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Abstract Aim This study aimed to compare the 12‐item and 36‐item versions of the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 using longitudinal data from community mental health outreach service users. Methods Using data from Tokorozawa City mental health outreach service users in Japan, total and domain WHODAS‐12 and WHODAS‐36 scores were compared. First, we examined score‐change differences by domain at the start of outreach services (T1) and 1 year later (T2) for each version. Next, we compared differences between the two versions using Pearson's correlation, Wilcoxon signed‐rank test, and Bland–Altman analysis. Results Among 20 participants, total scores and scores of some domains (i.e., cognition, getting along, life activities, and participation) were significantly lower at T2 than at T1 on both versions (p

Abstract Background The purpose of this study was to examine the effects of a brief family psychoeducation (BFP) programme provided by psychiatric visiting nurses on caregiver burden of family caregivers of people with schizophrenia through a cluster randomised controlled trial (cRCT). Methods The study was a two-arm, parallel-group cRCT. Forty-seven psychiatric visiting nurse agencies were randomly allocated to the BFP programme group (intervention group) or treatment as usual group (TAU; control group). Caregivers of people with schizophrenia were recruited by psychiatric visiting nurses using a randomly ordered list. The primary outcome was caregiver burden, measured using the Japanese version of the Zarit Burden Interview. Outcome assessments were conducted at baseline, 1-month follow-up, and 6-month follow-up. Intention-to-treat analysis was conducted to examine the effects of the BFP programme on caregiver burden. Results Thirty-four psychiatric visiting nurse agencies and 83 family caregivers of people with schizophrenia participated in the study. The participant attrition rate was less than 20%. Adherence to the program was 100%. Compared with TAU group, the BFP programme group had decreased caregiver burden. However, this improvement was not significant at 1-month follow-up (adjusted mean difference [aMD] = 0.27, 95% CI = − 5.48 to 6.03, p = 0.93, d = 0.01) or 6-month follow-up (aMD = − 2.12, 95% CI = − 7.80 to 3.56, p = 0.45, d = 0.11). Conclusions The BFP programme provided by psychiatric visiting nurses did not achieve significant decreases in caregiver burden. This result may be attributed to the difficulty in continuing the research due to the COVID-19 pandemic, which prevented us from achieving the targeted sample size necessary to meet the statistical power requirements, as well as to the participation of caregivers with relatively low burden. However, the program had the advantage of high adherence to treatment plan. Further studies should be conducted with a larger sample size and a more diverse sample that includes caregivers with a higher care burden. Trial registration The study protocol was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000038044) on 2019/09/18.

Introduction Individuals with mental illness and their families often undergo their recovery process in their communities. This study explored the long-term outcome trajectories of individuals and families who received case management services provided by multidisciplinary outreach teams in a community setting. The primary objective of this study was to determine whether trajectories of subjective quality of life (QoL) related to personal recovery were linked to those clinical and societal outcomes and changes in outreach service frequency.Methods and analysis The protocol of this 10-year multisite cohort study was collaboratively developed with individuals with lived experience of psychiatric disorders who had received services from participating outreach teams, and with family members in Japanese family associations. The participants in the study include patients and their key family members who receive services from 23 participating multidisciplinary outreach teams. The participant recruitment period is set from 1 October 2023 to 30 September 2025. If necessary, the recruitment period may be extended and the number of participating teams may be increased. The study will annually evaluate the following outcomes after participants’ initial utilisation of services from each team: QoL related to personal recovery, personal agency, feelings of loneliness, well-being and symptom and functional assessments. The family outcomes encompass QoL, well-being, care burden and family relationships. Several meetings will be held to monitor progress and manage issues during the study. Multivariate analyses with repeated measures will be performed to investigate factors influencing changes in the patients’ QoL scores as the dependent variable.Ethics and dissemination The study protocol was approved by the ethical committee of the National Center of Neurology and Psychiatry (no. A2023-065). The study findings will be reported in peer-reviewed publications and presented at relevant scientific conferences.Trial registration number UMIN-CTR, No. UMIN000052275.

Background/Objectives: Although the embodiment of action-related language is well-established in the mother tongue (L1), less is known about the embodiment of a second language (L2) acquired later in life through formal instruction. We used the high temporal resolution of ERPs and topographic ERP analyses to compare embodiment in L1 and L2 and to investigate whether L1 and L2 are embodied with different strengths at different stages of linguistic processing. Methods: Subjects were presented with action-related and non-action-related verbs in a silent reading task. Subjects were late French–German and German–French bilinguals, respectively, and we could therefore collapse across languages to avoid common confounding between language (French and German) and order of acquisition (L1, L2). Results: We could show distinct effects of embodiment and language. Embodiment affected only the sensory and lexical stages of processing with increased strength and power of the N1 component for motor vs. non-motor verbs, and language affected the lexical and semantic stages of processing with stronger P2/N400 components for L2 than for L1. Non-motor verbs elicited a stronger P1 component in L2. Conclusions: Our results suggest that processing words in L2 requires more effortful processing. Importantly, L1 and L2 are not embodied differently, and embodiment affects early and similar stages of processing in L1 and L2, possibly integrating other process of action–language interaction

Abstract Aims This study aimed to conduct a systematic review of studies on the outcomes of long-term hospitalisation of individuals with severe mental illness, considering readmission rates as the primary outcome. Methods Studies considered were those in which participants were aged between 18 and 64 years with severe mental illness; exposure to psychiatric hospitals or wards was long-term (more than one year); primary outcomes were readmission rates; secondary outcomes were duration of readmission, employment, schooling, and social participation; and the study design was either observational or interventional with a randomised controlled trial (RCT) design. Relevant studies were searched using MEDLINE, PsycINFO, Web of Science, CINAHL, and the Japan Medical Abstract Society. The final search was conducted on 1 February 2022. The risk of bias in non-randomised studies of interventions was used to assess the methodological quality. A descriptive literature review is also conducted. Results Of the 11,999 studies initially searched, three cohort studies (2,293 participants) met the eligibility criteria. The risk of bias in these studies was rated as critical or serious. The 1–10 years readmission rate for patients with schizophrenia who had been hospitalised for more than one year ranged from 33 to 55%. The average of readmission durations described in the two studies was 70.5 ± 95.6 days per year (in the case of a 7.5-year follow-up) and 306 ± 399 days (in the case of a 3–8-year follow-up). None of the studies reported other outcomes defined in this study. Conclusions The readmission rates in the included studies varied. Differences in the follow-up period or the intensity of community services may have contributed to this variability. In countries preparing to implement de-institutionalisation, highly individualised community support should be designed to avoid relocation to residential services under supervision. The length of stay for readmissions was shorter than that for index admissions. The results also imply that discharge to the community contributes to improved clinical outcomes such as improved social functioning. The validity of retaining patients admitted because of the risk of rehospitalisation was considered low. Future research directions have also been discussed.

Abstract Aim Studies showed that cognitive function affects occupational function in patients with schizophrenia. This study aimed to determine the effects of cognitive function on occupational function in Japanese patients with schizophrenia using the Brief Assessment of Cognition in Schizophrenia (BACS). Methods Participants were 198 outpatients with schizophrenia or schizoaffective disorder (66 females; mean age 34.5 ± 6.8 years). Occupational function was assessed using the work subscale of the Life Assessment Scale for Mental Ill (LASMI‐w). Multiple regression analysis was performed using the BACS as the independent variable and LASMI‐w as the dependent variable. Furthermore, we divided the LASMI‐w score into three groups, 21, and performed a multinomial logistic regression analysis. Results Multiple regression analysis revealed that LASMI‐w score was negatively associated with BACS composite score (β = −0.20, p

Abstract Aims This study investigated outcomes in community mental health research that were important to caregivers of people with schizophrenia. Methods Using an online survey conducted from August 1 to 31, 2020, data were collected from caregivers belonging to the LINE Schizophrenia Family Association. Caregivers identified outcomes important in community mental health research. Two researchers categorized caregivers' statements into research outcomes. Results A total of 132 caregivers completed the online selfreported questionnaire, and 296 caregiver statements were identified. Qualitative analysis identified 17 outcome categories. The caregivers tended to value having more free time, maintaining an appropriate relationship with people with schizophrenia, and being able to cope with their symptoms. Conclusions This exploratory study newly demonstrates the outcomes that caregivers of people with schizophrenia consider important in community mental health research. The findings may be useful in selecting outcomes for future studies of caregivers.

Abstract Aim This study aimed to clarify the association between treatment status (untreated or treated) at the start of community mental health outreach services and service intensity. Methods This retrospective cohort study was conducted using the Tokorozawa City mental health outreach service users' data. Treatment status at the start of service (exposure variable) and the service intensity (outcome variables) were taken from clinical records. Poisson regression and linear regression analyses were conducted. The frequency of medical or social service use 12 months after service initiation was also calculated. This study was approved by the Research Ethics Committee at the National Center of Neurology and Psychiatry (No. A2020‐081). Results Of 89 people, 37 (42%) were untreated. Family members in the untreated group were more likely to be targets or recipients of services than in the treated group (b = 0.707, p

Abstract The coronavirus disease 2019 (COVID‐19) vaccine is positively changing the health crises of this pandemic and is currently essential to overcome the COVID‐19 pandemic. The vaccine shows high efficacy against the infection and impairs the severity of symptoms. However, this vaccination is associated with concerns, such as vaccine‐associated adverse reactions, which are currently highlighted issues for clinicians. We experienced two cases of mild cutaneous adverse reaction following COVID‐19 vaccine administration, which was successfully controlled by prior administration of the antihistamine agent fexofenadine 3 days before COVID‐19 vaccination for 7 days.

Abstract Background Patient and public involvement (PPI) has become essential in health research. However, little is known about multiple stakeholders' perspectives on the implementation of PPI in community mental health research settings. The present study aimed to qualitatively analyse multiple stakeholders' views on PPI, including potential concerns, barriers and approaches. Methods This study involved conducting focus group interviews and collecting qualitative data from 37 participants in multiple stakeholder groups (patients = 6, caregivers = 5, service providers = 7, government staff = 5 and researchers = 14) in the community mental health field. The data were qualitatively analysed using a data‐driven approach that derived domains, themes and subthemes related to perspectives on PPI and to specific challenges and approaches for implementing PPI. Results The qualitative analysis identified four domains. The ‘Positive views and expectations regarding PPI’ domain consisted of themes related to supportive views of PPI in a mental health service research setting and improvements in the quality of research and service. The ‘General concerns about PPI’ domain included themes concerning the need for non‐PPI research and tokenism, excessive expectations concerning social changes and use of evidence from PPI research, and heavy burdens resulting from PPI. The ‘Specific issues regarding the implementation of PPI’ domain consisted of four themes, including academic systems, selection methods (e.g., representativeness and conflict of interest issues), relationship building, and ambiguous PPI criteria. In particular, all stakeholder groups expressed concerns about relational equality during PPI implementation in Japan. The ‘Approaches to PPI implementation’ domain included themes such as facilitating mutual understanding, creating a tolerant atmosphere, establishing PPI support systems (e.g., training, ethics and human resource matching) and empowering patient organizations. Conclusion The study replicated most of the barriers and approaches to PPI reported by qualitative research in Western counties. However, utilization of evidence produced by PPI research and partnership in the PPI process may be particularly serious issues in Japan. Future PPI studies should carefully address solutions that fit each culture. Patient or Public Contribution A patient‐researcher was involved in all stages of this project, from development of the research topic and the protocol to manuscript preparation.

Abstract Background Outcome selection in intervention studies is a critical issue for synthesizing evidence. This study is aimed to investigate outcomes used in Cochrane reviews assessing community‐based psychosocial interventions for adults with severe mental illness. Methods Cochrane reviews that evaluated a community‐based psychosocial intervention for adults with severe mental illness were searched electronically and manually. We extracted all outcomes specified in the Methods section in each Cochrane review. Outcomes that represent the same concept and context were synthesized into an outcome term. Outcome terms were categorized according to the existing taxonomy. Results We included 33 Cochrane reviews. Of the 216 outcome terms identified, 13 were used in more than half of the reviews: quality of life, mental state, admission to hospital, economic outcome, leaving the study early, social functioning, satisfaction, global state, relapse, adverse events/effects, carer satisfaction, employment, and duration of admission. Most outcome terms were categorized into the life impact core area (55%), followed by the resource use area (21%). Conclusions Our study provides a candidate outcome list for developing a core outcome set for severe mental illness and offers a basis for comparison for future outcome investigation on mental health research.

Abstract Aims The purpose of this study was to retrospectively investigate care difficulties experienced by caregivers of people with schizophrenia during COVID‐19 pandemic lockdowns in Japan (April 7‐May 25, 2020) and examine associations between these care difficulties during lockdowns and daily caregiver burden. Methods Data were collected from 132 participants of the LINE Schizophrenia Family Association using an online survey. Results Caregivers were mostly concerned about who would care for people with schizophrenia if caregivers become infected with COVID‐19. A significant association was found between higher daily caregiver burden and more difficult care experiences during COVID‐19 pandemic lockdowns (B = 0.58, 95% confidence interval, 0.40‐0.75, P

Abstract Background The Japanese version of the individualized Supported Employment Fidelity scale (JiSEF) was developed by modifying the 25‐item Individual Placement and Support Fidelity Scale (IPS‐25). While a preliminary study partly confirmed the concurrent validity with vocational outcomes, this replication study aimed to examine the stability of the concurrent validity and the inter‐rater reliability of the JiSEF and to test its convergent validity with IPS‐25. Methods Fidelity assessments were conducted in 2016 (n = 17), 2017 (n = 13), and 2018 (n = 18) to examine the employment rate and the fidelity scores at the agency level. We also evaluated the fidelity scores for the IPS‐25 in 2018. We examined the associations between the fidelity scale scores and vocational outcomes for the concurrent validity and between the fidelity scales for convergent validity. The inter‐rater reliability was examined in the 2016 and 2017 assessments. Results High intraclass correlation coefficients (0.93 in 2016 and 0.92 in 2017) were obtained for the inter‐rater reliability. The JiSEF score in each year was associated with the agency employment rate (r = 0.710, P = 0.001 in 2016; r = 0.722, P = 0.005 in 2017; and r = 0.665, P = 0.003 in 2018). A supplementary longitudinal data analysis also confirmed the association between the JiSEF score and the employment outcomes. Additionally, the JiSEF was significantly correlated with the IPS‐25 (r = 0.760, P

Psycholinguistic approaches that study the effects of language on mental representations have ignored a potential role of the grammaticalization of the future (i.e., how the future manifests linguistically). We argue that the grammaticalization of the future may be an important aspect, as thinking about the future is omnipresent in our everyday life. The aim of this study was to experimentally manipulate the degree of future time references (i.e., present and future verb tense and temporal adverbials) to address their impact on the perceived location of future events. Across four experiments, two in French and two in German, no effect was found, irrespective of our verb and adverbial manipulations, and contrary to our hypotheses. Bayes factors confirmed that our null effects were not due to a lack of power. We present one of the first empirical accounts investigating the role of the grammaticalization of the future on effects of mental representations. We discuss possible reasons for these null results and illustrate further avenues for future research.

Since the last decade, endoscopic submucosal dissection (ESD) has been used as the standard treatment for superficial gastrointestinal neoplasms. Trainees learning ESD frequently encounter difficulties such as vascularity, peristalsis, and fibrosis during the procedure. Because individual vascularity differs, it generally cannot be consistently avoided. Given that massive hemorrhages can prolong the procedure time and diminish treatment efficacy and that insufficient vessel handling may also increase postoperative bleeding, hemorrhage control during ESD becomes important to ensure procedure safety. This article discusses methods for controlling hemorrhage during gastric ESD. Endoscopists should have a basic understanding of the vascular architecture and the high‐density areas in blood vessels, which are susceptible to intraoperative hemorrhage. Efficient preventative coagulation should be performed in addition to mastering the techniques for hemorrhage control using hemostatic forceps. Techniques useful for preventing intraoperative hemorrhage at every step (e.g. submucosal injection, mucosal incision, and dissection) should be learned. Gaining procedural competence and learning hemorrhage control techniques not only during ESD but also in daily work would help provide safe and effective treatment.

Considering how fundamental and ubiquitous temporal information is in discourse (e.g., Zwaan & Radvansky, 1998), it seems rather surprising that the impact of the grammaticalization of the future on the way we perceive the future has only been scarcely studied. We argue that this may be due to its rather abstract nature and how it has been previously operationalized. In this review, we lay the foundation for studying the impact of the grammaticalization of the future on mental representations of the future by taking an interdisciplinary perspective, connecting cognitive sciences, linguistics, psycholinguistics, economics, and health psychology. More specifically, we argue that experimental psycholinguistics, combined with more applied domains, constitute a promising research avenue.

Introduction Development of a support system for families caring for people with schizophrenia in routine psychiatric care settings is an important issue worldwide. Regional mental health systems are inadequate for delivering effective services to such family members. Despite evidence that family psychoeducation (FPE) alleviates the burden of schizophrenia on families, its dissemination in routine clinical practice remains insufficient, suggesting the need for developing an effective and implementable intervention for family caregivers in the existing mental health system setting. In Japan, the visiting nurse service system would be a practical way of providing family services. Visiting nurses in local communities are involved in the everyday lives of people with schizophrenia and their families. Accordingly, visiting nurses understand their needs and are able to provide family support as a service covered by national health insurance. The purpose of this study is to discover whether a brief FPE programme provided by visiting nurses caring for people with schizophrenia will alleviate family burden through a cluster randomised controlled trial (cRCT).Methods and analysis The study will be a two-arm, parallel-group (visiting nurse agency) cRCT. Forty-seven visiting nurse agencies will be randomly allocated to the brief FPE group (intervention group) or treatment as usual group (control group). Caregivers of people with schizophrenia will be recruited by visiting nurses using a randomly ordered list. The primary outcome will be caregiver burden, measured using the Japanese version of Zarit Burden Interview. Outcome assessments will be conducted at baseline, 1-month follow-up and 6-month follow-up. Multiple levels of three-way interactions in mixed models will be used to examine whether the brief FPE programme will alleviate the burden on caregivers relative to treatment as usual.Ethics and dissemination The Research Ethics Committee of the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Japan (No 2019065NI) approved this study. The results will be published in a scientific peer-reviewed journal.Trial registration number UMIN000038044.

Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease.

BACKGROUND:The employment rate among people with severe mental illness has recently increased, though it is still low. The motivation to work appears to be an important role as an intermediate outcome measure in vocational rehabilitation programs. In addition, measuring the work motivation for people with severe mental illness appears to be essential to identify candidates who are likely to benefit and monitor candidates' motivation in a supported employment program. This study aimed to develop a new measure for assessing both intrinsic and extrinsic motivation to work among people with severe mental illness, as there are currently no well-established instruments of this kind. METHODS:A focus group interview and review of previous qualitative research were used to identify possible items for inclusion in the new scale. A provisional scale was constructed and further refined for content and format based on feedback from a researcher and also three peer workers with severe mental illness. The resulting provisional 38-item version of the scale was completed by 136 respondents with severe mental illness, and we performed exploratory factor analysis to identify latent constructs within the new measure. The finalized scale was analyzed for test-retest reliability, internal consistency, and convergent validity. RESULT:An exploratory factor analysis yielded a four-factor scale with 23 items. The finalized 23 items had high internal consistency (Cronbach's alpha = 0.91) and relatively high test-retest reliability (ICC = 0.83). The four subscales had fair internal consistency (Cronbach's alpha ≥ 0.69) and good test-retest reliability (ICC ≥ 0.61). Convergent validity was weakly supported by the significant positive correlations with the overall question on motivation to work (r ≥ 0.19, p < 0.01). Besides these correlations, only the "Pressure from others" subscale was negatively and significantly correlated with the negative symptoms evaluated using the Positive and Negative Syndrome Scale (r = -0.18, p = 0.04). CONCLUSIONS:This study used factor analysis to develop a new multidimensional scale assessing motivation for competitive employment among persons with severe mental illness. The scale showed acceptable levels of reliability and factor-based and convergent validity. The new measure can be used for measuring the motivation for competitive employment among people with severe mental illness, and it would be useful to identify candidates who are likely to benefit from a certain supported employment program, and to monitor interim progress of the state of participants' motivation in a program.

Introduction Development of a support system for families caring for people with schizophrenia in routine psychiatric care settings is an important issue worldwide. Regional mental health systems are inadequate for delivering effective services to such family members. Despite evidence that family psychoeducation (FPE) alleviates the burden of schizophrenia on families, its dissemination in routine clinical practice remains insufficient, suggesting the need for developing an effective and implementable intervention for family caregivers in the existing mental health system setting. In Japan, the visiting nurse service system would be a practical way of providing family services. Visiting nurses in local communities are involved in the everyday lives of people with schizophrenia and their families. Accordingly, visiting nurses understand their needs and are able to provide family support as a service covered by national health insurance. The purpose of this study is to discover whether a brief FPE programme provided by visiting nurses caring for people with schizophrenia will alleviate family burden through a cluster randomised controlled trial (cRCT). Methods and analysis The study will be a two-arm, parallel-group (visiting nurse agency) cRCT. Forty-seven visiting nurse agencies will be randomly allocated to the brief FPE group (intervention group) or treatment as usual group (control group). Caregivers of people with schizophrenia will be recruited by visiting nurses using a randomly ordered list. The primary outcome will be caregiver burden, measured using the Japanese version of Zarit Burden Interview. Outcome assessments will be conducted at baseline, 1-month follow-up and 6-month follow-up. Multiple levels of three-way interactions in mixed models will be used to examine whether the brief FPE programme will alleviate the burden on caregivers relative to treatment as usual. Ethics and dissemination The Research Ethics Committee of the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Japan (No 2019065NI) approved this study. The results will be published in a scientific peer-reviewed journal. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal hemoglobinuria (PNH) is a serious blood disorder characterized by dysregulated complement activation on blood cells. Eculizumab, the current standard therapy and a humanized anti-C5 mAb, relieves anemia and thrombosis symptoms of PNH patients by preventing complement-dependent intravascular hemolysis (IVH). However, up to 20% of PNH patients on long-term eculizumab treatment still suffer from significant anemia and are transfusion dependent because of extravascular hemolysis (EVH) of C3-opsonized PNH erythrocytes. In this study, we show that function-blocking anti-properdin (P) mAbs dose-dependently inhibited autologous, complement-mediated hemolysis induced by factor H dysfunction. Furthermore, anti--human P (hP) mAbs potently and dose-dependently inhibited acidified serum--induced hemolysis of PNH erythrocytes (Ham test). In contrast to erythrocytes rescued by anti-C5 mAb, nonlysed PNH erythrocytes rescued by anti-P mAb incurred no activated C3 fragment deposition on their surface. These results suggested that anti-P mAbs may prevent EVH as well as IVH of PNH erythrocytes. To test the in vivo efficacy of anti-hP mAbs in preventing EVH, we generated a P humanized mouse by transgenic expression of hP in P knockout mice (hP-Tg/P-/-). In a murine EVH model, complement-susceptible erythrocytes were completely eliminated within 3 d in control mAb-treated hP-Tg/P-/- mice, whereas such cells were protected and persisted in hP-Tg/P-/- mice treated with an anti-hP mAb. Collectively, these data suggest that anti-P mAbs can inhibit both IVH and EVH mediated by complement and may offer improved efficacy over eculizumab, the current standard therapy for PNH. [ABSTRACT FROM AUTHOR]

Complement is implicated in the pathogenesis of ischemia-reperfusion injury (IRI). The activation pathway(s) and effector(s) of complement in IRI may be organ specific and remain to be fully characterized. We previously developed a renal IRI model in decay-accelerating factor (DAF) and CD59 double-knockout (DAF-/-CD59-/-) mice. In this study, we used this model to dissect the pathway(s) by which complement is activated in renal IRI and to evaluate whether C3aR- or C5aR-mediated inflammation or the membrane attack complex was pathogenic. We crossed DAF-/-CD59-/- mice with mice deficient in various complement components or receptors including C3, C4, factor B (fB), factor properdin (fP), mannose-binding lectin, C3aR, C5aR, or Ig and assessed renal IRI in the resulting mutant strains. We found that deletion of C3, fB, fP, C3aR, or C5aR significantly ameliorated renal IRI in DAF-/-CD59-/- mice, whereas deficiency of C4, Ig, or mannose-binding lectin had no effect. Treatment of DAF-/- CD59-/- mice with an anti-C5 mAb reduced renal IRI to a greater degree than did C5aR deficiency. We also generated and tested a function-blocking anti-mouse fP mAb and showed it to ameliorate renal IRI when given to DAF-/-CD59-/- mice 24 h before, but not 4 or 8 h after, ischemia/reperfusion. These results suggest that complement is activated via the alternative pathway during the early phase of reperfusion, and both anaphylatoxin-mediated inflammation and the membrane attack complex contribute to tissue injury. Further, they demonstrate a critical role for properdin and support its therapeutic targeting in renal IRI. [ABSTRACT FROM AUTHOR]

Objective: Cognitive impairment is common in schizophrenia, and is associated with poor psychosocial functioning. Previous studies had inconsistently shown improvement in cognitive functions with cognitive remediation therapy. This study examined whether cognitive remediation is effective in improving both cognitive and social functions in schizophrenia in outpatient settings that provide learning-based psychiatric rehabilitation. This study is the first randomized controlled trial of cognitive remediation in Japan. Method: Study participants were individuals with schizophrenia from 6 outpatient psychiatric medical facilities who were randomly assigned either a cognitive remediation program or treatment as usual. The cognitive remediation intervention includes Cognitive training using computer software (CogPack; Japanese version) administered twice a week and a weekly group over 12 weeks and was based on the Thinking Skills for Work program. Most study participants were attending day treatment services where social skills training, psychoeducation for knowledge about schizophrenia, group activities such as recreation and sport, and other psychosocial treatment were offered. Cognitive and social functioning were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) and Life Assessment Scale for Mentally Ill (LASMI) at pre- and postintervention. Results: Of the 60 people with schizophrenia enrolled, 29 were allocated to the cognitive remediation group and 31 were allocated to the treatment as usual group. Processing speed, executive function, and the composite score of the BACS showed significantly greater improvement for the cognitive remediation group than the treatment as usual group. In addition, there was significant improvement in interpersonal relationships and work skills on the LASMI for the cognitive remediation group compared with the treatment as usual group. Changes from pretreatment to posttreatment in verbal fluency and interpersonal relationships were significantly correlated, as well as changes in attention and work skills. Conclusions and Implications for Practice: The present findings showed that providing cognitive remediation on addition to psychiatric rehabilitation contributed to greater improvement in both cognitive and social functioning than psychiatric rehabilitation alone. Cognitive remediation may enhance the efficacy of psychiatric rehabilitation improving social functioning. [ABSTRACT FROM AUTHOR]

Complement receptor 1-related gene/protein y (Crry) and decay-accelerating factor (DAF) are two murine membrane C3 complement regulators with overlapping functions. Crry deletion is embryonically lethal whereas DAF-deficient mice are generally healthy. Crry-/-DAF-/- mice were viable on a C3-/- background, but platelets from such mice were rapidly destroyed when transfused into C3-sufficient mice. In this study, we used the cre-lox system to delete platelet Crry in DAF-/- mice and studied Crry/DAF-deficient platelet development in vivo. Rather than displaying thrombocytopenia, Pf4-Cre+-Crryflox/flox mice had normal platelet counts and their peripheral platelets were resistant to complement attack. However, chimera mice generated with Pf4-Cre+-Crryflox/flox bone marrows showed platelets from C3-/- but not C3+/+ recipients to be sensitive to complement activation, suggesting that circulating platelets in Pf4-Cre+-Crryflox/flox mice were naturally selected in a complement-sufficient environment. Notably, Pf4-Cre+-Crryflox/flox mouse platelets became complement susceptible when factor H function was blocked. Examination of Pf4-Cre+-Crryflox/flox mouse bone marrows revealed exceedingly active thrombopoiesis. Thus, under in vivo conditions, Crry/DAF deficiency on platelets led to abnormal platelet turnover, but peripheral platelet count was compensated for by increased thrombopoiesis. Selective survival of Crry/DAF-deficient platelets aided by factor H protection and compensatory thrombopoiesis demonstrates the cooperation between membrane and fluid phase complement inhibitors and the body's ability to adaptively respond to complement regulator deficiencies. [ABSTRACT FROM AUTHOR]

Complement is implicated in asthma pathogenesis, but its mechanism of action in this disease remains incompletely understood. In this study, we investigated the role of properdin (P), a positive alternative pathway complement regulator, in allergen-induced airway inflammation. Allergen challenge stimulated P release into the airways of asthmatic patients, and P levels positively correlated with proinflammatory cytokines in human bronchoalveolar lavage (BAL). High levels of P were also detected in the BAL of OVA-sensitized and challenged but not naive mice. Compared with wild-type (WT) mice, P-deficient (P-/-) mice had markedly reduced total and eosinophil cell counts in BAL and significantly attenuated airway hyperresponsiveness to methacholine. Ab blocking of P at both sensitization and challenge phases or at challenge phase alone, but not at sensitization phase alone, reduced airway inflammation. Conversely, intranasal reconstitution of P to P-/- mice at the challenge phase restored airway inflammation to wild-type levels. Notably, C3a levels in the BAL of OVA-challenged P-/- mice were significantly lower than in wild-type mice, and intranasal coadministration of an anti-C3a mAb with P to P-/- mice prevented restoration of airway inflammation. These results show that P plays a key role in allergen-induced airway inflammation and represents a potential therapeutic target for human asthma. [ABSTRACT FROM AUTHOR]