Quinine blocks 5-HT and 5-HT3 receptor mediated peristalsis in both guinea pig and mouse ileum tissue

Introduction. Quinine is commonly used to treat malaria; however one of the principal side effects is gastrointestinal disturbances (White, 1992). 5-HT3 receptors modulate gut peristalsis (Chetty et al., 2006), and, as quinine has been shown to act as a 5-HT3 receptor antagonist (Thompson and Lummis, 2008) it is possible that these side effects result from actions at gut 5-HT3 receptors. To address this question, we examined the ability of quinine to antagonise 5-HT and 5-HT3 mediated peristalsis in guinea pig and mouse ileum. Methods. Ileum was excised from male guinea pigs (200-300g) and C57BL/6 mice (25-35g) following cervical dislocation. Ileum segments (3-5 cm) were mounted in 50 ml organ baths containing Tryode’s solution at 35-37 °C. Concentration-response curves were constructed for 5-HT and the selective 5-HT3 agonist 2-Me-5-HT (non-cumulative doses). Quinine was pre-applied for 10 min and inhibition measured using agonist concentrations that elicited a submaximal response. Results. Concentration-dependent contractions produced by 5-HT (pEC50 = 5.45 ± 0.17, n = 8) and the selective 5-HT3 agonist 2-Me-5-HT (5.01 ± 0.17, n = 11) were not significantly different (Student’s t-test, t = 0.619, df = 17, p = 0.544) in guinea pig ileum. Increasing concentrations of quinine were able to antagonise the activities of both 5-HT (pIC50 = 5.03 ± 0.2, n = 6) and 2-Me-5HT (pIC50 = 4.59 ± 0.26, n = 4). At mouse ileum, 5-HT (pEC50 = 7.57 ± 0.33, n = 9) was more potent (Student’s t-test, t = 3.6, df = 12, p = 0.004) than 2-Me-5-HT (pEC50 = 5.45 ± 0.58, n = 5). Quinine antagonised both the 5-HT (pIC50 = 4.87 ± 0.31, n = 7) and 2-Me-5-HT-induced (pIC50 = 6.18 ± 1.14, n = 4) contractions. Conclusions. These results support previous electrophysiological studies that identified quinine as an antagonist at recombinant 5-HT3 receptors with IC50 values comparable with those reported here (pIC50 = 4.87, Thompson et al., 2007). Further, we found that quinine completely blocked 5-HT induced contractions in mouse and guinea pig, raising the possibility that quinine targets other 5-HT receptors in the gut (e.g., 5-HT4 receptors) and may influence intestinal function

ALMA Observations of Circumnuclear Disks in Early Type Galaxies: 12CO(2-1) and Continuum Properties

We present results from an Atacama Large Millimeter/submillimeter Array (ALMA) Cycle 2 program to map CO(2-1) emission in nearby early-type galaxies (ETGs) that host circumnuclear gas disks. We obtained $\sim0.3''-$resolution Band 6 observations of seven ETGs selected on the basis of dust disks in Hubble Space Telescope images. We detect CO emission in five at high signal-to-noise ratio with the remaining two only faintly detected. All CO emission is coincident with the dust and is in dynamically cold rotation. Four ETGs show evidence of rapid central rotation; these are prime candidates for higher-resolution ALMA observations to measure the black hole masses. In this paper we focus on the molecular gas and continuum properties. Total gas masses and H$_2$ column densities for our five CO-bright galaxies are on average $\sim10^8$ $M_\odot$ and $\sim10^{22.5}$ cm$^{-2}$ over the $\sim$kpc-scale disks, and analysis suggests that these disks are stabilized against gravitational fragmentation. The continuum emission of all seven galaxies is dominated by a central, unresolved source, and in five we also detect a spatially extended component. The $\sim$230 GHz nuclear continua are modeled as power laws ranging from $S_\nu \sim \nu^{-0.4}$ to $\nu^{1.6}$ within the observed frequency band. The extended continuum profiles of the two radio-bright (and CO-faint) galaxies are roughly aligned with their radio jet and suggests resolved synchrotron jets. The extended continua of the CO-bright disks are coincident with optically thick dust absorption and have spectral slopes that are consistent with thermal dust emission.Comment: 20 pages, 10 figures; accepted for publication in Ap

Does video feedback analysis improve CPR performance in phase 5 medical students?

BACKGROUND: The use of simulation in medical education is increasing, with students taught and assessed using simulated patients and manikins. Medical students at Queen’s University of Belfast are taught advanced life support cardiopulmonary resuscitation as part of the undergraduate curriculum. Teaching and feedback in these skills have been developed in Queen’s University with high-fidelity manikins. This study aimed to evaluate the effectiveness of video compared to verbal feedback in assessment of student cardiopulmonary resuscitation performance. METHODS: Final year students participated in this study using a high-fidelity manikin, in the Clinical Skills Centre, Queen’s University Belfast. Cohort A received verbal feedback only on their performance and cohort B received video feedback only. Video analysis using ‘StudioCode’ software was distributed to students. Each group returned for a second scenario and evaluation 4 weeks later. An assessment tool was created for performance assessment, which included individual skill and global score evaluation. RESULTS: One hundred thirty eight final year medical students completed the study. 62 % were female and the mean age was 23.9 years. Students having video feedback had significantly greater improvement in overall scores compared to those receiving verbal feedback (p = 0.006, 95 % CI: 2.8–15.8). Individual skills, including ventilation quality and global score were significantly better with video feedback (p = 0.002 and p < 0.001, respectively) when compared with cohort A. There was a positive change in overall score for cohort B from session one to session two (p < 0.001, 95 % CI: 6.3–15.8) indicating video feedback significantly benefited skill retention. In addition, using video feedback showed a significant improvement in the global score (p < 0.001, 95 % CI: 3.3–7.2) and drug administration timing (p = 0.004, 95 % CI: 0.7–3.8) of cohort B participants, from session one to session two. CONCLUSIONS: There is increased use of simulation in medicine but a paucity of published data comparing feedback methods in cardiopulmonary resuscitation training. Our study shows the use of video feedback when teaching cardiopulmonary resuscitation is more effective than verbal feedback, and enhances skill retention. This is one of the first studies to demonstrate the benefit of video feedback in cardiopulmonary resuscitation teaching. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12909-016-0726-x) contains supplementary material, which is available to authorized users

Effect of the velopharynx on intraluminal pressures in reconstructed pharynges derived from individuals with and without sleep apnea

The most collapsible part of the upper airway in the majority of individuals is the velopharynx which is the segment positioned behind the soft palate. As such it is an important morphological region for consideration in elucidating the pathogenesis of obstructive sleep apnea (OSA). This study compared steady flow properties during inspiration in the pharynges of nine male subjects with OSA and nine body-mass index (BMI)- and age-matched control male subjects without OSA. The k–ωωSST turbulence model was used to simulate the flow field in subject-specific pharyngeal geometric models reconstructed from anatomical optical coherence tomography (aOCT) data. While analysis of the geometry of reconstructed pharynges revealed narrowing at velopharyngeal level in subjects with OSA, it was not possible to clearly distinguish them from subjects without OSA on the basis of pharyngeal size and shape alone. By contrast, flow simulations demonstrated that pressure fields within the narrowed airway segments were sensitive to small differences in geometry and could lead to significantly different intraluminal pressure characteristics between subjects. The ratio between velopharyngeal and total pharyngeal pressure drops emerged as a relevant flow-based criterion by which subjects with OSA could be differentiated from those without

Reduced waiting times using a fast switching dual-polarization DDQPSK receiver in a packet switched network

In this paper, we demonstrate a fast switching dual polarization DDQPSK packet switched receiver with very short waiting times. The system employs mth power DDQPSK decoding for high frequency offset tolerance, and Stokes parameter estimation for robust polarization demultiplexing

Reduced OSNR penalty for frequency drift tolerant coherent packet switched systems using doubly differential decoding

In this paper we will demonstrate the improved BER performance of doubly differential phase shift keying in a coherent optical packet switching scenario while still retaining the benefits of high frequency offset tolerance

Employing DDBPSK in optical burst switched systems to enhance throughput

We demonstrate that doubly differential decoding can demodulate phase shift keyed data much faster after the switching event of a tunable laser than usual mth power single differential decoding. This technique can significantly improve throughput of optical burst switched networks

Demonstrating doubly-differential quadrature phase shift keying in the optical domain

We report for the first time the experimental demonstration of doubly differential quadrature phase shift keying (DDQPSK) using optical coherent detection. This method is more robust against high frequency offsets (FO) than conventional single differential quadrature phase shift keying (SDQPSK) with offset compensation. DDQPSK is shown to be able to compensate large FOs (up to the baud rate) and has lower computational requirements than other FO compensation methods. DDQPSK is a simple algorithm to implement in a real-time decoder for optical burst switched network scenarios. Simulation results are also provided, which show good agreement with the experimental results for both SDQPSK and DDQPSK transmissions

Imaging Mismatch Repair and Cellular Responses to DNA Damage in Bacillus subtilis

Both prokaryotes and eukaryotes respond to DNA damage through a complex set of physiological changes. Alterations in gene expression, the redistribution of existing proteins, and the assembly of new protein complexes can be stimulated by a variety of DNA lesions and mismatched DNA base pairs. Fluorescence microscopy has been used as a powerful experimental tool for visualizing and quantifying these and other responses to DNA lesions and to monitor DNA replication status within the complex subcellular architecture of a living cell. Translational fusions between fluorescent reporter proteins and components of the DNA replication and repair machinery have been used to determine the cues that target DNA repair proteins to their cognate lesions in vivo and to understand how these proteins are organized within bacterial cells. In addition, transcriptional and translational fusions linked to DNA damage inducible promoters have revealed which cells within a population have activated genotoxic stress responses. In this review, we provide a detailed protocol for using fluorescence microscopy to image the assembly of DNA repair and DNA replication complexes in single bacterial cells. In particular, this work focuses on imaging mismatch repair proteins, homologous recombination, DNA replication and an SOS-inducible protein in Bacillus subtilis. All of the procedures described here are easily amenable for imaging protein complexes in a variety of bacterial species

Mismatch repair causes the dynamic release of an essential DNA polymerase from the replication fork

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/86887/1/MMI_7841_sm_SuppInfor.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/86887/2/j.1365-2958.2011.07841.x.pd