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Background: Macroscopic vascular invasion (MVI) significantly impacts survival in patients with hepatocellular carcinoma (HCC), warranting systemic therapy over locoregional therapy. Despite novel approaches, HCC with MVI has a poor prognosis compared to early-to intermediate-stage HCC. This study aimed to evaluate the safety and efficacy of carbon-ion radiotherapy (C-ion RT) for HCC characterized by MVI. Methods: This retrospective cohort study evaluated HCC patients with MVI treated using C-ion RT with a dose of 45.0–48.0 Gy/2 fractions or 52.8–60.0 Gy/4 fractions between 1995 and 2020 at our institution in Japan. We analyzed the prognostic factors and rates of local recurrence, survival, and adverse events. The local recurrence rate was determined using the cumulative incidence function, with death as a competing event. Survival rates were determined using the Kaplan–Meier method. The log-rank test for univariate analysis and the Cox proportional hazards model for multivariate analysis were used to compare subgroups. Results: In total, 76 patients with a median age of 71 years (range, 45–86 years) were evaluated. Among them, 68 had Child–Pugh grade A while eight had grade B disease. In 17 patients, the vascular tumor thrombus reached the inferior vena cava or main trunk of the portal vein. Over a median follow-up period of 27.9 months (range, 1.5–180.4 months), the 2-year overall survival, progression-free survival, and local recurrence rates were 70.0% (95% confidence interval [CI]: 57.7–79.4%), 32.7% (95% CI: 22.0–43.8%), and 8.9% (95% CI: 1.7–23.5%), respectively. A naïve tumor and a single lesion were significant prognostic factors for overall survival in the univariate analysis. Albumin-bilirubin grade 1 and a single lesion were independent prognostic factors in the multivariate analysis. Overall, four patients (5%) experienced grade 3 late adverse events, with no observed grade 4 or 5 acute or late adverse events. Conclusions: C-ion RT for HCC with MVI showed favorable local control and survival benefits with minimal toxicity. [ABSTRACT FROM AUTHOR]

The importance of salt intake in preventing heat-related illness (HRI) is well established, however, the specific method of ingestion has not been sufficiently studied. This study, therefore, aimed to investigate the optimal timing of salt intake to prevent HRI during hot outdoor work. We recruited 28 healthy male firefighters working at a fire department in Japan. They were provided a questionnaire to complete before and after receiving training in the summer season. We assessed their salt intake as before, during, and after training or none. In addition, they completed a brief self-administered diet history questionnaire to evaluate their daily salt and alcohol intake. HRI was determined through subjective and objective symptoms listed in the questionnaire, and environmental data were obtained from a national database. Subsequently, factors related to HRI were determined using a logistic regression model. The mean age of the participants was 31.0 ± 7.7 years. The study was performed within 250 working days, and we detected 28 HRI symptoms (11.2%). The median alcohol intake was 25.6 g/day when calculated according to the actual work system. Logistic mixed effect model analysis revealed that salt intake before training (OR: 5.893, 95% CI: 1.407–24.675), and salt intake before and during training (OR: 22.889, 95% CI: 4.276–122.516) were positively associated with HRI symptoms. The results indicate that inappropriate timing of salt intake increases the risks of HRI. Thus, a timely intake of salt in adequate amounts may be important in preventing these risks. [ABSTRACT FROM AUTHOR]

(1) Background: Remimazolam is a novel benzodiazepine that prevents postoperative nausea and vomiting (PONV), is more effective than volatile anesthetics, and was recently approved for use in Japan. (2) Methods: This prospective, double-blind, randomized controlled trial study aimed to compare the efficacy of remimazolam and propofol as general anesthetics in terms of the incidence of PONV after laparoscopic gynecological surgery (UMIN000046237). High-risk female patients who underwent general anesthesia with either remimazolam or propofol for the maintenance of anesthesia were enrolled. The primary outcome was the incidence of PONV in the two groups (i.e., REM versus PROP) 2 h and 24 h after surgery. The incidence of vomiting without nausea, rescue antiemetic use, and the severity of nausea were also evaluated. (3) Results: No significant differences in PONV were identified between the REM and PROP groups at 2 h or 24 h. Furthermore, no differences were observed in any of the measured parameters, and no adverse events were reported. (4) Conclusions: The results of the present study suggest that remimazolam may be as effective as propofol in preventing PONV; however, further investigation is necessary to identify possible differences between these two agents. [ABSTRACT FROM AUTHOR]

Introduction: Dotinurad is a newer urate-lowering agent that selectively inhibits urate transporter 1 in the renal proximal tubule and increases urinary urate excretion. Currently, little is known about the clinical efficacies of dotinurad in patients with hyperuricemia and hypertension. The aim of this study was to assess the clinical effects of a selective urate reabsorption inhibitor dotinurad on serum uric acid (SUA) levels and relevant vascular markers in patients with hyperuricemia and treated hypertension. Methods: This investigator-initiated, multicenter, prospective, single-arm, open-label, exploratory clinical trial in Japan enrolled patients with hyperuricemia and treated hypertension who received a 24-week dotinurad therapy (a starting dose at 0.5 mg once daily and up-titrated to 2 mg once daily). The primary endpoint was a percentage change in the SUA level from baseline to week 24. The secondary endpoints were cardiovascular and metabolic measurements, including changes in the cardio-ankle vascular index (CAVI) and derivatives of reactive oxygen metabolites (d-ROMs) concentration at week 24. Results: Fifty patients (mean age 70.5 ± 11.0 years, with 76.0% being men, and mean SUA level 8.5 ± 1.2 mg/dL) were included in the analysis. The percentage change from baseline in the SUA level at week 24 was − 35.8% (95% confidence interval [CI] − 39.7% to − 32.0%, P < 0.001), with approximately three quarters of patients achieving an SUA level of ≤ 6.0 mg/dL at week 24. The proportional changes from baseline in the geometric mean of CAVI and d-ROMs at week 24 were 0.96 (95% CI 0.92 to 1.00, P = 0.044) and 0.96 (95% CI 0.92 to 1.00, P = 0.044), respectively. Conclusion: In addition to meaningful SUA-lowering effects, 24 weeks of dotinurad therapy may favorably affect arterial stiffness and oxidative stress markers, suggesting off-target vascular protection of dotinurad. Further research is expected to verify our findings and elucidate the entire off-target effects of dotinurad. Trial registration jRCTs021210013, registration date June 24, 2021 [ABSTRACT FROM AUTHOR]

Aims: This retrospective cohort study aimed to evaluate the effect of the interaction between methotrexate and glucocorticoids on the risk of developing bacterial infections in patients with rheumatoid arthritis (RA) using biological disease‐modifying antirheumatic drugs (bDMARDs). Methods: We used the 2005–2018 JMDC claims database, a nationwide claims database in Japan. From the database of 7 175 048 patients, study patients were obtained by applying the following exclusion criteria: no use of bDMARDs; without information on the date of prescription; without RA as a disease; other than the new users of bDMARDs; and age <18 years. The exposures were glucocorticoids and methotrexate, and the outcome was bacterial infection. The interaction effects were examined using multivariate Cox regression analysis. Bacterial infections were identified according to antibiotic prescription and International Statistical Classification of Diseases and Related Health Problems, 10th revision codes. Results: A total of 2837 RA patients were identified, with a median age of 50 years. The incidence of infection was 16.8% (95% confidence interval: 15.5–18.3). The interaction term for the doses of glucocorticoids and methotrexate was significant. Additionally, a higher dose of glucocorticoid was a significant risk factor for developing bacterial infections on the side of high doses of methotrexate. The incidence of bacterial infections tended to increase significantly with increasing methotrexate doses coprescribed with glucocorticoids ≥5 mg or glucocorticoid doses coprescribed with methotrexate ≥8 mg. Conclusion: Our results indicate a potential association between methotrexate dose and bacterial infections during bDMARDs administration with glucocorticoids in patients with RA. [ABSTRACT FROM AUTHOR]

Understanding the seismic resistance mechanisms and safety limits of cross-laminated timber (CLT) buildings and performing an accurate evaluation of their seismic performance is critical in earthquake-prone areas such as Japan, the US, and Italy to ensure that human lives are protected against major earthquakes. However, the knowledge from shaking table tests of full-scale CLT buildings is limited, and most tests' maximum interstory drift is less than 4%. As a first step toward collapse analysis, this study replicated a full-scale two-story shake table experiment with a maximum interstory drift of 8.77%. The analysis software was developed by the authors and modified to consider the restoring force and the P–δ effect to replicate seismic behavior at large deformation. The skeleton curve parameters were employed in the analysis model and then changed. The results that matched the experimental results well were searched comprehensively by performing data assimilation. As a result, both the overall behavior (story shear force–interstory drift relationship) and the detailed behavior (uplift displacement of CLT wall foot of the first story) were consistent with the experimental results, indicating that the proposed analytical method can replicate the seismic behavior of CLT buildings even at large deformation. [ABSTRACT FROM AUTHOR]

To determine the metamorphic ages of the accretionary complexes in the Northern Chichibu Belt in SW Japan, K–Ar dating was conducted using weakly metamorphosed sedimentary rocks collected from the Kanto Mountains, Central Japan. Whole-rock ages were obtained for chert and red shale samples, and the mineral ages of fine-grained illite with a grain size of less than 4 μ m were obtained for chert, red shale, mudstone, acidic tuff, and basic tuff. The K–Ar ages of chert and red shale presented large variations, with systematically older ages compared to those of mudstone and tuff in the same strata. The influence of submarine hydrothermal activities on chert and red shale before subduction is a possible cause of this deviation. The illite samples, which were fractionated into four grain-size classes using a suspension method, yielded older ages and higher illite crystallinity (i.e., smaller values of Kübler's crystallinity index) for larger grain-size classes. The peak metamorphic ages were determined from the K–Ar ages of the 3–4 μ m class illite in mudstone and tuff. The Late Jurassic to the Earliest Cretaceous accretionary complex of the lowest structural unit (Kashiwagi Unit) was dated within a small range between 117–110 Ma, which is distinctly older than the K–Ar ages of white mica reported from the Sanbagawa Belt. The peak metamorphic age of acidic tuff (113 Ma) at the type locality of the Mikabu Greenstones indicates that the subducted Mikabu seamount is a constituent of the Kashiwagi Unit. The peak metamorphic ages of the Manba and Kamiyoshida Units were obtained as 132–107 Ma and 163–144 Ma, respectively. Major structural discontinuity is suggested within the Middle Jurassic accretionary complexes. [ABSTRACT FROM AUTHOR]

Introduction. The number of occupational therapists in Japan continues to increase, which has led to an urgent need to improve the educational environment for new graduate occupational therapists. This study attempted to identify the current state and challenges of the educational environment for new graduate occupational therapists in Japan. Methods. We employed a mixed method using quantitative and qualitative data from a questionnaire survey of 1055 chief occupational therapists in Japanese hospitals. The questionnaire consisted of (1) basic information about the respondent and their hospital, (2) educational environment for new graduate occupational therapists at the respondent's hospital, (3) time spent on in-hospital lectures and on-the-job training, and (4) challenges in the clinical education of new graduate occupational therapists. Text data was analysed qualitatively using text mining to create cooccurrence networks. Results. A total of 385 responses were obtained with a response rate of 36.5%. All hospitals had recruited new graduate occupational therapists in the last five years, but more than half of them did not have a philosophy and policy on education and had not prepared guidelines for the completion of occupational therapy education. The cooccurring network of issues in the educational environment for new graduate occupational therapists indicates the need to create standard guidelines, train supervisors, and develop a hospital education system. Conclusion. In the future, the needs of the educational environment for newly graduated occupational therapists should be investigated, and standardised educational guidelines should be developed. [ABSTRACT FROM AUTHOR]

In Japan, general medicine is still relatively new as a specialty, having been established in 2018 as the 19th primary specialty. The relevant research field has therefore not been fully established yet, and the detailed research areas in this field have not been identified. We conducted a descriptive questionnaire-based web survey of members of the Japanese Society of Hospital General Medicine. Respondents were asked to highlight their research topics from the following categories: diagnostic excellence, design (problem-solving and thinking methodology), symptomatology, physical examination, clinical epidemiology, home and community medicine, general medicine education, organizational management, hospital administration, and "none of the above (add description of your work if desired)". The respondents could choose multiple topics. There were 276 respondents (14% response rate), of whom 240 (86.9%) were male, 103 (37.3%) worked at universities, and 232 (84.1%) had previous research experience. Diagnostic excellence was the most common research topic category among generalists (n=87, 21.3%), followed by clinical epidemiology (n=83, 20.3%), symptomatology (n=41, 10.0%), home and community medicine (n=39, 9.6%), and general medicine education (n=36, 8.8%). Seventy-eight respondents (19.1%) chose "none of the above (add description of your work if desired)". The main research topics were in areas fundamental to diagnostic excellence, ie, diagnostics, diagnostic error, clinical epidemiology, and symptomatology. Home and community medicine and general medicine education were also included as research topics because of their diverse roles. The research interests of generalists are therefore diverse, and new areas and frameworks are likely to be created in the future. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] < 4000/μL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC < 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF. [ABSTRACT FROM AUTHOR]

When responding to disasters, emergency preparedness is essential to ensure that disaster activities are performed smoothly, safely and efficiently. Investigations on the Fukushima accident revealed that lack of preparedness, poor communication and unsuitable emergency measures contributed to an inadequate emergency response to the nuclear disaster. In this study, we conducted a questionnaire survey on the establishment of a personal radiation exposure dose among Disaster Medical Assistance Team (DMAT) members in Japan who might be involved in the initial response to a nuclear disaster. Establishing personal exposure doses for personnel can encourage emergency preparedness and inform decisions on appropriate role assignments during nuclear response activities. Valid responses were obtained from 178 participants, and the response distribution was as follows: 'Already have own acceptable dose standard,' 16 (9%); 'Follow own institution's standard (and know its value),' 30 (17%); 'Follow own institution's standard (but do not know its value),' 59 (33%); 'Haven't decided,' 63 (35%) and 'Don't understand question meaning,' 10 (6%). We also assessed intention to engage in nuclear disaster activities among respondents via engagement intent scores (EIS) and found that participants who had established personal exposure standards had significantly higher EIS scores than those who had not decided or who did not understand the question. Thus, educating potential nuclear disaster responders on personal exposure doses may contribute to a higher intention to engage in emergency responses and improve preparedness and response efficiency. [ABSTRACT FROM AUTHOR]

Simple Summary: Ramucirumab has been shown to be effective as a second-line agent after sorafenib in hepatocellular carcinoma (HCC) patients whose α-fetoprotein was ≥400 ng/mL. We performed a retrospective cohort study to investigate ramucirumab efficacy in a real-world setting. Progression-free survival (PFS) was consistent through treatment lines, modified albumin–bilirubin (mALBI) grade, Barcelona Clinic for Liver Cancer (BCLC) stage, and α-fetoprotein (AFP) level. By contrast, ascites was more frequently seen in mALBI 2b/3 patients and, therefore, should be carefully monitored. Background: The present study aimed to clarify the efficacy and safety of ramucirumab in a real-world setting, including patients who experienced two or more systemic treatments or whose hepatic reserve was deteriorated. Methods: In total, 79 patients with hepatocellular carcinoma (HCC) from 14 institutes throughout Japan were retrospectively analyzed. The response was evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and AEs were recorded according to the Common Terminology Criteria for AEs (CTCAE) version 5.0. Results: Median overall survival (OS) in the total cohort was 7.5 months (m). Median OS was 8.8 m in patients who were administered ramucirumab as a second-line treatment, while it was 7.3 m in third- or later-line treatment. Progression-free survival rates in the second- and third- or later-line therapies were 3.2 m and 3.2 m, respectively. The disease control rate (DCR) in the study was 43%. There were no statistically significant differences in DCR between the treatment courses. Regarding adverse events (AEs), the development of ascites was observed significantly more frequently in modified albumin–bilirubin (mALBI) 2b/3 patients than in mALBI 1/2a patients (54.5% vs. 25.0%, p = 0.03). Conclusions: Ramucirumab is useful as a second-line therapy and feasible as a third- or later-line treatment for HCC. [ABSTRACT FROM AUTHOR]

The room acoustical parameters reverberation time, RT; early decay time, EDT; clarity, C80; time gravity, Tg; bass ratio, BR; strength, G; initial time delay gap, ITDG; interaural cross-correlation coefficient, IACCE, the where binaural quality index BQI equals [1-IACCE3]; and stage support, ST1 were measured in 18 major chamber-music halls in Austria, Germany, the Netherlands, Czech Republic, Switzerland, and Japan, employing procedures in accordance with ISO 3382 (1997). In combination with the architectural data, the intrinsic objective parameters for the acoustics of chamber-music halls and their variation range were examined. The results of these studies reveal four pertinent orthogonal parameters: RT, G, ITDG, BQI. General design guidelines for a chamber-music hall are presented. [ABSTRACT FROM AUTHOR]

Background: Establishing an information-sharing system between medical professionals and welfare/care professionals may help prevent heart failure (HF) exacerbations in community-dwelling older adults. Therefore, we aimed to identify the ICF categories necessary for care managers to develop care plans for older patients with HF.Methods: A questionnaire was administered to 695 care managers in Hiroshima, Japan, on ICF items necessary for care planning. We compared the care managers according to their specialties (medical qualifications and welfare or care qualifications). Furthermore, we created a co-occurrence network using text mining, regarding the elements necessary for collaboration between medical and care professionals.Results: There were 520 valid responses (74.8%). Forty-nine ICF items, including 18 for body functions, one for body structure, 21 for activities and participation, and nine for environmental factors, were classified as "necessary" for making care plans for older people with HF. Medical professionals more frequently answered "necessary" than care professionals regarding the 11 items for body functions and structure and three items for activities and participation (p < 0.05). Medical-welfare/care collaboration requires (1) information sharing with related organisations; (2) emergency response; (3) a system of cooperation between medical care and non-medical care; (4) consultation and support for individuals and families with life concerns, (5) management of nutrition, exercise, blood pressure and other factors, (6) guidelines for consultation and hospitalisation when physical conditions worsen.Conclusions: Our findings showed that 49 ICF categories were required by care managers for care planning, and there was a significant difference in perception between medical and welfare or care qualifications qualifications. [ABSTRACT FROM AUTHOR]

Introduction: Future time perspective (FTP) means the capacity to foresee, anticipate, and plan for future desired outcomes, and it contributes to persistent treatment for type 2 diabetes mellitus (T2DM). However, the components of FTP specific to T2DM patients have not been clarified. This study aimed to explore the components of FTP and to examine the associations between such components and persistent/impersistent diabetes treatment. Methods: In this cross-sectional study, using qualitative and quantitative methods, 106 T2DM patients were enrolled by purposive sampling. The participants were interviewed in October and November 2018 by public health nurses in Koriyama City Public Health Center, Japan. In addition to the participants' status of treatment engagement (persistent/impersistent), their responses regarding reasons for persistent/impersistent treatment were collected and then summarized into nine subthemes, which were then merged into two main themes according to the presence or absence of FTP with a sense of T2DM ownership for analysis. Results: The main theme, "presence of FTP with a sense of T2DM ownership," included subthemes such as "securing social independence," "planning on living a long and healthy life," "prioritizing avoiding being a burden on family and friends," "valuing improvement of diabetes," "avoiding tragic results," "optimistically viewing treatment as a form of self-development," and "improving mental health," whereas the main theme, "absence of FTP with a sense of T2DM ownership," included "lack of consciousness of disease" and "living a dissipated life." The association between the presence of FTP with a sense of T2DM ownership and persistent treatment for T2DM was found using Fisher's exact test (p < 0.001). Conclusion: Health care professionals should support T2DM patients in having an FTP with a sense of T2DM ownership and purpose in life instead of treatment goals when such patients mention their dissipated life or lack of insight into the disease. [ABSTRACT FROM AUTHOR]

The Izu Ridge off the southern coast of Japan is composed of many seamounts and knolls and is an important fishery ground and hatchery for commercially important fish. As pelagic copepods link lower and higher trophic levels, we investigated the epipelagic copepods in the Izu Ridge using 28S DNA/RNA metabarcoding and microscopic approaches. In comparison with off-ridge regions, a low water temperature and high chlorophyll a concentration were observed in the Izu Ridge, possibly attributed to high levels of nutrients supplied by strong turbulences around the complex topography. We observed unique copepod communities with a large total biomass in the Izu Ridge, owing to the increased dominance of large copepod species. rRNA:rDNA (28S ratio) of these large species mainly showed positive correlations with the chlorophyll a concentration, suggesting a rapid response to the food supply. Migrating copepods were less dominant around the Izu Ridge with a shallow water depth. Higher species diversity and more rare species were detected in the Izu Ridge, which might be maintained by complex environment conditions including temporal and spatial variations in the concentration of chlorophyll a. Thus, the combined approach characterized copepod community structure and diversity supporting the rich pelagic ecosystems in the Izu Ridge. [ABSTRACT FROM AUTHOR]

Objectives: In this study, we examined the factors influencing the presence or absence of dental intervention in patients with pneumonia in an acute-care hospital, focusing on oral intake and its status. Design: Observational study. Setting: Teikyo University School of Medicine, Mizonokuchi Hospital. Participants: Patients ≥65 years of age who were admitted to the Teikyo University School of Medicine, Mizonokuchi Hospital between January 1, 2018 and December 31, 2019 with pneumonia who were referred to the Department of Rehabilitation with suspected dysphagia were included in the study. Fifty patients who underwent dental intervention were compared with 50 controls who had received no dental interventions prior to the opening of the dental department. Measurements: Time series matching was retrospectively performed using the Oral Health Assessment Tool (OHAT). From the medical records, age at admission, sex, pneumonia severity classification (age, dehydration, respiratory failure, orientation disturbance, and blood pressure [A-DROP] score), body mass index, Charlson's Comorbidity Index, OHAT, functional oral intake scale (FOIS) score at admission and discharge, and the length of hospital stay were retrieved; FOIS level ≥4 was defined as established oral intake. Results: The number of patients in the control group before matching was 179. Twelve patients with missing information and seven patients who died in the hospital were excluded from this study. Multivariable logistic regression analysis showed that dental intervention (odds ratio 3.0, p = 0.014) was associated with the establishment of oral intake at discharge. Multiple logistic regression analysis showed that dental intervention was a significant factor for FOIS at discharge (p = 0.002) and the length of hospital stay (p = 0.039). Conclusion: Oral management with dental intervention was associated with establishing oral intake and reducing hospital stay in patients with pneumonia, regardless of pneumonia severity or comorbidities. [ABSTRACT FROM AUTHOR]

Background: The high prevalence of low bone mass in young women in Japan has emerged as a serious health issue in recent years. Therefore, the aim of the present study was to reevaluate the relationship between genetic and dietary factors, as well as its influence on bone mass in young Japanese women, with particular emphasis on vitamin D receptor (VDR) gene polymorphisms and calcium intake.Methods: A total of 499 Japanese women aged 20-24 years were enrolled in the study. The bone mass of the calcaneus was assessed using the quantitative ultrasound method and expressed as the osteo sono-assessment index (OSI). VDR gene polymorphisms (BsmI, TaqI, ApaI, and FokI) were analyzed using DNA extracted from saliva. Calcium intake was assessed using the Food Frequency Questionnaire based on food groups (FFQg) and adjusted with the energy intake. Participants were divided into two groups based on the median calcium intake (250 mg/1000 kcal).Results: Consequently, bone mass was significantly different among the BsmI and TaqI genotypes after adjusting for body mass index (BMI) (p = 0.030 and 0.019, respectively). In addition, the BsmI AA and ApaI GT genotypes showed significant differences in bone mass between the calcium-intake groups, with low OSI in the low-calcium intake group and high OSI in the high-calcium intake group, respectively, even after adjusting for BMI (p = 0.020 and 0.038, respectively).Conclusions: These findings may prove instrumental in developing a logical approach towards preventing bone loss in young Japanese women. [ABSTRACT FROM AUTHOR]

Recent success of systemic therapeutic agents, including combination immunotherapy, could promote a change in the treatment strategy in patients with advanced hepatocellular carcinoma (HCC). Although hepatic arterial infusion chemotherapy (HAIC) is a treatment option for advanced HCC in Japan, it is not recommended by other guidelines. We discuss the clinical benefits of HAIC compared to sorafenib. The clinical benefits of HAIC are as follows: (1) even a patient with Child–Pugh B HCC (7 or 8 points) is a candidate for HAIC (2) Child–Pugh scores barely decline with the use of HAIC compared with sorafenib (3) HAIC is highly effective in patients with vascular invasion compared with sorafenib; and (4) survival in patients receiving HAIC may not be associated with skeletal muscle volume. In contrast, the disadvantages are problems related with the reservoir system. HAIC has clinical benefits in a subpopulation of patients without extrahepatic metastasis with Child–Pugh A HCC and vascular invasion (especially primary branch invasion or main portal vein invasion) or with Child–Pugh B HCC. [ABSTRACT FROM AUTHOR]

Background: Consuming drugs in conjunction with sexual intercourse may shape the perceived interdependence of drug use and sexual intercourse (PIDS). Additionally, the severity of drug problems may have a significant impact on PIDS. However, this relationship remains unverified. Therefore, this study investigates whether the severity of drug problems is associated with PIDS among adult males in drug addiction rehabilitation centers (DARC) in Japan.Methods: This study was a secondary analysis of the "DARC Follow-Up Study in Japan" conducted by the National Center of Neurology and Psychiatry in 2016, in which participants from 46 facilities completed a self-report questionnaire. A total of 440 males with drug dependence were included in the analysis. We analyzed participants' demographic characteristics, history of sexually transmitted disease diagnoses, and responses to questions related to drug use (e.g., primary drug use and PIDS). Additionally, we measured the severity of drug problems using the Japanese version of the Drug Abuse Screening Test-20 (DAST-20).Results: The median age of the participants was 42 years. The median DAST-20 score was 14.0, the primary drug was methamphetamine (61.4%) and new psychoactive substances (NPS: 13.6%). Multivariate analysis indicated that participants' experiences with unprotected sexual intercourse ("mostly a non-condom user": adjusted odds ratio (AOR) = 4.410), methamphetamine use (AOR = 3.220), new psychoactive substances use (AOR = 2.744), and the DAST-20 score (AOR = 1.093) were associated with PIDS.Conclusions: This study indicated that the frequency of unprotected sexual intercourse under the influence of drugs, methamphetamine and NPS use were strongly associated with PIDS. The severity of drug problems was also significantly associated with PIDS. It is necessary to develop culturally appropriate treatment programs adapted to the needs of patients who experience strong PIDS. [ABSTRACT FROM AUTHOR]

Approaching sustainability through landscapes helps appreciate the value of the diversity of human ways to live with nature that exists today. On the basis of fieldwork research in Japan, we explore the landscapes of natural parks, satoyama, and permaculture, all three recognized as sustainable and of high biodiversity value despite showing significant differences in terms of nature protection and landscape management strategies. We use the 'framework of the milieu' inspired by Watsuji Tetsurō and Augustin Berque to situate individual experiences and behaviours within the landscape's dynamics. It sheds light on the ideas of human-nature relations that underpin the understandings of sustainability as reflected in each landscape. We derive three corresponding landscape types: scenic, cultural, and ecotopian landscapes. We show that these types can be complementary insofar as they together support healthy ecosystems and fuel a sense of connectedness to nature. EDITED BY Jacqueline Loos [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) represents the most common indication for allogeneic hematopoietic cell transplantation (HCT). This study aimed to address the implementation status of allogeneic HCT for adults with AML in Japan and to provide a comprehensive overview of post-transplant outcomes. For this purpose, we analyzed data of 15,186 patients undergoing allogeneic HCT between 1992 and 2016 who were consecutively reported to the Japanese nationwide transplantation registry. The constant increase in the annual number of transplantations was clearly attributable to the growth of unrelated transplantation, and umbilical cord blood transplantation currently accounts for one-third of all allogeneic HCTs. The proportion of older patients has increased steadily since 2000, approximately, in parallel with the introduction of reduced-intensity conditioning. The probability of overall survival (OS) was estimated at 41% (95% confidence interval (CI), 40-42%) for the entire cohort, 56% (95% CI, 55-57%) for patients transplanted in complete remission (CR), and 22% (95% CI, 21-23%) for those transplanted in non-CR. Multivariate analysis identified age, sex, performance status, disease status, cytogenetic risk, donor type, graft source, sex mismatch between the donor and the recipient, and year of transplantation as factors significantly associated with OS. These findings represent the real-world data in Japan, showing the changes in transplantation practice and a detailed estimation of post-transplant outcomes. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia-lymphoma (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection that often occurs in HTLV-1-endemic areas, such as Japan, the Caribbean islands, Central and South America, Intertropical Africa, and the Middle East. In Japan, the nationwide estimation of the number of HTLV-1 carriers was at least 1.08 million in 2006–2007. Furthermore, in 2016, the nationwide annual incidence of newly infected with HTLV-1 was first estimated to be 3.8 per 100,000 person-years based on the age-specific seroconversion rates of blood donors in almost all areas of Japan. The incidence rate was three times higher in women than in men, and it was estimated that at least 4,000 new HTLV-1 infections occur yearly among adolescents and adults in Japan. As well known that HTLV-1 infection alone is not a sufficient condition for ATL to develop. To date, a variety of molecular abnormalities and host susceptibilities have been reported as candidate progression factors for the development of ATL in HTLV-1-carriers. In particular, quite recently in Japan, a variety of immunosuppressive conditions have been recognized as the most important host susceptibilities associated with the development of ATL from HTLV-1-carrier status. Furthermore, in 2013–2016 in Japan, a new nationwide epidemiological study of ATL was conducted targeting patients newly diagnosed with ATL in 2010–2011, from which the most current knowledge about the epidemiological characteristics of Japanese patients with ATL was updated as follows: (1) continuing regional unevenness of the distribution of people with HTLV-1, (2) further aging, with the mean age at diagnosis being 67.5 years, (3) declining M/F ratio, (4) increase of the lymphoma subtype, (5) sex differences in subtype distribution, (6) age differences in subtype distribution, and (7) comorbidity condition. In particular, 32.2% of ATL patients had comorbid malignancies other than ATL. However, the number of deaths due to ATL in Japan has been relatively stable, at around 1,000 patients annually, without significant decline from 1999 to 2017. Because the current epidemiological evidence about HTLV-1 and ATL is insufficient, further epidemiological studies are required. [ABSTRACT FROM AUTHOR]

Pelagic zooplankton samples from Lake Biwa, Japan, collected monthly since 1971, were analyzed for biomass and body size structure. Our aim was to clarify the relative effects of food availability and global warming vs. top‐down control by fish predation on long‐term trends. Annual mean biomass and density‐weighted body size were calculated and compared with water temperature, total phosphorus (TP), as a proxy of food amount, and catch per unit effort (CPUE) of Ayu (Plecoglossus altivelis altivelis), as a proxy of planktivorous fish predation pressure. Mean water temperature above 20 m increased by 0.94°C. TP increased until 1974 and then decreased until 1985, becoming stable after that. Ayu CPUE increased until 1987 and then declined. The study period can be divided into two nutritional phases: a high TP phase (1971–1985) and a low‐stable TP phase (1986–2010). Five zooplankton taxa, Eodiaptomus japonicus, Cyclopoida spp., Daphnia spp., Bosmina longirostris, and Diaphanosoma orientalis, were continuously dominant. Annual mean total crustacean biomass varied from 0.3 to 3.6 g dry weight m−2, slightly decreasing until 1993 but increasing thereafter. Generalized linear models showed that annual mean body sizes were affected by temperature and CPUE, whereas annual mean biomass was affected by TP and CPUE. These had no effect during the high TP phase, whereas only CPUE affected both traits during the low‐stable TP phase. We concluded that zooplankton biomass and body size long‐term trends were mostly influenced by fish predation and that eutrophication and global warming impacts might be affected by top‐down control. [ABSTRACT FROM AUTHOR]

The prognosis of aggressive adult T-cell leukemia-lymphoma (ATL) remains poor because of frequent infections and drug resistance. Dose-intensified chemotherapy followed by autologous stem cell transplantation failed to improve the prognosis of patients with ATL; however, we first revealed that allogeneic hematopoietic cell transplantation (allo-HCT) might improve their prognosis. We showed that reduced-intensity stem cell transplantation using peripheral blood was feasible for elderly patients. Further, the prognosis of patients in remission, who receive cord blood transplantation, has been recently improved and is equivalent to that of patients who receive transplants from other stem cell sources. As for the timing of HCT, the patients who underwent transplantation early showed better outcomes than those who underwent transplantation late. Based on the analysis of patients with aggressive ATL, including those who received transplants, we identified five prognostic factors for poor outcomes: acute-type ATL, poor performance status, high soluble interleukin-2 receptor levels, hypercalcemia, and high C-reactive protein level. Next, we developed a new prognostic index: the modified ATL-PI. The overall survival (OS) rates were significantly higher in patients who underwent allo-HCT than those who did not in the intermediate and high-risk groups stratified using the modified ATL-PI. Two new anti-cancer agents, mogamulizumab and lenalidomide, were recently approved for ATL patients in Japan. They are expected to induce longer survival in ATL patients when administered along with transplantation. However, a retrospective analysis that the risk of severe, acute, and corticosteroid-refractory graft-versus-host disease was higher in patients who received mogamulizumab before allo-HCT, and that mogamulizumab might increase the transplant-related mortality (TRM) rates and decrease the OS rates compared to those of patients who did not receive mogamulizumab. However, our recent study showed that administration of mogamulizumab before allo-HCT tended to improve the survival of patients with ATL. In conclusion, allo-HCT procedures for patients with aggressive ATL have considerably progressed and have helped improve the prognosis of these patients; however, many concerns still remain to be resolved. Further development of allo-HCT by using new molecular targeting agents is required for the improvement of cure rates in patients with ATL. [ABSTRACT FROM AUTHOR]

This study evaluates spatial variations in zooplankton community structure and potential controlling factors along the Japanese coast under the influence of the coastal branch of the Tsushima Warm Current (CBTWC). Variations in the density of morphologically identified zooplankton in the surface layer in May were investigated for a 15-year period. The density of zooplankton (individuals per cubic meter) varied between sampling stations, but there was no consistent west-east trend. Instead, there were different zooplankton community structures in the west and east, with that in Toyama Bay particularly distinct: Corycaeus affinis and Calanus sinicus were dominant in the west and Oithona atlantica was dominant in Toyama Bay. Distance-based redundancy analysis (db-RDA) was used to characterize the variation in zooplankton community structure, and four axes (RD1-4) provided significant explanation. RD2-4 only explained <4.8% of variation in the zooplankton community and did not show significant spatial difference; however, RD1, which explained 89.9%of variation, did vary spatially. Positive and negative species scores on RD1 represent warm- and cold-water species, respectively, and their variation was mainly explained by water column mean temperature, and it is considered to vary spatially with the CBTWC. The CBTWC intrusion to the cold Toyama Bay is weak and occasional due to the submarine canyon structure of the bay. Therefore, the varying bathymetric characteristics along the Japanese coast of the Japan Sea generate the spatial variation in zooplankton community structure, and dominance of warm-water species can be considered an indicator of the CBTWC. [ABSTRACT FROM AUTHOR]

Exploring a trade-off between quantity and quality of offspring allows differences in the fitness between alternative life histories to be accurately evaluated. We addressed the mechanism that maintains alternative life histories (small oceanic planktivores vs. large neritic benthivores) observed in a loggerhead sea turtle (Caretta caretta) population, which has been suggested to be environmental, based on the lack of genetic structure and a large difference in reproductive output. We examined whether maternal foraging habitat affects offspring quality, by measuring the morphology, emergence success, and righting response of hatchlings following incubation in a common open sand area over the whole nesting season at Yakushima Island, Japan, and by recording early growth and survival of offspring that were reared in a common environment at a Japanese aquarium. Furthermore, we tested whether sea turtles adjust egg size in response to temporal shifts of the incubation environment. There were no significant differences in any hatchling traits between oceanic and neritic foragers (which were classified by stable isotope ratios), except for clutches laid during the warmest period of the nesting season. There were also no significant differences in the growth and survival of offspring originating from the two foragers. The size of eggs from both foragers significantly increased as the season progressed, even though the rookery had heavy rainfall, negating the need to counteract heat-related reduction in hatchling morphology. In comparison, the sizes of adult body and clutches from both foragers did not vary significantly. The results further support our previous suggestions that the size-related foraging dichotomy exhibited by adult sea turtles does not have a genetic basis, but derives from phenotypic plasticity. Adjustment in reproductive investment may be associated with: (1) predation avoidance, (2) founder effect, and/or (3) annual variation in egg size. [ABSTRACT FROM AUTHOR]

Background: The Japanese Orthopedic Association first proposed the concept of "locomotive syndrome" in 2007. It refers to circumstances in which elderly people need nursing care services or are at high risk of requiring such services within a short time. Recently, the public health burden of providing nursing care for elderly individuals has increased. Therefore, locomotive syndrome, and the means of preventing it, are a major public health focus in Japan. The purpose of this study was to investigate the relationships of lifestyle factors, such as smoking, alcohol consumption, sleep duration, and dental health, with locomotive syndrome.Methods: We conducted a cross-sectional study using an internet panel survey. The participants comprised 747 individuals aged 30-90 years. Factors related to demographics (age, sex), general health (number of teeth, presence of periodontal disease), and lifestyle (smoking, alcohol consumption, sleep duration) were assessed. We also used the 25-question Geriatric Locomotive Function Scale to determine whether each participant had locomotive syndrome. Multivariate analysis was conducted using logistic regression to investigate the independent relationships between locomotive syndrome and lifestyle factors after adjusting for sex and age.Results: A greater proportion of women (17.7%) than men (11.2%) had locomotive syndrome (p < 0.05). Participants aged ≥65 years showed significantly higher percentages (men: 21.4%, women: 75.7%) of locomotive syndrome compared with those aged <65 years (p < 0.05). Logistic regression analysis revealed that older age (≥ 65 years), sex, current smoking status, number of existing teeth, and presence of periodontal disease were associated with locomotive syndrome, whereas sleep duration was not. The frequency of alcohol consumption, except for daily drinking, was also associated with locomotive syndrome.Conclusion: Our study indicates that lifestyle factors, such as smoking and number of existing teeth, may partly affect the prevalence of locomotive syndrome. Hence, lifestyle modifications, such as improving oral hygiene and promoting cessation of smoking, are important means to reduce the risk of locomotive syndrome and should be promoted by public health staff. [ABSTRACT FROM AUTHOR]

The Paracalanus parvus species complex is one of the most dominant and ecologically important copepod groups in the waters around Japan. However, the overall taxonomic classification of the species complex has not been sufficiently defined to date. In this study, both genetic and morphological analyses were performed on specimens of the P. parvus species complex collected along the "O-line", a monitoring line located at 138°E, south of Japan. Among the individuals collected, P. nanus specimens were clearly distinguishable morphologically, whereas other specimens could be classified into three reproductively isolated species. These distinctions are based on genetic analyses of the mitochondrial cytochrome oxidase subunit I (mtCOI) and nuclear large subunit (nLSU) ribosomal RNA. By comparing the genetic and morphological data with findings from previous studies, these three species were identified as P. tropicus, P. indicus, and an as-yet undescribed species (Paracalanus sp. (NWP)). The latter possesses a humped forehead and was found to be a dominant species within the surveyed continental slope area. As a distinguishing characteristic, the humped forehead was not consistently useful as it was prominent in only about half of the individuals collected. Morphological discrimination between this species and P. indicus was only made possible by comparing the relative length of exopod segment 3 on swimming leg 4. Despite morphological similarities among member species, ecological studies on the P. parvus species complex conducted around Japan may mostly concern the undescribed species, Paracalanus sp. (NWP), considering that P. indicus was found only in warmer waters in this study. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an effective local treatment modality as a cancer-specific laser ablation in malignancy of some organs including digestive tracts or bile duct. In Japan, PDT has been applied at the early period after the first clinical induction in 1980's. Although the useful efficacy was clarified, PDT has not been fully applied because of the phototoxicity of the porfimer sodium. The next generated talaporfin-sodium was used for PDT, in which phototoxicity was reduced and, however, the clinical efficacy for digestive tract malignancy has not yet been clarified. By proceeding the experimental and clinical trials, it is necessary to clarify the evidence of efficacy as a local powerful treatment with the conventional surgery, brachiotherapy and chemotherapy in the future step. [ABSTRACT FROM AUTHOR]

Seedlessness is a desirable characteristic for both fresh and processed citrus markets and one of the most important breeding objectives. In this paper, progress on studies for seedless breeding of citrus in Japan is reviewed. Among the several types of male sterility, anther abortion is the strictest male sterility in citrus and was shown to be controlled by both nuclear and cytoplasmic genes. Several seedless cultivars with male sterility have been developed. The mechanism and inheritance of the strictest female sterility derived from 'Mukaku Kishu' (Citrus kinokuni hort. ex Tanaka) were clarified and seedless cultivar and parental lines with this female sterility have been released. Some self-incompatible cultivars show seedlessness when coupled with parthenocarpy. S (self-incompatibility) genotypes of several cultivars have been estimated. Tetraploid plants, as parents of triploid offspring, were obtained from nucellar seedlings, and by ploidy mutation, colchicine treatment, and protoplast fusion. Triploid plants were produced from the combination of not only tetraploid and diploid crosses but also diploid and diploid crosses. New triploid seedless cultivars were bred by programmed cross-breeding and protoplast fusion. [ABSTRACT FROM AUTHOR]

Japanese Mamushi (Gloydius blomhoffii) has long been exploited for its medicinal value. We studied this snake's reproductive ecology on Hokkaido and assessed its vulnerability. We marked 299 individuals from 1999-2002 and kept 29 pregnant females in captivity until parturition. Pregnant females aggregated at gestation sites during summer and fall until just before parturition. Behavior suggestive of mating seasons was evident mostly in August and September. As expected, there was an apparent sex difference in body size in adults but not in neonates: females were larger than males. Consistent with previous reports, both neonates and adults were larger in Hokkaido than in southern Japan. The smallest pregnant female measured 44.8 cm in SVL, which was larger than values reported from southern regions. Offspring sex ratio was statistically equal: 88 males to 105 females. Litter size averaged 6.6 offspring. Longer females tended to produce larger litters and longer neonates. The proportion of pregnant to non-pregnant females, coupled with mark-recapture data, suggested that Mamushi females skip one or more years between reproductive bouts. Relative litter mass (RCM) was large (83% on average), and postpartum body condition was lower, especially so in females with larger RCM. Direct human-caused mortality was highest for pregnant females (70.2%), followed by nonpregnant females and then males. High adult mortality, particularly of pregnant females, raises a concern about population persistence, because Mamushi exhibit a slow life history. The tendency of pregnant females to aggregate at predictable locations further makes Mamushi populations vulnerable to human killing and exploitation. [ABSTRACT FROM AUTHOR]

Objectives. The epidemiological manifestations of ANCA-associated vasculitis (AAV) differ geographically. However, there have been no prospective studies comparing the incidence of AAV between Japan and Europe over the same time period using the same case definitions.Methods. The incidence of AAV was determined by a population-based method in Miyazaki prefecture, Japan, and Norfolk, UK, between 2005 and 2009. Patients with AAV were defined and classified according to the European Medicines Agency (EMEA) algorithm.Results. The number of incident cases of AAV in Japan and the UK were 86 and 50, respectively, and the average annual incidence over the 5-year period was 22.6/million (95% CI 19.1, 26.2) and 21.8/million (95% CI 12.6, 30.9) in Japan and the UK, respectively. The average age was higher in patients in Japan than in patients in the UK [mean (median), 69.7 (72) vs 60.5 (61) years]. Microscopic polyangiitis (MPA) was the predominant subtype in Japan (83%), while granulomatosis with polyangiitis (Wegener's) was more frequent in the UK (66%). As for the pattern of ANCA positivity, >80% of Japanese patients were pANCA/MPO positive, whereas two-thirds of UK patients were cANCA/PR3 positive. Renal involvement in MPA was very common in both countries, but was much less common in granulomatosis with polyangiitis in Japan compared with the UK.Conclusion. There was no major difference in AAV incidence between Japan and the UK, but this prospective study found MPA and MPO-ANCA to be more common in Japan and granulomatosis with polyangiitis and PR3-ANCA to be more common in the UK, in line with earlier reports. [ABSTRACT FROM PUBLISHER]

The freshwater fish community in subtropical Okinawa Island, Japan, was originally poor and is now mainly composed of alien fishes. Fishes caught in an impoundment of the Hija River and the Haebaru Reservoir were measured for carbon and nitrogen stable isotope ratios to estimate the trophic niches of the alien fishes. Fish fauna of the two habitats were mainly composed of alien fishes originating from Africa and South and Central America. Isotope ratios suggested that alien fishes included two trophic types -- food-partitioning types like armored catfish, Poeciliidae, and redbelly tilapia that each use a unique trophic niche, and food-overlapping types like cichlids that all have similar trophic niches. [ABSTRACT FROM AUTHOR]

This article presents information about the architectural acoustics of the Tokyo Opera City Concert Hall in Japan. The author believes that the inverted-V cross-section ceilings could be an improvement on the shoebox-shaped halls. Reverberation time calculations are much more accurately predicted in the inverted-V design. Several churches that have the inverted-V design and excellent acoustics are mentioned. The article also presents information on the acoustical engineering of the First Presbyterian Church of Stamford, Connecticut and efforts to restore it to its original design.

Miscanthus sinensis, a tall cespitose warm-season perennial grass, occurs widely in tree plantations across Japan as a major weed. A 4-year grazing trial was conducted in a young Chamaecyparis obtusa (an evergreen conifer) plantation in south-western Japan, in an effort to evaluate forest grazing as a management practice to utilize and control M. sinensis and to deepen a mechanistic understanding of the responses of this grass to herbivory. The plantation was continuously stocked by Japanese Black cattle during the grazing season from May–November (July–November in the first year) at rates of 0.38–0.63 animals ha−1. M. sinensis was always the major species selected by animals, with most of the plants (80–90%) in the paddocks being defoliated during the grazing season. Reflecting these, M. sinensis plants declined with time under grazing, mainly in shoot number per tuft and partly in leaf appearance rate and the weight of the youngest fully expanded leaf, leading to a drastic decrease in production of leaves (laminae) as a photosynthetic organ and a main feed component for animals. Animals did little fatal damage to C. obtusa trees. Performance of animals was acceptable for cows that had experienced forest grazing in preceding years, but needed improvement for inexperienced heifers and calves. The results demonstrate the potential value of cattle grazing in utilizing and controlling M. sinensis in young tree plantations, which enables multifunctional land use linking forest and animal industries. Further studies are necessary to explore the optimum grazing intensity that balances effective control and extended utilization of the grass. [ABSTRACT FROM AUTHOR]

Boreal Lake Baikal, temperate Lake Biwa, and tropical Lakes Malawi and Tanganyika each possess high biodiversities of benthic organisms in their littoral areas. Two general mechanisms influencing the evolutionary development of these high biodiversities can be hypothesized; i.e., a bottom-up constraint depending on the availability of food resources, and a top-down effect exerted by predators especially within the fish assemblage. The bottom-up constraint may be prominent where the abundance of benthic organisms in the grazing-food-chain is restricted by a seasonally lowest production, referring chiefly to attached algae, and large fluctuations in the abundance of primary producers provide a resource that is eventually utilized by benthic organisms of the detritus-food-chain. The top-down effect may be realized where the most of benthic organisms are supported by a constantly large primary production. These hypotheses help to explain, for the lakes we cite, the facts that diverse grazing-food-chain organisms live on the littoral bottom of tropical lakes where there is relatively constant large algal production due to suitable conditions of water temperature and light penetration through the year; while on the other hand, detritus-food-chain organisms are predominant on the littoral bottom of a boreal lake with seasonally fluctuating algal production and its pronounced lowest production in a year. In fish communities, segregations in habitat and food resource are important mechanisms allowing development of high species packing, while cohabitation within predatory fishes increases their feeding success due to the decrease of defensive efficiency by the threat of a variety of attacking methods. A further top-down effect may be exerted by scale-eating fishes, especially in Lake Tanganyika. The presence of such predatory and harmful members may promote more dense packing of prey members to increase their mutual defense efficiency. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To clarify the role of the T-lymphocyte-associated-4 (CTLA-4) polymorphism in the susceptibility to child-onset type 1 diabetes with regard to its clinical characteristics and complications with autoimmune thyroid disease (AITD) in the Japanese population. RESEARCH DESIGN AND METHODS -- The CTLA-4 49 A/G polymorphism was detected by the PCR-restriction fragment-length polymorphism (RFLP) method in 97 type 1 diabetic subjects and 20 patients with Graves' disease, a cohort which included 4 patients who also had type 1 diabetes. RESULTS -- The genotypes and allele frequencies of this polymorphism did not differ between the type 1 diabetic subjects and the control subjects. The G allele frequency was 63.9% in the type 1 diabetic subjects. The G allele frequency in the subgroup of patients with a high titer of autoantibodies to the GAD antibody (Ab) was 72.9% (P = 0.0499 vs. control subjects); in the subgroup of patients without HLA DRB1*0405, it was 72.6% (P = 0.0271 vs. control subjects); and in the subgroup of patients with a residual β-cell function, it was 78.6% (P = 0.0391 vs. control subjects). The G allele frequency in the patients with Graves' disease was also significantly higher at 78.1% (P = 0.0405 vs. control subjects). Furthermore, the frequency in our diabetic subjects complicated with Graves' disease was even higher (87.5%). CONCLUSIONS -- We have demonstrated that a distinct association exists between the G allele of CTLA-4 and high values of GAD Ab, residual β-cell function, and the absence of HLA-DRB1*0405. [ABSTRACT FROM AUTHOR]

The Mo contents and the relations between Mo and Cu or Cr contents were investigated in the organs of Japanese wild ducks (spotbill duck, pintail, wigeon, scaup and tufted duck). The highest Mo content in kidney and liver of the dabbling ducks were more than 30 μg g-1 dry weight (μg g-1 d. wt.), though that of diving ducks were less than 11 μg g-1 d. wt. The contents were lower in the ducks migrating within Japan, Eurasia and North America than those in the birds migrating between Japan and Eurasia. The contents of liver in all species were more than 50 and less than 5 μg g-1 d. wt. for Cu and Cr, respectively. Significant correlations were found between Mo and both elements in pintail and scaup, and Mo and Cr in tufted duck. These results suggest that the contamination of wild ducks reflects the reproductive area, and not the collected area. Mo contents closely correlated with the Cu and/or Cr contaminations. [ABSTRACT FROM AUTHOR]

Background: The autoimmune thyroid diseases (AITDs), such as Graves' disease (GD) and Hashimoto's thyroiditis (HT), appear to develop as a result of complex interactions between predisposing genes and environmental triggers. Susceptibility to AITDs is conferred by genes in the human leukocyte antigen (HLA) and genes unlinked to HLA, including the CTLA-4 gene. Recently, estrogen receptor (ER) β, located at human chromosome 14q23-24.1, was identifed. We analyzed a dinucleotide (CA)n repeat polymorphism located in the flanking region of ERβ gene in patients with AITDs and in normal subjects. High heterozygosity makes this polymorphism a useful marker in the genetic study of disorders affecting female endocrine systems. We also correlated a ERβ gene microsatellite polymorphism with bone mineral density (BMD) in the distal radius and biochemical markers of bone turnover in patients with GD in remission. Results: Fourteen different alleles were found in 133 patients with GD, 114 patients with HT, and 179 controls subjects. The various alleles were designated as allele*1 through allele*14 according to the number of the repeats, from 18 to 30. There was no significant difference in the distributions of ERβ alleles between patient groups and controls. Although recent study demonstrated a significant relation between a allele*9 in the ERβ gene and BMD in postmenopausal Japanese women, there were no statistically significant interaction between this allele and BMD in the distal radius, nor biochemical markers in patients with GD in remission. Conclusions: The present results do not support an association between the ERβ microsatellite marker and AITD in the Japanese population. We also suggest that the ERβ microsatellite polymorphism has at most a minor pathogenic importance in predicting the risk of osteoporosis as a complication of GD. [ABSTRACT FROM AUTHOR]

Objective: We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population.Research Design and Methods: We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis.Results: The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects.Conclusions: An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism. [ABSTRACT FROM AUTHOR]

Improving reproductive efficiency is required to strengthen the production base of high-quality Wagyu beef in Japan. We developed a deterministic profit function (P) for lifetime carcass production of Japanese Black cows to calculate economic values (EVs) for representative female reproductive and carcass traits. The total calving number per cow was expressed using the age at first calving (AFC) and calving interval (CI). Revenues and costs were calculated from calf market price (CaP) and carcass unit price (CUP). A cubic regression equation was developed with CaP as the response variable and calf market weight as the explanatory variable. A multiple linear regression equation was developed with CUP as the response variable and five carcass traits as explanatory variables. EVs were calculated using the first-order partial derivatives of P. The first-order partial derivative of CI was a function of CI with the quadratic term of CI in the denominator. Values of EVs for AFC and CI were negative, suggesting that earlier AFC and shorter CI increase the lifetime profit of Japanese Black cows through producing higher numbers of feeder cattle per cow. However, this might bring benefit to only calf-producing farmers. The results would contribute to achieving sustainable high-quality Wagyu beef production. [ABSTRACT FROM AUTHOR]

In-transit metastases (ITMs) in patients with malignant melanoma (MM) are associated with poor prognosis and a worse disease burden compared with MM without ITMs. A substantial population of patients with ITMs show no or only poor responses to newly developed therapies, such as immune checkpoint inhibitors or molecular-targeted agents. It is difficult to control the exudate and bleeding from ITMs when these medications are ineffective. In Japan, local injection of interferon-β (IFN-β) has been licensed for years as adjuvant therapy for MM. However, the evidence for IFN-β effectiveness for ITMs remains low. The present report describes a case of MM with multiple ITMs that did not respond to a programmed cell death-1 inhibitor and local injections of IFN-β at 3 million IU/day for 5 days/4 weeks but remitted upon increasing the amount of IFN-β injections to 10 consecutive days/4 weeks. Local IFN-β therapy could be an option for improving the quality of life of patients. [ABSTRACT FROM AUTHOR]

Stratigraphic records of impact ejecta preserved in a pelagic deep-sea setting occur within Upper Triassic successions of the subduction-generated accretionary complexes of central Japan. A significant biotic turnover in radiolarians occurred during the ~ 300 kyr time interval after the impact event, which is characterized by a remarkable reduction in the burial flux of radiolarian silica. However, the nature of the environmental conditions at this time remains unclear. To investigate the environmental changes that triggered a decline in radiolarian burial flux after the impact event, geochemical proxies (major, trace, and rare earth elements) were applied to the middle–upper Norian (Upper Triassic) bedded chert succession of the Mino Belt, central Japan. A progressive environmental deterioration is evident from (1) a post-impact shutdown of burial flux of primary and silica- and apatite-secreting organisms; and (2) a subsequent abrupt increase in chemical weathering associated with a sustained reduction in the burial flux of radiolarian silica. No significant redox changes were observed across the impact event. The continental weathering proxies suggest a transient increase in weathering intensity occurred during the decline of radiolarian burial flux, likely in response to a short-term warm and humid period. Our results delineate a remarkable record of progressive environmental changes in the Panthalassa Ocean after this large impact event. [ABSTRACT FROM AUTHOR]

Objective: It is well known that air temperature is closely related to health outcomes. We investigated the relationship between air temperature parameters and the number of deaths stratified by cause in Gifu prefecture, Japan. Methods: The number of deaths stratified by cause in Gifu prefecture Japan between January 2007 and December 2016 was obtained from the official homepage of Gifu prefecture, Japan. Air temperature parameters (°C), i.e., the mean air temperature, mean of the highest air temperature, mean of the lowest air temperature, the highest air temperature, and the lowest air temperature during the same period in Gifu city were also obtained from the Japan Meteorological Agency official home page. The relationship between air temperature parameters and the number of deaths was evaluated in an ecological study. Results: The number of deaths due to heart disease, cerebrovascular disease, pneumonia, accidents, or renal failure in January (coldest winter season in Japan) was the highest among the months. Simple correlation analysis also demonstrated a significant and negative relationship between air temperature parameters and the number of deaths due to heart disease, cerebrovascular disease, senility, pneumonia, accidents, and renal failure. Conclusion: Lower air temperature may be associated with a higher number of deaths due to diseases in Gifu prefecture, Japan. [ABSTRACT FROM AUTHOR]

The Hidaka collision zone, the collision boundary between the NE Japan and Kurile arcs, is known to be an ideal region to study the evolution of island arcs. The hypocenter of the 2018 Hokkaido Eastern Iburi earthquake (Mw 6.6) in the western part of the Hidaka collision zone was unusually deep for an inland earthquake, and the reverse fault that caused the earthquake has an uncharacteristically steep dip. In this study, we used three-dimensional inversion to reanalyze broadband magnetotelluric data acquired in the collision zone. The inverted resistivity model showed a significant area of high resistivity around the center of the collision boundary. We also identified a conductive zone beneath an area of serpentinite mélange in a zone of high P–T metamorphic rocks west of the high-resistivity zone. The conductive zone possibly reflects areas rich in pore fluids related to the formation and elevation of the serpentinites. Sensitivity tests indicated the need for additional magnetotelluric survey data to delineate the resistivity distribution around the epicentral area of the 2018 earthquake although the resistivity model showed a conductive zone in this area. [ABSTRACT FROM AUTHOR]

Background: Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. Methods: After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17–85 years; 54% female) were retrospectively analyzed. Results: Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P < 0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Conclusions: Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs. [ABSTRACT FROM AUTHOR]

Objective: The aim of this prospective clinical study was to evaluate the efficacy and safety of long-term proton pump inhibitor (PPI) treatment for two years in Japanese patients with reflux esophagitis (RE)., Methods: The efficacy and safety of two-year (104-week) treatment with rabeprazole (RPZ) 10 mg were studied in patients confirmed to have been cured of RE by PPI and who required long-term maintenance therapy with PPI. We performed serial endoscopy, checked gastroesophageal reflux disease (GERD) symptoms, adverse events, laboratory values and serum gastrin. We also monitored gastric mucosal histology, atrophy and polyps., Results: The endoscopic non-relapse rate for RE was 87.3% for the 104-week period. GERD symptoms improved based on the fact that the mean change from baseline in GERD symptom score after treatment was a negative value. Treatment was safe; and atrophy was found to have developed in virtually no cases. A few new benign fundic gland or hyperplastic polyps developed throughout the study, but no ECL carcinoids were found to have developed. Serum gastrin levels tended to increase up to 24 weeks, but there were no subsequent changes thereafter up to 104 weeks., Conclusion: The results confirmed oral RPZ 10 mg to be effective for maintenance therapy in Japanese patients with RE. Although effects on the gastric mucosa were not ruled out, long-term use of RPZ was confirmed to be safe overall.

Background and Purpose: The Ministry of Health, Labor, and Welfare of Japan approved the use of recombinant tissue-type plasminogen activator (rt-PA) for the treatment of acute ischemic stroke in October 2005. The impact of the regulatory approval of rt-PA on the processes of acute stroke management was examined., Methods: A prospective, multicenter, observational study was conducted between December 2004 and December 2005 in 84 Japanese institutes, including 24 institutes with a stroke unit. We enrolled 4620 consecutive patients who were hospitalized within 72 hours after the onset of completed ischemic stroke; 1089 of them were hospitalized after rt-PA was approved. The patients' characteristics and the processes of stroke management were compared before and after rt-PA approval., Results: Age, gender, stroke subtype, time from onset to hospital visit, and National Institutes of Health Stroke Scale score on admission were similar between the 2 periods. With approval, the percentage of patients treated with intravenous rt-PA therapy increased from 0.7% to 2.6% (P<0.001). The rate increased from 0.9% to 5.2% in institutes with a stroke unit (P<0.001) but did not increase in other institutes (P=0.587). Within 24 hours of stroke onset, conventional MRI (P=0.003), diffusion-weighted MRI (P<0.001), magnetic resonance angiography (P=0.001), carotid ultrasound (P=0.004), measurement of prothrombin time or activated partial thromboplastin time (P=0.034), and measurement of blood sugar (P=0.015) were performed more frequently after rt-PA approval., Conclusions: The present results indicate that the approval of intravenous rt-PA therapy resulted in dramatic changes in the processes of management for acute stroke patients.