Kelleherhessellund6033

BACKGROUND Balloon aortic valvuloplasty (BAV) has seen renewed interest since the advent of transcatheter aortic valve implantation (TAVI). The study aimed to characterise a contemporary BAV cohort and determinants of clinical outcomes. METHODS Patients undergoing BAV at a single tertiary centre were retrospectively reviewed over a 10-year period, and functional and mortality outcomes were reported with up to a 2-year follow-up. RESULTS 224 patients (aged 82.5±8.3 years; 48% female) underwent BAV over the study period. Indications were either destination treatment (39%) or bridge-to-valve replacement (61%)-including bridge-to-decision (29%), symptom relief while on the waitlist (27%), and temporary contraindications to TAVI/aortic valve replacement (AVR) (5%). The mean reduction of aortic mean pressure gradient was 38%. Procedural mortality occurred in 0.5%, stroke in 1.3%, and major bleeding in 0.9%. Twelve-month mortality was 36% overall, and 26% and 50% in the bridging and destination groups, respectively. New York HeartAssociation (NYHA) class improved by ≥1 at 30 days in 50%. Among the bridge-to-TAVI/AVR group, 40% proceeded to TAVI/AVR within 12 months following BAV. In multivariate analysis, active malignancy at baseline (OR 4.4, 95% CI 1.3 to 15.1, p=0.02), smoking history (OR 3.3, 95% CI 1.3 to 7.9, p less then 0.01), LVEF ≤30% at baseline (OR 3.2, 95% CI 1.3 to 7.6, p less then 0.01), destination treatment (OR 2.2, 95% CI 1.0 to 4.9, p=0.04) were all associated with 12-month mortality. CONCLUSIONS BAV remains a useful procedure with relatively low rates of complications, however, 1-year mortality rates are high. Contemporary indications for BAV include a bridge to definitive valve replacement or destination treatment. © 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.The H+/Ca2+ (calcium ion) antiporter (CAX) plays an important role in maintaining cellular Ca2+ homeostasis in bacteria, yeast, and plants by promoting Ca2+ efflux across the cell membranes. However, how CAX facilitates Ca2+ balance in response to dynamic cytosolic Ca2+ perturbations is unknown. Here, we identified a type of Ca2+ "mini-sensor" in YfkE, a bacterial CAX homolog from Bacillus subtilis. The mini-sensor is formed by six tandem carboxylate residues within the transmembrane (TM)5-6 loop on the intracellular membrane surface. Ca2+ binding to the mini-sensor triggers the transition of the transport mode of YfkE from a high-affinity to a low-affinity state. Molecular dynamics simulation and fluorescence resonance energy transfer analysis suggest that Ca2+ binding to the mini-sensor causes an adjacent segment, namely, the exchanger inhibitory peptide (XIP), to move toward the Ca2+ translocation pathway to interact with TM2a in an inward-open cavity. The specific interaction was demonstrated with a synthetic peptide of the XIP, which inhibits YfkE transport and interrupts conformational changes mediated by the mini-sensor. By comparing the apo and Ca2+-bound CAX structures, we propose the following Ca2+ transport regulatory mechanism of YfkE Ca2+ binding to the mini-sensor induces allosteric conformational changes in the Ca2+ translocation pathway via the XIP, resulting in a rearrangement of the Ca2+-binding transport site in the midmembrane. Since the Ca2+ mini-sensor and XIP sequences are also identified in other CAX homologs and/or Ca2+ transporters, including the mammalian Na+/Ca2+ exchanger (NCX), our study provides a regulatory mechanism for the Ca2+/cation transporter superfamily.The anterior body of many fishes is shaped like an airfoil turned on its side. With an oscillating angle to the swimming direction, such an airfoil experiences negative pressure due to both its shape and pitching movements. this website This negative pressure acts as thrust forces on the anterior body. Here, we apply a high-resolution, pressure-based approach to describe how two fishes, bluegill sunfish (Lepomis macrochirus Rafinesque) and brook trout (Salvelinus fontinalis Mitchill), swimming in the carangiform mode, the most common fish swimming mode, generate thrust on their anterior bodies using leading-edge suction mechanics, much like an airfoil. These mechanics contrast with those previously reported in lampreys-anguilliform swimmers-which produce thrust with negative pressure but do so through undulatory mechanics. The thrust produced on the anterior bodies of these carangiform swimmers through negative pressure comprises 28% of the total thrust produced over the body and caudal fin, substantially decreasing the net drag on the anterior body. On the posterior region, subtle differences in body shape and kinematics allow trout to produce more thrust than bluegill, suggesting that they may swim more effectively. Despite the large phylogenetic distance between these species, and differences near the tail, the pressure profiles around the anterior body are similar. We suggest that such airfoil-like mechanics are highly efficient, because they require very little movement and therefore relatively little active muscular energy, and may be used by a wide range of fishes since many species have appropriately shaped bodies.Even though humans are mostly not aware of their heartbeats, several heartbeat-related effects have been reported to influence conscious perception. It is not clear whether these effects are distinct or related phenomena, or whether they are early sensory effects or late decisional processes. Combining electroencephalography and electrocardiography, along with signal detection theory analyses, we identify two distinct heartbeat-related influences on conscious perception differentially related to early vs. late somatosensory processing. First, an effect on early sensory processing was found for the heartbeat-evoked potential (HEP), a marker of cardiac interoception. The amplitude of the prestimulus HEP negatively correlated with localization and detection of somatosensory stimuli, reflecting a more conservative detection bias (criterion). Importantly, higher HEP amplitudes were followed by decreases in early (P50) as well as late (N140, P300) somatosensory-evoked potential (SEP) amplitudes. Second, stimulus timing along the cardiac cycle also affected perception. During systole, stimuli were detected and correctly localized less frequently, relating to a shift in perceptual sensitivity. This perceptual attenuation was accompanied by the suppression of only late SEP components (P300) and was stronger for individuals with a more stable heart rate. Both heart-related effects were independent of alpha oscillations' influence on somatosensory processing. We explain cardiac cycle timing effects in a predictive coding account and suggest that HEP-related effects might reflect spontaneous shifts between interoception and exteroception or modulations of general attentional resources. Thus, our results provide a general conceptual framework to explain how internal signals can be integrated into our conscious perception of the world. Copyright © 2020 the Author(s). Published by PNAS.Honey bees (Apis mellifera) produce an enormous economic value through their pollination activities and play a central role in the biodiversity of entire ecosystems. Recent efforts have revealed the substantial influence that the gut microbiota exert on bee development, food digestion, and homeostasis in general. In this study, deep sequencing was used to characterize prokaryotic viral communities associated with honey bees, which was a blind spot in research up until now. The vast majority of the prokaryotic viral populations are novel at the genus level, and most of the encoded proteins comprise unknown functions. Nevertheless, genomes of bacteriophages were predicted to infect nearly every major bee-gut bacterium, and functional annotation and auxiliary metabolic gene discovery imply the potential to influence microbial metabolism. Furthermore, undiscovered genes involved in the synthesis of secondary metabolic biosynthetic gene clusters reflect a wealth of previously untapped enzymatic resources hidden in the bee bacteriophage community. Copyright © 2020 the Author(s). Published by PNAS.Metal-organic framework (MOF) glasses are a newly emerged family of melt-quenched glasses. Recently, several intriguing features, such as ultrahigh glass-forming ability and low liquid fragility, have been discovered in a number of zeolitic imidazolate frameworks (ZIFs) that are a subset of MOFs. However, the fracture behavior of ZIF glasses has not been explored. Here we report an observation of both cracking pattern and shear bands induced by indentation in a representative melt-quenched ZIF glass, that is, ZIF-62 glass (ZnIm1.68bIm0.32). The shear banding in the ZIF glass is in strong contrast to the cracking behavior of other types of fully polymerized glasses, which do not exhibit any shear bands under indentation. We attribute this anomalous cracking behavior to the easy breakage of the coordinative bonds (Zn-N) in ZIF glasses, since these bonds are much weaker than the ionic and covalent bonds in network glasses.Increased intraocular pressure (IOP) represents a major risk factor for glaucoma, a prevalent eye disease characterized by death of retinal ganglion cells; lowering IOP is the only proven treatment strategy to delay disease progression. The main determinant of IOP is the equilibrium between production and drainage of aqueous humor, with compromised drainage generally viewed as the primary contributor to dangerous IOP elevations. Drainage occurs through two pathways in the anterior segment of the eye called conventional and uveoscleral. To gain insights into the cell types that comprise these pathways, we used high-throughput single-cell RNA sequencing (scRNAseq). From ∼24,000 single-cell transcriptomes, we identified 19 cell types with molecular markers for each and used histological methods to localize each type. We then performed similar analyses on four organisms used for experimental studies of IOP dynamics and glaucoma cynomolgus macaque (Macaca fascicularis), rhesus macaque (Macaca mulatta), pig (Sus scrofa), and mouse (Mus musculus). Many human cell types had counterparts in these models, but differences in cell types and gene expression were evident. Finally, we identified the cell types that express genes implicated in glaucoma in all five species. Together, our results provide foundations for investigating the pathogenesis of glaucoma and for using model systems to assess mechanisms and potential interventions.People evaluate a stranger's trustworthiness from their facial features in a fraction of a second, despite common advice "not to judge a book by its cover." Evaluations of trustworthiness have critical and widespread social impact, predicting financial lending, mate selection, and even criminal justice outcomes. Consequently, understanding how people perceive trustworthiness from faces has been a major focus of scientific inquiry, and detailed models explain how consensus impressions of trustworthiness are driven by facial attributes. However, facial impression models do not consider variation between observers. Here, we develop a sensitive test of trustworthiness evaluation and use it to document substantial, stable individual differences in trustworthiness impressions. Via a twin study, we show that these individual differences are largely shaped by variation in personal experience, rather than genes or shared environments. Finally, using multivariate twin modeling, we show that variation in trustworthiness evaluation is specific, dissociating from other key facial evaluations of dominance and attractiveness.