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Background: Exposure to lead and cadmium has been linked to changes in lipid metabolism and the development of arteriosclerosis, but the role of lipoprotein profiles in this relationship is not well understood, including the potential role of novel lipid biomarkers. Methods: In this study, we enrolled 736 young Taiwanese subjects aged 12 to 30 years to assess the correlation between urine levels of lead and cadmium, lipoprotein profiles, and carotid intima-media thickness (CIMT). Results: Higher levels of lead and cadmium were significantly associated with higher levels of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), and CIMT. Participants with higher levels of lead and cadmium had the highest mean values of CIMT, LDL-C, sdLDL-C, and LDL-TG. In a structural equation model, lead had a direct and indirect association with CIMT through LDL-C and sdLDL-C, whereas cadmium had a direct association with CIMT and an indirect association through LDL-C. Conclusion: Our results suggest higher levels of lead and cadmium are associated with abnormal lipid profiles and increased CIMT. These heavy metals could have additive effects on lipids and CIMT, and the relationship between them may be mediated by lipoprotein levels. Further research is needed to determine the causal relationship.

Biliary atresia is the most common cause of childhood liver disease and is the main cause of liver replacement. The use of an effective early screening technique can efficiently improve the therapeutic effect on children with biliary atresia, especially those in the remote rural areas. This study introduces a novel method for detecting direct bilirubin by Raman spectroscopy using composite surface-enhanced Raman spectroscopy (SERS) chips. These chips were created by spreading silver nanowires on the nanostructure surface of an anodic aluminum oxide substrate. Experimental results demonstrated that the detection limit of direct bilirubin concentration vastly improved far below the disease criteria of bilirubin in adults and infants. Meanwhile, using only $10~\mu \text{L}$ of direct bilirubin, a wide detection range from 10−7 to 10−4 M was obtained, covering the clinic reference range with R2 of 0.98336 at the peak value of 1.616 cm−1. Furthermore, the results revealed that the proposed composite SERS substrates possessed good statistical relative standard deviation and reproducibility (N = 3) of 4.6% and 2.2%, respectively. Thus, the composite SERS chip combined with the Raman spectroscopy approach can be integrated with portable Raman spectrometer for the effective clinical detection of direct bilirubin.

Aims: Recent studies suggest elevated levels of small dense low-density lipoprotein cholesterol (sdLDL-C) can predict the risk of incident coronary heart disease (CHD), even in individuals considered to be at low risk for cardiovascular disease(CVD) based on their LDL-C levels. This study aims to prospectively investigate the association between sdLDL-C concentration and traditional and nontraditional CHD risk markers to explore the underlying roles of sdLDL-C in atherogenic processes. Methods: Between 2009 and 2011, 594 healthy volunteers aged 35–65 years were recruited as control subjects in a study of work-related risk factors and acute CHD. All participants fasted for 12–14 h, and venous blood samples were collected in the morning to measure serum lipid profiles and other CHD-related markers. A standard oral glucose tolerance test was performed on all participants to assess their subclinical diabetes and prediabetes status. Results: There were significantly positive associations between sdLDL-C concentration and traditional (age, smoking and alcohol drinking habit, blood pressure, body mass index (BMI), serum lipid profiles, and diabetes status) and nontraditional risk factors (complete blood counts, (CBC), fibrinogen, high-sensitivity C-reactive protein, and subclinical diabetes status) for CVD. After adjusting for confounding variables which include age, gender, BMI, hypertension, household income, and smoking and alcohol drinking habits, all atherosclerotic risk markers except D-dimer were significantly and positively associated with sdLDL-C. Conclusions: Our data indicated sdLDL-C is strongly associated with atherosclerotic risk markers, such as inflammation, thrombosis, hematological markers, and prediabetes. This study supports the hypothesis that sdLDL-C is a promising CVD risk biomarker.

In this study, a metal enhanced fluorescence (MEF) approach using the homemade Ag nanowires for enzyme free and electrodeless detection of direct bilirubin (d-BLR) was successfully developed. The average diameter and length of the fabricated Ag nanowires were measured to be around 80 nm and 25 μm, respectively. Solvent effect experiments found that EtOH is more suitable as the solvent for d-BLR. The experimental results found that the linear detection range is from 1 to 10 μM, which can be used for detecting abnormal d-BLR concentration from 5 to 10 μM. The MEF approach not only enhanced the bilirubin fluorescence, but also improved the linearity of the standard curve. Furthermore, we also found that the fluorescence intensity of the chip-based MEF is much higher than that of the solution-based MEF. It is believed that the proposed enzyme free and electrodeless d-BLR detection platform is highly feasible for clinical applications.

This study evaluated whether exposure to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) is associated with cardiovascular effects by examining a panel of 89 healthy subjects in Taipei, Taiwan. The subjects received two health examinations approximately 8months apart in 2013. Brachial-ankle pulse wave velocity (baPWV), a physiological indicator of arterial stiffness, and high-sensitivity C-reactive protein (hsCRP), a biomarker of vascular inflammations, were measured during each examination. Two exposure assessment methods were used for estimating the subjects' exposure to PM2.5 and NO2. The first method involved constructing daily land use regression (LUR) models according to measurements collected at ambient air quality monitoring stations. The second method required combining the LUR estimates with indoor monitoring data at the workplace of the subjects. Linear mixed models were used to examine the association between the exposure estimates and health outcomes. The results showed that a 10-μg/m(3) increase in PM2.5 concentration at a 1-day lag was associated with 2.1% (95% confidence interval: 0.7%-3.6%) and 2.4% (0.8%-4.0%) increases in baPWV based on the two exposure assessment methods, whereas no significant association was observed for NO2. The significant effects of PM2.5 remained in the two-pollutant models. By contrast, NO2, but not PM2.5, was significantly associated with increased hsCRP levels (16.0%-37.3% in single-pollutant models and 26.4%-44.6% in two-pollutant models, per 10-ppb increase in NO2). In conclusion, arterial stiffness might be more sensitive to short-term PM2.5 exposure than is inflammation.

The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has recommended that trialists evaluating treatments for chronic pain should consider reporting 9 patient-important outcome domains. We examined the extent to which clinical trials evaluating the effect of opioids for chronic non-cancer pain (CNCP) report outcome domains recommended by IMMPACT. We systematically searched electronic databases for English-language studies that randomized patients with CNCP to receive an opioid or a non-opioid control. In duplicate and independently, reviewers established the eligibility of each identified study and recorded all reported outcome domains from eligible trials. We conducted a priori regression analyses to explore factors that may be associated with IMMPACT-recommended outcome domains. Among 156 eligible trials, reporting of IMMPACT-recommended outcome domains was highly variable, ranging from 99% for pain to 7% for interpersonal functioning. Recently published trials were more likely to report the effect of treatment on physical functioning, emotional functioning, role functioning, sleep and fatigue, and participant disposition. Trials for which the corresponding author was from North America were more likely to report treatment effects on physical functioning and participant ratings of improvement and satisfaction with treatment. Trials published in higher impact journals were more likely to report treatment effects on emotional function, but less likely to report participant ratings of improvement and satisfaction with treatment. Most IMMPACT domains showed an increased rate of reporting over time, although many patient-important outcome domains remained unreported by over half of all trials evaluating the effects of opioids for CNCP.

Background Few studies have explored the association between perfluoroalkyl substances (PFAS) and reproductive hormones in adolescents and young adults. Objectives This study aimed to investigate the association of PFAS with reproductive hormones in adolescents and young adults. Methods We recruited 540 subjects aged 12–30 years from a 1992 to 2000 mass urine screening population and established a cohort from 2006 to 2008 via invitations by mail or/and telephone. Serum PFAS levels were analyzed with a Waters ACQUITY UPLC system coupled with a Waters Quattro Premier XE triple quadrupole mass spectrometer. Serum reproductive hormone levels were measured by immunoluminometric assay with an Architect random access assay system. PFAS levels were divided into different percentiles according to their detection limits in the multiple regression models to analyze associations between reproductive hormone levels and exposure with PFAS. Results The adjusted mean serum level of sex hormone-binding globulin (SHBG) decreased significantly in association with the 90th percentile categories of perfluorooctanoic acid (PFOA) compared with a reference category for the females in the 12–17-year-old group. The follicle-stimulating hormone (FSH) levels were significantly decreased in association with the different percentile categories of perfluorooctane sulfonate (PFOS) in the male 12–17-year-old group and the different percentile categories of perfluoroundecanoic acid (PFUA) in the female 12–17-year-old group. The serum FSH levels in the females aged 12–17 were also decreased in association with the different percentile categories of PFUA. On the other hand, there was a significantly negative association between the different percentile categories of PFOS and the serum testosterone level among the female 12–17-year-old group. Conclusions We found that the serum concentrations of PFOA, PFOS, and PFUA were negatively associated with the serum levels of SHBG, FSH, and testosterone in the young Taiwanese population and that these effects were the strongest in the females aged 12–17. Further studies are needed to determine whether these associations are causal.

OBJECTIVE The Friedewald equation has been used as the standard formula for the estimation of very low-density lipoprotein cholesterol (VLDL-C) to calculate the serum levels of low-density lipoprotein cholesterol (LDL-C). However, the usefulness of this formula in non-Caucasians has been challenged in recent years. The aim of this study was to assess the validity of the conventional and modified Friedewald equation in an ethnic Chinese adult population. METHODS We prospectively recruited 938 subjects from the Lipid Clinic of the National Taiwan University Hospital. The fasting lipids, including cholesterol, high-density lipoprotein cholesterol, LDL-C, VLDL-C, and triglycerides (TGs), of each participant were measured and we constructed a prediction model for the estimation of LDL-C by the modified Friedewald equation. RESULTS The constant values, used to estimate the VLDL-C concentration, were different in the Friedewald equation in the subgroups exhibiting different cardiovascular characteristics, ranging from 4.45 to 6.63, if we calculated the equation by a direct LDL-C measurement. According to the results of a stepwise multiple linear regression analysis excluding the TG levels ≥400 mg/dL, an equation for the individual constant Y estimation was as follows: Constant Y = 4.39 + (-0.59) if the age ≥50 years + 0.98 if men + TG group (2.06 if the TG levels were between 150-399 mg/dL; 1.07 if the TG levels were between 100-149 mg/dL) + (-0.49) if the cholesterol levels ≥240 mg/dL + the body mass index (BMI) group (0.8 if BMI ≥27 kg/m(2); 0.48 if BMI =24-27 kg/m(2)). CONCLUSION This modified Friedewald formula provides a new and simple equation for calculating the LDL-C levels in ethnic Chinese people.

Perfluorinated chemicals (PFCs) have been widely used for years in a variety of products worldwide. Although epidemiological findings have shown that PFC levels are positively associated with cholesterol and uric acid levels, it is unknown whether PFCs are associated with atherosclerosis.We recruited 664 subjects (12-30 years) from a population-based sample of adolescents and young adults based on a mass urine screening to determine the relationship between serum levels of PFCs and carotid intima-media thickness (CIMT).The median concentrations and ranges of perfluorooctanoic acid (PFOA), perfluorooctane sulfate (PFOS), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFUA) were 3.49 (0.75-52.2) ng/mL, 8.65 (0.11-85.90) ng/mL, 0.38 (0.38-25.4) ng/mL, and 6.59 (1.50-105.7) ng/mL, respectively. After controlling for age, gender, smoking status, systolic blood pressure, body mass index, low-density lipoprotein cholesterol, triglyceride, high-sensitivity C-reactive protein, and homeostasis model assessment of insulin resistance, multiple linear regression analysis revealed that CIMT increased significantly across quartiles of PFOS (0.434 mm, 0.446 mm, 0.458 mm, 0.451 mm; P for trend0.001). Subpopulation analysis showed the association between PFOS and CIMT was more evident and significant in females, non-smokers, subjects of age 12-19 years, BMI24, and those with APOE genotype of E2 carrier and E3/E3.Higher serum concentrations of PFOS were associated with an increase of carotid IMT in this cohort of adolescents and young adults. Further studies are warranted to clarify the causal relationship between PFOS and atherosclerosis.

STUDY DESIGN Questionnaire survey. OBJECTIVE To explore spine surgeons' attitudes toward the involvement of nonphysician clinicians (NPCs) to screen patients with low back or low back-related leg pain referred for surgical assessment. SUMMARY OF BACKGROUND DATA Although the utilization of physician assistants is common in several healthcare systems, the attitude of spine surgeons toward the independent assessment of patients by NPCs remains uncertain. METHODS We administered a 28-item survey to all 101 surgeon members of the Canadian Spine Society, which inquired about demographic variables, patient screening efficiency, typical wait times for both assessment and surgery, important components of low back-related complaints history and examination, indicators for assessment by a surgeon, and attitudes toward the use of NPCs to screen patients with low back and leg pain referred for elective surgical assessment. RESULTS Eighty-five spine surgeons completed our survey, for a response rate of 84.1%. Most respondents (77.6%) were interested in working with an NPC to screen patients with low back-related complaints referred for elective surgical assessment. Perception of suboptimal wait time for consultation and poor screening efficiency for surgical candidates were associated with greater surgeon interest in an NPC model of care. We achieved majority consensus regarding the core components for a low back-related complaints history and examination, and findings that would support surgical assessment. A majority of respondents (75.3%) agreed that they would be comfortable not assessing patients with low back-related complaints referred to their practice if indications for surgery were ruled out by an NPC. CONCLUSION The majority of Canadian spine surgeons were open to an NPC model of care to assess and triage nonurgent or emergent low back-related complaints. Clinical trials to establish the effectiveness and acceptance of an NPC model of care by all stakeholders are urgently needed.

Perfluorinated chemicals (PFCs) have been widely used in a variety of products worldwide for years. However, the effect of PFCs on thyroid function has not yet been clearly defined. We recruited 567 subjects (aged 12-30 years) in a population-based cohort of adolescents and young adults with abnormal urinalysis in the childhood to determine the relationship between serum level of PFCs and the levels of serum free thyroxine (T4) and thyroid stimulating hormone (TSH). The geometric means and geometric standard deviation concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUA) were 2.67 (2.96) ng/ml, 7.78 (2.42) ng/ml, 1.01 (3.48) ng/ml and 5.81 (2.92) ng/ml, respectively. Differences in the levels of free T4 and TSH across different categories of PFOA, PFOS and PFUA were insignificant. After controlling for confounding factors, multiple linear regression analyses revealed mean serum level of free T4 increased significantly across categories (60th, 60-89 and90th percentiles) of PFNA (P for trend =0.012 in the full model). The association between PFNA and free T4 was more significant in male subjects in age group 20-30, active smokers and in those with higher body mass index in stratified analysis. Serum concentrations of PFNA were associated with serum free T4 levels in adolescents and young adults.

OBJECTIVES This study aims to investigate whether psychosocial work-related hazards, measured by workplace justice and employment insecurity, are associated with depression and suboptimal health status in Taiwan's executive-level employees. METHODS There were 365 executives who have received a series of cardiovascular health examinations, blood sampling, and self-reported questionnaires, which included the psychosocial work-related hazards and the CES-D scale. Suboptimal health status was defined as the presence of dyslipidemia or prediabetes. RESULTS Executive-level employees perceived lower workplace justice and higher employment insecurity and had a significantly higher risk of depression (CES-D scores ≥16 or ≥23). However, workplace justice was identified as a significant determinant factor that was negative for dyslipidemia but protective for prediabetes. CONCLUSION This study supports the fact that psychosocial work-related hazards can independently contribute to the risk of developing depression, prediabetes, and dyslipemia in executives.

Objective To elucidate the association between human interleukin-10 (IL-10) genotypes and hepatitis B virus (HBV) precore/core gene mutation in children with chronic HBV infection. Study design The study group comprised of 21 children with chronic HBV infection with spontaneous hepatitis B e antigen (HBeAg) seroconversion who were followed for more than 10 years. Another nine children without HBeAg seroconversion served as the control subjects. Sera at the immune tolerance and inflammatory phase (alanine aminotransferase, >80 IU/L) were subjected to HBV precore/core sequence analysis. IL-10 -1082 polymorphism was also determined. Results HBV precore/core gene mutation increased significantly more in the inflammatory phase than in the tolerance phase (G1896A, 76.2% versus 4.8%; C1913A, 33.3% versus 0%; C2189A, 28.6% versus 4.8%; G2304A, 52.4% versus 14.3%) in study group (n = 21) but not the control group (n = 9). Subjects with the G/G genotype at the IL-10-1082 polymorphism site had higher C2189A mutation rate than the A allele carriers (P = .02). C2189A mutation carriers are associated with more viral load decrement from tolerance to inflammatory phase (P = .01) and earlier spontaneous HBeAg seroconversion (P = .01). Conclusions The G/G genotype at the IL-10 -1082 polymorphism is associated with higher C2189A mutations, lower HBV viral load at immune inflammatory phase, and earlier spontaneous HBeAg seroconversion than A allele carriers.

Importance Harms and benefits of opioids for chronic noncancer pain remain unclear. Objective To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain. Data Sources and Study Selection The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. Data Extraction and Synthesis Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence. Main Outcomes and Measures The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting. Results Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], −0.69 cm [95% CI, −0.82 to −0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, −0.60 cm [95% CI, −1.54 to 0.34 cm]; physical functioning: WMD, −0.90 points [95% CI, −2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, −0.13 cm [95% CI, −0.99 to 0.74 cm]; physical functioning: WMD, −5.31 points [95% CI, −13.77 to 3.14 points]), and anticonvulsants (pain: WMD, −0.90 cm [95% CI, −1.65 to −0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, −5.77 to 6.66 points]). Conclusions and Relevance In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

Background: This study aimed to investigate the roles of tumour necrosis factor-α (TNF-α) gene polymorphisms in the spontaneous clearance of HBsAg after a hepatitis B virus (HBV) infection. Methods: Polymorphisms in the TNF-α (−1031 T to C, −863 C to A, −857 C to T, −308 G to A and −238 G to A transition) gene were evaluated in 274 chronic HBV-infected patients and 194 patients with resolved HBV infection. The peripheral blood mononuclear cells (PBMC) isolated from 77 (28%) of the 274 chronic HBV-infected patients with negative HBeAg and positive antibody to HBeAg were stimulated with HBcAg. Data on TNF-α genotypes and phenotypes in subjects with/without the A allele at the TNF-α−863 promoter single nucleotide polymorphism (rs1800630) were compared. Results: The A allele in the −863 promoter region of the TNF-α gene was present in 154 (56.2%) chronic HBV-infected patients and 87 (44.8%) patients who recovered from HBV infection (odds ratio 1.58; P

AIM The aim of this study, the YOung TAiwanese Cohort (YOTA) Study, was to investigate the relationship between a childhood overweight/obese status and young adult preclinical atherosclerosis, including assessments of the carotid intima-media thickness (CIMT) and prehypertension or hypertension. METHODS From among children who participated in the 1992-2000 mass urine screening program in Taiwan, we recruited 303 subjects with an elevated blood pressure (EBP) and 486 subjects with a normal BP in childhood during the period of 2006-2008. These 789 young adults received health check-ups for cardiovascular health, including examinations of blood and urine parameters, anthropometrics, BP and the CIMT, a subclinical cardiovascular risk index. Data analyses were used to evaluate the associated risks in both childhood and young adulthood. RESULTS The school students with a childhood overweight/obese status had a higher risk of prehypertension or hypertension, with a relative risk of 3.20 (1.40-7.33) for being overweight and 6.51 (3.36-12.63) for being obese in young adulthood at an average age of 21. A childhood overweight/obese status also predicted a higher risk of having a thicker CIMT, with a relative risk of 2.82 (1.26-6.28) and 4.17 (2.21-7.85) for being overweight and obese in adulthood, respectively, after a mean follow-up of 8.5 years. The body mass index exhibited a consistent trend from childhood to adulthood, with an adjusted R square of 0.551. The participants who were not overweight/obese in childhood also demonstrated a higher risk of prehypertension or hypertension if they became overweight or obese in adulthood. CONCLUSIONS This study highlights the importance of preventing and treating an overweight or obese status in childhood for the primary prevention of cardiovascular disease in adulthood.

To evaluate the effects of alendronate on postmenopausal Chinese women with osteopenia, we treated 46 subjects daily with either 10 mg alendronate (N = 24) or placebo plus 500 mg calcium supplement (N = 22), and measured their bone mineral density (BMD) at the lumbar spine and hip, and urinary bone resorption markers before, during, and after the 1 year treatment period. The bone markers included N-telopeptide of type I collagen (NTx) and deoxypyridinoline (Dpd); both were corrected by the concentration of creatinine in the same sample (NTx/Cr and Dpd/Cr). Both NTx/Cr and Dpd/Cr decreased significantly by 44% and 28%, respectively (p < 0.05 for both), in 1 month in the active treatment group but did not change in the placebo group. BMD at the spine, femoral neck, trochanter, and Ward's triangle increased significantly by 6 months and showed a further increase through month 12 at the spine in the alendronate-treated group. Relative to the placebo group, BMD changes at various sites in the alendronate-treated group were higher at 12 months by 6%-11%. Thus, our data suggest that 10 mg alendronate daily resulted in significant increases in spine and hip BMD, and decreases of urinary resorption markers in the osteopenic postmenopausal Chinese women studied. The amplitude of responses was higher than in previous reports in the USA and Europe.

This study was performed to survey the vitamin D nutritional status of urban Chinese women, and to define its role in determining bone metabolic rate and bone mineral density (BMD). We measured serum 25-hydroxyvitamin D (25-OHD), the major storage form of vitamin D, and BMD, at the spine, hip, and total body skeleton, of 262 healthy Chinese women aged from 40 to 72 years, residing in Taipei city. Bone turnover markers, including serum osteocalcin, bone alkaline phosphatase isozyme, and C-terminal propeptide of type I procollagen, and a urinary bone resorption marker, N-terminal crosslinked fragment of type I collagen, were also measured. We found generally adequate vitamin D nutritional stores. The mean concentration of serum 25-OHD was 30.7 (SD = 8.2) ng/mL for all 262 subjects and there were no significant age-related changes. Those who had serum sampled during the summer showed higher serum 25-OHD levels (N = 138; mean +/- SD: 32.7 +/- 7.6 ng/mL) than those who had serum sampled during winter (N = 124; mean +/- SD: 28.5 +/- 8.3 ng/mL; Student's t-test, p < 0.001), but these two groups showed similar BMD and bone marker values. Those with serum 25-OHD concentration in the lowest or highest tertile did not show different BMD or bone marker values than those in the other tertiles. Multiple regression demonstrated no correlation between 25-OHD and any bone marker or BMD at any site. Thus, in this free-living urban Chinese population, in a subtropical region, we could not demonstrate a role of vitamin D stores in determining bone turnover rate or BMD in women aged 40-70 years.

Background Assessment of health effects of a forest environment is an important emerging area of public health and environmental sciences. Purpose To demonstrate the long-term health effects of living in a forest environment on subclinical cardiovascular diseases (CVDs) and health-related quality of life (HRQOL) compared with that in an urban environment. Materials and Methods This study included the detailed health examination and questionnaire assessment of 107 forest staff members (FSM) and 114 urban staff members (USM) to investigate the long-term health effects of a forest environment. Air quality monitoring between the forest and urban environments was compared. In addition, work-related factors and HRQOL were evaluated. Results Levels of total cholesterol, low-density lipoprotein cholesterol, and fasting glucose in the USM group were significantly higher than those in the FSM group. Furthermore, a significantly higher intima-media thickness of the internal carotid artery was found in the USM group compared with that in the FSM group. Concentrations of air pollutants, such as NO, NO2, NOx, SO2, CO, PM2.5, and PM10 in the forest environment were significantly lower compared with those in the outdoor urban environment. Working hours were longer in the FSM group; however, the work stress evaluation as assessed by the job content questionnaire revealed no significant differences between FSM and USM. HRQOL evaluated by the World Health Organization Quality of Life-BREF questionnaire showed FSM had better HRQOL scores in the physical health domain. Conclusions This study provides evidence of the potential beneficial effects of forest environments on CVDs and HRQOL.

Background To determine the effects of post-challenge hyperglycemia potentiate low-density lipoprotein cholesterol (LDL) particles on the risk of arterial stiffness in non-diabetic adults. Methods During 2009–2011, 592 adults without clinical diabetes (fasting glucose

Background Opioids are prescribed frequently and increasingly for the management of chronic non-cancer pain (CNCP). Current systematic reviews have a number of limitations, leaving uncertainty with regard to the benefits and harms associated with opioid therapy for CNCP. We propose to conduct a systematic review and meta-analysis to summarize the evidence for using opioids in the treatment of CNCP and the risk of associated adverse events. Methods and design Eligible trials will include those that randomly allocate patients with CNCP to treatment with any opioid or any non-opioid control group. We will use the guidelines published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to inform the outcomes that we collect and present. We will use the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to evaluate confidence in the evidence on an outcome-by-outcome basis. Teams of reviewers will independently and in duplicate assess trial eligibility, abstract data, and assess risk of bias among eligible trials. To ensure interpretability of our results, we will present risk differences and measures of relative effect for all outcomes reported and these will be based on anchor-based minimally important clinical differences, when available. We will conduct a priori defined subgroup analyses consistent with current best practices. Discussion Our review will evaluate both the effectiveness and the adverse events associated with opioid use for CNCP, evaluate confidence in the evidence using the GRADE approach, and prioritize patient-important outcomes with a focus on functional gains guided by IMMPACT recommendations. Our results will facilitate evidence-based management of patients with CNCP and identify key areas for future research. Trial registration Our protocol is registered on PROSPERO (CRD42012003023), http://www.crd.york.ac.uk/PROSPERO.

Objectives: To systematically summarize the randomized trial evidence regarding the relative effectiveness of cognitive behavioural therapy (CBT) in patients with depression in receipt of disability benefits in comparison to those not receiving disability benefits. Data Sources: All relevant RCTs from a database of randomized controlled and comparative studies examining the effects of psychotherapy for adult depression (http://www.evidencebasedpsychotherapies.org), electronic databases (MEDLINE, EMBASE, PSYCINFO, AMED, CINAHL and CENTRAL) to June 2011, and bibliographies of all relevant articles. Study Eligibility Criteria, Participants and Intervention: Adult patients with major depression, randomly assigned to CBT versus minimal/no treatment or care-as-usual. Study Appraisal and Synthesis Methods: Three teams of reviewers, independently and in duplicate, completed title and abstract screening, full text review and data extraction. We performed an individual patient data meta-analysis to summarize data. Results: Of 92 eligible trials, 70 provided author contact information; of these 56 (80%) were successfully contacted to establish if they captured receipt of benefits as a baseline characteristic; 8 recorded benefit status, and 3 enrolled some patients in receipt of benefits, of which 2 provided individual patient data. Including both patients receiving and not receiving disability benefits, 2 trials (227 patients) suggested a possible reduction in depression with CBT, as measured by the Beck Depression Inventory, mean difference [MD] (95% confidence interval [CI]) = -2.61 (-5.28, 0.07), p = 0.06; minimally important difference of 5. The effect appeared larger, though not significantly, in those in receipt of benefits (34 patients) versus not receiving benefits (193 patients); MD (95% CI) = -4.46 (-12.21, 3.30), p = 0.26. Conclusions: Our data does not support the hypothesis that CBT has smaller effects in depressed patients receiving disability benefits versus other patients. Given that the confidence interval is wide, a decreased effect is still possible, though if the difference exists, it is likely to be small.

In animals, perfluorinated chemicals (PFCs), specifically perfluorooctanoic acid (PFOA) and perfluorooctane sulfate (PFOS), function as peroxisome proliferator-activated receptor (PPAR) alpha agonists. However, the relevance of animal (primarily rodent) data to humans is unresolved. While plasma adiponectin level is very responsive to PPAR gamma agonist drugs, it has not been determined whether adiponectin level is related to serum PFCs concentrations. In the present study, 287 subjects (12-30 years of age) were recruited to determine the relationship between serum level of PFCs and serum level of adiponectin. The results showed males had higher serum PFOS concentrations than females and that those with metabolic syndrome had lower serum PFOA than controls. Besides, it showed regional elevations of the perfluoroundecanoic acid (PFUA) (median concentration: 7.11 ng/mL) in the study subjects. No relationship of PFOA, PFOS, PFUA, and the sum of all four PFCs was found to glucose homeostasis, adiponectin level, lipid profile, and inflammatory markers. The median and the range of perfluorononanoic acid (PFNA) concentration (in ng/mL; for four categories corresponding to the

Estrogen (1)(2)(3)(4)(5) may increase hepatic production of thyroxine-binding globulin (TBG) and decrease TBG clearance (6), thus increasing serum total thyroxine (tT4) (3)(4) and, to a lesser extent, total triiodothyronine (tT3) (3)(4). As a result, increased tT4 and tT3 are seen in states of excessive estrogen and/or progestin, such as pregnancy, estrogen replacement therapy (HRT) (5), and oral contraceptive usage (1). This phenomenon may cause problems in clinical diagnoses when tT4 or tT3 is used for these patients. On the other hand, estrogen has been shown to increase thyroid-stimulating hormone (TSH) and to decrease free thyroxine (fT4) through a mild inhibitory effect on the thyroid gland (4). Compound that are analogs of estrogens, such as tamoxifen, have been shown to increase TSH without decreasing fT4 (7)(8). Recently, a new category of therapeutic agents, collectively termed selective estrogen receptor modulators (SERMs), has been developed to treat patients with postmenopausal osteoporosis (9). Raloxifene …

This study aimed to investigate the roles of tumour necrosis factor-α (TNF-α) gene polymorphisms in the spontaneous clearance of HBsAg after a hepatitis B virus (HBV) infection.Polymorphisms in the TNF-α (-1031 T to C, -863 C to A, -857 C to T, -308 G to A and -238 G to A transition) gene were evaluated in 274 chronic HBV-infected patients and 194 patients with resolved HBV infection. The peripheral blood mononuclear cells (PBMC) isolated from 77 (28%) of the 274 chronic HBV-infected patients with negative HBeAg and positive antibody to HBeAg were stimulated with HBcAg. Data on TNF-α genotypes and phenotypes in subjects with/without the A allele at the TNF-α-863 promoter single nucleotide polymorphism (rs1800630) were compared.The A allele in the -863 promoter region of the TNF-α gene was present in 154 (56.2%) chronic HBV-infected patients and 87 (44.8%) patients who recovered from HBV infection (odds ratio 1.58; P0.01). The TNF-α-863 A allele genotype predicted lower TNF-α production by PBMC after in vitro HBcAg stimulation (P0.02).The A allele at the -863 locus of the promoter region of the TNF-α gene predicts lower HBcAg-inducible TNF-α secretion. It is also associated with chronicity of HBV infection.

Background/Purpose: Hyperuricemia is encountered frequently in patients with chronic kidney disease (CKD). We tested the hypothesis that uric acid influences glomerular filtration rate (GFR) and is associated with renal function decline in elderly Taiwanese subjects. Methods: We enrolled 800 elderly Taiwanese subjects for a health checkup. Estimated GFR (eGFR) was measured using the Modification of Diet in Renal Disease Study equation. eGFR＜60mL/min/1.73m^2 was used to analyze the prevalence and incidence of CKD. Significant renal function decline was defined as a decrease in eGFR of≥3mL/min/1.73m^2 per year. Results: The prevalence of CKD was 18.0% in the elderly subjects. Mean serum uric acid level was 6.6mg/dL in male and 5.6mg/dL in female subjects, and eGFR was 71.7mL/min/1.73m^2. Uric acid levels were associated independently and negatively with eGFR after adjusting for conventional factors of renal function decline. One hundred and sixty-two individuals (31.2%) had a significant decline in renal function. As uric acid level increased by 1mg/dL, the odds of a significant eGFR decline increased by 1.208. Conclusion: Serum uric acid level was associated with eGFR and decline in renal function in elderly Taiwanese subjects. Whether hypouricemic therapy could retard the progression of CKD deserves further in-depth study.

The bones of children grow at a faster rate during the first few years of childhood and puberty. Recently, advances in assays for biochemical markers of bone formation have provided noninvasive means to study bone growth and metabolism in children (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Because of the variations in the rate of bone growth in different age groups and possible ethnic differences, age-specific reference ranges for bone formation markers must be established in a particular pediatric population. Conventional bone formation markers such as osteocalcin (1) have been shown to correlate with serum concentrations of insulin-like growth factor-I and testosterone in children and adolescents. In pathological conditions, osteocalcin (2)(3)(4) is lower in growth hormone-deficient children and increases with replacement therapy. Osteocalcin, however, is labile and possesses problems in sample processing and storage (15). Recently, two other bone formation markers in serum, bone alkaline phosphatase isoenzyme (BAP) (16) and the carboxy-terminal propeptide of type-I procollagen (PICP) (17), were shown to be sensitive and specific markers …

Recent evidence suggests that high tissue matrix metalloproteinase-1 (MMP-1) and low adiponectin may serve as biomarkers of atherosclerosis. Results on the associations of circulating MMP-1 and adiponectin concentrations are scarce. We hypothesized that patients with multivessel coronary artery disease (CAD) have elevated high-sensitivity C-reactive protein (hs-CRP), MMP-1 but low adiponectin levels, and concomitant measurements of these biomarkers could improve predictive strength for advanced CAD.We analyzed concentrations of MMP-1, hs-CRP and adiponectin in 217 subjects with angiographically documented multivessel CAD (two-, or three-vessel disease by luminal stenosisor=50%) and 81 controls. MMP-1 and hs-CRP were notably higher in patients with CAD; while adiponectin was not significantly different between two groups. Levels of hs-CRP positively correlated with body mass index and left ventricular dysfunction (R(2)=0.16, P0.0001); while adiponectin was significantly associated with age, gender, and levels of cholesterol and triglyceride (R(2)=0.09, P0.0001). On the contrary, MMP-1 was not associated with any clinical cardiovascular risk factors, and still an independent predictor (OR=1.49, P0.0001) of multivessel CAD after the adjustment of clinical risk factors and hs-CRP.Elevated MMP-1 and hs-CRP, but not low adiponectin concentrations, could predict the presence of advanced coronary atherosclerosis. In addition, MMP-1 may serve as a more specific marker for significant CAD independent of hs-CRP.

Bone alkaline phosphatase (b-ALP; EC 3.1.3.1) is a tetrameric glycoprotein found on the cell surface of osteoblasts. Previous studies have shown that both b-ALP (1) and total ALP (2) can be considered markers of bone formation. Because postmenopausal osteoporosis in women and senile osteoporosis in both sexes are global epidemiological problems, biochemical markers of bone turnover have become important clinical tests. Such markers are used to identify subjects with rapid bone turnover (and thus bone loss) (3) and to monitor the therapeutic efficacy of various drugs (4). These two purposes mandate separate reference ranges for different sexes and age groups. To evaluate the age-related changes of these two markers in Chinese men and women, we measured both total ALP and b-ALP of healthy Chinese men (n = 156, ages 20–90 years) and women (n = 385, ages 40–70 years; 118 premenopausal and 267 postmenopausal), …

To investigate the clinical effects of raloxifene, one of the selective estrogen receptor modulators (SERMs), on the pituitary-ovary axis and prolactin, a prospective, randomized, double-blinded study on 59 healthy postmenopausal women was performed. Forty-eight women received raloxifene 60 mg daily. The other 11 received combined conjugated equine estrogen 0.625 mg and medroxyprogesterone acetate 5 mg daily (CCEP) as active controls. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and prolactin were measured at baseline and 1 yr after treatment. The mean levels of FSH and LH were significantly decreased in the raloxifene group (FSH: −10.7%; p

STUDY DESIGN A cross-sectional study on the distribution of bone mineral content in the third lumbar vertebrae. OBJECTIVES To evaluate the effects of age and gender on the distribution of bone mineral content in the third lumbar vertebrae. SUMMARY OF BACKGROUND DATA Compression fractures occur mainly at the vertebral body. Variations in the distribution of bone mass in a vertebra, if undefined, may bias the ability of the acquired bone mineral density values, which was usually measured posteroanteriorly, to predict the risk of fractures. METHODS The bone mineral content of the whole L3, including the L3 vertebral body and the posterior segment, was measured using a lateral approach with a dual energy radiograph absorptiometer on 177 healthy Taiwanese adults including 65 men and 55 premenopausal and 57 postmenopausal women. RESULTS The proportion of bone mineral content in the vertebral body was significantly lower in premenopausal women than in age-matched men (39.1 +/- 0.9% vs. 50.0 +/- 1.7%, P < 0.0001). Furthermore, whereas postmenopausal women showed a decreased proportion of bone mineral content in the vertebral body with increased age (about -0.0022 per year, P = 0.0001), premenopausal women and men showed a sustained proportion. CONCLUSIONS The proportion of bone mineral content distributed in the body of L3 vertebrae was lower in women than in men. The discrepancy of this parameter between the genders was even larger with increased ages.