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To examine the associations between lifestyle factors and quality of life (QOL) among Japanese children. Participants were 7794 children (3869 boys and 3925 girls) aged 9–10. They completed a questionnaire regarding lifestyles at baseline survey and were followed up for 3 years. In the follow-up survey, QOL was evaluated using a Japanese version of the COOP charts. Children rated their QOL as one of five response categories. Subjects rated as‘very well’ or‘pretty good’ were considered to have good QOL, and the remainder was assumed to have poor QOL. Logistic regression analysis was performed to evaluate the relationship between lifestyles or changes in lifestyles and QOL. In the multivariate analysis model, age, sex, body mass index (BMI), and lifestyle factors were simultaneously entered. During the follow-up period, children became more sedentary. Compared to children participating in physical activity‘very often’ at baseline, those who exercised‘almost never’ were more likely to have poor QOL[OR (95% CI): 1.92 (1.26–2.93)]. Children who developed or maintained undesirable lifestyles had high OR for poor QOL. Compared to children taking breakfast‘often’ during the follow-up period, those changing from‘often’ to‘seldom’ or those taking breakfast‘seldom’ were more likely to have poor QOL[1.61 (1.24–2.07), 2.05 (1.03–4.09), respectively]. When compared with children maintaining their participation in physical activity‘often’, those who changed from‘often’ to‘seldom’ and those who kept‘seldom’ were more likely to have poor QOL[2.10 (1.84–2.39), 2.21 (1.88–2.59), respectively]. This study shows that unfavourable lifestyles in childhood are associated with poor QOL in early adolescence. Early intervention could be worth considering to keeping desirable lifestyles during childhood. [ABSTRACT FROM AUTHOR]

Prokaryotes play crucial roles in hydrothermal vent ecosystems, yet their interactions with heavy metals are not well understood. This study explored the diversity of prokaryotic communities and their correlations with heavy metals and nutrient elements in hydrothermal sediments from Okinawa Trough. A total of 117 bacterial genera in 26 bacterial phyla and 10 archaeal classes in 3 archaeal phyla were identified, including dominant prokaryotic phyla Planctomycetes, Acidobacteria, Verrucomicrobia, and Euryarchaeota. Furthermore, Fe (39.61 mg/g), Mn (2.84 mg/g) and Ba (0.36 mg/g) were found to be the most abundant heavy metals in the Okinawa hydrothermal sediments. Notably, the concentrations of Zn, Ba, Mn, total organic carbon, and total nitrogen significantly increased, whereas the total sulfur concentration distinctively decreased at sampling sites farther from hydrothermal vents. These changes corresponded with reductions in prokaryotic abundance and diversity. Most heavy metals, including Mn, Fe, Co, Cu and As, presented significant positive correlations with a number of prokaryotic genera in the nearby sediment samples. In contrast, both positive and negative correlations with prokaryotes were observed in remote sediment. The keystone taxa include Magnetospirillum, GOUTA19, Lysobacter, Kaistobacter, Treponema, and Clostridium were detected through prokaryote interspecies interactions. The functional predictions revealed significant genes involved in carbon fixation, nitrogen/sulfur cycling, heat shock protein, and metal resistance pathways. Structural equation modeling confirmed that metal and nutrient elements directly influence the composition of prokaryotic communities, which in turn affects the relative abundance of functional genes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The aim of this study was to explore the effects of diet and habitat on the Hg levels of Japanese anchovy at different growth stages. We measured the amounts of Hg and stable carbon and nitrogen isotopes in the muscle and stable carbon and oxygen isotopes in the otoliths of 54 Japanese anchovy specimens obtained from the open seas of the Northwest Pacific Ocean (39°2'N ∼ 42°30'N, 154°02'E ∼ 161°29'E) between June and July 2021. Body length had a significant effect on δ 13 C bulk , δ 15 N bulk and M oto (P < 0.01). As individuals grew, δ 13 C bulk and δ 15 N bulk tended to gradually increase, but M oto tended to gradually decrease. The variation in the niches of Japanese anchovy at different growth stages showed that the standard ellipse-corrected area subsequently decreased with growth. It reached its smallest value in the 136-150 mm group, and there was no overlap between the 136-150 mm group and the other groups. The GAM results showed that Hg levels tended to decrease first and then increase with growth. There was a positive correlation between Hg levels and δ 18 O oto in fish. Hg levels increased gradually with increasing δ 15 N bulk . In our study, there may be a gradual shift in the diet of Japanese anchovy from phytoplankton to prey at higher trophic levels, and the depth of seawater in which the predators feed gradually increased with growth. Changes in diet and habitat were probably the main reasons for the increase in Hg levels., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guanyu Hu reports was provided by Shanghai Ocean University College of Marine Living Resource Sciences and Management. Guanyu Hu reports a relationship with Shanghai Ocean University College of Marine Living Resource Sciences and Management that includes: funding grants. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The eye lens is responsible for focusing objects at various distances onto the retina and its refractive power is determined by its surface curvature as well as its internal gradient refractive index (GRIN). The lens continues to grow with age resulting in changes to the shape and to the GRIN profile. The present study aims to investigate how the ageing process may influence lens optical development. Murine lenses of accelerated senescence-prone strain (SAMP8) aged from 4 to 50 weeks; senescence-resistant strain (SAMR1) aged from 5 to 52 weeks as well as AKR strain (served as control) aged from 6 to 70 weeks were measured using the X-ray interferometer at the SPring-8 synchrotron Japan within three consecutive years from 2020 to 2022. Three dimensional distributions of the lens GRIN were reconstructed using the measured data and the lens shapes were determined using image segmentation in MatLab. Variations in the parameters describing the lens shape and the GRIN profile with age were compared amongst three mouse strains. With advancing age, both the lens anterior and posterior surface flattens and the lens sagittal thickness increase in all three mouse strains (Anterior radius of curvature increase at 0.008 mm/week, 0.007 mm/week and 0.002 mm/week while posterior radius of curvature increase at 0.002 mm/week, 0.007 mm/week and 0.003 mm/week respectively in AKR, SAMP8 and SAMR1 lenses). Compared with the AKR strain, the SAMP8 samples demonstrate a higher rate of increase in the posterior curvature radius (0.007 mm/week) and the thickness (0.015 mm/week), whilst the SAMR1 samples show slower increases in the anterior curvature radius (0.002 mm/week) and its thickness (0.013 mm/week). There are similar age-related trends in GRIN shape in the radial direction (in all three types of murine lenses nr2 and nr6 increase with age while nr4 decrease with age consistently) but not in the axial direction amongst three mouse strains (nz1 of AKR lens decrease while of SAMP8 and SAMR1 increase with age; nz2 of all three models increase with age; nz3 of AKR lens increase while of SAMP8 and SAMR1 decrease with age). The ageing process can influence the speed of lens shape change and affect the GRIN profile mainly in the axial direction, contributing to an accelerated decline rate of the optical power in the senescence-prone strain (3.5 D/week compared to 2.3 D/week in the AKR control model) but a retardatory decrease in the senescence-resistant strain (2.1 D/week compared to the 2.3D/week in the AKR control model)., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Retifanlimab is a humanized monoclonal antibody targeting programmed death protein-1, and INCB001158 is an oral arginase inhibitor. This phase Ib study investigated retifanlimab, INCB001158, and their combination in Japanese patients with advanced solid tumors., Methods: Patients received retifanlimab (500 mg every 4 weeks [Q4W] i.v.) or escalating doses of INCB001158 (75 or 100 mg twice daily [BID]) monotherapy in Part 1 and combination of retifanlimab (500 mg Q4W) and INCB001158 (100 mg BID) in Part 2. Primary endpoints were safety, tolerability, dose-limiting toxicities (DLTs), and determination of recommended phase II doses in Japanese patients., Results: Eighteen patients (retifanlimab or INCB001158 monotherapy and combination; n = 6 each) were enrolled at 2 sites in Japan. There were no DLTs, fatal adverse events (AEs), or discontinuations due to AEs. Rash (all grade 1) was the most common treatment-emergent AE with retifanlimab (n = 6). Treatment-related AEs were reported with retifanlimab (n = 4) or INCB001158 (n = 2) monotherapy and with combination (n = 4); an immune-related AE (thyroid disorder, grade 2) was reported with combination. Two responses were observed with retifanlimab monotherapy (1 complete, 1 partial) and 1 stable disease (SD), for an overall response rate of 33.3% (95% confidence interval [CI], 4.3-77.7) and disease control rate (DCR) of 50% (95% CI, 11.8-88.2). Three patients had SD with INCB001158 monotherapy (DCR 50%; 95% CI, 11.8-88.2). No responses or SD were observed with combination therapy., Conclusion: Retifanlimab, INCB001158, and their combination had acceptable safety profiles. Promising retifanlimab antitumor activity warrants further investigation in Japanese patients., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Low estimated glomerular filtration rate (eGFR) is associated with an increased risk of arterial stiffness in participants with kidney damage. It is uncertain whether this association is due to eGFR itself or is mediated by the eGFR-associated increases in fasting blood glucose (FBG)., Method: The cross-sectional study included 865 Japanese participants with decreased kidney function, whose eGFR was less than 90 mL/min/1.73 m2, and recruited individuals who received medical healthcare. The mediating variable was FBG, with eGFR as the independent variable and brachial-ankle pulse wave velocity (baPWV) as the dependent variable. A mediation analysis was used to evaluate the mediating effect of FBG on the association between eGFR and arterial stiffness., Results: The mean age of the participants was 51.69 ± 9.25 years old, with 65.90% individuals being male. The mean values for FBG, eGFR, and baPWV were 5.46 ± 0.79 mmol/L, 68.83 ± 10.05 mL/min/1.73 m2, and 1,423.50 ± 247.78 cm/s, respectively. The mediation analysis revealed that eGFR had a significant direct effect on baPWV (β = -25.68 95% CI: -46.42, -7.45), and that FBG played a partial mediating role in the indirect effect of eGFR on baPWV (β = -3.54 95% CI: -11.88, -0.079). Mediation analysis showed that 12.10% of the effect of eGFR on risk of arterial stiffness was mediated through FBG., Conclusion: The study indicated that there is a mediating relationship between eGFR and FBG in people with decreased kidney function, which is associated with the risk of arterial stiffness. Therefore, the importance of FBG as a mediator should be acknowledged and taken into consideration., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Objective: The study aimed to conduct a bibliometric analysis of mucosal immunity in IgA nephropathy (IgAN) and indicate its current status, hot sopts, and direction of future studies., Methods: The literature data was collected from the Web of Science Core Collection. CiteSpace 6.1.R3 was employed to conduct a visualization bibliometric analysis of mucosal immunity in IgA nephropathy, including authors, countries, journals, keywords, organizations, references, the bursts of keywords and references, and the timeline of keyword clusters and reference clusters., Results: A total of 315 publications from 1990 to 2022 were included. The number of articles in this field has increased in recent years. Suzuki H, Coppo R, and Feehally J took the first place parallelly with 18 articles. Japan contributes the most articles, accounting for 27.3% of all the publications. The institutions with the most publications were Juntendo University and University of Alabama Birmingham. 453 keywords were concluded in the analysis, which mainly focus on the mucosal pathogenesis and therapy of the IgAN. The top five co-cited reference cluster are "aberrantly glycosylated IgA," "corticosteroids," "animal models," "o-glycosylationm" and "microRNA-630." The most recently burst of keyword is "tonsillectomy" and "gut.", Conclusion: This was the first bibliometric analysis to systematically analyze the mucosal immunity in IgAN, which obtained the current status and indicated the future research hotspots and development trends. The gut microbiota and the related therapy-targeted mucosal immunity might be the future research hotspot., (© 2024 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Introduction: The purpose of developing and adopting regulatory science (RS) for drug regulatory authorities (DRAs) is to enhance regulatory capacity by advancing the scientific approach for the evaluation of health-related products. While many DRAs around the world advocate the concept of RS, the implementation approaches of RS vary according to local needs and have not been systemically examined. This study aimed to systematically identify the evidence about how RS was developed, adopted, and advanced by the selected DRAs, and analyzed and compared the implementation experiences of RS development under the guidance of an implementation science framework., Methods: Documentary analysis of government documents and a scoping literature review were conducted, and data analysis was performed under the guidance of the PRECEDE-PROCEED Model (PPM). DRAs in the United States, the European Union, Japan, and China had officially launched RS initiatives and were therefore selected as the target countries in this study., Results: There is no common consensus on the definition of RS among the DRAs. However, these DRAs shared the same goal of developing and adopting RS, which was used to develop new tools, standards, and guidelines that could improve the effectiveness and efficiency of the risk and benefit assessment of the regulated products. Each DRA had decided its own priority areas for RS development and thus set specific objectives that might be technology-based (e.g., toxicology and clinical evaluation), process-based (e.g., partnership with healthcare systems and high-quality review/consultation services), or product-based (e.g., drug-device combination products and innovative emerging technologies). To advance RS, considerable resources had been allocated for staff training, advancing information technology and laboratory infrastructure, and funding research projects. DRAs also took multifaceted approaches to expand scientific collaborations through public-private partnerships, research funding mechanisms, and innovation networks. Cross-DRA communications were also reinforced through horizon scanning systems and consortiums to better inform and assist the regulatory decision-making process. The output measurements might be scientific publications, funded projects, DRAs interactions, and evaluation methods and guidelines. Improved regulatory efficiency and transparency leading to benefits to public health, patient outcomes, and translation of drug research and development as the key primary outcomes of RS development were anticipated but not yet clearly defined., Conclusion: The application of the implementation science framework is useful for conceptualizing and planning the development and adoption of RS for evidence-based regulatory decision-making. Continuous commitment to the RS development and regular review of the RS goals by the decision-makers are important for DRAs to meet the ever-changing scientific challenges in their regulatory decision-making process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shi, Chen, Hu and Ung.)

This study explores the effects of native prosodic system and segmental context on the perception of Cantonese tones by Mandarin and Japanese listeners. In Experiment 1, 13 Mandarin and 13 Japanese subjects took part in a two-alternative forced-choice discrimination test of Cantonese tones in different segmental contexts (familiar vs unfamiliar). In Experiment 2, 20 Mandarin listeners participated in a perceptual assimilation task that examined the cross-language perceptual similarity between Mandarin and Cantonese tones. Results showed that Mandarin listeners were comparable to Japanese counterparts in discriminability, but the former attended more to pitch contour differences while the latter were more sensitive to pitch height. Moreover, the effect of segmental context was significant exclusively in the Mandarin group, whereas the Japanese group performed stably across syllables in discriminating Cantonese tones. It seemed that unfamiliar context rendered lower perceptual similarity, which further hindered corresponding discrimination by the Mandarin group. In addition, segmental effects were mainly observed in the assimilation patterns of category goodness or uncategorized-categorized. These findings suggested that non-native tone perception could be modulated by listeners' native prosodic structures in a finer way.

Purpose: Cervical ossification of ligamentum flavum (COLF) is a rare clinical entity which can occasionally contribute to severe myeloradiculopathy. Many orthopedists are unfamiliar with or underestimate this pathology. Therefore, a comprehensive research is obligatory to reappraise the epidemiological, radiological, clinical and histopathological characteristics of COLF-myeloradiculopathy based on synthesis of individual patient data., Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, EMBASE, Scopus and Web of Science databases were searched for studies discussing COLF-myeloradiculopathy from the inception to December 2020., Results: A total of 94 cases from 54 studies were identified. The annual publications demonstrated a steady increase, and most reports were from Japan and China. The mean age was 58.76±13.39 years and nearly 60% of cases occurred in the 55-64 and 65-74 years age group. The male-female ratio was 1.4:1. Most cases belonged to East Asian population (60.64%). COLF predominately appeared in the lower cervical and cervicothoracic spine (76.60%) and mainly affected C4-5 (23.29%) and C5-6 (21.23%). Single-segment type ossification accounted for 62.76 and 45.45% of ossification lesions distributed bilaterally. The majority of COLF (81.1%) were spontaneous, and motor disturbance (76.4%), spinal ataxia (62.5%) and sensory disturbance (58.9%) were the most common manifestations. Histopathologically, it's a metaplastic process of endochondral ossification with the formation of mature lamellar bone which was distinguished from calcification of ligamentum flavum. About 21.28% of concurrent COLF and COPLL cases were identified as a separated group, with unique characteristics., Conclusion: COLF is an underappreciated but potentially growing pathogeny of myeloradiculopathy in aging population, though its distinct epidemiological, radiological, clinical and histopathological features are not fully supported by current evidence. However, our findings will provide several referential data for future researches to shed light on COLF., Competing Interests: The authors have declared no conflicts of interest., (© 2021 Zhang et al.)

Objective: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations., Methods: We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations., Results: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10 -8 ). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r g =-0.242) and non-albumin protein (r g =0.238)., Conclusion: This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cumulating evidence indicates that the systemic inflammatory response (SIR) plays a crucial role in the prognosis of various cancers. We aimed to generate a preoperative risk grade (PRG) by integrating SIR markers to preoperatively predict the long-term prognosis of intrahepatic cholangiocarcinoma (ICC)., Methods: 468 consecutive ICC patients who underwent hepatectomy between 2010 and 2017 were enrolled. The PRG and a nomogram were generated and their predictive accuracy was evaluated., Results: The PRG consisted of two non-tumor-specific SIR markers platelet-to-lymphocyte ratio (PLR) and albumin (ALB), which were both the independent predictors of overall survival (OS). Multivariate analysis showed that the PRG was significantly associated with OS (PRG = 1: hazard ratio (HR) = 3.800, p < 0.001; PRG = 2: HR = 7.585, p < 0.001). The C-index of the PRG for predicting survival was 0.685 (95% CI 0.655 to 0.716), which was statistically higher than that of the following systems: American Joint Committee on Cancer (AJCC) 8th edition (C-index 0.645), Liver Cancer Study Group of Japan (LCSGJ) (C-index 0.644) and Okabayashi (C-index 0.633) (p < 0.05). Besides, the C-index of the nomogram only consisting of the tumor-specific factors (serum carcinoembryonic antigen, carbohydrate antigen 19-9, tumor number) could be improved to 0.737 (95% CI 0.062-0.768) from 0.625 (95% CI 0.585-0.665) when the PRG was incorporated (p < 0.001)., Conclusions: The PRG integrating two non-tumor-specific SIR markers PLR and ALB was a novel method to preoperative predicting the prognosis of ICC.

Background: Predictions of primary liver cancer (PLC) incidence rates and case numbers are critical to understand and plan for PLC disease burden., Methods: Data on PLC incidence rates and case numbers from 1990 to 2017 were retrieved from the Global Burden of Disease database. The estimated average percentage change (EAPC) was calculated to quantify the trends of PLC age-standardized incidence rates (ASRs). Bayesian age-period-cohort models were constructed to project PLC incidence rates and case numbers through 2030., Results: Globally, the PLC case number doubled from 472 300 in 1990 to 953 100 in 2017. The case number will further increase to 1 571 200 in 2030, and the ASR will increase from 11.80 per 100 000 in 2018 to 14.08 per 100 000 in 2030. The most pronounced increases are observed in people afflicted by non-alcoholic steatohepatitis (NASH) and in older people. The trends of PLC incidence rates between 1990 and 2030 are heterogeneous among countries and can be summarized as five scenarios: (i) 46 countries that have and will continue to experience a persistent increase (e.g. Australia); (ii) 21 countries that experienced an initial decrease (or remained stable) but are predicted to increase (e.g. China); (iii) 7 countries that experienced an initial increase but are predicted to remain stable (e.g. USA); (iv) 29 countries that experienced an initial increase but are predicted to decrease (e.g. Egypt); and (v) 82 countries that have and will continue to experience a persistent decrease (e.g. Japan)., Conclusion: PLC incidence rates and case numbers are anticipated to increase at the global level through 2030. The increases in people afflicted by NASH and among older people suggest a dearth of attention for these populations in current prevention strategies and highlight their priority in future schedules for global control of PLC., (© The Author(s) 2020; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: Our study aimed to investigate the clinical outcomes and survival rates following porous tantalum rod surgery (PTRS) and conversion total hip arthroplasty (THA) subsequent to failed PTRS., Methods: A total of 38 subjects (40 hips) with osteonecrosis of the femoral head (ONFH) were included in this retrospective study between January 2008 and December 2011. All subjects were evaluated before surgery by using the Association Research Circulation Osseous (ARCO) classification system, the Japan Investigation Committee (JIC) classification and the Harris hip score (HHS). The endpoint of this study was set as final follow-up (including the survival time of PTRS and conversion THA). The rates of radiological progression were also evaluated. Patients who received conversion THA were further followed and compared to a control group of 58 patients with ONFH who underwent primary THA., Results: The mean follow-up time was 120.7 ± 9.2 (range, 104-143) months, and the overall survival rate was 75% at 96 months (ARCO stage II: 81.5%; stage III: 38.5%; JIC type C1: 83.3%; C2: 30%). The HHS before surgery was 59 (55-61), in contrast to 94 (91-96) at 96 months follow-up (P < 0.01). HHS in stage III show a significant poorer result compared to stage II at 24 months. HHS in Type C2 group show no significant difference compared to HHS before surgery at 24 and 60 months follow up (P = 0.91, P = 0.30). Twelve hips requiring secondary THA were followed for 66.9 ± 31.7 months, and control hips that underwent primary THA was followed for 75.4 ± 14.9 months. The HHS in the conversion group was 89 (86-93) and that in the primary THA group was 92 (79-95, P = 0.09) at the 5-year follow-up., Conclusion: In the mid-term follow-up, porous tantalum implants showed an encouraging survival rate in symptomatic patients in early stages (ARCO stage II) or with limited necrotic lesions (JIC type C1). In addition, our results did not demonstrated any difference between primary THA and conversion THA.

Background and Aims: Dutch tomato cultivars tend to have a greater yield than Japanese cultivars even if they are grown under the same conditions. Factors contributing to the increased yield of the Dutch cultivars were a greater light use efficiency and greater leaf photosynthetic rate. On the other hand, the relationship between tomato yields and anatomical traits is still unclear. The aim of this study is to identify the anatomical traits related to the difference in yield between Dutch and Japanese cultivars., Methods: Anatomical properties were compared during different growth stages of Dutch and Japanese tomatoes. Hormone profiles and related gene expression in hypocotyls of Dutch and Japanese cultivars were compared in the hypocotyls of 3- and 4-week-old plants., Key Results: Dutch cultivars have a more developed secondary xylem than Japanese cultivars, which would allow for greater transport of water, mineral nutrients and phytohormones to the shoots. The areas and ratios of the xylem in the hypocotyls of 3- to 6-week-old plants were larger in the Dutch cultivars. In reciprocal grafts of the Japanese and Dutch cultivars, xylem development at the scion and rootstock depended on the scion cultivar, suggesting that some factors in the scion are responsible for the difference in xylem development. The cytokinin content, especially the level of N6-(Δ 2-isopentenyl) adenine (iP)-type cytokinin, was higher in the Dutch cultivars. This result was supported by the greater expression of Sl-IPT3 (a cytokinin biosynthesis gene) and Sl-RR16/17 (a cytokinin-responsive gene) in the Dutch cultivars., Conclusions: These results suggest that iP-type cytokinins, which are locally synthesized in the hypocotyl, contribute to xylem development. The greater xylem development in Dutch cultivars might contribute to the high yield of the tomato., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The coronavirus disease (COVID-19) began to spread in mid-December 2019 from Wuhan, China, to most provinces in China and over 200 other countries through an active travel network. Limited by the ability of the country or city to perform tests, the officially reported number of confirmed cases is expected to be much smaller than the true number of infected cases., Objective: This study aims to develop a new susceptible-exposed-infected-confirmed-removed (SEICR) model for predicting the spreading progression of COVID-19 with consideration of intercity travel and the difference between the number of confirmed cases and actual infected cases, and to apply the model to provide a realistic prediction for the United States and Japan under different scenarios of active intervention., Methods: The model introduces a new state variable corresponding to the actual number of infected cases, integrates intercity travel data to track the movement of exposed and infected individuals among cities, and allows different levels of active intervention to be considered so that a realistic prediction of the number of infected individuals can be performed. Moreover, the model generates future progression profiles for different levels of intervention by setting the parameters relative to the values found from the data fitting., Results: By fitting the model with the data of the COVID-19 infection cases and the intercity travel data for Japan (January 15 to March 20, 2020) and the United States (February 20 to March 20, 2020), model parameters were found and then used to predict the pandemic progression in 47 regions of Japan and 50 states (plus a federal district) in the United States. The model revealed that, as of March 19, 2020, the number of infected individuals in Japan and the United States could be 20-fold and 5-fold as many as the number of confirmed cases, respectively. The results showed that, without tightening the implementation of active intervention, Japan and the United States will see about 6.55% and 18.2% of the population eventually infected, respectively, and with a drastic 10-fold elevated active intervention, the number of people eventually infected can be reduced by up to 95% in Japan and 70% in the United States., Conclusions: The new SEICR model has revealed the effectiveness of active intervention for controlling the spread of COVID-19. Stepping up active intervention would be more effective for Japan, and raising the level of public vigilance in maintaining personal hygiene and social distancing is comparatively more important for the United States., (©Choujun Zhan, Chi Kong Tse, Zhikang Lai, Xiaoyun Chen, Mingshen Mo. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 03.07.2020.)

Objective: To assess the effectiveness of bronchial thermoplasty (BT) in "real-world" patients with severe asthma at 2 years post therapy. Method: Outcomes of 70 patients with severe asthma undergoing bronchial thermoplasty from March 2014 to November 2017 in China-Japan Friendship Hospital were retrospectively analyzed two years post therapy. The scores of Asthma Control Test (ACT) and Mini Asthma Quality of Life Questionnaire (mini-AQLQ), the number of severe exacerbations, emergency department visits and hospitalizations for asthma symptoms in the past year, indicators of pulmonary function including forced expiratory volume in one second (FEV(1)), FEV(1) as a percentage of predicted value (FEV(1)%pred) and FEV(1)/forced vital capacity (FEV(1)/FVC), maintenance asthma medications, the cost of asthma drugs and the total annual cost of asthma treatment were evaluated and analyzed before and 2 years after BT therapy, and the subjective assessment about effectiveness of BT were given by the patients. Results: Before and 2 years after BT, the numbers of subjects suffering severe exacerbations in the past year were 70 (100%) and 37 (52.9%), and the numbers of total severe exacerbations were 575 and 162 respectively. The numbers of patients having emergency department visits due to asthma exacerbation were 46 (65.7%) and 9 (12.9%), and the numbers of emergency department visits were 186 and 19 respectively. The numbers of patients hospitalized due to asthma exacerbation were 43 (61.4%) and 16 (22.9%), and the numbers of total hospitalizations were 124 and 24, respectively. The rate of severe exacerbation, emergency department visit and hospitalization were significantly reduced two years after the treatment by 71.9%, 88.9% and 83.3% (all P <0.001). The scores of ACT and mini-AQLQ were significantly increased [22 (21, 24) vs 17 (13, 19), (5.57±0.89) vs (3.83±0.92); both P <0.001]. Two years after BT, 4 patients (5.7%) were weaned off inhaled corticosteroids (ICS) and long-acting β(2)-agonist (LABA), while 14 patients (37.8%) were weaned off oral corticosteroid (OCS), with daily dose of ICS and OCS significantly decreased (both P <0.05). The proportion of patients treated with montelukast sodium and theophylline was also significantly reduced after BT (40.0% vs 81.4%, 27.1% vs 71.4%; both P <0.001). In addition, the indicator of FEV(1), FEV(1)%pred and FEV(1)/FVC ratio were all greatly improved two years after the treatment [2.27 (1.84, 2.82) vs 2.10 (1.70, 2.61) L, (76.8±19.5)% vs (72.5±19.8)%, (66.3±13.6)% vs (63.8±13.0)%; all P <0.05]. The annual cost for asthma drug and asthma treatment after BT were significantly decreased ( P <0.001). Fifty-nine patients (84.3%) subjectively assessed the treatment as effective. Conclusion: The bronchial thermoplasty in "real-world" patients with severe asthma could significantly improve the asthma control, lung function and quality of life, and reduce severe exacerbations, emergency department visits and hospitalizations for asthma symptoms, while the maintenance asthma medications, the cost of asthma drugs and the total annual cost of asthma treatment are significantly decreased.

Objective: To investigate the effects of bronchial thermoplasty (BT) on airway remodeling, asthma control and quality of life in patients with severe asthma. Methods: From January to September 2019, 11 patients with severe asthma were recruited from China Japan Friendship Hospital to receive BT treatment. The treatment was performed over three sessions separated by 3-week intervals. The right lower lobe, the left lower lobe and the bilateral upper lobes were treated respectively. In this study, patients' self-control method was used. The timepoint before the first BT treatment was defined as pre-treatment group, and the timepoint before the third treatment was defined as post-treatment group. Histological staining was used to detect the airway remodeling of the left lower lobe in two groups, including the mass of airway smooth muscle (ASM) and collagen in airway wall, and the thickness of basement membrane. The cell classification of bronchoalveolar lavage fluid (BALF) from the left lower lobe and peripheral blood, total serum IgE, asthma control test (ACT), mini asthma quality of life questionnaire (miniAQLQ) and the forced expiratory volume in 1 second expressed as percent predicted (FEV(1)%pred) were evaluated in the two groups. The correlation was analyzed between airway remodeling and asthma control and quality of life. Results: Effects of BT in post-treatment group, compared with pre-treatment group: the mass of ASM and collagen in airway wall was significantly decreased [(9.8±2.5)% vs (25.8±7.7)%, (12.9±4.0)% vs (17.4±5.6)%] (both P< 0.05), while basement membrane thickness was not significantly different ( P> 0.05); the percentage of eosinophils in BALF and peripheral blood, and total serum IgE were not significantly different (all P> 0.05); ACT score and miniAQLQ score were significantly increased [(23.1±1.8) vs (13.8±6.2) points, (5.3±1.3) vs (3.6±1.5) points] (both P< 0.05), while FEV(1)% pred was not statistically different ( P> 0.05). The mass of ASM was negatively correlated with ACT score ( r= -0.712), miniAQLQ score ( r= -0.557) and FEV(1)%pred ( r= -0.477), while the mass of collagen was negatively correlated with ACT score ( r= -0.549) and miniAQLQ score ( r= -0.639) (all P< 0.05). Conclusion: BT treatment could improve airway remodeling, asthma control and quality of life in patients with severe asthma; besides, the reduction of remodeling is related to the improvements of asthma control and quality of life.

We investigated the degradation of polycyclic aromatic hydrocarbons (PAHs) during long-range transport. Aerosols were collected simultaneously at remote sites on Tuoji Island, China; Fukue Island, Japan; and the Cape Hedo Atmosphere and Aerosol Measurement Station (CHAAMS), Okinawa, Japan in April, October, and December from 2012 to 2013. These remote sites were convenient for investigating the degradation of PAHs during long-range transport. PAHs were analyzed via gas chromatography/mass spectrometry. We identified air masses that passed over all sites and combined our measurements with a chemical transport model. We estimated the relative contributions of the PAHs at the three sites by normalizing the PAH concentrations to elemental carbon. Benzo[a]pyrene persisted in 5-16% of samples. The results of this study are consistent with laboratory studies in which secondary organic aerosol (SOA) coatings protected PAHs from degradation by ozone. We detected an inhibition of the degradation PAHs by SOA coatings by collecting PAHs simultaneously at the three sites. To elucidate the major sources of the SOAs, we carried out a positive matrix factorization analysis to identify the major sources of SOA coating, which controls the lifetime of PAHs. In spring and winter, the contribution of vehicle emissions was higher (46%) at Tuoji Island than at CHAAMS (13%). In contrast, the contribution of coal combustion was higher at CHAAMS (59%) than at Tuoji Island (28%). This result implies that during long-range transport, PAHs derived from coal combustion are more slowly degraded than PAHs derived from vehicle emissions. We found that the viscosity of SOA coatings derived from vehicle emissions in China was low, and the corresponding PAHs were rapidly degraded. In contrast, the viscosity of SOA coatings derived from coal combustion was high, and degradation of the corresponding PAHs was relatively slow. These results imply that PAHs derived from coal combustion have long lifetime., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In recent years, there is a trend of low C/N ratio in municipal domestic wastewater, which results in serious problems for nitrogen removal from wastewater. The addition of an external soluble carbon source has been the usual procedure to achieve denitrification. However, the disadvantage of this treatment process is the need of a closed, rather sophisticated and costly process control as well as the risk of overdosing. Solid-phase denitrification using biodegradable polymers as biofilm carrier and carbon source was considered as an attractive alternative for biological denitrification. The start-up time of the novel process using PCL (polycaprolactone) as biofilm carrier and carbon source was comparable with that of conventional process using ceramsite as biofilm carrier and acetate as carbon source. Further, the solid-phase denitrification process showed higher nitrogen removal efficiency under shorter hydraulic retention time (HRT) and low carbon to nitrogen (C/N) ratio since the biofilm was firmly attached to the clear pores on the surface of PCL carriers and in this process bacteria that could degrade PCL carriers to obtain electron donor for denitrification was found. In addition, solid-phase denitrification process had a stronger resistance of shock loading than that in conventional process. This study revealed, for the first time, that the physical properties of the biodegradable polymer played a vital role in denitrification, and the different microbial compositions of the two processes was the main reason for the different denitrification performances under low C/N ratio.

Extracellular adenosine triphosphate (eATP), released following inflammatory stimulation or infection, is a potent signaling molecule in activating innate immune responses in fish. However, the regulation of eATP-mediated innate immunity in fish remains unknown. Ecto-nucleoside triphosphate diphosphohydrolase 1 (CD39) is a critical molecular switch for controlling the ATP levels in the extracellular space. CD39 plays a key role in regulating eATP-activated innate immune responses through the phosphohydrolysis of pro-inflammatory eATP to inactive AMP. Here, we identified and characterized a CD39 homolog (namely, poCD39) in the Japanese flounder Paralichthys olivaceus and analyzed its regulatory role in eATP-mediated innate immunity. Real-time quantitative PCR analysis revealed that poCD39 is ubiquitously present in all tested normal tissues with dominant expression in enriched Japanese flounder head kidney macrophages (HKMs). Immune challenge experiments demonstrated that poCD39 expression was upregulated by inflammatory stimulation and Edwardsiella tarda infection. Biochemical and immunofluorescence analysis revealed that poCD39 is a functional glycosylated membrane protein for the hydrolysis of eATP. Inhibition of poCD939 activity with the ecto-NTPDase inhibitor ARL 67156 resulted in increased IL-1beta gene expression and ROS production in Japanese flounder HKMs. In contrast, overexpression of poCD39 in Japanese flounder FG-9307 cells reduced eATP-induced pro-inflammatory cytokine IL-1beta gene expression. Finally, poCD39 expression was significantly induced by eATP stimulation in the HKMs, suggesting that eATP may provide a feedback mechanism for transcriptional regulation of fish CD39. Taken together, we identified and characterized a functional fish CD39 protein involved in regulating eATP-mediated innate immune responses in fish., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Economic cycles may lead to changes in corporate bond credit ratings. This paper utilizes the Markov model to describe transition probability matrixes of economic states for the separation of economic cycles. We develop a new model, which we term the Markov rating shopping dual reputation model, incorporating two reputation effects. This model is well suited to analyze the conditions of the dual rating incentive regulation and the constraint regulation for preventing rating inflation in collusion among credit rating agencies. Then, we apply the Markov regime switching-vector auto-regression (MS-VAR) to estimate the transition probability matrixes of America, England, Japan and China. Based on the numerical analysis and the simulations, the results show that a dual rating regulation can prevent the collusion of inflated ratings, as well as increased rating fees with the separation of economic cycles; additionally, when separating the economic cycles, a constraint regulation is more effective at reducing the risk of rating inflation in collusion and regulatory cost., Competing Interests: PZ is an employee of Purdue Technology Company Ltd of Shenzhen. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare no competing interests exist.

The red stingray Dasyatis akajei is distributed in both marine and freshwater, but little is known about its phylogeography and population structure. We sampled 107 individuals from one freshwater region and 6 coastal localities within the distribution range of D. akajei. Analyses of the first hypervariable region of mitochondrial DNA control region of 474 bp revealed only 17 polymorphism sites that defined 28 haplotypes, with no unique haplotype for the freshwater population. A high level of haplotype diversity and low nucleotide diversity were observed in both marine (h = 0.9393 ± 0.0104, π = 0.0069 ± 0.0040) and freshwater populations (h = 0.8333 ± 0.2224, π = 0.0084 ± 0.0063). Significant level of genetic structure was detected between four marine populations (TZ, WZ, ND and ZZ) via both hierarchical molecular variance analysis (AMOVA) and pairwise FST (with two exceptions), which is unusual for elasmobranchs detected previously over such short geographical distance. However, limited sampling suggested that the freshwater population was not particularly distinct (p > 0.05), but additional samples would be needed to confirm it. Demersal and slow-moving characters likely have contributed to the genetically heterogeneous population structure. The demographic history of D. akajei examined by mismatch distribution analyses, neutrality tests and Bayesian skyline analyses suggested a sudden population expansion dating to upper Pleistocene. The information on genetic diversity and genetic structure will have implications for the management of fisheries and conservation efforts.

Exfoliation syndrome (XFS) is the most common recognizable cause of open-angle glaucoma worldwide. To better understand the etiology of XFS, we conducted a genome-wide association study (GWAS) of 1,484 cases and 1,188 controls from Japan and followed up the most significant findings in a further 6,901 cases and 20,727 controls from 17 countries across 6 continents. We discovered a genome-wide significant association between a new locus (CACNA1A rs4926244) and increased susceptibility to XFS (odds ratio (OR) = 1.16, P = 3.36 × 10(-11)). Although we also confirmed overwhelming association at the LOXL1 locus, the key SNP marker (LOXL1 rs4886776) demonstrated allelic reversal depending on the ancestry group (Japanese: OR(A allele) = 9.87, P = 2.13 × 10(-217); non-Japanese: OR(A allele) = 0.49, P = 2.35 × 10(-31)). Our findings represent the first genetic locus outside of LOXL1 surpassing genome-wide significance for XFS and provide insight into the biology and pathogenesis of the disease.

Aberrant DNA methylation can be a potential genetic mechanism in non-small cell lung cancer (NSCLC). However, inconsistent findings existed among the recent association studies between cigarette smoking and gene methylation in lung cancer. The purpose of our meta-analysis was to evaluate the role of gene methylation in the smoking behavior of NSCLC patients. A total of 116 genes were obtained from 97 eligible publications in the current meta-analyses. Our results showed that 7 hypermethylated genes (including CDKN2A, RASSF1, MGMT, RARB, DAPK, WIF1 and FHIT) were significantly associated with the smoking behavior in NSCLC patients. The further population-based subgroup meta-analyses showed that the CDKN2A hypermethylation was significantly associated with cigarette smoking in Japanese, Chinese and Americans. In contrast, a significant association of RARB hypermethylation and smoking behavior was only detected in Chinese but not in Japanese. The genes with altered DNA methylation were likely to be potentially useful biomarkers in the early diagnosis of NSCLC.

Multiregional clinical trials provide the potential to make safe and effective medical products simultaneously available to patients globally. As regulatory decisions are always made in a local context, this poses huge regulatory challenges. In this article we propose two conditional decision rules that can be used for medical product approval by local regulatory agencies based on the results of a multiregional clinical trial. We also illustrate sample size planning for such trials.

Background: MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs of 20-25 nucleotides that play a key role in diverse biological processes. Japanese flounder undergo dramatic metamorphosis in their early development. The metamorphosis is characterized by morphological transformation from a bilaterally symmetrical to an asymmetrical body shape concomitant with extensive morphological and physiological remodeling of organs. So far, only a few miRNAs have been identified in fish and there are very few reports about the Japanese flounder miRNA., Methodology/principal Findings: Solexa sequencing technology was used to perform high throughput sequencing of the small RNA library from the metamorphic period of Japanese flounder. Subsequently, aligning these sequencing data with metazoan known miRNAs, we characterized 140 conserved miRNAs and 57 miRNA: miRNA* pairs from the small RNA library. Among these 57 miRNA: miRNA* pairs, twenty flounder miRNA precursors were amplified from genomic DNA. We also demonstrated evolutionary conservation of Japanese flounder miRNAs and miRNA* in the animal evolution process. Using miRNA microarrays, we identified 66 differentially expressed miRNAs at two metamorphic stages (17 and 29 days post hatching) of Japanese flounder. The results show that miRNAs might play a key role in regulating gene expression during Japanese flounder metamorphosis., Conclusions/significance: We identified a large number of miRNAs during flounder metamorphosis, some of which are differentially expressed at two different metamorphic stages. The study provides an opportunity for further understanding of miRNA function in the regulation of flounder metamorphosis and gives us clues for further studies of the mechanisms of metamorphosis in Japanese flounder.

A novel oxidation ditch system using anaerobic tanks and innovative dual dissolved oxygen (DO) control technology is proposed for biological nitrogen and phosphorus removal from domestic sewage. A continuous bench-scale experiment running for more than 300 days was performed to evaluate the system. Monitoring and controlling the airflow and recirculation flow rate independently using DO values at two points along the ditch permitted maintenance of aerobic and anoxic zone ratios of around 0.30 and 0.50, respectively. The ability to optimize aerobic and anoxic zone ratios using the dual DO control technology meant that a total nitrogen removal efficiency of 83.2-92.9% could be maintained. This remarkable nitrogen removal performance minimized the nitrate recycle to anaerobic tanks inhibiting the phosphorus release. Hence, the total phosphorus removal efficiency was also improved and ranged within 72.6-88.0%. These results demonstrated that stabilization of the aerobic and anoxic zone ratio by dual DO control technology not only resulted in a marked improvement of nitrogen removal, but it also enhanced phosphorus removal.

The urostyloid freshwater ciliate Pseudourostyla cristata was recorded for the first time from Lake Biwa, a 4-million-year-old lake located in Shiga Prefecture, Japan. Its morphology and morphogenesis were investigated using live observation and protargol impregnation, and the SSU ribosomal RNA gene was sequenced. Based on the current observations and previous descriptions, this species is readily recognized mainly by the following characters: body slender or broadly oval to elliptical, and dark grey in color; size in vivo about 170-400 x 40-150 microm; pellicle flexible and contractile, with extrusomes forming a hyaline seam underneath; ciliature comprising about 60-130 adoral membranelles, usually 1 buccal cirrus, 20-24 frontal, 2 frontoterminal, 17-26 pairs of midventral, and 5-16 transverse cirri, 4-6 left and 4-5 right marginal rows, and 8-10 dorsal kineties; 15-83 macronuclear nodules and 2-9 micronuclei; freshwater habitat. The main morphogenetic developments are: (1) the oral primordium for the proter originates de novo on the dorsal wall of the buccal cavity, and the dedifferentiated undulating membranes and some parental proximal membranelles join in the primordial development; the old adoral zone will be partly replaced by new structures; (2) the oral primordium for the opisthe occurs epiapokinetally left of the midventral complex between the adoral zone and the transverse cirri; (3) the fronto-midventral transverse cirral (FVT) anlagen develop separately in both dividers by dedifferentiation of most of the midventral cirri; (4) the single buccal cirrus is generated from the posterior end of FVT anlage II; (5) the leftmost frontal cirrus is derived from the anterior end of the undulating membranes anlage (FVT anlage I); (6) the marginal rows of each side are formed from a single anlage which arises within the rightmost row; (7) the dorsal kineties develop by intrakinetal basal body proliferation; and (8) the most posterior FVT anlage contributes the two fronto-terminal cirri at its anterior end. The present observations indicate that P. cristata has a wide geographic distribution, and possesses constant morphological and morphogenetic traits. Phylogenetic trees inferred from SSU rRNA gene sequences suggest paraphyly of the genus Pseudourostyla., (Copyright (c) 2008 Elsevier GmbH. All rights reserved.)

Objective: To examine daytime sleepiness and sleepiness interrelationship with sleep-wake patterns, eating habits, physical activity, and TV/video game time., Study Design: A cross-sectional survey with 9,261 school children (mean age of 12.8 years) from 93 junior high schools in Toyama prefecture, Japan., Results: The main outcome measures were daytime sleepiness during schooldays and sleepiness interrelationship with sleep-wake patterns, eating habits, physical activity, and visual media use. A total of 2,328 children (25.2%) reported sleepiness almost always and 4,401 (47.6%) sleepiness often. Regarding sex difference, a higher proportion of girls reported sleepiness in comparison to boys (79% vs 66%, P < .001). Higher body mass index values were associated with the presence of sleepiness. In girls with preferences for daily snack (versus those who reported no snack) sleepiness presented significantly (P < .001) higher values. Reduced sleep time was significantly associated with sleepiness. The prevalence of sleepiness did not significantly differ among groups who had 7.5 hours sleep or more. A dose-response relation was found between sleepiness and sleep disturbances, physical activity, and media use time., Conclusions: Sleep insufficiency represents a main cause for daytime sleepiness in Japanese junior high school children. Proper sleep habits, high physical activity level, and limited TV viewing time should be promoted among school children.

Objective: To assess the reliability and validity of the Japanese translation version of the Pediatric Quality of Life Inventory 4.0 Short Form 15 (PedsQL 4.0 SF15)., Methods: The PedsQL 4.0 SF15 was administered to 229 schoolchildren aged 6-13 years and 100 pediatric outpatients aged 5-18 years and their parents., Results: Internal consistency reliability exceeded 0.70 for both proxy-reported and self-reported scales. Test-retest reliability demonstrated large values for parent proxy-report (range: 0.68-0.79) and moderate to large values for child self-report (range: 0.46-0.73). Parent proxy-report health-related quality of life (HRQOL) was higher than child self-report in all scales except for School Functioning. The correlations between the reports of the parents and children were moderate to high. Gender differences were observed in Social Functioning, School Functioning, and Psychosocial Health Summary, with girls reporting higher HRQOL than boys. Factor analysis indicated that four factors were extracted from the PedsQL 4.0 SF15 and these four factors corresponded mainly to the four scales. Known groups validity was established for proxy-report and self-report with higher HRQOL being reported for healthy children than those with psychosomatic complaints including headache and abdominal pain., Conclusion: The Japanese translation version of the PedsQL 4.0 SF15 demonstrates good reliability and validity and could be used as a measure of HRQOL for transcultural comparisons of pediatric research in school settings and healthcare services research.

Objective: To investigate whether there is a relationship between sib-size, birth order and the risk of overweight in junior high school students., Method: Sib-size, birth order, height and weight of subjects and their parents, and other lifestyle factors were obtained through a questionnaire survey conducted between June and July 2002 from 7,959 junior high students in Toyama prefecture, Japan. Logistic regression analysis was performed to examine the associations. Boys and girls were analyzed separately., Results: Boys from three-child families showed a significantly lower risk of overweight than only boys (odds ratio (OR)=0.66, p=0.010), and girls from larger families have a significantly lower risk than only girls (p for trend=0.001). Compared to middle-born girls, only girls have a significantly higher risk of overweight (OR=2.22, p<0.001). The risk of overweight in boys was significantly lower with increasing number of elder sibling or sister. However, increasing of any one sibling almost had the same risk reduction effect on the risk of overweight in girls (OR ranged from 0.74 to 0.76, p<=0.001)., Conclusion: Children without siblings are the ones most at risk for overweight, especially in girls. Birth order and sib-size are possible risk factors for the development of overweight and obesity.

Background: Lifestyles are associated with physical and mental health status, as well as health-related quality of life (QOL) in adults. There is little information about relation between lifestyles and QOL in children. This study aims to examine the correlation among Japanese children., Methods: Subjects were from the Toyama Birth Cohort Study, a prospective, longitudinal survey of children born between 1989 and 1990 in Toyama Prefecture, Japan. When children were 12-13 years in 2002, a cross-sectional questionnaire-based survey was administered. The questionnaire designed to measure lifestyles included questions on eating, physical activity, sleep, and other factors. For QOL measurement, a validated Japanese version of the COOP Charts was used. Data from 7,887 children were available and logistic regression analyses were used., Results: Children with undesirable lifestyles, such as skipping breakfast, less participation in physical activity, longer television viewing, and later bedtime, were more likely to have poor QOL in domains of physical fitness, feelings, overall health, and quality of life. These correlations were independent of sex, BMI, social background, and somatic symptoms., Conclusions: Undesirable lifestyles are positively associated with impaired QOL among children. Further understanding of these relationships will facilitate the development of interventions to help children with poor QOL.

Study Objective: To determine gender and weekly differences in sleep patterns in Japanese children in junior high school., Design: A school-based study., Setting: N/A., Participants: Ninety-one children, aged 13 to 14 years, from junior high schools in Japan., Interventions: N/A., Measurements: Sleep patterns were measured using actigraphy (Actiwatch) for 7 consecutive days, in parallel with daily logs and a questionnaire., Results: Girls showed better indicators of sleep and higher degrees of motionless sleep during the week. Actual sleep values and sleep efficiency were higher and the fragmentation index was lower in girls compared to in boys. On weekends, bedtime was delayed, especially for boys--11:17 PM versus 10:49 PM for girls. A higher level of activity during sleep was more evident among boys, especially during weekends. Boys also showed a higher number of nighttime awakenings. Subjective complaints such as drowsiness and desire for a longer sleep time were significantly higher for the boys., Conclusion: Our findings support the hypothesis that, during the junior high school period, the majority of sleep-quality indicators in Japanese schoolchildren were better for girls than for boys. Boys' sleep was less efficient and more fragmented during the entire week in comparison to that of the girls. These objective findings are supported by subjective assessments. Additional studies should clarify whether these disparities are culturally determined or represent a universal gender-specific characteristic.

Three new acetylated flavonoid glycosides, 5,6,4'-trihydroxyflavone 7-O-alpha-L-2,3-di-O-acetylrhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (1), apigenin 7-O-alpha-L-3-O-acetylrhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (2), and apigenin 7-O-alpha-L-2,3-di-O-acetylrhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (3), were isolated from Scoparia dulcis together with the known compound eugenyl beta-D-glucopyranoside (4). Their structures were elucidated by spectroscopic analyses. Compounds 2 and 3 showed an enhancing activity of nerve growth factor-mediated neurite outgrowth in PC12D cells.

Background: The validity of sleep quality and quantity indices as reported by schoolchildren has not been established. The purpose of this study is to evaluate the relationship between subjective sleep habits estimation and objective measurement data in schoolchildren., Methods: The study consisted of 42 healthy junior high school children aged 13-14. Sleep log information was gathered over 7 consecutive days, using a sleep-monitoring device (Actiwatch) and a questionnaire which covered the following aspects for sleep quality and quantity: bed time, sleep latency, sleep start, sleep end, wake up and assumed sleep length. The means of the sleep indices for 5 weekdays were used for analysis. Pearson's correlation coefficients and paired t-tests were used to evaluate the correlation and difference between subjective and objective sleep parameters., Results: The correlation coefficient between subjective and objective records was 0.49 (p < 0.001) for sleep latency, 0.99 (p < 0.001) for sleep start time, 0.99 (p < 0.001) for sleep end time, and 0.97 (p < 0.001) for assumed sleep length. The difference between subjective and objective records was 7.67 min (95% confidence interval [CI]: 4.64-10.71) for sleep latency, and 0:02 min (95% CI: -0:01-0:05) for sleep start time, 0:02 min (95% CI: 0:01-0:03) for sleep end time, and 8.19 min (95% CI: 4.93-11.45) for assumed sleep length., Conclusions: Although children tended to overestimate sleeping hours, the correlation between subjective and objective sleep indices except sleep latency was quite high. Thus, children's sleep questionnaire can be applied to surveys for sleep habits screening.

Two new sterols, stigmast-5-ene 3beta,4beta,7alpha,22alpha-tetraol (1) and stigmast-5-ene 3beta,7alpha,22alpha-triol (2), were isolated from the aerial parts of a Paraguayan medicinal plant, Verbena littoralis, together with the known compounds ursolic acid (3) and oleanolic acid (4). The structures of 1 and 2 were elucidated by spectroscopic analyses. Compounds 2-4 showed an enhancing activity of nerve growth factor (NGF)-mediated neurite outgrowth in PC12D cells.

A registry based study was conducted to assess the variation in first-onset stroke with weekdays and seasons, in relation to the effects of age. Between 1 December 1991 and 30 November 1998, 10,729 first-onset stroke patients aged 25 or more were registered in Toyama Prefecture, Japan. We compared the weekly and seasonal variation in first-onset stroke by a one-way goodness-of-fit chi(2)-test. The relationship between seasonal variation in stroke onset and age was also evaluated by the method of Kendall's tau-b R x C tables with ordered categories. The frequency of onset of all strokes and cerebral infarctions (CI) was significantly higher on weekdays than at weekends (P < 0.01). More men had strokes and CI on a Monday (P < 0.01), and more women had cerebral hemorrhage (CH) on a Monday and CI at the end of the week. Stroke incidence was higher in patients aged less than 60 years (20.6%) than in those aged 60 years or over (18.7%) on a Monday compared to the weekend. By chi(2)-test, comparing observed with expected numbers of stroke onsets, weighted by the number of days in each 3-month period, the incidence of all strokes, CI and CH was significantly higher in winter and spring than in summer. The seasonal variation in the onset of stroke declined with age: all strokes (P < 0.001) and CH (P < 0.001) in both genders; subarachnoid hemorrhage (P < 0.001) only in men. Our study shows that the onset of stroke is more frequent on weekdays than on weekends, and may be associated with changes in psychophysiological stresses between working days and the weekend. We also observed a clear negative dose response relationship between seasonal variations in occurrence and age. It may be speculated that younger people have more change to work outdoors, exposing themselves to the winter environment. Their lifestyle and physiological condition may be different from those of older people.

The aim of this study was to evaluate the validity of sleeping hours of young children as reported by their parents. The subjects were 21 healthy children aged 3 to 4 years. They were asked to attach a small instrument for calculating sleeping hours objectively, over 3 consecutive nights. Parents reported the sleeping hours of their children during the study periods. The mean values were used in the analysis. Pearson's correlation coefficients and paired t-tests were used to evaluate the correlations and differences between the reported and objectively measured sleeping hours. The correlation coefficient and difference between the reported and assumed (objective sleeping hours representing the difference between times for falling asleep and waking) sleeping hours were 0.90 (p<0.001) and 0.79 hours (95% confidence interval: 0.59-0.99), respectively. The correlation coefficient and difference between the reported and actual (the assumed sleeping hours minus the sum of epochs being scored as awake during the assumed sleep) sleeping hours were 0.90 (p<0.001) and 0.92 hours (0.73-1.10), respectively. Although parents tended to overestimate the sleeping hours of their children, the correlation between the reported and objective sleeping hours is high, which indicates that reported sleeping hours could be used in a survey that requires data on relative differences in sleeping hours amongst a given population.

A survey of unexpected cardiac arrests, excluding those associated with cardiac surgery, that had occurred during anesthesia and surgery in the period 1980-1999 was conducted. There was no significant difference between the number of such cardiac arrests that occurred in the 1980 s (29/36,159, 0.080%) and the number in the 1990 s (33/37,643, 0.088%). According to the classification by Keenan et al., there were 3 cases (0.0083%) in the 80 s and 4 cases (0.0106%) in the 90 s that occurred due to anesthetic management. Cardiac arrests due to surgery itself significantly decreased from 21 cases in the 80 s to 6 cases in the 90 s, probably due to proper treatment for massive bleeding, a decrease in the number of cases of anaphylactic shock, and the development of novel anesthetics. Conversely, cardiac arrests due to preoperative conditions of the patients significantly increased from 5 cases in the 80 s to 23 cases in the 90 s. This increase seems to be due to an increase in the number of severe and multiple injuries and an increase in complicated major surgery. The increase in number of cases due to preoperative conditions also depends on coronary spasm and cardiac conduction insufficiency. Taking into consideration the improvement in intraoperative monitoring and the development of novel anesthetics in the 90 s, greater efforts should be made by anesthesiologists to reduce the incidence of cardiac arrest due to anesthetic management, and preoperative evaluation of surgical patients needs to be reconsidered.

Aim: To observe the G-2964A and C734A genetic polymorphisms of human CYP1A2 in Chinese population., Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed in genotyping analysis., Results: The allele frequencies of A-2964 were 0.25 and 0.22 in Qidong and Changsha populations, respectively. The incidences of A734 were 0.68 in Qidong population and 0.66 in Changsha population. No more than two low-inducibility/activity alleles were presented in one person., Conclusion: The distribution of the G-2964A and C734A genetic polymorphisms did not show significant difference between Chinese and Japanese populations. The incidence of C734A in Chinese was also similar to that in Caucasian population.

Background: The 13C urea breath test (UBT) is considered to be the most accurate way of diagnosing Helicobacter pylori infection. Our objective was to investigate the accuracy of the UBT in Japanese patients and the association of UBT values with histological findings., Materials and Methods: A total of 169 consecutive patients were studied by endoscopy with histology, by serology with IgG antibody and test serum pepsinogen (PG), and by UBT. The association between UBT values and histological findings and the PG I / II ratio were analyzed in H. pylori-positive patients., Results: Of 169 Japanese patients, 135 were H. pylori-positive on both histology and serology analysis, 27 were H. pylori-negative on both histology and serology analysis, and 7 patients showed differing results. Using a cutoff value of 2.5 per thousand, test sensitivity was 100%, while specificity was 96%. Among the 135 H. pylori-positive patients, a significant relation was observed between UBT value and H. pylori colonization density of the corpus and antrum, neutrophil activity of the antrum, atrophy, and intestinal metaplasia of the corpus in the H. pylori-positive patients. Also, UBT values correlated with the PG I /II ratio. In multivariate analysis, the PG I /II ratio was the most important factor related to UBT values (odds ration [OR], 4. 99; 95% confidence interval, 1.60-15.55)., Conclusions: The UBT is an accurate method for detecting H. pylori infection in the Japanese population, which shows a high prevalence of atrophic gastritis. Values are affected by H. pylori infection and by the severity of atrophic gastritis.

Non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is a common disorder of middle-aged individuals characterized by high blood glucose levels which, if untreated, can cause serious medical complications and lead to early death. Genetic factors play an important role in determining susceptibility to this disorder. However, the number of genes involved, their chromosomal location and the magnitude of their effect on NIDDM susceptibility are unknown. We have screened the human genome for susceptibility genes for NIDDM using non-and quasi-parametric linkage analysis methods in a group of Mexican American affected sib pairs. One marker, D2S125, showed significant evidence of linkage to NIDDM and appears to be a major factor affecting the development of diabetes mellitus in Mexican Americans. We propose that this locus be designated NIDDM1.

A recent dietary survey shows that protein, energy and the majority of the mineral and vitamin intakes of the people in China are sufficient to meet their physiologic requirements. However, the dietary energy derived from cereals appear to be high and the dietary protein derived from animal foods is low. Thus, to improve the nutritional status of the Chinese people, a greater consumption of animal food is encouraged. The goal of an adequate adult diet is to maintain optimal health through a balanced intake of energy and all the essential nutrients. This can be achieved in China by the increase in food production through agriculture, fishery and animal husbandry, and by national planning utilizing the Recommended Dietary Allowances as the standard. Children are the future of our country. Hence, research on child nutrition should receive priority, particularly in the area of protein and energy requirements of pre-school children.

The HLA systems of forty Japanese patients with adult-onset nephrotic syndrome and biopsy-proven minimal change were investigated. HLA-DRw8 was found in 35% of the patients and HLA-DQw3 in 95%, compared to 12.6 and 63.1% of the control, respectively (DRw8: and Pc less than 0.01, RR = 3.74; DQw3: Pc less than 0.02, RR = 11.1). The phenotype frequencies of all but one HLA-DR antigens, DR4, DR5, DRw8, and DRw9 associating with DQw3, were observed to increase (patient vs. control: DR4, 65 vs. 41.4%; DR5, 10 vs. 4.3%; DRw9, 20 vs. 23%). These results suggest that HLA-DQw3 may be a primary genetic marker associated with a major susceptibility gene to adult-onset minimal change nephrotic syndrome in the Japanese population.