Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty

BACKGROUND: The toxicity of released metallic particles generated in metal-on-metal (MoM) total hip arthroplasty (THA) using cobalt chromium (CoCr) has raised concerns regarding their safety amongst both surgeons and the public. Soft tissue changes such as pseudotumours and metallosis have been widely observed following the use of these implants, which release metallic by-products due to both wear and corrosion. Although activated fibroblasts, the dominant cell type in soft tissues, have been linked to many diseases, the role of synovial fibroblasts in the adverse reactions caused by CoCr implants remains unknown. To investigate the influence of implants manufactured from CoCr, the periprosthetic synovial tissues and synovial fibroblasts from patients with failed MoM THA, undergoing a revision operation, were analysed and compared with samples from patients undergoing a primary hip replacement, in order to elucidate histological and cellular changes. RESULTS: Periprosthetic tissue from patients with MoM implants was characterized by marked fibrotic changes, notably an increase in collagen content from less than 20% to 45-55%, an increase in α-smooth muscle actin positive cells from 4 to 9% as well as immune cells infiltration. Primary cell culture results demonstrated that MoM synovial fibroblasts have a decreased apoptosis rate from 14 to 6% compared to control synovial fibroblasts. In addition, synovial fibroblasts from MoM patients retained higher contractility and increased responsiveness to chemotaxis in matrix contraction. Their mechanical properties at a single cell level increased as observed by a 60% increase in contraction force and higher cell stiffness (3.3 kPa in MoM vs 2.18 kPa in control), as measured by traction force microscopy and atomic force microscopy. Further, fibroblasts from MoM patients promoted immune cell invasion by secreting monocyte chemoattractant protein 1 (MCP-1, CCL2) and induced monocyte differentiation, which could also be associated with excess accumulation of synovial macrophages. CONCLUSION: Synovial fibroblasts exposed in vivo to MoM THA implants that release CoCr wear debris displayed dramatic phenotypic alteration and functional changes. These findings unravelled an unexpected effect of the CoCr alloy and demonstrated an important role of synovial fibroblasts in the undesired tissue reactions caused by MoM THAs

Increased throughput and ultra-high mass resolution in DESI FT-ICR MS imaging through new-generation external data acquisition system and advanced data processing approaches

Desorption electrospray ionisation-mass spectrometry imaging (DESI-MSI) is a powerful imaging technique for the analysis of complex surfaces. However, the often highly complex nature of biological samples is particularly challenging for MSI approaches, as options to appropriately address mass spectral complexity are limited. Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) offers superior mass accuracy and mass resolving power, but its moderate throughput inhibits broader application. Here we demonstrate the dramatic gains in mass resolution and/or throughput of DESI-MSI on an FT-ICR MS by developing and implementing a sophisticated data acquisition and data processing pipeline. The presented pipeline integrates, for the first time, parallel ion accumulation and detection, post-processing absorption mode Fourier transform and pixel-by-pixel internal re-calibration. To achieve that, first, we developed and coupled an external high-performance data acquisition system to an FT-ICR MS instrument to record the time-domain signals (transients) in parallel with the instrument’s built-in electronics. The recorded transients were then processed by the in-house developed computationally-efficient data processing and data analysis software. Importantly, the described pipeline is shown to be applicable even to extremely large, up to 1 TB, imaging datasets. Overall, this approach provides improved analytical figures of merits such as: (i) enhanced mass resolution at no cost in experimental time; and (ii) up to 4-fold higher throughput while maintaining a constant mass resolution. Using this approach, we not only demonstrate the record 1 million mass resolution for lipid imaging from brain tissue, but explicitly demonstrate such mass resolution is required to resolve the complexity of the lipidome

Free electron laser-fourier transform ion cyclotron resonance mass spectrometry facility for obtaining infrared multiphoton dissociation spectra of gaseous ions

Contains fulltext : 98866.pdf (publisher's version ) (Open Access

Data from: Linking the vectorial capacity of multiple vectors to observed patterns of West Nile virus transmission

1. Theoretical models suggest that increased vector species participation in pathogen transmission significantly increases the prevalence of vector and host infections. However, there has been a lack of empirical evidence to support this. 2. We linked transmission potential of multiple vectors species to observed patterns of enzootic pathogen transmission by conducting longitudinal field surveillance of West Nile virus (WNv) infections in Culex spp. mosquitoes and avian host communities in the southeastern U.S. We then used a temperature-dependent vectorial capacity model as a predictor of WNv infections in mosquitoes and birds using general linear mixed effects models. 3. Two WNv-competent Culex spp. mosquitoes were present in our study sites, Culex restuans Theobald during the spring and Culex quinquefasciatus Say during the summer. Empirical evidence of WNv transmission was limited exclusively to time periods when night time temperatures were suitable for accelerated within-vector viral replication, susceptible avian hosts (i.e. hatch year birds) were abundant, and Culex quinquefasciatus was the primary Culex spp. vector in the mosquito community. 4. Contrary to theoretical predictions, increased presence of competent vector species through time did not significantly increase the prevalence of infections in the WNv enzootic system. 5. Synthesis and applications. We extend a commonly used theoretical framework to quantify transmission potential of vector-borne diseases, the vectorial capacity equation, to account for species-specific variations in temperature-dependent development and host feeding preference. By quantifying key vectorial capacity parameters using field data from southeast United States we quantified the relative contribution of two Culex spp. species (Culex pipiens quinquefasciatus and Culex restuans) to the transmission of West Nile virus (WNv). Our findings suggest that to reduce the risk of human exposure to WNv in urban environments, vector control should focus on the primary WNv vector, the members of the Culex pipiens complex. Additionally, vector control may be more effective if it coincides with the onset of the avian breeding season, when most WNv amplification occurs. Moreover, our results highlight relevant knowledge gaps pertaining to WNv transmission by secondary mosquito species that coexist either in time or space with Culex pipiens complex mosquitoes. A better understanding of secondary WNv vector species is greatly needed in order to appropriately gauge their role in pathogen transmission dynamics