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Background: Sarcopenic obesity (SO) is defined as a decrease in lean body mass and an increase in body fat mass (BFM) due to aging. Detecting SO in elderly women is important from the perspective of extending healthy life expectancy. While various indices of SO are currently used, there is no global consensus regarding diagnostic criteria for SO. This study aimed to examine the relationship between obesity indices (waist circumference (WC), body mass index (BMI), and body fat percentage (BFP)) and sarcopenia indices (total body muscle mass (TBM), appendicular lean mass (ALM), skeletal mass index (SMI)), and physical function (gait speed (GS), handgrip strength (HGS))., Methods: Subjects were 170 community-dwelling healthy elderly women aged 65-79 years (mean: 72.7 ± 5.78 years) who underwent measurements for WC, BMI, and BFP. A WC of ≥ 90cm was defined as the obese group, BMI was determined as weight (kg) divided by height squared (m 2 ) and a cutoff of ≥ 25 kg/m 2 was used to define the obesity group. BFM was measured using the bioelectrical impedance analysis (BIA) method and BFP was calculated from body weight and a cutoff of ≥ 30% was used to define the obesity group. TBM and ALM (kg) were measured using the BIA method, ALM (kg) was corrected for height (m 2 ) to obtain SMI (kg/m 2 ). Physical function was assessed by GS and HGS, which were measured by the 5-m walk test and a digital grip strength meter, respectively., Results: When obesity was assessed using BMI, WC and BFP, obese individuals had higher TBM, ALM and SMI, and lower GS among the sarcopenia indicators. HGS did not differ significantly between the non-obese and obese groups., Conclusion: Our findings suggest HGS is thought to reflect muscle strength without being affected by obesity indices, suggesting that it may be useful in detecting possible sarcopenia in obese individuals., (© 2024. The Author(s).)

Aim: Recently, new diagnostic criteria for acute-on-chronic liver failure (ACLF) were established in Japan. However, there is little evidence regarding the feasibility of classifying patients undergoing living-donor liver transplantation (LDLT). The aim was to re-evaluate the impact of these new diagnostic criteria on ACLF and the severity classification of patients undergoing LDLT., Methods: We collected data of 82 recipients who underwent LDLT for liver failure between 1997 and 2020 and reviewed it retrospectively., Results: Of the 82 patients with liver failure, 31 (37.8%) were diagnosed with ACLF; Grade 0 (n = 6), Grade 1 (n = 7), Grade 2 (n = 9), and Grade 3 (n = 9). There was no substantial difference in overall survival (OS) and the occurrence of postoperative complications between liver failure patients with and without ACLF. The OS after LDLT was significantly different among the four groups of ACLF patients (P = .036). Interestingly, ACLF Grade 3 patients had substantially lower OS compared to other ACLF groups even after LDLT (P = .006; 5-year OS rates, 33.3% vs. 85.9%)., Conclusion: Proper use of the new diagnostic criteria for ACLF in Japan demonstrated that the presence and severity of ACLF, especially the presence of multiple organ failures, leads to morbidity and mortality even in an LDLT setting. Considering that the patients with ACLF Grade 3 do not have the favorable outcomes of LDLT, deceased-donor liver transplantation usage, or LDLT before reaching the severity of Grade 3 may be suitable for further research., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Patients with vancomycin-resistant Enterococcus (VRE) colonization should be managed in an isolation room with contact precautions. We herein report a patient whose colorectal carriage of VRE was successfully decolonized using concomitant bowel irrigation with polyethylene glycol, probiotics, and oral antimicrobials, linezolid and orally-administered daptomycin, for release from isolation and contact precautions. We therefore would like to suggest a potential strategy for managing patients with VRE colonization.

Background: In Hokkaido, northern island of Japan, at least seven cases of falciparum malaria were reported by 1951. A survey conducted at that time was unsuccessful in implicating any mosquito species as the possible vector. Although active anopheline mosquito surveillance continued until the middle of the 1980s, there is very limited information on their current status and distribution in Japan. Therefore, this study is an update on the current status and distribution of anopheline mosquitoes in Hokkaido based on a 15-year entomological surveillance between 2001 and 2015., Methods: A survey of mosquitoes was conducted at 22 sites in Hokkaido, Japan, from 2001 to 2015. Adult mosquitoes were collected from cowsheds, lakesides, shrubs, and habitats ranging from open grassland to coniferous forest using a Centers for Disease Control and Prevention (CDC) miniature light trap enhanced with dry ice, aspirators, and sweeping nets. Larvae were collected from lakes, ponds, swamps, stagnant and flowing rivers, and paddy fields. All specimens were morphologically identified and subjected to polymerase chain reaction (PCR)-based sequence analysis of the internal transcribed spacer 2 ( ITS2) region of rDNA. Phylogenetic trees were reconstructed using the neighbor-joining method with the Kimura 2-parameter model on MEGA X version 10.2.2., Results: A total of 46 anopheline specimens were used for the phylogenetic analysis. During the survey, a new member of the Anopheles hyrcanus group, An. belenrae, was discovered in eastern Hokkaido in 2004. Anopheles belenrae has since then been consistently found and confirmed to inhabit only this area of Japan. Four members of the An. hyrcanus group, namely An. belenrae, An. engarensis, An. lesteri, and An. sineroides, have been found in Hokkaido. The results also suggest that An. sinensis, formerly a dominant species throughout Japan, has become a rarely found species, at least currently in Hokkaido., Conclusion: The updated distribution of anopheline mosquitoes in Hokkaido, Japan, showed considerable differences from that observed in previous surveys conducted from 1969 to 1984. In particular, areas where An. sinensis was previously distributed may have been greatly reduced in Hokkaido. The phylogenetic analysis revealed a novel An. hyrcanus group member identified as An. belenrae, described in South Korea in 2005. It is interesting that An. belenrae was confirmed to inhabit only eastern Hokkaido, Japan., (© 2021. The Author(s).)

Introduction: We investigated factors predicting the addition of disease-modifying antirheumatic drugs (DMARDs) after an initial methotrexate (MTX) monotherapy in rheumatoid arthritis (RA) patients to support an early decision on the DMARDs addition., Methods: This retrospective cohort study included 311 patients who were diagnosed with RA and started on MTX monotherapy at Showa University Hospital, Japan. The outcome was addition of DMARDs after an initial MTX monotherapy at 6 months. Baseline patient characteristics were compared between the DMARDs addition and MTX monotherapy continuation groups, and significant independent predictive factors for the addition of DMARDs were selected using multivariate analysis., Results: The median age of patients was 62 years (range 24-90), 170 patients (73%) were women, the median swollen 28-joint count (SJC28) was 3 (0-28), and the median tender 28-joint count (TJC28) was 5 (0-28). DMARDs were added in 65 (27.9%) patients. In the univariate analysis, higher TJC28 and SJC28, concomitant use of nonsteroidal anti-inflammatory drugs, and intra-articular glucocorticoid (GC) injection history were significantly associated with the DMARDs addition. In the multivariate analysis, by adding covariates to the variables identified in the univariate analysis, SJC28 (odds ratio [OR] 1.390 per 5 joints increase; 95% confidence interval [CI], 1.036-1.866) and intra-articular GC injection history (OR 3.678; 95% CI, 1.170-11.557) were independent predictors of DMARDs addition., Conclusion: A higher SJC28 and intra-articular GC injection history may be useful predictors of DMARDs addition after the initial MTX monotherapy. We expect that using these predictors will enable an earlier shift to a more aggressive treatment. Key Points ・We performed a retrospective cohort study with the addition of DMARDs as the outcome in patients with RA who were started on MTX monotherapy. ・A higher SJC28 (OR 1.390; 95% CI, 1.036-1.866) and an intra-articular GC injection history (OR 3.678; 95% CI, 1.170-11.557) may be useful predictors for the addition of DMARDs of initiating MTX monotherapy at 6 months. ・The use of such indicators may support an early decision on the addition of DMARDs after the initial MTX monotherapy.

NTRK fusion-positive tumors are known to be highly sensitive to TRK inhibitors, such as larotrectinib and entrectinib. Therefore, identification of patients who can potentially benefit from these inhibitors is important; however, the frequency of NTRK fusions in Japanese patients with colorectal cancer (CRC) is unknown. We performed pan-TRK staining using TMA-based immunohistochemistry (IHC) on samples from 971 consecutive Japanese CRC cases from a single institution. Positive cases were further analyzed using NanoString and subsequent targeted RNA sequencing. We found three positive cases using TRK-IHC. Furthermore, the Nanostring assay supported the presence of NTRK fusion in these cases. Subsequent targeted RNA-sequencing and RT-PCR revealed two cases with TPM3-NTRK1 and one with TPR-NTRK1. The TNM stages of these cases were stage I, stage IIA, and stage IIIB, and two showed microsatellite instability-high status. Next-generation sequencing analysis using Cancer hotspot panel revealed TP53 and SMAD4 mutations in separate cases. IHC of β-catenin did not show nuclear accumulation. We found three cases (0.31%) of CRC with NTRK1 fusion among 971 consecutive Japanese CRC cases. No potential driver alterations other than NTRK fusion were identified in these three patients.

Objective: Cisplatin(CDDP)is a key drug for head and neck cancer therapy, but frequently induces severe adverse events including renal dysfunction. Nedaplatin(CDGP)was developed and is used in Japan; it has certain benefits over CDDP. Unlike CDDP, CDGP treatment does not require hydration. However, CDGP is not used globally and thus safety information is lacking. Therefore, we surveyed safety profiles for CDGP-based chemotherapy., Methods: A survey was conducted at Showa University Hospital. Thirty-eight patients treated for head and neck cancer combined with radiotherapy(RTx)and tegafur- gimeracil-oteracil(S-1)between April 2012 and March 2015 were included. Laboratory-based adverse events(WBC, Hb, platelet[Plt], SCr, Alb)and oral mucositis were assessed according to CTCAE v5.0. Time-onset profiles for adverse events were evaluated after starting chemoradiotherapy., Results: In 38 patients, Plt nadir was observed following 40(30-70)Gy and sustained for 14(7-35)days. WBC patterns followed similar profiles, but for Hb, nadir was observed following 60(40- 70)Gy and was less frequently sustained throughout the RTx. Alb and SCr levels were not correlated with therapy. Oral mucositis was observed following 50(10-70)Gy., Conclusion: In conclusion, at approximately 40 Gy, we observed decreases in WBC and Plt, with an increase in oral mucositis. Based on these results, medical staffs must closely monitor patients, especially at doses within range of 40 Gy.

Background & Aims: Small-for-size graft (SFSG) syndrome is a major cause of graft loss after living donor liver transplantation (LDLT). Splenectomy (Spx) is an option to prevent this catastrophic complication, but its effect remains controversial. Herein, we aimed to elucidate the effect of simultaneous Spx on graft function and long-term outcomes after LDLT., Methods: Three hundred and twenty patients were divided into 2 groups: those undergoing (n = 258) and those not undergoing (n = 62) simultaneous Spx. To overcome selection bias, propensity score matching (PSM) was performed (n = 50 in each group)., Results: Before PSM, recipients undergoing simultaneous Spx showed better graft function on post-operative day (POD) 7 and 14, as well as lower sepsis frequency within 6 months after LDLT and better graft survival rates compared to those not undergoing Spx. After PSM, compared to patients not undergoing Spx, those undergoing Spx had a lower frequency of early graft dysfunction on POD 7 (p = 0.04); a lower frequency of SFSG syndrome (p = 0.01), lower serum total bilirubin levels (p = 0.001), and lower international normalized ratio (p = 0.004) on POD 14; lower sepsis frequency within 6 months after LDLT (p = 0.02), and better graft survival rates (p = 0.04). Univariate analysis revealed that not undergoing Spx (hazard ratio 3.06; 95% CI 1.07-11.0; p = 0.037) was the only risk factor for graft loss after LDLT., Conclusions: Simultaneous Spx may prevent SFSG syndrome and is a predictive factor for graft survival after LDLT. Simultaneous Spx is recommended when a small graft (≤35% of standard liver weight) is predicted preoperatively, or for patients with portal hypertension or high portal pressure (above 20 mmHg) after reperfusion in LDLT., Lay Summary: Living donor liver transplantation (LDLT) for patients with acute or chronic liver failure is an alternative to overcome the deceased donor shortage. The potential mismatch between graft and body size is a problem that needs to be solved for LDLT recipients. Herein, we evaluated the impact of simultaneous splenectomy and showed that it was associated with favorable outcomes in patients undergoing LDLT., Competing Interests: Conflicts of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Variants in the PROM1 gene are associated with cone (-rod) dystrophy, macular dystrophy, and other phenotypes. We describe the clinical and genetic characteristics of 10 patients from eight Japanese families with PROM1-associated retinal disorder (PROM1-RD) in a nationwide cohort. A literature review of PROM1-RD in the Japanese population was also performed. The median age at onset/examination of 10 patients was 31.0 (range, 10-45)/44.5 (22-73) years. All 10 patients showed atrophic macular changes. Seven patients (70.0%) had spared fovea to various degrees, approximately half of whom had maintained visual acuity. Generalized cone (-rod) dysfunction was demonstrated in all nine subjects with available electrophysiological data. Three PROM1 variants were identified in this study: one recurrent disease-causing variant (p.Arg373Cys), one novel putative disease-causing variant (p.Cys112Arg), and one novel variant of uncertain significance (VUS; p.Gly53Asp). Characteristic features of macular atrophy with generalized cone-dominated retinal dysfunction were shared among all 10 subjects with PROM1-RD, and the presence of foveal sparing was crucial in maintaining visual acuity. Together with the three previously reported variants [p.R373C, c.1551+1G>A (pathogenic), p.Asn580His (likely benign)] in the literature of Japanese patients, one prevalent missense variant (p.Arg373Cys, 6/9 families, 66.7%) detected in multiple studies was determined in the Japanese population, which was also frequently detected in the European population., (© 2020 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)

The retinitis pigmentosa 2 (RP2) gene is one of the causative genes for X-linked inherited retinal disorder. We characterized the clinical/genetic features of four patients with RP2-associated retinal disorder (RP2-RD) from four Japanese families in a nationwide cohort. A systematic review of RP2-RD in the Japanese population was also performed. All four patients were clinically diagnosed with retinitis pigmentosa (RP). The mean age at examination was 36.5 (10-47) years, and the mean visual acuity in the right/left eye was 1.40 (0.52-2.0)/1.10 (0.52-1.7) in the logarithm of the minimum angle of resolution unit, respectively. Three patients showed extensive retinal atrophy with macular involvement, and one had central retinal atrophy. Four RP2 variants were identified, including two novel missense (p.Ser6Phe, p.Leu189Pro) and two previously reported truncating variants (p.Arg120Ter, p.Glu269CysfsTer3). The phenotypes of two patients with truncating variants were more severe than the phenotypes of two patients with missense variants. A systematic review revealed additional 11 variants, including three missense and eight deleterious (null) variants, and a statistically significant association between phenotype severity and genotype severity was revealed. The clinical and genetic spectrum of RP2-RD was illustrated in the Japanese population, identifying the characteristic features of a severe form of RP with early macular involvement., (© 2020 The Authors. American Journal of Medical Genetics Part C: Seminars in Medical Genetics published by Wiley Periodicals LLC.)

The effects of prenatal exposure to household pesticides on fetal and neonatal growth have not been fully clarified. The present study aims to determine the effects of prenatal exposure to pesticides on neonates' body size and growth during the first month. This study included 93,718 pairs of pregnant women and their children from the Japan Environment and Children's Study. Participants completed self-reporting questionnaires during their second or third trimesters on their demographic characteristics and frequency of pesticide use during pregnancy. Child weight, length, and sex were obtained from medical record transcripts. Birth weight and length, as well as weight and length changes over the first month, were estimated using an analysis of covariance. Frequency of exposure to almost all pesticides had no effects on birth weight and length. However, we found small but significant associations (i) between the use of fumigation insecticides and decreased birth weight, and (ii) between frequencies of exposure to pyrethroid pesticides, especially mosquito coils/mats, and suppression of neonatal length growth. Prenatal exposure to household pesticides, especially those containing pyrethroids, might adversely influence fetal and postnatal growth trajectories.

Cormorant fishing is a traditional Japanese fishing method using captive Japanese cormorants (Phalacrocorax capillatus). Between June and July 2017, an avian pox outbreak was reported in captive cormorant populations throughout several distant cities in Japan. We examined the lesions obtained from two such affected cormorants, which were raised in distant cities. The affected cormorants were grossly characterized by the development of cutaneous nodules around the base of the beak. Histopathologically, these nodules consisted of marked epidermal hyperplasia with ballooning degeneration of spinous cells and eosinophilic intracytoplasmic inclusions (Bollinger bodies). The lesions displayed 4b core protein (P4b) of Avipoxvirus (APV) and DNA polymerase genes, which were detected by PCR. Moreover, the nucleotide sequences detected from both cormorants were found to be identical. No identical sequence was found in any international database. These findings suggest that both examined cormorants were infected with an identical APV, which has never been previously reported. According to the phylogenetic analysis, the detected sequences were observed to cluster in subclade A3, which consists mainly of the sequences detected from several marine birds, including other cormorant species. This observation suggests that the viruses might be maintained in Japanese cormorants in nature.

Inherited retinal disorder (IRD) is a leading cause of blindness, and CRX is one of a number of genes reported to harbour autosomal dominant (AD) and recessive (AR) causative variants. Eighteen patients from 13 families with CRX-associated retinal disorder (CRX-RD) were identified from 730 Japanese families with IRD. Ophthalmological examinations and phenotype subgroup classification were performed. The median age of onset/latest examination was 45.0/62.5 years (range, 15-77/25-94). The median visual acuity in the right/left eye was 0.52/0.40 (range, -0.08-2.00/-0.18-1.70) logarithm of the minimum angle of resolution (LogMAR) units. There was one family with macular dystrophy, nine with cone-rod dystrophy (CORD), and three with retinitis pigmentosa. In silico analysis of CRX variants was conducted for genotype subgroup classification based on inheritance and the presence of truncating variants. Eight pathogenic CRX variants were identified, including three novel heterozygous variants (p.R43H, p.P145Lfs*42, and p.P197Afs*22). A trend of a genotype-phenotype association was revealed between the phenotype and genotype subgroups. A considerably high proportion of CRX-RD in ADCORD was determined in the Japanese cohort (39.1%), often showing the mild phenotype (CORD) with late-onset disease (sixth decade). Frequently found heterozygous missense variants located within the homeodomain underlie this mild phenotype. This large cohort study delineates the disease spectrum of CRX-RD in the Japanese population.

Purpose: To determine the clinical and genetic characteristics of patients with GUCY2D -associated retinal disorder ( GUCY2D -RD)., Methods: Fifteen patients from 12 families with inherited retinal disorder (IRD) and harboring GUCY2D variants were ascertained from 730 Japanese families with IRD. Comprehensive ophthalmological examinations, including visual acuity (VA) measurement, retinal imaging, and electrophysiological assessment were performed to classify patients into three phenotype subgroups; macular dystrophy (MD), cone-rod dystrophy (CORD), and Leber congenital amaurosis (LCA). In silico analysis was performed for the detected variants, and the molecularly confirmed inheritance pattern was determined (autosomal dominant/recessive [AD/AR])., Results: The median age of onset/examination was 22.0/38.0 years (ranges, 0-55 and 1-73) with a median VA of 0.80/0.70 LogMAR units (ranges, 0.00-1.52 and 0.10-1.52) in the right/left eye, respectively. Macular atrophy was identified in seven patients (46.7%), and two had diffuse fundus disturbance (13.3%), and six had an essentially normal fundus (40.0%). There were 11 patients with generalized cone-rod dysfunction (78.6%), two with entire functional loss (14.3%), and one with confined macular dysfunction (7.1%). There were nine families with ADCORD, one with ARCORD, one with ADMD, and one with ARLCA. Ten GUCY2D variants were identified, including four novel variants (p.Val56GlyfsTer262, p.Met246Ile, p.Arg761Trp, p.Glu874Lys)., Conclusions: This large cohort study delineates the disease spectrum of GUCY2D -RD. Diverse clinical presentations with various severities of ADCORD and the early-onset severe phenotype of ARLCA are illustrated. A relatively lower prevalence of GUCY2D -RD for ADCORD and ARLCA in the Japanese population was revealed., Translational Relevance: The obtained data help to monitor and counsel patients, especially in East Asia, as well as to design future therapeutic approaches., Competing Interests: Disclosure: X. Liu, None; K. Fujinami, Astellas Pharma Inc. (C, F), Kubota Pharmaceutical Holdings Co. Ltd (C, F), Acucela Inc. (C, F), Novartis AG (C), Janssen Pharmaceutical K.K. (C), NightStar (C, F), SANTEN Company Limited (F), Foundation Fighting Blindness (F), Foundation Fighting Blindness Clinical Research Institute (F), Japanese Ophthalmology Society (F), Japan Retinitis Pigmentosa Society (F); K. Kuniyoshi, None; M. Kondo, None; S. Ueno, None; T. Hayashi, None; K. Mochizuki, None; S. Kameya, None; L. Yang, None; Y. Fujinami-Yokokawa, None; G. Arno, None; N. Pontikos, None; H. Sakuramoto, None; T. Kominami, None; H. Terasaki, None; S. Katagiri, None; K. Mizobuchi, None; N. Nakamura, None; K. Yoshitake, None; Y. Miyake, None; S. Li, None; T. Kurihara, Tsubota Laboratory, Inc. (F), Fuji Xerox Co., Ltd. (F), Kirin Company, Ltd. (F), Kowa Company, Ltd. (F), Novartis Pharmaceuticals (F), Santen Pharmaceutical Co., Ltd. (F), ROHTO Pharmaceutical Co., Ltd. (F); K. Tsubota, None; T. Iwata, None; K. Tsunoda, None, (Copyright 2020 The Authors.)

Biallelic variants in the EYS gene are a major cause of autosomal recessive inherited retinal disease (IRD), with a high prevalence in the Asian population. The purpose of this study was to identify pathogenic EYS variants, to determine the clinical/genetic spectrum of EYS-associated retinal disease (EYS-RD), and to discover disease-associated variants with relatively high allele frequency (1%-10%) in a nationwide Japanese cohort. Sixty-six affected subjects from 61 families with biallelic or multiple pathogenic/disease-associated EYS variants were ascertained by whole-exome sequencing. Three phenotype groups were identified in EYS-RD: retinitis pigmentosa (RP; 85.94%), cone-rod dystrophy (CORD; 10.94%), and Leber congenital amaurosis (LCA; 3.12%). Twenty-six pathogenic/disease-associated EYS variants were identified, including seven novel variants. The two most prevalent variants, p.(Gly843Glu) and p.(Thr2465Ser) were found in 26 and twelve families (42.6%, 19.7%), respectively, for which the allele frequency (AF) in the Japanese population was 2.2% and 3.0%, respectively. These results expand the phenotypic and genotypic spectrum of EYS-RD, accounting for a high proportion of EYS-RD both in autosomal recessive RP (23.4%) and autosomal recessive CORD (9.9%) in the Japanese population. The presence of EYS variants with relatively high AF highlights the importance of considering the pathogenicity of non-rare variants in relatively prevalent Mendelian disorders.

The study subjects were residents of Chikusei city, Japan, aged 40 years or older who attended annual health check-up programs and participated in the JPHC-NEXT Eye Study which performed non-mydriatic fundus photography of both eyes. The relationship of glaucomatous fundus changes such as optic disc cupping (cup to disc ratio ≥ 0.7) and retinal nerve fiber layer defect (NFLD) with the presence of epiretinal membrane (ERM) were examined cross-sectionally. A total of 1990 persons gave consent to participate in this study in 2013. The overall prevalence of ERM was 12.9%. Of these, 1755 had fundus photographs of sufficient quality and no history of intraocular surgery (mean age: 62.3 ± 10.0 years). After adjusting for age, sex and refractive error, NFLD was positively associated with the presence of ERM (odds ratio [OR]: 2.48; 95% confidence interval [CI]: 1.24, 4.96; P = 0.010), but optic disc cupping was not (OR: 1.33; CI: 0.71, 2.48; P = 0.37). The results did not necessarily suggest an association between glaucoma and ERM, but indicated an association between NFLD and ERM.

Objective: Recent attention has been focused on sedentary behavior (SB) affecting health outcomes, but the characteristics of indicators reflecting SB remain to be identified. This cross-sectional study aims to identify the characteristics of indicators of SB, focusing on the examination of correlations, reliability, and validity of sedentary variables assessed by the smartphone app., Method: Objectively measured data of SB of eligible 46 Japanese workers obtained from smartphones were used. We assessed the characteristics of current indicators being used with a 10-minute or 30-minute thresholds, in addition to the conventional indicators of total sedentary time, mean sedentary bout duration, and total number of sedentary bouts. They were evaluated from three perspectives: (a) association among the indicators, (b) reliability of the indicators, and (c) criterion validity., Results: Total sedentary time under 10 minutes (U10) and U30 had negative associations with Total sedentary time (r = -.47 and -.21 respectively). The correlation between Mean sedentary bout duration and Total number of sedentary bouts was -.84, whereas between Mean sedentary bout duration 10, 30 and Total number of sedentary bouts were -.54 and -.21, respectively. The intraclass correlation coefficients of almost all indicators were around .80. Mean sedentary bout duration, Mean sedentary bout duration 10, Total number of sedentary bouts, Total sedentary time 30, U30 and U10 have significant differences between three BMI groups., Conclusion: This study comprehensively revealed the rationale of advantage in the current indicator being used with a 10-minute or 30-minute threshold, rather than the conventional total amount of SB., (© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Background: Given that there are still considerable number of facilities which lack surgical specialists round the clock across the world, the ability to estimate the requirement for emergency surgery in victims of motor vehicle crashes (MVCs) can ensure appropriate resource allocation. In this study, a surgical intervention in victims of MVC (SIM) score was developed and validated, using independent patient cohorts., Methods: We retrospectively identified MVC victims in a nationwide trauma registry (2004-2016). Adults ≥ 15 years who presented with palpable pulse were included. Patients with missing data on the type/date of surgery were excluded. Patient were allocated to development or validation cohorts based on the date of injury. After missing values were imputed, predictors of the need for emergency thoracotomy and/or laparotomy were identified with multivariate logistic regression, and scores were then assigned using odds ratios. The SIM score was validated with area under the receiver operating characteristic curve (AUROC) and calibration plots of SIM score-derived probability and observed rates of emergency surgery., Results: We assigned 13,328 and 12,348 patients to the development and validation cohorts, respectively. Age, motor vehicle collision and vital signs on hospital arrival were identified as independent predictors for emergency thoracotomy and/or laparotomy, and SIM score was developed as 0-9 scales. The score has a good discriminatory power (AUROC = 0.79; 95% confidence interval = 0.77-0.81), and both estimated and observed rates of emergency surgery increased stepwise from 1% at a score ≤ 1 to almost 40% at a score ≥ 8 with linear calibration plots., Conclusions: The SIM score was developed and validated to accurately estimate the need for emergent thoracotomy and/or laparotomy in MVC victims., Competing Interests: The authors have declared that no competing interests exist.

Background:  Since venous thromboembolism (VTE) is one of the causes of maternal mortality, several guidelines recommend prophylaxis using low molecular weight heparin for women in high-risk groups. The number of large population-based studies examining predictors for VTE has been limited, and there has been no study based on a Japanese population., Objective:  Our objective was to examine VTE risk factor during the pregnancy and post-partum period., Materials and Methods:  A nationwide birth cohort study known as the 'Japan Environment and Children's Study (JECS)' was conducted by the Ministry of the Environment. The subjects consisted of 103,070 pregnancies recruited by the JECS between January 2011 and March 2014. Pregnant women completed the questionnaires during the first and second/third trimester. Their medical records were transcribed by physicians or research coordinators at registration, just after delivery and at 1 month after delivery., Results:  The frequency of VTE was 7.5 per 10,000 pregnancies (77 of 103,070) during the pregnancy and post-partum period. After the adjustment of multiple covariates for each factor, endometriosis and recurrent pregnancy loss (RPL) were identified as novel independent risk factors for VTE. Adjusted odds ratios were as follows: 2.70 (95% confidence interval, 1.21-6.00) for endometriosis and 6.13 (2.48-15.16) for RPL. Threatened abortion, threatened pre-term birth, pre-term birth and caesarean section were ascertained to be risk factors for VTE., Conclusion:  Careful attention should be given to novel predictors, such as endometriosis and a history of RPL, to prevent VTE during the pregnancy and post-partum period., Competing Interests: M.S.-O. received grants from the Japanese Ministry of Education, Science, and Technology for conducting studies on the topic of RPL in the different patient population, and payment for lectures from Kaken Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co., Aska Pharmaceutical Co. Ltd., Sekisui Medical Co. Ltd. and Siemens Japan. The remaining authors report no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Self-inflicted burn accounts for considerable morbidity and mortality in more economically developed countries, and there is a substantial debate regarding the pathophysiological relevance between self-inflicted burns and unfavorable outcomes. To validate whether self-inflicted injury is an independent predictor of high mortality regardless of the severity of burn, they conducted a retrospective observational study using the Japan Trauma Data Bank, a nationwide database including over 200 major tertiary care centers. Among 2006 patients with burn who had arrived at collaborating centers between 2004 and 2016, they included patients aged ≥15 years, those who did not present with cardiopulmonary arrest upon arrival, and those who had ≥10 percent total body surface area burns. Patients with missing survival data or unknown mechanism of injury were excluded. In total, 1094 patients were eligible, of whom 222 (20.3 percent) had self-inflicted burns. The patients were divided into the self-inflicted and non-self-inflicted groups, and propensity score was calculated using the demographic information of the patients, injury variables, time from injury to hospital arrival, and other survival predictors. Via a propensity score matching, 98 pairs were selected, and the self-inflicted group had a higher mortality than the non-self-inflicted group (43.9 vs 28.6 percent, hazard ratio = 1.77; 95% confidence interval = 1.10-2.86; P = .02). Inverse probability weighting and multivariate logistic regression were performed as sensitivity analyses, and results validated that self-inflicted burn was independently associated with increased in-hospital mortality. Therefore, patients with self-inflicted burns should receive judicious management, regardless of burn injury severity., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Problem: Several studies have reported the increased risk of preterm birth, premature rupture of membranes, and low birth weight in patients with recurrent pregnancy loss (RPL). There have been a limited number of large population-based studies examining adverse pregnancy and perinatal outcome after RPL. Multiple-imputed analyses (MIA) adjusting for biases due to missing data is also lacking., Method of Study: A nationwide birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted by the Ministry of the Environment. The subjects consisted of 104 102 registered children (including fetuses or embryos)., Results: No increased risk of a congenital anomaly, aneuploidy, neonatal asphyxia, or a small for date infant was observed among the children from women with a history of RPL. A novel increased risk of placental adhesion and uterine infection was found. The adjusted ORs using MIA in women with three or more PL were 1.76 (95% CI, 1.04-2.96) for a stillbirth, 1.68 (1.12-2.52) for a pregnancy loss, 2.53 (1.17-5.47) for placental adhesion, 1.87 (1.37-2.55) and 1.60 (.99-2.57) for mild and severe hypertensive disorders of pregnancy, respectively, 1.94 (1.06-3.55) for uterine infection, 1.28 (1.11-1.47) for caesarean section and .86 (.76-.98) for a male infant., Conclusion: MIA better quantified the risk, which could encourage women who might hesitate to attempt a subsequent pregnancy., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The clinical features of benign liver lesions misdiagnosed as hepatocellular carcinoma have not been fully described., Patients and Methods: This study included 187 patients who underwent hepatectomy at the Kyushu University Hospital following a diagnosis of solitary HCC of ≤3 cm in diameter., Results: Following hepatectomy, 9.6% patients were pathologically diagnosed with benign liver lesions. Univariate analysis showed that patient age ≤67 years, negativity for hepatitis C virus antigen, lesion size ≤1.5 cm, normal level of tumor markers, and absence of increase in tumor size were associated with benign lesions. Patient age ≤67 years and absence of tumor size increase were independent predictors of benign lesions., Conclusion: Benign liver lesions misdiagnosed as HCC were not infrequent, accounting for approximately 10% of resected cases. Age ≤67 years and absence of tumor size increase were independent predictors of benign liver lesions, and may help in the correct diagnosis of HCC., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Human herpesvirus-6 (HHV-6) is known to cause critical encephalitis, as a central nervous system infection, in some hematopoietic stem cell transplantation (HSCT) recipients. Chromosomally integrated human herpesvirus-6 (CIHHV-6) persistently shows HHV-6 DNA in blood, but this does not necessarily suggest active infection. The true clinical significance in HSCT is not clear. The prevalence of CIHHV-6 in Japan is reportedly 0.21%. We herein report two HSCTs: from a CIHHV-6-positive donor to a negative recipient and from a negative donor to a positive recipient. In the CIHHV-6-positive donor case, the recipient's plasma, which had been negative for HHV-6 before HSCT, became positive after transplantation and the level then remained high, although the subject was asymptomatic. In the CIHHV-6-positive recipient case, the patient's plasma viral load was high just after transplantation, although the subject was asymptomatic, and the load gradually decreased after engraftment. Antivirals had no effect on the viral load in either case. We should consider CIHHV-6 when the HHV-6 DNA load in blood persists asymptomatically after HSCT, to avoid misdiagnosis of reactivated HHV-6 infection and overuse of antivirals. It is also useful to monitor HHV-6 DNA in blood before HSCT, to distinguish HHV-6 reactivation from CIHHV-6.

Background and Study Aims: Recently, a novel fully covered and biflanged metal stent (BFMS)dedicated to the drainage of walled-off necrosis(WON) was developed. The aim of this study was to retrospectively evaluate the safety, efficacy, and cost performance of drainage of WON using the novel BFMS compared with a traditional plastic stent., Patients and Methods: A total of 70 patients with symptomatic WON were treated under endoscopic ultrasound (EUS) guidance. Initial drainage was conducted using the single gateway technique with placement of one or more plastic stents or a single BFMS.If drainage was unsuccessful,direct endoscopic necrosectomy (DEN)was performed., Results: There were no statistically significant differences in rates of technical success, clinical success,and adverse events between plastics stents and BFMS, despite the size of WON in the BFMS group being significantly larger than that in the plastic stent group (105.6 vs. 77.1 mm; P=0.003).The mean procedure times for the first EUS-guided drainage and for re-intervention were significantly shorter in the BFMS group than in the plastic stent group (28.8±7.1 vs. 42.6±14.2, respectively,for drainage, P<0.001; and 34.9±8.5 vs.41.8±7.6, respectively, for re-intervention, P<0.001). There was no statistically significant difference in the total cost between plastic stent and BFMS use in the treatment of WON ($5352vs. $6274; P=0.25)., Conclusions: Plastic stents and BFMS were safe and effective for the treatment of WON. In particular,BFMS placement appeared to be preferable for initial EUS-guided drainage and additional reintervention(e.g. DEN) as it reduced the procedure time. Prospective randomized controlled trials are warranted.

Aim: To evaluate the safety and clinical application of high-intensity focused ultrasound (HIFU) therapy for unresectable pancreatic cancer (PC)., Methods: Thirty PC patients (16 cases in stage III and 14 cases in stage IV) with visualized pancreatic tumors were admitted for HIFU therapy as an optional local therapy in addition to systemic chemotherapy or chemoradiotherapy. Informed consent was obtained. This study began at the end of 2008 and was approved by the ethics committee of our hospital [Institutional Review Board (IRB): 890]. The HIFU device used was the FEP-BY02 (Yuande Bio-Medical Engineering, Beijing, China)., Results: The mean tumor size after HIFU therapy changed to 30.9 ± 1.7 mm from 31.7 ± 1.7 mm at pre-therapy. There were no significant changes in tumor size, mean number of treatment sessions (2.7 ± 0.1 mm), or mean total treatment time (2.4 ± 0.1 h). The rate of symptom relief effect was 66.7%. The effectiveness of primary lesion treatment was as follows: complete response, 0; partial response, 4; stable disease, 22; progressive disease, 4. Treatment after HIFU therapy included 2 operations, 24 chemotherapy treatments, and 4 best supportive care treatments. Adverse events occurred in 10% of cases, namely pseudocyst formation in 2 cases and mild pancreatitis development in 1. However, no severe adverse events occurred in this study., Conclusion: We suggest that HIFU therapy is safe and has the potential to be a new method of combination therapy for PC.

Although lomerizine is used as a first-line prophylactic drug for migraines in Japan, approximately 30% of patients fail to respond to this treatment. On the basis of medical records, we investigated the involvement of clinical factors in response to lomerizine used in patients with migraine as primary headache and established a scoring system for predicting clinical responses to prophylactic therapy. Ninety-four consistent responders and 33 inconsistent responders to lomerizine were enrolled in this study. Multivariate stepwise logistic regression analysis revealed that migraine plus tension-type headache as primary headache and frequency of headache attacks were significant factors that contributed independently to negative response [odds ratio, 3.817 (no vs. yes; 95% confidence interval (CI), 1.264-11.628) and 5.814 (>15 episode days/month vs. 0-14 episode days/month; 95% CI, 2.381-14.286), respectively]. The predictive index (PI) of clinical responses to lomerizine in patients with migraine was calculated using the regression coefficients of two factors as an integer, where the score for inconsistent responders (1.00±0.71) was significantly higher than that for consistent responders (0.37±0.53, p<0.001). Sensibility of the low-scoring group (PI=0) was 75.8%, and specificity of the high-scoring group (PI=2) was 97.9%. Groups scoring low, intermediated and high included 11.6%, 35.4% and 80.0% of inconsistent responders, respectively. The PI value obtained might represent an appropriate scoring system to predict responses in these patients., (© 2013.)

Sudden death during bathing accounts for 10 to 15% of all out-of hospital cardiac arrests in Japan. Surveys in Tokyo revealed 1,085 victims of accidents during bathing transported by ambulance from October 1999 to March 2000. 53% of them were cardiac arrest and 25% were those who needed rescue from bath tub because of consciousness disturbance (rescued group). Clinical observation of the rescued group patients indicated they suffered from transient loss of consciousness probably because of elevated body temperature. The current hypothesis of the accidents during bathing is a unique type of heat illness exposed by high water temperature(41-43 degrees C). Geriatric population is vulnerable to the bathing induced heat illness.

Background and Objective: The Japanese Respiratory Society (JRS) scoring system is a useful tool for the early and simple presumptive diagnosis of atypical pneumonia (Mycoplasma pneumoniae and Chlamydia pneumoniae pneumonia). However, it has been suggested that it is difficult to diagnose atypical pneumonia in the elderly using this system. In the present study, we evaluated the accuracy and usefulness of the JRS scoring system for diagnosing atypical pneumonia in different age groups., Methods: Cases of M. pneumoniae (n = 262), C. pneumoniae (n = 98) and common bacterial pneumonia (n = 364) were analysed., Results: For both atypical pneumonias, the frequency of comorbid illnesses and being in a higher risk category were significantly greater in elderly (age ≥60 years) than in non-elderly patients (age <60 years). One or more additional aetiological factors were more frequently present in elderly than in non-elderly patients. The diagnostic sensitivity and specificity for atypical pneumonia were 39% and 88%, respectively, in the elderly group, and 86% and 88%, respectively, in the non-elderly group. When the patients were stratified into 10-year age groups, the diagnostic sensitivity was highest in the 18- to 29-year age group and decreased from the youngest to the oldest age group., Conclusions: These results indicate that it is difficult to distinguish between atypical pneumonia and bacterial pneumonia in the elderly using the JRS scoring system. When treating patients aged ≥60 years, physicians should use fluoroquinolones or β-lactam antibiotics + macrolides as empirical first-choice drugs so as to always provide antibiotic protection against potential atypical pathogens., (© 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.)

Background: Although the prevalence of macrolide-resistant Mycoplasma pneumoniae isolates in Japanese pediatric patients has increased rapidly, there have been no reports concerning macrolide-resistant M. pneumoniae infection in adolescents aged 16 to 19 years old. The purpose of this study was to clarify the prevalence and clinical characteristics of macrolide-resistant M. pneumoniae in adolescent patients with community-acquired pneumonia., Methods: A total of 99 cases with M. pneumoniae pneumonia confirmed by polymerase chain reaction (PCR) and culture were analyzed. Forty-five cases were pediatric patients less than 16 years old, 26 cases were 16 to 19-year-old adolescent patients and 28 cases were adult patients. Primers for domain V of 23S rRNA were used and DNA sequences of the PCR products were compared with the sequence of an M. pneumoniae reference strain., Results: Thirty of 45 pediatric patients (66%), 12 of 26 adolescent patients (46%) and seven of 28 adult patients (25%) with M. pneumoniae pneumonia were found to be infected with macrolide-resistant M. pneumoniae (MR patients). Although the prevalence of resistant strains was similar in pediatric patients between 2008 and 2011, an increase in the prevalence of resistant strains was observed in adolescent patients. Among 30 pediatric MR patients, 26 had an A-to-G transition at position 2063 (A2063G) and four had an A-to-G transition at position 2064 (A2064G). In 12 adolescent MR patients, 10 showed an A2063G transition and two showed an A2064G transition, and in seven adult MR patients, six showed an A2063G transition and one showed an A2064G transition., Conclusions: The prevalence of macrolide-resistant M. pneumoniae is high among adolescent patients as well as pediatric patients less than 16-years old. To prevent outbreaks of M. pneumoniae infection, especially macrolide-resistant M. pneumoniae, in closed populations including among families, in schools and in university students, physicians should pay close attention to macrolide-resistant M. pneumoniae.

Background/aims: ERCP-related procedures involve radiation exposure of patients and medical staff. We developed a novel protective lead shield which is attached around the fluoroscopy generator. Here we examine levels of radiation exposure to patients, endoscopists and assistants, and evaluate the usefulness of the newly designed protective shield., Methodology: Four-hundred and seventy-one ERCP procedures were performed from April 2006 to April 2007. At first, we compared the radiation dose of consecutive fluoroscopy conditions with pulse fluoroscopy of 15 per second and then the radiation dose with and without the protective shield. Next, we measured the radiation exposure of endoscopists and assistants in the clinical setting monitored by digital dosimeter during ERCP procedure., Results: The radiation dose was the most at the 45° direction. Using pulse fluoroscopy of 15 per second the radiation dose of patients and endoscopists decreased by about half. Using both pulse fluoroscopy of 15 per second and the protective shield, the radiation dose at the endoscopist's position was reduced up to 97%. The total fluoroscopy time was 5851 minutes in the 471 ERCP cases. Using pulse 15 and the protective lead shield, the radiation exposure dose of one endoscopist and two assistants were 2430.8, 2673.9 and 1375.0µSv, respectively., Conclusions: Novel protective lead shield in combination with pulse fluoroscopy can significantly reduce the radiation exposure leading to avoid unnecessary radiation exposure to patients and medical staff.

Migraine is a multifactorial disease with various factors, such as genetic polymorphisms and personality traits, but the contribution of those factors is not clear. To clarify the pathogenesis of migraine, the contributions of genetic polymorphisms and personality traits were simultaneously investigated using multivariate analysis. Ninety-one migraine patients and 119 non-headache healthy volunteers were enrolled. The 12 gene polymorphisms analysis and NEO-FFI personality test were performed. At first, the univariate analysis was performed to extract the contributing factors to pathogenesis of migraine. We then extracted the factors that independently contributed to the pathogenesis of migraine using multivariate stepwise logistic regression analysis. Using the multivariate analysis, three gene polymorphisms including monoamine oxidase A (MAOA) T941G, methylenetetrahydrofolate reductase (MTHFR) C677T, and tumor necrosis factor beta (TNF-β) G252Α, and the neuroticism and conscientiousness scores in NEO-FFI were selected as significant factors that independently contributed to the pathogenesis of migraine. Their odds ratios were 1.099 (per point of neuroticism score), 1.080 (per point of conscientiousness score), 2.272 (T and T/T or T/G vs G and G/G genotype of MAOA), 1.939 (C/T or T/T vs C/C genotype of MTHFR), and 2.748 (G/A or A/A vs G/G genotype of TNF-β), respectively. We suggested that multiple factors, such as gene polymorphisms and personality traits, contribute to the pathogenesis of migraine. The contribution of polymorphisms, such as MAOA T941G, MTHFR C677T, and TNF-β G252A, were more important than personality traits in the pathogenesis of migraine, a multifactorial disorder.

Objective: The Japan Respiratory Society documented a new category of guidelines for nursing and healthcare-associated pneumonia (NHCAP), which is distinct from community acquired pneumonia (CAP). The objective of this study was to determine the epidemiological differences between NHCAP patients in a teaching university hospital and a community hospital. In addition, to clarify the strategy for treatment of NHCAP, we investigated the role of atypical pathogens., Methods: We analyzed 250 NHCAP and 421 CAP cases in a university hospital and 349 NHCAP and 374 CAP cases in a community hospital., Results: Patient age and the incidences of poor general condition were significantly higher in the community hospital compared with those in the university hospital. The distribution and frequency of pathogens, especially multidrug-resistant (MDR) pathogens, were significantly different between the two hospitals. Central nervous system disorders, dementia and poor performance status, which was possibility related to aspiration pneumonia, were significantly more frequent in patients with NHCAP compared with those with CAP in both hospitals. Atypical pathogens were detected in a few cases in patients with NHCAP., Conclusion: There were many differences in the clinical characteristics between NHCAP patients in a university hospital and a community hospital even for hospitals located in the same area. Aspiration pneumonia was thought to be the main characteristic of NHCAP in both hospitals. Thus, all NHCAP patients did not need the same empiric therapy with a multidrug regimen directed against MDR pathogens. In addition, physicians rarely need to consider atypical pathogens in NHCAP treatment.

Our goal was to analyze minimum inhibitory concentration (MIC) data for Staphylococcus aureus isolated from surgical infections (SIs) and to look for correlations among the clinically available antimicrobials that were tested. Clinical isolates from SIs were collected by a multicenter surveillance group involving 34 institutions in Japan. During the period April 1998 to March 2007, 312 strains of S. aureus [71 methicillin susceptible (MSSA) and 241 methicillin resistant (MRSA)] were consecutively obtained from these institutions. MIC data for 18 clinically available antimicrobial agents [ABPC, CEZ, CTM, CMX, CPR, FMOX, CFPM, CZOP, IPM, MEMP, GM, ABK, MINO, CLDM, FOM, LVFX, VCM, and TEIC (abbreviations defined in Tables 2 and 3)] against these isolates was analyzed using a principal component analysis (PCA). PCA revealed that four principal components explained 71.1% of the total variance. The first component consisted of major contributions from MEPM and IPM. The second component consisted of major contributions from MINO. These two-first axes, which were strong and explained 54.2% of the total variance, were able to classify the clinical isolates into four clusters. Furthermore, the proportion of the four clusters provided the characteristics of the S. aureus that were clinically isolated at each institute. PCA is a clinically applicable method for analyzing MIC patterns. Such analyses might contribute to the establishment of a practical classification of antimicrobial agents and to the identification of the characteristic antimicrobial resistance patterns at each institute.

A case of exotic myiasis caused by tumbu fly (Cordylobia anthropophaga) parasitism acquired while travelling in the Republic of Namibia is reported. This is the fifth case reported in Japan, and is very unusual in that the patient was infected with 19 larvae. This is also the first case diagnosed using molecular methods in Japan. We cultured the extracted larvae in vitro and successfully obtained pupae.

We evaluated the clinical features of multidrug-resistant Pseudomonas aeruginosa cases determined by sputum culture between April, 2005 and December, 2006. The clinical features of most cases were: (1) pneumonia in the elderly with cerebrovascular diseases, (2) previous administration of carbapenems and antipseudomonal cephems, (3) PIPC, CAZ and ISP sensitve MDRP, (4) MRSA was isolated concurrently, (5) not necessary of therapy against MDRP, (6) good outcome.

Background/aims: The aim of this study was to investigate the effects of being overweight on autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) patients., Methodology/results: 44 AIH and 95 PBC patients were enrolled in this study. Body weight and body mass index (BMI) of AIH (57.6 +/- 10.4 kg and 23.8 +/- 2.9 kgm(-2), respectively) were higher than those of PBC (51.6 +/- 7.0 kg and 22.0 +/- 2.6 kgm(-2), respectively) (P < 0.001). The prevalence of overweight patients in AIH was also higher than those in PBC (P < 0.005). Being overweight and having 25 < or = BMI < 30 did not affect the progression of hepatic fibrosis in AIH and PBC. In comparison with the non-overweight with PBC, overweight patients with PBC tended not to be symptomatic, such as having itching or fatigue (P = 0.027)., Conclusions: Clinicians should be aware that not only non-alcoholic fatty liver disease but also PBC patients might be included among the overweight hepatic disease patients with unknown etiology.

In many benthic organisms with a planktonic larval stage, local populations have different morphology. Such difference may arise from some of the following proximate mechanisms. "Local recruitment (LR)": no larvae move between local populations, and segregated populations possess alleles coding for locally adaptive morphology. "Intragenerational selection (IS)": larvae move between local populations, and individuals with alleles for locally adaptive morphology survive after recruitment. "Phenotypic plasticity (PP)": larvae move between local populations and show phenotypic plasticity to adapt to a locality after recruitment. We examined which mechanism explains our finding that a planktonic developer Turbo coronatus coronatus (Gastropoda) had significantly longer spines on its shell on more exposed shores at scales of < 2 km. Experiments at Ishigaki Island, Okinawa, Japan, showed the following results. (a) Shorter- and longer-spined populations occurring within 2 km showed non-significant low psi(ST) values (-0.0040 to 0.00095) for the mitochondrial DNA COI region. This suggests no segregation of the local populations, supporting the mechanisms IS and PP. (b) T. c. coronatus generated significantly longer spines 70 days after being transplanted to the habitat of a longer-spined population, supporting IS and PP. (c) Individuals caged in the sea for 79 days generated longer spines than individuals in the laboratory, supporting PP. In conclusion, shore-specific morphology of T. c. coronatus arises most likely from phenotypic plasticity and possibly from intragenerational selection.

To evaluate postgraduate education for neurologists, we performed a questionnaire-based investigation in hospitals authorized by the Japanese Society of Neurology. The response rate to the questionnaire was 91%. The number of board-certified neurologists is usually less than 5, even in the authorized teaching hospitals. Most respondents thought that the postgraduate training programs already existing in many teaching hospitals are insufficient, but nevertheless useful. More staff may be needed for postgraduate education in neurology. The respondents considered that neurological education has generally functioned well, except in certain areas such as brain death judgment. On the other hand, the rotation of training in neurosurgery, psychiatry and child neurology is still inadequate. The problem of devising a suitable training rotation system in postgraduate education for neurologists has not yet been solved.

We investigated the status of the components and target genes of the Wnt signaling pathway in Japanese anaplastic thyroid cancers (ATCs) in the present study. Nuclear and cytoplasmic positive staining of beta-catenin, which might indicate the existence of alterations in the Wnt signaling pathway, were found in 40.9% and 63.6% of the 22 ATC samples, respectively. The beta-catenin, adenomatous polyposis coli (APC) and Axin 1 gene mutations were observed in 4.5%, 9.0%, and 81.8% of the 22 ATC samples, respectively. Overexpression of cyclin D1 and c-myc, which are the target genes of the Wnt signaling pathway, was observed in 27.3% and 59.1% of the ATC samples, respectively. There was no significant correlation between nuclear or cytoplasmic positive staining of beta-catenin and nuclear positive staining of cyclin D1 or c-myc. Taken together, the results of beta-catenin immunohistochemistry suggest that alterations in the Wnt signaling pathway are associated with carcinogenesis of ATC, but the frequency of beta-catenin gene mutation in our series is lower than that previously reported. Furthermore, cyclin D1 and c-myc frequently accumulated in ATC, independently of dysfunction in the Wnt signaling pathway.

Autosomal dominant leukodystrophy is an extremely rare disease. Here we report on a dominantly inherited disease in a Japanese family with slowly progressive clinical course. Their symptoms and signs started in early childhood and very slowly progressed. In most patients spastic gait was the initial symptom. Neurological manifestations were characterized by pyramidal signs, ataxia, and mental deterioration. In addition to these neurological signs, the skeletal anomalies such as scoliosis and congenital hip dislocation were also present. MR images showed no abnormality in the early stage, but T2-weighted images revealed high intensity areas in the cerebral and cerebellar white matter, and the dentate nucleus in the advanced stage. Proton MR spectroscopy showed decrease of N-acetylaspartate/creatine ratio and increase of choline/creatine ratio in the advanced stage. Proton MR spectroscopy revealed normal N-acetylaspartate/creatine ratio and increase of choline/creatine ratio in the early stage. We suggested that these patients had abnormality in the white matter when MRI was still normal. We considered that intracranial demyelination was gradually progressed as the symptoms got aggravated.

In 1994, the water quality standard of dialysate and substitution fluid for on-line HDF was established by the Kyushu Society for HDF. On the other hand, with the widespread use of high-flux membrane, reverse filtration and reverse diffusion became evident, and purification of the dialysate has become essential even for usual hemodialysis. By using ultrapure dialysate, new blood purification methods can be performed, such as internal filtration-enhanced hemodialysis, on-line HDF, and on-line HF. As a result, various clinical effects have been reported, such as improvement in anemia and in chronic inflammatory reactions. Suppression of complications involving long-term dialysis is expected, and even the prolongation of life expectancy. By using ultrapure dialysate as substitution fluid for saline solution, a fully automated dialysis machine has been developed. Furthermore, if fully automated consoles can be made smaller in size, they will contribute to the widespread use of home hemodialysis., (Copyright (c) 2004 S. Karger AG, Basel.)

Background: Although it has been reported that different hepatitis B virus (HBV) genotypes induce different clinical characteristics in patients with chronic liver diseases (CLD), there have been few reports that have detailed the distribution of HBV genotypes in acute forms of liver disease., Methods: HBV genotypes were determined in 61 patients who had acute forms of liver disease (45 had acute self limited hepatitis (AH) and 16 had fulminant hepatitis (FH)) and in 531 patients with CLD, including 19 patients with severe acute exacerbation of CLD. We also analysed the enhancer II, core promoter, and precore region sequences for the presence of mutations., Results: Expression of genotype B in patients with acute forms of liver disease was significantly greater than in those with CLD (39.3% v 11.7%, respectively; p<0.001). Furthermore, expression of genotype B was significantly greater in patients with FH than in those with AH (62.5% v 31.1%, respectively; p=0.027). The precore mutation A1896 and the core promoter mutation at nt 1753 and 1754 were found more frequently in FH than in AH, and genotype B was predominant in FH regardless of the presence of these mutations., Conclusions: HBV genotype B was found more frequently in patients with acute forms of liver disease than in patients with CLD, and more frequently in patients with FH than in those with AH. These results suggest that this HBV genotype may induce more severe liver damage than other viral genotypes, at least in patients from Chiba, Japan.

Aedes albopictus (Skuse), a mosquito vector of the dengue fever virus, is prevalent in Japan, distributed widely in Honshu Island with its northern limits between latitude 38 degrees to 40 degrees north. The factors affecting distribution of the species in the northern part of Japan were studied using the geographical information system (GIS). During 1998-2000, larval surveillance was carried out in 26 urban and rural areas in the Tohoku district, in the northern part of Honshu Island, by collecting larvae from artificial and natural habitats. Climatological analysis, using the GIS, showed that the following conditions accounted for the current distribution of Ae. albopictus: an annual mean temperature higher than 11 degrees C and a mean temperature of the coldest month, January, higher than -2 degrees C. A period with temperature above 11 degrees C in the confirmed area of the mosquito successively continues for more than 186 d per year. The accumulated temperature calculated from a temperature of 11 degrees C, which may be close to the developmental zero of Ae. albopictus, was over 1,350 degree-days. The relationship between the beginning of short-daylength, inducing egg diapause, and the monthly mean temperature during September and October necessary for successful larval development in the Tohoku district is also discussed. We also show the relationship between the current distribution of Ae. albopictus and the annual mean temperature in the United States. From these results it is predicted that Ae. albpictus will be established in some cities in northeast United States.

In order to improve the postgraduate training in neurology in Japan, practical program is proposed. It consists of 5 years. The first 2 years include internal medicine for 16 months, pediatrics for 2 months, neurosurgery for 2 months, emergency medicine for 2 months, and anesthesiology for 2 months. The next 3 years include neurology training in the ward and out-patient clinic in the University Hospital for one year followed by another year of neurology ward training at the affiliated hospital where they are exposed to see more acute neurological cases. In addition to these clinical training, they will study basic neurological sciences in neuroanatomy, and neurophysiology in the evening in the form of small group seminars and they are assigned to read EEG every week and attend EEG reading sessions. EMG, muscle biopsy, and sural nerve biopsy will be done under supervision when they are in charge of such cases who require those examinations. The last year program includes neurological consultation from the other departments, out-patient clinic, setting up neurological conferences, and elective course for 3 months. It is recommended that Japanese Neurological Society informs us several institutes where they can offer pediatric neurology training, and neuropathology training in several districts in Japan, since they have difficulty in getting training in these two specialties in many Japanese hospitals.

The present study investigates the differences in public attitudes towards the mentally ill in Bali (Indonesia) and Tokyo (Japan), the former being a non-industrialized society and the latter an industrialized society in Asia. Seventy-seven residents of Bali and 66 residents from Tokyo were examined by a devaluation-discrimination measure and a self-assessment questionnaire to gauge their reactions to five imaginary case study vignettes consisting of three cases of schizophrenia, one case of a depressive episode, and one case of obsessive-compulsive disorder. Balinese respondents had significantly lower devaluation-discrimination measure scores, indicating a more favorable global attitude towards persons with a history of psychiatric treatment than did respondents in Tokyo. However, the extent to which people were prejudicial against mental patients in the two societies varied with the kinds of mental disorders, with Balinese having a more positive attitude to schizophrenics but more negative to depressive and obsessive-compulsive patients.

In order to improve Japanese postgraduate adult neurology training, the author compared the ongoing training in Japan and 5 neurology training programs in the USA. Japanese neurology training lacks pediatric neurology, neurosurgery, psychiatry, and neuropathology in many institutions. In order to improve our neurology training we have to establish more systematic programs, and have to ask for cooperation of various departments. We have to improve interdepartmental relationship, and we have to include other institutions for establishing adequate rotation program. In Japan neurosurgery and psychiatry rotation can be done in the same hospital, but we may have to send the residents to other institutions to cover pediatric neurology and neuropathology.

Eighteen Swedish patients with familial amyloidotic polyneuropathy were tested for the met30 mutation of the transthyretin (TTR) (prealbumin) gene by RFLP analysis of genomic DNA using the restriction enzyme NsiI. The results confirmed previous findings that the Swedish variant of familial polyneuropathy has the same valine by methionine substitution at position 30, as seen in patients with FAP from Japan, Portugal or patients of Swedish descent from USA. However, two of the patients were homozygous, totally lacking the wild type allele. Measurable serum values for the variant transthyretin (TTR) was detected with a RIA-method in all the 18 Swedish FAP patients studied with a mean concentration of 12.1 +/- 5.1 (SD) mg/100 ml, (11.0 +/- 4.1 when the two homozygotes were excluded). In 45 Japanese patients the mean was 9.2 +/- 2.7 mg/100 ml. The variant TTR was not detected in the healthy controls. The value for the variant TTR was nearly twice that high in the two homozygous patients, 21.14 and 21.16 mg/100 ml, respectively. There was no correlation between the serum levels of variant TTR and the duration of disease or levels of serum albumin in the FAP-patients.