Matrix metalloproteinase MMP12 is associated with intervertebral disc degeneration

INTRODUCTION: Intervertebral disc (IVD) degeneration is associated with low back pain. However, the molecular changes during the degeneration process is not entirely clear. The loss of nucleus pulposus (NP) integrity is one of the early events of the degeneration. Chondrogenic markers, such as SOX9 and aggrecan, have been commonly used to assess the degree of IVD degeneration. Recent transcriptomic studies have proposed several other candidates that may mark IVD degeneration. These include cartilage oligomeric matrix protein (COMP), matrix gla protein (MGP)[1], fibulin 1 (FBLN1) [2], cytokeratin 18 (KRT18) [3], cadherin-2 (CDH2) [3], cytokeratin 19 (KRT19) [2], and Runt-related transcription factor 2 (RUNX2) [4]. Studies also demonstrated that degenerated NP attains a fibrocartilaginous phenotype [5,6] with increased ...postprin

Validation of the English version constitution in Chinese Medicine Questionnaire (CCMQ) among young adults in Malaysia

Constitution in Chinese Medicine Questionnaire (CCMQ) is widely used as a self-administered health instrument. It was used as the guiding tool for prognosis, prevention and treatment of various diseases. This study aims to validate an English version of the Constitution in Chinese Medicine Questionnaire (CCMQ) in Malaysia, which is comprised of nine domains with a total of 67 questions. The survey was conducted in three phases. Phase one involved translation and adaption where the Chinese version of the survey instrument was translated into the English version. In phase two, a Delphi was used to review, amend and validate the translated English version; and in phase three, 114 subjects (aged 18 to 30 years old) were included in the confirmatory factor analysis to determine its psychometric properties. The construct validity analysis of CCMQ showed a good fit for the hypothesised models. Composite reliability (CR) values ranging from 0.869 to 0.908, and average variance extracted (AVE) values ranged from 0.647 to 0.764, indicating good internal consistency reliability and convergent validity, respectively. The heterotrait-monotrait ratio of correlations (HTMT) values obtained for all the domains ranging from 0.151 to 0.652, which fulfilled the criteria of discriminant validity. The English version of the CCMQ was the first statistically validated instrument in Malaysia. It is a reliable and valid instrument for traditional Chinese medicine body constitution (TCMBC) study. Future research is needed to validate the CCMQ as a predicting tool in health-related outcome studies

Comparison of Small RNA Profiles of Glycine max and Glycine soja at Early Developmental Stages

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Prevalence and Predictors of Vitamin D Insufficiency in Children: A Great Britain Population Based Study

Objectives To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children In Great Britain. Design A nationally representative cross-sectional study survey of children (1102) aged 4–18 years (999 white, 570 male) living in private households (January 1997–1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (<50 nmol/L). Results Vitamin D levels (mean = 62.1 nmol/L, 95%CI 60.4–63.7) were insufficient in 35%, and decreased with age in both sexes (p<0.001). Young People living between 53–59 degrees latitude had lower levels (compared with 50–53 degrees, p = 0.045). Dietary intake and gender had no effect on vitamin D status. A logistic regression model showed increased risk of VDI in the following: adolescents (14–18 years old), odds ratio (OR) = 3.6 (95%CI 1.8–7.2) compared with younger children (4–8 years); non white children (OR = 37 [95%CI 15–90]); blood levels taken December-May (OR = 6.5 [95%CI 4.3–10.1]); on income support (OR = 2.2 [95%CI 1.3–3.9]); not taking vitamin D supplementation (OR = 3.7 [95%CI 1.4–9.8]); being overweight (OR 1.6 [95%CI 1.0–2.5]); <1/2 hour outdoor exercise/day/week (OR = 1.5 [95%CI 1.0–2.3]); watched >2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0–2.4]). Conclusion We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE) : study protocol for a randomized controlled trial

Peer reviewedPublisher PD

Awareness of vitamin D deficiency among at-risk patients

<p>Abstract</p> <p>Background</p> <p>Vitamin D deficiency is a significant problem for a growing proportion of the UK population. Individuals with dark or covered skin are at particularly high risk due to ethno-cultural, environmental and genetic factors. We assessed the level of awareness of vitamin D deficiency among at-risk patients in order to identify groups most in need of education.</p> <p>Findings</p> <p>A cross-sectional survey using a piloted questionnaire was conducted among consecutive at-risk patients without a diagnosis of Vitamin D deficiency arriving at a large inner city general practice in the North West of England over a five day period. The survey was completed by 221 patients. The mean age was 35 years. 28% of them (n = 61) had never heard about vitamin D. Older patients (p = 0.003) were less likely to have heard about vitamin D. 54% of participants were unaware of the commonest symptoms of vitamin D deficiency. 34% did not expose their skin other than their face in the last one year, and 11% did not include vitamin D rich foods in their diet.</p> <p>Conclusion</p> <p>The majority of at-risk patients are aware of vitamin D; nevertheless, there is a significant lack of knowledge among older people, who have higher morbidity. A programme of targeted education of the at-risk population is recommended.</p

Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. DESIGN: A proof of concept double-masked randomized controlled study. PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1. MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065

Exhaled nitric oxide in a population-based study of Southern California Schoolchildren

<p>Abstract</p> <p>Background</p> <p>Determinants of exhaled nitric oxide (FeNO) need to be understood better to maximize the value of FeNO measurement in clinical practice and research. Our aim was to identify significant predictors of FeNO in an initial cross-sectional survey of southern California schoolchildren, part of a larger longitudinal study of asthma incidence.</p> <p>Methods</p> <p>During one school year, we measured FeNO at 100 ml/sec flow, using a validated offline technique, in 2568 children of age 7–10 yr. We estimated online (50 ml/sec flow) FeNO using a prediction equation from a separate smaller study with adjustment for offline measurement artifacts, and analyzed its relationship to clinical and demographic characteristics.</p> <p>Results</p> <p>FeNO was lognormally distributed with geometric means ranging from 11 ppb in children without atopy or asthma to 16 ppb in children with allergic asthma. Although effects of atopy and asthma were highly significant, ranges of FeNO for children with and without those conditions overlapped substantially. FeNO was significantly higher in subjects aged > 9, compared to younger subjects. Asian-American boys showed significantly higher FeNO than children of all other sex/ethnic groups; Hispanics and African-Americans of both sexes averaged slightly higher than non-Hispanic whites. Increasing height-for-age had no significant effect, but increasing weight-for-height was associated with decreasing FeNO.</p> <p>Conclusion</p> <p>FeNO measured offline is a useful biomarker for airway inflammation in large population-based studies. Further investigation of age, ethnicity, body-size, and genetic influences is needed, since they may contribute to substantial variation in FeNO.</p

Impact of Tumor Grade on Prognosis in Pancreatic Cancer: Should We Include Grade in AJCC Staging?

AJCC staging of pancreatic cancer (PAC) is used to determine prognosis, yet survival within each stage shows wide variation and remains unpredictable. We hypothesized that tumor grade might be responsible for some of this variation and that the addition of grade to current AJCC staging would provide improved prognostication. The Surveillance, Epidemiology, and End Results (SEER) database (1991–2005) was used to identify 8082 patients with resected PAC. The impact of grade on overall and stage-specific survival was assessed using Cox regression analysis. Variables in the model were age, sex, tumor size, lymph node status, and tumor grade. For each AJCC stage, survival was significantly worse for high-grade versus low-grade tumors. On multivariate analysis, high tumor grade was an independent predictor of survival for the entire cohort (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.31–1.48) as well as for stage I (HR 1.28, 95% CI 1.07–1.54), stage IIA (HR 1.43, 95% CI 1.26–1.61), stage IIB (HR 1.38, 95% CI 1.27–1.50), stage III (HR 1.28, 95% CI 1.02–1.59), and stage IV (HR 1.58, 95% CI 1.21–2.05) patients. The addition of grade to staging results in a statistically significant survival discrimination between all stages. Tumor grade is an important prognostic variable of survival in PAC. We propose a novel staging system incorporating grade into current AJCC staging for pancreas cancer. The improved prognostication is more reflective of tumor biology and may impact therapy decisions and stratification of future clinical trials

Decomposing socioeconomic inequality for binary health outcomes: an improved estimation that does not vary by choice of reference group

BACKGROUND Decomposition of concentration indices yields useful information regarding the relative importance of various determinants of inequitable health outcomes. But the two estimation approaches to decomposition in current use are not suitable for binary outcomes. FINDINGS The paper compares three estimation approaches for decomposition of inequality concentration indices: Ordinary Least Squares (OLS), probit, and the Generalized Linear Model (GLM) binomial distribution and identity link. Data are from the Thai Health and Welfare Survey 2003. The OLS estimates do not take into account the binary nature of the outcome and the probit estimates depend on the choice of reference groups, whereas the GLM binomial identity approach has neither of these problems. CONCLUSIONS The GLM with binomial distribution and identity link allows the inequality decomposition model to hold, and produces valid estimates of determinants that do not vary according to choice of reference groups. This GLM approach is readily available in standard statistical packages.The study was conducted under the auspices of the overarching project "The Thai Health-Risk Transition: a National Cohort Study", funded by the Wellcome Trust UK (GR071587 MA) and the Australian National Health and Medical Research Council (268055)