Differentielle Expressionsmuster von MMP-2, MMP-9 und PCNA in verschiedenen Endometriosestadien und Endometriumkarzinomen

In der BRD ist die Endometriose eine häufige und durch ihre möglichen Symptome und Folgen eine wichtige Erkrankung. Untersucht wurde die Proliferationsaktivität von Darmendometriose im Vergleich zur Peritonealendometriose und zum Endometriumkarzinom anhand der Expression von MMP-2, MMP-9 und PCNA. Es zeigt sich, dass es Unterschiede im Expressionsverhalten der verschiedenen Antikörperfärbungen gibt. MMP-2 und PCNA sind vermehrt in der Darmendometriose im Vergleich zur Peritonealendometriose zu finden. Verglichen zum gut differenzierten Endometriumkarzinom erweist sich die Darmendometriose als stärker proliferierendes Gewebe. Mit der höchsten MMP 2 und MMP-9 Expression der drei Gewebearten bestätigt sich jedoch die Annahme, dass ein malignes Geschehen noch aggressiver und infiltrativer ist, als die Endometriose. Zum besseren Verständnis der Pathogenese der Endometriose und die sich hieraus mögliche Entwicklung einer individuelleren Therapie können die Ergebnisse einen Beitrag leisten

Shell Disease Syndrome Is Associated with Reduced and Shifted Epibacterial Diversity on the Carapace of the Crustacean Cancer pagurus

Crustaceans increasingly suffer from the black spot shell disease syndrome, which principally results from bacterial breakdown of their chitinous exoskeleton. Since Cancer pagurus is highly susceptible to this disease, we compared the bacterial communities of black spot affected and non-affected areas of the carapace by amplicon sequencing of 16S rRNA genes and 16S rRNA. Within each spot, bacterial communities of affected areas were less diverse compared to communities from non-affected areas. Communities of different affected spots were, however, more divergent from each other, compared to those of different nonaffected areas. This indicates a reduced and shifted microbial community composition caused by the black spot disease. Different communities found in black spots likely indicate different stages of the disease. In affected areas, Flavobacteriaceae rose up to one of the most abundant and active families, due to massive increase of Aquimarina spp., suggesting a significant role in shell disease syndrome. We isolated 75 bacterial strains from diseased and healthy areas, which primarily affiliated with Proteobacteria and Bacteroidetes, thus reflecting the dominant phyla detected by amplicon sequencing. The ability to degrade chitin was mainly found for Gammaproteobacteria and Aquimarina spp. within the Flavobacteriia, while the ability to use N-acetylglucosamine, the monomer of the polysaccharide chitin, was observed for most isolates, including many Alphaproteobacteria. Furthermore, one third of the isolates showed antagonistic properties. The combination of bacterial community analysis and the physiological properties of the isolates provides insights into a functional complex epibacterial community on the carapace of C. pagurus. Importance In recent years, the shell disease syndrome was detected for several ecologically and economically important crustacean species. Large proportions of populations are affected, e.g., >60% of the widely distributed species Cancer pagurus in different North Sea areas. Bacteria play a significant role in the development of different forms of shell disease, all characterized by microbial chitinolytic degradation of the outer shell. By comparing the bacterial communities of healthy and diseased areas of the shell of C. pagurus we could demonstrate that the disease causes a reduced bacterial diversity within affected areas, a phenomenon co-occurring also with many other diseases. Furthermore, the community composition dramatically changed, with some taxa rising to high relative abundances and showing increased activity, indicating a strong participation in shell disease. Characterization of bacterial isolates obtained from affected and non-affected spots provided deeper insights in their physiological properties and thus the possible role within the microbiome

Self-Assessment of Individual Differences in Language Switching

Language switching is omnipresent in bilingual individuals. In fact, the ability to switch languages (code switching) is a very fast, efficient, and flexible process that seems to be a fundamental aspect of bilingual language processing. In this study, we aimed to characterize psychometrically self-perceived individual differences in language switching and to create a reliable measure of this behavioral pattern by introducing a bilingual switching questionnaire. As a working hypothesis based on the previous literature about code switching, we decomposed language switching into four constructs: (i) L1 switching tendencies (the tendency to switch to L1; L1-switch); (ii) L2 switching tendencies (L2-switch); (iii) contextual switch, which indexes the frequency of switches usually triggered by a particular situation, topic, or environment; and (iv) unintended switch, which measures the lack of intention and awareness of the language switches. A total of 582 Spanish–Catalan bilingual university students were studied. Twelve items were selected (three for each construct). The correlation matrix was factor-analyzed using minimum rank factor analysis followed by oblique direct oblimin rotation. The overall proportion of common variance explained by the four extracted factors was 0.86. Finally, to assess the external validity of the individual differences scored with the new questionnaire, we evaluated the correlations between these measures and several psychometric (language proficiency) and behavioral measures related to cognitive and attentional control. The present study highlights the importance of evaluating individual differences in language switching using self-assessment instruments when studying the interface between cognitive control and bilingualism

Increased cortical curvature reflects white matter atrophy in individual patients with early multiple sclerosis

AbstractObjectiveWhite matter atrophy occurs independently of lesions in multiple sclerosis. In contrast to lesion detection, the quantitative assessment of white matter atrophy in individual patients has been regarded as a major challenge. We therefore tested the hypothesis that white matter atrophy (WMA) is present at the very beginning of multiple sclerosis (MS) and in virtually each individual patient. To find a new sensitive and robust marker for WMA we investigated the relationship between cortical surface area, white matter volume (WMV), and whole-brain-surface-averaged rectified cortical extrinsic curvature. Based on geometrical considerations we hypothesized that cortical curvature increases if WMV decreases and the cortical surface area remains constant.MethodsIn total, 95 participants were enrolled: 30 patients with early and advanced relapsing–remitting MS; 30 age-matched control subjects; 30 patients with Alzheimer's disease (AD) and 5 patients with clinically isolated syndrome (CIS).Results29/30 MS and 5/5 CIS patients showed lower WMV than expected from their intracranial volume (average reduction 13.0%, P<10−10), while the cortical surface area showed no significant differences compared with controls. The estimated WMV reductions were correlated with an increase in cortical curvature (R=0.62, P=0.000001). Discriminant analysis revealed that the curvature increase was highly specific for the MS and CIS groups (96.7% correct assignments between MS and control groups) and was significantly correlated with reduction of white matter fractional anisotropy, as determined by diffusion tensor imaging and the Expanded Disability Status Scale. As expected by the predominant gray and WM degeneration in AD, no systematic curvature increase was observed in AD.ConclusionWhole-brain-averaged cortical extrinsic curvature appears to be a specific and quantitative marker for a WMV–cortex disproportionality and allows us to assess “pure” WMA without being confounded by intracranial volume. WMA seems to be a characteristic symptom in early MS and can already occur in patients with CIS and should thus be considered in future MS research and clinical studies

Disability Weights for Chronic Mercury Intoxication Resulting from Gold Mining Activities: Results from an Online Pairwise Comparisons Survey

Steckling N, Devleesschauwer B, Winkelnkemper J, et al. Disability Weights for Chronic Mercury Intoxication Resulting from Gold Mining Activities: Results from an Online Pairwise Comparisons Survey. International Journal of Environmental Research and Public Health. 2017;14(1): 57

Synergistic assembly of hyperbranched polyethylenimine and fatty acids leading to unusual supramolecular nanocapsules

Self-assembly of hyperbranched polyethylenimine (PEI) and fatty acids leads to supramolecular inverted micellar structures that are able to irreversibly transfer water-soluble guest molecules into organic solvents.Perez Prieto, Julia, [email protected] ; Stiriba, Salah Eddine, [email protected]

Serum neurofilament levels reflect outer retinal layer changes in multiple sclerosis

Background:Serum neurofilament light chain (sNfL) and distinct intra-retinal layers are both promising biomarkers of neuro-axonal injury in multiple sclerosis (MS). We aimed to unravel the association of both markers in early MS, having identified that neurofilament has a distinct immunohistochemical expression pattern among intra-retinal layers. Methods:Three-dimensional (3D) spectral domain macular optical coherence tomography scans and sNfL levels were investigated in 156 early MS patients (female/male: 109/47, mean age: 33.3 ± 9.5 years, mean disease duration: 2.0 ± 3.3 years). Out of the whole cohort, 110 patients had no history of optic neuritis (NHON) and 46 patients had a previous history of optic neuritis (HON). In addition, a subgroup of patients (n = 38) was studied longitudinally over 2 years. Support vector machine analysis was applied to test a regression model for significant changes. Results:In our cohort, HON patients had a thinner outer plexiform layer (OPL) volume compared to NHON patients (B = −0.016, SE = 0.006, p = 0.013). Higher sNfL levels were significantly associated with thinner OPL volumes in HON patients (B = −6.734, SE = 2.514, p = 0.011). This finding was corroborated in the longitudinal subanalysis by the association of higher sNfL levels with OPL atrophy (B = 5.974, SE = 2.420, p = 0.019). sNfL levels were 75.7% accurate at predicting OPL volume in the supervised machine learning. Conclusions:In summary, sNfL levels were a good predictor of future outer retinal thinning in MS. Changes within the neurofilament-rich OPL could be considered as an additional retinal marker linked to MS neurodegeneration

Pharmacogenetic Analysis of Voriconazole Treatment in Children

Voriconazole is among the first-line antifungal drugs to treat invasive fungal infections in children and known for its pronounced inter- and intraindividual pharmacokinetic variability. Polymorphisms in genes involved in the metabolism and transport of voriconazole are thought to influence serum concentrations and eventually the therapeutic outcome. To investigate the impact of these genetic variants and other covariates on voriconazole trough concentrations, we performed a retrospective data analysis, where we used medication data from 36 children suffering from invasive fungal infections treated with voriconazole. Data were extracted from clinical information systems with the new infrastructure SwissPKcdw, and linear mixed effects modelling was performed using R. Samples from 23 children were available for DNA extraction, from which 12 selected polymorphism were genotyped by real-time PCR. 192 (49.1%) of 391 trough serum concentrations measured were outside the recommended range. Voriconazole trough concentrations were influenced by polymorphisms within the metabolizing enzymes CYP2C19 and CYP3A4, and within the drug transporters ABCC2 and ABCG2, as well as by the co-medications ciprofloxacin, levetiracetam, and propranolol. In order to prescribe an optimal drug dosage, pre-emptive pharmacogenetic testing and careful consideration of co-medications in addition to therapeutic drug monitoring might improve voriconazole treatment outcome of children with invasive fungal infections. Keywords: ABCC2; ABCG2; CYP2C19; CYP3A4; children; non-linear mixed effects modelling; pediatric pharmacology; pharmacogenetics; therapeutic drug monitoring; voriconazol

Myelination- and immune-mediated MR-based brain network correlates

Background Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by inflammatory and neurodegenerative processes. Despite demyelination being a hallmark of the disease, how it relates to neurodegeneration has still not been completely unraveled, and research is still ongoing into how these processes can be tracked non-invasively. Magnetic resonance imaging (MRI) derived brain network characteristics, which closely mirror disease processes and relate to functional impairment, recently became important variables for characterizing immune-mediated neurodegeneration; however, their histopathological basis remains unclear. Methods In order to determine the MRI-derived correlates of myelin dynamics and to test if brain network characteristics derived from diffusion tensor imaging reflect microstructural tissue reorganization, we took advantage of the cuprizone model of general demyelination in mice and performed longitudinal histological and imaging analyses with behavioral tests. By introducing cuprizone into the diet, we induced targeted and consistent demyelination of oligodendrocytes, over a period of 5 weeks. Subsequent myelin synthesis was enabled by reintroduction of normal food. Results Using specific immune-histological markers, we demonstrated that 2 weeks of cuprizone diet induced a 52% reduction of myelin content in the corpus callosum (CC) and a 35% reduction in the neocortex. An extended cuprizone diet increased myelin loss in the CC, while remyelination commenced in the neocortex. These histologically determined dynamics were reflected by MRI measurements from diffusion tensor imaging. Demyelination was associated with decreased fractional anisotropy (FA) values and increased modularity and clustering at the network level. MRI-derived modularization of the brain network and FA reduction in key anatomical regions, including the hippocampus, thalamus, and analyzed cortical areas, were closely related to impaired memory function and anxiety-like behavior. Conclusion Network-specific remyelination, shown by histology and MRI metrics, determined amelioration of functional performance and neuropsychiatric symptoms. Taken together, we illustrate the histological basis for the MRI-driven network responses to demyelination, where increased modularity leads to evolving damage and abnormal behavior in MS. Quantitative information about in vivo myelination processes is mirrored by diffusion-based imaging of microstructural integrity and network characteristics