Red blood cell membrane conductance in hereditary haemolytic anaemias

Congenital haemolytic anaemias are inherited disorders caused by red blood cell membrane and cytoskeletal protein defects, deviant hemoglobin synthesis and metabolic enzyme deficiencies. In many cases, although the causing mutation might be known, the pathophysiology and the connection between the particular mutation and the symptoms of the disease are not completely understood. Thus effective treatment is lagging behind. As in many cases abnormal red blood cell cation content and cation leaks go along with the disease, by direct electrophysiological measurements of the general conductance of red blood cells, we aimed to assess if changes in the membrane conductance could be a possible cause. We recorded whole-cell currents from 29 patients with different types of congenital haemolytic anaemias: 14 with hereditary spherocytosis due to mutations in α-spectrin, β-spectrin, ankyrin and band 3 protein; 6 patients with hereditary xerocytosis due to mutations in Piezo1; 6 patients with enzymatic disorders (3 patients with glucose-6-phosphate dehydrogenase deficiency, 1 patient with pyruvate kinase deficiency, 1 patient with glutamate-cysteine ligase deficiency and 1 patient with glutathione reductase deficiency), 1 patient with β-thalassemia and 2 patients, carriers of several mutations and a complex genotype. While the patients with β-thalassemia and metabolic enzyme deficiencies showed no changes in their membrane conductance, the patients with hereditary spherocytosis and hereditary xerocytosis showed largely variable results depending on the underlying mutation

A Tonnetz Model for pentachords

This article deals with the construction of surfaces that are suitable for representing pentachords or 5-pitch segments that are in the same $T/I$ class. It is a generalization of the well known \"Ottingen-Riemann torus for triads of neo-Riemannian theories. Two pentachords are near if they differ by a particular set of contextual inversions and the whole contextual group of inversions produces a Tiling (Tessellation) by pentagons on the surfaces. A description of the surfaces as coverings of a particular Tiling is given in the twelve-tone enharmonic scale case.Comment: 27 pages, 12 figure

Perioperative Propranolol Against Dental Anxiety: A Randomized Controlled Trial

Background: Promising results from a trauma reactivation study on post-traumatic stress disorder suggest that propranolol is capable of attenuating symptoms of traumatically induced mental disorders by blocking memory reconsolidation. Methods: A randomized, parallel, placebo-controlled, quadruple-blind trial was designed to determine the effectiveness of perioperative propranolol during exposure to dental extractions in reducing dental anxiety in patients with dental anxiety or dental phobia. Between November 2014 and December 2018, 52 patients with high levels of fear in anticipation of dental extractions who were referred to a department of oral and maxillofacial surgery for at least two tooth and/or molar removals with 1 month in between were included. On the first visit participants received either 120 mg of perioperative oral propranolol (n = 19) or placebo (n = 17), and a core fear memory was reactivated 1 h preoperatively. The primary outcome was change in severity of dental anxiety from baseline to 1-month follow-up, as indexed by the short version of the dental anxiety inventory (S-DAI). Secondary outcome measures were change in intra-operative state anxiety and specific phobia diagnoses. Results: Linear mixed model (LMM) yielded no statistically significant difference in change of dental trait anxiety from baseline to 1-month follow-up between propranolol and placebo groups (Cohen's d = 0.23). S-DAI scores decreased in both study arms from baseline to follow-up (propranolol arm: from 32.1 [SD = 7.3] to 29.1 [SD = 8.8]; placebo arm: from 31.6 [SD = 7.5] to 27.1 [SD = 6.5]). Also, administering propranolol was not associated with a significant difference in change of intra-operative state anxiety or phobia diagnoses between groups over time. Conclusions: The results do not concur with earlier findings regarding post-traumatic stress disorder, and suggest that individuals with traumatically induced fears or phobias do not benefit from the application of perioperative propranolol

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

The intestinal expulsion of the roundworm Ascaris suum is associated with eosinophils, intra-epithelial T cells and decreased intestinal transit time

Ascaris lumbricoides remains the most common endoparasite in humans, yet there is still very little information available about the immunological principles of protection, especially those directed against larval stages. Due to the natural host-parasite relationship, pigs infected with A. suum make an excellent model to study the mechanisms of protection against this nematode. In pigs, a self-cure reaction eliminates most larvae from the small intestine between 14 and 21 days post infection. In this study, we investigated the mucosal immune response leading to the expulsion of A. suum and the contribution of the hepato-tracheal migration. Self-cure was independent of previous passage through the liver or lungs, as infection with lung stage larvae did not impair self-cure. When animals were infected with 14-day-old intestinal larvae, the larvae were being driven distally in the small intestine around 7 days post infection but by 18 days post infection they re-inhabited the proximal part of the small intestine, indicating that more developed larvae can counter the expulsion mechanism. Self-cure was consistently associated with eosinophilia and intra-epithelial T cells in the jejunum. Furthermore, we identified increased gut movement as a possible mechanism of self-cure as the small intestinal transit time was markedly decreased at the time of expulsion of the worms. Taken together, these results shed new light on the mechanisms of self-cure that occur during A. suum infections

The ANTARES Optical Beacon System

ANTARES is a neutrino telescope being deployed in the Mediterranean Sea. It consists of a three dimensional array of photomultiplier tubes that can detect the Cherenkov light induced by charged particles produced in the interactions of neutrinos with the surrounding medium. High angular resolution can be achieved, in particular when a muon is produced, provided that the Cherenkov photons are detected with sufficient timing precision. Considerations of the intrinsic time uncertainties stemming from the transit time spread in the photomultiplier tubes and the mechanism of transmission of light in sea water lead to the conclusion that a relative time accuracy of the order of 0.5 ns is desirable. Accordingly, different time calibration systems have been developed for the ANTARES telescope. In this article, a system based on Optical Beacons, a set of external and well-controlled pulsed light sources located throughout the detector, is described. This calibration system takes into account the optical properties of sea water, which is used as the detection volume of the ANTARES telescope. The design, tests, construction and first results of the two types of beacons, LED and laser-based, are presented.Comment: 21 pages, 18 figures, submitted to Nucl. Instr. and Meth. Phys. Res.