統合失調症における大脳皮質下領域体積の非対称性に関する検討

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 齊藤 延人, 東京大学准教授 國松 聡, 東京大学講師 湯本 真人, 東京大学講師 森 墾, 東京大学講師 林 俊宏University of Tokyo(東京大学

Effects of Erbium-Doped: Yttrium Aluminum Garnet (Er: YAG) Laser on Bacteremia due to Scaling and Root Planing

INTRODUCTION: The aims of the present study were: [1] to evaluate whether Erbium-Doped: Yttrium, Aluminum and Garnet (Er: YAG) laser could be a prophylactic methods against transient bacteremia during scaling and root planing (SRP) [2] to confirm the efficacies of SRP with Er: YAG laser by clinical and microbiologic evaluations.METHODS: Twenty chronic periodontitis subjects were randomly treated for quadrant SRP with either conventional hand instrument (n=10) or Er: YAG laser (n=10) monotherapy. Peripheral blood samples were drawn at baseline and 6 minutes after initiation of SRP, and were cultured for the analysis of bacteremia. Clinical measurements of full mouth plaque control record (PCR), probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BOP) were made at baseline and 1 month after SRP. In addition, microbiologic analyses of subgingival samples were also performed at baseline and 1 month after SRP using the polymerase chain reaction Invader method.RESULTS: The incidence of bacteremia during SRP was 0% (0/10) in the Er: YAG laser group and 80% (8/10) in the hand instrument group, which was significantly different (P = 0.0003). All isolates from blood were facultative or obligate anaerobes and more than half of the microorganisms were species of streptococci. Intragroup comparison revealed that the mean PPD and CAL significantly decreased compared to baseline in both groups (P < 0.05). However, the percentage of BOP positive significantly decreased only in Er: YAG laser group (P = 0.005). In addition, the reductions of the subgingival bacterial counts between baseline and 1 month after SRP were also comparable between the two groups.CONCLUSION: The present study demonstrated that SRP with Er: YAG laser could not only be an alternative treatment for improvement of clinical and microorganisms situations but also a novel prophylactic method against transient bacteremia

黒色腫細胞において、miR-19bはPITX1 mRNAを標的としてhTERT mRNAの発現を制御する

Purpose: This article sheds light onto the increasing problem of product returns, which is exacerbated by growing e-commerce. Many retailers and academics are oblivious to the nature and scale of this challenge. Interdisciplinary research is needed to develop supporting theory, and cross-functional teams are required to implement measures addressing economic, ecological and social sustainability issues. Design/methodology/approach: The initial project adopted a multi-case study approach, whereby returns processes were mapped, vulnerabilities identified and a returns cost calculator was developed. Findings: Product returns processes are usually complicated, prone to internal and external fraud, inefficient and lack sustainability. They can generate considerable losses to the business, especially as returns data are often not systematically collected, monitored or reported to senior management. There are important implications for strategic and operational management, namely the need to develop a concept for Lean returns systems. Originality/value: Product returns are a unique and understudied but growing field in academic research, with only few publications over the last two decades. Yet the phenomenon is causing increasing problems in business and society. Robust solutions could achieve great financial and non-financial impacts.</p

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP

The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects

BackgroundThe effect of duration of illness and antipsychotic medication on the volumes of subcortical structures in schizophrenia is inconsistent among previous reports. We implemented a large sample analysis utilizing clinical data from 11 institutions in a previous meta-analysis.MethodsImaging and clinical data of 778 schizophrenia subjects were taken from a prospective meta-analysis conducted by the COCORO consortium in Japan. The effect of duration of illness and daily dose and type of antipsychotics were assessed using the linear mixed effect model where the volumes of subcortical structures computed by FreeSurfer were used as a dependent variable and age, sex, duration of illness, daily dose of antipsychotics and intracranial volume were used as independent variables, and the type of protocol was incorporated as a random effect for intercept. The statistical significance of fixed-effect of dependent variable was assessed.ResultsDaily dose of antipsychotics was positively associated with left globus pallidus volume and negatively associated with right hippocampus. It was also positively associated with laterality index of globus pallidus. Duration of illness was positively associated with bilateral globus pallidus volumes. Type of antipsychotics did not have any effect on the subcortical volumes.DiscussionA large sample size, uniform data collection methodology and robust statistical analysis are strengths of the current study. This result suggests that we need special attention to discuss about relationship between subcortical regional brain volumes and pathophysiology of schizophrenia because regional brain volumes may be affected by antipsychotic medication

White matter microstructural alterations across four major psychiatric disorders : mega-analysis study in 2937 individuals

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia