Statistical reporting of metabolomics data : experience from a high-throughput NMR platform and epidemiological applications

Introduction Meta-analysis is the cornerstone of robust biomedical evidence. Objectives We investigated whether statistical reporting practices facilitate metabolomics meta-analyses. Methods A literature review of 44 studies that used a comparable platform. Results Non-numeric formats were used in 31 studies. In half of the studies, less than a third of all measures were reported. Unadjusted P-values were missing from 12 studies and exact P-values from 9 studies. Conclusion Reporting practices can be improved. We recommend (i) publishing all results as numbers, (ii) reporting effect sizes of all measured metabolites and (iii) always reporting unadjusted exact P-values.Peer reviewe

The effect of drug ionization on lipid-based formulations for the oral delivery of anti-psychotics

Lipid-based formulations (LBFs) are well-known to improve the oral bioavailability of poorly water-soluble drugs (PWSDs) by presenting the drug to the gastrointestinal environment in a molecularly dispersed state, thus avoiding the rate-limiting dissolution step. Risperidone and lurasidone are antipsychotics drugs which experience erratic and variable absorption, leading to a low oral bioavailability. The aim of this research was to develop and investigate the performance of risperidone and lurasidone when formulated as an emulsion and silica-lipid hybrid (SLH). Lurasidone and risperidone were dissolved in Capmul® MCM at 100% and 80% their equilibrium solubility, respectively, prior to forming a sub-micron emulsion. SLH microparticles were fabricated by spray-drying a silica stabilised sub-micron emulsion to form a solid powder. The performances of the formulations were evaluated in simulated intestinal media under digesting conditions, where the emulsion and SLH provided a 17-fold and 23-fold increase in LUR solubilisation, respectively. However, the performance of RIS was reduced by 2.2-fold when encapsulated within SLH compared to pure drug. Owing to its pKa, RIS adsorbed to the silica and thus, dissolution was significantly hindered. The results reveal that LBFs may not overcome the challenges of all PWSDs and physiochemical properties must be carefully considered when predicting drug performance.</p

Location, location, location…site-specific GPCR phosphorylation offers a mechanism for cell-type-specific signalling

It is now established that most of the ∼800 G-protein-coupled receptors (GPCRs) are regulated by phosphorylation in a process that results in the recruitment of arrestins, leading to receptor desensitization and the activation of arrestin-dependent processes. This generalized view of GPCR regulation, however, does not provide an adequate mechanism for the control of tissue-specific GPCR signalling. Here, we review the evidence that GPCR phosphorylation is, in fact, a flexible and dynamic regulatory process in which GPCRs are phosphorylated in a unique manner that is associated with the cell type in which the receptor is expressed. In this scenario, phosphorylation offers a mechanism of regulating the signalling outcome of GPCRs that can be tailored to meet a specific physiological role