Activation of the sweet taste receptor T1R3 by sucralose attenuates VEGF-induced vasculogenesis in a cell model of the retinal microvascular endothelium

Background: One of the most prevalent microvascular complications for patients with diabetes is diabetic retinopathy (DR) associated with increased retinal endothelial blood vessel formation. Treatments to reduce vascularisation in the retinal endothelium are linked to improved sight in patients with DR. Recently we have demonstrated the novel protective role of the artificial sweetener, sucralose, and the sweet taste receptor, T1R3, in the pulmonary endothelium to reduce vascular leak. In the present study, we examined the role of sucralose and sweet taste receptors on vasculogenic processes (proliferation, migration, adhesion and tube formation) in a cell model of the retinal endothelium . Methods: We exposed human retinal microvascular endothelial cells (RMVEC) to VEGF as an in vitro model of DR in the presence and absence of T1R3 agonist sucralose. Results: In RMVEC, we observed increased VEGF-induced cell proliferation, migration, adhesion and tube formation, which was significantly attenuated by exposure to the artificial sweetener sucralose. Following siRNA knockdown of the sweet taste receptor, T1R3, but not T1R2, the protective effect of sucralose on VEGF-induced RMVEC vasculogenic processes was blocked. We further demonstrate that sucralose attenuates VEGF-induced Akt phosphorylation to protect the retinal microvasculature. Conclusion: These studies are the first to demonstrate a protective effect of an artificial sweetener, through the sweet taste receptor T1R3, on VEGF-induced vasculogenesis in a retinal microvascular endothelial cell line

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

The number and location of genes for 5S ribonucleic acid within the genome of Drosophila melanogaster

DNA was prepared from wild-type and two mutant stocks of Drosophila melanogaster that differed in their dosage of the nucleolar organizer region. The relative amounts of DNA from the nucleolar organizer region in these preparations of DNA were determined by hybridization with (3)H-labelled 28S rRNA. As expected, the amount of (3)H-labelled 28S rRNA that hybridized was directly related to the dosage of nucleolar organizer region. No positive correlation was observed between the amount of (3)H-labelled 5S RNA that hybridized and the dosage of nucleolar organizer region. Thus genes for 5S RNA are located primarily, if not exclusively, outside the nucleolar organizer region. The haploid genome of the wild-type D. melanogaster used in this work has 106 genes for 28S rRNA and 96–105 genes for 5S RNA