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BACKGROUND: Since the start of the COVID-19 pandemic, the number of people working at home has grown significantly. OBJECTIVE: This cohort study aimed to investigate whether the frequency of working at home was associated with changes in body mass index (BMI) and productivity from 2018 to 2020. METHOD: Frequency of working at home was self-reported. Participants were classified into three groups based on mean frequency of working at home per week (no working at home: ≦ 0.5 days, low frequency: 0.5 to 2.5 days, and high frequency: >2.5 days). Productivity was measured using a numerical rating scale, and BMI was calculated using height and weight. Changes in BMI and productivity were calculated by subtracting 2018 data from 2020 data. Linear regression analysis was performed by considering BMI and productivity change as outcomes and frequency of working at home as explanatory variable. RESULTS: BMI change in the high frequency group was significantly smaller than in the group that did not work at home (crude; coefficient: –0.27; 95% CI: –0.55––0.01, adjusted; coefficient: –0.30; 95% CI: –0.60––0.01). Frequency of working at home was not associated with productivity change. CONCLUSION: Working at home may be a solution for preventing BMI from increasing significantly.

The 3-min walk test (3MWT) has been used in the clinical setting.To present the 3MWT value and investigate its association with motor and respiratory functions of healthy older adults.Two hundred six older adults and 27 younger adults were enrolled. The 3MWT was assessed by the walking distance within 3 min. Knee extension muscle strength (KEMS), 5-repetition sit-to-stand (5 R-STS), Timed Up and Go (TUG), forced vital capacity (FVC), forced expiratory volume 1.0 (FEV1.0), maximal expiratory pressure (MEP), and maximal inspiratory pressure (MIP) were measured. The 3MWT distance was examined by age group (18-39, 60-69, 70-79, and 80-89 years). A multivariate regression analysis investigated the association between 3MWT and motor function test.The 3MWT values in each age group were 273-385, 233-414, 93-351, and 171-345 m for men and 215-375, 220-349, 198-325, and 174-332 m for women respectively. The 3MWT values were correlated with age, body mass index (BMI), KEMS, 5 R-STS, TUG, FVC, FEV1.0, MEP, and MIP. On the multivariate regression analysis, 3MWT was significantly associated with BMI (standard beta = -0.18; 95% confidence interval [CI], -3.20 to 0.83), KEMS (standard beta = 0.37; 95% CI, 0.06-0.13), 5 R-STS (standard beta = -0.13; 95% CI, -5.70 to -0.13), and TUG (standard beta = -0.36; 95% CI, -17.15 to -7.73) in older adults (adjusted RThe 3MWT distance decreased with age and was associated with motor and respiratory functions. No range trends were observed among groups. Our findings suggest that 3MWT reflects functional capacity.

Background: No consensus has been reached on which is better in terms of functional outcomes between simultaneous bilateral and unilateral total knee arthroplasty (TKA). As patient characteristics, such as age, sex, and body mass index, have significant effects on functional outcomes after TKA, we should match these factors before making comparisons. This study aimed to compare time courses in functional outcomes between simultaneous bilateral TKA and unilateral TKA after matching the patient characteristics. Methods: In this retrospective study, we reviewed the clinical records of patients admitted to our hospital. After excluding the patients who did not meet the criteria, 43 underwent simultaneous bilateral TKA and 382 underwent unilateral TKA were included in this study. We performed propensity score matching for age, sex, and body mass index between simultaneous bilateral and unilateral TKA patients. We measured pain intensity, knee extensor strength, and knee-specific functional outcomes using the new knee society score, including total score, symptoms, patient satisfaction, patient expectations, and functional activities preoperatively and at 3 and 12 months postoperatively. Two-way repeated analysis of variance was performed to compare the time courses in functional outcomes between simultaneous bilateral and unilateral TKA. Results: After propensity score matching, 40 patients each for underwent bilateral TKA and unilateral TKA were selected. Knee extensor strength in simultaneous bilateral TKA patients was significantly lower than that in unilateral TKA patients at 3 months postoperatively (p = 0.04). A significant interaction was observed between the effects of time and group on knee extensor strength (F [1, 78] = 3.338; interaction: p = 0.042; η2 = 0.052). No significant interactions were found among the other variables measured. Conclusions: Patients who underwent simultaneous bilateral TKA showed delayed recovery in knee extensor strength at 3 months postoperatively, but recovered to the same level at 12 months postoperatively. Patients who underwent simultaneous bilateral TKA should undergo postoperative rehabilitation focused on alleviating delayed recovery in knee extensor strength during the acute phase.

Objective: Knee pain (KP) and low-back pain (LBP) are common sites of pain and major public health issues among older adults. We investigated the combined association of bilateral KP and LBP with objectively measured physical activity (PA) among adults with knee osteoarthritis (OA). Methods: We recruited 150 knee OA adults and measured steps and PA intensity, including sedentary behavior (SB), low PA (LPA), and moderate-to-vigorous PA, using an accelerometer. KP and LBP were measured using a numerical rating scale. They were classified into 4 groups based on the presence of KP and LBP: with the only unilateral KP (UKP), with the combined UKP and LBP (UKP and LBP), with the bilateral KP (BKP), and with the combined bilateral KP and LBP (BKP and LBP). One-way analysis of covariance was performed to compare physical activity variables (intensity or steps) between the four groups. Results: Overall, 126 patients were enrolled. The prevalence of UKP, BKP, UKP and LBP, and BKP and LBP were 29.4%, 23.8%, 18.3%, and 28.6%. The proportion of SB was higher in the BKP and LBP group than in the other groups (F = 6.51, p < 0.01). The proportion of LPA was lower in the BKP and LBP group than in the other groups (F = 6.21, p < 0.01). Conclusions: The proportions of SB and LPA were significantly worse in knee OA adults with BKP and LBP than in those with UKP. Our findings may be a basis for considering knee OA adults for improving PA.

Objective Deep vein thrombosis (DVT) is a severe complication after total knee arthroplasty (TKA). Performing self-calf massage may decrease the incidence of DVT. The purpose of this study was to investigate whether self-calf massage is effective for preventing DVT after TKA. Method In all, 165 patients participated in the present study. Patients were randomized to one of two groups: the self-calf massage group or the control group. In the control group, patients started regular physical therapy. In the self-calf massage group, in addition to regular physical therapy, patients were instructed to massage their calf muscles 30 times from the distal to proximal side. This procedure was repeated three times and was completed in 2 mins during the 2 days following TKA. All patients were evaluated for DVT on postoperative day 3 using lower limb vein ultrasonography. Results The incidence of DVT was significantly lower in the self-calf massage group than in the control group. Self-calf massage was associated with a lower incidence of DVT, whereas age and female sex were risk factors for DVT. Conclusion This study showed that the self-calf massage may be beneficial for the prevention of DVT after TKA.

Background Flatfoot is characterized as a lower longitudinal arch and is a common foot deformity in older adults. Foot intrinsic muscle dysfunction has been considered as one of the factors for a lower medial longitudinal arch. The objective of this study was to investigate the association of the navicular drop with the thickness of foot intrinsic muscles in older adults. Research question: Which intrinsic muscle contributes most to support the medial longitudinal arch in older adults? Methods We studied 88 community-dwelling older adults (mean age 74.2 ± 6.2 years). We measured the navicular height, the calcaneus inclination, and hallux valgus angle on the right foot in the sitting and standing positions using a 3D foot scanner. Then, we calculated the navicular drop and changes in the calcaneus inclination from the sitting to the standing position. The muscle thickness of the flexor hallucis brevis (FHB), flexor digitorum brevis (FDB), and abductor hallucis (AbH) was measured on the right foot using Bmode ultrasonography. Results Multiple regression analysis demonstrated that FHB thickness was significantly associated with navicular height in the standing positions (β = 8.568, P = 0.016) as well as navicular drop (β = −9.495, P = 0.037) after adjusting for age, sex, height, weight, and hallux valgus angle. There was no association with FDB or AbH. The thickness of any intrinsic muscle was not associated with the calcaneus inclination or changes in the calcaneus inclination. Significance Our data suggest that FHB plays an important role in preventing navicular drop and that intrinsic muscles likely do not contribute to the rearfoot angle in older adults.

We aimed to compare the variables of pain intensity, pain trajectory, and the number of analgesics administered during the acute phase between total and unicompartmental knee arthroplasties. This prospective cohort study recruited 445 patients who planned to undergo knee arthroplasty. Pain intensity was evaluated during hospitalization, and 1 month postoperatively using a numerical rating scale. Pain trajectory (slope and intercept) was calculated using pain intensity data from postoperative days 1 to 4. The number of analgesics administered for worsening pain was monitored during hospitalization. Multiple linear regression analysis with adjustment for potential confounders was conducted to investigate the impact of surgery type on pain variables. Data for 208 and 189 patients who had undergone total and unicompartmental knee arthroplasties, respectively, were included in this study. Pain intensity and pain trajectory were similar between the two surgeries. The number of analgesics administered on postoperative day 3 (p = 0.01) and day 4 (p = 0.03), as well as total number (p = 0.01), were lower for unicompartmental knee arthroplasty than for total knee arthroplasty. Multiple linear regression analysis showed that the type of surgery affected the total number of analgesics administered (β = − 1.24, p

Prolonged sedentary behavior (SB) may affect clinical improvements following total knee arthroplasty (TKA). We aim to assess preoperative SB effect on improvements in clinical outcomes after TKA. We hypothesized that patients with high proportion of preoperative SB have small improvements in clinical outcomes after TKA.We recruited 115 adults with knee osteoarthritis (OA), planning to undergo TKA. Knee-specific functional outcomes were assessed using the new knee society score (KSS), including total score, symptoms, patient satisfaction, patient expectations, and functional activities. Gait function was assessed using the timed up and go (TUG) test. SB was measured using a triaxial accelerometer. Multiple linear regression analysis was performed to investigate preoperative SB effect on improvements in clinical outcomes 6 months postoperatively by adjusting for several factors as potential confounders.Of 115 patients, 82 were included. High proportion of preoperative SB had a significant negative effect on recovery at 6 months in the new KSS total score [β, -0.83, 95% confidence interval (CI), -1.53 to -0.12; p = 0.02], symptoms (-0.15, -0.28 to -0.02; p = 0.03), patient satisfaction (-0.22, -0.42 to -0.02; p = 0.03), and functional activities (-0.40, -0.76 to -0.04; p = 0.03) after adjusting for potential confounders.A high proportion of preoperative SB was a risk factor for reduced improvements in knee-specific functional outcomes after TKA. To prevent poor functional recovery after TKA, it is essential to understand the preoperative lifestyle factors and intervene proactively during acute postoperative phase in patients with high SB proportion.Key Points• Preoperative high proportion of SB had a negative effect on improvement in new KSS total scores, symptoms, patient satisfaction, and functional activities.• When considering clinical outcomes after TKA, clinicians should closely monitor patients with high proportions of preoperative SB to prevent poor functional recovery.

In June 2016, the Ministry of the Environment of Japan announced a program "EXTEND2016" on the implementation of testing and assessment for endocrine active chemicals, consisting of a two-tiered strategy. The aim of the Tier 1 screening and the Tier 2 testing is to identify the impacts on the endocrine system and to characterize the adverse effects to aquatic animals by endocrine disrupting chemicals detected in the aquatic environment in Japan. For the consistent assessment of the effects on reproduction associated with estrogenic, anti-estrogenic, androgenic, and/or anti-androgenic activities of chemicals throughout Tier 1 screening to Tier 2 testing, a unified test species, Japanese medaka (Oryzias latipes), has been used. For Tier 1 screening, the in vivo Fish Short-Term Reproduction Assay (OECD test guideline No. 229) was conducted for 17 chemicals that were nominated based on the results of environmental monitoring, existing knowledge obtained from a literature survey, and positive results in reporter gene assays using the estrogen receptor of Japanese medaka. In the 17 assays using Japanese medaka, adverse effects on reproduction (i.e., reduction in fecundity and/or fertility) were suggested for 10 chemicals, and a significant increase of hepatic vitellogenin in males, indicating estrogenic (estrogen receptor agonistic) potency, was found for eight chemicals at the concentrations in which no overt toxicity was observed. Based on these results, and the frequency and the concentrations detected in the Japanese environment, estrone, 4-nonylphenol (branched isomers), 4-tert-octylphenol, triphenyl phosphate, and bisphenol A were considered as high priority candidate substances for the Tier 2 testing.

Our research aims at developing a meal-assistance robot with vision system and multi-gripper that enables frail elderly to live more independently. This paper presents a development of a chopstick-type gripper for a meal-assistance robot, which is capable of adapting its shape and contact force with the target food according to the size and the stiffness. By solely using position control of the driving motor, the above feature is enabled without relying on force sensors. The gripper was designed based on the concept of planar 2-DOF under-actuated mechanism composed of a pair of four-bar chains having a torsion spring at one of the passive joints. To clarify the gripping motion and relationship among the contact force, food&rsquo, s size and stiffness, and gripping position, kineto-elasto-static analysis of the mechanism was carried out. It was found from the result of the analysis that the mechanism was able to change its gripping force according to the contact position with the target object, and this mechanical characteristic was utilized in its grasp planning in which the position for the gripping the object was determined to realize a simple control system, and sensitivity of the contact force due to the error of the stiffness value was revealed. Using a three-dimensional (3D) printed prototype, an experiment to measure the gripping force by changing the contact position was conducted to validate the mechanism feature that can change its gripping force according to the size and the stiffness and the contact force from the analysis results. Finally, the gripper prototype was implemented to a 6-DOF robotic arm and an experiment to grasp real food was carried out to demonstrate the feasibility of the proposed grasp planning.

Our research aims to develop an adaptive control system for photovoltaic systems with energy storage that adapts after changing different kinds of conditions. In particular, for efficient controlling of battery storage, the precise prediction of electricity consumption is required. Due to the complexity of the proposed research, in this paper, we proposed the simplification of the complexity of the long short-term memory model for the forecasting of the electric energy consumption from a house cooperative in Karlstad, Sweden. Based on the experimental results, there is a 1.233 kWh of mean absolute error and 1.859 kWh of root-mean square error for the predicted energy consumption (validated from testing data collected 7 days after the collected training data for the selected deep learning model).

Knee osteoarthritis (OA) and fear of falling (FoF) are important factors contributing to trunk oscillation during walking. It is of a clinical importance to clarify the association of FoF with trunk oscillation during walking in older adults with knee OA (knee OA adults). The purpose of this study was to investigate the association of FoF with trunk oscillation during walking in knee OA adults. Forty-one patients who met the criteria participated in the study and were classified into two groups based on their answer to a question on FoF. An accelerometer was attached at the level of the third lumbar vertebra (L3) and the seventh cervical vertebra (C7), and the accelerations at L3 and C7 were measured during a 10-m gait test. Using these data, the acceleration-derived gait indices, such as stride time variability (STV), root mean square (RMS), and autocorrelation at the trunk in the anteroposterior (AP) and mediolateral (ML) directions, were computed. FoF was associated with a higher STV value and a smaller RMS value in the ML direction at L3. The decreased trunk oscillation in the ML direction in knee OA adults with FoF may reflect a positive, compensatory adaptation for trunk control. Knee OA adults with FoF decreased trunk oscillation during walking than those without FoF.

ObjectiveThis study aimed to investigate the effectiveness of workplace active rest programme (WARP) on chronic low back pain (LBP) among office workers.DesignA closed cohort, stepped-wedge cluster randomised trial was conducted. The total duration of the study was 16 weeks (4 weeks for each step). Sequence allocation was randomised, but no one was blinded.SettingThis study was conducted in three offices in a Japanese electronics company. One office was for the administrative department, the others are for the engineering department.ParticipantsWe recruited 29 office workers with LBP greater than 3 months. LBP due to specific injury or disease was excluded. The median age was 38 years, and 26 (90%) were male. All participants completed the study.InterventionsIn the intervention phase, participants performed WARP comprising frequent stand-up and individualised brief exercise/physical activity during work. Physical therapists held an LBP workshop and developed tailor-made programmes before introducing WARP. We instructed participants to perform WARP at five timings during work. Control phase was set before the intervention and participants stayed as usual.Primary and secondary outcome measuresThe primary outcome was pain intensity of LBP assessed using the Brief Pain Inventory. The secondary outcomes were work productivity loss measured using the Work Limitations Questionnaire, LBP disability assessed using the Roland-Morris Disability Questionnaire, psychosocial subscale assessed using the STarT Back Screening Tool and physical activity measured using triaxial accelerometers. These outcomes were collected at baseline and at 4-month follow-up evaluation.ResultsIn the intention-to-treat analysis, WARP did not show any significant effects on pain intensity (β, 0.01; 95% CI −0.50 to 0.52) and on the secondary outcomes. The median adherence to WARP was 28.6% (IQR, 16.8–41.1), which was equal to 1.43 times per day. No adverse effect was observed.ConclusionsThe present study was unable to confirm the effectiveness of active rest in improving LBP. Hence, further study needs to investigate its effectiveness.Trial registration numberUMIN000033210.

Objective To compare the association of cough peak flow (CPF) with aging in community-dwelling older adults and to investigate the relationship between physical fitness and CPF in these individuals. Method Two hundred twenty two community-dwelling older adults were enrolled. CPF was assessed as a cough function parameter. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1.0) were assessed as respiratory function. Maximal expiratory pressure (MEP) and inspiratory pressure (MIP) were assessed as respiratory muscle strength. The 3-minute walk test (3MWT) performance was assessed as a physical fitness. Participants were divided into the following age groups: 60-64, 65-69, 70-74, 75-79 and 80-89 years. One way analysis of variance were computed for comparison between age group, sex and CPF. Multivariate regression analyses were used to investigate the association of CPF with 3MWT. Results The value of CPF significantly decreased in the 75-79 and 80-89 years group than 60-64 years group in men and in the 80-89 years group than 65-69 years group in women. The value of CPF were 545.5, 497.2, 403.3, 354.8 and 325.4 L/min in the 60-64, 65-69, 70-74, 75-79 and 80-89-year group in men and 263.4, 278.8, 264.5, 214.0, and 193.6 L/min in the corresponding age groups in women, respectively. 3MWT (p = 0.041) was significantly associated with CPF. Conclusions Cough function tends to decrease with aging in community-dwelling elderly. Physical fitness is associated with cough function.

Background: We investigate the association with knee flexion range of motion (ROM) during the acute phases and that at 12 months after total knee arthroplasty (TKA). We also clarified the cut-off ROM during the acute phases in predicting the goal of knee flexion ROM at 12 months. Methods: In this retrospective study, 193 patients with knee osteoarthritis (female:144 patients, age:73.2 ± 7.7 years) who underwent unilateral TKA at an orthopedic clinic were recruited. They underwent assessments of knee flexion ROM at 5 days, 1 month, and 12 months after TKA. The goal of knee flexion ROM at 12 months after TKA was set at 120°. Single and logistic-regression analyses were performed with the dependent variables including the outcome of the goal of knee flexion ROM at 12 months, and the independent variables included knee flexion ROM at 5 days and 1 month, separately. We calculated the cut-off ROM at 5 days and 1 month for predicting the goal of knee flexion ROM at 12 months with receiver operating curve analysis. Results: Knee flexion ROM at 5 days and 1 month were significantly associated with the goal of that at 12 months (p < 0.01). The cut-off ROM were 85° at 5 days and 105° at 1 month separately. Conclusions: Our results suggest the importance of early improvement in knee flexion ROM after TKA, and that at 1 month postoperatively indicates the likelihood of achievement of the goal of knee flexion ROM at 12 months after TKA.

In order to reduce the amount of choline acetate ([Cho][OAc]), (a less expensive, more biodegradable and biocompatible ionic liquids) used in the pretreatment of sugarcane bagasse, [Cho][OAc] combined with organic solvents pretreatments were attempted. The glucose yields after a 72-h enzymatic saccharification of sugarcane bagasse pretreated with [Cho][OAc] combined with organic cosolvents dimethyl sulfoxide (DMSO), N-methyl-2-pyrrolidone (NMP), or ethylene glycol (EG) at a weight ratio of 1:1 keeping at 130 °C for 180 min were approximately equal to those from the bagasse treated with [Cho][OAc] alone. The result indicated that the combination use of the cosolvents made it possible to reduce 50% of amount used of [Cho][OAc]. The enhancement effect of the [Cho][OAc]/cosolvent pretreatment on enzymatic saccharification could be attributed to an equal or greater effect on removal of hemicelluloes and lignin compared to the [Cho][OAc] treatment alone, although a lower effect on reduction in cellulose: which was supported by componential and X-ray diffraction (XRD) analyses. The bagasse pretreated with [Cho][OAc]/DMSO (1:1 w/w) used in simultaneous saccharification and fermentation using Saccharomyces cerevisiae BA11, and ethanol was produced with a corresponding to conversion ratio of 69.9%.

The prevalence of chronic kidney disease (CKD) as well as Alzheimer's disease (AD) increases with age. With the aging of the population in Japan, there is an increasing likelihood that patients with CKD will receive donepezil hydrochloride (DPZ), an antidementia drug, in the near future. Nevertheless, there have been few reports on how to use DPZ in patients with severe CKD. We report on 2 CKD stage 5 patients who received DPZ under different prescriptions. In case 1, 3 mg/day of DPZ was initially administered for 4 months, after which the dose was increased to 5 mg/day. In case 2, 5 mg was administered twice a week. The plasma concentration of DPZ was measured and the effectiveness was assessed using the Mini-Mental Health State Examination and the Hasegawa Dementia Rating Scale. We found that (1) only a slight increase in the plasma concentration of DPZ was observed with a dose of 3 mg daily, (2) there was a significant increase in the plasma concentration with a dose of 5 mg daily, and (3) when 5 mg of DPZ was administered twice a week, the plasma concentration did not differ significantly from healthy controls who had received 5 mg daily. Although cognitive function was improved best when the 5-mg dose was administered daily with no apparent side effects, the plasma concentration came close to reaching a toxic level at this dose. Careful follow-up may be essential when DPZ is used at 5 mg/day or greater in severe CKD patients.

Thyroid hormones are essential for the regulation of a wide range of biological processes associated with normal development and metabolism in vertebrates. For the screening of chemicals with a potential thyroid hormone and anti-thyroid hormone activities, we have established transient transactivation assay systems using thyroid hormone receptors (TRα and TRβ) from three frog species (Xenopus laevis, Silurana tropicalis and Rana rugosa), a fish (Oryzias latipes), an alligator (Alligator mississippiensis) and a human (Homo sapiens). In all species examined, similar transcriptional activities were found for triiodothyronine (T3 : 10(-11) M in TRα and 10(-10) M in TRβ) and thyroxine (T4 : 10(-9) M in TRα and 10(-8) M in TRβ). Analogs of thyroid hormone (3,5,3',-triiodothyroacetic acid and 3,3',5,5'-tetraiodothyroacetic acid) exhibited weaker activity, requiring 10-fold higher concentrations for induction of activity when compared with T3 and T4 . These results provide support for the usefulness of in vitro screening assay systems as part of an approach to test chemicals for potential thyroid hormone receptor activity. In addition, we observed that T3 -stimulated transcriptional activity of the O. latipes TRα was inhibited by 10(-5) M tetrabromobisphenol A (TBBPA). In contrast, TR antagonist activities on TRα were not encountered in other species, even with TBBPA concentrations at 10(-5) M. In vitro transactivation assay systems using TRs from various species can be used for the screening of chemicals with thyroid-receptor agonist and antagonist activities. They also can be used for studies that examine evolutionary differences among species in the potency of TR activation.

Estrogens are essential for normal reproductive activity in both males and females as well as for ovarian differentiation during a critical developmental stage in most vertebrates. To understand the molecular mechanisms of estrogen action and to evaluate estrogen receptor ligand interactions in amphibians, we isolated cDNAs encoding the estrogen receptors (ERα and ERβ) from the Japanese firebelly newt (Cynops pyrrhogaster), Tokyo salamander (Hynobius tokyoensis), axolotl (Ambystoma mexicanum), and Raucous toad (Bufo rangeri). Full-length amphibian ER cDNAs were obtained using 5′ and 3′ rapid amplification of cDNA ends. The predicted amino acid sequences of these amphibian ERs showed a high degree of amino acid sequence identity (over 70%) to each other. We analyzed the relationships of these amphibian ER sequences to other vertebrate ER sequences by constructing a phylogenetic tree. We verified that these were bona fide estrogen receptors using receptor dependent reporter gene assays. We analyzed the effects of natural estrogens, ethinylestradiol, and DDT and its metabolites on the transactivation of the four amphibian species listed above, and Xenopus tropicalis ERs and found that there were species-specific differences in the sensitivity of these ERs to hormones and environmental chemicals. These findings will expand our knowledge of endocrine-disrupting events in amphibians.

There is a growing international concern that commonly used environmental contaminants have the potential to disrupt the development and functioning of the reproductive system in amphibians. One such chemical of interests is the herbicide atrazine. Effects of atrazine on sex differentiation were studied using wild-type Xenopus laevis tadpoles and all-ZZ male cohorts of X. laevis tadpoles, produced by mating wild-type ZZ male to sex-reversed ZZ male (female phenotype). Stage 49 tadpoles were exposed to 0.1-100 ppb atrazine or 0.27 ppb (1 nM) 17beta-estradiol (E(2)) until all larvae completed metamorphosis (stage 66). Metamorphosis, gonadal morphology and histology, CYP19 (P450 aromatase) mRNA induction, and hepatic vitellogenin (VTG) induction were investigated. Effects of atrazine on VTG-induction were also assessed in vitro in primary-cultured X. laevis hepatocytes. Atrazine had no effect on metamorphosis of developing wild-type or all-male X. laevis larvae. Statistical increase in female ratios was observed in 10 and 100 ppb atrazine groups in comparison with control group. While no hermaphroditic froglet was observed in all atrazine groups. In ZZ males, sex reversal was induced by 0.27 ppb E(2), but not by atrazine at concentrations of 0.1 and 1.0 ppb. In addition, neither P450 aromatase mRNA in the gonad nor hepatic VTG were induced by atrazine. Furthermore, VTG was not induced by 1000 ppb atrazine in primary-cultured hepatocytes. Our results indicate that female ratios in developing X. laevis tadpoles were increased by 10 and 100 ppb atrazine under the present experimental conditions. While the other endpoints showed no effect in the range of 0.1-100 ppb atrazine. These results suggest that effect of atrazine on sexual differentiation was not caused by estrogenic action and has no induction ability of P450 aromatase gene in gonad.

The purposes of this study are to construct a simple dioxin detection system using peptides that bind to dioxin, and to test the system on real environmental samples. In this method, dioxin and N-NBD-3-(3',4'-dichlorophenoxy)-1-propylamine (NBD-DCPPA) are competitively bound to the peptides synthesized on beads. The fluorescence intensity of the bead decreases with increasing dioxin concentration. The concentration of dioxin is determined by measuring the fluorescence intensity using a fluorescence microscope equipped with a CCD camera. The fluorescence microscope system was equipped with a motor-driven stage and could be used with 96-well microplates and analytical software that automatically measured the fluorescence intensity of the bead images in the wells. Dioxin detection conditions, reaction temperature, number of beads and concentration of the organic solvent were optimized. About 0.5 nM (150 pg mL(-1)) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TeCDD) could be detected under the optimized conditions. Environmental soil samples were subjected to the detection system using the peptide beads. Although the results obtained correlated poorly with the toxicity equivalency quantity (TEQ) concentration obtained by a GC/MS method, our method is robust enough as a prescreening method to detect at least 250 pg-TEQ g(-1), the survey level for soil as stipulated in the law concerning special measures against dioxins in Japan.

Estrogens are essential for normal reproductive activity in females and males and for ovarian differentiation during a critical developmental stage in many vertebrates. To understand the molecular mechanisms of estrogen action and to evaluate estrogen receptor ligand interactions in the Japanese giant salamander ( Andrias japonicus ), we isolated cDNA encoding the estrogen receptor (ER) from the liver. A full-length Japanese giant salamander ER cDNA (jgsER) was obtained using 5′ and 3′ rapid amplification cDNA ends (RACE). The deduced amino acid sequence of the jgsER showed high identity to the Xenopus ERα (ESR1) (77.7%). We have applied both the conventional ERE-luciferase reporter assay system and the GAL4-transactivation system to characterize this receptor. In two different transient transfection assay systems using mammalian cells, the jgsER protein displayed estrogen-dependent activation of transcription. The GAL4-transactivation system showed about 10-fold greater activity of the estrogen receptor by hormone when compared to the conventional ERE-luciferase reporter assay system. Tissue distribution of ERα mRNA was examined and kidney, ovary and liver exhibited expression. This is the first isolation of an estrogen receptor from a salamander and also is the first functional cDNA obtained from the Japanese giant salamander, an endangered species considered a special natural monument of Japan.

Bisphenol A (BPA), known to be a xenoestrogen, is widely used in industry and dentistry. In the present study, we investigated the effects of BPA on the early development of Xenopus laevis embryos. Stage 6 embryos were exposed to 10-100 microM BPA. Developmental abnormalities were observed when the embryos were exposed to at least 20 microM BPA, with marked developmental abnormalities, such as crooked vertebrae and developmental defects of the head and abdomen, detected in all embryos up to stage 40. Interestingly, apoptosis occurred specifically in central nervous tissue cells of the brain and spinal cord, as assessed by histological analysis. BPA-induced malformations and apoptosis were not observed in embryos exposed to BPA after stage 10. When embryos were exposed to 10 microM 17beta-estradiol (E2), abnormalities were also observed until stage 40. However, the abnormalities induced by BPA and E2 were different and E2 exposure did not induce apoptosis in the central nervous system. Our results indicated that the developmental abnormalities and apoptosis induced by BPA exposure were not inhibited by the addition of E2. In conclusion, we demonstrated that BPA induced marked malformations and specific apoptosis of central nervous system cells during early development of X. laevis embryos, and that these BPA effects appeared to be due to non-estrogenic activities on developmental processes.

Juvenile hormone (JH) and JH agonists have been reported to induce male offspring production in various daphnid species including Daphnia magna. We recently established a short-term in vivo screening assay to detect chemicals having male offspring induction activity in adult D. magna. Diofenolan has been developed as a JH agonist for insect pest control, but its male offspring induction activity in daphnids has not been investigated yet. In this study, we found that the insect growth regulator (IGR) diofenolan exhibited a potent male offspring induction activity at low ng/L to μg/L concentrations, as demonstrated by the short-term in vivo screening assay and the recently developed TG211 ANNEX 7 test protocol. A two-hybrid assay performed using the D. magna JH receptor confirmed that diofenolan had a strong JH activity. Global whole body transcriptome analysis of D. magna exposed to 10 ng/L diofenolan showed an up-regulation of JH-responsive genes and modulation of several genes involved in the ecdysone receptor signaling pathway. These results clearly demonstrate that diofenolan has strong JH activity and male offspring induction activity, and that a combination of modified standardized regulatory testing protocols and rapid in vitro and in vivo screening assays are able to identify potential endocrine disruptors in D. magna. The observation that diofenolan modulates multiple endocrine signaling pathways in D. magna suggests that further investigation of potential interference with growth, development and reproduction is warranted.

We have previously reported the results of mizoribine (MZR) treatment for elderly patients with membranous nephropathy (MN). Here, we retrospectively compared these patients with those who had been initially treated with prednisolone (PSL) alone. The subjects were patients with MN aged ≥65 years who were examined between April 2007 and September 2010 and followed for at least 1 year. The median period until the start of treatment in the MZR group (MZR-G) was 60 days. The urinary protein level at the start of MZR treatment was 3.89 ± 2.3 g/gCr. Urinary protein in the group not treated with MZR (N-MZR-G) was 1.0 ± 1.1 g/gCr, showing a tendency to improve in patients with nephrotic syndrome relative to the MZR-G (p = 0.055). The PSL dose in the MZR-G versus N-MZR-G at 1 year was 5.7 ± 3.0 versus 6.25 ± 2.5 mg/day, the urinary protein level was 0.19 ± 0.2 versus 0.13 ± 0.1 g/gCr, and the remission rate was 80 versus 75 %. In the MZR-G, the total PSL dose at 1 year after the start of MZR treatment was 5,058 ± 1,904 versus 6,649 ± 875 mg in the N-MZR-G. Adverse events occurred in 3/5 patients (60 %) in the MZR-G and in 3/4 patients (75 %) in the N-MZR-G. Elderly patients with MN who respond poorly to PSL treatment may be treated successfully with MZR.

The flow induced noise from an expansion cavity-type muffler increases abruptly for some sizes of mufflers and flow velocities. This phenomenon is strongly related to the resonance of the tail pipe and the cavity of the muffler ; therefore, it is called the predominance of resonance″When the cavity length is increased, the measured resonance frequency shows periodic jumps. The cause of the predominance of resonance is assumed to be the generation of vortex rings with a particular frequency in the cavity. The generation of vortex rings is verified by analyzing fluctuating velocities in the cavity when the predominance of resonance occurs. The phenomenon is induced not only by the tail pipe resonance, but also by the cavity resonance. It is suggested that there exists the feedback phenomenon from the sound to the flow and it is strongly related to the sound pressure level in the cavity.