Hammondli8399

BACKGROUND Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. METHODS Using whole genome sequencing (WGS), a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6,340 invasive GBS recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in eight states. RESULTS Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in eleven clonal complexes (CCs) comprised of multilocus sequence types (MLSTs) identical or closely related to STs 1, 8, 12, 17, 19, 22, 23, 28, 88, 452 and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with non-susceptibility to one or more β-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin-nonsusceptible (MIC 2µg/ml). Nearly all isolates possessed capsule genes, 1-2 of the three main pilus gene clusters, and one of four homologous Alpha/Rib family determinants. Presence of hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. CONCLUSIONS This first comprehensive, population-based quantitation of strain features in the United States suggests current vaccine candidates should have good coverage. Beta-lactams remain appropriate for first line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.Soft tissues observed in clinical medical images are often prestrained in tension by internal pressure or tissue hydration. For a native disc, nucleus swelling occurs in equilibrium with osmotic pressure induced by the high concentration of proteoglycan in the nucleus. The objective of this computational study was to investigate the effects of nucleus swelling on disc geometry, fiber orientation, and mechanical behavior by comparing those of prestrained and zero-pressure (unswelled) discs. Thermoelastic analysis techniques were repurposed in order to determine the zero-pressure disc geometry which, when pressurized, matches the prestrained disc geometry observed in clinical images. The zero-pressure geometry was then used in simulations to approximately represent a degenerated disc, which loses the ability of nucleus swelling but has not undergone distinct soft tissue remodeling/deterioration. Our simulation results demonstrated that the loss of nucleus swelling caused a slight change in the disc geometry and fiber orientation, but a distinct deterioration in the resistance to intervertebral rotations (i.e., sagittal bending, lateral bending, and axial torsion). Different from rotational loading, in compression (with a displacement of 0.45 mm applied), a much larger stiffness (3.02 KN/mm) and a greater intradiscal pressure (0.61 MPa) were measured in the zero-pressure disc, compared to the prestrained disc (1.41 KN/mm and 0.52 MPa). This computational study could be useful to understand mechanisms of disc degeneration, and guide the future design of disc tissue engineering material. Copyright (c) 2020 by ASME.BACKGROUND Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. OBJECTIVES We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions. METHODS We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were allocated to MedDiet + extra-virgin olive oil, MedDiet + nuts, or control diet. Plasma metabolites were measured using a targeted approach by LC-tandem MS. We tested the associations of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with subsequent T2D risk using weighted Cox regression models and is-related metabolites that was significantly associated with T2D risk in a Mediterranean population at high cardiovascular disease risk. A MedDiet could counteract the detrimental effects of these metabolites.This trial was registered at controlled-trials.com as ISRCTN35739639. Copyright © The Author(s) 2020.BACKGROUND Arterial stiffness-typically assessed from non-invasive measurement of pulse wave velocity along a straight portion of the vascular tree between the right common carotid and femoral arteries-is a reliable predictor of cardiovascular risk in patients with essential hypertension. METHODS We reviewed how carotid-femoral pulse wave velocity increases with age and is significantly higher in hypertension (than in age- and gender-matched individuals without hypertension), particularly when hypertension is associated with diabetes mellitus. RESULTS From the elastic aorta to the muscular peripheral arteries of young healthy individuals, there is a gradual but significant increase in stiffness, with a specific gradient. This moderates the transmission of pulsatile pressure towards the periphery, thus protecting the microcirculatory network. POMHEX purchase The heterogeneity of stiffness between the elastic and muscular arteries causes the gradient to disappear or be inversed with aging, particularly in long-standing hypertension. CONCLUSIONS In hypertension therefore, pulsatile pressure transmission to the microcirculation is augmented, increasing the potential risk of damage to the brain, the heart, and the kidney. Furthermore, elevated pulse pressure exacerbates end-stage renal disease, particularly in older hypertensive individuals. With increasing age, the elastin content of vessel walls declines throughout the arterial network, and arterial stiffening increases further due to the presence of rigid wall material such as collagen, but also fibronectin, proteoglycans, and vascular calcification. Certain genes, mainly related to angiotensin and/or aldosterone, affect this aging process and contribute to the extent of arterial stiffness, which can independently affect both forward and reflected pressure waves. © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.