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IntroductionDepression can be considered to be a common psychological response to adversity or loss from which an individual may recover quickly based on a natural resilience mechanism. In major depressive disorder, however, we see that biopsychosocial factors exist that can prevent this natural resilience mechanism from taking effect.ObjectivesTo investigate neurotransmitter pathways linked with antidepressant response, genetic epidemiological studies and a literature assessment of biopsychosocial factors were conducted.MethodsNewly admitted patients with a depressive episode according to the criteria of ICD-10 (F32 or F33) who had not been on antidepressant medication for at least 6 months were recruited. More than half the patients have never been treated with antidepressant medication during their entire life. The patients’ depression was of at least moderate severity as measured by the Hamilton’s Depression Rating Scale (HAMD-17).To determine the effect of adrenergic pathway genes to antidepressant response, the outcome was measured by the difference in HAMD-17 score between entry and two weeks of treatment after two and four weeks of treatment and entry and four weeks of treatment. Multiple linear regression was conducted to identify the independent factor associated with ΔHAMD-17 between the three time periods, including age, sex, depression diagnosis, type of antidepressant taken and selected SNPs.Literature assesement utilised a snowball technique, building on prior literature reviews conducted. The selection of included literature was determined by the authors.ResultsThe Tomosk cohort was mainly women, with less than 20% of patient being male. The cohort was dynamic thus the number of participants involved in each investigation varied. Most patients took SSRIs, specifically sertraline, paroxetine, escitalopram, fluoxetine and fluvoxamine. Comparing the medication taken, ΔHAMD-17 was significantly more improved in participants taking tricyclic antidepressants at 0 - 2 weeks and 0 - 4 weeks.From our literature assesment, we determined that targeted therapy can undermine the influence of biopsychosocial factors and allow natural resilience to bring depression to an end. Many mental activities is not exclusively individual, but depends on the sociocultural context as people are part of a community.ConclusionsDepressive disorders can be understood as a rather habitual dysregulation of human behavior which, unlike normal behavior, is not limited by natural resilience in time and severity. Our investigations looked at polymorphisms impacting serotonergic, dopaminergic and adrenergic neurotransmissions and enzymes.While some associations were found, it did not match our literature findings. For future investigation, epidemiological and pathogenetic biological psychiatric research should be aimed at identifying biopsychosocial factors that frustrate the natural recovery process.Disclosure of InterestNone Declared

Objectives:A large-scale postmarketing surveillance (PMS) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis (RA).Methods:The PMS study was performed for all patients with RA who were treated with infliximab. They were consecutively registered in the PMS study at the initiation of infliximab treatment and were prospectively monitored with all adverse events noted for a period of 6 months. All case reports, which include safety-related events, were collected monthly.Results:Adverse drug reactions (ADRs) were assessed for 6 months in 5000 patients who were consecutively enrolled in the PMS study. The incidence rates of total and serious ADRs were 28.0% and 6.2%, respectively. “Infections” or “respiratory disorders” were most commonly observed among serious ADRs. Bacterial pneumonia developed in 2.2%, tuberculosis in 0.3%, suspected Pneumocystis jiroveci pneumonia (PCP) in 0.4% and interstitial pneumonitis in 0.5%. Bacterial pneumonia (for which individuals of male gender, of older age and those with advanced rheumatoid arthritis and comorbid respiratory disease were most at risk) began to develop immediately after the start of treatment, while tuberculosis, PCP and interstitial pneumonitis developed about 1 month later. Serious infusion reactions were observed in 0.5% and were more likely to occur in patients who had participated in previous clinical trials of infliximab.Conclusion:This postmarketing surveillance study of patients treated with infliximab showed that infliximab in combination with low-dose MTX was well tolerated in Japanese patients with active RA.

Multifilling with La, Ba, Ga, and Ti in p -type skutterudite and Yb, Ca, Al, Ga, and In in n -type skutterudite remarkably reduces their thermal conductivity, resulting in enhancement of their dimensionless figure of merit ZT to ZT  = 0.75 for p -type (La,Ba,Ga,Ti) 1 (Fe,Co) 4 Sb 12 and ZT  = 1.0 for n -type (Yb,Ca,Al,Ga,In) 0.7 (Co,Fe) 4 Sb 12 . A thermoelectric module technology suitable for these skutterudites including diffusion barrier and electrode materials has been established. The diffusion barrier materials allow the electrode to coexist stably with the p / n skutterudites in the module’s working temperature range of room temperature to 600°C. Under conditions of hot/cold-side temperatures of 600°C/50°C, a skutterudite module with size of 50 mm × 50 mm × 7.6 mm exhibited generation performance of 32 W power output and 8% thermoelectric conversion efficiency.

Due to their excellent thermoelectric (TE) performance, skutterudite materials have been selected by many laboratories and companies for development of TE modules to recover power from waste heat at high temperatures (300°C to 600°C). After years of effort, we have developed reliable n - and p -type skutterudite materials showing maximum figure of merit ( ZT ) of 1.0 at 550°C and 0.75 at 450°C, respectively. In this work, we systematically investigated the performance of a module made using these two kinds of skutterudite. We demonstrate ∼7.2% conversion efficiency for temperature of 600°C at the hot side of the module and 50°C at the cold side, and show that the module had excellent stability in the high-temperature environment. Further improving the TE performance of our skutterudites, the conversion efficiency reached ∼8.5% under the same condition.

To develop gene-modified T-cell-based antileukemia adoptive immunotherapy, concomitant administration of CD4 + and CD8 + T cells that have been gene modified using identical HLA class I-restricted leukemia antigen-specific T-cell receptor ( TCR ) gene transfer has not yet been fully investigated. Here, using CD4 + and CD8 + T cells that had been gene modified with a retroviral vector expressing HLA-A*24:02-restricted and Wilms’ tumor 1 (WT1)-specific TCR -α/β genes and siRNAs for endogenous TCRs (WT1- siTCR /CD4 + T cells and WT1- siTCR /CD8 + T cells), we examined the utility of this strategy. WT1- siTCR /CD4 + T cells sufficiently recognized leukemia cells in an HLA class I-restricted manner and provided target-specific Th1 help for WT1- siTCR /CD8 + T cells. By using a xenografted mouse model, we found that WT1- siTCR /CD4 + T cells migrated to leukemia sites and subsequently attracted WT1- siTCR /CD8 + T cells via chemotaxis. Therapy-oriented experiments revealed effective enhancement of leukemia suppression mediated by concomitant administration of WT1- siTCR /CD4 + T cells and WT1- siTCR /CD8 + T cells. Importantly, this augmented efficacy in the presence of WT1- siTCR /CD4 + T cells was correlated with longer survival and enhanced formation of memory T cells by WT1- siTCR /CD8 + T cells. Collectively, our experimental findings strongly suggest that this strategy would be clinically advantageous for the treatment of human leukemia.

BackgroundGlycosylation is an important post-translational modification of proteins. Modification of glycan structure has been reported in some disease conditions such as rheumatoid arthritis (RA). RA is a chronic, systemic autoimmune disease where many inflammatory cytokines play pathological roles. In patients with RA, a significant defect in the galactosyltransferase enzyme activity results in a change in the galactosylation of immunoglobulin G (IgG). Autoantibodies against IgG lacking galactose frequently appear in RA patients and this change has been demonstrated to be associated with disease activities in RA. Although the precise mechanism is still not known, it is likely that the abnormal glycosylation processes may pathologically associate with RA. We hypothesize that this kind of glycosylation abnormalities occurs in the development of immune competent cells in the bone marrow (BM). Ochi et al reported an abnormality of BM cells contributes to the pathogenesis of RA in human and animal models (Arthritis Res Ther. 2007). Especially, they reported the presence of abnormal myeloid cells expressing the difucosyl type 2 chain structure (a specific marker of human undifferentiated cells) in RA patients' BM. This fact encouraged us to focus on bone marrow cells.ObjectivesThis study is to clarify the abnormal expression of glycosylation-related genes in bone marrow cells of RA patients and to analyze the network regulation of immune and inflammatory responses related to glycosylation abnormalities in RA.MethodsComprehensive gene expression analysis was conducted using DNA microarray on the BM cells of 28 RA patients and 11 healthy individuals (HI). According to the gene lists based on the Glyco Gene Database (GGDB) and Lectin Frontier Database (LfDB), glycosylation-related genes were extracted among the differentially expressed genes in RA compared with HI. Network analysis was performed using Ingenuity Pathway AnalysisR (IPA).Results1416 down regulated and 1673 up regulated genes were identified by more than two-fold change in the expression in RA compared to HI. In these differentially expressed genes, 50 glycosylation related genes decreased and 54 genes increased significantly. The decreased genes included A4GALT, B4GALT (encoding galactosyltransferases), UGCG (glucosyltransferase), FUT8 (fucosyltransferase) and EXT1,2 (exostoses) listed as top-five changed genes. On the other hand, the increased genes included many lectin genes such as ITGAL (encoding integrin), LGAL (galectin) and SIGLEC (sialic acid binding lectin). IPA analysis showed that the differentially expressed genes composed networks with inflammatory cytokines including TNF and IL-1. Moreover, they composed a network relevant to a dendritic cells and NK cells functions.ConclusionsThis is the first report that abnormal expression of glycosylation related genes in the bone marrow cells of RA patients. The down-regulation of genes of glycan synthesis and up-regulation of lectin genes might associate with the pathogenesis of RA.Disclosure of InterestNone declared

PurposeWe investigated the relationship between the affected lobe and symptom onset in prenatally diagnosed congenital pulmonary airway malformation (CPAM).Methods53 CPAM patients diagnosed prenatally were reviewed retrospectively by creating 2 groups according to symptom onset. Group Sneo: (symptomatic during the neonatal period; n = 13) and group S > neo: (symptomatic after the neonatal period; n = 40) were compared for type of CPAM, affected lobes, types of symptoms/infections, treatment, duration of follow-up, and histopathology. Requirement for surgery (Sx) was then used to create three subgroups: Sneo + Sx, S > neo + Sx, and Sx−.ResultsSome cases had multiple affected lobes. In Sneo, symptoms developed in 55.6%, 50.0%, 0%, 0%, and 36.8% of right upper lobes (RUL), right middle lobes (RML), right lower lobes (RLL), left upper lobes (LUL), and left lower lobes (LLL) diagnosed with CPAM, prenatally. In S > neo, symptoms developed in 0%, 0%, 6.3%, 55.6%, and 33.3% of RUL, RML, RLL, LUL, and LLL diagnosed with CPAM, prenatally.ConclusionIn prenatally diagnosed CPAM, RUL and RML lesions are more likely to become symptomatic in neonates, and LUL lesions in infants. Surgery is recommended before the onset of respiratory infections after 1 year of age.

Filled skutterudite is a promising material for thermoelectric power generation because its ZT value is relatively high. However, mass production of high-performance thermoelectric materials remains a challenge. This study focused on the sintering process of thermoelectric materials. Large-diameter n -type (Yb or La, Ca, Al, Ga, In) 0.8 (Co, Fe) 4 Sb 12 skutterudite sintering bodies with a small thickness were successfully produced by the spark plasma sintering (SPS) method. When direct current flows through the thermoelectric sintering body during the SPS pulse, the Peltier effect causes a temperature difference within the sintering body. To eliminate the Peltier effect, an electrical insulating material was inserted between the punch (electrode) and the sintering body. In this way, an n -type La-filled skutterudite sample with a diameter of 200 mm, thickness of 21 mm, and weight of 5 kg was successfully produced. The thermoelectric properties and microstructures of the sample were almost the same throughout the whole sintering body, and the dimensionless figure of merit reached 1.0 at 773 K.

KAGRA is a 3-km interferometric gravitational wave telescope located in the Kamioka mine in Japan. It is the first km-class gravitational wave telescope constructed underground to reduce seismic noise, and the first km-class telescope to use cryogenic cooling of test masses to reduce thermal noise. The construction of the infrastructure to house the interferometer in the tunnel, and the initial phase operation of the interferometer with a simple 3-km Michelson configuration have been completed. The first cryogenic operation is expected in 2018, and the observing runs with a full interferometer are expected in 2020s. The basic interferometer configuration and the current status of KAGRA are described.

By using a p -type (La, Ba, Ga, Ti) 1 (Fe, Co) 4 Sb 12 skutterudite with a dimensionless figure of merit, ZT , = 0.75 at 500°C and an n -type (Yb, Ca, Al, Ga, In) 0.7 (Co, Fe) 4 Sb 12 skutterudite with ZT = 1.0 at 500°C, we fabricated a thermoelectric power-generation module capable of working at high temperatures (up to 600°C). When its hot and cold sides were at 600°C and 30°C, respectively, the power output of a 50 mm × 50 mm × 7.6 mm skutterudite module was 34 W and its thermoelectric conversion efficiency was 8%. In a durability test with the module’s hot and cold sides continuously maintained at 600°C and 80°C, respectively, for 8000 h, power generation first decreased by approximately 6% in the initial 300 h then remained constant.