Interaction of the tetracyclines with double-stranded RNAs of random base sequence: new perspectives on the target and mechanism of action

The 16S rRNA binding mechanism proposed for the antibacterial action of the tetracyclines does not explain their mechanism of action against non-bacterial pathogens. In addition, several contradictory base pairs have been proposed as their binding sites on the 16S rRNA. This study investigated the binding of minocycline and doxycycline to short double-stranded RNAs (dsRNAs) of random base sequences. These tetracyclines caused a dose-dependent decrease in the fluorescence intensities of 6-carboxyfluorescein (FAM)-labelled dsRNA and ethidium bromide (EtBr)-stained dsRNA, indicating that both drugs bind to dsRNA of random base sequence in a manner that is competitive with the binding of EtBr and other nucleic acid ligands often used as stains. This effect was observable in the presence of Mg2+. The binding of the tetracyclines to dsRNA changed features of the fluorescence emission spectra of the drugs and the CD spectra of the RNA, and inhibited RNase III cleavage of the dsRNA. These results indicate that the double-stranded structures of RNAs may have a more important role in their interaction with the tetracyclines than the specific base pairs, which had hitherto been the subject of much investigation. Given the diverse functions of cellular RNAs, the binding of the tetracyclines to their double-stranded helixes may alter the normal processing and functioning of the various biological processes they regulate. This could help to explain the wide range of action of the tetracyclines against various pathogens and disease condition

Delivering exceptionally safe transitions of care to older people : a qualitative study of multidisciplinary staff perspectives

Background Transitions of care are often risky, particularly for older people, and shorter hospital stays mean that patients can go home with ongoing care needs. Most previous research has focused on fundamental system flaws, however, care generally goes right far more often than it goes wrong. We explored staff perceptions of how high performing general practice and hospital specialty teams deliver safe transitional care to older people as they transition from hospital to home. Methods We conducted a qualitative study in six general practices and four hospital specialties that demonstrated exceptionally low or reducing readmission rates over time. Data were also collected across four community teams that worked into or with these high-performing teams. In total, 157 multidisciplinary staff participated in semi-structured focus groups or interviews and 9 meetings relating to discharge were observed. A pen portrait approach was used to explore how teams across a variety of different contexts support successful transitions and overcome challenges faced in their daily roles. Results Across healthcare contexts, staff perceived three key themes to facilitate safe transitions of care: knowing the patient, knowing each other, and bridging gaps in the system. Transitions appeared to be safest when all three themes were in place. However, staff faced various challenges in doing these three things particularly when crossing boundaries between settings. Due to pressures and constraints, staff generally felt they were only able to attempt to overcome these challenges when delivering care to patients with particularly complex transitional care needs. Conclusions It is hypothesised that exceptionally safe transitions of care may be delivered to patients who have particularly complex health and/or social care needs. In these situations, staff attempt to know the patient, they exploit existing relationships across care settings, and act to bridge gaps in the system. Systematically reinforcing such enablers may improve the delivery of safe transitional care to a wider range of patients. Trial registration The study was registered on the UK Clinical Research Network Study Portfolio (references 35272 and 36174)