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I would like to congratulate the Journal of Biochemistry (JB) on its 100th anniversary. I served as the Editor-in-Chief for four years starting in 2010 and succeeded Dr Naoyuki Taniguchi. [ABSTRACT FROM AUTHOR]

Cryptomeria japonica (sugi) and Chamaecyparis obtusa (hinoki) are major Japanese timber species whose plantation area accounts for 44 and 25%, respectively, of the plantation forests in Japan. Physiology, anatomy and ecology of the species have been intensively studied for this half century, which now forms a huge stock of information. These data, however, were scattered in diverse sources, including papers, bulletins of research institutes, reports of other kinds and books, and were presented in nonstandardized, diverse styles in each source. This paper provides a database (SugiHinoki DB) that compiles 177 plant traits of sugi and hinoki from 364 primary sources published since 1950. The compiled traits include physiological, morphological, anatomical and biochemical features that are recognized as relevant to life history strategies, vegetation modeling and global change responses. Collected data have been obtained under different environmental conditions, for plants with different ages and for organs with a different age or different position, which provide information of within‐species variation for a given trait. Each data entry is accompanied by detailed ancillary information describing the site of measurement, stand of measurement and detailed measurement conditions, which help users account for data variations as a consequence of phenotypic plasticity and genetic variations and to filter data. To provide data in a consistent format, the data and the ancillary information were standardized, and units were converted. After data compilation, outliers were detected by calculating interquartile range for each trait per each species. As of August 2019, SugiHinokiDB contains 24,683 data entries (16,410 for sugi, 8,273 for hinoki). As sugi and hinoki are major plantation species in Japan, the data mostly came from study sites in Japan (from Hokkaido in the north to Yakushima island in Kyushu to the south) but were also obtained from arboretums or plantation forests in Taiwan, Korea and China. Data were largely obtained from plants in plantation forests but also from plants in natural forests and under experimental conditions. The improved availability of trait data offered by SugiHinokiDB provides new research opportunities, such as the intensive parameterization of vegetation models for a more accurate prediction of climate change impacts. [ABSTRACT FROM AUTHOR]

The article provides information on the Japanese Biochemical Society. The society was founded on April 4, 1925 by Samuro Kakiuchi, a professor of biochemistry at the University of Tokyo. The major activities of the society include the organization of meetings, publication, international cooperation, and advice to the Science Council of Japan. The society is responsible for the publishing of the "Journal of Biochemistry," which publishes several original papers in English.

Physiologically based pharmacokinetic (PBPK) models are useful in bridging drug exposure in different ethnic groups, and there is increasing regulatory application of this approach in adults. Reported pediatric PBPK models tend to focus on the North European population, with few examples in other ethnic groups. This study describes the development and verification of a Japanese pediatric PBPK population. The development of the model was based on the existing North European pediatric population. Japanese systems and clinical data were collated from public databases and the literature, and the underlying demographics and equations were optimized so that physiological outputs represented the Japanese pediatric population. The model was tested using 14 different small molecule drugs, eliminated by a variety of pathways, including cytochrome P450 3A4 (CYP3A4) metabolism and renal excretion. Given the limitations of the clinical data, the overall performance of the model was good, with 44/62 predictions for PK parameters (area under the plasma drug concentration–time curve, AUC; maximum serum concentration, Cmax; clearance, CL) being within 0.8‐ to 1.25‐fold, 56/62 within 0.67‐ to 1.5‐fold, and 61/62 within 0.5‐ to 2.0‐fold of the observed values. Specific results for the 5 CYP3A4 substrates showed 20/31 cases were predicted within 0.8‐ to 1.25‐fold, 27/31 within 0.67‐ to 1.5‐fold, and all were within 0.5‐ to 2.0‐fold of the observed values. Given the increased regulatory use of pediatric PBPK in drug development, expanding these models to other ethnic groups are important. Considering qualifying these models based on the context of use, there is a need to expand on the current research to include a larger range of drugs with different elimination pathways. Collaboration among academic, industry, model providers, and regulators will facilitate further development. [ABSTRACT FROM AUTHOR]

The article offers information on clinical practice guidelines for endometriosis in Japan. It examines fundamental knowledge in clearly elaborating current perspectives on the review of the diagnosis and treatment, in addition to the advance over the last 10 years, as of December 2022. It further explores therapeutic strategies.

In this article, the author comments on two letters to the editors on a report from the Working Group of the Molecular Biology Society of Japan which have been published in this issue of the journal. The author further says that the publication of these two letters will help in preventing similar misconduct from occurring in the future.

Purpose: The purpose of this study was to examine whether long-term ingestion of low-dose milk protein supplementation causes a greater increase in muscle mass and strength of older adults during low-to-moderate intensity exercise training intervention than isocaloric carbohydrate. Methods: In a randomized, double-blind, and placebo-controlled design, 122 healthy older adults (60–84 year) received either an acidified milk protein drink containing 10 g of milk protein (MILK; n = 61) or an isocaloric placebo drink (PLA; n = 61) daily throughout 6 months of body weight and medicine ball exercise training. Measurements before and after the intervention included body composition, physical performance and blood biochemistry. Results: Lean body mass significantly increased in the MILK group (+ 0.54 kg, p < 0.001), but did not change in the PLA group (− 0.10 kg, p = 0.534). The increases in the MILK group were significantly greater than in the PLA group (p = 0.004). Fat mass (− 0.77 kg) and plasma uric acid levels (− 0.3 mg/dL) significantly decreased only in the MILK group (p < 0.001), with a significant group difference (p = 0.002 and p < 0.001, respectively). Most of the physical performance tests significantly improved in both groups, but no group differences were found. Conclusion: We conclude that low-dose milk protein supplementation (10 g of protein/day) combined with low-to-moderate intensity exercise training is associated with increased muscle mass, but not improved physical performance compared to carbohydrate combined with exercise in healthy older adults. This study was registered in the UMIN Clinical Trials Registry (UMIN000032189). [ABSTRACT FROM AUTHOR]

Objective: To evaluate how cardiovascular diseases harm labor force participation (LFP) among the Japanese population and verify the validity of plasma biomarkers as instrumental variables of cardiovascular diseases after adjusting for a broad set of confounders including dietary intake. Design: Using nationally representative repeated cross-sectional surveys in Japan, the Comprehensive Survey of Living Conditions and National Health and Nutrition Survey, with plasma biomarkers as instrumental variables for quasi-randomization. Setting: Onset of cardiovascular diseases in those receiving regular treatment for hypertension, intracerebral hemorrhage, intracerebral infarction, angina pectoris, myocardial infarction, or other types of cardiovascular diseases. Participants: A total of 65,615 persons aged ≥ 20 years (35,037 women and 30,578 men) who completed a survey conducted every three years from 1995 through 2013. Main outcome measures: Respondent employment and weekly working hours during each survey year. Results: Cardiovascular diseases significantly and remarkably reduced the probability of working by 15.4% (95% CI: -30.6% to -0.2%). The reduction in working probability was detected for women only. Respondents aged ≥ 40 years were less likely to work once diagnosed and the reduction was enlarged for those aged ≥ 65 years, while those aged < 40 years appeared to be unaffected. Probability of engaging in manual labor significantly decreased once diagnosed; however, no impact was found for cognitive occupations. Among employed respondents, the adverse effects of cardiovascular diseases decreased working hours by five hours per week. Validity of the biomarker instrumental variables was generally verified. Conclusions: A vicious circle is suggested between LFP and unfavorable health. However, the effects vary across age, sex, and occupation type, even after adjusting for causal effects, which could cause a downward bias in LFP impact. Attributes: cardiovascular disease, labor force participation, instrumental variable method as quasi-randomization, plasma biomarker, Comprehensive Survey of Living Conditions, National Health and Nutrition Survey. [ABSTRACT FROM AUTHOR]

Background: In the current meta-analysis, we aimed to systematically review and summarize the eligible studies evaluating the association between dietary acid load in terms of potential renal acid load (PRAL) and net-endogenous acid production (NEAP) with anthropometric parameters and serum lipids in adult population. Methods: In a systematic search from PubMed, Scopus, Web of Sciences and Cochrane electronic databases up to December 2018, relevant studies were included. Cross-sectional, case control or cohort studies evaluating the association between PRAL and NEAP with the mean values of body mass index (BMI), waist circumference (WC), low and high density lipoprotein cholesterol (LDL, HDL), triglyceride (TG), total cholesterol (TC) and the prevalence of obesity were included. Results: According to our results, having higher dietary acid load content in terms of high PRAL scores was associated with higher triglyceride concentrations (weighted mean difference (WMD): 3.468; confidence interval (CI): -0.231, 7.166, P = 0.04) and higher obesity prevalence (30% and 27% in highest versus lowest categories). Accordingly, being in the highest category of NEAP was associated with higher prevalence of obesity (25% and 22% in highest versus lowest category). In subgroup analysis, higher PRAL scores was associated with higher BMI in women (WMD: 0.122; CI: -0.001, 0.245; P = 0.049) and higher NEAP in men (WMD: 0.890; CI: 0.430, 1.350; P < 0.001). There was no association between dietary acid load and other studied parameters. Conclusions: In the current meta-analysis, high dietary acid load content was associated with higher serum triglyceride concentrations and higher obesity prevalence. Reducing dietary acid load content might be a useful preventive strategy against obesity and metabolic disorders. [ABSTRACT FROM AUTHOR]

Background: The crushed-tablet rivaroxaban concentration has been previously reported to be lower than the non-crushed concentration. However, the rivaroxaban concentration of fine granules has not yet been investigated. The anticoagulation intensity of rivaroxaban with fine granules, tablets, and crushed tablets was compared in acute stroke patients to assess the efficacy of each form. Methods and findings: Hospitalized patients over 75 years old with acute stroke who started taking rivaroxaban from April 2012 to September 2017 were included. Blood samples were drawn just before and 4 hours after taking rivaroxaban on a median of 5 days after treatment initiation for concentration measurements (C0h, C4h) based on an anti-factor Xa chromogenic assay. Of 114 patients (49 female, 83±5 years old), 97 had ischemic strokes, 9 had transient ischemic attacks, and 8 had intracerebral hemorrhages. Rivaroxaban was administered a median of 7 days after onset. Of these, 38 patients were given the 15 mg dose, and 76 were given the 10 mg dose. In the 15 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group, with no significant difference compared to the tablet group [C0h: 27.6±6.8 vs 4.0±4.1 (P = 0.01) vs. 33.3±25.2 ng/ml, (P = 0.51), respectively], as was C4h [223.0±66.6 vs 103.0±79.5 (P = 0.02) vs. 229.5±121.6 ng/ml (P = 0.88)]. In the 10 mg dose group, C0h was significantly higher in the fine granule group than in the crushed tablet group and comparable to that in the tablet group [23.2±7.9 vs 7.5±6.2 (P<0.01) vs 19.0±15.8 ng/ml, (P = 0.35)], as was C4h [150.7±85.4 vs 85.1±46.8 (P<0.01) vs 189.8±92.7 ng/ml (P = 0.18)]. Conclusions: The rivaroxaban concentration with fine granules was consistent with that in the tablet group and higher than that in the crushed tablet group. [ABSTRACT FROM AUTHOR]

Although insufficient dietary protein intake is a known risk factor for age-related muscle weakness, the optimal age at which higher protein intake is required to prevent muscle weakness is yet to be determined. Using a population-based panel survey of community-dwelling people aged 50–75 years, this cross-sectional study aimed to find the age threshold at which a higher protein intake is associated with higher muscle strength. We utilized a dataset from the Japanese Study of Aging and Retirement conducted between 2007 and 2011. Dietary protein intake was estimated using a validated dietary questionnaire and energy-adjusted via density method. Grip strength was measured using a Smedley-type handheld dynamometer. We calculated the marginal effect (and 95% confidence intervals) of protein intake on grip strength with stratification by age using multiple linear regression analyses with robust variance adjusting for potential confounders. There were 9,485 observations from 5,790 participants in the final analysis. Marginal effects of protein intake on grip strength increased with age, and it reached significance and had a positive impact only among men aged ≥75 years and women aged ≥65 years. With an additional 1% energy of protein intake, grip strength was increased by 0.10 kg and 0.19 kg for men and women aged ≥75 years, respectively. Our result indicated the possibility that women needed a high protein intake from a younger age compared with men. Further studies are needed to clarify from when a higher protein intake is recommended to prevent muscle weakness. [ABSTRACT FROM AUTHOR]

The article reports that Japan's most prestigious university is investigating the basis of several papers published by a faculty member over the past 7 years. Officials at the University of Tokyo say it's the first case of its kind in the institution's history. The matter involves a group led by Kazunari Taira, a professor of chemistry and biological chemistry in the Graduate School of Engineering. Taira was unable to produce the raw data or experimental notes to support a string of papers from his lab that were published in top-tier journals, according to an interim report by an investigative committee looking into the matter. Yoichiro Matsumoto, a mechanical engineer who led the investigating committee, says that the case has caught university officials flat-footed. He says that they don't have an example of how such a situation would ordinarily be handled. Both Matsumoto and a university spokesperson say that this is the first time such an allegation has surfaced at the university, known as Todai. According to a report released by the investigating committee, the society questioned the reproducibility of the results reported in 11 papers that appeared between 1998 and 2004 in journals that include Nature, Nature Biotechnology, and the Proceedings of the National Academy of Sciences U.S.

Background. Children and adolescents with papillary thyroid carcinomas (PTCs) have generally excellent prognoses despite their frequent extended disease. The tumor growth of young patients’ PTCs might show spontaneous slowing postoperatively. We compared young PTC patients’ postoperative thyroglobulin-doubling time (Tg-DT) with their preoperative hypothetical tumor volume-doubling time (hTV-DT). Methods. Fourteen PTC patients aged ≤18 years who underwent total thyroidectomy at Kuma Hospital in 1998–2016 had biochemically persistent disease postoperatively. We calculated their Tg-DTs and estimated their preoperative TV-DTs with the tumor size and the patient’s age at surgery, presuming that a single cancer cell was present at the patient’s birth. Results. Twelve patients had positive Tg-DTs ranging from 2.0 to 147 years, and the remaining two had negative Tg-DTs, indicating slow growth or even regression. The hTV-DTs were 0.3–0.6 years (median 0.5 years), which were significantly shorter than the Tg-DTs (p<0.001), indicating much faster growth preoperatively. The analyses of the nine patients without radioactive iodine administration (RAI) gave similar results (p<0.01). Conclusions. Irrespective of RAI, the patients’ postoperative Tg-DTs were significantly longer than their preoperative hTV-DTs and were negative values in two patients, indicating that the growth of these young patients’ PTCs had spontaneously slowed or even regressed postoperatively. [ABSTRACT FROM AUTHOR]

Objectives: Excessively short and long sleep durations are associated with type 2 diabetes, but there is limited information about the association between sleep quality and diabetes. Accordingly, the present study was performed to investigate this relationship. Materials and methods: The subjects were 3249 patients with type 2 diabetes aged 20 years or older. Sleep quality was assessed by using the Pittsburgh Sleep Quality Index (PSQI). A higher global PSQI score indicates worse sleep quality, and a global PSQI score >5 differentiates poor sleepers from good sleepers. Results: The mean global PSQI score was 5.94 ± 3.33, and 47.6% of the patients had a score of 6 or higher. Regarding the components of the PSQI, the score was highest for sleep duration, followed by subjective sleep quality and then sleep latency in decreasing order. When the patients were assigned to HbA1c quartiles (≤ 6.5%, 6.6–7.0%, 7.1–7.8%, and ≥ 7.9%), the top quartile had a significantly higher global PSQI score than the other quartiles. The top HbA1c quartile had a sleep duration of only 6.23 ± 1.42 hours, which was significantly shorter than in the other quartiles. Also, sleep latency was 25.3 ± 31.8 minutes in the top quartile, which was significantly longer (by approximately 20 minutes) than in the other quartiles. When analysis was performed with adjustment for age, gender, BMI, smoking, and other confounders, the global PSQI score was still significantly higher and sleep duration was shorter in the top HbA1c quartile (HbA1c ≥ 7.9%). Conclusions: Japanese patients with type 2 diabetes were found to have poor subjective sleep quality independently of potential confounders, especially those with inadequate glycemic control. Impairment of sleep quality was associated with both increased sleep latency and a shorter duration of sleep. [ABSTRACT FROM AUTHOR]

Quercetin is a polyphenol found in food that has numerous health benefits. This study investigated the relationship between quercetin metabolism, gut microbiota composition, and dietary intake in elderly Japanese subjects. A food frequency questionnaire was used to assess dietary intake during the week prior to stool sample collection. Fecal suspensions from 56 subjects were anaerobically incubated with quercetin and fecal microbiota composition was analyzed by next-generation sequencing. Inter-individual variations in quercetin concentration and fecal microbiota composition at family level suggested differences in microbial quercetin metabolism. The abundance of Sutterellaceae (r = −0.292) and Oscillospiraceae (r = −0.334) was negatively correlated whereas that of Fusobacteriaceae (r = 0.361) and Enterobacteriaceae (r = 0.321) was positively correlated with quercetin concentration. Niacin (r = −0.313), vitamin B6 (r = −0.297), vitamin B12 (r = −0.266), vitamin D (r = −0.301), and ratio of animal protein to total protein (r = −0.27) were also negatively correlated with quercetin concentration. Bacterial abundance was positively or negatively related to intake of food components. This is the first report describing the relationship between fecal quercetin metabolism, human microbiota, and dietary intake in the elderly. [ABSTRACT FROM AUTHOR]

Background: While body mass index (BMI) is the most widely used anthropometric measure, its association with all-cause mortality is generally J-shaped or U-shaped. A body shape index (ABSI) is a recently formulated anthropometric measure that shows linear relationship to all-cause mortality, especially in Caucasian cohorts. We aimed to address the relationship between ABSI and all-cause mortality in Asians and to assess the influence of sex difference and of chronic kidney disease (CKD) on this relationship. Methods: This was a longitudinal cohort study assessing the association of ABSI, BMI, waist circumference (WC), and waist-to-height ratio (WHtR) with all-cause mortality in a Japanese nationwide Specific Health Checkup database. The study enrolled 160,625 participants followed-up between 2008 and 2012. We calculated the all-cause mortality risk associated with a 1-standard deviation increase (+1SD) in ABSI, BMI, WC, or WHtR in cohorts stratified by sex and the presence of CKD. Results: During the 4-year follow up, 1.3% of participants died. In men, ABSI (+1SD) significantly increased the risk for all-cause mortality after adjusting for other known risk factors including CKD; hazard ratio (HR) and 95% confidence intervals (CI) of non-CKD cohort, 1.30 (1.18 to 1.43), p<0.01; HR and 95%CI of CKD cohort, 1.16 (1.01 to 1.34), p = 0.04. In women, ABSI (+1SD) did not show significant association with all-cause mortality, especially in the CKD cohort; HR and 95% CI of non-CKD cohort, 1.07 (0.99 to 1.17), p = 0.09; HR and 95%CI of CKD cohort, 0.98 (0.84 to 1.14), p = 0.78. Conversely, BMI (+1SD) was associated with significantly lower risk in men, although minimal association was found in women. WC and WHtR showed little association with all-cause mortality. On stratification per ABSI quartiles, mortality risk increased linearly and significantly with ABSI in men, but not in women with CKD. Both BMI and WC showed significant but U-shaped association with mortality in the non-CKD cohort and in men with CKD. WHtR also showed significant U-shaped association with mortality in men. Conclusions: In the Japanese population, ABSI showed significant and linear correlation with mortality risk in men but not in women, especially in the presence of CKD. [ABSTRACT FROM AUTHOR]

A novel Vibrio strain, JCM 31412T, was isolated from seawater collected from the Inland Sea (Setonaikai), Japan, and characterized as a Gram-negative, oxidase-positive, catalase-negative, facultatively anaerobic, motile, ovoid-shaped bacterium with one polar flagellum. Based on 16S rDNA gene identity, strain JCM 31412T showed a close relationship with type strains of Vibrio brasiliensis (LMG 20546T, 98.2% identity), V. harveyi (NBRC 15634T, 98.2%), V. caribbeanicus (ATCC BAA-2122T, 97.8%) and V. proteolyticus (NBRC 13287T, 97.8%). The G+C content of strain JCM 31412T DNA was 46.8%. Multi-locus sequence analysis (MLSA) of eight loci (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA and topA; 5535bp) further clustered strain JCM 31412T in the Nereis clade, genus Vibrio. Phenotypically, strain JCM 31412T differed from the closest related Vibrio species in its utilization of melibiose and raffinose, and its lack of casein and gelatin hydrolysis. It was further differentiated based on its fatty acid composition, specifically properties of C12:03OH and summed features, which were significantly different from those of V. brasiliensis, V. nigripulchritudo and V. caribbeanicus type strains. Overall, the results of DNA-DNA hybridization, and physiological and biochemical analysis differentiated strain JCM 31412T from other described species of the genus Vibrio. Based on these polyphasic taxonomic findings, it was therefore concluded that JCM 31412T was a novel Vibrio species, for which the name Vibrio japonicus sp. nov. was proposed, with JCM 31412T (= LMG 29636T = ATCC TSD-62T) as the type strain. [ABSTRACT FROM AUTHOR]

The prediction of the lineage dynamics of influenza B viruses for the next season is one of the largest obstacles for constructing an appropriate influenza trivalent vaccine. Seasonal fluctuation of transmissibility and epidemiological interference between the two major influenza B lineages make the lineage dynamics complicated. Here we construct a parsimonious model describing the lineage dynamics while taking into account seasonal fluctuation of transmissibility and epidemiological interference. Using this model we estimated the epidemiological and evolutional parameters with the time-series data of the lineage specific isolates in Japan from the 2010–2011 season to the 2014–2015 season. The basic reproduction number is similar between Victoria and Yamagata, with a minimum value during one year as 0.82 (95% highest posterior density (HPD): 0.77–0.87) for the Yamagata and 0.83 (95% HPD: 0.74–0.92) for Victoria, the amplitude of seasonal variation of the basic reproduction number is 0.77 (95% HPD:0.66–0.87) for Yamagata and 1.05 (95% HPD: 0.89–1.02) for Victoria. The duration for which the acquired immunity is effective against infection by the Yamagata lineage is shorter than the acquired immunity for Victoria, 424.1days (95% HPD:317.4–561.5days). The reduction rate of susceptibility due to immune cross-reaction is 0.51 (95% HPD: 0.084–0.92) for the immunity obtained from the infection with Yamagata against the infection with Victoria and 0.62 (95% HPD: 0.42–0.80) for the immunity obtained from the infection with Victoria against the infection with Yamagata. Using estimated parameters, we predicted the dominant lineage in 2015–2016 season. The accuracy of this prediction is 68.8% if the emergence timings of the two lineages are known and 61.4% if the emergence timings are unknown. Estimated seasonal variation of the lineage specific reproduction number can narrow down the range of emergence timing, with an accuracy of 64.6% if the emergence times are assumed to be the time at which the estimated reproduction number exceeds one. [ABSTRACT FROM AUTHOR]

The article highlights the International Symposium on Enzyme Chemistry that was held on October 15-23, 1957 in Japan. Participants include A. Braunstein of Soviet Union, J. Brachet of Belgium, F. Dickens of Great Britain, and C. Fromageot of France. The different scientific sections discussed topics on mechanisms of enzymatic group transfer, formation of proteins and enzymes, and enzyme systems of hydrogen, oxygen, and electron transfer.

Preterm low-birth-weight infants remain difficult to manage based on adequate laboratory tests. The aim of this study was to establish blood reference intervals (RIs) in those newborns who were admitted to and survived in the neonatal intensive care unit (NICU). A multicenter prospective study was conducted among all infants admitted to 11 affiliated NICUs from 2010 to 2013. The clinical information and laboratory data were registered in a network database designed for this study. The RIs for 26 items were derived using the parametric method after applying the latent abnormal values exclusion method. The influence of birth weight (BW) and gestational age (GA) on the test results was expressed in terms of the standard deviation ratio (SDR), as SDRBW and SDRGA, respectively. A total of 3189 infants were admitted during the study period; 246 were excluded due to a lack of blood sampling data, and 234 were excluded for chromosomal abnormalities (n = 108), congenital anomalies requiring treatment with surgical procedures (n = 76), and death or transfer to another hospital (n = 50). As a result, 2709 infants were enrolled in this study. Both the SDRGA and SDRBW were above 0.4 in the test results for total protein (TP), albumin (ALB), alanine aminotransferase (ALT), and red blood cells (RBC); their values increased in proportion to the BW and GA. We derived 26 blood RIs for infants who were admitted to NICUs. These RIs should help in the performance of proper clinical assessments and research in the field of perinatal-neonatal medicine. [ABSTRACT FROM AUTHOR]

Aims: Glutamic acid decarboxylase autoantibodies (GADAb) differentiate slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) from phenotypic type 2 diabetes, but many GADAb-positive patients with diabetes do not progress to insulin-requiring diabetes. To characterize GADAb-positive patients with adult-onset diabetes who do not require insulin therapy for >5 years (NIR-SPIDDM), we conducted a nationwide cross-sectional survey in Japan. Methods: We collected 82 GADAb-positive patients who did not require insulin therapy for >5 years (NIR-SPIDDM) and compared them with 63 patients with insulin-requiring SPIDDM (IR-SPIDDM). Clinical and biochemical characteristics, HLA-DRB1-DQB1 haplotypes, and predictive markers for progression to insulin therapy were investigated. Results: Compared with the IR-SPIDDM group, the NIR-SPIDDM patients showed later diabetes onset, higher body mass index, longer duration before diagnosis, and less frequent hyperglycemic symptoms at onset. In addition, C-peptide, LDL-cholesterol, and TG were significantly higher in the NIR-SPIDDM compared to IR-SPIDDM patients. The NIR-SPIDDM group had lower frequency of susceptible HLA-DRB1*04:05-DQB1*04:01 and a higher frequency of resistant HLA-DRB1*15:01-DQB1*06:02 haplotype compared to IR-SPIDDM. A multivariable analysis showed that age at diabetes onset (OR = 0.82), duration before diagnosis of GADAb-positive diabetes (OR = 0.82), higher GADAb level (≥10.0 U/ml) (OR = 20.41), and fasting C-peptide at diagnosis (OR = 0.07) were independent predictive markers for progression to insulin-requiring diabetes. An ROC curve analysis showed that the optimal cut-off points for discriminating two groups was the GADAb level of 13.6 U/ml, age of diabetes onset of 47 years, duration before diagnosis of 5 years, and fasting C-peptide of 0.65 ng/ml. Conclusions: Clinical, biochemical and genetic characteristics of patients with NIR-SPIDDM are different from those of IR-SPIDDM patients. Age of diabetes onset, duration before GADAb-positivity, GADAb level, and fasting C-peptide at diagnosis must be carefully considered in planning prevention trials for SPIDDM. [ABSTRACT FROM AUTHOR]

Background: Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. Methods and Findings: We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. Conclusions: Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase. [ABSTRACT FROM AUTHOR]

Serum uric acid (UA) has strong anti-oxidant properties. Muscle strength and mass decrease with age, and recently, this decrease has been defined as sarcopenia. Sarcopenia may be triggered by oxidative stress. We investigated whether serum UA is associated with handgrip strength (HGS), which is a useful indicator of sarcopenia, among Japanese community-dwelling elderly persons. The present study included 602 men aged 72 ± 7 years and 847 women aged 71 ± 6 years from a rural village. We examined the cross-sectional relationship between serum UA and HGS. In both genders, HGS increased significantly with increased serum UA levels. A multiple linear regression analysis using HGS as an objective variable and various confounding factors as explanatory variables showed that in men age, drinking status, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and estimated glomerular filtration ratio (eGFRCKDEPI) were independently and significantly associated with HGS, and in women, serum UA as well as age, body mass index, drinking status, diastolic blood pressure, and eGFRCKDEPI were independently and significantly associated with HGS. In women, age and multivariate-adjusted HGS were significantly higher in the Quartile-3 (4.8–5.4 mg/dL) and Quartile-4 groups (5.5–9.3 mg/dL) of serum UA than in the lower groups (0.7–4.7 mg/dL). These results suggest that serum UA may have a protective role in aging-associated decline in muscle strength in community-dwelling elderly women. [ABSTRACT FROM AUTHOR]

A carbapenem-resistant strain of Pseudomonas aeruginosa, NCGM1984, was isolated in 2012 from a hospitalized patient in Japan. Immunochromatographic assay showed that the isolate was positive for IMP-type metallo-β-lactamase. Complete genome sequencing revealed that NCGM1984 harbored two copies of blaIMP-34, located at different sites on the chromosome. Each blaIMP-34 was present in the same structures of the class 1 integrons, tnpA(ISPa7)-intI1-qacG-blaIMP-34-aac(6')-Ib-qacEdelta1-sul1-orf5-tniBdelta-tniA. The isolate belonged to multilocus sequence typing ST235, one of the international high-risk clones. IMP-34, with an amino acid substitution (Glu126Gly) compared with IMP-1, hydrolyzed all β-lactamases tested except aztreonam, and its catalytic activities were similar to IMP-1. This is the first report of a clinical isolate of an IMP-34-producing P. aeruginosa harboring two copies of blaIMP-34 on its chromosome. [ABSTRACT FROM AUTHOR]

Although Japanese herbal medicines (JHMs) are widely used in Japan, only a few studies have investigated their effects on nonalcoholic steatohepatitis (NASH). In the present study, we examined the effect of 4 kinds of JHMs [sho-saiko-to (TJ-9), inchin-ko-to (TJ-135), juzen-taiho-to (TJ-48), and keishi-bukuryo-gan (TJ-25)] on a mouse model of NASH. Db/db mice were divided into 6 groups: control diet (control), methionine- and choline-deficient diet (MCD), and MCD diet supplemented with TJ-9, TJ-135, TJ-48, and TJ-25 (TJ-9, TJ-135, TJ-48, and TJ-25, respectively). All mice were sacrificed after 4 weeks of treatment, and biochemical, pathological, and molecular analyses were performed. Serum alanine aminotransferase levels and liver histology, including necroinflammation and fibrosis, were significantly alleviated in the TJ-9 and TJ-48 groups compared with the MCD group. The expression level of transforming growth factor (TGF)-β1 mRNA in the liver was significantly suppressed by TJ-48. Although the differences were not statistically significant, the expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were lower, and those of peroxisome proliferators-activated receptor (PPAR)γ were higher in the TJ-9 and/or TJ-48 groups than in the MCD group. Similarly, even though the results were not statistically significant, malondialdehyde levels in liver tissues were lower in the TJ-9 and TJ-48 groups than in the MCD group. We showed that JHMs, especially TJ-9 and TJ-48, inhibited the necroinflammation and fibrosis in the liver of a mouse model of NASH, even though the mechanisms were not fully elucidated. Further studies are needed in the future to investigate the possibility of clinical application of these medicines in the treatment for NASH. [ABSTRACT FROM AUTHOR]

Fatty acid has been suggested to be involved in development of diabetes. However, its association is unclear among Japanese populations, which consume large amounts of fish rich in n-3 polyunsaturated fatty acids. The present cross-sectional study examined the association of individual dietary fatty acids and dietary fatty acid patterns with abnormal glucose metabolism among 1065 Japanese employees, aged 18–69 years. Impaired glucose metabolism is defined if a person has a history of diabetes, current use of anti-diabetic drug, fasting plasma glucose of 110 mg/dl (≥6.1 mmol/L) or greater, or hemoglobin A1C of 6.0% (≥42 mmol/mol) or greater. Dietary intake was assessed with a self-administered diet history questionnaire. Dietary fatty acid patterns were extracted by principal component analysis. Odds ratios of impaired glucose metabolism according to tertile categories of each fatty acids and dietary fatty acid patterns were estimated using logistic regression with adjustment for potential confounding variables. A higher intake of polyunsaturated fatty acid, n-6 fatty acid, linoleic acid, and oleic acid were significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.03, 0.01, 0.02, and 0.04, respectively). Alpha-linolenic acid was marginally significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.12). Of three fatty acid patterns identified, a higher plant oil pattern score, which characterized by high intake of alpha-linolenic acid, linoleic acid, and oleic acid, was associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.03). No association was observed for other patterns. In conclusion, plant source fatty acids might be protectively associated with development of diabetes in Japanese adults. [ABSTRACT FROM AUTHOR]

Aim To determine whether periodontitis and three prominent members of the periodontal flora are associated with the development of preeclampsia (hypertension plus proteinuria) Materials and Methods The samples were composed of 127 systemically healthy women. Within 5 days after labour, clinical periodontal parameters and Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia in subgingival plaque were evaluated. Maternal serum IgG antibody specific for each bacteria was determined by enzyme-linked immunosorbent assay. Multivariate logistic regression analysis was used to control for confounders (maternal age, body mass index before pregnancy, parity, and smoking). Results Eighteen women were affected with preeclampsia. The number of A.actinomycetemcomitans was shown to be significantly associated with preeclampsia in the logistic regression model (odds ratio; 1.7, 95% confidence interval; 1.1-2.7). There were statistically significant differences between the preeclamptic and control groups in body mass index before pregnancy, pre-term birth and low birthweight (respectively, p = 0.014, p = 0.010 and p < 0.0001). We found no statistically significant association between preeclampsia and periodontal clinical parameters or the presence of periodontitis. Conclusion In systemically healthy pregnant women, our findings suggested that the levels of maternal subgingival A. actinomycetemcomitans DNA were elevated in preeclamptic women. [ABSTRACT FROM AUTHOR]

In Mie Prefecture in Japan, rice blast isolates resistant to melanin biosynthesis inhibitors targeting scytalone dehydratase (SDH) were first observed in 2005. To analyze the distribution of the resistant isolates, 527 isolates were collected from wide areas in this prefecture during 2006 and 2007. Almost half of the isolates collected (233 of 527 isolates) carried a point mutation in the SDH gene conferring the resistant phenotype. To compare population structures of resistant and sensitive isolates, we analyzed the isolates with repetitive-element-based PCR DNA fingerprinting using a single primer complementary to a sequence in the terminal inverted repeat of transposable element Pot2. A majority of the resistant isolates were classified into a single DNA fingerprint haplotype, Mie1. Despite its prevalence in the resistant isolates, Mie1 was not found in the sensitive isolates. Furthermore, in a dendrogram constructed from the DNA fingerprint data, Mie1 and six other haplotypes formed a cluster composed of resistant isolates alone. These results suggest that the resistant isolates that belonged to the Mie1 haplotype had migrated from regions outside Mie Prefecture and selectively propagated in a short period in this prefecture. [ABSTRACT FROM AUTHOR]

Rice production is a substantial source of atmospheric CH4, which is second only to CO2 as a contributor to global warming. Since CH4 is produced in anaerobic soil environments, water management is expected to be a practical measure to mitigate CH4 emissions. In this study, we used a process-based biogeochemistry model (DNDC-Rice) to assess the CH4 mitigation potentials of alternative water regimes (AWR) for rice fields at a regional scale. Before regional application, we tested DNDC-Rice using site-scale data from three rice fields in Japan with different water regimes. The observed CH4 emissions were reduced by drainage of the fields, but were enhanced by organic amendments. DNDC-Rice gave acceptable predictions of variation in daily CH4 fluxes and seasonal CH4 emissions due to changes in the water regime. For regional application, we constructed a GIS database at a 1 × 1 km mesh scale that contained data on rice field area, soil properties, daily weather, and farming management of each cell in the mesh, covering 3.2% of the rice fields in Japan's Hokkaido region. We ran DNDC-Rice to simulate CH4 emissions under five simulated water regimes: the conventional water regime and four AWR scenarios with gradually increasing drainage. We found that AWR can reduce CH4 emission by up to 41% compared with the emission under conventional water regime. Including the changes in CO2 and nitrous oxide emissions, potential mitigation of greenhouse gas (GHG) was 2.6 Mg CO2 Eq. ha−1 yr−1. If this estimate is expanded to Japan's total rice fields, expected GHG mitigation is 4.3 Tg CO2 Eq. yr−1, which accounts for 0.32% of total GHG emissions from Japan. For a reliable national-scale assessment, however, databases on soil, weather, and farming management must be constructed at a national scale, as these factors are widely variable between regions in Japan. [ABSTRACT FROM AUTHOR]

The capacity and pathway of bisphenol A [BPA; 2,2-bis(4-hydroxyphenyl)propane] degradation in Sphingomonas sp. strain AO1, which was isolated from the soil of a vegetable-growing field in Japan, were investigated. The bacterial strain was able to grow in a basal mineral salt medium containing BPA as the sole carbon source (BSMB medium), and was able to degrade 115 μg ml-1 BPA in 6 h in L medium. Several BPA metabolites were detected in the culture supernatant by HPLC and then identified by GC-MS and LC-MS-MS. These compounds were confirmed to be the same as those reported for other BPA- degrading bacteria. BPA degradation by cells in the basal mineral salt medium was induced by BPA, and activity was detected only in the intracellular soluble fraction in the presence of coenzymes, such as NADH, NAD+ NADPH or NADP+. The addition of metyrapone, a cytochrome P450 inhibitor, to BSMB medium resulted in a decrease in BPA degradation and cell growth. The BPA-degradation activity of the intracellular soluble fraction was also inhibited by the cytochrome P450 inhibitor. Carbon monoxide difference spectra indicated that cytochrome P450 was present in the cells and that the amount of cytochrome P450 corresponded to the cellular BPA-degradation activity. Our results provide evidence that the cytochrome P450 system is involved in BPA metabolism in Sphingomonas sp. strain AO1. [ABSTRACT FROM AUTHOR]

Pays tribute to biochemist Yagi Kunio of Japan. Childhood; Education; Contributions to biochemistry research; Reputation as an outstanding scientist and academic stateman.