Search

Background: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study. Methods: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35-69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted. Results: The mean follow-up period was 11 years, and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR 0.73; 95% CI, 0.55-0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction. Conclusion: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk. [ABSTRACT FROM AUTHOR]

Background and Objectives: Androgen deprivation therapy (ADT) for prostate cancer has greatly improved treatment outcomes. As patient survival rates have increased, reports of decreased bone density and increased bone fractures as side effects of ADT have emerged. The prevalence of osteoporosis in Japanese men was 4.6%. The purpose of this study was to evaluate the effect of osteoporosis treatment in prostate cancer patients who underwent ADT in Japan. Materials and Methods: The subjects were 33 male patients who had undergone ADT for prostate cancer, who were noted to have decreased bone density. Mean age was 76.2 ± 7.7 years (64–87). Medications included vitamin D in one case, bisphosphonates (BP) in 27 cases, and denosumab in five cases. The evaluation method examined the rate of change in bone mineral density (BMD) before osteoporosis treatment and 1 year after. For comparison, a group without osteoporosis treatment intervention (n = 33) was selected, and matched for prostate cancer treatment and age. The rate of change in trabecular bone score (TBS) was also calculated. Results: The percentage changes in BMD before and 1 year after treatment were as follows: lumbar spine, 7.1 ± 5.8% in the treatment group versus −3.9 ± 4.1% in the no treatment group; femoral neck, 5.5 ± 6.2% in the treatment group versus −0.9 ± 3.9% in the no treatment group; total femur, 6.6 ± 6.4% in the treatment group versus the no treatment group which was −1.7 ± 3.2%. In all cases, there was a clear significant difference (p < 0.01). The percent change in TBS was further calculated in the same manner. There was no significant difference between the two groups: +1.7 ± 3.8% in the treated group versus +0.3 ± 4.1% in the untreated group. Conclusions: Osteoporosis treatment in Japanese patients with prostate cancer on ADT therapy was found to significantly increase BMD compared to the untreated group. BP and denosumab were found to be very effective in increasing BMD. [ABSTRACT FROM AUTHOR]

Objective: Although small fish are an important source of micronutrients, the relationship between their intake and mortality remains unclear. This study aimed to clarify the association between intake of small fish and all-cause and cause-specific mortality. Design: We used the data from a cohort study in Japan. The frequency of the intake of small fish was assessed using a validated FFQ. The hazard ratio (HR) and 95 % confidence interval (CI) for all-cause and cause-specific mortality according to the frequency of the intake of small fish by sex were estimated using a Cox proportional hazard model with adjustments for covariates. Setting: The Japan Multi-Institutional Collaborative Cohort Study. Participants: A total of 80 802 participants (34 555 males and 46 247 females), aged 35–69 years. Results: During a mean follow-up of 9·0 years, we identified 2482 deaths including 1495 cancer-related deaths. The intake of small fish was statistically significantly and inversely associated with the risk of all-cause and cancer mortality in females. The multivariable-adjusted HR (95 % CI) in females for all-cause mortality according to the intake were 0·68 (0·55, 0·85) for intakes 1–3 times/month, 0·72 (0·57, 0·90) for 1–2 times/week and 0·69 (0·54, 0·88) for ≥ 3 times/week, compared with the rare intake. The corresponding HR (95 % CI) in females for cancer mortality were 0·72 (0·54, 0·96), 0·71 (0·53, 0·96) and 0·64 (0·46, 0·89), respectively. No statistically significant association was observed in males. Conclusions: Intake of small fish may reduce the risk of all-cause and cancer mortality in Japanese females. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to examine whether dietary diversity is associated with cognitive impairment, including mild cognitive impairment (MCI), in community‐dwelling older Japanese adults. Methods: This cross‐sectional study was carried out in a general community setting. MCI and global cognitive impairment (GCI) were assessed using the Mini‐Mental State Examination and National Center for Geriatrics and Gerontology‐Functional Assessment Tool, which are multicomponent neurocognitive tests that include memory attention, executive function and processing speed. Dietary diversity was assessed using the diet variety score. The diet variety score assessed the 1‐week consumption frequency of 10 food groups, and either 0 or 1 point was allocated to each category based on the following responses: (i) "eat almost every day" (1 point); and (ii) "not eaten almost daily" (0 points). Older adults with a diet variety score of ≥3 points were defined as having high dietary diversity. Results: Data included 8987 older adults (mean age 73.9 ± 5.5 years; men 44.3%). The overall prevalences of MCI and GCI were 17.1% (n = 1538) and 8.4% (n = 753), respectively. The proportion of patients with a high dietary diversity was 69.9% (n = 6286). Multinomial logistic regression analysis revealed high dietary diversity was associated with MCI (OR 0.83, 95% CI 0.73–0.94) and GCI (OR 0.77, 95% CI 0.65–0.92) after adjusting for covariates. Conclusions: This study had a large sample size of older Japanese adults, and showed that high dietary diversity was associated with a lower proportion of MCI and GCI among older adults. Geriatr Gerontol Int 2024; 24: 75–81. [ABSTRACT FROM AUTHOR]

Objectives: Bladder cancer, especially non‐muscle invasive bladder cancer (NMIBC), is one of the most costly cancers owing to its long‐term management. Photodynamic diagnosis‐assisted transurethral resection of bladder tumor (PDD‐TURBT) reduces the risk of intravesical recurrence. However, its impact on healthcare economics in Japan remains unclear. We evaluated the comprehensive medical costs of Japanese healthcare economics regarding PDD‐TURBT. Methods: This large‐scale, multicenter, retrospective study included a dataset of 1531 patients who were diagnosed with primary NMIBC who underwent initial TURBT between April 2006 and June 2021. A one‐to‐one propensity‐score matching analysis was used for an unbiased comparison based on postTURBT follow‐up periods. The total medical costs, including hospitalization, surgical procedures for TURBT and salvage radical cystectomy, adjuvant intravesical therapies, and follow‐up examinations, were compared between white light (WL)‐TURBT and PDD‐TURBT groups. Results: After propensity‐score matching, 468 patients each of WL‐ and PDD‐TURBT groups were matched. Total costs were 510 337 128 and 514 659 328 ¥ in WL‐ and PDD‐TURBT groups, respectively. The costs of adjuvant intravesical therapies, follow‐up examinations, and salvage radical cystectomy in PDD‐TURBT group were equivalent to or lower than those in WL‐TURBT group. Furthermore, total costs of high‐ and highest‐risk NMIBC in PDD‐TURBT group were either equivalent or lower compared to those in WL‐TURBT group. Conclusions: The total costs associated with PDD‐TURBT were higher compared to WL‐TURBT, while there is the potential of PDD‐TURBT to reduce the burden on healthcare economics in limited cases. [ABSTRACT FROM AUTHOR]

Background: Care fragmentation, characterized by the uncoordinated involvement of multiple healthcare providers, leads to inefficient and ineffective healthcare, posing a significant challenge in managing patients with multimorbidity. In this context, "polydoctoring," where patients see multiple specialists, emerges as a crucial aspect of care fragmentation. This study seeks to develop an indicator to assess polydoctoring, which can subsequently enhance the management of multimorbidity. Methods: Baseline survey data from the Kawasaki Aging and Wellbeing Project (KAWP) involving independent community‐dwelling older adults aged 85–89 were utilized in this cross‐sectional study. Polydoctoring measure was defined as the number of regularly visited facilities (RVFs). The association of RVF with the Fragmentation of Care Index (FCI) and the outcome measures of polypharmacy and ambulatory care costs were examined as indicators of care fragmentation. Results: The analysis comprised 968 participants, with an average of 4.70 comorbid chronic conditions; 65.3% of the participants had two or more RVFs, indicating polydoctoring. A significant correlation between RVF and FCI was observed. Modified Poisson regression analyses revealed associations between higher RVF and increased prevalence ratio of polypharmacy. Likewise, a higher RVF was associated with higher outpatient medical costs. Conclusions: RVF was significantly correlated with FCI, polypharmacy, and higher outpatient medical costs. Unlike complex indices, RVF is simple and intuitively comprehensible. Further research is needed to evaluate the impact of care fragmentation on patient outcomes, considering factors such as RVF thresholds, patient multimorbidity, and social support. Understanding the influence of polydoctoring can enhance care quality and efficiency for patients with multimorbidity. [ABSTRACT FROM AUTHOR]

Wetland biodiversity is currently declining on a global scale. Wetland biodiversity understanding is critical for determining the wetlands' conservation value. In this study, Macroplea Samouelle, 1819 (Coleoptera: Chrysomelidae) was discovered in Aomori Prefecture, Honshu Island, Japan. Only two Macroplea species have been recorded in Japan, M. japana (Jacoby, 1885) and M. mutica (Fabricius, 1792). Macroplea japana had been unrecorded for 60 years before being rediscovered in Honshu Island in 2022, and a single adult M. mutica female was discovered in Hokkaido Prefecture in 2003. The discovered individuals were concluded to be M. mutica based on morphological and molecular analyses. Although morphological differences were observed with the Eurasian M. mutica individuals, the male genitalia was nearly identical to M. mutica. For the molecular phylogenetic analysis based on COI and 28S sequences, Macroplea individuals in Japan were clustered with M. mutica on the Eurasian Continent. This is the first record of this species on Honshu Island (and the second in Japan), as well as the first record of adult males. This species would require conservation policies and additional distributional surveys. [ABSTRACT FROM AUTHOR]

Objectives Schizophrenia is a mental illness that presents with thought disorders including delusions and disorganized speech. Thought disorders have been regarded as a consequence of the loosening of associations between semantic concepts since the term "schizophrenia" was first coined by Bleuler. However, a mechanistic account of this cardinal disturbance in terms of functional dysconnection has been lacking. To evaluate how aberrant semantic connections are expressed through brain activity, we characterized large-scale network structures of concept representations using functional magnetic resonance imaging (fMRI). Study Design We quantified various concept representations in patients' brains from fMRI activity evoked by movie scenes using encoding modeling. We then constructed semantic brain networks by evaluating the similarity of these semantic representations and conducted graph theory-based network analyses. Study Results Neurotypical networks had small-world properties similar to those of natural languages, suggesting small-worldness as a universal property in semantic knowledge networks. Conversely, small-worldness was significantly reduced in networks of schizophrenia patients and was correlated with psychological measures of delusions. Patients' semantic networks were partitioned into more distinct categories and had more random within-category structures than those of controls. Conclusions The differences in conceptual representations manifest altered semantic clustering and associative intrusions that underlie thought disorders. This is the first study to provide pathophysiological evidence for the loosening of associations as reflected in randomization of semantic networks in schizophrenia. Our method provides a promising approach for understanding the neural basis of altered or creative inner experiences of individuals with mental illness or exceptional abilities, respectively. [ABSTRACT FROM AUTHOR]

Aims: There are no previous studies focusing on collaborative follow‐ups between hospitals and clinics for patients discharged after acute heart failure (AHF) in Japan. The purpose of this study was to determine the status of collaboration between hospitals and clinics for patients with AHF in Japan and to compare patient characteristics and clinical outcomes using a large Japanese observational database. Methods and results: Of 4056 consecutive patients hospitalized for AHF in the Kyoto Congestive Heart Failure registry, we analysed 2862 patients discharged to go home, who were divided into 1674 patients (58.5%) followed up at hospitals with index hospitalization (hospital follow‐up group) and 1188 (41.5%) followed up in a collaborative fashion with clinics or other general hospitals (collaborative follow‐up group). The primary outcome was a composite of all‐cause death or heart failure (HF) hospitalization within 1 year after discharge. Previous hospitalization for HF and length of hospital stay longer than 15 days were associated with hospital follow‐up. Conversely, ≥80 years of age, hypertension, and cognitive dysfunction were associated with collaborative follow‐up. The cumulative 1‐year incidence of the primary outcome, all cause death, and cardiovascular death were similar between the hospital and collaborative follow‐up groups (31.6% vs. 29.6%, P = 0.51, 13.1% vs, 13.9%, P = 0.35, 8.4% vs. 8.2%, P = 0.96). Even after adjusting for confounders, the difference in risk for patients in the hospital follow‐up group relative to those in the collaborative follow‐up group remained insignificant for the primary outcome, all‐cause death, and cardiovascular death (HR: 1.11, 95% CI: 0.97–1.27, P = 0.14, HR: 1.10, 95% CI: 0.91–1.33, P = 0.33, HR: 0.96, 95% CI: 0.87–1.05, P = 0.33). The cumulative 1‐year incidence of HF hospitalization was higher in the hospital follow‐up group than in the collaborative follow‐up group (25.5% vs. 21.3%, P = 0.02). The risk of HF hospitalization was higher in the hospital follow‐up group than in the collaborative follow‐up group (HR: 1.19, 95% CI: 1.01–1.39, P = 0.04). Conclusions: In patients hospitalized for AHF, 41.5% received collaborative follow‐up after discharge. The risk of HF hospitalization was higher in the hospital follow‐up group than in the collaborative follow‐up, although risk of the primary outcome, all‐cause death, and cardiovascular death were similar between groups. [ABSTRACT FROM AUTHOR]

Background: Medical screening using ultrasonography (US) has been performed on young baseball players for early detection of osteochondritis dissecans (OCD) of the humeral capitellum. Deep learning (DL) and artificial intelligence (AI) techniques are widely adopted in the medical imaging research field. Purpose/Hypothesis: The purpose of this study was to calculate the diagnostic accuracy using DL for US images of OCD. We hypothesized that using DL for US imaging would improve the prediction accuracy of OCD. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: A total of 40 elbows (mean age of patients, 12.1 years) that were suspected of having OCD at a medical checkup and later confirmed by radiographs and magnetic resonance imaging were included in the study. The affected elbows were used as the OCD group and the contralateral elbows as the control group. From US videos, 100 images per elbow were captured from different angles, and 4000 images of the elbows were prepared for both groups. Of these, 80% were randomly selected by DL models and used as training data; the remaining were used as test data. Transfer learning was conducted using 3 pretrained DL models. The confusion matrix and the area under the receiver operating characteristic curve (AUC) were used to evaluate the model, and the visualization of the areas deemed important by the DL models was also performed. Furthermore, OCD regions were detected using an automatic image recognition model based on DL. Results: Classification of the OCD image by the DL model was performed; the best accuracy score was 0.87; the recall was 1.00. AUC was high for all DL models. Visualization of important features showed that AI predicted the presence of OCD by focusing on the irregularity or discontinuity of the surface of subchondral bone. In the detection of OCD task, the mean average precision was 0.83. Conclusion: The DL on US images identified OCD with high accuracy. The important features detected by the DL models correspond to the areas used by clinicians in screening the US images. The OCD was also detected with high accuracy using the object detection model. The AI model may be used in medical screening for OCD. [ABSTRACT FROM AUTHOR]

Background: In Japan there are limited opportunities for pediatricians to learn gastrointestinal (GI) endoscopy. This study investigated whether a short‐term intensive training for 2 weeks in an adult GI setting enabled pediatricians to acquire basic technical competence for pediatric GI endoscopic procedures. Methods: This was a retrospective case series of pediatricians who underwent 2 weeks of intensive endoscopy training at an adult endoscopy unit in a community hospital. The numbers of esophagogastroduodenoscopy (EGD) and ileocolonoscopy procedures each pediatrician performed were evaluated. All enrolled pediatricians were asked to answer questionnaires regarding the 2 week intensive GI endoscopy training program. Results: There were 17 enrolled pediatricians, of whom 13 were men; average age 32 years (range 27–54). The median (range) numbers of EGDs and ileocolonoscopies performed by each pediatrician during the 2‐week training period were 102 (66–144) and 14 (1–48), respectively. Fifteen out of 17 pediatricians experienced more than 100 GI endoscopies during the 2 weeks. All pediatricians performed biopsies as part of some EGD procedures. All 17 pediatricians found this program satisfactory. All pediatricians became cable of performing pediatric EGD (i.e., for children ≤15 years) after this training program. Sixteen pediatricians have continued to perform pediatric GI endoscopy since this training program. Conclusions: A short‐term intensive training program for 2 weeks in an adult GI setting enabled pediatricians to acquire basic technical competence for pediatric endoscopic procedures. [ABSTRACT FROM AUTHOR]

Background: The coronavirus disease 2019 (COVID-19) causes extensive coagulopathy and a potential benefit of anticoagulation therapy has been documented for prevention of thromboembolic events. Bleeding events has also been reported as a notable complication; whereas, the incidence, risks, and clinical impact of bleeding remain unclear. Method: The CLOT-COVID Study was a nationwide, retrospective, multicenter cohort study on consecutive hospitalized patients with COVID-19 in Japan between April 2021 and September 2021. In this sub-analysis, we compared the characteristics of patients with and without major bleeding; moreover, we examined the risk factors for and clinical impact of bleeding events. Results: Among 2882 patients with COVID-19, 57 (2.0%) had major bleeding. The incidence of major bleeding increased with COVID-19 severity as follows: 0.5%, 2.3%, and 12.3% in patients with mild, moderate, and severe COVID-19, respectively. COVID-19 severity, history of major bleeding, and anticoagulant type/dose were independently and additively associated with the bleeding incidence. Compared with patients without major bleeding, those with major bleeding exhibited a longer duration of hospitalization (9 [6–14] vs 28 [19–43] days, P < 0.001) and higher mortality during hospitalization (4.9% vs. 35.1%, P < 0.001). Conclusions: In the real-world clinical practice, the incidence of major bleeding was not uncommon, especially in patients with severe COVID-19. Independent risk factors for major bleeding included history of major bleeding, COVID-19 severity, and anticoagulant use, which could be associated with poor clinical outcomes including higher mortality. Precise recognition of the risks for bleeding may be helpful for an optimal use of anticoagulants and for better outcomes in patients with COVID-19. [ABSTRACT FROM AUTHOR]

Objective: This nationwide study aimed to reveal the prevalence of ankylosing spondylitis (AS), non-radiographic axial spondyloarthritis (nr-ax SpA), and the positivity rate of human leukocyte antigen (HLA) among such patients in Japan. Methods: The first survey was conducted in 2221 randomly selected facilities (26.3%) in September 2018, where the patients with AS/nr-ax SpA were taken care of from January to December 2017. We estimated the total number of these patients using response and extraction rates. A second survey was conducted in 117 facilities (49.8%) to assess for HLA-B27 positivity rate and clinical features. Results: The estimated total numbers of the patients with AS and nr-ax SpA were 3200 (95% confidence interval [CI]: 2400-3900) and 800 (530-1100), suggesting that the prevalence values of AS and nr-ax SpA in general population were 2.6/100,000 (0.0026%) and 0.6/100,000 (0.0006%), respectively. Although 55.5% (76/137) of patients with AS were HLA-B27-positive, those whose age of onset was estimated to be over 50 years tended to undergo less HLA-B27 testing. Conclusion: This study revealed the lower prevalence of AS/nr-ax SpA in Japan, compared to those in other countries. Further studies are required to reveal the association of HLA-B27 with the clinical features. [ABSTRACT FROM AUTHOR]

Background/objectives: Low-carbohydrate diets (LCD) are useful for weight reduction, and 50-55% carbohydrate consumption is associated with minimal risk. Genetic differences were related to nutritional consumption, food preferences, and dietary patterns, but whether particular genetic differences in individuals influence LCD adherence is unknown.Subjects/methods: We conducted a GWAS on adherence to LCD utilizing 14,076 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a previously validated semiquantitative food frequency questionnaire to estimate food consumption. Association of the imputed variants with the LCD score by Halton et al. we used linear regression analysis adjusting for sex, age, total dietary energy consumption, and components 1 to 10 by principal component analysis. We repeated the analysis with adjustment for alcohol consumption (g/day) in addition to the above-described variables.Results: Men and women combined analysis without adjustment for alcohol consumption; we found 395 variants on chromosome 12 associated with the LCD score having P values <5 × 10-8. A conditional analysis with the addition of the dosage data of rs671 on chromosome 12 as a covariate, P values for all 395 SNPs on chromosome 12 turned out to be insignificant. In the analysis with additional adjustment for alcohol consumption, we did not identify any SNPs associated with the LCD score.Conclusion: We found rs671 was inversely associated with adherence to LCD, but that was strongly confounded by alcohol consumption. [ABSTRACT FROM AUTHOR]

Purpose: The association between metabolic syndrome (MetS) and the risk of death from cancer is still a controversial issue. The purpose of this study was to examine the associations of MetS and metabolically unhealthy obesity (MUHO) with cancer mortality in a Japanese population. Methods: We used data from the Japan Multi-Institutional Collaborative Cohort Study. The study population consisted of 28,554 eligible subjects (14,103 men and 14,451 women) aged 35–69 years. MetS was diagnosed based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the Japan Society for the Study of Obesity (JASSO), using the body mass index instead of waist circumference. The Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for total cancer mortality in relation to MetS and its components. Additionally, the associations of obesity and the metabolic health status with cancer mortality were examined. Results: During an average 6.9-year follow-up, there were 192 deaths from cancer. The presence of MetS was significantly correlated with increased total cancer mortality when the JASSO criteria were used (HR = 1.51, 95% CI 1.04–2.21), but not when the NCEP-ATP III criteria were used (HR = 1.09, 95% CI 0.78–1.53). Metabolic risk factors, elevated fasting blood glucose, and MUHO were positively associated with cancer mortality (P <0.05). Conclusion: MetS diagnosed using the JASSO criteria and MUHO were associated with an increased risk of total cancer mortality in the Japanese population. [ABSTRACT FROM AUTHOR]

Background: Small bowel adenocarcinomas (SBAs) are rare and there is little comprehensive data on SBA genomic alterations for Asian patients. This study aimed to profile genomic alterations of SBA in Japanese patients using targeted next-generation sequencing (NGS).Methods: We examined 22 surgical resections from patients with primary SBA. SBA genomic alterations were analyzed by NGS. Mismatch repair (MMR) status was determined by immunohistochemical analysis. Mucin phenotypes were classified as gastric (G), intestinal (I), gastrointestinal (GI), and null (N) types on MUC2, MUC5AC, MUC6, and CD10 immunostaining.Results: The most common genomic alterations found in SBA tumors were TP53 (n = 16), followed by KRAS (n = 6), APC (n = 5), PIK3CA (n = 4), CTNNB1 (n = 3), KIT (n = 2), BRAF (n = 2), CDKN2A (n = 2), and PTEN (n = 2). Deficient MMR tumors were observed in 6 out of 22 patients. Tumor mucin phenotypes included 2 in G-type, 12 in I-type, 3 in GI-type, and 5 in N-type. APC and CTNNB1 mutations were not found in G-type and GI-type tumors. KRAS mutations were found in all tumor types except for G-type tumors. TP53 mutations were found in all tumor types. Although no single gene mutation was associated with overall survival (OS), we found that KRAS mutations were associated with significant worse OS in patients with proficient MMR tumors.Conclusions: SBA genomic alterations in Japanese patients do not differ significantly from those reports in Western countries. Tumor localization, mucin phenotype, and MMR status all appear to impact SBA gene mutations. [ABSTRACT FROM AUTHOR]

Purpose: Cerebral hyperperfusion syndrome (CHS) is a critical complication after carotid artery stenting (CAS). However, few CAS studies have evaluated immediate and temporary changes in ipsilateral cerebral blood flow (CBF) quantitatively. The study was performed to evaluate immediate changes in CBF after CAS and subsequent CBF changes in patients with cerebral hyperperfusion (HP) using 123I-IMP SPECT. Methods: The subjects were 223 patients with chronic extracranial carotid artery stenosis who underwent CAS in our department between March 2010 and March 2020. Quantitative CBF and cerebrovascular reactivity to acetazolamide in the middle cerebral artery were assessed before CAS by 123I-IMP SPECT. CBF was also measured immediately after CAS by 123I-IMP SPECT. When HP was detected, CBF was measured again 3 and 7 days after CAS. Results: The median (interquartile range) ipsilateral quantitative CBF change after CAS was − 0.1% (− 9.5–8.2%), and the upper value of the 95% CI of the quantitative CBF change was 48.2%. Thus, we defined HP after CAS as an increase in quantitative CBF of > 48.2% compared with the preoperative value. Of 223 patients, 5 (2.2%) had HP, and 4 of these patients (80%) developed CHS. In the CHS patients, HP was maintained for about 3 days and improved after about 7 days. Conclusion: An immediate CBF increase of > 48.2% after CAS may lead to development of CHS. In CHS after CAS, HP persisted for about 1 week and postoperative management may be required for at least 1 week. [ABSTRACT FROM AUTHOR]

Background: Advanced glycation end products (AGEs) are end products of protein glycation that bind to the receptor for AGEs (RAGE) and activate nicotinamide adenine dinucleotide phosphate oxidase (NOX), resulting in increased oxidative stress and rotator cuff fragility. Stump classification using the signal intensity ratio of the tendon rupture site to the deltoid muscle in the coronal view of T2-weighted fat-suppressed magnetic resonance imaging (MRI) scans is an indicator of clinical outcomes after rotator cuff repair surgery. Comparing the signal intensities of the deltoid (D) and rotator cuff tears (C), Ishitani et al. classified C/D <0.8 as type 1, 0.8 to 1.3 as type 2, and >1.3 as type 3. Hypothesis/Purpose: It was hypothesized that the oxidative stress and collagen degeneration that occur in the rotator cuff due to accumulation of AGEs can be assessed on MRI scans (stump classification). Therefore, this study aimed to compare AGE-related factors in the rotator cuff tear site tissues based on stump classification. Study Design: Descriptive laboratory study. Methods: The authors included 30 patients (11 with type 1, 9 with type 2, and 10 with type 3; mean age, 62.3 years) who underwent surgery for complete rotator cuff tears at our hospital. Tendon tissue was harvested from the torn rotator cuff site during surgery for tissue and cell evaluation. Results: There was no significant difference in the mean age according to stump classification. The number of patients with diabetes was significantly larger in type 3 than in the other types (P <.05). Tissue evaluation showed significantly higher expression of AGE and RAGE staining in type 3 than in the other types (~6.7-fold; P <.01). Cell evaluation showed that the expression rates of reactive oxygen species and apoptosis were significantly higher in type 3 than in the other types (~4.3-fold; P <.01). Gene expression by real-time polymerase chain reaction showed significantly higher RAGE (~5.1-fold), NOX (~5.3-fold), and IL (~3.0-fold) in type 3 than in the other types (P <.05). Conclusion: Stump classification type 3 exhibited the highest accumulation of AGEs and the highest oxidative stress and apoptosis, suggesting a high degree of degeneration and inflammation. Imaging based on stump classification reflects the degeneration and fragility of the torn rotator cuff site. Clinical Relevance: This study provides evidence of a relationship between stump classification, which reflects rotator cuff fragility on MRI, and pathologies related to advanced glycation end products. [ABSTRACT FROM AUTHOR]

Background: The survival rate of chronic dialysis patients in Japan remains the highest worldwide, so there is value in presenting Japan's situation internationally. We examined whether aggregate figures on dialysis patients in the National Database of Health Insurance Claims and Special Health Checkups of Japan (NDB), which contains data on insured procedures of approximately 100 million Japanese residents, complement corresponding figures in the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR). Methods: Subjects were patients with medical fee points for dialysis recorded in the NDB during 2014–2018. We analyzed annual numbers of dialysis cases, newly initiated dialysis cases– and deaths. Results: Compared with the JRDR, the NDB had about 6–7% fewer dialysis cases but a similar number of newly initiated dialysis cases. In the NDB, the number of deaths was about 6–10% lower, and the number of hemodialysis cases was lower, while that of peritoneal dialysis cases was higher. The cumulative survival rate at dialysis initiation was approximately 6 percentage points lower in the NDB than in the JRDR, indicating that some patients die at dialysis initiation. Cumulative survival rate by age group was roughly the same between the NDB and JRDR in both sexes. Conclusion: The use of the NDB enabled us to aggregate data of dialysis patients. With the definition of dialysis patients used in this study, analyses of concomitant medications, comorbidities, surgeries, and therapies will become possible, which will be useful in many future studies. [ABSTRACT FROM AUTHOR]

The spatial genetic structures of insects are reflected in their habitats. Coastal insects tend to have less genetic differentiation than subterranean insects. However, the general pattern of population structure of coastal species residing in subterranean habitats is unknown. Thalassoduvalius masidai (Coleoptera: Carabidae: Trechinae), endemic to Japan, is a coastal and subterranean beetle. Here, we hypothesized that T. masidai populations disperse among regions by ocean currents, floods and tsunamis, despite their habitat being underground. To test this hypothesis, we performed a phylogeographical analysis of T. masidai using single nucleotide polymorphism data from multiplexed inter-simple sequence repeat genotyping by sequencing (MIG-seq) and the mitochondrial COI gene. The phylogenetic network and tree and STRUCTURE analyses indicated that T. masidai populations were divided into three groups: the western Seto Inland Sea–Izu Peninsula coasts, the eastern Seto Inland Sea–Kii Peninsula coasts and the Japan Sea coasts. The genetic diversity of T. masidai was higher in sites with lower longitude and latitude. These results suggest that T. masidai migrated and dispersed from the south-western area of Japan by ocean currents, despite its underground habitat. The genetic analysis data from the present study would also be helpful for the conservation and taxonomic revision of this species. [ABSTRACT FROM AUTHOR]

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1–3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake. [ABSTRACT FROM AUTHOR]

Background: We determined the prevalence of current cigarette smokers and alcohol drinkers among cancer survivors and subjects with no history of cancer in Japan and compared the findings with nationally representative studies in other countries. Methods: We conducted a cross-sectional study of baseline data from a prospective cohort study. A self-administered questionnaire was surveyed during 2013-2015 with residents aged =20 years attending a community-based cardiometabolic screening program in Miyagi prefecture in north-eastern Japan. Subjects with past cancer histories were classified as cancer survivors. Sex-specific, age-standardized prevalence of current smokers, and drinkers were calculated. Age-adjusted prevalence ratios (PRs: the cancer survivors' rate divided by the rate of subjects with no history of cancer) and 95% confidence intervals (CIs) were estimated with log-binomial regressions. Results: 36,786 subjects, including 2760 cancer survivors, responded and provided usable information (58.9% of recruited subjects). For men, the age-standardized prevalence of current smokers and drinkers among survivors was 18.8% and 74.4%, respectively, with an age-adjusted PR (95%CI) of 0.76 (0.66-0.86, p < 0.001) and 0.95 (0.91-0.98, p = 0.002), respectively. For women, the figures were 6.1%, 37.9%, 0.84 (0.67-1.06, p = 0.138) and 0.96 (0.90-1.03, p = 0.313), respectively. The U.S., the U.K, and Australian studies generally showed no substantially lower prevalence of current smokers or drinkers in survivors than in subjects with no history of cancer (PR = 0.75), while Korean studies did (PR < 0.75). Conclusions: A considerable proportion of Japanese cancer survivors, especially men, remained currently smoking and drinking. Consistent with Western studies, the rates were not substantially lower than those among subjects with no history of cancer. [ABSTRACT FROM AUTHOR]

Objectives PsA is characterized by enthesitis, synovitis and osseous involvement in the peripheral and axial joints. Few studies have examined axial involvement in PsA using imaging techniques. Here we examined axial involvement in PsA patients using MRI. In addition, we determined the efficacy of 24 week adalimumab treatment in improving the MRI findings of spondylitis and sacroiliitis. Methods This was a prospective, open-label, single-arm study in patients with PsA. Adalimumab was administered to patients for a total of 24 weeks. MRI examinations were conducted at baseline and at week 24 of adalimumab treatment. Results Thirty-seven patients with PsA were included in this study. Spondylitis was observed in at least one site of the positive scan in 91% (n  = 31) of patients with PsA. The number of arthritic sites in the cervical, thoracic and lumbar regions of the spine was 48, 67 and 53, respectively. All patients had MRI-determined sacroiliitis of grade ≥1 severity while 28 patients (82%) had grade ≥2 sacroiliitis in at least one sacroiliac region. Sacroiliac arthritis was statistically more severe on the right side than on the left side (P  < 0.05). In 34 patients with PsA, the thoracic spine was the most common site of spondylitis. In addition, 24 week adalimumab treatment led to an improvement in the mean number of spondylitis sites and the mean grade of sacroiliitis. Conclusion Treatment with adalimumab for 24 weeks resulted in improvement in spondylitis and sacroiliitis. [ABSTRACT FROM AUTHOR]

Kusatsu-Shirane volcano is one of the active volcanoes in Japan. Phreatic explosions occurred in Mt. Shirane in 1983 and most recently, in 2018, in Mt. Motoshirane. Information on the subsurface structure is crucial for understanding the activity of volcanoes with well-developed hydrothermal systems where phreatic eruptions occur. Here, we report aeromagnetic surveys conducted at low altitudes using an unmanned helicopter. The survey aimed to obtain magnetic data at a high spatial resolution to map the magnetic anomaly and infer the magnetization intensity distribution in the region immediately after the 2018 Mt. Motoshirane eruption. The helicopter used in the survey was YAMAHA FAZER R G2, an autonomously driven model which can fly along a precisely programmed course. The flight height above the ground and a measurement line spacing were set to ~ 150 m and ~ 100 m, respectively, and the total flight distance was 191 km. The measured geomagnetic total intensity was found to vary by ~ 1000 nT peak-to-peak. The estimated magnetization intensity derived from measured data showed a 100 m thick magnetized surface layer with normal polarity, composed of volcanic deposits of recent activities. Underneath, a reverse-polarity magnetization was found, probably corresponding to the Takai lava flow in the Early Quaternary period (~ 1 Ma) mapped in the region. Our results demonstrate the cost-effectiveness and accuracy of using drone magnetometers for mapping the rugged terrain of volcanoes. [ABSTRACT FROM AUTHOR]

Background/objectives: Individual eating habits may be influenced by genetic factors, in addition to environmental factors. Previous studies suggested that adherence to Japanese food patterns was associated with a decreased risk of all-cause and cardiovascular disease mortality. We conducted a genome-wide association study (GWAS) in a Japanese population to find genetic variations that affect adherence to a Japanese food pattern.Subjects/methods: We analyzed GWAS data using 14,079 participants from the Japan Multi-Institutional Collaborative Cohort study. We made a Japanese food score based on six food groups. Association of the imputed variants with the Japanese food score was performed by linear regression analysis with adjustments for age, sex, total energy intake, alcohol intake (g/day), and principal components 1-10 omitting variants in the major histocompatibility region.Results: We found one SNP in the 14q11.2 locus that was significantly associated with the Japanese food score with P values <5 × 10-8. Functional annotation revealed that the expression levels of two genes (BCL2L2, SLC22A17) were significantly inversely associated with this SNP. These genes are known to be related to olfaction and obesity.Conclusion: We found a new SNP that was associated with the Japanese food score in a Japanese population. This SNP is inversely associated with genes link to olfaction and obesity. [ABSTRACT FROM AUTHOR]

SASH1 has been reported as a causal gene of lentiginous phenotypes with and without heredity, including an autosomal dominant type characterized by lentigines predominantly on sun‐exposed areas such as the face and limbs. Recently, cases of dyschromatosis with SASH1 mutations have been reported worldwide; however, only one case has been reported from Japan. Here, we analyzed six Japanese patients who characteristically showed many lentigines on sun‐exposed areas, using next‐generation sequencing. We identified five novel heterozygous mutations in SASH1 (p.I586M, p.S531Y, p.R644W, p.T525R, and p.S516I) in our patients and their families. The p.R644W substitution identified in two unrelated families was the first mutation located in the sterile alpha motif 1 (SAM1) domain. The degree and location of the lentigines were variable across individuals, even if they shared the same SASH1 mutation. All mutations were predicted to be deleterious by six different algorithms used to evaluate the functional impact of a variation. In addition, immunohistopathological findings and RNA sequencing results suggested that SASH1 mutations were associated with an increase in the number of melanocytes, acceleration of melanogenesis, and upregulated hair keratin expression. [ABSTRACT FROM AUTHOR]

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P <5×10−8), and eight variants on three chromosomes (chromosomes 12, 14, 15) had genome-wide suggestive levels of significance (P <1×10−6). With an independent data set from the J-MICC Shizuoka Study (n = 2,447), the association of the SGMS2 SNP with blood PSA levels was not replicated. Although our GWAS failed to detect novel loci associated with serum PSA levels in the Japanese cohort, it confirmed the significant effects of previously reported genetic loci on PSA levels in Japanese. Importantly, our results confirmed the significance of KLK3 SNPs also in Japanese, implying that consideration of individual genetic information in prostate cancer diagnosis may be possible in the future. [ABSTRACT FROM AUTHOR]

Objective: Although eating disorders (EDs) surged in the late 1900s and are now recognized worldwide, the time trend of ED characteristics remains unknown. This study aimed to clarify changes in characteristics of anorexia nervosa restricting type (AN‐R) over 30 years. Methods: We conducted a cross‐sectional study and examined 996 female treatment‐seeking patients with AN‐R in Japan from 1988 to 2018. Demographics, body mass index (BMI), and Eating Disorder Inventory scores were compared among three groups in accordance with the time of initial consultation: Group 1 (1988–1998), Group 2 (1998–2008), Group 3 (2008–2018). Results: The mean BMI at the initial consultation significantly decreased by 0.6 kg/m2 (from 14.0 kg/m2 in Group 1 to 13.4 kg/m2 in Group 3). Groups 2 and 3 scored significantly higher in drive for thinness, interpersonal distrust, and interoceptive awareness than those in Group 1. The range of onset age is wider and the number of late‐onset AN‐R with prolonged delay in treatment has increased over time. Discussion: This study shows that AN‐R has increased in physical and psychopathological severity over the past 30 years in Japan. Interdisciplinary research is needed to clarify the relationship between AN‐R and time trend. [ABSTRACT FROM AUTHOR]

Objectives: To assess the clinicopathologic features of Multicentric Castleman disease (MCD) patients in Japan. Methods: We assessed baseline data for 342 Japanese MCD patients with a biopsy-proven diagnosis, enrolled in a prospective, observational study for tocilizumab treatment. Results: Of 342 patients, 86.0% had plasma-cell type. None had a family history of MCD. Median disease duration of MCD was 3.7 years. Mean body weight and body mass index tended to be lower than those in the general Japanese population. The most common clinical presentations besides lymphadenopathy included fatigue (61.7%), pulmonary involvement (42.7%), and splenomegaly (41.8%). Secondary amyloidosis was reported in 34 patients (9.9%). Laboratory abnormalities included decreased hemoglobin and albumin, and increased acute-phase proteins, serum immunoglobulins, and interleukin-6 (IL-6). IL-6 levels among the MCD patients tested in this study were correlated with levels of albumin, hemoglobin, triglyceride, total cholesterol, C-reactive protein, fibrinogen and immunoglobulin G (Spearman's correlation coefficient, |r| =0.28-0.59). Conclusion: The clinical features and laboratory abnormalities are similar to those previously reported in other countries, besides higher rates of pulmonary involvement, secondary amyloidosis, and ECG abnormalities. Our results imply that IL-6 is involved in MCD pathogenesis. These findings would be informative for diagnosis and appropriate treatment for MCD. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of chest CT to differentiate coronavirus disease 2019 (COVID-19) pneumonia in non-high-epidemic area in Japan.Materials and Methods: This retrospective study included 21 patients clinically suspected COVID-19 pneumonia and underwent chest CT more than 3 days after the symptom onset: six patients confirmed COVID-19 pneumonia by real-time reverse-transcription polymerase chain reaction (RT-PCR) and 15 patients proved uninfected. Using a Likert scale and its receiver operating characteristic curve analysis, two radiologists (R1/R2) evaluated the diagnostic performance of the five CT criteria: (1) ground glass opacity (GGO)-predominant lesions, (2) GGO- and peripheral-predominant lesions, (3) bilateral GGO-predominant lesions; (4) bilateral GGO- and peripheral-predominant lesions, and (5) bilateral GGO- and peripheral-predominant lesions without nodules, airway abnormalities, pleural effusion, and mediastinal lymphadenopathy.Results: All patients confirmed COVID-19 pneumonia had bilateral GGO- and peripheral-predominant lesions without airway abnormalities, mediastinal lymphadenopathy, and pleural effusion. The five CT criteria showed moderate to excellent diagnostic performance with area under the curves (AUCs) ranging 0.77-0.88 for R1 and 0.78-0.92 for R2. The criterion (e) showed the highest AUC.Conclusion: Chest CT would play a supplemental role to differentiate COVID-19 pneumonia from other respiratory diseases presenting with similar symptoms in a clinical setting. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy and safety of adalimumab in psoriatic arthritis (PsA) patients in Japan. Methods: In this open-label, single-arm study conducted at six sites from October 2014 to June 2016 (UMIN000016543), PsA patients (≤20 years old) with inadequate response to nonsteroidal anti-inflammatory drugs received adalimumab subcutaneously (80mg initially, then 40mg every other week; 24 weeks total). Primary endpoint was American College of Rheumatology 20% improvement (ACR20) response rate at week 12. Results: Of 42 enrolled patients, 37 were treated (mean (SD) age, 56.2 (13.0) years; male, 27 (73.0%)). ACR20, ACR50, and ACR70 response rates were 40.5%, 24.3%, and 16.2% at week 12 and increased to 45.9%, 37.8%, and 21.6% at week 24, respectively. Psoriasis Area and Severity Index (PASI) 50 response rates were unchanged at weeks 12 and 24 (73%), but PASI75 and PASI90 increased from 40.5% and 21.6% to 59.5% and 40.5%, respectively. Other indices such as Physician's Global Assessment score, C- reactive protein-based disease activity score in 28 joints, Bath Ankylosing Spondylitis Disease Activity Index, and serum biomarker levels were significantly improved. No unexpected adverse events were reported. Conclusion: Similar to the global population, adalimumab was efficacious and well tolerated in Japanese treatment-experienced PsA patients. [ABSTRACT FROM AUTHOR]

Aim: Gingyogedokusan (GGGS) is a herbal medicine approved for upper respiratory infections in Japan, and could be utilized for the treatment of influenza. We conducted a multi‐center, prospective trial, comparing GGGS against oseltamivir in patients with influenza, but failed to include enough participants for conventional analysis. We further conducted a Bayesian analysis, however, using the Markov chain Monte Carlo (MCMC) method, by utilizing our original data. Methods: We used our data from 2010 and 2011, which compared GGGS and oseltamivir. A total of 10 patients were diagnosed with influenza and enrolled in the study (six for GGGS and four for oseltamivir). We conducted MCMC to elucidate posterior distributions for outcomes. Outcomes were time to alleviation of symptoms, time to recovery of activity level, time to recovery of health status, and time to resolution of fever. Results: Calculated mean time to alleviate symptoms was 3.99 days for GGGS, while it was 5.66 days in the oseltamivir group (difference of 1.66 days, 95% credible interval: −3.64 to 6.46). The posterior probability of the mean time for the oseltamivir group being longer than that for the GGGS group was 69%. Likewise, that probability was 81% for recovery of activity level, 86% for health status, and 24%, for fever resolution. Conclusion: According to Bayesian analysis, GGGS appears to have superiority over oseltamivir in resolving symptoms, although fever may resolve earlier with oseltamivir use. This is a proof of concept study, to encourage further research into the efficacy of GGGS for the treatment of influenza. [ABSTRACT FROM AUTHOR]

Background: The Japanese government has established a law encouraging early detection and treatment of developmental disorders in children. Child behavior problems (CBP) tend to be recognized at school as a result of developmental disorders. The aim of this study was to identify factors associated with CBP in Japan. We hypothesized that factors other than developmental disorders are important in explaining CBP. Methods: The study was conducted between February and March 2015. Parents of 3,515 children aged 2–5 years attending one of 34 public nursery schools in Takamatsu, Kagawa, Japan received self‐administered questionnaires addressing parental socioeconomic factors, mental health, parenting style (i.e. hostile, overreactive, or lax), developmental disorders in children, and CBP. A multiple regression analysis was applied to explore associations between CBP and possible factors. Results: Overall, 1,410 mothers were eligible to participate in the study. Children diagnosed with developmental disorders accounted for 7.8% of the sample, while on the Eyberg Child Behavior Inventory 17% of children had behavior problems needing clinical intervention. After adjustment for confounding factors, as well as for the diagnosis of developmental disorders, poor mental status and all three dysfunctional parenting styles had strong associations with CBP, and hostile, overreactive, and lax parenting had standardized β‐values (β) of 0.29, 0.28, and 0.15, respectively (P < 0.01). A problematic relationship between the parents was also significantly associated with CBP (β = −0.29, P < 0.01). Conclusion: When CBP are identified, parenting skills, mental health status and parental relationships should be considered along with the possibility of developmental disorders in the development of interventions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of the interleukin-6 receptor antibody tocilizumab in patients with Takayasu arteritis (TAK).Methods: Patients with TAK who had relapsed within the previous 12 weeks were induced into remission with oral glucocorticoid therapy. In this double-blind, placebo-controlled trial, patients were randomly assigned 1:1 to receive weekly tocilizumab 162 mg or placebo subcutaneously, and oral glucocorticoids were tapered 10 %/week from week 4 to a minimum of 0.1 mg/kg/day until 19 patients relapsed. The primary endpoint was time to relapse of TAK, defined as ≥2 of the following: objective systemic symptoms, subjective systemic symptoms, elevated inflammation markers, vascular signs and symptoms or ischaemic symptoms.Results: The intent-to-treat and safety populations included 18 tocilizumab-treated and 18 placebo-treated patients. The per-protocol set (PPS) included 16 tocilizumab-treated and 17 placebo-treated patients. HRs for time to relapse of TAK were 0.41 (95.41% CI 0.15 to 1.10; p=0.0596) in the intent-to-treat population (primary endpoint) based on relapse in eight tocilizumab-treated and 11 placebo-treated patients and 0.34 (95.41% CI 0.11 to 1.00; p=0.0345) in the PPS. The secondary endpoints, time to relapse assessed by Kerr's definition and clinical symptoms only, were consistent with the primary endpoint. Serious adverse events were reported in one tocilizumab-treated and two placebo-treated patients. There were no serious infections and no deaths.Conclusion: Although the primary endpoint was not met, the results suggest favour for tocilizumab over placebo for time to relapse of TAK without new safety concerns. Further investigation is warranted to confirm the efficacy of tocilizumab in patients with refractory TAK.Trial Registration Number: JapicCTI-142616. [ABSTRACT FROM AUTHOR]

We report the discovery of the deep-sea fungus, Alisea longicolla on a wood log artificially immersed at 495 m depths in deep sea, off the Nansei Islands, Japan. Three different species of wood logs, whale bones and coconuts were deployed at approximate depths of 250, 500, 1000, 2000, 3000 and 5000 m. Densely colonised A. longicolla was found on the Ubame oak (Quercus phillyraeoides) wood log from the 500 m deployment site, which was collected 1302 d (about 3 y and 7 mo) after the deployment. Alisea longicolla was originally described as a new genus of deep-sea ascomycete within the family Halosphaeriaceae, associated with sunken wood collected in 630–791 m water depths off the Vanuatu Islands. Our results provide further evidence to support that A. longicolla may be an endemic deep-sea fungus, and it grows slowly but is active and reproductive in deep-sea environments. The occurrence of obligate deep-sea fungi appears to be very rare in the environments and few data is available. Further investigation on A. longicolla will extend our understanding of the ecology, physiology and evolution of deep-sea fungi. • Alisea longicolla was found on a wood log artificially immersed in deep sea (495 m). • Alisea longicolla is active and reproductive in deep-sea environments. • This fungus may be widely distributed in the tropical to subtropical South Pacific Ocean. [ABSTRACT FROM AUTHOR]

Post-thrombotic syndrome (PTS) is the most common chronic complication of deep vein thrombosis (DVT). Identifying high-risk patients for the development of PTS might be useful for its prevention. The COMMAND VTE Registry is a multicenter registry that enrolled 3027 consecutive patients with acute symptomatic venous thromboembolisms (VTEs) in Japan between January 2010 and August 2014. The current study population consisted of 1298 patients with lower extremities DVTs who completed 3-year follow-up for those who developed PTS and those without PTS. We investigated risk factors for the development of PTS at the time of DVT diagnosis, using a multivariable logistic regression analysis. Of the entire 1298 study patients, 169 (13%) patients were diagnosed with PTS within 3 years. The rate for anticoagulation discontinuation during follow-up was not significantly different between those with and without PTS. Chronic kidney disease (OR 2.21, 95% CI 1.45–3.39, P < 0.001), leg swelling (OR 4.15, 95% CI 2.25–7.66, P < 0.001), absence of transient risk factors for VTEs (OR 2.39, 95% CI 1.55–3.67, P < 0.001), active cancer (OR 3.66, 95% CI 2.30–5.84, P < 0.001), and thrombophilia (OR 2.07, 95% CI 1.06–4.04, P = 0.03) were independent risk factors for the development of PTS. In this real-world Japanese DVT registry, we could identify several important risk factors for the development of PTS at the time of DVT diagnosis. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between depressive symptoms and plasma amino acid related metaboli in older adults. Methods: A total of 152 older adults aged ≥65 years, residing in Niigata, Japan, were used for analysis. We evaluated depressive symptoms using the Geriatric Depression Scale‐15, which has been validated in older community‐dwelling individuals, and used a cut off score of ≥5 to classify participants as having depressive symptoms. We used high‐performance liquid chromatography‐electrospray ionization mass spectrometry to measure the concentrations of plasma amino acid‐related metabolites, and carried out logistic regression analysis to assess the association between depressive symptoms and plasma amino acid‐related metabolites. Results: Of the 119 older adults (mean age 76.3 years) included in the analysis, 22 were classified as having depressive symptoms (depressive group). There were no significant differences in physical and cognitive impairments between participants in the depressive and non‐depressive groups. The plasma α‐aminobutyric acid (AABA) level was significantly lower in the depressive group than in the non‐depressive group (P < 0.001). Logistic regression analysis showed the best‐fit model, which included AABA, leucine, threonine, hydroxyl proline and histidine levels (area under the receiver operating characteristic curve 0.8346; 95% confidence interval 0.7365–0.9326). In particular, the plasma AABA level was strongly associated with depressive symptoms. Conclusions: Plasma AABA level is significantly associated with depression symptoms in older community‐dwelling adults in Japan. Thus, plasma AABA might serve as a potential marker of depression in older adults aged ≥65 years. Geriatr Gerontol Int 2019; 19: 254–258. [ABSTRACT FROM AUTHOR]

Background: It is important to screen for alcohol consumption and drinking customs in a standardized manner. The aim of this study was 1) to investigate whether the AUDIT score is useful for predicting hazardous drinking using optimal cutoff scores and 2) to use multivariate analysis to evaluate whether the AUDIT score was more useful than pre-existing laboratory tests for predicting hazardous drinking.Methods: A cross-sectional study using the Alcohol Use Disorders Identification Test (AUDIT) was conducted in 334 outpatients who consulted our internal medicine department. The patients completed self-reported questionnaires and underwent a diagnostic interview, physical examination, and laboratory testing.Results: Forty (23 %) male patients reported daily alcohol consumption ≥ 40 g, and 16 (10 %) female patients reported consumption ≥ 20 g. The optimal cutoff values of hazardous drinking were calculated using a 10-fold cross validation, resulting in an optimal AUDIT score cutoff of 8.2, with a sensitivity of 95.5 %, specificity of 87.0 %, false positive rate of 13.0 %, false negative rate of 4.5 %, and area under the receiver operating characteristic curve of 0.97. Multivariate analysis revealed that the most popular short version of the AUDIT consisting solely of its three consumption items (AUDIT-C) and patient sex were significantly associated with hazardous drinking. The aspartate transaminase (AST)/alanine transaminase (ALT) ratio and mean corpuscular volume (MCV) were weakly significant.Conclusions: This study showed that the AUDIT score and particularly the AUDIT-C score were more useful than the AST/ALT ratio and MCV for predicting hazardous drinking. [ABSTRACT FROM AUTHOR]

Objectives: To determine the tentative diagnostic criteria and disease severity classification for Castleman disease (CD) and describe the clinical and pathologic features among human herpesvirus 8 (HHV-8) negative idiopathic multicentric CD (iMCD) in the Japanese population. Methods: We established the working groups for the research of CD in Japan and had meetings to discuss and define the tentative diagnostic criteria and disease severity classification for CD. We subsequently analyzed 142 patients classified into iMCD by using the nationwide Japanese patient registry. Results: We proposed the preliminary diagnostic criteria and disease severity classification for CD based on our discussion. In addition, we made a proposal for the disease activity score. We identified clinical and pathological features of patients with iMCD diagnosed by these diagnostic criteria. In the disease severity classification, 37, 33 and 30% patients were categorized into mild, moderate and severe diseases, respectively. Conclusion: This is the first proposal for diagnosis and classification of CD by the Japanese group. Further studies are required to validate whether they can distinguish CD from other inflammatory diseases and to determine their sensitivity and specificity. [ABSTRACT FROM AUTHOR]

This paper addresses the issue of Japanese e-government benefits evaluation and stresses the need to develop a new measurement tool to evaluate e-government services from the perspective of the Japanese citizen and government service provider. While research has used SERVQUAL, SERVPERF and Importance-Performance Analysis (IPA) as evaluation tools to measure quality of services, most of these tools are developed to evaluate quality of services from the perspective of the user (citizen) or service provider. In this paper, we propose a new evaluation tool, namely Satisfaction-Satisfaction Matrix (SSM), to gauge both the perceptions of the citizen and service provider concerning the performance of egovernment services. The matrix not only acts as a useful tool to identify satisfaction responses, but also serves as a strategic decision making aid in the allocation of resources for improving e-government services. [ABSTRACT FROM AUTHOR]

The present study was undertaken to construct an algorithm for an advanced automatic collision notification system based on national traffic accident data compiled by Japanese police. While US research into the development of a serious-injury prediction algorithm is based on a logistic regression algorithm using the National Automotive Sampling System/Crashworthiness Data System, the present injury prediction algorithm was based on comprehensive police data covering all accidents that occurred across Japan. The particular focus of this research is to improve the rescue of injured vehicle occupants in traffic accidents, and the present algorithm assumes the use of an onboard event data recorder data from which risk factors such as pseudo delta-V, vehicle impact location, seatbelt wearing or non-wearing, involvement in a single impact or multiple impact crash and the occupant’s age can be derived. As a result, a simple and handy algorithm suited for onboard vehicle installation was constructed from a sample of half of the available police data. The other half of the police data was applied to the validation testing of this new algorithm using receiver operating characteristic analysis. An additional validation was conducted using in-depth investigation of accident injuries in collaboration with prospective host emergency care institutes. The validated algorithm, named the TOYOTA-Nihon University algorithm, proved to be as useful as the US URGENCY and other existing algorithms. Furthermore, an under-triage control analysis found that the present algorithm could achieve an under-triage rate of less than 10% by setting a threshold of 8.3%. [ABSTRACT FROM AUTHOR]

The high spatiotemporal heterogeneity makes it difficult to ensure the representation of samples in estuarine studies. Using Japanese eels as natural samplers (n = 881), we revealed the spatial heterogeneity of energy flow among three successive estuarine segments (upper, middle, and lower estuaries) of the Hamana Lake−Miyakoda River system on the Pacific side of central Honshu, Japan. In the upper estuary which serves as the nursery ground for eels, the predominant small eels (body weight <30 g) fed mainly on polychaetes (58.8% IRI [index of relative importance]), mainly Hediste atoka. This polychaete species depends on the detritus food chain driven by terrestrial inputs, and the detritus food chain appears to be predominant in the upper estuary. However, large eels (body weight >150 g) fed directly on terrestrial subsidies in the form of fallen insects (49.0% IRI) and earthworms (20.2% IRI), indicating that the detritus food chain does not directly affect the diet of large eels. Terrestrial subsidies in the form of living organisms do not contribute to the diet of eels in the adjacent middle estuary, which is the main growth habitat for eels within an estuary. However, small eels depend on terrestrial subsidies by feeding on oysters (71.6% IRI), which assimilate terrestrial particulate organic matter. The predominant medium eels were highly dependent on the high diversity and biomass of prey groups, as indicated by the high % IRI values of several groups, such as infaunal bivalves (31.7% IRI), oysters (19.0% IRI), amphipods (22.6% IRI), and polychaetes (16.4% IRI). Eelgrass beds usually serve as shelters and foraging areas for medium and large eels in the lower estuary. Despite the high species diversity around seagrass meadows, the eels concentrated on infaunal bivalves (85.4% IRI) with high biomass, predominantly Anadara sp. In addition to being tools for monitoring fauna, eels as natural samplers provide insights into the energy flow in ecosystems. [Display omitted] • Eels as natural samplers provide new insight into energy flow in an estuary. • The detritus food chain isn't linked to the diet of large eels in the upper estuary. • High species diversity and biomass of prey ensure food supply in the middle estuary. • High species diversity in seagrass meadows does not contribute to the eels' diets. • Estuarine segments should be considered for managing estuaries. [ABSTRACT FROM AUTHOR]

This article investigates the marine reservoir effects from apparent age differences among molluskan shells, birds, and sea mammals from the Hamanaka 2 archaeological site, Rebun Island, Japan, which was occupied during the latter half of the Late Jomon period (1300−1200 cal BC). The radiocarbon ages were younger in the order of charred wood

Background: The hospitalization rate for acute coronary syndrome (ACS) for people aged ≤50 has remained stable over the past decade. Increased serum levels of n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are associated with a decreased incidence of cardiovascular events and mortality in older patients; however, it is currently unknown whether reduced serum levels of n-3 PUFAs is also a risk factor for ACS in patients aged ≤50 years.Methods and Results: We retrospectively reviewed 102 (male/ female 73/29) Japanese ACS patients whose serum levels of EPA/arachidonic acid (AA) and DHA/AA were evaluated on admission. The EPA/AA ratio was the lowest in patients aged ≤50 compared to patients aged 51-74 and ≥75. Pearson correlation analysis showed that early ACS onset was associated with low EPA/AA and DHA/AA ratios, and multiple regression analysis determined that decreased ratios of EPA/AA and DHA/AA, and male sex, current smoker status, increased body mass index and triglyceride levels, independently correlated with early ACS onset. Conversely, low-density and high-density lipoproteins, glycated hemoglobin, and hypertension did not correlate with early ACS onset. Subgroup analyses of male patients revealed that decreased ratios of EPA/AA and DHA/AA independently correlated with early ACS onset.Conclusion: Decreased EPA/AA and DHA/AA ratios may be risk factors for early onset of ACS, suggesting that reduced EPA/AA and DHA/AA may represent targets for preventing ACS in Japanese young people. [ABSTRACT FROM AUTHOR]

Purpose: Although a few prospective studies have addressed the question as to which biomarker of infection in adult patients with febrile neutropenia (FN) is superior, procalcitonin (PCT) or C-reactive protein (CRP), the results have been inconsistent and inconclusive. This was possibly due to the poor sensitivity of previous PCT tests that have a functional sensitivity of 0.5 ng/ml. Methods: Between November 2010 and February 2012, we prospectively compared the diagnostic utility of serum high-sensitivity (hs) PCT (lower limit of detection, 0.02 ng/ml) and CRP levels for detecting bacterial infection in patients with FN. Serum was collected within 72 h after the onset of FN in patients with hematological disorders. Results: Seventy-five febrile episodes were evaluable. The areas under the receiver operating characteristic curves for life-threatening infection defined as septic shock and bacteremia caused by non-coagulase negative staphylococcus were 0.824 (95 % CI 0.711-0.937; P = 0.001) for hsPCT and 0.673 (0.505-0.842; P = 0.068) for CRP, respectively. In contrast, CRP, but not hsPCT, tended to increase significantly with the clinical severity, as indicated by the diagnostic classification ( P = 0.002 for trend). Conclusions: The serum hsPCT test may be more useful than the serum CRP test in the detection of life-threatening infection at an early phase after the onset of FN. In contrast, the serum CRP test may be more useful in diagnosing the severity of infection. However, neither of these tests was able to differentiate the cause of FN with a low probability of fatal outcome. [ABSTRACT FROM AUTHOR]

Aim The present study was carried out to clarify tube feeding utilization and the prevalence of swallowing difficulty among residents in geriatric long-term settings, and to elucidate the implementation of swallowing assessment at four different types of facilities in Japan. Methods We mailed a questionnaire to a total of 4334 facilities. Results We received responses from 1137 (26.2%) facilities, including 440 (29.0%) from 1517 nursing homes, 275 (29.2%) from 941 long-term care facilities, 205 (18.1%) from 1134 sanatorium medical facilities and 217 (29.2%) from 742 rehabilitation hospitals. The number of tube-fed residents per 100 beds in each facility was 11.6 at the nursing homes, 7.4 at the long-term care facilities, 36.3 at the sanatorium medical facilities and 7.9 at the rehabilitation facilities. The number of residents per 100 beds with swallowing difficulty was 23.7 in the nursing homes, 15.6 in the long-term care facilities, 19.2 in the sanatorium medical facilities and 15.4 in the rehabilitation hospitals. The percentages of facilities that assessed swallowing difficulty were 31.8% of the nursing homes, 63.0% of the long-term care facilities, 77.9% of the sanatorium medical facilities and 91.7% of the rehabilitation hospitals. Conclusion A large number of residents using a feeding tube and with difficult swallowing were observed in geriatric long-term settings without adequate evaluation of swallowing function. Geriatr Gerontol Int 2014; 14: 577-581. [ABSTRACT FROM AUTHOR]

Episyenite is a quartz-depleted vuggy rock resulting from hydrothermal alteration of granitic rocks. This is the first report of its existence in an island arc, which is identified in a deep drill core of the Toki Cretaceous granite distributed in central Japan. In order to understand the petrographical features of the episyenite, neutron porosity measurement, geochemical analysis, microscopic observation, and X-ray computed tomography scanning were carried out. The results show remarkably high porosity (35.4 %) due to interconnecting vugs and the removal of quartz, plagioclase, and biotite. The Rb-Sr isotopic results and the paragenetic sequence of secondary minerals in the vugs suggest that the hydrothermal alteration process can be divided into an episyenitization stage and a later hydrothermal stage. At the episyenitization stage (70.6 ± 3.1 Ma) ca. 6 million years after the emplacement of the unaltered granite (76.3 ± 1.5 Ma), dissolution of quartz, biotite, and plagioclase occurred and was followed by the precipitation of albite, vermicular chlorite, and platy calcite. The episyenitization is considered as a local alteration of the Toki granite in an isotopically closed system. At the later hydrothermal stage, illite and secondary quartz precipitated from circulating meteoric-derived water in the dissolution vugs. Superimposing alteration at the later hydrothermal stage is limited, which results in the preservation of the episyenite in an almost primitive condition. [ABSTRACT FROM AUTHOR]

Objective. To re-evaluate the roles of HLA-DRB1 alleles in susceptibility to SLE and RA and their effects on autoantibody status in large-scale Japanese cohorts.Methods. A total of 656 SLE, 2410 RA and 911 control subjects, who were all Japanese, were genotyped for HLA-DRB1 alleles using sequence-specific oligonucleotide probes. The association of alleles with disease susceptibility was tested by logistic regression analysis and by the relative predispositional effect method. The association with autoantibody status was examined by the standard χ2 test.Results. HLA-DRB1*15:01, *09:01, *08:02 and *04:01 were significantly associated with SLE susceptibility, while shared epitope (SE) alleles and DRB1*09:01 were associated with RA susceptibility. The compound heterozygote of DRB1*09:01/*15:01 conferred an increased risk for SLE compared with the homozygotes for DRB1*09:01 and *15:01 and was associated with earlier onset of disease, whereas the compound effect of DRB1-SE/*09:01 was not clear in RA. DRB1*09:01 was significantly associated with the appearance of anti-Sm antibody in SLE as well as ACPA in RA, while protectively associated with anti-dsDNA antibody in SLE. No significant interaction was observed between DRB1*09:01 and smoking status for the appearance of ACPA, unlike that observed in SE alleles in RA.Conclusion. We identified HLA-DRB1 alleles associated with SLE and RA in a Japanese population and demonstrated a shared susceptibility of DRB1*09:01 between the diseases as well as its effect on autoantibody production. [ABSTRACT FROM PUBLISHER]

Objective Systemic sclerosis (SSc) is an autoimmune disease for which multiple susceptibility genes have been reported. Genome-wide association studies have shown that large numbers of susceptibility genes are shared among autoimmune diseases. Recently, our group identified 9 novel susceptibility genes associated with rheumatoid arthritis (RA) in a Japanese population. The aim of this study was to elucidate whether the 18 genes that displayed associations or suggestive associations for RA in our previous study are associated with SSc in Japanese. Methods We performed an association study that included 415 patients with SSc and 16,891 control subjects, followed by a replication study that included 315 patients and 21,054 control subjects. The 18 markers reported to display association with RA were analyzed for their associations with SSc in the first study, and 5 markers were further analyzed in the replication study. The inverse variance method was used to evaluate the associations of these markers with SSc in a combined study. Results In the phospholipase D4 gene ( PLD4), rs2841277 displayed a significant association with SSc in Japanese patients ( P = 0.00017). We observed that rs2841280 in exon 2 of PLD4 was in strong linkage disequilibrium with rs2841277 and introduced an amino acid alteration. We also observed associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 ( P = 0.0000095 and P = 0.0030, respectively), both of which displayed associations with SSc in a European population. Conclusion We determined that PLD4 is a novel susceptibility gene for SSc in Japanese, thus confirming the involvement of PLD4 in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected in our Japanese population. SSc and RA appear to share relatively large proportions of their genetic backgrounds. [ABSTRACT FROM AUTHOR]