How glucagon-like peptide 1 receptor agonists work

Recent years, glucagon-like peptide 1 receptor agonists (GLP-1RAs) have become central in the treatment of type 2 diabetes (T2D). In addition to their glucose-lowering properties with low risk of hypoglycaemia, GLP-1RAs reduce body weight and show promising results in reducing cardiovascular risk and renal complications in high-risk individuals with T2D. These findings have changed guidelines on T2D management over the last years, and GLP-1RAs are now widely used in overweight patients with T2D as well as in patients with T2D and cardiovascular disease regardless of glycaemic control. The currently available GLP-1RAs have different pharmacokinetic profiles and differ in their ability to improve glycaemia, reduce body weight and in their cardio- and renal protective potentials. Understanding how these agents work, including insights into their pleiotropic effects on T2D pathophysiology, may improve their clinical utilisation and be useful for exploring other indications such as non-alcoholic steatohepatitis and neurodegenerative disorders. In this review, we provide an overview of approved GLP-1RAs, their clinical effects and mode of actions, and we offer insights into the potential of GLP-1RAs for other indications than T2D. Finally, we will discuss the emerging data and therapeutic potential of using GLP-1RAs in combinations with other receptor agonists.

Synthetic Biology towards Improved Flavonoid Pharmacokinetics

Flavonoids are a structurally diverse class of natural products that have been found to have a range of beneficial activities in humans. However, the clinical utilisation of these molecules has been limited due to their low solubility, chemical stability, bioavailability and extensive intestinal metabolism in vivo. Recently, the view has been formed that site-specific modification of flavonoids by methylation and/or glycosylation, processes that occur in plants endogenously, can be used to improve and adapt their biophysical and pharmacokinetic properties. The traditional source of flavonoids and their modified forms is from plants and is limited due to the low amounts present in biomass, intrinsic to the nature of secondary metabolite biosynthesis. Access to greater amounts of flavonoids, and understanding of the impact of modifications, requires a rethink in terms of production, more specifically towards the adoption of plant biosynthetic pathways into ex planta synthesis approaches. Advances in synthetic biology and metabolic engineering, aided by protein engineering and machine learning methods, offer attractive and exciting avenues for ex planta flavonoid synthesis. This review seeks to explore the applications of synthetic biology towards the ex planta biosynthesis of flavonoids, and how the natural plant methylation and glycosylation pathways can be harnessed to produce modified flavonoids with more favourable biophysical and pharmacokinetic properties for clinical use. It is envisaged that the development of viable alternative production systems for the synthesis of flavonoids and their methylated and glycosylated forms will help facilitate their greater clinical application.

A survey on the current clinical application and practice of helical tomotherapy in mainland China

Aim:To assess helical tomotherapy (TOMO) current clinical application and practice in mainland China.Materials and methods:Data were collected for all TOMO units clinically operational in mainland China by 30 April 2016, including (a) the distribution of installation and staffing levels; (b) types of cancers treated; (c) utilisation efficiency; (d) quality assurance; (e) maintenance; (f) optional features; and (g) satisfaction levels. The data were collected as a census and analysed qualitatively and quantitatively.Results:As of 30 April 2016, 23 TOMO units were used clinically by 22 hospitals in mainland China. In the same period, 22,558 cancer patients were treated. For TOMO units with more than a year of clinical utilisation, a median of 378 cases were treated annually per machine. The median daily operation was 10·5 hours, and treatment headcount was 38·3 patients. The median service outage rate was 2·6%, and the most common cause was malfunction of the multi-leaf collimator. In terms of overall satisfaction levels, 3 hospitals were very satisfied, 16 were satisfied and 3 considered their satisfaction level as average.Findings:The overall operation of TOMO is good, but there are some problems due to running at full capacity, lack of clinical efficacy research and insufficient quality assurance regulations.

Review of the Clinical Use of Fluoroscopy in Hand Surgery

Fluoroscopy is a commonly used tool in hand surgery. There have been recent advances in the technology and its clinical utilisation. Indications include assessment of joint and fracture fixation and stability, particularly when combined with minimally invasive techniques. Recent developments include surgeon operated mini C-arm image intensifiers. We present a review of the clinical utilisation of fluoroscopy in hand surgery including recent developments, Australian legislation, safety issues, strategies to reduce radiation exposure and clinical examples for imaging distal radius and scaphoid fracture fixation.