Failure of Primary Total Knee Arthroplasty: Establishing a Baseline for Retrieval Analysis Using Well-Functioning Necropsy Specimens

Introduction. Total knee arthroplasty (TKA) is an effective treatment for end-stage osteoarthritis of the knee. While many patients have positive functional and pain outcomes following primary TKA, a subset of patients have suboptimal outcomes, such as unexplained pain or aseptic loosening of the implant components necessitating revision of the index procedure. The understanding of the exact etiology of these suboptimal outcomes of primary TKA is in its infancy. In order to elucidate the etiology of failure in primary TKAs, a baseline for the factors contributing to arthroplasty failure and dissatisfaction must first be established. The purpose of this study was to investigate the relationship between soft tissue laxity, inflammatory cytokine concentrations, tissue metal concentrations, and wear scores of well-functioning implants retrieved from cadaveric specimens to determine the role of each of these factors in implant survivorship. It was hypothesized that decreased joint laxity would increase metal concentrations in the periprosthetic tissue, that cytokines specifically tied to the innate immune system would be elevated in laxer joints, and, lastly, that elevated inflammatory cytokines in the synovial fluid would be associated with elevated periprosthetic tissue metal concentrations. Methodology. A total of 33 cadaveric specimens with primary TKA were obtained from two sources, the Medical Education and Research Institute (Memphis, TN) and RestoreLife USA (Elizabethton, TN), as part of institution review board approved multi-institutional orthopaedic retrieval program. Prior to testing and retrieval, fluoroscopically-assisted radiographs were taken to assess if any evidence of radiolucencies were present and all replacements were determined to be well-fixed per the images. Synovial fluid was then aspirated from the joint, processed, and stored in a -80˚C freezer. Each specimen was mounted into a custom knee testing platform and the IE rotation, varus-valgus (VV) deflection, and AP translation was measured at 0˚, 30˚, 60˚, and 90˚ of flexion. After collection of the laxity data, tissue samples were collected from the supra- and infra-patellar regions, the medial and lateral gutter, and from the tibia. The polyethylene inserts were assessed for wear on the condylar, backside, and stabilizing post surfaces, when applicable, and the femoral condyle was assessed for damage. A bead-based multiplex assay using the Luminex MAGPIX platform (R&D Systems, Minneapolis, MN) was performed on the synovial aspirates for simultaneous detection of various inflammatory cytokines including: IL-1β, IL-6, MCP-1, and MIP-3α. Inductively coupled plasma mass spectrometry (ICP-MS) was performed at Brooks Applied Labs (Bothel, WA) on the periprosthetic tissue samples for determination of tissue cobalt (Co), chromium (Cr), and titanium (Ti) concentrations. Finally, statistical analysis was conducted using SigmaPlot (Systat Software, Chicago, IL) to elucidate whether any correlations existed between the aforementioned factors. Results. Decreased IE laxity at full extension was inversely correlated with increased Co concentrations in the periprosthetic tissues (ρ=-0.64, p=0.02) with a sample size (n) of 13 and a 95% confidence interval (CI) from -0.88 to -0.14. At 90° of flexion, anterior laxity was inversely correlated with Co concentrations (ρ=-0.66, p=0.03, n=11, 95% CI: -0.90 vi to -0.10). At 60° of flexion, anterior laxity was inversely correlated with Cr concentrations (ρ=-0.63, p=0.03, n=13, 95% CI: -0.88 to -0.12). Anterior laxity at 90° of flexion was also inversely correlated with Cr concentrations (ρ=-0.81, p=0.003, n=11, 95% CI: -0.95 to -0.41). Lastly, posterior laxity at 90° of flexion was inversely correlated with Cr concentrations in the periprosthetic tissues (ρ=-0.74, p=0.01, n=11, 95% CI: -0.93 to -0.25). At 60° of flexion, IE rotational laxity was inversely correlated with IL-1β concentrations (ρ=-0.55, p=0.02, n=18, 95% CI: -0.81 to -0.11). At 60° of flexion, VV laxity was inversely correlated with TNF-α concentrations (ρ=-0.78, p=2x10-4 , n=14, 95% CI -0.93 to -0.43). Additionally, VV laxity was inversely correlated with IL-1β concentrations (ρ=-0.48, p=0.04, n=18, 95% CI: -0.77 to -0.02) at 60° of flexion. At full extension, VV laxity was inversely correlated with IL-6 concentrations (ρ=-0.46, p=0.04, n=19, 95% CI: -0.76 to -0.01). Anterior laxity was directly correlated with IL-6 concentrations (ρ=0.53, p=0.02, n=18, 95% CI: 0.08 to 0.80) at 90° of flexion. Additionally, anterior laxity was directly correlated with MCP-1 concentrations (ρ=0.62, p=0.006, n=18, 95% CI: 0.22 to 0.84) at 90° of flexion. Cr was inversely correlated with IL-6 (ρ=-0.52, p=0.01, n=21, 95% CI: -0.78 to -0.11). Cr was also inversely correlated with MIP-3α (ρ=-0.46, p=0.04, n=21, 95% CI: -0.74 to -0.04). Discussion. The specimens included in this study consisted of primary TKA implants that were retrieved at necropsy and were determined to be well-fixed per fluoroscopic analysis. The first objective of this study was to establish a baseline of different factors that likely contribute to failure of primary total knee replacements. This study provided semi-quantitative assessment of wear of the condylar surface, backside surface, and stabilizing post, when applicable, and of damage to the bearing surface of the femoral components. Joint laxity was measured using a custom knee testing platform that had been previously studied and utilized in published journal articles and theses. Inflammatory cytokine profiles in the synovial fluid samples were presented and measureable levels of metal debris was found in the periprosthetic tissue samples. The second objective of this study was to determine if any significant relationships arose in correlation analysis of the latter three aforementioned factors. An inverse trend was observed between joint laxity and tissue metal concentrations, such that decreased laxity induced metal release from the implant components. A direct trend was observed specifically between increased anteroposterior laxity and elevated inflammatory cytokines. Lastly, an inverse trend was found between decreased tissue metal concentrations and increased inflammatory cytokines. The third, and future, objective of this study is to utilize these measurements and observations for comparison with failed implants retrieved at time of revision. While some meaningful relationships were observed in this study, there were several limitations that must be noted. Firstly, this study had a relatively small sample size. Secondly, the cohort included a wide range of implants including cruciate-retaining, posterior-stabilized, fixed bearing, mobile bearing, monoblock, and modular designs fabricated from different material

Relativistic Landau resonances

The possible interactions between plasma waves and relativistic charged particles are considered. An electromagnetic perturbation in the plasma is formulated as an elliptically polarized wave, and the collisionless plasma is described by a distribution in phase space, which is realized in cylindrical coordinates. The linearized Vlasov equation is solved in the semi-relativistic limit, to obtain the distribution function in the rest frame of the observer. The perturbed currents supported by the ionized medium are then calculated, so that an expression can be written for the total amount of energy available for transfer through the Landau mechanism. It is found that only certain modes of the perturbed current are available for this energy transfer. The final expressions are presented in terms of Stokes parameters, and applied to the special cases of a thermal as well as a nonthermal plasma. The thermal plasma is described by a Maxwellian distribution, while two nonthermal distributions are considered: the kappa distribution and a generalized Weibull distribution

Multiseriate cortical sclerenchyma enhance root penetration in compacted soils

Mechanical impedance limits soil exploration and resource capture by plant roots. We examine the role of root anatomy in regulating plant adaptation to mechanical impedance and identify a root anatomical phene in maize (Zea mays) and wheat (Triticum aestivum) associated with penetration of hard soil: multiseriate cortical sclerenchyma (MCS). We characterize this trait and evaluate the utility of MCS for root penetration in compacted soils. Roots with MCS had a greater cell wall to lumen ratio and a distinct UV emission spectrum in outer cortical cells. Genome-wide association mapping revealed that MCS is heritable and genetically controlled. We identified a candidate gene associated with MCS. Across all root classes and nodal positions, maize genotypes with MCS had 13% greater root lignin concentration compared to genotypes without MCS. Genotypes without MCS formed MCS upon exogenous ethylene exposure. Genotypes with MCS had greater lignin concentration and bending strength at the root tip. In controlled environments, MCS in maize and wheat was associated improved root tensile strength and increased penetration ability in compacted soils. Maize genotypes with MCS had root systems with 22% greater depth and 39% greater shoot biomass in compacted soils in the field compared to lines without MCS. Of the lines we assessed, MCS was present in 30-50% of modern maize, wheat, and barley cultivars but was absent in teosinte and wild and landrace accessions of wheat and barley. MCS merits investigation as a trait for improving plant performance in maize, wheat, and other grasses under edaphic stress

Enigmatic presence of mitochondrial complex I in Trypanosoma brucei bloodstream forms

The presence of mitochondrial respiratory complex I in the pathogenic bloodstream stages of Trypanosoma brucei has been vigorously debated: increased expression of mitochondrially encoded functional complex I mRNAs is countered by low levels of enzymatic activity that show marginal inhibition by the specific inhibitor rotenone. We now show that epitope-tagged versions of multiple complex I subunits assemble into α and β subcomplexes in the bloodstream stage and that these subcomplexes require the mitochondrial genome for their assembly. Despite the presence of these large (740- and 855-kDa) multisubunit complexes, the electron transport activity of complex I is not essential under experimental conditions since null mutants of two core genes (NUBM and NUKM) showed no growth defect in vitro or in mouse infection. Furthermore, the null mutants showed no decrease in NADH:ubiquinone oxidoreductase activity, suggesting that the observed activity is not contributed by complex I. This work conclusively shows that despite the synthesis and assembly of subunit proteins, the enzymatic function of the largest respiratory complex is neither significant nor important in the bloodstream stage. This situation appears to be in striking contrast to that for the other respiratory complexes in this parasite, where physical presence in a life-cycle stage always indicates functional significance

Root angle in maize influences nitrogen capture and is regulated by calcineurin B-like protein (CBL)-interacting serine/threonine-protein kinase 15 (ZmCIPK15)

Crops with reduced nutrient and water requirements are urgently needed in global agriculture. Root growth angle plays an important role in nutrient and water acquisition. A maize diversity panel of 481 genotypes was screened for variation in root angle employing a high-throughput field phenotyping platform. Genome-wide association mapping identified several single nucleotide polymorphisms (SNPs) associated with root angle, including one located in the root expressed CBL-interacting serine/threonine-protein kinase 15 (ZmCIPK15) gene (LOC100285495). Reverse genetic studies validated the functional importance of ZmCIPK15, causing a approximately 10° change in root angle in specific nodal positions. A steeper root growth angle improved nitrogen capture in silico and in the field. OpenSimRoot simulations predicted at 40 days of growth that this change in angle would improve nitrogen uptake by 11% and plant biomass by 4% in low nitrogen conditions. In field studies under suboptimal N availability, the cipk15 mutant with steeper growth angles had 18% greater shoot biomass and 29% greater shoot nitrogen accumulation compared to the wild type after 70 days of growth. We propose that a steeper root growth angle modulated by ZmCIPK15 will facilitate efforts to develop new crop varieties with optimal root architecture for improved performance under edaphic stress

The biogeochemical impact of glacial meltwater from Southwest Greenland

Biogeochemical cycling in high-latitude regions has a disproportionate impact on global nutrient budgets. Here, we introduce a holistic, multi-disciplinary framework for elucidating the influence of glacial meltwaters, shelf currents, and biological production on biogeochemical cycling in high-latitude continental margins, with a focus on the silica cycle. Our findings highlight the impact of significant glacial discharge on nutrient supply to shelf and slope waters, as well as surface and benthic production in these regions, over a range of timescales from days to thousands of years. Whilst biological uptake in fjords and strong diatom activity in coastal waters maintains low dissolved silicon concentrations in surface waters, we find important but spatially heterogeneous additions of particulates into the system, which are transported rapidly away from the shore. We expect the glacially-derived particles – together with biogenic silica tests – to be cycled rapidly through shallow sediments, resulting in a strong benthic flux of dissolved silicon. Entrainment of this benthic silicon into boundary currents may supply an important source of this key nutrient into the Labrador Sea, and is also likely to recirculate back into the deep fjords inshore. This study illustrates how geochemical and oceanographic analyses can be used together to probe further into modern nutrient cycling in this region, as well as the palaeoclimatological approaches to investigating changes in glacial meltwater discharge through time, especially during periods of rapid climatic change in the Late Quaternary

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Correction: Comparing the genomes of Helicobacter pylori clinical strain UM032 and mice-adapted derivatives

Abstract is not available in fulltext.Published versio

A Functional Nuclear Localization Sequence in the C. elegans TRPV Channel OCR-2

The ability to modulate gene expression in response to sensory experience is critical to the normal development and function of the nervous system. Calcium is a key activator of the signal transduction cascades that mediate the process of translating a cellular stimulus into transcriptional changes. With the recent discovery that the mammalian Cav1.2 calcium channel can be cleaved, enter the nucleus and act as a transcription factor to control neuronal gene expression, a more direct role for the calcium channels themselves in regulating transcription has begun to be appreciated. Here we report the identification of a nuclear localization sequence (NLS) in the C. elegans transient receptor potential vanilloid (TRPV) cation channel OCR-2. TRPV channels have previously been implicated in transcriptional regulation of neuronal genes in the nematode, although the precise mechanism remains unclear. We show that the NLS in OCR-2 is functional, being able to direct nuclear accumulation of a synthetic cargo protein as well as the carboxy-terminal cytosolic tail of OCR-2 where it is endogenously found. Furthermore, we discovered that a carboxy-terminal portion of the full-length channel can localize to the nucleus of neuronal cells. These results suggest that the OCR-2 TRPV cation channel may have a direct nuclear function in neuronal cells that was not previously appreciated