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Background Locomotive syndrome (LS) is a high risk condition that requires nursing care. It is important to investigate the prevalence of and factors related to LS to maintain a healthy life expectancy for patients; however, only a few reports have focused on the relationship between LS and total hip arthroplasty (THA). The purpose of this study was to evaluate the prevalence of LS and to identify factors associated with LS in patients more than 10 years after THA. Methods This is a cross-sectional cohort study. Patients were assessed via a mail survey that included items regarding demographic data, cardiometabolic and motor disorders, the incidence of falls, physical activity level, and the 25-question Geriatric Locomotive Function Scale (GLFS-25) questionnaire. LS was defined as having a score ≥16 on the GLFS-25, and the respondents were categorized into two groups: an LS group and a non-LS group. The prevalence of LS was calculated in each gender and age group. Differences in variables between the groups were determined using the unpaired t-test and chi-squared test. Results A total of 593 patients were included in the study (mean age, 70.4 years; 525/593 females). According to the GLFS-25, 164 patients (27.7%; 21.1% men and 28.8% women) were classified as having LS, which increased with age. In addition, compared with the non-LS group, the LS group had a significantly higher prevalence of motor diseases, cardiometabolic diseases, and falls and significantly lower levels of activity. Conclusion These findings suggest that the prevalence of LS in patients more than 10 years after THA is 27.7%. The result suggest that the prevalence of LS in patients more than 10 years after THA is similar to the prevalence of LS in the general elderly population. Furthermore, LS is related to not only motor diseases but also cardiometabolic diseases.

Metabolic syndrome (MetS) is cluster of metabolic diseases, including abdominal obesity, hyperglycemia, high blood pressure, and dyslipidemia, that directly escalate the risk of type 2 diabetes, heart disease, and stroke. Thioredoxin-interacting protein (TXNIP) is a binding protein for thioredoxin, a molecule that is a key inhibitor of cellular oxidation, and thus regulates the cellular redox state. Epigenetic alteration of the TXNIP-encoding locus has been associated with components of MetS. In the present study, we sought to determine whether the level of TXNIP methylation in blood is associated with MetS in the general Japanese population. DNA was extracted from the peripheral blood cells of 37 subjects with and 392 subjects without MetS. The level of TXNIP methylation at cg19693031 was assessed by the bisulfite-pyrosequencing method. We observed that TXNIP methylation levels were lower in MetS subjects (median 74.9%, range 71.7-78.4%) than in non-MetS subjects (median 77.7%, range 74.4-80.5%; p = 0.0024). Calculation of the confounding factor-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for hypomethylation revealed that subjects with MetS exhibited significantly higher ORs for hypomethylation than did those without MetS (OR, 2.92; 95% CI, 1.33-6.62; p = 0.009). Our findings indicated that lower levels of TXNIP methylation are associated with MetS in the general Japanese population. Altered levels of DNA methylation in TXNIP at cg19693031 might play an important role in the pathogenesis of ‍MetS.

Objectives: Prolonged muscle weakness after total hip arthroplasty (THA) remains a problem. Despite increasing physical activity up to 3 years after surgery, muscle strength was decreased to 80–90% of the healthy side 2 years after THA. The objective of the present study was to identify the nutritional factors related to muscle weakness 1 year after THA. Methods: Persons who underwent THA were divided into 2 groups according to the cutoff point of knee extensor strength that represents functional limitation: a normal-strength group of 71 persons and a muscle weakness group of 91 persons. The investigators assessed lower limb isometric strength, the 10-m timed gait test, and daily intakes of energy and nutrients from preoperative to 1 year after THA. The differences in nutrient intakes between the 2 groups (normal-strength group and muscle weakness group) were examined by multiple logistic regression analysis. Results: There was a significant difference between the groups in energy intake. Daily protein intake was related to knee extension strength gain above the cutoff point 1 year after THA. Conclusions and Implications: The present study suggested that to prevent prolonged muscle weakness after THA, a sufficient protein intake as well as an exercise intervention may be needed even half a year or after.

Objective: To evaluate the prevalence of frailty and associated factors among community-dwelling older adults who have undergone total hip arthroplasty (THA). Materials and methods: This study, which employed a cross-sectional, observational design, was conducted between April and November 2020. The participants were older adults (⩾65 years) who had undergone primary THA at the study hospital. Based on Fried’s modified phenotype, frailty was stratified into 3 degrees according to the presence of 3 or more of the following components: weight loss, weakness, exhaustion, low activity level, and slow walking speed. Multinomial logistic regression was used to analyse the associations of frailty with its potential risk factors. Results: The data of 518 participants were analysed. The overall prevalence of frailty and prefrailty was 11.4% and 51.0%, respectively. The multinomial logistic regression analysis showed that calf circumference (odds ratio [OR] 0.716, 95% confidence interval [CI], 0.611–0.839; p Conclusions: Frailty was highly prevalent in community-dwelling older adults after THA. Further, its potential associations with calf circumference, hip abductor and knee extensor muscle strength, TUG performance, and fall history highlight the significance of these factors for interventions.

To expand the applicability of the third-generation DNA sequencing technologies for the brewing industry, the new experimental protocols for quality control (QC) brewery laboratories have been deve...

Sarcopenia is a multifaceted geriatric syndrome associated with the loss of muscle mass. We examined the relationship between low muscle mass and inflammatory cytokines in the context of aging. This study involved 299 participants (127 men and 172 women; mean age 63.3 ± 9.8 years) who underwent health checkups for body composition and inflammatory cytokine (TNF-alpha, IL-6, and MCP-1) levels. Muscle mass was determined using the skeletal muscle mass index. We divided the participants into the normal (N) and low muscle mass (L) groups and compared the levels of inflammatory cytokines in nonelderly ( p < 0.05 ). However, there was no significant difference in the inflammatory cytokine levels between the groups. Among the elderly subjects, the TNF-alpha level was significantly lower in the L group than in the N group ( p < 0.05 ), whereas there were no significant differences in the IL-6 and MCP-1 levels. Moreover, TNF-alpha was identified as a risk factor for the L group in the logistic regression analysis (Exp (B) 0.935, 95% CI: 0.876–0.997, p = 0.04 ). Although a low TNF-alpha level is a risk factor for low muscle mass, inflammatory cytokine levels are not necessarily elevated in elderly individuals with the loss of muscle mass.

Objective: Postoperative complications and non-periprosthetic fractures (NPPFs), which was defined as a fracture existing non- periprosthetic implant, after total hip arthroplasty (THA) have a negative effect on the patients' ability to perform activities of daily living. Thus, investigating these incidences of patients after THA will be valuable as it lead to a more strategic physical therapy interventions and advanced research to prevent these problems. The purpose of this study was to investigate the incidence of postoperative complications related to implants and NPPFs in patients after THA, a more than 10-year follow-up. Methods: This is a retrospective cohort study. A total 892 patients with hip osteoarthritis who underwent primary THA were analyzed (age at surgery was 45-79 years; 805 women; the average follow-up period was 12.4-year). The postoperative complications related to implants and NPPFs were calculated using data from their medical records. Results: The postoperative complications occurred in 37 patients, and NPPFs occurred in 72 patients, who were significantly older, and hip and knee OA diagnosis, compared to patients without NPPFs ( p

Objectives Carotenoids are plant pigments found in many vegetables, functioning as antioxidants scavenging singlet molecular oxygen and peroxyl radicals. No longitudinal study exists on the relationship between carotenoids and knee osteoarthritis (KOA) development. We aimed to determine the incidence of KOA development for 10 years in community-dwelling people in Japan and assess its association with serum carotenoids. Methods Data of 440 participants (174 men, 266 women) with health-screening records for at least 10 years were analysed. We defined KOA development as advancing from K/L grade 0/1 at the initial check-up to grade ≥2 in a unilateral knee during a 10-year follow-up period. Serum carotenoid levels were measured using high-performance liquid chromatography. We used the Cox hazard model for multivariate analysis and investigated each carotenoid’s impact on KOA development. Results KOA developed in 33.4% of patients; the annual KOA development rate was significantly higher among women than among men (p Conclusion The annual rate of KOA development was higher in women, and retinol was associated with KOA development in women.

BackgroundDNA methylation plays an important role in the pathogenesis and progression of cardiovascular disease (CVD) but the prospective association of DNA methylation with CVD has not been evaluated. Here, we conducted a prospective study to examine whether long interspersed nuclear element-1 (LINE-1) DNA methylation is associated with CVD mortality in a Japanese population.MethodsWe targeted 822 Japanese who participated in a health check-up in 1990 and had no clinical history of cancer, stroke or ischaemic heart disease. DNA was extracted from peripheral blood mononuclear cells and LINE-1 DNA methylation at three CpG sites was measured using a pyrosequencing method. We used propensity score (PS) matching to reduce the effect of potential confounding.ResultsDuring 18 118.7 persons-years of follow-up, there were 329 deaths from all-causes and 85 deaths from CVD. In PS-matched analysis, a significantly higher HR for CVD mortality was observed in the hypermethylation group than in the hypomethylation group for elderly participants (HR 2.77; 95% CI 1.55 to 4.93). No significant association between LINE-1 DNA methylation and CVD was observed for middle-aged participants.ConclusionsBased on this prospective study, we suggest that LINE-1 DNA hypermethylation is associated with increased CVD mortality risk in an elderly population.

Purpose: Cetuximab inhibits epidermal growth factor receptor (EGFR) signaling in cancer and skin cells, thereby inducing anti-cancer effects and skin disorders. The present study aimed to evaluate the relationships between serum cetuximab and EGFR-related markers, and adverse effects in head and neck cancer patients.Methods: Thirty-four head and neck cancer patients receiving weekly intravenous cetuximab were enrolled. Serum cetuximab levels were determined just before dosing. Blood samples for determination of serum EGFR-related markers including soluble epidermal growth factor receptor (sEGFR) and interleukin-6 (IL-6) were obtained. The severities of skin disorders, their medications, and hypomagnesemia treatment were also assessed.Results: Serum levels of cetuximab and sEGFR were negatively and positively correlated with that of IL-6, respectively. The serum cetuximab level was 2-fold higher in the patients with a grade 2–3 skin rash than with a grade 0–1 rash. The serum cetuximab cut-off value related to severe skin rash was 71 μg/mL (sensitivity, 59%; and specificity, 94%). The use of a strong topical corticosteroid for skin rash was also associated with a higher serum cetuximab level. Serum levels of sEGFR and IL-6 had no correlations with the skin disorder severities or their medications. Hypomagnesemia treatment using intravenous magnesium sulfate was not related to serum cetuximab and EGFR-related markers.Conclusions: Head and neck cancer patients with a higher serum IL-6 level tended to have a lower serum cetuximab level. Serum cetuximab had positive correlations to skin rash severity and its medication in the study population.

The easy Z-score imaging system (eZIS) analysis is used for the diagnosis of dementia by cerebral blood flow on single photon emission computed tomography (SPECT). Differences in the acquisition and reconstruction conditions in SPECT may affect the eZIS analysis results. The present study aimed to construct our institutional normal database (NDB) and Alzheimer’s disease (AD)-specific volumes of interest (VOIs) in eZIS analysis, and to compare the differential diagnostic ability between healthy controls (HC) and patients with AD in the image reconstruction filtered back projection (FBP) and ordered subset expectation maximization (OSEM) methods. An NDB was constructed at our institution from 30 healthy individual using the FBP and OSEM reconstruction methods. We divided 51 HC and 51 AD patients into two groups, one for AD disease-specific VOI construction (HC, AD) and the other for NDB verification (HC, AD); image reconstruction was performed using FBP and OSEM. The areas of reduced blood flow in AD patients were compared with those of HC using the two types of image reconstruction methods. We used AD disease-specific VOI and NDB from each reconstruction method in eZIS analysis and compared the differential diagnostic ability for HC and AD with the different reconstruction methods. Comparing the areas of reduced blood flow in AD patients using the different image reconstruction methods, OSEM showed decreased blood flow in the medial region of the temporal lobes compared to FBP. Comparing the differential diagnostic ability for HC and AD using eZIS, the Severity, Extent, and Ratio showed higher values in the analysis performed using OSEM image reconstruction compared to FBP. With the 99mTc-ECD SPECT, the eZIS analysis equipped with our institutional AD-specific VOI and NDB using OSEM image reconstruction could distinguish HC from AD better than eZIS analysis using FBP image reconstruction. This study is registered in UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000042362.

This study aimed to evaluate the influence of CYP2D6 activity and cachexia progression on the enantiomeric alteration of plasma tramadol and its demethylated metabolites in head and neck cancer patients. Fifty-three head and neck cancer patients receiving oral tramadol were enrolled. The plasma concentrations of tramadol, O-desmethyltramadol (ODT), and N-desmethyltramadol (NDT) enantiomers were determined. The CYP2D6 activity score (AS) and degree of cachexia progression were assessed according to genotype and the Glasgow Prognostic Score (GPS), respectively. The enantiomeric ratio of NDT was (+)-form dominant in all patients. CYP2D6 AS had negative correlations with the plasma concentrations of (+)-NDT and (−)-NDT. The plasma concentrations of (+)-tramadol and (+)-ODT were higher in patients with GPS 1 or 2 than in those with GPS 0. Lower metabolic ratios to NDT enantiomers were observed in patients with GPS 1 or 2. In patients with GPS 1 or 2, the plasma (−)-tramadol was associated with the incidence of central nervous system symptoms. In conclusion, CYP2D6 AS partially explained the contribution of CYP2D6 activity to plasma tramadol and its demethylated metabolite enantiomers. Additionally, cachexia progression elevated the plasma (+)-tramadol and (+)-ODT levels through the reduction of N-demethylation of (+)-tramadol.

Previous reports suggest that a headrest significantly influences cerebral blood flow (CBF) in the anterior and posterior regions by image reconstruction and attenuation correction (AC). The present study aimed to clarify the influence of a headrest on the process of reconstruction and AC of brain SPECT images. Methods: We evaluated the influence on CBF in the anterior, middle, and posterior regions of the brain in filtered back projection (FBP)-Chang AC, ordered subset expectation maximization method (OS-EM)-Chang AC, OS-EM-CT-based AC (CTAC), and OS-EM No-AC (no correction for attenuation) with /without a headrest. Subjects were Seventeen healthy volunteers who underwent 99mTc-ECD SPECT. We compared the anterior (A+B)/posterior (G) and the middle region (D+F)/posterior (G) ratios of 99mTc-ECD SPECT images in each group. Results: There are significant differences in A+B/G ratios between with and without a headrest in FBP-Chang AC, OS-EM-Chang AC, and NoAC. On the other hand, there are no significant differences in A+B/G ratios regardless of a headrest in OS-EM-CTAC. There are significant differences in D+F /G ratios between with and without a headrest in FBP-Chang AC, and NoAC. There are no significant differences in D+F /G ratios regardless of a headrest in OS-EM-CTAC and OS-EM-Chang AC. Conclusion: The headrest’s influence on image reconstruction and AC should be considered in FBP-Chang AC, OS-EM-Chang AC, and NoAC except for OS-EM CTAC.

This phase 3 multicenter study, including 26‐week treatment and extension periods, evaluated the efficacy and safety of adalimumab in Japanese patients with active ulcers due to pyoderma gangrenosum. Patients received adalimumab 160 mg at week 0, 80 mg at week 2, and then 40 mg every week starting at week 4. Of the 22 enrolled patients, 12 (54.5%, P

Osteoporosis is a disease characterized by deterioration of bone tissue and mass, with an increasing global prevalence. Therefore, the discovery of biomarkers for osteoporosis would help to guide appropriate treatment. Circulating microRNAs (miRNAs) have become increasingly recognized as biomarkers for detecting diseases. However, few studies have investigated the association of circulating miRNA with osteoporosis in the general population. The aim of this study was to identify miRNA associated with osteoporosis in a general resident health check-up for potential use as an osteoporosis biomarker. We conducted a cross-sectional study as part of a health check-up program and recruited 352 volunteers (139 men, 213 women, mean age 64.1±9.6 years). Osteoporosis was diagnosed according to the WHO classification. Twenty-two candidate microRNAs were screened through real-time quantitative PCR, and miRNAs associated with osteoporosis were analyzed using logistic regression analysis including other risk factors. In total, 95 females and 30 males were diagnosed with osteoporosis with bone mineral density tests (BMD: T‐score<−2.5). We found that miR195 was significantly lower in females, while miR150 and miR222 were significantly higher in males. The results of the logistic regression analysis indicated that in females, higher age and lower miR195 (odds ratio: 0.45, 95% confidential interval: 0.03–0.98) were significant risk factors for lower BMD, while the presence of a smoking habit and lower miR150 (odds ratio: 1.35, 95% confidential interval: 1.02–1.79) were significant risk factors for osteoporosis. Serum levels of miR195 and miR150 are independently associated with low bone mineral density in females and males, respectively.

Until 30 years ago, only a limited number of bacterial and wild yeast species had been recognized as beer spoilers. However, the number of spoilage species have been rapidly increasing since then, ...

Background: MicroRNAs (miRNAs) play crucial roles in the development of various diseases, including chronic kidney disease (CKD). Although previous studies in clinically severe patients have investigated associations between CKD and miRNAs, with particular attention on renal fibrosis, relationships in a general population have yet to be established. The aim of this study was to examine the relationship between expression level of circulating miRNAs and CKD in a middle-aged Japanese population. Methods: A final total of 513 individuals (216 men and 297 women) who participated in the health check-up program in 2012 were included in our analysis. Quantitative real-time polymerase chain reaction was used to determine expression levels of 22 miRNAs. Estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine level, sex, and age. Participants with eGFR

Non-alcoholic fatty liver disease (NAFLD) is closely associated with obesity, metabolic syndrome, and type II diabetes mellitus. Recently, circulating microRNAs (miRNAs) have been proposed as useful disease biomarkers. We examined whether circulating miRNAs, such as miR-20a, miR-27a, and miR-126, were useful biomarkers for NAFLD. We conducted a cross-sectional analysis of 527 subjects aged 39 years or older who had undergone a health examination in the Yakumo Study. Of the residents, 92 were diagnosed with NAFLD using a registered medical sonographer. Serum miR-20a, miR-27a and miR-126 levels were measured by quantitative real-time PCR. We then calculated the odds ratios for serum miRNA level changes according to the severity of NAFLD using normal liver status as the reference group. Serum levels of miR-20a and 27a, but not miR-126, were significantly lower in NAFLD subjects than normal subjects. Serum miR-20a and miR-27a levels were significantly lower in both male and female severe NAFLD subjects. Logistic regression analysis showed a significant relationship between low circulating miR-20a and 27a levels and severe NAFLD. Down-regulated circulating miR-20a and 27a levels were significantly associated with severe NAFLD in the general population. Circulating miR-20a and miR-27a may be useful biomarkers for severe NAFLD.

Cerebrospinal fluid (CSF) mask correction has been developed to reduce the influence by CSF area dilatation for 123I-FP-CIT accumulation. In this study, we assessed the effect of CSF mask correction on the specific binding ratio (SBR) for 25 patients with idiopathic normal pressure hydrocephalus (iNPH). The SBRs with and without CSF mask correction were calculated, and changes in quantitative values were verified. Additionally, the volume removed from striatal and background (BG) volume of interest (VOI) by the CSF mask correction was calculated, the volumes removed were compared to verify their effect on SBR. Twenty and five patients had low and high SBRs, respectively, after CSF mask correction. The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively, than those in the striatal region. In conclusion, the SBR before and after CSF mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results may indicate that CSF mask correction is effective in patients with iNPH. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826.

Background DNA methylation plays an important role in progression of cardiovascular disease (CVD). The methylation status of long interspersed nuclear element-1 (LINE-1) reflects the global DNA methylation level and is associated with lipid profiles and glycemia. We conducted a longitudinal study to examine the association between LINE-1 DNA methylation and CVD mortality in a Japanese elderly population. Methods We targeted for 357 subjects (143 men and 214 women) who were more than 60 years, participated in the health checkup in 1990, and had no clinical history of cancer, stroke, or ischemic heart disease. During 29 years of follow-up period, total 69 subjects were died from CVD, and died of cerebrovascular disease (CBD) and ischemic heart disease (IHD) were 25 and 13, respectively. LINE-1 DNA methylation was measured using PBMCs. We defined the hypermethylation group as greater than median of the LINE-1 DNA methylation levels and hypomethylation group as others. Multivariable Hazard ratios (HRs) for each disease mortality were calculated by the Cox proportional hazard model. We adjusted for age, sex, smoking habits, and alcohol consumption. Results Significantly higher HRs for CVD and CBD mortality were observed in the hypermethylation group compared to the hypomethylation group (CVD: HR 1.67 [95%CI 1.02-2.73], CBD: HR 3.29 [95%CI 1.29-8.40]). However, IHD mortality did not associated with LINE-1 DNA methylation. Conclusions We found that LINE-1 DNA hypermethylation in PBMCs was associated with high CVD mortality, especially CBD mortality. Key messages Higher levels of LINE-1 methylation in PBMCs can be a predictive marker for CBD risk

Background Although dementia is a huge problem in public health, no fundamental biomarker has been established to detect cognitive decline at the early stage. MicroRNAs (miRNAs) regulate gene expression, and are associated with the development of various diseases. Methods The subjects of this prospective study were 162 (75 men, 87 women) residents who attended a health examination in Yakumo town in Hokkaido, in 2012 and re-attended at least once while 2013 to 2015. Serum samples were collected in 2012 and serum miRNA were measured by qRT-PCR. We used a short version of the Mini-Mental State Examination (SMMSE) to screen cognitive function, and calculated the change in SMMSE score per year. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) of serum miRNA levels for cognitive decline (decrease of greater than 0.5 points per year) using the lowest tertile group of miRNAs as the reference by logistic regression analysis. Results The mean age and change in SMMSE score of the subjects was 63.9±9.6 years and -0.03±1.19 points. Odds ratios (ORs) for cognitive decline were significantly higher in the highest tertile of serum miR-221 (OR = 3.24, 95%CI=1.20-8.72) and miR-222 (OR = 4.01, 95%CI=1.36-11.80) even if confounding factors were adjusted. Conclusions High serum levels of miR-221 and -222 were significantly associated with cognitive decline. Key messages High serum levels of miR-221 and -222 may be potential candidate biomarkers for prediction of cognitive decline.

Dairy products have been indicated as a risk factor for prostate cancer. However, only a few epidemiological studies have reported dairy products as being a risk factor for prostate cancer in Japan, reporting contradictory results. We therefore investigated the association between the intake of dairy products and the occurrence of prostate cancer through a large‐scale cohort study. The Japan Collaborative Cohort study analyzed approximately 110,000 residents from various Japanese districts who participated in our questionnaire survey during 1988–1990. The subjects of the present study were 26,464 men (age range: 40–79 years) from 24 districts wherein cancer incidence was reported. Their clinical course was followed up until 2009. Hazard ratios (HRs) were calculated using Cox's proportional hazards model, adjusted for age, survey area, family history of prostate cancer, body mass index, and total energy intake. For diet, we calculated the HRs associated with intermediate and high consumption of dairy products and compared them with those associated with low consumption. There were 412 cases of prostate cancer in the survey population. As dairy products, milk, yogurt, cheese, and butter were evaluated. Among them, milk consumption was associated with a significant risk (HR = 1.37, p = 0.009) and a dose‐dependent response (p for trend = 0.009) adjusted for age and family history of prostate cancer, stratified by area. Milk and yogurt consumption showed a significantly positive risk and a dose–response relationship adjusted for age, family history of prostate cancer, body mass index, and total energy intake, stratified by area. In summary, a high intake of dairy products such as milk increased the risk of developing prostate cancer in Japanese men., This study investigates the association between consumption of dairy product and development of prostate cancer using a large‐scale cohort study in Japan. Our study makes a significant contribution to the literature because we were able to show statistically significant associations and dose–response relationships between high intake of milk and yogurt and prostate cancer, even after adjusting for potential confounders including body mass index and total energy intake.

Background: Kawasaki Disease (KD) is associated with diffuse and systemic vasculitis of unknown aetiology and mainly affects infants and children. Intravenous immunoglobulin (IVIG) treatment reduces the risk of developing coronary aneurysms, but some children have IVIG-resistant KD, and they are at an increased risk of developing coronary artery injury. Here, we investigated the effect of recombinant human soluble thrombomodulin (rTM), which has anticoagulation, anti-inflammatory and cytoprotective properties, on the development of coronary arteritis in a mouse model of vasculitis. Methods: To prepare an animal model of KD-like vasculitis, Candida albicans water-soluble fraction (CAWS) was intraperitoneally injected into DBA/2 mice for 5 consecutive days, and then rTM (0, 0.2, 1, and 4 mg/kg body weight) was injected. rTM administration was performed at two intervals: one is for 10 consecutive days from the first day and the other is for 5 consecutive days from the 1st to 15th days. Histopathological analysis of the heart was performed 20, 27, 34, and 48 days after CAWS treatment, and the gene expression of anti-inflammatory cytokine interleukin-10 (IL-10), pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α), and tissue factor (TF) in the heart and spleen was investigated.Results: Five consecutive doses of rTM (4 mg/kg) from 1 to 14 days after CAWS treatment significantly suppressed cardiac hypertrophy and arteritis by 34 days after CAWS treatment. The gene expression analysis of samples prepared from the heart and spleen of mice treated with CAWS and/or rTM showed that rTM administration increased the level of IL-10 in the heart. This increase was observed until day 27 and was not observed thereafter. The expression of TNF-α was observed in the heart of mice treated with CAWS and was not altered by rTM treatment. However, in the spleen, CAWS treatment reduced the IL-10 level and increased the TF level, whereas rTM treatment restored normal levels of both factors.Conclusions: These findings suggest that rTM specifically increases IL-10, decreases TF, and suppresses CAWS-induced vasculitis without affecting TNF-α production. Therefore, rTM can be used as a treatment for KD.

Color speckle metrics of an RGB-combined white laser beam emitted from an optical fiber output of two types of RGB laser module are measured. A new method for eliminating the effects of a fiber far field pattern from the measured 2D speckle data is employed to calculate the speckle metrics with a statistical accuracy. In this method, unspeckled 2D data of the far field pattern can be directly measured by opening the iris of the speckle measurement equipment. As a result, white photometric speckle contrast and color speckle distribution in CIE1931 chromaticity diagram are, for the first time, successfully obtained by eliminating the far field pattern effects.

Background The Dietary Inflammatory Index (DII) is a comprehensive, literature-derived index for assessing the effect of dietary constituents on inflammatory biomarkers. Several studies have shown an association between DII score and mortality, but there are limited prospective studies in Asian populations. Objectives The aim of this study was to investigate the association between DII score and risk of all-cause, total cardiovascular disease (CVD), stroke, coronary heart disease (CHD), total cancer, digestive cancer, and noncancer/non-CVD mortality in the Japanese population. Methods A total of 58,782 Japanese participants aged 40-79 y who were enrolled in the Japan Collaborative Cohort Study during 1988-1990 were included in the analysis. DII scores were calculated based on a food-frequency questionnaire. HRs and 95% CIs for mortality according to DII quintiles were estimated using Cox proportional hazards models. Results During the median follow-up period of 19.3 y, a total of 11,693 participants died. The multivariable HR for all-cause mortality for the highest compared with the lowest DII quintiles was 1.13 (95% CI: 1.05, 1.21). For CVD mortality, the highest multivariable HRs were 1.30 (95% CI: 1.13, 1.49), 1.29 (95% CI: 1.05, 1.59), and 1.30 (95% CI: 0.96, 1.76) for total CVD, stroke, and CHD, respectively. No significant associations were observed between DII and risk of total cancer, digestive cancer, and noncancer/non-CVD mortality. Conclusion Our findings suggest that a higher DII was associated with an increased risk of all-cause and CVD mortality among Japanese adults.

MicroRNAs (miRNAs) dysregulate gene expression by binding to target messenger RNAs, and play an important role in the pathogenesis of various diseases, including cancers, cardiovascular diseases and diabetes. Circulating miRNAs have increasingly been recognized as biomarkers for detecting and diagnosing those diseases. Few studies have investigated the association of circulating miRNA with the early stages of cognitive impairment, such as mild cognitive impairment, in the general population. The purpose of this study was to examine the association between cognitive function and several serum miRNAs levels related to amyloid precursor protein (APP) proteolysis in a Japanese general population who had never been diagnosed with dementia.We conducted a cross-sectional study of 337 Japanese subjects (144 men, 193 women) who attended a health examination. The short form of the Mini-Mental State Examination (SMMSE) was used to assess cognitive function. Serum levels of 6 miRNAs (let-7d, miR-17, miR-20a, miR-27a, miR-34a, miR-103a) were measured by quantitative real-time polymerase chain reaction.Multivariable-adjusted odds ratios (ORs) for lower SMMSE score (SMMSE score28) were significantly increased in the lowest tertile of serum miR-20a (OR, 2.08; 95% confidence interval (CI), 1.09-4.04) and miR-103a (OR, 1.91; 95%CI, 1.00-3.69) compared to the highest tertile. Moreover, serum levels of miR-20a, -27a, and -103a were linearly and positively associated with SMMSE scores after adjustment for confounding factors.Low serum levels of miR-20a, -27a, and -103a are independently associated with cognitive impairment.

Cluster of differentiation 36 (CD36) is a membrane receptor expressed on a wide variety of human cells. CD36 polymorphisms are reportedly associated with oral fat perception, dietary intake and metabolic disorders. The present study examined associations of two CD36 polymorphisms (rs1761667 and rs1527483) and dietary fat intake, and metabolic phenotypes in a Japanese population. This cross-sectional study was conducted based on clinical information collected from health check-ups in Japan (n 495). Dietary nutrient intake was estimated from a validated short FFQ and adjusted for total energy intake using the residual method. Mean blood pressure was calculated from systolic blood pressure (SBP) and diastolic blood pressure (DBP). Hypertension was defined as SBP ≥ 130 mmHg and/or DBP ≥ 85 mmHg, or use of antihypertensive drugs. Genotyping was performed using PCR with confronting two-pair primers method. Mean age was 63·4 (sd 9·9) years. Individuals with the AA genotype showed higher total fat and MUFA intake (standardised β = 0·110 and 0·087, P = 0·01 and 0·05, respectively) compared with the GG and GA genotypes. For metabolic phenotypes, the AA genotype of rs1761667 had a lower blood pressure compared with the GG genotype (standardised β = –0·123, P = 0·02). Our results suggested that the AA genotype of rs1761667 in the CD36 gene was associated with higher intake of total fat and MUFA and lower risk of hypertension in a Japanese population.

Purpose. Osteoporosis is a common age-related disorder leading to increased bone fragility and risk of fracture. Early diagnosis of osteoporosis is a vital step in providing early therapeutic intervention. Serum cystatin C is a marker of early renal dysfunction, a predictor of cardiovascular and inflammatory diseases, and an inhibitor of the differentiation of osteoclast precursor cells. The purpose of this study was to evaluate the relationship between serum cystatin C and osteoporosis. Methods. We enrolled 46 subjects who attended a health checkup and underwent measurement of bone status by quantitative ultrasound and determination of the level of serum cystatin C. A comparative study was conducted between those with and without osteoporosis for all subjects collectively and in two subgroups aged Results. Serum cystatin C levels were strongly correlated with age, creatinine, and bone status data, with significant negative correlations with stiffness, T-score, and percentage of young adult mean. Among patients with osteoporosis, serum cystatin C was significantly higher even after adjustment for age and sex, whereas no significant difference was noted in creatinine. For patients aged ≥ 65 years, serum cystatin C was significantly higher in subjects with osteoporosis, although there was no significant difference in age between normal subjects and those with osteoporosis. Conclusions. To the best of our knowledge, this is the first study to demonstrate an association between serum cystatin C and osteoporosis. Serum cystatin C is significantly higher in osteoporosis and in particular may be a useful marker for osteoporosis among middle and elderly people aged ≥ 65 years. Measurement of serum cystatin C can be carried out easily and may contribute to early diagnosis and treatment of osteoporosis.

Objective: We investigated whether elderly patients treated for a proximal femoral fracture would be able to return home. Patients and Methods: The subjects of this study were 834 patients. We defined the acute care hospital group as patients who returned home from the acute care hospital and the kaihukuki group as patients who were transferred from an acute care hospital to a rehabilitation hospital. We recorded the proportion of patients who returned home. We also analyzed walking ability and the Barthel index (BI) of patients. Results: After 2013, the proportion of patients who returned home from the acute care hospital fell below 20%. The proportion of patients who returned home from the kaihukuki hospital stayed within the 75–85% range. The BI before injury and at discharge was 86 and 76 points, respectively, in the acute care hospital group. The acute care hospital group included patients who walked without an aid before the injury or when leaving the hospital. In the kaihukuki group, the BI before an injury, at admission, and at discharge from the rehabilitation hospital was 85, 56, and 74 points, respectively. In the kaihukuki group, the ability of patients to walk recovered more slowly than that of patients in the acute care hospital group. Conclusion: Walking ability and BI are important factors for determining whether patients with a proximal femoral fracture are able to return home.

Purpose To elucidate the correlation between lactoferrin concentration in the tear film and signs and symptoms of severe dry eye disease (DED) using a novel microfluidic paper-based analytical device (μPAD) and enzyme-linked immunosorbent assay (ELISA). Methods Twenty-four patients were recruited at the Keio University Hospital. Using a novel μPAD, lactoferrin concentrations were measured in 4 patients with GVHD-related DED, 3 patients with other types of DED and 2 controls (Group A). For validation by ELISA, 22 patients (7 patients from Group A) comprising 9 patients with GVHD-related DED, 6 patients with other types of DED and 7 controls were examined (Group B). The link between lactoferrin concentration and clinical data about the severity of aqueous tear deficient DED was also investigated by both μPAD and ELISA. Results The lactoferrin concentration in tear fluid of the DED patients was positively correlated between μPAD and ELISA (p = 0.006, r = 0.886). The tear fluid of the GVHD patients showed low or undetectable lactoferrin concentration. Analysis by ELISA demonstrated that lactoferrin concentrations in the tear film from the GVHD patients were significantly lower than those from the non-GVHD patients (p = 0.010576). ELISA revealed lactoferrin concentration correlated with the value of Schirmer test and tear film breakup time, whereas it was inversely correlated with OSDI, fluorescein and rose bengal scores. Conclusions The novel μPAD may pave the way for measuring lactoferrin concentration in tear fluid from DED patients. Our results suggested that lactoferrin concentration in tear fluid reflect the severity of DED.

Background Long-term results in muscle strength, physical activity (PA), and functional improvement after total hip arthroplasty (THA) have not been studied. The purpose of this study was to evaluate the deficits in functional performance, PA, and high fall rate in patient 10 years after THA compared to healthy adults. Methods The subjects were 58 patients who underwent primary THA for unilateral hip osteoarthritis 10 years, and 46 healthy adults. Hip abductor strength, balance function (single-leg stance time), Maximal Walking Speed (MWS), fall rate, and PA (IPAQ short ver.) were evaluated. The unpaired t-test and χ2 test were used to assess differences between the groups. Statistical significance was set at p value

Aim: Aberrant global DNA methylation is involved in the development of several diseases, including cardiovascular disease (CVD). We investigated whether the methylation of long interspersed nuclear element-1 (LINE-1) in leukocytes is associated with dyslipidemia, a major risk factor for CVD, in the Japanese general population. Methods: We conducted a cross-sectional study consisting of 420 Japanese subjects (187 men and 233 women) without a clinical history of cancer, stroke, or ischemic heart disease. LINE-1 DNA methylation levels in leukocytes were measured using a pyrosequencing method. Results: Significantly higher odds ratios (ORs) for hypermethylation were observed in the high LDL cholesterol and high LDL/HDL ratio groups than the corresponding normal group (high LDLC group: OR, 1.88; 95% confidence interval [CI], 1.20–2.96, high LDL/HDL ratio group: OR, 1.90; 95% CI, 1.20–3.01). Subjects with 2 or more lipid abnormalities had significantly higher ORs for hypermethylation than those with no lipid abnormality (OR, 2.31; 95% CI, 1.11–4.82). Conclusion: LINE-1 DNA hypermethylation in leukocytes was associated with CVD risk profiles: high LDLC, high LDL/HDL ratio, and the degree of abnormal lipid metabolism. Abbreviations:ANOVA, analysis of variance; BMI, body mass index; CI, confidence interval; CRP, C-reactive protein; CVD, cardiovascular disease; DNMT, DNA methyltransferase; EDTA, ethylenediaminetetraacetic acid; HDLC, high-density lipoprotein cholesterol; IL-6, interleukin-6; KLF2, Kruppel-like factor 2; LDLC, low-density lipoprotein cholesterol; LINE-1, long interspersed nuclear element-1; OR, odds ratio; PCR, polymerase chain reaction; SD, standard deviation; TC, total cholesterol; TG, triglyceride

The ratio of human nonmercaptalbumin (HNA) and reduced albumin (HMA) may be a new marker for oxidative stress. Locomotive syndrome (LS) is reduced mobility due to impairment of locomotive organs. We investigated whether the HNA/HMA ratio could be a new biomarker of LS. This study included 306 subjects (mean age 64.24 ± 10.4 years) who underwent LS tests, grip strength, walking speed, and tests for HNA and HMA. Oxidative stress was measured by the ratio of HMA (f(HMA) = (HMA/(HMA + HNA) × 100)), and the subjects were divided into normal (N group, f[HMA] ≥ 70%) and low (L group, f[HMA] &lt, 70%) groups. There were 124 non-elderly (&lt, 65 years) and 182 elderly subjects (≥65 years). There were no significant differences in LS, grip strength, and walking speed between the L and N groups in the non-elderly subjects. However, significant differences were found in the elderly subjects. In logistic regression analysis, there was an association between f(HMA) and the LS severity at older ages. LS in the elderly is associated with a decline in HMA and, thus, an increase in oxidative stress. Thus, f(HMA) is a new biomarker of LS.

Background: High tidal ventilation with inflammation causes ventilator-induced lung injury (VILI). We previously found that recombinant thrombomodulin (rTM) has a protective effect regarding non-septic VILI caused by high-tidal-volume (HV) ventilation with high oxygen levels. This study aimed to investigate the preventive effect of rTM on VILI caused by sepsis and HV ventilation. Methods: A total of 46 adult male rats were subcutaneously administered either 3mg/kg of rTM or saline. Twelve hours later, the rats were underwent cecal ligation and puncture (CLP). At 2 h after this procedure, the rats were placed on a ventilator set at either low tidal volume [(LV) 6 ml/kg] or high tidal volume (HV 35 ml/kg) ventilation for another 2 h. Results: After 2 h of mechanical ventilation, the PaO2 was significantly lower and BALF protein was significantly higher in HV rats than in LV rats. The rTM did not improve oxygenation or BALF protein levels. Also in HV rats, lung tissue interleukin-6 and monocyte chemotactic protein-1 mRNA levels were significantly higher in the rTM-treated rats.Conclusion: rTM does not improve oxygenation in a non-DIC, CLP-pretreated, high-tidal-ventilation rat model.

This chapter focuses on group discussion sessions targeting the Priority Areas of the Sendai Framework for Disaster Risk Reduction 2015–2030. Day one group discussion session efforts were on Priority Area One—Understanding Disaster Risks; and Day two emphasis was on Priority Areas 2, 3 and 4.

Obesity is a major public health problem worldwide owing to the substantial increase in risk of metabolic diseases. Hypoxia-inducible factors (HIFs) regulate transcriptional responses to hypoxic stress. DNA methylation in the CpG sites of intron 1 of HIF3A is associated with body mass index in the whole blood and adipose tissue. This study investigates the correlation between DNA methylation of HIF3A and parameters of obesity, including thickness of visceral (VAT) and subcutaneous adipose tissues, in the general Japanese population. Participants (220 men and 253 women) who underwent medical examination were enrolled in this cross-sectional study. We used pyrosequencing to quantify DNA methylation (CpG sites of cg16672562, cg22891070, and cg27146050) in HIF3A. DNA methylation of HIF3A was only different in women. Multiple regression analysis showed that DNA methylation level at cg27146050 was associated with thickness of VAT in women. DNA methylation level at cg27146050 also correlated with body mass index and percentage of body fat in women after excluding smokers and non-smokers who quit smoking with the last 5 years. DNA methylation in the CpG site (cg27146050) of HIF3A correlated with parameters of obesity in Japanese women.

Appropriate soft tissue balance and accurate alignment are important for successful total knee arthroplasty (TKA). However, the optimal technique for establishing and measuring soft tissue balancing remains unclear. The aim of this study was to analyze the intraoperative medial and lateral gap pattern using digital knee balancer in posterior-stabilized (PS) TKA.This study involved 55 patients with medial osteoarthritis who underwent a primary TKA using an image-free navigation system. The extension gap and the flexion gap at 90° knee flexion were assessed using an offset seesaw-type digital balancer. Continuous joint distraction force from 10 lb to 60 lb was applied. Medial gap, lateral gap, and varus angle were measured.The medial bone gap difference between extension and flexion was constant regardless of the distraction force from 20 lb to 60 lb. The lateral bone gap was significantly greater than the medial bone gap in extension and flexion from 30 lb to 60 lb (P 0.05). The varus angle changed depending on the distraction force, especially in flexion. The varus angle in flexion was significantly greater than that in extension from 40 lb to 60 lb (P 0.05).The medial bone gap is a reliable indicator unaffected by the distraction force during surgery and is useful for adjusting the medial gap in extension and flexion appropriately to ensure medial stability in PS-TKA. The digital knee balancer and navigation system support both precise gap assessment and surgery.

Background and Purpose Since falls after total hip arthroplasty (THA) cause severe complications such as dislocation and fractures around the femoral stem, it is important to investigate what factors predict of falls. Thus, investigating predictors of falls in patients waiting for THA would be valuable as it lead to more strategic interventions to prevent these problems. The purpose of this study was to evaluate the predictors of falls in patients during the first year after THA. Methods This is a prospective cohort study. A total of 157 patients who underwent THA for unilateral hip osteoarthritis were analyzed. The incidence of falls during the first year after THA was monitored, and patients were classified into a “faller” and “non‐faller” group. The following factors were compared between the two groups: demographic data (age, sex, body mass index, leg length discrepancy, length of hospital stay, and history of falling), preoperative hip abductor muscle strength, functional performance (single leg stance and maximum walking speed), pain during walking, and physical activity. Results On multivariate logistic regression analysis, preoperative hip abductor muscle strength on the affected side and a history of falling were predictors of falls during the first year after THA. On subsequent receiver operating characteristic curve analysis, preoperative hip abductor muscle strength on the affected side was retained as a significant predictor, with a cut‐off strength of 0.46 Nm/kg differentiating the faller and non‐faller groups with a specificity of 73.6%, specificity of 50.0%, and area under the curve of 70.2%. Conclusions Finding from the present study suggested that clinicians should focus on low preoperative hip abductor muscle strength on the affected side and a history of falling to prevent falls during the first year after THA.

Objective MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression and play essential roles in the pathogenesis of cardiovascular disease. Previous cross-sectional studies showed that the levels of several circulating miRNA are associated with hypertension, but there are no prospective longitudinal studies using a general population. The aim of this study is to evaluate the impact of circulating vascular-related miRNA (miR-126, miR-221, and miR-222) on changes in blood pressure and new-onset hypertension in a Japanese population. Methods We conducted a 5-year longitudinal study using 192 health examination participants (87 men and 105 women). Serum miRNAs were measured using quantitative reverse transcription-PCR. Information regarding lifestyle and health condition was obtained using a self-administered questionnaire. Logistic regression analyses were performed to calculate odds ratios and 95% confidence intervals for new-onset hypertension in the 5-year period between the low and high group of serum miRNAs. Results Serum levels of miR-126, miR-221, and miR-222 were significantly and negatively associated with changes in SBP and the rate of change of SBP. Serum miR-126, miR-221, and miR-222 levels were significantly lower in new-onset hypertensive patients compared with normotensive individuals. The confounding factors adjusted odds ratios of each 1 increment in serum miR-126, miR-221, and miR-222 levels were 0.82 (95% confidence interval: 0.69-0.98), 0.79 (0.68-0.91), and 0.61 (0.46-0.81) for new-onset hypertension, respectively. Conclusion Low serum levels of miR-126, miR-221, and miR-222 were associated with increased blood pressure and new-onset of hypertension. These circulating miRNAs are potential candidate biomarkers for the prediction of hypertension.

OBJECTIVES: Nonalcohol fatty liver disease (NAFLD) is one of the considerable health problems in the world. NAFLD is a representative phenotype in the liver reflecting individual's lifestyle. Previous studies suggested that a single nucleotide polymorphism (SNP) in the CD36 gene was associated with dietary fat intake and fat metabolism. Therefore, we hypothesized that this SNP may be associated with fatty liver (FL) and NAFLD. We conducted this cross-sectional study to examine the association between two CD36 polymorphisms (rs1761667 and rs1527483) and FL and NAFLD in a Japanese population. METHODS: A total of 525 local residents participated in the health check-up in Yakumo town, Hokkaido, Japan. This cross-sectional study was conducted based on clinical information collected in this health check-up. Among all participants, 57 people were excluded due to the inadequate informed consent, clinical history of liver disease. Genotyping of two polymorphisms in the CD36 gpgbrkkene was performed by using the PCR-CTPP method. Ultrasound examination was performed by four qualified ultrasonographers. In this present, NAFLD was defined as 1) presence of FL and 2) a daily alcohol consumption

Background: Sciatic nerve palsy is a serious complication after total hip arthroplasty (THA). This is the first study to report the relationship between the sciatic nerve and the acetabulum on magnetic resonance imaging (MRI) before THA. Methods: 235 patients underwent 261 elective, primary THAs via the mini-incision posterolateral approach. We measured the horizontal distance (mm) and vertical distance (mm) from the posterior edge of the acetabulum to the sciatic nerve by T1-weighted imaging on an axial section of the centre of the femoral head. We defined the Dysplastic Group as having a posterior acetabular sector angle (PASA) Results: The horizontal and vertical distances were (mean ± SD) 8.0 ± 9.2 mm and 14 ± 5.0 mm from the posterior edge of the acetabulum to the lateral edge of the sciatic nerve, respectively. The acetabular anteversion (AA), anterior acetabular sector angle (AASA), and PASA were (mean ± SD) 19 ± 6.7°, 49 ± 8.4°, and 87 ± 8.6°, respectively. The horizontal and vertical distances were positively correlated ( p < 0.0001). AA and PASA were positively correlated with the horizontal distances ( p < 0.0001) as well as with the vertical distances ( p = 0.0017 and p = 0.0438, respectively). The horizontal and vertical distances were significantly shorter in the Dysplastic Group than in the Non-dysplastic Group ( p < 0.0001 and p = 0.021, respectively). Conclusions: In cases of posterior acetabular dysplasia we have to be mindful of the course of the sciatic nerve.