Citations

Background: Few studies have addressed the results of educational efforts concerning proper use of McDonald criteria (MC) revisions outside multiple sclerosis (MS) subspecialty centers. Neurology residents and MS subspecialist neurologists demonstrated knowledge gaps for core elements of the MC in a recent prior study. Objective: To assess comprehension and application of MC core elements by non-MS specialist neurologists in the United States who routinely diagnose MS. Methods: Through a cross-sectional study design, a previously developed survey instrument was distributed online. Results: A total of 222 neurologists completed the study survey. Syndromes atypical for MS were frequently incorrectly considered “typical” MS presentations. Fourteen percent correctly identified definitions of both “periventricular” and “juxtacortical” lesions and 2% correctly applied these terms to 9/9 images. Twenty-four percent correctly identified all four central nervous system (CNS) regions for satisfaction of magnetic resonance imaging (MRI) dissemination in space. In two presented cases, 61% and 71% correctly identified dissemination in time (DIT) was not fulfilled, and 85% and 86% subsequently accepted nonspecific historical symptoms without objective evidence for DIT fulfillment. Conclusion: The high rate of knowledge deficiencies and application errors of core elements of the MC demonstrated by participants in this study raise pressing questions concerning adequacy of dissemination and educational efforts upon publication of revisions to MC.

The NCCN Guidelines for Older Adult Oncology address specific issues related to the management of cancer in older adults, including screening and comprehensive geriatric assessment (CGA), assessing the risks and benefits of treatment, preventing or decreasing complications from therapy, and managing patients deemed to be at high risk for treatment-related toxicity. CGA is a multidisciplinary, in-depth evaluation that assesses the objective health of the older adult while evaluating multiple domains, which may affect cancer prognosis and treatment choices. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines providing specific practical framework for the use of CGA when evaluating older adults with cancer.

Radiofrequency ablation (RFA) is a common treatment of atrial fibrillation. However, current treatment is associated with a greater than 20% recurrence rate, in part due to inadequate monitoring of tissue viability during ablation. Spectral parameters, in particular cyclic variation of integrated backscatter (CVIB), have shown promise as early indicators of myocardial recovery from ischemia. Our aim was to demonstrate the use of spectral parameters to differentiate atrial myocardium before and after radiofrequency ablation. An AcuNav 10 F catheter was used to collect radiofrequency signals from the posterior wall of the left atrium of patients before and immediately after RFA for AF. The normalized power spectrum was obtained and three spectral parameters (integrated backscatter [IB], slope, and intercept) were extracted across two continuous heart cycles. Parameters were gated for ventricular end-diastole and compared before and after ablation. Additionally, the cyclic variation of each of these three parameters was generated as an average of the variation across the two recorded heart cycles. Data from 14 patients before and after ablation demonstrated a significant difference in the magnitude of the cyclic variation of integrated backscatter (9.0 vs. 6.0 dB, p < .001) and cyclic variation of the intercept (14.0 vs. 11.5 dB, p = .04). No significant difference was noted in the magnitude of the cyclic variation of the slope. Among spectral parameters gated for end-diastole, significant differences were noted in the slope (−4.39 vs. −3.73 dB/MHz, p = .002) and intercept (16.8 vs. 11.9 dB, p = .002). No significant difference was noted in the integrated backscatter. Spectral parameters are able to differentiate atrial myocardium before and immediately following ablation and may be useful in monitoring atrial ablations.

How to catch a dynamic state AMP-activated protein kinase (AMPK) is a key sensor of energy status in eukaryotes. Its dynamic structure is regulated by allosteric factors including phosphorylation and binding of nucleotides and metabolites. Yan et al. developed conformation-specific antibodies that trap AMPK in a fully inactive state that has experienced a large, domain-level rotation. Biophysical experiments in cells and in vitro are consistent with the structural work and support a model in which the activation loop is fully exposed in the completely inactive, dephosphorylated state. These structures inform our understanding of the complex allosteric behavior in this crucial metabolic regulator. Science , abe7565, this issue p. 413

Introduction: Myxomatous mitral valve disease (MMVD) is a degenerative condition characterized by tissue fibrosis and matrix remodeling which ultimately progresses to leaflet prolapse. While recent work has shown that transforming growth factor beta (TGF-β) signaling contributes to the pathogenesis of MMVD, upstream regulators of this and other pathways remain poorly understood. Hypothesis: We sought to use high-throughput RNA sequencing coupled with microRNA (miRNA) sequencing to identify novel molecular targets as well as upstream regulators contributing to MMVD. Methods: We conducted mRNA and miRNA sequencing on normal (n = 10) and myxomatous human mitral valve samples (n = 10). Differential expression was identified using linear modeling and parallel random forest analyses. Canonical pathways were identified by Ingenuity Pathway Analyses (IPA). Predicted miRNA targets were identified using TargetScanHuman 6.2. Results: We found 2784 mRNAs that were differentially expressed between normal and myxomatous mitral valves, which IPA largely categorized in to pro-fibrotic, matrix remodeling and cellular proliferation signaling. In miRNA sequenced from the same samples, 67 miRNAs were differentially-expressed between normal and myxomatous mitral valves. Increased expression of TGF-β ligands, collagen isoforms, and matrix metalloproteinases were associated with reductions in miRNAs predicted to target them. Conversely, mRNA levels of the “protective” genes TGFβ-induced factor homeobox 1, salt-inducible kinase 1, TIMP metallopeptidase inhibitor 4, and cyclin-dependent kinase inhibitor 1C mRNA levels were decreased in myxomatous tissue, and miRNAs predicted to target these genes (e.g., miR-656, miR-379-3p, miR-664a-3p, and miR-34c-5p) were significantly increased. Conclusions: Collectively, these data not only identify novel genes that are differentially regulated in MMVD, but also suggest miRNAs may play an active role in suppressing key protective molecules in MMVD. Thus, anti-mIRs therapy may be a viable therapeutic target to restore anti-fibrotic and anti-proliferative molecules in the valve and slow progression of MMVD. Future mechanistic studies will lay a critical foundation for translational work in these areas.

While fundamental principles of anatomy are well‐established in early medical training, continued retention of anatomical knowledge is dependent on value, importability and relevance to surgical practice. As novel reconstructive strategies emerge, surgeons must account for individual patient factors and comorbidities in predicting patient outcome. Mastery of planning requires precise knowledge of local anatomy and reconstructive techniques, warranting reconnection with prior anatomic knowledge. Finding dedicated time to learn anatomy through self‐guided approach, is often challenging in a busy practice and CPD opportunities become a highly valued resource. In recent years, two mainstream professional dermatology societies have provided a platform for delivery of anatomy based clinical sessions. This study aims to assess value of point of care delivery of relevant anatomy and its role in improving perception of surgical confidence amongst procedural dermatologists in a CPD course. Assessment of core knowledge and knowledge gaps was conducted through the American College of Mohs Surgery (ACMS). Objectives were designed by a team of anatomists and clinicians based on a series of challenging cases. Anatomy sessions were offered at a large general session (>300 participants) and a small group hands‐on flap based session (n=20) Key anatomic teaching points relating to danger zones, safe zones and functional impairment were highlighted. Videos of real‐time dissection using a layered approach of targeted anatomy were created and supplemented with 3D‐printed models. For challenging anatomy encountered during Mohs reconstruction, patient defects were re‐created on the cadaver highlighting pertinent anatomy. Qualitative and quantitative analyses were conducting using course review for general session and confidence rating using Likert scale of anatomy based objectives for small group session. While 60–90 minute general session was sufficient for anatomist‐clinician team to facilitate discussion, participants indicated strong desire for increased session time. Videos and high quality photography were seen as outstanding tools for demonstrating anatomy within surgical field. Participants strongly valued anatomist/clinician partnership and relevance of material to everyday practice. Session review data (n=78) indicated session objectives “improved their ability to provide excellent patient care by helping close practice gaps”( 89.74%), helped “identify practice gaps in knowledge, performance and outcomes” (83.33%) and material presented was relevant to their Mohs and dermatologic practice (100%). Within small group session (n=11), only 18% had access to anatomy facility and material, with 100% agreeing/strongly agreeing that anatomy education was critical to their current practice. Analysis of perceived confidence in anatomic knowledge post course showed significant improvement in confidence in identifying, isolating and visualizing relevant anatomical (p<0.05). Positive impact of collaborative teaching of anatomy outside a mainstream academic setting using targeted point of care delivery through the use of technology (video), products of technology (photography and 3D‐printed material) and patient based clinical discussion to improve physician confidence was demonstrated. In era of authentic learning, anatomists share a responsibility for bringing point‐of‐care content for improved patient care. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .