A small stretch of poor codon usage at the beginning of dengue virus open reading frame may act as a translational checkpoint.

OBJECTIVE: Rare codons were previously shown to be enriched at the beginning of the dengue virus (DENV) open reading frame. However, the role of rare codons in regulating translation efficiency and replication of DENV remains unclear. The present study aims to clarify the significance of rare codon usage at the beginning of DENV transcripts using the codon adaptation index (CAI). METHODOLOGY: CAIs of the whole starting regions of DENV transcripts as well as 18-codon sliding windows of the regions were analyzed. RESULTS: One of the intriguing findings is that those rare codons do not typically result in uniformly low CAI in the starting region with rare codons. However, it shows a notable local drop in CAI around the 50th codon in all dengue serotypes. This suggests that there may be a translational checkpoint at this site and that the rare codon usage upstream to this checkpoint may not be related to translational control.

Ultrasound screening for cholangiocarcinoma could detect premalignant lesions and early-stage diseases with survival benefits: a population-based prospective study of 4,225 subjects in an endemic area.

BACKGROUND: Thailand has a high incidence of cholangiocarcinoma (CCA), particularly in the north and northeastern regions. Most CCA patients come at a late, unresectable stage and presently no optimal screening test for CCA has been established. We determined the prevalence of CCA in a remote northern village and explored if screening could lead to early detection and survival benefits. METHODS: A 5-year population-based study was started in October, 2011 for consented Thai individuals, aged 30-60 years. The screening program comprised blood testing, stool examination and serial ultrasonography every 6 months. RESULTS: During the first 3 years, 4,225 eligible individuals were enrolled. CCA was detected in 32 patients, with a mean age of 51.9 years (41-62 years), and 21/32 cases were at a curative resectable stage. The prevalence rate of CCA was 165.7 per 100,000 and one- and two-year incidence rate was 236.7/100,000 and 520.7/100,000, respectively. One- and 2-year overall survival rates of CCA patients were 90.9 and 61.5 %, respectively. Prognosis was better in resectable cases with 100 % 1-year and 77.8 % 2-year survival rates. Interestingly, premalignant pathological lesions (stage 0) were identified in 11 cases with 100 % 3-year survival rate. Serum biomarkers and alkaline phosphatase were not sufficient to detect early-stage disease. In 22 patients, stool samples were positive for Opistorchis viverrini, based on polymerase chain reaction. CONCLUSION: Detection of premalignant lesions and early-stage resectable CCA by ultrasonography resulted in improved clinical outcome. Ultrasonography should be offered as a first screening tool for CCA in an endemic area until other useful biological markers become available.