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idoxine cannot be administered, we suggest performing ECTR only in patients with seizures refractory to GABAA receptor agonists (weak recommendation, very low quality of evidence). Oxidative stress and fibrosis are hallmarks of cardiomyopathy-induced heart failure yet are not effectively targeted by current frontline therapies. Here, the therapeutic effects of the anti-oxidant, N-acetylcysteine (NAC), were compared and combined with an acute heart failure drug with established anti-fibrotic effects, serelaxin (RLX), in a murine model of cardiomyopathy. Adult male 129sv mice were subjected to repeated isoprenaline (25 mg·kg )-induced cardiac injury for five consecutive days and then left to undergo fibrotic healing until Day 14. Subgroups of isoprenaline-injured mice were treated with RLX (0.5 mg·kg ·day ), NAC (25 mg·kg ·day ) or both combined, given subcutaneously via osmotic minipumps from Day 7 to 14. Control mice received saline instead of isoprenaline. Isoprenaline-injured mice showed increased left ventricular (LV) inflammation (~5-fold), oxidative stress (~1-2.5-fold), cardiomyocyte hypertrophy (~25%), cardiac remodelling, fibrosis (~2-2.5-fold) and dysfunction by Day 14 after injury. NAC alone blocked the cardiomyopathy-induced increase in LV superoxide levels, to a greater extent than RLX. Additionally, either treatment alone only partly reduced several measures of LV inflammation, remodelling and fibrosis. In comparison, the combination of RLX and NAC prevented the cardiomyopathy-induced LV macrophage infiltration, remodelling, fibrosis and cardiomyocyte size, to a greater extent than either treatment alone after 7 days. The combination therapy also restored the isoprenaline-induced reduction in LV function, without affecting systolic BP. These findings demonstrated that the simultaneous targeting of oxidative stress and fibrosis is key to treating the pathophysiology and dysfunction induced by cardiomyopathy.These findings demonstrated that the simultaneous targeting of oxidative stress and fibrosis is key to treating the pathophysiology and dysfunction induced by cardiomyopathy.IgA nephropathy (IgAN) is the most common type of glomerulonephritis worldwide, which follows a chronic but nonetheless highly variable course of progression. IgA immune complexes are the primary source of renal deposits in IgAN. Apart from the presence of granular IgA1 deposits in the glomerular mesangium and mesangial hypercellularity as common features, the detailed process of IgA1 deposition and clearance in the kidney remains unclear. We sought to examine the dynamics of IgA deposition and tissue plasticity in response to deposits including their intrarenal clearance. We followed a synthetic approach to produce a recombinant fusion between IgA Fc (rIgA) and a biotin tag, which was subsequently induced with streptavidin (SA) to form an oligomeric poly-IgA mimic. Both uninduced rIgA (mono-rIgA) and polymeric SA-rIgA (poly-rIgA) were injected intravenously into Wistar rats. Plasma IgA levels and renal and liver histology were examined in a time series. In contrast to mono-rIgA, this synthetic poly-rIgA analmage. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.The radiation of archosauromorph reptiles in the Triassic Period produced an unprecedented collection of diverse and disparate forms with a mix of varied ecologies and body sizes. Some of these forms were completely unique to the Triassic, whereas others were converged on by later members of Archosauromorpha. One of the most striking examples of this is with Triopticus primus, the early dome-headed form later mimicked by pachycephalosaurid dinosaurs. Here we fully describe the cranial anatomy of Triopticus primus, but also recognize a second dome-headed form from a Upper Triassic deposit in present-day India. The new taxon, Kranosaura kuttyi gen. et sp. nov., is likely the sister taxon of Triopticus primus based on the presence of a greatly expanded skull roof with a deep dorsal opening (possibly the pineal opening) through the dome, similar cranial sculpturing, and a skull table that is expanded more posterior than the posterior extent of the basioccipital. However, the dome of Kranosaura kuttyi gen. et sp. nov. extends anterodorsally, unlike that of any other archosauromorph. Histological sections and computed tomographic reconstructions through the skull of Kranosaura kuttyi gen. et sp. Crenolanib in vitro nov. further reveal the uniqueness of the dome of these early archosauromorphs. Moreover, our integrated analysis further demonstrates that there are many ways to create a dome in Amniota. The presence of 'dome-headed' archosauromorphs at two localities on the western and eastern portions of Pangea suggests that these archosauromorphs were widespread and are likely part of more assemblages than currently recognized. The modulation transfer function (MTF) is widely used as an objective metric of spatial resolution of medical imaging systems. Despite advances in capability for three-dimensional (3D) isotropic spatial resolution in computed tomography (CT) and cone-beam CT (CBCT), MTF evaluation for such systems is typically reported only in the axial plane, and practical methodology for assessment of fully 3D spatial resolution characteristics is lacking. This work reviews fundamental theoretical relationships of two-dimensional (2D) and 3D spread functions and reports practical methods and test tools for analysis of 3D MTF in CBCT. Fundamental aspects of 2D and 3D MTF measurement are reviewed within a common notational framework, and three MTF test tools with analysis code are reported and made available online (https//istar.jhu.edu/downloads/) (a) a multi-wire tool for measurement of the axial plane MTF [denoted as M T F ( f r considered to have isotropic resolution. Measurement of M T F ( f r ; φ = 45 ∘ ) provided a practical 1D measure of the underlying 3D MTF characteristics and is extensible to other CT or CBCT systems offering high, isotropic spatial resolution.

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