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Several studies have indicated that approximately 25 % of patients treated with aspirin exhibit high on-treatment platelet reactivity (HTPR), which is potentially associated with cardiovascular events (CVEs). However, this association is still controversial, since the mechanisms by which HTPR contributes to CVEs remain unclear and a no standardised definition of HTPR has been established. To determine whether HTPR is associated with CVE recurrence and what type of assay would best predict CVE recurrence, we conducted a multicentre prospective cohort study of 592 stable cardiovascular outpatients treated with aspirin monotherapy for secondary prevention. Their HTPR was determined by arachidonic acid- or collagen-induced aggregation assays using two different agonist concentrations. Residual cyclooxygenase (COX)-1 activity was assessed by measuring serum thromboxane (TX)B2 or urinary 11-dehydro TXB2. Shear-induced platelet thrombus formation was also examined. We followed all patients for two years to evaluate how these seven indexes were related to the recurrence of CVEs (cerebral infarction, transient ischaemic attack, myocardial infarction, unstable angina, revascularisation, other arterial thrombosis, or cardiovascular death). Of 583 patients eligible for the analysis, CVEs occurred in 69 (11.8 %). A Cox regression model identified several classical risk factors associated with CVEs. However, neither HTPR nor high residual COX-1 activity was significantly associated with CVEs, even by applying cut-off values suggested in previous reports or a receiver-operating characteristic analysis. In conclusion, recurrence of CVEs occurred independently of HTPR and residual COX-1 activity. Thus, our findings do not support the use of platelet or COX-1 functional testing for predicting clinical outcomes in stable cardiovascular patients.

The ozone profile records of a large number of limb and occultation satellite instruments are widely used to address several key questions in ozone research. Further progress in some domains depends on a more detailed understanding of these data sets, especially of their long-term stability and their mutual consistency. To this end, we made a systematic assessment of fourteen limb and occultation sounders that, together, provide more than three decades of global ozone profile measurements. In particular, we considered the latest operational Level-2 records by SAGE II, SAGE III, HALOE, UARS MLS, Aura MLS, POAM II, POAM III, OSIRIS, SMR, GOMOS, MIPAS, SCIAMACHY, ACE-FTS and MAESTRO. Central to our work is a consistent and robust analysis of the comparisons against the ground-based ozonesonde and stratospheric ozone lidar networks. It allowed us to investigate, from the troposphere up to the stratopause, the following main aspects of satellite data quality: long-term stability, overall bias, and short-term variability, together with their dependence on geophysical parameters and profile representation. In addition, it permitted us to quantify the overall consistency between the ozone profilers. Generally, we found that between 20-40 km the satellite ozone measurement biases are smaller than ±5 %, the short-term variabilities are less than 5-12% and the drifts are at most ±5% decade -1 (or even ±3 % decade -1 for a few records). The agreement with ground-based data degrades somewhat towards the stratopause and especially towards the tropopause where natural variability and low ozone abundances impede a more precise analysis. In part of the stratosphere a few records deviate from the preceding general conclusions; we identified biases of 10% and more (POAM II and SCIAMACHY), markedly higher single-profile variability (SMR and SCIAMACHY), and significant long-term drifts (SCIAMACHY, OSIRIS, HALOE, and possibly GOMOS and SMR as well). Furthermore, we reflected on the repercussions of our findings for the construction, analysis and interpretation of merged data records. Most notably, the discrepancies between several recent ozone profile trend assessments can be mostly explained by instrumental drift. This clearly demonstrates the need for systematic comprehensive multi-instrument comparison analyses.

Background: Statins have neuroprotective effects against ischemic stroke. However, associations between pre-stroke statin treatment and initial stroke severity and between the treatment and functional outcome remain controversial. This study aimed at determining these associations in ischemic stroke patients., Methods: Among patients registered in the Fukuoka Stroke Registry from June 2007 to October 2014, 3,848 patients with ischemic stroke within 24 h of onset, who had been functionally independent before onset, were enrolled in this study. Ischemic stroke was classified as cardioembolic or non-cardioembolic infarction. Primary and secondary study outcomes were mild neurological symptoms defined as a National Institutes of Health Stroke Scale score of ≤4 on admission and favorable functional outcome defined as a modified Rankin Scale score of ≤2 at discharge, respectively. Multivariable logistic regression models were used to quantify associations between pre-stroke statin treatment and study outcomes., Results: Of all 3,848 participants, 697 (18.1%) were taking statins prior to the stroke. The frequency of mild neurological symptoms was significantly higher in patients with pre-stroke statin treatment (64.1%) than in those without the treatment (58.3%, p < 0.01). Multivariable analysis showed that pre-stroke statin treatment was significantly associated with mild neurological symptoms (OR 1.31; 95% CI 1.04-1.65; p < 0.01). Sensitivity analysis in patients with dyslipidemia (n = 1,998) also showed the same trend between pre-stroke statin treatment and mild neurological symptoms (multivariable-adjusted OR 1.26; 95% CI 0.99-1.62; p = 0.06). In contrast, the frequency of favorable functional outcome was not different between patients with (67.0%) and without (65.3%) the treatment (p = 0.40). Multivariable analysis also showed no significant association between pre-stroke statin treatment and favorable functional outcome (OR 1.21; 95% CI 0.91-1.60; p = 0.19). Continuation of statin treatment, however, was significantly associated with favorable functional outcome among patients with pre-stroke statin treatment (multivariable-adjusted OR 2.17; 95% CI 1.16-4.00; p = 0.02)., Conclusions: Pre-stroke statin treatment in ischemic stroke patients was significantly associated with mild neurological symptoms within 24 h of onset. Pre-stroke statin treatment per se did not significantly influence the short-term functional outcome; however, continuation of statin treatment during the acute stage of stroke seems to relate with favorable functional outcome for patients with pre-stroke statin treatment., (© 2016 S. Karger AG, Basel.)

Background and Purpose: The relationship between blood pressure (BP) variability and functional outcome in patients with acute ischemic stroke remains unclear. This study aimed to elucidate whether in-hospital day-by-day BP variability is associated with functional outcome after acute ischemic stroke., Methods: Using the Fukuoka Stroke Registry, we included 2566 patients with a first-ever ischemic stroke who had been functionally independent before the onset and were hospitalized within 24 hours. BP was measured daily, and its variability was assessed by SD, coefficients of variance, and variations independent of mean. Poor functional outcome was assessed by modified Rankin Scale scores ≥3 at 3 months., Results: After adjustment for multiple confounding factors including age, sex, risk factors, stroke features, baseline severity, thrombolytic therapy, antihypertensive agents, and mean BP, day-by-day BP variability during the subacute stage (4-10 days after onset) was independently associated with a poor functional outcome (multivariable-adjusted odds ratios [95% confidence interval] in the top versus bottom quartile of systolic BP variability, 1.51 [1.09-2.08] for SD; 1.63 [1.20-2.22] for coefficients of variance; 1.64 [1.21-2.24] for variations independent of mean). Similar trends were also observed for diastolic BP variability. These trends were unchanged in patients who were not treated with antihypertensive drugs. In contrast, no association was found between indices of BP variability during the acute stage and functional outcome after adjusting for potential confounders., Conclusions: These data suggest that intraindividual day-by-day BP variability during the subacute stage is associated with the 3-month functional outcome after acute ischemic stroke., (© 2015 American Heart Association, Inc.)

Metallothioneins (MTs) are cysteine-rich proteins that act as antioxidants. A case-control study was conducted to assess the effects of gene polymorphisms in the MT region on the risk of lung cancer in Japanese subjects: 769 lung cancer cases and 939 non-cancer controls. Associations were evaluated using logistic regression models with adjustment for potential confounders (age, sex, and lifestyle factors including smoking, drinking, and green-yellow vegetable intake). We found five polymorphisms in the MT-1 gene region that showed statistically significant associations with lung cancer. Of these polymorphisms, rs7196890 showed the strongest association (odds ratio: 1.30, P = 0.004, 95% confidence interval: 1.09-1.55). The impact of the polymorphism decreased with the increase of smoking, and virtually no association with lung cancer was observed among heavy smokers whose pack-year values were 30 or more (odds ratio: 1.02, P = 0.93, 95% confidence interval: 0.67-1.55). These results suggest that polymorphisms in the MT gene are moderately associated with the risk of lung cancer and that the associations are modified by lifestyle factors., (© 2014 Wiley Periodicals, Inc.)

Problem: Although pharmacotherapy is an effective treatment for many psychiatric disorders in children and adolescents, medication adherence rates among children are low. This study clarifies factors affecting children's medication adherence and the role of parental involvement., Method: Patients aged 7-17 years with a history of psychotropic medication treatment and their mothers were included in this study. Each mother and child completed self-administered questionnaires. Thirty mother-child pairs who fully completed the questionnaires were included in the analysis., Results: Medication adherence was greater in children and mothers when mothers felt that "children's symptoms improved with treatment and medication." Medication adherence in children and mothers significantly correlated with the child's reported trust in their parent., Conclusions: The results suggest the need for psychosocial support that considers the influence of mothers on medication adherence in children treated in child psychiatry departments., (© 2015 Wiley Periodicals, Inc.)

Objective: Thiazide diuretics are reported to have antioxidant effects and reduce pulse pressure (PP). The aim of this study was to elucidate whether hydrochlorothiazide additionally exerts such effects in stroke patients under treatment with losartan., Methods: This study was an open-label, randomized, multicenter study. Patients with a history of chronic stroke and treatment with angiotensin receptor blockers or angiotensin-converting enzyme inhibitors for essential hypertension were enrolled. Fifty-five hypertensive patients were randomly assigned to two groups: those further treated with hydrochlorothiazide and those further treated with non-diuretic antihypertensive drugs., Results: Both groups showed a significant decrease in PP over six months (hydrochlorothiazide group: 67±12 mmHg to 58±12, p<0.001; non-diuretic group: 72±12 to 61±12, p<0.001), although no significant differences were observed between the two groups. The malondialdehyde-modified low-density lipoprotein levels did not change significantly after treatment in either group., Conclusion: In this study, hydrochlorothiazide treatment did not provide any additional benefits over non-diuretic antihypertensive drugs in terms of antioxidant effects or reducing PP.

[Purpose] Auditory hypersensitivity has been widely reported in patients with autism spectrum disorders. However, the neurological background of auditory hypersensitivity is currently not clear. The present study examined the relationship between sympathetic nervous system responses and auditory hypersensitivity induced by different types of auditory stimuli. [Methods] We exposed 20 healthy young adults to six different types of auditory stimuli. The amounts of palmar sweating resulting from the auditory stimuli were compared between groups with (hypersensitive) and without (non-hypersensitive) auditory hypersensitivity. [Results] Although no group × type of stimulus × first stimulus interaction was observed for the extent of reaction, significant type of stimulus × first stimulus interaction was noted for the extent of reaction. For an 80 dB-6,000 Hz stimulus, the trends for palmar sweating differed between the groups. For the first stimulus, the variance became larger in the hypersensitive group than in the non-hypersensitive group. [Conclusion] Subjects who regularly felt excessive reactions to auditory stimuli tended to have excessive sympathetic responses to repeated loud noises compared with subjects who did not feel excessive reactions. People with auditory hypersensitivity may be classified into several subtypes depending on their reaction patterns to auditory stimuli.

This study's objective was to investigate the efficacy of sensory integration therapy (SIT) for children with high-functioning autism spectrum disorder (HFASD). The subjects were 20 HFASD children with IQs above 70 selected from previously collected data. Eight participated in individual SIT sessions, and 12 participated in group therapy (GT) including social skill training, communication training, kinetic activities, and child-parent play for 8-10 months. Changes in Total score and five Index scores on the Japanese version of the Miller Assessment for Preschoolers before and after therapy between children in the SIT and GT groups were compared. The results showed that Total score and all Index scores except for Verbal Index increased significantly in the SIT group, while only Total score increased in the GT group. Furthermore, the SIT group showed more improvement compared with the GT group in Total score and on Coordination, Non-verbal, and Complex Index scores. SIT might have a more positive effect on motor coordination abilities, non-verbal cognitive abilities, and combined abilities of sensory motor and cognition in children with HFASD when compared with GT. This study has limitations such as being an analysis of previously collected data. Further study should be conducted with a randomized control trial., (Copyright © 2013 John Wiley & Sons, Ltd.)

Revision of ICD-11 will be submitted for approval at the general assembly in 2015. The influence of the ICD revision will be marked in the field of psychiatry. The trend in developing ICD-11-PHC is promoting cooperation with primary carers. The goals of the revision of ICD-11-PHC are as follows: 1) To produce a classification system that corresponds more closely to common mental disorders encountered in general medical practice; 2) The "co-morbidity" we want practitioners to recognize is that between physical and psychological disorders; 3) To allow dimensions of severity of some common disorders to be recognized, rather than case/non-case distinctions. The ICD-11-PHC draft consists of 28 categories and detailed clinical descriptions. The number of categories has increased in the ICD-11-PHC draft in comparison with ICD-10-PHC. Anxiety disorders such as neurasthenia, and phobic disorders and panic disorder have been deleted. On the other hand, new diagnostic categories such as autistic spectrum disorder, PTSD, and personality disorder have been introduced. Furthermore, name changes such as anxious depression, bodily stress syndrome, health anxiety, and persistent psychotic disorders have been suggested. We should be aware of such new diagnostic concepts. In addition, it is thought that it is necessary for us to deepen our understanding of ICD-11, which will be important in the future.

Despite intensive treatment, steroid-resistant nephrotic syndrome (NS) often progresses to endstage renal disease. Therefore, a more accurate and quick histological diagnosis is required to properly treat such patients. The aim of this study was to introduce a novel approach to the histological diagnosis of pediatric NS by low vacuum scanning electron microscopy (LVSEM) and to describe the morphological differences in glomeruli between steroid-sensitive and steroid-resistant NS specimens. The subjects were three patients with steroid-sensitive NS and four patients with steroid-resistant NS. Conventional renal biopsy paraffin sections were stained with platinum-blue (Pt-blue) or periodic acid methenamine silver (PAM) and directly observed under LVSEM at magnifications between ×50 and ×10,000. The Pt-blue-stained sections showed three-dimensional structural alterations in glomerular podocytes and foot processes. PAM-stained sections showed changes in the structure and thickness of the glomerular basement membrane (GBM). Consequently, many round-shaped podocytes and elongated primary foot processes were exclusively recognized in steroid-resistant NS, although irregularities in foot process interdigitation, fusions, effacements, and microvillus transformations were observed in both steroid-sensitive and steroidresistant NS. Irregularities in thickness and the wrinkling of GBMs were clearly detected in steroid-resistant NS. The evaluation by LVSEM is probably useful for the renal histological diagnosis of pediatric NS.

The relationship between the poststroke blood pressure (BP) and functional outcomes in patients with acute ischemic stroke is still controversial. The aim of the present study was to elucidate the impact of the poststroke BP on the clinical outcomes of acute ischemic stroke. Among the patients in the Fukuoka Stroke Registry, 1874 patients with first-ever acute ischemic stroke (within 24 hours of onset) who had been functionally independent before onset were prospectively enrolled in the present study. The poststroke BP levels were defined as the average values during the 48 hours after onset. The study outcomes were a good neurological recovery, neurological deterioration, and a poor functional outcome. The higher poststroke BP levels were significantly associated with a lower probability of a good neurological recovery and elevated risks of neurological deterioration and a poor functional outcome after adjusting for potential confounding factors. The multivariate-adjusted odds ratios (95% confidence interval) in the highest quintile of systolic BP (versus the lowest quintile as a reference) were 0.51 (0.37-0.71) for a good neurological recovery, 1.92 (1.15-3.27) for neurological deterioration, and 2.51 (1.69-3.74) for a poor functional outcome. Similar associations were observed when we applied the poststroke diastolic BP or pulse pressure. No evidence of the J-curve phenomenon was observed for each association. These results suggest that a high poststroke BP was significantly associated with unfavorable clinical outcomes in patients with acute ischemic stroke. There was no evidence of the J-curve phenomenon between the poststroke BP levels and the clinical outcomes.

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are genetic disorders caused by mutations of the type IV collagen genes COL4A3, COL4A4, and/or COL4A5. We here aimed to investigate the three-dimensional ultrastructure of the glomerular basement membrane (GBM) in order to introduce a novel method of diagnosing AS and TBMN. The subjects were 4 patients with AS and 6 patients with TBMN. Conventional renal biopsy paraffin sections from AS and TBMN patients were stained with periodic acid methenamine silver (PAM) and observed directly under low vacuum scanning electron microscopy (LVSEM). The PAM-positive GBMs were clearly visible under LVSEM through the overlying cellular components. The GBMs showed characteristic coarse meshwork appearances in AS, and thin and sheet-like appearances in TBMN. At the cut side view of the capillary wall, the GBMs in AS appeared as fibrous inclusions between a podocyte and an endothelial cell, while the GBMs in TBMN showed thin linear appearances. These different findings of GBMs between AS and TBMN were easily observed under LVSEM. Thus, we conclude that three-dimensional morphological evaluation by LVSEM using conventional renal biopsy paraffin sections will likely be useful for the diagnosis of AS and TBMN, including for retrospective investigations.

Aims: The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for identifying abnormalities in prefrontal brain activity in children with autism spectrum disorders (ASD) as they inferred the mental states of others., Methods: The subjects were 16 children with ASD aged between 8 and 14 years and 16 age-matched healthy control children. Oxygenated hemoglobin concentration was measured in the subject's prefrontal brain region on NIRS during tasks expressing a person's mental state (MS task) and expressing an object's characteristics (OC task)., Results: There was a significant main effect of group (ASD vs control), with the control group having more activity than the ASD group. But there was no significant main effect of task (MS task vs OC task) or hemisphere (right vs left). Significant interactions of task and group were found, with the control group showing more activity than the ASD group during the MS task relative to the OC task., Conclusions: NIRS showed that there was lower activity in the prefrontal brain area when children with ASD performed MS tasks. Therefore, clinicians might be able to use NIRS and these tasks for conveniently detecting brain dysfunction in children with ASD related to inferring mental states, in the clinical setting., (© 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.)

Schizophrenia exhibits wide variation in epidemiological characteristics. Through the past few decades, we have learned much about schizophrenia epidemiology, providing important findings for etiological research, clinical care and public health. In this article, we provide overview of current research on incidence, prevalence, risk factors, mortality and outcome of schizophrenia. Contrary to traditional understanding, the incidence and prevalence of schizophrenia show prominent variation between locations. Risk factors for schizophrenia include urbanicity, migration, sex, season of birth and pregnancy and birth complications. Schizophrenia patients have an increased mortality risk compared with the general population. Recent studies about outcome show not so tragic, especially in regard to social functioning. Over the recent decades, circumstances have been changing around schizophrenia. As to treatment, for example, 'the second generation antipsychotics' have replaced conventional ones and 'early intervention' is developing. However, we have only limited evidences of current schizophrenia. Further epidemiological development is needed.

Background: A combination of factors such as substance abuse problems, medication noncompliance, and insufficient insight are generally known to increase the risk of violent behavior. However, little is known regarding the psychological impact on caregivers who are traumatized by the violent behavior of a family member with schizophrenia. Therefore, we carried out an investigation to measure this impact., Method: A questionnaire was given to 116 caregivers of individuals with schizophrenia in family support groups in Seoul and Daegu, Korea. Their responses were then evaluated using the 22-item version of the Impact of Event Scale-Revised (IES-R), the 8-item short version of the Zarit Caregiver Burden Interview (ZBI-8), and the 15-item version of the Mental Illness and Disorder Understanding Scale (MIDUS)., Results: The mean (SD) IES-R score was 26.69 (17.83) (range, 1-84). Multiple regression analysis showed that the psychological impact of traumatic experiences was significantly associated with the following factors: medical non-adherence (P<0.01), living without the patient (P<0.01), and caregiver burden (P<0.05)., Conclusion: Our results from the present study suggest that even when family caregivers live apart from the patient, they still experience the harmful psychological impact of trauma from the patient's violent behavior. The psychological impact continued as a result of the huge caregiver burden and the medication non-adherence of the family member with schizophrenia in spite of receiving long-term treatment and multiple hospitalizations. The present findings suggest the need for improved community-based service for preventive long-term care, including medication adherence, for outpatients with schizophrenia instead of multiple hospitalizations., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The WHO recognizes the importance of a psychiatric diagnostic system in primary care. Regarding the revision of ICD-11 primary health care (ICD-11-PHC), a working group is organized and acts positively. The WG makes the draft of ICD-11-PHC. Some new and interesting disease names, such as ANXIOUS DEPRESSION and BODILY STRESS SYNDROME (BSS), are incorporated in ICD-11-PHC. Revision to ICD-11 continues, and an international Field Trial of ICD-11-PHC by the WHO is planned. Participation in the Field Trial of Japanese researchers is expected. We psychiatrists should closely follow trends in interesting new knowledge in ICD-11-PHC.

Many epidemiological studies have demonstrated that ambient particulate matter poses consistent risks for respiratory and cardiovascular disorders. The translocation of inhaled particles is one hypothesis that could explain such systemic effects. The objectives of this study were to conduct a systematic review of previous reports on particle translocation from the respiratory system and to discuss factors important for translocation. A PubMed search was conducted in August 2011 for the period from 1967 with four main keyword domains (particle, translocation, detection site, and exposure route). The systematic review identified 61 original articles written in English that met the specified criteria (i.e., information on experiment and particle detection). Categorical regression analysis was performed with the site of particle detection as the objective variable, and particle size, particle material, animal species, and exposure route as the explanatory variables. All explanatory variables showed statistically significant effects. The effects for particle size and particle material were large, while the effects for animal species and exposure route were relatively small. There was a broad relationship between particle size and detection site: ≤50 nm for brain and remote organs; ≤1 μm for blood; and ≤10 μm for lung tissues. However, these results should be considered within the context of several limitations, such as deficiency of information.

Aim:   This prospective study was designed to examine whether consumption of a branched-chain amino acid (BCAA)-enriched nutrient mixture as a late-evening snack (LES) helps maintain and/or improve liver functioning in liver cirrhosis (LC) patients who have undergone radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC)., Methods:   An equal number (10) of 30 LC patients who had undergone RFA for HCC was randomly assigned to a standard diet group (control) group, a morning BCAA (M-BCAA) administration group, or a LES with BCAA (LES-BCAA) administration group. Liver function testing was performed and Child-Pugh scores (CPS) calculated for each group to assess the improvement at 1, 4 and 12 weeks post-RFA., Results:   Compared to the control and M-BCAA groups, the LES-BCAA group experienced a rapid and significant improvement in albumin and total serum bilirubin levels and in CPS that began during the initial post-RFA period. These results indicate that LES with BCAA supplementation significantly improved the CPS of the LES-BCAA group at 4 and 12 weeks post-RFA. Although no patients experienced serious adverse effects, two patients who had been diagnosed with diabetes mellitus before undergoing RFA required blood sugar management to improve glycemic control and one subject withdrew due to supplement-induced vomiting., Conclusion:   LES with BCAA supplementation significantly and rapidly improves liver functioning and CPS in LC patients who have undergone RFA for HCC. Control of blood sugar levels is necessary when calorie-containing BCAA is administrated to LC patients with impaired glucose tolerance., (© 2012 The Japan Society of Hepatology.)

Most studies that investigate the impact of mental disorders on work performance have been conducted in Western countries, but this study examines the impact of common mental disorders on sick leave and on-the-job work performance in a community sample of Japanese workers. Data from the World Mental Health Japan survey were analyzed. A subsample of 530 workers aged 20-60years were interviewed using the WHO Composite International Diagnostic Interview 3.0. The WHO Health and Work Performance Questionnaire, was used to assess sick days and on-the-job work performance for the previous 30days. Linear regression was used to estimate the impact of mental disorders on these indicators of work performance over 12months. Mood disorders, including major depressive disorder, and alcohol abuse/dependence were significantly associated with decreased on-the-job performance. There were no significant associations between mental disorders and sick/absent days. Consistent with previous studies, major depression has a great impact on on-the-job work performance in Japan. The lost productivity was estimated at approximately 28-30 lost days per year. A similar decrease in on-the-job work performance was found for alcohol abuse/dependence, which is stronger than that in other countries, probably attributable to greater tolerance of problematic drinking at Japanese worksites., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Japanese suicide rate is one of the highest among industrialized nations, especially following the economic crisis of the 1990s, with more than 30000 suicides every year since 1998. Previous studies have pointed out to relationships between overwork and/or job stress, and death and other health risks, and suggested several possible avenues for releasing stress and emotional burden, including suicidal ideation, through talking with intimate friends, family, and specialists, such as counselors and physicians. The present study was performed to explore the potential role of owners and managers of bars and izakaya-pub establishments in mitigating stress of middle-aged and elderly Japanese men by having informal conversations with them. A self-administered questionnaire was posted to all bars and izakaya-pubs registered in Ohmura-city, Nagasaki prefecture, in December 2009. Among 260 bars and izakaya-pubs, a total of 103 owners and managers completed the questionnaire. More than half of the respondents experienced engaging in conversations with their customers regarding customers' various personal and private issues. The most frequently talked about problem was that regarding work (56.3%). Regardless of sex and age of the respondents, those with longer working experience in bar and izakaya-pub establishments were more likely to have had customers confiding in them financial problems including debts/loans (adjusted odds ratio: 5.48, p = 0.033). Owners and managers of bars and izakaya-pubs may be in a position to act as "listeners", to whom middle-aged and elderly men can talk about their personal problems casually and without having to worry about conflict of interests, and direct those in need to professional counseling.

Objectives: The impact of chronic kidney disease (CKD) on clinical outcomes after acute ischemic stroke is still not fully understood. The aim of the present study was to elucidate how CKD and its components, proteinuria and low estimated glomerular filtration rate (eGFR), affect the clinical outcomes after ischemic stroke., Methods: The study subjects consisted of 3,778 patients with first-ever ischemic stroke within 24 hours of onset from the Fukuoka Stroke Registry. CKD was defined as proteinuria or low eGFR (<60 mL/min/m(2)) or both. The study outcomes were neurologic deterioration (≥2-point increase in the NIH Stroke Scale during hospitalization), in-hospital mortality, and poor functional outcome (modified Rankin Scale score at discharge of 2 to 6). The effects of CKD, proteinuria, and eGFR on these outcomes were evaluated using a multiple logistic regression analysis., Results: CKD was diagnosed in 1,320 patients (34.9%). In the multivariate analyses after adjusting for confounding factors, patients with CKD had significantly higher risks of neurologic deterioration, in-hospital mortality, and poor functional outcome (p <0.001 for all). Among the CKD components, a higher urinary protein level was associated with an elevated risk of each outcome (p for trend < 0.001 for all), but no clear relationship between the eGFR level and each outcome was found., Conclusions: CKD is an important predictor of poor clinical outcomes after acute ischemic stroke. Proteinuria independently contributes to the increased risks of neurologic deterioration, mortality, and poor functional outcome, but the eGFR may not be relevant to these outcomes.

Aim:  'Internalized stigma' is a construct that reflects the degree to which a person accepts beliefs endorsed by society about mental illness. Among people with schizophrenia spectrum disorders, internalized stigma has been found to moderate the associations between insight and social function, hope, and self-esteem. Among families of patients with schizophrenia, internalized stigma may not only hinder help-seeking but also result in the families attempting to provide care themselves, without assistance from mental health services. Little is known about internalized stigma among service providers, especially psychiatric nurses in Japan. Therefore, we investigated the correlation between internalized stigma and 'beliefs about the most appropriate form of hospitalization' among psychiatric nurses., Methods: The subjects were 215 psychiatric nurses employed in psychiatric hospitals who completed the personal stigma scale, perceived stigma scales, and Difficulty of Community Living Scale (DCLS) with respect to a chronic schizophrenia case vignette., Results: Internalized stigma was positively correlated with greater 'beliefs about the most appropriate form of hospitalization' among psychiatric nurses. We also showed that stronger 'beliefs about the social disadvantages of schizophrenia patients in the community' was positively correlated with stronger 'beliefs about the most appropriate form of hospitalization'., Conclusion: The present findings suggest that the psychiatric nurses employed at Japanese psychiatric hospitals have a pessimistic view of the community living of people with schizophrenia and their families. And these psychiatric nurses' beliefs were related to their understanding of the deeply dependent relationship between patients and families, and was related to the Confucian ideal., (© 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.)

The rat controls the form of its tail, from straight to curved, by contraction and relaxation of its four tail muscles. The tendons of these muscles insert on any of the cranial articular, transverse, and hemal processes of each of 24 coccygeal vertebrae (Co5-Co28). In this study, we isolated for the four coccygeal muscles each muscular fascicle segment inserting on any process of the coccygeal vertebrae. We measured the length and weight of all muscular fascicles and tendons, and then divided all muscular fascicles into four groups based on their insertion: Co5-Co10, Co11-Co16, Co17-Co22, and Co23-Co28. Moreover, we used soft X-ray imaging to investigate the geometrical relationship between neighboring coccygeal vertebrae. Additionally we carried out serial sectioning at the sacral and caudal portions, and traced the course of the tendons of coccygeal muscles from their origin to the Co4 level. We discuss which muscles and tendons play important roles when coccygeal vertebrae bend along and rotate around the longitudinal axis.

Aim: Major depression is expected to become the leading contributor to disease burden worldwide by 2020. Previous studies have shown that the societal cost of depression is not less than that of other major illnesses, such as cardiovascular diseases or AIDS. Nevertheless, the cost of depression in Japan has never been examined. The goal of the present study was to estimate the total cost of depression in Japan and to clarify the characteristics of this burden., Methods: A prevalence-based approach was adopted to measure the total cost of depression. The total cost of depression was regarded as being comprised of the direct cost, morbidity cost and mortality cost. Diagnoses included in this study were depressive episodes and recurrent depressive disorder according to the ICD-10 or major depressive disorder according to the DSM-IV. Data were collected from publicly available statistics and the World Mental Health Japan Survey database., Results: The total cost of depression among adults in Japan in 2005 was estimated to be ¥2.0 trillion. The direct cost was ¥0.18 trillion. The morbidity cost was ¥0.92 trillion, while the mortality cost was ¥0.88 trillion., Conclusion: The societal costs caused by depression in Japan are enormous, as in other developed countries. Low morbidity costs and extremely high mortality costs are characteristic in Japan. Effective interventions for preventing suicide could reduce the societal costs of depression., (© 2011 The Authors. Psychiatry and Clinical Neurosciences © 2011 Japanese Society of Psychiatry and Neurology.)

Objective: Down syndrome (DS) patients share certain neuropathological features with Alzheimer disease patients. A randomized, double-blind, placebo-controlled study was performed to investigate the efficacy and safety of donepezil, an Alzheimer disease drug, for DS patients., Method: Twenty-one DS patients with severe cognitive impairment were assigned to take donepezil (3 mg daily) or a placebo for 24 weeks, and evaluated for activities in daily lives by concisely modified International Classification of Functioning, Disability and Health (ICF) scaling system., Results: ICF scores significantly increased without any adverse effects in the donepezil group in comparison to those in the placebo control. Among the individual functions tested, there was a dramatic improvement in the global mental functions and in specific mental functions., Conclusions: Donepezil may effectively and safely improve overall functioning of DS patients with severe cognitive impairment.

Sex differences in opportunities to use alcohol or drugs, and transition to use, were investigated in 15 surveys, in 2001-2004 (Europe 6; Americas 3; Africa 2, Asia 3; Oceania 1). The paper focuses on 18-29 year olds (N = 9,873). The World Mental Health Survey Initiative oversaw the surveys; each country obtained its own funding. A complex picture emerged with different results for alcohol and for drugs and for opportunity to use and the transition to use. Sex differences in opportunity to use alcohol were small except in Lebanon and Nigeria, whereas for drugs, the largest differences were in Mexico and Colombia.

Aim:   The diagnosis of Wilson disease is based on the results of several clinical and biochemical tests. This study aimed to clarify the clinical features and spectrum of Wilson disease, including severe Wilson disease., Methods:   Between 1985 and 2009, 10 patients with clinical, biochemical or histological evidence of Wilson disease were either diagnosed or had a previously established diagnosis confirmed at Fukuoka University Hospital. Severe Wilson disease was defined by a serum prothrombin time ratio of more than 1.5 or serum prothrombin activity of less than 50%. The 10 Wilson disease patients were divided into two groups, one containing three non-severe patients and the other containing seven severe patients, and the biochemical features of the patients in these two groups were compared., Results:   The mean age at diagnosis was 21.5 ± 11.7 years (range, 7-39). Decreased serum ceruloplasmin, enhanced 24-h urinary copper excretion, presence of Kayser-Fleischer rings and histological signs of chronic liver damage were confirmed in 100%, 100%, 66.7% and 100% of patients, respectively. Severe Wilson disease patients had higher levels of serum ceruloplasmin and serum copper (P < 0.05, P < 0.05, respectively) than non-severe patients., Conclusion:   In severe Wilson disease patients, the serum ceruloplasmin and serum copper levels were higher than those in non-severe Wilson disease patients., (© 2010 The Japan Society of Hepatology.)

The DSM-IV and ICD-10 are both operational diagnostic systems that classify known psychological disorders according to the number of criteria symptoms. Certain discrepancies between the criteria exist and may lead to some inconsistencies in psychiatric research. The purpose of this study was to investigate these differences in the assessment of depression with item response theory (IRT) analyses. The World Mental Health-Japan (WMHJ) Survey is an epidemiological survey of the general population in Japan. We analyzed data from the WMHJ completed by 353 respondents who had either depressive mood or diminished interest. A two-parameter logistic model was used to evaluate the characteristics of the symptoms of the DSM-IV and ICD-10. IRT analyses revealed that the symptoms about psychomotor activity, worthlessness and self-reproach were more informative and suggestive of greater severity, while the symptoms about dietary habits were less informative. IRT analyses also revealed that the ICD-10 seems more sensitive to the mild range of the depression spectrum compared to the DSM-IV. Although there were some variations in severity among respondents, most of the respondents diagnosed with a severe or moderate depressive episode according to the ICD-10 were also diagnosed with a major depressive episode according to the DSM-IV., (Copyright © 2010 John Wiley & Sons, Ltd.)

Renal biopsy paraffin sections were examined by low vacuum scanning electron microscopy (LVSEM) in the backscattered electron (BSE) mode, a novel method for rapid pathological analysis which allowed detailed and efficient three-dimensional observations of glomeruli. Renal samples that had been already diagnosed by light microscopy (LM) as exhibiting IgA nephropathy, minor glomerular abnormalities, and membranous glomerulonephritis (GN) were rapidly processed in the present study. Unstained paraffin sections of biopsy samples on glass slides were deparaffinized, stained with platinum blue (Pt-blue) or periodic acid silver-methenamine (PAM), and directly observed with a LVSEM. Overviews of whole sections and detailed observations of individual glomeruli were immediately performed at arbitrary magnifications between ×50 to ×18,000. Cut surface views and surface views of glomeruli were demonstrated at the same time. On Pt-blue-stained sections, podocytes, endothelia, mesangium, and glomerular basement membranes (GBMs) could be distinguished due to the different yields of BSE signals, and pathological features were investigated in every sample. The abnormal surface appearances of podocytes with foot processes and the varying thicknesses of GBM were revealed three-dimensionally, features difficult to observe under LM and transmission electron microscopy. PAM-positive GBM alterations in membranous GN were distinctly visualized through overlying cells without cell removal under LVSEM at high magnification. Not only prominent spike formation but also slight protrusions were clearly revealed in the side views of GBM. Crater-like or hole-like structures were shown in the en face views of GBM. Accordingly, LVSEM is expected to provide a novel approach to the pathological diagnosis of human glomerular diseases using conventional renal biopsy sections.

There have been an increasing number of aged patients with malignancies. But, there are some patients who can not receive anti-cancer therapy due to poor activities of daily living and/or aging, etc. In Japan, medical practice at cancer patients' home has been expected for best supportive care, and most physicians believe that home chemotherapy is difficult because cancer patients frequently develop complications. We herein report a case of an 89-year-old female affected by malignant lymphoma who received a home chemotherapy and achieved a good remission. The clinical course of the present case suggested that with careful preparations, home chemotherapy might be feasible and one of therapeutic options for cancer patients.

Purpose: To describe the prevalence of illicit and non-medical use of drugs, the age of first use, and their correlates in the general population of Japan, based on data collected between 2002 and 2004 as part of the World Mental Health (WMH) surveys., Methods: Participants included were a subsample (n = 887) of the total 2,436 Japanese-speaking respondents aged >or=20 years, randomly sampled from residents in seven cities/municipalities in Japan. Face-to-face household surveys were conducted using the Japanese version of the fully structured WHO WMH Survey Initiative version of the Composite International Diagnostic Interview., Results: Lifetime prevalence of marijuana and cocaine use, non-medical use of prescribed drugs such as tranquilizers, stimulants and analgesics, and use of other substances was 1.5, 0.3, 6.4 and 2.4%, respectively. Lifetime use of marijuana was significantly greater among men. Prescription drug abuse/misuse was significantly more common among the middle-aged (35-49 years) group and those who were married/cohabitating. The 12-month prevalence of marijuana and non-medical use was 0.3 and 1.9%, respectively. Age of first use was likely to be early adulthood. Non-medical use was significantly related to mood disorder, anxiety disorder, intermittent explosive disorder and alcohol abuse/dependence., Conclusions: The present study confirmed lower prevalence of drug use in Japan than in other countries, such as the United States. However, the non-medical use of psychotropic drugs seems more common in Japan.

We examined whether the time-averaged maximum velocity (TAMV), flow volume (FV) or cross-sectional area (CA) in the vertebral arteries (VA) as determined by ultrasonography was related to vascular lesions or variations in the intracranial part of the posterior circulation. Three hundred nine patients without severe stenosis in the carotid circulation (159 males, 150 females, mean age of 69.1 years) underwent both colour duplex ultrasonography and magnetic resonance angiography (MRA) and were thus analyzed. According to the MRA findings, the patients were divided as follows; 22 patients with severe stenosis in the bilateral PCA or VA or basilar artery (V group) and 287 patients without (N group). The N group was then further divided as follows; 144 patients with no (P0 group); 89 with one (P1) and 54 with both posterior communicating arteries (P2) detected on MRA. TAMV, FV and CA were compared among these groups. Both TAMV and FV of V group were significantly lower than those of N group (35.3 vs. 42.6 cm/sec in TAMV, 98.2 vs. 135.3 mL/min in FV, p < 0.001 and 0.0001, respectively). The FVs and CAs in the P0 through P2 groups were all significantly different according to the number of posterior communicating arteries (149.3 vs. 128.0 vs. 109.8 mL/min, 22.5 vs. 20.2 vs. 16.5 mm2, both p < 0.001) while TAMVs in these groups did not differ substantially. The FV in both VAs were thus found to be related to the vascular lesions or variations in the posterior circulation.

The present study introduces a novel method for the direct observation of histological paraffin sections by low vacuum scanning electron microscopy (LVSEM) with platinum blue (Pt-blue) treatment. Pt-blue was applied not only as a backscattered electron (BSE) signal enhancer but also as a histologically specific stain. In this method, paraffin sections of the rat tongue prepared for conventional light microscopy (LM) were stained on glass slides with a Pt-blue staining solution (pH 9) and observed in a LVSEM using BSE detector. Under LVSEM, overviews of whole sections as well as three-dimensional detailed observations of individual cells and tissues could be easily made at magnifications from x40 to x10,000. Each kind of cell and tissue observed in the section could be clearly distinguished due to the different yields of BSE signals, which depended on the surface structures and different affinities to Pt-blue. Thus, we roughly classified cellular and tissue components into three groups according to the staining intensity of Pt-blue observed by LM and LVSEM: 1) a strongly stained (deep blue by LM and brightest by LVSEM) group which included epithelial tissue, endothelium and mast cells; 2) a moderately stained (light blue and bright) group which included muscular tissue and nervous tissue; 3) an unstained or weakly stained (colorless and dark) group which included elastic fibers and collagen fibers. We expect that this method will prove useful for the three-dimensional direct observation of histological paraffin sections of various tissues by LVSEM with higher resolutions than LM.

This study was designed to investigate whether different vascular endothelial growth factor (VEGF) genotypes are associated with ascites formation in cirrhotic patients. Seventy cirrhotic patients were included in the study: 25 cirrhotic patients with ascites and 45 cirrhotic patients without ascites. Patient characteristics were investigated and compared between the two groups. With regard to VEGF genotype, 42 patients were C/C and 28 patients were T/T or C/T. The genotypes T/T or C/T were observed in 23 cases (51%) among the non-ascites group, but in only five cases (20%) among the ascites group. Serum levels of albumin and creatinine, and the VEGF genotypes were significantly different between the two groups. Multiple regression analysis showed that serum levels of creatinine and the VEGF genotypes were significantly correlated with ascites formation. Thus, it can be concluded that VEGF genotyping might be a valuable susceptibility marker for ascites formation in cirrhotic patients.

The MRN complex (Mre11/RAD50/NBS1) and ATM (ataxia telangiectasia, mutated) are critical for the cellular response to DNA damage. ATM disruption causes ataxia telangiectasia (A-T), while MRN dysfunction can lead to A-T-like disease (ATLD) or Nijmegen breakage syndrome (NBS). Neuropathology is a hallmark of these diseases, whereby neurodegeneration occurs in A-T and ATLD while microcephaly characterizes NBS. To understand the contrasting neuropathology resulting from Mre11 or Nbs1 hypomorphic mutations, we analyzed neural tissue from Mre11(ATLD1/ATLD1) and Nbs1(DeltaB/DeltaB) mice after genotoxic stress. We found a pronounced resistance to DNA damage-induced apoptosis after ionizing radiation or DNA ligase IV (Lig4) loss in the Mre11(ATLD1/ATLD1) nervous system that was associated with defective Atm activation and phosphorylation of its substrates Chk2 and p53. Conversely, DNA damage-induced Atm phosphorylation was defective in Nbs1(DeltaB/DeltaB) neural tissue, although apoptosis occurred normally. We also conditionally disrupted Lig4 throughout the nervous system using Nestin-cre (Lig4(Nes-Cre)), and while viable, these mice showed pronounced microcephaly and a prominent age-related accumulation of DNA damage throughout the brain. Either Atm-/- or Mre11(ATLD1/ATLD1) genetic backgrounds, but not Nbs1(DeltaB/DeltaB), rescued Lig4(Nes-Cre) microcephaly. Thus, DNA damage signaling in the nervous system is different between ATLD and NBS and likely explains their respective neuropathology.

Background: Although often considered of minor significance in themselves, evidence exists that early-onset phobic disorders might be predictors of later more serious disorders, such as major depressive disorder (MDD). The purpose of this study is to investigate the association of phobic disorders with the onset of MDD in the community in Japan., Methods: Data from the World Mental Health Japan 2002-2004 Survey were analyzed. A total of 2,436 community residents aged 20 and older were interviewed using the WHO Composite International Diagnostic Interview 3.0 (response rate, 58.4%). A Cox proportional hazard model was used to predict the onset of MDD as a function of prior history of DSM-IV specific phobia, agoraphobia, or social phobia, adjusting for gender, birth-cohort, other anxiety disorders, education, and marital status at survey., Results: Social phobia was strongly associated with the subsequent onset of MDD (hazard ratio [HR]=4.1 [95% CI: 2.0-8.7]) after adjusting for sex, birth cohort, and the number of other anxiety disorders. The association between agoraphobia or specific phobia and MDD was not statistically significant after adjusting for these variables., Conclusions: Social phobia is a powerful predictor of the subsequent first onset of MDD in Japan. Although this finding argues against a simple neurobiological model and in favor of a model in which the cultural meanings of phobia play a part in promoting MDD, an elucidation of causal pathways will require more fine-grained comparative research.

We have reported that xeroderma pigmentosum group A (Xpa) gene-knockout mice [Xpa (-/-) mice] are deficient in nucleotide excision repair (NER) and highly sensitive to UV-induced skin carcinogenesis. Although xeroderma pigmentosum group A patients show growth retardation, immature sexual development, and neurological abnormalities as well as a high incidence of UV-induced skin tumors, Xpa (-/-) mice were physiologically and behaviorally normal. In the present study, we kept Xpa (-/-) mice for 2 years under specific pathogen-free (SPF) conditions and found that the testis diminished in an age-dependent manner, and degenerating seminiferous tubules and no spermatozoa were detected in the 24-month-old Xpa (-/-) mice. In addition, a higher incidence of spontaneous tumorigenesis was observed in the 24-month-old Xpa (-/-) mice compared to Xpa (+/+) controls. Xpa (-/-) mice provide a useful model for investigating the aging and internal tumor formation in XPA patients.

Aim: Suicide is a major public health concern in Japan but little is known about the prevalence of and risk factors for suicidal ideation, plans, and attempts. The aim of the present study was to clarify the prevalence of and risk factors for important suicide-related outcomes., Methods: Important suicide-related outcomes and risk factors were assessed in face-to-face interviews with 2436 adult respondents in seven areas as part of the World Health Organization (WHO) World Mental Health Survey Initiative. Mental disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI)., Results: The lifetime prevalence estimates of suicidal ideation, plans, and attempts were 10.9%, 2.1%, and 1.9%, respectively. Risk of suicide plans and attempts was highest when suicidal ideation occurred at an early age and within the first year of ideation. In middle-aged individuals, the period after first employment and the presence of mental disorders were risk factors., Conclusions: Risk of suicide plans and attempts is highest when suicidal ideation occurred at an earlier age and within the first year of ideation. Mental disorders are as predictive of the suicide-related outcomes examined here, and comorbidity is an important predictor.

We examined whether selected circulatory diseases (heart disease, stroke, diabetes and hypertension) were associated with an increased risk of major depression in the Japanese community population. Face-to-face household surveys were carried out in 7 areas, and a total of 2,436 persons participated (overall response rate: 58.4%) from 2002 to 2004. The WHO Composite International Diagnostic Interview 3.0 was used to diagnose major depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and additional interviews assessed the presence of circulatory diseases. Using data from a random subsample of the respondents (n=832), we conducted Cox proportional hazards models to calculate hazard ratios for the onset of major depression with comorbid circulatory diseases as a time-dependent covariate. Heart attack was significantly associated with the onset of major depression (hazard ratio [HR], 7.51 [95% Confidential Interval (CI), 1.36-41.45]) after adjusting for sex, birth cohort, smoking, alcohol intake, and education. Heart disease (HR, 2.12 [95% CI, 0.79-5.70]), diabetes (HR, 2.36 [95% CI, 0.42-13.34]) and hypertension (HR, 0.97 [95% CI, 0.37, 2.50]) were not significantly associated. There were no subjects who developed major depression after stroke. These results suggest that heart attack, and maybe also heart disease and diabetes, affect the onset of major depression.

Background and Aim: Hepatocellular carcinoma (HCC) is frequently associated with paraneoplastic hypercholesterolemia. In familial hypercholesterolemia, genetic mutation of the low-density lipoprotein (LDL) receptor gene has been recognized as being a pathogenesis of the disease. We investigate the expression of a LDL receptor protein and gene abnormalities of a LDL receptor in HCC cells in cases with paraneoplastic hypercholesterolemia., Methods: Eleven patients with HCC associated with paraneoplastic hypercholesterolemia and seven patients with HCC who did not have hypercholesterolemia were studied. Paraffin-embedded tissues were obtained at operative resection, autopsy, or biopsy. Immunohistochemistry was performed using a monoclonal antibody against human LDL receptors. Confocal laser-scanning microscopy was used to observe the FITC-labeled LDL receptor. DNA samples were extracted from paraffin-embedded tissues. Since a LDL receptor gene is located on chromosome 19p13.2, a microsatellite marker, D19S413, was used to analyze the chromosomes., Results: Immunoreactive LDL receptors were observed all over the surface of non-tumorous hepatocytes. However, expression of the LDL receptor was significantly decreased in all HCC cells derived from the 11 patients with hypercholesterolemia. In contrast, the expression was retained in the HCC cells of all patients without hypercholesterolemia. In two patients with hypercholesterolemia, DNA analysis revealed a loss of heterozygosity on chromosome 19p13.2., Conclusion: We demonstrated reduced expression of the LDL receptor in HCC cases with paraneoplastic hypercholesterolemia. LDL receptor genes with genomic disorders may cause decreased expression of the LDL receptor protein, leading to feed-back failure of the cholesterol regulation system, as seen in familial hypercholesterolemia. This is the first report considering the mechanism behind the development of paraneoplastic hypercholesterolemia in HCC.

Background and Purpose: Sorbin and SH3-domain-containing-1 (SORBS1) is an important adaptor protein in insulin-signalling pathway, and its genetic polymorphism may regulate the activity of insulin resistance. We investigated the association between the SORBS1 T228A polymorphism and ischaemic stroke., Methods: Genotyping was achieved by a rapid-cycle PCR and melting curve analysis using fluorescent probes in 1049 incident cases of ischaemic stroke and 1049 age- and sex-matched control subjects recruited from the Hisayama study., Results: The allele distributions of the SORBS1 T228A polymorphism were similar amongst cases and controls. The multivariate-adjusted odds ratio (OR) of the AA genotype for ischaemic stroke was 2.897 (95% CI, 0.907-8.018) compared with the TT genotype. In terms of stroke subtype, there was a trend toward a difference in the AA genotypes for lacunar infarction, compared with the TT genotype (OR = 8.740, P = 0.0510), and combined TT and TA genotypes (OR = 8.768, P = 0.0505). The other polymorphisms genotyped were not associated with any subtypes of ischaemic stroke. T228A polymorphism of SORBS1 was not associated with the prevalence of diabetes., Conclusions: The AA genotype of SORBS1 T228A polymorphism may play a role in lacunar infarction in the Japanese population.

Background and Purpose: Lymphotoxin alpha (LTA), one of the tumor necrosis factor family proteins, is an important proinflammatory cytokine and appears to play a putative role in the inflammatory process of atherosclerosis. Recent genetic studies have suggested that variations in the gene encoding LTA, which affect its expression and biological function, may contribute to the development of vascular diseases. We conducted a case-control study to clarify the association of LTA gene polymorphisms with ischemic stroke in a large Japanese population., Methods: Genotyping for LTA A252G and C804A polymorphisms was achieved by a rapid-cycle polymerase chain reaction and melting curve analysis using fluorescent probes in 1,044 incident cases of ischemic stroke recruited from the Fukuoka Stroke Registry and 1,044 age- and sex-matched control subjects recruited from the Hisayama Study., Results: The overall distribution of allele and genotype for each polymorphism was similar between stroke patients and control subjects. The allele frequencies of 252G and 804A were slightly lower in stroke patients than in control subjects; however, conditional logistic regression analysis adjusted for potential risk factors found no association between the risk of ischemic stroke and either polymorphism. In terms of stroke subtype, we also found no association of these polymorphisms with any subtypes of ischemic stroke., Conclusions: Neither the A252G nor C804A polymorphism of the LTA gene was associated with stroke overall and any subtypes of ischemic stroke in the Japanese population., ((c) 2008 S. Karger AG, Basel.)

We examined whether central or peripheral administration of interleukin-1beta (IL-1beta) might change levels of nitric oxide (NO) and hydroxyl radical (*OH) in the medial prefrontal cortex (mPFC). Extracellular levels of NO metabolites (NOx(-)) and 2,3-dihydroxybenzoic acid (2,3-DHBA), as a marker of *OH production, were determined with an in vivo microdialysis technique in conscious rats. In the mPFC, central administration of IL-1beta into the mPFC resulted in dose-dependent increases in levels of both NOx(-) and 2,3-DHBA. In contrast, peripheral administration of IL-1beta significantly increased NOx(-) levels but not 2,3-DHBA levels. Perfusion of Mn(III) tetrakis (4-benzoic acid) porphyrin chloride, a superoxide (O(2)(-)) dismutase mimic, into the mPFC reduced the increases in levels of 2,3-DHBA induced by centrally administered IL-1beta, but enhanced the increases in levels of NOx(-) induced by centrally administered IL-1beta. The present results show a different response in free radical productions in the mPFC between central and peripheral administration of IL-1beta. This finding should be useful for our understanding of the response of NO and free radicals such as *OH and O(2)(-) in the mPFC after central and peripheral administration of IL-1beta.

Two new screening scales for psychological distress, the K6 and K10, have been developed using the item response theory and shown to outperform existing screeners in English. We developed their Japanese versions using the standard back-translaton method and included them in the World Mental Health Survey Japan (WMH-J), which is a psychiatric epidemiologic study conducted in seven communities across Japan with 2436 participants. The WMH-J used the WMH Survey Initiative version of the Composite International Diagnostic Interview (CIDI) to assess the 30-day Diagnostic and Statistical Manual of Mental Disorders--Fourth Edition (DSM-IV). Performance of the two screening scales in detecting DSM-IV mood and anxiety disorders, as assessed by the areas under receiver operating characteristic curves (AUCs), was excellent, with values as high as 0.94 (95% confidence interval = 0.88 to 0.99) for K6 and 0.94 (0.88 to 0.995) for K10. Stratum-specific likelihood ratios (SSLRs), which express screening test characteristics and can be used to produce individual-level predicted probabilities of being a case from screening scale scores and pretest probabilities in other samples, were strikingly similar between the Japanese and the original versions. The Japanese versions of the K6 and K10 thus demonstrated screening performances essentially equivalent to those of the original English versions.

The C242T polymorphism of p22phox, a component of NAD(P)H oxidase, may have an impact on cardiovascular diseases; however, the association between this polymorphism and brain infarction is not fully understood. Here, we investigate the relationship between the C242T polymorphism and brain infarction in Japan. We recruited 1055 patients with brain infarction and 1055 control subjects. A chi-squared test revealed that the T-allele frequency was lower in patients with cardioembolic infarction (5.6%) than in control subjects (11.0%, P < 0.001); however, allele frequencies in patients with lacunar and atherothrombotic infarction (11.2%) were not significantly different from those in control subjects (11.0%). A multivariate-adjusted conditional logistic regression analysis also revealed no association between CT + TT genotype, and lacunar and atherothrombotic infarction (odds ratio = 0.97, 95% confidence interval: 0.72-1.32). To investigate the functional effects of the C242T polymorphism, we examined superoxide production in COS-7 cells cotransfected with Nox4 and p22phox of each genotype. The superoxide-producing activity in those cells expressing p22phox with the T allele was not significantly different from that in cells expressing p22phox with the C allele. The present results suggest that the p22phox C242T polymorphism may have a protective effect against cardioembolic infarction, but is not related to lacunar and atherothrombotic infarction in Japan.

A 57 year-old woman was admitted to our hospital because of large hepatocellular carcinoma (HCC). Laboratory data showed hypercholesterolemia, thrombocytosis and hypoglycemia. Based on several examinations and the clinical course, we diagnosed HCC with paraneoplastic syndrome. It is rare that 3 paraneoplastic phenomena occur in a patient with HCC. In particular, paraneoplastic thrombocytosis is very rare in paraneoplastic syndrome associated with HCC.

This paper reports cross-national data concerning back or neck pain comorbidity with mental disorders. We assessed (a) the prevalence of chronic back/neck pain, (b) the prevalence of mental disorders among people with chronic back/neck pain, (c) which mental disorder had strongest associations with chronic back/neck pain, and (d) whether these associations are consistent across countries. Population surveys of community-dwelling adults were carried out in 17 countries in Europe, the Americas, the Middle East, Africa, Asia, and the South Pacific (N=85,088). Mental disorders were assessed with the Composite International Diagnostic Interview, third version (CIDI 3.0): anxiety disorders (generalized anxiety disorder, panic disorder/agoraphobia, posttraumatic stress disorder, and social anxiety disorder), mood disorders (major depression and dysthymia), and alcohol abuse or dependence. Back/neck pain was ascertained by self-report. Between 10% and 42% reported chronic back/neck pain in the previous 12 months. After adjusting for age and sex, mental disorders were more common among persons with back/neck pain than among persons without. The pooled odds ratios were 2.3 [95% CI=2.1-2.5] for mood disorders, 2.2 [95% CI=2.1-2.4] for anxiety disorders, and 1.6 [95% CI=1.4-1.9] for alcohol abuse/dependence in people with versus without chronic back/neck pain. Although prevalence rates of back/neck pain were generally lower than in previous reports, mental disorders were associated with chronic back/neck pain. The strength of association was stronger for mood and anxiety disorders than for alcohol abuse/dependence. The association of mental disorders with back/neck pain showed a consistent pattern across both developed and developing countries.