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Mechanistic target of rapamycin (mTOR) pathway plays a role in features common to both excess salt/aldosterone and cardiovascular/renal diseases. Dietary sodium can upregulate mTORC1 signaling in cardiac and renal tissue, and inhibition of mTOR can prevent aldosterone associated, salt-induced hypertension. The impact of sex and age on mTOR's role in volume homeostasis and the regulation of aldosterone secretion is largely unknown. We hypothesize that both age and sex modify mTOR's interaction with volume homeostatic mechanisms. The activity of three volume homeostatic mechanisms---cardiovascular, renal and hormonal (aldosterone- sodium retaining and brain natriuretic peptide (BNP)- sodium losing)---were assessed in mTORC1 deficient (Raptor +/-) and wildtype male and female littermates at two different ages. The mice were volume stressed by giving a liberal salt (LibS) diet. Raptor +/- mice of both sexes when they aged 1) reduced their blood pressure; 2) increased left ventricular internal diameter during diastole; 3) decreased renal blood flow; and 4) increased mineralocorticoid receptor expression. Aldosterone levels did not differ by sex in young Raptor +/- mice. However, as they aged, compared to their littermates, aldosterone decreased in males but increased in females. Finally, given the level of Na+ intake, BNP was inappropriately suppressed, but only in Raptor +/- males. These data indicate that Raptor +/- mice, when stressed with a LibS diet, display inappropriate volume homeostatic responses, particularly with aging, and the mechanisms altered, differ by sex. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Management of pediatric drowning often includes evaluation and treatment of infectious disease. There are few data describing the infections associated with pediatric drowning. METHODS A descriptive retrospective study was designed, and patients aged 24 hours to our institution after a drowning were included from January 2011 through June 30, 2017. Data collection included patient demographics, submersion injury details, resuscitation details, patient admission details, chest radiograph on admission, use of intubation and mechanical ventilation, hospital length of stay, culture data, antimicrobial use, and mortality. Descriptive statistical methods (mean and standard deviation, median and range, percentage) were used to characterize the patient population, and Fisher exact test was used to evaluate the association between antimicrobial use in the first 72 hours of admission and mortality. RESULTS A total of 114 patients met study criteria (male, 59.7%; median age, 3.7 years [range, 0.15-17.79 yeares. © The Author(s) 2020. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.OBJECTIVES To evaluate in vitro activity of the novel β-lactamase boronate inhibitor taniborbactam (VNRX-5133) combined with cefepime or meropenem against 500 urinary Gram-negative bacilli. METHODS Cefepime/taniborbactam and 14 comparators were tested by broth microdilution or agar dilution methods. A total of 450 Enterobacteriaceae and 50 Pseudomonas aeruginosa were selected from 2017 to 2019 based on different β-lactamase-producing or resistance phenotypes. For carbapenem-non-susceptible isolates, the modified carbapenem inactivation method (mCIM), EDTA-CIM (eCIM) and amplification of carbapenemase genes were performed. For NDM-producing isolates and those with cefepime/taniborbactam MICs >8 mg/L, the MICs of meropenem/taniborbactam and/or mutations in PBP3 were investigated. RESULTS Taniborbactam improved cefepime activity with the same efficiency as avibactam improved ceftazidime activity against 66 KPC-2 producers, 30 non-carbapenemase-producing carbapenem-non-susceptible Enterobacteriaceae and 28 merope. aeruginosa. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email journals.permissions@oup.com.INTRODUCTION The Out-of-Hospital Cardiac Arrest (OHCA) Outcomes project is a national research registry. One of its aims is to explore sources of variation in OHCA survival outcomes. This study reports the development and validation of risk prediction models for return of spontaneous circulation (ROSC) at hospital handover and survival to hospital discharge. METHODS AND RESULTS The study included OHCA patients who were treated during 2014 and 2015 by emergency medical services (EMS) from 7 English National Health Service ambulance services. The 2014 data were used to identify important variables and to develop the risk prediction models, which were validated using the 2015 data. Model prediction was measured by area under the curve (AUC), Hosmer-Lemeshow test, Cox calibration regression and Brier score. All analyses were conducted using mixed effects logistic regression models. https://www.selleckchem.com/products/Chlorogenic-acid.html Important factors included age, gender, witness/bystander cardiopulmonary resuscitation (CPR) combined, aetiology and initial rhythm. Interaction effects between witness/bystander CPR with gender, aetiology and initial rhythm and between aetiology and initial rhythm were significant in both models. The survival model achieved better discrimination and overall accuracy compared with the ROSC model (AUC=0.86 vs 0.67, Brier score=0.072 vs 0.194, respectively). Calibration tests showed over- and under-estimation for the ROSC and survival models, respectively. A sensitivity analysis individually assessing Index of Multiple Deprivation scores and location in the final models substantially improved overall accuracy with inconsistent impact on discrimination. CONCLUSION Our risk prediction models identified and quantified important pre-EMS intervention factors determining survival outcomes in England. The survival model had excellent discrimination. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email journals.permissions@oup.com.
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