Project description:Adhesion formation after flexor tendon repair remains a clinical problem. Early postoperative motion after tendon repair has been demonstrated to reduce adhesion formation while increasing tendon strength. It is hypothesized that during mobilization, tendon cells experience mechanical shear forces that alter their biology in a fashion that reduces scar formation but also activates key genes involved in tendon healing. To test this hypothesis, primary intrinsic tenocyte cultures were established from flexor tendons of 20 Sprague-Dawley rats and sheared at 50 rpm (0.41 Pa) using a cone viscometer for 6 and 12 hours. Total RNA was harvested and compared with time-matched unsheared controls using cDNA microarrays and Northern blot analysis. Microarray analysis demonstrated that mechanical shear stress induced an overall "antifibrotic" expression pattern with decreased transcription of collagen type I and collagen type III. Shear stress down-regulated profibrotic molecules in the platelet-derived growth factor, insulin-like growth factor, and fibroblast growth factor signaling pathways. In addition, shear stress induced an overall decrease in transforming growth factor (TGF)-beta signaling pathway molecules with down-regulation of TGF-beta2, TGF-beta3, TGF-RI, and TGF-RII expression. Moreover, sheared tendon cells increased expression of matrix metalloproteinases and decreased expression of tissue inhibitors of metalloproteinase, an expression pattern consistent with an antifibrotic increase in extracellular matrix degradation. However, up-regulation of genes implicated in tendon healing, specifically, vascular endothelial growth factor-A and several bone morphogenetic proteins. Interestingly, the known mechanoresponsive gene, TGF-beta1, also implicated in tendon healing, was differentially up-regulated by shear stress. Northern blot validation of our results for TGF-beta1, TGF-beta2, TGF-beta3, and collagen type I demonstrated direct correlation with microarray data. Groups of assays that are related as part of a time series. Keywords: time_series_design

Project description:BackgroundPostoperative adhesions constitute a substantial clinical problem in hand surgery. Fexor tendon injury and repair result in adhesion formation around the tendon, which restricts the gliding function of the tendon, leading to decreased digit mobility and impaired hand recovery. This study evaluated the efficacy and safety of the peptide PXL01 in preventing adhesions, and correspondingly improving hand function, in flexor tendon repair surgery.MethodsThis prospective, randomised, double-blind trial included 138 patients admitted for flexor tendon repair surgery. PXL01 in carrier sodium hyaluronate or placebo was administered around the repaired tendon. Efficacy was assessed by total active motion of the injured finger, tip-to-crease distance, sensory function, tenolysis rate and grip strength, and safety parameters were followed, for 12 months post-surgery.ResultsThe most pronounced difference between the treatment groups was observed at 6 months post-surgery. At this timepoint, the total active motion of the distal finger joint was improved in the PXL01 group (60 vs. 41 degrees for PXL01 vs. placebo group, p = 0.016 in PPAS). The proportion of patients with excellent/good digit mobility was higher in the PXL01 group (61% vs. 38%, p = 0.0499 in PPAS). Consistently, the PXL01 group presented improved tip-to-crease distance (5.0 vs. 15.5 mm for PXL01 vs. placebo group, p = 0.048 in PPAS). Sensory evaluation showed that more patients in the PXL01 group felt the thinnest monofilaments (FAS: 74% vs. 35%, p = 0.021; PPAS: 76% vs. 35%, p = 0.016). At 12 months post-surgery, more patients in the placebo group were considered to benefit from tenolysis (30% vs. 12%, p = 0.086 in PPAS). The treatment was safe, well tolerated, and did not increase the rate of tendon rupture.ConclusionsTreatment with PXL01 in sodium hyaluronate improves hand recovery after flexor tendon repair surgery. Further clinical trials are warranted to determine the most efficient dose and health economic benefits.Trial registrationClinicalTrials.gov NCT01022242; EU Clinical Trials 2009-012703-25.

Project description:Adhesion formation after flexor tendon repair remains a clinical problem. Early postoperative motion after tendon repair has been demonstrated to reduce adhesion formation while increasing tendon strength. It is hypothesized that during mobilization, tendon cells experience mechanical shear forces that alter their biology in a fashion that reduces scar formation but also activates key genes involved in tendon healing. To test this hypothesis, primary intrinsic tenocyte cultures were established from flexor tendons of 20 Sprague-Dawley rats and sheared at 50 rpm (0.41 Pa) using a cone viscometer for 6 and 12 hours. Total RNA was harvested and compared with time-matched unsheared controls using cDNA microarrays and Northern blot analysis. Microarray analysis demonstrated that mechanical shear stress induced an overall "antifibrotic" expression pattern with decreased transcription of collagen type I and collagen type III. Shear stress down-regulated profibrotic molecules in the platelet-derived growth factor, insulin-like growth factor, and fibroblast growth factor signaling pathways. In addition, shear stress induced an overall decrease in transforming growth factor (TGF)-beta signaling pathway molecules with down-regulation of TGF-beta2, TGF-beta3, TGF-RI, and TGF-RII expression. Moreover, sheared tendon cells increased expression of matrix metalloproteinases and decreased expression of tissue inhibitors of metalloproteinase, an expression pattern consistent with an antifibrotic increase in extracellular matrix degradation. However, up-regulation of genes implicated in tendon healing, specifically, vascular endothelial growth factor-A and several bone morphogenetic proteins. Interestingly, the known mechanoresponsive gene, TGF-beta1, also implicated in tendon healing, was differentially up-regulated by shear stress. Northern blot validation of our results for TGF-beta1, TGF-beta2, TGF-beta3, and collagen type I demonstrated direct correlation with microarray data. Groups of assays that are related as part of a time series. Computed

Project description:Quality of life is enhanced by engagement in meaningful activities and participation using our hands. In African countries, people rely predominantly on the use of their hands to engage in economic productive activities, including agricultural, fishing, mining and construction, that are largely performed by machines in high-income contexts. Anecdotal evidence suggests a high incidence of flexor tendon injuries that are managed using protocols that were adopted from high-income countries and implemented without considering contextual differences. African therapists use discretion in selecting protocols thereby presenting inconsistency in tendon management. This result in challenges with ascertaining the most effective protocol, factors that influence protocols and the extent of evidence about flexor tendon rehabilitation in Africa. Therefore, this scoping review aims to provide evidence currently available on the rehabilitation of flexor tendons in African countries. This will synthesise the advantages and disadvantages of the current protocols and make proposals that are contextually relevant and cost-effective for rehabilitation of tendon injuries. METHODS AND ANALYSIS: The research will follow the scoping review methodological framework developed by Arksey and O'Malley (2005). The search strategy was developed and will be used to retrieve articles from eight databases. Further literature will be searched in the bibliography of the identified eligible articles. Grey literature will be searched in scientifically reliable websites, organisations and other sources. Articles will be reviewed by two independent researchers and opinion will be sought from a third reviewer when disagreement prevails on the inclusion quality of an article. All relevant articles that meet the criteria will be analysed using Weft QDA. ETHICS AND DISSEMINATION: The scoping review paper will be discussed with local therapists. Thereafter, findings will be published in the year 2021 and sent to rehabilitation associations in respective African countries.

Project description:ObjectivesTo understand help-seeking by male victims of domestic violence and abuse (DVA) and their experiences of support services by systematically identifying qualitative and mixed-method studies and thematically synthesising their findings.DesignSystematic review and qualitative evidence synthesis. Searches were conducted in 12 databases and the grey literature with no language or date restrictions. Quality appraisal of the studies was carried out using the Critical Appraisal Skills Programme tool. Reviewers extracted first and second order constructs related to help-seeking, identified themes and combined them by interpretative thematic synthesis.SettingDVA experienced by male victims and defined as any incident or pattern of incidents of controlling coercive or threatening behaviour, violence or abuse among people aged 18 or over who are or have been intimate partners or family members, regardless of gender or sexuality.ParticipantsMale victims of DVA.InterventionsAny intervention which provides practical and/or psychological support to male victims of DVA including but not limited to DVA-specific services, primary healthcare and sexual health clinics.Primary and secondary outcome measuresQualitative data describing help-seeking experiences and interactions with support services of male victims of domestic violence RESULTS: We included twelve studies which were published between 2006 and 2017. We grouped nine themes described over two phases (a) barriers to help-seeking: fear of disclosure, challenge to masculinity, commitment to relationship, diminished confidence/despondency and invisibility/perception of services; and (b) experiences of interventions and support: initial contact, confidentiality, appropriate professional approaches and inappropriate professional approaches.ConclusionThe recent publication of the primary studies suggests a new interest in the needs of male DVA victims. We have confirmed previously identified barriers to help-seeking by male victims of DVA and provide new insight into barriers and facilitators to service provision.Prospero registration numberCRD42016039999.

Dataset Information

Neck and Back Sprain and Hand Flexor Tendon Repair Are More Common in Victims of Domestic Violence Compared With Patients Who Were Not Victims of Domestic Violence: A Comparative Study of 1,204,596 Patients Using the National Trauma Data Bank.

Publications

Neck and Back Sprain and Hand Flexor Tendon Repair Are More Common in Victims of Domestic Violence Compared With Patients Who Were Not Victims of Domestic Violence: A Comparative Study of 1,204,596 Patients Using the National Trauma Data Bank.

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