Effect of Sparc knockout on the extracellular matrix of mouse periodontal ligament cells.

The periodontal ligament (PDL) is a critical component in maintaining tooth stability. It is composed of cells and an extracellular matrix (ECM), each with unique roles in tissue function and homeostasis. Secreted protein acidic and rich in cysteine (SPARC), a calcium-binding matricellular glycoprotein, plays a crucial role in regulating ECM assembly and turnover, alongside facilitating cellular-ECM interactions. In the present study, mass spectrometry-based proteomics was used to assess the impacts of Sparc-knockout (KO) on PDL-derived cells. Results demonstrated that Sparc-KO significantly reduces ECM production and alters its composition with increased levels of type I collagen. Despite this increase in Sparc-KO, type I collagen was not likely to be effectively integrated into the fibrils due to collagen cross-linking impairment. Furthermore, the pathway and process enrichment analyses suggested that SPARC plays a protective role against ECM degradation by antagonistically interacting with cell-surface collagen receptors. These findings provide detailed insights into the multifaceted role of SPARC in ECM organization, including its impact on ECM production, collagen regulation, and interactions with various cellular compartments. A better understanding of these complex mechanisms is crucial for comprehending the causes of periodontal disease and tissue regeneration, where precise control of ECM organization is necessary.

Prospective association of daily ambulatory activity with metabolic syndrome in middle-aged and older Japanese adults: the Toon Health Study.

BACKGROUND: This cohort study aimed to examine the relationship between objectively measured daily ambulatory activity (AA) variables and the onset of metabolic syndrome (MetS) in middle-aged and older Japanese individuals. METHODS: A total of 1,034 participants (women, 76.8%; mean age, 56.9 years) who were initially free from MetS, underwent objective assessment of daily AA using a uniaxial accelerometer at baseline. The number of steps, time accumulated in light-intensity AA (LIAA), moderate-to-vigorous intensity AA (MVAA), and total AA (LIAA + MVAA) were calculated. The diagnostic criteria outlined by the Japanese standards were employed to define the presence of MetS. To explore the association between AA variables and MetS onset, both multivariate logistic regression and a restricted cubic spline model were used while controlling for variables such as age, sex, education, alcohol habit, smoking habit, energy intake, and the number of MetS components present at baseline. RESULTS: Over the course of the 5-year follow-up period, 116 participants (11.2%) developed MetS. In terms of the number of steps, LIAA, and total AA, the third quartile had significantly lower multivariate adjusted odds ratios for MetS onset than the first quartile. The odds ratios (95% confidence intervals) were 0.386 (0.197-0.755), 0.527 (0.285-0.975), and 0.392 (0.206-0.745), respectively. In the spline model, an L-shaped association with MetS was observed for the number of steps (p for nonlinearity = 0.066), LIAA (p for nonlinearity = 0.034), and total AA (p for nonlinearity = 0.040). CONCLUSIONS: Among the variables related to AA, the index of daily amount AA, in particular, may be linked to the onset of MetS.

Association of depressive symptoms with incident fractures: the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT).

This 5-year longitudinal study investigated the relationship between depressive symptoms and fracture risk in a large Japanese cohort. Depressive symptoms were a significant risk factor for hip fractures in women. PURPOSE: A relationship between depressive symptoms and fractures has not been clearly demonstrated. We aimed to investigate the relationship between depressive symptoms and 5-year fracture risk in the Japan Public Health Center-based Prospective Study for the Next Generation. METHODS: From 2011 to 2016, 114,092 participants were enrolled, and a follow-up survey was conducted 5 years later. We analyzed 30,552 men and 38,063 women aged 40-74 years who had no past fractures at baseline. Presence of depressive symptoms was defined as a modified 11-item Center for Epidemiological Studies Depression Scale score of 8 or higher, a history of depression, or use of antidepressants. Subjects were asked to report vertebral, upper limb, and/or hip fractures, except for traffic or work accidents, that occurred during the follow-up period. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for fracture were analyzed via logistic regression analysis to evaluate the relationship between depressive symptoms and fracture. RESULTS: Women with depressive symptoms demonstrated a high AOR for hip fractures (AOR: 2.78, 95% CI: 1.30 - 5.92); this result was consistent in post menopause women. In men, this association was not found for any age group or any type of fracture. CONCLUSIONS: Depressive symptoms in women may increase the risk of hip fractures. Further studies are required to explore this relationship in more detail.

Tongue pressure and maxillofacial muscle activities during swallowing in patients with mandibular prognathism.

BACKGROUND: Coordination among lip, cheek and tongue movements during swallowing in patients with mandibular prognathism remains unclear. OBJECTIVES: This study aimed to identify the temporal sequences of tongue pressure and maxillofacial muscle activities during swallowing in patients with mandibular prognathism and compared characteristics with those of healthy volunteers. METHODS: Seven patients with mandibular prognathism (mandibular prognathism group) and 25 healthy volunteers with individual normal occlusion (control group) were recruited. Tongue pressures and masseter, orbicularis oris, mentalis and supra- and infrahyoid muscle activities while swallowing gel were measured simultaneously using a sensor sheet system with five measurement points and surface electromyography, respectively. Onset time, offset time and durations of tongue pressure and muscle activities were analysed. RESULTS: In the mandibular prognathism group, tongue pressure was often produced first in more peripheral parts of the palate. Offset of tongue pressure in the posteromedian and peripheral parts of the palate and maxillofacial muscle activities except for orbicularis oris were delayed. Duration of tongue pressure in the anteromedian part of the palate was significantly shorter and durations of masseter, mentalis and suprahyoid muscle activities were significantly longer. Times to onset of orbicularis oris and suprahyoid muscle activities based on first onset of tongue pressure were significantly shorter. CONCLUSION: These results suggest that patients with mandibular prognathism may exhibit specific patterns of tongue pressure production and maxillofacial muscle activities during swallowing.

The effect of age on the relationship between body mass index and risks of incident stroke subtypes: The JPHC study.

OBJECTIVE: The associations between body mass index (BMI) and stroke subtypes, particularly intracerebral hemorrhage, have not been consistent. Such inconsistencies may be due to differences in the age at which BMI was obtained. We examined the possible age modifications in the association between BMI and stroke risk. MATERIALS AND METHODS: We followed 88,754 participants, aged 40-69 years at baseline (1990-1994), of the Japan Public Health Center-based prospective (JPHC) study for stroke incidence. BMI was obtained using self-reported body weight and height, which were categorized using the following cut-off points: 18.5, 21, 23, 25, 27.5, and 30 kg/m2. Time-dependent Cox proportional hazards models that updated BMI and covariates using 5- and 10-year questionnaire responses were used to estimate hazard ratios and 95 % confidence intervals. The analyses were stratified by age group (40-59 and ≥60 years) and the age of the individuals was updated. RESULTS: During the median follow-up period of 19 years, we documented 4,690 strokes, including 2,781 ischemic strokes and 1,358 intracerebral hemorrhages. After adjusting for sex, age, smoking, alcohol consumption, leisure-time physical activity, history of hypertension, dyslipidemia, and diabetes mellitus, we observed a positive linear association between BMI and ischemic stroke (linear trend, p < 0.001) in both age groups (interaction p>0.05). In contrast, a curvilinear association between BMI and intracerebral hemorrhage was observed in both the middle (curvilinear trend, p=0.017) and the older group (curvilinear trend, p=0.098) (interaction p>0.05). CONCLUSION: BMI and stroke associations did not vary significantly with age, although the association may differ according to subtype.

Positive association between serum resistin and smoking was strongest in homozygotes of the G-A haplotype at c.-420 C>G and c.-358 G>A in RETN promoter: the Toon Genome Study.

Resistin is mainly expressed in human monocytes/macrophages and is associated with insulin resistance, inflammation, and atherosclerosis. Serum resistin is strongly correlated with the G-A haplotype defined by single nucleotide polymorphisms (SNPs) c.-420 C>G (SNP-420) (rs1862513) and c.-358 G>A (SNP-358) (rs3219175) in the promoter region of the human resistin gene (RETN). Smoking is also associated with insulin resistance. We investigated the association between smoking and serum resistin and the effect of the G-A haplotype on this association. Participants were recruited under the Toon Genome Study (an observational epidemiology research in the Japanese population). Of these, 1975 subjects genotyped for both SNP-420 and SNP-358 were analyzed for serum resistin by grouping them based on smoking status and G-A haplotype status. RETN mRNA, isolated from whole blood cells, was evaluated in smokers (n = 7) and age-, sex-, and BMI-matched non-smokers (n = 7) with the G-A haplotype homozygotes. Serum resistin tended to be higher in current smokers who smoked more cigarettes per day (P for trend < 0.0001). The positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes, followed by heterozygotes and non-carriers (interaction P < 0.0001). This positive association was stronger in the G-A homozygotes than the C-G homozygotes (interaction P < 0.0001). RETN mRNA was 1.40-fold higher in smokers than non-smokers with the G-A homozygotes (P = 0.022). Therefore, the positive association between serum resistin and smoking was strongest in the G-A haplotype homozygotes defined by RETN SNP-420 and SNP-358.

Impact of Cardiovascular Disease on the Death Certificate Diagnosis of Heart Failure, Ischemic Heart Disease, and Cerebrovascular Disease　- The Japan Public Health Center-Based Prospective Study.

BACKGROUND: There is considerable interest in the trending discrepancy between ischemic heart disease (IHD) and heart failure (HF) in vital statistics. Clinically, acute myocardial infarction (AMI) and stroke are closely associated with HF, but their contribution to HF as the underlying cause of death (UCD) is unclear.Methods and Results: In 1990 and 1992-1993, we enrolled a total of 140,420 residents of Japanese nationality (aged 40-69 years) from 11 public health center areas. We prospectively examined the occurrence of cardiovascular disease (CVD), including AMI, sudden cardiac death within 1 h (SCD), and stroke, and analyzed the 14,375 participants without a history of CVD at baseline who died during the 20-year follow-up. A time-dependent Cox proportional hazards model was used to estimate hazard ratios and the population attributable fraction (PAF) of AMI, AMI+SCD, stroke, and CVD for deaths due to HF, IHD, and cerebrovascular disease as the UCD, adjusted for individuals' lifestyles and comorbid conditions. The PAF of AMI for HF deaths was 2.4% (95% confidence interval [CI] 1.7-2.9%), which increased to 12.0% (95% CI 11.6-12.2%) for AMI+SCD. The PAF of CVD-attributed HF deaths was estimated to be 17.6% (95% CI 15.9-18.9%). CONCLUSIONS: HF as the UCD was partly explained by CVD. The data imply that most HF deaths reported in vital statistics may be associated with underlying causes other than CVD.

Risk and population attributable fraction of stroke subtypes in Japan.

BACKGROUND: Associations of major risk factors for stroke with total and each type of stroke as well as subtypes of ischemic stroke and their population attributable fractions had not been examined comprehensively. METHODS: Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n=14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥ 25 kg/m2), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (< 40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fraction (PAF) was estimated using the hazard ratios and the prevalence of risk factors among cases. RESULTS: Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic and large-artery occlusive strokes were 36.7 and 44.5% and 61.5%, respectively. CONCLUSION: Although there are differences according to the subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.

Long-term Response of Helicobacter pylori Antibody Titer After Eradication Treatment in Middle-aged Japanese: JPHC-NEXT Study.

BACKGROUND: Helicobacter pylori (H. pylori) is an established causative factor of gastric cancer. Although the expansion of insurance coverage has led to an increase in the number of patients treated for H. pylori, the population impact of eradication treatment for H. pylori has been scarcely investigated. This study aimed to clarify the long-term responses of H. pylori antibody titer after eradication treatment using large scale cross-sectional data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). METHODS: A total of 55,282 Japanese participants aged 40 to 74 years residing in 16 areas provided blood samples from 2011 through 2016. From these, treated (n = 6,276) and untreated subjects who were seropositive for H. pylori or had serological atrophy (n = 22,420) formed the study population (n = 28,696). Seropositivity was defined as an anti-H. pylori IgG titer of ≥10 U/mL. Antibody level was compared among subjects according to self-reported treatment history as untreated, and treated for less than 1 year (<1Y), 1 through 5 years (1-5Y), and 6 or more years ago (6Y+). RESULTS: Median serum antibody titer was 34.0 U/mL, 7.9 U/mL, 4.0 U/mL, and 2.9 U/mL for the untreated, <1Y, 1-5Y, and 6Y+ groups, respectively. While those treated for H. pylori within the previous year had a 76.8% lower antibody titer compared to untreated subjects, approximately 41% of subjects were still seropositive. CONCLUSION: A significant reduction in H. pylori antibody titer occurs within 1 year after eradication treatment, but that a long period is needed to achieve complete negative conversion.

Association between birth weight and prevalence of cardiovascular disease and other lifestyle-related diseases among Japanese population: JPHC-NEXT Study.

BACKGROUND: An association between birth weight and cardiovascular disease (CVD) in adulthood has been observed in many countries; however, only a few studies have been conducted in Asian populations. METHODS: We used data from the baseline survey (2011-2016) of the Japan Public Health Center-based Prospective Study for the Next Generation Cohort, which included 114,105 participants aged 40-74 years. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were calculated from the prevalence of present and past histories of CVD and other lifestyle-related diseases, including hypertension, diabetes, hyperlipidemia, and gout, by birth weight, using Poisson regression. RESULTS: The prevalence of CVD increased with lower birth weight, with the highest prevalence among those with birth weight under 1,500 grams (males 4.6%; females 1.7%) and the lowest one among those with birth weight at or over 4,000g (males 3.7%: females 0.8%). Among 88.653 participants (41,156 males and 47,497 females) with complete data on possible confounders, birth weight under 1,500g was associated with a higher prevalence of CVD (aPR 1.76 [95%CI 1.37-2.26]), hypertension (aPR 1.29 [95%CI 1.17-1.42]), and diabetes (aPR 1.53 [95%CI 1.26-1.86]) when a birth weight of 3,000-3,999 grams was used as the reference. Weaker associations were observed for birth weight of 1500-2499 grams and 2500-2999 grams, while no significant associations were observed for birth weight at or over 4000 g. The association between birth weight and the prevalence of hyperlipidemia was less profound, and no significant association was observed between birth weight and gout. CONCLUSION: Lower birth weight was associated with a higher prevalence of CVD, hypertension, and diabetes in the Japanese population.

Effects of stress contagion on anxiogenic- and orofacial inflammatory pain-like behaviors with brain activation in mice.

The conditions of stress contagion are induced in bystanders without direct experiences of stressful events. This study determined the effects of stress contagion on masseter muscle nociception in mice. Stress contagion was developed in the bystanders after cohabitating with a conspecific mouse subjected to social defeat stress for 10 days. On Day 11, stress contagion increased anxiety- and orofacial inflammatory pain-like behaviors. The c-Fos and FosB immunoreactivities evoked by masseter muscle stimulation were increased in the upper cervical spinal cord, while c-Fos expressions were increased in the rostral ventromedial medulla, including the lateral paragigantocellular reticular nucleus and nucleus raphe magnus in stress contagion mice. The level of serotonin in the rostral ventromedial medulla was increased under stress contagion, while the number of serotonin positive cells was increased in the lateral paragigantocellular reticular nucleus. Stress contagion increased c-Fos and FosB expressions in the anterior cingulate cortex and insular cortex, both of which were positively correlated with orofacial inflammatory pain-like behaviors. The level of brain-derived neurotrophic factor was increased in the insular cortex under stress contagion. These results indicate that stress contagion can cause neural changes in the brain, resulting in increased masseter muscle nociception, as seen in social defeat stress mice.

Dietary behaviours and related lifestyles according to the presence or absence of skipping breakfast in Japanese adults: the JPHC-NEXT study.

OBJECTIVE: To assess dietary behaviours and related lifestyles according to the presence or absence of skipping breakfast. DESIGN: We analysed the cross-sectional data from a baseline survey of a large-scale population-based cohort study in Japan conducted in 2011-2016. Participants provided information on dietary behaviours and lifestyles through a self-administered questionnaire. Skipping breakfast was defined as not eating breakfast at least once a week and was classified according to the frequency of skipping breakfast as 1-2, 3-4 or ≥5 times/week. SETTING: Sixteen municipalities in seven prefectural areas across Japan under the Japan Public Health Centre-based prospective study for the Next Generation. PARTICIPANTS: 112 785 residents (51 952 males and 60 833 females) aged 40-74 years. RESULTS: After adjustment for age, socio-demographic status, drinking status and smoking status, individuals who skipped breakfast at least once a week, compared with those who ate breakfast every day, were more likely to have adverse dietary behaviours such as frequent eating out (multivariable OR = 2·08, 95 % CI (1·96, 2·21) in males and 2·15, 95 % CI (1·99, 2·33) in females), frequent eating instant foods (1·89, 95 % CI (1·77, 2·01) in males and 1·72, 95 % CI (1·56, 1·89) in females). They had late bedtime (1·85, 95 % CI (1·75, 1·95) in males and 1·98, 95 % CI (1·86, 2·11) in females) and living alone (2·37, 95 % CI (2·17, 2·58) in males and 2·02, 95 % CI (1·83, 2·21) in females), using the logistic regression model. CONCLUSIONS: Both adult males and females who skipped breakfast were likely to eat out, to have a dietary habit of eating instant foods and have lifestyles such as late bedtime and living alone than those who ate breakfast.

Ift88 regulates enamel formation via involving Shh signaling.

OBJECTIVES: The ciliopathies are a wide spectrum of human diseases, which are caused by perturbations in the function of primary cilia. Tooth enamel anomalies are often seen in ciliopathy patients; however, the role of primary cilia in enamel formation remains unclear. MATERIALS AND METHODS: We examined mice with epithelial conditional deletion of the ciliary protein, Ift88, (Ift88fl / fl ;K14Cre). RESULTS: Ift88fl / fl ;K14Cre mice showed premature abrasion in molars. A pattern of enamel rods which is determined at secretory stage, was disorganized in Ift88 mutant molars. Many amelogenesis-related molecules expressing at the secretory stage, including amelogenin and ameloblastin, enamelin, showed significant downregulation in Ift88 mutant molar tooth germs. Shh signaling is essential for amelogenesis, which was found to be downregulated in Ift88 mutant molar at the secretory stage. Application of Shh signaling agonist at the secretory stage partially rescued enamel anomalies in Ift88 mutant mice. CONCLUSION: Findings in the present study indicate that the function of the primary cilia via Ift88 is critical for the secretory stage of amelogenesis through involving Shh signaling.

Occlusal Evaluation Using Modified Huddart and Bodenham Scoring System Following 2-Stage Palatoplasty With Hotz Plate: A Comparison Among 3 Different Surgical Protocols.

OBJECTIVE: This study aimed to determine if the change in technique of soft palate closure or timing of hard palatal repair induced occlusal changes in patients with complete unilateral cleft lip and palate (CUCLP). DESIGN: Retrospective study. SETTINGS: A medical and dental hospital in Japan. SUBJECTS: A total of 96 patients with CUCLP treated with 2-stage palatoplasty were included in the study and categorized into 3 groups (G1, G2, and G3) according to the protocol used. INTERVENTIONS: G1 underwent soft palate repair using Perko method at 1.5 years of age and hard palate repair using vomer flap procedure at 5.5 years of age. Furlow method was used for soft palate repair in G2 at 1.5 years of age and hard palate repair using vomer flap procedure at 5.5 years of age. The Furlow method was used to repair the soft palate in G3 at 1.5 years of age and vomer flap procedure was used to repair the hard palate at 4 years of age. MAIN OUTCOME MEASURES: Two evaluators assessed the dental arch relationship using the modified Huddart/Bodenham (mHB) index on 2 separate occasions. RESULTS: Intra- (intraclass correlation coefficient [ICC]: 0.962) and inter-examiner (ICC: 0.950) reliability showed very good agreement. The frequency of crossbite present in the major and minor segments gradually decreased with each change in protocol. Mean segmental scores showed no significant difference between 3 protocols (P > .05). Good inter-arch alignment occurred with all 3 surgical protocols (G1:82.6%, G2:89.8%, and G3:91.7%). CONCLUSIONS: There was no significant difference in the dental arch relationship outcomes between the 3 surgical protocols. The dentition status was comparable with all surgical protocols, even after the changes.

Preventive role of community-level social capital in the need for long-term care and impairment in instrumental activities of daily living: a multilevel analysis.

BACKGROUND: Individual-level social capital is an important determinant of older adults' long-term care needs; however, there is scant evidence regarding community-level social capital. Therefore, we investigated the association between community-level social capital and the prevalence of the need for long-term care among older adults. METHODS: Between January and February 2018, a cross-sectional survey was conducted among all older adults (n = 13,558) aged 65 to 74 years in a rural municipality in Japan (total population, n = 72,833). A self-reported questionnaire was used to identify community-level social capital, comprising civic participation, social cohesion, and reciprocity. A multilevel logistic regression analysis was performed to estimate the odds ratios of the need for long-term care and a decline in social activity competence as assessed by instrumental activities of daily living. For the analysis, the community levels were divided into 76 voting districts and adjusted for daily life, lifestyle, socioeconomic status, health conditions, and the three social capital subscale scores at the individual level. RESULTS: After adjusting for the covariates, we observed a tendency that a higher community level of reciprocity was associated with a lower prevalence of long-term care needs (OR: 0.86, 95% confidence interval: 0.75-1.00), whereas a high community level of social cohesion was associated with a significantly reduced decline in instrumental activities of daily living (OR per standard deviation increase: 0.87, 95% confidence interval: 0.79-0.96). No significant association was found with civic participation. Similarly, individual-level social capital was associated with the need for long-term care and decline in instrumental activities of daily living. CONCLUSIONS: Our findings suggest that good community-level reciprocity or social cohesion as well as good individual social capital status may help prevent the need for long-term care among older adults.

A point system to predict the future risk of obesity in 10-year-old children.

BACKGROUND: A 4-year longitudinal study was conducted to develop a model and a point system for predicting childhood obesity. METHODS: This study included 1,504 Japanese 10-year-old children who underwent health check-ups between 2011 and 2015. Multivariable logistic regression analysis was conducted using the explanatory variables overweight and lifestyle. Obesity was defined as percentage overweight (POW) ≥ 20% calculated by the following equation: (actual weight - standard weight by height and sex)/standard weight by height and sex × 100 (%). The model was validated using the Hosmer-Lemeshow test on 10-year-olds. RESULTS: Our prediction model for development of childhood obesity was based on seven binary variables: sex, lack of sleep, ≥2-h use of television/ games/ smartphone, hypertension, dyslipidemia, hepatic dysfunction, and being overweight. The area under the curve of the receiver operating characteristic curve was 0.803 (95% confidence interval, 0.740 to 0.866). When validated in non-obese children (n = 415), there was no significant difference between actual and predicted numbers of children with obesity (Hosmer-Lemeshow chi-square = 7.90, p = 0.18). CONCLUSIONS: The validated prediction model and point score for obesity development were shown to be useful tools for predicting the future 4-year risk of developing obesity among 10 years-old children. The point system may be useful for reducing the occurrence of childhood obesity and promoting better health.

Latent profile analysis approach to the relationship between daily ambulatory activity patterns and metabolic syndrome in middle-aged and elderly Japanese individuals: The Toon Health Study.

BACKGROUND: This cross-sectional study aimed to identify the accumulation patterns of objectively measured ambulatory activity (AA) variables in the Japanese middle-aged and elderly individuals and examine the relationship of these derivative patterns with metabolic syndrome (MetS). METHODS: A total of 1850 participants (66.1% women, mean age: 57.7 years) provided objectively assessed AA data using a uniaxial accelerometer. The number of steps, time accumulated in light-intensity AA (LIAA) and moderate-to-vigorous intensity AA (MVAA), and the ratio of MVAA to total AA (LIAA + MVAA) were calculated. Latent profile analysis was used to identify groups of participants based on their distinct AA patterns. Logistic regression models were used to assess the association of groups with MetS after adjusting for age, sex, alcohol intake, and cigarette smoking. RESULTS: Four distinct groups were identified: Group A had few steps and low levels of LIAA and MVAA; group B had a certain number of steps and recommended level of MVAA but low level of LIAA; group C had a certain number or more of steps, high level of LIAA, and recommended level of MVAA; group D had an extremely high number of steps and high levels of both LIAA and MVAA. The multivariate-adjusted odds ratio (95% CI) for MetS in groups B, C, and D relative to group A were 0.857 (0.611-1.201), 0.679 (0.500-0.922), and 0.434 (0.259-0.730), respectively. Groups C and D had significantly lower odds ratio of MetS compared to group A. CONCLUSION: AA pattern involving a certain number or greater of steps accumulated through not only MVAA but also LIAA may help reduce the risk of MetS compared to inactive AA pattern.

Pharmacokinetics and effect of maslinic acid with physical exercise on grip strength and trunk muscle mass in healthy Japanese individuals.

Age-related changes in physical function are closely associated with daily activity impairment among the elderly. Continuous maslinic acid intake may improve skeletal muscle mass; however, the concentration-dependent benefits of maslinic acid for physical functionality remain unclear. Therefore, we evaluated the bioavailability of maslinic acid and examined the effect of maslinic acid intake on skeletal muscle and quality of life in the healthy Japanese elderly. Five healthy adult men were administered test diets containing 30, 60, or 120 mg of maslinic acid. Analysis of plasma maslinic acid revealed concentration-dependent elevations in blood maslinic acid levels (p<0.01). Next, 69 healthy Japanese adult men and women were administered a placebo or 30 or 60 mg of maslinic acid continuously for 12 weeks with physical exercise in a randomized, double-blind, placebo-controlled trial. The trunk muscle mass (p<0.05) and vitality score according to the Short-Form-8 (p<0.05) were significantly higher in the 60 mg maslinic acid group than in the placebo group. Additionally, grip strength was significantly higher in the 30 (p<0.05) and 60 mg (p<0.05) groups than in the placebo group. Overall, maslinic acid intake with physical exercise improved muscle strength, muscle mass, and quality of life in a maslinic acid-intake-dependent manner.

Involvement of Rab11 in osteoblastic differentiation: Its up-regulation during the differentiation and by tensile stress.

Rab GTPases, the largest group of small monomeric GTPases, have been shown to participate in membrane trafficking involving many cellular processes. However, their roles during osteoblastic differentiation remain to be elucidated. In this study, we investigated Rab GTPase involvement in osteoblastic differentiation. Protein levels of a series of Rabs (Rab4, Rab5, Rab7, Rab9a, Rab11a/b, and Rab27) were increased during osteoblastic differentiation of MC3T3-E1 cells, and the Rab11a/b levels were particularly pronounced in the presence of Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, an activator of osteoblastogenesis. We subsequently investigated the functional contribution of Rab11a and Rab11b during osteoblastic differentiation. The alkaline phosphatase (ALP) levels were reduced by Rab11b depletion but not by Rab11a depletion. Because our result suggested that Rab11a and Rab11b could be regulated downstream of Runx2 (Runt-related transcription factor 2), a key transcription factor for osteoblastic differentiation, we investigated the effects of the double knockdown of Runx2 and Rab11a or Rab11b on osteoblastic phenotypes. The double knockdown significantly reduced ALP activity as well as collagen deposition compared with single Runx2 knockdown. Furthermore, the Rab11a and Rab11b response to mechanical stress in vivo was investigated using a mouse orthodontic tooth movement model. Rab11a and Rab11b expression was enhanced in the periodontal ligament, where bone formation is activated by tensile stress. This study shows that Rab11a and Rab11b are regulated downstream of Runx2 in osteoblastic differentiation, and their expressions are also controlled by tensile stress.

Secondhand smoke and the risk of incident cardiovascular disease among never-smoking women.

The prospective association between secondhand smoke (SHS) and the risk of incident cardiovascular disease (CVD) remains unclear. This study was the first to examine the association between SHS and risks of ischemic heart disease (IHD), stroke, and total CVD in a large cohort in Asia. The study followed 24,232 never-smoking women aged 40-59 from around Japan (Akita, Iwate, Nagano, Niigata, Ibaraki, Kochi, Nagasaki, and Okinawa prefectures). Their husbands were classified into never, former, and current smokers. After adjustment for age, body mass index, alcohol consumption, histories of hypertension and diabetes mellitus, medication use for hyperlipidemia, menopausal status, and public health center areas, the hazard ratios (HRs) of CVD according to husbands' smoking status were estimated by Cox proportional hazards models. During the 440,360 person-years follow-up, 846 women had total CVDs (103 IHDs, 744 strokes). The proportional hazard assumption was not assured during the total follow-up from 1990 to 2012, but so was then the follow-up of < and ≥ 10 person-years were examined separately. The multivariable HRs (95% confidence intervals) associated with husbands' current versus non-current smoking was 2.02 (1.19-3.45) for IHD, 1.18 (0.98-1.42) for stroke, and 1.25 (1.05-1.49) for total CVD in the follow-up of ≥10 person-years. The SHS from husbands may raise the risk of IHD among middle-aged never-smoking women.