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Adipose-derived mesenchymal stem cells markedly attenuated brain infarct size and improved neurological function in rats. The mechanisms for neuronal cell death have previously been defined in stress states to suggest that an influx of calcium ions into the neurons activates calpain cleavage of p35 into p25 forming a hyperactive complex that induces cell death. Now we report that p5, a 24-residue peptide derived from p35, offers protection to neurons and endothelial cells in vitro. In vivo administration of human adipose-derived mesenchymal stem cells (hADMSCs) loaded with this therapeutic peptide to post-stroke rats had no effect on the infarct volume. Nevertheless, the treatment led to improvement in functional recovery in spatial learning and memory (water maze), bilateral coordination and sensorimotor function (rotating pole), and asymmetry of forelimb usage (cylinder test). However, the treatment may not impact on cutaneous sensitivity (adhesive tape removal test). In addition, the double immunofluorescence with human cell-specific antibodies revealed that the number of surviving transplanted cells was higher in the peri-infarcted area of animals treated with hADMSCs + P5 than that in hADMSC-treated or control animals, concomitant with reduced number of phagocytic, annexin3-positive cells in the peri-infarcted region. However, the combination therapy did not increase the vascular density in the peri-infarcted area after stroke. In conclusion, administration of hADMSC-loaded p5 peptide to post-stroke rats created conditions that supported survival of drug-loaded hADMSCs after cerebral ischemia, suggesting its therapeutic potential in patients with stroke. Electronic supplementary material The online version of this article (10.1007/s12975-020-00805-0) contains supplementary material, which is available to authorized users.

The valine⁶⁶methionine (Val⁶⁶Met) polymorphism (rs6265) of the brain-derived neurotrophic factor (BDNF) gene has been shown to influence autonomic arousal pathways, which in turn predict elevated syndromal anxiety in healthy humans. We examined whether the BDNF variant is associated with an increased risk of generalized anxiety disorder (GAD), one of the most prevalent anxiety disorders, through altering parasympathetic stress/relaxation reactivity. A total of 2,250 Han Chinese adults (750 GAD patients and 1,500 healthy controls) were included in the genotyping. High-frequency heart rate variability, an index of vagal (parasympathetic) activity, was measured during the supine-standing-supine test (5 min in each position); vagal withdrawal and vagal activation were calculated as baseline supine minus standing and recovery supine minus standing, respectively. Analysis of healthy participants indicated that Val/Val homozygotes displayed significantly blunted vagal withdrawal and vagal activation compared with Met allele carriers. After analyzing the entire sample, these effects remained significant. Furthermore, both attenuated vagal response patterns were found to be significantly associated with a higher incidence of GAD. Lastly, the path analysis identified a significant indirect effect of BDNF on the risk of GAD via diminishing vagal response to either orthostatic stress or supine relaxation. Even when further testing the subsample comprising only comorbidity- and medication-free GAD patients and healthy controls to minimize the confounding bias, the results still remained. Our findings demonstrate that individuals carrying the BDNF Val/Val genotype, compared to Met-carriers, may be at higher risk of GAD due to blunted vagal reactivity in response to both stress and relaxation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

PurposeGenome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP).MethodsWe performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment.ResultsThrough candidate gene approaches, 3 SNPs in the RUNX2 binding site were selected. A novel SNP rs6086746 in the PLCB4 promoter was identified to be associated with osteoporosis in Chinese populations. Patients with AA allele had higher risk of osteoporosis than those with GG+AG (adjusted OR = 6.89; 95% confidence intervals: 2.23–21.31, p = 0.001). Moreover, the AA genotype exhibited lower bone mass density (p < 0.05). Regarding mRNA expression, there were large differences in the correlation between PLCB4 and different RUNX2 alleles (Cohen’s q = 0.91). Functionally, the rs6086746 A allele reduces the RUNX2 binding affinity, thus enhancing the suppression of PLCB4 expression (p < 0.05).ConclusionsOur results provide further evidence to support the important role of the SNP rs6086746 in the etiology of osteopenia/osteoporosis, thereby enhancing the current understanding of the susceptibility to osteoporosis. We further studied the mechanism underlying osteoporosis regulation by PLCB4.

The Trabecular Bone Score (TBS) is an indirect measurement of bone quality, and studies have shown that TBS is an independent predictor of fracture risk. This cross-sectional investigation aimed to explore the relationship between metabolic syndrome (MetS) and TBS using data from the 2005–2006 US National Health and Nutrition Examination Survey. The association between individual MetS components and TBS was examined. There was a significant linear decrease in TBS with an increase in the number of MetS components. The β coefficients of TBS among participants with 3 and ≥4 MetS components were −0.015 and −0.041 (p=0.006 and p

Background A chronic inflammatory state is a prominent feature in patients with end-stage renal disease (ESRD). Nuclear factor-kappa B (NF-κB) is a transcription factor that regulates the expression of genes involved in inflammation. Some genetic studies have demonstrated that the NF-κB genetic mutation could cause kidney injury and kidney disease progression. However, the association of a gene polymorphism in the transcription factor binding site of NF-κB with kidney disease is not clear. Methods We used the Taiwan Biobank database, the University of California, Santa Cruz, reference genome, and a chromatin immunoprecipitation sequencing database to find single nucleotide polymorphisms (SNPs) at potential binding sites of NF-κB. In addition, we performed a case–control study and genotyped 847 patients with ESRD and 846 healthy controls at Tri-Service General Hospital from 2015 to 2016. Furthermore, we used the ChIP assay to identify the binding activity of different genotypes and used Luciferase reporter assay to examine the function of the rs9395890 polymorphism. Result The results of biometric screening in the databases revealed 15 SNPs with the potential binding site of NF-κB. Genotype distributions of rs9395890 were significantly different in ESRD cases and healthy controls (P = 0.049). The ChIP assay revealed an approximately 1.49-fold enrichment of NF-κB of the variant type TT when compared to that of the wild-type GG in rs9395890 (P = 0.027; TT = 3.20 ± 0.16, GT = 2.81 ± 0.20, GG = 1.71 ± 0.18). The luciferase reporter assay showed that the NF-κB binding site activity in T allele was slightly higher than that in G allele, though it is not significant. Conclusions Our findings indicate that rs9395890 is associated with susceptibility to ESRD in Taiwan population. Electronic supplementary material The online version of this article (10.1186/s12882-019-1471-2) contains supplementary material, which is available to authorized users.

BackgroundAltered heart rate variability (HRV), an index of autonomic nervous system function, has been reported in generalized anxiety disorder (GAD), but the results have been mixed. Thus, the present study, using a large sample size and better methodology, aims to examine whether GAD is associated with impaired HRV, both at rest and in response to posture challenges.MethodsIn total, 1832 participants were recruited in this study, consisting of 682 patients with GAD (including 326 drug- and comorbidity-free GAD patients) and 1150 healthy controls. Short-term HRV was measured during the supine-standing-supine test (5-min per position). Propensity score matching (PSM), a relatively novel method, was used to control for potential confounders.ResultsAfter PSM algorithm, drug- and comorbidity-free GAD patients had reductions in resting (baseline) high-frequency power (HF), an index for parasympathetic modulation, and increases in the low-frequency/HF ratio (LF/HF), an index for sympathovagal balance as compared to matched controls. Furthermore, the responses of HF and LF/HF to posture changes were all attenuated when compared with matched controls. Effect sizes, given by Cohen's d, for resting HF and HF reactivity were 0.42 and 0.36–0.42, respectively.ConclusionsGAD is associated with altered sympathovagal balance, characterized by attenuation in both resting vagal modulation and vagal reactivity, with an almost medium effect size (Cohen's d ≈ 0.4), regardless of medication use or comorbidity status.

Accumulating evidence indicates the association between obesity and lung function. However, no previous study has examined whether obesity affects lung function in normal weight participants with high body fat. We hypothesized that subjects with normal weight obesity (NWO) were inversely associated with lung function in Taiwan. The study sample was composed of participants who attended health examinations at the Tri-Service General Hospital from 2010 to 2016. A total of 7801 eligible participants who were classified as NWO were divided into quartiles by percentage body fat (PBF), which was measured by bioelectrical impedance analysis (BIA). A multivariable linear regression was performed to assess the association between PBF quartiles and pulmonary function. The relationship between PBF and the presence of obstructive and restrictive lung diseases was analyzed by a logistic regression. PBF quartiles were closely associated with reduced forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in all adjusted models. This relationship remained significant in the male population, and a dose-dependent effect was observed. Increased PBF was associated with increased risks for the presence of restrictive lung diseases. These results presented a novel finding that body fat exhibited an inverse association with pulmonary function in NWO subjects. More comprehensive management of subjects with normal weight but high body fat, which might contribute to metabolic dysfunction and impaired pulmonary function, is needed.

Osteoporosis is one of the major complications in chronic hepatitis B virus (HBV) and hepatitis C (HCV) infection. However, few studies had examined the relationship between hepatic viral infection with bone loss. Our aim was to investigate the association between hepatic viral infection with bone mineral density (BMD) in a cross-sectional study. Participants who attended the health examinations at the Tri-Service General Hospital (TSGH), Taiwan, were enrolled in the study. Diagnosis of viral hepatitis was confirmed by the serum viral markers of hepatitis B surface antigen (HBsAg) and anti-HCV, and BMD measurement was performed by the bone densitometry. Subjects were divided into four groups by the presence of viral markers. The association between hepatic viral infection and BMD was examined by a multivariate linear regression model. HBV infection was inversely associated with BMD after full adjusting with β values of −0.17 (95% CI: −0.29, −0.05) (p β = −0.16, 95% CI = −0.31, −0.01) (p

(1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor α (ERα) has been considered to play a key role due to a large gender difference in its expression. ERα is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case–control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren–Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78–1.20) and adjusted-OR: 0.90 (95% CI: 0.71–1.15) in allele model] in the present case–control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case–control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59–1.04)] with a high heterogeneity (I2: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56–1.95), I2: 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.

Klotho protein is an anti-aging protein and plays multiple roles in ion-regulation, anti-oxidative stress, and energy metabolism through various pathways. Metabolic syndrome is a combination of multiple conditions that compose of multiple risk factors of cardiovascular disease and type 2 diabetes. Gene regulation and protein expression are discovered associated with metabolic syndrome. We aimed to figure out the correlation between Klotho protein and metabolic syndrome in generally healthy adults. A cross-sectional study of 9976 respondents ≥ 18 years old from the US National Health and Nutrition Examination Survey (2007–2012) by utilizing their soluble Klotho protein concentrations. Multivariate linear regression models were used to analyze the effect of soluble Klotho protein on the prevalence of metabolic syndrome. Soluble Klotho protein concentration was inversely correlated with the presence of metabolic syndromes (p = 0.013) and numbers of components that met the definition of metabolic syndrome (p < 0.05). The concentration of Soluble Klotho protein was negatively associated with abdominal obesity and high triglyceride (TG) in the adjusted model (p < 0.05). Soluble Klotho protein is correlated with changing metabolic syndrome components in adults, especially central obesity and high TG levels. Despite conventional function as co-factor with fibroblast growth factor-23 (FGF23) that regulates phosphate and vitamin D homeostasis, FGF23-independent soluble Klotho protein may act on multiple signal pathways in different organs and tissue in roles of anti-aging and protection from metabolic syndrome.

The association between anthropometric indices with chronic kidney disease (CKD) was examined previously. However, the effect of body fat on renal function was not determined clearly. Our aim was to investigate the association of percent body fat (PBF) and renal function in adult population from health examination in Tri-Service General Hospital (2010–2016). 35087 participants aged 20 years and older were enrolled in the study. PBF was measured by bioelectrical impedance analysis (BIA). Estimation of renal function was performed by Taiwanese MDRD equation. Optimal cut-off values of PBF was accessed by a receiver–operator characteristic (ROC) curve analysis. Multivariate regression models were used in the relationship among changes of PBF, renal function, and future CKD. In terms of baseline PBF for CKD, optimal cut-off values of PBF in males and females were 21.55 and 40.75. The changes of PBF were more closely associated with renal function decline than waist circumference (WC) with β values of −0.173 (95% CI: −0.233, −0.112) and −0.077 (95% CI: −0.104, −0.049), respectively. After stratified by gender, this relationship remained significant in male population with β values of −0.276 (95% CI: −0.371, −0.181) and −0.159 (95% CI: −0.207, −0.112), respectively. Female subjects with increased baseline PBF over cut-off values had increased risk for predicting the future CKD with odd ratios (ORs) of 2.298 (95% CI: 1.006–5.252). Body fat had detrimental impact on renal function and development of CKD in adult population. Measurement of PBF for surveillance of renal function impairment was warranted.

Background In 2010, the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0) was developed, based on the concept of the International Classification of Functioning, Disability and Health (ICF). The ICF provides a common language and framework for health and health-related status and attempts to integrate the biopsychosocial model as a multidimensional perspective in understanding functioning. Activities and participation (AP) is one salient component of the ICF refers to the execution of a task by an individual, and how such tasks are involved in their daily life. It is essential to examine the gap between the general adult population and adults with disabilities. This gap may be attributed to health status, personal factors, and natural and social environments, which include social and health services and policies. The purposes: (1) To develop a normative activity and participation (AP) value for the adult population and people with disabilities; and (2) to compare the gap in AP normative values between the two groups in Taiwan. Methods We use the WHODAS 2.0 to survey and develop a normative AP value for the general adult population, and used secondary data from National Disability Eligibility Determination System (NDEDS) of Taiwan to describe the AP functioning distribution of adult with disability. There were 1100 participants, selected by stratified proportional sampling from two cities. There were also 144,850 participants who were adults with disability, selected from the secondary database in Taiwan. Results and conclusions The AP curve for the disabled population increased rapidly at the beginning. The summary score was 13.21 in the performance at 90 percentile for the general population and 82.61 score for disabled adults that the similar gap in every domain, its means that there are significant functioning difference and health equality in general adults population and adults with disabilities. This presents a substantial challenge for both the government and the whole population of Taiwan, to begin considering how to reduce the gap in AP functioning and promote equality for people with disabilities, using social welfare policy. It is important to make sure disabled people have the same rights to be included in society as anybody else and better access to things in all areas of life that are according to Convention on the Rights of Persons with Disabilities (CRPD).

Decreased resting vagal (parasympathetic) tone is implicated in the development of stress-related disorders, including anxiety and depression. Chronic stress elevates the expression of serotonin 2A receptors (5-HT2A), while activation of 5-HT2A leads to inhibition of parasympathetic synaptic transmission. The T allele of the promoter variant, rs6311 (C > T), of the 5-HT2A gene has been shown to increase the 5-HT2A expression in vitro and to be associated with anxiety and depressive disorders. We thus hypothesized that the 5-HT2A functional polymorphism may influence resting vagal activity among persons with chronically high levels of perceived stress. A total of 1138 well-defined healthy, medication-free Han Chinese were included for 5-HT2A genotyping. The Perceived Stress Scale (PSS) was used to measure the level of perceived stress during the last month and participants were divided into low and high PSS groups. Resting-state heart rate variability (HRV) was used to assess autonomic function. No significant between-genotype difference was found in any HRV variable in the low PSS group (n = 610). However, in the high PSS group (n = 528), high frequency power and root mean square of successive heartbeat interval differences (both HRV indices of parasympathetic activity) were significantly reduced in T/T genotype carriers compared to C/C homozygotes. Our findings are the first to show that individuals homozygous for the high-expressing 5-HT2A (T) allele exhibit diminished resting vagal tone—an index of stress vulnerability—when experiencing chronically elevated levels of perceived stress. The present results may advance our understanding of the genetic mechanism underlying individual differences in susceptibility to stress.

Background A tri-allelic serotonin transporter promoter polymorphism ( 5-HTTLPR/rs25531 ) more effectively determines the levels of transcriptional efficacy than that with the bi-allelic 5-HTTLPR polymorphism in vitro. Both are reportedly associated with personality traits of negative emotionality, but with conflicting findings. One explanation for this is that a gender difference may play a role in genetic contribution. Here, we hypothesized that the tri-allelic genotype of the serotonin transporter is more closely linked to neuroticism, an anxiety- and depression-related trait, than the bi-allelic variation, particularly in a gender-dependent way. Methods The genotypes of the 5-HTTLPR and rs25531 loci were determined in 1139 well-defined physically and mentally healthy Han Chinese (550 men, 589 women; mean age 38.3±10.3 years). All participants completed the neuroticism measure of the short-form Maudsley Personality Inventory (MPI). The levels of anxiety and depression were assessed by the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI), respectively. Results A significant tri-allelic genotype-by-gender interaction effect was found in the MPI-neuroticism measure. S′S′ homozygotes were associated with higher neuroticism than L′ allele carriers in men. Also, both the BAI and BDI scores were higher in the S′S′ homozygotic men. In the bi-allelic analyses, however, there was only an association between SS genotype and MPI-neuroticism in men. Limitations Sub-analyses by gender-stratification may reduce the statistical power. Conclusions Our findings confirm that gender differences exist in the genetic contributions of the serotonin transporter in human neuroticism, and anxiety/depression. Our data provide further support for rs25531, strengthening the effects of 5-HTTLPR .

The prevalence of obesity was increasing and became a growing problem worldwide. Obesity increased the risk of developing metabolic abnormalities and was associated adverse health outcomes. Our aim was to examine the associations among different combinations of obesity phenotypes (high body mass index > 27 kg/m2 (O), high waist circumference (male > 90 cm, female > 80 cm) (W), fatty liver (F) and percentage body fat in top 40% (P)) and cardiometabolic diseases (type 2 diabetes mellitus (DM), hypertension (HTN), metabolic syndrome (MetS)). A total of 48426 eligible subjects were categorized based on the different definitions. After adjusting for all covariables, participants with O + F + P combination were more likely associated with the presence of DM. Participants with O + W combination were more associated with the presence of HTN than others. Participants with O + W + F + P had higher risk for the presence of MetS than others. The study addressed the associations between different obesity phenotypes and DM and HTN in the adult population. Better understanding the pathophysiological mechanisms underlined individual vulnerability and progression of cardiometabolic insults.

Emerging evidences had reported the positive relationship between obesity and intraocular pressure (IOP). The aim of the present study was to investigate the association between hepatic steatosis and IOP in an adult Taiwanese population. Seven thousand seven hundred twelve males and 6325 females who received a health examination at the Tri-Service General Hospital during the period from 2010 to 2016 were included in this study. IOP was measured by noncontact tonometry. Hepatic steatosis was diagnosed by abdominal ultrasound examination. Multivariate regression analyses were used to assess the associations among various anthropometric parameters and IOP. After adjusting for pertinent covariables, hepatic steatosis had a closer association with increased IOP than percentage body fat, body mass index, or waist circumference (β = 0.017, 95% confidence interval [CI] = 0.006, 0.028). This relationship remained significant among males in the study population (β = 0.015, 95% CI = 0.001, 0.029). Furthermore, hepatic steatosis was significantly correlated with increased risk of high IOP (odd ratios = 1.235, 95% CI = 1.041–1.465). Our study highlights that hepatic steatosis is a better index for assessing the relationship with increased IOP than other anthropometric parameters. Underlying pathophysiological mechanisms regulating the association between hepatic steatosis and increasing IOP and even the risk of glaucoma should be examined in further studies.

ObjectivesTo use the extended theory of planned behaviour (TPB) to predict smoking cessation counsellors’ intentions to offer smoking cessation support.DesignCross-sectional studySettingTaiwanese militaryParticipantsA survey of 432 smoking cessation counsellors was conducted in 2017.Primary and secondary outcome measuresAll participants completed a self-administered questionnaire that solicited information concerning demographics, smoking behaviour, self-rated suitability for being a counsellor, the knowledge and skills learnt from training courses and the TPB construct.ResultsThe factors of perceived behavioural control (β=0.590, pConclusionsTo encourage smoking cessation counsellors to offer cessation support to smokers, policies should aim to increase their perceived behavioural control, knowledge and self-rated suitability for being a counsellor.

Emerging studies have shed light on the association between Helicobacter pylori (HP) infection and cardiometabolic risk. However, there is no evidence to support a causal link for the relationship in the general population. Our aim was to determine whether HP infection is associated with the risks of incident type II diabetes mellitus (DM) in a population-based cohort consisting of adults from the general population. A total of 69235 adults enrolled in the study obtained health examinations at the Tri-Service General Hospital in Taiwan from 2010 to 2016. HP infection detection was performed by rapid urease tests (RUTs), and endoscopic examinations were used to diagnose gastroesophageal reflux disease (GERD), gastric ulcers (GUs) and duodenal ulcers (DUs). Cross-sectional and longitudinal analyses were performed to examine the association between HP infection and cardiometabolic diseases using logistic regression and Cox regression in a large population-based study. HP infection was significantly associated with the presence of metabolic syndrome (MetS) (OR = 1.26, 95%CI: 1.00-1.57) and DM (OR = 1.59, 95%CI: 1.17-2.17) only in male subjects, and abnormal endoscopic findings were also correlated with cardiometabolic diseases. Our findings demonstrated that participants with HP infection had an elevated risk of developing incident DM (HR = 1.54, 95%CI: 1.11-2.13). In addition, endoscopic findings of a DU (HR = 1.63, 95%CI: 1.02-2.63), rather than GERD or a GU, were also predictive of incident DM. In this cohort, HP infection was a statistically significant predictor of incident DM among male population.

The functional Val

BACKGROUND Low gait speed is associated with inflammation and muscle strength. Follistatin, a glycosylated plasma protein, is involved in inflammatory diseases, bone metabolism, muscle strength and cognition. However, research regarding the relationship between follistatin and gait speed in elderly individuals is limited. In this study, we aimed to examine the association between follistatin and gait speed in older adults. METHODS This cross-sectional, observational study included 205 ambulatory individuals aged ≥ 65 years. The baseline measures included 15-foot walking time, a structured questionnaire, grip strength and biomarkers, including follistatin and myostatin levels. Multiple linear regression was used to determine the change in gait speed for each 1 pg/mL increase in serum follistatin level. An extended model approach with a quartile-based analysis of serum follistatin levels was conducted. RESULTS In the linear regression model, the β coefficient, representing the change in gait speed for each 1 pg/mL increase in serum follistatin level, was -0·308 (P < 0·001). After additional adjustment for relevant covariates, the β coefficient changed slightly, although the negative correlation remained (all P ≤ 0·001). After controlling for multiple covariates, participants in the highest serum follistatin level quartile had a significantly lower gait speed than those in the lowest quartile (all P for trend < 0·001). CONCLUSIONS A higher follistatin level was independently associated with lower gait speed in community-dwelling elderly individuals; this suggests that serum follistatin level may be an indicator of mobility in elderly persons and may more particularly represent lower extremity function.

Supplemental Digital Content is available in the text, Bioelectrical impedance analysis (BIA) is currently the most commonly used method in clinical practice to measure body composition. However, the bioelectrical impedance analyzer is not designed according to different countries, races, and elderly populations. Because different races may have different body compositions, a prediction model for the elderly population in Taiwan should be developed to avoid population bias, thereby improving the accuracy of community evaluation surveys. Dual energy X-ray absorptiometry (DXA) was used as a standard method for comparison, and impedance analysis was used for the development of a highly accurate predictive model that is suitable for assessing the body composition of elderly people. This study employed a cross-sectional design and recruited 438 elderly people who were undergoing health examinations at the health management center in the Tri-Service General Hospital as study subjects. Basic demographic variables and impedance analysis values were used in four predictive models, namely, linear regression, random forest, support vector machine (SVM), and eXtreme Gradient Boosting (XGBoost) models, to predict DXA body composition. The data from 354 study subjects were used to develop the predictive model, while the data from 84 study subjects were used to validate the accuracy of the predictive model. The body composition of elderly people as estimated by InBody 720 was highly correlated with that estimated by DXA. The correlation coefficient between InBody 720 and DXA for muscle mass was 0.969, and that for fat mass was 0.935. Consistency analysis results showed that InBody 720 tends to underestimate muscle mass and fat mass. A comparison of the accuracy of the linear regression, random forest, SVM, and XGBoost models showed that the linear regression has the highest accuracy. The correlation coefficient between the new model and DXA for muscle mass and fat mass were 0.977 and 0.978, respectively. The new predictive model can be used to monitor the nutrition status of elderly people and identify people with sarcopenia in the community.

Family history was one of the major risk factors for developing adverse health outcomes such as metabolic syndrome (MetS), type 2 diabetes mellitus (DM) and hypertension (HTN). Our aim was to examine the relationship between different family histories and cardiometabolic events, including DM, stroke, myocardial infarction (MI), and HTN. Participants who attended the health examinations at the Tri-Service General Hospital from 2010 to 2016 were enrolled in the study and were categorized into four groups by representing different family history. A multivariable logistic regression model was used for the associations between various family history with the cardiometabolic events. Subjects with family history of DM were divided into quartiles by percentage body fat (PBF) to be analyzed for these adverse outcomes. In the cross-sectional analysis, subjects with family history of DM had significant association with MetS (OR = 1.34 [95%CI: 1.17–1.54]) and DM (OR = 3.03 [95%CI: 2.44–3.76]), and those with family history of HTN were positively associated with HTN (OR = 1.60 [95%CI: 1.41–1.81]). Notably, those with family history of DM in higher PBF quartiles had substantially increased association of cardiometabolic events (MetS: OR = 15.20 [95%CI: 9.87–23.39]; DM: OR = 3.35 [95%CI: 1.91–5.90]; HTN: 2.81 [95%CI: 1.84–4.29]). Individuals with family history of DM were positively associated with MetS and DM, and those with family history of HTN was associated with HTN. Family history assessment was requested especially in obese population for screening adverse health outcomes.

Accumulated evidence has suggested associations between glucose abnormalities and insulin resistance with hepatitis C virus (HCV) and hepatitis B virus (HBV) infections. However, few studies have reported the effect of hepatitis virus infections on body composition. Our aim was to explore the association of hepatitis virus infections with percent body fat (PBF) in a cross-sectional analysis. A total of 69226 subjects obtained from the health examinations at Tri-Service General Hospital (TSGH) from 2010 to 2016 were enrolled in the study. Participants were divided into subgroups based on the presence of hepatitis B surface antigen (HBsAg) and anti-HCV. PBF was measured by bioelectrical impedance analysis (BIA). A multivariable linear regression model was applied to test the association of hepatitis virus infections with PBF and glycemic status. In male participants, hepatitis virus infections were closely associated with increased PBF, especially in those subjects with HCV/HBV coinfection. HCV/HBV coinfection was positively correlated with fasting plasma glucose and postprandial glucose while HCV and HBV mono-infection were not. The impact of hepatitis virus infection on increased PBF was observed in general population with gender difference. A further study on the treatment of hepatitis virus infection might help prevent the development of obesity-related diseases.

A growing amount of evidence suggests that thyroid-stimulating hormone (TSH) is associated with cardiometabolic risk. However, there have been few longitudinal studies. The aim of this study was to explore the causal relationship between TSH and metabolic syndrome (MetS) in a large population-based longitudinal study. From 2010 to 2016 at the Health Management Center at Tri-Service General Hospital, 25,121 eligible patients were enrolled in our cross-sectional analyses. Cox proportional hazard models were used to investigate the longitudinal association among hypertension (HTN), prediabetes (pre-DM), MetS, diabetes (DM) and TSH levels (N = 12,463). The average follow-up time was 7.2 years. In the cross-sectional analysis, the OR for MetS was 1.06 (95% CI = 1.03–1.09; P< 0.05), while the ORs for DM, pre-DM or HTN were not statistically significant (all P> 0.05). After dividing TSH levels into four quartiles, the ORs for the presence of MetS determined by comparing the highest TSH quartile with the lowest TSH quartile were 1.37 (95% CI = 1.18–1.60), 1.42 (95% CI = 1.20–1.67), and 1.44 (95% CI = 1.22–1.69) (all, P

Adverse systemic effect caused by betel nut had been reported for decades. Our aim was to determine whether betel nut had detrimental impact on the development of colorectal polyps in general population. Participants who attended health examinations at the Tri-Service General Hospital (TSGH) from 2010 to 2016 were included in the study. The habit of betel nut chewing was obtained from a self-reported questionnaire. Colorectal polyps were diagnosed by colonoscopies operated by experienced physicians. A logistic regression model was used for the association between betel nut chewing with the presence of colorectal polyps. After adjustment for pertinent information such as age, gender, biochemistry data and personal history, the odd ratios (ORs) of colorectal polyps among betel nut chewers was 1.49 (95%CI: 1.14–1.94). Besides, betel nut chewers in the higher percentage body fat (PBF) group had higher risk for developing colorectal polyps with ORs of 2.07 (95%CI:1.23–3.47). Subjects with habit of betel nut chewing were associated with an increased risk of colorectal polyps in Taiwanese general population. Screening for betel nut chewing history and encouraging cessation might offer improved quality of life. A further research for this association was warranted.

Objective The effect of obesity-induced metabolic abnormalities on bone mineral density (BMD) and osteoporosis are well established. However, the association between metabolically healthy obesity (MHO) and BMD remains unclear. Our aim was to investigate whether different obesity phenotypes in MHO were associated with BMD in a cross-sectional study. Methods All eligible adults receiving a health examination at the Tri-Service General Hospital from 2010 to 2016 were included. They were categorized based on body mass index (BMI) or percentage body fat (PBF). The associations between BMI or PBF and BMD were analyzed by adjusting for pertinent covariables. Results Males with normal weight and overweight and females with underweight and normal weight were associated with reduced BMD (β = 0.221, 95%CI = -0.354, -0.088; β = -0.155, 95%CI = -0.286, -0.023) (β = -0.736, 95%CI = -1.043, 0.429; β = -0.340, 95%CI = -0.567, -0.112), respectively. Females in Q1 had close to significant associations with reduced BMD (β = -0.253, 95%CI = -0.465, -0.041). Normal weight, overweight, Q2, and Q3 had stronger prediction of low BMD with ORs of 0.402 (95%CI = 0.204–0.791), 0.539 (95%CI = 0.321–0.905), 0.694 (95%CI = 0.490–0.982), and 0.466 (95%CI = 0.342–0.636), respectively. The relationship remained significant in male population that PBF was associated with reduced BMD with ORs of 0.435 (95%CI = 0.203, 0.935), 0.494 (95%CI = 0.247, 0.991), 0.268 (95%CI = 0.120, 0.597) in Q1, Q2, Q3 respectively. Conclusion Increased PBF had a significant association with low BMD in the MHO population. Obesity defined by PBF might be a useful indicator for low BMD. The association between body fat and bone health deserves further investigation regarding the potential pathophysiological mechanisms.

Disability became increasingly common with age, and crude rates of disability were rising around the globe. The aim of this study was to investigate the association between calf circumference (CC) and disability in the U.S. elderly population. From the 1999–2006 National Health and Nutrition Examination Survey, a total of 4,245 participants with an age range of 60–84 years were included. Disability was defined as the total number of difficulties within the following 5 major domains of disability, such as activities of daily living (ADL), instrumental ADL, general physical activities, lower extremity mobility, and leisure and social activities. The association between CC and disability was investigated through the regression model adjusted for multiple covariates. According to the fully adjusted model regarding disability, the β coefficients for each quartile of increasing CC were −0.041 for quartile 2 (P = 0.096), −0.060 for quartile 3 (P = 0.027), and −0.073 for quartile 4 (P = 0.026) respectively, compared with lowest quartile. There was a negative association between CC and disability among the elderly population. Calf circumference may be a novel risk assessment for disability of elderly people.

OBJECTIVE Substantial research has shown that anxiety disorders are associated with decreased cardiac vagal tone, which is a known risk factor for cardiac vulnerability. A functional nerve growth factor (NGF) polymorphism (rs6330, c.104C > T, p.Ala35Val) has been associated with anxiety such that in males but not females, T-allele carriers exhibit higher levels of trait anxiety. Here we investigate whether the nonsynonymous NGF variant has an effect on cardiac autonomic control. METHODS From 705 adults initially screened for medical and psychiatric illnesses, a final cohort of 580 healthy Han Chinese (352 men, 228 women; mean [standard deviation] age = 34.46 [8.45] years) was included in the NGF genotyping (C/C: 428% [73.8%] and T-allele carriers: 152% [26.2%]). Short-term heart rate variability was used to assess cardiac autonomic function. RESULTS There were significant genotype-by-sex interaction effects (p < .05) on high-frequency power (HF) and root mean square of successive heartbeat interval differences (RMSSD), both indices of cardiac vagal control. Even after adjusting for possible confounders, men with any T allele showed lower HF and RMSSD compared with men with the C/C genotype. Women, however, showed an opposite but nonsignificant pattern. CONCLUSIONS The studied NGF polymorphism modulates autonomic outflow to the heart in a sex-dependent manner. The findings support the view that male T-allele carriers are at increased susceptibility for anxiety by association with low vagal activity and suggest a potential sex-specific genetic link between the highly comorbid anxiety disorders and cardiovascular diseases.

Metabolic disorders are prevalent worldwide and have recently become public health problems recently. Previous studies have proposed different body composition indices for predicting future cardiovascular risks. We hypothesized an association among fat-to-muscle ratio (FMR), metabolic syndrome (MetS), hypertension (HTN), prediabetes, type 2 diabetes mellitus (DM), and cardiovascular risk in an adult population. A total of 66829 eligible subjects composed of 34182 males and 32647 females aged 20 years or older were obtained from health examinations in the Tri-Service General Hospital from 2011 to 2017. The body composition indices included fat and muscle mass measured by bioelectrical impedance analysis. A multivariable regression model was performed in a large population-based cross-sectional study. FMR was significantly associated with MetS, prediabetes, DM and HTN in all models of both genders. Based on quartile analysis, higher FMR had higher predictive ability for adverse health outcomes. The association between different definitions of MetS and the Framingham risk score was analyzed, and FMR-incorporated MetS was more useful for predicting higher Framingham risk scores than traditional definitions. FMR was a useful indicator for the presence of adverse cardiometabolic risks. Compared to traditional definition of MetS, FMR-incorporated MetS had a greater ability to predict incident cardiovascular risks. FMR seemed to be a simple and effective index for the early prevention and management of cardiometabolic events.

Treatment of furcation-involved molars presents a clinical challenge. This study retrospectively investigates the demographic parameters affecting treatment decisions and outcomes of root-resected molars using a nationwide population-based dataset.De-identified data from 471 eligible patients were obtained from a representative cohort composed of 1 million of Taiwan's population. Demographic factors that influence treatment decisions and outcomes of root-resected teeth were examined. Cox regression was performed to statistically analyze the factors.The overall survival rate for root-resected molars was 91.1%. The survival times of the extracted and surviving teeth were 303.0 ± 274.6 and 551.8 ± 327.2 days, respectively (P0.001). The analyzed patient-related factors, such as living district, urbanization level, medical institution, and monthly income, have remarkable influence on treatment decisions; however, there is no statistically significant difference in survival rate between root-resected molars receiving flap surgery and those that do not (P = 0.504). After adjusting for other factors, patients aged74 years have 3.33 times (hazard ratio = 3.33; 95% CI = 1.04 to 10.66; P = 0.043) higher rates of molar extraction than younger counterparts.The overall survival rate of root-resected molars was satisfactory. Patients with advanced age (74 years) had a higher risk of extraction occurrence on resected molars. Patient-related factors may influence the treatment decision of whether molars receive flap surgery. These findings suggest that demographic factors should be carefully evaluated before and after performing root-resection procedures because these factors may eventually impact the outcome of root-resected molars.

Background: Several polymorphisms in the angiotensin-converting enzyme (ACE) and ACE2 genes are associated with the development of end-stage renal disease (ESRD). Certain genetic polymorphisms may modify the deleterious effects of environmental factors such as cigarette smoking and may also modify the inherited risk. We investigated the association of six ACE and ACE2 polymorphisms with ESRD to determine whether a relationship exists between gene–smoking interactions and ESRD. Materials and methods: We performed a case-control association study and genotyped 683 ESRD patients and 653 healthy controls. All subjects were genotyped for ACE (I/D, G2350A and A-240T) and ACE2 (G8790A, A1075G and G16854C) gene polymorphisms by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Significant associations were observed between ACE I/D and G2350A polymorphisms and ESRD. There was no difference in ACE2 genotype distribution between ESRD patients and healthy controls. Haplotype analysis showed that DAA and DAT haplotypes were risk factors for ESRD. Moreover, a gene–environment interaction was observed between ACE I/D polymorphism and cigarette smoking. Conclusion: ACE I/D and ACE G2350A polymorphisms were associated with the development of ESRD. The interaction between ACE I/D polymorphism and smoking is also associated with an enhanced risk of ESRD.

Neuropeptide Y (NPY) is involved in resilience to stress and higher vagal (parasympathetic) activity has been associated with greater stress resilience. Thus, we examined whether rs16147, a functional promoter polymorphism (C>T) of the NPY gene, could influence vagal tone during chronic high stress levels. NPY genotyping, chronic psychological stress level measurement (using the Perceived Stress Scale [PSS]), cardiac autonomic function assessment (using short-term heart rate variability [HRV]) were performed in 1123 healthy, drug-free Han Chinese participants who were divided into low- and high-PSS groups. In the high-PSS group (n = 522), the root mean square of successive heartbeat interval differences and high frequency power (both HRV indices of parasympathetic activity) were significantly increased in T/T homozygotes compared to C/C homozygotes. However, no significant between-genotype difference was found in any HRV variable in the low-PSS group (n = 601). Our results are the first to demonstrate that functional NPY variation alters chronic stress-related vagal control, suggesting a potential parasympathetic role for NPY gene in stress regulation.

Metabolic syndrome (MetS) has been reported to cause considerable psychoneuroimmunology (PNI) disturbances such as, psychological distress, autonomic nervous imbalance, and impaired immune function. Associations among these psychoneuroimmunology (PNI) factors and their integrated effects with MetS and risk components of MetS necessitate further exploration.This study investigated associations among psychoneuroimmunological factors, their integrated effects with MetS and risk components of MetS.This was a cross-sectional study. Participants were recruited from two health management centers at a medical center in Northern Taiwan. Demographics and data on psychological distress (e.g., perceived stress and depression) were collected using self-reported questionnaires. Heart rate variability (HRV) and C-reactive protein values (CRP) were measured to evaluate participants' autonomic nervous function and immune reaction. The risk components of MetS (e.g., elevated blood pressure, impaired fasting glucose, dyslipidemia, and abdominal obesity) were identified according to the Taiwan-specific definition of MetS and were determined based on participants' health examination profiles.A total of 345 participants with complete data were included for data analysis. Compared with healthy controls, participants with MetS exhibited higher depression scores (11.2±8.5 vs. 8.7±7.0), higher CRP values (2.1±2.5 vs. 0.7±1.0), and lower HRV (total power: 758.7±774.9 vs. 1064.4±1075.0). However, perceived stress in participants with MetS did not significantly differ from that of their healthy counterparts (p0.05). Univariate analyses indicated that associations among psychoneuroimmunological factors and MetS risk components were statistically heterogeneous: a) perceived stress and depression were significantly associated only with high blood glucose (p0.05); b) CRP was significantly associated with all MetS risk components (p0.05); and c) HRV was significantly associated with high triglycerides and high fasting blood glucose (p0.05). Multivariate analysis indicated that the integrated effects of depression, CRP, and HRV were significantly associated with MetS (p0.01) after controlling for age and education level.Higher depression scores, higher CRP values, and lower HRV are independently and additively associated with MetS and risk components of MetS. Accordingly, a multidisciplinary approach to alleviating psychological distress, immune dysfunction, and autonomic nervous imbalance is recommended for promoting well-being in people with subclinical metabolic abnormalities or MetS to minimize downstream health consequences.

The aim of this study was to investigate the association between postprandial glucose and intraocular pressure in a relatively healthy population. We examined 1,439 adults getting a health check-up in a health promotion center at Tri-Service General Hospital (TSGH) in Taiwan between 2012 and 2013. All participants underwent examinations to measure metabolic variables and intraocular pressure. Multiple linear regression analyses were performed to assess the relationship between postprandial glucose and intraocular pressure. The levels of postprandial glucose were divided into quartiles with subjects in the lowest quartile being regarded as the reference group to perform quartile-based analysis. Covariate adjustment was designed for three models for further analysis. Subjects with higher quartiles of postprandial glucose level had a higher systolic blood pressure, a greater waist circumference and an elevated fasting glucose level (all p < 0.001). The β coefficient with adjusted covariates showed a significant positive association between postprandial glucose and intraocular pressure. The trends of intraocular pressure across increasing quartiles of postprandial glucose were statistically significant (all p for trend < 0.001). Thus, higher levels of postprandial glucose positively correlated with elevated intraocular pressure.

Metabolic syndrome (MetS) increases the risk of cardiovascular events. Heart rate variability (HRV) represents autonomic functioning, and reduced HRV significantly increases cardiovascular mortality. The aims of the present paper are to assess the prevalence of MetS in adults with intellectual disabilities (ID), the difference in short-term HRV between the healthy and ID population, and the association of short-term HRV with MetS. In this study, we analyzed 129 ID subjects who participated in routine health check-ups in October 2010. We measured their metabolic components and evaluated the relationships of MetS with short-term HRV indices. The study found that MetS and obesity are common in persons with ID. ID subjects have significantly lower HRV than healthy adults, and persons with ID persons with MetS have significantly lower HRV than ID subjects without MetS. The individual components of MetS are differentially associated with HRV in ID men and women. Metabolic syndrome adversely affects autonomic cardiac control, and reduced autonomic cardiac control could contribute to an increased risk of subsequent cardiovascular events in individuals who exhibit metabolic syndrome. Sex differences in vagal activity and sympathovagal balance may partly explain the greater increase in cardiovascular risk associated with MetS in ID women compared with ID men.

The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or adolescents with ID. A cross-sectional design was conducted in three Taiwanese public special schools to analyze annual health examination chart of students with ID. There were 1041 aged 3-21 years children and adolescents with ID participated in the study. The results show elevated rate of GOT and GPT were 3.7% and 7.2%, the study indicates the elevated GPT in children and adolescents with ID is higher than the general school aged children in Taiwan. In multiple linear regression models show that the factors of BMI, HBsAg, TC and UA can significantly explain the GOT value (R(2)=0.275). Those factors of gender, BMI, HBsAg, TC and UA can significantly explain 44.4% variation of GPT value (R(2)=0.444). To prevent the further liver disease burden in people with ID, the study highlights that the health care professionals should assess liver functions of this group of people, and to inform their caregivers the importance of implement regular liver health check-up.

The aims of the preset study were to describe the profile of serum uric acid, the prevalence of hyperuricemia and its risk factors among children and adolescents with intellectual disabilities. We conducted a cross-sectional study of 941 children and adolescents with intellectual disabilities (aged 4–18 years) who participated in annual health examinations in three special schools in Taiwan. This study indicated 30.6% boys and 17.9% girls with intellectual disabilities were with hyperuricemia in Taiwan. The factors of gender, age and BMI were variables that can significantly predict the hyperuricemia occurrence in this vulnerable population. Those children and adolescents with intellectual disabilities were boys (OR = 2.93, 95% CI = 2.02–4.26) and older age (OR = 6.49, 95% CI = 2.19–19.21) were more likely to be hyperuricemia. With regard to BMI to hyperuricemia occurrence, those children and adolescents with intellectual disabilities were overweight (OR = 1.16–3.21, 95% CI = 1.16–3.21) and being obese (OR = 4.95–11.58, 95% CI = 4.95–11.58) was more likely to have a hyperuricemia than the normal weight group. This study provides the general profile of serum uric acid, hyperuricemia and its risk factors of children and adolescents with intellectual disabilities. Medical professionals should be highly alert to the possible consequences of hyperuricemia and provide useful information about the clinical manifestation of this condition for caregivers of children and adolescents with intellectual disabilities.

The objectives of this study were to examine trends related to the staffing of disability welfare institutions caring for people with disabilities in Taiwan. Nationwide data from the 2002 to 2007 “ Service Manpower in Disability Welfare Institutions ” report, which are derived mainly from the Department of Statistics, Ministry of the Interior, Taiwan, were analyzed. The data included number of workers, job type and gender distribution of staff working in welfare institutions catering for the disabled. We also used the disabled population and those who had been admitted to institutional care to analyze the service load per staff member. Based on analyses of current governmental statistics, the results showed that staff numbers in institutions for the disabled increased from 6191 to 7820 (20.8% increase), and the female/male ratio these staff increased from 4.18 to 4.51 from 2002 to 2007. Educator/training personnel (33.3–36.7%) accounted for a higher proportion of staff than other job categories, and each staff member served 5.8–6.3 persons with disabilities on average. The second largest group was living assistant (18.4–20.5%; 9.9–11.8), and the remaining personnel were administrative staff (13.5–14.6%; 13.9–15.9), nursing staff (6.4–8.7%; 24.9–32.0), social workers (6.2–7.5%; 28.8–32.8), and counseling staff (3.8–6.3%; 21.9–57.1). Curve estimation tests showed a significant change over the period of the study in the number of disabled people attended to on average by administrative staff, social workers, nurses and other staff. The results highlight the requirement for further study to explore the needs of the majority service provider – female staff – to provide them with adequate professional or psychological support to enable them to work with people with disabilities in institutions. In addition, further analysis should focus on a review of staff numbers for different types of institutions, to examine their adequacy.

In current health examination setting, people frequently undergo heart rate variability (HRV) analysis and colonoscopy on the same day. However, it remains unclear whether the bowel preparation before colonoscopy affects HRV. This study aimed to evaluate the association between HRV and bowel preparation. We conducted a cross-sectional observational study of 1755 people from January 2012 to December 2013 in Taipei, Taiwan. The participants, aged 45 to 65 years, received health examinations that included a physical examination, blood tests, and an HRV analysis. Among these people, 1099 additionally received a colonoscopy on the same day and underwent bowel preparation 1 day before the colonoscopy. The association between HRV and bowel preparation was derived by a multivariable linear regression with adjusted confounding factors. Bowel preparation was associated with a lower standard deviation of the normal-to-normal intervals (SDNN), the root mean square of the successive differences (RMSSD), low-frequency power (LF), and high-frequency power (HF) (all P

Recent studies have revealed that the inflammatory process plays a role in the pathogenesis of osteoarthritis (OA). The S100 family and receptor for advanced glycation end products (RAGE) participate in regulating inflammation, even in the production of matrix metalloproteinases (MMPs). MMP-1 degrades cartilage, which may result in OA development. Moreover, polymorphisms in RAGE, S100A8, and MMP-1 have a marked effect on ligand binding and transcription regulating. In this study, we investigated the potential genetic contribution of the RAGE, S100A8, and MMP-1 genes to OA. We performed a matched case-control association study and genotyped OA patients and healthy controls, who were analyzed by polymerase chain reaction-restriction fragment length polymorphism assays. A total of 207 patients were diagnosed with knee OA and underwent total knee replacement. The control group included 207 individuals who had standard X-rays of the knee joints to confirm K/L < 2 and were matched by age and gender. Single-nucleotide polymorphisms in RAGE (-429T/C, -374T/A, and 557G/A), S100A8 (rs3795391A/G), and MMP-1 (-1607 1G/2G, -755G/T, and -519A/G) were evaluated. RAGE -374T/A, S100A8 rs3795391A/G, MMP-1 -1607 1G/2G, -755G/T, and -519A/G showed no significant difference between OA patients and healthy controls. RAGE -429T/C and 557G/A showed a significant association between OA patients and healthy controls (P = 0.016 and 0.047, respectively). In haplotype analyses, no RAGE and MMP-1 haplotypes showed associations with OA. Our results suggest that the investigated polymorphism in the RAGE gene play a role in OA in the Han Chinese population.

Objective To investigate the importance of the WOMAC index score, health-related quality of life and physical performance in each domain affected by knee osteoarthritis (OA) and to identify gender differences in the importance of these domains and physical performances. Material and methods We performed a population-based study for radiographic knee OA among participants aged more than 65 years. Demographic data were collected and anthropometric measurement, radiographic assessment, the WOMAC index score, the short-form 12 (SF-12), the Timed and Up to Go Test (TUGT) and the Five Times Sit to Stand Test (FTSST) were performed. Result There were 901 individuals (409 males and 492 females) aged 74.04±6.92 (male: 76.35±7.33; female: 72.12±5.92) years included in this study. The WOMAC scores of participants with OA were higher than those without OA in males and females (male: 11.97±15.79 vs 8.23±12.84, p

Working memory (WM) is impaired in prediabetes. We hypothesized that culinary herbs and spices may decrease insulin resistance (IR) and improve WM in prediabetes. Healthy people aged ≥60 years with prediabetes (fasting blood glucose 100-125 mg/dL) (47 men and 46 women) whose food and culinary herb intakes were established with a food frequency questionnaire had body composition assessed and fasting glucose and insulin measured. Working memory and Mini-Mental State Examination (MMSE) were assessed on the same occasion. The contributions to associations between WM and diet, body fat, and IR were estimated by linear regression. Compared with nonusers, cinnamon users had significantly less frequent physical activity (2.9 vs. 4.4 times per week) and more often used fresh ginger (93.3% vs. 64.1%) and ginger in cooking (60.0% vs. 32.1%). Cinnamon users also had a better WM (2.9 vs. 2.5, P < .001). Cinnamon had a significant effect (users were 0.446 higher), but not ginger or curry usage, in predicting WM. For sociodemographic variables, only education (years) was significant in predicting WM (β = 0.065). Other significant determinants of WM were total fat mass (kilograms) (β = -0.024) and MMSE (β = 0.075). After adjustment for age and sex, cinnamon use, education, and MMSE remained significant individual predictors. In the final model, in which all variables listed were adjusted simultaneously, cinnamon users still had a significantly higher WM than nonusers. Cinnamon usage is associated with a better WM, not accounted for by dietary quality or IR, in untreated prediabetes.

Evidence indicates that reduced cardiac vagal (parasympathetic) tone, a robust cardiovascular risk factor, is a trait vulnerability marker of major depressive disorder (MDD). The Ser205/Ser205 genotype of the functional polymorphism (Ser205Leu) of the nerve growth factor receptor (NGFR), also called p75 neurotrophin receptor (p75NTR), gene is reported to increase the risk of MDD. Here, we hypothesized that the NGFR Ser205Leu polymorphism may have an effect on vagal control. A sample of 810 healthy, drug-free, unrelated Han Chinese (413 males, 397 females; mean age 35.17 ± 8.53 years) was included in the NGFR genotyping. Short-term heart rate variability (HRV) was used to assess vagus-mediated autonomic function. Potential HRV covariates, such as mood/anxiety status and serum metabolic parameters, were assessed. Homozygotes of the Ser205 allele had significantly lower high frequency power and root mean square of successive heartbeat interval differences, both HRV indices of vagal modulation, compared to Leu205 allele carriers. Even after adjusting for relevant confounders, these associations remained significant. Further stratification by sex revealed that the associations were observed only in males. Our results implicate that decreased parasympathetic activity is associated with the NGFR Ser205/Ser205 genotype in a gender-specific manner, suggesting a potential role of NGFR polymorphism in modulating cardiac autonomic function.

Background Hearing loss was a common, chronically disabling condition in the general population and had been associated with several inflammatory diseases. Metabolic syndrome, which was associated with insulin resistance and visceral obesity, was considered a chronic inflammatory disease. To date, few attempts had been made to establish a direct relationship between hearing loss and metabolic syndrome. The aim of the present study was to investigate the relationship between metabolic syndrome and hearing loss by analyzing the data in the reports of the National Health and Nutrition Examination Survey 1999–2004. Methods This study included 2100 participants aged ≤ 65 years who enrolled in the National Health and Nutrition Examination Survey (1999–2004). We examined the relationship between the presence of different features of metabolic syndrome in the participants and their pure-tone air-conduction hearing thresholds, including low-frequency and high-frequency thresholds. Results After adjusting for potential confounders, such as age, medical conditions, and smoking status, the participants with more components of metabolic syndrome were found to have higher hearing thresholds than those with fewer components of metabolic syndrome (p < 0.05 for a trend). The low-frequency hearing threshold was associated with individual components of metabolic syndrome, such as abdominal obesity, high blood pressure, elevated triglycerides, and a low level of high-density lipoprotein cholesterol (HDL-C) (p < 0.05 for all parameters). Conclusions The results indicated that the presence of a greater number of components of metabolic syndrome was significantly associated with the hearing threshold in the US adult population. Among the components of metabolic syndrome, the most apparent association was observed between low HDL and hearing loss.

Cognitive impairment develops with pre-diabetes and dementia is a complication of diabetes. Natural products like turmeric and cinnamon may ameliorate the underlying pathogenesis.People ≥ 60 years (n=48) with newly-recognised untreated pre-diabetes were randomised to a double-blind metabolic study of placebo, turmeric (1 g), cinnamon (2 g) or both (1 g2 g respectively), ingested at a white bread (119 g) breakfast. Observations were made over 6 hours for pre- and post-working memory (WM), glycaemic and insulin responses and biomarkers of Alzheimer's disease (AD)(0, 2, 4 and 6 hours): amyloid precursor protein (APP), γ-secretase subunits presenilin-1 (PS1), presenilin-2 (PS2), and glycogen synthase kinase (GSK-3β). Differences between natural product users and non-users were determined by Students t and chi square tests; and between pre-test and post-test WM by Wilcoxon signed rank tests. Interaction between turmeric and cinnamon was tested by 2-way ANOVA. Multivariable linear regression (MLR) took account of BMI, glycaemia, insulin and AD biomarkers in the WM responses to turmeric and cinnamon.No interaction between turmeric and cinnamon was detected. WM increased from 2.6 to 2.9 out of 3.0 (p=0.05) with turmeric, but was unchanged with cinnamon. WM improvement was inversely associated with insulin resistance (r=-0.418, p0.01), but not with AD biomarkers. With MLR, the WM responses to turmeric were best predicted with an R2 of 34.5%; and with significant turmeric, BMI and insulin/glucose AUC beta-coefficients.Co-ingestion of turmeric with white bread increases working memory independent of body fatness, glycaemia, insulin, or AD biomarkers.背景：認知功能失調伴隨糖尿病前期與失智症是糖尿病的併發症之ㄧ。天然食品如薑黃及 肉桂可改善此致病機轉。本研究為評估薑黃肉桂如何影響糖尿病前期患者認知功能之代謝 研究。方法：對象為三軍總醫院參加老人健檢者，納入條件為其空腹血糖介於100-126 mg/dL，共計48 位參與者。經由雙盲性別分層隨機分派至服用口服降血糖藥物或其組合、 薑黃、肉桂或其組合及控制組共4 組，每組12 名，男女各半。參與者須於報到後抽取空 腹血液、實施工作記憶前測及測量基本體位資料。再於8 時服用早餐及受試藥物，各組分 別為安慰劑、薑黃1 克、肉桂2 克、肉桂2 克與薑黃1 克等。隨後每隔2 小時採集血液， 共4 次，於最後1 次抽血完畢後，再測工作記憶分數。利用RT-PCR 技術測得APP、 PS1、PS2、GSK-3βmRNA 表現量。利用t 檢定及卡方檢定比較天然食品使用者及非使用 者平均值之差異；魏克森符號等級檢定工作記憶前測及後測的分數。利用雙因子變異數分 析檢定薑黃與肉桂兩植物成分之交互作用。複迴歸模式分析校正身體質量指數、血糖、胰 島素濃度、阿茲海默症相關之生物標記後，薑黃肉桂對工作記憶之影響。結果：薑黃與肉 桂兩植物成分並無交互作用產生。有服用薑黃者工作記憶平均分數由2.6 增加至2.9 分， 為邊緣性顯著（p=0.05），服用肉桂者工作記憶前後測平均分數沒有顯著差異。工作記憶 分數之改善與胰島素阻抗呈負相關 （r=-0.418, p0.01），但與阿茲海默症之相關生物標記 無顯著相關。複迴歸分析結果顯示服用薑黃、BMI 及胰島素阻抗為工作記憶分數最佳預測 因子。結論：本研究觀察到的薑黃改善認知效果，可能並非透過假設之降血糖途徑或降低 生物標記基因表現量而來，推測薑黃有其他保護神經元機制。

The Val/Val genotype of the brain-derived neurotrophic factor (BDNF) polymorphism (Val66Met) has been reported to affect human anxiety-related phenotypes. Substantial research has demonstrated that anxiety is associated with sympathetic activation, while sex steroid hormones have been shown to exert differential actions in regulating BDNF expression. Thus, we examined whether the BDNF variant modulates autonomic function in a gender-dependent manner. From 708 adults initially screened for medical and psychiatric illnesses, a final cohort of 583 drug-free healthy Han Chinese (355 males, 228 females; age 34.43±8.42 years) was recruited for BDNF genotyping (Val/Val: 136, 23.3%, Val/Met: 294, 50.4%, and Met/Met: 153, 26.2%). Time- and frequency-domain analyses of heart rate variability (HRV) were used to assess autonomic outflow to the heart. Significant genotype-by-gender interaction effects were found on HRV indices. Even after adjusting for possible confounders, male participants bearing the Val/Val genotype had significant increases in low frequency (LF), LF% and LF/high frequency (HF) ratio, indicating altered sympathovagal balance with increased sympathetic modulation, compared to male Met/Met homozygotes. Females, however, showed an opposite but non-significant pattern. These results suggest that the studied BDNF polymorphism is associated with sympathetic control in a gender-specific way. The findings here support the view that male subjects with the Val/Val genotype have increased risk of anxiety by association with sympathetic activation.

Recent studies have suggested that polymorphisms in toll-like receptor 9 (TLR-9), an endosomal TLR, are associated with knee osteoarthritis (OA). TLR-3, -7, and -8 are also found on the surface of endosomes and to investigate whether similar associations exist with polymorphisms in these TLR genes we performed a two-stage case-control study and genotyped 11 TLR single nucleotide polymorphisms (SNPs) in 823 OA cases and 594 healthy controls by polymerase chain reaction restriction fragment length polymorphism assays. Real-time PCR was performed to assess the functional expression of an identified promoter polymorphism in TLR-3 following dexamethasone stimulation of articular chondrocytes. An association between TLR-3 SNPs at rs3775296 and rs3775290 and OA was identified in both populations. In males the allelic frequencies of TLR-7 rs179010 and TLR-8 rs5744080 were significantly different between OA cases and healthy controls. The ATCA, CTCA, and CCTA haplotypes of TLR-3 were associated with OA susceptibility. A significant difference in TLR-3 gene expression following dexamethasone treatment was seen among the various genotypes of rs3775296 (p = 0.004). Our findings indicate that a SNP in the promoter region of TLR-3 is associated with elevated TLR-3 gene expression and susceptibility to knee OA in a Chinese Han population.

The aim of the present study was to describe the seasonal influenza vaccination rate and to examine its determinants for children and adolescents with intellectual disabilities (ID) living in the community. A cross-sectional survey was conducted to analyze the data on seasonal influenza vaccination rate among 1055 ID individuals between the ages of 12-18 years. The results found that 22.9% of the study participants used the vaccine during the past three years, and the vaccination rate among different age groups varied from 18.1 to 26.5%. There was no gender difference of seasonal influenza vaccination rate among age groups. Multilevel logistic regression analysis revealed that ID individuals with moderate (OR = 1.59, 95% CI = 1.08-2.34) or severe (OR = 2.31, 95% CI = 1.20-4.45) disability, with an illness (OR = 1.64, 95% CI = 1.02-2.63), who have general health exams (ever used, OR = 1.57, 95% CI = 1.03-2.40; regularly used, OR = 1.89, 95% CI = 1.05-3.41) were more likely to have seasonal influenza vaccination than their counterparts. The present study highlights that the substantial disparity in receipt of seasonal influenza vaccine in children and adolescents with ID reflects the effects of disability level, disease condition, and general health exam experience and suggests the need for greater attention to factors affecting ID individuals to improve their preventive health care.

Objective: To investigate the potential mechanisms underlying the in vivo effect of recombinant bactericidal/permeability-increasing protein (rBPI 21 ) on endogenous bacteria or endotoxin translocation and lipopolysaccharide-binding protein/CD14 expression secondary to thermal injury. Design: Prospective, randomized, controlled animal study. Setting: College hospital animal research laboratory. Subjects: Thirty-six male Wistar rats weighing 250-300 g. Interventions: The rats were anesthetized, and a 35% total body surface area full-thickness bum was created. Animals were randomized to receive treatment with either rBPI 21 or the control protein (albumin), rBPI 21 (2 mg/kg body wt, BPI group) or a protein control preparation (burn group) in the same dose was administered in an intravenous bolus at 30 mins and 4 hrs after thermal injury. All animals were killed at 12 and 24 hrs postburn (six to ten rats for each interval). In addition, eight rats were taken as normal controls. Measurement and Main Results: Our data showed that treatment with rBPI 21 was effective in preventing endotoxin translocation secondary to severe bums. Meanwhile, tissue lipopolysaccharide-binding protein, CD14, and tumor necrosis factor-a mRNA expression in various organs were inhibited markedly by rBPI 21 secondary to acute insults (p

Background The purpose of this study was to identify the incidence of frailty and to investigate the relationship between frailty status and health-related quality of life (HRQoL) in the community-dwelling elderly population who utilize preventive health services. Methods People aged 65 years and older who visited a medical center in Taipei City from March to August in 2011 for an annual routine check-up provided by the National Health Insurance were eligible. A total of 374 eligible elderly adults without cognitive impairment had a mean age of 74.6±6.3 years. Frailty status was determined according to the Fried frailty criteria. HRQoL was measured with Short Form-36 (SF-36). Multiple regression analyses examined the relationship between frailty status and the two summary scales of SF-36. Models were adjusted for the participants' sociodemographic and health status. Results After adjusting for sociodemographic and health-related covariables, frailty was found to be more significantly associated (p