A 12-year-old girl with absent radial pulse: arterial thoracic outlet syndrome with subclavian artery aneurysm and thrombosis of the brachial artery

Brachial arterial occlusion is rare in children and adolescents. Once a traumatic cause is excluded, the differential diagnosis consists of a variety of rare conditions. We report the case of a 12-year-old girl whose presenting symptoms—an absent radial pulse and Raynaud's phenomenon of the right hand—could be easily mistaken for a vasculitis. She was found to have arterial thoracic outlet syndrome with right subclavian artery compression and aneurysm formation caused by an anomalous first rib and consecutive thromboembolic occlusion of the brachial artery. The diagnosis and differential diagnosis of this condition are reviewe

Simultaneous OH-PLIF and schlieren imaging of flame acceleration in an obstacle-laden channel

Flame acceleration in stoichiometric H_2/O_2 at 12 and 25 kPa initial pressure in an obstacle-laden square cross-section channel was studied experimentally using planar laser-induced fluorescence imaging of hydroxyl radicals (OH-PLIF) and simultaneous high-speed schlieren imaging. Results were obtained resolving the explosion front structure as it develops immediately after ignition as a slow-flame to the eventual formation of a shock-flame complex in the fast-flame regime. The images provide a novel level of detail and allow for the determination of the effects of turbulence-flame and shock-flame interaction. In the slow-flame regime, vortex shedding off obstacle edges occurs over long time-scales, vortices are convected downstream and turbulent combustion takes place in the obstacle wakes. The fast-flame regime is marked by the presence of compression waves (and shock waves) which interact with the flame and cause macroscopic deformation of the flame and small-scale wrinkling due to Richtmyer-Meshkov instability. A quasi-steady fast-flame is characterized by the close proximity of the precursor shock and the turbulent flame. The flow-field that governs the flame shape is established impulsively by the precursor shock. Shock-flame interactions lead to flame front perturbations on both small and large scales. The OH-PLIF technique makes it possible to discern the flame front from other density interfaces that appear in the complex fast-flame structure observed in schlieren images and also eliminates the line-of-sight integration limitation

Gastric emptying after overnight fasting and clear fluid intake: a prospective investigation using serial magnetic resonance imaging in healthy children†

Background Current guidelines recommend preoperative fasting of 2 h for clear fluids, which is often exceeded in routine clinical practice. Existing data on residual gastric volumes in children do not consider fluid intake within <2 h and rely on the aspiration of gastric contents via a gastric tube. This study evaluated the emptying of clear fluids from the stomach using magnetic resonance imaging (MRI). Methods Healthy volunteers aged 6-14 years were asked to fast overnight. MRI scans to assess gastric volumes were obtained before and immediately after drinking 7 ml kg−1 of diluted raspberry syrup and then every 30 min up to 120 min. Volumes were determined by a blinded investigator and indexed gastric fluid/air volumes (GFVw/GAVw) and half-life (t1/2) of GFVw course after clear fluid intake were calculated. Results Sixteen children, median age 9.2 (range 6.4-12.8) years, were investigated. Median (range) GFVw was 0.62 (0.15-0.97) ml kg−1 before and 6.68 (4.77-7.78) ml kg−1 immediately after fluid intake, and 2.92 (0.43-5.04), 1.27 (0.28-3.62), 0.42 (0.07-2.49), and 0.32 (0.04-1.13) ml kg−1 30, 60, 90, and 120 min thereafter. Median GFVw declined exponentially (t1/2=26.1 min). Median individual t1/2 was 23.6 (range 17.9-47.8) min. GAVw showed considerable intra- and inter-individual variation. Conclusions In healthy school children, gastric emptying after ingestion of clear fluid occurs with a median half-life time of <30 min but with considerable inter-individual variatio

Functional architecture of olfactory ionotropic glutamate receptors.

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate chemical communication between neurons at synapses. A variant iGluR subfamily, the Ionotropic Receptors (IRs), was recently proposed to detect environmental volatile chemicals in olfactory cilia. Here, we elucidate how these peripheral chemosensors have evolved mechanistically from their iGluR ancestors. Using a Drosophila model, we demonstrate that IRs act in combinations of up to three subunits, comprising individual odor-specific receptors and one or two broadly expressed coreceptors. Heteromeric IR complex formation is necessary and sufficient for trafficking to cilia and mediating odor-evoked electrophysiological responses in vivo and in vitro. IRs display heterogeneous ion conduction specificities related to their variable pore sequences, and divergent ligand-binding domains function in odor recognition and cilia localization. Our results provide insights into the conserved and distinct architecture of these olfactory and synaptic ion channels and offer perspectives into the use of IRs as genetically encoded chemical sensors. VIDEO ABSTRACT

The possibilities and prospects of obtaining high-resolution information (below 30 Å) on biological material using the electron microscope: Some comments and reports inspired by an EMBO workshop held at Gais, Switzerland, October 1973

Commercially available electron microscopes routinely provide resolution of some 2-4 Å, as determined on the spacing of crystalline lattices of certain stable, small-molecular substances. On biological material either macromolecules or macromolecular assemblies— ‘biologically significant' details below some 20 Å have hitherto not been observed.we consider as ‘biologically significant' those structural details observed or contained in electronmicrographs which are consistent with, or confirmed by, other data obtained from biochemical or functional experiments or by other physical methods (optical, magnetic, electric

Effect of different quantities of a sugared clear fluid on gastric emptying and residual volume in children: a crossover study using magnetic resonance imaging

Background Gastric emptying in the first 2 h after 7 ml kg−1 of sugared clear fluid has recently been investigated in healthy children using magnetic resonance imaging (MRI). This study aims to compare gastric volume and emptying half-life during 1 h after 3 or 7 ml kg−1 sugared clear fluid intake. Methods Fourteen healthy volunteer children aged 11.1 (8.2-12.5) yr were investigated prospectively after administration of 3 and 7 ml kg−1 diluted raspberry syrup in a randomized order, after overnight fasting (baseline). Gastric content volume (GCVw) was assessed with a 1.5 Tesla MRI scanner in a blinded fashion. Data are presented as median (range) and compared using the Wilcoxon test. Results Baseline GCVw was 0.39 (0.04-1.00) and 0.34 (0.07-0.75) before intake of 3 and 7 ml kg−1 syrup, respectively (P=0.93). GCVw was 0.45 (0.04-1.55)/1.33 (0.30-2.60) ml kg−1 60 min after ingestion of 3/7 ml kg−1 syrup (P=0.002). Thus GCVw had declined to baseline after 3 ml kg−1 (P=0.39) but not after 7 ml kg−1 (P=0.001) within 60 min. T1/2 was 20 (10-62)/27 (13-43) min (P=0.73) after 3/7 ml kg−1. Conclusion In healthy volunteer children, residual GCVw 1 h after intake of 3 ml kg−1 syrup is significantly smaller than that after 7 ml kg−1 and within the range of baselin

Acid-sensing ion channel 1a drives AMPA receptor plasticity following ischemia and acidosis in hippocampal CA1 neurons

The CA1 region of the hippocampus is particularly vulnerable to ischemic damage. While NMDA receptors play a major role in excitotoxicity, it is thought to be exacerbated in this region by two forms of post-ischemic AMPA receptor (AMPAR) plasticity - namely, anoxic long-term potentiation (a-LTP), and a delayed increase in the prevalence of Ca2+ -permeable GluA2-lacking AMPARs (CP-AMPARs). The acid-sensing ion channel 1a (ASIC1a) which is expressed in CA1 pyramidal neurons, is also known to contribute to post-ischemic neuronal death and to physiologically induced LTP. This raises the question - does ASIC1a activation drive the post-ischemic forms of AMPAR plasticity in CA1 pyramidal neurons? We have tested this by examining organotypic hippocampal slice cultures (OHSCs) exposed to oxygen glucose deprivation (OGD), and dissociated cultures of hippocampal pyramidal neurons (HPN) exposed to low pH (acidosis). We find that both a-LTP and the delayed increase in the prevalence of CP-AMPARs are dependent on ASIC1a activation during ischemia. Indeed, acidosis alone is sufficient to induce the increase in CP-AMPARs. We also find that inhibition of ASIC1a channels circumvents any potential neuroprotective benefit arising from block of CP-AMPARs. By demonstrating that ASIC1a activation contributes to post-ischemic AMPAR plasticity, our results identify a functional interaction between acidotoxicity and excitotoxicity in hippocampal CA1 cells, and provide insight into the role of ASIC1a and CP-AMPARs as potential drug targets for neuroprotection. We thus propose that ASIC1a activation can drive certain forms of CP-AMPAR plasticity, and that inhibiting ASIC1a affords neuroprotection

Extracellular Matrix Proteins and Tumor Angiogenesis

Tumor development is a complex process that relies on interaction and communication between a number of cellular compartments. Much of the mass of a solid tumor is comprised of the stroma which is richly invested with extracellular matrix. Within this matrix are a host of matricellular proteins that regulate the expression and function of a myriad of proteins that regulate tumorigenic processes. One of the processes that is vital to tumor growth and progression is angiogenesis, or the formation of new blood vessels from preexisting vasculature. Within the extracellular matrix are structural proteins, a host of proteases, and resident pro- and antiangiogenic factors that control tumor angiogenesis in a tightly regulated fashion. This paper discusses the role that the extracellular matrix and ECM proteins play in the regulation of tumor angiogenesis

Quantitative evaluation of aortic valve regurgitation in 4D flow cardiac magnetic resonance: at which level should we measure?

PURPOSE To find the best level to measure aortic flow for quantification of aortic regurgitation (AR) in 4D flow CMR. METHODS In 27 congenital heart disease patients with AR (67% male, 31 ± 16 years) two blinded observers measured antegrade, retrograde, net aortic flow volumes and regurgitant fractions at 6 levels in 4D flow: (1) below the aortic valve (AV), (2) at the AV, (3) at the aortic sinus, (4) at the sinotubular junction, (5) at the level of the pulmonary arteries (PA) and (6) below the brachiocephalic trunk. 2D phase contrast (2DPC) sequences were acquired at the level of PA. All patients received prior transthoracic echocardiography (TTE) with AR severity grading according to a recommended multiparametric approach. RESULTS After assigning 2DPC measurements into AR grading, agreement between TTE AR grading and 2DPC was good (κ = 0.88). In 4D flow, antegrade flow was similar between the six levels (p = 0.87). Net flow was higher at level 1-2 than at levels 3-6 (p < 0.05). Retrograde flow and regurgitant fraction at level 1-2 were lower compared to levels 3-6 (p < 0.05). Reproducibility (inter-reader agreement: ICC 0.993, 95% CI 0.986-0.99; intra-reader agreement: ICC 0.982, 95%CI 0.943-0.994) as well as measurement agreement between 4D flow and 2DPC (ICC 0.994; 95%CI 0.989 - 0.998) was best at the level of PA. CONCLUSION For estimating severity of AR in 4D flow, best reproducibility along with best agreement with 2DPC measurements can be expected at the level of PA. Measurements at AV or below AV might underestimate AR

Myocardial Deformation in Fontan Patients Assessed by Cardiac Magnetic Resonance Feature Tracking: Correlation with Function, Clinical Course, and Biomarkers

Cardiac MR (CMR) is a standard modality for assessing ventricular function of single ventricles. CMR feature-tracking (CMR-FT) is a novel application enabling strain measurement on cine MR images and is used in patients with congenital heart diseases. We sought to assess the feasibility of CMR-FT in Fontan patients and analyze the correlation between CMR-FT strain values and conventional CMR volumetric parameters, clinical findings, and biomarkers. Global circumferential (GCS) and longitudinal (GLS) strain were retrospectively measured by CMR-FT on Steady-State Free Precession cine images. Data regarding post-operative course at Fontan operation, and medication, exercise capacity, invasive hemodynamics, and blood biomarkers at a time interval ± 6 months from CMR were collected. Forty-seven patients underwent CMR 11 ± 6 years after the Fontan operation; age at CMR was 15 ± 7 years. End-diastolic volume (EDV) of the SV was 93 ± 37 ml/m2, end-systolic volume (ESV) was 46 ± 23 ml/m2, and ejection fraction (EF) was 51 ± 11%. Twenty (42%) patients had a single right ventricle (SRV). In single left ventricle (SLV), GCS was higher (p < 0.001), but GLS was lower (p = 0.04) than in SRV. GCS correlated positively with EDV (p = 0.005), ESV (p < 0.001), and EF (p ≤ 0.0001). GLS correlated positively with EF (p = 0.002), but not with ventricular volumes. Impaired GCS correlated with decreased ventricular function (p = 0.03) and atrioventricular valve regurgitation (p = 0.04) at echocardiography, direct atriopulmonary connection (p = 0.02), post-operative complications (p = 0.05), and presence of a rudimentary ventricle (p = 0.01). A reduced GCS was associated with increased NT-pro-BNP (p = 0.05). Myocardial deformation can be measured by CMR-FT in Fontan patients. SLVs have higher GCS, but lower GLS than SRVs. GCS correlates with ventricular volumes and EF, whereas GLS correlates with EF only. Myocardial deformation shows a relationship with several clinical parameters and NT-pro-BNP. Keywords: Biomarkers; CMR; CMR-FT; Fontan; Strai