Overall, there is insufficient evidence to recommend one laparoscopic entry technique over another.An open-entry technique is associated with a reduction in failed entry when compared to a closed-entry technique, with no evidence of a difference in the incidence of visceral or vascular injury.An advantage of direct trocar entry over Veress needle entry was noted for failed entry and vascular injury. The evidence was generally of very low quality with small numbers of participants in most studies; our findings should be interpreted with caution.

In humans, loss of function mutations in the SAMHD1 (AGS5) gene cause a severe form of Aicardi-Goutières syndrome (AGS), an inherited inflammatory-mediated encephalopathy characterized by increased type I IFN activity and upregulation of IFN-stimulated genes (ISGs). In particular, SAMHD1-related AGS is associated with a distinctive cerebrovascular pathology that commonly leads to stroke. Although inflammatory responses are observed in immune cells cultured from Samhd1 null mouse models, these mice are physically healthy, specifically lacking a brain phenotype. We have investigated the use of zebrafish as an alternative system for generating a clinically relevant model of SAMHD1-related AGS. Using temporal gene knockdown of zebrafish samhd1, we observe hindbrain ventricular swelling and brain hemorrhage. Furthermore, loss of samhd1 or of another AGS-associated gene, adar, leads to a significant upregulation of innate immune-related genes and an increase in the number of cells expressing the zebrafish type I IFN ifnphi1. To our knowledge, this is the first example of an in vivo model of AGS that recapitulates features of both the innate immune and neurological characteristics of the disease. The phenotypes associated with loss of samhd1 and adar suggest a function of these genes in controlling innate immune processes conserved to zebrafish, thereby also contributing to our understanding of antiviral signaling in this model organism.

Aicardi-Goutières syndrome (AGS) is an inflammatory disorder resulting from mutations in TREX1, RNASEH2A/2B/2C, SAMHD1 or ADAR1. Here we provide molecular, biochemical and cellular evidence for the pathogenicity of two synonymous variants in RNASEH2A. Firstly, the c.69G>A (p.Val23Val) mutation causes the formation of a splice donor site within exon 1, resulting in an out of frame deletion at the end of exon 1, leading to reduced RNase H2 protein levels. The second mutation, c.75C>T (p.Arg25Arg), also introduces a splice donor site within exon 1, and the internal deletion of 18 amino acids. The truncated protein still forms a heterotrimeric RNase H2 complex, but lacks catalytic activity. However, as a likely result of leaky splicing, a small amount of full-length active protein is apparently produced in an individual homozygous for this mutation. Recognition of the disease causing status of these variants allows for diagnostic testing in relevant families.