Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.

Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.

Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.

Changes in susceptibility of to antimalarial drugs in Uganda over time: 2019-2024.

Background: The treatment and control of malaria in Africa is challenged by drug resistance, including transporter, folate pathway, and PfK13 mutations that mediate resistance to aminoquinolines, antifolates, and artemisinins, respectively. Characterization of drug susceptibility informs optimal control strategies.

Methods: We characterized ex vivo susceptibilities to nine drugs of isolates collected from individuals presenting with uncomplicated falciparum malaria in eastern (2019-2024) and northern (2021-2024) Uganda using a growth inhibition assay and the dihydroartemisinin (DHA) ring survival assay (RSA).

Gametocyte production and transmission fitness of African and Asian isolates with differential susceptibility to artemisinins.

The emergence of parasites partially resistant to artemisinins (ART-R) poses a significant threat to recent gains in malaria control. ART-R has been associated with PfKelch13 (K13) mutations, which differ in fitness costs. This study investigates the gametocyte production and transmission fitness of African and Asian isolates with different K13 genotypes across multiple mosquito species.

Distinct gut microbial signature and altered short chain fatty acid metabolism at disease onset in a rat preclinical model of superimposed preeclampsia.

Chronic hypertension is an increasingly prevalent condition that constitutes a risk factor for superimposed preeclampsia during pregnancy. In this study, we assessed the gut microbiome in a rat model of superimposed preeclampsia to characterize the microbial signature associated with defective placentation processes identified at the preclinical disease stage. The blood pressure profile, renal function parameters and fetal phenotype were evaluated in pregnant Stroke-prone Spontaneously Hypertensive Rats (SHRSP) and their normotensive controls.