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Evidence is limited regarding the association between low-carbohydrate diet (LCD) score and mortality among Asians, a population that consumes a large amount of carbohydrates.The present study examined the association between low-carbohydrate diet (LCD) score (based on percentage of energy as carbohydrate, fat, and protein) and the risk of total and cause-specific mortality among Asians.This study was a prospective cohort study in Japan with follow-up for a median of 16.9 years involving 43008 men and 50646 women aged 45-75 years. Association of LCD score, LCD score based on animal sources of protein and fat, and LCD score based on plant sources of protein and fat with risk of mortality was assessed using Cox proportional hazards model.A U-shaped association was observed between LCD score and total mortality: the multivariable-adjusted hazard ratios (HRs) (95% CI) of total mortality for lowest through highest scores were 1.00, 0.95 (0.91, 1.01), 0.93 (0.88, 0.98), 0.93 (0.88, 0.98), and 1.01 (0.95, 1.07) (P-non-linearity0.01). A similar association was found for mortality from cardiovascular disease (CVD) and heart disease. LCD score based on carbohydrate, animal protein, and animal fat also showed a U-shaped association for total mortality (P-non-linearity0.01). In contrast, LCD score based on carbohydrate, plant protein, and plant fat was linearly associated with lower total (HR, 0.89; 95% CI: 0.83, 0.94 for highest versus lowest quintile), CVD [0.82 (0.73, 0.92)], heart disease [0.83 (0.71, 0.98)], and cerebrovascular disease [0.75 (0.62, 0.91) mortality.Both LCD with high animal protein and fat and high-carbohydrate diet with low animal protein and fat were associated with higher risk of mortality. Meanwhile, LCD high in plant-based sources of protein and fat was associated with a lower risk of total and CVD mortality.

Introduction and Objectives Erectile dysfunction (ED) usually occurs in the surgical treatment of prostate cancer (PC). Since many patients are reluctant to discuss ED when facing PC treatment, some patients choose non-nerve sparing radical prostatectomy and later seek for ED treatment. We had 5 cases of patients who were treated with combination therapy of intracavernous injection (ICI) therapy of prostaglandin E1 (PGE1) and PDE5 inhibitors for ED after non-nerve sparing RP and retrospectively investigated the effectiveness of the combination therapy. Material and Methods The mean age when the patients had RP was 65.4 years. Following the 2016 National Comprehensive Cancer Network (NCCN) risk classification guidelines, 2 patients had high risk, and 3 had intermediate risk. The mean period up to the introduction of ICI from the date of RP was 40.2 months (12-120 months). All patients were given PDE5 inhibitors 3-4 weeks prior to ICI therapy. Erection was evaluated by the induction of ICI of 20 μg of prostaglandin E1 (PGE1), using Erection Hardness Score of 1 to 4; a score of 3 or 4 was classified as successful. Self-injection regimen was introduced by the physicians after the evaluation, and a total of 5 patients were tested. Results The response was Grade 1 in 1 patient, Grade 3 in 3 cases, Grade 4 in 1 case. The effectiveness rate was 80%. Penile self-injection therapy was adopted by 4 patients, and IIEF-5 and SHIM score improved from 5.3 to 17.5 and 4.3 to 14.8, respectively. No drug adverse effect was observed in the 4 cases. Conclusions Combination of ICI therapy and PDE5 inhibitors can be a candidate for ED patients who unluckily chose non-nerve sparing radical prostatectomy when treated prostate carcinoma. Disclosure Work supported by industry: no.

In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded. © 2021. The Author(s). Published by the American Astronomical Society..

BackgroundPatient with rheumatoid arthritis (RA) have disease-related problems such as joint deformity, disease duration, disease activity, activities in daily life (ADL), quality of life, pain, and fatigue. All these problems correlate interactively.ObjectivesAim of this study is to clarify association among these problems statistically using retrospective cohort data.MethodsPatients with RA who were followed up more than three years were recruited. Their EuroQol-5th dimension (EQ5D) as an indicator of quality of life (QOL), simplified disease activity index (SDAI) as an indicator of disease activity, Health Assessment Questionnaire Disability Index (HAQ) as an indicator of ADL, pain score using visual analog scale (PS-VAS), and fatigue score using visual analog scale (FS-VAS), were monitored every three months. Sharp/van der Heijde score (SHS) as an indicator of joint deformity was calculated annually. Association among average values of these factors and patient’s sex, age, disease duration (DD), and anti-citrullinated polypeptide antibodies (ACPA) titer were evaluated using multivariate linear regression analysis. Statistical significance was set within 5%.ResultsA total of 447 patients, in whom 120 male and 327 female included, were analyzed. Mean age, disease duration, EQ5D score, SDAI score, HAQ score, SHS, PS-VAS, and FS-VAS during follow-up were 71.6-year-old, 12.9 years, 0.831, 4.26, 0.413, 46.9, 22.5, and 23.2, respectively.EQ5D score correlated significantly with age, HAQ score, SDAI score, SHS, PS-VAS, FS-VAS, and DD using univariate models. In these, age, HAQ score, and FS-VAS correlated significantly using multivariate model (correlation coefficients (CC): 0.927). HAQ score correlated significantly with age, EQ5D score, SDAI score, SHS, PS-VAS, FS-VAS, and DD using univariate models. In these, EQ5D score, SHS, and FS-VAS correlated significantly using multivariate model (CC: 0.910). SDAI score correlated significantly with female gender, EQ5D score, HAQ score, SHS, PS-VAS, and FS-VAS using univariate models. In these, SHS and PS-VAS correlated significantly using multivariate model (CC: 0.620). SHS correlated significantly with age, female gender, EQ5D score, HAQ score, SDAI score, PS-VAS, and DD using univariate models. In these, HAQ score, SDAI score, and DD correlated significantly using multivariate model (CC: 0.685). PS-VAS correlated significantly with EQ5D, HAQ score, SDAI score, SHS, and FS-VAS using univariate models. In these, SDAI score and FS-VAS correlated significantly using multivariate model (CC: 0.732). FS-VAS correlated significantly with EQ5D score, HAQ score, SDAI score, and PS-VAS using univariate models. In these, EQ5D score, HAQ score, and PS-VAS correlated significantly using multivariate model (CC: 0.715). ACPA did not correlated with any factors significantly.ConclusionThese results suggested that EQ5D score, namely QOL is influenced by various disease-related factors and aging, especially correlated with ADL and fatigue closely. The HAQ score, namely ADL level is influenced by fatigue level and joint deformity directly. The SDAI score, namely disease activity level correlated with pain level and joint deformity level, and correlates with the other factors indirectly. A schematic figure that represents relationships among factors were shown in Figure 1. These information would beneficial for conducting treatment protocol of RA.Disclosure of InterestsNone declared

BackgroundPatients with difficult-to-treat rheumatoid arthritis (D2T RA) are the most serious problem in recent systemic RA treatment protocols [1].ObjectivesPrognosis after biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) is beneficial when predicted in patients with D2T RA. Predictors of post b/tsDMARDs in D2T RA patients were investigated using retrospective cohort data.MethodsRA patients more than 1 year after the start of newly administered b/tsDMARDs were recruited. The patients were divided into two groups according to the EULAR definition of D2T RA [2]. Patients who met the criteria were classified into the D2T RA group and others into the non-D2T RA group. The incidence of the clinical features described in the criteria of D2T RA and the rheumatoid disease comorbidity index (RDCI) [3] were compared between the two groups at the time of drug initiation (baseline). The primary endpoint was “Success or Failure” 1 year after baseline. Success was defined as b/tsDMARD persisted in remission as the 28 joint disease activity score with erythrocyte sedimentation rate (DAS28) ≤ 2.6, or as b/tsDMARD was discontinued upon achieving clinical remission. The Failure was defined as other decisions such as discontinuation due to failure, adverse events, or characteristic patient problems. In the discontinued cases, the monitoring value at the last observation was carried forward to 1 year.Cox regression analysis was used to assess each variant as a potential risk factor for Failure. Receiver operating characteristic analysis (ROC) was tested on variants with significantly higher risk ratios, and Kaplan-Meier survival analysis was also tested for cut-off indices.Results71 cases of the D2T RA and 259 cases of the non-D2T RA group were analyzed. As shown in Table 1, the clinical characteristics of the D2T RA group were significantly worse than those of the non-D2T RA group.Higher DAS28 had a significantly higher risk ratio for the Failure from month 3 in the D2T RA group, whereas from baseline in the non-D2T RA group (Figure 1-A). Other factors in the D2T RA group at and after baseline listed in the Table 1 had no significant risk ratios. PS-VAS and EQ5D score had significant higher risk ratios in the non-D2T RA group using univariate models, however, only DAS28 had significant higher risk ratio using multivariate model. The cut-off index (COI) and the area under the curve (AUC) using ROC for each observational period in the two groups were shown in Figure 1-B. Results of Kaplan-Meier survival analyses were shown in Figure 1-C. Hazard ratios of DAS28 > COI exceeded 2.5 even from months 3 with high sensitivity (p < 0.001) in the D2T RA group.ConclusionThese results indicated that higher DAS 28 suggested a failure prognosis at 12 months after initiation in D2T RA and non-D2T RA patients. Even in patients with D2T RA, strict disease activity control is most important for prognostic management, with 1-year prognosis predictable in the first 3 months. However, this study is a short-term prognostic predictor, and accumulation of short-term predictions is a long-term predictor.References[1]Roodenrijs NMT, et al. Rheumatology (Oxford) 2021;60:3778-3788. doi:10.1093/rheumatology/keaa860[2]Nagy G, et al. Ann Rheum Dis 2021;80:31-35.[3]England BR, et al. Arthritis Care Res 2015;67:865-872. doi: 10.1002/acr22456.Disclosure of InterestsNone declared

BackgroundPresence of anti-citrullinated polypeptide antibodies (ACPA) is one risk factor of bone erosion of the joint in patients with rheumatoid arthritis (RA). However, bone absorption in the whole body is still not clarified in a longitudinal study.ObjectivesThe aim of this study is to clarify effects of ACPA on bone mineral density (BMD) decrease using dual-energy X-ray absorptiometry (DXA) in patient with RA using retrospective longitudinal cohort study.MethodsPatient with RA who were measured BMD in lumbar spine (LS) and total hip (TH) using dual-energy X-ray absorptiometry (DXA) at first consultation (baseline) and were treated for more than five years, were recruited. Follow-up started at BMD measurement and continued until the development of the first fracture or censoring at death, loss to follow-up or end of the study. Every patients have been followed up with monitoring of SDAI and Health Assessment Questionnaire Disability Index (HAQ) at every another to three months. Sharp/van der Heijde Score (SHS) was measured at baseline and every another year thereafter. BMD were measured every six months. Relationship between BMD and candidate risk factors including ACPA positivity and serum titer level, and other variants for BMD loss were evaluated statistically using linear regression analysis. Evaluations were performed for the absolute value of BMD and Z-score at baseline, mean value of these during follow-up, and change from baseline. Change of Z-score during follow-up was also compared between groups what classified according to ACPA positivity (ACPA positive/negative group).ResultsA total of 222 patients were recruited including 17 male (7.7%) and 205 female (92.3%). The mean age of the patients was 69.2 years old. Mean disease duration at baseline and follow-up length after baseline were 6.4 and 63.3 months, respectively. Mean SDAI score, HAQ score and SHS at baseline were 22.2, 0.516, and 6.6, respectively. The mean ACPA level and positive rate were 202.1 and 77.5%, respectively.Higher ACPA titer level correlated significantly low BMD and Z-score in TH (pppChange of Z-score in the ACPA positive group was significantly lower than in the ACPA negative group despite no significant difference of disease activity between the two groups demonstrated (pTable 1.Comparison of the two groupsparametersACPA-positive (n=172)ACPA-negative (n=50)p-valuefemale (%)91.396.50.10at baselineage (year-old)65.471.3disease duration (months)7.74.6RF (IU/L)138.3 (197.1)21.5 (49.3)SDAI26.3 (24.0)21.0 (17.8)HAQ0.496 (0.618)0.553 (0.639)0.48SHS8.4 (8.2)3.5 (5.0)BMD in LS (g/cm2)0.825 (0.167)0.849 (0.156)0.23BMD in H (g/cm2)0.700 (0.140)0.710 (0.132)0.75Z-score in LS-0.246 (1.300)0.123 (1.392)Z-score in TH-0.062 (1.034)0.261 (1.020)at follow-upfollow-up length (months)64.865.40.65SDAI4.5 (3.1)5.1 (4.4)0.22HAQ0.495 (0.616)0.516 (0.544)0.32SHS8.1 (8.2)3.4 (4.8)BMD in LS (g/cm2)0.839 (0.171)0.870 (0.165)0.16BMD in TH (g/cm2)0.710 (0.118)0.713 (0.115)0.99Z-score in LS-0.008 (1.361)0.368 (1.426)Z-score in TH0.129 (0.902)0.396 (0.891)0.11anti-osteoporotic drug administered, ever (%)73.469.80.72GCS administered, ever (%)35.832.90.68The values are presented as mean (SD) unless indicated otherwise.Statistically significant within 0.05 are shown as bold styles.ConclusionPresence of ACPA potentially have an independent risk of BMD decrease. Its action affects regardless gender and age.Disclosure of InterestsNone declared

BackgroundEach Janus Kinase Inhibitor (JAK-i) has different selectivity of JAKs, such as JAK1, JAK2, JAK3, and TIK2. However, little has been known regarding mode of action due to the selectivity difference in clinical practice for treating rheumatoid arthritis (RA).ObjectivesThe aim of this study is to compare difference of efficacy and safety in two JAK-i; between tofacitinib (TOF) and baricitinib (BAR) in clinical practice using one-center retrospective cohort.MethodsWithin the case which administered TOF or BAR to the RA patient who the effect was insufficient in the existing treatment and the disease activity was over the middle disease activity using simplified disease activity index (SDAI). At the start of administration (baseline), 5 mg tablets of TOF were taken twice a day or 4 mg tablets of BAR were taken one a day. Patients were divided by drug and included their sex, age at onset, anti-cyclic citrullinated polypeptide antibodies (ACPA) titer, length of RA history at onset, Sharp/van der Heijde score (SHS) at onset, Naïve/Not Naive for biologic DMARDs or JAK-i, 28-joints disease activity score (DAS28), SDAI, Health Assessment Questionnaire Disability Index (HAQ-DI), and pain score with visual analog scale (PS-VAS). It was classified into large joint and small joint, and the point was independently scored by swelling and pressure pain by size and position in each joint. Total score of the involved joints for each part; upper-extremities, lower extremities, big joints, and small joints (UES/LES/BJS/SJS), rheumatoid factor (RF) titer, serum matrix metalloprotease-3 (MMP-3) level, serum creatinine (Cr) level, and estimated glomerular filtration rate (eGFR) of each part were measured. The mean values of each group were obtained at baseline, 1, 2, 3, 6, 9, and 12 months, and the two groups were statistically compared using the Mann-Whitney U-test. As a sub-analysis, each drug group was divided into bio or JAK-i naive, age ≥ 70 years, disease duration ≥ 10 years, SHS ≥ 100. The change of DAS28 under each 2 divided condition was compared using Mann-Whitney U-test. Similar comparison was carried out with RA patient who administered golimumab (GOL) as a control group. The significance level was less than 5%.Continuation rate (the withdrawal after the remission introduction is put in the continuation) in 12 months after baseline was also compared.ResultsA total of 82 patients were picked up, in whom 22 TOF group, 31 BAR group, and 29 GOL group included. Both DAS28 and SDAI were consistently lower in the BAR than in the other 2 groups from 1 month after baseline. SDAI in the BAR was significantly lower than in the GOL at 3 months after the baseline. The HAQ-DI score at 6 months after baseline was significantly lower in the BAR than in the GOL. PS-VAS in the GOL was significantly higher than the other two groups at 2, 3 and 6 months after baseline. In the joint point, BJS in the BAR was significantly lower than that in the GOL at 2, 3, and 6 month after baseline. SJS in the GOL was significantly lower than that in the TOF at 6 and 12 months after baseline. There was no significant difference in MMP -3, RF, Cr and eGFR between the 3 groups in any observation month, but Cr increased after the start in the BAR group and eGFR tended to decrease.In the sub-analysis, the decrease of DAS28 at 1 year after baseline with a history of ≥ 10 years was significantly greater than in those with a history of < 10 years in the TOF, as well as DAS28 at 1 year in those with SHS ≥ 100 decreased significantly more than that in those < 100. These phenomena was not observed in the BAR group.The continuation rate at 12 months after the start of administration was 86.4% in the TOF, 89.3% in the BAR and 69.0% in the GOL.ConclusionEven JAK-i characteristics in action differs for each drug. It is needed to choose appropriate drug based on these drug characteristics.Disclosure of InterestsNone declared

BackgroundIn a previous article, we introduced a novel index of osteoporosis that represented as T-score ≤ -2.5, which constituted the combined criteria of age, serum creatinine-to-cystatin C ratio (Cr/CysC), and tartrate-resistant acid phosphatase-5b.ObjectivesWe hypothesized that serum cystine C to creatine ratio (CysC/Cr), that is the reciprocal of Cr/CysC, might function as a predictive marker of incident osteoporotic fractures in elderly population and tested this hypothesis in a retrospective cohort study.MethodsSubjects were 50 years of age or older who had their lumbar spine and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, and simultaneously had their CysC/Cr measured. The dates of BMD and CysC/Cr measurements were set as baseline. The primary outcomes were incidental major osteoporotic fractures (MOF), including vertebral fractures, proximal femur fractures, proximal humerus fractures, and distal radius fractures. Follow-up was continued until the first fracture occurred, was terminated at death, was lost to follow-up, or was completed. In these patients, the relationship between baseline developmental MOF and variants was investigated using Cox regression analysis. The variants were candidate risk factors for MOF for positivity and negativity. After identifying risk factors using univariate models, multivariate model was undergone in order to relative higher risk in the factors. Receivers operating characteristic analyses (ROC) were conducted in order to determine cut-off index (COI) of these factors. Kaplan-Meier survival analysis was tested in order to determine hazard ratio for presenting these risk factors.ResultsA total of 175 patients, 38 men and 137 women, were included in the dataset. The mean age at baseline was 70.2 years, ranged from 50 to 98 years, and the mean follow-up was 30.4 months. Mean BMD at baseline was 0.734 and 0.659 g/cm2 (T-score: -2.21 and -2.04) in lumbar spine and femoral neck, respectively, and mean CysC/Cr at baseline was 1.49. fall-ability, LSD, and pr-MOF, were present in, 59, 113, and 77, respectively. Administration of OPD, vitamin-D, GCS, and polypharmacy were present in 92, 170, 12, and 47, respectively (Table 1).Table 1.Results of receiver operation characteristics and Kaplan-Meier survival analysis for each factorFactorcut-off indexarea under the curvep-valueHazard ratio (95%CI)p-valueCysC/Cr> 1.3450.614< 0.016.32 (2.87 – 13.92)< 0.01LSDpresent0.626< 0.013.60 (1.67 – 7.73)< 0.05Fall-abilitypresent0.703< 0.0014.83 (2.16 – 10.21)< 0.001CKDpresent0.612< 0.052.56 (1.06 – 6.20)< 0.05pr-MOFpresent0.685< 0.0014.81 (2.08 – 9.39)< 0.001In Cox regression analysis, the presence of prevalent MOF (pr-MOF), fall-ability, lifestyle-related diseases (LSD), chronic kidney diseases (CKD) ≥ Grade3a, and higher CysC/Cr had significant higher risk ratios with univariate models. In these, the presence of LSD and fall-ability had significant higher risk ratios with multivariate model. All the binary factors had COI as the presence of each event such with 0.626, 0.703, 0.612, and 0.685 of area under the curve for LSD, Fall-ability, CKD, and pr-MOF, respectively. CysC/Cr also had COI (1.345) with 0.614 of the area under the curve.In the Kaplan-Meier survival analysis, CysC/Cr > COI, Fall-ability, pr-MOF, LSD, CKD ≥ Grade 3 b was significantly higher in descending order of Hazard ratio (6.32, 4.83, 4.81, 3.60, 2.56, respectively) (Table 1).ConclusionThese results suggest that CysC/Cr may be a predictor of MOF or a risk factor if it exceeds the COI. This value is the reciprocal of Cr/CysC, and if Cr/CysC reflects muscle mass, CysC/Cr is assumed to reflect low relative muscle mass. It is supposed that this is also affected by sex difference and age. There seems to be a correlation between MOF and CysC/Cr. Early measurement of CysC/Cr facilitates screening for fractures. As a result, it may be easier to implement fracture prevention programs such as drug interventions such as OPD and exercise habit guidance.Disclosure of InterestsNone declared

BackgroundPatients with rheumatoid arthritis (RA) who have a difficult-to-treat condition (D2T RA) are often a burden to both patients and rheumatologists.ObjectivesThe aim of this study was to determine the risk factors for failure to treat in patients with refractory conditions and to find them relevant to prevention.MethodsPatients with RA who were treated under treat-to-target (T2T) strategy more than one year were picked up. Their background characteristics such as sex, age, disease duration, anti-citrullinated polypeptide antibodies titer (ACPA), and disease duration, were collected, and their simplified disease activity index (SDAI) score, Health Assessment Questionnaire Disability Index (HAQ) score, pain score measured with visual analog scale (PS), EuroQol 5th-dimensions score (EQ5D) were monitored every three months. Sharp/van der Heijde score (SHS) was calculated annually.Difficult-to-treat status was determined in according to the EULAR definition of D2T RA [1], and pre-D2T RA status was determined as follows: (Category-1) a failure history of one kind of action in biologic or targeted synthetic disease modifying anti-rheumatic drug (b/tsDMARD) and switched to another b/tsDMARD with other action mechanism or (Category-2) one or more of following status; mean SDAI score in recent three months exceeded 11 (MDA), three consecutive administration of glucocorticoid steroid no less than 7.5mg in prednisolone equivalent (GCS), rapid radiographic progression with 5 or more in SHS than last time (RRP), or decrease of EQ5D score less than -0.2 in recent 6 months (dEQ5D). Patients were recruited when Category-1 or -2 was matched in treating, and their results were determined in the last observation for each category. When second d/tsDMARD was failed until last observation in patient matched Category-1, the patient was judged as “failure”, and the other patient was judged as “success”. When Category-2 continued until last observation, the patient was judged as “failure”, and escaped from the category, the patient was judged as “success”. Risk factors for failure in background characteristics and monitored items in treating were evaluated for each category using binary logistic regression analysis.ResultsA total of 47 in Category-1 and 491 patients in Category-2 were recruited.In Category-1 matched patients, female were 83.0% and mean age was 71.3. Mean SDAI score, HAQ score, PS, EQ5D score, and SHS at failure of b/tsDMARD (baseline) were 15.5, 0.457, 40.1, 0.811, and 72.9, respectively. Numbers of the first b/tsDMARD were 32 TNF inhibitors, 8 IL-6 inhibitors, 6 abatacepts, and 1 JAK inhibitor. Numbers of the second after the first were 13 IL-6 inhibitors and 19 JAK inhibitors after THF inhibitor, whereas 3 TNF inhibitors, 2 abatacepts, and 3 JAK inhibitors after IL-6 inhibitor failure, 1 TNF inhibitor, 1 IL-6 inhibitor, and 4 JAK inhibitors after abatacept failure, and 1 TNF inhibitor after 1 JAK inhibitor failure. In these, success counted 18 and failure counted 29. Significant risk factors for Category-1 failure were higher ACPA, higher SDAI score, higher HAQ score, and higher SHS at baseline (pIn Category-2 matched patients, numbers of each status at first (baseline) were 455 MDAs, 20 GCSs, 17 RRPs, and 9 dEQ5Ds. Numbers in success and failure for each status at baseline were 315 and 140 for MDA, 16 and 4 for GCS, 9 and 0 for RRP, and 7 and 2 for dEQ5D, respectively. Significant risk factors for each failure status were higher mean SDAI score after baseline for MDA, higher HAQ score at baseline for GCS, and higher mean PS after baseline for dEQ5D (pConclusionClinical background factors besides disease activity such as ACPA, HAQ score, and SHS at baseline were important for preventing fall-in D2T_RA. However, most weighted factor was disease activity control after falling in MDA status. Tight disease activity control is the overriding factor.References[1]Nagy G, et al. Ann Rheum Dis 2021;80:31-5.Disclosure of InterestsNone declared.

Summary Background & aims The associations between dietary magnesium intake and stroke and coronary heart disease (CHD) incidences are inconsistent and not established in Asian. We aimed to determine the association between dietary magnesium intake and the risk of stroke and CHD in a Japanese population. Subjects/Methods We studied 85,293 Japanese subjects by questionnaire at baseline (age 45–74 years, without cardiovascular disease or cancer in 1995 and 1998 for Cohorts I and II, respectively). The participants were followed until the end of 2009 and 2010 in Cohorts I and II, respectively. Dietary magnesium intake was estimated from a self-administered 138-item food-frequency questionnaire. Results After 1,305,738 person-years of follow-up, 4110 strokes and 1283 cases of CHD were documented. The multivariable-adjusted hazard ratios (HRs, 95% confidence intervals, 95%CIs) of CHD for the fourth and fifth quintiles of dietary magnesium intake were 0.70 (0.50–0.99) and 0.66 (0.44–0.97) in men (P for trend = 0.036), respectively, and third quintile of dietary magnesium intake was 0.61 (0.39–0.96) in women (P for trend = 0.241), compared with the lowest quintile in men and women. We observed no decreased risks of incident stroke in men or women with higher dietary magnesium intakes. Conclusions Higher dietary magnesium intake was associated with a reduced risk of CHD in Japanese men.

This large-scale population-based cohort study in Japan was conducted to clarify the effects of menstrual and reproductive factors on the risk of later-life vertebral fractures in women. Significant associations were seen for later menarche, irregular menstruation, and shorter reproductive years, corresponding to the effect of reproductive hormonal disturbance on bone metabolism. This study investigated the association between menstrual and reproductive factors and the risk of later-life vertebral fractures in women. Participants were 43,652 women aged 40–69 years who were followed in the 10-year survey of the Japan Public Health Center-based prospective (JPHC) study. Menstrual/reproductive factors were as follows: age at menarche and menopause, menstrual regularity and cycle length, natural or surgical menopause, years since menopause, reproductive years, parity, age at first birth, number of births, breastfeeding, and female hormone use. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression analysis with adjustment for well-known fracture risk factors and menstrual/reproductive factors. During the 10-year period, 250 women reported first onset of vertebral fractures. Menarche at ≥16 years [OR (95% CI) = 2.08 (1.24–3.48)] compared to ≤ 13 years and irregular menstruation [1.42 (1.01–2.00)] compared to regular menstruation showed significantly higher adjusted ORs. Longer reproductive years had significant inverse association [0.96 (0.92–0.99)] in menopausal women. Women with both menarche ≥ 15 years and irregular menstruation had higher adjusted ORs (95% CI) [2.37 (1.51–3.73) in all women, 2.25 (1.35–3.76) in menopausal women] compared to women without these, and both factors had significant interaction, particularly in menopausal women (additive p = 0.025, multiplicative p = 0.0499). Menstrual and reproductive factors, corresponding to the effect of reproductive hormonal disturbance on bone metabolism, might affect the risk of later-life vertebral fractures.

Background Few studies have assessed associations of non-enzymatic antioxidant capacity (NEAC) in the overall diet with all-cause or specific mortality, and their results have been inconsistent. Objectives The present study investigated the association between dietary NEAC and all-cause or cause-specific mortality. Methods The study was a large-scale population-based prospective cohort study in Japan consisting of 42,520 men and 50,207 women aged 44-76 y, who had no history of cancer, stroke, ischemic heart disease, or chronic liver disease. We evaluated FFQ-based dietary NEAC with use of published databases in which the NEACs of individual foods were analyzed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Dietary NEAC was calculated by multiplying the estimated NEAC with the consumed amount and summing up those values for all foods, and was categorized in quartiles. We identified death and cause of death with use of residential registry and death certificates. HRs and 95% Cls for death from the second survey, which was conducted from April 1995 to December 2014 were estimated with Cox proportional hazards regression analysis. Results After 1,498,308 person-years of follow-up, 12,978 total deaths occurred. The multivariable-adjusted HRs (95% Cls) for all-cause mortality for the highest compared with the lowest quartile of FRAP and ORAC were 0.85 (0.80, 0.89) and 0.84 (0.79, 0.89), respectively. Dietary NEACs were inversely associated with mortality from cardiovascular disease (CVD), but not from cancer. The multivariable-adjusted HRs (95% Cls) for CVD for the highest compared with the lowest quartile of FRAP and ORAC were 0.83 (0.75, 0.92) and 0.79 (0.70, 0.89), respectively. Conclusions Higher dietary NEACs from FRAP and ORAC were associated with lower risk of all-cause mortality and mortality from CVD in Japanese adults.

Objectives: Adult height is reported to be related with the risk of various diseases. Some previous studies also suggest a possible link between height and oral health, but no study has been conducted in Japan. The current study aimed at examining if height was linked with the dentition status in Japanese adults. Methods: The subjects were 1,214 adults(mean age: 65.5 ±5.76 years, men: 565, women: 649) who lived in Akita Prefecture, Japan. A selfcomplete questionnaire survey and clinical dental examination were conducted. Results: After adjustment for confounding variables, the number of total teeth (p for trend =0.022), and the sub-categories of anterior (p for trend=0.040) or posterior teeth (p for trend =0.027) significantly increased with an increment of height in men. The increasing trend of prevalence of having fewer than 24 teeth with the decrease of height was not significant but approached the significant level (p for trend=0.073). There was not a significant relationship between height and prevalence of subjects who were edentate. On the other hand, no corresponding significant associations between height and dentition status were found in women. Conclusion: A potential positive relationship between adult height and the number of teeth was suggested in men. The current findings imply the importance to promote both oral and general health by improving nutrition and diet as well as preventing and treating problems or diseases at an early age, in achieving good oral health later in life.

Background In this study, we demonstrated our new device for open donor liver surgery with left-sided heptectomy by use of the real-time moving windows (RTMW) method with 8-cm transverse skin incision for living donors from the viewpoints of cosmetic, economic, and safety procedures. Methods After the upper abdominal 8-cm transverse skin incision was made, the subcutaneous area was exfoliated and the reverse T-shaped-abdominal incision was made, as in open surgery. After that, the 2 Kent hooks for the upper region and the 2 surgical arms for the lower region were placed. The operative fields of hepatic vein, hepatic hilus, and common hepatic artery were explored, respectively, by use of the RTMW method with the use of the 4 surgical hooks. Hepatic parenchymal dissection was carried out with the use of CUSA and laparosonic coagulating shears. Manipulations of 3 hepatic vessels and the hepatic duct were done by the usual procedure of open surgery. Results This operative procedure could be performed without laparoscopic techniques. The operative time was 7 hours, without blood transfusion. The operative course was uneventful, and the patient was discharged on postoperative day 11. Conclusions Our RTMW method for donor left-sided hepatectomy is considered to be a useful operative procedure from the viewpoints of donor safety, cosmetic advantage, and cost performance.

Aims Coping strategies may be significantly associated with health outcomes. This is the first study to investigate the association between baseline coping strategies and cardiovascular disease (CVD) incidence and mortality in a general population cohort. Methods and results The Japan Public Health Center-based prospective Study asked questions on coping in its third follow-up survey (2000–04). Analyses on CVD incidence and mortality included 57 017 subjects aged 50–79 without a history of CVD and who provided complete answers on approach- and avoidance-oriented coping behaviours and strategies. Cox regression models, adjusted for confounders, were used to determine hazard ratios (HRs) according to coping style. Mean follow-up time was 7.9 years for incidence and 8.0 years for mortality. The premorbid use of an approach-oriented coping strategy was inversely associated with incidence of stroke (HR = 0.85; 95% CI, 0.73–1.00) and CVD mortality (HR = 0.74; 95% CI, 0.55–0.99). Stroke subtype analyses revealed an inverse association between the approach-oriented coping strategy and incidence of ischaemic stroke (HR = 0.79; 95% CI, 0.64–0.98) and a positive association between the combined coping strategy and incidence of intra-parenchymal haemorrhage (HR = 2.03; 95% CI, 1.01–4.10). Utilizing an avoidance coping strategy was associated with increased mortality from ischaemic heart disease (IHD) only in hypertensive individuals (HR = 3.46; 95% CI, 1.07–11.18). The coping behaviours fantasizing and positive reappraisal were associated with increased risk of CVD incidence (HR = 1.24; 95% CI, 1.03–1.50) and reduced risk of IHD mortality (HR = 0.63; 95% CI, 0.40–0.99), respectively. Conclusion An approach-oriented coping strategy, i.e. proactively dealing with sources of stress, may be associated with significantly reduced stroke incidence and CVD mortality in a Japanese population-based cohort.

We propose a particle method (MPS method) which can analyse the large deformation, splitting and coalescence of liquid as a new calculation method and a gas-liquid coupling method of finite volume method which can stably solve the compressible flow. By doing this, we aim to solve the interface resolution problem in the interface capture method and to establish a complicated gas-liquid multiphase flow analysis method that can deal with large deformation case. At the temperature of 300K, the validity of the flow field is consistent with the reference. The processes from the acceleration and deformation of a droplet to the solidification of the droplet on a substrate are successfully being observed. The shape of the splat is influence by substrate temperature.

Self-reported measures of oral health are often used to assess oral health in populations or groups, but their validity or reliability needs repeated confirmation. The objective of this cross-sectional study was to evaluate the validity of self-reported tooth counts and masticatory status, using data obtained from a sample of Japanese adults. A total of 2356 adults aged 40 to 75 years participated in a questionnaire survey and a clinical oral examination from 2013 through 2016. Self-reported measures were compared with clinically measured values. For tooth counts, mean clinical and self-reported tooth counts in all participants were 23.68 and 23.78 teeth, and no significant difference was detected. Spearman's, Pearson's and intra-class correlation coefficients between clinical and self-reported tooth counts were 0.771, 0.845 and 0.843, respectively. According to the Bland-Altman analysis, the mean difference between clinical and self-reported tooth counts was -0.098 (95% CI: -0.242, 0.047). The upper limit of agreement was 6.919 (95% CI: 6.669, 7.169), and the lower limit of agreement was -7.115 (95% CI: -7.365, -6.865). No significant fixed or proportional bias was observed. For masticatory status, the crude or age- and gender-adjusted mean numbers of total teeth, posterior teeth and 3 kinds of functional tooth units significantly decreased with the deterioration of masticatory status. This study indicated that self-reports were within an acceptable range of clinical measures. Therefore, self-reports were considered valid alternatives to clinical measures to estimate tooth counts and masticatory status in a current Japanese adult population.

Background: As the population ages, the number of elderly individuals using a wheelchair is increasing. A standard wheelchair with a vertical backrest (S-WC) pushes on a kyphotic spine and exacerbates forward head posture. Forward head posture limits cervical movement. We used a new wheelchair (N-WC) that does not exacerbate thoracic kyphosis. The N-WC does not have a flat backrest, but has a support belt for the thorax and pelvis. The purpose of this study was to compare head-neck angle, cervical range of motion, and cervical muscle activity in the N-WC and the S-WC in healthy elderly women. Methods: We measured head-neck alignment, trunk tilt angle, cervical muscle activity, and pressure distribution on the backrest. Data from 17 subjects were analyzed. Results: Head-neck angle was close to neutral in the N-WC. The trunk was tilted further back and the area over which pressure was distributed on the backrest was expanded in the N-WC. Cervical range of motion and cervical muscle activity during neck extension were significantly greater in the N-WC than in the S-WC, but during neck flexion, there was no significant difference between the wheelchairs. Conclusion: In the N-WC, head-neck alignment was close to the neutral posture because the wheelchair support belt accommodated kyphosis and did not push the spine forward, so cervical muscle activity may be reduced when at rest. These results suggest that the N-WC prevented forward head posture and improved cervical movement and muscle activity. (C) 2014 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.

Background and aims Higher intake of fish or n-3 polyunsaturated fatty acids (PUFAs) has been associated with reduced risk of coronary heart disease (CHD). However, it is unclear whether increased blood levels of n-3 PUFAs are associated with reduced risk of CHD in the Japanese population. Methods The relationship between circulating levels of n-3 PUFAs (eicosapentaenoic acid + docosapentaenoic acid + docosahexaenoic acid) and risk of CHD was examined in a nested case-control study among participants in the Japan Public Health Center (JPHC)-based Study Cohort. Plasma n-3 PUFA phospholipid levels were measured at baseline by gas chromatography in 209 cases with CHD and 418 controls matched for sex, age, date of blood draw, time elapsed since last meal before blood collection, and study location. The CHD cases (n = 209) comprised 168 cases of myocardial infarction and 41 of sudden cardiac death, otherwise classified as 157 non-fatal and 52 fatal coronary events, respectively. Mean duration of follow-up was 13.5 years. Results Multivariate conditional logistic analysis showed no significant association between n-3 PUFAs and risk of total CHD. The odds ratio (OR) for the highest versus lowest quartiles of plasma n-3 PUFAs was 0.79 (95% confidence interval [95% CI]: 0.41–1.51, p for trend = 0.51). Subtype analysis of CHD revealed that the multivariate ORs for the highest versus lowest quartiles for n-3 PUFAs were 0.91 (95% CI: 0.43–1.89, p for trend = 0.90) for myocardial infarction, 0.08 (95% CI: 0.01–0.88, p for trend = 0.04) for sudden cardiac death, 0.89 (95% CI: 0.42–1.89, p for trend = 0.97) for nonfatal coronary events, and 0.12 (95% CI: 0.02–0.75, p for trend = 0.03) for fatal coronary events. Conclusions Plasma n-3 PUFA levels were not associated with risk of total CHD but were inversely associated with risks of sudden cardiac death and fatal coronary events among middle-aged Japanese individuals.

This study assessed the effects of physical activity on a 10-year incidence of self-reported vertebral fractures in adult women of a large Japanese cohort. Medium levels of strenuous activity and long-duration sedentary activity were associated with a lower incidence of vertebral fractures; association patterns appear to be different from hip fractures. Physical activity helps prevent hip fracture, but little is known about the longitudinal association between physical activity and vertebral fractures. The purpose of this study was to evaluate the effects of physical activity on the 10-year incidence of symptomatic vertebral fractures using data from the Japan Public Health Center-based Prospective Study. Baseline studies were conducted in 1993–1994, and the follow-up study was conducted 10 years later. We analyzed 23,757 women aged 40–69 years. At baseline, physical activity was assessed as a predictor by using a questionnaire. Subjects were asked to report vertebral fractures that occurred during the 10-year follow-up period. Relative risks (RRs) adjusted for confounders were estimated by multiple logistic regression analysis. The 10-year cumulative incidence of vertebral fractures was 0.67 %. Those who engaged in strenuous physical activity of

Seafood/fish intake has been regarded as a protective factor for coronary heart disease (CHD), while smoking is a strong risk factor. To examine whether associations between smoking and risk of CHD are modified by seafood/fish intake, we studied 72,012 Japanese men and women aged 45-74 years who completed 2 food frequency questionnaires, 5 years apart, during the period 1995-2009. After 878,163 person-years of follow-up, 584 incident cases of CHD (101 fatal and 483 nonfatal), including 516 myocardial infarctions, were documented. There was a clear dose-response association between smoking and CHD risk among subjects with a low seafood/fish intake (

Introduction Isothiocyanate (ITC) found in cruciferous vegetables are known for its chemopreventive properties that inhibits phase-I enzyme and activates phase-II enzymes. In epidemiologic studies, dietary ITC has been indicated in prevention of various types of cancer, such as lungs and bladder. Food frequency questionnaire (FFQ) is commonly used to assess ITC intake, which combines with laboratory data on the ITC content of specific cruciferous vegetables. Although availability of ITC depends on the contribution of plant myrosinase in the hydrolysis of glucosinolates, ITC content is measured on the basis of raw cruciferous vegetables in general. To our knowledge, no prospective studies have considered the effect of cooking. Using such databases could limit the study outcome of dietary ITC and disease relationships due to overestimation of ITC intake. Here, we aim to evaluate the validity of FFQ in the estimation of isothiocyanate using 12-day weighed food record (WFR) as the reference method by taking cooking methods into account. Methods Two hundred and forty participants (98 men and 142 women) aged 40–74 years from five areas in the JPHC-NEXT validation study were asked to respond to the 172-item FFQ and provide 12-day WFR as reference. Dietary ITC was calculated by combining the newly developed ITC database after consideration of popular cooking methods used in Japan. As we calculated the percentage of both raw and cooked cruciferous vegetable intake from WFR, cooked ITC intake was estimated from FFQ by weighing the average percentage of raw and cooked cruciferous vegetable on the ITC value. Spearman's correlation coefficients between estimates from FFQ and WFR were calculated and corrected for intra-individual variation of the WFR. Reproducibility of ITC intake was also assessed between 2 FFQs administered at an interval of 1-year. Results The mean intake of isothiocyanate according to FFQ was slightly lower than intake by WFR in men and higher in women. Percentage of difference of ITC were −3% for men and +19% in women. Deattenuated Spearman's correlation coefficient for ITC was 0.36 for men and 0.60 for women. Results were virtually unchanged when we applied the sex-unique percentage of raw and cooked cruciferous vegetable intake from WFR to derive correlation coefficients. Conclusions In conclusion, the validity of FFQ in estimating ITC was moderate. The reason for slightly poor correlation of ITC in men, is probably due to larger variance as a results of smaller sample size than in women. Additional confirmation may be warranted by using urinary isothiocyanate, which reflects the true intake of ITC.

Introduction Inflammation is related to the development of many cancers. Diet plays an important role in the regulation of inflammation. The dietary inflammatory index (DII®) is a literature-derived dietary index designed to assess the impact of diet on individual inflammation status. However, most validation studies of DII conducted to date have been done in Western countries, indicating the need for evaluation in Asian populations. The aim of this study was to validate DII scores derived from a food frequency questionnaire (FFQ) with high-sensitive C-reactive protein (hs-CRP) levels in participants undergoing cancer screening in Japan. Methods In cancer screenings conducted from 2009 to 2013 in the National Cancer Center in Japan, 7919 participants aged 40–70 years answered the FFQ and received blood analysis for hs-CRP. Of these, we excluded participants with a body mass index (BMI) of 40 kg/m2 (n = 13); missing data on smoking status (n = 1) or metabolic equivalents (Mets, n = 1); history of cancer, stroke, or myocardial infarction (n = 877); extreme energy intake (upper and lower 2.5 percentiles, n = 349); missing data on alcohol consumption (n = 120); and missing data of hs-CRP, or hs-CRP > 1.0 mg/dL (n = 84). Finally, 6474 participants (3825 for men and 2649 for women) were included in this analysis. DII was calculated from crude intake from the FFQ and adjusted for energy using the density method. Adjusted geometric mean levels of hs-CRP were calculated using a multivariable linear regression model by quartiles of DII score. P for trend across quartiles of DII score were calculated using DII quartiles as continuous variables. Further, logistic regression analysis was also applied to estimate odds ratio (OR) [95% confidence interval (95% CI)] of hs-CRP > 0.3 mg/dL across quartiles of DII score. These statistical models were adjusted by age, body mass index (BMI), smoking status, and metabolic equivalents. Results Mean (standard deviation, SD) energy-adjusted DII for men and women was 0.62 (1.93) and −1.01 (2.25), respectively. Mean (SD) hs-CRP levels for men and women was 0.09 (0.11) mg/dL and 0.07 (0.10) mg/dL, respectively. We found a significant positive association between DII scores and geometric means of hs-CRP levels in men (P 0.3 mg/dL was 1.17 (1.02–1.35) in men and 0.99 (0.79–1.24) in women. On stratified analysis by age and BMI in women, a marginal positive association was observed in women with 25 ≤ BMI Conclusions DII assessed by FFQ was correlated with hs-CRP level in Japanese men, but not in Japanese women.

Summary Porphyromonas gingivalis is a Gram-negative anaerobic oral black-pigmented bacterium closely associated with chronic periodontitis. Lipopolysaccharide (LPS) derived from P. gingivalis is shown to be unusual because the LPS contains a greater number of lipid A species, such as tri-, tetra-, and/or penta-acylated lipid As. In this study, a lipid A possessing penta-fatty acyl chains derived from P. gingivalis strain 381 (compound PG-381–5FA) was synthesized, and examined for its immunobiological activities, compared with a tri-acylated lipid A (compound PG-381–3FA) synthesized previously. Compound PG-381-5FA, similar to compound PG-381-3FA, demonstrated weaker activity in a Limulus test as compared with Escherichia coli-type synthetic lipid A (compound 506). Compound PG-381-5FA, followed by compound PG-381-3FA, induced KC, interleukin-6, and tumour necrosis factor-α production in peritoneal macrophages from LPS-responsive C3H/HeN mice, but not in those from LPS-hyporesponsive C3H/HeJ mice. Furthermore, compound PG-381-5FA, as well as compound PG-381-3FA, activated nuclear factor-κB via Toll-like receptor (TLR)4/mD-2, but not TLR2, in a manner similar to compound 506, and worked as an antagonist for compound 506-induced cell activation. In the case of human peripheral blood mononuclear cells, compound PG-381-5FA showed much stronger IL-6-inducing activity than compound PG-381-3FA. The present results demonstrate that the chemical synthesis of a penta-acylated lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, is attributable to immune cell activation through TLR4, similar to that of compound 506.

Eu 2+ doped CaS nanoparticles were prepared by two kinds of methods, alkoxide and co-precipitation. The as-prepared samples did not show any emission, while the heated samples showed the red emission corresponding to the 4f 6 5d 1 → 4f 7 transition of Eu 2+ . No signal of Eu 2+ was observed in the electron paramagnetic resonance spectra of the as-prepared samples, while the heated samples showed two sets of sextet hyperfine lines corresponding to two isotopes of Eu 2+ with the mass numbers of 151 and 153. Accordingly, these results indicate that Eu 2+ ions were incorporated into CaS during subsequent heating to show the red emission.

The purpose of this study is to clinically confirm the adhesive effect of a vinyl-thiol primer (V-Primer) for precious alloys. Further, we examined the failure of resin-bonded bridges (RBBs) in order to improve the clinical longevity of RBBs, and to analyse the causes of failure. Twenty-six RBBs were bonded with V-primer and Super Bond C & B between May 1987 and December 1997 in the Dental Clinic of the Health Sciences University of Hokkaido. The RBBs were made of silver-palladium-gold alloy or metal-ceramic gold alloys. V-primer was effective in bonding Super Bond C & B to the RBBs made of silver-palladium-gold alloys. Ten prostheses had functioned satisfactorily for 8-11 years. However, six of the 26 RBBs had become detached. In four of the six failed RBBs, the type of bond failure was a mixture fracture in the resin-enamel interface. Our results suggest that: (1) V-primer is effective on RBBs made of silver-palladium-gold alloys. (2) Mechanical retention is necessary for retainers to improve the longevity of RBBs when the V-primer is applied to RBBs made of precious alloys without copper. (3) The RBB should not be applied to abutment teeth that have differences in tooth mobility.

Aim To evaluate and compare the efficiency of root-end preparations using ultrasonic retrotips coated with diamond and zirconium nitride. Methodology Eighty-five extracted single-rooted teeth were root filled, and then resected 3 mm from their apices. Root-end cavities were prepared with KiS (zirconium nitride-coated retrotip), CT-5 (stainless steel tip) or diamond-coated (DC) ultrasonic retrotips, and 10 teeth served as controls. Thirty teeth were used for evaluation of the time required to prepare the root-end cavity, the number of microcracks produced on the resected surface and the number of dentinal tubule openings on the root-canal wall using scanning electron microscope (SEM) images. A further 55 teeth were used for evaluation of dye penetration following filling of the root-end cavities with Super EBA. The degree of dye penetration in millimetres was measured under the microscope after 7 days of immersion in India ink. Statistical analyses were performed using the one-way anova and Scheffe's F-test as the post hoc test. Results There was no significant difference in the number of microcracks and dentinal tubule openings present in the root apices prepared by the three retrotips. The time required for root-end cavity preparation using the DC retrotip was significantly less than that using the other groups (P

Background — Vein graft disease limits the late results of coronary revascularization. C-type natriuretic peptide (CNP) inhibits the growth of vascular smooth muscle cells. Given the effects of CNP on cGMP cascade, we hypothesized that transfected CNP genes modulate endothelial repair and thrombogenicity in the vein graft. Methods and Results — Autologous rabbit jugular vein grafts were incubated ex vivo in a solution of adenovirus vectors containing CNP gene ( Ad.CNP ) or Escherichia coli lac Z gene ( Ad.LacZ ) and then interposed in the carotid artery. Reendothelialization, mural thrombi formation, and intima/media ratio were evaluated on the 14th and 28th postoperative days. More reendothelialization was seen in Ad.CNP -infected grafts than in Ad.LacZ -infected grafts both at 14 days (0.81±0.05 versus 0.30±0.14, P P Ad.CNP -infected grafts than in Ad.LacZ -infected grafts. Neointimal thickening was significantly suppressed in the Ad.CNP group. The in vitro wound assay with human coronary artery endothelial cells revealed significant potentiation of the wound repair process by CNP and atrial natriuretic peptide administration. Conclusions — Infected Ad.CNP accelerated reendothelialization and suppressed thrombosis and neointimal hyperplasia. The method may potentially prevent vein graft disease in patients undergoing coronary artery revascularization.

Systematic review of observational studies has revealed that fish consumption and levels of n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid are associated with a reduced risk of depression. A reverse J-shaped effect of n-3 PUFAs was suggested. However, there is limited evidence from populations with high fish consumption and no studies have used a standard psychiatrist-based diagnosis of major depressive disorder (MDD). Therefore, this population-based, prospective study investigated the association of dietary fish, n-3 PUFA, and n-6 PUFA consumption with risk of psychiatrist-diagnosed MDD in Japan. A total of 12 219 subjects were enrolled from the Saku area in 1990. Of these, we extracted 1181 participants aged 63–82 years who completed food frequency questionnaires in both 1995 and 2000 and also underwent a mental health examination in 2014–2015. Odds ratios (ORs) and 95% confidence intervals (CIs) for MDD according to fish intake and PUFA quartiles were calculated. Current MDD was diagnosed in 95 patients. We found a reduced risk of MDD in the third quartile for fish intake (111.1 g per day, OR=0.44, 95% CI=0.23–0.84), second quartile for EPA (307.7 mg per day, OR=0.54, 95% CI=0.30–0.99) and third quartile for docosapentaenoic acid (DPA) (123.1 mg per day, OR=0.42, 95% CI=0.22–0.85). ORs adjusted for cancer, stroke, myocardial infarction and diabetes remained significant for fish and DPA intake. Our results suggest that moderate fish intake could be recommended for the prevention of MDD in aged Japanese individuals.

We examined the association between green tea consumption and mortality due to all causes, cancer, heart disease, cerebrovascular disease, respiratory disease, injuries, and other causes of death in a large-scale population-based cohort study in Japan.We studied 90,914 Japanese (aged between 40 and 69 years) recruited between 1990 and 1994. After 18.7 years of follow-up, 12,874 deaths were reported. The association between green tea consumption and risk of all causes and major causes of mortality was assessed using the Cox proportional hazards regression model with adjustment for potential confounders.Hazard ratios for all-cause mortality among men who consumed green tea compared with those who drank less than 1 cup/day were 0.96 (0.89-1.03) for 1-2 cups/day, 0.88 (0.82-0.95) for 3-4 cups/day, and 0.87 (0.81-0.94) for more than 5 cups/day (P for trend.001). Corresponding hazard ratios for women were 0.90 (0.81-1.00), 0.87 (0.79-0.96), and 0.83 (0.75-0.91; P for trend.001). Green tea was inversely associated with mortality from heart disease in both men and women and mortality from cerebrovascular disease and respiratory disease in men. No association was found between green tea and total cancer mortality.This prospective study suggests that the consumption of green tea may reduce the risk of all-cause mortality and the three leading causes of death in Japan.

Introduction: The objective of this study was to examine the evolution of antidepressant switch and adjunctive therapy. Methods: This chart review was conducted at 6 primary psychiatric clinics or hospitals, in Tokyo, Japan. A chart review of longitudinal prescriptions was conducted regarding 633 outpatients with major depressive disorder for up to 2 years after their first visit. Patients who had already received antidepressants prior to the visit were excluded. Results: 22.6% (N=143) of the patients completed or continued the outpatient treatment over the 2 years while 27 (4.3%), 23 (3.6%), and 439 (69.4%) patients discontinued it due to hospitalization, referral to another clinic, and loss to follow-up, respectively. A total of 597 episodes of antidepressant treatment were identified. Among them, 482 episodes (80.7%) were associated with the suggested dose ranges while antidepressant drugs were under-dosed in 19.3% (N=115) of the episodes. 50 patients (7.9%) received adjunctive therapy; it was employed after a median of only one antidepressant had been tried. Conclusion: Psychiatrists may be hasty in prescribing an adjunctive therapy in the treatment of depression.

Objective Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women. Design Prospective cohort study. Setting Ten public health centre areas in Japan. Population Forty nine thousand one hundred and twenty-one women of age 45–74 years who responded to a 5-year follow-up survey questionnaire. Methods Intakes of soy foods as well as other covariates were assessed in 1995–1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Main outcome measure Incidence of endometrial cancer. Results During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94–1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84–1.22). Conclusion In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk.

Mucormycosis is an uncommon but frequently fatal infectious complication after solid organ transplantation. We describe successful treatment of invasive mucormycosis in a liver transplant recipient by wound debridement, a right above-elbow arm amputation, and antifungal medications. Early recognition, prompt operative intervention, and initiation of an appropriate antifungal treatment are very important in the management of mucormycosis, a potentially life-threatening infection.

Background—The pathogenesis of ulcerative colitis is unclear, but cytotoxic T lymphocytes infiltrating the mucosa have been implicated in mucosal damage. The Fas ligand (FasL), expressed on cytotoxic T lymphocytes, induces apoptosis in cells expressing Fas.Aim—To analyse FasL expression in affected colonic mucosa to ascertain Fas-FasL interaction in ulcerative colitis.Methods—FasL mRNA was quantified in colonic mucosal specimens from healthy subjects and patients with ulcerative colitis or Crohn’s disease, using the competitive reverse transcription polymerase chain reaction. FasL mRNA localisation was determined by in situ hybridisation. Expression of Fas in colonic mucosa was analysed immunohistochemically. Phenotypes of lamina propria lymphocytes that expressed FasL were analysed by flow cytometry.Results—FasL mRNA was strongly expressed in active ulcerative colitis lesions, but not in those associated with active Crohn’s disease or active proctitis-type ulcerative colitis. In situ hybridisation showed that FasL mRNA expression occurred in mononuclear cells infiltrating lesions. Fas was expressed in epithelial cells in ulcerative colitis and Crohn’s disease, and in normal subjects. Cytometry showed that FasL was expressed in CD3 lymphocytes infiltrating the lamina propria in active lesions.Conclusions—FasL is expressed in CD3 lymphocytes infiltrating into ulcerative colitis but not Crohn’s disease lesions, suggesting that Fas-FasL induced apoptosis participates in the mucosal damage of ulcerative colitis.

Aim: The serum undercarboxylated osteocalcin (ucOC) level, a biochemical bone marker of vitamin K insufficiency, is often affected by anti-osteoporosis drugs. There have been no reports regarding the relationship between ucOC and teriparatide. Subjects and methods: We conducted a prospective observational study of 26 female rheumatoid arthritis (RA) patients. The patients were divided into 3 groups: those who underwent a direct switch from anti-resorptive drugs to teriparatide (12 cases), those who started teriparatide without pre-treatment (5 cases), and the control patients (9 cases). The median age (interquartile range) of the patients in each group was 75 (67–77), 82 (78–84), and 69 (62–80) yr, respectively. All patients, except controls, received 48-week treatments of teriparatide. We analyzed the median 48-week changes from baseline of the serum ucOC levels with the Steel-Dwass method. Results: The median change from baseline in the direct switch group was higher than that in other groups (p

Serum undercarboxylated osteocalcin (ucOC) is a biochemical bone marker of vitamin K insufficiency. It had been reported that bone resorption inhibitors tend to decrease the serum ucOC level in patients with primary osteoporosis. In rheumatoid arthritis (RA) patients, these results have never been reported.We investigated risk factors which could change serum ucOC level in post-menopausal women with RA (no.=100).Twenty patients received no bone resorption inhibitor (control), 30 received raloxifene (RLX), while 50 received alendronate (ALN). This cross-sectional study was limited to patients with low RA disease activity (Disease Activity Score-28 ≤3.2). We measured serum ucOC, and the data were analyzed by multivariable analysis, including ucOC and the other variables.Scheffe's F test demonstrated a significant difference in serum ucOC levels between controls and the RLX group (p0.01), and between controls and the ALN group (p0.01). Serum ucOC levels were low in both treated groups. An adjusted multivariate analysis was performed for the variables: bone resorption inhibitor use, serum alkaline phosphatase, glucocorticoid dose, age, estimated glomerular filtration rate and matrix metalloproteinase 3. As a result, serum ucOC inversely correlated with bone resorption inhibitor use (p0.01) and oral glucocorticoid dose (p0.01), which were independent risk factors of lowering ucOC.Bone resorption inhibitors and glucocorticoids were independent risk factors for lowering serum ucOC levels in post-menopausal RA patients.

OBJECTIVE How honestly patients report their symptoms and medication adherence to their physicians has not been adequately addressed in patients with depression. We therefore conducted a large-scale Internet survey in an effort to discover how successful physicians are in eliciting the truth from their patients and also to examine reasons for patients' truth-concealing behaviors. METHOD 2,354 participants who had received treatment for depression within the past year and had been diagnosed with depression by Patient Health Questionaire were identified from 323,226 registrants at the Macromill database through screening procedures. Participants were asked to complete a questionnaire regarding their treatment for depression with a special focus on patient-physician relationship. This study was conducted from December 7 to 13, 2010, in Japan. RESULTS 2,020 participants successfully completed the questionnaire. Overall, 70.2% of responders reported that they had withheld the truth from their physicians. A logistic regression model found significant associations of such a behavior with female sex (95% CI, 1.15-1.74; P = .001), younger age (95% CI, 0.49-0.97; P = .030), and a lower degree of satisfaction in mutual communication (95% CI, 3.17-6.58; P < .001). 69.2% and 52.6% of the participants refrained from telling about their "daily activities" and "symptoms," respectively. Female participants were more likely to hide the facts concerning "adherence to prescribed medication" and "figures such as body temperature and weight." 31.9% of participants had discontinued the treatment without consulting their physician, which was again more frequent in females, younger persons, and those who were not satisfied with communication with their physician. CONCLUSIONS While the findings obtained herein need to be replicated in other patient populations, a majority of patients with depression were reluctant to uncover the truth, which emphasizes the need for more fine-tuned suspicion among physicians about symptoms and medication adherence.

The input voltage reflection coefficient on a tapered microstrip transmission line is analyzed and a new Fourier transform pair is derived which introduces echo time and frequency as variables. Calculations of the input reflection coefficient take into account the frequency dispersion-characteristics of the effective permittivity. An efficient method is proposed for analysis and synthesis of microstrip tapers and numerical results are presented for microstrip exponential tapers and microstrip Chebyshev tapers. >

Background Adherence has recently been suggested to be divided into these two components: persistence (i.e., whether patients continue treatment or not) and compliance (i.e., whether patients take doses as instructed). However, no study has yet assessed these two clinically relevant components at the same time in adherence to antidepressant treatment in the clinical outpatient setting. Methods In this retrospective chart-review, 6-month adherence to antidepressants was examined in 367 outpatients with a major depressive disorder (ICD-10) (170 males; mean ± SD age 37.6 ± 13.9 years), who started antidepressant treatment from April 2006 through March 2007. Additionally, we evaluated Medication Possession Rate (MPR), defined as the total days a medication was dispensed to patients divided by the treatment period. Results Only 161 patients (44.3%) continued antidepressant treatment for 6 months. Among 252 patients who discontinued their initial antidepressant, 63.1% of these patients did so without consulting their physicians. Sertraline use was associated with a higher persistence rate at month 6 (odds ratio 2.59 in comparison with sulpiride), and the use of anxiolytic benzodiazepines had a positive effect on persistence to antidepressant treatment only at month 1 (odds ratio 2.14). An overall MPR was 0.77; 55.6% of patients were considered compliant (i.e., a MPR of ≥ 0.8). Conclusion Given a high rate of antidepressant discontinuation without consulting their physicians, closer communication between patients and their physicians should be encouraged. Although the use of anxiolytic benzodiazepines was associated with a higher persistence to antidepressant treatment at month 1, the use of these drugs should be avoided as a rule, given their well-known serious adverse effects.

By mimicking Meissner’s corpuscles, carbon microcoils (CMCs) were embedded into an elastic resin to produce biomimetic proximity/tactile sensors. The CMC sensors were found to have a high elasticity, high sensitivity, high discrimination ability, and a high performance, as well as being easily made in a micron size. These sensors have potential applications in robotic surgery, medical treatment, and diagnosis, etc.

Deficiency in nitric oxide (NO) is a major factor leading to deterioration and progression of certain glomerular diseases. Agents enhancing NO availability and potentiality are renoprotective. Irsogladine maleate (IM), an anti-ulcer drug, is reported to improve gastric blood flow via NO-dependent mechanisms. We, therefore, asked whether and how IM interacted with NO on glomerular mesangial cells.Mesangial cells were exposed to IM and NO donors. Activation of cAMP signalling pathways was assessed by intracellular cAMP, phosphorylation of VASP, activation of the cAMP response element (CRE) and expression of CRE-regulated proteins.IM alone did not affect cell proliferation. However, it greatly enhanced the growth-inhibitory effect of NO donor S-nitroso-N-acetylpenicillamine (SNAP). IM acted synergistically with NO on suppression of mitogen-activated protein kinase activation, induction of gap junction protein connexin43, increase of intracellular cAMP, and phosphorylation of VASP. With the use of the CRE-SEAP-based reporting system, IM and SNAP cooperatively activated cAMP response elements (CRE). A similar activation of cAMP was induced by IM with two different NO donors, the sGC activator Bay 41-2272 and the cGMP analogue 8-bromo-cGMP. The effects of SNAP and IM on cAMP activation were mimicked by phosphodiesterase 3 (PDE3) and PDE4 inhibitors. In addition, IM markedly augmented cytokine-induced expression of iNOS, production of NO and activation of CRE.The effects of NO were greatly potentiated by IM through synergistic activation of cAMP pathway. Combined therapy with IM and NO may be developed for certain renal diseases.

The purpose of this study is to clinically confirm the adhesive effect of a vinyl-thiol primer (V-Primer) for precious alloys. Further, we examined the failure of resin-bonded bridges (RBBs) in order to improve the clinical longevity of RBBs, and to analyse the causes of failure. Twenty-six RBBs were bonded with V-primer and Super Bond CB between May 1987 and December 1997 in the Dental Clinic of the Health Sciences University of Hokkaido. The RBBs were made of silver-palladium-gold alloy or metal-ceramic gold alloys. V-primer was effective in bonding Super Bond CB to the RBBs made of silver-palladium-gold alloys. Ten prostheses had functioned satisfactorily for 8-11 years. However, six of the 26 RBBs had become detached. In four of the six failed RBBs, the type of bond failure was a mixture fracture in the resin-enamel interface. Our results suggest that: (1) V-primer is effective on RBBs made of silver-palladium-gold alloys. (2) Mechanical retention is necessary for retainers to improve the longevity of RBBs when the V-primer is applied to RBBs made of precious alloys without copper. (3) The RBB should not be applied to abutment teeth that have differences in tooth mobility.

To evaluate and compare the efficiency of root-end preparations using ultrasonic retrotips coated with diamond and zirconium nitride.Eighty-five extracted single-rooted teeth were root filled, and then resected 3 mm from their apices. Root-end cavities were prepared with KiS (zirconium nitride-coated retrotip), CT-5 (stainless steel tip) or diamond-coated (DC) ultrasonic retrotips, and 10 teeth served as controls. Thirty teeth were used for evaluation of the time required to prepare the root-end cavity, the number of microcracks produced on the resected surface and the number of dentinal tubule openings on the root-canal wall using scanning electron microscope (SEM) images. A further 55 teeth were used for evaluation of dye penetration following filling of the root-end cavities with Super EBA. The degree of dye penetration in millimetres was measured under the microscope after 7 days of immersion in India ink. Statistical analyses were performed using the one-way ANOVA and Scheffe's F-test as the post hoc test.There was no significant difference in the number of microcracks and dentinal tubule openings present in the root apices prepared by the three retrotips. The time required for root-end cavity preparation using the DC retrotip was significantly less than that using the other groups (P0.01). Positive controls showed dye penetration throughout the length of the root-end cavity, and negative controls showed no dye penetration. There was no significant difference between the three experimental groups in dye penetration.In this laboratory study, the time required to prepare root-end cavities using KiS retrotips was the same as that using CT-5 retrotips, and longer than that using DC retrotips. There was no significant difference in the number of microcracks or dye penetration between the three kinds of retrotips.