Ethylmercury and Hg2+ induce the formation of neutrophil extracellular traps (NETs) by human neutrophil granulocytes

Humans are exposed to different mercurial compounds from various sources, most frequently from dental fillings, preservatives in vaccines, or consumption of fish. Among other toxic effects, these substances interact with the immune system. In high doses, mercurials are immunosuppressive. However, lower doses of some mercurials stimulate the immune system, inducing different forms of autoimmunity, autoantibodies, and glomerulonephritis in rodents. Furthermore, some studies suggest a connection between mercury exposure and the occurrence of autoantibodies against nuclear components and granulocyte cytoplasmic proteins in humans. Still, the underlying mechanisms need to be clarified. The present study investigates the formation of neutrophil extracellular traps (NETs) in response to thimerosal and its metabolites ethyl mercury (EtHg), thiosalicylic acid, and mercuric ions (Hg²⁺). Only EtHg and Hg²⁺ triggered NETosis. It was independent of PKC, ERK1/2, p38, and zinc signals and not affected by the NADPH oxidase inhibitor DPI. Instead, EtHg and Hg²⁺ triggered NADPH oxidase-independent production of ROS, which are likely to be involved in mercurial-induced NET formation. This finding might help understanding the autoimmune potential of mercurial compounds. Some diseases, to which a connection with mercurials has been shown, such as Wegener’s granulomatosis and systemic lupus erythematosus, are characterized by high prevalence of autoantibodies against neutrophil-specific auto-antigens. Externalization in the form of NETs may be a source for exposure to these self-antigens. In genetically susceptible individuals, this could be one step in the series of events leading to autoimmunity.     

Differentiating societal costs of disability worsening in multiple sclerosis

Journal of Neurology - In multiple sclerosis (MS), confirmed disability progression (CDP) can be either the result of progression independent of relapse activity (PIRA) or relapse-associated...     

Correction to: Differentiating societal costs of disability worsening in multiple sclerosis

Journal of Neurology - The original version of this article unfortunately contained a mistake. The captions of Fig. 2 and Fig. 3 are mismatched.     

Examining pitch and numerical magnitude processing in congenital amusia: A quasi-experimental pilot study

Introduction: Congenital amusia is a developmental disorder associated with deficits in pitch height discrimination or in integrating pitch sequences into melodies. This quasi-experimental pilot study investigated whether there is an association between pitch and numerical processing deficits in congenital amusia. Since pitch height discrimination is considered a form of magnitude processing, we investigated whether individuals with amusia present an impairment in numerical magnitude processing, which would reflect damage to a generalized magnitude system. Alternatively, we investigated whether the numerical processing deficit would reflect a disconnection between nonsymbolic and symbolic number representations. Method: This study was conducted with 11 adult individuals with congenital amusia and a control comparison group of 6 typically developing individuals. Participants performed nonsymbolic and symbolic magnitude comparisons and number line tasks. Results were available from previous testing using the Montreal Battery of Evaluation of Amusia (MBEA) and a pitch change detection task (PCD). Results: Compared to the controls, individuals with amusia exhibited no significant differences in their performance on both the number line and the nonsymbolic magnitude tasks. Nevertheless, they showed significantly worse performance on the symbolic magnitude task. Moreover, individuals with congenital amusia, who presented worse performance in the Meter subtest, also presented less precise nonsymbolic numerical representation. Conclusions: The relationship between meter and nonsymbolic numerical discrimination could indicate a general ratio processing deficit. The finding of preserved nonsymbolic numerical magnitude discrimination and mental number line representations, with impaired symbolic number processing, in individuals with congenital amusia indicates that (a) pitch height and numerical magnitude processing may not share common neural representations, and (b) in addition to pitch processing, individuals with amusia may present a deficit in accessing nonsymbolic numerical representations from symbolic representations. The symbolic access deficit could reflect a widespread impairment in the establishment of cortico-cortical connections between association areas.     

Three‐dimensional imaging and analysis of human cartilage degeneration using Optical Coherence Tomography

Optical Coherence Tomography (OCT) is an evolving imaging technology allowing non‐destructive imaging of cartilage tissue at near‐histological resolution. This study investigated the diagnostic value of real time 3‐D OCT in comparison to conventional 2‐D OCT in the comprehensive grading of human cartilage degeneration. Fifty‐three human osteochondral samples were obtained from eight total knee arthroplasties. OCT imaging was performed by either obtaining a single two‐dimensional cross‐sectional image (2‐D OCT) or by collecting 100 consecutive parallel 2‐D OCT images to generate a volumetric data set of 8 × 8 mm (3‐D OCT). OCT images were assessed qualitatively according to a modified version of the DJD classification and quantitatively by algorithm‐based evaluation of surface irregularity, tissue homogeneity, and signal attenuation. Samples were graded according to the Outerbridge classification and statistically analyzed by one‐way ANOVA, Kruskal Wallis and Tukey's or Dunn's post‐hoc tests. Overall, the generation of 3‐D volumetric datasets and their multiple reconstructions such as rendering, surface topography, parametric, and cross‐sectional views proved to be of potential diagnostic value. With increasing distance to the mid‐sagittal plane and increasing degeneration, score deviations increased, too. In conclusion, 3‐D imaging of cartilage with image analysis algorithms adds considerable potential diagnostic value to conventional OCT diagnostics. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:651–659, 2015.