Bicuspid aortic valves undergo excessive strain during opening: A simulation study

ObjectiveThe objective of this study was to examine the influence of the morphologic characteristics of the bicuspid aortic valve on its disease progression by comparing the motion, stress/strain distribution, and blood flow of normal and stenotic tricuspid valves using simulation models.MethodsBicuspid, stenotic tricuspid with commissural fusion or thickened leaflet, and normal aortic valves were modeled with internal blood flow. Blood flow and the motion of aortic valve leaflets were studied using fluid–structure interaction finite element analysis, and stress/strain (curvature) distributions were calculated during the cardiac cycle. To mimic disease progression, we modified the local thickness of the leaflet where the bending stress was above a threshold.ResultsTransvalvular pressure gradient was greater in the bicuspid valve compared with the stenotic tricuspid valve with a similar valvular area. The bending strain (curvature) increased in both stenotic tricuspid and bicuspid valves, but a greater increase was observed in the bicuspid valve, and this was concentrated on the midline of the fused leaflets. During disease progression analysis, severity of the stenosis increased only in the bicuspid aortic valve model in terms of valvular area and pressure gradient.ConclusionsThe characteristic morphology of the bicuspid valve creates excessive bending strain on the leaflets during ventricular ejection. Such mechanical stress may be responsible for the rapid progression of this disease

ODB: a database of operons accumulating known operons across multiple genomes

Operon structures play an important role in co-regulation in prokaryotes. Although over 200 complete genome sequences are now available, databases providing genome-wide operon information have been limited to certain specific genomes. Thus, we have developed an ODB (Operon DataBase), which provides a data retrieval system of known operons among the many complete genomes. Additionally, putative operons that are conserved in terms of known operons are also provided. The current version of our database contains about 2000 known operon information in more than 50 genomes and about 13 000 putative operons in more than 200 genomes. This system integrates four types of associations: genome context, gene co-expression obtained from microarray data, functional links in biological pathways and the conservation of gene order across the genomes. These associations are indicators of the genes that organize an operon, and the combination of these indicators allows us to predict more reliable operons. Furthermore, our system validates these predictions using known operon information obtained from the literature. This database integrates known literature-based information and genomic data. In addition, it provides an operon prediction tool, which make the system useful for both bioinformatics researchers and experimental biologists. Our database is accessible at

Classes of Multichannel EEG Microstates in Light and Deep Hypnotic Conditions

The study assessed the brain electric mechanisms of light and deep hypnotic conditions in the framework of EEG temporal microstates. Multichannel EEG of healthy volunteers during initial resting, light hypnosis, deep hypnosis, and eventual recovery was analyzed into temporal EEG microstates of four classes. Microstates are defined by the spatial configuration of their potential distribution maps (‹potential landscapes') on the head surface. Because different potential landscapes must have been generated by different active neural assemblies, it is reasonable to assume that they also incorporate different brain functions. The observed four microstate classes were very similar to the four standard microstate classes A, B, C, D [Koenig, T. etal. Neuroimage, 2002;16: 41-8] and were labeled correspondingly. We expected a progression of microstate characteristics from initial resting to light to deep hypnosis. But, all three microstate parameters (duration, occurrence/second and %time coverage) yielded values for initial resting and final recovery that were between those of the two hypnotic conditions of light and deep hypnosis. Microstates of the classes B and D showed decreased duration, occurrence/second and %time coverage in deep hypnosis compared to light hypnosis; this was contrary to microstates of classes A and C which showed increased values of all three parameters. Reviewing the available information about microstates in other conditions, the changes from resting to light hypnosis in certain respects are reminiscent of changes to meditation states, and changes to deep hypnosis of those in schizophrenic state

Selective Cyclooxygenase-2 Inhibitor Prevents Cisplatin-induced Tumorigenesis in A/J Mice

Cisplatin is used to treat lung cancer;however, it is also a known carcinogen. Cyclooxygenase-2 (COX-2) inhibitors have been shown to prevent carcinogen-induced experimental tumors. We investigated the effect of a COX-2 inhibitor, celecoxib, on cisplatin-induced lung tumors. One hundred twenty 4-week-old A/J mice were divided into 6 groups:group 1, no treatment;group 2, low-dose celecoxib (150mg/kg);group 3, high-dose celecoxib (1,500mg/kg);group 4, cisplatin alone;group 5, cisplatin plus low-dose celecoxib;and group 6, cisplatin plus high-dose celecoxib. Mice in groups 4-6 were administered cisplatin (1.62mg/kg, i.p.) once a week for 10 weeks between 7 and 16 weeks of age. All mice were sacrificed at week 30. Tumor incidence was 15.8% in group 1, 25% in group 2, 26.3% in group 3, 60% in group 4, 50% in group 5, and 50% in group 6. Tumor multiplicity was 0.2, 0.3, 0.3, 1.3, 1.0, and 0.6 in groups 1-6, respectively. Tumor multiplicity in the cisplatin-treated mice was reduced by celecoxib treatment in a dose-dependent manner (p＜0.05, group 4 vs. group 6). Celecoxib significantly reduced COX-2 expression in cisplatin-induced tumors (p＜0.01, group 4 vs. group 6)

SPARQL-enabled identifier conversion with Identifiers.org

Motivation: On the semantic web, in life sciences in particular, data is often distributed via multiple resources. Each of these sources is likely to use their own International Resource Identifier for conceptually the same resource or database record. The lack of correspondence between identifiers introduces a barrier when executing federated SPARQL queries across life science data. Results: We introduce a novel SPARQL-based service to enable on-the-fly integration of life science data. This service uses the identifier patterns defined in the Identifiers.org Registry to generate a plurality of identifier variants, which can then be used to match source identifiers with target identifiers. We demonstrate the utility of this identifier integration approach by answering queries across major producers of life science Linked Data. Availability and implementation: The SPARQL-based identifier conversion service is available without restriction at http://identifiers.org/services/sparql. Contact: [email protected]

Thymoma-associated Graft-versus-Host Disease-like Erythroderma

We report a 40-year-old woman with recurrent thymoma associated with myasthenia gravis, in whom an unusual form of erythroderma developed. A histological examination revealed a graft-versus-host disease (GVHD)-like reaction. After high-dose steroid therapy, the metastatic thymoma lesion in the abdominal cavity was reduced in size from 9.5 × 6 × 7.5 cm to 4 × 3 × 1 cm in diameter. Nevertheless, the GVHD-like erythroderma become aggravated, her condition worsened, and the patient finally suffered from respiratory failure and died of sepsis. A GVHD-like reaction may be a rare presentation of thymoma-associated immunological disorders such as myasthenia gravis or pure red cell aplasia. Herein, we discuss the present case and review pertinent reports of thymoma cases associated with GVHD

The effect of cognitive behavioral therapy on future thinking in patients with major depressive disorder: A randomized controlled trial

BackgroundPessimistic thinking about the future is one of the cardinal symptoms of major depression. Few studies have assessed changes in pessimistic thinking after undergoing cognitive behavioral therapy (CBT). A randomized clinical trial (RCT) was conducted with patients diagnosed with major depressive disorder (MDD) to determine whether receiving a course of CBT affects pessimistic future thinking using a future thinking task.MethodsThirty-one patients with MDD were randomly assigned to either CBT (n = 16) or a talking control (TC) (n = 15) for a 16-week intervention. The main outcomes were the change in response time (RT) and the ratio of the responses for positive valence, measured by the future thinking task. Secondary outcomes included the GRID-Hamilton Depression Rating Scale, the Beck Depression Inventory-Second Edition (BDI-II), the Dysfunctional Attitude Scale (DAS), and the word fluency test (WFT).ResultsRegarding the main outcomes, the CBT group showed reduced RT for the positive valence (within-group Cohen’s d = 0.7, p = 0.012) and negative valence (within-group Cohen’s d = 0.6, p = 0.03) in the distant future condition. The ratio of positive valence responses in both groups for all temporal conditions except for the distant past condition increased within group (distant future: CBT: Cohen’s d = 0.5, p = 0.04; TC: Cohen’s d = 0.8, p = 0.008; near future: CBT: Cohen’s d = 1.0, p < 0.001; TC: Cohen’s d = 1.1, p = 0.001; near past: CBT: Cohen’s d = 0.8, p = 0.005; TC: Cohen’s d = 1.0, p = 0.002). As for secondary outcomes, the CBT group showed greater improvement than the TC group regarding the need for social approval as measured by the DAS (p = 0.012).ConclusionPatients with MDD who received CBT showed a reduced RT for the positive and negative valence in the distant future condition. RT in the future thinking task for depressed patients may be a potential objective measure for the CBT treatment process. Because the present RCT is positioned as a pilot RCT, a confirmatory trial with a larger number of patients is warranted to elucidate the CBT treatment process that influences future thinking.Clinical trial registrationhttps://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000021028, identifier UMIN000018155

Non-HDL-C and CVD

Aims: We aimed to investigate the association between non-high-density lipoprotein cholesterol (non-HDL-C) levels and the risk of cardiovascular disease (CVD) and its subtypes. Methods: In this contemporary cohort study, we analyzed the data of 63,814 Japanese employees aged ≥ 30 years, without known CVD in 2012 and who were followed up for up to 8 years. The non-HDL-C level was divided into 5 groups: ＜110, 110-129, 130-149, 150-169, and ≥ 170 mg/dL. The Cox proportional hazards model was used to calculate the hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) for CVD and its subtypes associated with each non-HDL-C group, considering 130-149 mg/dL as the reference group. Results: During the study period, 271 participants developed CVD, including 78 myocardial infarctions and 193 strokes (102 ischemic strokes, 89 hemorrhagic strokes, and 2 unknowns). A U-shaped association between non-HDL-C and stroke was observed. In the analysis of stroke subtypes, the multivariable-adjusted HR (95% CI) for hemorrhagic stroke was 2.61 (1.19–5.72), 2.02 (0.95–4.29), 2.10 (1.01–4.36), and 1.98 (0.96-4.08), while that for ischemic stroke was 1.54 (0.77-3.07), 0.91 (0.46-1.80), 0.73 (0.38-1.41), and 1.50 (0.87-2.56) in the ＜110, 110-129, 150-169, and ≥ 170 mg/dL groups, respectively. Individuals with elevated non-HDL-C levels had a higher risk of myocardial infarction. Conclusions: High non-HDL-C levels were associated with an increased risk of myocardial infarction. Moreover, high and low non-HDL-C levels were associated with a high risk of stroke and its subtypes among Japanese workers