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BACKGROUND: To investigate the use of calcineurin inhibitors (CNIs) in pregnant Japanese women and to evaluate their safety in infants. METHODS: Data were extracted from the claims database of the Japan Medical Data Center. The prevalence of CNIs was evaluated 180 days before pregnancy onset, during pregnancy, and within180-days post partum. We investigated the characteristics of the infants, including the presence of major malformations and their diagnoses, for 1 year after birth. RESULTS: A total of 91,865 pregnancies in 80,049 women were included. Fifty-three women were prescribed CNIs between 180-day before pregnancy onset and 180-day postpartum; 35 of the 53 women were prescribed the drugs during pregnancy, and 10 of their infants were born preterm. Three were diagnosed with major congenital malformations, such as patent ductus arteriosus. Six preterm infants presented with infant respiratory distress syndrome. CONCLUSIONS: No congenital anomalies were clearly attributable to the use of CNIs during pregnancy. [ABSTRACT FROM AUTHOR]

In the present study, variations in ambient gamma dose rate associated with snow cover were examined in a radioactive-contaminated site in Fukushima Prefecture, Japan. The ambient gamma dose rates decreased with increasing snow depth. The reduction trends were different between fresh snow (0.1–0.2 g/cm3) and granular snow (0.3–0.4 g/cm3) depending on snow density. Snow cover water content (snow water equivalent) calculated from snow depth and density was a key parameter governing the reduction in the ambient gamma dose rate. The ambient gamma dose rates reduced to 0.6 and 0.5 at 4 g/cm2 and 8 g/cm2 of snow water equivalent, respectively. Based on gamma-ray flux density distributions, the ambient gamma dose rates from the primary gamma rays decreased more compared to those from scattered gamma rays due to snow cover. [ABSTRACT FROM AUTHOR]

Background and Objectives: Previous reports suggest that several serum biomarkers play roles in the pathogenesis, inflammatory response, and oxidative stress in periodontitis caused by bacterial infections, linking chronic periodontitis to atherosclerotic vascular disease (ASVD). The aim of this preliminary study was to investigate, in a Japanese cross‐sectional community survey, potential serum biomarkers of periodontitis that are associated with ASVD and chronic periodontitis. Material and Methods: The study cohort included a total of 108 male subjects who underwent annual health examinations. Serum biomarkers (high‐sensitivity C‐reactive protein [hs‐CRP], proprotein convertase subtilisin/kexin type 9 [PCSK9], interleukin‐6, tumor necrosis factor‐α, soluble CD14, myeloperoxidase, matrix metalloproteinase‐3, adiponectin, total bilirubin [TBIL], and serum lipids) were analyzed to determine their association (if any) with periodontal parameters. Aortic stiffness was evaluated using the brachial‐ankle aortic pulse wave velocity (PWV) index and the cardio‐ankle vascular index (CAVI). Results: The concentrations of PCSK9 and hs‐CRP were increased (P = .001 and .042, respectively), and the concentration of TBIL was decreased (P = .046), in subjects with periodontal disease (determined as a probing depth of ≥4 mm in at least one site) compared with periodontally healthy subjects. The ratio of low‐density lipoprotein cholesterol (LDL‐C) to high‐density lipoprotein cholesterol and the concentrations of triglycerides, remnant‐like particles‐cholesterol, and oxidized LDL were elevated in subjects with periodontal disease compared with periodontally healthy subjects (P = .038, .007, .002, and .049, respectively). Multivariate regression analyses indicated that the number of sites with a pocket depth of ≥4 mm was associated with the concentration of PCSK9 and inversely associated with the concentration of TBIL independently (standardized β = .243, P = .040; standardized β = −.443, P = .0002; respectively). Analysis of receiver operating characteristic curves of PCSK9 indicated moderate accuracy for predicting the presence of disease sites (probing depth ≥ 4 mm) (area under the curve = 0.740). No significance in the values of PWV and CAVI was observed between subjects with periodontal disease and periodontally healthy subjects. Conclusion: In Japanese male subjects, the concentrations of serum PCSK9 and TBIL were correlated with periodontal parameters. Moreover, PCSK9 could be a candidate biomarker for diagnosing chronic periodontitis, and may also have potential to evaluate the risk for periodontitis to cause ASVD. Longitudinal studies of larger populations are necessary to confirm the exact association of periodontitis with increased serum PCSK9 and decreased TBIL. [ABSTRACT FROM AUTHOR]

The Great East Japan Earthquake of 11 March 2011, caused the Fukushima Daiichi Nuclear Power Plant Accident, which resulted in the release of a large amount of radioactive materials into the environment, and there is a serious concern about the radiation effects on the health of residents living in the affected areas. The evaluation of exposure dose is fundamental for the estimation of health effects, and whenever possible, the exposure dose should be evaluated by actual measurements as opposed to estimations. Here, the outline of the exposure doses of residents estimated from surveys or obtained by measurements is described. Fukushima Health Management Survey reported the results for 460 408 residents during the first 4 months after the accident; 66.3% received doses <1 mSv, 94.9% received <2 mSv, 99.7% received <5 mSv and the maximum dose was 25 mSv. Thus, it was demonstrated that the results from personal dosemeter measurements were comparable to the estimations. The dose assessment of internal exposure of 184 205 residents conducted by Fukushima Prefecture by using whole body counter showed that 99.986% received <1 mSv, with the maximum dose being 3 mSv. Regarding exposure of the thyroid, there is not enough data for the Fukushima accident, but it is presumed that thyroid doses are much lower than those from Chernobyl. The outline of exposure doses of residents in result of the accident is still being clarified, questions and uncertainties in dose assessment remain and further efforts for more accurate dosimetry are required continuously. [ABSTRACT FROM AUTHOR]

Baryon spectroscopy is important to understand Quantum Chromodynamics at low energies. In this purpose, a series of π and η photoproduction experiments was carried out with an electro-magnetic calorimeter FOREST at Research Center for Electron Photon Science, Tohoku University. The incident tagged bremsstrahlung photon energy ranges from 550 to 1,150 MeV. The differential and total cross sections obtained for π and η photoproduction processes on the proton are consistent with the SAID and MAID calculations. The analysis of π and η photoproduction on the neutron is underway. [ABSTRACT FROM AUTHOR]

A new thoron (220Rn) experimental room (TER) was established at National Institute of Radiological Sciences in 2011 to respond to the appearance of new passive devices for 220Rn and its progeny (212Pb, 212Bi) measurement. The room volume is 21.7 m3 with a low air exchange rate, 0.016 h−1. Environmental parameters, such as temperature, relative and absolute humidities, wind speed, aerosol distribution and concentration, are monitored, but not controlled. Commercially available lantern mantles (500 pcs), which can generate maximum concentrations of 6000 Bq m−3 of 220Rn and 2000 Bq m−3 of its progeny, are used as a 220Rn source. Based on preliminary results from the TER, stable and homogenised concentrations of 220Rn and its progeny can be ensured; therefore, in the near future the room will be used for testing measuring instruments. [ABSTRACT FROM AUTHOR]

Environmental radiation at Izu-Oshima Island was observed 6 months after the accident at the Fukushima Daiichi Nuclear Power Plant (F1-NPP). A car-borne survey of the dose rate in air was conducted over the entire island and the results were compared with measurements performed in 2005 (i.e. before the accident). The activity concentrations of 134Cs and 137Cs were also measured using a germanium detector. The dose rate in air was found to be 2.9±1.2 times higher than that in 2005 and 134Cs was detected on Izu-Oshima Island. These results are attributed to the accident at the F1-NPP. [ABSTRACT FROM AUTHOR]

Radon and thoron exhalation rates from the ground surface were estimated in three islands of Okinawa Prefecture, a subtropical region of Japan. In situ measurements of the exhalation rates were conducted at a total of 88 points using an accumulation technique with a ZnS(Ag) scintillation detector. The radon and thoron exhalation rates were calculated to be 1–137 (arithmetic mean: 21) mBq m−2 s−1 and 32–6244 (1801) mBq m−2 s−1, respectively. In the surface soil samples collected at 53 measurement points, 238U and 232Th series concentrations were estimated to be 17.9–254.0 (64.0) Bq kg−1 dry and 17.8–136.1 (58.8) Bq kg−1 dry, respectively. The maximum rates and concentrations were observed in the dark red soil area. Recent studies strongly suggest that the base material of the soils may be the eolian dust derived from the southeastern part of China, a high background radiation area. The eolian dust is, therefore, considered to be an enhancer for the radon and thoron exhalations in Okinawa. [ABSTRACT FROM AUTHOR]

Radon and thoron exhalation rates and gamma-ray dose rate in different places in Hiroshima Prefecture were measured. Exhalation rates were measured using an accumulation chamber method. The radon exhalation rate was found to vary from 3 to 37 mBq m−2 s−1, while the thoron exhalation rate ranged from 40 to 3330 mBq m−2 s−1. The highest radon exhalation rate (37 mBq m−2 s−1) and gamma-ray dose rate (92 nGy h−1) were found in the same city (Kure City). In Kure City, indoor radon and thoron concentrations were previously measured at nine selected houses using a radon–thoron discriminative detector (Raduet). The indoor radon concentrations varied from 16 to 78 Bq m−3, which was higher than the average value in Japan (15.5 Bq m−3). The indoor thoron concentration ranged from ND (not detected: below a detection limit of approximately 10 Bq m−3) to 314 Bq m−3. The results suggest that radon exhalation rate from the ground is an influential factor for indoor radon concentration. [ABSTRACT FROM AUTHOR]

Radon and thoron concentration in the outdoor environment are affected by the magnitude of the exhalation rate that can vary diurnally and seasonally. This paper presents measurement results of radon and thoron exhalation rates and gamma-ray dose rate in different season at same location points in Gunma Prefecture Japan. Exhalation rates were measured by the MSZ instrument which is based on the accumulation method. Three measurement points Katashina Village, Midori City and Takasaki City were selected for measurement. Soil water saturation and soil temperature were measured to investigate their relationship with exhalation rate. The diurnal variation of exhalation rate may be correlated with soil temperature but no clear relationship was found between them. The gamma-ray dose rate do not vary significantly at the same places even in different season. The average radon exhalation rates were 11 ± 2, 2 ± 1, 5 ± 3 and 11 ± 4 mBq m s for spring, summer, autumn and winter, respectively. Those for thoron were 1,100 ± 100, 120 ± 30, 250 ± 80 and 860 ± 140 mBq m s. Thus there was a variation of radon and thoron exhalation rate with different seasons. The radon and thoron exhalation rates in the summer and autumn surveys are higher than those in the spring and winter surveys which were affected by rainfall. It indicates that water saturation is an influential factor for radon and thoron exhalation rates. [ABSTRACT FROM AUTHOR]

Summary Age composition, growth, and reproductive biology of the non-native Indian glassy fish Parambassis ranga (Hamilton, 1822) were surveyed in the Haebaru Reservoir on Okinawa-jima Island, southern Japan. Standard lengths (SLs) of males and females ranged from 19.7 to 44.0 mm and from 19.2 to 52.4 mm, respectively. The overall sex ratio was significantly female-biased, with the monthly percentage of females ranging from 71.4 to 100.0. Marginal growth analysis of sectioned otoliths revealed opaque zones formed annually from November to May. Observed age ranged from 0 to 3 years for both sexes, although the 1-year age class comprised the majority of the sampled population. Von Bertalanffy growth parameters were L∞ = 48.8 mm (SL), K = 0.43 year−1, and t0 = −1.47 years for males, and L∞ = 43.7 mm, K =0.72 year−1, and t0 = −1.29 years for females. Length at 50% maturity was estimated to be 25.8 mm SL, and maturation was within 1 year after hatching. The main spawning season of P. ranga was estimated to occur from February to October, peaking in April. [ABSTRACT FROM AUTHOR]

The differential and total cross sections were measured for the γp → ηp and γd → ηpn reactions at Eγ ≤ 1150 MeV by using an electro-magnetic (EM) calorimeter SCISSORS II at the Laboratory of Nuclear Science (LNS), Tohoku University. The total cross section on the deuteron shows a bump around Eγ = 1 GeV, while no bump is observed in the same energy region of that on the proton. This bump is attributed to be a nucleon resonance excited from the neutron, and it is a candidate of anti-decuplet penta-quark baryons with hidden strangeness. It was difficult, however, to detect all the γ's coming from η decay since the solid angle of SCISSORS II was only 12.6% in total. Statistics of the detected η produced events is poor and systematic uncertainty of the obtained cross section is not small due to low acceptance. A new EM calorimeter complex called FOREST with a solid angle of about 4π sr has been constructed. The spin and parity of the relevant resonance are expected to be determined by the experiments with FOREST. [ABSTRACT FROM AUTHOR]

Thoron exhalation rates from the ground surface were measured at 57 sites on Okinawa Island, Japan, using a ZnS(Ag) scintillation detector equipped with photomultiplier. The arithmetic means ± SD, median ± SD, minimum and maximum of the rates (unit: Bq m−2 s−1) were estimated to be 1.9 ± 1.4, 1.6 ± 0.3, 0.04 and 6.2, respectively. The soils distributed on the island are generally classified into dark red soils, residual regosols, as well as red and yellow soils. While it was assumed that the soils were originated from the bedrock, recent studies suggested that the main material of dark red soils is the East Asian eolian dust. In the dark red soils area, the exhalation rate is relatively higher than that in the other areas. This suggested that the eolian dust was an enhancer for the environmental thoron concentration on Okinawa Island. [ABSTRACT FROM PUBLISHER]

Abstract: The second GeV bremsstrahlung photon beamline has been constructed for meson photo-production experiments at Research Center for Electron Photon Science, Tohoku University, where a 1200MeV electron synchrotron called STretcher Booster (STB) has been in operation primarily for Quark Nuclear Physics. An internal radiator is employed to produce the bremsstrahlung photon beam out of circulating electrons in the STB ring. A photon tagging system is placed inside one of the bending magnets of the ring. The tagged energy of the photon beam ranges from 740 to 1150MeV for 1200MeV operation of the STB synchrotron. The details of the tagging system and the characteristics of the photon beam are described. [Copyright &y& Elsevier]

It has been postulated that immune modulation and activation play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM), but evidence for this has not yet been well documented. We explored the changes in peripheral immunocompetent cells in relationship to the severity of T2DM in 142 patients, and 34 healthy individuals in Japan. A severity index with 0-12 grades was derived based on the HbA1c level and the number of complications. By multiple regression analysis, the severity index was positively associated with neutrophil counts and negatively associated with platelet and CD19+ lymphocyte counts. However, we did not observe any significant changes in other lymphocyte subsets such as CD4+, CD8+, and CD56+. These results suggest that poor diabetic control may be marked by changes in some blood cell types. [ABSTRACT FROM AUTHOR]

A light duty truck diesel engine fuelled with dimethyl ether (DME) using a jerk type in line DME injection system, which meets the Japan 2009 Emission Regulation, was developed. It includes lower exhaust emission technology such as a large exhaust gas recirculation system with air throttled and inter cooled turbocharging. The National Traffic Safety Office, Environment Laboratory, and Bosch Corporation have demonstrated low emission engines which reduce NO [ABSTRACT FROM AUTHOR]

To study the genetic mutation, which could cause problems in spermatogenesis, we screened the point mutations of the FSH receptor gene (C566T) in idiopathic azoospermic men in Japan. We performed mutational analysis of the FSH receptor in 54 Japanese patients diagnosed for azoospermia with Sertoli cell-only (SCO) syndrome (n = 33), hypospermatogenesis (n = 11) and maturation arrest (n = 10). For mutation screening of the FSH receptor, polymerase chain reaction (PCR) amplification from genomic DNA with flanking intronic primers were used. On BsmI digestion, all patients demonstrated homozygous, normal exon 7 alleles with 51 and 27 bp fragments. The absence of any 78 bp fragments demonstrated that no heterozygous or homozygous mutant alleles were present in any patients. None of the 54 patients showed a C566T FSH receptor mutation. We could not confirm that the genomic mutation of the FSH receptor (C566T) is a common cause in Japanese azoospermic patients. [ABSTRACT FROM AUTHOR]

Due to the rocky neighborhood, consisting of mostly granite with high radium content, an elevated radon concentration was found in a territory of Gifu prefecture situated in the middle of Japan. Radon concentrations in water were measured and were found to be considerably high. Since indoor radon and radon progeny concentrations might be relatively high, their concentrations were also analyzed. Besides the radon and radon progeny, thoron and thoron progeny concentrations were also investigated. Dose estimations for radon and thoron in indoor air are discussed. [ABSTRACT FROM AUTHOR]

Objective To clarify the clonality of bilateral tumours by genetic analysis of bilateral renal cell carcinomas (RCCs) using the VHL gene, which is inactivated in ≈ 60% of RCCs and which plays a causal role in the development of most cases of nonpapillary RCC. Patients and methods The study included 20 patients; seven had von Hippel‐Lindau disease, three had papillary RCC and 10 had nonpapillary RCC. Paraffin‐embedded blocks of tumour tissue were obtained from two of the three patients with papillary RCC and from nine of 10 with nonpapillary disease; all three exons of VHL were examined by direct sequencing. Results As reported previously, no VHL mutations were found in papillary tumours. However, in five of the nine nonpapillary cases, VHL mutations were identified in tumours on one or both sides. Three of the tumours had the same mutation on both sides, confirming a common origin. In the remaining two patients, the mutation status differed between the sides, confirming a bilateral primary origin. The former cases were characterized by a relatively large tumour on one side and multiple tumours on the other. Conclusions In nonpapillary RCC multiplicity may suggest a metastatic origin. Such genetic information will be useful in treating and following patients with bilateral renal tumours. [ABSTRACT FROM AUTHOR]

Background: Although incidence and mortality have decreased, gastric cancer (GC) is still a public health issue globally. The international collaborative study for cancer survival using population-based cancer registry showed that the survival of GC was higher in Korea and Japan than other countries, including the United States of America (US). Aim: We examined the determinant factors of the high survival in Japan, compared with the US, with particular focus on the impact of the number of lymph nodes (LNs) examined for surgically treated patients. Methods: We obtained data on 88,447 cases from the nationwide GC registration project, the Japanese Gastric Cancer Association (JGCA), from 2004-2007. We also obtained 18,995 GC cases from US population-based cancer registry data from the Surveillance, Epidemiology, and End Results Program (SEER), diagnosed from 2004-2010. We estimated five-year relative survival and applied a multivariate excess hazard model to compare the two countries. We considered the effect of LNs examined on differences in survival. Results: Five-year relative survival in Japan was 79.8%, compared with 40.1% in the US. After controlling for confounding factors, we still observed significantly higher survival in Japan. The distribution of number of LNs examined showed notable differences between two countries. In over 50% of patients in the US, only 1 to 15 LNs were examined. A higher number of LNs examined showed better survival in both countries. The differences in excess death from cancer between countries were reduced in the category when more than 30 LNs were examined. Conclusion: Although it is difficult to remove biases to compare the two countries, stage migration, related to the more detailed retrieving strategy for LNs in Japan, is a key explanation for high survival in Japan. [ABSTRACT FROM AUTHOR]

Total body potassium has been measured for a Japanese adult male group using two whole-body counters. The total body potassium data were analyzed to present the longitudinal data on body potassium concentration in aging individuals. The data for each individual showed that potassium concentration decreased linearly with age from30 y to 60 y of age. The average decrease rate was -0.0154 1 0.0049 g K kg body wt-1 y-1. On the other hand, a subject group for each of the 23 years (1975-1998) of the study was divided into three age groups. The same age groups were followed with the course of time to analyze changes in potassium concentration due to otherfactors besides age. The follow-up study of the same age groups indicated that the average potassium concentration decreased with the course of the 23-y study and that the decrease was due to other factors besides age. The decrease in the average potassium concentration for study subjects is the major cause of the decrease in the average annual dose from 40K. The average annual dose for subjects aged 30-59 y was 194 mu Gy in 1975, changing to 166 mu Gy in 1998. The decrease in the average annual dose was about 14% over the 23-y study period. [ABSTRACT FROM AUTHOR]

Abstract: Radon and thoron and their progeny were measured using different methods in a dwelling in Gifu prefecture, Japan. The results indicate a considerably higher background level concerning radon and thoron compared to the average in Japan. [Copyright &y& Elsevier]

Abstract: Photoproduction of the from the deuteron and the carbon nucleus has been investigated at the Laboratory of Nuclear Science, Tohoku University in Sendai. The Neutral Kaon Spectrometer and the Neutral Kaon Spectrometer 2 were developed to detect pairs coming from the decay of the . The resulting momentum spectra for inclusive photoproduction were compared with theoretical calculations based on isobar models for , utilizing the spectator hypothesis. An upgrade of the inner detectors to enhance the acceptance for the coincidence measurement of the and Λ is underway. We expect that the exclusive and kinematically complete measurement of the reaction will provide us with direct access to the center-of-mass observables that are important for further understanding the mechanism for strangeness photoproduction. [Copyright &y& Elsevier]

Abstract: High thoron concentrations have been investigated in various living environments with radon–thoron discriminative measurements; however, behavior of the thoron and its decay products and their effects on human health have not been clearly elucidated yet. In Japan, some kinds of building materials rich in natural radionuclides of thorium series, such as clay and soil plaster, are commonly used for construction and/or surface finishing of wall in traditional Japanese style houses. Measurements with different types of monitor for thoron and its decay products were carried out to investigate general characteristics of thoron in Japanese living environments. From the result of the measurements, thoron concentrations ranged from almost 0 to more than thousands Bq m−3. Extremely high concentrations can be found in the places near wall surface, and it decreases drastically as distance from the surface of the wall increases. Thoron concentration was found to be changed drastically with time. The equilibrium equivalent thoron concentrations (EETC) ranged from nearly 0 to about 6 Bq m−3. Correlation between the thoron concentration and EETC was not good. This report summarized the results of an investigation of thoron in living environments of Japan. [Copyright &y& Elsevier]

Abstract: It has been reported that several clear hydrological and geochemical anomalies were recorded before the 1995 Kobe earthquake (January 17, 1995). Remarkable changes of radon concentration in air and in groundwater were observed from November 1994 until the time of the earthquake. All of our data was monitored within the aftershock region. The increases in the atmospheric radon may reflect formation of microcracks in the granitic rocks. [Copyright &y& Elsevier]

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study uses an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants, and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability and functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Background: The optimal interval of colonoscopy (CS) surveillance in cases with Lynch syndrome (LS), and stratification according to the causative mismatch repair gene mutation, has received much attention. To verify a feasible and effective CS surveillance strategy, we investigated the colorectal cancer (CRC) incidence at different intervals and the characteristics of precancerous colorectal lesions of LS cases., Methods: This retrospective multicenter study was conducted in Japan. CRCs and advanced adenomas (AAs) in 316 LS cases with germline pathogenic variants (path&#95;) were analyzed according to the data of 1,756 registered CS., Results: The mean time interval for advanced CRCs (ACs) detected via CS surveillance was 28.7 months (95% confidence interval: 13.8-43.5). The rate of AC detection within (2.1%) and beyond 2 years (8.7%) differed significantly (p = 0.0003). AAs accounted for 43%, 46%, and 41% of lesions < 10 mm in size in the MLH1-, MSH2-, and MSH6-groups, respectively. The lifetime incidence of metachronous CRCs requiring intestinal resection for path&#95;MLH1, path&#95;MSH2, and path&#95;MSH6 cases was 34%, 23%, and 14% in these cases, respectively. The cumulative CRC incidence showed a trend towards a 10-year delay for path&#95;MSH6 cases as compared with that for path&#95;MLH1 and path&#95;MSH2 cases., Conclusions: In cases with path&#95;MLH1, path&#95;MSH2, and path&#95;MSH6, maintaining an appropriate CS surveillance interval of within 2 years is advisable to detect of the colorectal lesion amenable to endoscopic treatment. path&#95;MSH6 cases could be stratified with path&#95;MLH1 and MSH2 cases in terms of risk of metachronous CRC and age of onset., (© 2024. Japanese Society of Gastroenterology.)

A microbiological study was conducted on 41 insect product samples (29 raw frozen [21 domestic and 8 imported], 10 powdered, and 2 processed), which were commercially available in Japan. The total aerobic count for raw frozen insects was 5.61 log cfu/g (range: 2.52-8.40), whereas the powdered insect count was 2.89 log cfu/g (range: 1.00-4.57). The bacterial count was significantly higher in raw frozen insects ( p < 0.05). The coliform count for the raw frozen insects ranged from <1 to 6.90 log cfu/g, and that for the powdered insects ranged from <1 to 1.00 log cfu/g. The number of samples with values above the detection limit was significantly higher in raw frozen insects ( p < 0.05). The detection frequencies of aerobic spores (<1-4.63 log cfu/g), anaerobic spores (<0-4.40 log cfu/g), and Bacillus cereus (<1.7-3.83 log cfu/g) showed no sample type-related significant difference. Listeria spp. was isolated from four samples of raw frozen insects, one of which was Listeria monocytogenes . We did not detect any of the following: Salmonella spp., Shiga toxin-producing E. coli (STEC), Campylobacter jejuni/coli , or pathogenic Yersinia . We isolated insect products retailed in Japan harboring food poisoning bacteria, including L. monocytogenes and B. cereus . In particular, raw frozen products displayed high levels of hygienic indicator bacteria.

Background and Aims: Brugada syndrome (BrS) is an inherited arrhythmia with a higher disease prevalence and more lethal arrhythmic events in Asians than in Europeans. Genome-wide association studies (GWAS) have revealed its polygenic architecture mainly in European populations. The aim of this study was to identify novel BrS-associated loci and to compare allelic effects across ancestries., Methods: A GWAS was conducted in Japanese participants, involving 940 cases and 1634 controls, followed by a cross-ancestry meta-analysis of Japanese and European GWAS (total of 3760 cases and 11 635 controls). The novel loci were characterized by fine-mapping, gene expression, and splicing quantitative trait associations in the human heart., Results: The Japanese-specific GWAS identified one novel locus near ZSCAN20 (P = 1.0 × 10-8), and the cross-ancestry meta-analysis identified 17 association signals, including six novel loci. The effect directions of the 17 lead variants were consistent (94.1%; P for sign test = 2.7 × 10-4), and their allelic effects were highly correlated across ancestries (Pearson's R = .91; P = 2.9 × 10-7). The genetic risk score derived from the BrS GWAS of European ancestry was significantly associated with the risk of BrS in the Japanese population [odds ratio 2.12 (95% confidence interval 1.94-2.31); P = 1.2 × 10-61], suggesting a shared genetic architecture across ancestries. Functional characterization revealed that a lead variant in CAMK2D promotes alternative splicing, resulting in an isoform switch of calmodulin kinase II-δ, favouring a pro-inflammatory/pro-death pathway., Conclusions: This study demonstrates novel susceptibility loci implicating potentially novel pathogenesis underlying BrS. Despite differences in clinical expressivity and epidemiology, the polygenic architecture of BrS was substantially shared across ancestries., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The control of digital dermatitis (DD) among cattle is crucial; however, effective and environmentally-sound control measures have yet to be identified. From the monitoring data of DD which were recorded during regular hoof trimmings in a farm in Hokkaido, Japan, we detected a decrease in the DD prevalence in a herd where an anaerobic bacterial fermentation enhancer (ABFE) was distributed. The possible effect of ABFE was analyzed using a retrospective repeated cross-sectional design. The prevalence of DD decreased over time in the ABFE-distributed group. Furthermore, a selected regression model indicated the time-dependent enhancement of the decreasing trend. While potential coincidental factors may influence, this study provides a basis for further research on the preventive effect of ABFE against DD.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated., (© 2024 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Background and Aim: Inflammatory bowel disease (IBD) frequently affects younger patients and poses various challenges concerning pregnancy and childbirth. Maintaining good disease control throughout pregnancy is crucial, but expectant and pregnant patients may worry about the fetal impact of medications, leading to treatment discontinuation due to uncertainty about this issue. This study investigated the real-world drug-prescribing practices for pregnant patients with IBD in Japan and their potential connection to major congenital malformations (MCMs)., Methods: Overall, 277 female IBD patients who gave birth between 2010 and 2019 were selected from the JMDC claims database. The prescribing patterns of IBD medications and MCMs in the patients' offspring were analyzed., Results: Among pregnant IBD patients, 74.4% received at least one medication from 90 days before pregnancy to 90 days after delivery. Trends in medication prescriptions during pregnancy in 2010-2019 revealed consistent use of oral 5-ASA, variable use of topical medications, a decrease in systemic steroids, and an increase in biologics. The prevalence of MCMs in children born to IBD-affected mothers did not differ significantly between those who did and did not receive IBD medications (8.6% vs 6.8%). Although circulatory system MCMs were slightly more common in the IBD medication group (4.9% vs 1.4%), this difference was not significant. Logistic regression analysis did not reveal an association between MCM risk and first-trimester use of IBD medications, including corticosteroids and biologics., Conclusions: This study provides insights into medication patterns in pregnant IBD patients and suggests no increased risk of MCMs associated with first-trimester IBD medication use., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Visual assessment of mammographic breast composition remains the most common worldwide, although subjective variability limits its reproducibility. This study aimed to investigate the inter- and intra-observer variability in qualitative visual assessment of mammographic breast composition through a multi-institutional observer performance study for the first time in Japan., Methods: This study enrolled 10 Japanese physicians from five different institutions. They used the new Japanese breast-composition classification system 4th edition to subjectively evaluate the breast composition in 200 pairs of right and left normal mediolateral oblique mammograms (number determined using precise sample size calculations) twice, with a 1-month interval (median patient age: 59 years [range 40-69 years]). The primary endpoint of this study was the inter-observer variability using kappa (κ) value., Results: Inter-observer variability for the four and two classes of breast-composition assessment revealed moderate agreement (Fleiss' κ: first and second reading = 0.553 and 0.587, respectively) and substantial agreement (Fleiss' κ: first and second reading = 0.689 and 0.70, respectively). Intra-observer variability for the four and two classes of breast-composition assessment demonstrated substantial agreement (Cohen's κ, median = 0.758) and almost perfect agreement (Cohen's κ, median = 0.813). Assessments of consensus between the 10 physicians and the automated software Volpara® revealed slight agreement (Cohen's κ; first and second reading: 0.104 and 0.075, respectively)., Conclusions: Qualitative visual assessment of mammographic breast composition using the new Japanese classification revealed excellent intra-observer reproducibility. However, persistent inter-observer variability, presenting a challenge in establishing it as the gold standard in Japan., (© 2024. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.)

Acute graft-versus-host disease (aGvHD) is a major complication after allogeneic hematopoietic stem cell transplantation in Japan and other countries. Nearly one-third of patients do not respond to standard systemic steroid therapy and no standard second-line treatment has been established in Japan. We report efficacy and safety findings of ruxolitinib versus best available therapy (BAT) from a subgroup analysis of the international, phase 3 REACH2 study in Japanese patients with steroid-refractory aGvHD. The primary endpoint was overall response rate (ORR) at day 28. Overall, 9 patients received ruxolitinib and 21 received BAT. The ORR at day 28 (88.9% vs 52.4%) and durable ORR at day 56 (66.7% vs 28.6%) were higher with ruxolitinib versus BAT. The estimated cumulative incidence of loss of response at 6 months was 12.5% with ruxolitinib and 18.2% with BAT. The median failure-free survival was longer with ruxolitinib versus BAT (2.73 vs 1.25 months). The most common adverse events up to day 28 in the ruxolitinib and BAT groups were anemia (55.6% vs 19.0%) and thrombocytopenia (44.4% vs 4.8%, respectively). Ruxolitinib showed better efficacy outcomes and a consistent safety profile compared with BAT in the Japanese subgroup, and the findings were consistent with overall study results., (© 2024. The Author(s).)

Background and Aim: Direct-acting antivirals (DAAs) have been accessible in Japan since 2014. The aim of this study is to compare how the prognosis of patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCV-HCC) changed before and after DAA development., Methods: A retrospective analysis of 1949 Japanese HCV-HCC patients from January 2000 to January 2023 categorized them into pre-DAA (before 2013, n = 1169) and post-DAA (after 2014, n = 780) groups. Changes in clinical features and prognosis were assessed., Results: Despite no significant differences in BCLC stage between groups, the post-DAA group exhibited higher rates of sustained virological response (SVR) (45.6% vs. 9.8%), older age (73 vs 69 years), lower levels of AST (40 vs 56 IU/L), ALT (31 vs 46 IU/L), and AFP (11.7 vs 23.6 ng/mL), higher platelet count (13.5 vs 10.8 × 10 4 /μL), better prothrombin time (88.0% vs 81.9%), and better ALBI score (-2.54 vs -2.36) (all P < 0.001). The post-DAA group also showed higher rates of curative treatments (74.1% vs 65.2%) and significantly improved recurrence-free survival (median 2.8 vs 2.1 years). Adjusted for inverse probability weighting, overall survival was superior in the post-DAA group (median 7.4 vs 5.6 years, P < 0.001). Subanalysis within the post-DAA group revealed significantly shorter overall survival for patients without SVR (median 4.8 years vs NA vs NA) compared to pre-SVR or post-SVR patients (both P < 0.001). No significant difference in OS was observed between the pre-SVR and post-SVR groups (P = 1.0)., Conclusion: The development of DAA therapy has dramatically improved the prognosis of HCV-HCC patients., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Kimono is being reevaluated for its sustainability aspects, such as having fewer offcuts in the production process due to its structural differences from Western-style clothes and its high reusability due to the adaptability to individuals' body shapes. On the other hand, once a common attire for daily wear in Japan, kimono has transitioned to being worn only on special events and the kimono-related industry has also shrunk. To stimulate demand for kimono, it is essential to familiarize younger generations with its potential as daily wear., Methods: A questionnaire survey on perceptions of kimono was conducted among two groups in Japan: 211 college students and 50 kimono enthusiasts. The questionnaire included demographic questions and psychometric scales, primarily focusing on their kimono experiences, challenges associated with wearing kimono, their perceptions of kimono and Western-style clothes, and their attitudes towards kimono., Results: The results revealed that a majority of students had worn kimono before, though they found it difficult to move while wearing it. In contrast, kimono enthusiasts evaluated it as easier to move, hard to become disheveled, and casual. They also rated the ease of wearing Western-style clothes lower compared to students, and this tendency intensified with the length of enthusiast experience. Furthermore, the findings indicated that enthusiasts regarded the kimono more as daily wear compared to students, while still deriving enjoyment from it as formal attire in special events., Conclusions: These results suggest that the cognition that Western-style clothes are easy to move and kimono is not may change with experiences. Therefore, providing opportunities for people in Japan to acquire how to wear kimono in comfortable ways possibly impacts their perceptions of kimono., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Miyashiro K et al.)

Objectives: NS-87/CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin. NS-87/CPX-351 exerts antileukemic action by maintaining a synergistic molar ratio of cytarabine to daunorubicin of 5:1 within the liposome while in circulation. Patients with high-risk acute myeloid leukemia (AML), which includes therapy-related AML and AML with myelodysplasia-related changes (AML-MRC), have poorer outcomes than those with other AML., Methodology: This open-label phase 1/2 (P1/2) study was conducted in 47 Japanese patients aged 60-75 years with newly diagnosed high-risk AML to evaluate the pharmacokinetics, safety, and efficacy of NS-87/CPX-351., Results: In the 6 patients enrolled in the P1 portion, no dose-limiting toxicities (DLTs) were reported, and 100 units/m 2 during the induction cycle was found to be acceptable. Cytarabine and daunorubicin had a long half-life in the terminal phase (32.8 and 28.7 h, respectively). In the 35 patients enrolled in the P2 portion, composite complete remission (CRc; defined as complete remission [CR] or CR with incomplete hematologic recovery [CRi]) was achieved in 60.0% (90% CI: 44.7-74.0) of the patients. Adverse events due to NS-87/CPX-351 were well tolerated., Outcomes: NS-87/CPX-351 can be considered as a frontline treatment option for Japanese patients with high-risk AML., (© 2024. The Author(s).)

Background and Aim: While several predictive models for the development of hepatocellular carcinoma (HCC) have been proposed, including those for patients with chronic hepatitis C virus (HCV) infection who have achieved sustained virologic response (SVR), the best model may differ between regions. We compared the ability of six reported models to stratify the risk of post-SVR HCC in Japan, where rigorous surveillance and early detection of HCC is common., Methods: A total of 6048 patients with no history of HCC who achieved SVR by oral direct-acting antiviral drugs were enrolled in this nationwide study. Patients continued HCC surveillance every 6 months after SVR. The incidence of post-SVR HCC was compared between risk groups using the aMAP score, FIB-4 index, Tahata model, GAF4 criteria, GES score, and ADRES score., Results: During the observation period with a median duration of 4.0 years after SVR, post-SVR HCC developed in 332 patients (5.5%). All six models performed significantly at stratifying the incidence of HCC. However, Harrell's C-index was below 0.8 for all models (range, 0.660-0.748), indicating insufficient stratification ability., Conclusion: Although all six proposed models demonstrated a good ability to predict the development of post-SVR HCC, their ability to stratify the risk of post-SVRHCC was unsatisfactory. Further studies are necessary to identify the best model for assessing the risk of post-SVR HCC in regions where early detection of HCC is common., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Driver oncogenes are investigated upfront at diagnosis using multi-CDx systems with next-generation sequencing techniques or multiplex reverse-transcriptase polymerase chain reaction assays. Additionally, from 2019, comprehensive genomic profiling (CGP) assays have been available in Japan for patients with advanced solid tumors who had completed or were expected to complete standard chemotherapy. These assays are expected to comprehensively detect the driver oncogenes, especially for patients with non-small cell lung cancer (NSCLC). However, there are no reports of nationwide research on the detection of driver oncogenes in patients with advanced NSCLC who undergo CGP assays, especially in those with undetected driver oncogenes at diagnosis. In this study, we investigated the proportion of driver oncogenes detected in patients with advanced NSCLC with undetectable driver oncogenes at initial diagnosis and in all patients with advanced NSCLC who underwent CGP assays. We retrospectively analyzed data from 986 patients with advanced NSCLC who underwent CGP assays between August 2019 and March 2022, using the Center for Cancer Genomics and Advanced Therapeutics database. The proportion of driver oncogenes newly detected in patients with NSCLC who tested negative for driver oncogenes at diagnosis and in all patients with NSCLC were investigated. Driver oncogenes were detected in 451 patients (45.7%). EGFR was the most common (16.5%), followed by KRAS (14.5%). Among the 330 patients with undetected EGFR, ALK, ROS1, and BRAF V600E mutations at diagnosis, 81 patients (24.5%) had newly identified driver oncogenes. CGP assays could be useful to identify driver oncogenes in patients with advanced NSCLC, including those initially undetected, facilitating personalized treatment., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aim: To investigate the factors associated with introducing visiting-pharmacist services for community-dwelling older adults in Japan., Methods: We conducted a nested case-control study using claims data in a cohort from a city in Tokyo. Patients aged ≥65 years who received visiting-pharmacist services for the first time between April 2014 and March 2020 were considered case patients. A maximum of four controls to each case patient were randomly selected on the basis of sex, age, health insurance systems, and month-year. Medical and long-term care service usage and patient condition were assessed using claims data from the index and preceding months, along with long-term care needs certification data. Multivariable conditional logistic regression analysis was conducted to estimate the adjusted odds ratios with 95% confidence intervals for factors associated with visiting-pharmacist service introduction., Results: A total of 22 949 participants (4591 cases and 18 358 controls) were included, with a median age of 85 years; 59.3% were women. The adjusted odds ratios (95% confidence intervals) of the three most related factors were 27.61 (23.98-31.80) for physicians' home visits, 5.83 (5.08-6.70) for hospitalization, and 4.97 (4.16-5.95) for designated-facility admission. Factors such as prescribing ≧10 medications, visiting nursing, and cancer were positively associated. In contrast, low household income and a high need for support due to cognitive function or disability were negatively associated., Conclusions: This study provides insights into the introduction of visiting-pharmacist services for older adults in Japan. Geriatr Gerontol Int 2024; 24: 344-351., (© 2024 Japan Geriatrics Society.)

BACKGROUND Clazosentan is an endothelin receptor antagonist approved in Japan for preventing cerebral vasospasm and vasospasm-associated cerebral ischemia and infarction. This study included elderly patients aged ≥75 years with aneurysmal subarachnoid hemorrhage (SAH) and aimed to evaluate the factors associated with discontinuing anti-vasospasm therapy with clazosentan. MATERIAL AND METHODS In this single-center retrospective observational study, we extracted diagnostic and therapeutic work-up data of consecutive 40 patients with SAH treated with clazosentan infusion (10 mg/h) as first-line anti-vasospasm therapy between May 2022 and August 2023. Patient data were compared between the discontinued and completed groups, and related factors for the discontinuation were further analyzed. RESULTS Clazosentan was discontinued in 22% (n=9) of patients due to intolerable dyspnea accompanied by hypoxemia at 5±3 days after therapy initiation, in which 44% (n=4) were elderly (≥75 years). Patients who discontinued clazosentan therapy showed significantly lower urine volumes compared with those who completed the therapy (P<0.05). Multivariate regression analysis revealed that day-to-day urine volume variance and older age were independent risk factors for drug cessation (P<0.05). The cut-off value for predicting clazosentan discontinuation was -0.7 mL/kg/h with sensitivity of 86% and specificity of 75% (area under the curve: 0.76±0.10; 95% confidence interval: 0.56-0.96; P=0.035). CONCLUSIONS Our results suggest that approximately 20% of SAH patients suffered from intolerable respiratory symptoms attributable to hypoxemia. We found that both reduced day-to-day urine volume variation and older age are independent risk factors for drug discontinuation.

Atopic dermatitis (AD) places a burden on work productivity. Recently, dupilumab was approved for AD, but its impact on work productivity in Japanese patients has not been reported. Furthermore, data on the effect of long-term treatment with dupilumab on work productivity are limited. We investigated the work productivity and activity in Japanese patients with moderate-to-severe AD, utilizing the Japanese version of the Work Productivity and Activity Impairment (WPAI-AD-Japan) questionnaire. Furthermore, we examined the impact of dupilumab on work productivity. Adult moderate-to-severe AD patients treated with dupilumab for more than 12 months from March 2020 to June 2022 who filled out the WPAI-AD-Japan questionnaire were included. Twenty-eight adult AD patients were analysed. Absenteeism was low (mean: 5.3%), but presenteeism, work productivity loss and activity impairment were high (36.8%, 39.7%, 48.9%, respectively). Significant positive correlations were observed between work productivity loss and visual analogue scale (VAS) score of pruritus and between activity impairment and dermatology life quality index (DLQI). Dupilumab treatment significantly reduced presenteeism, work productivity loss and activity impairment at both 6 and 12 months. The extent of their amelioration was numerically higher at 12 months than at 6 months. The reduction rates in presenteeism, work productivity loss and activity impairment were positively correlated with the reduction rates in DLQI and VAS score of pruritus at 12 months. Dupilumab improved work productivity in Japanese AD patients. Long-term remission of pruritus and improved quality of life are important for comprehensive improvement of work productivity., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

We analyzed the behavior of patient with a focus on patient-sharing based on the methodology of network analysis. We used an administrative healthcare claims database from September of the years 2008-2020 to identify shared patients with hypertension. The patients' behavior of visiting multiple medical facilities was extracted as graphical data, and we calculated density and centrality as indicators to evaluate the structure of the patient sharing network. Our findings indicate that density, reciprocity, and transitivity increased over time, and that centrality and PageRank were correlated.