The Q223R polymorphism in the leptin receptor associates with objectively measured light physical activity in free-living Japanese

AbstractPhysical activity (PA) is associated with reductions in the risk of all-cause mortality and in the prevalence of cardiovascular disease and stroke. Nevertheless, a large proportion of the general population may not be sufficiently active. PA level has been reported to be influenced by genetic factors, and we investigated whether Q223R polymorphism in the leptin receptor (LEPR) gene was associated with PA level. A total of 556 Japanese adults aged 24–65years old participated in this cross-sectional study. The duration and intensity of PA were objectively evaluated by triaxial accelerometry. Q223R polymorphism was determined by the TaqMan method. The distribution of Q223R polymorphism was: QQ 0.7%, QR 22.6%, and RR 76.6%. The relation between the LEPR genotype and PA level was analyzed by ANCOVA with age and sex as covariates in the Q dominant genetic model. There were significant differences between LEPR genotypes and the time spent in light PA or inactive time. The subjects with RR genotype showed significantly shorter time spent in light PA (RR genotype: 559.4±102.9min/day, QQ/QR genotype: 579.9±103.1min/day) and longer inactive time (RR genotype: 815.5±107.5min/day, QQ/QR genotype: 792.3±107.7min/day) than the subjects with QQ/QR genotype (P<0.05). There were no such differences in the time spent in moderate or vigorous PA. These results suggest that the variety of PA level, especially spontaneous PA in humans, is partly caused by diversity in the LEPR gene

PO-158 Association Of Glucose Metabolism and Physical Activity By Chronotype in Elderly Japanese Adults: There is no full text article associated with this abstract

Objective Chronotype is a trait determining individual circadian preference in behavioral and biological rhythm relative to external light-dark cycle. Although evening chronotype has been reported to be associated with bad glucose control and low physical activity in middle-aged adults, it is not known whether it is true in elderly people. Therefore, the aim of this study was to investigate the relationship between glucose metabolism and physical activity by chronotype (circadian rhythm) in elderly Japanese adults. Methods A cross-sectional study was conducted in 178 adults (72 men and 106 women), aged 60-79 years, who were classified into three chronotype groups, ”definitely morning type (DMT)”, “moderately morning type (MMT)” and “neither type (NET)”, based on the Morningness/Eveningness Questionnaire scores (MEQ-Score). All participants were required to report their daily rhythms of behavior, such as meal time and sleep-wake cycle. Additionally, their physical activity were measured by an uniaxial accelerometer (Kenz Lifecorder EX, SUZUKEN, Nagoya, Japan). Energy intake was assessed by a brief self-administered diet-history questionnaire. Blood was drawn for biochemical analysis after an overnight fast. Results BMI and serum insulin in the DMT group was significantly higher than MMT and NET groups in male. The DMT group had a significantly shorter time interval between dinner and sleep than the other two groups, both in male and female. After adjustment for covariates (age, smoking and alcohol status, energy intakes, moderate-vigorous physical activity (MVPA) and sleep duration), the BMI, serum insulin, fasting blood glucose (FBG) and HOMA-IR in the DMT group was significantly higher than other groups. However, after adjustment for the time interval between dinner and sleep, the significant difference had disappeared. There was significant difference in terms of low-intensity physical activity between male and female. And MVPA in the DMT group, the subjects with low MVPA (&lt;23Mets·hour/week) had higher FBG, serum insulin and HOMA-IR than the subjects with high MVPA (&gt;23Mets·hour/week) in men, but not in women. Conclusions This study demonstrated that the DMT group with early sleep-wake lifestyle had higher BMI, &nbsp;FBG, serum insulin and HOMA-IR, specially in elderly Japanese men with low MVPA, but not in women

Optineurin with amyotrophic lateral sclerosis-related mutations abrogates inhibition of interferon regulatory factor-3 activation

Optineurin has been shown to be involved in primary open-angle glaucoma. We recently found that optineurin is involved in familial amyotrophic lateral sclerosis (ALS). On the other hand, optineurin has been shown to inhibit transcription factors related to innate immunity such as NF-kappa B and interferon regulatory factor-3 (IRF3). In the present study, the effect of ALS-associated optineurin mutations on IRF3 activation was investigated. Optineurin inhibited IRF3 activation induced by melanoma differentiation-associated gene 5 or Toll-IL-1 receptor domain-containing adaptor-inducing interferon-beta. The inhibition was abrogated by mutations related to ALS but not by a mutation related to glaucoma. Reporter assay indicated that the JAK-STAT signaling pathway was not affected by optineurin. These results show that ALS-related optineurin is involved in the IRF3 activation pathway. Pathogenesis of ALS may be associated with some kind of innate immunity, especially that against virus infection, through IRF3 activation

Simultaneous Validation of Seven Physical Activity Questionnaires Used in Japanese Cohorts for Estimating Energy Expenditure: A Doubly Labeled Water Study

Background: Physical activity questionnaires (PAQs) used in large-scale Japanese cohorts have rarely been simultaneously validated against the gold standard doubly labeled water (DLW) method. This study examined the validity of seven PAQs used in Japan for estimating energy expenditure against the DLW method.Methods: Twenty healthy Japanese adults (9 men; mean age, 32.4 [standard deviation {SD}, 9.4] years, mainly researchers and students) participated in this study. Fifteen-day daily total energy expenditure (TEE) and basal metabolic rate (BMR) were measured using the DLW method and a metabolic chamber, respectively. Activity energy expenditure (AEE) was calculated as TEE − BMR − 0.1 × TEE. Seven PAQs were self-administered to estimate TEE and AEE.Results: The mean measured values of TEE and AEE were 2,294 (SD, 318) kcal/day and 721 (SD, 161) kcal/day, respectively. All of the PAQs indicated moderate-to-strong correlations with the DLW method in TEE (rho = 0.57–0.84). Two PAQs (Japan Public Health Center Study [JPHC]-PAQ Short and JPHC-PAQ Long) showed significant equivalence in TEE and moderate intra-class correlation coefficients (ICC). None of the PAQs showed significantly equivalent AEE estimates, with differences ranging from −547 to 77 kcal/day. Correlations and ICCs in AEE were mostly weak or fair (rho = 0.02–0.54, and ICC = 0.00–0.44). Only JPHC-PAQ Short provided significant and fair agreement with the DLW method.Conclusions: TEE estimated by the PAQs showed moderate or strong correlations with the results of DLW. Two PAQs showed equivalent TEE and moderate agreement. None of the PAQs showed equivalent AEE estimation to the gold standard, with weak-to-fair correlations and agreements. Further studies with larger sample sizes are needed to confirm these findings

Accuracy of 12 Wearable Devices for Estimating Physical Activity Energy Expenditure Using a Metabolic Chamber and the Doubly Labeled Water Method: Validation Study

Background: Self-monitoring using certain types of pedometers and accelerometers has been reported to be effective for promoting and maintaining physical activity (PA). However, the validity of estimating the level of PA or PA energy expenditure (PAEE) for general consumers using wearable devices has not been sufficiently established.Objective: We examined the validity of 12 wearable devices for determining PAEE during 1 standardized day in a metabolic chamber and 15 free-living days using the doubly labeled water (DLW) method.Methods: A total of 19 healthy adults aged 21 to 50 years (9 men and 10 women) participated in this study. They followed a standardized PA protocol in a metabolic chamber for an entire day while simultaneously wearing 12 wearable devices: 5 devices on the waist, 5 on the wrist, and 2 placed in the pocket. In addition, they spent their daily lives wearing 12 wearable devices under free-living conditions while being subjected to the DLW method for 15 days. The PAEE criterion was calculated by subtracting the basal metabolic rate measured by the metabolic chamber and 0.1×total energy expenditure (TEE) from TEE. The TEE was obtained by the metabolic chamber and DLW methods. The PAEE values of wearable devices were also extracted or calculated from each mobile phone app or website. The Dunnett test and Pearson and Spearman correlation coefficients were used to examine the variables estimated by wearable devices.Results: On the standardized day, the PAEE estimated using the metabolic chamber (PAEEcha) was 528.8±149.4 kcal/day. The PAEEs of all devices except the TANITA AM-160 (513.8±135.0 kcal/day; P>.05), SUZUKEN Lifecorder EX (519.3±89.3 kcal/day; P>.05), and Panasonic Actimarker (545.9±141.7 kcal/day; P>.05) were significantly different from the PAEEcha. None of the devices was correlated with PAEEcha according to both Pearson (r=−.13 to .37) and Spearman (ρ=−.25 to .46) correlation tests. During the 15 free-living days, the PAEE estimated by DLW (PAEEdlw) was 728.0±162.7 kcal/day. PAEE values of all devices except the Omron Active style Pro (716.2±159.0 kcal/day; P>.05) and Omron CaloriScan (707.5±172.7 kcal/day; P>.05) were significantly underestimated. Only 2 devices, the Omron Active style Pro (r=.46; P=.045) and Panasonic Actimarker (r=.48; P=.04), had significant positive correlations with PAEEdlw according to Pearson tests. In addition, 3 devices, the TANITA AM-160 (ρ=.50; P=.03), Omron CaloriScan (ρ=.48; P=.04), and Omron Active style Pro (ρ=.48; P=.04), could be ranked in PAEEdlw.Conclusions: Most wearable devices do not provide comparable PAEE estimates when using gold standard methods during 1 standardized day or 15 free-living days. Continuous development and evaluations of these wearable devices are needed for better estimations of PAEE

Defect of Interferon γ Leads to Impaired Wound Healing through Prolonged Neutrophilic Inflammatory Response and Enhanced MMP-2 Activation.

Interferon (IFN)-&gamma; is mainly secreted by CD4+ T helper 1 (Th1), natural killer (NK) and NKT cells after skin injury. Although IFN-&gamma; is well known regarding its inhibitory effects on collagen synthesis by fibroblasts in vitro, information is limited regarding its role in wound healing in vivo. In the present study, we analyzed how the defect of IFN-&gamma; affects wound healing. Full-thickness wounds were created on the backs of wild type (WT) C57BL/6 and IFN-&gamma;-deficient (KO) mice. We analyzed the percent wound closure, wound breaking strength, accumulation of leukocytes, and expression levels of COL1A1, COL3A1, and matrix metalloproteinases (MMPs). IFN-&gamma;KO mice exhibited significant attenuation in wound closure on Day 10 and wound breaking strength on Day 14 after wound creation, characteristics that are associated with prolonged neutrophil accumulation. Expression levels of COL1A1 and COL3A1 mRNA were lower in IFN-&gamma;KO than in WT mice, whereas expression levels of MMP-2 (gelatinase) mRNA were significantly greater in IFN-&gamma;KO than in WT mice. Moreover, under neutropenic conditions created with anti-Gr-1 monoclonal antibodies, wound closure in IFN-&gamma;KO mice was recovered through low MMP-2 expression levels. These results suggest that IFN-&gamma; may be involved in the proliferation and maturation stages of wound healing through the regulation of neutrophilic inflammatory responses

Approaches in improving hypoxia and environmental capability at a mooring place in Shinagawa campus of Tokyo University of Marine Science and Technology

貧酸素水塊改善を目的として本学品川キャンパス係船場にてソーラーシーオアシス並びにマイクロバブルによる貧酸素改善実験を行った。また，実験を行う以前から係船場の環境特性を把握するため，水質の調査も行った。係船場の環境は東京湾と比べ水温が高く，塩分が低い。これは周辺にある芝浦水再生センターや品川，大井火力発電所の放流水の影響であることが示唆された。また，年間を通じて成層しており，底層の貧酸素状態は2006年5月－11 月，2007年6月－11 月に起きていた。ソーラーシーオアシスの実験では，装置内外のDO 差は平均で0.91 mg L-1高い値が示された。この差の変化は，取水口部分のDO とよく対応していた。マイクロバブルの実験では，空気流量が1.0 L min-1の場合には，径の大きな気泡が発生しその周囲のみDO が高くなったが，それと連動して底層の海水が上昇し海底付近では効果が見られなかった。空気流量が0.2 L min-1の場合には海水の上昇は確認されず，等密度面に添って緩やかに酸素を供給した。しかし，その量は貧酸素状態を解消するに至らず今後さらなる改良が望まれる。We conducted experiments using a Solar-Sea-Oasis (SSO) and a microbubble generator (MB) to improve hypoxic condition at mooring place in Tokyo University of Marine Science and Technology. Prior to the experiments, we measured water quality (temperature, salinity and dissolved oxygen concentration (DO)) to assess the hydrographic condition in this mooring place. Hydrographic parameters or recorded temperature and salinity in the area were higher and lower respectively, than those measured in Tokyo Bay (Stn. F3). These data indicate intrusion of effluent water from Wastewater Treatment Plant and Shinagawa and Oi Thermal Power Plant near the mooring place. Water column was stratified all year round and was hypoxic at the bottom during May-November 2006 and June-November 2007. In SSO experiments, the difference of DO between the inner and outer side of SSO apparatus was 0.91 mg L-1 in average. The trend of DO record traced at the SSO intake or the sea surface corresponded with that difference. When air flow rate was 1.0 L min-1 in MB experiments, DO near the sea bottom did not increase, due to large size bubbles rising from the bottom up to the upper layer. Conversely, the rising of bubbles was not observed, and DO modestly increased along same density layer when air flow rate was 0.2 L min-1. However it was not enough to improve hypoxia and further improvement is thus required.東京海洋大学大学院海洋科学技術研究科東京海洋大学大学院海洋科学技術研究科東京海洋大学海洋科学部海洋環境学科東京海洋大学海洋工学部海洋電子機械工学科東京海洋大学大学院海洋科学技術研究科東京水産大学水産学部海洋環境学

Drug retention rates and relevant risk factors for drug discontinuation due to adverse events in rheumatoid arthritis patients receiving anticytokine therapy with different target molecules

Objective: To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA). Method: This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patientyears (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan-Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied. Results: The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE. Conclusions: Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept

Visceral fat area is a strong predictor of leukocyte cell-derived chemotaxin 2, a potential biomarker of dyslipidemia.

Leukocyte cell-derived chemotaxin 2 (LECT2) is a hepatokine linking obesity to skeletal muscle insulin resistance. Although previous studies reported that obesity was associated with high levels of circulating LECT2 in human, the associations of detailed body fat distribution with LECT2 levels have not been examined. Furthermore, although animal study suggested that exercise decreased circulating LECT2 levels, it remains unknown whether physical fitness is associated with LECT2 levels in human. We therefore examined the relationship of plasma LECT2 levels with various adiposity indices and cardiorespiratory fitness (CRF) in middle-aged and elderly Japanese men. Furthermore, we examined the relationship of LECT2 levels with the presence of metabolic syndrome, hypertension, insulin resistance and dyslipidemia to determine the clinical significance of measuring circulating LECT2.This was a cross-sectional study of 143 Japanese men (age: 30-79 years). Participants' plasma LECT2 levels were measured by an enzyme-linked immunosorbent assay. To assess their abdominal fat distributions, visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using magnetic resonance imaging. CRF was assessed by measuring peak oxygen uptake ([Formula: see text]).All adiposity indices measured in this study were positively correlated with plasma LECT2 levels, while [Formula: see text] was negatively correlated with LECT2 levels after adjustment for age. The correlations, except for VFA were no longer significant with further adjustment for VFA. Stepwise multiple linear regression analysis revealed that VFA was the strongest predictor of plasma LECT2 levels. Plasma LECT2 levels differed based on the presence of metabolic syndrome and dyslipidemia, but not hypertension and insulin resistance. Logistic regression analyses revealed that plasma LECT2 levels were significantly associated with dyslipidemia independently of VFA; VFA was not significantly associated with dyslipidemia after adjustment for LECT2.VFA was the strongest predictor of plasma LECT2 that is a potential biomarker linking visceral obesity to dyslipidemia