Search

Objective Recently, rational polypharmacy approaches have been proposed, regardless of the lower risk and cost of monotherapy. Considering monotherapy as first-line treatment and polypharmacy as rational treatment, a balanced attitude toward polypharmacy is recommended. However, the high prevalence of polypharmacy led the Japanese government to establish a polypharmacy reduction policy. Based on this, the association between the policy and psychiatrists’ attitude toward polypharmacy has been under debate.Methods We developed an original questionnaire about Psychiatrists’ attitudes toward polypharmacy (PAP). We compared the PAP scores with the treatment decision-making in clinical case vignettes. Multiple regression analyses were performed to quantify associations of explanatory variables including policy factors and PAP scores. The anonymous questionnaires were administered to psychiatrists worldwide.Results The study included 347 psychiatrists from 34 countries. Decision-making toward polypharmacy was associated with high PAP scores. Multiple regression analysis revealed that low PAP scores were associated with the policy factor (β=-0.20, p=0.004). The culture in Korea was associated with high PAP scores (β=0.34, p

Interpersonal difficulties are often observed in major depressive disorder (MDD), while the underlying psychological and biological mechanisms have not yet been elucidated. In the present case–control study, a PC-based trust game was conducted for 38 drug-free MDD patients and 38 healthy controls (HC). In the trust game, participants invested money in a partner (trusting behaviors), and also rated each partner’s attractiveness (preference for others). In addition, blood biomarkers including metabolites were measured. Both MDD and HC males exhibited more trusting behaviors compared to females. MDD males’ preference for ordinary-attractive partners (lay-person photographs) was lower than HC males, whereas their preference for high-attractive females (fashion-model photographs) was similar levels to HC males. This tendency in MDD males could reflect a “focused (narrowed) preference for females”. As for blood biomarker analysis, the levels of 37 metabolites including acetylcholine, AMP, GMP, nicotinic acid and tryptophan were significantly different between two groups. Interestingly, among male participants, acetylcholine and nicotinic acid were negatively correlated with the level of focused preference for photographed females. In sum, we have revealed some behavioral, psychological and biological traits of trusting behaviors and preference for others especially in MDD males. Larger studies should be conducted to validate our preliminary findings.

A severe form of pathological social withdrawal, 'hikikomori,' has been acknowledged in Japan, spreading worldwide, and becoming a global health issue. The pathophysiology of hikikomori has not been clarified, and its biological traits remain unexplored.Drug-free patients with hikikomori (Long-chain acylcarnitine levels were remarkably higher in patients with hikikomori; bilirubin, arginine, ornithine, and serum arginase were significantly different in male patients with hikikomori. The discriminative random forest model was highly performant, exhibiting an area under the ROC curve of 0.854 (confidential interval = 0.648-1.000). To predict hikikomori severity, a partial least squares PLS-regression model was successfully created with high linearity and practical accuracy. In addition, blood serum uric acid and plasma cholesterol esters contributed to the stratification of cases.These findings reveal the blood metabolic signatures of hikikomori, which are key to elucidating the pathophysiology of hikikomori and also useful as an index for monitoring the treatment course for rehabilitation.

Aim Hikikomori, a form of pathological social withdrawal, has been suggested to have comorbidity with autism spectrum disorder (ASD). This study aimed to clarify how characteristics of hikikomori are associated with ASD, including undiagnosed autism spectrum conditions (ASC), in clinical settings. Methods A total of 416 clinical patients were recruited through the Mood Disorder/Hikikomori Clinic at Kyushu University Hospital. A total of 103 hikikomori cases and 221 clinical controls without hikikomori conditions were extracted using a semi-structured interview, and completed a series of self-rated scales, including the Japanese version of the Autism-Spectrum Quotient (AQ-J). Results Compared to non-hikikomori controls, hikikomori cases were more likely to have higher autistic tendency based on the AQ-J. The cases showed more severe subjective depressive symptoms based on the self-rated Beck Depression Inventory II, whereas no significant difference was found on interview-based severity evaluation using the Hamilton Depression Rating Scale. Comparison within hikikomori cases based on the AQ-J cut-off score revealed that hikikomori cases with high ASC were significantly more likely to have higher traits of modern-type depression, smaller social networks, and less social support. Conclusion The present data suggest that hikikomori sufferers are more likely to have autistic tendency, and that hikikomori sufferers with high ASC may have much more difficulty in social communication and social interaction. In addition, those with high ASC may also have lower self-esteem and higher complaint tendencies as aspects of modern-type depression traits, which may relate to the occurrence of hikikomori. Thus, evaluating autistic tendencies is important for appropriate interventions in hikikomori. Further investigations should be conducted to validate our pilot findings using structured diagnostic systems of ASD.

Lower serum levels of low-density lipoprotein cholesterol (LDL-C) have been suggested to indicate higher suicide risk and various psychiatric symptoms. Previously, we reported that lower serum LDL-C levels are associated with loneliness, social phobia, isolated life with little social support, and lower trust in others among young non-clinical females. Thus, we hypothesize that schizoid personality traits may be associated with lower serum LDL-C. We here verified this hypothesis using non-clinical data and clinical data with schizophrenia. Using the database from the Midlife in Japan (MIDJA), a cohort of residents living in Tokyo, we analyzed whether schizoid-related interpersonal characteristics were associated with LDL-C. In addition, we assessed the association between blood biomarkers including LDL-C and schizoid personality traits in 101 adult non-clinical volunteers. Finally, we evaluated the interaction between LDL-C and social decision making of patients with schizophrenia. In female non-clinical volunteers, serum LDL-C level was a predictive factor and negatively correlated with schizoid personality traits. Female patients with schizophrenia, whose serum LDL-C levels were lower, tended not to trust other females. The present findings suggest that LDL-C may influence schizoid personality traits in females, which provide a basis for further investigation into the biological aspects of schizoid personality disorder.

Aim Understanding premorbid personality is important, especially when considering treatment selection. Historically, the premorbid personality of patients with major depression in Japan was described as Shuchaku-kishitsu [similar to Typus melancholicus], as proposed by Shimoda in the 1930s. Since around 2000, there have been increased reports in Japan of young adults with depression who have had premorbid personality differing from the traditional type. In 2005, Tarumi termed this novel condition 'dysthymic-type depression,' and more recently the condition has been called Shin-gata/Gendai-gata Utsu-byo [modern-type depression (MTD)]. We recently developed a semi-structured diagnostic interview to evaluate MTD. Development of a tool that enables understanding of premorbid personality in a short time, especially at the early stage of treatment, is desirable. The object of this study was to develop a self-report scale to evaluate the traits of MTD, and to assess the scale's psychometric properties, diagnostic accuracy, and biological validity. Methods A sample of 340 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis. Diagnostic accuracy of the MTD traits was compared against a semi-structured interview. Results The questionnaire contained 22 items across three subscales, thus we termed it the 22-item Tarumi's Modern-Type Depression Trait Scale: Avoidance of Social Roles, Complaint, and Low Self-Esteem (TACS-22). Internal consistency, test-retest reliability, and convergent validity were all satisfactory. Among patients with major depression, the area under the curve was 0.757 (sensitivity of 63.1% and specificity of 82.9%) and the score was positively correlated with plasma tryptophan. Conclusion The TACS-22 possessed adequate psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its ability to support clinical assessment of MTD is warranted.

Aim Hikikomori, a form of severe social withdrawal, is an emerging issue in mental health, for which validated measurement tools are lacking. The object was to develop a self-report scale of hikikomori, and assess its psychometric properties and diagnostic accuracy. Methods A sample of 399 participants from clinical and community settings completed measures. Psychometric properties were assessed with factor analysis; diagnostic accuracy was compared against a semi-structured diagnostic interview. Results The Hikikomori Questionnaire contained 25 items across three subscales representing socialization, isolation, and emotional support. Internal consistency, test-retest reliability, and convergent validity were all satisfactory. The area under the curve was 0.86 (95% confidence interval, 0.80-0.92). A cut-off score of 42 (out of 100) was associated with a sensitivity of 94%, specificity of 61%, and positive predictive value of 17%. Conclusion The 25-item Hikikomori Questionnaire (HQ-25) possesses robust psychometric properties and diagnostic accuracy in an initial sample of Japanese adults. Additional research on its psychometric properties and ability to support clinical assessment of hikikomori is warranted.

Background Early intervention in depression has been critical to prevent its negative impact including suicide. Recent blood biomarker studies for major depressive disorder (MDD) have suggested that tryptophan-kynurenine and lipid related metabolites are involved in the pathophysiology of MDD. However, there have been limited studies investigating these blood biomarkers in first-episode drug-naive MDD, which are particularly important for early intervention in depression. Methods As an exploratory pilot case-control study, we examined the above blood biomarkers, and analyzed how these biomarkers are associated with clinical variables in first-episode drug-naive MDD patients, based on metabolome/lipidome analysis. Results Plasma tryptophan and kynurenine levels were significantly lower in MDD group (N = 15) compared to healthy controls (HC) group (N = 19), and plasma tryptophan was the significant biomarker to identify MDD group (area under the curve = 0.740). Lower serum high density lipoprotein-cholesterol (HDL-C) was the predictive biomarker for severity of depression in MDD group (R2 = 0.444). Interestingly, depressive symptoms were variously correlated with plasma tryptophan-kynurenine and lipid related metabolites. Moreover, plasma tryptophan-kynurenine metabolites and cholesteryl esters (CEs) were significantly correlated in MDD group, but not in HC group. Limitations This study had small sample size, and we did not use the multiple test correction. Conclusions This is the first study to suggest that not only tryptophan-kynurenine metabolites but also HDL-C and CEs are important blood biomarkers for first-episode drug-naive MDD patients. The present study sheds new light on early intervention in clinical practice in depression, and further clinical studies especially large-scale prospective studies are warranted.

Direct conversion technique to produce induced-neuronal (iN) cells from human fibroblasts within 2 weeks is expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. Here, we present unique gene expression profiles in iN cells from patients with neurofibromatosis type 1 (NF1), a single-gene multifaceted disorder with comparatively high co-occurrence of autism spectrum disorder (ASD). Microarray-based transcriptomic analysis on iN cells from male healthy controls and male NF1 patients (NF1-iN cells) revealed that 149 genes expressions were significantly different (110 upregulated and 39 downregulated). We validated that mRNA of MEX3D (mex-3 RNA binding family member D) was lower in NF1-iN cells by real-time PCR with 12 sex-mixed samples. In NF1-iN cells on day 14, higher expression of FOS mRNA was observed with lower expression of MEX3D mRNA. Interestingly, BCL2 mRNA was higher in NF1-iN cells on day 5 (early-period) but not on day 14. Our data suggest that aberrant molecular signals due to NF1 mutations may disturb gene expressions, a subset of which defines continuum of the neuronal phenotypes of NF1 with ASD. Further translational studies using induced pluripotent stem (iPS) cell-derived neuronal cells are needed to validate our preliminary findings especially confirming meanings of analysis using early-period iN cells.

Fibromyalgia is a refractory disease characterized by chronic intractable pain and psychological suffering, the cause of which has not yet been elucidated due to its complex pathology. Activation of immune cells in the brain called microglia has attracted attention as a potential underlying pathological mechanism in chronic pain. Until recently, however, technological and ethical considerations have limited the ability to conduct research using human microglia. To overcome this limitation, we have recently developed a technique to create human-induced microglia-like (iMG) cells from human peripheral blood monocytes. In this study, we created the iMG cells from 14 patients with fibromyalgia and 10 healthy individuals, and compared the activation of iMG cells between two groups at the cellular level. The expression of tumor necrosis factor (TNF)-α at mRNA and protein levels significantly increased in ATP-stimulated iMG cells from patients with fibromyalgia compared to cells from healthy individuals. Interestingly, there was a moderate correlation between ATP-induced upregulation of TNF-α expression and clinical parameters of subjective pain and other mental manifestations of fibromyalgia. These findings suggest that microglia in patients with fibromyalgia are hypersensitive to ATP. TNF-α from microglia may be a key factor underlying the complex pathology of fibromyalgia.

Viral infections during fetal and adolescent periods, as well as during the course of schizophrenia itself have been linked to the onset and/or relapse of a psychosis. We previously reported that the unique antipsychotic aripiprazole, a partial D2 agonist, inhibits the release of tumor necrosis factor (TNF)-α from interferon-γ-activated rodent microglial cells. Polyinosinic-polycytidylic acid (polyI:C) has recently been used as a standard model of viral infections, and recent in vitro studies have shown that microglia are activated by polyI:C. Aripiprazole has been reported to ameliorate behavioral abnormalities in polyI:C-induced mice. To clarify the anti-inflammatory properties of aripiprazole, we investigated the effects of aripiprazole on polyI:C-induced microglial activation in a cellular model of murine microglial cells and possible surrogate cells for human microglia. PolyI:C treatment of murine microglial cells activated the production of TNF-α and enhanced the p38 mitogen-activated protein kinase (MAPK) pathway, whereas aripiprazole inhibited these responses. In addition, polyI:C treatment of possible surrogate cells for human microglia markedly increased TNF-α mRNA expression in cells from three healthy volunteers. Aripiprazole inhibited this increase in cells from two individuals. PolyI:C consistently increased intracellular Ca2+ concentration ([Ca2+]i) in murine microglial cells by influx of extracellular Ca2+. We demonstrated that transient receptor potential in melastatin 7 (TRPM7) channels contributed to this polyI:C-induced increase in [Ca2+]i. Taken together, these data suggest that aripiprazole may be therapeutic for schizophrenia by reducing microglial inflammatory reactions, and TRPM7 may be a novel therapeutic target for schizophrenia. Further studies are needed to validate these findings.

We present all-fiber tunable lasers using single-mode–multimode–single-mode (SMS) structures involving a liquid cladding in the multimode section. We make use of large thermooptic coefficients of the refractive-index liquids to tune the laser oscillation wavelength. The oscillation wavelength is changed over a range of 100 nm from 1858 nm to 1958 nm by controlling the temperature of the SMS structures in the Tm/Ho-codoped fiber ring resonators.

Background Neuroinflammation is suggested to be a crucial factor in the pathophysiology of major depressive disorder (MDD). Analysis of neuron-derived exosomes (NDE) in peripheral blood has recently been highlighted to reveal the pathophysiology of brain diseases without using brain biopsy. Currently, human NDE studies require a considerable amount of peripheral blood to measure multiple substances inside exosomes. Previously, NDE-based clinical studies focusing on MDD have not been reported. Methods As an exploratory pilot case-control study between healthy controls (HC) and drug-free MDD patients (each; N = 34), we searched for NDE-related blood biomarkers with a small amount of peripheral blood using a novel sandwich immunoassay between anti-neuron antibody and antibodies against CD81 (an exosome marker) and against other proteins related to neuroinflammation and synaptic functions. Results Most neuron-related blood biomarkers had moderately to strongly positive correlation with CD81 (NDE), thus we normalized the above biomarkers by CD81 (quantity of each biomarker/CD81) to predict NDE-related blood substances. Interleukin 34 (IL34)/CD81 levels were significantly higher in MDD group compared to HC group. Synaptophysin (SYP), SYP/CD81, and tumor necrosis factor receptor 1 (TNFR1)/CD81 were positively correlated with severities of depression and/or various sub-symptoms. Limitations We did not actually extract NDE from peripheral blood. Conclusions Using a small amount of peripheral blood, we have successfully detected possible NDE-related blood biomarkers. This is the first study to suggest that not only SYP and TNFR1 but also IL34 are important blood biomarkers for patients with MDD. Further studies are warranted to evaluate the present study.

Japan's prototype of depression was traditionally a melancholic depression based on the premorbid personality known as shūchaku-kishitsu proposed by Mitsuzo Shimoda in the 1930s. However, since around 2000, a novel form of depression has emerged among Japanese youth. Called 'modern type depression (MTD)' by the mass media, the term has quickly gained popularity among the general public, though it has not been regarded as an official medical term. Likewise, lack of consensus guidelines for its diagnosis and treatment, and a dearth of scientific literature on MTD has led to confusion when dealing with it in clinical practice in Japan. In this review article, we summarize and discuss the present situation and issues regarding MTD by focusing on historical, diagnostic, psychosocial, and cultural perspectives. We also draw on international perspectives that begin to suggest that MTD is a phenomenon that may exist not only in Japan but also in many other countries with different sociocultural and historical backgrounds. It is therefore of interest to establish whether MTD is a culture-specific phenomenon in Japan or a syndrome that can be classified using international diagnostic criteria as contained in the ICD or the DSM. We propose a novel diagnostic approach for depression that addresses MTD in order to combat the current confusion about depression under the present diagnostic systems.

Background Suicide is a crucial global health concern and effective suicide prevention has long been warranted. Mental illness, especially depression is the highest risk factor of suicide. Suicidal risk is increased in people not only with mental illness but also with physical illnesses, thus medical staff caring for physically-ill patients are also required to manage people with suicidal risk. In the present study, we evaluated our newly developed suicide intervention program among medical staff. Methods We developed a 2-h suicide intervention program for medical staff, based on the Mental Health First Aid (MHFA), which had originally been developed for the general population. We conducted this program for 74 medical staff members from 2 hospitals. Changes in knowledge, perceived skills, and confidence in early intervention of depression and suicide-prevention were evaluated using self-reported questionnaires at 3 points; pre-program, immediately after the program, and 1 month after program. Results This suicide prevention program had significant effects on improving perceived skills and confidence especially among nurses and medical residents. These significant effects lasted even 1 month after the program. Limitations Design was a single-arm study with relatively small sample size and short-term follow up. Conclusions The present study suggests that the major target of this effective program is nurses and medical residents. Future research is required to validate the effects of the program with control groups, and also to assess long-term effectiveness and actual reduction in suicide rates.

Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.

In the past few years, there is a growing interest in automated negotiation in which software agents facilitate negotiation on behalf of their users and try to reach joint agreements. The potential value of developing such mechanisms becomes enormous when negotiation domain is too complex for humans to find agreements (e.g. e-commerce) and when software components need to reach agreements to work together (e.g. web-service composition). Here, one of the major challenges is to design agents that are able to deal with incomplete information about their opponents in negotiation as well as to effectively negotiate on their users’ behalves. To facilitate the research in this field, an automated negotiating agent competition has been organized yearly. This paper introduces the research challenges in Automated Negotiating Agent Competition (ANAC) 2014 and explains the competition set up and results. Furthermore, a detailed analysis of the best performing five agents has been examined.

The objective of the present study was to elucidate the involvement of FOXO3 in the activation of bovine primordial follicles. In immunohistochemistry, FOXO3 was detected in all of the oocytes in primordial and primary follicles. The FOXO3 decreased after treatment with FOXO3 small interfering RNAs (siRNAs). Ovarian tissues containing dominantly primordial follicles were treated with FOXO3 siRNAs and then xenografted to severe combined immune deficiency (SCID) mice. Two months after xenografting, some primordial follicles developed to the secondary and tertiary stages, and the total percentage of these developing follicles (secondary and tertiary follicles: 18 ± 7%) was higher than in the control grafts treated with control siRNA (7 ± 1%). It is thought that bovine primordial follicle activation is regulated by the FOXO3-dependent mechanism and that knockdown of FOXO3 induces the release of primordial follicles from FOXO3 suppression, initiating their growth.

Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition, modification of these metabolites by diet and/or medications may be a novel therapeutic target for depression. To clarify these aspects, clinical trials measuring metabolites before/after interventions should be conducted. Larger cohort studies including non-clinical subjects are also warranted to clarify our pilot findings.

The role of microglia in stress responses has recently been highlighted, yet the underlying mechanisms of action remain unresolved. The present study examined disruption in working memory due to acute stress using the water-immersion resistant stress (WIRS) test in mice. Mice were subjected to acute WIRS, and biochemical, immunohistochemical, and behavioral assessments were conducted. Spontaneous alternations (working memory) significantly decreased after exposure to acute WIRS for 2h. We employed a 3D morphological analysis and site- and microglia-specific gene analysis techniques to detect microglial activity. Morphological changes in hippocampal microglia were not observed after acute stress, even when assessing ramification ratios and cell somata volumes. Interestingly, hippocampal tumor necrosis factor (TNF)-α levels were significantly elevated after acute stress, and acute stress-induced TNF-α was produced by hippocampal-ramified microglia. Conversely, plasma concentrations of TNF-α were not elevated after acute stress. Etanercept (TNF-α inhibitor) recovered working memory deficits in accordance with hippocampal TNF-α reductions. Overall, results suggest that TNF-α from hippocampal microglia is a key contributor to early-stage stress-to-mental responses.

Abrasive jet machining is used widely for processing brittle materials. A circular nozzle is used commonly, but the cutting performance of circular nozzle is not so good to process a large area and then the use of a rectangular nozzle, slot nozzle, is considered. Many researchers have been trying to reveal the processing mechanism of abrasive jet machining by experimental and theoretical methods, but it is not known sufficiently.In this study, in order to improve the cutting performance of abrasive jet machining nozzle a new two-dimensional rectangular nozzle with a large aspect ratio is proposed and the cutting performance are examined precisely by experiments. The considerations of mechanism of abrasive jet machining and cutting characteristics are given by experiments.Results show that (1) setting circular cylinder in rectangular nozzle perpendicular to the mainstream and extending the nozzle outlet can process uniformly, (2) larger cutting efficiency is obtained comparing with the conventional circular blasting nozzle for validity of dispersion and discharge on flow of particles, (3) relationships between removal rate and particle velocity, particle diameter and mass loading ratio follow power law, (4) relationship between removal rate and surface roughness of cutting material follows power law independent of any machining conditions.

Recently micro-blasting process has been widely used to process brittle material, and at that time a conventional circular nozzle was commonly used. But, the cutting performance of the circular nozzle does not process a large area well so the use of a slot nozzle is considered. In this study, in order to improve the cutting performance of the micro-blasting nozzle, a new slot nozzle with a large aspect ratio is proposed and the flow characteristics and cutting performance are examined precisely by experimental and numerical analysis. Main results show that (1) setting the circular vane in the slot nozzle perpendicular to the stream can diffuse particle flow uniformly at the nozzle exit and then particle velocity distribution becomes uniform, (2) expanding the nozzle outlet at an angle, uniform air and particle velocity distributions at the nozzle exit can be obtained, (3) in spite of setting. obstacles in the nozzle, a fine cutting efficiency is obtained compared to the conventional micro-blasting circular nozzle.

Enantiomer-selective polymerization of (RS)-(phenoxymethyl)thiirane (RS-1) was carried out with ZnEt 2 /L-α-amino acid as an initiator system, and the effect of the initiator system on the enantiomer selectivity was examined with various amino acids. All polymerizations heterogeneously proceeded, and every initiating system was effective in producing optically active polymers. For the polymerization of RS-1 with diethylzinc (ZnEt 2 )/L-leucine (1/1), the conversion was 43.7% in 12 days, and the number-average molecular weight of the polymer was 18,000. The enantiomer selectivity was maximum when the molar ratio of the two components in the ZnEt 2 /L-α-amino acid system was 1:1. When the ZnEt 2 /L-leucine (1/1) system was used in the polymerization, the best result was obtained with an enantiomer-selectivity value of 5.36. During the polymerization, the S enantiomer was preferentially consumed, and the isotactic-rich polymer was enriched in the S configurational units produced.

Microglia have been implicated in various neurological and psychiatric disorders in rodent and human postmortem studies. However, the dynamic actions of microglia in the living human brain have not been clarified due to a lack of studies dealing with in situ microglia. Herein, we present a novel technique for developing induced microglia-like (iMG) cells from human peripheral blood cells. An optimized cocktail of cytokines, GM-CSF and IL-34, converted human monocytes into iMG cells within 14 days. The iMG cells have microglial characterizations; expressing markers, forming a ramified morphology, and phagocytic activity with various cytokine releases. To confirm clinical utilities, we developed iMG cells from a patient of Nasu-Hakola disease (NHD), which is suggested to be directly caused by microglial dysfunction, and observed that these cells from NHD express delayed but stronger inflammatory responses compared with those from the healthy control. Altogether, the iMG-technique promises to elucidate unresolved aspects of human microglia in various brain disorders.

Delirium, causing diverse mental and behavioral symptoms due to disturbance of consciousness, is very common, especially in geriatric patients. 1 In palliative medicine, delirium distresses patients, their family, and caregivers, 2 worsening the quality of the end stages of life. We herein report two cases of successful treatment of multifactorial delirium in patients with terminal cancer by a tetracy

In order to solve scalability problems of routing and addressing architec-tures of the current Internet, Locator/ID Separation Protocol (LISP) has been proposed. LISP requires mapping resolutions between a locator and an ID and such resolutions may impact on communications. In this paper, we empirically show its impact on in-itiating end-to-end bidirectional communications based upon actual LISP environment. We then discuss solutions to overcome impacts and imply that Data Probe may be a solution by applying it only to DNS queries, responses, TCP SYN and SYN+ACK.

Psychiatric disorders have long and dominantly been regarded to be induced by disturbances of neuronal networks including synapses and neurotransmitters. Thus, the effects of psychotropic drugs such as antipsychotics and antidepressants have been understood to modulate synaptic regulation via receptors and transporters of neurotransmitters such as dopamine and serotonin. Recently, microglia, immunological/inflammatory cells in the brain, have been indicated to have positive links to psychiatric disorders. Positron emission tomography (PET) imaging and postmortem studies have revealed microglial activation in the brain of neuropsychiatric disorders such as schizophrenia, depression and autism. Animal models of neuropsychiatric disorders have revealed the underlying microglial pathologies. In addition, various psychotropic drugs have been suggested to have direct effects on microglia. Until now, the relationship between microglia, neurotransmitters and psychiatric disorders has not been well understood. Therefore, in this review, at first, we summarize recent findings of interaction between microglia and neurotransmitters such as dopamine, serotonin, norepinephrine, acetylcholine and glutamate. Next, we introduce up-to-date knowledge of the effects of psychotropic drugs such as antipsychotics, antidepressants and antiepileptics on microglial modulation. Finally, we propose the possibility that modulating microglia may be a key target in the treatment of various psychiatric disorders. Further investigations and clinical trials should be conducted to clarify this perspective, using animal in vivo studies and imaging studies with human subjects.