Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative disorders whose pathogenesis remains largely unknown. Here using TDP-43A315T mice, an ALS and FTD model with profound cortical pathology, we demonstrated that hyperactive somatostatin interneurons disinhibited layer 5 pyramidal neurons (L5-PN) and contributed to their excitotoxicity. Focal ablation of somatostatin interneurons efficiently restored normal excitability of L5-PN and alleviated neurodegeneration, suggesting a novel therapeutic target for ALS and FTD.

Purpose To evaluate the role of magnetization transfer (MT) magnetic resonance (MR) imaging for the characterization of intestinal fibrosis compared with contrast material-enhanced and diffusion-weighted MR imaging and its capability for differentiating fibrotic from inflammatory strictures in humans with Crohn disease (CD) by using surgical histopathologic analysis as the reference standard. Materials and Methods Institutional review board approval and informed consent were obtained for this prospective study. Abdominal MT imaging, contrast-enhanced imaging, and diffusion-weighted imaging of 31 consecutive patients with CD were analyzed before elective surgery. The bowel wall MT ratio normalized to skeletal muscle, the apparent diffusion coefficient (ADC), and the percentage of enhancement gain were calculated; region-by-region correlations with the surgical specimen were performed to determine the histologic degree of fibrosis and inflammation. The performance of MT imaging was validated in five new patients. One-way analysis of variance test, Spearman rank correlation, and receiver operating characteristic curve were used for statistical analysis. Results Normalized MT ratios strongly correlated with fibrosis scores (r = 0.769; P = .000) but did not correlate with inflammation scores (r = -0.034; P = .740). Significant differences (F = 49.002; P = .000) in normalized MT ratios were found among nonfibrotic, mildly, moderately, and severely fibrotic walls. The normalized MT ratios of mixed fibrotic and inflammatory bowel walls were significantly higher than those of bowel walls with only inflammation present (t = -8.52; P = .000). A high accuracy of normalized MT ratios was shown with an area under the receiver operating characteristic curve (AUC) of 0.919 (P = .000) for differentiating moderately to severely fibrotic bowel walls from nonfibrotic and mildly fibrotic bowel walls, followed by ADC (AUC, 0.747; P = .001) and the percentage of enhancement gain (AUC, 0.592; P = .209). The sensitivity, specificity, and AUC of MT imaging for diagnosing moderate to severe fibrosis in the validation data set were 80% (12 of 15), 100% (three of three), and 0.9 (P = .033), respectively. Conclusion MT imaging outperforms ADC and contrast-enhanced imaging in detecting and distinguishing varying degrees of bowel fibrosis with or without coexisting inflammation. MT imaging could potentially be used as a method to differentiate fibrotic from inflammatory intestinal strictures in patients with CD. RSNA, 2018 Online supplemental material is available for this article.

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DWI enables to accurately grade inflammatory activity in patients of ileocolonic CD and may be better suited than conventional MRE for monitoring the activity of CD.

High-mobility group box protein-1 seems to act as a late cytokine mediator in the pathogenesis of severe acute pancreatitis. Pyrrolidine dithiocarbamate might inhibit the activation of nuclear factor-kappaB to blockade tumor necrosis factor-alpha, thereby indirectly suppressing the high-mobility group box protein-1 and reducing pancreatic tissue damage in rats with severe acute pancreatitis.

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To assess the diagnostic efficacy of diffusion-weighted MR imaging (DWI) for evaluating inflammatory activity in patients with Crohn's disease (CD). A total of 47 CD patients underwent MR enterography (MRE) and DWI using 3 b values of 50, 400, and 800 s/mm.2 Apparent diffusion coefficients (ADCs) of inflamed and normal bowel wall were calculated. The conventional MRE findings and DWI signal intensities were qualitatively scored from 0 to 3. The correlation between Crohn disease activity index (CDAI) and both ADCs and magnetic resonance imaging scores was analyzed. Receiver-operating characteristic curve analysis was used to determine the diagnostic accuracy of CD activity. Of the 47 patients, 25 were active CD (CDAI≥150) and 22 were inactive (CDAI<150). Diffusion-weighted MR imaging and MRE + DWI scores of active CD were significantly higher than that of inactive CD (both P < 0.001). Apparent diffusion coefficients in inflamed segments of active CD were lower than that of inactive CD (P < 0.001). The DWI scores (r = 0.74, P < 0.001), ADCs (r = −0.71, P < 0.001), MRE scores (r = 0.54, P < 0.001), and MRE + DWI scores (r = 0.66, P < 0.001) were all correlated with CDAI. The areas under the receiver-operating characteristics curves for ADCs, DWI scores, MRE scores, and MRE + DWI scores ranged from 0.83 to 0.98. The threshold ADC value of 1.17 × 10−3 mm2/s allowed differentiation of active from inactive CD with 100% sensitivity and 88% specificity. Diffusion-weighted MR imaging and ADC correlated with CD activity, and had excellent diagnostic accuracy for differentiating active from inactive CD.