Filtration‐histogram based magnetic resonance texture analysis (Mrta) for the distinction of primary central nervous system lymphoma and glioblastoma

Primary central nervous system lymphoma (PCNSL) has variable imaging appearances, which overlap with those of glioblastoma (GBM), thereby necessitating invasive tissue diagnosis. We aimed to investigate whether a rapid filtration histogram analysis of clinical MRI data supports the distinction of PCNSL from GBM. Ninety tumours (PCNSL n = 48, GBM n = 42) were analysed using pre‐treatment MRI sequences (T1‐weighted contrast‐enhanced (T1CE), T2‐weighted (T2), and apparent diffusion coefficient maps (ADC)). The segmentations were completed with proprietary texture analysis software (TexRAD version 3.3). Filtered (five filter sizes SSF = 2–6 mm) and unfil-tered (SSF = 0) histogram parameters were compared using Mann‐Whitney U non‐parametric test-ing, with receiver operating characteristic (ROC) derived area under the curve (AUC) analysis for significant results. Across all (n = 90) tumours, the optimal algorithm performance was achieved using an unfiltered ADC mean and the mean of positive pixels (MPP), with a sensitivity of 83.8%, specificity of 8.9%, and AUC of 0.88. For subgroup analysis with >1/3 necrosis masses, ADC permit-ted the identification of PCNSL with a sensitivity of 96.9% and specificity of 100%. For T1CE‐derived regions, the distinction was less accurate, with a sensitivity of 71.4%, specificity of 77.1%, and AUC of 0.779. A role may exist for cross‐sectional texture analysis without complex machine learning models to differentiate PCNSL from GBM. ADC appears the most suitable sequence, especially for necrotic lesion distinction

Signaling to Actin Dynamics

No abstract available

MicroRNA-Related Cofilin Abnormality in Alzheimer's Disease

Rod-like structures composed of actin and the actin-binding protein cofilin are found in Alzheimer's disease (AD) patients. However, the mechanisms underlying formation of these structures and their pathological consequences are still largely unknown. We found that microRNAs 103 and 107 repress translation of cofilin, and that reduced levels of miR-103 or miR-107 are associated with elevated cofilin protein levels and formation of rod-like structures in a transgenic mouse model of AD. These results suggest that microRNAs may play an important role in cytoskeletal pathology in AD

Low Dose Isoflurane Exerts Opposing Effects on Neuronal Network Excitability in Neocortex and Hippocampus

The anesthetic excitement phase occurring during induction of anesthesia with volatile anesthetics is a well-known phenomenon in clinical practice. However, the physiological mechanisms underlying anesthetic-induced excitation are still unclear. Here we provide evidence from in vitro experiments performed on rat brain slices that the general anesthetic isoflurane at a concentration of about 0.1 mM can enhance neuronal network excitability in the hippocampus, while simultaneously reducing it in the neocortex. In contrast, isoflurane tissue concentrations above 0.3 mM expectedly caused a pronounced reduction in both brain regions. Neuronal network excitability was assessed by combining simultaneous multisite stimulation via a multielectrode array with recording intrinsic optical signals as a measure of neuronal population activity

Three-Dimensional Neurophenotyping of Adult Zebrafish Behavior

The use of adult zebrafish (Danio rerio) in neurobehavioral research is rapidly expanding. The present large-scale study applied the newest video-tracking and data-mining technologies to further examine zebrafish anxiety-like phenotypes. Here, we generated temporal and spatial three-dimensional (3D) reconstructions of zebrafish locomotion, globally assessed behavioral profiles evoked by several anxiogenic and anxiolytic manipulations, mapped individual endpoints to 3D reconstructions, and performed cluster analysis to reconfirm behavioral correlates of high- and low-anxiety states. The application of 3D swim path reconstructions consolidates behavioral data (while increasing data density) and provides a novel way to examine and represent zebrafish behavior. It also enables rapid optimization of video tracking settings to improve quantification of automated parameters, and suggests that spatiotemporal organization of zebrafish swimming activity can be affected by various experimental manipulations in a manner predicted by their anxiolytic or anxiogenic nature. Our approach markedly enhances the power of zebrafish behavioral analyses, providing innovative framework for high-throughput 3D phenotyping of adult zebrafish behavior

Using shared goal setting to improve access and equity : a mixed methods study of the Good Goals intervention in children's occupational therapy

Peer reviewedPublisher PD

The fraction of activated N-methyl-d-Aspartate receptors during synaptic transmission remains constant in the presence of the glutamate release inhibitor riluzole

Excessive N-methyl-d-aspartate (NMDA) receptor activation is widely accepted to mediate calcium-dependent glutamate excitotoxicity. The uncompetitive, voltage-dependent NMDA receptor antagonist memantine has been successfully used clinically in the treatment of neurodegenerative dementia and is internationally registered for the treatment of moderate to severe Alzheimer′s disease. Glutamate release inhibitors (GRIs) may also be promising for the therapy of some neurodegenerative diseases. During the clinical use of GRIs, it could be questioned whether there would still be a sufficient number of active NMDA receptors to allow any additional effects of memantine or similar NMDA receptor antagonists. To address this question, we determined the fraction of NMDA receptors contributing to postsynaptic events in the presence of therapeutically relevant concentrations of the GRI riluzole (1 μM) using an in vitro hippocampal slice preparation. We measured the charge transfer of pharmacologically isolated excitatory synaptic responses before and after the application of the selective, competitive NMDA receptor antagonist D-AP5 (100 μM). The fraction of activated NMDA receptors under control conditions did not differ from those in the presence of riluzole. It is therefore likely that NMDA receptor antagonists would be able to exert additional therapeutic effects in combination therapy with GRIs

Androgens Contribute to Sex Differences in Myocardial Remodeling under Pressure Overload by a Mechanism Involving TGF-β

Background: In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Methodology/Principal Findings: Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-bs, Smads 2 and 3, collagens, fibronectin, b-myosin heavy chain and a-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson’s trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-bs and the treatment with a neutralizing antibody to TGF-b prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-bs and TGF-b target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-b expression was confirmed i

Morphology of the earliest reconstructable tetrapod Parmastega aelidae.

The known diversity of tetrapods of the Devonian period has increased markedly in recent decades, but their fossil record consists mostly of tantalizing fragments1-15. The framework for interpreting the morphology and palaeobiology of Devonian tetrapods is dominated by the near complete fossils of Ichthyostega and Acanthostega; the less complete, but partly reconstructable, Ventastega and Tulerpeton have supporting roles2,4,16-34. All four of these genera date to the late Famennian age (about 365-359 million years ago)-they are 10 million years younger than the earliest known tetrapod fragments5,10, and nearly 30 million years younger than the oldest known tetrapod footprints35. Here we describe Parmastega aelidae gen. et sp. nov., a tetrapod from Russia dated to the earliest Famennian age (about 372 million years ago), represented by three-dimensional material that enables the reconstruction of the skull and shoulder girdle. The raised orbits, lateral line canals and weakly ossified postcranial skeleton of P. aelidae suggest a largely aquatic, surface-cruising animal. In Bayesian and parsimony-based phylogenetic analyses, the majority of trees place Parmastega as a sister group to all other tetrapods