Venous or arterial samples for activated clotting time measurements: a systematic review.

OBJECTIVE The systematic review aims to investigate the effect of sampling source on activated clotting time (ACT) measurement within cardiovascular surgery and cardiac catheterisation. It also examines the evidence surrounding novel clot assessment techniques and associated sampling variation. METHODS A comprehensive electronic search was conducted using PubMed, MEDLINE, Scopus, Cochrane database, and Google Scholar until 20th June 2020. All studies reporting sampling source variability of ACT in cardiac surgery, vascular surgery and cardiac catheterisation were included. RESULTS Fourteen studies were included in the systematic review. Inconsistent reports of variability were seen in cardiac surgery and cardiac catheterisation. There were no studies directly examining ACT variability in vascular surgery. Novel clot assessment techniques have been validated in cardiac surgery, but measurements vary depending on sampling source. CONCLUSION Sampling source should be kept consistent to facilitate effective haemostatic strategies. More research is needed regarding variability in vascular surgery and novel clot assessment techniques

Lentiviral delivery of short hairpin RNAs protects CD4 T cells from multiple clades and primary isolates of HIV

Viral heterogeneity is a major hurdle for potential therapeutic use of RNA interference (RNAi) against HIV-1. To determine the extent of RNAi tolerance to mutations, we tested 3 viral target sites with differing propensity for mutations: a highly variable rev sequence, a gag sequence conserved only among clade B isolates, and a vif sequence highly conserved across clades. Lentiviral expression of all 3 shRNAs inhibited replication of the homologous HIVIIIB strain. However, they differed in their ability to protect primary CD4 T cells against multiple isolates within and across HIV clades. The least conserved rev sequence inhibited only 2 of 5 clade B isolates. The gag sequence (conserved within clade B) protected 5 of 5 clade B isolates but not other clade viruses with 2 or 3 mutations in the central region. In contrast, the vif sequence, which was conserved across clades except for single mutations at positions 14 and 17, inhibited viruses from 5 different clades. Moreover, siRNAs with introduced mutations at sites of gag sequence polymorphisms showed reduced antiviral activity, whereas mutations in vif siRNA only modestly decreased silencing. Thus, although 1 or 2 mutations at peripheral sites are tolerated, mutations in the central target cleavage region abolish RNAi activity