Identify gene changes in articular cartilage of the medial tibial plateau (MTP) at 2, 4 and 8 weeks after destabilisation of the medial meniscus (DMM) in mice. Compare our data with previously published datasets to ascertain dysregulated pathways and genes in osteoarthritis (OA). RNA was extracted from the ipsilateral and contralateral MTP cartilage, amplified, labelled and hybridized on Illumina WGv2 microarrays. Results were confirmed by real-time polymerase chain reaction (PCR) for selected genes. Transcriptional analysis and network reconstruction revealed changes in extracellular matrix and cytoskeletal genes induced by DMM. TGFβ signalling pathway and complement and coagulation cascade genes were regulated at 2 weeks. Fibronectin (Fn1) is a hub in a reconstructed network at 2 weeks. Regulated genes decrease over time. By 8 weeks fibromodulin (Fmod) and tenascin N (Tnn) are the only dysregulated genes present in the DMM operated knees. Comparison with human and rodent published gene sets identified genes overlapping between our array and eight other studies. Cartilage contributes a minute percentage to the RNA extracted from the whole joint (<0.2%), yet is sensitive to changes in gene expression post-DMM. The post-DMM transcriptional reprogramming wanes over time dissipating by 8 weeks. Common pathways between published gene sets include focal adhesion, regulation of actin cytoskeleton and TGFβ. Common genes include Jagged 1 (Jag1), Tetraspanin 2 (Tspan2), neuroblastoma, suppression of tumourigenicity 1 (Nbl1) and N-myc downstream regulated gene 2 (Ndrg2). The concomitant genes and pathways we identify may warrant further investigation as biomarkers or modulators of OA.

Background: Advances in natural language processing and other machine learning techniques have led to the development of automated agents (chatbots) that mimic human conversation. These systems have mainly been used in commercial settings, and within medicine, for symptom checking and psychotherapy. The aim of this systematic review was to determine the acceptability and implementation success of chatbots in the follow-up of patients who have undergone a physical healthcare intervention. Methods: A systematic review of MEDLINE, MEDLINE In-process, EMBASE, PsychINFO, CINAHL, CENTRAL and the grey literature using a PRISMA-compliant methodology up to September 2020 was conducted. Abstract screening and data extraction were performed in duplicate. Risk of bias and quality assessments were performed for each study. Results: The search identified 904 studies of which 10 met full inclusion criteria: three randomised control trials, one non-randomised clinical trial and six cohort studies. Chatbots were used for monitoring after the management of cancer, hypertension and asthma, orthopaedic intervention, ureteroscopy and intervention for varicose veins. All chatbots were deployed on mobile devices. A number of metrics were identified and ranged from a 31 per cent chatbot engagement rate to a 97 per cent response rate for system-generated questions. No study examined patient safety. Conclusion: A range of chatbot builds and uses was identified. Further investigation of acceptability, efficacy and mechanistic evaluation in outpatient care pathways may lend support to implementation in routine clinical care.

Wire localization is historically the most common method for guiding excision of non-palpable breast lesions, but there are limitations to the technique. Newer technologies such as magnetic seeds may allow some of these challenges to be overcome. The aim was to compare safety and effectiveness of wire and magnetic seed localization techniques. Women undergoing standard wire or magnetic seed localization for non-palpable lesions between August 2018 and August 2020 were recruited prospectively to this IDEAL stage 2a/2b platform cohort study. The primary outcome was effectiveness defined as accurate localization and removal of the index lesion. Secondary endpoints included safety, specimen weight and reoperation rate for positive margins. Data were accrued from 2300 patients in 35 units; 2116 having unifocal, unilateral breast lesion localization. Identification of the index lesion in magnetic-seed-guided (946 patients) and wire-guided excisions (1170 patients) was 99.8 versus 99.1 per cent (P = 0.048). There was no difference in overall complication rate. For a subset of patients having a single lumpectomy only for lesions less than 50 mm (1746 patients), there was no difference in median closest margin (2 mm versus 2 mm, P = 0.342), re-excision rate (12 versus 13 per cent, P = 0.574) and specimen weight in relation to lesion size (0.15 g/mm² versus 0.138 g/mm², P = 0.453). Magnetic seed localization demonstrated similar safety and effectiveness to those of wire localization. This study has established a robust platform for the comparative evaluation of new localization devices.

More than 40% of individuals will develop osteoarthritis (OA) during their lifetime, yet there are currently no licensed disease-modifying treatments for this disabling condition. Common polymorphic variants in ALDH1A2 , which encodes the key enzyme for synthesis of all-trans retinoic acid (atRA), are associated with severe hand OA. Here, we sought to elucidate the biological significance of this association. We first confirmed that ALDH1A2 risk variants were associated with hand OA in the U.K. Biobank. Articular cartilage was acquired from 33 individuals with hand OA at the time of routine hand OA surgery. After stratification by genotype, RNA sequencing was performed. A reciprocal relationship between ALDH1A2 mRNA and inflammatory genes was observed. Articular cartilage injury up-regulated similar inflammatory genes by a process that we have previously termed mechanoflammation, which we believe is a primary driver of OA. Cartilage injury was also associated with a concomitant drop in atRA-inducible genes, which were used as a surrogate measure of cellular atRA concentration. Both responses to injury were reversed using talarozole, a retinoic acid metabolism blocking agent (RAMBA). Suppression of mechanoflammation by talarozole was mediated by a peroxisome proliferator–activated receptor gamma (PPARγ)–dependent mechanism. Talarozole was able to suppress mechano-inflammatory genes in articular cartilage in vivo 6 hours after mouse knee joint destabilization and reduced cartilage degradation and osteophyte formation after 26 days. These data show that boosting atRA suppresses mechanoflammation in the articular cartilage in vitro and in vivo and identifies RAMBAs as potential disease-modifying drugs for OA.

Splinting techniques are widely used in medicine to inhibit the movement of arthritic joints. Studies into the effectiveness of splinting as a method of pain reduction have generally yielded positive results, however, no significant difference has been found in clinical outcomes between splinting types. Tactile sensing has shown great promise for the integration into splinting devices and may offer further information into applied forces to find the most effective methods of splinting. Hall effect-based tactile sensors are of particular interest in this application owing to their low-cost, small size, and high robustness. One complexity of the sensors is the relationship between the elastomer geometry and the measurement range. This paper investigates the design parameters of Hall effect tactile sensors for use in hand splinting. Finite element simulations are used to locate the areas in which sensitivity is high in order to optimise the deflection range of the sensor. Further simulations then investigate the mechanical response and force ranges of the elastomer layer under loading which are validated with experimental data. A 4 mm radius, 3 mm-thick sensor is identified as meeting defined sensing requirements for range and sensitivity. A prototype sensor is produced which exhibits a pressure range of 45 kPa normal and 6 kPa shear. A proof of principle prototype demonstrates how this can be integrated to form an instrumented splint with multi-axis sensing capability and has the potential to inform clinical practice for improved splinting.