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Background: In intensive case management (ICM), users receive a wide variety of services of varying content, which makes it difficult to understand the global features of ICM programs., Aims: The aim of this study was to examine the features of ICM programs using network analysis., Methods: A total of 233 ICM users in two Japanese medical institutions were recruited to participate. All received services were recorded for 2 months. In the network analysis, nodes represented types of ICM services and edges between two nodes depicted when over 5% of participants received both types of services., Results: We found high centrality values for 'H5. Hospital-based counseling', 'O13. Outreach support for mental health medications', 'H13. Hospital-based support for mental health medication', 'T5. Counseling via telecommunication', 'H3. Hospital-based coordination of services in the medical institution' and 'T2. Coordination of services with other institutions via telecommunication'. These results indicated that these services were associated with various other types of services. Social functioning was related to 'O13. Outreach support for mental health medication', whereas need for ICM was related to 'H13. Hospital-based support for mental health medications', 'T5. Counseling via telecommunication' and 'T2. Coordination of services with other institutions via telecommunication'., Conclusion: Based on these findings, we speculated that there are at least five types of core services in ICM: regular face-to-face contact, outreach services, hospital-based services, easy contacts and coordination. These findings clarified the features of ICM programs, which may help improve the understanding of case managers' practice.

Gastric adenocarcinoma cells secrete sulfomucins, but their role in gastric tumorigenesis remains unclear. To address that question, we generated A4gnt / Chst4 double-knockout (DKO) mice by crossing A4gnt knockout (KO) mice, which spontaneously develop gastric adenocarcinoma, with Chst4 KO mice, which are deficient in the sulfotransferase GlcNAc6ST-2. A4gnt / Chst4 DKO mice lack gastric sulfomucins but developed gastric adenocarcinoma. Unexpectedly, severe gastric erosion occurred in A4gnt / Chst4 DKO mice at as early as 3 weeks of age, and with aging these lesions were accompanied by gastritis cystica profunda (GCP). Cxcl1, Cxcl5, Ccl2 , and Cxcr2 transcripts in gastric mucosa of 5-week-old A4gnt / Chst4 DKO mice exhibiting both hyperplasia and severe erosion were significantly upregulated relative to age-matched A4gnt KO mice, which showed hyperplasia alone. However, upregulation of these genes disappeared in 50-week-old A4gnt / Chst4 DKO mice exhibiting high-grade dysplasia/adenocarcinoma and GCP. Moreover, Cxcl1 and Cxcr2 were downregulated in A4gnt / Chst4 DKO mice relative to age-matched A4gnt KO mice exhibiting adenocarcinoma alone. These combined results indicate that the presence of sulfomucins prevents severe gastric erosion followed by GCP in A4gnt KO mice by transiently regulating a set of inflammation-related genes, Cxcl1, Cxcl5, Ccl2 , and Cxcr2 at 5 weeks of age, although sulfomucins were not directly associated with gastric cancer development.

Background: A good therapeutic relationship between patient and psychiatrist is vital for effective mental health care. However, no instruments to assess this relationship are available in Japan. This study aimed to develop a Japanese version of a Scale To Assess Therapeutic Relationship (STAR-J), which measures such relationships from the viewpoints of both the patient (STAR-J-P) and clinician (STAR-J-C). We examined the tool's psychometric properties, including factor structure, internal consistency, convergent validity, and test-retest reliability among psychiatric outpatients and psychiatrists. Methods: Study participants comprised 139 outpatients and 10 psychiatrists. Exploratory factor analysis was conducted to investigate factor structure; to confirm cross-validity, confirmatory factor analysis was conducted using a different sample constituting 195 participants in an assertive community treatment program and their 91 case managers. Cronbach's alpha was used to assess internal consistency. For STAR-J-P only, the intra-class correlation coefficient (ICC) was computed for 17 patients to determine test-retest reliability. Spearman's correlation coefficients were calculated to examine convergent validity with service satisfaction, empowerment, and medication adherence. Results: We identified a two-factor structure for STAR-J-P and a one-factor structure for STAR-J-C. Cronbach's alphas for the two STAR-J-P factors were 0.897 and 0.645, and that for the STAR-J-C factor was 0.949. The ICCs for STAR-J-P factors 1 and 2 were 0.765 and 0.630, respectively. STAR-J-P and STAR-J-C were not significantly correlated. STAR-J-P factors 1 and 2 showed significant correlations with service satisfaction (factor 1: ρ = 0.648, p < 0.001; factor 2: ρ = 0.238, p = 0.005) and medication adherence (factor 1: ρ = 0.508, p < 0.001; factor 2: ρ = 0.347, p < 0.001), but only factor 1 showed a significant relationship with empowerment (ρ = 0.283, p = 0.001). STAR-J-C was significantly correlated only with empowerment (ρ = 0.207, p = 0.017). Conclusions: STAR-J appears to be a useful instrument for assessing therapeutic relationships in the Japanese psychiatric outpatient setting. Further studies should test its validity and applicability in different mental health service settings., (Copyright © 2019 Matsunaga, Yamaguchi, Sawada, Shiozawa and Fujii.)

We developed and validated a childhood eating disorder outcome scale based on outcomes associated with body mass index standard deviation score (BMI-SDS). This prospective observational study included 131 children with eating disorders (aged 5-15 years). Participants' outcomes scales were completed at the first visit and at 1, 3, 6, and 12 months. The scale evaluated 12 outcomes: body weight change (BW), eating attitude (EA), fear of being fat (FF), body image distortion (BD), menstruation (ME), perceived physical condition (PC), attending school (AS), disease recognition by school (RS), family function (FA), disease recognition by parent (RP), social adaptation (SA), and relationships with friends (RF). Responses to all items were on a four-point Likert scale. Exploratory factor analysis was used to determine the number of factors based on the 12 outcomes. The relation between outcome scale scores and BMI-SDS over the 12-month follow-up period was analyzed. Two types of factors were extracted: disease-specific factors (EA, FF, BD) and biopsychosocial factors (BW, PC, AS, FA, SA, RF). Three items (ME, RS, RP) were excluded because they showed no significant loading effect. There was a significant negative correlation between the outcome scale and BMI-SDS, and changes in outcome scale scores from baseline to 12 months were significantly associated with improvement in BMI-SDS. We developed a childhood eating disorder outcome scale characterized by disease-specific and biopsychosocial factors. Biopsychosocial management combined with a therapeutic approach for disease-specific symptoms may support body weight recovery for children with eating disorders., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: Several previous observational studies have reported the risk factors associated with readmission in people with mental illness. While patient-reported experiences and outcomes have become increasingly important in healthcare, only a few studies have examined these parameters in terms of their direct association with readmission in an acute psychiatric setting. This project will investigate multiple factors associated with readmission and community living in acute psychiatric patients in Japan. This study will primarily investigate whether patient-reported experiences at discharge, particularly quality of life (QoL), are associated with future readmission and whether readmission after the index hospitalization is associated with changes in patient-reported outcomes during the study period. Here, we describe the rationale and methods of this study., Methods: This multicenter prospective cohort study is being conducted in 21 participating Japanese hospitals, with a target sample of approximately 600 participants admitted to the acute psychiatric ward. The study has four planned assessment points: time of index admission (T1), time of discharge (from the index admission) (T2), 6 months after discharge from the index admission (T3), and 12 months after discharge from the index admission (T4). Participants will complete self-reported measures including a QoL scale, a subjective disability scale, and an empowerment- and self-agency-related scale at each assessment point; additionally, service satisfaction, subjective view of need for services, and subjective relationships with family members will be assessed at T2 and T3. We will assess the participants' hospitalization during the study period and evaluate several potential individual- and service-level factors associated with readmission and patient-reported experiences and outcomes. Multivariate analyses will be conducted to identify potential associations between readmission and patient-reported experiences and outcomes., Discussion: The present study may produce evidence on how patient-reported experiences at discharge influence readmission and on the influence of readmission on the course of patient-reported outcomes from admission to community living after discharge. The study may contribute to improving care for both patients' subjective views of their own health conditions and their community lives in an acute psychiatric setting. Trial registration University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) UMIN000034220. Registered on September 20, 2018., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Background: In Japan, the mental health system has been shifting from hospitalization-based to community-based care; some organizations have gradually begun providing intensive case management (ICM) services. We developed an Intensive Case Management Screening Sheet (ICMSS) to screen for the need for ICM in people with mental illness., Methods: The aim of this study was to examine the psychometric properties and discriminative ability of ICMSS. Subjects consisted of 911 people with mental illness. The ICMSS score was rated by a professional such as a nurse, social worker, or occupational therapist., Results: Exploratory factor analysis showed a one-factor structure with 14 items. The factor structure was supported by confirmatory factor analysis (comparative fit index, 0.98; Tucker-Lewis index, 0.97; root mean square error test of close fit, 0.05). In the receiver operating characteristic analysis for discriminating between users and non-users of ICM services, the area under the curve (AUC) for ICMSS was significantly larger than for Global Assessment of Functioning and Personal and Social Performance Scale, indicating better discriminative ability. However, the AUC for ICMSS was moderate. Thus, we suggest that the need for ICM services is determined by quantitative assessment (i.e., ICMSS) and clinical judgment., Conclusion: ICMSS is a brief tool for mental health professionals that will be useful in routine clinical practice. We expect that ICMSS will be used as a measure that reflects the views of professionals from various disciplines in Japanese institutions., Competing Interests: The authors declare that they have no competing interests.

Purpose: This study assessed the symptoms, treatment, social systems use, and perception of living conditions of patients with young-onset Parkinson's disease (YOPD), and investigated the support needed by them., Method: Among the 252 people who completed our questionnaire, we defined YOPD patients as those diagnosed as young onset or those with onset at ≤40 years. The data were compared with others., Results: There were 24 patients with YOPD (9.5%) (average age: 61.7 years), with an average disease duration 6.4 years longer (p < 0.01) and time until diagnosis 0.7 years longer (p < 0.1) than those of other patients. This group took 1.6 times more types of medicines, and time to their next appointment was 8.6 days shorter than that of other patients (p < 0.05). Patients with YOPD had more pulsive walking and more sweating (p < 0.05), and more motor fluctuation (p < 0.1). More patients with YOPD had a physical disability certificate but felt they were not obtaining the required services (p < 0.05). 45.0% of the YOPD group wanted to work more, more used information and communication equipment (p < 0.05), and more felt their medications were adequate (p < 0.1)., Conclusions: Increased awareness of YOPD is needed. YOPD patients have motor fluctuation because of the longer disease duration. Thus, the support of doctors and nurses, and frequent examination visits, are indispensable for controlling symptoms to achieve middle age developmental tasks. Increased support for care-giving, leisure-time activities, and work is also necessary and may help maintain the desire to work in this group.

Objectives: To evaluate the expression of annexin A1 protein in patients with renal cell carcinoma., Methods: Annexin A1 expression was examined in renal cell carcinoma specimens from 27 patients, and their disease-free survival was analyzed using the log-rank test. Annexin A1 knockdown in the human renal cell carcinoma cell line Caki-1 was carried out, and its proliferation, invasion, motility and adhesion were compared with those of control cells., Results: In 13 out of 27 patients, annexin A1 was highly expressed in the membrane of renal cell carcinoma tumor cells, whereas in the rest of the patients, annexin A1 expression was weak or negligible in the membrane of those cells. Patients with high annexin A1 expression had significantly poorer disease-free survival than those with weak or negligible annexin A1 expression (P = 0.031). In the renal cell carcinoma cell line, annexin A1 knockdown cells showed significantly decreased proliferation, invasion, motility and adhesion relative to control cells, and expressed lower relative levels of membrane-type 1 matrix metalloproteinase and hypoxia-inducible factor 1-alpha transcripts, showing a potential pathway regulated by annexin A1., Conclusion: Annexin A1 is associated with renal cell carcinoma malignant potential and could serve as a marker of poor prognosis., (© 2018 The Japanese Urological Association.)

Background: Ramucirumab, an antiangiogenic agent, often causes proteinuria as a characteristic adverse effect. We retro- spectively evaluated proteinuria and clarified the significance of the protein/creatinine ratio by using single urine samples from patients with advanced gastric cancer who were treated with ramucirumab., Methods: Twenty-three patients who received ramucirumabb etween June 2015 and April 2016 were enrolled. A total of 199 urinalysis specimens were qualitatively analyzed to obtain urine protein levels and the protein/creatinine ratio, and the values were compared., Results: Frequency of proteinu- ria was 43.5%(grade 1: 26.1%, grade 2: 8.7%, and grade 3: 8.7%). The protein/creatinine ratio was less than 2 in -, ±, and 1+ based on the urine protein qualitative examination; 12.5% of 2+ and 71.4% of 3+ or 4+ had a protein/creatinine ratio over 2., Conclusions: In patients with gastric cancer, treated with ramucirumab, the protein/creatinine ratio should be examined in cases of 2+, 3+ or 4+ via a qualitative examination.

Fecal DNA metabarcoding is currently used in various fields of ecology to determine animal diets. Contamination of non-food DNA from complex field environments is a considerable challenge to the reliability of this method but has rarely been quantified. We evaluated plant DNA contamination by sequencing the chloroplast trnL P6 loop region from food-controlled geese feces. The average percentage of contaminant sequences per sample was 1.86%. According to the results of generalized linear models, the probability of contamination was highest in samples placed in wet soil. The proportion of contaminant sequences was lowest at the earliest sampling point and was slightly higher in samples placed in open conditions. Exclusion of rare OTUs (operational taxonomic units) was effective for obtaining reliable dietary data from the obtained sequences, and a 1% cutoff reduced the percentage of contaminated samples to less than 30%. However, appropriate interpretation of the barcoding results considering inevitable contamination is an important issue to address. We suggest the following procedures for fecal sampling and sequence data treatment to increase the reliability of DNA metabarcoding diet analyses: (i) Collect samples as soon as possible after deposition, (ii) avoid samples from deposits on wet soil, and (iii) exclude rare OTUs from diet composition estimations.

Concern about mental health issues and the treatment of mentally disordered offenders attracts considerable public attention. This study aimed to gather the experiences and opinions of people who have experienced admission to a psychiatric ward in order to grasp their reaction to, and understanding of, the legislation behind the involuntary admission of psychiatric patients. A web-based questionnaire survey was conducted with a total of 379 participants, using a cross-sectional, exploratory design. The data were analyzed using a chi-squared test, Fisher's exact test, and a logistic regression analysis. According to the results, many patients were satisfied with their treatment during psychiatric admission; however, only few participants said that they had been given an adequate explanation for their involuntary treatment. Most participants expected qualified assistance after discharge, although the prospect of a regular visit from an official was not entirely supported by the participants. Patient satisfaction was relevant to the discussion of their needs after discharge and in developing a crisis plan during admission. These findings suggest that psychiatric patients accept inpatient treatment as long as they receive an adequate explanation. More qualified care such as relapse prevention would be expected to lead to better satisfaction. For them to welcome regular visits from an official, patients may need more information and discussion., Competing Interests: The authors declare no potential conflicts of interest concerning the research, authorship, and publication of this article.

With the acceleration of deinstitutionalization might increase families' chances of suffering violence by patients. This study clarified parents' coping processes with violence experienced from patients with schizophrenia. The grounded theory approach was used, and 26 parents were interviewed. We identified a four-stage coping process: (1) hope for treatment, (2) living with violence, (3) trying to solve violence, and (4) last solution for violence. This coping process had two illness-related characteristics: (1) a process of coping with two main stressful events (the illness and violence), and (2) the need for long-term appraisal of violence because of its unclear causes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: Constipation is a serious problem for persons with mental and physical disabilities in Japan. However, prophylaxis is extremely difficult because the major causes of constipation in these individuals are related to their mental and physical disabilities. Constipation can be successfully treated with glycerol enemas (GEs) and other aperients. As constipation is a lifetime issue for these persons, dietary regimens to prevent constipation can be important., Methods: This study evaluated the probiotic effects of kefir-fermented milk for preventing constipation in 42 persons with mental and physical disabilities. The participants were administered 2 g of lyophilized kefir with each meal for 12 weeks and their bowel movements, the administration of GE and other aperients, and stool shape were recorded., Results: The intake of kefir significantly reduced constipation, compared with the baseline status. Some individuals showed complete relief of constipation, whereas others showed no effect., Conclusion: Despite individual variations, consuming kefir daily could prevent constipation., (© 2017 Japan Academy of Nursing Science.)

There have been several violence-related deaths in Japan due to family violence by persons with severe mental illness against their caregivers. However, it is not often acknowledged that these violent acts are mainly directed at family members. This study aimed to clarify what acts of violence family caregivers experienced from their relative with schizophrenia, and how frequently these violent incidents occurred in their lifetime. We also examined caregivers' thoughts of death about themselves and their relatives, as well as their consultation efforts and escape from the violence perpetrated by their relative. Of the 277 caregivers, 87.7% had experienced psychological violence and 75.8% had experienced physical violence perpetrated by their relative. Of 210 caregivers who had experienced physical violence, 26.7% had thought of murder-suicide and 31.0% had wished for their relative's death. Family violence by persons with schizophrenia is not rare but a common occurrence in Japan and may have fatal consequences.

We have reported an autopsy case of neuromyelitis optica (NMO) that exhibited persisting active inflammatory lesions in the central nervous system (CNS) despite a 45-year-long treatment with oral corticosteroids. To our knowledge, our case had received the longest course of maintenance treatment. This case study suggests that the current treatment of NMO with immunosuppressive agents may offer a good prospect for improving life expectancy. On the other hand, it also suggest that microscopic active lesions which were clinically silent and difficult to detect by neurological examination or MRI studies may persist in the CNS in patients with NMO, despite prolonged and continuous immunosuppressive treatment.

Fascin1 is an actin-bundling protein involved in cancer cell migration and has recently been shown also to have roles in virus-mediated immune cell responses. Because viral infection has been shown to activate immune cells and to induce interferon-β expression in human cancer cells, we evaluated the effects of fascin1 on virus-dependent signaling via the membrane- and actin-associated protein RIG-I (retinoic acid-inducible gene I) in colon cancer cells. We knocked down fascin1 expression with shRNA retrovirally transduced into a DLD-1 colon cancer and L929 fibroblast-like cell lines and used luciferase reporter assays and co-immunoprecipitation to identify fascin1 targets. We found that intracellular poly(I·C) transfection to mimic viral infection enhances the RIG-I/MDA5 (melanoma differentiation-associated gene 5)-mediated dimerization of interferon regulatory factor 3 (IRF-3). The transfection also significantly increased the expression levels of IRF-7, interferon-β, and interferon-inducible cytokine IP-10 in fascin1-deleted cells compared with controls while significantly suppressing cell growth, migration, and invasion. We also found that fascin1 constitutively interacts with IκB kinase ϵ (IKKϵ) in the RIG-I signaling pathway. In summary, we have identified fascin1 as a suppressor of the RIG-I signaling pathway associating with IκB kinase ϵ in DLD-1 colon cancer cells to suppress immune responses to viral infection., (© 2018 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: B cells play an important role in the development of multiple sclerosis (MS), but can also exhibit regulatory functions through IL-10 production. Toll-like receptors (TLR) and CD40 signaling are likely to be involved in this process., Objective: To investigate the ability of MS B cells to produce IL-10 in response to TLR stimulation in the presence or absence of CD40 co-stimulation., Methods: Peripheral blood mononuclear cells obtained from 34 MS patients and 24 matched healthy participants (HS) were stimulated through either TLR4 or TLR9 alone, or together with CD40. Intracellular cytokine production was analyzed by flow cytometry., Results: The frequency of IL-10-producing cells in total B cells after either TLR9 or CD40 stimulation was significantly lower in MS than HS, regardless of disease phase. The frequency of IL-10 producing B cells after TLR4 stimulation did not differ significantly between HS and MS, regardless of disease phase. TLR4 and CD40 co-stimulation synergistically increased the frequency of IL-10-producing but not pro-inflammatory cytokine-producing B cells at MS relapse. This effect was observed in both CD27 - naïve and CD27 + memory B cells. The frequency of IL-10-producing B cells following CD40 stimulation was significantly higher in interferon-β responders than non-treated MS patients. Finally, we confirmed that the frequency of IL-10-producing B cells positively correlated with IL-10 production quantity by B cells using magnetic-isolated B cells., Conclusions: Cross-talk between TLR4 and CD40 signaling plays a crucial role in regulating IL-10 production by B cells during MS relapses, which may promote recovery from relapse. CD40 signaling in B cells is involved in the response to interferon-β in MS. Collectively, TLR4 and CD40 signaling in B cells may provide a promising target for MS therapy., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Primary lung cancer is the most frequent cause of cancer-related deaths worldwide. Cisplatin has been used as a key drug in the treatment for patients with lung cancer; however, most of the patients failed to respond to cisplatin within several months, and the mechanisms underlying the cisplatin resistance have not been fully elucidated. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is a key adaptor protein in the formation of inflammasomes. ASC is also involved in apoptotic signaling. Importantly, ASC expression is decreased in lung cancer and various cancers, but its precise function in tumor progression remains unknown. To explore the hitherto unknown role of ASC in lung cancer, we initially searched for lung cancer cell lines with higher expression levels of ASC using Cancer Cell Line Encyclopedia (CCLE) database, thereby identifying the A549 human non-small cell lung cancer cell line. Accordingly, with retroviral shRNA, the expression of ASC was forced to decrease in A549 cells. Stable ASC-knockdown cells, thus established, showed the increased activities of proliferation, motility, and invasion, compared with control cells. Importantly, ASC-knockdown cells also became resistant to cisplatin, but not to other anti-cancer agents, 5-fluorouracil and paclitaxel. Bcl-2 and phospho-Src levels were increased in ASC-knockdown cells. A Bcl-2 inhibitor, ABT-199, induced an apoptotic response in ASC-knockdown cells, and dasatinib, a Src inhibitor, blocked cell invasiveness. Thus, ASC may be involved in tumor suppression and cell death via Bcl-2 and pSrc. Targeting Bcl-2 and Src in ASC-downregulated populations of lung cancer may improve treatment outcome.

We describe for the first time the diagnosis of Schizophyllum commune infection in a captive cheetah. Eosinophilic plasmacytic conjunctivitis was detected histopathologically in a biopsy specimen. Both a second surgical specimen and drainage fluid from a gingival mass and fistula contained fungal hyphae in giant cells with granulomatous inflammation. Allergic S. commune mycosis was suspected at this point. A monokaryotic isolate was characterized morphologically, and then identified genetically. Treatment with itraconazole and pimaricin was effective.

Pancreatic cancer is lethal, as it is often detected late. Thus, novel biomarkers of precursor lesions are needed to devise timely therapies. Pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) are major precursors of pancreatic cancer. In normal gastric mucosa, gastric gland mucin-specific O-glycans are unique in having α1,4-linked N-acetylglucosamine (αGlcNAc) residues attached to MUC6. Recently we reported that αGlcNAc functions as a tumor suppressor for differentiated-type gastric adenocarcinoma (Karasawa et al., J Clin Invest 122, 923, 2012). MUC6 is also expressed in pancreatic neoplasms, including PanIN and IPMN, but the role of αGlcNAc expression in pancreatic neoplasms remains unknown. Here, we analyze expression patterns of αGlcNAc, MUC6 and MUC5AC in pancreatic neoplasms and compare them with progression from PanIN to invasive ductal adenocarcinoma (IDAC) (the PanIN-IDAC sequence; 20 cases) and from IPMN to IPMN with associated invasive carcinoma (IPMNAIC) (the IPMN-IPMNAIC sequence; 20 cases). At both sequences, the frequency of MUC6-positive and αGlcNAc-positive lesions decreased with tumor progression. We then compared expression levels of αGlcNAc and MUC6 at each step of the progression. At the PanIN-IDAC sequence, αGlcNAc expression significantly decreased relative to MUC6 in low-grade PanIN (P = 0.021), high-grade PanIN/intraductal spread of IDAC (P = 0.031) and IDAC (P = 0.013). At the IPMN-IPMNAIC sequence, decreased αGlcNAc expression was also observed in low-grade IPMN exhibiting gastric-type morphology (P = 0.020). These results suggest that decreased expression of αGlcNAc relative to MUC6 occurs early and marks the initiation of tumor progression to pancreatic cancer., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Recently, sarcopenia has attracted attention as therapeutic target because it constitutes a risk factor for metabolic and cardiovascular diseases. We focused 5-aminolevulinic acid (ALA) which act as electron carriers in the mitochondrial electron transport system. The mice that received ALA for 8 weeks gained muscle strength and endurance, and exhibited increased muscle mass and mitochondrial amount. Administration of ALA to sarcopenia mice aged 100 weeks and chronic kidney disease (CKD) model mice also increased muscle mass and improved physical performance. Metabolome analysis revealed increased branched-chain amino acids (BCAAs) levels in the skeletal muscle of ALA-treated mice. Quantitative PCR analysis revealed decreased expression levels in branched-chain amino acid transaminases (BCATs) that degrade BCAAs and other muscle-degrading factors, and increased levels of mitochondria-activating factors. We also studied in cultured myocytes and obtained compatible results. ALA-treated mice tended to increase body weight, but reduced blood glucose level. These suggested that ALA treatment not only activated muscle mitochondria but also enhanced muscle mass through an increase in BCAAs contents, as to improve muscle strength, endurance and glucose tolerance in mice. In these ways, muscle mitochondrial activation with ALA is suggested to be useful for the treatment of sarcopenia and glucose intolerance.

Kasugamycin (KSM), an aminoglycoside antibiotic isolated from Streptomyces kasugaensis cultures, has been used against rice blast disease for more than 50 years. We cloned the KSM biosynthetic gene (KBG) cluster from S. kasugaensis MB273-C4 and constructed three KBG cassettes (i.e., cassettes I-III) to enable heterologous production of KSM in many actinomycetes by constitutive expression of KBGs. Cassette I comprised all putative transcriptional units in the cluster, but it was placed under the control of the P neo promoter from Tn5. It was not maintained stably in Streptomyces lividans and did not transform Rhodococcus erythropolis. Cassette II retained the original arrangement of KBGs, except that the promoter of kasT, the specific activator gene for KBG, was replaced with P rpsJ , the constitutive promoter of rpsJ from Streptomyces avermitilis. To enhance the intracellular concentration of myo-inositol, an expression cassette of ino1 encoding the inositol-1-phosphate synthase from S. avermitilis was inserted into cassette II to generate cassette III. These two cassettes showed stable maintenance in S. lividans and R. erythropolis to produce KSM. Particularly, the transformants of S. lividans induced KSM production up to the same levels as those produced by S. kasugaensis. Furthermore, cassette III induced more KSM accumulation than cassette II in R. erythropolis, suggesting an exogenous supply of myo-inositol by the ino1 expression in the host. Cassettes II and III appear to be useful for heterologous KSM production in actinomycetes. Rhodococcus exhibiting a spherical form in liquid cultivation is also a promising heterologous host for antibiotic fermentation.

Aim: The study aimed to develop two Japanese versions of King's Stigma Scale, a full version (KSS-J-1) and a short version (KSS-J-2), through psychometric property testing., Methods: The sample included 112 people with mental illness. We tested the constructs of the scales using both confirmatory and exploratory factor analyses. Internal consistency and test-retest reliability were tested. We examined convergent validity with self-esteem or perceived stigma, and different group validity, using the Kessler Psychological Distress Scale (K6)., Results: Whereas a relatively weak model fit (comparative fit index = 0.66, Tucker-Lewis index = 0.63, root mean square error of approximation = 0.097) of KSS-J-1 (full version: 28 items) was found, KSS-J-2 (short version: 17 items), produced by exploratory factor analysis, had a moderate model fit (comparative fit index = 0.90, Tucker-Lewis index = 0.89, root mean square error of approximation = 0.063). High internal consistency (KSS-J-1, ω = 0.82-0.89; KSS-J-2, ω = 0.86-0.89) and moderate test-retest reliability (KSS-J-1, interclass correlation = 0.56-0.88; KSS-J-2, interclass correlation = 0.45-0.85) were reported. Some subscales and the entire scale of KSS-J-1 were significantly correlated with self-esteem and perceived stigma. Conversely, only two subscales in KSS-J-2 were significantly correlated with self-esteem. The scores of each subscale and the entire score for both KSS-J-1 and KSS-J-2 in the high psychological distress group were higher than the low group (KSS-J-1, d = 0.61-0.83; KSS-J-2, d = 0.47-0.70), except for the Discrimination subscale in KSS-J-2., Conclusion: Both Japanese versions of King's Stigma Scale can be utilized depending on their intended use., (© 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.)

Excess mortality in persons with severe mental disorders (SMD) is a major public health challenge that warrants action. The number and scope of truly tested interventions in this area remain limited, and strategies for implementation and scaling up of programmes with a strong evidence base are scarce. Furthermore, the majority of available interventions focus on a single or an otherwise limited number of risk factors. Here we present a multilevel model highlighting risk factors for excess mortality in persons with SMD at the individual, health system and socio-environmental levels. Informed by that model, we describe a comprehensive framework that may be useful for designing, implementing and evaluating interventions and programmes to reduce excess mortality in persons with SMD. This framework includes individual-focused, health system-focused, and community level and policy-focused interventions. Incorporating lessons learned from the multilevel model of risk and the comprehensive intervention framework, we identify priorities for clinical practice, policy and research agendas., (© 2017 World Psychiatric Association.)

ASC (apoptosis-associated speck-like protein containing a CARD) is a key adaptor molecule of inflammasomes that mediates inflammatory and apoptotic signals. Aberrant methylation-induced silencing of ASC has been observed in a variety of cancer cells, thus implicating ASC in tumor suppression, although this role remains incompletely defined especially in the context of closely neighboring cell proliferation. As ASC has been confirmed to be silenced by abnormal methylation in HT1080 fibrosarcoma cells as well, this cell line was investigated to characterize the precise role and mechanism of ASC in tumor progression. The effects of ASC were examined using in vitro cell cultures based on comparisons between low and high cell density conditions as well as in a xenograft murine model. ASC overexpression was established by insertion of the ASC gene into pcDNA3 and pMX-IRES-GFP vectors, the latter being packed into a retrovirus and subjected to reproducible competitive assays using parental cells as an internal control, for evaluation of cell viability. p21 and p53 were silenced using shRNA. Cell viability was suppressed in ASC-expressing transfectants as compared with control cells at high cell density conditions in in vitro culture and colony formation assays and in in vivo ectopic tumor formation trials. This suppression was not detected in low cell density conditions. Furthermore, remarkable progression of apoptosis was observed in ASC-introduced cells at a high cell density, but not at a low one. ASC-dependent apoptosis was mediated not by p21, p53, or caspase-1, but rather by cleavage of caspase-9 as well as by suppression of the NF-κB-related X-linked inhibitor-of-apoptosis protein. Caspase-9 cleavage was observed to be dependent on gap junction formation. The remarkable effect of ASC on the induction of apoptosis through caspase-9 and gap junctions revealed in this study may lead to promising new approaches in anticancer therapy., Competing Interests: The authors have declared that no competing interests exist.

Chronic kidney disease (CKD) impairs physical performance in humans, which leads to a risk of all-cause mortality. In our previous study, we demonstrated that a reduction in muscle mitochondria rather than muscle mass was a major cause of physical decline in 5/6 nephrectomized CKD model mice. Because ghrelin administration has been reported to enhance oxygen utilization in skeletal muscle, we examined the usefulness of ghrelin for a recovery of physical decline in 5/6 nephrectomized C57Bl/6 mice, focusing on the epigenetic modification of peroxisome proliferator activated receptor gamma coactivator-1α (PGC-1α), a master regulator of mitochondrial biogenesis. The mice were intraperitoneally administered acylated ghrelin (0.1 nmol/gBW; three times per week) for a month. Muscle strength and exercise endurance were measured by using a dynamometer and treadmill, respectively. Mitochondrial DNA copy number was determined by quantitative PCR. The methylation levels of the cytosine residue at 260 base pairs upstream of the translation initiation point (C-260) of PGC-1α, which has been demonstrated to decrease the expression, was evaluated by methylation-specific PCR and bisulfite genomic sequencing methods after the ghrelin administration. Ghrelin administration improved both muscle strength and exercise endurance in the mice and was associated with an increase in muscle mass and muscle mitochondrial content. Ghrelin administration decreased the methylation ratio of C-260 of PGC-1α in the skeletal muscle and increased the expression. Therefore, ghrelin administration effectively reduced the physical decline in 5/6 nephrectomized mice and was accompanied with an increased mitochondrial content through de-methylation of the promoter region of PGC-1α in the muscle.

Objective . The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese. Methods . The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally. Results . The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area ( r = -0.411, p < 0.0001), fasting glucose ( r = -0.330, p < 0.0001), HbA1c ( r = -0.231, p = 0.0146), and systolic blood pressure ( r = -0.224, p = 0.0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR ( r = -0.416, p < 0.0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects. Conclusion . We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.

Eye disorders are one of the characteristic adverse events associated with S-1 chemotherapy. In this retrospective study, we investigated the frequency and outcome of eye disorders associated with S-1 chemotherapy in gastric cancer patients. This retrospective study included 75 advanced gastric cancer patients who received S-1 monotherapy between January 2014 and December 2015. We retrospectively evaluated the frequency, Grade, and treatment of eye disorders. Eye disorders were observed in 16 patients(21%). The median time of onset was 3(range, 1-8)months. Grade 2 watering eyes, eye discharge, and conjunctivitis were reported in 14, 8, and 4 patients, respectively. Artificial tears, fluorometholone eye-drops, and both of these treatments were used in 7, 1, and 8 patients, respectively. Ophthalmologic examination was performed for 3 patients. No delay or reduction of S-1 therapy was required for the eye disorders. Eye disorders associated with S-1 therapy in gastric cancer patients did not affect treatment if managed properly using eye drops.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease. Fingolimod, a highly effective disease-modifying drug for MS, retains CCR7 + central memory T cells in which autoaggressive T cells putatively exist, in secondary lymphoid organs, although relapse may still occur in some patients. Here, we analyzed the T cell phenotypes of fingolimod-treated, fingolimod-untreated patients, and healthy subjects. The frequency of CD56 + T cells and granzyme B-, perforin-, and Fas ligand-positive T cells significantly increased during fingolimod treatment. Each T cell subpopulation further increased during relapse. Interestingly, T cells from fingolimod-treated patients exhibited interferon-γ biased production, and more myelin basic protein-reactive cells was noted in CD56 + than in CD56 - T cells. It is likely that the altered T cell phenotypes play a role in MS relapse in fingolimod-treated patients. Further clinical studies are necessary to investigate whether altered T cell phenotypes are a biomarker for relapse under fingolimod therapy.

Background: The REGARD and RAINBOW trials showed that ramucirumab(RAM)alone and RAM plus paclitaxel(PTX) were effective therapies for advanced gastric cancer patients previously treated with chemotherapy. In this retrospective study, we evaluated the safety and efficacy of RAM alone and PTX plus RAM in such patients., Methods: Patients who were received RAM at 8mg/kg or RAM plus PTX at 80mg/m2(on days 1, 8, and 15 of a 28-day cycle)between June 2015 and March 2016 were enrolled in this study. We compared the clinical outcome of RAM alone(RAM group, n=10)with that of RAM plus PTX(PTX+RAM group, n=13)., Results: The RAM group contained many more patients with poor performance status or prior chemotherapy of 2 or more regimens than the PTX+RAM group. All patients in both groups received chemotherapy on an outpatient basis. One case of grade 3 or 4 hematological adverse events was found in the RAM group and 6 cases were found in the PTX+RAM group. The overall response rate was 10% in the RAM group and 30% in the PTX+RAM group. Progression-free survival was 54 days in the RAM group and 187 days in the PTX+RAM group(p=0.0374). Overall survival was 158 days in the RAM group and was not reached in the PTX+RAM group(p=0.1091)., Conclusions: RAM alone and RAM plus PTX can be administered safely on an outpatient basis and are beneficial for advanced gastric cancer patients previously treated with chemotherapy.

Most violence by patients with mental illness is perpetuated against family members rather than the general public. However, there is insufficient research to reach a consensus on factors related to family violence for this population. Thus, the current study aimed to clarify factors related to physical violence by patients with schizophrenia towards their parents in Japan. A self-administrated survey was distributed through family groups to families with a relative with a psychiatric disorder. Questionnaires completed by 400 parents of patients with schizophrenia were analyzed. Of the 400 parents, almost two-thirds experienced "no physical violence" and close to one-third experienced "physical violence" during the past year. Results of a mixed-effects logistic regression revealed that physical violence was significantly related to the patients' gender (female rather than male), multiple patient hospitalizations (3 or more times as compared to never hospitalized), low annual household income (less than US$20K as compared to over US$40K), and higher hostility and criticism of family interactions. Family violence maybe reduced through education on communication strategies for both parents and patients., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Disorders of cytoskeletal remodeling and signal transduction are frequently involved in cancer progression. In particular, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) has been reported a proapoptotic molecule that is epigenetically silenced in several human cancers. ASC is a well-characterized adaptor protein involved in the formation of multiprotein oligomers, called inflammasomes, and plays a crucial role in the activation and secretion of interleukin-1β and interleukin-18 in innate immune cells. However, the function of ASC in the regulation of tumor progression remains elusive. The present investigation examined the involvement of ASC in cancer progression and the acquisition of metastatic ability. To determine the effect of ASC depletion in in vitro and in vivo model systems, ASC was stably knocked down in B16 murine melanoma cell lines using retroviral transduction of shRNA. ASC suppression increased the motility of B16BL6 cells in scratch assays and augmented invasiveness as assessed by a Matrigel-coated transwell system. Invadopodia formation and Src phosphorylation level were markedly enhanced in ASC-knockdown cells as well. Since caspase-8 has been reported to enhance cellular migration by Tyr380 phosphorylation via Src, we examined Tyr380 phosphorylation of caspase-8 in ASC-knockdown cells and found it to be elevated in ASC-knockdown cells but attenuated by z-VAD-fmk or z-IETD-fmk. Moreover, ASC ablation increased pulmonary metastasis in mice after intravenous injection of B16BL6 cells. Our cumulative findings indicate that ASC suppresses cancer metastasis and progression via the modulation of cytoskeletal remodeling and the Src-caspase-8 signaling pathway., (© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: The second lumbrical-interossei latency difference test (2LINT) is used frequently for electrodiagnosis of carpal tunnel syndrome (CTS). A premotor potential observed with 2LINT has been identified as a median-nerve sensory nerve action potential. We evaluated the utility of the premotor potential latency analysis (i.e., premotor potential study; PPS) for CTS electrodiagnosis., Methods: Sensitivity, specificity, and percentage "no evoked response" (%NER) values were compared prospectively among PPS, median-nerve sensory nerve-conduction studies (NCSs) for digits 1, 2, and 4, and palmar mixed NCS., Results: Sixty-four healthy control hands and 104 hands with CTS were enrolled in this study. PPS sensitivity was superior to other sensory/mixed NCSs (75% vs. 42%-62%). All NCS specificities were acceptable (95%-97%). The %NER of PPS was lower than that of other NCSs (13% vs. 25%-44%)., Conclusion: Premotor potential could be evoked in more CTS hands and was the most sensitive among median-nerve sensory and mixed NCSs. Therefore, we could use the 2LINT with PPS as median and ulnar motor NCS as well as median sensory NCS.

This paper describes the rationale, design, and methods of the Treatment for Anxiety in Autism Spectrum Disorders study, a three-site randomized controlled trial investigating the relative efficacy of a modular CBT protocol for anxiety in ASD (Behavioral Interventions for Anxiety in Children with Autism) versus standard CBT for pediatric anxiety (the Coping Cat program) and a treatment-as-usual control. The trial is distinct in its scope, its direct comparison of active treatments for anxiety in ASD, and its comprehensive approach to assessing anxiety difficulties in youth with ASD. The trial will evaluate the relative benefits of CBT for children with ASD and investigate potential moderators (ASD severity, anxiety presentation, comorbidity) and mediators of treatment response, essential steps for future dissemination and implementation.

A 64-year-old man consulted for an abnormal shadow in November 2012. Chest computed tomography showed a thicking and small nodules of the left pleura and pleural effusion with mediastinal and supracravicular lymphnodes swelling. The cytological study of the pleural effusion showed individual atypical cells surrounded by many lymphocyte. The atypical cells are large, round or ovoid and had welldefined borders, abundant eosinophilic, glassy cytoplasm, and round or elliptic nuclei with clear eosinophilic nucleoli resembling decidua cells. According to immunohistochemistry study, cells were positive for calretinin, EMA, cytokeratinAE1/AE3, WT-1, D2-40 and negative for CEA, desmin, TTF-1, Ber-EP4, synaptophysin, S-100 compatible with deciduoid mesothelioma. The cytological features are important and useful for diagnosis of deciduoid mesothelioma.

Background: Deficits of motivation have been considered to be a core feature of schizophrenia, and recent studies have begun to reveal the biological and psychological characteristics and mechanisms underlying the deficits in motivation in schizophrenia patients. The aims of the present study were to investigate the characteristics of motivation in schizophrenia patients using the General Causality Orientations Scale (GCOS), and the impacts of motivational orientations on the functional outcomes in schizophrenia patients., Methods: A total of 53 outpatients with schizophrenia and 38 healthy controls were recruited for this study. The GCOS was used to assess individual tendencies in respect of three different motivational orientations: the autonomy, controlled, and impersonal orientations, corresponding to intrinsic motivation, extrinsic motivation, and amotivation, respectively. The cognitive functioning, psychiatric symptoms, social functioning, and quality of life of the subjects were also assessed., Results: The score for autonomy orientation was significantly lower in the patient group than that in the control group, while no significant differences were found between the two groups in respect of the scores for the other two orientations. The autonomy orientation was associated with various clinical variables, and regression analysis identified as one of the variables with the highest predictive accuracy for social functioning., Conclusions: Intrinsic motivation measured by the GCOS in schizophrenia patients was significantly lower than that in healthy controls. The deficits of intrinsic motivation were broadly associated with the clinical features and were a determinant of social functioning. Development of treatments for enhancing intrinsic motivation would be essential for functional recovery in schizophrenia patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The objective was to clarify whether dietary palmitic acid supplementation affects glucose-stimulated insulin secretion (GSIS) and the endoplasmic reticulum (ER) stress pathway in pancreatic islets in mice. Eight-week-old male C57BL/6J mice were randomly divided into three treatment diet groups: control diet, palmitic acid-supplemented diet (PAL) and oleic acid-supplemented diet (OLE). After 2 weeks of treatment, intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test were performed. GSIS was assessed by pancreatic perfusion in situ with basal (100 mg/dL) glucose followed by a high (300 mg/dL) glucose concentration. We measured mRNA levels of ER stress markers such as C/EBP homologous protein (CHOP), immunoglobulin heavy-chain binding protein (BIP) and X-box binding protein (XBP)-1 using real-time polymerase chain reaction (PCR) analyses in isolated islets. Immunohistochemical staining was also performed. Mice fed PAL showed significantly decreased glucose tolerance (p < 0.05). In the perfusion study, GSIS was significantly suppressed in the PAL group (p < 0.05). Semi-quantitative RT-PCR revealed that islet CHOP, BIP, and XBP-1 mRNA expression were significantly increased in the PAL group (p < 0.05). TUNEL-positive β-cells were not detected in all groups. Dietary palmitic acid-supplementation for 2 weeks might suppress GSIS and induce ER stress in pancreatic islets in mice, in the early stage of lipotoxicity.

Background: Some patients cannot draw three subjects on the same page during the synthetic house-tree-person drawing test (S-HTP). We call this phenomenon "no synthetic sign". The aim of this study was to clarify the pathological meaning of no synthetic sign and investigate its use for the early detection of developmental disorders at a pediatric primary care center., Methods: We administered the S-HTP to 283 people who consulted the child psychosomatic medical clinic of Okayama University Hospital in 2007-2012. We diagnosed developmental disability based on DSM-IV-TR criteria and compared findings between the different diagnostic groups., Results: A total of 241 patients completed the S-HTP (S-HTP group) and 22 patients were not able to complete the S-HTP, but did complete the HTP (an original version of the S-HTP) or tree test (HTP group). Significantly more people in the HTP group had autism spectrum disorder (ASD) compared with the S-HTP group. Full-scale intelligence quotient was significantly lower in the HTP group compared with the S-HTP group., Conclusions: There were two types of patients with no synthetic sign. The first involved patients with a suspected mental age younger than 5 years 11 months. The second type consisted of patients with ASD. Although drawing ability reflects multiple domains, it may help in early identification of children with developmental problems and facilitate earlier initiation of interventions., (© 2015 Japan Pediatric Society.)

Because a physical decline correlates with an increased risk of a wide range of disease and morbidity, an improvement of physical performance is expected to bring significant clinical benefits. The primary cause of physical decline in 5/6 nephrectomized (5/6Nx) chronic kidney disease model mice has been regarded as a decrease in muscle mass; however, our recent study showed that a decrease in muscle mitochondria plays a critical role. In the present study, we examined the effects of a gastric hormone ghrelin, which has been reported to promote muscle mitochondrial oxidation, on the physical decline in the chronic kidney disease model mice, focusing on the epigenetic modulations of a mitochondrial activator gene, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Ghrelin treatment improved a decline in exercise endurance of 5/6Nx mice, associated with an increase in both of the muscle mass and mitochondrial amount. The expression level of PGC-1α was decreased in the skeletal muscle of 5/6Nx mice, which was associated with an increase in the methylation ratio of the cytosine residue at 260 base pairs upstream of the initiation point. Conversely, ghrelin treatment de-methylated the cytosine residue and increased the expression of PGC-1α. A representative muscle anabolic factor, IGF-1, did not affect the expression of PGC-1α and muscle mitochondrial amount, although it increased muscle mass. As a result, IGF-1 treatment in 5/6Nx mice did not increase the decreased exercise endurance as effectively as ghrelin treatment did. These findings indicate an advantage of ghrelin treatment for a recovery of physical decline.

Background: In cases of untreated schizophrenia, the patients' entourage often does not recognize the psychotic symptoms of the patient and the possibility that the patient may attempt suicide. The aim of this study was to investigate the discrepancies between the subjective experiences and observed behaviors in near-fatal suicide attempters with untreated schizophrenia., Methods: A semi-structured interview was carried out with seven near-fatal suicide attempters with untreated schizophrenia to examine the subjective experiences at the time of the suicide attempt. The families of the patients were also interviewed to determine their recognition of the patients' psychotic symptoms and the suicidal ideation. The interview data were analyzed qualitatively., Results: Six subjects were undergoing exacerbation of the psychotic symptoms at the time of exhibiting the suicide-related ideation. One subject had been in a prolonged depressive state before attempting suicide. Although all the patients experienced severe distress due to psychotic symptoms and depressive mood, they all exhibited only low level or no help-seeking behavior, and six of seven families had not recognized the change in the patient's mental condition., Conclusions: Appropriate information about schizophrenia should be provided to the general public so that any help-seeking by the patients with this disease is not overlooked. In addition, accessible early intervention services for psychosis should be established.

Clinically elevated anxiety is a common, impairing feature of autism spectrum disorders (ASD). A modular CBT program designed for preteens with ASD, Behavioral Interventions for Anxiety in Children with Autism (BIACA; Wood et al., 2009) was enhanced and modified to address the developmental needs of early adolescents with ASD and clinical anxiety. Thirty-three adolescents (11-15 years old) were randomly assigned to 16 sessions of CBT or an equivalent waitlist period. The CBT model emphasized exposure, challenging irrational beliefs, and behavioral supports provided by caregivers, as well as numerous ASD-specific treatment elements. Independent evaluators, parents, and adolescents rated symptom severity at baseline and posttreatment/postwaitlist. In intent-to-treat analyses, the CBT group outperformed the waitlist group on independent evaluators' ratings of anxiety severity on the Pediatric Anxiety Rating Scale (PARS) and 79% of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment, as compared to only 28.6% of the waitlist group. Group differences were not found for diagnostic remission or questionnaire measures of anxiety. However, parent-report data indicated that there was a positive treatment effect of CBT on autism symptom severity. The CBT manual under investigation, enhanced for early adolescents with ASD, yielded meaningful treatment effects on the primary outcome measure (PARS), although additional developmental modifications to the manual are likely warranted. Future studies examining this protocol relative to an active control are needed., (Copyright © 2014. Published by Elsevier Ltd.)

Objective: To compare sensitivities between 7 principal nerve conduction studies (NCS) for diagnosing carpal tunnel syndrome (CTS)., Method: In 104 CTS and 64 control hands, following "Standard" NCSs were examined simultaneously: (1) Median sensory NCS; (2) segmental wrist-palm sensory NCS; (3) 4th digit latency difference; (4) 1st digit latency difference and (5) palmar mixed nerve latency difference. As "Guideline" and "Option" NCSs, we also examined: (6) Median motor distal latency and (7) second lumbrical-interossei latency difference (2LILD). Forty-nine CTS hands were divided into a milder subgroup only if action potentials could be recorded using all tests applied; that is, those with any absent potentials were excluded from the subgroup. Sensitivities and specificities were compared to each other., Results: In all CTS hands, the sensitivity of test (1), (2), (3), (4), (5), (6) and (7) was 83, 87, 92, 90, 90, 70 and 92%, respectively. In the milder subgroup, it was 67, 78, 84, 82, 84, 43, and 84% in the same order. There was no statistical difference between Standard tests and 2LILD. Specificities of all tests were over 95%., Conclusions: All "Standard" tests and 2LILD have high comparable sensitivities. Therefore, 2LILD should be recommended as "Standard" NCS detecting CTS.

The head is the body region that most frequently incurs fatal and serious injuries of cyclists in collisions against vehicles. Many research studies investigated helmet effectiveness in preventing head injuries using accident data. In this study, the impact attenuation characteristics of three Japanese child bicycle helmets were examined experimentally in impact tests into a concrete surface and a vehicle. A pedestrian adult headform with and without a Japanese child bicycle helmet was dropped onto a concrete surface and then propelled into a vehicle at 35 km/h in various locations such as the bonnet, roof header, windshield and A-pillar. Accelerations were measured and head injury criterion (HIC) calculated. In the drop tests using the adult headform onto a concrete surface from the height of 1.5m, the HIC for a headform without a child helmet was 6325, and was reduced by around 80% when a child helmet was fitted to the headform. In the impact tests, where the headform was fired into the vehicle at 35 km/h at various locations on a car, the computed acceleration based HIC varied depending on the vehicle impact locations. The HIC was reduced by 10-38% for impacts headforms with a child helmet when the impact was onto a bonnet-top and roof header although the HIC was already less than 1000 in impacts with the headform without a child helmet. Similarly, for impacts into the windshield (where a cyclist's head is most frequently impacted), the HIC using the adult headform without a child helmet was 122; whereas when the adult headform was used with a child helmet, a higher HIC value of more than 850 was recorded. But again, the HIC values are below 1000. In impacts into the A-pillar, the HIC was 4816 for a headform without a child helmet and was reduced by 18-38% for a headform with a child helmet depending on the type of Japanese child helmet used. The tests demonstrated that Japanese child helmets are effective in reducing accelerations and HIC in a drop test using an adult headform onto a relatively rigid hard surface, i.e., simulating a road surface or concrete path. However, when the impact tests are into softer surfaces, the child helmet's capacity to decrease accelerations is accordingly reduced. Impacts into the windshield, while below the critical HIC value of 1000, indicated higher HIC values for a headform with a child helmet compared to an adult headform without a child helmet. The unpredictable nature of the results indicates further research work is required to assess how representative the stiffness of an adult headform is when compared to an actual head., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

This study compared cognitive behavioral therapy (CBT) and treatment-as-usual (TAU) in terms of effects on observed social communication-related autism symptom severity during unstructured play time at school for children with autism spectrum disorders (ASD). Thirteen children with ASD (7-11 years old) were randomly assigned to 32 sessions of CBT or community-based psychosocial treatment (TAU) for 16 weeks. The CBT program is based on the memory retrieval competition model and emphasizes the development of perspective-taking through guided behavioral experimentation supplemented with reflective Socratic discussion and supported by parent training and school consultation to promote generalization of social communication and emotion regulation skills. Trained observers blind to treatment condition observed each child during recess on two separate days at baseline and again at posttreatment, using a structured behavioral observation system that generates frequency scores for observed social communication-related autism symptoms. CBT outperformed TAU at posttreatment on the frequency of self-isolation, the proportion of time spent with peers, the frequency of positive or appropriate interaction with peers, and the frequency of positive or appropriate peer responses to the target child (d effect size range 1.34-1.62). On average, children in CBT were engaged in positive or appropriate social interaction with peers in 68.6% of observed intervals at posttreatment, compared to 25% of intervals for children in TAU. Further investigation of this intervention modality with larger samples and follow-up assessments is warranted.

Background: Until the recent enactment of the Medical Treatment and Supervision Act (MTSA) in 2005, neither legislations nor facilities for mentally disordered offenders were available in Japan. The aim of the country's forensic mental health services, based on this new law, is to improve the social reintegration of mentally disordered offenders. In order to provide optimal psychiatric care to these individuals, specialised court proceedings, treatment facilities, and concrete guidelines have been established. The aim of this study was to review the current status of the new system and to clarify future challenges for improving services., Methods: The authors collected official statistics regarding the new system published separately by the Ministry of Health, Labour and Welfare, the Ministry of Justice, and the Supreme Court of Japan. We aggregated the data and examined the system's current implementation status, nationwide., Results: There were 2,750 requests for enrolment in the MTSA system between its initiation in 2005 and 31 December 2012. Of those requests, 2,724 cases had been concluded in court. In 63.1% of the cases, an inpatient treatment order had been made; 82.4% of those inpatients were diagnosed with schizophrenia. By the end of March 2012, two patients completing treatment under the MTSA had re-committed a serious offense. While overall designated inpatient and outpatient treatment facilities have reached national targets in terms of resources and beds available, a regional gap in MTSA designated facilities remains and the number of patients under inpatient treatment order is on the increase., Conclusions: Overall, the MTSA system has been running smoothly without encountering any serious problems. However, several concerns have emerged, such as the accumulation of patients under inpatient treatment order and insufficient regional resources. To more successfully promote the reintegration of mentally disordered offenders, improvements in outpatient treatment and welfare services are crucial. In order to install effective measures to help improve the system, a nationwide database of patients being treated under order of the MTSA should be properly built and maintained.

We validated the utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy (1H MRS) as an adjunct screening technique for dementia due to Alzheimer's disease (AD). We examined the posterior cingulate gyri of 228 subjects using VSRAD and 1H MRS in addition to conventional cerebrospinal fluid biomarkers at baseline. At the 3-year follow-up, the 228 subject were classified as follows: 93 healthy subjects, 42 MCI-non-converters (MCI-NC), 25 MCI-converters to AD (MCI-C), 44 AD, 8 dementia with Lewy bodies (DLB), 5 normal pressure hydrocephalus, and 11 patients with other neurological diseases. Our results demonstrated that subjects with increased medial temporal atrophy (MTA) severity on VSRAD, increased Cho/Cr, MI/Cr ratio, and decreased NAA/Cr and NAA/MI ratio on 1H MRS at baseline were at risk of dementia due to AD. Receiver operating characteristic analysis showed that severity of MTA and the NAA/MI ratio distinguished patients with AD and MCI-C from controls. Furthermore, the 118 subjects without dementia and MTA showing only a decreased NAA/MI ratio at baseline developed to MCI-C, AD, and DLB 3 years later. 1H MRS detected biochemical abnormalities preceding brain atrophy and cognitive decline. VSRAD combined with 1H MRS may be routinely applied to screen for MCI/AD and prodromal AD in clinical practice.

Purpose: To ascertain whether conventional treatment can improve visual function in adults with amblyopia., Methods: Sixteen patients aged 21-67 years old were instructed to wear glasses for refractive correction and to patch the non-amblyopic eye for at least 1 h per day. Visual acuity, measured with crowded optotypes for distance and near acuity, was checked every 3 months, and followed for a mean (SD) of 14.1 (4.2) months. Prognostic factors related to the subsequent results, an improvement of 3 or more lines logMAR in distance visual acuity, were evaluated., Results: Of 16 patients, 5 (31 %) improved 3 or more lines of distance and 5 (31 %) in near acuity. The mean improvement in distance was 2.4 lines logMAR (95 % CI 1.4-3.5) and 2.4 lines logMAR for near acuity (95 % CI 1.5-3.3). Patients aged under 45 years (p = 0.0357) and with severe amblyopia (p = 0.0337), defined as a corrected distance visual acuity of worse than -0.699 logMAR, were associated with a good response., Conclusions: Conventional treatment may improve the visual acuity of amblyopic eyes even in adult patients.