Primary leiomyosarcoma of the skin: a comprehensive review on diagnosis and treatment

Sarcomas are a heterogeneous group of mesenchymal tumors which can affect bone and soft tissue. Leiomyosarcoma (LMS) is a rare subtype localized to the skin or subcutaneous tissue. Due to the heterogeneity of sarcomas, reviews and guidelines with an in-depth focus specifically on primary LMS of the skin are sparse. This article is intended to provide an up to date and systematic overview on diagnosis, treatment, and surveillance of this rare entity to provide a framework for decision making and management for dermato-oncologists. We discuss novel treatment options for advanced disease such as targeted therapy with kinase inhibitors and immune checkpoint blockade which may improve the prognosis even in advanced stages of LMS.     

Age-dependent changes in the neural substrates of empathy in autism spectrum disorder

In typical development, empathic abilities continue to refine during adolescence and early adulthood. Children and adolescents with autism spectrum disorders (ASD) show deficits in empathy, whereas adults with ASD may have developed compensatory strategies. We aimed at comparing developmental trajectories in the neural mechanisms underlying empathy in individuals with ASD and typically developing control (TDC) subjects. Using an explicit empathizing paradigm and functional magnetic resonance imaging, 27 participants with ASD and 27 TDC aged 12–31 years were investigated. Participants were asked to empathize with emotional faces and to either infer the face’s emotional state (other-task) or to judge their own emotional response (self-task). Differential age-dependent changes were evident during the self-task in the right dorsolateral prefrontal cortex, right medial prefrontal cortex, right inferior parietal cortex, right anterior insula and occipital cortex. Age-dependent decreases in neural activation in TDC were paralleled by either increasing or unchanged age-dependent activation in ASD. These data suggest ASD-associated deviations in the developmental trajectories of self-related processing during empathizing. In TDC, age-dependent modulations of brain areas may reflect the ‘fine-tuning’ of cortical networks by reduction of task-unspecific brain activity. Increased age-related activation in individuals with ASD may indicate the development of compensatory mechanisms.     

Cnesterodon decemmaculatus Juveniles as Test Organisms in Toxicity Assessment: Cadmium Case

The poeciliid Cnesterodon decemmaculatus is one of the native species of southern South America recently recommended for use as a test species in biomonitoring. Therefore, it is important to characterize its responses to stress conditions caused by pollution. The aim of this work was to determine the toxicity of the reference toxicant cadmium (Cd) and to evaluate the lethality response of juveniles of C. decemmaculatus exposed to an environmental sample with a high degree of pollution (Luján River, Buenos Aires, Argentina). The LC₅₀ values at 24 and 96 h were 6.00 and 2.27 mg Cd/L, respectively. The uptake of Cd was significantly greater in the first 24 h in relation to the total time of exposure in the bioassay. The toxicity of the water was in agreement with the level of contamination. A Cd contaminant pulse exerted an important additive effect on the toxicity of the environmental sample. The results provide information regarding the sensitivity of a native species to be used as a test organism in environmental monitoring.     

Synthetic quantitative MRI through relaxometry modelling

Quantitative MRI (qMRI) provides standardized measures of specific physical parameters that are sensitive to the underlying tissue microstructure and are a first step towards achieving maps of biologically relevant metrics through in vivo histology using MRI. Recently proposed models have described the interdependence of qMRI parameters. Combining such models with the concept of image synthesis points towards a novel approach to synthetic qMRI, in which maps of fundamentally different physical properties are constructed through the use of biophysical models. In this study, the utility of synthetic qMRI is investigated within the context of a recently proposed linear relaxometry model. Two neuroimaging applications are considered. In the first, artefact‐free quantitative maps are synthesized from motion‐corrupted data by exploiting the over‐determined nature of the relaxometry model and the fact that the artefact is inconsistent across the data. In the second application, a map of magnetization transfer (MT) saturation is synthesized without the need to acquire an MT‐weighted volume, which directly leads to a reduction in the specific absorption rate of the acquisition. This feature would be particularly important for ultra‐high field applications. The synthetic MT map is shown to provide improved segmentation of deep grey matter structures, relative to segmentation using T₁‐weighted images or R₁ maps. The proposed approach of synthetic qMRI shows promise for maximizing the extraction of high quality information related to tissue microstructure from qMRI protocols and furthering our understanding of the interrelation of these qMRI parameters.     

Apoptotic signal transduction and T cell tolerance

The healthy immune system makes use of a variety of surveillance mechanisms at different stages of lymphoid development to prevent the occurrence and expansion of potentially harmful autoreactive T cell clones. Disruption of these mechanisms may lead to inappropriate activation of T cells and the development of autoimmune and lymphoproliferative diseases [such as multiple sclerosis, rheumatoid arthritis, lupus erythematosus, diabetes and autoimmune lymphoproliferative syndrome (ALPS)]. Clonal deletion of T cells with high affinities for self-peptide-MHC via programmed cell death (apoptosis) is an essential mechanism leading to self-tolerance. Referred to as negative selection, central tolerance in the thymus serves as the first checkpoint for the developing T cell repertoire and involves the apoptotic elimination of potentially autoreactive T cells clones bearing high affinity T cell receptors (TCR) that recognize autoantigens presented by thymic epithelial cells. Autoreactive T cells that escape negative selection are held in check in the periphery by either functional inactivation (“anergy”) or extrathymic clonal deletion, both of which are dependent on the strength and frequency of the TCR signal and the costimulatory context, or by regulatory T cells. This review provides an overview of the different molecular executioners of cell death programs that are vital to intrathymic or extrathymic clonal deletion of T cells. Further, the potential involvement of various apoptotic signaling paradigms are discussed with respect to the genesis and pathophysiology of autoimmune disease.     

Escherichia coli biofilm formation and dispersion under hydrodynamic conditions on metal surfaces

The aim of this study was to analyze the impact of hydrodynamic forces on the multiplication of E. coli, and biofilm formation and dispersion. The experiments were provided in a flow chamber simulating a cleaning-in-place system. Biofilm biomass was measured using a crystal violet dye method. The results show that hydrodynamic forces affect not only biofilm formation and dispersion but the multiplication of E. coli in the first place. We found more biofilm biomass on the rough surface than on the smooth one. The results of the biofilm formation test show that laminar flow promotes the biofilm growth over 72 h, meanwhile turbulent flow after 48 h causes decrease in biomass. The results of the biofilm dispersion test, in contrast, show that laminar flow removed less biofilm from both materials that turbulent flow did. Therefore, taking into account these findings in cleaning-in-place technology can substantially reduce E. coli multiplication and biofilm formation.