Mucosal IFNλ1 mRNA-based immunomodulation effectively reduces SARS-CoV-2 induced mortality in mice.

RNA vaccines elicit protective immunity against SARS-CoV-2, but the use of mRNA as an antiviral immunotherapeutic is unexplored. Here, we investigate the activity of lipidoid nanoparticle (LNP)-formulated mRNA encoding human IFNλ1 (ETH47), which is a critical driver of innate immunity at mucosal surfaces protecting from viral infections. IFNλ1 mRNA administration promotes dose-dependent protein translation, induction of interferon-stimulated genes without relevant signs of unspecific immune stimulation, and dose-dependent inhibition of SARS-CoV-2 replication in vitro.

Acceptability of multiple coated mini-tablets in comparison to syrup in infants and toddlers: a randomised controlled study.

Objectives: Drug treatment of children is often limited to liquid formulations or manipulation of adult solid oral dosage forms because of the lack of age-appropriate formulations, concerns around particle aspiration and paediatric acceptability. Recent research revealed that the administration of mini-tablets has substantial advantages in improving dose accuracy and avoiding issues related to drug stability, storage conditions, potentially toxic excipients and taste masking (especially effective when the mini-tablets are coated). Most trials were performed with single and multiple mini-tablets.

Variability of MRI Aortic Stiffness Measurements in a Multicenter Clinical Trial Setting: Intraobserver, Interobserver, and Intracenter Variability of Pulse Wave Velocity and Aortic Strain Measurement.

Purpose: To assess intraobserver, interobserver, and scan-rescan variability of MRI aortic stiffness measurements in a multicenter trial setting.

Materials And Methods: This study was a retrospective analysis of prospectively collected data in a multicenter prospective clinical trial (clinicaltrials.gov ID NCT01870739).

Clinical Investigation of Metabolic and Renal Clearance Pathways Contributing to the Elimination of Fevipiprant Using Probenecid as Perpetrator.

Fevipiprant, an oral, nonsteroidal, highly selective, reversible, and competitive prostaglandin D receptor 2 antagonist, is eliminated by glucuronidation and by direct renal excretion predominantly via organic anion transporter (OAT) 3. This study aimed to assess the effect of simultaneous UDP-glucuronosyltransferase (UGT) and OAT3 inhibition by probenecid on the pharmacokinetics of fevipiprant and its acyl glucuronide (AG) metabolite to support the dosing recommendation of fevipiprant in the presence of drugs inhibiting these pathways; however, phase III clinical trial results did not support its submission. This was a single-center, open-label, single-sequence, two-period crossover study in healthy subjects.

On the optimal temporal resolution for phase contrast cardiovascular magnetic resonance imaging: establishment of baseline values.

Background: The aim of this study is to quantify the frequency content of the blood velocity waveform in different body regions by means of phase contrast (PC) cardiovascular magnetic resonance (CMR) and Doppler ultrasound. The highest frequency component of the spectrum is inversely proportional to the ideal temporal resolution to be used for the acquisition of flow-sensitive imaging (Shannon-Nyquist theorem).

Methods: Ten healthy subjects (median age 33y, range 24-40) were scanned with a high-temporal-resolution PC-CMR and with Doppler ultrasound on three body regions (carotid arteries, aorta and femoral arteries).