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Aims: Acute myocardial infarction (AMI) causes irreversible damage to cardiomyocytes due to the discontinuation of oxygen supply and leads to systemic oxidative stress. It has been reported that high-density lipoprotein (HDL) particles have antioxidant capacity, and reduced antioxidant capacity is associated with decreased cholesterol efflux capacity (CEC). The purpose of this study was to clarify the usefulness of CEC measurement in patients with AMI., Methods: We investigated the association between CEC and oxidative stress status in a case-control study. This study included 193 AMI cases and 445 age- and sex-matched controls. We examined the associations of CEC with HDL-cholesterol (HDL-C) and oxidized human serum albumin (HSA), an index of systemic oxidative stress status, and the effect of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which has been reported to affect HDL-C level and risk for MI, on these associations., Results: Both bivariable and multivariable analyses showed that CEC was positively correlated with HDL-C levels in both AMI cases and controls, with a weaker correlation in AMI cases than in controls. In AMI cases, oxidized HSA levels were associated with CEC in both bivariable and multivariable analyses, but not with HDL-C. These associations did not differ among the ALDH2 genotypes., Conclusions: CEC, but not HDL-C level, reflects systemic oxidative stress status in patients with AMI. CEC measurement for patients with AMI may be useful in that it provides information on systemic oxidative stress status as well as atherosclerosis risk.

Aims: High levels of high-density lipoprotein cholesterol (HDL-C) are not necessarily effective in preventing atherosclerotic cardiovascular disease, and cholesterol efflux capacity (CEC) has attracted attention regarding HDL functionality. We aimed to elucidate whether drinking habits are associated with CEC levels, while also paying careful attention to confounding factors including serum HDL-C levels, other life style factors, and rs671 ( ＊ 2), a genetic polymorphism of the aldehyde dehydrogenase 2 (ALDH2) gene determining alcohol consumption habit., Methods: A cross-sectional study was performed in 505 Japanese male subjects who were recruited from a health screening program. Associations of HDL-C and CEC levels with drinking habits and ALDH2 genotypes were examined., Results: The genotype frequencies of ALDH2 ＊ 1/ ＊ 1 (homozygous wild-type genotype), ＊ 1/ ＊ 2 and ＊ 2/ ＊ 2 (homozygous mutant genotype) were 55%, 37% and 8%, respectively. Both HDL-C and CEC levels were higher in ALDH2 ＊ 1/ ＊ 1 genotype carriers than in ＊ 2 allele carriers. Although HDL-C levels were higher in subjects who had a drinking habit than in non-drinkers, CEC levels tended to be lower in subjects with ≥ 46 g/day of alcohol consumption than in non-drinkers. Furthermore, CEC levels tended to be lower in ALDH2 ＊ 1/ ＊ 1 genotype carriers with a drinking habit of ≥ 46 g/day than non-drinkers, while for ＊ 2 allele carriers, CEC levels tended to be lower with a drinking habit of 23-45.9 g/day compared to no drinking habit., Conclusions: Our results suggest that heavy drinking habits may tend to decrease CEC levels, and in the ALDH2 ＊ 2 allele carriers, even moderate drinking habits may tend to decrease CEC levels.

Melinjo seed extract (MSE) contains large amounts of polyphenols, including dimers of trans-resveratrol (e.g. gnetin C, L, gnemonoside A, B and D), and has been shown to potentially improve obesity. However, there is no clinical evidence regarding the anti-obesity effects of MSE, and its mechanisms are also unclear. We investigated the hypothesis that MSE supplementation increases the adiponectin (APN) multimerization via the up-regulation of disulfide bond A oxidoreductase-like protein (DsbA-L) under either or both physiological and obese conditions. To investigate the effect of MSE on the physiological condition, 42 healthy young volunteers were enrolled in a randomized, double-blind placebo-controlled clinical trial for 14 days. The participants were randomly assigned to the MSE 150 mg/day, MSE 300 mg/day or placebo groups. Furthermore, in order to investigate the effect of MSE on APN levels under obese conditions, we administered MSE powder (500 or 1000 mg/kg/day) to control-diet- or high-fat-diet (HFD)-fed C57BL/6 mice for 4 weeks. All participants completed the clinical trial. The administration of MSE 300 mg/day was associated with an increase in the ratio of HMW/total APN in relation to the genes regulating APN multimerization, including DsbA-L. Furthermore, this effect of MSE was more pronounced in carriers of the DsbA-L rs191776 G/T or T/T genotype than in others. In addition, the administration of MSE to HFD mice suppressed their metabolic abnormalities (i.e. weight gain, increased blood glucose level and fat mass accumulation) and increased the levels of total and HMW APN in serum and the mRNA levels of ADIPOQ and DsbA-L in adipose tissue. The present study suggests that MSE may exert beneficial effects via APN multimerization in relation to the induction of DsbA-L under both physiological and obese conditions.

There were few reports of oxytocin (OXT) concentrations of autism spectrum disorder (ASD) patients with severe intellectual disabilities. We measured serum OXT concentrations in 79 hospitalized patients with severe intellectual disabilities (16-60 years old, 50 males and 29 females, 54 ASD patients) and investigated the associations between serum OXT concentration, symptom scores, sex differences, and autism spectrum disorder. There were no significant effects of diagnosis, severity of intellectual disabilities, and total score of the Japanese version of the Aberrant Behavior Checklist (ABC-J), the Childhood Autism Rating Scale-Tokyo Version (CARS-TV), and the Japanese version of the Repetitive Behavior Scale-Revised (RBS-R). However, there were sex differences in the correlations between OXT concentrations and subscale scores in the ASD group. The male ASD group (n = 39) showed negative correlations between RBS-R Self-injurious and Sameness subscale scores and serum OXT concentrations. In the female ASD group(n = 15), CARS-TV Nonverbal communication subscale scores and RBS-R Compulsive subscale scores were seen to positively correlate with serum OXT concentrations. These findings suggest that OXT functions differ in males and females with severe intellectual disabilities and that OXT partly affects autism and related to some of the repetitive behaviors and nonverbal communication, in ASD patients with severe intellectual disabilities., (Copyright © 2018. Published by Elsevier B.V.)

The antitumor and actin-depolymerizing marine macrolide aplyronine A (ApA) synergistically binds to tubulin in association with actin, and prevents spindle formation and mitosis. While the crystal structure of the actin ApA complex was solved in 2006, its interaction with the tubulin heterodimer has not been clarified. To investigate the binding modes of ApA as a unique protein-protein interaction (PPI)-inducer between these two cytoskeletal proteins, we prepared its photoaffinity acetylene and fluorescent derivatives with the aid of molecular modeling studies for probe design. Among these three derivatives, the ApA-PPA-TAMRA probe specifically photoreacted with both actin and tubulin in vitro. However, the photolabeling yield of tubulin was quite low (up to ∼1%), and one of the major side-reactions was the addition of a water molecule to the carbene species generated from an aryldiazirine moiety on the hydrophilic surface of actin., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Mathematical analysis by finite element modeling methods was used in conjunction with laboratory bench experiments in selecting appropriate stiffness parameters for internal fixation plate designs. Bench experiments performed included tests of an idealized plated magnesium tube and of a plated canine femur. Finite element modeling of the plate-tube and plate-bone structures was also performed, and the computed results were compared with those obtained experimentally. Three types of internal fixation plates--one "rigid" control plate and two less rigid experimental plates--were examined using both the finite element and experimental models. These plates were further examined by finite element modeling of a plated human femur during single stance loading. In all cases, the "rigid" control plate was found to shield the underlying bone from stress, while both experimental plates were found to have significantly less bone stress shielding. Our findings suggest that an improved plate design should have a low axial stiffness but moderate bending and torsional stiffnesses to facilitate fracture healing and bone remodeling without causing osteopenia.

The finite element method (FEM), an advanced method of computer simulation, is used to examine biomechanical studies of hydrocephalus. Biot's theory of consolidation, which describes the mechanical behavior of a porous medium containing viscous fluid, is applied to represent the coupled behavior of tissue and fluid in the hydrocephalic brain. A computer simulation of the hydrocephalic process is carried out by FEM to evaluate the mathematical model. A two-dimensional finite element model is constructed using a horizontal computed tomographic (CT) slice of the brain. Specifying the material properties of the brain parenchyma, the loading characteristics, and the boundary conditions, the change of interstitial pressure, intracerebral stress distribution, and ventricular configuration are computed and graphically represented. The results of the computer simulation are compared with the findings of CT and magnetic resonance imaging of hydrocephalic patients. The progress of periventricular cerebrospinal fluid edema and ventricular enlargement is well represented by the mathematical model. The model demonstrated that stress concentration in the brain tissue and increased parenchymal hydraulic conductivity play an important role in the generation of periventricular cerebrospinal fluid edema.

Growth force proposed as an etiological factor in idiopathic scoliosis was analysed by a mathematical simulation; the results were compared with clinical roentgenograms of patients with idiopathic scoliosis. Growth force is a self-equilibrating internal stress derived from unbalanced growth between two adjacent structures with different growth rates. In the simulation, the localized growth force made the whole spinal column buckle. Two hundred anteroposterior roentgenograms were then compared with the buckling curves. The three most similar buckling curves for each roentgenogram were selected. Of the 600 selected curves, 406 were considered to have produced a high similarity. The curves produced by a growth force extending over a small area, especially at the mid-lower thoracic and lumbar regions, were qualified as curves with a high similarity. The growth force thus does not appear uniformly all over the spinal column but locally and at the mid-lower thoracic or lumbar region. This growth force may represent a factor in the etiology of idiopathic scoliosis.