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Older adults with pCAP were less likely to be admitted to ICU or required mechanical ventilation, given their higher mortality and goals of care. Of pCAP deaths, 67% and 90% were in the ≥65 and ≥50 age cohorts, respectively. CONCLUSIONS Adults hospitalised with pCAP in the age cohort of 50-64 years contribute significantly to the burden of illness, suggesting that an age-based recommendation for adults aged ≥50 years should be considered in order to optimise the impact of pneumococcal vaccination programmes in Canada. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Snail is a transcription factor that regulates many cellular events involved in development, homeostasis, and disease. In hepatocellular carcinoma (HCC), Snail induces epithelial-to-mesenchymal transition that confers invasive properties on tumor cells during HCC progression and malignancy. Snail activation observed in HCC mouse models suggests its involvement in not only progression, but also onset of HCC. However, it remains unclear whether Snail directly contributes to HCC initiation or whether it supports HCC initiation promoted by other oncogenes. In this study, we generated mouse models for liver-specific and hepatocyte-specific overexpression of Snail to reveal the independent roles of Snail in liver homeostasis and disease. Our data demonstrated that enforced Snail expression resulted in liver and hepatocyte enlargement, inflammatory cell infiltration in the liver, lipid accumulation in hepatocytes, substantial increases in serum alanine transaminase and bile acids, yellow discoloration of tissues caused by bilirubin accumulation, and liver tumorigenesis. Snail overexpression suppressed mRNA expression of the tight junction components claudins and occludin and that of proteins associated with bile acid metabolism, leading to disruption of the biliary canaliculus formed among hepatocytes and excretion of abnormal amounts of unusual bile acids from hepatocytes. In conclusion, enforced Snail expression in hepatocytes is sufficient for induction of steatohepatitis and liver tumorigenesis through disruption of the biliary canaliculus and bile acid homeostasis in the liver. BACKGROUND Abnormal 12-lead electrocardiogram (ECG) can predict cardiovascular events, including sudden cardiac death. We tested the hypothesis that ECG provides useful information on guiding implantable cardioverter defibrillator (ICD) therapy into individuals with impaired left ventricular ejection fraction (LVEF). METHODS Retrospective data of primary prevention ICD implantations from 14 European centers were gathered. selleck compound The registry included 5111 subjects of whom 1687 patients had an interpretable pre-implantation ECG available (80.0% male, 63.3 ± 11.4 years). Primary outcome was survival without appropriate ICD shocks or heart transplantation. A low-risk ECG was defined as a combination of ECG variables that were associated with the primary outcome. RESULTS A total of 1224 (72.6%) patients survived the follow-up (2.9 ± 1.7 years) without an ICD shock, 224 (13.3%) received an appropriate shock and 260 (15.4%) died. Low-risk ECG defined as QRS duration less then 120 ms, QTc interval less then 450 ms for men and less then 470 ms for women, and sinus rhythm, were met by 515 patients (30.5%). Multivariable Cox regression showed that the hazard (HR) for death, heart transplantation or appropriate shock were reduced by 42.5% in the low-risk group (HR 0.575; 95% CI 0.45-0.74; p  less then  0.001), compared to the high-risk group. The HR for the first appropriate shock was 42.1% lower (HR 0.58; 95% CI 0.41-0.82; p = 0.002) and the HR for death was 48.0% lower (HR 0.52; 95% CI 0.386-0.72; p  less then  0.001) in the low-risk group. CONCLUSION Sinus rhythm, QRS less then 120 ms and normal QTc in standard 12-lead ECG provides information about survival without appropriate ICD shocks and might improve patient selection for primary prevention ICD therapy. BACKGROUND Growing evidence has indicated that microRNAs (miRNAs) are involved in the progression of calcific aortic valve disease (CAVD), a progressive pathological condition with no effective pharmacological therapy. This study was set out with the aim to investigate possible roles of miR-195 in CAVD. METHODS AND RESULTS Initially, the differential expressed genes (DEGs) associated with CAVD were screened out and miRNAs potentially regulating VWF were predicted from microarray analysis. Next, we quantified VWF and miR-195 expression in isolated aortic valve interstitial cells (AVICs) and aortic valve tissues, followed by confirmation of the target relationship between miR-195 and VWF using the dual luciferase reporter assay. Furthermore, we evaluated the biological functions of miR-195 and VWF on ALP activity, cell differentiation, and the levels of miR-195, VWF, Runx2, OCN, ALP, p38 and phosphorylated p38 in AVICs. VWF was highly expressed, while miR-195 was poorly expressed in CAVD. Furthermore, miR-195 targeted VWF and negatively regulated its expression. Upregulation of miR-195 or silencing VWF could reduce ALP activity, calcified deposition, and the mRNA and protein levels of Runx2, OCN, and ALP by inhibiting the p38-MAPK signaling pathway, thereby ameliorating aortic valve calcification in vitro. CONCLUSIONS On all accounts, miR-195 can potentially inhibit aortic valve calcification by repressing VWF and p38-MAPK signaling pathway, highlighting a theoretical basis for pharmacological treatment of CAVD. This is a report of the 2019 Annual Meeting of the AAP National Conference and Exhibition-Section on Surgery held from October 25 through October 27 in New Orleans, Louisiana. BACKGROUND Cross-sectional imaging (CSI) may be clinically unnecessary in the evaluation of pectus excavatum (PE). The purpose of our study was to prospectively evaluate the accuracy and reliability of the modified percent depth (MPD), derived from caliper-based external measurements, in identifying PE. METHODS Children 11-21 years old presenting for evaluation of PE or to obtain thoracic cross-sectional imaging for other indications were measured to derive the Modified Percent Depth. The Haller Index (HI) and Correction Index (CI) were calculated from CSI. Receiver-Operator Characteristic (ROC) analysis was used to compare the sensitivity and specificity of MPD, HI, and CI. Interrater reliability was assessed using Spearman's correlation coefficient and Cohen's Kappa coefficient. RESULTS Of 199 patients, 76 (38%) had severe PE. Median age was 16 years (range = 11-21). The median Modified Percent Depth was 21.4% (IQR = 16.2-26.3) among those with PE versus 4.1% (IQR = 1.7-6.4) in those without (p  0.71, p  less then  0.