Royal Devon and Exeter Hospital

About: Royal Devon and Exeter Hospital is a healthcare organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Randomized controlled trial. The organization has 2282 authors who have published 2526 publications receiving 78866 citations. The organization is also known as: RD&E.

Anterior Cruciate Ligament Mechanoreceptors and their Potential Importance in Remnant-Preserving Reconstruction: A Review of Basic Science and Clinical Findings.

Abstract: Mechanoreceptors, within the anterior cruciate ligament (ACL), are believed to have importance in proprioception, contributing to dynamic knee stability. The potential for reinnervation of the ACL graft is one of the proposed advantages of remnant-preserving reconstruction. The aim of this review is to summarize advances in the basic science underpinning this function, alongside recent clinical studies, to define the current role for remnant-preservation. A comprehensive systematic review was performed using PubMed and Medline searches. Studies were analyzed with particular focus placed on the methodology used to either identify mechanoreceptors or test proprioception. Contemporary work, using immunohistological staining, has shown mechanoreceptors primarily within proximity to the bony attachments of the ACL (peripherally in the subsynovial layer). The number of these receptors has been shown to decrease rapidly, following rupture, with adhesion to the posterior cruciate ligament slowing this decline. Recent studies have shown proprioceptive deficits, in both the injured and contralateral knees, with the clinical relevance of findings limited by testing methodology and the small differences found. The advantages of remnant-preservation, seen primarily in animal studies, have not been shown in systematic reviews or meta-analysis of clinical studies. The potential for reinnervation of the graft is likely time-dependent and reliant on continued loading of the remnant. Therefore, current clinical use and future research should focus on preserving remnants within 6 months of injury that remain loaded by adherence to the posterior cruciate ligament. Subsequent testing should account for central neurological changes and focus on clinically relevant outcomes.

Elevated circulating follistatin associates with an increased risk of type 2 diabetes.

Abstract: The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04-1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09-1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.

The role of bariatric surgery in the treatment of diabetes

Abstract: The obesity epidemic contributes to approximately 44% of the world’s type 2 diabetes burden. Bariatric surgery is an effective treatment for type 2 diabetes mellitus in patients with morbid obesity as it improves glycaemia, blood pressure, lipids and inflammation. This review describes the evidence supporting the addition of bariatric surgery to the treatment algorithms used by diabetologists. We emphasize the need to view bariatric surgery as an adjuvant therapy which should not be used instead of but rather together with best medical therapy.

Porcine dermis implants in soft-tissue reconstruction: current status.

Abstract: Soft-tissue reconstruction for a variety of surgical conditions, such as abdominal wall hernia or pelvic organ prolapse, remains a challenge. There are numerous meshes available that may be simply categorized as either synthetic or biologic. Within biologic meshes, porcine dermal meshes have come to dominate the market. This review examines the current evidence for their use and the limitations of knowledge. Although there is increasing evidence to support their safety, long-term follow-up studies that support their efficacy are lacking. Numerous clinical trials that remain ongoing may help elucidate their precise role in soft-tissue reconstruction.

Integrating healthcare and research genetic data empowers the discovery of 49 novel developmental disorders

Abstract: De novo mutations (DNMs) in protein-coding genes are a well-established cause of developmental disorders (DD). However, known DD-associated genes only account for a minority of the observed excess of such DNMs. To identify novel DD-associated genes, we integrated healthcare and research exome sequences on 31,058 DD parent-offspring trios, and developed a simulation-based statistical test to identify gene-specific enrichments of DNMs. We identified 299 significantly DD-associated genes, including 49 not previously robustly associated with DDs. Despite detecting more DD-associated genes than in any previous study, much of the excess of DNMs of protein-coding genes remains unaccounted for. Modelling suggests that over 500 novel DD-associated genes await discovery, many of which are likely to be less penetrant than the currently known genes. Research access to clinical diagnostic datasets will be critical for completing the map of dominant DDs.