During microbial reductive dechlorination of tetrachloroethene (PCE) and trichloroethene (TCE), trans-1, 2-dichloroethene (trans-DCE) has been observed to be produced predominantly by certain mixed and pure cultures. However, the reductive dehalogenase (RDase) genes involved in trans-DCE generation remain elusive. In this study, identification and transcriptional analysis of RDases were conducted on trans-DCE-producing Dehalococcoides sp. strain MB. Two pairs of degenerate primers targeting the conserved regions of RDases in known Dehalococcoides species were applied to amplify the putative RDase genes of strain MB. Cloning and restriction analysis revealed the presence of seven unique RDase gene fragments (dceA1 to dceA7) that possess sequence identity to known RDase genes. Gene expression analysis of the PCE-grown culture MB exhibited 10-fold regulation of the RDase gene dceA6 (designated mbrA gene), suggesting that it is involved in the production of trans-DCE. This is in agreement with the molecular size of the most abundant protein that is resolved on the denaturing protein gel. Complete sequence of the mbrA gene was obtained by chromosome walking, and the upstream of it is a regulator of transcription, indicating that the expression of this functional gene is tightly controlled in the microbe. The mbrA gene was subsequently found to be present in other trans-DCE-producing cultures containing Dehalococcoides sp. The new mbrA gene identified in this study may serve as an important biomarker for evaluating, predicting and elucidating the biological production of trans-DCE in the chloroethene-contaminated sites.
Colorectal cancer (CRC) is the most common cancer in Singapore. We sought to evaluate the long-term cost-effectiveness of targeted genetic testing and surveillance programs in individuals at high risk of hereditary non-polyposis colorectal cancer (HNPCC), as compared to an unselective clinical surveillance program alone in Singapore. A Markov model analysis from the healthcare service provider's perspective was developed to follow over a lifetime a cohort of cancer-free 21-year-old individuals, who were first-degree relatives of HNPCC patients with a known mutation. Genetic testing strategy provided a lifetime saving of Singapore dollars (SGD) 13,588 per person and gained additional life years of 0.01, as compared to clinical surveillance alone, by sparing non-mutation carriers from unnecessary and invasive intensive clinical surveillance (assuming 100% compliance with recommended surveillance programs in both strategies). Sensitivity analyses showed that as long as the compliance rate in mutation carriers was not lower than that for individuals without genetic testing, pursuing a genetic testing strategy would either be a more favorable option with discounted incremental cost-effectiveness ratios ranging from SGD 6,961 to 17,289 per life year gained or a dominant status achieved (more life year gained and less costly). Genetic testing for individuals at high risk of HNPCC allows targeted clinical surveillance to be directed at mutation carriers, ensuring efficient use of healthcare resources and reduces CRC-related mortality. It can be regarded as a cost-effective strategy in Singapore, if an improved compliance with recommended surveillance protocol is achieved in proven mutation carriers.
BackgroundKidney disease is the 9th leading cause of death in Singapore. While preventive effects have focused on early detection and education, little is known about the knowledge level of chronic kidney disease (CKD) locally. We seek to evaluate the knowledge of CKD among primary care patients.MethodsWe conducted a cross-sectional survey of a convenience sample of 1520 patients from 3 primary care centers. Those with existing CKD or on dialysis were excluded. Knowledge was assessed based on 7 questions on CKD in the self-administered questionnaire. One point was given for each correct answer with a maximum of 7 points.Results1435 completed all 7 questions on CKD. Mean age was 48.9 ±15.0 (SD) years. 50.9% were male. 62.3% had a secondary and below education and 52.4% had a monthly household income of ≤ $2000. 43.7% had chronic diseases. Mean score was 3.44 ± 1.53 (out of a maximum of 7). Median score was 4. In multivariate logistic regression, being older {>60 years [Odds Ratio (OR) 0.50, 95% Confidence Interval (CI) 0.32-0.79]; 40–60 years (OR 0.62, 95% CI 0.43,0.89)}, less educated [up to primary education (OR 0.33, 95% CI 0.22-0.49)], having a lower monthly household income [
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