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Macroalgal canopies, which provide nutrients and habitats for many invertebrates and fishes in coastal waters, are disappearing worldwide. The simultaneous assessment of changes in macroalgae and fish distribution before and after coastal desertification, including deeper coastal waters where beyond macroalgae growth need attention. Therefore, we investigated their spatial distribution in the coastal waters off southwestern Japan in late autumn and winter using the acoustic method combined with visual observation. The number of fish schools was higher in late autumn than in winter, while they had similar acoustic backscattering strength (Sv) and school size, tended to be distributed in shallower waters. The number was lower after the macroalgae disappeared in both seasons, while the average Sv was higher, and the size was larger. They were distributed in similar water depths during the winter season. Fewer fish schools and higher Sv were observed in deeper waters after the macroalgae disappeared. We concluded that more fishes moved to shallower waters in the autumn than in the winter because of higher water temperatures. Macroalgae benefited small juvenile fishes in both shallow and deep coastal waters. Further studies on the distribution of specific species are expected for the assessment and restoration of the macroalgal ecosystem. [ABSTRACT FROM AUTHOR]

Acoustic telemetry and microchemical analysis of otolith strontium-calcium ratios were used to evaluate how exotic brown trout Salmo trutta have responded to Japanese riverine environments of south-western Hokkaido by observing their migratory patterns. The existence of anadromous S. trutta was also verified. Most S. trutta caught in rivers for otolith analysis were freshwater residents (95·6%), whereas those caught in the sea were mainly smolts (91·3%), which had just migrated from rivers during spring. Anadromous S. trutta ( n = 6) were captured in rivers and in the sea, confirming the existence of mature pre- and post-spawning fish. According to telemetry results, both mature and immature S. trutta used the river in winter, and their estimated sea-run timings showed individual differences. Through the combination of these two methods, migratory patterns on various spatio-temporal scales were observed. This first documentation of the presence of both male and female anadromous S. trutta in the same region within Japan indicated the risk of further colonization of exotic S. trutta via oceanic migration. [ABSTRACT FROM AUTHOR]

Background and Objective: Pooled analyses of previous randomized controlled trials reported that antifibrotics improved survival in patients with idiopathic pulmonary fibrosis (IPF), but the results were only based on short-term outcome data from selected patients who met strict criteria. Observational studies/meta-analyses also suggested that antifibrotics improve survival, but these studies failed to control for immortal time bias that considerably exaggerates drug effects. Therefore, whether antifibrotics truly improve long-term survival in patients with IPF in the real world remains undetermined and requires external validity., Methods: We used data from the Japanese National Claims Database to estimate the intention-to-treat effect of antifibrotics on mortality. To address immortal time bias, we employed models treating antifibrotic initiation as a time-dependent covariate and target trial emulation (TTE), both incorporating new-user designs for antifibrotics and treating lung transplantation as a competing event., Results: Of 30,154 patients with IPF, 14,525 received antifibrotics. Multivariate Fine-Gray models with antifibrotic initiation as a time-dependent covariate revealed that compared with no treatment, nintedanib (adjusted hazard ratio [aHR], 0.85; 95% confidence interval [CI], 0.81-0.89) and pirfenidone (aHR, 0.89; 95% CI, 0.86-0.93) were associated with reduced mortality. The TTE model also replicated the associations of nintedanib (aHR, 0.69; 95% CI, 0.65-0.74) and pirfenidone (aHR, 0.81; 95% CI, 0.78-0.85) with reduced mortality. Subgroup analyses confirmed this association regardless of age, sex, and comorbidities, excluding certain subpopulations., Conclusions: The results of this large-scale real-world analysis support the generalizability of the association between antifibrotics and improved survival in various IPF populations., (© 2024. The Author(s).)

Although the frequency of community-acquired infections caused by Klebsiella pneumoniae subsp. ozaenae (K. ozaenae) is low, they are often detected in sputum specimens. In addition, lung abscesses, necrotizing pneumonia, and urinary tract infections caused by K. ozaenae have also been reported. We herein report the first detection of K. ozaenae as an etiological agent of bacterial meningitis in Japan. Cases of K. ozaenae meningitis complicated by diabetes mellitus and sinusitis have been reported elsewhere. When Klebsiella pneumoniae is detected in such cases, it is important to use other detection methods in addition to mass spectrometry for correct identification.

Eelgrass beds provide a habitat for many high-value fishery resources, and provisioning services, one of the ecosystem services, need to be quantified. However, few examples have been evaluated spatially. We determined the distribution of eelgrass beds in Lake Notoro, a marine lagoon in Hokkaido, Japan, and quantified the provisioning services by the eelgrass beds in relation to Pandalus latirostris, a fishery resource. Acoustic measurement surveys of the eelgrass beds and catch surveys of the shrimp were conducted in July and August 2015. The relationship between catch per unit effort (CPUE) of shrimp and the distribution of eelgrass beds was shown. The estimated distribution area of eelgrass beds was 7.07 km 2 . Shrimp was frequently caught at water depths of 3-5 m, approximately 200 m from the edge of the eelgrass beds. The expected catch of shrimp in the fishing area of Lake Notoro in 2015 was 25.37 tons and US$ 463.6 thousand. Eelgrass beds were found to affect the fisheries production not only on the inside but also at the edge and outside. The entire coastal space should be evaluated, while considering the effect of the distribution of eelgrass beds, to quantify the provisioning services., (© 2024. The Author(s).)

Background: This study aimed to evaluate the changes in glycemic control and diabetic complications over time in Japanese patients with juvenile-onset type 1 diabetes mellitus and to clarify the factors associated with the progression of diabetic complications., Methods: We tracked 129 patients with type 1 diabetes mellitus (21.8 ± 4.1 years old [mean ± SD] with a diabetes duration of 12.6 ± 5.7 years) for up to 19 years and analyzed data on glycated hemoglobin (HbA1c) and indicators related to the severity of diabetic complications (estimated glomerular filtration rate [eGFR], urinary albumin excretion rate [UAE], carotid intima-media thickness [CIMT], and brachial-ankle pulse wave velocity [baPWV]) using linear mixed model and decision tree analysis., Results: Although the HbA1c and UAE levels improved over time, the eGFR, CIMT, and baPWV worsened. Decision tree analysis showed that HbA1c and the glycoalbumin/HbA1c ratio for eGFR; HbA1c and systolic blood pressure for UAE; low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, glycoalbumin/HbA1c ratio, and body mass index (BMI) for CIMT; and HbA1c for baPWV were associated factors., Conclusions: In this retrospective observational study, glycemic control and albuminuria improved; however, renal function and arteriosclerosis worsened over time. HbA1c levels, glycemic excursion, and blood pressure are associated with nephropathy progression. HbA1c levels, glycemic excursion, lipid levels, and BMI are associated with the progression of atherosclerosis., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: During the coronavirus disease pandemic in Japan, all patients with respiratory symptoms were initially tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study describes the respiratory pathogens detected from patients who tested negative for SARS-CoV-2 at the Saitama Institute of Public Health from January to December 2020., Methods: We performed pathogen retrieval using multiplex real-time polymerase chain reaction on samples from patients with acute respiratory diseases who tested negative for SARS-CoV-2 in Saitama in 2020 and analysed the results by age and symptoms., Results: There were 1530 patients aged 0-104 years (1727 samples), with 14 pathogens detected from 213 patients (245 samples). Most pathogens were human metapneumovirus (25.4%, 54 cases), rhinovirus (16.4%, 35 cases) and Mycoplasma pneumoniae (13.1%, 23 cases). Human metapneumovirus, human coronavirus (but not NL63) and M. pneumoniae were detected in almost all age groups without any significant bias. Seasonal human coronaviruses, human metapneumovirus, M. pneumoniae and several other pathogens were detected until April 2020., Discussion: Multiple respiratory pathogens were circulating during 2020 in Saitama, including SARS-CoV-2 and influenza viruses. We suggest introducing a system that can comprehensively monitor the regional prevalence of all viruses that cause acute respiratory infections., Competing Interests: The authors have no conflicts of interest to declare., ((c) 2023 The authors; licensee World Health Organization.)

Background: Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease and is subdivided into eosinophilic and noneosinophilic forms. There are few reports investigating the nasal microbiome and its pathological functions in patients with CRS., Objective: We sought to analyze factors contributing to variations of the nasal microbiome in CRS, and on the basis of these factors, to elucidate whether the bacterial metabolites were related to the pathogenesis., Methods: Nasal swabs were collected, and the V3 to V4 variable region of the 16S ribosomal RNA gene was amplified and sequenced. Factors contributing to variations of the nasal microbiome in patients with CRS were compared. The most influential factor was whether CRS was eosinophilic, and we compared α- and β-diversity, bacterial species, and predictive bacterial functions between the 2 patient groups. In addition, the metabolites of the key bacteria were extracted, and we evaluated the predicted bacterial functions in airway epithelial cells., Results: In total, 110 patients with CRS and 33 control subjects were enrolled. On the basis of the factors of variation, it was found that patients with eosinophilic CRS (n = 65) had different microbiomes with weighted UniFrac β-diversity and lower α-diversity compared with those with noneosinophilic CRS (n = 45). A higher abundance of Fusobacterium nucleatum and an increased LPS pathway were observed in patients with noneosinophilic CRS compared with those with eosinophilic CRS. In airway epithelial cells, LPS derived from F nucleatum suppressed the expression levels of ALOX15 induced by T H 2 cytokines., Conclusions: The differences in the nasal microbiome may play a key role in the pathophysiology of CRS., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives: The "Guidelines for Ensuring the Safety and Health of Older Workers (hereafter referred to as "Guidelines")," formulated in 2021, require employers to implement measures that proactively prevent occupational accidents among older workers. This study aimed to clarify the status of awareness of the Guidelines and workplace improvement efforts with consideration of older workers, focusing on company size., Methods: Overall, 780 businesses in Wakayama Prefecture, Japan, were randomly selected from a Wakayama Occupational Health Support Center workplace list. Anonymous self-administered questionnaires were distributed by mail. The questionnaires comprised questions about the workplace, status of awareness of the Guidelines, comprehensive management of safety and health, considerations for working conditions, workers, workload reduction, work posture, work environment, and safety and health., Results: One hundred and seventy-one businesses (effective response rate: 21.9%) provided questionnaires with complete responses. For the Guidelines, 39.0% of small-sized (less than 50 employees) businesses answered, "never even heard of the name," while many medium-sized (50-99 employees) and large-sized (100 or more employees) businesses answered that they had heard of the name but did not exactly know about it (33.3% of medium-sized businesses and 47.8% of large-sized businesses). Regarding the system that subsidizes the expenses required for the improvement of a working environment for older workers to work safely and securely (hereinafter referred to as the subsidy system), many businesses of all sizes answered that they had "never even heard of the name." In the comprehensive management of safety and health, half of the businesses of all sizes had developed a system that made it easy to consult about the risk against occupational accidents of older workers. Regardless of size, more than half of businesses were able to consider working conditions and workers. However, there were only a few items where more than half of the businesses considered workload reduction, work posture, work environment, and safety and health, regardless of business size. It became clear that workplace improvement had not progressed very much., Conclusions: These results suggest that to promote workplace improvement that considers older workers, it is necessary to disseminate the Guidelines and proactively take on workplace improvement by utilizing the subsidy system.

Background: Autoimmune pulmonary alveolar proteinosis (APAP) and congenital/hereditary PAP were labeled intractable diseases in Japan in 2015. Since then, patients registered in the National Database of Designated Incurable Diseases (NDDID) who met certain requirements became eligible for medical subsidies. Epidemiological studies using recent data are needed for the development of management protocols for patients with PAP., Methods: We conducted the first nationwide study describing the epidemiology and characteristics of PAP using data for patients registered in the Japanese NDDID between 2015 and 2020. We focused on patient demographics, diagnosis, disease severity score (DSS), symptoms, test results, and treatment., Results: We identified 110 patients with PAP, among whom 96.4% had APAP/idiopathic PAP (IPAP). The median age was 58 years, with a slight male predominance. Most patients had a DSS ≥3 (64.5%) and reported symptoms (e.g., dyspnea on exertion). High-resolution computed tomography typically revealed ground glass opacity and crazy paving appearances. Pulmonary function was relatively preserved, except for carbon monoxide diffusing capacity. Only 27.4% of patients underwent therapeutic whole-lung lavage and/or bronchoalveolar lavage, while 25% required long-term oxygen therapy. Serum Krebs von den Lungen-6, surfactant protein D, and lactate dehydrogenase levels significantly and positively correlated with the DSS., Conclusions: Most patients registered in the NDDID have APAP/IPAP with a DSS ≥3, and about one-quarter require long-term oxygen therapy and infrequent lavages. Our results provide important details of the current prevalence and clinical practice related to APAP/IPAP with a DSS ≥3 in Japan., Competing Interests: Conflict of Interest K.M. has no conflict of interest. H.H. has no conflict of interest. Y.I. received honoraria for lecture fees and for serving as a steering committee board member from Boehringer Ingelheim (none of which are related to this manuscript). T. Suzuki. belongs to endowed departments sponsored by Nippon Boehringer Ingelheim Co., Ltd., and AstraZeneca K.K. T. Suda. has no conflict of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Objectives: This study investigated the occurrence rate of psychiatric disorders comorbid with gambling disorder, and their clinical significance in the severity of gambling disorder using a retrospective cross-sectional design., Methods: The medical records of 359 patients (men/women, 326/33; median age, 37.0 years) with gambling disorder as the primary disorder from 12 treatment facilities specializing in addiction (9 clinics and 3 hospitals) in Japan were studied. We investigated patients' comorbid psychiatric disorders, demographic and clinical characteristics, and the severity of gambling disorder based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition., Results: Of all patients, 58.3% had comorbidities (tobacco use disorder, 20.9%; alcohol use disorder, 13.9%; major depressive disorder, 13.1%; behavioral addictions, 13.1%; attention-deficit hyperactivity disorder, 6.1%; etc.). Statistical analysis indicated that as the number of comorbid psychiatric disorders increased, psychosocial problems also increased (e.g., proportion of adverse childhood experiences [ P < 0.001], and history of suicide attempts [ P = 0.009]). In the multivariable analysis, behavioral addictions ( β = 0.666; t = 3.151) were significantly associated with gambling disorder severity. Specifically, individuals with gambling disorder comorbid with behavioral addictions including kleptomania, excessive buying, and excessive sex-related behavior may present more severe gambling problems than those without behavioral addictions., Conclusions: Patients with gambling disorder should be carefully assessed for psychiatric comorbidities and interventions should reflect the individual diagnosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 American Society of Addiction Medicine.)

Objectives: The support from businesses to create a balance between work schedules and treatment regimens among employees suffering from illnesses, such as cancer and diabetes, seems to be insufficient. This study aimed to investigate efforts of businesses to support the balance of work schedules and treatment regimens among employees with illness, focusing on company size and to identify potential workplace improvements for such employees., Methods: Overall, 789 businesses in Wakayama Prefecture, Japan were randomly selected from a workplace list of the Wakayama Occupational Health Support Center. Anonymous questionnaires were distributed by mail. The questionnaires consisted of question items on workplace, current employees who had suffered or were suffering from cancer (employees with cancer), employees with illnesses (diseases such as cancer and diabetes), and support for businesses and employees., Results: Questionnaires with complete responses were collected from 187 businesses (response rate: 23.7%). The ratios of businesses where employees with cancer were engaged or had been engaged were 43.4% for small-sized (less than 50 employees), 70.9% for medium-sized (50-99 employees), and 83.1% for large-sized (100 and more employees) businesses. In all business sizes, the most common support in reinstatement or hiring employees with cancer was "absenteeism for treatment." The most common difficulty that occurred in the workplace due to the presence of employees with cancer was "the insufficient number of workers." The information from the attending physician, etc. necessary for deciding the reinstatement was mostly "the current health condition and physical strength." Additionally, in all business sizes, the most common support for employees with illness to balance work schedule and treatment regimens was "considering measures suitable to the situation such as hospital visits and physical condition." The most common challenge was "securing alternative personnel." The information from the attending physician, etc. necessary for deciding the reinstatement was "the current health condition and physical strength," similar to that for employees with cancer. More than 60% of the businesses of varying sizes reported being unaware of the work-treatment balance support coordinator., Conclusions: Considering measures suitable to the situation, such as hospital visits and physical condition, securing alternative personnel, and actively disseminating information regarding work-treatment balance support coordinators are recommended as workplace improvements for employees with illnesses.

To evaluate whether continuous subcutaneous insulin infusion attenuates the progression of diabetic complications, we retrospectively extracted data from 35 individuals who had developed type 1 diabetes mellitus aged ≤20 years and whose treatment had been changed from multiple daily injections to continuous subcutaneous insulin infusion. The annual changes in estimated glomerular filtration rate, urinary albumin excretion rate, carotid intima-media thickness and brachial-ankle pulse wave velocity during each treatment period were calculated. Although mean glycated hemoglobin under the continuous subcutaneous insulin infusion treatment was lower than that under the multiple daily injection treatment, there were no significant differences in annual changes in diabetic nephropathy and atherosclerosis between the two treatment periods. This pilot study showed that, in Japanese patients with juvenile-onset type 1 diabetes mellitus, there was no significant difference in the progression of diabetic nephropathy and atherosclerosis, at least in the early stage, between the two treatments., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown., Methods: Patients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: (1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and (2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups., Results: Among a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8-7.7 months) and overall survival (OS) (11.4 months, 95% CI 7.4-27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1-7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6-29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC., Conclusions: ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC., (© 2021. The Author(s).)

We conducted a nationwide retrospective analysis of 116 hepatitis B virus (HBV) surface antigen (HBsAg)-positive patients with diffuse large B-cell lymphoma (DLBCL) and 278 HBsAg-negative patients with DLBCL, as a control cohort, who received rituximab-containing regimens as an induction chemotherapy at 30 Japanese medical centers between January 2004 and December 2014. Hepatitis was defined as an absolute serum alanine aminotransferase (ALT) level of ≥100 U/L. HBV reactivation-related hepatitis was defined as hepatitis with an absolute serum HBV DNA level of ≥3.3 log IU/mL or an absolute increase of ≥2 log compared with the baseline value. HBsAg-positive patients were divided into three groups based on anti-HBV prophylactic therapy: no nucleos(t)ide analogue (non-NA, n = 9), lamivudine (LAM, n = 20), and entecavir (ETV, n = 87). The 4-year cumulative incidence (CI) of hepatitis in HBsAg-positive and HBsAg-negative patients was 21.1% and 14.6% (P = .081), respectively. The 4-year CI of HBV reactivation-related hepatitis was higher in HBsAg-positive patients than in HBsAg-negative patients (8.0% vs 0.4%; P < .001). Among HBsAg-positive patients, the 4-year CI of HBV reactivation-related hepatitis was the highest in the non-NA group (33.3%), followed by the LAM (15.0%) and ETV (3.8%) groups (P < .001). Of note, 3 non-NA patients (33%) and 1 LAM patient (5%) (but no ETV patients) died due to HBV hepatitis. Based on Cox multivariate analysis, HBsAg positivity was not associated with poor overall survival. Prophylactic use of ETV would reduce the occurrence of HBV reactivation-related hepatitis and mortality in HBsAg-positive DLBCL patients receiving rituximab-containing chemotherapy., (© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Context: T-cadherin (T-cad) is a glycosylphosphatidylinositol (GPI)-anchored cadherin that mediates adiponectin to induce exosome biogenesis and secretion, protect cardiovascular tissues, promote muscle regeneration, and stimulate therapeutic heart protection by transplanted mesenchymal stem cells. CDH13, the gene locus of T-cad, affects plasma adiponectin levels most strongly, in addition to affecting cardiovascular disease risk and glucose homeostasis. Recently, it has been suggested that T-cad exists in human serum, although the details are still unclear., Objective: To validate the existence of T-cad forms in human serum and investigate the association with clinical parameters of type 2 diabetes patients., Methods: Using newly developed monoclonal antibodies against T-cad, pooled human serum was analyzed, and novel T-cad enzyme-linked immunosorbent assays (ELISAs) were developed. The serum T-cad concentrations of 183 Japanese type 2 diabetes patients were measured in a cross-sectional observational study. The main outcome measure was the existence of soluble T-cad in human serum., Results: There were 3 forms of soluble T-cad: a 130-kDa form with a prodomain, a 100-kDa mature form, and a 30-kDa prodomain in human serum. Using newly developed ELISAs to measure them simultaneously, we found that the 130-kDa form of T-cad positively correlated with plasma adiponectin (r = 0.28, P < .001), although a physiological interaction with adiponectin was not observed in serum. The unique 30-kDa prodomain was associated with several clinical parameters in diabetes patients., Conclusion: We identified 3 novel forms of soluble T-cad. Their importance as disease markers and/or biomarkers of adiponectin function and the possible bioactivity of the respective molecules require further investigation., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: Hangeshashinto is a Japanese Kampo medicine applied for the treatment of oral mucositis and gastroenteritis. Hangeshashinto exhibits broad-spectrum antibacterial activity and suppresses prostaglandin (PG)E2 production in the mucosa and has the ability to improve the inflammatory condition. In addition to these effects, because cAMP, a composition of Hangeshashinto, facilitates ciliary beat, Hangeshashinto could also improve the physiological function of the nasal mucosa, consist of ciliated epithelium, but details were unknown., Methods: This study was aimed to investigate the effects of Hangeshashinto on the nasal mucosa. Healthy nasal mucosal sections were collected from the nasal septum of ten Japanese white rabbits, placed in a collagen dish for tissue culture, and rinsed with two different concentrations of Hangeshashinto solution (1.0%, n = 10 and 2.5%, n = 10) and cAMP solution (50µM, n=10 and 100 µM, n=10) or saline (control, n = 10). Ciliary beat frequency (CBF) as a physiological function of the nasal mucosa was recorded at 1, 3 and 7 days after rinsing, and histological evaluation of epithelial damage was performed at 7 days after rinsing., Results: CBF in the 1.0% but not in the 2.5% Hangeshashinto group, increased at 3 and 7 days compared with that in the control group (p < 0.05). This trend was also observed in the CBF in the 100 µM cAMP group, significant difference was not observed between the CBF of the 1.0% Hangeshashinto group and the 100 µM cAMP group at 1, 3 and 7 days after rinsing (p > 0.05). Histological score only in the 2.5% Hangeshashinto group was lower than that in the control group (p < 0.05), while a significant decline was not observed in the other groups compared to that in the control group (p > 0.05)., Conclusion: Our results suggest that 1.0% Hangeshashinto solution facilitates the physiological function of the nasal mucosa by promoting ciliary functions without histological damage of cilia epithelium. When applied with the appropriate concentration, Hangeshashinto could have ability to improve the physiological functions of the nasal mucosal epithelium., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2020. Published by Elsevier B.V.)

Amiodarone is an effective antiarrhythmic drug. However, it is associated with changes in thyroid function in euthyroid patients due to its high iodine content and intrinsic drug effects. Studies have been conducted in iodine-deficient and iodine-sufficient countries; however, data from countries with excessive iodine intake are lacking. Thus, this study aimed to evaluate the effect of long-term amiodarone treatment on thyroid function in euthyroid Japanese patients. Japanese adults aged ≥18 years who were treated with amiodarone for at least 90 consecutive days were included in this retrospective chart review. Patients with abnormal thyroid function test results at baseline were excluded. Serial changes in thyroid function tests at baseline and at days 30, 90, 180, 270, and 360 were analyzed using a mixed-effects model for repeated measures. In total, 46 patients with a mean age of 63.7 years were evaluated. The mean TSH level significantly increased from 1.62 μIU/mL at baseline to 3.43, 2.75, 2.84, 2.78, and 2.65 μIU/mL at days 30, 90, 180, 270, and 360, respectively. The mean free T 4 level significantly increased from 1.3 ng/dL at baseline to 1.4, 1.5, 1.5, 1.5, and 1.5 ng/dL at days 30, 90, 180, 270, and 360, respectively. The mean free T 3 level significantly decreased from 2.8 pg/mL at baseline to 2.4, 2.3, 2.3, 2.4, and 2.4 pg/mL at days 30, 90, 180, 270, and 360, respectively. In conclusion, significant changes in thyroid function persisted not only in the acute phase but also in the chronic phase of long-term amiodarone treatment.

Brachial-ankle pulse wave velocity (baPWV) has been used as a simple and convenient method of evaluating arterial stiffness and is considered useful for screening subclinical vascular damage in primary care settings and in large populations. The aim of this study was to determine the reference values of baPWV in adolescents based on age and sex to evaluate and classify vascular abnormalities in this age population. Noninvasive baPWV measurements using an oscillometric device were carried out in 5936 participants aged 12-18 years who had no history of syndromic obesity, hypertension, dyslipidemia, diabetes mellitus, or renal disease. Of these, we extracted data from 4524 healthy adolescents free from atherosclerotic risk factors and constructed sex-specific reference percentiles normalized to age using the LMS method. The baPWV increased with age and was significantly higher in males than in females. Multivariate regression analysis demonstrated that age, body mass index, and blood pressure were the major determinants of baPWV for both males and females. Among a sample of 3825 adolescents, including individuals with risk factors, the prevalence of central obesity, raised blood pressure, raised triglycerides, reduced high-density lipoprotein cholesterol, and impaired fasting glycemia significantly increased along with the standardized baPWV z-score level. In addition, there was a graded nature regarding the association between the baPWV z-score and the clustering number of the metabolic syndrome components. These results suggest that the proposed reference values of baPWV could help classify vascular abnormalities of adolescents caused by the presence of risk factors and thereby contribute to determining individuals with cardiovascular risk in this age population.

Recent progress in research on glucagon and α-cells highlights their pathophysiological roles in diabetes. We previously showed that plasma glucagon levels measured by newly developed enzyme-linked immunosorbent assay were dysregulated in patients with type 1 diabetes with respect to plasma glucose levels, suggesting dysregulated secretion. In the current study, the annual change in plasma glucagon levels was assessed in these same patients. We found that the plasma glucagon levels in the 66 Japanese patients involved in the study were significantly correlated between both years. In addition, they were significantly associated with serum blood urea nitrogen levels in a multivariate linear regression analysis, as reported in our previous study. The statistical correlation in glucagon levels between annual checkups and the sustained significant correlation between glucagon and blood urea nitrogen suggest a constant dysregulation of glucagon in association with altered amino acid metabolism in patients with type 1 diabetes., (© 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

We examined the associations of obesity and high salt intake with blood pressure (BP) in a cross-sectional sample of 1679 healthy Japanese adolescents (827 females and 852 males) aged 12-18 years (mean age: 14.9 years) who had no history of treatment for hypertension, diabetes mellitus, or renal disease. Brachial arterial BP of the subject was measured at the left arm using a digital BP monitor with an appropriate cuff size. The weight status was evaluated by body mass index (BMI), and obesity was determined according to the age- and sex-specific cut-off values for adolescents. All subjects were interviewed by dietitians using a food frequency questionnaire to obtain data on their average daily salt intake. In the study subjects, obesity and high salt intake were associated with a significantly increased BP except for diastolic BP in females. In multiple regression analyses, both BMI (z-score) and salt intake were found to be major determinants of systolic BP and diastolic BP after adjustment for potential confounders, including age, sex, and serum lipid and glucose parameters. The association between salt intake and BP values was more pronounced among individuals with obesity than among those with normal weight. These results suggest that high salt intake is associated with BP elevation in healthy adolescents, and the association may become stronger by the presence or severity of obesity.

Pancreas transplantation (PTx) has been performed worldwide for patients with type 1 diabetes accompanied with end-stage renal disease or uncontrollable glycemic fluctuation. Nevertheless, risk factors of posttransplant glucose intolerance, which is responsible for progress of diabetic complications, remains unclear, especially in cases without pancreatic graft function loss. Therefore, this study was conducted to search for predictive factors of future glucose tolerance in PTx recipients without pancreatic graft function loss. Subjects were selected from among 41 Japanese patients with type 1 diabetes who received PTx between 2000 and 2016 in Osaka University Hospital, and 24 subjects free from rejections and thromboses were analyzed. Several examinations to evaluate insulin secretion and insulin sensitivity within 6 months after transplantation (initial examination) were performed. Glucose tolerance was evaluated by 120-minute post-load plasma glucose level during 75-g oral glucose tolerance tests (OGTT), referred to as PG OGTT 120, at the initial examination and between 1 year and 2 years posttransplantation (maintenance period). The initial examination factors that were correlated with PG OGTT 120 in the maintenance period were PG OGTT 120 [r = 0.52 (p = 0.01)], insulinogenic index [r = -0.65 (p < 0.01)], and the ratio of incremental area under the curve of insulin to that of plasma glucose (iAUCR) calculated from data of OGTT [r = -0.65 (p < 0.01)]. Insulinogenic index [β = -0.28 (p = 0.02)] and iAUCR [β = -0.29 (p = 0.02)] were still significantly correlated with PG OGTT 120 in the maintenance period after adjustment for PG OGTT 120 at the initial examination. In conclusion, insulinogenic index and iAUCR from OGTT performed in the early posttransplantation period were predictive factors of future glucose intolerance.

The present study describes the variation in lipid components from 15 species of seaweeds belonging to the Chlorophyta, Ochrophyta, and Rhodophyta phyla collected in tropical (Indonesia) and temperate (Japan) areas. Analyses were performed of multiple components, including chlorophylls, carotenoids, n-3 and n-6 polyunsaturated fatty acids (PUFAs), and alpha tocopherol (α-Toc). Chlorophyll (Chl) and carotenoid contents varied among phyla, but not with the sampling location. Chl a and b were the major chlorophylls in Chlorophyta. Chl a and Chl c were the main chlorophylls in Ochrophyta, while Chl a was the dominant chlorophylls in Rhodophyta. β-Carotene and fucoxanthin were detected as major seaweed carotenoids. The former was present in all species in a variety of ranges, while the latter was mainly found in Ochrophyta and in small quantities in Rhodophyta, but not in Chlorophyta. The total lipids (TL) content and fatty acids composition were strongly affected by sampling location. The TL and n-3 PUFAs levels tended to be higher in temperate seaweeds compared with those in tropical seaweeds. The major n-3 PUFAs in different phyla, namely, eicosapentaenoic acid (EPA) and stearidonic acid (SDA) in Ochrophyta, α-linolenic acid (ALA) and SDA in Chlorophyta, and EPA in Rhodophyta, accumulated in temperate seaweeds. Chlorophylls, their derivatives, and carotenoids are known to have health benefits, such as antioxidant activities, while n-3 PUFAs are known to be essential nutrients that positively influence human nutrition and health. Therefore, seaweed lipids could be used as a source of ingredients with health benefits for functional foods and nutraceuticals., Competing Interests: The authors declare no conflict of interest.

The present study investigated histological subtypes of lymphoma in patients newly diagnosed with malignant lymphoma in the human T-cell leukemia virus type 1 (HTLV-1) endemic area of Japan, and further analyzed the clinicopathological features and clinical outcomes of patients with primary sinonasal lymphoma. We retrospectively examined 151 patients aged 18-90 years in Fukuoka, Japan. Subtypes of lymphoma were determined according to the WHO classification. Among the 151 patients, 104 were diagnosed with malignant lymphoma, including 96 at the time of initial diagnosis. Ninety-two of the 96 lymphomas (96%) were non-Hodgkin lymphoma. Mature B-cell neoplasms comprised 78% (n = 75). Primary lymphoma of the sinonasal cavity was found in six patients (6%). The histological subtype of sinonasal lymphoma was diffuse large B-cell lymphoma (DLBCL) in all six tumors. Furthermore, overall survival was significantly different among three distinct DLBCL patient groups, including primary sinonasal lymphoma patients (p = 0.0016; 3-year overall survival: sinonasal DLBCL group, 53%; DLBCL of the CNS group, 0%; other DLBCL group, 83%). Our study suggests that primary DLBCL of the sinonasal tract is a distinct disease entity of DLBCL.

Objectives: The support from businesses to create a balance between work schedules and treatment regimens among employees suffering from cancer seems to be insufficient. The aims of this study were to investigate efforts to find a balance between work schedules and treatment regimens among cancer patients focusing on company size and to identify potential workplace improvements for these employees., Methods: Seven hundred and seventy businesses in Wakayama Prefecture, Japan, were randomly selected from a workplace list consisting of businesses that had received support from either the Wakayama Occupational Health Support Center or the Regional Occupational Health Center. An anonymous questionnaire was distributed by mail. It consisted of question items on the workplace, support systems, current employees who had suffered or were suffering from cancer (cancer patient employees), their reinstatement, promoting reinstatement and employment of cancer patient employees, and job description of respondents., Results: A completed questionnaire was collected from 188 businesses (response rate: 24.4%). Among small-sized businesses (less than 50 employees), 55% carried out or recommended consultation for cancer screening. This ratio was higher than that of medium-sized businesses (50-99 employees) or large-sized businesses (100 or more employees). Approximately 20% of the businesses had a support system for employees who were working while undergoing cancer treatment, and more small-sized businesses had a system of annual paid leave by the hour than the medium-sized or large-sized businesses. Among the small-sized businesses, 51% had a system of sick leave for regular employees, but this ratio was significantly lower than that among the large-sized businesses. Approximately 20% of businesses had established a system of paid sick leave for regular employees. Reinstatement of employment was possible in over 80% of the businesses. The condition for reinstatement that was most frequently stipulated was that the employee's doctor had provided a medical certificate stating that the employee was able to return to work. However, among small-sized businesses, the condition that colleagues at the workplace were willing to accept him/her was more frequently stipulated., Conclusions: Cancer screening, annual paid leave by the hour, and institutionalization of sick leave are recommended as workplace improvements for cancer patient employees.

Background and Objective: Acute exacerbation (AE) is a leading cause of death in patients with idiopathic pulmonary fibrosis (IPF). Although optimal treatment for AE-IPF remains unclear, high-dose corticosteroids (CS) with/without immunosuppressants, including intravenous cyclophosphamide (IVCY), are often used as empirical therapy. However, the survival benefit of adding IVCY to CS therapy is unknown. We investigated the efficacy of this therapy in patients with AE-IPF., Methods: Overall, 102 consecutive patients with IPF with a first idiopathic AE were included. Post-AE survival rates and treatment safety were retrospectively assessed. Efficacy of CS + IVCY therapy for the first AE was compared with that of CS monotherapy using a propensity score-matched analysis., Results: The post-AE 90-day survival rate of the entire cohort was 64.7%. On the basis of the propensity scores, 26 matched patient pairs were made. Characteristics of matched patients with AE-IPF treated with CS (matched CS group) and those with CS + IVCY (matched CS + IVCY group) were well balanced. No significant between-group differences were observed in post-AE 90-day survival rates (84.6% vs 76.9%; P = 0.70), cumulative survival rates (P = 0.57 by log-rank test) or incidence of adverse events ≥ CTCAE (Common Terminology Criteria for Adverse Events) v5.0 grade 3 (61.5% vs 65.4%; P = 1.00)., Conclusion: The propensity score-matched analysis demonstrated that compared with CS monotherapy, CS + IVCY therapy did not significantly improve post-AE survival in patients with AE-IPF. Further studies are warranted to assess the efficacy of CS + IVCY therapy for AE-IPF., (© 2019 Asian Pacific Society of Respirology.)

Background: Muscle wasting, common and progressive in uremic patients, is associated with a high probability for morbidity, lower health-related quality of life (HRQOL), and mortality. However, exercise tolerance in peritoneal dialysis (PD) patients has not been fully elucidated. The aim of this study was to evaluate exercise capacity, its determinants, and its association with HRQOL in PD patients., Methods: Outpatients treated with PD at Keio University Hospital from December 2016 to March 2018 were included in this single-center cross-sectional observational study. Exercise capacity was assessed by incremental shuttle walking test (ISWT) and handgrip and quadriceps strength. In addition to evaluation of PD-related parameters, HRQOL was assessed by the Kidney Disease Quality of Life-Short Form questionnaire., Results: Among the 50 recruited PD outpatients, age and PD vintage were 63.8 ± 9.6 and 3.8 ± 2.8 years, respectively. Physical examination revealed ISWT of 312.0 ± 138.2 m, handgrip strength of 27.5 ± 6.9 kg, and quadriceps strength of 23.3 ± 10.0 kg. Multivariate analysis showed that younger age and male sex were significantly associated with higher ISWT and handgrip and quadriceps strength. Skeletal mass index (SMI) remained a significant predictor of handgrip and quadriceps strength. Moreover, only ISWT was strongly correlated with higher HRQOL scores, including physical, mental, and kidney-specific domains, even after adjustment for age and sex., Conclusions: Exercise tolerance in PD patients was partially determined by age, sex, and SMI. Moreover, this is the first study to demonstrate the strong relationship between aerobic capacity and HRQOL in PD patients., (Copyright © 2019 International Society for Peritoneal Dialysis.)

Currently, the clinical dynamics of glucagon need to be revised based on previous data obtained from conventional glucagon radioimmunoassays. In the present study, we evaluated plasma glucagon levels in type 1 diabetes patients using a newly-developed sandwich enzyme-linked immunosorbent assay, and its association with clinical parameters and markers of diabetes complications were statistically assessed. The plasma glucagon level in 77 Japanese type 1 diabetes patients was 28.1 ± 17.7 pg/mL, and comparable with that reported previously for type 2 diabetes patients. However, the values were widely spread and did not correlate with plasma glucose values. Additionally, the average glucagon levels in patients in a hypoglycemic state (glucose level <80 mg/dL) did not increase (21.7 ± 12.2 pg/mL). The average glucagon level of patients experiencing hypoglycemia unawareness was significantly lower. Plasma glucagon levels evaluated using the new enzyme-linked immunosorbent assay were dysregulated in type 1 diabetes patients in respect to plasma glucose levels, suggesting dysregulation of secretion., (© 2018 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: We sought to investigate the contextual effect of workplace bullying on subsequent individual psychological distress and intention to leave., Methods: A longitudinal study was conducted among 3142 Japanese employees in the public sector. Both the baseline and follow-up questionnaires inquired about demographic and occupational characteristics, workplace bullying, psychological distress, and intention to leave., Results: The results of three-level (individual-division-department) multilevel analyses revealed that division-level workplace bullying was associated with increased individual-level psychological distress after adjustment for individual experience of workplace bullying, while the association between individual experience of bullying and psychological distress was not statistically significant in the same model., Conclusion: The results of the current study suggest that the presence of bullying in the workplace can have a detrimental effect on employees' mental health even if they are not personally victimized.

Background: We evaluated the efficacy and safety of a modified FOLFIRINOX regimen for chemotherapy-naïve patients with metastatic pancreatic cancer., Methods: Patients with untreated metastatic pancreatic cancer (MPC) received modified FOLFIRINOX (intravenous oxaliplatin 85 mg/m 2 , irinotecan 150 mg/m 2 , 5-FU infusion 2400 mg/m 2 over 46 h, no bolus 5-FU). The primary endpoints were overall survival and the incidence of grade 3 or higher neutropenia. No patients received prophylactic pegfilgrastim., Results: Sixty-nine pts. were enrolled from 39 institutions in Japan. The median overall survival was 11.2 months [95% confidence interval (CI) 9.0-]. The median progression-free survival was 5.5 months (95% CI 4.1-6.7). The response rate was 37.7% (95% CI 26.3-50.2), and the disease control rate was 78.3% (95% CI 66.7-87.3). The incidence of grade 3 or higher neutropenia was 47.8%. Serious adverse events occurred in six patients (8.7%). All AE proportions were less than those in the previous Japanese full-dose phase II study. One patient died due to interstitial pneumonia related to treatment., Conclusion: This is the first prospective study of modified FOLFIRINOX in Asia. Modified FOLFIRINOX in this study has an improved safety profile with maintained efficacy in MPC without prophylactic pegfilgrastim.

Background and purpose Neurological deterioration in acute penetrating artery territory infarction is unpredictable and associated with unfavorable clinical outcomes. The aim of this prospective study was to clarify the cause of neurological worsening and predict clinical outcomes using blood biomarkers. Methods Eight Japanese stroke centers participated. Blood samples were obtained within 24 h (the first sampling) and on day 7 in hospital (the second sampling) in patients with penetrating artery territory infarction, arriving within two days of stroke onset. Symptomatic worsening was defined as a minimum increase of one point on the National Institutes of Health Stroke Scale. Poor outcome was defined as a modified Rankin Scale score of ≥3 at 90 days after ictus. Results Of the 89 patients, 25 (28%) had symptomatic worsening, and 25 (28%) had a poor outcome. Although tumor necrosis factor-alpha, high-sensitivity C-reactive protein levels were significantly increased in both groups at the second sampling, soluble lectin-like oxidized low-density lipoprotein receptor-1, CD40 ligand, and pro-adrenomedullin levels were significantly increased and ADAMTS13 activity was decreased in symptomatic worsening patients ( p < 0.05 for all). After multivariate adjustment, a low number of CD34+ cells at the first sampling was an independent predictor of poor outcome (odds ratio, 0.20; 95% confidence interval, 0.04-0.74, p = 0.011, per 1 cell/µl increase). Conclusions Blood biomarkers associated with atherosclerotic processes seem to be an indication for symptomatic worsening, and the number of CD34+ cells may help to predict three-month functional outcome in patients with penetrating artery territory infarction.

Eelgrass beds are an important source of primary production in coastal ecosystems. Understanding seasonal variation in the abundance and distribution of eelgrass is important for conservation, and the objectives of this study were to 1) monitor seasonal variation in eelgrass beds using an acoustic monitoring method (Quantitative echo sounder) and 2) broadly quantify the carbon circulation function. We obtained acoustic data of eelgrass beds in coastal areas north and east of Ikunojima Island. Surveys were conducted nine times over the 3-year period from 2011 to 2013 in order to monitor seasonal variation. Acoustic data were obtained and used to estimate the spatial distribution of eelgrass by geostatistical methods. To determine supporting services, we determined carbon sink and carbon fixation by eelgrass beds using data from the National Research Institute of Fisheries and Environment of Inland Sea (2011). The height and distribution of eelgrass beds were at a maximum in May and at a minimum in November of each year. Distribution trends were different between the north and east areas. Supporting services showed the same patterns throughout the year. The area of distribution was considered to be coincident with the life history of eelgrass. Distribution differed by area and changed yearly due to the effects of bottom characteristics and wind direction. Quantifying the supporting services of eelgrass beds was shown to be useful for managing the conservation of coastal ecosystems.

Recent studies in streams and ponds have demonstrated that the distribution and biomass of aquatic organisms can be estimated by detection and quantification of environmental DNA (eDNA). In more open systems such as seas, it is not evident whether eDNA can represent the distribution and biomass of aquatic organisms because various environmental factors (e.g., water flow) are expected to affect eDNA distribution and concentration. To test the relationships between the distribution of fish and eDNA, we conducted a grid survey in Maizuru Bay, Sea of Japan, and sampled surface and bottom waters while monitoring biomass of the Japanese jack mackerel (Trachurus japonicus) using echo sounder technology. A linear model showed a high R(2) value (0.665) without outlier data points, and the association between estimated eDNA concentrations from the surface water samples and echo intensity was significantly positive, suggesting that the estimated spatial variation in eDNA concentration can reflect the local biomass of the jack mackerel. We also found that a best-fit model included echo intensity obtained within 10-150 m from water sampling sites, indicating that the estimated eDNA concentration most likely reflects fish biomass within 150 m in the bay. Although eDNA from a wholesale fish market partially affected eDNA concentration, we conclude that eDNA generally provides a 'snapshot' of fish distribution and biomass in a large area. Further studies in which dynamics of eDNA under field conditions (e.g., patterns of release, degradation, and diffusion of eDNA) are taken into account will provide a better estimate of fish distribution and biomass based on eDNA.

Purpose: Orteronel (TAK-700) is a non-steroidal, selective, reversible inhibitor of 17,20-lyase. We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC)., Methods: We conducted a phase 1 study in men with progressive and chemotherapy-naïve CRPC. Patients received orteronel orally at doses of 200-400 mg twice daily (BID) with or without oral prednisolone (5 mg BID). Dose-limiting toxicity (DLT) was assessed during Cycle 1 (28 days). Patients could continue study treatment until any of criteria for treatment discontinuation were met. Gonadotropin-releasing hormone therapy was continued in patients without prior orchidectomy., Results: Fifteen patients were enrolled and administered at least one dose of orteronel. No DLTs were reported during Cycle 1 in this study. Adverse events (AEs) were reported in all 15 patients. Most common AEs (>30%) were hyperlipasemia (47%), hyperamylasemia (40%), and constipation (33%). Acute pancreatitis (Grades 2 and 3) and pancreatitis (Grade 1) were complicated in three patients during the study. Dose-dependent increase in plasma orteronel concentrations was indicated over the 200-400 mg BID dose range. Prednisolone coadministered did not alter PK of orteronel. Serum testosterone was rapidly suppressed below the lower limit of quantification across all doses. Of 15 subjects, 13 achieved at least a 50% reduction from baseline in prostate-specific antigen., Conclusions: Orteronel at doses up to 400 mg BID was tolerable in Japanese CRPC patients. The present results support further evaluation of orteronel with or without prednisolone.

Objectives: Medications or lifestyle changes to prevent or improve hypertension often press considerable efforts on patients suffering from mild hypertension. Capsules including Umezu polyphenols (UP), polyphenols in Japanese plums, may help them to control their blood pressure (BP). The aim of this study is to evaluate the effectiveness of UP on BP and its safety., Methods: A total of 15 healthy workers without antihypertensive medication who had some concerns about their BP, preferably normal-high BP or hypertension level 1, were randomized in a double-blind manner into UP ingesting and placebo groups. Each subject was instructed to take four capsules daily for 12 weeks (daily UP dose, 800 mg for the UP ingesting group; and 0 mg for the placebo group). These subjects were followed for 12 weeks, and their BP both at home and at the examination site, as well as self-perceived quality-of-life outcomes and possible side effects, was monitored during that period. Group × time interactions on BP changes were examined., Results: All of the 15 subjects completed the 12-week intervention trial. The BP changes did not significantly differ between the UP ingesting and placebo groups, neither at the examination site nor at home. But during the study period, no adverse effects were observed., Conclusions: No remarkable effect of UP on BP was observed. However, a higher dose of UP was confirmed safe and high in adherence in this 12-week randomized controlled trial. Its effect on BP and other outcomes shall be confirmed in a larger sample.

Carotenoids are a class of naturally occurring pigment, carrying out important biological functions in photosynthesis and involved in environmental responses including nutrition in organisms. Saproxanthin and myxol, which have monocyclic carotenoids with a γ-carotene skeleton, have been reported to show a stronger antioxidant activity than those with β-carotene and zeaxanthin. In this research, a yellow-orange bacterium of strain 11shimoA1 (JCM19538) was isolated from a seaweed collected at Nabeta Bay (Shizuoka, Japan). The 16S rRNA gene sequence of strain 11shimoA1 revealed more than 99.99 % similarity with those of Jejuia pallidilutea strains in the family Flavobacteriaceae. Strain 11shimoA1 synthesized two types of carotenoids. One of them was (3R, 3'R)-zeaxanthin with dicyclic structure and another was identified as (3R, 2'S)-2'-isopentenylsaproxanthin, a novel monocyclic carotenoid with pentenyl residue at C-2' position of saproxanthin, using FAB-MS, (1)H NMR, and CD analyses. Culturing strain 11shimoA1 in an alkaline medium at pH 9.2 resulted in a markedly increased in production of 2'-isopentenylsaproxanthin per dry cell weight, but a decreased in zeaxanthin production as compared to their respective production levels in medium with pH 7.0. These carotenoids are likely to play some roles in the adaptation of the bacterium to the environmental conditions.

Objectives: The aim of this study was to investigate the clinical characteristics of HAVS in a tropical environment in comparison with a temperate environment., Methods: We conducted a series medical examinations among the forestry, construction and automobile industry workers in Malaysia adopting the compulsory medical examination procedure used by Wakayama Medical University for Japanese vibratory tools workers. We matched the duration of vibration exposure and compared our results against the Japanese workers. We also compared the results of the Malaysian tree fellers against a group of symptomatic Japanese tree fellers diagnosed with HAVS., Results: Malaysian subjects reported a similar prevalence of finger tingling, numbness and dullness (Malaysian=25.0%, Japanese=21.5%, p=0.444) but had a lower finger skin temperature (FST) and higher vibrotactile perception threshold (VPT) values as compared with the Japanese workers. No white finger was reported in Malaysian subjects. The FST and VPT of the Malaysian tree fellers were at least as bad as the Japanese tree fellers despite a shorter duration (mean difference=20.12 years, 95%CI=14.50, 25.40) of vibration exposure., Conclusions: Although the vascular disorder does not manifest clinically in the tropical environment, the severity of HAVS can be as bad as in the temperate environment with predominantly neurological disorder. Hence, it is essential to formulate national legislation for the control of the occupational vibration exposure.

Objectives: Compared to other public employees, police officers have higher absence rates due to heart diseases, and ischemic heart disease (IHD) is one of the most frequent causes of death in their occupational life. The aim of this study was to investigate the prevalence of the risk factors for IHD among police officers and to examine its association with working conditions and lifestyles., Methods: First, 58 male police officers who developed IHD from 1996 to 2011 and 116 age- and rank-matched controls who were free from cerebro- and cardiovascular diseases were compared with respect to the prevalence of traditional risk factors five years before the onset of IHD. Then, the prevalence of IHD risk factors, and the frequency of metabolic syndrome (MetS) by age group, working condition and lifestyle were investigated in a cross-sectional survey of data of 1,539 male police officers and 153 male office workers in a prefectural police force., Results: In the case control study, the IHD cases had significantly higher prevalences of hypertension (p<0.001), hyper-LDL-cholesterolemia (p<0.05), glucose intolerance (p<0.05), and hyperuricemia (p<0.05) before the onset of IHD. Multiple logistic regression analysis revealed that hypertension (odds ratio [95% confidence interval] : 3.96 [1.82-8.59]), glucose intolerance (3.28 [1.34-8.03]), hypo-HDL-cholesterolemia (2.26 [1.03-4.97]), and hyper-LDL-cholesterolemia (2.18 [1.03-4.61]) were independently associated with the development of IHD (model chi-square, p<0.001; correct classification rate, 77.0%). In the cross sectional analyses, among the police officers, abdominal obesity (waist circumference of ≥ 85 cm) was significantly more frequent (57.3% vs. 35.3%, p<0.001) and the prevalence of dyslipidemia and glucose intolerance increased with age more remarkably than in the general office workers. In the age-group of 45-59 years, the clustering number of risk factors in individuals (1.8 vs. 1.4, p<0.01) and the frequency of MetS (25.0 vs. 15.5, p<0.1) were greater in the police officers than the office workers. Among the police officers, subjects with MetS had significantly higher rates of shift work (33.6% vs. 25.4%, p<0.01), lack of sound sleep (42.5% vs. 33.7%, p<0.01), and heavy drinking (12.8 vs. 6.3%, p<0.01) than those without MetS., Conclusions: In this study, the development of IHD in police officers was significantly associated with traditional risk factors, especially with hypertension, dyslipidemia and glucose intolerance. The increase with age of the prevalence of IHD risk factors and the frequency of MetS were greater in police officers than office workers. Irregular working conditions, such as shift work, long working time, and unfavorable lifestyles, e.g. alcohol drinking and poor sleeping conditions, may influence the higher prevalence of risk factors for IHD in police officers.

Objectives: The purpose of this study was to determine the factors related to changes in the burden of caregivers who look after the elderly at home, as well as factors related to the institutionalization of the elderly who require care. The types of care services associated with reducing caregivers' burden and continuing in-home care were also studied., Methods: The study subjects were adults aged ≥65 years who used the services of in-home care management centres located in Osaka Prefecture, Japan, and their caregivers. This 2-year longitudinal study began in October 2007, with a total of three surveys undertaken once a year. The survey methods included self-administered questionnaires and the review of clinical records., Results: Dementia and its accompanying behavioural disturbances were found to be significantly related to the increased burden of caregivers and the institutionalization of those requiring care. A significantly higher proportion of caregivers with an increasing burden or those who maintained a high level of burden used day care services compared to those in the other groups., Conclusion: Preventive intervention against dementia and its accompanying behavioural disturbances should be considered in the day care service to reduce caregivers' burden and to decrease institutionalization.

Objectives: The purpose of this study was to clarify the occurrence of Raynaud's phenomenon among workers using an impact wrench for a long time., Methods: The subjects were 704 workers regularly using an impact wrench and taking special medical examinations for vibration syndrome from 1981 to 2008. Raynaud's phenomenon was observed in 39 subjects during the observation period., Results: The mean operating years at the occurrence of Raynaud's phenomenon was 25.5 ± 8.3 (standard deviation) yr. The mean total operating time (geometric average) at the occurrence of Raynaud's phenomenon was 11,689 h. By the person-year method, the incidence rate of Raynaud's phenomenon was 6.27 persons per 1,000 person-years. The estimated risk of developing Raynaud's phenomenon did not increase until 12 years after starting to operate an impact wrench but increased exponentially after that. The vibration level of an impact wrench (from 4.9 m/s(2) to 22.6 m/s(2)) exceeded the occupational exposure limit value (4.9 m/s(2)). Various countermeasures, such as introducing automatically apparatus and keeping the working environment warm to protect from cold exposure, were taken at the factory., Conclusions: These findings showed that the rate of occurrence of Raynaud's phenomenon was not high, although the vibration level of the impact wrench was high. This may result from various countermeasures to prevent the occurrence of Raynaud's phenomenon. A long period of exposure to vibration had the potential to lead to the occurrence of Raynaud's phenomenon even under various countermeasures.

Japanese edible brown seaweeds, Eisenia bicyclis (Arame), Kjellmaniella crassifolia (Gagome), Alaria crassifolia (Chigaiso), Sargassum horneri (Akamoku), and Cystoseira hakodatensis (Uganomoku) were assayed for total phenolic content (TPC), fucoxanthin content, radical scavenging activities (DPPH, peroxyl radical, ABTS, and nitric oxide), and antioxidant activity in a liposome system. Among the solvents used for extraction, methanol was the most effective to extract total phenolics (TPC) from brown seaweeds. Among 5 kinds of brown seaweeds analyzed, methanol extract from C. hakodatensis was the best source for antioxidants. The high antioxidant activity of the extract was based not only on the high content of phenolics, but on the presence of fucoxanthin. No significant correlation (P > 0.05) was observed between TPC per gram extract with DPPH radical scavenging activity of the methanol extracts. These observed discrepancy would be due to structural variations in the phenolic compounds, and different levels of fucoxanthin in the extracts. The present study also demonstrated the synergy in the antioxidant activity of the combination of brown seaweed phenolics and fucoxanthin.

The study identified seasonal habitat use by endangered adult Sakhalin taimen Hucho perryi and the environmental characteristics of their habitat (water depth, amount of riparian forest and sinuosity). Fifteen adult H. perryi with acoustic tags were tracked by towing an acoustic receiver with a canoe in the Bekanbeushi River system in eastern Hokkaido Island, Japan, during each month from late April to late November 2008. Individuals mainly used midstream (shallower than downstream) habitats in all seasons. These locations were generally characterized by relatively dense riparian forests and high sinuosity, indicating the presence of pools. In spring, individuals used habitats with less riparian forest cover compared to mean value of the river channel. From spring to autumn, adult H. perryi selected limnologically complex habitats with meandering channels. From summer to autumn, individuals selected habitats with more riparian forest cover. The inverse relationship between H. perryi detection and riparian forest area in spring was a result of seasonal defoliation in deciduous riparian forests., (© 2010 The Authors. Journal of Fish Biology © 2010 The Fisheries Society of the British Isles.)

Although maternal smoking during pregnancy has been shown to be associated with an increased risk of offspring attention-deficit/hyperactivity disorder (ADHD) in Western countries, there is no empirical evidence in non-Caucasian. Purpose of the present study is to examine the relationship between maternal smoking during pregnancy and offspring ADHD in Japanese population. A case-control study design was adopted. A total of 90 pairs of children with ADHD and mothers as well as 270 corresponding control pairs were recruited throughout the study period. A psychiatrist interviewed all the mothers of children with ADHD and control children and elicited information regarding their lifestyles during pregnancy, including active and passive smoking or drinking habits, as well as psychosocial and perinatal factors. Diagnosis of ADHD was made by each physician in charge according to DSM-IV diagnostic criteria. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) with adjustments for other possible confounding factors. Maternal active smoking during pregnancy was associated with an approximately twofold increased risk of offspring ADHD, even after adjusting for socioeconomic and perinatal confounding factors (OR 1.8 95% CI 0.9-3.6). However, the association was obviously attenuated when factors regarding parental psychopathological vulnerability were controlled (OR 1.3 95% CI 0.6-2.9). On the other hand, maternal passive smoking during pregnancy failed to show any material association with ADHD. These results suggested that a significant part of the association between maternal smoking during pregnancy, and ADHD might be explained by genetic factors including parental psychopathological vulnerability., (© Springer-Verlag 2009)

Objective: To investigate the relationships of self-reported physical health, social and spiritual satisfactions with subjective mental health according to gender and life stage., Methods: Self-reported questionnaires with questions regarding subjective health status and lifestyles were sent to 1905 community residents aged 20 years or older selected by random sampling in Wakayama Prefecture, Japan. Subjective mental health, physical health, social and spiritual satisfactions as measures of subjective health status were assessed using a visual analogue scale. Multiple logistic regression analysis was used to evaluate the relationships between the subjective mental health and the other three components of the subjective health status with adjustment for life style factors related to the subjective mental health in the subjects without missing values of relevant factors (n=1,752). The subjects were divided into three life stages depending on their ages: young (20-39), middle (40-59), and old (60 or more)., Results: Overall, the poor statuses of the three components, namely, physical health, social and spiritual satisfactions, were significantly associated with poor mental health in both genders at any life stage. However, detailed analysis revealed some interesting characteristics. In young men, social dissatisfaction was strongly associated with poor mental health whereas spiritual dissatisfaction in addition to social dissatisfaction was strongly associated with poor mental health in young women. In the middle aged group, both social and spiritual dissatisfactions were strongly associated with poor mental health in both genders. On the other hand, poor physical health status was strongly associated with poor mental health in the old aged group., Conclusions: These results suggest the importance of the mental health interventions under consideration for each life stage and gender.

Background: Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated. In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer (SPIRITS) trial, we aimed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone., Methods: In this phase III trial, chemotherapy-naive patients with advanced gastric cancer were enrolled between March 26, 2002, and Nov 30, 2004, at 38 centres in Japan, and randomly assigned to S-1 plus cisplatin or S-1 alone. In patients assigned to S-1 plus cisplatin, S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily for 3 consecutive weeks, and 60 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period, within a 5-week cycle. Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks, followed by a 2-week rest period, within a 6-week cycle. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportions of responders, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00150670., Findings: 305 patients were enrolled; seven patients were ineligible or withdrew consent, therefore, 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone. Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin (13.0 months [IQR 7.6-21.9]) than in those assigned to S-1 alone (11.0 months [5.6-19.8]; hazard ratio for death, 0.77; 95% CI 0.61-0.98; p=0.04). Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone (median progression-free survival 6.0 months [3.3-12.9] vs 4.0 months [2.1-6.8]; p<0.0001). Additionally, of 87 patients assigned S-1 plus cisplatin who had target tumours, one patient had a complete response and 46 patients had partial responses, ie, a total of 54% (range 43-65). Of 106 patients assigned S-1 alone who had target tumours, one patient had a complete response and 32 had partial responses, ie, a total of 31% (23-41). We recorded more grade 3 or 4 adverse events including leucopenia, neutropenia, anaemia, nausea, and anorexia, in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone. There were no treatment-related deaths in either group., Interpretation: S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer.

The objective of this study was to evaluate the usefulness of laser Doppler imaging (LDPI) of the skin blood flow for assessing peripheral vascular impairment in the hand-arm vibration syndrome (HAVS). The subjects were 46 male patients with HAVS, aged 50 to 69 yr, and 31 healthy male volunteers of similar age as controls. A cold provocation test was carried out by immersing a subject's hand on his more severely affected side into cold water at a temperature of 10 degrees C for 10 min. Repeated image scanning of skin blood flow of the index, middle, and ring fingers was performed every 2 min before, during, and after the cold water immersion using a PMI-II laser Doppler perfusion imager. The mean blood perfusion values in the distal phalanx area of the fingers were calculated on each image. The patients suffering from vibration-induced white finger (VWF, n=20) demonstrated significantly lower skin blood perfusion at each interval of the test as compared with those without VWF (n=26) and the controls (p<0.01, ANOVA). The blood perfusions in the HAVS patients were associated with the severity of the symptoms as classified by the Stockholm Workshop scale for vascular staging. When a subject was considered to be positive if any of the tested fingers showing a decreased blood perfusion and/or a delayed recovery pattern, the sensitivity was 80.0%, and the specificity was 84.6% and 93.5% for patients without VWF and the controls, respectively. These results suggest that the LDPI technique could provide detailed and accurate information that may help detect the existence of impaired vascular regulation to cold exposure in the fingers of workers exposed to hand-transmitted vibration.

gamma-Glutamyl carboxylation, a reaction essential for the activity of vitamin K-dependent proteins, requires the concerted actions of gamma-glutamyl carboxylase (GGCX), vitamin K 2, 3-epoxide reductase complex 1 (VKORC1), and the chaperone calumenin (CALU). We evaluated the contribution of genetic polymorphisms in VKORC1, GGCX, and CALU to interindividual variation in the activities of plasma protein C and protein S. We sequenced these 3 genes in 96 Japanese individuals and geno-typed 9 representative single-nucleotide polymorphisms in 3655 Japanese individuals representative of the general population. The mean activity of protein C in women bearing the GG genotype of GGCX 8016G>A (130.8% +/- 1.5%, n = 156) was significantly greater (P = .002) than that of individuals with either the AG (126.8% +/- 0.7%, n = 728) or the AA (125.4% +/- 0.6%, n = 881) genotype, after adjusting for confounding factors. The GGCX 8016G>A change leads to the substitution of Gin for Arg at amino acid residue 325 (Arg 325 Gln). This effect was comparable to that of a previously defined polymorphism in the protein C promoter. Mean protein S activity was influenced by the VKORC1 3730G>A and CALU 20943T>A genotypes, after adjusting for confounding factors. Thus, polymorphisms in genes involved in the vitamin K-dependent gamma-carboxylation reaction influence interindividual variation in the activities of protein C and protein S in the general population.