Calcium entry via TRPV1 but not ASICs induces neuropeptide release from sensory neurons

Inflammatory mediators induce neuropeptide release from nociceptive nerve endings and cell bodies, causing increased local blood flow and vascular leakage resulting in edema. Neuropeptide release from sensory neurons depends on an increase in intracellular Ca2+ concentration. In this study we investigated the role of two types of pH sensors in acid-induced Ca2+ entry and neuropeptide release from dorsal root ganglion (DRG) neurons. The transient receptor potential vanilloid 1 channel (TRPV1) and acid-sensing ion channels (ASICs) are both H+-activated ion channels present in these neurons, and are therefore potential pH sensors for this process. We demonstrate with in situ hybridization and immunocytochemistry that TRPV1 and several ASIC subunits are co-expressed with neuropeptides in DRG neurons. Activation of ASICs and of TRPV1 led to an increase in intracellular Ca2+ concentration. While TRPV1 has a high Ca2+ permeability and allows direct Ca2+ entry when activated, we show here that ASICs of DRG neurons mediate Ca2+ entry mostly by depolarization-induced activation of voltage-gated Ca2+ channels and only to a small extent via the pore of Ca2+-permeable ASICs. Extracellular acidification led to release of the neuropeptide calcitonin gene-related peptide from DRG neurons. The pH dependence and the pharmacological profile indicated that TRPV1, but not ASICs, induced neuropeptide secretion. In conclusion, this study shows that although both TRPV1 and ASICs mediate Ca2+ influx, TRPV1 is the principal sensor for acid-induced neuropeptide secretion from sensory neurons

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

Incidental findings of mass lesions on neuroimages in children

Increasing use of neuroimaging in children has led to more incidental findings of CNS mass lesions, the management of which is uncertain. The authors' aims in this study are to describe these mass lesions and their evolution, as well as to discuss the management options and determine the prevalence of incidental CNS mass lesions at their pediatric clinic. A retrospective study was undertaken in children with primary CNS tumors who were younger than 18 years old and were admitted to the University Children's Hospital of Zurich, Switzerland, between January 1995 and December 2010. In 19 (5.7%) of 335 patients with newly diagnosed CNS tumors, the diagnosis of a CNS mass lesion was an incidental finding. Reasons for obtaining neuroimages in these 19 patients were head trauma (in 6 patients); research protocols (in 3); nasal/orbital malformations (in 2); endocrinological and psychiatric evaluations (in 2); and vertebral bone anomaly without neurological signs, absence seizures, congenital ataxia, recurrent vomiting, developmental delay, and "check-up" at the explicit request of the parents (in 1 patient each). Seven patients underwent immediate surgery for low-grade glioma (4 patients) and craniopharyngioma, ependymoma, and choroid plexus papilloma (1 patient each); and 12 were treated conservatively or were observed. Ten of 12 conservatively treated patients remained stable (median follow-up time 1.8 years) and the other 2 underwent delayed surgery because of tumor progression (medulloblastoma in one patient and fibrillary astrocytoma in the other). Clinicians are increasingly challenged by the discovery of incidental CNS mass lesions. A subgroup of such lesions (with typical imaging patterns such as tectal glioma and dysembryoplastic neuroepithelial tumor) can be monitored conservatively, clinically, and radiographically. Future prospective studies are needed to define optimal management strategies based on larger collections of natural histories, as well as to assess the true prevalence of incidental CNS mass lesions

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

Counting using deep learning regression gives value to ecological surveys

Many ecological studies rely on count data and involve manual counting of objects of interest, which is time-consuming and especially disadvantageous when time in the field or lab is limited. However, an increasing number of works uses digital imagery, which opens opportunities to automatise counting tasks. In this study, we use machine learning to automate counting objects of interest without the need to label individual objects. By leveraging already existing image-level annotations, this approach can also give value to historical data that were collected and annotated over longer time series (typical for many ecological studies), without the aim of deep learning applications. We demonstrate deep learning regression on two fundamentally different counting tasks: (i) daily growth rings from microscopic images of fish otolith (i.e., hearing stone) and (ii) hauled out seals from highly variable aerial imagery. In the otolith images, our deep learning-based regressor yields an RMSE of 3.40 day-rings and an [Formula: see text] of 0.92. Initial performance in the seal images is lower (RMSE of 23.46 seals and [Formula: see text] of 0.72), which can be attributed to a lack of images with a high number of seals in the initial training set, compared to the test set. We then show how to improve performance substantially (RMSE of 19.03 seals and [Formula: see text] of 0.77) by carefully selecting and relabelling just 100 additional training images based on initial model prediction discrepancy. The regression-based approach used here returns accurate counts ([Formula: see text] of 0.92 and 0.77 for the rings and seals, respectively), directly usable in ecological research

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

The Role of Dysregulated Glucose Metabolism in Epithelial Ovarian Cancer

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and also one of the most poorly understood. Other health issues that are affecting women with increasing frequency are obesity and diabetes, which are associated with dysglycemia and increased blood glucose. The Warburg Effect describes the ability of fast-growing cancer cells to preferentially metabolize glucose via anaerobic glycolysis rather than oxidative phosphorylation. Recent epidemiological studies have suggested a role for hyperglycemia in the pathogenesis of a number of cancers. If hyperglycemia contributes to tumour growth and progression, then it is intuitive that antihyperglycemic drugs may also have an important antitumour role. Preliminary reports suggest that these drugs not only reduce available plasma glucose, but also have direct effects on cancer cell viability through modification of molecular energy-sensing pathways. This review investigates the effect that hyperglycemia may have on EOC and the potential of antihyperglycemic drugs as therapeutic adjuncts

Assessing the length of the mandibular ramus and the condylar process: a comparison of OPG, CBCT, CT, MRI, and lateral cephalometric measurements

SummaryBackground/Objectives: To compare different imaging procedures [cone beam computed tomography (CBCT), computed tomography (CT), magnetic resonance imaging (MRI), orthopantomography (OPG), and lateral cephalometry (LC)] for assessing the mandibular height [ramus height (RH)] and condylar process (CondProc) length as they reflect mandibular growth. Materials/Methods: The RH and CondProc of eight cadaver heads (each side separately) were measured using CBCT, CT, MRI, OPG, and LC. They were measured twice by two independent observers parallel to the posterior border of the mandibular ramus. An intraclass correlation coefficient (ICC) was used to assess the inter- and intraobserver reliability. The coefficient of variation was used to elucidate precision. Bland-Altman (BA) plots were used to assess the agreement between the procedures and the intra- and interobserver measurements. Results: All procedures, with the exception of LC, showed good intra- and interobserver agreement (maximum range of agreement: 5.3mm) and excellent reliability (ICC > 0.9). The BA plot analysis for the CondProc and RH showed similar ranges of agreement between MRI, CT, and CBCT (maximum 6.4mm) but higher ranges for OPG and LC. The MRI and OPG values were generally smaller. Conclusions/Implications: All 3D imaging procedures yielded nearly equal results when used to measure the CondProc and RH. MRI is recommended because it avoids ionizing radiation and has higher sensitivity in the detection of inflammation. A 2-year threshold for detecting growth in the follow-up period should be taken into account for all 3D imaging methods. Measuring the RH is recommended for the follow-up of condylar growth because reference values for annual increments are publishe