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To investigate the effects of brain-derived neurotrophic factor (BDNF) overexpression in the ventrolateral periaqueductal gray (vlPAG) on behavioral changes in epilepsy-migraine comorbid rats.
Learn More >The proinflammatory alarmins S100A8 and S100A9 are among the most abundant proteins in neutrophils and monocytes but are completely silenced after differentiation to macrophages. The molecular mechanisms of the extraordinarily dynamic transcriptional regulation of and genes, however, are only barely understood. Using an unbiased genome-wide CRISPR/Cas9 knockout based screening approach in immortalized murine monocytes we identified the transcription factor C/EBPδ as a central regulator of and expression. We showed that S100A8/A9 expression and thereby neutrophil recruitment and cytokine release were decreased in C/EBPδ KO mice in a mouse model of acute lung inflammation. and expression was further controlled by the C/EBPδ-antagonists ATF3 and FBXW7. We confirmed the clinical relevance of this regulatory network in subpopulations of human monocytes in a clinical cohort of cardiovascular patients. Moreover, we identified specific C/EBPδ-binding sites within and promoter regions, and demonstrated that C/EBPδ-dependent JMJD3-mediated demethylation of H3K27me is indispensable for their expression. Overall, our work uncovered C/EBPδ as a novel regulator of and expression. Therefore, C/EBPδ represents a promising target for modulation of inflammatory conditions that are characterised by and overexpression.
Learn More >Chronic pain is prevalent after stroke and has a significant impact on quality of life. Research demonstrates the efficacy of psychological interventions for mixed chronic pain conditions. This review aimed to assess evidence on the effectiveness of psychological interventions for chronic pain in people with stroke. PubMed, PsychINFO, Embase, and CINAHL were searched from inception to 31 January 2021 at all levels of evidence. Psychological interventions assessing chronic pain in adults following stroke as a primary outcome were included. All outcomes related to pain quality were included (e.g., intensity, frequency, duration). Study quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Case Reports and Risk of Bias in N-of-1 Trials (RoBiNT) Scale. Three single case reports were included. A narrative synthesis was performed, indicating that psychological interventions may reduce chronic post-stroke pain; however, overall quality appraisal of the included studies was poor, owing to the low internal validity found in the single- case report designs. The limited evidence suggests that psychological interventions may have clinical utility in reducing chronic post-stroke pain. However, owing to the paucity and quality of studies found, the results must be treated with caution. More rigorous research is needed.
Learn More >To study the long-term effect of 16 weeks of etanercept treatment on disease activity and radiographic changes in patients with suspected non-radiographic axial spondyloarthritis (nr-axSpA).
Learn More >Erenumab is a monoclonal antibody (mAb) against the calcitonin gene related peptide (CGRP) receptor and is commonly used in migraine prophylaxis. Pivotal and open-label studies show a good safety and tolerability. However, little is known about possible predictors, dose dependence and time course of development of adverse events (AEs) during the treatment under real-world conditions.
Learn More >Headache is a common complaint in childhood and adolescence. Differentiating benign primary headaches from ominous secondary headaches is often difficult. Clinicians usually seek red flags to determine the need for neuroimaging. We aimed to evaluate the diagnostic values of red flags in pediatric headaches.
Learn More >Chronic pain is associated with profound negative effects, and racial disparities are well-documented in chronic pain treatment. In addition, Black patients report poorer communication with providers and exhibit lower levels of patient activation (self-management self-efficacy) than White patients. Although the causes of healthcare disparities are complex and require intervention at multiple levels, empowering patients is one critical path to achieving health equity. The current study is a coaching intervention focused on increasing patient activation and building communication skills for Black patients with chronic pain.
Learn More >The transition from acute to chronic pain is critically important but not well understood. Here, we investigated the pathophysiological mechanisms underlying the transition from acute to chronic low back pain (LBP) and performed transcriptome-wide analysis in peripheral immune cells of 98 participants with acute LBP, followed for 3 months. Transcriptomic changes were compared between patients whose LBP was resolved at 3 months with those whose LBP persisted. We found thousands of dynamic transcriptional changes over 3 months in LBP participants with resolved pain but none in those with persistent pain. Transient neutrophil-driven up-regulation of inflammatory responses was protective against the transition to chronic pain. In mouse pain assays, early treatment with a steroid or nonsteroidal anti-inflammatory drug (NSAID) also led to prolonged pain despite being analgesic in the short term; such a prolongation was not observed with other analgesics. Depletion of neutrophils delayed resolution of pain in mice, whereas peripheral injection of neutrophils themselves, or S100A8/A9 proteins normally released by neutrophils, prevented the development of long-lasting pain induced by an anti-inflammatory drug. Analysis of pain trajectories of human subjects reporting acute back pain in the UK Biobank identified elevated risk of pain persistence for subjects taking NSAIDs. Thus, despite analgesic efficacy at early time points, the management of acute inflammation may be counterproductive for long-term outcomes of LBP sufferers.
Learn More >While the efficacy of dupilumab for the treatment of adults with moderate-to-severe atopic dermatitis (AD) has been demonstrated in several clinical trials, patients in such trials may not necessarily reflect the real-world clinical practice setting. This study evaluated the real-world effectiveness of dupilumab in adults with moderate-to-severe AD based on physician global assessment, percent body surface area affected, and patient-reported itch.
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