Joint tissues release extracellular vesicles (EVs) that potentially sustain joint homeostasis and contribute to osteoarthritis (OA) pathogenesis. EVs are putative novel therapeutics for OA, and transport biologically active molecules (including small non-coding RNAs (SNCRNAs)) between cells. This study identified altering SNCRNA cargo in EVs in OA which may act as early diagnostic markers and treatment targets. OA was surgically induced in four skeletally mature Standardbred horses using an osteochondral fragment model in the left middle carpal joint. The right joint underwent sham surgery. Synovial fluid (SF) and plasma were obtained weekly throughout the 70-day study. EVs were isolated using size exclusion chromatography and characterised using nanoparticle tracking (Nanosight), and exosome fluorescence detection and tetraspanin phenotyping (Exoview). RNA was extracted from EVs derived from SF (sham and OA joints) and plasma collected at days 10, 35, 42, 49, 56, 63, and subjected to small RNA sequencing on a NovaSeq SP100 flow cell (Illumina). Nanosight-derived EV characteristics of size and concentration were not significantly different following disease induction. The diameter of the temporal population of plasma and SF-derived exosomes changed significantly for CD9 and CD81 following OA induction with significant temporal, and disease-related changes in CD63 and CD81 protein expressin in plasma and SF. In SF and plasma-derived EVs snoRNAs, snRNAs, tRNAs, lncRNA, y-RNA, piRNAs and scRNA were found. Following pairwise analysis of all-time points we identified 27 miRs DE in plasma and 45 DE miRs in SF. Seven were DE in plasma and SF; miR-451, miR-25, miR-215, miR-92a, miR-let-7c, miR-486-5p, miR-23a. In plasma and SF 35 and 21 snoRNAs were DE with four DE in plasma and SF; U3, snord15, snord46, snord58. This work has identified alterations to OA EV sncRNAs in plasma and SF providing a greater understanding of the role of EVs in early OA.
We implemented an exhaustive operative and supervision algorithm for surgical treatment of hip fractures primarily based on own previously published literature. The purpose was to improve supervision and reduce the rate of reoperations. 2000 consecutive unselected patients above 50 years admitted with a hip fracture were included, 1000 of these prospectively after implementation of the algorithm. Demographic parameters, hospital treatment and reoperations within the first postoperative year were assessed from patient records. The algorithm dictated the surgical treatment based on three objective patient parameters: age, new mobility score and fracture classification on pre-operative anterior-posterior and axial radiographs. Intra capsular fractures were treated with two parallel implants, a sliding hip screw, an arthroplasty or resection of the femoral head. Extra capsular fractures were treated with a sliding hip screw or an intramedullary nail. Supervision of junior registrars was mandatory for the prosthesis and intramedullary nail procedures.Introduction
Materials and methods
To compare the effectiveness of the McKenzie method and spinal manipulation when used adjunctive to information and advice for patients with clinical signs suggestive of disc-related symptoms for duration of more than 6 Weeks. The conclusions drawn from previous randomised studies have been contradictory. The need for studies testing treatment strategies to specific diagnostic subgroups has been emphasised.Purpose
Background
During the operative procedure, the lateral femoral wall was fractured in 6% (9/158) of patients, in which an IMHS was performed versus 28% (42/153) operated with a DHS (p<
0.001). Among the DHS, a fractured lateral femoral wall was confirmed to be a predictor of a reoperation (31% (13/42) of patients with a fractured lateral femoral wall versus 8% (9/111) with an intact lateral femoral wall, p<
0.001). As in other studies, the different reoperation rate would have been overseen in the main group of AO/ OTA type 31A1-2 PTF fractures (4% (6/164) IMHS versus 6% (30/471) DHS, p=0.196).
After implementing the guideline, the rate of unsupervised junior registrars performing operations declined from 20% (188/938) to 6% (21/336, p<
0.001 X2). The rate of reoperations declined from 15% (139/938) to 10% (35/336, p=0.044 X2, p=0.043 log.reg.), with a 20% (85/436) to 13% (23/174) decline for intracapsulary and an 11% (54/502) to 7% (12/162) decline for extracapsulary fractures.
In 1993 standardized, lateral radiographs of the lumbar spine were recorded and the bone mineral density (BMD) was estimated by digital x-ray radiogrammetry of standardised hand x-rays.