Survey for teachers about picture book that convey the significance of class activities (1)

This study examined the usefulness of picture book that convey the significance of class activities for teachers. From the results, the developed picture book is (1) the teacher feels that the child may lead to the understanding of the consensus building process and the meaning of cooperation, and (2) teachers feel that it is particularly useful for third and fourth graders, but also for other grades., and (3)it was shown that many teachers considered using it for future practice and found it useful as a tool for learning teachers' guidance and advice.These results suggested a certain usefulness of it.この研究は，日本学術振興会科学研究費助成事業 基盤研究（C）課題番号18K02758：多様性に富む共生社会構築に向けた小学校用「多様性把握シート」の作成と活用（代表若松昭彦）によって行われた

Suicidal ideation and burnout among psychiatric trainees in Japan

AIM: Burnout is a psychological condition that may occur in all workers after being exposed to excessive work-related stresses. We investigated suicidal ideation and burnout among Japanese psychiatric trainees as a part of the Burnout Syndrome Study (BoSS) International.  METHODS: In the Japanese branch, 91 trainees fully completed suicide ideation and behaviour questionnaire (SIBQ) and Maslach Burnout Inventory-General Survey (MBI-GS).  RESULTS: Passive suicidal ideation was reported by 38.5% of Japanese trainees and 22.0% of them had experienced active suicidal ideation. The burnout rate among Japanese subjects was 40.0%. These results were worse compared to the all 1980 trainees who fully completed the main outcome measure in BoSS International, 25.9%, 20.4% and 36.7%, respectively.  CONCLUSIONS: Our results suggest a higher risk of suicide among Japanese residents. Japan has a higher suicide rate than other countries. Early detection of, and appropriate intervention for, suicidal ideation is important in preventing suicide in psychiatry residents

Pathway to psychiatric care in Japan: A multicenter observational study

<p>Abstract</p> <p>Background</p> <p>This study examines pathways to psychiatric care in Japan using the same method as the collaborative study carried out in 1991 under the auspices of the World Health Organization.</p> <p>Methods</p> <p>Thirteen psychiatric facilities in Japan were involved. Of the 228 patients who contacted psychiatric facilities with any psychiatric illness, eighty four visiting psychiatric facilities for the first time were enrolled. Pathways to psychiatric care, delays from the onset of illness to treatment prior to reaching psychiatrists were surveyed.</p> <p>Results</p> <p>Thirty three patients (39.4%) directly accessed mental health professionals, 32 patients (38.1%) reached them via general hospital, and 13 patients (15.5%) via private practitioners. The patients who consulted mental health professionals as their first carers took a longer time before consulting psychiatrists than the patients who consulted non-mental health professionals as their first carers. The patients who presented somatic symptoms as their main problem experienced longer delay from the onset of illness to psychiatric care than the patients who complained about depressive or anxiety symptoms. Prior to the visit to mental health professionals, patients were rarely informed about their diagnosis and did not receive appropriate treatments from their physicians. Private practitioners were more likely to prescribe psychotropics than physicians in general hospitals, but were less likely to inform their patients of their diagnosis.</p> <p>Conclusion</p> <p>This first pathway to psychiatric care study in Japan demonstrated that referral pathway in Japan heavily relies on medical resources. The study indicates possible fields and gives indications, underlining the importance of improving skills and knowledge that will facilitate the recognition of psychiatric disorders presenting with somatic and depressive symptoms in the general health care system and by private practitioners.</p

Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia.

BACKGROUND: Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL. METHODS: Using leukaemia patient specimens, we performed bioinformatic analyses to identify target genes/pathways. To test inhibition of target pathways in vivo, we created pre-clinical therapeutic mouse patient-derived xenograft (PDX)-models by transplanting human MLL-ALL leukaemia initiating cells (LIC) into immune-deficient NSG mice. Finally, we conducted B-cell lymphoma-2 (BCL-2) homology domain 3 (BH3) profiling to identify BH3 peptides responsible for treatment resistance in MLL-leukaemia. FINDINGS: Src family kinases (SFKs) and Fms-like tyrosine kinase 3 (FLT3) signaling pathway were over-represented in MLL-ALL cells. PDX-models of infant MLL- ALL recapitulated GC-resistance in vivo but RK-20449, an inhibitor of SFKs and FLT3 eliminated human MLL-ALL cells in vivo, overcoming GC-resistance. Further, we identified BCL-2 dependence as a mechanism of treatment resistance in MLL-ALL through BH3 profiling. Furthermore, MLL-ALL cells resistant to RK-20449 treatment were dependent on the anti-apoptotic BCL-2 protein for their survival. Combined inhibition of SFKs/FLT3 by RK-20449 and of BCL-2 by ABT-199 led to substantial elimination of MLL-ALL cells in vitro and in vivo. Triple treatment combining GCs, RK-20449 and ABT-199 resulted in complete elimination of MLL-ALL cells in vivo. INTERPRETATION: SFKs/FLT3 signaling pathways are promising targets for treatment of treatment-resistant MLL-ALL. Combined inhibition of these kinase pathways and anti-apoptotic BCL-2 successfully eliminated highly resistant MLL-ALL and demonstrated a new treatment strategy for treatment-resistant poor-outcome MLL-ALL. FUNDING: This study was supported by RIKEN (RIKEN President\u27s Discretionary Grant) for FI, Japan Agency for Medical Research and Development (the Basic Science and Platform Technology Program for Innovative Biological Medicine for FI and by NIH CA034196 for LDS. The funders had no role in the study design, data collection, data analysis, interpretation nor writing of the report

Fluid flow and interlinked feedback loops establish left-right asymmetric decay of Cerl2 mRNA

Breaking of left-right symmetry in mouse embryos requires fluid flow at the node, but the precise action of the flow has remained unknown. Here we show that the left-right asymmetry of Cerl2 expression around the node, a target of the flow, is determined post-transcriptionally by decay of Cerl2 mRNA in a manner dependent on its 3' untranslated region. Cerl2 mRNA is absent specifically from the apical region of crown cells on the left side of the node. Preferential decay of Cerl2 mRNA on the left is initiated by the leftward flow and further enhanced by the operation of Wnt-Cerl2 interlinked feedback loops, in which Wnt3 upregulates Wnt3 expression and promotes Cerl2 mRNA decay, whereas Cerl2 promotes Wnt degradation. Mathematical modelling and experimental data suggest that these feedback loops behave as a bistable switch that can amplify in a noise-resistant manner a small bias conferred by fluid flow.Ministry of Education, Culture, Sports, Science, and Technology of Japan; Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corporation (JST); GCOE of Osaka University; FCTinfo:eu-repo/semantics/publishedVersio

Novel, Objective, Multivariate Biomarkers Composed of Plasma Amino Acid Profiles for the Diagnosis and Assessment of Inflammatory Bowel Disease

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). METHODOLOGY AND PRINCIPAL FINDINGS: We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898-0.983) and 0.894 (95%CI: 0.853-0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853-0.935) and 0.849 (95%CI: 0.770-0.928), and correlated with clinical disease activity indexes for CD (r(s) = 0.592, 95%CI: 0.385-0.742, p<0.001) or UC (r(s) = 0.598, 95%CI: 0.452-0.713, p<0.001), respectively. CONCLUSIONS AND SIGNIFICANCE: In this study, we demonstrated that established multivariate indexes composed of plasma amino acid profiles can serve as novel, non-invasive, objective biomarkers for the diagnosis and monitoring of IBD, providing us with new insights into the pathophysiology of the disease

Kinetics and Dynamics on the Formation of S_2(X^3Σ^-_g, a^1Δ_g) in the S(^1D) + OCS Reaction

Selective detection of single vibrational level of the X and a states of S2. Detection of highly vibrationally excited S2(X, a) generated in the S(1D) + OCS reaction. About half of the available energy is deposited into the vibrational motion of S2(X, a). Determination of the overall rate coefficient for the S(1D) + OCS reaction.学会名:22nd International Symposium on Gas Kinetics ; 会期:2012年6月18日(月)～22日(金) ; 開催地:アメリカ,コロラド州,ボールダー(Boulder) ; 発表者:Katsuyoshi Yamasaki ; 発表形式:ポスタ

Rapid and Controllable Hydrogen/Deuterium Exchange on Aromatic Rings of α-Amino Acids and Peptides

Novel hydrogen/deuterium exchange for aromatic α-amino acids and their corresponding peptides were performed through the use of deuterated trifluoromethanesulfonic acid (TfOD). Detailed analysis of the exchange revealed that equal hydrogen/deuterium exchange was observed for phenylalanine, and specific exchange at the ortho-positions of phenol for tyrosine was also detected. The stereochemistry of the aromatic α-amino acids was retained under the exchange conditions. The hydrogen/deuterium exchange properties for these aromatic α-amino acids are identical for peptides that contain several aromatic α-amino acids. The exchange proceeded significantly faster than previous methods. Detailed analysis of the exchange revealed that the method could be controlled by temperature, time, and the amount of reagent

Synthesis of Methoxy-Substituted Diazirinyl Phenylalanine – A Novel Photoreactive Aspartame Derivative for Functional Analysis of Sweet Receptors

Photoreactive phenylalanine derivatives are well known as functional analysis reagents for target biomolecules. The photophores are commonly introduced at 4-position on benzene. Aspartame, which consists of dipeptide L-Asp-L-Phe-OMe, is one of the most utilized artificial sweeteners, and substitution effects on its benzene ring have been reported. Substitution at the 4-position, however, does not maintain its sweetness properties. Trifluoromethyl- diazirine, which is one of the most reliable photophores, was introduced to a different site on phenylalanine and the new photoreactive phenylalanine was converted to aspartame derivatives. The new aspartame derivative had slightly higher sweetness potency than sucrose standard solution

Photoactive ligands probing the sweet taste receptor. Design and synthesis of highly potent diazirinyl D-phenylalanine derivatives

Some D-Amino acids such as D-tryptophan and D-phenylalanine are well known as naturally-occurring sweeteners. Photoreactive D-phenylalanine derivatives containing trifluoromethyldiazirinyl moiety at 3- or 4-position of phenylalanine, were designed as sweeteners for functional analysis with photoaffinity labeling. The trifluoromethyldiazirinyl D-phenylalanine derivatives were prepared effectively with chemo-enzymatic methods using L-amino acid oxidase and were found to have potent activity toward the human sweet taste receptor