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.

Rab32 connects ER stress to mitochondrial defects in multiple sclerosis

Abstract: Endoplasmic reticulum (ER) stress is a hallmark of neurodegenerative diseases such as multiple sclerosis (MS). However, this physiological mechanism has multiple manifestations that range from impaired clearance of unfolded proteins to altered mitochondrial dynamics and apoptosis. While connections between the triggering of the unfolded protein response (UPR) and downstream mitochondrial dysfunction are poorly understood, the membranous contacts between the ER and mitochondria, called the mitochondria-associated membrane (MAM), could provide a functional link between these two mechanisms. Therefore, we investigated whether the guanosine triphosphatase (GTPase) Rab32, a known regulator of the MAM, mitochondrial dynamics, and apoptosis, could be associated with ER stress as well as mitochondrial dysfunction. We assessed Rab32 expression in MS patient and experimental autoimmune encephalomyelitis (EAE) tissue, via observation of mitochondria in primary neurons and via monitoring of survival of neuronal cells upon increased Rab32 expression. We found that the induction of Rab32 and other MAM proteins correlates with ER stress proteins in MS brain, as well as in EAE, and occurs in multiple central nervous system (CNS) cell types. We identify Rab32, known to increase in response to acute brain inflammation, as a novel unfolded protein response (UPR) target. High Rab32 expression shortens neurite length, alters mitochondria morphology, and accelerates apoptosis/necroptosis of human primary neurons and cell lines. ER stress is strongly associated with Rab32 upregulation in the progression of MS, leading to mitochondrial dysfunction and neuronal death.

Monogenic diabetes: a gateway to precision medicine in diabetes

Abstract: Monogenic diabetes refers to diabetes mellitus (DM) caused by a mutation in a single gene and accounts for approximately 1%-5% of diabetes Correct diagnosis is clinically critical for certain types of monogenic diabetes, since the appropriate treatment is determined by the etiology of the disease (eg, oral sulfonylurea treatment of HNF1A/HNF4A-diabetes vs insulin injections in type 1 diabetes) However, achieving a correct diagnosis requires genetic testing, and the overlapping of the clinical features of monogenic diabetes with those of type 1 and type 2 diabetes has frequently led to misdiagnosis Improvements in sequencing technology are increasing opportunities to diagnose monogenic diabetes, but challenges remain In this Review, we describe the types of monogenic diabetes, including common and uncommon types of maturity-onset diabetes of the young, multiple causes of neonatal DM, and syndromic diabetes such as Wolfram syndrome and lipodystrophy We also review methods of prioritizing patients undergoing genetic testing, and highlight existing challenges facing sequence data interpretation that can be addressed by forming collaborations of expertise and by pooling cases

Management of Periprosthetic Joint Infection After Total Hip Arthroplasty Using a Custom Made Articulating Spacer (CUMARS); the Exeter Experience

Abstract: Periprosthetic joint infection (PJI) after THA is a major complication with an incidence of 1%-3%. We report our experiences with a technique using a custom-made articulating spacer (CUMARS) at the first of two-stage treatment for PJI. This technique uses widely available all-polyethylene acetabular components and the Exeter Universal stem, fixed using antibiotic loaded acrylic cement. Seventy-six hips were treated for PJI using this technique. Performed as the first of a two-stage procedure, good functional results were commonly seen, leading to postponing second stage indefinitely with retention of the CUMARS prosthesis in 34 patients. The CUMARS technique presents an alternative to conventional spacers, using readily available components that are well tolerated, allowing weight bearing and mobility, and achieving comparable eradication rates.

Dynamic compression plates for Vancouver type B periprosthetic femoral fractures: A 3-year follow-up of 18 cases

Abstract: Background There is no consensus on the best surgical treatment of periprosthetic femoral fractures. We report our experience with a dynamic compression plate.Patients and methods We reviewed the results of 18 periprosthetic femoral fractures treated with open reduction and internal fixation using the dynamic compression plate (DCP). There were 7 Vancouver type B1, 2 type B2 and 9 type B3 fractures. 16 cases had previously undergone at least one revision procedure. In addition to a DCP plate, all B2 and B3 fractures were revised to cemented prostheses, and all B3 fractures were revised with impaction grafting. Mean follow-up was 39 months.Results The mean healing time for those 11 cases that united was 13 months. One B1-type and one B3-type fracture with plate fracture within 8 months of surgery failed to heal. Furthermore, one B1-type fracture and one B2-type fracture failed and developed nonunion. 3 patients died, from causes not related to surgery, within 8 months after surgery without signs of healing...