Visualization of the intracavitary blood flow in systemic ventricles of Fontan patients by contrast echocardiography using particle image velocimetry

<p>Abstract</p> <p>Background</p> <p>Flow patterns in univentricular hearts may have clinical value. Therefore, it is our objective to asses and characterize vortex flow patterns with Fontan circulation in comparison with healthy controls.</p> <p>Methods</p> <p>Twenty-three patients (8 Fontan and 15 normal patients) underwent echocardiography with intravenous contrast agent (Sonovue^®) administration. Dedicated software was used to perform particle image velocimetry (PIV) and to visualize intracavitary flow in the systemic ventricles of the patients. Vortex parameters including vortex depth, length, width, and sphericity index were measured. Vortex pulsatility parameters including relative strength, vortex relative strength, and vortex pulsation correlation were also measured.</p> <p>Results</p> <p>The data from this study show that it is feasible to perform particle velocimetry in Fontan patients. Vortex length (VL) was significantly lower (0.51 ± 0.09 vs 0.65 ± 0.12, <it>P </it>= 0.010) and vortex width (VW) (0.32 ± 0.06 vs 0.27 ± 0.04, <it>p </it>= 0.014), vortex pulsation correlation (VPC) (0.26 ± 0.25 vs -0.22 ± 0.87, <it>p </it>= 0.05) were significantly higher in Fontan patients. Sphericity index (SI) (1.66 ± 0.48 vs 2.42 ± 0.62, <it>p </it>= 0.005), relative strength (RS) (0.77 ± 0.33 vs 1.90 ± 0.47, <it>p </it>= 0.0001), vortex relative strength (VRS) (0.18 ± 0.13 vs 0.43 ± 0.14, <it>p </it>= 0.0001) were significantly lower in the Fontan patients group.</p> <p>Conclusions</p> <p>PIV using contrast echocardiography is feasible in Fontan patients. Fontan patients had aberrant flow patterns as compared to normal hearts in terms of position, shape and sphericity of the main vortices. The vortex from the Fontan group was consistently shorter, wider and rounder than in controls. Whether vortex characteristics are related with clinical outcome is subject to further investigation.</p

Memory and synaptic plasticity are impaired by dysregulated hippocampal O-GlcNAcylation

O-GlcNAcylated proteins are abundant in the brain and are associated with neuronal functions and neurodegenerative diseases. Although several studies have reported the effects of aberrant regulation of O-GlcNAcylation on brain function, the roles of O-GlcNAcylation in synaptic function remain unclear. To understand the effect of aberrant O-GlcNAcylation on the brain, we used Oga+/- mice which have an increased level of O-GlcNAcylation, and found that Oga+/- mice exhibited impaired spatial learning and memory. Consistent with this result, Oga+/- mice showed a defect in hippocampal synaptic plasticity. Oga heterozygosity causes impairment of both long-term potentiation and long-term depression due to dysregulation of AMPA receptor phosphorylation. These results demonstrate a role for hyper-O-GlcNAcylation in learning and memory.ope

Mechanism of cellular rejection in transplantation

The explosion of new discoveries in the field of immunology has provided new insights into mechanisms that promote an immune response directed against a transplanted organ. Central to the allograft response are T lymphocytes. This review summarizes the current literature on allorecognition, costimulation, memory T cells, T cell migration, and their role in both acute and chronic graft destruction. An in depth understanding of the cellular mechanisms that result in both acute and chronic allograft rejection will provide new strategies and targeted therapeutics capable of inducing long-lasting, allograft-specific tolerance

Accurate detection of complex structural variations using single-molecule sequencing

Structural variations are the greatest source of genetic variation, but they remain poorly understood because of technological limitations. Single-molecule long-read sequencing has the potential to dramatically advance the field, although high error rates are a challenge with existing methods. Addressing this need, we introduce open-source methods for long-read alignment (NGMLR; https://github.com/philres/ngmlr ) and structural variant identification (Sniffles; https://github.com/fritzsedlazeck/Sniffles ) that provide unprecedented sensitivity and precision for variant detection, even in repeat-rich regions and for complex nested events that can have substantial effects on human health. In several long-read datasets, including healthy and cancerous human genomes, we discovered thousands of novel variants and categorized systematic errors in short-read approaches. NGMLR and Sniffles can automatically filter false events and operate on low-coverage data, thereby reducing the high costs that have hindered the application of long reads in clinical and research settings