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Detection of shallow slow earthquakes offers insight into the near-trench part of the subduction interface, an important region in the development of great earthquake ruptures and tsunami generation. Ocean-bottom monitoring of offshore seismicity off southern Kyushu, Japan, recorded a complete episode of low-frequency tremor, lasting for 1 month, that was associated with very-low-frequency earthquake (VLFE) activity in the shallow plate interface. The shallow tremor episode exhibited two migration modes reminiscent of deep tremor down-dip of the seismogenic zone in some other subduction zones: a large-scale slower propagation mode and a rapid reversal mode. These similarities in migration properties and the association with VLFEs strongly suggest that both the shallow and deep tremor and VLFE may be triggered by the migration of episodic slow slip events. [ABSTRACT FROM AUTHOR]

Background: Stage B heart failure (HF) refers to structural heart disease without signs or symptoms of HF, so that early intervention may delay or prevent the onset of overt HF. However, stage B HF is a very broad concept, and risk stratification of such patients can be challenging., Methods and Results: We conducted a prospective study of data for 1646 consecutive patients with HF from the KUNIUMI (Kobe University Heart Failure Registry in Awaji Medical Center) registry chronic cohort. The definition of HF stages was based on current guidelines for classification of 29 patients as stage A HF, 761 as stage B HF, 827 as stage C HF, and 29 patients as stage D HF. The primary end point was the time-to-first-event defined as cardiovascular death or HF hospitalization within 2.0 years of follow-up. A maximum of 6 adjustment factor points was assigned based on Cox proportional hazards analysis findings for the hazard ratio (HR) of independent risk factors for the primary end point: 1 point for anemia, estimated glomerular filtration rate <45 mL/min per 1.73 m 2 , brain natriuretic peptide ≥150 pg/mL, and average ratio of early transmitral flow velocity to early diastolic mitral annular velocity >14, and 2 points for clinical frailty scale >3. Patients with stage B HF were stratified into 3 groups, low risk (0-1 points), moderate risk (2-3 points), and high risk (4-6 points). Based on this scoring system (BEEAF 2 [brain natriuretic peptide, estimated glomerular filtration rate, ratio of early transmitral flow velocity to early diastolic mitral annular velocity, anemia, and frailty]), the outcome was found to become worse in accordance with risk level. High-risk patients with stage B HF and patients with stage C HF showed similar outcomes., Conclusions: Our scoring system offers an easy-to-use evaluation of risk stratification for patients with stage B HF.

Aims/introduction: Despite the emergence of new drugs with novel mechanisms of action, treatment options for older people and those with chronic kidney disease are still limited., Materials and Methods: Using a medical database compiled from Diagnostic Procedure Combination hospitals, we retrospectively analyzed treatment status, glycemic control and kidney function over 3 years after the first oral antidiabetic drugs in Japanese adults with type 2 diabetes who were aged ≥65 years., Results: Among 5,434 study participants, 3,246 (59.7%) were men, the median age was 72.0 years, the baseline median hemoglobin A1c was 7.1% and the baseline median estimated glomerular filtration rate was 66.6 mL/min/1.73 m 2 . Treatment was intensified in 40.0% of people during the 3-year observation period, and the median time to the first treatment intensification was 198 days. Insulin was the most commonly used agent for treatment intensification (36.9%, 802/2,175). Hemoglobin A1c of <7.0% was achieved in 3,571 (65.7%) at 360 ± 90 days. Multivariable logistic regression analysis found that baseline age, hemoglobin A1c and estimated glomerular filtration rate were negatively associated with achieving hemoglobin A1c of <7.0% at 360 ± 90 days., Conclusions: In older Japanese adults with type 2 diabetes, those with a lower estimated glomerular filtration rate were more likely to achieve hemoglobin A1c of <7.0%. To safely manage blood glucose levels in older adults with chronic kidney disease, physicians should remain vigilant about the risk of iatrogenic hypoglycemia., (© 2024 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Frequently consuming processed and ready-to-eat (RTE) foods is regarded as unhealthy, but evidence on the relationships with circulating metabolic parameters is lacking. Japanese residents of a metropolitan area, 20 to 50 years of age, were studied in terms of anthropometric and biochemical parameters, including circulating trans fat and serum phospholipid fatty acid levels. Processed foods, except drinks and dairy items, were categorized according to requirements for additional ingredients and cooking before eating. Processed and RTE foods were divided according to fat and/or oil content into non-fatty or fatty foods. The participants were grouped into tertiles based on the energy percent (En%) derived from fatty-RTE foods. Fatty-RTE En% showed negative associations with fish, soybean and soybean products, dairy, eggs, vegetables, seaweed/mushrooms/konjac, fruit and non-oily seasonings reflecting lower dietary fiber, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and mineral and vitamin intakes, while the associations with fat/oil, confectionaries, and sweet beverages were positive. Fatty-RTE En% consumption was positively associated with alkaline phosphatase, leucine aminopeptidase, direct bilirubin, elaidic acid, and C18:2 but inversely associated with HDL cholesterol, C15:0, C17:0, EPA, and DHA. A higher fatty-RTE food intake was suggested to contribute to unbalanced nutrient intakes, as reflected in lipid metabolic parameters. Further large-scale studies are needed to evaluate the quality and impacts of RTE foods.

Spinal muscular atrophy (SMA) is a common devastating neuromuscular disorder, usually involving homozygous deletion of the SMN1 gene. Newly developed drugs can improve the motor functions of infants with SMA when treated in the early stage. To ensure early diagnosis, newborn screening for SMA (SMA-NBS) via PCR-based genetic testing with dried blood spots (DBSs) has been spreading throughout Japan. In Hyogo Prefecture, we performed a pilot study of SMA-NBS to assess newborn infants who underwent routine newborn metabolic screening between February 2021 and August 2022. Hyogo Prefecture has ~40,000 live births per year and the estimated incidence of SMA is 1 in 20,000-25,000 based on genetic testing of symptomatic patients with SMA. Here, we screened 8336 newborns and 12 screen-positive cases were detected by real-time PCR assay. Multiplex ligation-dependent probe amplification assay excluded ten false positives and identified two patients. These false positives might be related to the use of heparinized and/or diluted blood in the DBS sample. Both patients carried two copies of SMN2 , one was asymptomatic and the other was symptomatic at the time of diagnosis. SMA-NBS enables us to prevent delayed diagnosis of SMA, even if it does not always allow treatment in the pre-symptomatic stage.

Background: Emergency medical service (EMS) providers are the first medical professionals to make contact with patients in an emergency. However, the frequency of care by EMS providers for severely injured children is limited. Vital signs are important factors in assessing critically ill or injured patients in the prehospital setting. However, it has been reported that documentation of pediatric vital signs is sometimes omitted, and little is known regarding the performance rate of vital sign documentation by EMS providers in Japan. Using a nationwide data base in Japan, this study aimed to evaluate the relationship between patients' age and the documentation of vital signs in prehospital settings., Methods: This study was a secondary data analysis of the Japan Trauma Data Bank. The inclusion criterion was patients with severe trauma, as defined by an Injury Severity Score ≥ 16. Our primary outcome was the rate of recording all four basic vital signs, namely blood pressure, heart rate, respiratory rate, and level of consciousness in the prehospital setting among different age groups. We also compared the prehospital vital sign completion rate, that is, the rate at which all four vital signs were recorded in a prehospital setting based on age groups. Multivariate analysis was performed to evaluate factors associated with the prehospital vital sign completion rate., Results: We analyzed 75,777 severely injured patients. Adults accounted for 94% (71400) of these severely injured patients, whereas only 6% of patients were children. The rate of prehospital recording of vital signs was lower in children ≤5 years than in adult patients for all four vital signs. When the adult group was used as a reference, the adjusted odds ratios of vital sign completion rate in infants (0 years), younger children (1-5 years), older children (6-11 years), and teenagers (12-17 years) were 0.09, 0.30, 0.78, and 0.87, respectively., Conclusions: Analysis of the nationwide trauma registry showed that younger children tended to have a lower rate of vital sign documentation in prehospital settings., (© 2022. The Author(s).)

White matter lesions (WML) commonly occur in older brains and are quantifiable on MRI, often used as a biomarker in Aging research. Although algorithms are regularly proposed that identify these lesions from T2-fluid-attenuated inversion recovery (FLAIR) sequences, none so far can estimate lesions directly from T1-weighted images with acceptable accuracy. Since 3D T1 is a polyvalent and higher-resolution sequence, it could be beneficial to obtain the distribution of WML directly from it. However a serious difficulty, both for algorithms and human, can be found in the ambiguities of brain signal intensity in T1 images. This manuscript shows that a cross-domain ConvNet (Convolutional Neural Network) approach can help solve this problem. Still, this is non-trivial, as it would appear to require a large and varied dataset (for robustness) labelled at the same high resolution (for spatial accuracy). Instead, our model was taught from two-dimensional FLAIR images with a loss function designed to handle the super-resolution need. And crucially, we leveraged a very large training set for this task, the recently assembled, multi-sites Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) cohort. We describe the two-step procedure that we followed to handle such a large number of imperfectly labeled samples. A large-scale accuracy evaluation conducted against FreeSurfer 7, and a further visual expert rating revealed that WML segmentation from our ConvNet was consistently better. Finally, we made a directly usable software program based on that trained ConvNet model, available at https://github.com/bthyreau/deep-T1-WMH., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: To develop a nomogram of urinary volume and flow based on the data of Japanese men without lower urinary tract symptoms and multiple flows per participant whose characteristics were clear., Methods: Overall, 101 Japanese male volunteers without lower urinary tract symptoms aged between 20 and 59 years were enrolled. A portable uroflowmeter (P-Flowdiary®) was used to record urinary information (flow rate and volume) for 2 successive days. The model (quadratic, linear, or logarithmic regression) most fit for the relationship between maximum flow rate and voided volume was determined. The maximum flow rate at > 150 mL was compared among the 20-29-, 30-39-, 40-49-, and 50-59-year age groups. Nomograms appropriate for the age groups were created., Results: The mean age, International Prostate Symptom Score, and Overactive Bladder Symptom Score were 38.5 years, 0.42, and 0.24, respectively. The quadratic regression model was the most fit because its mean coefficient determination was 0.93 ± 0.06. The mean maximum flow rate was significantly lower in the 50-59-year age group (21.8 ± 5.05 mL/s, P < 0.01) than in the younger groups (24.14 ± 4.94, 24.05 ± 6.99, and 24.64 ± 5.72 mL/s). The 2 nomograms are Y = 28.99 {1 - exp(- 0.01 × X)} and Y = 25.67 {1 - exp(- 0.01 × X)} for the 20-49- and 50-59-year age groups, respectively., Conclusions: The nomogram can predict maximum flow rate based on voided volume in Japanese men aged 20-59 years without lower urinary tract symptoms., (© 2022. The Author(s).)

The Injury Severity Score (ISS) is widely used in trauma research worldwide. An ISS cutoff value of ≥16 is frequently used as the definition of severe injury in Japan. The mortality of patients with ISS ≥16 has decreased in recent years, owing to the developing the trauma care system. This study aimed to analyze the prevalence, in-hospital mortality, and odds ratio (OR) for mortality in Japanese injured patients by age, injury mechanism, injury region, and injury severity over 10 years. This study used the Japan Trauma Data Bank (JTDB) dataset, which included 315,614 patients registered between 2009 and 2018. 209,290 injured patients were utilized. This study evaluated 10-year trends of the prevalence and in-hospital mortality and risk factors associated with in-hospital mortality. The overall in-hospital mortality was 10.5%. During the 10-year study period in Japan, the mortality trend among all injured patient groups with ISS 0-15, 16-25, and ≥26 showed significant decreases (p <0.001). Moreover, the mortality risk of patients with ISS ≥26 was significantly higher than that of patients with ISS 0-15 and 16-25 (p <0.001, OR = 0.05 and p<0.001, OR = 0.22). If we define injured patients who are expected to have a mortality rate of 20% or more as severely injured, it may be necessary to change the injury severity definition according to reduction of trauma mortality as ISS cutoff values to ≥26 instead of ≥16. From 2009 to 2018, the in-hospital mortality trend among all injured patient groups with ISS 0-15, 16-25, and ≥26 showed significant decreases in Japan. Differences were noted in mortality trends and risks according to anatomical injury severity., Competing Interests: The authors have declared that no competing interests exist.

COVID-19 vaccine-related myocarditis has been reported worldwide. We herein report two Japanese cases with suspected vaccine-related myocarditis. A 27-year-old man was admitted with chest pain 4 days after the second vaccination. An electrocardiogram (ECG) did not reveal any significant abnormalities. The second patient, a 37-year-old man, was admitted with chest pain 9 days after the first vaccination. His ECG exhibited ST-elevation in multiple leads. In both cases, cardiac magnetic resonance imaging findings were consistent with myocarditis. They recovered with symptomatic relief within a few days. These cases suggest that the benefit of COVID-19 vaccination exceeds the risk of vaccine-related myocarditis.

Background: Glucose dysmetabolism is an important risk factor for dementia., Objective: We investigated the associations of diabetes mellitus, the levels of glycemic measures, and insulin resistance and secretion measures with dementia and its subtypes in a cross-sectional study., Methods: In this study, 10,214 community-dwelling participants were enrolled. Hemoglobin A1c (HbA1c), the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR), the HOMA of percent β-cell function (HOMA-β), and the glycated albumin (GA) was evaluated. The associations of each measure with Alzheimer's disease (AD) and vascular dementia (VaD) were investigated., Results: The multivariable-adjusted odds ratios (ORs) of AD were significantly higher in participants with diabetes mellitus than in those without diabetes (1.46 [95% CI: 1.08-1.97]). Higher HbA1c levels were significantly associated with AD at diabetes (≥6.5%) and even at prediabetes (5.7 %-6.4 %) levels; multivariable-adjusted ORs for AD in participants at the diabetes level were 1.72 (95% CI: 1.19-2.49), and those in participants at the prediabetes level were 1.30 (95% CI: 1.00-1.68), compared with those in normal participants. Moreover, higher GA levels were associated with AD. No associations were observed between the diabetic status or the levels of glycemic measures and VaD. In addition, no significant relationships were observed between insulin resistance and secretion measurements and AD and VaD., Conclusion: Our findings indicate that diabetes mellitus and hyperglycemia are significantly associated with AD, even in individuals at the prediabetes level.

Background: The predictive value of the cardio-ankle vascular index (CAVI) for estimating the efficacy outcome of catheter ablation (CA) in atrial fibrillation (AF) patients is unclear. We aimed to examine the predictive performance of the CAVI for recurrences of atrial arrhythmias after CA., Methods: We enrolled a total of 193 patients with AF (paroxysmal 126 and non-paroxysmal 67) who underwent initial CA procedures at our institute, and CAVI measurements were conducted between January 2016 and March 2017. We evaluated recurrences of atrial arrhythmias after the first CA procedure as a clinical outcome. The CAVI value was assessed and the enrolled patients were divided according to the optimal CAVI value cut-off point (9.5) in the atrial arrhythmia recurrence group., Results: During a mean follow-up of 31.3 (17.5-43.0) months, 74 (32.5%; PaAF 41 and 49.3%; non-PaAF 33) patients had recurrences of atrial arrhythmias. The recurrence ratio of atrial arrhythmias was significantly higher in patients with a high CAVI (≥9.5) than those with a low CAVI (<9.5) (log rank test; p = 0.018). A univariate analysis showed the association between higher CAVI values and recurrences of atrial arrhythmias (p = 0.072). Multivariate analyses using a Cox proportional hazard model after adjusting for other clinical factors revealed that the CAVI value was determined to be a significant predictive factor of a recurrence of atrial arrhythmias after CA (Hazard ratio: 1.44, 95% confidence interval: 1.17-1.78, p < 0.01)., Conclusions: The CAVI was significantly associated with a recurrence of atrial arrhythmias after CA in AF patients., (© 2021 Wiley Periodicals LLC.)

Background: Few registries have provided precise information concerning incidence rates for acute heart failure syndrome (AHFS) in Japan., Methods and results: All hospitals with acute care beds in Awaji Island participated in the Kobe University heart failure registry in Awaji Medical Center (KUNIUMI Registry), a retrospective, population-based AHFS registration study, enabling almost every patient with AHFS in Awaji Island to be registered. From 1 January 2015 to 31 December 2017, 743 patients with de novo AHFS had been registered. Mean age was 82.1±11.5 years. Using the general population of Japan as of 2015 as a standard, age- and sex-adjusted incidence rates for AHFS were 133.8 per 100,000 person-years for male and 120.0 for female. In 2015, there were an estimated 159,702 new-onset patients with AHFS, which was predicted to increase to 252,153 by 2040, and reach a plateau. The proportion of patients aged >85 years accounted for 42.6% in 2015, which was predicted to increase up to 62.5% in 2040. The proportion of patients with heart failure with preserved ejection fraction was estimated at 52.0% in 2015, which was predicted to increase gradually to 57.3% in 2055., Conclusions: The present analysis suggested that the number of patients with de novo AHFS keeps increasing with progressive aging in Japan. Establishment of countermeasures against the expanding burden of HF is urgently required.

Background: Recent reports have revealed that patients who experienced early rehospitalization for heart failure (HF) had worse prognoses in terms of all-cause and cardiovascular deaths as compared to those who did not. However, precipitating factors for early rehospitalization for HF remain unknown. In this study, we assessed the precipitating factors for early rehospitalization and their impact in patients with HF., Methods and Results: We consecutively included 242 patients (mean age: 80.4 years, females: 46.3%) with a history of rehospitalization for HF. They were divided into 2 groups: the early rehospitalization group (71 patients who were readmitted within 3 months of discharge) and the late rehospitalization group (171 patients who were readmitted after more than 3 months following discharge). During the mean follow-up period of 1,144 days (range: 857-1,417 days), 121 patients (50.0%) died. Kaplan-Meier analysis revealed that patients in the early rehospitalization group had worse prognosis (all-cause death and cardiovascular death) than those in the late rehospitalization group (log-rank p<0.001). As the major precipitating factor for rehospitalization, poor compliance with the doctor's instructions on fluid and physical activity restrictions (determined by the patients or their families admittance of non-compliance with the instructions given at the time of discharge) was higher in the early rehospitalization group than in the late rehospitalization group [poor compliance with fluid restriction: 19.7% vs. 7.6% (p = 0.006), poor compliance with physical activity restriction: 21.1% vs. 9.4% (p = 0.013)]., Conclusions: We concluded that early hospital readmission in patients with HF was associated with higher mortality rates. Compared to late rehospitalization, precipitating factors for early rehospitalization were more strongly dependent on the self-care behaviors of the patients. A more effective approach, such as multidisciplinary intervention, is essential to prevent early hospital readmission and subsequent poor prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Objective: Hospital characteristics, such as hospital type and admission time, have been reported to be associated with survival in adult out-of-hospital cardiac arrest (OHCA) patients. However, findings regarding the effects of hospital types on pediatric OHCA patients have been limited. The aim of this study was to analyze the relationship between the hospital characteristics and the outcomes of pediatric OHCA patients., Methods: This study was a retrospective secondary analysis of the Japanese Association for Acute Medicine-out-of-hospital cardiac arrest registry. The period of this study was from 1 June 2014 to 31 December 2015. We enrolled all pediatric patients (those 0-17 years of age) experiencing OHCA in this study. We enrolled all types of OHCA. The primary outcome of this study was 1-month survival after the onset of cardiac arrest., Results: We analyzed 310 pediatric patients (those 0-17 years of age) with OHCA. In survivors, the rate of witnessed arrest and daytime admission was significantly higher than nonsurvivors (56% vs. 28%, p < 0.001: 49% vs. 31%; p = 0.03, respectively). The multiple logistic regression model showed that daytime admission was related to 1-month survival (odds ratio, OR: 95% confidence interval, CI, 3.64: 1.23-10.80) (p = 0.02). OHCA of presumed cardiac etiology and witnessed OHCA were associated with higher 1-month survival. (OR: 95% CI, 3.92: 1.23-12.47, and 6.25: 1.98-19.74, respectively). Further analyses based on the time of admission showed that there were no significant differences in the proportions of patients with witnessed arrest and who received bystander cardiopulmonary resuscitation and emergency medical service response time by admission time., Conclusion: Pediatric OHCA patients who were admitted during the day had a higher 1-month survival rate after cardiac arrest than patients who were admitted at night., Competing Interests: The authors have declared that no competing interests exist.

Background: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion of SMN1 exons 7 and 8. However, exon 8 is retained in some cases, where SMN2 exon 7 recombines with SMN1 exon 8, forming a hybrid SMN gene. It remains unknown how the hybrid SMN gene contribute to the SMA phenotype., Method: We analyzed 515 patients with clinical suspicion for SMA. SMN1 exons 7 and 8 deletion was detected by PCR followed by enzyme digestion. Hybrid SMN genes were further analyzed by nucleotide sequencing. SMN2 copy number was determined by real-time PCR., Results: SMN1 exon 7 was deleted in 228 out of 515 patients, and SMN1 exon 8 was also deleted in 204 out of the 228 patients. The remaining 24 patients were judged to carry a hybrid SMN gene. In the patients with SMN1 exon 7 deletion, the frequency of the severe phenotype was significantly lower in the patients with hybrid SMN gene than in the patients without hybrid SMN gene. However, as for the distribution of SMN2 exon 7 copy number among the clinical phenotypes, there was no significant difference between both groups of SMA patients with or without hybrid SMN gene., Conclusion: Hybrid SMN genes are not rare in Japanese SMA patients, and it appears to be associated with a less severe phenotype. The phenotype of patients with hybrid SMN gene was determined by the copy number of SMN2 exon 7, as similarly for the patients without hybrid SMN gene., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Medication non-adherence in the elderly population is a major problem, preventing them from obtaining optimal therapeutic effects. Identifying the factors affecting medication adherence is crucial for improving and maintaining health among the elderly population and enhance healthcare economy. The purpose of this study was to examine the prevalence of self-reported medication adherence, and identify the associated factors and the influence of health-related quality of life (HRQOL) in the Japanese community-dwelling elderly population. This cross-sectional study was part of the Nakajima study and targeted inhabitants aged ≥60 years who underwent health examinations in 2017. Data regarding medication adherence were acquired through interviews and self-administered questionnaires. Medication adherence were assessed using a visual analog scale, and HRQOL was assessed by EuroQol five-dimensional questionnaire with 3 levels. Among the 455 participants, low and high medication adherence were seen in 9.7% and 66.2% of the participants, respectively (visual analog scores <80% and ≥95%, respectively). Medication adherence was significantly lower in participants taking medications ≥3 times daily than in those taking medications once or twice daily; a regimen involving drug administration ≥3 times daily had significantly lower odds of medication adherence. The use of a drug profile book and HRQOL had significant positive association with medication adherence. Our results suggest that low dosing frequency and using a drug profile book was positively associated with medication adherence among elderly persons, which in turn could enhance their QOL.

Background: In-hospital mortality in trauma patients has decreased recently owing to improved trauma injury prevention systems. However, no study has evaluated the validity of the Trauma and Injury Severity Score (TRISS) in pediatric patients by a detailed classification of patients' age and injury severity in Japan. This retrospective nationwide study evaluated the validity of TRISS in predicting survival in Japanese pediatric patients with blunt trauma by age and injury severity., Methods: Data were obtained from the Japan Trauma Data Bank during 2009-2018. The outcomes were as follows: (1) patients' characteristics and mortality by age groups (neonates/infants aged 0 years, preschool children aged 1-5 years, schoolchildren aged 6-11 years, and adolescents aged 12-18 years), (2) validity of survival probability (Ps) assessed using the TRISS methodology by the four age groups and six Ps-interval groups (0.00-0.25, 0.26-0.50, 0.51-0.75, 0.76-0.90, 0.91-0.95, and 0.96-1.00), and (3) the observed/expected survivor ratio by age- and Ps-interval groups. The validity of TRISS was evaluated by the predictive ability of the TRISS method using the receiver operating characteristic (ROC) curves that present the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, area under the receiver operator characteristic curve (AUC) of TRISS., Results: In all the age categories considered, the AUC for TRISS demonstrated high performance (0.935, 0.981, 0.979, and 0.977). The AUC for TRISS was 0.865, 0.585, 0.614, 0.585, 0.591, and 0.600 in Ps-interval groups (0.96-1.00), (0.91-0.95), (0.76. - 0.90), (0.51-0.75), (0.26-0.50), and (0.00-0.25), respectively. In all the age categories considered, the observed survivors among patients with Ps interval (0.00-0.25) were 1.5 times or more than the expected survivors calculated using the TRISS method., Conclusions: The TRISS methodology appears to predict survival accurately in Japanese pediatric patients with blunt trauma; however, there were several problems in adopting the TRISS methodology for younger blunt trauma patients with higher injury severity. In the next step, it may be necessary to develop a simple, high-quality prediction model that is more suitable for pediatric trauma patients than the current TRISS model.

Purpose: To elucidate the extension patterns of the hyperintense areas on diffusion-weighted magnetic resonance imaging (DW-MRI) in patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD)., Methods: We collected the DW-MRI of dCJD cases identified by the CJD Surveillance Committee in Japan, between April 1999 and February 2018. The dCJD cases were classified into non-plaque and plaque-types. The relationship among the abnormal signals, the pathological classification, and the sites of grafting were analyzed., Results: We collected DW-MRI of 11 patients with dCJD, all of whom were methionine homozygous at codon 129 of the prion protein gene. The age at onset was 41 (26-76) [median (range)] years, the age at dural grafting was 19 (10-53) years, and the incubation period was 22 (16-29) years. Eight dCJD cases were classified as non-plaque-type and three cases were plaque-type. Five of the non-plaque-type cases and all the plaque-type cases were pathologically confirmed. Brain DW-MRI was performed 3 (1-22) months after the onset. Most of the non-plaque-type cases showed brighter hyperintensity in the cerebral cortex and basal ganglia on the side of dural grafting. Subsequent DW-MRI showed widespread hyperintense lesions in the brain. Regarding the plaque-type cases, initial scans showed hyperintensity in the basal ganglia and the thalamus in one patient. Another patient's lesion was confined to the basal ganglia. The third patient showed no abnormalities seven months post-onset; however, serial images showed a hyperintensity confined to the thalamus., Conclusions: Non-plaque and plaque-types demonstrated different patterns of propagation of distinct prion strains., (Copyright © 2020. Published by Elsevier B.V.)

Aims/introduction: In Japan, an insulin pump with predictive low-glucose management (PLGM) was launched in 2018. It automatically suspends insulin delivery when the sensor detects or predicts low glucose values. The aim of this study was to analyze the safety and efficacy of PLGM in patients treated in a Japanese center., Materials and Methods: We carried out a retrospective observational analysis of 16 patients with type 1 diabetes mellitus and one patient after pancreatectomy. They switched from the MiniMed 620G device to the 640G device with PLGM. The primary outcome was the change in the percentage of time in hypoglycemia. The secondary outcome was the change in HbA1c (%) over a period of 3 months. We also explored the presence of "post-suspend hyperglycemia" with the 640G device., Results: After changing to the 640G device, the percentage of time in hypoglycemia (glucose <50 mg/dL) significantly decreased from 0.39% (0-1.51%) to 0% (0-0.44%; P = 0.0407). The percentage of time in hyperglycemia (glucose >180 mg/dL) significantly increased from 25.53% (15.78-44.14%) to 32.9% (24.71-45.49%; P = 0.0373). HbA1c significantly increased from 7.6 ± 1.0% to 7.8 ± 1.1% (P = 0.0161). From 1.5 to 4.5 h after the resumption of insulin delivery, the percentage of time in hyperglycemia was 32.23% (24.2-53.75%), but it was significantly lower, 2.78% (0-21.6%), when patients manually restarted the pump within 30 min compared with automatic resumption 31.2% (20-61.66%; P = 0.0063)., Conclusions: Predictive low-glucose management is an effective tool for reducing hypoglycemia, but possibly elicits "post-suspend hyperglycemia." This information is useful for achieving better blood glucose control in the patients treated with PLGM., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: It remains unclear whether transcatheter arterial embolisation (TAE) is as safe and effective for paediatric patients with blunt torso trauma as it is for adults in Japan, owing to few trauma cases and sporadic case reports. The study aimed to compare the efficacy and safety of TAE performed in paediatric (age ≤ 15 years) and adult patients with blunt torso trauma., Methods: This was a single-centre, retrospective chart review study that included blunt torso trauma patients who underwent TAE in the trauma centre from 2012 to 2017. The comparative study was carried out between a 'paediatric patient group' and an 'adult patient group'. The outcome measures for TAE were the success of haemorrhage control and complications and standardised mortality ratio (SMR)., Results: A total of 504 patients with blunt torso trauma were transported to the trauma centre, out of which 23% (N = 114) with blunt torso trauma underwent TAE, including 15 paediatric and 99 adult patients. There was no significant difference between the use of TAE in paediatric and adult patients with blunt torso trauma (29% vs 22%, P = .221). The paediatric patients' median age was 11 years (interquartile ranges 7-14). The predicted mortality rate and SMR for paediatric patients were lower than those for adult patients (18.3% vs 25.9%, P = .026, and 0.37 vs 0.54). The rate of effective haemorrhage control without repeated TAE or additional surgical intervention was 93% in paediatric patients, which was similar to that in adult patients (88%). There were no complications in paediatric patients at our centre. There were no significant differences in the proportion of paediatric patients who underwent surgery before TAE or urgent blood transfusion (33% vs 26%, P = .566, or 67% vs 85%, P = .084)., Conclusions: It is possible to provide an equal level of care related to TAE for paediatric and adult patients as it relates to TAE for blunt torso trauma with haemorrhage in the trauma centre. Alternative haemorrhage control procedures should be established as soon as possible whenever the patients reach a haemodynamically unstable state.

It has been shown that community-level social capital may affect residents' health. The present mixed ecological study assesses the evidence for an association between the community-level social capital and the individual level of self-rated health. The Hakui City Health Interview Survey targeted 15,242 people aged 40 years and older from 11 communities. Among them, 6578 residents responded to the questionnaire (response rate, 43.2%). We examined whether the community-level social capital (general trust, norm, and civic participation) was associated with the individual level of self-rated health. Overall, 1919 (29.1%) answers of self-rated poor health were identified. Community-level civic participation was negatively associated with poor self-rated health after adjusting for individual demographic factors, individual social capitals, and community-level economic status, whereas community-level general trust, and norm were not significant. The findings suggest the importance of fostering communities with high civic participation to reduce the poor health status of residents., Competing Interests: Moeko Noguchi-Shinohara has belonged to an endowment department, supported with an unrestricted grant from RICHO Co. Ltd. since April 2019. There are no other conflicts of interest relating to employment, consultancy, patents, products in development or marketed products. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Lettuce-associated respiratory allergy has never been reported before. The aim of this study was to clarify the clinical condition of lettuce-associated respiratory allergy and to identify the lettuce antigen which induces allergic symptoms., Methods: We distributed questionnaires to 1168 lettuce farmers and performed medical examinations in those who exhibited respiratory symptoms related to occupational exposure to lettuce. We analysed specific IgE-binding proteins in the sera of patients through immunoblotting analysis and determined molecular characterization of the IgE-binding bands using liquid chromatography-mass spectrometry., Results: A total of 932 farmers (80%) responded to the questionnaire. Of those, 7% exhibited lettuce-associated respiratory symptoms, during harvesting and packaging. Thirteen patients were diagnosed with allergy to lettuce and agreed to undergo further examinations. The percentage of activated basophils in these patients was significantly higher compared with that reported in negative controls (P < .05). Lettuce-specific IgE (ImmunoCAP ® ) and skin prick testing was positive in 46% and 62% of patients, respectively. Notably, occupational lettuce-allergic asthma was detected in one patient through specific bronchial provocation testing. The IgE-binding bands recognized in the sera of >50% of patients were identified as epidermis-specific secreted glycoprotein EP1-like (51 kDa)., Conclusion: The present analysis identified a novel lettuce allergen. This allergen may have clinically useful applications, such as specific IgE testing and allergen-specific immunotherapy., (© 2020 John Wiley & Sons Ltd.)

Objective: Foods reducing postprandial hyperglycemia could suppress the postprandial blood glucose response after the next meal (a "second-meal" effect). However, the second-meal effect of refined barley flour bread has not been evaluated. The aim of this study is to determine whether consumption of refined barley flour bread reduces postprandial glucose concentrations after this and the subsequent meal., Methods: We enrolled 23 healthy young Japanese adults and conducted a randomized, double-blind, placebo-controlled, crossover study. The participants consumed refined barley flour bread containing 2.5 g β-glucan or refined wheat flour bread in a first meal, then consumed three rice balls as a second meal. Their postprandial blood glucose concentrations were measured 0, 15, 30, 45, 60, 90, and 120 min after both meals. Participants with fasting glucose concentrations above the diagnostic threshold for diabetes were excluded., Results: The blood glucose concentration 30 min after the first meal was significantly lower (P < 0.05) if refined barley flour bread (7.1 ± 1.0 mmol/L) rather than refined wheat flour bread (7.7 ± 1.2 mmol/L) was consumed. Significantly lower glucose concentrations after the second meal measured at 60 (P < 0.05, barley flour bread: 8.7 ± 1.8 mmol/L, wheat flour bread: 9.3 ± 1.7 mmol/L) and 90 min (P < 0.01, barley flour bread: 7.8 ± 1.4 mmol/L, wheat flour bread: 8.8 ± 2.1 mmol/L) were lower in participants who had previously consumed the refined barley flour bread., Conclusions: Consumption of bread made with refined barley flour lowers postprandial blood glucose concentration after this and a subsequent meal compared with the consumption of refined wheat flour bread in healthy young Japanese adults., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: The associations between trans fatty acids and dementia have been unclear. We investigated the prospective association between serum elaidic acid (trans 18:1 n-9) levels, as an objective biomarker for industrial trans fat, and incident dementia and its subtypes., Methods: In total, 1,628 Japanese community residents aged 60 and older without dementia were followed prospectively from when they underwent a screening examination in 2002-2003 to November 2012 (median 10.3 years, interquartile range 7.2-10.4 years). Serum elaidic acid levels were measured using gas chromatography/mass spectrometry and divided into quartiles. The Cox proportional hazards model was used to estimate the hazard ratios for all-cause dementia, Alzheimer disease (AD), and vascular dementia by serum elaidic acid levels., Results: During the follow-up, 377 participants developed some type of dementia (247 AD, 102 vascular dementia). Higher serum elaidic acid levels were significantly associated with greater risk of developing all-cause dementia ( p for trend = 0.003) and AD ( p for trend = 0.02) after adjustment for traditional risk factors. These associations remained significant after adjustment for dietary factors, including total energy intake and intakes of saturated and polyunsaturated fatty acids (both p for trend <0.05). No significant associations were found between serum elaidic acid levels and vascular dementia., Conclusions: The findings suggest that higher serum elaidic acid is a possible risk factor for the development of all-cause dementia and AD in later life. Public health policy to reduce industrially produced trans fatty acids may assist in the primary prevention of dementia., (© 2019 American Academy of Neurology.)

Background: Polymerase chain reaction (PCR) analysis using DNA from dried blood spot (DBS) samples on filter paper is a critical technique for spinal muscular atrophy (SMA) newborn screening. However, DNA extraction from DBS is time-consuming, and elimination of PCR inhibitors from DBS is almost impossible., Methods: Exon 7 of the two homologous SMA-related genes, survival motor neuron (SMN) 1 and SMN2, of five SMA patients and five controls were amplified by PCR with a punched-out circle of the DBS paper. Two types of DNA preparation methods were tested; DNA-extraction (extracted DNA was added in a PCR tube) and non-DNA-extraction (a punched-out DBS circle was placed in a PCR tube). As for the DNA polymerases, two different enzymes were compared; TaKaRa Ex Taq™ and KOD FX Neo™. To test the diagnostic quality of PCR products, RFLP (Restriction fragment length polymorphism) analysis with DraI digestion was performed, differentiating SMN1 and SMN2., Results: In PCR using extracted DNA, sufficient amplification was achieved with TaKaRa Ex Taq™ and KOD FX Neo™, and there was no significant difference in amplification efficiency between them. In direct PCR with a punched-out DBS circle, sufficient amplification was achieved when KOD FX Neo™ polymerase was used, while there was no amplification with TaKaRa Ex Taq™. RFLP analysis of the direct PCR products with KOD FX Neo™ clearly separated SMN1 and SMN2 sequences and proved the presence of both of SMN1 and SMN2 in controls, and only SMN2 in SMA patients, suggesting that the direct PCR products with KOD FX Neo™ were of sufficient diagnostic quality for SMA testing., Conclusion: Direct PCR with DNA polymerases like KOD FX NeoTM has potential to be widely used in SMA newborn screening in the near future as it obviates the DNA extraction process from DBS and can precisely amplify the target sequences in spite of the presence of PCR inhibitors.

Introduction: It remains unclear whether trauma centers are effective for the treatment of injured pediatric patients. The aim of this study was to evaluate children's mortality before and after the establishment a trauma center by using standard mortality ratios (SMR) and a modified observed-expected chart., Methods: This was a single center, retrospective chart review study that included injured pediatric patients (age <16 years) who were transported to our trauma center by the emergency medical services from 2012 to 2016 in Japan., Results: Our study included 143 subjects: 45 (31%) were preschoolers aged < 6 years, and 43 (30%) had an injury severity score (ISS) ≥ 16. After the trauma centers established, the number of patients increased (70% increase per month), as did the number of the patients with an ISS of 41-75. The percentage of indirect transportations was significantly higher in the trauma center than in the non-trauma center (49% vs. 28%; p < 0.05). The SMR was significantly lower in the trauma-center than in the non-trauma center (0.461 vs. 0.589; p < 0.05). The mean value of the modified observed-expected chart was significantly higher in the trauma-center than in the non-trauma center (4.6 vs. 2.3; p < 0.05). For the patients who were directly transferred to our center, the transfer distance was greater in the trauma-center than in the non-trauma center (6.8 vs. 6.2 km; p < 0.05). The time interval from hospital admission to initiation of computed tomography (15.5 vs. 33 minutes; p < 0.05) and to definitive care (44 vs. 64.5 minutes; p < 0.05) decreased in the after group compared to the non-trauma center., Conclusions: The results of our study revealed that the centralization of pediatric injured pediatric patients in trauma centers improved the mortality rate in this population in Japan., Competing Interests: The authors have declared that no competing interests exist.

Background: Both cigarette smoking and diabetes mellitus are well-established risk factors for development of dementia. However, the interaction between smoking and diabetes is yet unknown., Objective: In this study, we clarify association between smoking, diabetes, and dementia risk in older adults., Methods: Participants in this study included community residents aged 65 years and older who had participated in a health checkup in 2006, followed for 10 years (n = 9,403) and had long-term care insurance information data. Furthermore, the risk estimates of smoking status and diabetes diagnosis on dementia adjusted for the competing risk of death prior to dementia were analyzed., Results: During follow-up, 2,647 participants developed dementia. The smoking status-diabetes interaction on development of dementia was statistically significant (p≤0.001). Among those patients exposed to both factors, 17% of risk of development of dementia was attributable to the interaction of these factors. Current smokers with diabetes had significantly greater risks of development of dementia than never smokers without diabetes (reference): multivariable-adjusted risk of dementia in current smokers without diabetes (subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.05-1.48); never smokers with diabetes (1.31, 1.16-1.47); and current smokers with diabetes (1.86, 1.39-2.48). However, no such association was noted for former smokers with and without diabetes., Conclusions: Current smoking, but not former smoking, was associated with increased risk of development of dementia in older adults with and without diabetes. Moreover, the synergistic effect of current smoking and diabetes on dementia was noted.

Background: Triage has an important role in providing suitable care to the largest number of casualties in a disaster setting, but there are no secondary triage methods suitable for children. This study developed a new secondary triage method named the Pediatric Physiological and Anatomical Triage Score (PPATS) and compared its accuracy with current triage methods., Methods: A retrospective chart review of pediatric patients under 16 years old transferred to an emergency center from 2014 to 2016 was performed. The PPATS categorized the patients, defined the intensive care unit (ICU)-indicated patients if the category was highest, and compared the accuracy of prediction of ICU-indicated patients among PPATS, Physiological and Anatomical Triage (PAT), and Triage Revised Trauma Score (TRTS)., Results: Among 137 patients, 24 (17.5%) were admitted to ICU. The median PPATS score of these patients was significantly higher than that of patients not admitted to ICU (11 [IQR: 9-13] versus three [IQR: 2-4]; P<.001). The optimal cut-off value of the PPTAS was six, yielding a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 95.8%, 86.7%, 60.5%, and 99.0%. The area under the receiver-operating characteristic curve (AUC) was larger for PPTAS than for PAT or TRTS (0.95 [95% CI, 0.87-1.00] versus 0.65 [95% CI, 0.58-0.72]; P<.001 and 0.79 [95% CI, 0.69-0.89]; P=.003, respectively). Regression analysis showed a significant association between the PPATS and the predicted mortality rate (r2=0.139; P<.001), ventilation time (r2=0.320; P<.001), ICU stay (r2=0.362; P<.001), and hospital stay (r2=0.308; P<.001)., Conclusions: The accuracy of PPATS was superior to other methods for secondary triage of children. Toida C , Muguruma T , Abe T , Shinohara M , Gakumazawa M , Yogo N , Shirasawa A , Morimura N . Introduction of pediatric physiological and anatomical triage score in mass-casualty incident. Prehosp Disaster Med. 2018;33(2):147-152.

Background: Antioxidants like vitamins C and E may minimize the risk for Alzheimer's disease., Objective: We examined whether vitamins C and E modify the apolipoprotein E (APOE) E4-related risks for developing cognitive decline., Methods: We conducted a population-based prospective study including Japanese residents aged 65 years from Nakajima, Japan. The participants received an evaluation of cognitive function and underwent blood tests including tests for vitamins C and E levels and APOE phenotypes. The APOE E4-by-gender-by-vitamin C or E interactions on developing cognitive decline were analyzed., Results: Of 606 participants with normal cognitive function determined using a baseline survey (2007-2008), 349 completed the follow up survey between 2014 and 2016. In women with APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin C concentration tertile [multivariate OR 0.10 (95% CI 0.01-0.93)] compared with the lowest tertile. In men without APOE E4, significantly reduced risk for cognitive decline was observed for the highest blood vitamin E concentration tertile [multivariate OR 0.19 (0.05-0.74)] as compared with the lowest tertile., Conclusion: Our results demonstrate significant beneficial effects of vitamins C and E in reducing the risk of cognitive decline in women with APOE E4 and men without APOE E4, respectively.

In many cohort studies of dementia, while differences in sociodemographic characters between responders and non-responders of dementia screening have been reported, differences in dementia beliefs have been relatively less known. The aims of this study were to clarify dementia beliefs and to explore potential impacts on an intention to attend a future dementia screening in public screeners and in-home screeners, respectively. We performed a cross-sectional population-based study using a question about an intention to attend a future dementia screening and a questionnaire on dementia beliefs. Subjects were all residents aged 65 years or older in the north area of Nakajima, Japan (n = 385). All subjects were asked to attend a public dementia screening first. An in-home dementia screening was subsequently conducted in subjects with non-responders to a public screening. The questionnaire consisted of four dementia beliefs: "perceived susceptibility," "perceived severity," "perceived barriers," and "perceived benefits." Public screeners significantly expressed an intention to attend a future dementia screening more than in-home screeners (p = 0.002). In in-home screeners, low "perceived severity" were significantly associated with an intention to attend a future dementia screening [adjusted OR (95% CI) = 0.51 (0.32-0.80)]. In both public and in-home screeners, high "perceived benefits" were significantly associated with an intention to attend a future dementia screening [adjusted OR (95% CI) = 2.13 (1.46-3.10); adjusted OR (95% CI) = 2.56 (1.22-5.35), respectively]. It is necessary to reduce "perceived severity" among in-home screeners to increase dementia screening participants.

Aim: Many cohort studies have shown that increased trans fatty acid (TFA) intake increases the risk of developing coronary heart disease. However, whether TFA intake is directly associated with the development of diabetes mellitus (DM) remains unknown., Methods: We performed the 75-g oral glucose tolerance test in two Japanese cohorts: a cohort of 454 native Japanese living in Hiroshima, Japan, and a cohort of 426 Japanese-Americans living in Los Angeles, USA, who shared identical genetic predispositions but had different lifestyles. Serum elaidic acid concentration was measured and compared, and its association with insulin resistance was assessed., Results: Serum elaidic acid concentrations were significantly higher in the Japanese-Americans (median, 18.2 µmol/L) than in the native Japanese (median, 11.0 µmol/L). The serum elaidic acid concentrations in the native Japanese DM group (16.0 µmol/L) were significantly higher compared with those in the normal glucose tolerance (10.8 µmol/L) and impaired glucose tolerance (11.7 µmol/L) groups. Multiple linear regression analyses showed that serum elaidic acid concentrations were significantly positively associated with homeostasis model assessment for insulin resistance (HOMA-IR) values after adjusting for various factors., Conclusions: These results suggest that excessive TFA intake worsens insulin resistance and increases the risk of developing DM even in the native Japanese, whose intakes of animal fat and simple carbohydrates were presumed to be lower than those of the Japanese-Americans.

Background: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by a mutation in SMN1. SMA is classified into three subtypes (types 1, 2, 3) based on achieved motor milestones. Although NAIP and SMN2 are widely accepted as SMA-modifying factors, gender-related modifying factors or gender effects on the clinical phenotype are still controversial., Methods: A total of 122 Japanese patients with SMA, of which SMN1 was homozygously deleted, were analyzed from the perspective of the achieved motor milestone, NAIP status and SMN2 copy number., Results: A predominance of male patients was observed in SMA type 3 (the walker group) without NAIP-deletion or with high SMN2 copy number (3 or 4 copies)., Conclusion: We suggest the presence of gender-related modifiers on disease severity in SMA patients. The modifiers may contribute only in the presence of NAIP and a high copy number of SMN2.

Purpose: We objectively investigated the relationship between sleep quality/efficiency and factors associated with micturition using at-home electroencephalogram assessment., Materials and Methods: Participants were recruited from among those enrolled in the Fujiwara-kyo Study, a community based longitudinal evaluation that began in Nara Prefecture, Japan, in 2007. Included participants were men at least 65 years old who woke up in the middle of the night/early morning at least 3 times per week with the urge to void. We evaluated lower urinary tract symptoms using the I-PSS and subjective sleep quality using the Pittsburgh Sleep Quality Index. Uroflowmetry and 3-day frequency volume charting measurements were also obtained. Electroencephalogram recordings were obtained during sleep to evaluate objective sleep quality., Results: Final analysis included data from 47 participants. I-PSS-quality of life score and slow wave sleep time were independent predictors of good subjective sleep quality as determined by Pittsburgh Sleep Quality Index scores. Nocturnal urinary volume was an independent predictor of greater sleep efficiency. Maximum flow rate was an independent predictor of longer slow wave sleep time., Conclusions: In elderly men with nocturia, sleep quality is associated with lower urinary tract function. Higher subjective sleep quality is associated with longer slow wave sleep time and less severe lower urinary tract symptoms. Higher objective sleep quality is further associated with a higher urinary flow rate and lower nocturnal urinary volume., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of the current study was to assess our multidisciplinary approach consisting of early application of neurology-oriented intensive care, aggressive artificial liver support and liver transplantation at the appropriate time for infants with acute liver failure., Design: Retrospective cohort study., Setting: A tertiary pediatric medical center in Japan., Patients: Seventeen infants younger than 12 months with acute liver failure who subsequently underwent liver transplantation between February 2006 and June 2011., Interventions: None., Measurements and Main Results: The patients varied from 1 to 11 months, with a median of 6 months. The median body weight was 8.0 kg (range, 2.7-10 kg). With respect to the encephalopathy grading before liver transplantation, four cases were categorized as grade II, seven cases were categorized as grade III, and five cases were categorized as grade IV. Continuous veno-venous hemodiafiltration and plasma exchange were applied to all the infants until liver transplantation. Bilirubin, ammonia, prothrombin time/international normalized ratio and creatinine decreased significantly after continuous veno-venous hemodiafiltration + plasma exchange (p < 0.001). The median value of catecholamine index changed from 10 to 0 (range, 0-20.6). Notably, among the 16 infants who underwent electroencephalography assessment, five did not show slow waves throughout their stay, and one who did so before treatment ceased to show any after treatment. The all patients underwent living-donor liver transplantation and were subsequently discharged from the PICU. The overall survival rate was 88% (15/17) with a median follow-up period of 28 months (range, 2-64 mo). Regarding the neurological outcomes of the survivors, 73% (11/15) had no neurological morbidities and 20% (3/15) had mild disabilities., Conclusions: Our multidisciplinary approach for infants with acute liver failure achieved favorable outcomes. Further investigations are needed to examine the efficacy of the artificial liver support.

A novel GII.P17-GII.17 variant norovirus emerged as a major cause of norovirus outbreaks from December 2014 to March 2015 in Japan. Named Hu/GII/JP/2014/GII.P17-GII.17, this variant has a newly identified GII.P17 type RNA-dependent RNA polymerase, while the capsid sequence displays amino acid substitutions around histo-blood group antigen (HBGA) binding sites. Several variants caused by mutations in the capsid region have previously been observed in the GII.4 genotype. Monitoring the GII.17 variant's geographical spread and evolution is important.

Background: Adverse effects of dietary intake of trans-fatty acids (TFA) on the incidence of coronary artery disease (CAD) are well recognized in Western countries. The risk of TFA, however, has not been well clarified in Japan. We investigated the association of serum TFA concentration with serum lipid profile, coronary risk factors, and prevalence of CAD., Methods and results: A total of 902 patients, who were hospitalized at Kobe University Hospital from July 2008 to March 2012 and gave written informed consent, were enrolled in this study. Among them, 463 patients had CAD, and 318 patients had metabolic syndrome (MetS). Serum TFA, elaidic acid (trans-9-C18:1) and linolelaidic acid (trans-9, 12-C18:2), were measured on gas chromatography/mass spectrometry. Serum TFA level had a positive correlation with body mass index, waist circumference, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B48, and an inverse correlation with age and high-density lipoprotein cholesterol. Fasting serum TFA, by age quartile in the young generation with CAD and/or MetS, was higher than that in patients without CAD and/or MetS. On multivariate logistic regression, TFA was identified as a CAD risk after adjustment for classical risk factors., Conclusions: Serum TFA concentration was elevated in young patients with CAD and/or MetS. Diet-derived TFA may cause a serious health problem, particularly in the young generation in Japan.

Objective: It has been reported that high-density lipoprotein (HDL) loses anti-inflammatory function and promotes atherosclerosis under pathological conditions. However, no pharmacological therapy to improve HDL function is currently available. We aimed to evaluate the effect of oral administration of eicosapentaenoic acid (EPA) on HDL function., Methods: Japanese patients with dyslipidemia were treated with EPA (1800 mg/day, 4 weeks), and anti-inflammatory functions of HDL were assessed utilizing in vitro cell-based assays., Results: The EPA treatment did not change serum cholesterol and triglyceride levels, but it significantly increased EPA concentrations in the serum and HDL fraction. The EPA/arachidonic acid ratio in the HDL was in proportion to that in the serum, suggesting that the orally administered EPA was efficiently incorporated into the HDL particles. The HDL after EPA treatment showed significantly increased activity of anti-oxidative enzyme, paraoxonase-1. In addition, the EPA-rich HDL significantly improved endothelial cell migration, and markedly inhibited cytokine-induced expression of vascular cell adhesion molecule-1, in human umbilical vein endothelial cells, compared to HDL before the EPA treatment. Moreover, the EPA-rich HDL augmented cholesterol efflux capacity from macrophages., Conclusion: Oral administration of EPA regenerated anti-oxidative and anti-inflammatory functions of HDL, and promoted cholesterol efflux from macrophages. Therefore, EPA may transform "dysfunctional HDL" to "functional", in patients with coronary risk factors., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background/aims: It has been reported that Th2 cytokines down-regulate antitumor immunity, while activation of Th1 cells promotes such immunity. The aim of this study was to assess changes of host immunity in relation to efficacy in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) treated by combined intra-arterial chemotherapy (CIAC)., Methodology: Forty-three adult Japanese LC patients who had aHCC received CIAC. Blood samples were collected before and after CIAC., Results: Eleven of the 43 patients showed a partial response (group PR) and 21 patients had stable disease (group SD), but 11 patients showed no response (group PD). There were no significant differences of Th1 or Th2 cells between before and after CIAC in each group. However, groups SD and PD had higher levels of Th2 cells than in group PR before and after CIAC. The percentage of regulatory T (Treg) cells in group PD was significantly increased after CIAC compared with before CIAC, whereas groups PR and SD showed significant decrease after CIAC., Conclusions: The percentage of Th2 cells is useful for predicting the response to CIAC and the percentage of Treg cells is useful for assessment of efficacy in LC patients with aHCC receiving CIAC.

For a brief period, an increased incidence of elevated anti-acetylcholine receptor antibody titer was observed in patients with myasthenia gravis (MG) in Kanazawa, Japan. The purpose of this study was to examine the predictive factors associated with this antibody titer elevation. Decreased odds of titer elevation were seen in patients with early-onset MG than in those with late-onset MG. In patients with non-thymoma-related MG, thymectomy prevented the antibody titer elevation. Our data suggest that late-onset MG may have a different immunogenic response and the thymus might play an immunoregulatory role against extrinsic factors in some types of MG., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: More than 60% of patients worldwide with Creutzfeldt-Jakob disease (CJD) associated with dura mater graft (dCJD) have been diagnosed in Japan. The remarkable frequency of dura mater grafts in Japan may possibly contribute to the elevated incidence of dCJD, but reasons for the disproportionate use of this procedure in Japan remain unclear. We investigated differences between dCJD patients in Japan and those elsewhere to help explain the more frequent use of cadaveric dura mater and the high incidence of dCJD in Japan., Methods: We obtained data on dCJD patients in Japan from the Japanese national CJD surveillance programme and on dCJD patients in other countries from the extant literature. We compared the demographic, clinical and pathological features of dCJD patients in Japan with those from other countries., Results: Data were obtained for 142 dCJD patients in Japan and 53 dCJD patients elsewhere. The medical conditions preceding dura mater graft transplantation were significantly different between Japan and other countries (p<0.001); in Japan, there were more cases of cerebrovascular disease and hemifacial spasm or trigeminal neuralgia. Patients with dCJD in Japan received dura mater graft more often for non-life-threatening conditions, such as meningioma, hemifacial spasm and trigeminal neuralgia, than in other countries., Conclusions: Differences in the medical conditions precipitating dura mater graft may contribute to the frequent use of cadaveric dura mater and the higher incidence of dCJD in Japan.

Purpose: Acute encephalopathy is the most serious complication of pediatric viral infections, such as influenza and exanthema subitum. It occurs worldwide, but is most prevalent in East Asia. Recently, there have been sporadic case reports of epilepsy/febrile seizure and acute encephalopathy with a neuronal sodium channel alpha 1 subunit (SCN1A) mutation. To determine whether SCN1A mutations are a predisposing factor of acute encephalopathy, we sought to identify SCN1A mutations in a large case series of acute encephalopathy including various syndromes., Methods: We analyzed the SCN1A gene in 87 patients with acute encephalopathy, consisting of 20 with acute necrotizing encephalopathy (ANE), 61 with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), and six with nonspecific (unclassified) acute encephalopathy., Key Findings: Three patients had distinct point mutations. Two of them had epileptic seizures prior to acute encephalopathy. Clinical and neuroradiologic findings of acute encephalopathy were diverse among the three patients, although all had a prolonged and generalized seizure at its onset. The first patient with V982L had partial epilepsy and AESD. The second patient with M1977L had febrile seizures and nonspecific acute encephalopathy. The third patient with R1575C had no seizures until the onset of ANE. M1977L was a novel mutation, whereas the remaining two, V982L and R1575C, have previously been reported in cases of Dravet syndrome and acute encephalopathy, respectively., Significance: These findings provide further evidence that SCN1A mutations are a predisposing factor for the onset of various types of acute encephalopathy., (Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.)

Background:  Cytochrome P450 (CYP) 2C19 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after drug-eluting stent (DES) implantation, but its contribution to lesion outcome after DES implantation is unclear., Methods and Results:  The study included 160 Japanese patients who received clopidogrel and underwent DES implantation with follow-up angiography. Patients were divided into 3 groups by CYP2C19 polymorphism: extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). The incidence of major adverse cardiac events (MACE) and target lesion revascularization (TLR) were compared among the 3 groups. Optical coherence tomography (OCT) was performed for 120 patients to evaluate the incidence of intra-stent thrombi. Of the 160 patients, the proportion of EM, IM, and PM was 37.5%, 48.1%, and 14.4%, respectively. The incidence of TLR and MACE was more frequent in IM and PM than EM (TLR: 18.2% and 26.1% vs. 3.3%, P=0.008, MACE: 22.1% and 30.4% vs. 5.0%, P=0.005). Among the 120 patients who underwent follow-up OCT, intra-stent thrombi were more frequently detected in IM and PM than in EM (45.6% and 63.2% vs. 20.5%, P=0.005). The incidence of TLR was significantly higher in patients with than in those without intra-stent thrombi (27.7% vs. 6.8%, P=0.003)., Conclusions:  CYP2C19 loss-of-function polymorphism might be associated with the incidence of MACE and TLR in association with intra-stent thrombi.

Background:  The cytochrome P450 (CYP) 2C19*2 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after stent implantation. Despite the high frequency of this polymorphism in Japanese patients, its contribution to cardiac events and stent thrombi after drug-eluting stent (DES) implantation is not clear in this population., Methods and Results:  One hundred Japanese patients received clopidogrel and underwent follow-up optical coherence tomography (OCT) after DES implantation. The patients were divided into 2 groups: those with at least one CYP2C19*2 allele (*2 carriers) and non-carriers. The incidence of stent thrombosis and major adverse cardiac events (MACE; ie, death, myocardial infarction, and target vessel revascularization) was compared between the 2 groups. In addition, OCT was used to evaluate the incidence of intra-stent thrombus, defined as a mass protruding into the lumen with significant attenuation. Of the 100 patients, 42 were *2 carriers. No remarkable differences in the baseline characteristics were noted. Although MACE did not differ significantly between the 2 groups, a subclinical intra-stent thrombus was detected more frequently in *2 carriers than in non-carriers (52.3% vs. 15.5%, P=0.0002). Multivariate logistic regression analysis showed that the presence of the CYP2C19*2 polymorphism was the only independent predictive factor for intra-stent thrombus (P=0.00006)., Conclusions:  From these results it is suggested that CYP2C19*2 polymorphism is associated with subclinical thrombus formation among Japanese patients receiving clopidogrel. (Circ J 2011; 75: 99-105).

We analysed the epidemiological data and clinical features of patients with prion diseases that had been registered by the Creutzfeldt-Jakob Disease Surveillance Committee, Japan, over the past 10 years, since 1999. We obtained information on 1685 Japanese patients suspected as having prion diseases and judged that 1222 patients had prion diseases, consisting of definite (n=180, 14.7%) and probable (n=1029, 84.2%) cases, except for dura mater graft-associated Creutzfeldt-Jakob disease which also included possible cases (n=13, 1.1%). They were classified into 922 (75.5%) with sporadic Creutzfeldt-Jakob disease, 216 (17.7%) with genetic prion diseases, 81 (6.6%) with acquired prion diseases, including 80 cases of dura mater graft-associated Creutzfeldt-Jakob disease and one case of variant Creutzfeldt-Jakob disease, and three cases of unclassified Creutzfeldt-Jakob disease (0.2%). The annual incidence rate of prion disease ranged from 0.65 in 1999 to 1.10 in 2006, with an average of 0.85, similar to European countries. Although methionine homozygosity at codon 129 polymorphism of the prion protein gene was reported to be very common (93%) in the general Japanese population, sporadic Creutzfeldt-Jakob disease in Japan was significantly associated with codon 129 homozygosity (97.5%), as reported in western countries. In sporadic Creutzfeldt-Jakob disease, MM1 type (Parchi's classification) is the most common, as in western countries. Among atypical sporadic Creutzfeldt-Jakob disease cases, the MM2 type appeared most common, probably related to the very high proportion of methionine allele in the Japanese population. As for iatrogenic Creutzfeldt-Jakob disease, only dura mater graft-associated Creutzfeldt-Jakob disease cases were reported in Japan and, combined with the data from previous surveillance systems, the total number of dura mater graft-associated Creutzfeldt-Jakob disease was 138, comprising the majority of worldwide dura mater graft-associated Creutzfeldt-Jakob disease patients. Regarding genetic prion diseases, the most common mutation of prion protein gene was V180I (41.2%), followed by P102L (18.1%), E200K (17.1%) and M232R (15.3%), and this distribution was quite different from that in Europe. In particular, V180I and M232R were quite rare mutations worldwide. Patients with V180I or M232R mutations rarely had a family history of prion diseases, indicating that a genetic test for sporadic cases is necessary to distinguish these from sporadic Creutzfeldt-Jakob disease. In conclusion, our prospective 10-year surveillance revealed a frequent occurrence of dura mater graft-associated Creutzfeldt-Jakob disease, and unique phenotypes of sporadic Creutzfeldt-Jakob disease and genetic prion diseases related to the characteristic distribution of prion protein gene mutations and polymorphisms in Japan, compared with those in western countries.

Recent progress in genotyping technology and the development of public databases has enabled large-scale genome-wide association tests with diseases. We performed a two-stage genome-wide association study (GWAS) of bipolar disorder (BD) in Japanese cohorts. First we used Affymetrix 100K GeneChip arrays in the analysis of 107 cases with bipolar I disorder and 107 controls, and selected markers that were nominally significant (P < 0.01) in at least one of the three models (1,577 markers in total). In the follow-up stage, we analyzed these markers using an Illumina platform (1,526 markers; 51 markers were not designable for the platform) and an independent sample set, which consisted of 395 cases (bipolar I + II) and 409 controls. We also assessed the population stratification of current samples using principal components analysis. After the two-stage analysis, 89 markers remained nominally significant (allelic P < 0.05) with the same allele being consistently over-represented in both the first and the follow-up stages. However, none of these were significant after correction for multiple-testing by false discovery rates. Sample stratification was virtually negligible. Collectively, this is the first GWAS of BD in the Japanese population. But given the small sample size and the limited genomic coverage, these results should be taken as preliminary., (2009 Wiley-Liss, Inc.)

The Creutzfeldt-Jakob Disease (CJD) Surveillance Committee has identified 1,241 patients with prion diseases during 1999-2009, including 953 with sporadic CJD (sCJD) (76.8%), 207 with genetic prion diseases (16.7%), 78 with environmentally acquired prion diseases (6.3%), and 3 with unclassified CJD. Among atypical cases of sCJD, most common was MM2 type including the cortical and thalamic forms. The genetic cases included 84 with a PrP V180I mutation (40.6%), 37 with a P102L mutation (17.9%), 34 with a E200K mutation (16.4%), 32 with a M232R mutation (15.5%), 4 with a P105L mutation (1.9%), and so on. The environmentally acquired cases included 77 with dura mater graft-associated CJD (dCJD) and one with variant CJD (vCJD). Combined with the results by the previous surveillance systems, a total number of dCJD in Japan was 135. The vCJD patient had a history of short stay in the UK and presented with periodic electroencephalogram in the late stage. Although there was no evidence of association of surgical procedures or blood transfusion with sCJD, 4.5% of the sCJD patients underwent operations after the onset of sCJD, including neurosurgical for 0.8% and ophthalmic for 1.9%, requiring more attention on prion diseases to reduce the iatrogenic risk.

Up to February 2008, a total of 132 patients with dura mater graft-associated Creutzfeldt-Jakob disease (dCJD) have been identified in Japan, accounting for a majority of the world's patients with dCJD. The patients received dura mater grafts from 1978 to 1993. Lyodura (B. Braun, Melsungen, Germany) was used for all the patients in whom the brand name of the dura mater could be identified. After the incubation period of 1 to 25 years (mean, 11.8 years), CJD appeared from 1985 through to 2006. We analyzed clinical, pathological, and molecular features in 74 patients with dCJD who had been prospectively registered by the CJD Surveillance Committee. The cases of dCJD could be classified into two distinct clinicopathological phenotypes: a non-plaque type, showing typical features identical with those of classic CJD, and a plaque type, characterized by atypical features, including slow progression, lack of or late occurrence of periodic sharp wave complexes on EEG, and plaque formation in the brain. The plaque type accounted for one-third of the pathologically confirmed or clinically diagnosed cases of dCJD. The non-plaque type was associated with methionine homozygosity at codon 129 (129M/M) of the PrP gene in all patients, except for in one patient with the 129M/valine (V) genotype and type 1 protease-resistant PrP (PrP(res)), whereas the plaque type was always associated with the 129M/M genotype and the intermediate type between types 1 and 2 of PrP(res) in all cases. Thus, the clinicopathological and molecular features of the plaque type are distinct from those of the non-plaque type, suggesting contamination of the dura mater grafts with different prion strains.

Background: Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral problems including hyperphagia, emotional aberration, and compulsion-like behaviors. This combination of behavioral problems is likely to be caused by damage to the orbitofrontal cortices and anterior temporal lobes or to circuits involving them., Objectives: To investigate the prevalence of eating and non-eating behavioral disturbances in PWS by using assessment tools developed originally for patients with frontotemporal dementia and with frontal lobe injury., Method: The questionnaire consisted of 35 questions related to three categories of behavior: eating behaviors (including four domains: appetite, food preference, eating habits, and other oral behaviors), stereotypy (including four domains: roaming, speaking, movements, and daily rhythm), and collecting behaviors. It was administered in Japan to the parents of 250 individuals aged 1-42 years with a clinical diagnosis of PWS., Results: The prevalence rates of symptoms in all categories were high. Each domain involved in eating behaviors was significantly correlated with stereotypy and collecting behaviors. The prevalence rates and severity scores of some eating and non-eating behaviors were higher in the older groups., Conclusion: Abnormal eating behaviors, stereotyped behaviors, and collecting behaviors were common in the PWS subjects. There was also a potential link between abnormal eating and non-eating behaviors related to frontal behavioral syndromes. It is likely that these behavioral abnormalities reflect dysfunction of the orbitofrontal cortices and anterior temporal lobes.

We studied 1809 patients with oral cancer who visited and were treated, in 2002, at the 148 institutions certified as training facilities by the Japanese Society of Oral and Maxillofacial Surgeons. Of these institutions, 39 are dental university hospitals, 44 are medical university hospitals, 64 are general hospitals, and for 1 institution, the classification was not known. The patients consisted of 1071 (59.2%) males and 738 (40.8%) females (male: female ratio, 1.45:1), who had a average age of 65.2 years. The tongue (40.2%) was the most common site affected, followed by the gingiva (32.7%), buccal mucosa (10.1%), and oral floor (9.0%). There were 6 cases of multiple intraoral cancers. On histopathological examinations, squamous cell carcinoma (88.7%) was the most common type found, followed by adenoid cystic carcinoma (2.1%), and mucoepidermoid carcinoma (1.7%). Cases classified as T2N0 were the most common (32.1%), followed by T1N0 (21.4%), T4N0 (8.0%), and T2N1 (7.6%). Distant metastasis occurred in 17 patients (1.0%). Nonepithelial tumors, among which malignant melanoma was the most common type, accounted for 1.8% of the tumors. The sizes of the nonepithelial malignant tumors ranged from 1.0 to 7.0 cm, with an average size of 3.7 cm.