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Background: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness, with severe outcomes in older adults. Information on the prevalence, hospitalization rate, and impact on the health-related quality of life (HRQoL) of RSV in older adults with acute respiratory infections (ARI) in outpatient settings in Japan is limited., Methods: This multi-center epidemiological study included outpatients aged ≥60 years presenting with ARI between August 2021 and February 2023. Nasal and throat swabs were collected and tested by reverse transcription polymerase chain reaction (RT-PCR). The prevalence of RT-PCR-confirmed RSV (cRSV)-ARI, cRSV-lower respiratory tract disease (LRTD), and other respiratory viruses was calculated by season, region, age group, and RSV subtype. HRQoL was assessed via patient-reported outcomes., Results: The study included 923 ARI episodes (cRSV-ARI: N = 24; non-cRSV-ARI: N = 899). In years 1 and 2 (August 2021-July 2022 and August 2022-February 2023), the prevalence of cRSV-ARI was 2.5% and 2.8%, respectively. There was a predominance of RSV-B and RSV-A subtypes in years 1 and 2, respectively. In years 1 and 2 combined, 37.5% of cRSV-ARI cases had lower respiratory tract infection; all cRSV-LRTD cases occurred in those aged 60-74 years. RSV-ARI cases reported throat, chest, and respiratory symptoms, leading to impaired functioning and HRQoL., Conclusions: During the observed study period, RSV was circulating among older adults in Japan. RSV was a leading cause of ARI and LRTD. More data are needed to fully clarify the burden of RSV among older adults in Japan., Competing Interests: Declaration of Competing interest Eliazar Sabater Cabrera has been employed by and has held financial equities in GSK; Daniel Molnar was employed by and held financial equities in GSK during the conduct of the study and preparation of the manuscript; Silvia Damaso has been employed by and has held financial equities in GSK; Jean-Yves Pirçon has been employed by and has held financial equities in GSK; Maria Moitinho de Almeida has been employed by and has held financial equities in GSK; Victor Preckler Moreno was employed by and held financial equities in GSK when the study was conducted; Taizo Matsuki was employed by and held financial equities in GSK when the study was conducted, and is currently employed by MSD; Hiroshi Takahashi received funding from GSK to conduct this study; Daisuke Himeji received funding from GSK to conduct this study. Yasushi Fukushima received funding from GSK to conduct this study. These authors declare no other financial or non-financial relationships and activities. Hiroyuki Ohbayashi declares no financial or non-financial relationships and activities and no conflicts of interest; Takayuki Sakurai declares no financial or non-financial relationships and activities and no conflicts of interest; Arihiro Kiyosue declares no financial or non-financial relationships and activities and no conflicts of interest., (Copyright © 2024 [Author/Employing Institution]. Published by Elsevier B.V. All rights reserved.)

Background/aims: We assessed the associations between retinopathy of prematurity (ROP) and continuous measurements of oxygen saturation (SpO 2 ), and developed a risk prediction model for severe ROP using birth data and SpO 2 data., Methods: This retrospective study included infants who were born before 30 weeks of gestation between August 2009 and January 2019 and who were screened for ROP at a single hospital in Japan. We extracted data on birth weight (BW), birth length, gestational age (GA) and minute-by-minute SpO 2 during the first 20 days from the medical records. We defined four SpO 2 variables using sequential measurements. Multivariate logistic regression was used to develop a model that combined birth data and SpO 2 data to predict treatment-requiring ROP (TR-ROP). The model's performance was evaluated using the area under the receiver operating characteristic curve (AUC)., Results: Among 350 infants, 83 (23.7%) required ROP treatment. The SpO 2 variables in infants with TR-ROP differed significantly from those with non-TR-ROP. The average SpO 2 and high SpO 2 showed strong associations with GA (r=0.73 and r=0.70, respectively). The model incorporating birth data and the four SpO 2 variables demonstrated good discriminative ability (AUC=0.83), but it did not outperform the model incorporating BW and GA (AUC=0.82)., Conclusion: Data obtained by continuous SpO 2 monitoring demonstrated valuable associations with severe ROP, as well as with GA. Differences in the distribution of average SpO 2 and high SpO 2 between infants with TR-ROP and non-TR-ROP could be used to establish efficient cut-off values for risk determination., Competing Interests: Competing interests: None declared. 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., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Adrenocortical carcinoma is a rare condition, with limited comprehensive reports from Japan. This study aimed to review Japan's data on adrenocortical carcinoma by assessing information from 46 patients-with adrenocortical carcinoma across 10 Japanese university hospitals., Methods: We conducted a retrospective multi-institutional analysis of the clinical characteristics of adrenocortical carcinoma in Japan. We evaluated data from 46 patients across 10 university hospitals over 10 years and analyzed the relationship between clinicopathological characteristics and overall survival., Results: Five- and 10-year overall survival rates were 59% and 53%, respectively. Overall survival was significantly different among the tumor-node-metastasis system for adrenocortical carcinoma of the American Joint Committee on Cancer/International Union Against Cancer, with the worst prognosis in stage IV (p = 0.0044). In our cohort, neither the Weiss score nor the Ki-67 proliferation index correlated with overall survival. Adjuvant treatment did not yield improved overall survival, whereas resection of the primary tumor in stage IV disease was significantly associated with improved overall survival (p = 0.0262). Out of the cases evaluated for plasma hormones, plasma cortisol, aldosterone, testosterone, and DHEA-S levels were measured at 23%, 42%, 29%, and 62%, respectively, demonstrating higher levels than the upper normal limits., Conclusion: Patients with stage IV adrenocortical carcinoma had a poor prognosis; however, resection of the primary tumor in stage IV disease was associated with prolonged survival. The results of this study are expected to contribute to future treatment of adrenocortical carcinoma in Japan., (© 2024 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

To investigate mycobacterial cases of farmed yellowtail fish in coastal areas of western Japan (Kagoshima, Kyushu), where aquaculture fisheries are active, Mycobacterium pseudoshottsii, the causative agent, was isolated from six neighboring fishing ports in 2012 and 2013. A phylogenetic ana-lysis revealed that the strains isolated from one fishing port were closely related to those isolated from other regions of Japan, suggesting the nationwide spread of a single strain. However, strains from Japan were phylogenetically distinct from those from the Mediterranean and the United States; therefore, worldwide transmission was not observed based on the limited data obtained on the strains exami-ned in this study. The present results demonstrate that a bacterial genomic ana-lysis of infected cases, a mole-cular epidemiology strategy for public health, provides useful data for estimating the prevalence and transmission pathways of M. pseudoshottsii in farmed fish. A bacterial genome ana-lysis of strains, such as that performed herein, may play an important role in monitoring the prevalence of this pathogen in fish farms and possible epidemics in the future as a result of international traffic, logistics, and trade in fisheries.

Great earthquakes along the Nankai megathrust in south-western Japan feature in the top priority list of Japan's disaster management agenda. In May 2019, an alert system was incepted to issue public warnings when the probability of an earthquake occurrence along the Nankai megathrust became higher than usual. One of the cases that trigger the issuance of public warnings is when a great earthquake occurred and another one of the same scale is anticipated within a short period of time. Although such "twin ruptures" have occurred multiple times along the Nankai megathrust, the quantification of the probability of such twin ruptures has never been attempted. Based on global statistics and local earthquake occurrence history, we estimated the probability of a successive occurrence of two M8 or larger earthquakes within 3 years globally and along the Nankai megathrust to be 5.0-18% and 4.3-96%, respectively. The timing of the second earthquake followed the Omori-Utsu law in global statistics, which allowed the estimation of the probability for the successive occurrence of Nankai megathrust earthquakes in arbitrary time frames. The predicted probability for the one-week timeframe was 100-3600-fold higher than that of the norm, endorsing the necessity for the warning scheme., (© 2023. The Author(s).)

Background: Tezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced exacerbations by 56% compared with placebo in adults and adolescents with severe, uncontrolled asthma. This analysis evaluated the efficacy and safety of tezepelumab in NAVIGATOR patients recruited in Japan., Methods: NAVIGATOR was a phase 3, multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Endpoints assessed included: the annualized asthma exacerbation rate (AAER) over 52 weeks (primary endpoint) and the change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) and Asthma Control Questionnaire (ACQ)-6 score. The safety of tezepelumab was also assessed., Results: Overall, 97 patients recruited in Japan were randomized (tezepelumab, n = 58; placebo, n = 39). The AAER over 52 weeks was 1.54 (95% confidence interval [CI]: 0.90, 2.64) with tezepelumab compared with 3.12 (95% CI: 1.82, 5.35) with placebo (rate ratio: 0.49 [95% CI: 0.25, 0.99]; 51% reduction). For tezepelumab and placebo, the least-squares mean (standard error) change from baseline to week 52 for pre-bronchodilator FEV 1 was 0.23 (0.06) L and 0.19 (0.07) L and the ACQ-6 score was -1.12 (0.15) and -0.97 (0.19), respectively. The frequency of adverse events was similar between treatment groups (tezepelumab, 86.2%; placebo, 87.2%)., Conclusions: Tezepelumab reduced exacerbations compared with placebo, and was well tolerated, in NAVIGATOR patients with severe, uncontrolled asthma recruited in Japan., (Copyright © 2022 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Background: Empagliflozin, a glucose-lowering drug licensed for type 2 diabetes (T2D), demonstrated tolerability and effectiveness overall in a post-marketing surveillance (PMS) study in Japan. However, the impact of body mass index (BMI) is unclear., Research Design and Methods: This was a prespecified sub-analysis of the prospective, 3-year, PMS study of empagliflozin in Japan where the primary endpoint was adverse drug reactions (ADRs). We evaluated results according to BMI., Results: We enrolled 7931 T2D patients treated with empagliflozin. Baseline mean age was 58.7 years; 63.01% were male. Baseline BMI was <20 kg/m 2 in 2.06% of patients, while 21.28%, 37.35%, and 24.97% had BMI 20-<25, 25-<30 and ≥30 kg/m 2 , respectively. ADRs occurred in 19 (11.66%), 203 (12.03%), 411 (13.88%), and 295 (14.90%) patients with BMI <20, 20-<25, 25-<30 and ≥30 kg/m 2 , respectively. Excessive/frequent urination was the most frequent ADR of special interest in all BMI subgroups except 20-<25 kg/m 2 (urinary tract infection). Mean change in glycated hemoglobin from baseline was -0.75%, with similar magnitude across BMI subgroups. Body-weight reduction seemed dependent on BMI, with almost no change in the <20 kg/m 2 subgroup., Conclusions: Empagliflozin appeared well tolerated and effective in Japanese T2D patients regardless of BMI, although the number of patients with BMI <20 kg/m 2 was small in this study.

Background: Empagliflozin, a sodium-glucose co-transporter-2 inhibitor, was licensed for treating type 2 diabetes (T2D) in Japan and elsewhere in recent years. We conducted a post-marketing surveillance study of empagliflozin in Japan., Research Design and Methods: This was a 3-year, prospective, multicenter, observational study of the safety and effectiveness of empagliflozin in T2D patients in Japanese clinical practice who had not previously received this medication. The primary endpoint was the incidence of adverse drug reactions (ADRs)., Results: Of 8145 patients enrolled from 1103 sites, 7931 received ≥1 dose of empagliflozin. Mean age was 58.7 years (10.5% aged ≥75), glycated hemoglobin (HbA1c) 8.0%, body mass index 28.1 kg/m 2 (<20 kg/m 2 in 2.1%); 63.0% were male and most had comorbidities (renal impairment in ~62%). Median treatment duration was 36.5 months. ADRs occurred in 1024 (12.91%) patients overall (serious ADRs in 2.09%) and 120 patients aged ≥75 years (14.46%). ADRs of special interest included hypoglycemia (0.44% of patients), urinary tract infections (1.07%), genital infections (0.66%), volume depletion (0.50%), diabetic ketoacidosis (0%), and lower limb amputation (0.04%). Overall mean change in HbA1c from baseline was -0.75%., Conclusions: Empagliflozin is effective and generally well tolerated in Japanese patients, and ADRs are consistent with its known safety profile.

Tuberculosis remains a major public health concern. Millions of tuberculosis cases and associated deaths have been reported worldwide. The Indo-Oceanic lineage Mycobacterium tuberculosis is common in Southeast Asia and causes extrapulmonary lesions. Only a few case studies on this lineage with genetic analysis using whole-genome sequencing have been reported in the literature. We present a case of disseminated tuberculosis, characterized by a variety of extrapulmonary lesions and paradoxical reactions, caused by the Indo-Oceanic lineage M. tuberculosis in a woman in Myanmar. A 22-year-old Burmese woman had arthritis in the right knee, with unknown aetiology, and was referred to our hospital. Computed tomography of the trunk revealed multiple nodular shadows in both lungs; swollen mediastinal lymph nodes; and small, low-density areas in the spleen. M. tuberculosis was detected in the sputum sample, joint aspirate, subcutaneous tumor, and exudate. She experienced a variety of paradoxical reactions together with aggressive tuberculosis dissemination in all areas of the body. Whole-genome sequencing of the DNA of MTB obtained from sputum and the right cervical subcutaneous abscess confirmed the Indo-Oceanic lineage of M. tuberculosis, the predominant strain in Myanmar. The Indo-Oceanic lineage M. tuberculosis causes disseminated tuberculosis all over the body including the periungual region. When patients show unusual symptoms, physicians should consider the introduction of new strains from foreign countries. Genetic analyses of the strains are recommended to define and confirm the lineages., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This study aimed to produce a Theileria-free grazing system for Holstein heifers reared on a dairy farm in the Hita area, Kyushu, Japan. In the grazing area, spreading of T. orientalis infection was confirmed in 2009. To eradicate the T. orientalis infection, four measures were conducted: 1) 7-year deferred grazing; 2) grazing only T. orientalis-uninfected heifers; 3) anemia check by red blood cell parameters at least once per month; and 4) protecting heifers from blood-sucking T. orientalis-infected ticks. Grazing was restarted in 2017 in the same area and continued to 2021. During last 2 years of pasturing (2020-2021) all of the 129 heifers were confirmed to be T. orientalis-free. In summary, it is possible to establish a T. orientalis-free grazing system by conducting appropriate measures.

Objectives: Fluoroquinolone (FQ)- and third-generation cephalosporin-resistant Escherichia coli are increasing in Japan. In the early 2000s, the FQ-resistant E. coli clone ST131 increased in clinical settings worldwide. It frequently produces extended-spectrum β-lactamases (ESBLs) such as CTX-M. This study aimed to explore the characteristics of FQ-resistant E. coli isolated in Japan during 2008-2009 and 2020., Methods: We compared FQ-resistant E. coli clinical isolates from urine samples collected in 2020 (151 isolates) with a FQ-resistant E. coli collection isolated in 2008-2009 (42 isolates). Identification of E. coli ST131 clades and bla CTX-M were determined by multiplex PCR. Sequence types of non-ST131 isolates were determined by whole-genome sequencing., Results: Although the prevalence of ST131 was comparable in 2020 (74.2%) and 2008-2009 (78.6%), the subclades differed during the two time periods (C1-nM27: 40.2% in 2008-2009 vs. 78.8% in 2020; C1-M27: 32.1% in 2008-2009 vs. 9.1% in 2020). The incidence of bla CTX-M among ST131 isolates increased from 27.3% in 2008-2009 to 64.3% in 2020. bla CTX-M was found in 80.6% and 93.8% of C1-M27 and C2 in 2020, respectively, and bla CTX-M possession in C1-nM27 increased from 19.2% in 2008-2009 to 40% in 2020. FQ-resistant ST1193 was detected only in 2020 (17.9% of 151 isolates, of which 14.8% possessed bla CTX-M )., Conclusion: Increased resistance of E. coli to FQs and third-generation cephalosporins in Japan can be attributed to the accumulation of bla CTX-M in C1-nM27 and the increase of C1-M27 and C2 clades with high bla CTX-M possession, alongside the spread of ST1193., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Early detection and treatment are paramount for the timely control of Mycobacterium avium infections. Herein, we designed a LAMP assay targeting a widely used species-specific marker IS1245 for the rapid detection of M. avium and evaluated its applicability using human (n = 137) and pig (n = 91) M. avium isolates from Japan. The developed assay could detect as low as 1 genome copy of M. avium DNA within 30 minutes. All 91 (100%) M. avium isolates from pigs were detected positive while all other tested bacterial species were negative. Interestingly, among the 137 clinical M. avium isolates, 41 (30%) were undetectable with this LAMP assay as they lacked IS1245, the absence of which was revealed by PCR and whole-genome sequencing. These findings highlighted genotypic differences in M. avium strains from humans and pigs in Japan and how this diversity can influence the applicability of a detection tool across different geographic areas and hosts., (Copyright © 2021 Elsevier Inc. All rights reserved.)

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer., (© 2021. The Japanese Society for Clinical Molecular Morphology.)

Objective: This study evaluated the cell invasion ability (CIA) of Streptococcus agalactiae isolates from humans and companion animals and clarified the relationship between CIA populations and their microbiological features., Methods: Human-origin and companion animal-origin isolates were collected along with host information. We measured CIA using human-lineage colon cancer epithelium (Caco-2) and keratinocyte (HaCaT) cell lines, via virulence-associated gene profiling (bca-rib-bac-lmb-cylE-hylB-pavA-pilB-spb1-srtC1-brpA), capsular genotyping, multilocus sequence typing, and antimicrobial resistance (AMR) phenotyping/genotyping. Significant differences in data regarding CIA into epithelium and keratinocytes and those of isolates from different hosts were assessed. We analyzed the association of CIA populations with the virulence genotypes, capsular genotypes, sequence types/clonal complexes, and AMR phenotypes/genotypes., Results: A comparative analysis was performed between human (n = 15) and canine (n = 17) non-invasive isolates. There was a difference in CIA data between Caco-2 and HaCaT cells using human and animal isolates. For percent invasion ability into Caco-2 cells, we designated values ≥ 0.1 as high-frequency CIA and values < 0.1 as low-frequency CIA. Fourteen isolates harbored high-frequency and 18 isolates harbored low-frequency strains. There was no association between the high-frequency population and the virulence genotypes, capsular genotypes, sequence types/clonal complexes, and AMR phenotypes/genotypes., Conclusion: This is the first report assessing the invasion ability of S. agalactiae into HaCaT and Caco-2 cells. Our observations suggest that S. agalactiae is more capable of entering Caco-2 rather than HaCaT., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This study evaluated the cell invasion ability (CIA) of Streptococcus canis isolates, and clarified the relationship between high-frequency CIA and its microbiological features. Of the companion animal-origin isolates (n = 117) that were obtained in 2017, 40 isolates were randomly selected with the host information, with two human blood-origin isolates included. CIA was measured using human colon carcinoma epithelium and the hemolytic activity (HA) using sheep blood, along with S. canis M-like protein (SCM) allele typing, sequence type (ST) determination, and antimicrobial resistance (AMR) phenotyping/genotyping. CIA measurements revealed that 19 and 24 isolates had high- and low-frequencies, respectively. HA assessment revealed that 24 and 19 isolates were categorized as high- and low- level, respectively. No difference was observed in the high-/low-level HA between the high- /low-frequency CIA populations. A significant difference was found in the high-/low-frequency CIA between the SCM group I/II populations. Additionally, a significantly higher CIA was found in the SCM allele type 10/type 11 than in the others. A significant association was observed between high-frequency CIA and the ST21/ST41 populations. No difference was found in the high-/low-frequency CIA between the presence and absence of the AMR phenotype/genotype. These observations suggest a relationship between high-frequency CIA and its microbiological characteristics (SCM allele type 10/type 11 or ST21/ST41).

The objective of the present study was to investigate the prevalence of Theileria orientalis infection and the influence of this disease on dairy grazing heifers in Kyushu by monitoring red blood cell (RBC) indexes, and to evaluate the efficacy of diminazene diaceturate treatment of T. orientalis-infected animals. A monthly epidemiological survey was conducted for Holstein heifers, which were reared from 10 to 16 months of age on a large commercial dairy farm and grazed on eight independent grasslands from April to November, 2009. During the survey, a total of 2,803 blood samples were collected from the 891 grazing heifers, in which the prevalence of T. orientalis infection was 52.4%. Compared with the heifers before infection, heifers with high parasitemia (more than 100 parasites per 10 4 RBC) had significantly decreased RBC indexes, such as RBC count, hemoglobin concentration, and hematocrit (P<0.05), whereas heifers with low parasitemia (less than 100 parasites per 10 4 RBC) had similar RBC indexes as those before infection. Treatment with diminazene diaceturate had lower efficacy in heifers with high parasitemia than those with low parasitemia (40.7% and 73.2% became negative, respectively, P<0.05). In summary, T. orientalis infection is a potentially serious problem in Kyushu, and it is important to routinely implement control programs for heifers that are grazed on grasslands in this region.

Estimations of individuals' polyphenol intake contributes to the understanding of the health benefits of dietary polyphenol. We developed a food frequency questionnaire for polyphenol intake (FFQ) and a short-form FFQ for polyphenol intake (SF-FFQ) for assessing the polyphenol intake of Japanese. The aim of this study was to compare the relative validity of polyphenol intake derived from the FFQ with that from the SF-FFQ, using a 4-consecutive-d dietary record (DR) as the reference. Sixty Japanese subjects aged 30-69 y completed the 4-d DR and the two FFQs regarding their polyphenol intake in November 2019. The polyphenol intake values estimated by the DR, FFQ, and SF-FFQ were 1,057±524 mg/d, 1,061±537 mg/d and 1,015±491 mg/d, respectively. No significant differences were present in the estimated polyphenol intake between the 4-d DR and both FFQs. The correlation coefficient with the DR was 0.779 for the FFQ and 0.814 for the SF-FFQ. These results indicate that the total polyphenol intake in a Japanese population were accurately estimated by the FFQ and SF-FFQ.

A mannan-degrading halophilic archaeal strain, MD130-1 T , was isolated from a commercial salt sample. Cells were motile, rod-shaped, and stained Gram-negative. Colonies were pink pigmented. Strain MD130-1 T was able to grow at 1.5-4.6 M NaCl (optimum, 3.6 M) at pH 6.0-8.0 (optimum, pH 7.0) and at 25-50 °C (optimum, 40 °C). The DNA G+C content was 62.1 mol% (genome). The orthologous 16S rRNA gene sequence showed the highest similarity (99.4 %) to those of Haloarcula japonica JCM 7785 T and Haloarcula hispanica JCM 8911 T . The values of genome relatedness between strain MD130-1 T and Haloarcula species were 84.33-85.96 % in ANIb and 30.4-32.9 % using GGDC formula 2. The polar lipids of strain MD130-1 T were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and triglycosyl diether-2. Based on the results of phenotypic and phylogenetic analyses, the strain represents a new species of the genus Haloarcula , for which the name Haloarcula mannanilytica sp. nov. is proposed. The type strain is MD130-1 T (=JCM 33835 T =KCTC 4287 T ) isolated from commercial salt made in Ishikawa prefecture, Japan.

Objective: To examine the association of specific Z-score categories of birth weight for gestational age with child health and neurodevelopment using a large nationwide survey in Japan, focusing on term infants., Study Design: We included 36 321 children born in 2010. Hospitalization up to 66 months of age was used as an indicator of health status, and responses to questions about age-appropriate behaviors at 30 and 66 months of age were used to indicate neurobehavioral development. We conducted binomial log-linear regression analyses, controlling for child and parental variables. A restricted cubic spline function was used to model the relationship., Results: Compared with children with birth weight appropriate for gestational age (-1.28 to 1.28 SDs of expected birthweight for gestational age), children who were small for gestational age (SGA) (<-1.28 SD) had higher risks of hospitalization and unfavorable neurobehavioral development, and the risks increased as SGA status became more severe. Compared with the appropriate for gestational age group, the adjusted risk ratios for hospitalization for all causes were 2.5 (95% CI, 1.7-3.6), 1.3 (95% CI, 1.1-1.6), and 1.1 (95% CI, 1.0-1.2) for children who were severely, moderately, and mildly SGA and 1.0 (95% CI, 0.9-1.1), 1.1 (95% CI, 0.9-1.2), and 1.4 (95% CI, 0.9-2.1) for children who were mildly, moderately, and severely large for gestational age, respectively. Severely large for gestational age children also had higher risks of unfavorable neurobehavioral development. These results were supported by spline analyses., Conclusions: Among term infants, the risks of unfavorable child health and neurodevelopment increased with the severity of SGA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Our aim was to investigate the incidence and prevalence of clinical mastitis, peracute mastitis, metabolic disorders, and peripartum disorders, and to examine factors affecting the prevalence of each disease in cows raised on a large dairy farm in a temperate climate in Japan. The present study was performed on a large commercial dairy farm with approximately 2500 Holstein cows. Data were collected from 2014 to 2018, and involved 9663 calving records for 4256 cows., Results: The incidence rate on the farm was 21.9% for clinical mastitis, 10.4% for peracute mastitis, 2.9% for metabolic disorders, and 3.2% for peripartum disorders. The prevalence rates for clinical mastitis, peracute mastitis, metabolic disorders, and peripartum disorders were 28.0, 13.3, 3.7, and 4.0%, respectively. In all four diseases, the probability of time to occurrence for each disease was associated with parity and calving season (P < 0.05). Regarding metabolic disorders and peripartum disorders, the probability of occurrence decreased during the first 10 days after calving., Conclusions: Our results showed that clinical mastitis occurred most often in this temperate zone, and that metabolic disorders and peripartum disorders occurred from calving to day 10 post-calving.

We report a case of non-necrotizing soft tissue infection and streptococcal toxic shock syndrome (STSS) caused by a novel emm subtype (emm76.10) of group A Streptococcus pyogenes (GAS). A 54-year-old Japanese woman suffering from fever, fatigue, and lower abdominal pain along with erythema for 3 days was admitted to our hospital. Additionally, she presented with hypotension and multiple organ failure. Exploratory incision was performed due to the presence of STSS and for an examination of the necrotizing soft tissue infection from her lower abdomen to the left thigh. Tissue cultures from the exudates and fascia yielded positive results for GAS growth, although blood cultures returned as negative. After 15 days of antimicrobial therapy, she recovered fully without any complications. Genotyping of the isolate indicated a novel emm subtype (emm76.10), with 5 amino acid substitutions in the emm76.0 subtype sequence and the full-length sequence of 780 bp. This isolate was resistant to tetracyclines, macrolides-lincosamides, and fluoroquinolones, owing to the presence of antibiotic resistance determinants, tet(M) and erm(B), and point mutations, Ser79Phe/Ser81Phe, in the quinolone resistance-determining regions of parC/gyrA. In conclusion, our observations suggest the importance of early-stage exploratory incision and drainage from the infected region for the isolation and characterization of causative bacteria to facilitate selection of appropriate antibiotics for treatment.

Background: Treatment of VRE is of clinical concern. While certain numbers of vanD-type VRE have been isolated, only two vanD5-harbouring Enterococcus faecium isolates have been reported in Canada and Japan., Methods: We report the isolation of vanD5-type E. faecium and the first ever determination of the whole-genome sequence to investigate the possible mechanisms of the acquisition of the vanD5 gene cluster in E. faecium., Results: Two vanD5-harbouring vancomycin-resistant E. faecium were isolated from the skin (SMVRE19) and faeces (SMVRE20) of a patient with a skin ulcer in Japan. The isolates exhibited vancomycin and teicoplanin MIC values of 128 mg/L, whilst the previous isolates of vanD5-harbouring E. faecium were only resistant to vancomycin. SMVRE19 and SMVRE20 were clones related to ST18, which is also seen in vanA- and vanB-type VRE. These isolates harboured an insertion element, ISEfm1, in the ddl gene, similar to a previously described teicoplanin-resistant vanD3-type E. faecium. The vanD5 gene cluster was integrated into the SMVRE20 chromosome as a part of a large genomic island (approximately 127 kb), similar to other recently spreading vanD variants in the Netherlands. The genomic island shared the greatest similarity with a part of the Blautia coccoides genome sequence, except for the region surrounding the vanD gene cluster., Conclusions: This study reports that emergence of vancomycin- and teicoplanin-resistant vanD5-type E. faecium occurred via acquisition of the vanD5 cluster and ISEfm1 insertion into ddl. Considering the genetic similarity between the various VRE strains, the current study should serve as a warning against the spread of vanD5-type VRE., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: We aimed to determine novel alleles and their prevalence in Streptococcus canis M-like protein (SCM) and to elucidate association of their alleles with sequence types (STs)/clonal complexes (CCs) and antimicrobial resistance (AMR) phenotypes/genotypes., Methods: We amplified and sequenced scm, by using primers reported by Pinho recently, for 40 isolates in 2015 and 2017, in which the sequences could not be determined with conventional primers. Isolates, for which SCM alleles, STs, and AMR phenotypes/genotypes were previously determined, were included as controls. A phylogenetic tree of SCM amino acid sequences was constructed. Alleles, based on the tree positions with their prevalence, as well as STs/CCs and AMR phenotypes/genotypes were characterized., Results: Although one isolate possessed SCM allele type 1, 39 isolates had novel allele types 10-15, based on cluster analysis. The 11 and 12 allele types were firstly found in this study. We designated novel allele types as group II and non-novel allele types as group I. Prevalence of group II alleles was 29.9% and 16.2% in 2015 and 2017. Prevalent group II types were allele 10 (10.3%), allele 11 (2.7%), and allele 15 (3.3%) through both periods. There was a significant difference in distribution of STs/CCs between groups I/II SCM populations. We found significant differences in distribution of macrolide/lincosamide AMR genotype (7.7% vs. 26.8%) and AMR rates of fluoroquinolone (0% vs. 12.5%) between the two populations., Conclusion: Our study presents group II scm sequences and their prevalence among diseased companion animals in Japan, with association of their alleles with STs., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This study assessed whether Streptococcus agalactiae isolates from companion animals differed from those of human origin. Beta-hemolytic S. agalactiae was collected from a veterinary laboratory center and a university hospital. Strains were identified using 16S rRNA amplicon sequencing and amplification of the species-specific dltS gene. We conducted virulence gene profiling, capsular genotyping, determination of clonal complex (CC), and antimicrobial resistance (AMR) phenotyping or genotyping. The 20 non-invasive isolates obtained from animals and 15 non-invasive isolates from adult humans were comparatively analyzed in this study. We found significant differences in the virulence gene profiles of bca-rib-lmb-cylE (40.0% vs. 93.3%) and the possession of bac (30.0% vs. 0%) between animal-origin and human-origin non-invasive strains. We observed a significant difference in the distribution of CC1 between the two non-invasive populations. There were significant differences in the prevalence of tetracycline resistance genotypes (60.0% vs. 20.0%) and absence of AMR genotypes (30.0% vs. 80.0%), and AMR rates of tetracycline (35.0% vs. 0%) and fluoroquinolone (20.0% vs. 66.7%) between the two non-invasive populations. These observations suggest that there were different features, in terms of virulence gene profile, CC, and AMR genotype/phenotype in the non-invasive isolates of animal origin compared to those of human origin.

Aims/introduction: The objective of the present study was to clarify the association of the type and number of first-degree family history of diabetes (FHD) with the clinical characteristics, especially with residual β-cell function, in type 2 diabetes patients., Materials and Methods: A total of 1,131 type 2 diabetes patients were recruited and divided into four groups according to FHD information as follows: (i) patients without FHD (FHD-); (ii) those with at least one sibling who had diabetes without parental diabetes (FHD+); (iii) those with one parent (FHD++); or (iv) those with both parents (FHD+++) who had diabetes with or without a sibling with diabetes., Results: The percentages of the FHD-, FHD+, FHD++ and FHD+++ groups were 49.4%, 13.4%, 34.0% and 3.2%, respectively. Patients in the FHD++ and FHD+++ groups were significantly younger at the time of diabetes diagnosis (P < 0.001) than those in the FHD- and FHD+ groups, even after adjusting for confounding factors. In addition, the levels of insulin secretion were significantly lower in the patients in the FHD+, FHD++ and FHD+++ groups than those in the FHD- group (P < 0.05) after adjusting for confounding factors, and the patients in the FHD+++ group presented with the lowest levels of insulin secretion among the four groups., Conclusions: Our results showed that in type 2 diabetes patients, the degree of the associations between FHD and clinical characteristics differs according to the number and the type of FHD. In particular, FHD in both parents is most strongly associated with impaired residual β-cell function., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Purpose: Several epidemiological studies have demonstrated the health benefits of polyphenols, but the associations between polyphenol intake and mortality including total and major causes of death remain unclear. We investigated the associations between subjects' total polyphenol intake and their mortality from all causes, cardiovascular disease (CVD), cancer, and other causes of death in a population-based cohort study in Japan., Methods: A total of 29,079 residents of Takayama City, Japan were analyzed. Their dietary intake was assessed using a validated semi-quantitative food-frequency questionnaire (FFQ) in 1992. Mortality was ascertained over the subsequent 16 years. The dietary polyphenol intake was calculated by matching the subjects' food consumption data with our original polyphenol content database., Results: A total of 5339 deaths occurred during the follow-up. After multivariable adjustment, the highest quartile of total polyphenol intake compared with the lowest quartile was significantly associated with a lower risk of all-cause mortality (HR: 0.93, 95% CI: 0.82-0.99, p trend = 0.003). The subjects in the highest quartile showed significantly lower CVD mortality compared to those in the lowest quartile, and among the types of CVD mortality, a strong inverse association was observed for stroke mortality. Inverse associations were also observed for mortality from other causes, specifically digestive disease. The total polyphenol intake was not significantly associated with the risk of cancer mortality., Conclusions: The results of this prospective study indicate that dietary total polyphenol intake in Japanese is inversely associated with all-cause mortality and mortality from cardiovascular and digestive diseases.

Objectives : Honeybee stings often lead to anaphylactic shock. We surveyed Japanese beekeepers to examine whether adrenaline auto-injectors are properly used after honeybee stings. Methods : We contacted representatives of the Japanese Beekeeping Association in all 47 prefectures for assistance distributing allergist-developed questionnaires. Representatives in 33 prefectures distributed questionnaires to their members and we received valid responses from 826 beekeepers. Results : Adrenaline auto-injectors had been prescribed to only 46 of the 826 participants (5.6%) to prevent systemic reaction (SR) to honeybee stings. Of the 33 beekeepers who experienced a honeybee sting after adrenaline auto-injector prescription, 16 (48.5%) developed SRs; 9 of these 16 (56.3%) were treated with an adrenaline auto-injector. Conclusions : Japanese beekeeping organizations should consider encouraging medical institutions to prescribe adrenaline auto-injectors. Furthermore, physicians and other health care workers should better educate beekeepers and others who have been prescribed an adrenaline auto-injector in order to improve compliance and raise awareness of the risk posed by SRs.

Background: Budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) is a triple fixed-dose combination for COPD. The long-term safety of triple therapy for COPD has not been investigated in Japanese patients. In this 28-week extension study (NCT03262012), we investigated the long-term safety and tolerability of BGF MDI in Japanese patients with moderate-to-very severe COPD who completed the 24-week Phase III randomized, double-blind, multicenter KRONOS study (NCT02497001)., Materials and Methods: Patients randomized to BGF MDI 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice-daily in KRONOS continued treatment for up to 28 additional weeks. Safety was evaluated over 52 weeks via adverse event (AE) monitoring, electrocardiograms, clinical laboratory testing, and vital sign measurements., Results: The safety population included 416 patients who received BGF MDI (n=139), GFF MDI (n=138), BFF MDI (n=70), or BUD/FORM DPI (n=69). Treatment-emergent AE (TEAE) rates were similar across treatment groups (range: 82.6-82.9%). The most frequent TEAEs overall were nasopharyngitis (32.2%) and bronchitis (9.9%). The incidence of major adverse cardiovascular events was low across groups (range: 0.0-2.9%). Over 52 weeks, the incidence of confirmed pneumonia was 9.4% (BGF MDI), 3.6% (GFF MDI), 5.7% (BFF MDI), and 2.9% (BUD/FORM DPI); in the 28-week extension period, rates were comparable across groups (range: 2.9-5.7%). Six deaths were reported (0.7-2.2% per group); none were considered treatment-related. No clinically meaningful trends were observed in electrocardiograms, laboratory parameters, or vital signs over time in any of the treatment groups., Conclusion: All treatments were well tolerated over 52 weeks, and the safety profile of BGF MDI was generally comparable to dual long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) and inhaled corticosteroid (ICS)/LABA therapies. These findings support the long-term tolerability of BGF MDI in Japanese patients with COPD., Competing Interests: MI reports personal fees from AstraZeneca, during the conduct of the study; and personal fees from Kyorin, Nippon Boehringer Ingelheim, and Novartis Pharma, outside of the submitted work. YI reports personal fees from GlaxoSmithKline, Nippon Boehringer Ingelheim, Nobelpharma, and Shionogi & Co. Ltd, outside of the submitted work. OH reports personal fees from AstraZeneca, Nippon Boehringer Ingelheim, and Novartis Pharma; and research funding from AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Nippon Boehringer Ingelheim, and Novartis Pharma. GTF reports grants, personal fees, and non-financial support from AstraZeneca during the conduct of the study; grants, personal fees, and non-financial support from AstraZeneca, Boehringer Ingelheim, Novartis, Pearl – a member of the AstraZeneca Group, and Sunovion; grants and personal fees from Theravance; and personal fees from Circassia, GlaxoSmithKline, Innoviva, Mylan, and Verona, outside of the submitted work. KFR reports personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi Pharmaceuticals, InterMune, Novartis, Sanofi, and Teva; and grants from the Ministry of Education and Science, Germany, outside of the submitted work. NH, HO, and MT are employees of AstraZeneca K.K., Japan. EB, SB, MA, CR, and PD are employees of AstraZeneca. KdA is a former employee of AstraZeneca. The authors report no other conflicts of interest in this work., (© 2019 Ichinose et al.)

Background: KRONOS, a Phase III, multicenter, randomized, double-blind study (NCT02497001) conducted in Canada, China, Japan, and the USA, assessed the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), a triple fixed-dose combination therapy, relative to dual therapies in patients with moderate-to-very severe COPD. Here we present findings from the Japanese subgroup of KRONOS., Methods: Patients received BGF MDI 320/18/9.6μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12μg twice-daily for 24 weeks. The primary endpoint was the change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV 1 ) over Weeks 12-24. Symptoms, quality of life, exacerbations, and safety were also assessed., Results: In total, 416 Japanese patients (21.9% of the global KRONOS population) were randomized and treated with BGF MDI (n=139), GFF MDI (n=138), BFF MDI (n=70), or BUD/FORM DPI (n=69). Nominally significant improvements in the change from baseline in morning pre-dose trough FEV 1 over Weeks 12-24 were observed for BGF MDI vs GFF MDI (least squares mean [LSM] difference 37 mL, 95% confidence interval [CI] 3, 72; P =0.0337) and BFF MDI (67 mL; 95% CI 25, 109; P =0.0020). Treatment with BGF MDI led to a nominally significant reduction in the rate of moderate/severe exacerbations vs GFF MDI (rate ratio 0.40, 95% CI 0.19, 0.83; P =0.0142). Compared with dual therapies, numerical improvements were observed with BGF MDI for Transition Dyspnea Index focal score and the change from baseline in Evaluating Respiratory Symptoms in COPD total score ( P ≤0.3899). All treatments were generally well tolerated., Conclusion: BGF MDI nominally significantly improved lung function and numerically improved symptoms vs GFF MDI and BFF MDI. BGF MDI nominally significantly reduced exacerbations vs GFF MDI in Japanese patients with COPD. Efficacy and safety findings were generally comparable to those in the global KRONOS population., Competing Interests: MI reports personal fees from AstraZeneca, during the conduct of the study; and personal fees from Kyorin, Nippon Boehringer Ingelheim, and Novartis Pharma, outside of the submitted work. YI reports personal fees from GlaxoSmithKline, Nippon Boehringer Ingelheim, Nobelpharma, and Shionogi & Co., outside of the submitted work. OH reports personal fees from AstraZeneca, Nippon Boehringer Ingelheim, and Novartis Pharma; and research funding from AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Kyorin Pharm, Nippon Boehringer Ingelheim, Novartis Pharma, and Ono Pharm. GTF reports grants, personal fees, and non-financial support from AstraZeneca during the conduct of the study; grants, personal fees, and non-financial support from AstraZeneca, Boehringer Ingelheim, Novartis, Pearl – a member of the AstraZeneca Group, and Sunovion; grants and personal fees from Theravance; and personal fees from Circassia, GlaxoSmithKline, Innoviva, Mylan, Sanofi, and Verona, outside of the submitted work. KFR reports personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi Pharmaceuticals, InterMune, Novartis, Sanofi, Roche, and Teva; and grants from the Ministry of Education and Science, Germany, outside of the submitted work. NH, HO, and MT are employees of AstraZeneca K.K., Japan. EB, SB, MA, PD, and CR are employees of AstraZeneca. KdA is a former employee of AstraZeneca. The authors report no other conflicts of interest in this work., (© 2019 Ichinose et al.)

Modern lifestyles demand a number of products derived from petroleum-based sources that eventually cause carbon emissions. The quantification of lifestyle and household consumption impacts upon carbon emissions from both the embodied CO 2 (EC) and materially retained carbon (MRC) viewpoints is critical to deriving amelioration policies and meeting emission reduction goals. This study, for the first time, details a methodology to estimate both EC and MRC for Japan, focusing on petrochemicals and woody products utilizing the time series input-output table, physical value tables and the national survey of family income and expenditure, leveraging time series input-output-based material flow analysis (IO-MFA), and structural decomposition analysis (SDA). Findings elucidated hot spots of deleterious consumption by age of householder and the critical factors which underpin them including intensity effects, pattern effects, and demographic shifts over time. Although demographic shifts associated with an aging, shrinking population in Japan decreased EC and MRC, the negative effect reduced in size over time during 1990-2005. Policy implications identify the potential to mitigate approximately 21% of required household emission reductions by 2030 through strategies including recycling initiatives and the recovery of carbon from products covered within current recycling laws and hot spot sectors which are not currently considered such as apparel.

Purpose: We aimed to externally validate the performance of new screening criteria for retinopathy of prematurity (ROP) developed in the Postnatal Growth and Retinopathy of Prematurity (G-ROP) study among a Japanese cohort., Design: Validation of screening criteria., Methods: We reviewed premature infants screened for ROP between September 2009 and May 2017 at a single institution. The G-ROP criteria, except hydrocephalus, were applied as a prediction model for infants with both a known outcome of ROP and serial measurements of weight gain. We assessed sensitivity and specificity for treatment-requiring ROP, and reduction in the number of infants who receive ROP screening and in the number of retinal examinations., Results: Of 692 premature infants screened for ROP, 537 had information of ROP outcome and weight gain. In this cohort, 81 infants required treatment for ROP; in 218 infants, ROP regressed spontaneously; and 238 infants did not develop any ROP. The G-ROP model reached a sensitivity of 100% (95% confidence interval [CI], 95.4%-100%) and specificity of 28.9% (95% CI, 24.9%-33.2%). No infants required any treatment for ROP before the date of risk determination. The number of infants requiring screening and the number of examinations would have been reduced by 24.5% and 12.9%, respectively., Conclusions: This is the first validation study of the G-ROP criteria in a developed country other than North America. The criteria demonstrated high sensitivity in this Japanese cohort, even though the criterion of hydrocephalus was excluded., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We determined the whole-genome sequence (WGS) of Streptococcus canis strain TA4 harboring the M-like protein gene (scm); the strain was isolated from a human patient presenting with bacteremia. The potential of type II-A clustered regularly interspaced short palindromic repeats (CRISPR) array-based typing was evaluated, and the genetic relation was elucidated between spacer genogroups and scm prevalence and/or polymorphisms among the isolates from 19 diseased companion animals and the human patient. CRISPRFinder and CRISPRCasFinder detected the type II-A locus with the same repeat sequences in strain TA4 and another WGS of S. canis strain, isolated from a cow with mastitis. An optimized PCR-based amplification method was used to sequence the region covering the locus around the leader and terminal repeat sequences. Among the 20 isolates sequenced, 16 strains (including TA4) were identified with the CRISPR array. We conducted comparative analysis of the homologous spacer sequences and performed grouping based on the successive common ancestral spacer types. These 16 isolates were assigned to five genogroups (A to E) with scm being absent in genogroup A. We found a relationship between genogroups C and E and allele type 1 of the deduced M-like protein. These preliminary findings suggest the feasibility of CRISPR array-based typing and a genetic relation between the spacer genogroups and scm prevalence and/or polymorphisms in the isolates.

This study aimed to identify the species and assess the antimicrobial resistance (AMR) of β-hemolytic streptococci isolated from companion animals in Japan. Strains were isolated from clinical specimens of 131 companion animals that exhibited symptoms in April-May 2017. We identified strains by 16S rRNA sequencing and assessed their antimicrobial susceptibility using the broth microdilution method. AMR genes erm(A)-erm(B)-mef(A) and tet(M)-tet(O)-tet(K)-tet(L)-tet(S) in all isolates were amplified by PCR. 16S rRNA sequencing identified β-hemolytic streptococcal species as Streptococcus canis (n = 117, 89.3%), S. agalactiae (n = 7), S. dysgalactiae subsp. equisimilis (n = 5), S. dysgalactiae subsp. dysgalactiae (n = 1), and S. equi subsp. zooepidemicus (n = 1). Overall AMR rates were 39.7% for minocycline, 19.8% for erythromycin, and 17.6% for clindamycin, with a minimum inhibitory concentration (MIC 90 ) of > 4, > 2, and > 1 μg/mL, respectively. AMR genotyping showed the presence of single or mixed types: erm(B)-mef(A) and tet(M)-tet(O)-tet(L)-tet(S). There was a significant relationship between tetracycline-resistance genotypes and open pus/skin-derived specimens. These observations identify some unique features of β-hemolytic streptococcal isolates from companion animals in Japan, such as the dominant isolation of S. canis and resistance to tetracycline, macrolide, and lincosamide antibiotics, in terms of species identification and AMR properties.

Purpose: The Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) program is known to improve team and clinical performance, but the relationship to psychological stress has not been clarified. The purpose of this paper is to evaluate team performance, clinical performance and psychological stress simultaneously in a simulation-based training combined with or without the TeamSTEPPS program., Design/methodology/approach: This randomized, controlled, prospective pilot study was performed to reveal TeamSTEPPS impact on psychological stress. The course included an emergency care training course, the TeamSTEPPS program, and a scenario simulation. Ten medical student teams were randomly allocated two groups: a TeamSTEPPS group and a non-TeamSTEPPS group. Team performance, clinical performance and psychological stress were evaluated simultaneously in the course; i.e., questionnaire evaluation and an observational evaluation for team performance; an assessor's evaluation and a simulator's evaluation for clinical performance. Autonomic nervous activity, represented by salivary amylase levels and heart rate variability, were measured as psychological stress indicators., Findings: Team performance and clinical performance were significantly better in the TeamSTEPPS group, while psychological stress did not differ between the groups., Originality/value: This is the first study to examine the relationship between TeamSTEPPS and psychological stress. Although only preliminary conclusions can be drawn from this small-scale study, results suggest that the TeamSTEPPS program improved team and clinical performance without increasing psychological stress.

The intake of polyphenols among Japanese has been estimated in several adult populations, but there has been no information regarding their intake among young adults, especially in those in their twenties. We conducted a food frequency questionnaire (FFQ)-based dietary assessment four times a year (once in each season) among Japanese university students and evaluated the total polyphenol intake across and within seasons. Forty-nine subjects (aged 20.7±0.6 y) completed our FFQ regarding polyphenol intake in February, May, August, and November 2016. We then calculated their total polyphenol intake using our polyphenol content database. The mean intake of total polyphenol across the seasons was 567±236 mg/d, which was largely sourced from beverages (62%). No significant differences were found in the total polyphenol intake or polyphenol intake from beverages among the four seasons. By contrast, we observed significant seasonal differences in the subjects' polyphenol intake from food; the polyphenol intake from food in February (255 mg/d) was significantly higher than that in May (215 mg/d), August (187 mg/d) and November (196 mg/d) (p<0.0001). These findings should assist in future estimations of dietary polyphenol intakes that consider differences according to age and season.

Since 2011, Nagasaki University has been assisting the reconstruction efforts of Kawauchi Village in the Fukushima Prefecture, which was the first village to declare it safe for residents to return to their homes. In April 2013, Nagasaki University and the Kawauchi government office concluded an agreement concerning comprehensive cooperation toward reconstruction of the village. The present study evaluates the internal and external exposure doses of residents and conducted a risk communication based on each resident's radiation dose. Furthermore, researchers began a comprehensive support of Tomioka residents who have returned to their hometown in 2017. Based on the experiences in Kawauchi village, it is clear that the cooperation of residents, local authorities and specialists is essential for the recovery of areas affected by the nuclear disaster. Accumulated experiences and practices should be carefully evaluated and recorded to prepare for future unexpected nuclear disasters.

Streptococcus canis (Sc)-origin M-like protein (SCM) binds to plasminogen and immunoglobulin G and facilitates anti-phagocytic properties. We aimed to determine the prevalence and diversity of the scm gene in Sc isolates from diseased companion animals in Japan and to propose potential SCM alleles of amino acid (AA) sequences. We collected β-hemolytic streptococci from diseased animals with host information nationwide in 2015 and 2017. After Sc identification and scm gene amplification and sequencing, the gene's prevalence and relationship between its presence and host information were determined. Furthermore, phylogenetic trees of AA sequences were constructed, and classification and distribution of SCM alleles based on variations of AA sequences were conducted. The scm detection rates were 70.6% (n = 48, 2015) and 82.9% (n = 97, 2017). There was a relationship between scm presence and Tokyo in 2015 and 2017. We found an association between scm detection and dogs in 2017 alone. Major sequence sizes were 1311 bp, 1308 bp, and 1305 bp. Using the phylogenetic trees of AA sequences, we confirmed shared positions of five identical sequence patterns in both periods. Nine SCM alleles were determined with six signal-peptide types. Most prevalent alleles were type 1, type 2, and type 4 in both periods. Our observations suggest prevalence and diversity of scm in animal-origin Sc isolates in Japan., (Copyright © 2018 Elsevier B.V. All rights reserved.)

β-Lactam-resistant Haemophilus influenzae is a clinical concern. A high prevalence (>40%) of β-lactamase-negative high-level ampicillin-resistant H. influenzae (high-BLNAR) isolates in Japan has been reported. However, the reasons for the expansion are unknown. High-BLNAR strains possess an amino acid substitution, either Asn526Lys (group III) or Arg517His (group III-like) in addition to Ser385Thr, in penicillin-binding protein 3 (PBP3). To determine the current prevalence of high-BLNAR strains and the mechanisms behind their expansion in Japan, their prevalence, PBP3 types, multilocus sequence types, and susceptibilities to quinolones approved in Japan as alternatives were determined. Sixty percent of H. influenzae clinical isolates (62/104 isolates) were β-lactamase-negative ampicillin-resistant H. influenzae (BLNAR) strains. Among BLNAR isolates, 92% (57/62 isolates) were high-BLNAR strains. Most isolates were classified as belonging to group III, which contained many genotypes (11 PBP3 types and 25 sequence types). These results indicated that the expansion of high-BLNAR isolates was multiclonal and such strains are still predominant in Japanese clinical settings. One high-BLNAR isolate harbored the novel amino acid substitution Asn526Met in addition to Ser385Thr in PBP3, suggesting a new group (group IV). No quinolone-resistant H. influenzae isolates were identified. The MICs for the quinolones (moxifloxacin, garenoxacin, and tosufloxacin) were similar to that for levofloxacin, whereas sitafloxacin exhibited a lower MIC. However, we obtained 4 H. influenzae isolates with decreased quinolone susceptibility with the amino acid substitution Ser84Leu in GyrA, and 3 of those isolates were high-BLNAR isolates. In summary, this study shows that multiclonal high-BLNAR strains predominate in a Japanese university hospital. Isolates remain sensitive to quinolones, but vigilance is required to prevent the development of fluoroquinolone resistance in high-BLNAR strains., (Copyright © 2018 American Society for Microbiology.)

Background: Rabeprazole at 10 or 20 mg twice daily (b.i.d.) has been reported to be highly effective in the treatment of proton pump inhibitor (PPI)-resistant reflux esophagitis (RE) that is refractory to the standard once-daily PPI regimen. We evaluated the efficacy and safety of rabeprazole maintenance therapy at 10 mg once daily (q.d.) or b.i.d. for longer than 8 weeks., Methods: Patients with RE refractory to standard PPI regimens for at least 8 weeks were enrolled. They were treated with rabeprazole at 10 or 20 mg b.i.d. for 8 weeks during the open-label treatment period. After endoscopic examination, those with confirmed healing entered the subsequent double-blind maintenance therapy. During this period, the subjects were randomized to receive rabeprazole 10 mg q.d. (control) or 10 mg b.i.d. The primary endpoint was the endoscopic no-recurrence rate at Week 52., Results: In total, 517 subjects entered the treatment, and 359 subjects continued on maintenance therapy. The full analysis set for central assessment included 343 subjects. The no-recurrence rate at Week 52 was significantly higher in the b.i.d. group (73.9%; p < 0.001, χ 2 test) than in the q.d. group (44.8%). In particular, the b.i.d. regimen was more effective in all subgroups with Los Angeles Classification Grade B to D at treatment entry., Conclusions: In the maintenance treatment of PPI-resistant RE, rabeprazole at 10 mg b.i.d. exerted a stronger recurrence-preventing effect than 10 mg q.d. over 52 weeks. No particular safety issues were noted during long-term administration. ClinicalTrials.gov number: NCT02135107.

To achieve the goals of Paris Agreement, global society is directing much effort in substantially reducing greenhouse gas (GHG) emissions. In addition to energy-related efforts, prevention of carbon release into the atmosphere with carbon capture and storage (CCS) and/or utilization of biomass resources is considered indispensable to achieving the global objective. In this study, considering carbon-containing goods as carbon reservoirs in our society similar to forests and reservoirs enabling CCS, the flow of materially utilized carbon was quantified by input-output-based material flow analysis (IO-MFA). As a result, in 2011, 6.3 Mt-C of petroleum-derived carbon and 7.9 Mt-C of wood-derived carbon were introduced to the Japanese society as end-use products (e.g., automobiles and constructions) in various forms (e.g., plastics and synthetic rubbers). The total amount (14.2 Mt-C) corresponded to 4.1% (52.1 Mt-CO 2 ) of annual CO 2 emission in Japan in 2011. Subsequently, by referring to the technology that can treat carbon in the target forms in end-of-life products, the recoverability of carbon as a material has been discussed with respect to each form and end-use of carbon. By numerically showing the necessity and potential of implementing appropriate technologies, this study provides scientific direction for policymakers to establish a quality carbon cycle in our society.

Since the accident at the Chernobyl Nuclear Power Plant, it has become well known that radiocesium tends to concentrate in wild mushrooms. During the recovery process after the accident at the Fukushima Daiichi Nuclear Power Station (FDNPS), it is important to perform follow-up measurements of the activity concentrations of radiocesium in mushrooms. We evaluated the activity concentrations of the detected artificial radionuclides (radiocesium) in wild mushrooms collected from Kawauchi village, which is within 30 km of the FDNPS, in 2015, four years after the accident. We found that the radiocesium was determined in 147 of 159 mushroom samples (92.4%). Based on the average mushroom consumption of Japanese citizens (6.28 kg per year), we calculated committed effective doses ranging from <0.001 to 0.6 mSv. Although committed effective doses are relatively limited, even if residents have consumed mushrooms several times, continuous monitoring of the radiocesium in mushrooms in Fukushima is needed for sustained recovery from the nuclear disaster.

Polyphenol intake has been estimated in some populations; however, information about day-to-day and individual differences in polyphenol intake has not been well-evaluated. In this study, we aimed to examine within- and between-individual variation in polyphenol intake in Japanese male workers. First, 56 male subjects (aged 37.9±10.4 y) completed detailed 7-d dietary records (DR). We then calculated their total polyphenol intake using our polyphenol content database and the within- and between-individual variations. We also estimated the minimum number of days of dietary assessment required both to rank individuals within a group and to assess an individual's usual polyphenol intake with acceptable accuracy. The estimated daily total polyphenol intake was 965±471 mg/d, which was largely sourced from beverages. The day-to-day variation (CV w ) for polyphenol intake was 43.6%, and the variation between the individuals in the population (CV b ) for polyphenol intake was 45.9%. A 4-d DR was required to rank individuals within a group with high correlation coefficients (r=0.9), and a 19-d DR was required to assess the individual's usual polyphenol intake with 20% deviation. The CV w for polyphenol intake was intermediate between those of the other nutrients, but the CV b for polyphenol intake was largest among the nutrients. These results suggest that the dietary intake of polyphenols should be carefully estimated considering its within- and between-individual variation.

Aim: Several studies have demonstrated that polymorphisms within the fat-mass and obesity-associated gene (FTO) are associated with type 2 diabetes (T2D). However, whether the effects of the FTO locus on T2D susceptibility are independent of fat-mass increases remains controversial. To investigate this issue, we examined the association of FTO variants with T2D and various aspects of BMI history during adult life in a Japanese population., Methods: We genotyped SNPs within FTO (rs1121980 and rs1558902) in 760 Japanese patients with T2D who had reached a lifetime maximum BMI (BMImax) before or at the time of diagnosis and 693 control individuals with information regarding their BMImax., Results: The BMImax showed the strongest association with T2D risk among the BMIs evaluated in this study. In the sex-combined analysis, FTO SNPs were not associated with any of the BMI variables or with T2D, but in sex-stratified analyses, both SNPs were significantly associated with the BMImax and rs1558902 was associated with T2D in men. The association of the SNPs with T2D remained significant after adjustments for the current BMI and age, whereas the T2D association of the SNP was no longer significant after adjustments for BMImax and age., Conclusions: These results suggest that the effects of FTO polymorphisms on T2D susceptibility in Japanese men are mediated through their effect on increasing the BMImax before or at the time of diagnosis., Competing Interests: The authors have declared that no competing interests exist.

Estimating polyphenol intake contributes to the understanding of polyphenols' health benefits. However, information about human polyphenol intake is scarce, especially in the elderly. This study aimed to estimate the dietary intake and major sources of polyphenols and to determine whether there is any relationship between polyphenol intake and micronutrient intake in healthy elderly Japanese. First, 610 subjects (569 men, 41 women; aged 67.3 ± 6.1 years) completed food frequency questionnaires. We then calculated their total polyphenol intake using our polyphenol content database. Their average total polyphenol intake was 1492 ± 665 mg/day, the greatest part of which was provided by beverages (79.1%). The daily polyphenol intake differed largely among individuals (183-4854 mg/day), also attributable mostly to beverage consumption. Coffee (43.2%) and green tea (26.6%) were the major sources of total polyphenol; the top 20 food items accounted for >90%. The polyphenol intake did not strongly correlate with the intake of any micronutrient, suggesting that polyphenols may exert health benefits independently of nutritional intake. The polyphenol intake in this elderly population was slightly higher than previous data in Japanese adults, and beverages such as coffee and green tea contributed highly to the intake.

Background: Ves v 5 and Pol d 5, which constitute antigen 5, are recognized as the major, most potent allergens of family Vespidae. Several studies have reported the diagnostic sensitivity of the novel recombinant (r)Ves v 5 and rPol d 5 allergens in routine clinical laboratory settings by analyzing a group of Vespula and Polistes venom-allergic patients. In this study, we analyzed the sensitivity to venom specific (s)IgE by spiking with rVes v 5 and rPol d 5 in Japanese patients suspected of Hymenoptera venom allergy., Methods: Subjects were 41 patients who had experienced systemic reactions to hornet and/or paper wasp stings. Levels of serum sIgE against hornet and paper wasp venom by spiking with rVes v 5 and rPold d 5, respectively, as improvement testing, compared with hornet and paper wasp venom, as conventional testing, were measured by ImmunoCAP., Results: Of the 41 patients, 33 (80.5%) were positive (≥0.35 UA/ml) for hornet and/or paper wasp venom in conventional sIgE testing. sIgE levels correlated significantly (P < 0.01) between hornet (R = 0.92) or paper wasp venom (R = 0.78) in improvement testing and conventional testing. To determine specificity, 20 volunteers who had never experienced a Hymenoptera sting were all negative for sIgE against these venoms in both improvement and conventional testing. Improved sensitivity was seen in 8 patients negative for sIgE against both venoms in conventional testing, while improvement testing revealed sIgE against hornet or paper wasp venom in 5 (total 38 (92.7%)) patients., Conclusions: The measurement of sIgE following spiking of rVes v 5 and rPol d 5 by conventional testing in Japanese subjects with sIgE against hornet and paper wasp venom, respectively, improved the sensitivity for detecting Hymenoptera venom allergy. Improvement testing for measuring sIgE levels against hornet and paper wasp venom has potential for serologically elucidating Hymenoptera allergy in Japan., (Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Cardiovascular risk remains uncertain in patients with cardiovascular disease despite achieving target lipid levels. Serum levels of lipoprotein(a) [Lp(a)] can be risk factors for adverse events. The aim of this study was to determine the role of Lp(a) as a residual risk factor in patients who achieve target lipid levels by the time of treatment by percutaneous coronary intervention (PCI). A total of 3,508 patients were treated by PCI from 1997 to 2011 at our institution. Among them, we analyzed consecutive 569 patients who achieved target lipid levels of low-density lipoprotein cholesterol <100 mg/dl, high-density lipoprotein cholesterol ≥40 mg/dl, and triglycerides <150 mg/dl at PCI. A total of 411 eligible patients were assigned to groups according to Lp(a) levels of ≥30 mg/dl (high Lp(a); n = 119) or <30 mg/dl (low Lp(a); n = 292). The primary outcome was a composite of all-cause death and acute coronary syndrome. The median follow-up period was 4.7 years. Cumulative event-free survival was significantly worse for the group with high Lp(a) than with low Lp(a) group (p = 0.04). Multivariate analysis selected a high Lp(a) level as an independent predictor of primary outcomes (hazard ratio 1.68, 95% confidence interval 1.03 to 2.70, p = 0.04). In conclusion, a high Lp(a) value (≥30 mg/dl) could be associated with a poor prognosis after PCI even for patients who achieved target lipid levels., (Copyright © 2015 Elsevier Inc. All rights reserved.)

As a result of the accident at the Fukushima Daiichi Nuclear Power Plant (FNPP) on 11 March 2011, a huge amount of radionuclides, including radiocesium, was released and spread over a wide area of eastern Japan. Although three years have passed since the accident, residents around the FNPP are anxious about internal radiation exposure due to radiocesium. In this study, we screened internal radiation exposure doses in Iwaki city of Fukushima prefecture, using a whole-body counter. The first screening was conducted from October 2012 to February 2013, and the second screening was conducted from May to November 2013. Study participants were employees of ALPINE and their families who underwent examination. A total of 2,839 participants (1,366 men and 1,473 women, 1-86 years old) underwent the first screening, and 2,092 (1,022 men and 1,070 women, 1-86 years old) underwent the second screening. The results showed that 99% of subjects registered below 300 Bq per body in the first screening, and all subjects registered below 300 Bq per body in the second screening. The committed effective dose ranged from 0.01-0.06 mSv in the first screening and 0.01-0.02 mSv in the second screening. Long-term follow-up studies are needed to avoid unnecessary chronic internal exposure and to reduce anxiety among the residents by communicating radiation health risks.

Objectives: To evaluate if esomeprazole prevents recurrent peptic ulcer in adult patients with a history of peptic ulcer receiving low-dose acetylsalicylic acid (ASA, aspirin) for cardiovascular protection in East Asia., Methods: In this prospective, randomised, double-blind, placebo-controlled trial conducted in Japan, Korea and Taiwan, eligible patients receiving low-dose ASA for cardiovascular protection (81-324 mg/day) were randomised to esomeprazole 20 mg/day or placebo for ≤72 weeks. All patients received concomitant mucosal protection (gefarnate 100 mg/day). The primary endpoint was time to ulcer recurrence (Kaplan-Meier analysis). Efficacy findings are presented up to week 48, as per a planned interim analysis within the study protocol., Results: A total of 364 patients (79.9% men; mean age, 67.1 years) comprised the full analysis set (esomeprazole, n=182; placebo, n=182). There was a statistically significant difference in the time to ulcer recurrence between esomeprazole and placebo (HR 0.09; 96.65% CI 0.02 to 0.41; p<0.001). The estimated ulcer-free rate at week 12 was 99.3% (esomeprazole) and 89.0% (placebo). The high estimated ulcer-free rate for esomeprazole was maintained through to week 48 (98.3% vs. 81.2% of placebo-treated patients). No factors, other than female gender, reduced time to ulcer recurrence in addition to the effect of esomeprazole (p<0.001). Treatment with esomeprazole was generally well tolerated., Conclusions: Daily esomeprazole 20 mg is efficacious and well tolerated in reducing the recurrence of peptic ulcer in East-Asian patients with a history of ulcers who are taking low-dose ASA for cardiovascular protection., Clinicaltrialgov Identifier: NCT01069939., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)