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Background: Little is known about how to effectively increase bystander cardiopulmonary resuscitation (CPR), so we evaluated the 10-year trend of the proportion of bystander CPR in an area with wide dissemination of chest compression-only CPR (CCCPR) training combined with conventional CPR training., Methods and results: We conducted a descriptive study after a community intervention, using a prospective cohort from September 2010 to December 2019. The intervention consisted of disseminating CCCPR training combined with conventional CPR training in Toyonaka City since 2010. We analyzed all non-traumatic out-of-hospital cardiac arrest (OHCA) patients resuscitated by emergency medical service personnel. The primary outcome was the trend of the proportion of bystander CPR. We conducted multivariate logistic regression models and assessed the adjusted odds ratio (AOR) using a 95% confidence interval (CI) to determine bystander CPR trends. Since 2010, we have trained 168,053 inhabitants (41.9% of the total population of Toyonaka City). A total of 1,508 OHCA patients were included in the analysis. The proportion of bystander CPR did not change from 2010 (43.3%) to 2019 (40.0%; 1-year incremental AOR 1.02 [95% CI: 0.98-1.05])., Conclusions: The proportion of bystander CPR did not increase even after wider dissemination of CPR training. In addition to continuing wider dissemination of CPR training, other strategies such as the use of technology are necessary to increase bystander CPR.

Pyrola japonica, a member of the family Ericaceae, is a mixotroph that grows on forest floors and obtains carbon (C) from both its photosynthesis and its mycorrhizal fungi. Its mycorrhizal community is dominated by Russulaceae. However, the mechanism of its C acquisition and its flexibility are not well understood. Our aim was to assess the impact of disturbance of the mycorrhizal fungal communities on C acquisition by P. japonica. We repeatedly applied a fungicide (Benomyl) to soils around P. japonica plants in a broad-leaved forest of central Japan, in order to disturb fungal associates near roots. After fungicide treatment, P. japonica roots were collected and subjected to barcoding by next-generation sequencing, focusing on the ITS2 region. The rate of mycorrhizal formation and α-diversity did not significantly change upon fungicide treatments. Irrespective of the treatments, Russulaceae represented more than 80% of the taxa. Leaves and seeds of the plants were analysed for 13 C stable isotope ratios that reflect fungal C gain. Leaf and seed δ 13 C values with the fungicide treatment were significantly lower than those with the other treatments. Thus the fungicide did not affect mycorrhizal communities in the roots, but disturbed mycorrhizal fungal pathways via extraradical hyphae, and resulted in a more photosynthetic behaviour of P. japonica for leaves and seeds., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We investigated the impact of the Coronavirus disease 2019 (COVID-19) pandemic on the management of endocrine and metabolic disorders in Japan. We conducted a cross-sectional nationwide questionnaire survey targeting board-certified endocrinologists under the auspices of the Japan Endocrine Society. The questionnaire consisted of multiple-choice questions and open-ended responses. Out of approximately 2,700 specialists, 528 (19.5%) opted to participate, suggesting a high level of interest in COVID-19 management among endocrinologists. The study found that almost half of participants had encountered cases of endocrine and metabolic disorders following COVID-19 infection or vaccination. Conditions related to thyroid diseases, glucose metabolism disorders/diabetes, and hypothalamic-pituitary disorders were particularly prevalent. Diabetes and obesity were identified as having high rates of severe cases or fatalities due to COVID-19. The study also highlighted challenges in routine diagnosis and treatment, emphasizing the potential benefits of combining remote consultations with in-person visits to optimize the frequency of examinations and check-ups during infectious disease outbreak which disrupts access to healthcare providers. The insights obtained from this survey are expected to contribute to ensuring appropriate healthcare provision for patients with endocrine and metabolic disorders by using flexible consultation formats, particularly even in the conditions where medical access may be limited due to future outbreaks of emerging or re-emerging infectious diseases.

Background: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset., Methods and Results: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/)., Conclusions: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum β-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan., Competing Interests: Declaration of competing interest Koichiro Wada received speaker honoraria from Janssen Pharmaceuticals, Inc. Satoshi Takahashi received speaker honoraria from Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Shin Ito received research funding from Hologic, Inc., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Mounting evidence suggests that body mass index (BMI) is inversely associated with the risk of lung cancer. However, relatively few studies have explored this association in Asian people, who have a much lower prevalence of obesity than Caucasians. We pooled data from 10 prospective cohort studies involving 444,143 Japanese men and women to address the association between BMI and the risk of lung cancer. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in each cohort using the Cox proportional hazards model. A meta-analysis was undertaken by combining the results from each cohort. Heterogeneity across studies was evaluated using Cochran's Q and I 2 statistics. During 5,730,013 person-years of follow-up, 6454 incident lung cancer cases (4727 men and 1727 women) were identified. Baseline BMI was inversely associated with lung cancer risk in men and women combined. While leanness (BMI <18.5) was associated with a higher risk of lung cancer (HR 1.35; 95% CI, 1.16-1.57), overweight and obesity were associated with a lower risk, with HRs of 0.77 (95% CI, 0.71-0.84) and 0.69 (95% CI, 0.45-1.07), respectively. Every 5 kg/m 2 increase in BMI was associated with a 21% lower risk of lung cancer (HR 0.79; 95% CI, 0.75-0.83; p < 0.0001). Our pooled analysis indicated that BMI is inversely associated with the risk of lung cancer in the Japanese population. This inverse association could be partly attributed to residual confounding by smoking, as it was more pronounced among male smokers., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Since a single forest walk (Shinrin-yoku or forest bathing) session is reported to improve sleep temporarily, occasional forest walks may have a positive effect on daily sleep. Therefore, this study aimed to examine whether more frequent forest walking is associated with better daily sleep conditions. Data from the second survey of the Japan Multi-Institutional Collaborative Cohort (J-MICC) Daiko Study conducted among residents of Nagoya City, Japan, were used. The study design was a cross-sectional study. In total, 2044 participants (529 men and 1515 women; age, mean ± standard deviation: 58.8 ± 9.9 years) were included in the analysis. Frequent forest walks were associated with a low percentage of insomnia symptoms (Insomnia Severity Index ≥10) in women, but not in men. The adjusted odds ratio for the group that rarely took forest walks with reference to the group that engaged in the activity once a month or more often was 2.04 (95% confidence interval: 1.29-3.23) in women. Forest walk frequency was not significantly associated with sleep duration or sleep efficiency as measured by actigraphy in either men or women. In conclusion, the results suggested that increasing the frequency of forest walks or Shinrin-yoku may be effective in preventing insomnia in women.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score., Methods: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model., Results: Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls., Conclusion: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR., (© 2023. The Author(s).)

Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were β-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan., Competing Interests: Declaration of competing interest Satoshi Takahashi received speaker honoraria from MSD K.K., Fujirebio Inc. and research funding from Shino-Test Corporation, Roche Diagnostic K.K., Fujirebio Inc., and Abbott Japan Co., Ltd. Shingo Yamamoto received speaker honoraria from MSD K.K., Fuso Pharmaceutical Industries, Ltd., Daiichi Sankyo Co., Ltd. and scholarship donations from Takeda Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Ono Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd. and research funding from Takeda Pharmaceutical Co., Ltd. Tetsuya Matsumoto received speaker honoraria from MSD K.K., Pfizer Japan Inc., and Kyorin Pharmaceutical Co., Ltd., and research funding from Kewpie Corporation., Biofermin Pharmaceutical Co., Ltd. Hiroyuki Nishiyama received research funding from Chugai Pharmaceutical Co., Ltd. Kazumasa Matsumoto received research funding from Sysmex Corporation. Junichi Inokuchi received research funding from Chugai Pharmaceutical Co., Ltd., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background Many prenatal factors are reported to be associated with congenital heart defects (CHD) in offspring. However, these associations have not been adequately examined using large-scale birth cohorts. Methods and Results We evaluated a data set of the Japan Environmental and Children's Study. The primary outcome was a diagnosis of CHD by age 2 years. We defined the following variables as exposures: maternal baseline characteristics, fertilization treatment, maternal history of diseases, socioeconomic status, maternal alcohol intake, smoking, tea consumption, maternal dietary intake, and maternal medications and supplements up to 12 weeks of gestation. We used multivariable logistic regression analysis to assess the associations between various exposures and CHD in offspring. A total of 91 664 singletons were included, among which 1264 (1.38%) had CHD. In multivariable analysis, vitamin A supplements (adjusted odds ratio [aOR], 5.78 [95% CI, 2.30-14.51]), maternal use of valproic acid (aOR, 4.86 [95% CI, 1.51-15.64]), maternal use of antihypertensive agents (aOR, 3.80 [95% CI, 1.74-8.29]), maternal age ≥40 years (aOR, 1.59 [95% CI, 1.14-2.20]), and high maternal hemoglobin concentration in the second trimester (aOR, 1.10 per g/dL [95% CI, 1.03-1.17]) were associated with CHD in offspring. Conclusions Using a Japanese large-scale birth cohort study, we found 6 maternal factors to be associated with CHD in offspring.

Background: We aimed to investigate the association between blood urea nitrogen to creatinine ratio (BCR) and survival with favourable neurological outcomes in patients with out-of-hospital cardiac arrest (OHCA)., Methods: This prospective, multicentre, observational study conducted in Osaka, Japan enrolled consecutive OHCA patients transported to 16 participating institutions from 2012 through 2019. We included adult patients with non-traumatic OHCA who achieved a return of spontaneous circulation and whose blood urea nitrogen and creatinine levels on hospital arrival were available. Based on BCR values, they were divided into: 'low BCR' (BCR <10), 'normal BCR' (10 ≤ BCR < 20), 'high BCR' (20 ≤ BCR < 30), and 'very high BCR' (BCR ≥ 30). We evaluated the association between BCR values and neurologically favourable outcomes, defined as cerebral performance category score of 1 or 2 at one month after OHCA., Results: Among 4415 eligible patients, the 'normal BCR' group had the highest favourable neurological outcome [19.4 % (461/2372)], followed by 'high BCR' [12.5 % (141/1127)], 'low BCR' [11.2 % (50/445)], and 'very high BCR' groups [6.6 % (31/471)]. In the multivariable analysis, adjusted odds ratios for 'low BCR', 'high BCR', and 'very high BCR' compared with 'normal BCR' for favourable neurological outcomes were 0.58 [95 % confidence interval (CI 0.37-0.91)], 0.70 (95 % CI 0.49-0.99), and 0.40 (95 % CI 0.21-0.76), respectively. Cubic spline analysis indicated that the association between BCR and favourable neurological outcomes was non-linear (p for non-linearity = 0.003). In subgroup analysis, there was an interaction between the aetiology of arrest and BCR in neurological outcome (p for interaction <0.001); favourable neurological outcome of cardiogenic OHCA patients was lower when the BCR was higher or lower, but not in non-cardiogenic OHCA patients., Conclusions: Both higher and lower BCR were associated with poor neurological outcomes compared to normal BCR, especially in cardiogenic OHCA patients., Competing Interests: Declaration of competing interest All the authors declare that they have no potential conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Biliary tract cancer (BTC) has not been considered a tobacco-related cancer, largely because of inconclusive results from epidemiological studies. We herein evaluate the association between cigarette smoking and risk of death from BTC by anatomic subsite and sex using data from a large, prospective cohort study in Japan., Methods: The present study included 97,030 Japanese individuals who were enrolled in 1988-1990 and followed until 31 December 2009. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for the association of BTC with cigarette smoking, including smoking status, number of cigarettes smoked per day, and pack-years of smoking., Results: During a mean follow-up of 16.2 years, we documented 484 deaths (187 from gallbladder cancers and 297 from cancers of other and unspecified biliary tract parts). After adjustment for sex, age, body mass index, alcohol consumption, and history of gallstones, current smokers had a higher risk of death due to BTC (RR = 1.35, 95% CI = 1.01-1.79) than never smokers. In the analyses by anatomic subsite, current smoking was associated with an increased risk of death from gallbladder cancer (RR = 1.89 95% CI = 1.19-3.02), whereas no evidence of an association was noted for cancers of other and unspecified biliary tract parts (RR = 1.10, 95% CI = 0.77-1.58). Moreover, mortality risk increased with an increasing number of cigarettes smoked per day and pack-years of smoking, particularly for gallbladder cancer in men., Conclusion: Cigarette smoking is associated with an increased risk of death from BTC, particularly gallbladder cancer, in Japanese men., (© 2022. The Author(s).)

Dysnatremia is an electrolytic disorder commonly associated with mortality in various diseases. However, little is known about dysnatremia in out-of-hospital cardiac arrest (OHCA) cases. Here, we investigated the association between serum sodium level on hospital arrival and neurological outcomes after OHCA. This nationwide hospital-based observational study (The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry) enrolled patients with OHCA between 2014 and 2017. We included adult patients aged ≥ 18 years with non-traumatic OHCA who achieved return of spontaneous circulation (ROSC) and whose serum sodium level on hospital arrival was available. Based on the serum sodium level, patients were divided into three levels: hyponatremia (Na < 135 mEq/L), normal sodium level (Na ≥ 135 or ≤ 145 mEq/L), and hypernatremia (Na > 145 mEq/L). The primary outcome was 1-month survival with favourable neurological outcomes. Altogether, 34 754 patients with OHCA were documented, and 5160 patients with non-traumatic OHCA and who achieved ROSC were eligible for our analyses. The proportion of favourable neurological outcomes was highest in patients with normal sodium levels at 17.6% (677/3854), followed by patients with hyponatremia at 8.2% (57/696) and patients with hypernatremia at 5.7% (35/610). Moreover, hyponatremia and hypernatremia were associated with a decreased probability of favourable neurological outcomes compared with normal sodium level (vs. hyponatremia, adjusted odds ratio [AOR] 0.97, 95% confidence interval [CI] 0.95-0.99; vs. hypernatremia, AOR 0.96, 95% CI 0.94-0.98). Hypo- and hypernatremia on hospital arrival were associated with a decreased probability of favourable neurological outcomes in patients with non-traumatic OHCA who achieved ROSC., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: The association between spontaneous initial body temperature on hospital arrival and neurological outcomes has not been sufficiently studied in patients after out-of-hospital cardiac arrest (OHCA)., Methods: From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all patients with OHCA of medical origin aged > 18 years for whom resuscitation was attempted and who were transported to participating hospitals between 2012 and 2019. We excluded patients who were not witnessed by bystanders and treated by a doctor car or helicopter, which is a car/helicopter with a physician. The patients were categorized into three groups according to their temperature on hospital arrival: ≤35.9 °C, 36.0-36.9 °C (normothermia), and ≥ 37.0 °C. The primary outcome was 1-month survival, with a cerebral performance category of 1 or 2. Multivariable logistic regression analyses were performed to evaluate the association between temperature and outcomes (normothermia was used as the reference). We also assessed this association using cubic spline regression analysis., Results: Of the 18,379 patients in our database, 5014 witnessed adult OHCA patients of medical origin from 16 hospitals were included. When analyzing 3318 patients, OHCA patients with an initial body temperature of ≥37.0 °C upon hospital arrival were associated with decreased favorable neurological outcomes (6.6% [19/286] odds ratio, 0.51; 95% confidence interval, 0.27-0.95) compared to patients with normothermia (16.4% [180/1100]), whereas those with an initial body temperature of ≤35.9 °C were not associated with decreased favorable neurological outcomes (11.1% [214/1932]; odds ratio, 0.78; 95% confidence interval, 0.56-1.07). The cubic regression splines demonstrated that a higher body temperature on arrival was associated with decreased favorable neurological outcomes, and a lower body temperature was not associated with decreased favorable neurological outcomes., Conclusions: In adult patients with OHCA of medical origin, a higher body temperature on arrival was associated with decreased favorable neurologic outcomes., (© 2022. The Author(s).)

Background and Objectives: The incidence of coronavirus disease 2019 (COVID-19) has increased in Wakayama, Japan, due to the spread of the highly infectious B.1.1.7 variant. Before this event, the medical systems were almost unaffected. We aimed to assess the clinical characteristics of patients hospitalized with COVID-19 and the risk factors for therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. Materials and Methods: This single-center retrospective study enrolled 185 patients with mild to moderate COVID-19 hospitalized in our hospital without intensive care between 14 March and 31 May 2021. Results: In this period, 125 (67.6%) of the 185 patients had the B.1.1.7 variant. Sixty-three patients (34.1%) required remdesivir treatment. Age upon admission and length of hospitalization were significantly different between remdesivir treatment and careful observation groups (mean (standard deviation); 59.6 (14.7) versus 45.3 (20.6) years; p < 0.001 and median (interquartile range); 10 (9-12) versus 9 (8-10) years; p < 0.001). One patient was transferred to another hospital because of disease progression. At hospital admission, age ≥60 years (odds ratio (OR) 6.90, p < 0.001), a previous history of diabetes mellitus (OR 20.9, p = 0.002), B.1.1.7 variant (OR 5.30; p = 0.005), lower respiratory symptoms (OR 3.13, p = 0.011), headache (OR 3.82, p = 0.011), and fever ≥37.5 °C (OR 4.55, p = 0.001) were independent risk factors to require remdesivir treatment during the admission. Conclusions: Many patients with mild to moderate COVID-19 required the therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. From the clinical data obtained at admission, these risk factors could contribute to a prediction regarding the requirement of remdesivir treatment in cases of mild to moderate COVID-19.

The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC 90 ) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 μg/ml (2 μg/ml), 1 μg/ml (0.5 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.125 μg/ml (0.063 μg/ml), 0.125 μg/ml (0.125 μg/ml), 0.25 μg/ml (0.25 μg/ml), 0.031 μg/ml (0.031 μg/ml), 0.25 μg/ml (0.125 μg/ml), and 0.016 μg/ml (0.008 μg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Helicobacter pylori (H. pylori) infection is considered the leading cause of gastric cancer. Gastric cancer is currently a common cancer with high incidence and mortality rates, but it is expected that the incidence rate will gradually decrease as the H. pylori infection prevalence decreases in the future. When evaluating the effectiveness of gastric cancer prevention strategies, it is essential to note the differences in long-term cumulative risks between H. pylori-infected and uninfected populations, but this has not yet been precisely evaluated. In our study, we aimed to estimate the cumulative incidence risks of developing gastric cancer from birth to 85 years among H. pylori-infected and uninfected populations by using population-based cancer registry data and birth year-specific H. pylori infection prevalence rates. Death from gastric cancer and other causes of death were considered in the estimations of the adjusted cumulative incidence risks stratified by sex and H. pylori infection status. After performing 5000 Monte Carlo simulations with repeated random sampling using observed cancer incidence in selected three prefectures (Fukui, Nagasaki, Yamagata) of prefectural population-based cancer registry in Japan, the mean adjusted cumulative incidence risk for gastric cancer in the H. pylori-infected population was 17.0% for males and 7.7% for females and 1.0% for males and 0.5% for females in the uninfected population. These results calculated with Japanese cancer registry data may be useful in considering and evaluating future prevention strategies for gastric cancer in Japan., (© 2021 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined., Methods and results: ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria., Conclusions: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.

Background: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants., Methods: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples., Results: The baseline survey included 92,610 adults (mean age: 55.2 [standard deviation, 9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women., Conclusions: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.

An individual may contract coronavirus disease 2019 (COVID-19) and influenza simultaneously; hence, adequate measures must be undertaken for the next winter in Japan. In preparation for the future, this study aimed to clarify the incidence of influenza coinfection in patients with COVID-19 during the previous winter. We conducted a retrospective study of the medical records of 193 patients diagnosed with COVID-19 between January 31, 2020, and April 23, 2020, in a single hospital. We evaluated the incidence of COVID-19 and influenza coinfection. Using rapid diagnostic testing, we found that no patient with COVID-19 was coinfected with influenza. Coinfection with influenza and COVID-19 was rare during the past winter in Japan.

Importance: Repeat expansion of CGG in LRP12 has been identified as the causative variation of oculopharyngodistal myopathy (OPDM). However, to our knowledge, the clinicopathologic features of OPDM with CGG repeat expansion in LRP12 (hereafter referred to as OPDM&#95;LRP12) remain unknown., Objective: To identify and characterize the clinicopathologic features of patients with OPDM&#95;LRP12., Design, Setting, and Participants: This case series included 208 patients with a clinical or clinicopathologic diagnosis of oculopharyngeal muscular dystrophy (OPDM) from January 1, 1978, to December 31, 2020. Patients with GCN repeat expansions in PABPN1 were excluded from the study. Repeat expansions of CGG in LRP12 were screened by repeat primed polymerase chain reaction and/or Southern blot., Main Outcomes and Measures: Clinical information, muscle imaging data obtained by either computed tomography or magnetic resonance imaging, and muscle pathologic characteristics., Results: Sixty-five Japanese patients with OPDM (40 men [62%]; mean [SD] age at onset, 41.0 [10.1] years) from 59 families with CGG repeat expansions in LRP12 were identified. This represents the most common OPDM subtype among all patients in Japan with genetically diagnosed OPDM. The expansions ranged from 85 to 289 repeats. A negative correlation was observed between the repeat size and the age at onset (r2 = 0.188, P = .001). The most common initial symptoms were ptosis and muscle weakness, present in 24 patients (37%). Limb muscle weakness was predominantly distal in 53 of 64 patients (83%), but 2 of 64 patients (3%) had predominantly proximal muscle weakness. Ptosis was observed in 62 of 64 patients (97%), and dysphagia or dysarthria was observed in 63 of 64 patients (98%). A total of 21 of 64 patients (33%) had asymmetric muscle weakness. Aspiration pneumonia was seen in 11 of 64 patients (17%), and 5 of 64 patients (8%) required mechanical ventilation. Seven of 64 patients (11%) developed cardiac abnormalities, and 5 of 64 patients (8%) developed neurologic abnormalities. Asymmetric muscle involvement was detected on computed tomography scans in 6 of 27 patients (22%) and on magnetic resonance imaging scans in 4 of 15 patients (27%), with the soleus and the medial head of the gastrocnemius being the worst affected. All 42 muscle biopsy samples showed rimmed vacuoles. Intranuclear tubulofilamentous inclusions were observed in only 1 of 5 patients., Conclusions and Relevance: This study suggests that OPDM&#95;LRP12 is the most frequent OPDM subtype in Japan and is characterized by oculopharyngeal weakness, distal myopathy that especially affects the soleus and gastrocnemius muscles, and rimmed vacuoles in muscle biopsy.

Background: In Japan, there are ongoing efforts to shift the gastric cancer prevention and control policy priorities from barium-based screening to Helicobacter pylori (H. pylori)-oriented primary prevention. A comprehensive summary of the evidence regarding the effects of H. pylori eradication on the risk of gastric cancer could inform policy decisions., Methods: We conducted a systematic review and meta-analysis of published studies evaluating the effectiveness of H. pylori eradication for the prevention of gastric cancer in otherwise healthy individuals (primary prevention) and early gastric cancer patients (tertiary prevention)., Results: In total, 19 studies were included. Three moderate-quality observational cohort studies showed that H. pylori eradication may be associated with a decreased risk of gastric cancer in healthy asymptomatic Japanese people. There is moderate certainty regarding the effectiveness of H. pylori eradication in patients with gastrointestinal diseases, such as peptic ulcers. A meta-analysis of 10 observational studies with otherwise healthy individuals (mainly peptic ulcer patients) yielded an overall odds ratio of 0.34 (95% CI: 0.25-0.46). Regarding tertiary prevention, the overall odds ratio for developing metachronous gastric cancer was 0.42 (95% CI: 0.35-0.51) in the eradication group in a meta-analysis of nine studies involving early gastric cancer patients who underwent endoscopic resection., Conclusion: H. pylori eradication is effective in preventing gastric cancer in the Japanese population, regardless of symptoms. Well-designed, large cohort studies are warranted to determine the long-term efficacy and safety of H. pylori eradication in the context of reducing the gastric cancer burden through population-based screening and treatment., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Although consumption of vegetable and 100% fruit juices are an acceptable alternative for vegetable and fruit intake, information about their actual effects on kidney function is sparse. The aim of this study was to determine the association between the consumption of vegetable and fruit juices and changes in kidney function in a Japanese population over a 5-y period., Methods: In this prospective study, we analyzed 2755 Japanese (742 men and 2013 women) individuals who participated in both the baseline and follow-up surveys in the Daiko study (a study within the Japan Multi-Institutional Collaborative Cohort study). Estimated glomerular filtration rate (eGFR) was calculated by age, sex, and serum creatinine level. For each beverage, we categorized all participants into four groups-rare (rarely consumed), low (≤2 cups/wk), moderate (3-4 cups/wk), or frequent (≥5 cups/wk) consumers of the beverage-based on a food frequency questionnaire., Results: The mean baseline and follow-up eGFR (SD) were 82.4 (14.6) and 72.2 (12.6), respectively. In fully adjusted regression analyses, moderate consumption of vegetable juice was associated a lower decline in eGFR compared with the rare consumption group (β = -1.30; P = 0.01). Moreover, stratified analyses revealed that this significant association remained in those who were young, female, non-obese, normotensive, smoked cigarettes, consumed alcohol, or exercised. However, no significant association was found in analyses for fruit juices., Conclusions: This 5-y prospective study suggested an association between self-reported moderate consumption of vegetable juice and changes (possibly smaller decline) in kidney function in a relatively healthy Japanese population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Nivolumab is an increasingly used standard care treatment for heavily pretreated patients with advanced gastric cancer, with increasing clinical use in Japan. Data from retrospective studies on various tumors have shown the objective response rate to cytotoxic chemotherapy potentially improves after an exposure to immune checkpoint inhibitors. Based on these data, we conducted the multicenter observational REVIVE study to evaluate the efficacy and safety of cytotoxic chemotherapy in nivolumab-refractory or nivolumab-intolerant patients with advanced gastric cancer. Patients who are refractory or intolerant to nivolumab and scheduled to receive irinotecan monotherapy, oxaliplatin combination treatment or oral trifluridine/tipiracil hydrochloride therapy will be included. The primary end point is overall survival of nivolumab-pretreated patients with advanced gastric cancer after the cytotoxic chemotherapy. Clinical trial registration: UMIN000032182 (umin.ac.jp).

Background: Pancreatic cancer treatment is evolving, but few studies have examined a nationwide trend in the treatment patterns. The purpose of this study was to clarify real-world treatment patterns for pancreatic cancer in Japan., Methods: This retrospective study examined the treatment patterns among 68 479 patients, who had pancreatic cancer diagnosis in Medical Data Vision claims database from 2010 to 2018. We extracted relevant data on treatment options, including chemotherapy, surgery and their combination. For patients who had undergone chemotherapy, we sought to analyse the use of different chemotherapy regimens. In addition, we examined the trend in treatment patterns by age group (<59, 60-69, 70-79, ≥80)., Results: The trend in treatment options of pancreatic cancer remained stable from 2010 to 2018, with chemotherapy being the most common therapeutic option and surgery performed in approximately half that of chemotherapy. On the other hand, the use of chemotherapy regimen had changed during the same period. Although gemcitabine was the most commonly administrated single-agent regimen in 2010, gemcitabine + nab-paclitaxel was the most frequently used therapeutic agent in 2018. In the older age groups (age ≥80), the majority of patients was untreated (supposedly received supportive care), and the use of conventional regimens such as gemcitabine or S-1 was common among those undergoing chemotherapy., Conclusions: Although chemotherapy has been the main treatment option for pancreatic cancer, the regimens of choice have increased significantly during the last decade. With accumulating evidence on combination chemotherapy, treatment options may further evolve in the future., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Due to the changes in consumer demand and generational transformations, Kyoto's traditional craft industry has suffered substantial revenue losses in recent years. This research aimed to characterize Kyoto's traditional craft industry by analyzing the supplier-customer network involving individual firms within the Kyoto region. In the process, we clarify the community structure, key firms, network topological characteristics, bow-tie structure, robustness, the vulnerability of the supplier-customer network as crucial factors for sustainable growth. The community and bow-tie structure analysis became clear that the traditional craft industry continues to occupy an important position in Kyoto's industrial network. Furthermore, we clarify the relationship between modern and traditional craft industries' network characteristics and their relative profitability and productivity. It became evident that the traditional craft industry has a different network structure from the modern consumer games and electric machinery industries. The modern industries have the strongly coupled component, and the attendant firms there create high value-added and play a significant role in driving the entire industry, while more traditional craft industries, such as the Nishijin silk fabrics and Kyoto doll industries, do not have this strongly coupled component. Moreover, the traditional crafts industry does not have a central firm or a dense network for integrating information, which is presumed to be a factor in the decline of the traditional craft industry., Competing Interests: The authors have declared that no competing interests exist.

In February 2013, Japan became the first country in the world to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system. Now that eradication therapy is covered by NHI, its usage has increased dramatically, and gastric cancer deaths have begun to decrease. We undertook a detailed epidemiological analysis to investigate effects of expanded NHI coverage for H. pylori eradication therapy on gastric cancer deaths in specific age groups. Numbers of gastric cancer deaths were determined by referencing data from Ministry of Health, Labour and Welfare reports and "Cancer Statistics in Japan - 2018" published by the Foundation for Promotion of Cancer Research. Gastric cancer deaths across all age groups have been clearly decreasing since 2013, but deaths of people aged 80 years and older are still increasing. The number of gastric cancer deaths in people aged in their 80s was 2 times higher than in people aged in their 70s and 4 times higher than in people aged in their 60s. The number of people in their 80s who had an endoscopy was less than half that of people in their 60s and 70s. The eradication therapy has increased dramatically, and gastric cancer deaths are clearly decreasing in Japan. However, this decrease in deaths has not extended to elderly adults aged in their 80s, which suggests that measures to prevent gastric cancer in people aged 80 years and older will be critical to achieving the mission of eliminating gastric cancer in Japan., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

The aim of this study was to further examine the relationship between milk intake and stroke mortality among the Japanese population. We used data from the Japan Collaborative Cohort (JACC) Study (total number of participants = 110,585, age range: 40-79) to estimate the posterior acceleration factors (AF) as well as the hazard ratios (HR) comparing individuals with different milk intake frequencies against those who never consumed milk at the study baseline. These estimations were computed through a series of Bayesian survival models that employed a Markov Chain Monte Carlo simulation process. In total, 100,000 posterior samples were generated separately through four independent chains after model convergency was confirmed. Posterior probabilites that daily milk consumers had lower hazard or delayed mortality from strokes compared to non-consumers was 99.0% and 78.0% for men and women, respectively. Accordingly, the estimated posterior means of AF and HR for daily milk consumers were 0.88 (95% Credible Interval, CrI: 0.81, 0.96) and 0.80 (95% CrI: 0.69, 0.93) for men and 0.97 (95% CrI: 0.88, 1.10) and 0.95 (95% CrI: 0.80, 1.17) for women. In conclusion, data from the JACC study provided strong evidence that daily milk intake among Japanese men was associated with delayed and lower risk of mortality from stroke especially cerebral infarction.

Background: Regorafenib demonstrated survival benefits as salvage therapy for patients with metastatic colorectal cancer. However, severe toxicities frequently occurred early in the treatment with the standard dose (160 mg/day), resulting in a dose reduction or interruption. To improve the tolerability and maintain sufficient efficacy, we conducted a phase II study of regorafenib with a lower starting dose (120 mg/day)., Patients and Methods: Regorafenib was initiated at 120 mg/day, and the dosage was increased to 160 mg/day on day 15 of the first cycle for patients who had met the dose escalation criteria. The primary endpoint was the disease control rate (DCR). The pharmacokinetics of the total and unbound regorafenib and its active metabolites (M2, M5) were assessed., Results: A total of 70 patients were enrolled from September 2016 to December 2017. Only 6 patients achieved dose escalation to 160 mg on day 15 as planned. For the 68 evaluable patients, the DCR was 32.4% (95% confidence interval, 21.5%-44.8%), which was less than the threshold (30%) of our statistical hypothesis. The serum concentrations of total regorafenib for patients whose dose was escalated to 160 mg/day were significantly lower than those of the patients whose dose was not escalated (median, 3978 vs. 7244 nM; P = .027). The serum unbound concentrations of the sum of regorafenib and the active metabolites correlated significantly with the maximum grade of regorafenib-related symptomatic adverse events in the first cycle (11,138 vs. 19,096 pM; P = .035)., Conclusion: Regorafenib with a low starting dose of 120 mg/day did not achieve the expected DCR. A relationship of unbound exposure with toxicity was found., (Copyright © 2019 Elsevier Inc. All rights reserved.)

A moderately thermophilic and heterotrophic bacterial strain, LA T , was isolated from microbial mats sampled at a hot spring in Nakabusa, Nagano, Japan. The cells of strain LA T were aerobic, Gram-stain-negative, non-sporulating, non-motile and rod-shaped (2.0-4.1 µm long). The formation of dense cell aggregates in liquid medium was a unique characteristic of the strain. Strain LA T grew optimally at 50°C and at pH 7.5. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the nearest neighbour of strain LA T was Schleiferia thermophila JCM 30197 T with 94.1 % sequence similarity. The draft genome sequence of strain LA T (2 671 880 bp) showed 18.0 % digital DNA-DNA hybridization, 70.9 % average nucleotide identity and 72.1 % average amino acid identity (AAI) values in comparison with the genome sequence of S. thermophila JCM 30197 T (2 606 763 bp); the 16S rRNA gene sequence similarity and AAI values are lower than the cutoffs used for assignment to a separate genus. On the basis of phenotypic features, major cellular fatty acid composition, genome sequencing and phylogenetic position, a novel genus and species are proposed for strain LA T , to be named Thermaurantimonas aggr egans (= JCM 31826 T =DSM 106522 T ).

The aim of this study is to show the combined effect of weight gain within normal weight range in adulthood and parental HT on the prevalence of HT. The study subjects were 44,998 individuals (19,039 men and 25,959 women) with normal weight (body mass index [BMI] 18.5-24.9) aged 35-69 years who participated in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. They were categorized into six groups by weight gain from age 20 years (<10 kg, and ≥10 kg) and by the number of parents having HT (no parent, one parent, and both parents). Odds ratios for HT were estimated after adjustment for age, sex, current BMI, estimated daily sodium intake, and other confounding factors. The prevalence of HT (31.5% in total subjects) gradually increased with greater weight gain from age 20 years and with greater number of parents with HT. Subjects who gained weight ≥10 kg and having both parents with HT showed the highest risk of having HT compared with those who gained weight <10 kg without parental HT (59.8% vs. 24.9%, odds ratio 4.25, 95% CI 3.53-5.13 after adjustment). This association was similarly observed in any category of age, sex, and BMI. Subjects who gained weight within normal range of BMI and having one or both parent(s) with HT showed the higher risk of having HT independent of their attained BMI in their middle ages. Thus, subjects having parent(s) with HT should avoid gaining their weight during adulthood, even within normal range of BMI, to reduce the risk of having HT.

Background: Mental health has become a major public health issue worldwide. Biological and epidemiological studies suggest diet has a role in the prevention or cure of mental disorders. However, further research is required to elucidate the relationship between diet and mental health. This study aimed to investigate associations between dietary intake of nutrients (macronutrients, vitamins, calcium, and fatty acids) and food groups (fish, meat and chicken, dairy products, and vegetables) and mental health among middle-aged Japanese in cross-sectional and prospective studies., Methods: In total, 9298 men and women that participated in two areas of the Japan Multi-Institutional Collaborative Cohort Study were eligible for analysis at the baseline (cross-sectional) survey. Of these, 4701 participants were followed for about 5 years and included in the follow-up (prospective) analysis. The 12-item General Health Questionnaire (GHQ) was used to assess participants' general mental health status over the past several weeks. The average intake of 46 foods over the past year was assessed by a validated food frequency questionnaire. We also evaluated lifestyle and medical factors using a self-administered questionnaire. A cross-sectional logistic regression analysis was performed to estimate odds ratios for a GHQ score ≥ 4 (poor mental health) according to dietary intake of foods/nutrients at baseline. The prospective study used baseline dietary and lifestyle factors and GHQ scores at follow-up., Results: The cross-sectional logistic regression analysis showed vegetables, protein, calcium, vitamin D, carotene and n-3 highly-polyunsaturated fatty acids were inversely associated with a GHQ score ≥ 4. On the other hand, mono-unsaturated fatty acids showed a positive association with higher GHQ score. The prospective logistic regression analysis found dairy products, calcium, vitamin B 2 , and saturated fatty acids were inversely correlated with a GHQ score ≥ 4. Calcium was associated with GHQ scores in both the cross-sectional and follow-up studies. In the follow-up study, the multivariable-adjusted odds ratio for a GHQ score ≥ 4 was 0.71 (95% confidence interval, 0.55-0.92) for the highest versus lowest quartiles of calorie-adjusted dietary calcium intake., Conclusion: Consuming particular nutrients and foods, especially calcium and dairy products, may lead to better mental health in Japanese adults.

Objectives: This study evaluated the safety and tolerability of anifrolumab, a monoclonal antibody targeting the type I interferon (IFN) receptor, in Japanese patients with moderate-to-severe systemic lupus erythematosus (SLE). Methods: In this open-label, phase 2, dose-escalation study, patients received intravenous (IV) anifrolumab 100, 300, or 1000 mg every 4 weeks from days 29 to 337 (Stage 1). Patients who completed Stage 1 continued anifrolumab 300 mg every 4 weeks for 156 weeks (Stage 2). The primary objective was to evaluate the safety of anifrolumab for 48 weeks (Stage 1) and 156 weeks (Stage 2). The pharmacokinetics and pharmacodynamics of anifrolumab were also assessed. Results: Of 20 patients enrolled in Stage 1, 17 received IV anifrolumab 100 mg ( n  = 6), 300 mg ( n  = 5), or 1000 mg ( n  = 6). Adverse events (AE) and serious AE (SAE) incidences were similar between dose cohorts. SAEs occurred in 41% (Stage 1) and 33% (Stage 2) of patients; AEs leading to discontinuation occurred in 24% (Stage 1) and 22% (Stage 2) of patients. Anifrolumab had non-linear pharmacokinetics after the first and last dose and dose-dependently suppressed the IFN gene signature. Conclusion: Anifrolumab was well tolerated among Japanese patients with moderate-to-severe SLE.

Phototrophic microbial mats are assemblages of vertically layered microbial populations dominated by photosynthetic microorganisms. In order to elucidate the vertical distribution and diversity of phototrophic microorganisms in a hot spring-associated microbial mat in Nakabusa (Japan), we analyzed the 16S rRNA gene amplicon sequences of the microbial mat separated into five depth horizons, and correlated them with microsensor measurements of O 2 and spectral scalar irradiance. A stable core community and high diversity of phototrophic organisms dominated by the filamentous anoxygenic phototrophs, Roseiflexus castenholzii and Chloroflexus aggregans were identified together with the spectral signatures of bacteriochlorophylls (BChls) a and c absorption in all mat layers. In the upper mat layers, a high abundance of cyanobacteria (Thermosynechococcus sp.) correlated with strong spectral signatures of chlorophyll a and phycobiliprotein absorption near the surface in a zone of high O 2 concentrations during the day. Deeper mat layers were dominated by uncultured chemotrophic Chlorobi such as the novel putatively sulfate-reducing "Ca. Thermonerobacter sp.", which showed increasing abundance with depth correlating with low O 2 in these layers enabling anaerobic metabolism. Oxygen tolerance and requirements for the novel phototroph "Ca. Chloroanaerofilum sp." and the uncultured chemotrophic Armatimonadetes member type OS-L detected in Nakabusa hot springs, Japan appeared to differ from previously suggested lifestyles for close relatives identified in hot springs in Yellowstone National Park, USA. The present study identified various microenvironmental gradients and niche differentiation enabling the co-existence of diverse chlorophototrophs in metabolically diverse communities in hot springs.

Introduction: Despite the excellent prognosis associated with pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), some patients still develop recurrence. Here, we investigated the outcomes of breast cancer patients with pCR, as well as the clinical and pathological predictors of cancer recurrence in these patients., Materials and Methods: Of the 1599 breast cancer patients treated with NAC, we evaluated 394 patients who achieved pCR between January 2007 and December 2016. pCR was defined as no evidence of invasive cancer in breast. Residual in situ ductal and axillary lymph node diseases were not considered. We analyzed the outcomes using the Kaplan-Meier method. We assessed the association of clinical and pathological predictors with cancer recurrence using the cox proportional hazards regression model., Results: The median follow-up time was 63 months. The 5-year disease-free survival rate was 92.3%. Cancer recurrence was observed in 28 patients (7.1%): local recurrence 8 patients (2.0%), visceral metastasis 10 patients (2.5%), and brain metastasis 10 patients (2.5%). Brain metastases were found in patients with HER2 type breast cancer. The significant predictors of cancer recurrence were HER2 positivity (p = 0.04), clinical tumor size (p < 0.01), and lymph node metastasis (p < 0.01) before NAC on univariate analysis and only lymph node metastasis on multivariate analysis., Conclusion: Patients achieving pCR to NAC showed excellent outcomes. Advanced clinical stage, large tumor size, presence of lymph node metastasis, and HER2 positivity before NAC were identified as significant predictors of cancer recurrence. Residual in situ ductal and lymph node diseases after NAC were not significant predictors., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: A voided volume (VV) of <50% of the expected bladder capacity for age is considered small VV. It was recommended that a VV ≥50% of expected bladder capacity for age is required to assess uroflowmetry (UFM) curves because a small VV causes changes in UFM curve characteristics. However, no clear consensus has been reached on the criterion for evaluating UFM curve patterns., Objective: The aim of the study was to evaluate the reproducibility and characteristics of UFM curve patterns in children with daytime urinary incontinence (DUI) and with a variety of VVs., Methods: This study investigated 119 children (79 boys and 40 girls) with primary DUI who underwent UFM 3 times on the same day and were classified into two groups: small VV (<50% of expected bladder capacity for age) in 0-1 of the 3 UFM measurements (group 1; normal VV) or in 2-3 of the 3 UFM measurements (group 2; small VV). The authors then evaluated the agreement of UFM curve patterns among the 3 measurements, classifying complete, partial, or no agreement according to the number of identical curve patterns. The authors also evaluated the most characteristic patterns of UFM curve patterns for each group., Results: Group 1 comprised 45 children, and group 2 comprised 74 children. Rates of complete agreement (group 1, 24/45; group 2, 30/74), partial agreement (group 1, 19/45; group 2, 35/74), and no agreement (group 1, 2/45; group 2, 9/74) did not differ significantly between groups (p = 0.226). Bell curve patterns were significantly more common in group 1 than in group 2 (p = 0.025). Frequency of the tower pattern was significantly higher in group 2 than in group 1 (p = 0.006) (Summary table)., Discussion: No differences in agreement rates of UFM curve patterns were seen between two groups (small and normal VV). The authors thus suggest that UFM curve patterns can be validly assessed in children with DUI and with small VV. It was found that the bell pattern was significantly more common among children with normal VV, whereas the tower pattern was significantly more common among children with small VV. The tower pattern reflects an overactive bladder. The present results suggest that some children have DUI that is not attributable to urgency., Conclusion: Reproducibility of UFM curve patterns might be properly assessed even in children with DUI and with small VV. This result suggests the presence of various pathological conditions other than the conditions with urgency underlying DUI., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The prevention of hypertension starts with the awareness of risk. Our aim was to construct a simple and well-validated risk model for nonhypertensive people in Japan consisting of basic clinical variables, using a dataset for two areas derived from the Japan Multi-Institutional Collaborative Cohort Study. We constructed a continuous-value model using data on 5105 subjects participating in both the baseline survey and a second survey conducted after 5 years. The area under the receiver operating characteristic curve (AUC) and the Hosmer-Lemeshow χ 2 statistic for the entire cohort were 0.826 and 7.06, respectively. For validation, the entire cohort was randomly divided 100 times into derivation and validation sets at a ratio of 6:4. The summarized median AUC and the Hosmer-Lemeshow χ 2 statistic were 0.83 and 12.2, respectively. The AUC of a point-based model consisting of integer scores assigned to each variable was 0.826 and showed no difference, compared with the continuous-value model. This simple risk model may help the general population to assess their risks of new-onset hypertension.

Forest walking or Shinrin-yoku is a health promotion activity in Japan. Although some studies have reported the acute effects of walking a few hours in forested areas in reducing blood pressure level compared to other environments, studies investigating whether successive walking has long-term effects in lowering blood pressure levels or lowering prevalence of hypertension are rare. This study aimed to reconfirm the presence or absence of an association between the frequency of forest walking and prevalence of hypertension in a Japanese population. This J-MICC Daiko Study was conducted targeting residents in Nagoya City. A total of 5,109 participants (1,452 men and 3,657 women; age, mean ± standard deviation: 52.5 ± 10.3 years) were included in the analysis. Age-adjusted blood pressure level by frequency of forest walking was not significant. After adjusting for age and lifestyle, the adjusted odds ratios (aORs) of the most frequent group (n=88, 1.7%; once a week or more group) relative to the less than once a month group (n=4,558, 89.2%) for prevalence of hypertension were not also significant [0.80 (95% CI: 0.40-1.62) for men and 1.48 (95% CI: 0.73-3.00) for women]. This study reconfirmed that either lowering blood pressure level or lowering the prevalence of hypertension is not associated with frequency of forest walking, similar to the results of our previous J-MICC Shizuoka Study. Given that these two studies were cross-sectional studies, cohort studies investigating the causal relationship are required to evaluate the effect of frequent forest walking on the prevention of hypertension., Competing Interests: The authors declare that they have no conflicts of interest.

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

The Japanese Surveillance Committee conducted a second nationwide surveillance of antimicrobial susceptibility patterns of uropathogens responsible for acute uncomplicated cystitis (AUC) in premenopausal patients aged 16-40 years old at 31 hospitals throughout Japan from March 2015 to February 2016. In this study, the susceptibility of causative bacteria (Escherichia coli, Klebsiella pneumoniae, Staphylococcus saprophyticus) for various antimicrobial agents was investigated by isolation and culturing of organisms obtained from urine samples. In total, 324 strains were isolated from 361 patients, including E. coli (n = 220, 67.9%), S. saprophyticus (n = 36, 11.1%), and K. pneumoniae (n = 7, 2.2%). The minimum inhibitory concentrations (MICs) of 20 antibacterial agents for these strains were determined according to the Clinical and Laboratory Standards Institute (CLSI) manual. At least 93% of the E. coli isolates showed susceptibility to fluoroquinolones and cephalosporins, whereas 100% of the S. saprophyticus isolates showed susceptibility to fluoroquinolones and aminoglycosides. The proportions of fluoroquinolone-resistant and extended-spectrum β-lactamase (ESBL)-producing E. coli strains were 6.4% (13/220) and 4.1% (9/220), respectively. The antimicrobial susceptibility of K. pneumoniae was retained during the surveillance period, while no multidrug-resistant strains were identified. In summary, antimicrobial susceptibility results of our second nationwide surveillance did not differ significantly from those of the first surveillance. Especially the numbers of fluoroquinolone-resistant and ESBL-producing E. coli strains were not increased in premenopausal patients with AUC in Japan., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess the renal and non-renal efficacy of mycophenolate mofetil (MMF) in Japanese patients with systemic lupus erythematosus (SLE)., Methods: We conducted a retrospective study to assess the renal and non-renal efficacies of MMF in Japanese patients with systemic lupus erythematosus (SLE). We analyzed 14 patients with lupus nephritis (LN) who were given MMF, and 13 patients who received monthly intravenous cyclophosphamide (IVCY) as induction therapy, and a further 19 patients without LN who were treated with MMF, and 13 patients who took tacrolimus (TAC) to reduce glucocorticoid dosages. We assessed the therapeutic effects of each therapeutic regime on renal and non-renal disease manifestations over a six-month period after treatment initiation., Results: Median urine protein to creatinine ratios in the MMF and IVCY groups significantly decreased from 2.2 to 0.7 g/gCr and from 3.3 to 0.5 g/gCr, respectively. Significant improvements in serum immunological variables (serum complements C3 and C4 and the anti-double stranded DNA antibody) and reductions in the SLE disease activity index (SLEDAI) and daily prednisolone dosages were observed in each group with LN. MMF and TAC significantly improved SLEDAI and serum immunological variables and reduced daily prednisolone dosages in patients without LN., Conclusion: The present results demonstrated that MMF might be an effective treatment for renal and non-renal manifestations in Japanese patients with SLE and has potential as a good therapeutic alternative and steroid-sparing agent.

Gout is a common arthritis caused by elevated serum uric acid (SUA) levels. Here we investigated loci influencing SUA in a genome-wide meta-analysis with 121,745 Japanese subjects. We identified 8948 variants at 36 genomic loci ( P <5 × 10 -8 ) including eight novel loci. Of these, missense variants of SESN2 and PNPLA3 were predicted to be damaging to the function of these proteins; another five loci- TMEM18 , TM4SF4 , MXD3-LMAN2 , PSORS1C1-PSORS1C2 , and HNF4A -are related to cell metabolism, proliferation, or oxidative stress; and the remaining locus, LINC01578 , is unknown. We also identified 132 correlated genes whose expression levels are associated with SUA-increasing alleles. These genes are enriched for the UniProt transport term, suggesting the importance of transport-related genes in SUA regulation. Furthermore, trans-ethnic meta-analysis across our own meta-analysis and the Global Urate Genetics Consortium has revealed 15 more novel loci associated with SUA. Our findings provide insight into the pathogenesis, treatment, and prevention of hyperuricemia/gout., Competing Interests: The authors declare no competing interests.

Background: There is a high incidence of type 2 diabetes in Asian adults, even those with a normal body mass index (BMI) (<25.0 kg/m2). For example, it has been shown that a slightly increased BMI (>23 kg/m2) at middle age is a risk factor for type 2 diabetes in Asians. In this historical cohort study, we investigated whether a slightly increased BMI at college age was also a risk factor for future diabetes in Japanese men., Methods: Six hundred and sixty-one male alumni who graduated from a physical education school between 1971 and 1991 and who responded to follow-up investigation between 2007 and 2017 were included in this study. Participants were categorized into four categories: college BMI of <21.0 kg/m2, 21.0-22.0 kg/m2, 22.0-23.0 kg/m2, and ≥23.0 kg/m2, and the incidence and risk ratio of diabetes were compared between groups., Results: The median follow-up period was 32 years (interquartile range, IQR: 27-36), which included 20,983 person-years of observation. Subjects were 22 (22-22) years old at college graduation, and 55 (50-59) years old at the final follow-up investigation. During the study period, 56 men developed diabetes; the prevalence rates for the lowest to highest BMI categories were 4.4%, 7.6%, 10.5%, and 11.3%, respectively, and their adjusted hazard ratios were 1.00 (reference), 1.77 (95% CI: 0.68-4.30), 2.42 (1.00-5.84), and 2.53 (1.06-6.07), respectively (p = 0.03 for trend)., Conclusion: Our data suggest that a BMI over 22.0 kg/m2 at college age is a risk factor for diabetes later in life in Japanese men., Competing Interests: The authors have declared that no competing interests exist.

Background: Although self-rated health (SRH) independently predicts mortality, the biological background of this association remains unexplained. This study aimed to examine the association between SRH and serum high-sensitivity C-reactive protein (hsCRP) level., Methods: Subjects were 899 participants aged 35-69 years (237 men and 662 women) in the Daiko Study, part of the Japan Multi-Institutional Collaborative Cohort Study. They were enrolled from 2008 to 2010. Of the subjects, 666 participated in a second survey 5 years later. Lifestyle factors and SRH were assessed using a self-administered questionnaire. Serum hsCRP level was measured using a latex-enhanced immunonephelometric assay. The association between SRH and serum hsCRP level was evaluated using a general linear model with covariates. We further longitudinally investigated whether higher serum hsCRP level at baseline predicts poor SRH after 5 years using an unconditional logistic regression model., Results: A higher serum hsCRP level was significantly associated with poor SRH at baseline after adjusting for covariates (p for trend = 0.023). The age- and sex-adjusted odds ratio and 95% confidence interval (CI) for poor SRH after 5 years was 1.45 (95% CI: 0.76-2.78) for the highest tertile compared with the lowest tertile of serum hsCRP level at baseline with a significant linear trend (p for trend = 0.033), although the risk increase disappeared after adjustment for other covariates., Conclusions: The present study demonstrated that poor SRH is cross-sectionally associated with higher serum hsCRP level. However, the longitudinal data did not support the relationship between serum hsCRP level at baseline and future SRH. Further longitudinal studies that include data on mortality and multiple inflammatory markers are warranted to elucidate the possible role of low-grade inflammation in the association between SRH and mortality risk.

Background: The efficacy of primary prophylactic granulocyte colony-stimulating factor (G-CSF) in preventing febrile neutropenia (FN) in patients treated with docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy remains controversial. We compared the incidence of FN in patients treated with and without primary prophylactic G-CSF., Methods: We performed a retrospective analysis of 142 patients with locally advanced head and neck or esophageal cancer treated with TPF between January 2009 and March 2017. Among them, 116 patients started TPF without primary prophylactic G-CSF (control group) while 26 patients were given primary prophylactic G-CSF from day 7 of the first cycle of TPF (prophylactic group)., Results: The incidence of grade 4 neutropenia during the first cycle of TPF was significantly higher in the control group than in the prophylactic group [58.6% (n = 68) vs. 30.8% (n = 8), p = 0.02]. However, the incidence of FN in the first cycle was not significantly different between the two groups [32 patients (27.5%) in the control group and 8 patients (30.8%) in the prophylactic group (p = 0.62)]. In addition, the mean relative dose intensity throughout all cycles of TPF, as well as the survival time and response after TPF, were also not significantly different between the two groups., Conclusions: Primary prophylactic G-CSF from day 7 of the first cycle of TPF did not reduce the incidence of FN. Our findings suggest that the timing of primary prophylactic G-CSF, as recommended by the American Society of Clinical Oncology guidelines, should be modified to reduce the incidence of FN in TPF.

Purpose: Although several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication studies have produced inconsistent results., Methods: We conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study., Results: We found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples., Conclusions: We identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.

Brief exposure to passive smoking immediately elevates blood pressure. However, little is known about the association between exposure to passive smoking and chronic hypertension. We aimed to examine this association in a cross-sectional study, after controlling multiple potential confounders.Participants included 32,098 lifetime nonsmokers (7,216 men and 24,882 women) enrolled in the Japan Multi-Institutional Collaborative Cohort Study. Passive smoking was assessed using a self-administered questionnaire. The single question about exposure to passive smoking had five response options: "sometimes or almost never," "almost every day, 2 hours/day or less," "almost every day, 2 to 4 hours/day," "almost every day, 4 to 6 hours/day," and "almost every day, 6 hours/day or longer." Hypertension was defined as any of the following: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or use of antihypertensive medication. Multivariate-adjusted odds ratio (OR) and 95% confidence interval (CI) for hypertension were estimated by exposure level to passive smoking using unconditional logistic regression models.The multivariate-adjusted OR for hypertension in those exposed almost every day was 1.11 (95% CI: 1.03-1.20) compared with those exposed sometimes or almost never. The OR for a 1-hour per day increase in exposure was 1.03 (95% CI: 1.01-1.06, Pfor trend = .006). This association was stronger in men than in women; the ORs were 1.08 (95% CI: 1.01-1.15, Pfor trend = .036) and 1.03 (95% CI: 1.00-1.05, Pfor trend = .055), respectively.Our findings suggest importance of tobacco smoke control for preventing hypertension.

The objective of this study was to investigate the clinical significance of the Wnt/β-catenin signaling pathway in glucocorticoid-induced osteoporosis. A total of 91 patients with systemic autoimmune diseases who received initial glucocorticoid therapy with prednisolone (30-60 mg daily) were prospectively enrolled. We measured serum levels of N-terminal peptide of type I procollagen (P1NP), bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), N-telopeptide cross-linked type I collagen (NTX), sclerostin, Dickkopf-1 (Dkk-1), and Wnt3a before starting glucocorticoid therapy and every week for 4 weeks after its initiation. The effects of dexamethasone on expression of mRNA and protein of sclerostin and Dkk-1 by cultured normal human osteoblasts (NHOst) were evaluated by RT-PCR and ELISA, respectively. Serum levels of sclerostin and Dkk-1 increased significantly by 1 week of glucocorticoid therapy and then decreased from the second week onward. Serum Wnt3a tended to decrease and serum P1NP showed a significant decrease. However, TRACP-5b was significantly elevated from the first week of treatment onwards. In vitro study, dexamethasone increased Dkk-1 mRNA expression in cultured NHOst, but sclerostin mRNA was not detected. Dexamethasone also increased Dkk-1 protein production by osteoblasts, whereas sclerostin protein was not detected. Bone formation might be impaired at least in the first week of the initiation of glucocorticoid therapy by increase of the serum Wnt signaling inhibitors; however, their reductions in the subsequent weeks were contradictory to the maintained suppression of the bone formation markers after glucocorticoid therapy for patients with systemic autoimmune diseases.

Erythrocyte count and volume are the commonly used hematological indices for anemia that change in various diseases. To date, however, only one study ever exists that addressed erythrocyte trait-associated single nucleotide polymorphisms (SNPs) in a Japanese population. Because that study was performed in patients with various diseases, we confirmed the reported associations in a general population. Participants in the current study were from the Shizuoka component of the Japan Multi-Institutional Collaborative Cohort Study, which included 4971 men and women aged 35 to 69years who were recruited between 2006 and 2007. We analyzed the association of seven selected SNPs with the following erythrocyte traits: red blood cell count, hemoglobin (Hb) and hematocrit (Ht) levels, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. The erythrocyte traits were regressed on a number of minor alleles of selected SNPs. Then we compared our findings with those from a genome-wide association study performed in a Japanese population. We replicated the association of ABO rs495828, PDGFRA-KIT rs218237, USP49-MED20-BSYL-CCND3 rs3218097, C6orf182-CD164 rs11966072, TERT rs2736100, and TMPRSS6 rs5756504 with erythrocyte traits in our independent Japanese population. In addition, we found a significant interaction between TERT rs2736100 and smoking habit that affected Hb and Ht levels., (Copyright © 2017. Published by Elsevier B.V.)