8 research outputs found
Evaluation of acute effect of light-emitting diode (LED) phototherapy on muscle deoxygenation and pulmonary oxygen uptake kinetics in patients with diabetes mellitus: study protocol for a randomized controlled trial
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
Structural basis for phospholipase A2-like toxin inhibition by the synthetic compound Varespladib (LY315920)
The World Health Organization recently listed snakebite envenoming as a Neglected Tropical Disease,
proposing strategies to significantly reduce the global burden of this complex pathology by 2030. In
this context, effective adjuvant treatments to complement conventional antivenom therapy based on
inhibitory molecules for specific venom toxins have gained renewed interest. Varespladib (LY315920)
is a synthetic molecule clinically tested to block inflammatory cascades of several diseases associated
with elevated levels of secreted phospholipase A2 (sPLA2). Most recently, Varespladib was tested
against several whole snake venoms and isolated PLA2 toxins, demonstrating potent inhibitory activity.
Herein, we describe the first structural and functional study of the complex between Varespladib and
a PLA2-like snake venom toxin (MjTX-II). In vitro and in vivo experiments showed this compound’s
capacity to inhibit the cytotoxic and myotoxic effects of MjTX-II from the medically important South
American snake, Bothrops moojeni. Crystallographic and bioinformatics analyses revealed interactions
of Varespladib with two specific regions of the toxin, suggesting inhibition occurs by physical blockage
of its allosteric activation, preventing the alignment of its functional sites and, consequently, impairing
its ability to disrupt membranes. Furthermore, based on the analysis of several crystallographic
structures, a distinction between toxin activators and inhibitors is proposed.Universidad de Costa Rica/[741-B5-602]/UCR/Costa RicaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP
Biophysical studies suggest a new structural arrangement of crotoxin and provide insights into its toxic mechanism
Phospholipase A2 Isolated from the Venom of Crotalus durissus terrificus Inactivates Dengue virus and Other Enveloped Viruses by Disrupting the Viral Envelope
Protein complexes in snake venom
10.1007/s00018-009-0050-2Cellular and Molecular Life Sciences66172851-2871CMLS