AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

Comparison between AI and human expert performance in acute pain assessment in sheep.

This study explores the question whether Artificial Intelligence (AI) can outperform human experts in animal pain recognition using sheep as a case study. It uses a dataset of N = 48 sheep undergoing surgery with video recordings taken before (no pain) and after (pain) surgery. Four veterinary experts used two types of pain scoring scales: the sheep facial expression scale (SFPES) and the Unesp-Botucatu composite behavioral scale (USAPS), which is the 'golden standard' in sheep pain assessment.

Population pharmacokinetics and dosing simulations of temocillin in liver-transplanted paediatric patients: a prospective, open-label, non-randomized study.

Objectives: Temocillin is a β-lactam antibiotic used for preventing or treating bacterial infections in liver-transplanted children. We characterized its pharmacokinetics in plasma and ascitic fluid and proposed dosing regimens that maximize the achievement of effective drug exposures in this patient group.

Methods: Patients aged 6-36 months received 25 mg/kg/12 h (n = 14) or 25 mg/kg/8 h (n = 23).

Functional Regrowth of Norepinephrine Axons in the Adult Mouse Brain Following Injury.

It is widely believed that axons in the central nervous system of adult mammals do not regrow following injury. This failure is thought, at least in part, to underlie the limited recovery of function following injury to the brain or spinal cord. Some studies of fixed tissue have suggested that, counter to dogma, norepinephrine (NE) axons regrow following brain injury.

MARC1 downregulation reduces hepatocyte lipid content by increasing beta-oxidation.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic. MASLD has a strong genetic component, and a common missense variant (rs2642438) in the mitochondrial amidoxime-reducing component 1 (MARC1) gene confers protection against its onset and severity. However, there are contrasting results regarding the mechanisms entangling this protection.