Depressive symptoms are frequent among drug users, but not associated with hepatitis C infection.

AIM: To compare the prevalence and severity of depressive symptoms among drug users with and without hepatitis C virus (HCV) infection. METHODS: This was a cross-sectional survey study carried out at the 2 major drug treatment centres on the island of Funen, Denmark. Participants were drug users presenting to the 2 treatment centres. Individuals with chronic hepatitis B virus or HIV infection were excluded. Participants completed the Major Depression Inventory (MDI) questionnaire when presenting at the centres. Patients with MDI scores indicating severe depression (total MDI score ≥ 35) were referred for treatment evaluation. Hepatitis C status was classified by the presence of anti-HCV as a marker of HCV exposure and HCV-RNA as a marker of ongoing infection. RESULTS: Two hundred and sixty-eight patients were included, of whom 235 (88%) had complete serological testing; 100 (43%, 95% confidence interval (CI) 36-49%) had chronic hepatitis C. The median MDI score was 22 (interquartile range 12-33); 32% (95% CI 26-39%) had a score compatible with depression and 14% (95% CI 10-19%) were rated as severe depression. Depression was not associated with hepatitis C (HCV-infected 29%, non-infected 35%; p = 0.25). Forty-one percent (11/27) of the evaluated participants started antidepressant treatment. CONCLUSIONS: Our study demonstrated a high prevalence of depressive symptoms among drug users, but this was not more frequent among HCV-infected patients. The high overall prevalence of depression underlines the relevance of screening for depression in patients who are drug users.

Actinobaculum schaalii, a common uropathogen in elderly patients, Denmark.

Actinobaculum schaalii can cause urinary tract infections and septicemia but is difficult to identify by cultivation. To obtain a fast diagnosis and identify A. schaalii, we developed a TaqMan real-time quantitative PCR. Routine urine samples were obtained from 177 hospitalized patients and 75 outpatients in Viborg County, Denmark, in 2008-2009. The PCR detected A. schaalii in 22% of samples from patients >60 years of age. This assay showed that A. schaalii is more common than implied by routine cultivation. In 90% of PCR-positive urine samples, other common uropathogens were identified. This finding suggests that A. schaalii is a common, undetected, bacterial pathogen. Our results suggest that A. schaalii may be a more common pathogen than previously thought, especially in patients with unexplained chronic urinary tract infections, who are often treated with trimethoprim or ciprofloxacin, to which A. schaalii is resistant.

Correlation between mechanical strength of messenger RNA pseudoknots and ribosomal frameshifting.

Programmed ribosomal frameshifting is often used by viral pathogens including HIV. Slippery sequences present in some mRNAs cause the ribosome to shift reading frame. The resulting protein is thus encoded by one reading frame upstream from the slippery sequence and by another reading frame downstream from the slippery sequence. Although the mechanism is not well understood, frameshifting is known to be stimulated by an mRNA structure such as a pseudoknot. Here, we show that the efficiency of frameshifting relates to the mechanical strength of the pseudoknot. Two pseudoknots derived from the Infectious Bronchitis Virus were used, differing by one base pair in the first stem. In Escherichia coli, these two pseudoknots caused frameshifting frequencies that differed by a factor of two. We used optical tweezers to unfold the pseudoknots. The pseudoknot giving rise to the highest degree of frameshifting required a nearly 2-fold larger unfolding force than the other. The observed energy difference cannot be accounted for by any existing model. We propose that the degree of ribosomal frameshifting is related to the mechanical strength of RNA pseudoknots. Our observations support the "9 A model" that predicts some physical barrier is needed to force the ribosome into the -1 frame. Also, our findings support the recent observation made by cryoelectron microscopy that mechanical interaction between a ribosome and a pseudoknot causes a deformation of the A-site tRNA. The result has implications for the understanding of genetic regulation, reading frame maintenance, tRNA movement, and unwinding of mRNA secondary structures by ribosomes.

Maintenance of the correct open reading frame by the ribosome.

During translation, a string of non-overlapping triplet codons in messenger RNA is decoded into protein. The ability of a ribosome to decode mRNA without shifting between reading frames is a strict requirement for accurate protein biosynthesis. Despite enormous progress in understanding the mechanism of transfer RNA selection, the mechanism by which the correct reading frame is maintained remains unclear. In this report, evidence is presented that supports the idea that the translational frame is controlled mainly by the stability of codon-anticodon interactions at the P site. The relative instability of such interactions may lead to dissociation of the P-site tRNA from its codon, and formation of a complex with an overlapping codon, the process known as P-site tRNA slippage. We propose that this process is central to all known cases of +1 ribosomal frameshifting, including that required for the decoding of the yeast transposable element Ty3. An earlier model for the decoding of this element proposed 'out-of-frame' binding of A-site tRNA without preceding P-site tRNA slippage.