doxycycline hyclate (Targadox)

Mechanism underlying the high regulatory performance of the doxycycline riboswitch G12.

Hoetzel J J, Walbrun A A, Schäfer M M, Wang T T et al.

Synthetic riboswitches provide protein-independent, modular control of gene expression, yet selecting aptamers that reliably couple ligand binding to regulatory switching remains challenging. Here, we identify and mechanistically characterise G12, a doxycycline-binding aptamer with remarkably high regulatory performance in yeast and human cells. We provide evidence that RNA Capture-SELEX efficiently enriches aptamers with ligand-responsive conformational switching. We compared conventional SELEX and RNA Capture-SELEX using the same starting library followed by NGS analysis and in vivo screening, which led to the identification of G12. G12 binds doxycycline with low-nanomolar affinity and strict discrimination against close derivatives, thus enabling high-dynamic-range riboswitch control of translation in yeast and splicing in human cells. Single-molecule force spectroscopy with optical tweezers revealed that doxycycline stabilises a folding intermediate independent of the closing stem P1, which primarily acts as a scaffold for correct aptamer folding. Mutational analysis and chemical probing identified tertiary contacts between loops L2 and L3 in this intermediate state. Stopped-flow fluorescence spectroscopy further supported a two-step binding mechanism consistent with efficient regulatory switching. Together, these findings deepen our understanding of regulatory aptamer selection and function and expand the synthetic biology toolbox with a high-performance doxycycline-responsive riboswitch.

Unlocking hidden hospital beds: national medical ward flow measures to make inpatient delays visible.

Cliff Abigail A

Australia's hospital performance framework measures emergency department throughput and elective surgery waiting times, but ignores the inpatient journey where older Australian patients face invisible delays. This Perspective proposes National Medical Measures, simple ward-level flow indicators, to make delay patterns observable throughout the acute episode. The National Health Reform Agreement Addendum 2026-2031 requires Health Ministers to develop performance indicators for long-stay patients and cross-sector interfaces; this policy window should include ward-flow measurement. These measures would deliver national visibility of inpatient delays for the first time, establishing the baseline evidence needed to inform earlier clinical intervention, future target setting, and capacity planning.

Artificial intelligence and hypertension management: experience the journey but fasten your seatbelt.

Ram C Venkata S CVS

Patient journey mapping in an open-door psychiatric inpatient unit.

Cuevas-Esteban Jorge J, Ruiz-Garros Esther E, Romero-Diaz Encarnacion E, Motta-Rojas Nicole N et al.

Open-door policies in inpatient psychiatric care have been increasingly adopted to enhance patient autonomy and reduce coercive practices. However, systematic methods for evaluating patient experiences in these settings remain limited. This study applied Patient Journey Mapping in an acute psychiatric unit operating a structured, time-limited (6 hours/day) open-door policy to comprehensively analyze the hospitalization experience. An exploratory sequential mixed-methods design was used. Qualitative data were first collected through focus groups with patients (n = 18), following GRAMMS guidelines, to identify critical touchpoints across the hospitalization journey. Quantitative data were then collected from patients (n = 32) using an adapted Likert-type ordinal scale to assess satisfaction with the identified touchpoints. Data were analyzed using content analysis methods. The analysis delineated the main phases of hospitalization and identified key experiential touchpoints, including "Moments of Truth," "Moments of Pain," and "Wow Moments," which substantially shaped patients' perceptions of care quality. Open-door policies were perceived as supporting autonomy and reducing psychological distress. However, several challenges remained, particularly regarding the admission process, privacy during medication administration, and communication about structured activities. Patient Journey Mapping provides a useful patient-centered approach for evaluating experiences in open-door psychiatric inpatient settings. The findings highlight opportunities to optimize service delivery, strengthen therapeutic environments, and support recovery-oriented practices in acute psychiatric care.