 2 Diabetes as a Risk Factor for End-Stage Renal Disease in Patients With Diabetic Kidney Disease.

INTRODUCTION: Compared with the typical onset of type 2 diabetes in middle age or older, type 2 diabetes with early age of onset has a higher risk of diabetes-related complications. It is unclear whether the early age of diabetes diagnosis would affect the development of end-stage renal disease (ESRD) in patients with diabetic kidney disease (DKD) who are at higher risk of ESRD. METHODS: We enrolled 1,111 type 2 diabetes patients with DKD in this study. We used the age at diabetes diagnosis of younger than 40 years to define early-onset diabetes and 40 years or older to define late-onset diabetes. Medical history, anthropometry, and laboratory indicators were documented. ESRD was defined by estimated glomerular filtration rate (eGFR) of less than 15 mL/min/1.73 m2 or dialysis. Logistic regression analysis was used to explore the association between early-onset diabetes and ESRD. RESULTS: Early-onset diabetes patients had a longer diabetes duration, higher body mass index, and worse blood lipid metabolism profile. Compared with late-onset diabetes patients, patients with early-onset diabetes had a prevalence of ESRD that was twofold higher (9.2% vs 4.3%; P = .009). Univariate analysis showed that early-onset diabetes was a risk factor for ESRD in patients with DKD (P < .05). In multivariate logistic regression analysis, even after adjusting for sex, traditional metabolic factors, drug factors, and diabetes duration, the risk of ESRD in patients with early-onset diabetes was still 3.58-fold higher than in subjects with late-onset (95% CI, 1.47-8.74; P = .005). CONCLUSIONS: In patients with DKD, early-onset type 2 diabetes is an independent risk factor of ESRD.

Optimal Cut-Offs of Body Mass Index and Waist Circumference to Identify Obesity in Chinese Type 2 Diabetic Patients.

PURPOSE: The prevalence of general obesity (commonly defined by body mass index (BMI) in kg/m2) and abdominal obesity (commonly assessed by waist circumference (WC)) has increased rapidly in China. The aim of this study was to investigate the diagnostic accuracy of traditional cut-offs for BMI or WC to identify general or abdominal obesity in Chinese type 2 diabetic patients and propose optimal cut-offs. PATIENTS AND METHODS: BMI and WC were obtained from 1539 type 2 diabetic patients. Body fat percentage and visceral fat area measured by dual-energy x-ray absorptiometry were set as the gold standard to identify general and abdominal obesity. We assessed the diagnostic power of traditional cut-offs for BMI and WC to define obesity, and analyzed receive operating characteristic (ROC) curves to obtain the optimal cut-offs to identify obesity in Chinese type 2 diabetic patients. RESULTS: In Chinese type 2 diabetic patients, the optimal BMI was 25 kg/m2 with the best trade-off between sensitivity and specificity (men: 74.6% (95% CI: 70.7-78.2%) and 65.1% (95% CI: 59.7-70.3%), AUC 0.78 (95% CI: 0.75-0.81), p<0.05; women: 65.8% (95% CI: 60.3-71.0%) and 80.3% (95% CI: 75.7-84.3%), AUC 0.80 (95% CI: 0.77-0.83), p<0.05) in both genders. The optimal WC was 93 cm in men and 90 cm in women with the best trade-off between sensitivity and specificity (men: 87.2% (95% CI: 84.3-89.8%) and 80.2% (95% CI: 74.9-84.8%), AUC 0.91 (95% CI: 0.88-0.92), p<0.05; women: 81.0% (95% CI: 76.9-84.6%) and 88.7% (95% CI: 83.9-92.4%), AUC 0.92 (95% CI: 0.90-0.94), p<0.05). CONCLUSION: For the Chinese patients with type 2 diabetes, the optimal cut-offs for BMI or WC to identify general or abdominal obesity need to be reconsidered.

Serial Interval and Generation Interval for Imported and Local Infectors, Respectively, Estimated Using Reported Contact-Tracing Data of COVID-19 in China.

The emerging virus, COVID-19, has caused a massive outbreak worldwide. Based on the publicly available contact-tracing data, we identified 509 transmission chains from 20 provinces in China and estimated the serial interval (SI) and generation interval (GI) of COVID-19 in China. Inspired by different possible values of the time-varying reproduction number for the imported cases and the local cases in China, we divided all transmission events into three subsets: imported (the zeroth generation) infecting 1st-generation locals, 1st-generation locals infecting 2nd-generation locals, and other transmissions among 2+. The corresponding SI (GI) is respectively denoted as SI10 ( GI10 ), SI21 ( GI21 ), and SI3+2+ ( GI3+2+ ). A Bayesian approach with doubly interval-censored likelihood is employed to fit the distribution function of the SI and GI. It was found that the estimated SI10=6.52 (95% CI:5.96-7.13) , SI21=6.01 (95%CI:5.44-6.64) , SI3+2+=4.39 (95% CI:3.74-5.15) , and GI10=5.47 (95% CI:4.57-6.45) , GI21=5.01 (95% CI:3.58-7.06) , GI3+2+=4.25 (95% CI:2.82-6.23) . Thus, overall both SI and GI decrease when generation increases.

The appropriate remodeling of extracellular matrix is the key molecular signature in subcutaneous adipose tissue following Roux-en-Y gastric bypass.

AIMS: We sought to reveal the key molecular signature in subcutaneous adipose tissue (scAT) following Roux-en-Y gastric bypass (RYGB), through bioinformatics analysis and further verification in vivo. MAIN METHODS: We obtained a transcriptome data of scAT from RYGB and sham-operated rats from the Gene Expression Omnibus. The differentially expressed genes (DEGs) were screened and the DEGs-related Gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Also, the protein-protein interaction (PPI) network was constructed among the DEGs. Furthermore, we established an experimental rat model to verify the bioinformatics findings. KEY FINDINGS: Using the method of bioinformatics, a total of 602 genes were found to be differentially expressed in scAT between the RYGB group and the sham-operated group. GO analysis showed that DEGs were significantly enriched in extracellular matrix(ECM) -associated functions or processes. KEGG pathway analysis revealed that the protein digestion and absorption pathway and ECM-receptor interaction pathway were the most significantly enriched pathways. The genes encoding ECM components and ECM remodeling-related proteins interact substantially in the PPI network. Then the results of rat experimental verified that the gene expression levels of ECM components(Collagen I and III) and ECM cross-linking related proteins(lysyl oxidase and lysyl oxidase-like 1) decreased and ECM dagradation-related proteins increased in scAT following RYGB. These beneficial results were positively associated with improved insulin resistance (IR). SIGNIFICANCE: Appropriate ECM remodeling, primarily the reduction of ECM deposition and cross-linking and the increase of ECM dagradation, may be the key molecular signature in scAT following RYGB.

Gene expression profiles of glomerular endothelial cells support their role in the glomerulopathy of diabetic mice.

Endothelial dysfunction promotes the pathogenesis of diabetic nephropathy (DN), which is considered to be an early event in disease progression. However, the molecular changes associated with glomerular endothelial cell (GEC) injury in early DN are not well defined. Most gene expression studies have relied on the indirect assessment of GEC injury from isolated glomeruli or renal cortices. Here, we present transcriptomic analysis of isolated GECs, using streptozotocin-induced diabetic wildtype (STZ-WT) and diabetic eNOS-null (STZ-eNOS-/-) mice as models of mild and advanced DN, respectively. GECs of both models in comparison to their respective nondiabetic controls showed significant alterations in the regulation of apoptosis, oxidative stress, and proliferation. The extent of these changes was greater in STZ-eNOS-/- than in STZ-WT GECs. Additionally, genes in STZ-eNOS-/- GECs indicated further dysregulation in angiogenesis and epigenetic regulation. Moreover, a biphasic change in the number of GECs, characterized by an initial increase and subsequent decrease over time, was observed only in STZ-eNOS-/- mice. This is consistent with an early compensatory angiogenic process followed by increased apoptosis, leading to an overall decrease in GEC survival in DN progression. From the genes altered in angiogenesis in STZ-eNOS-/- GECs, we identified potential candidate genes, Lrg1 and Gpr56, whose function may augment diabetes-induced angiogenesis. Thus, our results support a role for GEC in DN by providing direct evidence for alterations of GEC gene expression and molecular pathways. Candidate genes of specific pathways, such as Lrg1 and Gpr56, can be further explored for potential therapeutic targeting to mitigate the initiation and progression of DN.

A Comprehensive Risk Analysis of Transportation Networks Affected by Rainfall-Induced Multihazards.

Climate change and its projected natural hazards have an adverse impact on the functionality and operation of transportation infrastructure systems. This study presents a comprehensive framework to analyze the risk to transportation infrastructure networks that are affected by natural hazards. The proposed risk analysis method considers both the failure probability of infrastructure components and the expected infrastructure network efficiency and capacity loss due to component failure. This comprehensive approach facilitates the identification of high-risk network links in terms of not only their susceptibility to natural hazards but also their overall impact on the network. The Chinese national rail system and its exposure to rainfall-related multihazards are used as a case study. The importance of various links is comprehensively assessed from the perspectives of topological, efficiency, and capacity criticality. Risk maps of the national railway system are generated, which can guide decisive action regarding investments in preventative and adaptive measures to reduce risk.

A Novel Visceral Adiposity Index for Prediction of Type 2 Diabetes and Pre-diabetes in Chinese adults: A 5-year prospective study.

The Chinese visceral adiposity index (CVAI) is a recently developed indicator of visceral adiposity. We investigated the predictive value of the CVAI for the development of dysglycemia (pre-diabetes and type 2 diabetes) and compared its predictive power with that of the Visceral adiposity index (VAI) and various anthropometric indices. This community-based study included 2,383 participants. We assessed the predictive power of adiposity indices by performing univariate and multivariate binary logistic regression analysis and calculating the area under the receiver-operating characteristic (ROC) curve according to their quartiles. Logistic regression analysis showed that individuals in higher CVAI quartiles at baseline were more likely to develop dysglycemia than those in lower CVAI quartiles. The area under the ROC curve for CVAI was significantly higher than that of other adiposity indices. In addition, among the various adiposity indices tested, the CVAI had the greatest Youden index for identifying dysglycemia in both genders. Our data demonstrate that the CVAI is a better predictor of type 2 diabetes and pre-diabetes than the VAI, BMI, waist circumference, waist-to-hip ratio and waist-to-height ratio in Chinese adults.

Increased ß-Cell Mass in Obese Rats after Gastric Bypass: A Potential Mechanism for Improving Glycemic Control.

BACKGROUND Over the past few decades, bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), has become widely considered the most effective treatment for morbid obesity. In most cases, it results in enhanced glucose management in patients with obesity and type 2 diabetes (T2D), which is observed before significant weight loss. However, what accounts for this effect remains controversial. To gain insight into the benefits of RYGB in T2D, we investigated changes in the ß-cell mass of obese rats following RYGB. MATERIAL AND METHODS RYGB or a sham operation was performed on obese rats that had been fed a high-fat diet (HFD) for 16 weeks. Then, the HFD was continued for 8 weeks in both groups. Additional normal chow diet (NCD) and obese groups were used as controls. RESULTS In the present study, RYGB induced improved glycemic control and enhanced ß-cell function, which was reflected in a better glucose tolerance and a rapidly increased secretion of insulin and C-peptide after glucose administration. Consistently, rats in the RYGB group displayed increased ß-cell mass and islet numbers, which were attributed in part to increased glucagon-like peptide 1 levels following RYGB. CONCLUSIONS Our data indicate that RYGB can improve b-cell function via increasing ß-cell mass, which plays a key role in improved glycemic control after RYGB.

Effects of high-dose phytoestrogens on circulating cellular microparticles and coagulation function in postmenopausal women.

BACKGROUND/PURPOSE: Estrogen in hormone replacement therapy causes homeostatic changes. However, little is known regarding the safety of high-dose phytoestrogen on coagulation and hematological parameters in healthy postmenopausal women. This study evaluated the effects of high-dose soy isoflavone (300 mg/day) on blood pressure, hematological parameters, and coagulation functions including circulating microparticles in healthy postmenopausal women. METHODS: The original study is a 2-year prospective, double-blind, placebo-controlled study. In total, 431 postmenopausal women (from 3 medical centers) were randomly assigned to receive either high-dose isoflavone or placebo for 2 years. At baseline, 6 months, 1 year, and 2 years after treatment, blood pressure, body weight, liver function tests, hematological parameters, and lipid profiles were measured. The 1(st) year blood specimens of 85 cases of 144 eligible participants (from one of the three centers) were analyzed as D-dimer, von Willebrand factor antigen, factor VII, plasminogen activator inhibitor type 1, and circulating cellular microparticles, including the measurement of monocyte, platelet, and endothelial microparticles. RESULTS: In the isoflavone group, after 1 year, the changes in liver function tests, hematological parameters, and coagulation tests were not different from those of the control. Triglyceride levels were significantly lower after 6 months of isoflavone treatment than the placebo group, but the difference did not persist after 1 year. Endothelial microparticles increased steadily in both groups during the 1-year period but the trend was not affected by treatment. CONCLUSION: The results of the present study indicate that high-dose isoflavone treatment (300 mg/day) does not cause hematological abnormalities or activate coagulation factors.

Logical gaps in the approximate solutions of the social learning game and an exact solution.

After the social learning models were proposed, finding solutions to the games becomes a well-defined mathematical question. However, almost all papers on the games and their applications are based on solutions built either upon an ad-hoc argument or a twisted Bayesian analysis of the games. Here, we present logical gaps in those solutions and offer an exact solution of our own. We also introduce a minor extension to the original game so that not only logical differences but also differences in action outcomes among those solutions become visible.

Stability of mixed-strategy-based iterative logit quantal response dynamics in game theory.

Using the Logit quantal response form as the response function in each step, the original definition of static quantal response equilibrium (QRE) is extended into an iterative evolution process. QREs remain as the fixed points of the dynamic process. However, depending on whether such fixed points are the long-term solutions of the dynamic process, they can be classified into stable (SQREs) and unstable (USQREs) equilibriums. This extension resembles the extension from static Nash equilibriums (NEs) to evolutionary stable solutions in the framework of evolutionary game theory. The relation between SQREs and other solution concepts of games, including NEs and QREs, is discussed. Using experimental data from other published papers, we perform a preliminary comparison between SQREs, NEs, QREs and the observed behavioral outcomes of those experiments. For certain games, we determine that SQREs have better predictive power than QREs and NEs.