The fusion protein SS18-SSX1 employs core Wnt pathway transcription factors to induce a partial Wnt signature in synovial sarcoma.

Expression of the SS18/SYT-SSX fusion protein is believed to underlie the pathogenesis of synovial sarcoma (SS). Recent evidence suggests that deregulation of the Wnt pathway may play an important role in SS but the mechanisms whereby SS18-SSX might affect Wnt signaling remain to be elucidated. Here, we show that SS18/SSX tightly regulates the elevated expression of the key Wnt target AXIN2 in primary SS. SS18-SSX is shown to interact with TCF/LEF, TLE and HDAC but not β-catenin in vivo and to induce Wnt target gene expression by forming a complex containing promoter-bound TCF/LEF and HDAC but lacking β-catenin. Our observations provide a tumor-specific mechanistic basis for Wnt target gene induction in SS that can occur in the absence of Wnt ligand stimulation

Severe acute respiratory syndrome coronavirus 2 infection in patients with hematological malignancies in the Omicron era: Respiratory failure, need for mechanical ventilation and mortality in seronegative and seropositive patients

Background: Patients with hematological malignancies (HM) have a high risk of severe coronavirus disease 2019 (COVID-19), also in the Omicron period.Material and methods: Retrospective single-center study including HM patients with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV2) infection from January 2022 to March 2023. Study outcomes were respiratory failure (RF), mechanical ventilation (MV), and COVID-related mortality, comparing patients according to SARS-CoV2 serology.Results: Note that, 112 patients were included: 39% had negative SARS-CoV2 serology. Seronegative were older (71.5 vs. 65.0 years, p = 0.04), had more often a lymphoid neoplasm (88.6% vs. 69.1%, p = 0.02), underwent anti-CD20 therapy (50.0% vs. 30.9% p = 0.04) and had more frequently a severe disease (23.0% vs. 3.0%, p = 0.02) than seropositive.Kaplan-Meier showed a higher risk for seronegative patients for RF (p = 0.014), MV (p = 0.044), and COVID-related mortality (p = 0.021). Negative SARS-CoV2 serostatus resulted in a risk factor for RF (hazards ratio [HR] 2.19, 95% confidence interval [CI] 1.03-4.67, p = 0.04), MV (HR 3.37, 95% CI 1.06-10.68, p = 0.04), and COVID-related mortality (HR 4.26, 95% CI 1.09-16.71, p = 0.04).Conclusions: HM patients with negative SARS-CoV2 serology, despite vaccinations and previous infections, have worse clinical outcomes compared to seropositive patients in the Omicron era. The use of serology for SARS-CoV2 diagnosis could be an easy tool to identify patients prone to developing complications

Dissociation of Motor Task-Induced Cortical Excitability and Pain Perception Changes in Healthy Volunteers

Background: There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks. Methodology/Principal Findings Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements. Conclusions/Significance: Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

High-definition tDCS of the temporo-parietal cortex enhances access to newly learned words

Learning associations between words and their referents is crucial for language learning in the developing and adult brain and for language re-learning after neurological injury. Non-invasive transcranial direct current stimulation (tDCS) to the posterior temporo-parietal cortex has been suggested to enhance this process. However, previous studies employed standard tDCS set-ups that induce diffuse current flow in the brain, preventing the attribution of stimulation effects to the target region. This study employed high-definition tDCS (HD-tDCS) that allowed the current flow to be constrained to the temporo-parietal cortex, to clarify its role in novel word learning. In a sham-controlled, double-blind, between-subjects design, 50 healthy adults learned associations between legal non-words and unfamiliar object pictures. Participants were stratified by baseline learning ability on a short version of the learning paradigm and pairwise randomized to active (20 mins; N = 25) or sham (40 seconds; N = 25) HD-tDCS. Accuracy was comparable during the baseline and experimental phases in both HD-tDCS conditions. However, active HD-tDCS resulted in faster retrieval of correct word-picture pairs. Our findings corroborate the critical role of the temporo-parietal cortex in novel word learning, which has implications for current theories of language acquisition

Transcranial direct current stimulation combined with upper limb functional training in children with spastic, hemiparetic cerebral palsy: study protocol for a randomized controlled trial

The aim of the proposed study is to perform a comparative analysis of functional training effects for the paretic upper limb with and without transcranial direct current stimulation over the primary motor cortex in children with spastic hemiparetic cerebral palsy