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Despite the substantial commonality, "healthy" and "common" aging genes also showed distinct function enrichment, and "common" aging genes had a higher enrichment for disease genes; 3. Disease-associated gene regulations were overall different from aging gene regulations. However, for genes regulated by both, their regulation directions were largely consistent, implying some aging processes could increase the susceptibility to disease development; and 4. Possible protective mechanisms were associated with some "healthy" aging gene regulations. In summary, our work highlights several unique features of GTEx "healthy" aging program. This new knowledge could potentially be used to develop interventions to promote the human healthspan. © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.BACKGROUND There is no effective method to predict paravalvular regurgitation prior to transcatheter aortic valve replacement (TAVR). METHODS We retrospectively analyzed pre-TAVR computed tomography (CT) scans of 20 patients who underwent TAVR for severe, calcific aortic stenosis and subsequently printed 3-dimensional (3D) aortic root models of each patient. Models were printed using Ninjaflex thermoplastic polyurethane (TPU) (Ninjatek Manheim, PA) and TPU 95A (Ultimaker, Netherlands) on Ultimaker 3 Extended 3D printer (Ultimaker, Netherlands). The models were implanted at nominal pressure with same sized Sapien balloon-expandable frames (Edwards Lifesciences, CA) as received in-vivo. Ex-vivo implanted TAVR models (eTAVR) were scanned using Siemens SOMATOM flash dual source CT (Siemens, Malvern, PA) and then analyzed with Mimics software (Materialize NV, Leuven, Belgium) to evaluate relative stent appositions. eTAVR were then compared to post-TAVR echocardiograms for each patient to assess for correlations of identified and predicted paravalvular leak (PVL) locations. RESULTS A total of 20 patients (70% male) were included in this study. The median age was 77.5 (74-83.5) years. Ten patients were characterized to elicit mild (9/10) or moderate (1/10) PVL, and 10 patients presented no PVL. In patients with echocardiographic PVL, eTAVR 3D model analyses correctly identified the site of PVL in 8/10 cases. In patients without echocardiographic PVL, eTAVR 3D model analyses correctly predicted the lack of PVL in 9/10 cases. CONCLUSION 3D printing may help predict the potential locations of associated PVL post-TAVR, which may have implications for optimizing valve selection and sizing. © 2020 Wiley Periodicals, Inc.OBJECTIVE To evaluate dogs treated with hemodialysis for severe metaldehyde intoxication and to compare them with conventionally-managed patients. DESIGN Retrospective study (2012-2017). SETTING University teaching hospital. ANIMALS Data from 18 dogs with severe metaldehyde intoxication were analyzed. Eleven dogs were treated with intermittent hemodialysis and 7 managed conventionally. INTERVENTIONS None. MEASUREMENT AND MAIN RESULTS Metaldehyde poisoning was diagnosed based on clinical signs and toxicological analysis or presence of turquoise material in the gastrointestinal content. Clinical signs, additional treatments, dialysis prescription, duration of anesthesia and hospitalization, complications, and outcome were documented. Results were analyzed by t-test, Mann-Whitney U-test, and Chi-square test. P less then 0.05 was considered significant. Dialysis was performed for median (range) 180 min (150-420 min) with median of 2.28 L/kg (1.66-4.48 L/kg) blood volume processed. In the hemodialysis group, anesthesia was discontinued at a median of 3.0 hours (1.5-6.7 h) after starting dialysis. The conventional-group received general anesthesia for a median of 17.5 hours (7.0-30.5 h). No further anticonvulsive treatment was necessary for the hemodialysis group. Time to hospital discharge was shorter in dialyzed dogs (median 18 h; 15-41 h) compared to conventionally treated dogs (median 89 h; 61-168 h; P = 0.0014). Aspiration pneumonia was reported in 5 conventionally treated dogs and none of the dialyzed dogs (P = 0.001). Five dialyzed dogs developed hematoma at the dialysis catheter site. One dog in each group was euthanized. CONCLUSION Hemodialysis significantly decreases the requirement for anesthesia and length of hospitalization in dogs with metaldehyde intoxication. Aspiration pneumonia occurred less often in dialyzed patients. Prospective studies are warranted to confirm the clinical utility of hemodialysis in dogs with metaldehyde poisoning. © Veterinary Emergency and Critical Care Society 2020.AIMS Women with heart failure (HF) are under-represented in individual randomized clinical trials (RCTs). Little is known about sex-specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectrum of left ventricular ejection fraction (LVEF). METHODS AND RESULTS Individual patient data fixed-effect meta-analysis was performed using 6167 patients (31.4% were women) recruited in three placebo-controlled RCTs Randomized Aldactone Evaluation Study (RALES), Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) and Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT)-Americas. Compared to men, women were older, had higher body mass index and lower glomerular filtration rate. They also had higher LVEF and poorer New York Heart Association functional class and were less likely to be taking angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Placebo-arm event rates were lower for women compared with men (15.4 vs. 22.1 per 100 person-year; P = 0.002). https://www.selleckchem.com/products/Acadesine.html MRAs reduced consistently, in men and women, the relative risk for cardiovascular death or HF hospitalization (P for interaction = 0.83), cardiovascular death (P for interaction = 0.44) and all-cause death (P for interaction = 0.19). These findings remained consistent after adjustment for potential confounders, regardless of LVEF. There was no sex-specific impact of MRA on the rate of hyperkalaemia and worsening renal function during the median 22 months of follow-up. CONCLUSION In three large MRA RCTs, women were substantially different from men with regard to their clinical features and event rates. Nonetheless, this meta-analysis supports a consistent and beneficial MRA effect regardless of sex. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.
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