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A letter to the editor is presented about a sensitive technique for imaging and effective monitoring of staining of the ocular surface defects.

G-protein coupled receptor-55 (GPR55), an endocannabinoid receptor, is a novel anti-diabetic target. This study aimed to assess the metabolic functionality of GPR55 ligands using CRISPR/Cas9 gene editing to determine their regulatory role in beta cell function and incretin-secreting enteroendocrine cells. A clonal Gpr55 knockout beta cell line was generated by CRISPR/Cas9 gene editing to investigate insulin secretion and Gpr55 signalling. Acute effects of GPR55 agonists were investigated in high fat fed (HFD) diabetic HsdOla:TO (Swiss TO) mice. Atypical and endogenous endocannabinoid ligands (10 -7 -10 -4 M) stimulated insulin secretion (p < 0.05-0.001) in rodent (BRIN-BD11) and human (1.1B4) beta cells, with 2-2.7-fold (p < 0.001) increase demonstrated in BRIN-BD11 cells (10 -4 M). The insulinotropic effect of Abn-CBD (42 %), AM251 (30 %) and PEA (53 %) were impaired (p < 0.05) in Gpr55 knockout BRIN-BD11 cells, with the secretory effect of O-1602 completely abolished (p < 0.001). Gpr55 ablation abolished the release of intracellular Ca 2+ upon treatment with O-1602, Abn-CBD and PEA. Upregulation of insulin mRNA by Abn-CBD and AM251 (1.7-3-fold; p < 0.01) was greatly diminished (p < 0.001) in Gpr55 null cells. Orally administered Abn-CBD and AM251 (0.1 μmol/kgBW) improved GIP (p < 0.05-p < 0.01), GLP-1 (p < 0.05-p < 0.001), glucose tolerance (p < 0.001) and circulating insulin (p < 0.05-p < 0.001) in HFD diabetic mice. Abn-CBD in combination therapy with DPP-IV inhibitor (Sitagliptin) resulted in greater improvement in glucose tolerance (p < 0.05) and insulin release (p < 0.05). Antagonism of Gpr55 in-vivo attenuated the glucoregulatory effects of Abn-CBD (p < 0.05). Conclusively, GPR55 agonists enhance insulin, GIP and GLP-1 release, thereby promoting GPR55 agonist monotherapy and combinational therapy as a novel approach for the treatment of type-2-diabetes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Endothelial cells (EC) are targets in gene therapy and regenerative medicine, but they are inefficiently transduced with adeno-associated virus (AAV) vectors of various serotypes. To identify barriers hampering efficient transduction and to develop an optimized AAV variant for EC transduction, we screened an AAV serotype 2-based peptide display library on primary human macrovascular EC. Using a new high-throughput selection and monitoring protocol, we identified a capsid variant, AAV-V EC , which outperformed the parental serotype as well as first-generation targeting vectors in EC transduction. AAV vector uptake was improved, resulting in significantly higher transgene expression levels from single-stranded vector genomes detectable within a few hours post-transduction. Notably, AAV-V EC transduced not only proliferating EC but also quiescent EC, although higher particle-per-cell ratios had to be applied. Also, induced pluripotent stem cell-derived endothelial progenitor cells, a novel tool in regenerative medicine and gene therapy, were highly susceptible toward AAV-V EC transduction. Thus, overcoming barriers by capsid engineering significantly expands the AAV tool kit for a wide range of applications targeting EC.

The work load of forensic medical officers (FMOs) who provide medical cover for the Coleraine and Limavady district command units (DCU) of the police service of Northern Ireland (PSNI) in dealing with domestic violence was investigated over a three year period from 1st April 2003 to 31st March 2006. A total of 128 cases involving domestic violence were identified during this three year period. There was a significant increase from 4% (32/791) in the first year to 6.6% (56/851, p<0.01) in the number of cases of identified domestic violence in the second year which dropped to 4.2% (40/956) in the third year. Victims were identified in 38% of these domestic violence cases with 62% being identified as assailants. It was noted that there was a significant difference in the proportion of male assailants (96.2%) from female assailants (3.8%). Fifty-four percent of victims were noted to have injuries in accordance with the more serious injury categories of assault of actual bodily harm (AOABH) and grievous bodily harm (GBH). Domestic incidents occurred at the home in 91% of cases, with the FMO being the primary contact in 97% of cases. Alcohol was implicated in 56% of all domestic violence cases recorded.

This review was undertaken to identify the evolutionary process in the current understanding of allegations of drug facilitated sexual assault (DFSA), so that those who work in this field may gain a better understanding of the complexities involved in such cases. Several definitions of DFSA are provided as well as a list of intoxicating substances which have so far been incriminated in this crime. Perception and alcohol use is addressed, whilst an examination of intoxication and victim outcomes reveals disturbing but important information which needs to be centrally placed within health education campaigns with a degree of urgency. The review identifies the effects of alcohol on sexual behaviour, drinking patterns and specific quantitative research indicating very high alcohol levels in some instances. In practical terms, suggestions are made following Operation Matisse, to address prevention, early detection and easier identification of DFSA cases so that victims' needs are prioritised and appropriately addressed.