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Arthritogenic alphavirus infections often result in debilitating musculoskeletal disorders that affect the joints, muscle, and bone. In order to evaluate the infection profile of primary human skeletal muscle and chondrocyte cells to Ross River virus (RRV) in vitro, cells were infected at a multiplicity of infection (MOI) of 1 over a period of two days. Viral titers were determined by plaque assay and cytokine expression by Bio-Plex® assays using the supernatants harvested. Gene expression studies were conducted using total RNA isolated from cells. Firstly, we show that RRV RNA is detected in chondrocytes from infected mice in vivo. Both human primary skeletal muscle and chondrocyte cells are able to support productive RRV infection in vitro. We also report the production of soluble host factors including the upregulation of heparanase (HPSE) and inflammatory host factors such as interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated on activation, normal T cell expressed and secreted), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α), which are also present during clinical disease in humans. Our study is the first to demonstrate that human chondrocyte cells are permissive to RRV infection, support the production of infectious virus, and produce soluble factors including HPSE, which may contribute to joint degradation and the pathogenesis of disease.

Purpose Carpal tunnel syndrome (CTS) is characterized anatomically by enlargement of the median nerve (MN) at the wrist. To better understand the 3D morphology and volume of the enlargement, we studied its volume using automated segmentation of ultrasound (US) images in 10 volunteers and 4 patients diagnosed with CTS. Method US images were acquired axially for a 4 cm MN segment from the proximal carpal tunnel region to mid-forearm in 10 volunteers and 4 patients with CTS, yielding over 18,000 images. We used U-Net with ConvNet blocks to create a model of MN segmentation for CTS study, compared to manual measurements by two readers. Results The average Dice Similarity Coefficient (DSC) on the internal and external validation datasets was 0.82 and 0.81, respectively, and the area under the curve (AUC) was 0.92 and 0.88, respectively. The inter-reader correlation DSC was 0.83, and the AUC was 0.98. The correlation between U-Net and manual tracing was best when the MN was near the surface. A US phantom mimicking the MN, imaged at varied scanning speeds from 7 to 45 mm/s, showed the volume measurements were consistent. Conclusion Our AI model effectively segmented the MN to calculate MN volume, which can now be studied as a potential biomarker for CTS, along with the already established biomarker, cross-sectional area.

Carpal tunnel syndrome (CTS) is a common musculoskeletal disorder, characterized by thickening and fibrosis of the subsynovial connective tissue (SSCT). Risk factors for CTS includes sex, metabolic dysfunction and age. In this study we hypothesized that a high-fat diet (HFD), a common driver of metabolic dysfunction, would promote SSCT thickening in CTS and that this response would be sex dependent. To test this, we examined the effects of HFD and sex on SSCT thickening and markers of fibrosis using our established CTS rabbit model of SSCT thickening. Forty-eight (24 male, 24 female) adult rabbits were split into four groups including HFD or standard diet with and without CTS induction. SSCT was collected for histological and gene expression analysis. HFD promoted SSCT thickening and upregulated profibrotic genes, including TGF-β. Fibrotic genes were differentially expressed in males and females. Interestingly while the overall prevalence of CTS is greater in women than in men, under conditions of metabolic dysfunction men have a higher incidence. This suggests a focus on metabolic and sex specific therapeutic strategies for the treatment of patients with CTS.

Carpal tunnel syndrome (CTS) is a common musculoskeletal disorder, characterized by fibrosis of the subsynovial connective tissue (SSCT) mediated by transforming growth factor beta (TGF-β). Risk factors for CTS include metabolic dysfunction and age. Additionally, the incidence of CTS is higher in women. In this study we hypothesized that a high-fat diet (HFD), a common driver of metabolic dysfunction, would promote SSCT fibrosis found in CTS and that this response would be sex dependent. To test this, we examined the effects of HFD and sex on SSCT fibrosis using our established rabbit model of CTS. Forty-eight (24 male, 24 female) adult rabbits were divided into four groups including HFD or standard diet with and without CTS induction. SSCT was collected for histological and gene expression analysis. HFD promoted SSCT thickening and upregulated profibrotic genes, including TGF-β. Fibrotic genes were differentially expressed in males and females. Interestingly while the prevalence of CTS is greater in women than in men, the converse is observed in the presence of metabolic dysfunction. This work recapitulates this clinical observation and begins to elucidate the sex-based differences found in SSCT fibrosis. This knowledge should drive further research and may lead to metabolic and sex specific therapeutic strategies for the treatment of patients with CTS.Carpal tunnel syndrome (CTS) is a common musculoskeletal disorder, characterized by fibrosis of the subsynovial connective tissue (SSCT) mediated by transforming growth factor beta (TGF-β). Risk factors for CTS include metabolic dysfunction and age. Additionally, the incidence of CTS is higher in women. In this study we hypothesized that a high-fat diet (HFD), a common driver of metabolic dysfunction, would promote SSCT fibrosis found in CTS and that this response would be sex dependent. To test this, we examined the effects of HFD and sex on SSCT fibrosis using our established rabbit model of CTS. Forty-eight (24 male, 24 female) adult rabbits were divided into four groups including HFD or standard diet with and without CTS induction. SSCT was collected for histological and gene expression analysis. HFD promoted SSCT thickening and upregulated profibrotic genes, including TGF-β. Fibrotic genes were differentially expressed in males and females. Interestingly while the prevalence of CTS is greater in women than in men, the converse is observed in the presence of metabolic dysfunction. This work recapitulates this clinical observation and begins to elucidate the sex-based differences found in SSCT fibrosis. This knowledge should drive further research and may lead to metabolic and sex specific therapeutic strategies for the treatment of patients with CTS.

Les personnes âgées sont davantage touchées par la peur du crime et de la victimisation, tout en étant à faible risque pour les dommages que n’importe quel autre groupe de la population canadienne. Le crime, la victimisation et la peur ne sont pas ressentis d’une manière uniforme chez les citoyens canadiens et résidents plus âgées, en partie parce que les personnes âgées ne forment pas un groupe homogène. Faire partie d’une minorité ethnique, religieuse ou sexuelle, ou d’être fragile mentalement, peuvent avoir un impact sur la perception et l’expérience du risque d’un individu. Cette analyse explore la victimisation des personnes âgées, tout en soulignant le manque de cohérence dans les données disponibles. Older people are more affected by fear of crime and the possibility of victimization, despite their being at lower risk of harm, than any other population group in Canada. Crime, victimization, and fear are not experienced uniformly among older Canadian citizens and residents, partly because older people do not form a homogeneous group. Being part of an ethnic, religious, or sexual minority, or being mentally frail, can have an impact on an individual’s perceptions and experience of risk. This analysis explores older people’s victimization and fear of crime, while it highlights the lack of consistency in the available data.