Relationship between the combination of polyunsaturated fatty acids intake and psychological distress during pregnancy: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

No studies have examined the association of the combination of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs intake with psychological distress during pregnancy. To examine these associations, we divided Japanese pregnant women into 25 groups based on combining quintiles of n-3 PUFAs intake and quintiles of n-6 PUFAs intake. We conducted multivariable logistic regression analyses to assess the risk of psychological distress during pregnancy (Kessler Psychological Distress Scale ≥ 5 or 13). Compared to the third quintile of both n-3 PUFAs and n-6 PUFAs intake, the groups with unbalanced intake, high intake of both, and low intake of both were associated with a higher risk of both Kessler Psychological Distress Scale ≥ 5 and 13 in early and mid-pregnancy. Further research is needed to identify the precise combination of n-3 PUFAs and n-6 PUFAs intake associated with the lowest psychological distress during pregnancy.

A Novel IFITM5 Variant Associated with Phenotype of Osteoporosis with Calvarial Doughnut Lesions: A Case Report.

Osteogenesis imperfecta (OI) and other decreased bone density disorders comprise a heterogeneous group of heritable diseases with skeletal fragility. Recently, it was discovered that mutations in SGMS2, encoding sphingomyelin synthetase 2, result in aberrant sphingomyelin metabolism and lead to a novel form of OI termed osteoporosis with calvarial doughnut lesions (OP-CDL) with moderate to severe skeletal fragility and variable cranial hyperostotic lesions. This study describes a Japanese family with the skeletal phenotype of OP-CDL. The affected individuals have moderately severe, childhood-onset skeletal fragility with multiple long-bone fractures, scoliosis and bone deformities. In addition, they exhibit multiple CDLs or calvarial bumps with central radiolucency and peripheral radiopacity. However, SGMS2 sequencing was normal. Instead, whole-exome sequencing identified a novel IFITM5 missense mutation c.143A>G (p.N48S) (classified as a VUS by ACMG). IFITM5 encodes an osteoblast-restricted protein BRIL and a recurrent c.-14C>T mutation in its 5' UTR region results in OI type V, a distinctive subtype of OI associated with hyperplastic callus formation and ossification of the interosseous membranes. The patients described here have a phenotype clearly different from OI type V and with hyperostotic cranial lesions, feature previously unreported in association with IFITM5. Our findings expand the genetic spectrum of OP-CDL, indicate diverse phenotypic consequences of pathogenic IFITM5 variants, and imply an important role for BRIL in cranial skeletogenesis.

Copy number loss in the region of the ASPN gene in patients with acetabular dysplasia: ASPN CNV in acetabular dysplasia.

OBJECTIVES: We have previously investigated an association between the genome copy number variation (CNV) and acetabular dysplasia (AD). Hip osteoarthritis is associated with a genetic polymorphism in the aspartic acid repeat in the N-terminal region of the asporin (ASPN) gene; therefore, the present study aimed to investigate whether the CNV of ASPN is involved in the pathogenesis of AD. METHODS: Acetabular coverage of all subjects was evaluated using radiological findings (Sharp angle, centre-edge (CE) angle, acetabular roof obliquity (ARO) angle, and minimum joint space width). Genomic DNA was extracted from peripheral blood leukocytes. Agilent's region-targeted high-density oligonucleotide tiling microarray was used to analyse 64 female AD patients and 32 female control subjects. All statistical analyses were performed using EZR software (Fisher's exact probability test, Pearson's correlation test, and Student's t-test). RESULTS: CNV analysis of the ASPN gene revealed a copy number loss in significantly more AD patients (9/64) than control subjects (0/32; p = 0.0212). This loss occurred within a 60 kb region on 9q22.31, which harbours the gene for ASPN. The mean radiological parameters of these AD patients were significantly worse than those of the other subjects (Sharp angle, p = 0.0056; CE angle, p = 0.0076; ARO angle, p = 0.0065), and all nine patients required operative therapy such as total hip arthroplasty or pelvic osteotomy. Moreover, six of these nine patients had a history of operative or conservative therapy for developmental dysplasia of the hip. CONCLUSIONS: Copy number loss within the region harbouring the ASPN gene on 9q22.31 is associated with severe AD. A copy number loss in the ASPN gene region may play a role in the aetiology of severe AD.Cite this article: T. Sekimoto, M. Ishii, M. Emi, S. Kurogi, T. Funamoto, Y. Yonezawa, T. Tajima, T. Sakamoto, H. Hamada, E. Chosa. Copy number loss in the region of the ASPN gene in patients with acetabular dysplasia: ASPN CNV in acetabular dysplasia. Bone Joint Res 2017;6:439-445. DOI: 10.1302/2046-3758.67.BJR-2016-0094.R1.

A resonating broken symmetry configuration interaction approach for double-exchange magnetic systems.

The correct description for ion-radical systems has recently attracted much attention from density functional theory (DFT) researchers. Although several hybridization schemes using exact (Hartree-Fock) exchange and DFT exchange-correlation functionals have been proposed, it has been reported that such treatments do not work for the description of ion-radical systems. In this study we show that combining the exact exchange term in the Kohn-Sham DFT (or the Hartree-Fock equation) with the following resonating configuration interaction method is effective for the description of double-exchange type molecular magnetic interactions. The results are analyzed in relation to the 'many-electron self-interaction' concept that was recently proposed by DFT researchers.

Cyclopentadithiophene (CPDT) dimer dication: bipolaron model for quaterthiophenes.

[structure: see text] Cyclopentadithiophene (CPDT) dimers in which both 3,3' and 4' ',3' " positions were bridged with 1,3-dioxalane, carbonyl, or dicyanovinylidene were prepared. These compounds have small HOMO-LUMO gaps (1.03-2.25 eV). The electrochemical oxidation of a dicyanovinylidene-bridged CPDT dimer gave a dication that had a quinoid-like structure.

Release from or through a wax matrix system. I. Basic release properties of the wax matrix system.

Release properties from a wax matrix tablet was examined. To obtain basic release properties, the wax matrix tablet was prepared from a physical mixture of drug and wax powder (hydrogenated caster oil) at a fixed mixing ratio. Properties of release from the single flat-faced surface or curved side surface of the wax matrix tablet were examined. The applicability of the square-root time law and of Higuchi equations was confirmed. The release rate constant obtained as g/min(1/2) changed with the release direction. However, the release rate constant obtained as g/cm2 x min(1/2) was almost the same. Hence it was suggested that the release property was almost the same and the wax matrix structure was uniform independent of release surface or direction at a fixed mixing ratio. However, these equations could not explain the entire release process. The applicability of a semilogarithmic equation was not as good compared with the square-root time law or Higuchi equation. However, it was revealed that the semilogarithmic equation was available to simulate the entire release process, even though the fit was somewhat poor. Hence it was suggested that the semilogarithmic equation was sufficient to describe the release process. The release rate constant was varied with release direction. However, these release rate constants were expressed by a function of the effective surface area and initial amount, independent of the release direction.

Denaturation and aggregation of hen egg lysozyme in aqueous ethanol solution studied by dynamic light scattering.

We applied dynamic light scattering technique on the model system of hen egg lysozyme in salt-free aqueous ethanol solution to study the mechanism of denaturation and aggregation of protein. At low ethanol concentration [0-63% (v/v)], the fast relaxation mode was observed, which was caused by lysozyme molecules in the solution interacting with each other with strong repulsive electrostatic force. At 45 and 63% (v/v) ethanol, the slow relaxation mode was also observed, which showed translational diffusive nature, similar to that observed in salt-free polyelectrolyte solution. At 72 or 81% (v/v) ethanol, the slow mode disappeared, leaving only the fast mode. However, the mutual diffusion coefficients obtained from the fast mode at 72 and 81% (v/v) ethanol decreased by about one order of magnitude compared with those from the fast mode at 0-63% (v/v). The reported alcohol-induced conformational transformation of lysozyme molecules at >60% (v/v) ethanol from their native structure to an alpha-helix-rich structure might cause such drastic decrease in the mutual diffusion coefficients. At the highest ethanol concentration of 90% (v/v), the slow mode reappeared, and its relaxation rate was decreasing with elapsed time, which is possibly due to the growth of aggregates of lysozyme molecules. X-ray diffraction results suggested that the intermolecular beta-sheet formation caused the aggregation. Thus, our results indicated that the change in molecular structure of lysozyme closely relates to the diffusion of molecules and their aggregation.

The association between intravenous haloperidol and prolonged QT interval.

Although intravenous haloperidol (HAL) is an effective medication that is often prescribed to treat agitation, several instances of torsade de pointes or prolonged QT interval have been reported. To investigate the association between intravenous HAL and QT prolongation and between intravenous HAL and ventricular tachyarrhythmia, a cross-sectional cohort study was performed that included measuring corrected QT intervals (QTc) on an emergency basis before intravenous HAL and continuously monitoring electrocardiographic (ECG) findings after intravenous HAL. During a 2-month period, 47 patients received intravenous injections to control psychotic disruptive behavior. According to clinical practice, patients were divided as follows. The FZ-alone group was treated with intravenous flunitrazepam (FZ), and the FZ-plus-HAL group received intravenous FZ followed by intravenous HAL. Although the difference in the mean QTc immediately after intravenous FZ between the two groups was not significant, the mean QTc after 8 hours in the FZ-plus-HAL group was longer than that in the FZ-alone group (p < 0.001). Four patients in the FZ-plus-HAL group had a QTc of more than 500 msec after 8 hours. The change in QTc during 8 hours significantly differed between the two groups (t = 2.64, p > 0.05). Furthermore, the change in QTc was moderately correlated with the dose of intravenous HAL, as evidenced by a coefficient of correlation of 0.48 (p < 0.001). However, ventricular tachyarrhythmia was not detected among 307 patients within a 1-year period, although the ECG was continuously monitored for at least 8 hours after intravenous HAL. The modest nature of QTc prolongation and the apparent absence of ventricular tachyarrhythmia under continuous ECG monitoring indicate that QTc prolongation associated with intravenous HAL is not necessarily dangerous. However, in an emergency situation, clinicians cannot exclude patients predisposed to torsade de pointes, such as those with inherited ion channel disorders. Therefore, clinicians should be aware of the association between intravenous HAL and QT prolongation.

Spectral analysis of human tremor during cognitive tasks.

Many stresses occur in our daily lives. Some of these are part of diseases of the nervous system such as ataxia and neuroses. Certain body tremors may be related to these stresses. The rhythmic movement of various muscle groups, similar to a fast circadian rhythm, is defined as a tremor. These tremors, occurring during cognitive tasks, have been recorded by one-dimensional accelerometer in use in our laboratory. In this expanded study, we recorded three-dimensional body displacements with an optical motion capture system while subjects were performing the tasks of intent listening, reading and mental arithmetic calculations. The recorded displacements were subjected to spectral analysis using the Fast Fourier transform (FFT). The results indicate that the body vibration amplitude spectrum caused by mental arithmetic is significantly increased in the frequency rage of 0.5 to 0.7 Hz, when compared to those recorded during other tasks. The induced tremor, as well as general invisible body micro-vibration, were obtained from the three-dimensional body displacements.

A Web-based home helper support system.

A web-based "Home Helper" support system has been developed for improving scheduling and record keeping efficiency and for eliminating unnecessary travel. This support system consists of a wireless internet mobile phone for each "Home Helper" and a server at the main office. After each visit, the Home Helpers send their care reports via the mobile phone to the office server. This server computer then creates the "filings" automatically and in appropriate format for insurance and government use.

NaCl-activated nucleoside diphosphate kinase from extremely halophilic archaeon, Halobacterium salinarum, maintains native conformation without salt.

Enzymes from extremely halophilic archaea are readily denatured in the absence of a high salt concentration. However, we have observed here that a nucleoside diphosphate kinase prepared from Halobacterium salinarum was active and stable in the absence of salt, though it has the amino acid composition characteristic of halophilic enzymes. Recombinant nucleoside diphosphate kinase expressed in Escherichia coli requires salt for activation in vitro, but once it acquires the proper folding, it no longer requires the presence of salts for its activity and stability.

Mut-Test to detect substances suppressing spontaneous mutation due to oxidative damage.

Since it has been considered that suppression of spontaneous mutation in cells is related to suppression of spontaneous carcinogenesis, it is significant to detect substances which suppress spontaneous mutation in bacterial cells such as Escherichia coli and Salmonella typhimurium in the environment. However, since the frequency of spontaneous mutation in bacteria is usually very low, generally 10(-8)-10(-10),it is difficult to determine significant suppressive ability of such substances on spontaneous mutation. A new method, Mut-Test, was developed by us, applying Luria & Delbruck fluctuation test, to detect substances which suppress spontaneous mutation using E. coli mutT mutant in which spontaneous mutation frequency due to oxidative damage is enhanced to approximately 500-1000 times of the wild type strain. Suppressive abilities of two hydroxyl radical scavengers: D(-)-mannitol and thiourea, were examined and clear positive results were obtained, suggesting that the radical scavengers are suitable as the positive control for the test. Using Mut-Test, suppressive abilities of four vitamins: L-ascorbic acid, beta-carotene, folic acid and riboflavin; 10 polyphenols: caffeic acid, ellagic acid, (-)-epicatechin, (-)-epicatechin gallate, (-)-epigallocatechin, gallic acid, pyrocatechol, pyrogallol, quercetin and tannic acid which are recognized as antimutagens, were examined. Furthermore, the concentrations for 50% of suppressive abilities of five positive samples, L-ascorbic acid, folic acid, caffeic acid, pyrocatechol and pyrogallol were compared. Negative results were obtained in nine samples, riboflavin, tannic acid, etc. suggesting that their antimutagenic effect on cells may not be related to oxidative damage in cells.

Formation of large DNA aggregates induced by spermidine.

The formation of large DNA aggregates induced by spermidine was investigated by UV absorptiometry and polarizing microscopy. The present results reveal that it is stepwise and involves the following morphological variations: fiber, fiber bundles, and a highly condensed phase. Furthermore, the influence of DNA concentration on not only the spermidine concentration required for the DNA aggregation but also the concentration of free spermidine during the aggregation is analyzed.

Characterization of nucleoside diphosphate kinase from moderately halophilic eubacteria.

Nucleoside diphosphate kinase was purified to apparent homogeneity from naturally isolated moderately halophilic eubacteria by ATP-agarose and phenyl-5PW column chromatographies. The molecular mass of this enzyme was 15 kDa by time-of-flight mass-spectrometry. This protein showed anomalous mobility on SDS-PAGE which is typical of a halophilic protein. It was stable and active over a wide range of salt concentrations, from 0 to 4.0 M NaCl.

Anaerobic transformation of chlorophenols in methanogenic sludge unexposed to chlorophenols.

Transformation of all 19 chlorophenol (CP) isomers was investigated in a laboratory anaerobic methanogenic sludge that had not been exposed to synthetic chemicals. Concentration of CP was analyzed over time to calculate disappearance rate constants using first-order reaction kinetics and all possible CP degradation pathways were estimated. The rate constants ranged between 0.46 x 10(-3) and 0.161 day(-1). CPs were transformed via dechlorination. The chlorine atom at the ortho-position was the most easily dechlorinated, whereas dechlorination rate at the para-position was lowest. The overall pathways of CP transformation were much less diverse than that we previously found for contaminated sediment. The Dolfing hypothesis of microbial selection of the most thermodynamically favorable pathways was not applicable for CP transformation in this study as well as previous study performed by our group.

Prolonged QT interval in acute psychotic patients.

Some recent clinical studies indicate that hypokalemia is characteristic for acute psychotic patients at the time of emergency admission. As hypokalemia is one of the major causes for prolonged QT interval, it was hypothesized that acute psychotic patients could show prolonged QT interval. Sixty-seven drug-free, acute psychotic patients were evaluated for corrected QT (QTc) interval, as well as demographic and clinical characteristics at the time of emergency admission. The mean QTc interval of psychiatric emergency patients was prolonged, and the mean QTc interval of psychiatric emergency patients was longer than that of psychiatric outpatients (t=5.20, P<0.0001). Age- or gender-related difference, circadian fluctuation of QT interval, medication, concomitant disease, obesity, and serum electrolytes except potassium were not major causes. There was a significant negative correlation as evidenced by a coefficient of correlation of -0.28 (P<0.05). As psychiatric emergency patients often receive parenteral antipsychotics, which may have adverse effects on prolonged QT interval, paying attention to QT interval might have some clinical significance on emergency admission.

A system for the ambulatory recording and analysis of nonlinear heart rate dynamics.

The study of cardiac dynamics is a topic of great clinic and experimental concern. However, the ability to apply methods from the emerging field of nonlinear dynamics to cardiac time series has been limited by the demand for large amounts of relatively artifact-free data. Both the ability to collect such data and the capacity to analysis such large data sets represents limits. In the present paper we describe a system that allows for the collection of large amounts of high quality data and the analysis of large data sets. The recording system consists of a miniature, single-module electrocardiogram-recording device. This module consists of an integrated three-electrode device that is attached to the chest of the subject. A low power 8-bit micro-controller detects the R-spike and stores the time between R-spikes in milliseconds on a 512 KB EEPROM. This system can record continuously for over four days. The output of this system is down-loaded to a PC and the RR intervals fed to a suite of digital signal processing programs. Among other things, estimates of Approximate Entropy and Poincaire plots are generated. This system will expand the capability of researchers and clinicians to investigate nonlinear cardiac dynamics in ambulatory subjects.

A microcomputer-based data acquisition system for ECG, body and ambient temperatures measurement during bathing.

A data acquisition system employing a low power 8 bit microcomputer has been developed for heart rate variability monitoring before, during and after bathing. The system consists of three integral chest electrodes, two temperature sensors, an instrumentation amplifier, a low power 8-bit single chip microcomputer (SMC) and a 4 MB compact flash memory (CFM). The ECG from the electrodes is converted to an 8-bit digital format at a 1 ms rate by an A/D converter in the SMC. Both signals from the body and ambient temperature sensors are converted to an 8-bit digital format every 1 second. These data are stored by the CFM. The system is powered by a rechargeable 3.6 V lithium battery. The 4 x 11 x 1 cm system is encapsulated in epoxy and silicone, yielding a total volume of 44 cc. The weight is 100 g.

Human fetal skin fibroblast migration stimulated by the autocrine growth factor bFGF is mediated by phospholipase A(2) via arachidonic acid without the involvement of pertussis toxin-sensitive G-protein.

We reported previously that human fetal skin fibroblast migration into a denuded area was stimulated by an autocrine factor, basic fibroblast growth factor (bFGF). Since the signal transduction pathway of this migration is unknown, we attempted to clarify it by comparing this fibroblast migration with a previously reported bovine endothelial cell migration into a wounded area stimulated by an addition of bFGF, in which the bFGF signal was mediated by phospholipase A(2)-coupled G-protein and phospholipase A(2) (PLA(2)) via arachidonic acid. Our study demonstrated that pertussis toxin, a specific inhibitor of PLA(2)-coupled G-protein, did not suppress human fetal skin fibroblast migration, but 2-(p-amylcinnamyl)amino-4-chlorobensoic acid (ONO-RS-082), a PLA(2) inhibitor, did. Since ONO-RS-082 is a non-specific PLA(2) inhibitor, a cytoplasmic, Ca-dependent PLA(2) (cPLA(2)) inhibitor, AACOCF3, was examined. AACOCF3 suppressed cell migration in certain concentrations. The PLA(2) inhibitor-suppressed cell migration was restored by adding arachidonic acid, and cell migration suppressed by anti-bFGF antibodies was restored by adding arachidonic acid. In addition, pertussis toxin did not suppress arachidonic acid release, which shows an action of PLA(2), but AACOCF3 did. These results indicate that human fetal skin fibroblast migration stimulated by an autocrine factor, bFGF, was mediated by PLA(2) via arachidonic acid without the involvement of PLA(2)-coupled G-protein.

Inhibitory effects of human serum on human fetal skin fibroblast migration: migration-inhibitory activity and substances in serum, and its age-related changes.

In order to clarify the environmental factors modulating cell migration, we investigated the effects of human serum on cell migration, and found that serum from adult donors strongly (by 48%) suppressed the migration of human fetal skin fibroblasts into a denuded area in a cell monolayer. Human serum from old donors inhibited cell migration more strongly than that from adult donors. Next, we investigated the properties of migration-inhibitory activity of human serum and serum proteins in order to identify migration-inhibitory substances. Human serum from adult donors strongly suppressed the migration of human fetal skin fibroblasts, although it stimulated cell proliferation more strongly than fetal bovine serum (FBS), indicating that the inhibitory effects of human serum on cell migration was not due to its toxic effects. The inhibition of cell migration by human serum was concentration dependent. It was demonstrated that the inhibition did not depend on the inhibitory effects of human serum on collagen synthesis. The migration-inhibitory activity was seen in fractions over 100 kDa, as determined by an ultrafiltration membrane, and no inhibitory activity was observed in fractions under 100 kDa. On the other hand, it was not detected either in fractions over 100 kDa or under 100 kDa in FBS. Among the over 100 kDa human serum proteins examined, gamma-globulin, alpha2-macroglobulin, and low density lipoprotein (LDL) suppressed fibroblast migration in a concentration-dependent manner. However, among the three, cell migration-inhibiting activity of gamma-globulin almost disappeared when cell migration was conducted in 10% FBS-supplemented medium. These results indicated that alplha2-macroglobulin and LDL were candidate substances for cell migration-inhibiting activity in human serum.