Mesenchymal stem cells constitute a pool of cells present throughout the lifetime in numerous niches, characteristic of unlimited replication potential and the ability to differentiate into mature cells of mesodermal tissues in vitro. The therapeutic potential of these cells is, however, primarily associated with their capabilities of inhibiting inflammation and initiating tissue regeneration. Owing to these properties, mesenchymal stem cells (derived from the bone marrow, subcutaneous adipose tissue, and increasingly urine) are the subject of research in the settings of kidney diseases in which inflammation plays the key role. The most advanced studies, with the first clinical trials, apply to ischemic acute kidney injury, renal transplantation, lupus and diabetic nephropathies, in which beneficial clinical effects of cells themselves, as well as their culture medium, were observed. The study findings imply that mesenchymal stem cells act predominantly through secreted factors, including, above all, microRNAs contained within extracellular vesicles. Research over the coming years will focus on this secretome as a possible therapeutic agent void of the potential carcinogenicity of the cells.

More heath care resources need to be made available to the homeless beyond standard medical care. Concrete suggestions are discussed in the text.

Background: Knowledge regarding the impact of body composition measures on pharmacokinetics of antipsychotics is limited. Aims: Our aim was to investigate the impact of body weight and body mass index on clozapine pharmacokinetics using a therapeutic drug monitoring database. Methods: A large therapeutic drug monitoring dataset of clozapine plasma concentrations considering three patient subgroups was analysed: a control group (CLZ0, 20–30 kg/m2, n=266), a group with high body mass index (CLZhigh, body mass index ⩾30 kg/m2, n=162) and with low body mass index values (CLZlow, body mass index <20 kg/m2, n=27). Comparisons of plasma and dose-adjusted plasma concentrations (C/D) of clozapine were based on the Spearman’s correlation ( rs), Kruskal Wallis and Mann-Whitney-U tests. For percentages we used the Pearson chi-square test (χ2). To assess effects of confounders we used bootstrapping analysis of covariates. Results/outcomes: Regarding demographic characteristics, groups differed only for sex percentage with more females than males in CLZlow and CLZhigh compared to CLZ0 ( p=0.001 for χ2 test). Plasma and C/D values were positively associated with body mass index ( rs=0.108, p=0.022 and rs=0.156, p=0.001 respectively). Intergroup differences were observed for plasma and dose-adjusted concentrations of clozapine ( p=0.031 and p=0.029 for Kruskal Wallis respectively): post-hoc pairwise comparisons showed higher plasma concentrations and C/D of clozapine in CLZhigh compared to CLZ0 ( p=0.014 and p=0.007 respectively for Mann-Whitney U-test), by mean 21 and 18%, respectively. Differences for C/D values remained after accounting for sex ( p=0.02). Conclusions/interpretation: In obese patients, bioavailability, distribution or elimination of clozapine may be altered due to increased clozapine deposits in fat tissue and hepatic enzyme activity changes.

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