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Objective: Irritability is listed as a common side effect of psychostimulant medications. However, psychostimulants have been demonstrated as an effective treatment in reducing irritability and aggression in children with attention-deficit/hyperactivity disorder (ADHD). The goal of this study was to quantify the risk of irritability as a side effect of psychostimulant treatment for ADHD., Data Sources and Study Selection: A PubMed search was conducted on August 18, 2013, to identify all double-blind, randomized, placebo-controlled trials published in English examining the efficacy of psychostimulant medications in the treatment of children with ADHD. Trials were excluded if (1) they required additional psychiatric or medical comorbidity in addition to ADHD, (2) they involved fewer than 20 subjects (parallel group trials), or (3) children received psychostimulant medication for less than 1 week., Data Extraction: A fixed-effects meta-analysis was used to examine the risk ratio of irritability reported as a side effect in children treated with psychostimulants compared to placebo. Stratified subgroup analysis and meta-regression were used to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of irritability., Results: From 92 potentially eligible trials, the meta-analysis identified 32 trials involving 3,664 children with ADHD that reported data on irritability as a side effect. The relative risk of irritability significantly differed between psychostimulant classes (test for subgroup differences χ²₁ = 7.6, P = .006). Methylphenidate derivatives were associated with a significantly decreased risk of irritability compared to placebo (risk ratio [RR] = 0.89 [95% CI, 0.82 to 0.96], z = -2.87, P = .004, k = 32, I² = 50%), whereas amphetamine derivatives were associated with a significantly increased risk of irritability (RR = 2.90 [95% CI, 1.26 to 6.71], z = 2.5, P = .01, k = 5, I² = 0%)., Conclusions: This meta-analysis suggests an increased risk of irritability may be confined to amphetamine-derived psychostimulants. Future meta-analyses examining the effects of amphetamine and methylphenidate derivatives on irritability as a continuous measure, as well as head-to-head trials between methylphenidate and amphetamine derivatives examining effects on irritability, will be important to replicate the findings of this meta-analysis., (© Copyright 2017 Physicians Postgraduate Press, Inc.)

Background: Orthopedic surgeries of lower extremities such as total knee arthroplasty (TKA), total hip arthroplasty (THA), and hip fracture surgery (HFS) are widely considered to carry a high risk of developing deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE). Growing attention to epidemiological studies using a healthcare database led us to quantify the risks using a Japanese database to reveal recent medical care for such events., Methods: The study comprised 36,947 patients who had undergone orthopedic surgeries of the lower extremities and whose medical information from April 2008 to September 2013 was available. The source population of the database was derived from 100 acute-care hospitals with Diagnosis Procedure Combination. The events were defined by diagnosis, medication, imaging, and laboratory tests., Results: A breakdown of patients who underwent orthopedic surgeries by type of surgery showed 13.6% for TKA, 10.4% for THA, 56.8% for HFS, 1.5% for rupture of Achilles tendon, and 18.0% for simple fracture of lower extremities. The incidence for DVT, PTE, and bleeding events by type of surgery was 1.3, 0.2, and 1.0% for TKA; 0.9, 0.2, and 1.1% for THA; and 0.4, 0.1, and 1.8% for HFS, respectively. The population for risk factor analysis consisted of patients with similar background factors who underwent TKA, THA, or HFS. The statistically significant risk factors for PTE analyzed by the backward elimination procedure in a multivariate model were female sex, history of venous thromboembolism (VTE), thrombophilia, and varicose veins of lower extremity., Conclusions: The incidence of DVT, PTE, and bleeding events and the risk factors for DVT and PTE in patients by type of orthopedic surgeries of lower extremities found in our study are considered to be rational as they reflect evidence from real-world cases., Trial Registration: University Hospital Medical Information Network Clinical Trials Registry UMIN000012667.

Objectives: Longitudinal associations between total bilirubin (TB) and prediabetes have not been reported. This study investigated cross-sectional and longitudinal associations between TB and prediabetes., Methods: Cross-sectional associations between TB and prediabetes were investigated in 3681 nondiabetic subjects. Longitudinal associations between TB and prediabetes over 6 years were investigated in 2149 subjects who were normoglycemic at baseline. Prediabetes was defined as fasting plasma glucose (FPG) levels of ≥5.6 mmol/L or glycated hemoglobin levels of ≥5.7% excluding diabetes., Results: The prevalence of prediabetes was 25.4%, and the cumulative incidence of prediabetes during 6 years was 25.5% in a Japanese health screening population. Prevalent prediabetes was significantly associated with the quintiles of TB in nonsmoking men (trend, p<0.001) and women (trend, p=0.012), but not in smoking men (trend, p=0.689). Incident prediabetes was not significantly associated with the quintiles of TB, while it was positively associated with 1 standard deviation increase in TB in nonsmoking men (hazard ratio [95% confidence interval]; 1.21 [1.07 to 1.37], p=0.002)., Conclusions: TB levels were significantly inversely associated with prevalent prediabetes in nonsmokers, but not in smokers, whereas an inverse association between TB levels and incident prediabetes seemed to be unlikely., (Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

A simple and sensitive method for the determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage in human urine, was developed using automated on-line in-tube solid-phase microextraction (SPME) coupled with stable isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS). Creatinine was also analyzed simultaneously to normalize urine volume by the in-tube SPME LC-MS/MS method, and 8-OHdG and creatinine were separated within 3 min using a Zorbax Eclipse XDB-C8 column. Electrospray MS/MS for these compounds was performed on an API 4000 triple quadruple mass spectrometer in the positive ion mode by multiple reaction monitoring. The optimum in-tube SPME conditions were 20 draw/eject cycles of 40 μL of sample at a flow rate of 200 μL/min using a Carboxen 1006 PLOT capillary column as an extraction device. The extracted compounds were easily desorbed from the capillary by passage of the mobile phase, and no carryover was observed. The calibration curve for 8-OHdG using its stable isotope-labeled internal standard was linear in the range of 0.05-10 ng/mL, and the detection limit was 8.3 pg/mL. The intra-day and inter-day precision (relative standard deviations) were below 3.1% and 9.6% (n=5), respectively. This method was applied successfully to the analysis of urine samples without any other pretreatment and interference peaks, with good recovery rates above 91% in spiked urine samples. The limits of quantification of 8-OHdG and creatinine in 0.1 mL urine samples were about 0.32 and 0.69 ng/mL (S/N=10), respectively. This method was utilized to assess the effects of smoking, green tea drinking and alcohol drinking on the urinary excretion of 8-OHdG., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: To date, the optimal surgical strategy for remnant gastric cancer has not been determined. The purpose of this study was to clarify the significance of lymphadenectomy with splenectomy in remnant gastric cancer surgery., Methods: This retrospective cohort study was conducted at the Kumamoto Regional Medical Center. The primary endpoint was overall survival after surgery. We retrospectively analyzed the clinicopathologic features, surgical treatments, and long-term prognosis of remnant gastric cancer patients treated with total gastrectomy., Results: A total of 80 patients with gastric cancer in the remnant stomach after distal gastrectomy and who underwent total gastrectomy were enrolled in the study. Splenectomy was performed in 38 patients. Lymph node metastasis in the splenic hilum was not observed in the patients with pT1/pT2 tumors, whereas nodal metastasis at the splenic hilum was detected in 30.4% of the patients with pT3/pT4 tumors. The survival rate of the patients with pT3/pT4 tumors who underwent splenectomy was significantly higher than that of the patients who did not undergo splenectomy, although there was no difference in the patients with pT1/pT2 tumors. Among the patients classified as R0, the survival rate of the patients with pT3/pT4 tumors who underwent splenectomy was significantly higher than that of the patients who did not undergo splenectomy., Conclusion: Lymphadenectomy with splenectomy in radical surgery is beneficial for patients with advanced (pT3/pT4) remnant gastric cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: There have been few studies regarding the relationship between respiratory function and incident diabetes in East Asian populations in whom obesity is not prevalent., Methods: This is a 6-year follow-up study in a Japanese health-screening population that included 1874 men and 1093 women. Using Cox regression models, hazard ratios (HRs) of incident diabetes for percent vital capacity (%VC) and forced expiratory volume in 1 second divided by forced vital capacity (FEV1/FVC) were calculated. Diabetes was defined as simultaneous fasting plasma glucose (FPG) ≥7.0 mmol/L and glycated hemoglobin (A1C) ≥6.5% or use of antidiabetic medications., Results: During the 6-year follow-up period (mean of 4.8 years), 71 men (3.8%) and 18 women (1.7%) developed diabetes. The HRs (95% confidence intervals [CIs]) of incident diabetes for each 1 SD increase in %VC and the lowest tertile of %VC compared with the highest tertile were 0.81 (0.66 to 1.00) (p=0.045) and 1.78 (1.01 to 3.16) (p=0.048), respectively, adjusted for sex, age, body mass index, antihypertensive drug use and A1C levels. After further adjustment for log high-sensitivity C-reactive protein, the HRs (95% CI) of incident diabetes for each 1 SD increase in %VC and the lowest tertile of %VC were 0.82 (0.67 to 1.01) (p=0.063) and 1.69 (0.95 to 3.01) (p=0.073), respectively. The association between FEV1/FVC and incident diabetes was not significant., Conclusions: %VC, but not FEV1/FVC, was significantly associated with incident diabetes in a Japanese health-screening population in whom obesity was not prevalent., (Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Objective Many studies on the cost of Parkinson disease (PD) have been published; however, there are limited studies pertaining to this issue in Asia. This study looks to assess the direct medical costs of patients with PD at a university hospital in Japan by calculating the average monthly direct medical costs of PD patients from July to December 2008. Methods We enrolled 724 consecutive patients (411 women and 313 men) with PD who were registered in Japan's "Specified Disease Treatment Research Program" and obtained data on the total direct medical costs of all patients. Results Values are reported as the mean (standard deviation). The major finding of the direct medical cost analysis was that the outpatient clinic cost per subject (n=715) was USD 485.74 (376.31) per month. A multivariate analysis revealed that a younger age, the presence of wearing-off, hallucination, and longer disease duration increased the direct medical cost significantly. Disease severity had no influence on the direct medical costs. A longer disease duration was significantly correlated with higher hospitalization costs. Conclusion The direct medical cost of PD in Japan was found to be similar to that in Western countries. Costs due to productivity loss exceeded the direct costs, and they may be reduced through the better integration of PD patients in the work environment.

Low urine pH, a plausible predictor for chronic kidney disease and metabolic disorders, is often observed in obese individuals. However, the association between low urine pH and low body weight is equivocal. We examined clinical parameters including urine pH and body mass index (BMI) in a cross-sectional study of 3629 apparently healthy Japanese adults aged 25-80 years who underwent a health-screening check-up. Urine pH was lower and the prevalence of proteinuria was significantly higher in subjects with BMI of ≥ 27.0 kg/m(2) compared with those with BMI of 21.0-22.9 kg/m(2). By contrast, hematuria was more prevalent in subjects with BMI of ≤ 20.9 kg/m(2). Logistic regression analysis showed that BMI of ≥ 27.0 kg/m(2) was significantly associated with low urine pH (≤ 5.5), which remained significant after adjustment for relevant confounders including age, sex, proteinuria, estimated glomerular filtration rate, urine density, hematuria, smoking status, and daily alcohol drinking. However, the association disappeared after further adjustment for serum uric acid. In contrast, the association between low urine pH and BMI of ≤ 19.0 kg/m(2) was significant after adjustment for age and sex and rather strengthened by the further adjustment for serum uric acid. In conclusion, low urine pH may be independently associated with low BMI. However, the underlying mechanisms of low urine pH in low body weight may differ from those in high body weight.

Background: High serum sodium (sNa) concentrations may be associated with hypertension, which deteriorates kidney function. However, it is equivocal whether high sNa concentrations are associated with impaired kidney function independently of blood pressure (BP) or serum chloride (sCl). Therefore, we addressed this issue in an apparently healthy population., Methods: Clinical variables including estimated glomerular filtration rate (eGFR) were examined in 3603 men and women (aged 25-75 years) who underwent health-screening check-ups. sNa concentrations were classified into five categories., Results: Most parameters, including age and BP, increased with increasing sNa, whereas eGFR decreased. Logistic regression analysis showed that, compared with low-normal sNa (≤ 140 mEq/l), high sNa (≥ 144 mEq/l) was significantly associated with elevated BP (≥ 130/85 mmHg) even after adjustment for blood hematocrit, eGFR, serum potassium (sK) concentration and sCl. The highest sNa category was significantly associated with reduced eGFR (< 60 ml/min/1.73 m(2)) independently of elevated BP. Unlike adjustment for sK, adjustment for sCl strengthened the association between high sNa and elevated BP but attenuated the association between high sNa and reduced eGFR., Conclusions: These results suggest that high sNa concentrations, even within the normal range, are independently associated with elevated BP and impaired kidney function. These associations may be substantially modified by sCl.

Cancer of unknown primary is associated with unknown biology and dismal prognosis. The most common primary sites of cancer of unknown primary were usually the lungs in autopsy studies, and intrahepatic cholangiocarcinoma is rare. We describe the case of a 57-year-old male patient with systemic lymph node metastasis. Imaging examination failed to reveal primary cancer; however, immunostaining of cytokeratins 7, 19, and 20 of a metastatic axillary lymph node suggested a pancreaticobiliary cancer as a primary lesion. He died of liver abscess and sepsis, and then, autopsy indicated occult intrahepatic cholangiocarcinoma. We discuss the clinical course of this rare cholangiocarcinoma including the diagnostic procedure and also present a review of the English literature regarding patients with cancer of unknown primary.

Background: Gastric conduit ischemia is sometimes correlated with anastomosis-related morbidities after esophagectomy and pharyngolaryngectomy.1 (-) 5 A lack of connection between the right and left gastroepiploic vessels and intraoperative injury to these vessels could cause conduit ischemia. In addition, tensioned anastomosis due to a short gastric tube also could contribute to anastomotic leaks. This report introduces a reconstruction technique using a pedunculated gastric tube with duodenal transection for these cases., Methods: Creation of a gastric tube in the greater curvature of the stomach is performed with linear staplers. Only the right gastroepiploic vessels are preserved. The gastric tube is finally fashioned with a width of approximately 4 cm. The peripheral right gastroepiploic vessels to the pylorus are sacrificed. After the bulbs are transected, a pedunculated gastric tube is moved, with confirmation whether it has sufficient length for anastomosis in the neck. After the anal side of the gastric tube is transected, Roux-en-Y gastrointestinal anastomosis is performed. Finally, esophagogastric or pharyngogastric anastomosis is performed., Results: Between November 2011 and September 2014, 18 patients underwent the reported reconstruction technique due to short gastric tubes in 10 patients and a lack of connection between the right and left gastroepiploic vessels in 8 patients. Anastomotic leaks occurred in three patients (16.7 %), conduit necrosis in no patients, and strictures in no patients, respectively. Two patients had an anastomotic grade 2 leak, and one patient had an anastomotic grade 3 leak., Conclusion: The current reconstruction technique is a good alternative for patients at risk of conduit ischemia and patients with a short gastric tube after esophagectomy and pharyngolaryngectomy.

Doubly labeled water (DLW) can be used to measure energy expenditure in free-ranging animals, but questions have been raised about its accuracy in different species or contexts. We investigated whether differences in the extent of isotope elimination affects the precision and accuracy of the DLW method, which can vary according to the experimental design or metabolic rate of the species. Estimated total energy expenditure by the DLW method (TEEdlw) was compared with actual total energy expenditure simultaneously measured via respirometry (TEEresp) in streaked shearwaters Calonectris leucomelas, a pelagic seabird. Subjects were divided into three groups with different experimental conditions: at rest on the ground for 24 h (Group A) or for 48 h (Group B), and at rest on the water for 24 h (Group C). TEEdlw in Group A matched TEEresp, whereas there was an overestimation of TEEdlw in both Groups B and C compared with TEEresp. However, compared with Group A, TEEdlw in Groups B and C had reduced the isotopic analytical variability and thus higher precision. The best regression model (TEEdlw = 1.37 TEEresp - 14.12) showed a high correlation (R(2) = 0.82) between TEEdlw and TEEresp and allows a correction factor for field metabolic rates in streaked shearwaters. Our results demonstrate that the commonly made assumption that the DLW method is not appropriate for individual-based estimates may be incorrect in certain circumstances. Although a correction factor may be necessary when using the DLW method to estimate metabolic rate, greater levels of isotope eliminations provides DLW estimates with high precision, which can adequately represent relative individual estimates. Nevertheless, the DLW method, should be used with caution when characterizing interspecies difference of energy expenditures., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Chagas disease is a zoonosis caused by the parasite Trypanosoma cruzi and transmitted by insect vectors to several mammals, but little is known about its spatial epidemiology. We assessed the spatial distribution of T. cruzi infection in vectors and small mammals to test if mammal infection status is related to the proximity to vector colonies. During four consecutive years we captured and georeferenced the locations of mammal species and colonies of Mepraia spinolai, a restricted-movement vector. Infection status on mammals and vectors was evaluated by molecular techniques. To examine the effect of vector colonies on mammal infection status, we constructed an infection distance index using the distance between the location of each captured mammal to each vector colony and the average T. cruzi prevalence of each vector colony, weighted by the number of colonies assessed. We collected and evaluated T. cruzi infection in 944 mammals and 1976 M. spinolai. We found a significant effect of the infection distance index in explaining their infection status, when considering all mammal species together. By examining the most abundant species separately, we found this effect only for the diurnal and gregarious rodent Octodon degus. Spatially explicit models involving the prevalence and location of infected vectors and hosts had not been reported previously for a wild disease.

Aims: To compare high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) as a predictor of incident diabetes in a population where obesity is not prevalent., Methods: This is a retrospective 6-year follow-up study in a Japanese health screening population including 1874 men and 1094 women. Using Cox regression methods, hazard ratios (HRs) of incident diabetes for hs-CRP and WBC adjusting for fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and other confounders were calculated, and using areas under receiver operating characteristic curve (AUCs), diabetes-predicting abilities of hs-CRP and WBC were compared. Diabetes was defined as FPG ≥ 126 mg/dL and HbA1c ≥ 6.5 % or use of antidiabetic medication., Results: During the 6-year follow-up period (mean ± SD, 4.8 ± 1.7 years), 71 men (3.8 %) and 19 women (1.7 %) developed incident diabetes. The fully adjusted HRs [95 % confidence intervals (CIs)] of incident diabetes for each 1 SD increase in log hs-CRP and WBC were 1.20 (0.92-1.56) (p = 0.174) and 1.01 (0.78-1.30) (p = 0.946), respectively. The fully adjusted HRs (95 % CIs) of incident diabetes for the highest tertile of hs-CRP and WBC compared with the lowest tertile were 2.57 (1.05-6.27) (p = 0.039) and 1.20 (0.53-2.70) (p = 0.665), respectively. The AUCs (95 % CIs) of hs-CRP and WBC for the discrimination of incident diabetes were 0.73 (0.68-0.77) and 0.67 (0.62-0.72), respectively., Conclusions: Hs-CRP, but not WBC, was independently associated with incident diabetes in a Japanese health screening population where obesity is not prevalent.

Objective: Anxiety is a commonly reported side-effect of psychostimulant treatment. Our goal was to quantify the risk of anxiety as a side effect of psychostimulant treatment for attention-deficit/hyperactivity disorder (ADHD)., Methods: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with ADHD. We used a fixed-effects meta-analysis to examine the risk ratio of anxiety reported as a side effect in children treated with psychostimulants compared with those treated with placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dosage, duration of use, and trial design on the measured risk of anxiety., Results: We identified 23 studies involving 2959 children with ADHD for inclusion in our meta-analysis. The risk of anxiety associated with psychostimulant treatment was significantly lower than that experienced with placebo (relative risk [RR] = 0.86 [95% CI: 0.77, 0.95], z = -2.90, p < 0.05). Higher doses of psychostimulants were associated with a reduced measured risk of anxiety of psychostimulants when compared with placebo (β = -0.0039 [95% CI: -0.00718, -0.00064], z = -2.34, p = 0.019)., Conclusions: Meta-analysis suggests that treatment with psychostimulants significantly reduced the risk of anxiety when compared with placebo. This finding does not rule out the possibility that some children experience increased anxiety when treated with psychostimulants, but suggests that those risks are outweighed by the number of children who experience improvement in anxiety symptoms (possibly as a secondary effect of improved control of ADHD symptoms). Clinicians should consider rechallenging children with ADHD who report new-onset or worsening anxiety with psychostimulants, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants.

Objective: Clinical practice currently restricts the use of psychostimulant medications in children with tics or a family history of tics for fear that tics will develop or worsen as a side effect of treatment. Our goal was to conduct a meta-analysis to examine the risk of new onset or worsening of tics as an adverse event of psychostimulants in randomized, placebo-controlled trials., Method: We conducted a PubMed search to identify all double-blind, randomized, placebo-controlled trials examining the efficacy of psychostimulant medications in the treatment of children with attention-deficit/hyperactivity disorder (ADHD). We used a fixed effects meta-analysis with risk ratio of new onset or worsening tics in children treated with psychostimulants compared to placebo. We used stratified subgroup analysis and meta-regression to examine the effects of stimulant type, dose, duration of treatment, recorder of side effect data, trial design, and mean age of participants on the measured risk of tics., Results: We identified 22 studies involving 2,385 children with ADHD for inclusion in our meta-analysis. New onset tics or worsening of tic symptoms were commonly reported in the psychostimulant (event rate = 5.7%, 95% CI = 3.7%-8.6%) and placebo groups (event rate = 6.5%, 95% CI = 4.4%-9.5%). The risk of new onset or worsening of tics associated with psychostimulant treatment was similar to that observed with placebo (risk ratio = 0.99, 95% CI = 0.78-1.27, z = -0.05, p = .962). Type of psychostimulant, dose, duration of treatment, recorder, and participant age did not affect risk of new onset or worsening of tics. Crossover studies were associated with a significantly greater measured risk of tics with psychostimulant use compared to parallel group trials., Conclusion: Meta-analysis of controlled trials does not support an association between new onset or worsening of tics and psychostimulant use. Clinicians may want to consider rechallenging children who report new onset or worsening of tics with psychostimulant use, as these symptoms are much more likely to be coincidental rather than caused by psychostimulants., (Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate longitudinal associations between serum cholinesterase (ChE) and lipid status., Methods: Hazard ratios (HRs) of incident hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia for baseline ChE and correlation coefficients between baseline ChE and changes in LDL cholesterol, log triglycerides and HDL cholesterol during 5 years were calculated in a health screening population., Results: During the 5-year follow-up period, 337 men (22.9%) and 208 women (26.3%), 330 men (24.3%) and 114 women (12.4%) and 137 men (8.3%) and 117 women (12.7%) developed hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia, respectively. The HRs of incident hyper-LDL cholesterolemia, hypertriglyceridemia and hypo-HDL cholesterolemia for each 1 SD increase in baseline ChE were 1.15 (p = 0.009) in men and 1.17 (p = 0.017) in women, 1.25 (p < 0.001) in men and 1.37 (p < 0.001) in women and 1.15 (p = 0.113) in men and 1.12 (p = 0.248) in women, respectively adjusted for BMI and other confounders, while the HRs were not significant after further adjusted for each baseline lipid level except for the HR of hypertriglyceridemia in women (HR, 1.22 (p = 0.047)). The baseline ChE was inversely correlated with the changes in LDL cholesterol (r = -0.117, p < 0.001) and log triglycerides (r = -0.114, p < 0.001) in men and the change in LDL cholesterol (r = -0.191, p < 0.001) in women., Conclusion: ChE was positively associated with incident hyper-LDL cholesterolemia and hypertriglyceridemia adjusted for BMI, while with only incident hypertriglyceridemia in women after further adjusted for the baseline lipid level., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate cross-sectional and longitudinal associations between serum total bilirubin (TB) and dyslipidemia., Methods: Odds ratios (ORs) of prevalent dyslipidemia for TB were calculated in 2113 men and 1265 women. Correlation coefficients between baseline TB as well as the change in TB over 5 years and baseline log triglycerides, baseline HDL cholesterol and the changes in log triglycerides and HDL cholesterol over 5 years were calculated. Hazard ratios (HRs) of incident hypertriglyceridemia and hypo-HDL cholesterolemia for TB over 5 years were calculated in 1324 men and 915 women and 1583 men and 884 women, respectively., Results: The ORs of prevalent hypertriglyceridemia and hypo-HDL cholesterolemia for each one SD increase in TB were 0.83 (p < 0.001) in men and 0.71 (p = 0.074) in women and 0.64 (p < 0.001) in men and 0.78 (p = 0.089) in women, respectively adjusted for age, smoking, and other confounders. The baseline TB was significantly correlated with baseline log triglycerides and HDL cholesterol both in men and women while the change in TB was significantly correlated with the changes in log triglycerides and HDL cholesterol in men and the change in HDL cholesterol in women. The HRs of incident hypertriglyceridemia and hypo-HDL cholesterolemia for each one SD increase in TB were 0.99 (p = 0.848) in men and 0.74 (p = 0.033) in women and 1.08 (p = 0.345) in men and 0.85 (p = 0.220) in women, respectively adjusted for age, smoking, and other confounders., Conclusion: Baseline TB was significantly associated with both prevalent hypertriglyceridemia and hypo-HDL cholesterolemia in men and with incident hypertriglyceridemia in women., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: J waves can be observed in individuals of the general population, but electrocardiographic characteristics are poorly understood., Objective: The purpose of this study was to examine the J-wave dynamicity in a general patient population., Methods: The responses of J waves (>0.1 mV above the isoelectric line in 2 contiguous leads) to varying RR intervals were analyzed. Patients with aborted sudden cardiac death, documented ventricular fibrillation, or a family history of sudden cardiac death were excluded. The J-wave amplitude was measured at baseline, in beats with short RR intervals in conducted atrial premature beats (APBs) or atrial stimulation during the electrophysiology study, and in the beats next to APBs with prolonged RR intervals., Results: Mainly notched J waves were identified in 94 of 701 (24.5%) general patients (13.4%), and APBs were present in 23 of 94 (24.5%) patients. The mean baseline amplitude of J waves was 0.20 ± 0.06 mV at the baseline RR interval of 853 ± 152 ms, 0.25 ± 0.11 mV at the RR interval in the conducted APB of 545 ± 133 ms (P = .0018), and 0.19 ± 0.08 mV at the RR interval of 1146 ± 314 ms (P = .3102). The clinical characteristics were not different between patients with and without tachycardia-dependent augmentation of J waves. Augmentation of J waves was confirmed by the electrophysiology study: 0.28 ± 0.12 mV vs 0.42 ± 0.11 mV at baseline and in the beats of atrial stimulation, respectively (P = .0001). However, no bradycardia-dependent augmentation (>0.05 mV) was observed. Such tachycardia-dependent augmentation can represent depolarization abnormality rather than repolarization abnormality., Conclusion: J waves in a general patient population were augmented at shorter RR intervals, but not at prolonged RR intervals. Mechanistically, conduction delay is most likely responsible for this., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: We have previously shown that serum levels of glyceraldehyde-derived advanced glycation end products (Gly-AGEs) are elevated under oxidative stress and/or diabetic conditions and associated with insulin resistance, endothelial dysfunction and vascular inflammation in humans. Further, Gly-AGEs not only evoke oxidative and inflammatory reactions in endothelial cells (ECs) through the interaction with a receptor for AGEs (RAGE), but also mimic vasopermeability effects of AGE-rich serum purified from diabetic patients on hemodialysis. These observations suggest that Gly-AGE-RAGE system might be a therapeutic target for vascular complications in diabetes. However, since incubation of glyceraldehyde with proteins will generate a large number of structurally distinct AGEs, it remains unclear what type of AGE structures could mediate the deleterious effects of Gly-AGEs on ECs., Aims and Methods: Therefore, in this study, we examined (1) whether glyceraldehyde-derived pyridinium (GLAP), one of the Gly-AGEs generated by the incubation of lysine with glyceraldehyde, elicited reactive oxygen species (ROS) generation and inflammatory and thrombogenic gene expression in human umbilical vein ECs (HUVECs) via the interaction with RAGE and (2) if DNA aptamers raised against Gly-AGEs or GLAP (AGE-aptamer or GLAP-aptamer) inhibited the binding of GLAP to RAGE and subsequently suppressed the harmful effects of GLAP on HUVECs., Results: GLAP stimulated ROS generation in a bell-shaped manner; GLAP at 10 μg/ml increased ROS generation in HUVECs by 40%, which was blocked by the treatment with RAGE-antibody (RAGE-Ab). Ten μg/ml GLAP significantly up-regulated mRNA levels of RAGE, monocyte chemoattractant protein-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and plasminogen activator inhibitor-1 in HUVECs, which were also suppressed by RAGE-Ab. AGE-aptamer or GLAP-aptamer significantly blocked these deleterious effects of GLAP on HUVECs. Moreover, quartz crystal microbalance analyses revealed that GLAP actually bound to RAGE and that AGE-aptamer or GLAP-aptamer inhibited the binding of GLAP to RAGE., Conclusions: The present study suggests that GLAP might be a main glyceraldehyde-related AGE structure in Gly-AGEs that bound to RAGE and subsequently elicited ROS generation and inflammatory and thrombogenic reactions in HUVECs. Blockade of the GLAP-RAGE interaction by AGE-aptamer or GLAP-aptamer might be a novel therapeutic strategy for preventing vascular injury in diabetes.

Objective: The purpose of this study was to investigate the procedures for efficiently diagnosing Sjögren's syndrome to reduce patient burden., Methods: This study analyzed data from 254 Japanese patients diagnosed with Sjögren's syndrome out of 4967 who visited our clinic complaining of xerostomia., Results: Of the 254 Sjögren's syndrome patients, 140 fulfilled the criteria proposed by the Committee on Sjögren's Syndrome of the Ministry of Health and Welfare of Japan, 228 fulfilled the criteria proposed by the American-European Consensus Group, and 69 fulfilled the criteria proposed by the American College of Rheumatology. Numbers of definitive cases varied with each set of criteria. Logistic regression analysis was used to analyze useful examination items for definitive diagnosis of Sjögren's syndrome, demonstrating that anti-Ro/SSA (odds ratio (OR), 7.165), lip biopsy (OR, 4.273), sialography (OR, 2.402), and ANA (OR, 0.678) correlated significantly with definitive diagnosis of Sjögren's syndrome., Conclusions: These results suggest that the following diagnostic procedure for Sjögren's syndrome would reduce burden on patients. When clinicians choose examination items for diagnosing Sjögren's syndrome, they should first select which criteria to use. Then, to minimize the number of examination items, examinations should be performed in order of anti-SSA antibody, lip biopsy, and parotid gland sialography.

Objective: The purpose of this study is to investigate the relationships between serum cholinesterase and body weight change, in addition to incident obesity defined as a body mass index (BMI) of 25 kg/m(2) or greater., Methods: A retrospective 5-year follow-up study was conducted. The crude incidence and hazard ratios (HRs) of obesity adjusted for the BMI and other confounders were calculated for cholinesterase quartiles in 1,412 men and 921 women. Partial correlation coefficients (PCCs) were calculated between cholinesterase and changes in the BMI during the 5-year follow-up period adjusted for age and other confounders and the change in the BMI were compared among cholinesterase quartiles in 1,223 men and 681 women., Results: During the 5-year follow-up period, 149 men (10.6%) and 65 women (7.1%) developed obesity. The adjusted HRs of obesity decreased, although the crude incidence of obesity increased along the quartiles of cholinesterase in men. The adjusted HRs of obesity for the first (lowest), second and third quartiles of cholinesterase were 2.02 (p=0.006), 1.45 (p=0.122), and 1.28 (p=0.265), respectively compared with the highest quartile in men. The PCC between the baseline level of cholinesterase and change in the BMI was -0.16 (p<0.001) in men. The mean changes in BMI for 5 years were 0.31 kg/m(2), 0.17 kg/m(2), 0.01 kg/m(2) and -0.04 kg/m(2), respectively in the first, second, third and fourth quartiles of cholinesterase in men (p=0.005). Neither incident obesity nor weight gain was significantly associated with cholinesterase in women., Conclusion: The serum cholinesterase level was inversely associated with body weight change, as well as incident obesity, after adjusted for the BMI in men.

Galaxias maculatus (Pisces: Galaxiidae) commonly known as "puye" has a disjunct distribution along the Southern Hemisphere including landlocked and migratory populations at latitudes over 30°S in South America, Australia, Tasmania, and New Zealand. Chilean artisanal fishery of G. maculatus has become less important as a resource due to multiple factors including overexploitation, pollution, introduction of predators, and competitors. At the same time, the current conservation status of the species in Chile is still uncertain. Here, we used mtDNA control region sequences (925bp) to investigate main patterns of genetic diversity and structure in populations from 2 biogeographic areas along the Chilean coast. Extremely high levels of genetic diversity characterize the species, suggesting a low amount of influence of the last glacial cycle over its demography compared with other studies in freshwater and marine South American fishes. However, we recognized contrasting genetic patterns between the Intermediate Area (between 30°S and 42°S) and the Magellanic Province (between 42°S and 56°S). On the one hand, over a narrow geographical range (<200 km) each Intermediate Area estuarine population constitutes a different genetic unit. On the other hand, the Magellanic populations of the species exhibited low levels of differentiation in an area extending for more than 500 km. Such differences may be a consequence of different coastal configurations, oceanographic regimes, and Quaternary glacial histories. Finally, our results support the existence of different stock units for G. maculatus and this information should be integrated in future management strategies and aquaculture programs for this species., (© The American Genetic Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To investigate longitudinal relationships between obesity/inflammation and kidney stone formation in a population where obesity is not prevalent., Methods: Using Cox regression models, associations between kidney stone formation and body mass index, waist circumference, high-sensitivity C-reactive protein and other possible risk factors were retrospectively examined in a health screening Japanese population including 1726 men and 992 women., Results: During 4 years of follow up (mean 3.2 years), kidney stones were formed in 238 men (34.5 per 1000 person-years) and 82 women (20.7 per 1000 person-years). In men, when the possible risk factors were separately examined as continuous parameters, body mass index (P = 0.030) and waist circumference (P = 0.025) were significantly, and log C-reactive protein (P = 0.092) were marginally, associated with kidney stone formation. However, none of these parameters was independently associated with kidney stone formation after fully adjusted. In women, none of the aforementioned three parameters was associated with kidney stone formation. As a categorical parameter, the higher two quintiles of C-reactive protein were significantly associated with kidney stone formation compared with the lower two quintiles in men (P = 0.026)., Conclusions: Overweight and C-reactive protein are weakly associated with kidney stone formation in Japanese men. Inflammation might be an underlying mechanism of the association between obesity and kidney stone formation., (© 2014 The Japanese Urological Association.)

Background and Aim: Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome (MS). Monosodium glutamate (MSG)-treated ICR mice is a useful model of MS and NASH, but it shows the different patterns of steatosis from human NASH. Because inbred aged DIAR (ddY, Institute for Animal Reproduction) mice spontaneously show the similar pattern of steatosis as NASH, we analyzed their liver pathology after administering MSG., Methods: MSG-treated DIAR mice (DIAR-MSG) and untreated DIAR mice (DIAR-controls) were sacrificed and assessed histopathologically at 29, 32, 40, 48, and 54 weeks of age. The NASH activity score, body mass index, blood glucose level, and oral glucose tolerance test were also assessed., Results: The body mass index and blood glucose levels of DIAR-MSG were significantly higher than controls. The oral glucose tolerance test revealed a type 2 diabetes pattern in DIAR-MSG. The livers of DIAR-MSG mice showed macrovesicular steatosis, lobular inflammation with neutrophils, and ballooning degeneration after 29 weeks. At 54 weeks, mild fibrosis was observed in 5/6 DIAR-MSG and 2/5 DIAR-control mice. In imaging mass spectrometry analysis, cholesterol as well as triglyceride accumulated in the liver of DIAR-MSG mice. Atypical liver nodules were also observed after 32 weeks in DIAR-MSG, some with cellular and structural atypia mimicking human hepatocellular carcinoma. The NASH activity score of DIAR-MSG after 29 weeks was higher than that of control mice, suggesting the development of NASH., Conclusions: DIAR-MSG had NASH-like liver pathology and liver nodules typically associated with MS symptoms. DIAR-MSG provides a valuable animal model to analyze NASH pathogenesis and carcinogenesis., (© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Objective: To investigate cross-sectional and longitudinal associations between serum total bilirubin (TB) and LDL cholesterol., Methods: It is a retrospective observational study. Cross-sectional and longitudinal associations between TB and hyper-LDL cholesterolemia were investigated in a health screening population. Odds ratios (ORs) of coexisting hyper-LDL cholesterolemia for TB were calculated in 3,866 subjects, Spearman's correlation coefficients between baseline TB and LDL cholesterol at baseline and after 4 years were calculated in 1,735 subjects who did not use antihyperlipidemic drugs and hazard ratios (HRs) of incident hyper-LDL cholesterolemia for TB were calculated in 1,992 followed subjects., Results: The ORs (p values) of coexisting hyper-LDL cholesterolemia for each 1 SD increase in TB was 1.04 (0.998) adjusted for sex, age, smoking, LDL cholesterol and other confounders. Spearman's correlation coefficients (p values) between baseline TB and LDL cholesterol at baseline and after 4 years and changes in LDL cholesterol were -0.026 (0.271), -0.078 (0.001) and -0.062 (0.010), respectively. Among 1,992 followed subjects, 481 developed hyper-LDL cholesterolemia during 4 years (60.4 per 1,000 person-years). The HRs (95% confidence intervals; p values) of incident hyper-LDL cholesterolemia for each 1 SD increase in TB was 0.86 (0.77-0.96; 0.006) adjusted for sex, age, smoking, LDL cholesterol, body mass index, triglycerides, HDL cholesterol, fasting glucose and other confounders. The quintiles of TB were significantly associated with the incident hyper-LDL cholesterolemia adjusted for the above covariates (p for trend = 0.008)., Conclusion: A decrease in TB predicted incident hyper-LDL cholesterolemia in a health screening population., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Serum levels of uric acid (UA) are associated with metabolic syndrome (MetS). However, no study has been aimed to investigate whether baseline UA is a predictor of MetS in a Japanese population. The multivariable adjusted hazard ratios (HRs) of MetS through 3 years were calculated for each 1 SD increase in baseline UA, for the higher quartiles of baseline UA compared with the lowest quartile, and for baseline hyperuricemia defined as ≥7.0 mg/dl for men and ≥6.0 mg/dl for women in apparently healthy 1,606 men aged 51.7 ± 9.4 years and 953 women aged 51.6 ± 9.4 years who visited a medical check-up center in Japan. The HRs (95 % confidence interval; p value) were 1.282 (1.097-1.499; 0.002) in men and 1.354 (1.041-1.762; 0.024) in women for 1 SD increase in baseline UA, 2.206 (1.344-3.620; 0.002) in men and 3.110 (1.121-8.627; 0.029) in women for the highest quartile of baseline UA compared with the lowest quartile, and 1.900 (1.376-2.622; <0.001) in men and 2.088 (1.040-4.190; 0.038) in women for baseline hyperuricemia adjusting for the pre-existing components of MetS, age, smoking, drinking, physical activity, use of antihypertensive, antihyperlipidemic, and antidiabetic medications and histories of coronary heart disease and stroke. However, no significant association was found between longitudinal changes in UA and incident MetS. Baseline UA is an independent predictor of MetS in a Japanese health screening population.

Background: Longitudinal associations between leukocyte subtype counts and LDL cholesterol have not been reported., Methods and Results: This is a retrospective observational study in a health screening population. Spearman's correlation coefficients were calculated between leukocyte subtype counts and LDL cholesterol levels at baseline and after four years. Using Cox regression models, hazard ratios (HRs) of hyper-LDL cholesterolemia for leukocyte subtype counts during four years of follow-up were calculated adjusted for age, sex, high-sensitivity C-reactive protein (hs-CRP) and other confounders. Spearman's correlation coefficients ( p values) between changes in counts of neutrophil, lymphocyte, monocyte, basophil and eosinophil and changes in LDL cholesterol levels through 4 years were 0.02 (0.494), 0.12 (<0.001), 0.06 (0.016), 0.02 (0.524) and 0.03 (0.257), respectively among 1735 subjects who visited our medical check-up center, did not use anti-hyperlipidemic drugs and revisited after 4 years. Among 1992 followed subjects, 481 developed hyper-LDL cholesterolemia during four years (60.4 per 1000 person-years). The HRs (95% confidence intervals; p values) of hyper-LDL cholesterolemia for each one SD increase in counts of neutrophil, lymphocyte, monocyte, basophil and eosinophil were 1.08 (0.99-1.19; 0.085), 1.14 (1.04-1.25; 0.005), 1.05 (0.95-1.15; 0.339), 1.01 (0.92-1.11; 0.858) and 1.04 (0.95-1.14; 0.397), respectively., Conclusions: Lymphocyte count and LDL cholesterol were longitudinally positively correlated and lymphocyte count was associated with incidence of hyper-LDL cholesterolemia independently of hs-CRP in a health screening population.

Background: Advanced glycation end products (AGE) and their receptor (RAGE) interaction elicit inflammatory and proliferative reactions in arteries, thus playing a role in cardiovascular disease. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. However, effects of AGE-aptamer on vascular injury remain unknown. In this study, we examined whether and how AGE-aptamer inhibits neointimal hyperplasia in balloon-injured rat carotid arteries., Methods: Male Wistar rats (weighting ca. 400 g at 11 weeks old) were anesthetized with sodium pentobarbital. The left common carotid artery was balloon-injured 3 times with 2F Fogaty catheter inserted through the femoral artery. Then the rats received continuous intraperitoneal infusion (3 μg/day) of either AGE-aptamer or control-aptamer by an osmotic mini pump for 2 weeks. 14 days after the procedure, the left common carotid arteries were excised for morphometric, immunohistochemical and western blot analyses., Results: Compared with control-aptamer, AGE-aptamer significantly suppressed neointima formation after balloon injury and reduced AGE accumulation, oxidative stress generation, proliferation cell nuclear antigen-positive area, macrophage infiltration, RAGE and platelet-derived growth factor-BB (PDGF-BB) expression levels in balloon-injured carotid arteries., Conclusion: The present study suggests that AGE-aptamer could prevent balloon injury-induced neointimal hyperplasia by reducing PDGF-BB and macrophage infiltration via suppression of the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for suppressing neointima formation after balloon angioplasty., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Autonomic nervous dysfunction is considered to be one of the mechanisms of metabolic syndrome (MetS). The aim of this study is to investigate whether resting heart rate, a marker of autonomic nervous dysfunction, is a predictor of MetS in apparently healthy non-obese [body mass index (BMI) <25 kg/m(2)] Japanese men. This is an observational study through 3 years in apparently healthy Japanese 1,265 men and 793 women without MetS and with no history of cardiovascular disease and no use of antihypertensive, antidiabetic, or antihyperlipidemic medication at baseline. Hazard ratios (HRs) of incident MetS were calculated for each 1 SD increase in heart rate stratified by gender and obesity. Incidence of MetS for each tertile of heart rate and HRs of MetS for the highest tertile (T3) compared with the lowest tertile (T1) were calculated stratified by gender and obesity. The HRs [95% confidence intervals (CIs)] of MetS for each 1 SD increase in heart rate were 1.319 (1.035-1.681) (p = 0.025) in non-obese men, 1.172 (0.825-1.665) (p = 0.377) in obese men, 1.115 (0.773-1.608) (p = 0.560) in non-obese women, and 1.401 (0.944-2.078) (p = 0.094) in obese women adjusted for BMI, age, smoking, alcohol drinking, and physical activity. The HRs (95% CIs) of MetS for T3 were 2.138 (1.071-4.269) (p = 0.031) in non-obese men and 1.341 (0.565-3.180) (p = 0.506) in obese men adjusted for pre-existing five components of MetS, age, smoking, alcohol drinking, and physical activity. In conclusion, an increase in resting heart rate was a significant predictor of MetS in non-obese Japanese men.

Objective: The serum albumin level has been reported to be positively associated with blood pressure in some cross-sectional studies. However, the longitudinal relationships between the serum albumin level and incident hypertension have been poorly studied., Methods: The incidence of hypertension was calculated for each quartile of serum albumin in 1,385 normotensive men and 855 normotensive women without cardiovascular disease at baseline who revisited for four years thereafter. The hazard ratios (HRs) of incident hypertension were calculated for each one SD increase in the serum albumin level and for the higher quartiles of serum albumin compared with the lowest quartile adjusted for smoking, alcohol drinking, body mass index, proteinuria, estimated glomerular filtration rate, uric acid, fasting glucose, log triglycerides, log high-sensitivity C-reactive protein, white blood cell count, hemoglobin, and systolic blood pressure., Results: During four years of follow-up (mean; 3.1 years), 242 men (17.5%) and 89 women (10.4%) developed hypertension. The incidence of hypertension significantly decreased through the quartiles of albumin (p for trend=0.012). The HR (95% confidence interval (CI); p value) of hypertension for each one SD increase in the serum albumin level was 0.779 (0.696-0.872; <0.001). Compared with the lowest quartile of serum albumin, the HRs (95% CIs; p values) of hypertension for the second, third and fourth quartiles were 0.765 (0.574-1.018; 0.066), 0.628 (0.440-0.895; 0.010) and 0.520 (0.364-0.742; <0.001), respectively., Conclusion: A decreased serum albumin level was found to be a significant predictor of hypertension in a Japanese health screening population.

Objective: There have been no previous studies regarding the relationship between the respiratory function and incident diabetes in East Asian women in whom obesity is not prevalent., Methods: Using Cox regression models, hazard ratios (HRs) for incident diabetes for each one SD increase in the percent vital capacity (%VC), a parameter of restrictive pulmonary dysfunction, forced expiratory volume in one second over forced vital capacity (FEV1/FVC), a parameter of obstructive pulmonary dysfunction, and log high-sensitivity C-reactive protein (hs-CRP) were calculated in 1,704 men and 1,016 women among a Japanese health screening population., Results: Over the four-year study period (mean of 3.4 years), 54 men (3.2%) and 19 women (1.9%) developed diabetes. The HRs [95% confidence intervals (CIs); p values] for incident diabetes for each one SD increase in %VC and log hs-CRP were 0.81 (0.61-1.06; 0.127) and 1.29 (0.97-1.73; 0.085), respectively in men, and 0.55 (0.35-0.88) 0.012 and 2.50 (1.37-4.57; 0.003), respectively in women adjusted for age, fasting glucose and body mass index. The FEV1/FVC was not found to be significantly associated with incident diabetes in any regression models. The Spearman's correlation coefficients between %VC and hs-CRP was -0.11 (p<0.001) in men and -0.08 (p=0.007) in women. The HRs (95% CIs; p values) for each one SD increase in %VC and hs-CRP were 0.86 (0.65-1.13; 0.278) and 1.26 (0.94-1.70; 0.125), respectively in men, and 0.56 (0.34-0.94; 0.028) and 2.95 (1.49-5.81; 0.002), respectively in women, further adjusted for each other, systolic blood pressure, triglycerides and HDL cholesterol., Conclusion: A low %VC was found to be associated with incident diabetes, independent of hs-CRP in women among a Japanese health screening population.

Controversies concerning the association between obesity and acute myocardial infarction (AMI) are still ongoing in Japan. We investigated the association between obesity defined by body mass index of 25 kg/m(2) or higher and AMI by a case-control study using data from 1199 AMI cases and 4056 apparently healthy controls. The analysis was performed in age- and sex-matched samples of 621 case-control pairs younger than 80 years and in crude samples aged 40-79 years divided into 10-year age groups. Prevalence of obesity, diabetes, current smoking, hypertension, and hypercholesterolemia were compared between cases and controls, and a multivariable odds ratio (OR) of AMI was calculated for each risk factor in various age groups. The OR (95 % confidence interval (CI)) of AMI for obesity was 1.63 (1.23-2.17), P = 0.0008 in men younger than 80 years; 2.65 (1.41-5.00), P = 0.0025 in women younger than 80 years; 2.23 (1.46-3.41), P = 0.0002 in men aged 59 years or younger; 1.34 (0.90-2.01), P = 0.1510 in men aged 60-79 years; and 2.98 (1.56-5.71), P = 0.0010 in women aged 60-79 years using paired samples. The OR (95 % CI) of AMI for obesity was 4.92 (2.53-9.58), P < 0.0001 in men aged 40-49 years; 1.54 (1.07-2.21), P = 0.0197 in men aged 50-59 years; 1.07 (0.69-1.66), P = 0.7717 in men aged 60-69 years; 2.24 (1.20-4.20), P = 0.0118 in men aged 70-79 years; 2.48 (1.12-5.48), P = 0.0245 in women aged 60-69 years; and 3.05 (1.46-6.37), P = 0.0029 in women aged 70-79 years using crude samples. The association between obesity and AMI was age- and gender-dependent in a Japanese population.

To compare high-sensitivity C-reactive protein (hs-CRP) and white blood cell count (WBC) as a predictor of metabolic syndrome (MetS). Hazard ratios (HRs) adjusted for age, smoking, and other confounding covariates and areas under receiver operating characteristic curve (AUCs) of hs-CRP and WBC for developing MetS were calculated in 1,463 men and 920 women from a Japanese health screening population who were free from MetS, diabetes, histories of coronary heart disease, and stroke at baseline and followed through 3 years. The adjusted HRs (95% confidence interval-CI; p value) of MetS for each 1 SD increases in log hs-CRP, and log WBC were 1.345 (1.166-1.553; <0.001) and 1.406 (1.188-1.664; <0.001), respectively, in men and 1.388 (1.110-1.736; 0.004) and 1.358 (1.072-1.721; 0.011), respectively, in women. However, the HRs became nonsignificant after further adjusted for the components of MetS. The AUCs (95% CI; p value) of hs-CRP and WBC for predicting MetS were 0.616 (0.573-0.660; <0.001) and 0.613 (0.566-0.659; <0.001), respectively, in men and 0.636 (0.573-0.698; <0.001) and 0.606 (0.538-0.673; 0.003), respectively, in women. Hs-CRP and WBC equally predict development of MetS, but both are poor predictors of MetS in a Japanese health screening population where obesity is not prevailing.

Serum total bilirubin (TB) is a potent antioxidant and inversely associated with metabolic syndrome (MetS) in Asian populations. However, there has been no study which is aimed to investigate whether TB is a risk factor for MetS or not. We investigated cross-sectional and longitudinal associations between TB and MetS in 2,435 Japanese men and 1,436 Japanese women. The odds ratios [95 % confidence interval (CI)] of coexisting MetS for each 1 SD increase in log TB were 0.850 (0.754-0.958) (p = 0.008) in men and 0.809 (0.656-0.998) (p = 0.047) in women adjusted for sex, age, smoking, and other confounding covariates. Those for the third and fourth quartiles of TB compared with the lowest quartile were 0.720 (0.537-0.965) (p = 0.028) and 0.737 (0.530-1.052) (p = 0.095), respectively, in men and 0.822 (0.473-1.427) (p = 0.486) and 0.704 (0.362-1.369) (p = 0.301), respectively, in women. There was a tendency that TB and MetS changed inversely to each other. The similarly adjusted hazard ratios of developing MetS for each 1 SD increase in log TB and for the higher quartiles of TB compared with the lowest quartile were not significant either in men or in women. TB is inversely associated with MetS but not a risk factor for MetS in Japanese men and women.

Study Objectives: To investigate the efficacy of melatonin compared to placebo in improving sleep parameters in patients with primary sleep disorders., Design: PubMed was searched for randomized, placebo-controlled trials examining the effects of melatonin for the treatment of primary sleep disorders. Primary outcomes examined were improvement in sleep latency, sleep quality and total sleep time. Meta-regression was performed to examine the influence of dose and duration of melatonin on reported efficacy., Participants: Adults and children diagnosed with primary sleep disorders., Interventions: Melatonin compared to placebo., Results: Nineteen studies involving 1683 subjects were included in this meta-analysis. Melatonin demonstrated significant efficacy in reducing sleep latency (weighted mean difference (WMD) = 7.06 minutes [95% CI 4.37 to 9.75], Z = 5.15, p<0.001) and increasing total sleep time (WMD = 8.25 minutes [95% CI 1.74 to 14.75], Z = 2.48, p = 0.013). Trials with longer duration and using higher doses of melatonin demonstrated greater effects on decreasing sleep latency and increasing total sleep time. Overall sleep quality was significantly improved in subjects taking melatonin (standardized mean difference = 0.22 [95% CI: 0.12 to 0.32], Z = 4.52, p<0.001) compared to placebo. No significant effects of trial duration and melatonin dose were observed on sleep quality., Conclusion: This meta-analysis demonstrates that melatonin decreases sleep onset latency, increases total sleep time and improves overall sleep quality. The effects of melatonin on sleep are modest but do not appear to dissipate with continued melatonin use. Although the absolute benefit of melatonin compared to placebo is smaller than other pharmacological treatments for insomnia, melatonin may have a role in the treatment of insomnia given its relatively benign side-effect profile compared to these agents.

Objective: Although metabolic syndrome (MS) is considered to be a predictor of diabetes and cardiovascular disease, its value for predicting diabetes beyond the levels of fasting glucose (FG) and hemoglobin A1c (HbA1c) remains questionable. In this study, we evaluated the usefulness of MS and Japanese MS (JMS) as predictors of diabetes., Methods: This study is a longitudinal study using data for 2,034 subjects who visited our Medical Check-up Center in both 2008 and 2011 and were free from diabetes at baseline. The odds ratios (ORs) of developing diabetes in 2011 for MS and JMS were calculated after being adjusted for FG, age, sex and antihypertensive and antihyperlipidemic medication use, then further adjusted for HbA1c. The optimal cutoff points for FG, HbA1c and body mass index (BMI) to discriminate the development of diabetes and their sensitivities/specificities were obtained from receiver operating characteristic curves. These sensitivities/specificities were compared with the sensitivities/specificities of MS and JMS., Results: The ORs (95% confidence intervals (CIs)) of developing diabetes for MS and JMS were 1.36 (0.57-3.23) (p=0.484) and 3.23 (1.25-8.36) (p=0.016), respectively, after being adjusted for FG and 1.06 (0.39-2.86) (p=0.915) and 2.34 (0.79-6.95) (p=0.126), respectively, after being further adjusted for HbA1c. The sensitivities/specificities of FG, HbA1c, BMI, MS and JMS were 0.625/0.897, 0.828/0/919, 0.625/0.734, 0.375/0.911, and 0.375/0.941, respectively., Conclusion: MS and JMS were found to be poor predictors of diabetes in a Japanese health screening population.

Objective: Both increased serum levels of low-density lipoprotein cholesterol (LDLC) and metabolic syndrome (MetS) are associated with obesity and have been established to be risk factors of cardiovascular disease. However, studies on the relationship between LDLC and MetS have been limited., Methods: Cross-sectional (n=3,871) and longitudinal (n=2,558) associations between LDLC and MetS were examined in a Japanese health screening population., Results: The odds ratio (OR) [95% confidence interval (CI)] of coexisting MetS for each one SD increase in the LDLC level was 1.25 [1.12-1.40] (p<0.001) adjusted for body mass index (BMI) and other confounding covariates and 1.12 [0.97-1.28] (p=0.119) adjusted for numerical values of the components of MetS and other confounding covariates. The similarly adjusted ORs [95% CIs] for the highest quartile of LDLC (Q4) compared with the lowest quartile (Q1) were 1.76 [1.22-2.54] (p=0.002) and 1.46 (0.93-2.30) (p=0.101), respectively. The hazard ratio (HR) [95% CI] for developing MetS for each one SD increase in the LDLC level was 1.24 [1.10-1.40] (p<0.001) adjusted for BMI and other confounding covariates and 1.19 [1.05-1.34] (p=0.006) adjusted for the pre-existing dichotomous five components of MetS and other confounding covariates. The similarly adjusted HRs [95% CIs] for developing MetS for Q4 compared with Q1 were 1.71 [1.17-2.51] (p=0.006) and 1.61 [1.08-2.40] (p=0.020), respectively., Conclusion: The LDLC level is associated with coexisting MetS and functions as a predictor of the development of MetS, independent of BMI or the pre-existing components of MetS, in a Japanese health screening population.

Objective: The associations between atrial fibrillation (AF) or complete right bundle branch block (RBBB) and other laboratory tests have not been examined sufficiently in healthy populations., Methods: These associations were examined with multivariable logistic regression analyses using data from 6,381 apparently healthy subjects including 46 subjects with AF and 100 subjects with RBBB., Results: The mean age, body mass index (BMI), hemoglobin, the prevalence of male sex and a history of coronary heart disease (CHD) were significantly higher in subjects with AF or RBBB than without. The odds ratio (OR) (95% confidence interval (CI)) of AF was 1.62 (1.28-2.05) p<0.0001 for each 1 g/dL increment of hemoglobin and 1.07 (0.36-3.21) p=0.90 and 4.32 (1.29-14.43) p=0.017, respectively for the second and the third tertiles of hemoglobin compared with the first tertile after adjusting for sex, age, BMI, CHD, and other confounding covariates. The OR (95% CI) of RBBB was 1.53 (1.32-1.77) p<0.0001 for each 1 g/dL increment of hemoglobin and 2.53 (1.06-6.00) p=0.036, 3.10 (1.12-8.61) p=0.030, and 4.03 (0.91-17.82) p=0.066, respectively, for the second, third, and fourth quartiles of hemoglobin compared with the first quartile after adjusting for sex, age, BMI, CHD, and other confounding covariates., Conclusion: An increased blood levels of hemoglobin was independently associated with AF and RBBB after adjusting for sex, age, BMI, CHD, and other confounding covariates in apparently healthy subjects.

Among the ongoing attempts to enhance cognitive performance, an emergent and yet underrepresented venue is brought by hemoencefalographic neurofeedback (HEG). This paper presents three related advances in HEG neurofeedback for cognitive enhancement: a) a new HEG protocol for cognitive enhancement, as well as b) the results of independent measures of biological efficacy (EEG brain maps) extracted in three phases, during a one year follow up case study; c) the results of the first controlled clinical trial of HEG, designed to assess the efficacy of the technique for cognitive enhancement of an adult and neurologically intact population. The new protocol was developed in the environment of a software that organizes digital signal algorithms in a flowchart format. Brain maps were produced through 10 brain recordings. The clinical trial used a working memory test as its independent measure of achievement. The main conclusion of this study is that the technique appears to be clinically promising. Approaches to cognitive performance from a metabolic viewpoint should be explored further. However, it is particularly important to note that, to our knowledge, this is the world's first controlled clinical study on the matter and it is still early for an ultimate evaluation of the technique.

The aim of this study was to investigate the association between leukocyte subtype counts and hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia. Logistic regressions using hyper-LDL cholesterolemia, hypertriglyceridemia, and hypo-HDL cholesterolemia as a dependent variable and total leukocyte, basophil, eosinophil, neutrophil, lymphocyte, and monocyte counts as an independent variable were calculated adjusting for age, body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), smoking, drinking, and physical activity in apparently healthy Japanese men (1,803) and women (1,150). The odds ratio (OR) of hyper-LDL cholesterolemia for total leukocyte, eosinophil, and lymphocyte counts, the OR of hypertriglyceridemia for total leukocyte, eosinophil, neutrophil, and lymphocyte counts, and the OR of hypo-HDL cholesterolemia for total leukocyte, neutrophil, and lymphocyte counts were significant in men, and the OR of hyper-LDL cholesterolemia, for lymphocyte count, and the OR of hypo-HDL cholesterolemia for eosinophil count were significant in women. Lymphocyte count was significantly associated with hyper-LDL cholesterolemia independently of hs-CRP in apparently healthy Japanese.