Definition of two agonist types at the mammalian cold-activated channel TRPM8.

Various TRP channels act as polymodal sensors of thermal and chemical stimuli, but the mechanisms whereby chemical ligands impact on TRP channel gating are poorly understood. Here we show that AITC (allyl isothiocyanate; mustard oil) and menthol represent two distinct types of ligands at the mammalian cold sensor TRPM8. Kinetic analysis of channel gating revealed that AITC acts by destabilizing the closed channel, whereas menthol stabilizes the open channel, relative to the transition state. Based on these differences, we classify agonists as either type I (menthol-like) or type II (AITC-like), and provide a kinetic model that faithfully reproduces their differential effects. We further demonstrate that type I and type II agonists have a distinct impact on TRPM8 currents and TRPM8-mediated calcium signals in excitable cells. These findings provide a theoretical framework for understanding the differential actions of TRP channel ligands, with important ramifications for TRP channel structure-function analysis and pharmacology

The Intercultural Skills Graduates and Businesses in Europe Need Today

This ERASMUS+ funded project, “Developing the cross-cultural skills of graduates in response to the needs of European enterprise”, is developed in response to recent research highlighting the importance of intercultural competencies for graduates wanting to work in Europe, the employers’ needs, and the intercultural competencies and skills higher education institutions provide. This project aims to develop the intercultural competencies of graduates in the EU by enhancing the quality and relevance of their knowledge and skills to enable them to be active professionals in the European working environment. Five Higher Education Institutions have participated in this study: University of Worcester (Project lead, UK), London South Bank University (UK), UC Leuven-Limburg (Belgium), Halmstad University (Sweden), and Bursa Uludağ University (Turkey). The diversity of these partners, their respective regional and national contexts, and their experience in working together with regional businesses are central to achieve the project aims. As the first output of the project, this report presents results based on two types of analysis methods and data collected from four European countries (UK, Sweden, Belgium, and Turkey). Firstly, two surveys and the quantitative analysis of data collected from 585 student surveys responses and 403 employer survey responses and secondly, on an analysis of qualitative data collected through 50 interviews with employees in European organizations and 50 interviews with students studying in European universities

Standardization of the Fully Stapled Laparoscopic Roux-en-Y Gastric Bypass for Obesity Reduces Early Immediate Postoperative Morbidity and Mortality: A Single Center Study on 2606 Patients

Various techniques of laparoscopic Roux-en-Y gastric bypass have been described. We completely standardized this procedure to minimize its sometimes substantial morbidity and mortality. This study describes our experience with the standardized fully stapled laparoscopic Roux-en-Y gastric bypass (FS-LRYGB) and its influence on the 30-day morbidity and mortality.status: publishe

Ideal versus corrected body weight for dosage of sugammadex in morbidly obese patients

Summary To date, the dosing of sugammadex is based on real body weight without taking fat content into account. We compared the reversal of profound rocuronium-induced neuromuscular blockade in morbidly obese patients using doses of sugammadex based on four different weight corrections. One hundred morbidly obese patients, scheduled for laparoscopic bariatric surgery under propofolsufentanil anaesthesia, were randomly assigned four groups: ideal body weight; ideal body weight + 20%; ideal body weight + 40%; and real body weight. Patients received sugammadex 2 mg.k

In vivo evaluation of a vibration analysis technique for the per-operative monitoring of the fixation of hip prostheses

<p>Abstract</p> <p>Background</p> <p>The per-operative assessment of primary stem stability may help to improve the performance of total hip replacement. Vibration analysis methods have been successfully used to assess dental implant stability, to monitor fracture healing and to measure bone mechanical properties. The objective of the present study was to evaluate in vivo a vibration analysis-based endpoint criterion for the insertion of the stem by successive surgeon-controlled hammer blows.</p> <p>Methods</p> <p>A protocol using a vibration analysis technique for the characterisation of the primary bone-prosthesis stability was tested in 83 patients receiving a custom-made, intra-operatively manufactured stem prosthesis. Two groups were studied: one (n = 30) with non cemented and one (n = 53) with partially cemented stem fixation. Frequency response functions of the stem-femur system corresponding to successive insertion stages were compared.</p> <p>Results</p> <p>The correlation coefficient between the last two frequency response function curves was above 0.99 in 86.7% of the non cemented cases. Lower values of the final correlation coefficient and deviations in the frequency response pattern were associated with instability or impending bone fracture. In the cases with a partially cemented stem an important difference in frequency response function between the final stage of non cemented trial insertion and the final cemented stage was found in 84.9% of the cases. Furthermore, the frequency response function varied with the degree of cement curing.</p> <p>Conclusion</p> <p>The frequency response function change provides reliable information regarding the stability evolution of the stem-femur system during the insertion. The protocol described in this paper can be used to accurately detect the insertion end point and to reduce the risk for intra-operative fracture.</p

Elastic principal manifolds and their practical applications

Principal manifolds serve as useful tool for many practical applications. These manifolds are defined as lines or surfaces passing through "the middle" of data distribution. We propose an algorithm for fast construction of grid approximations of principal manifolds with given topology. It is based on analogy of principal manifold and elastic membrane. The first advantage of this method is a form of the functional to be minimized which becomes quadratic at the step of the vertices position refinement. This makes the algorithm very effective, especially for parallel implementations. Another advantage is that the same algorithmic kernel is applied to construct principal manifolds of different dimensions and topologies. We demonstrate how flexibility of the approach allows numerous adaptive strategies like principal graph constructing, etc. The algorithm is implemented as a C++ package elmap and as a part of stand-alone data visualization tool VidaExpert, available on the web. We describe the approach and provide several examples of its application with speed performance characteristics.Comment: 26 pages, 10 figures, edited final versio