Pathophysiological mechanisms of catecholamine and cocaine-mediated cardiotoxicity.

Overactivation of the sympatho-adrenergic system is an essential mechanism providing short-term adaptation to the stressful conditions of critical illnesses. In the same way, the administration of exogenous catecholamines is mandatory to support the failing circulation in acutely ill patients. In contrast to these short-term benefits, prolonged adrenergic stress is detrimental to the cardiovascular system by initiating a series of adverse effects triggering significant cardiotoxicity, whose pathophysiological mechanisms are complex and only partially elucidated. In addition to the development of myocardial oxygen supply/demand imbalance induced by the sustained activation of adrenergic receptors, catecholamines can damage cardiomyocytes by fostering mitochondrial dysfunction, via two main mechanisms. The first one is calcium overload, consecutive to β-adrenergic receptor-mediated activation of protein kinase A and subsequent phosphorylation of multiple Ca(2+)-cycling proteins. The second one is oxidative stress, primarily related to the transformation of catecholamines into "aminochromes," which undergo redox cycling in mitochondria to generate copious amounts of oxygen-derived free radicals. In turn, calcium overload and oxidative stress promote mitochondrial permeability transition and cardiomyocyte cell death, both via the apoptotic and necrotic pathways. Comparable mechanisms of myocardial toxicity, including marked oxidative stress and mitochondrial dysfunction, have been reported with the use of cocaine, a common recreational drug with potent sympathomimetic activity. The aim of the current review is to present in detail the pathophysiological processes underlying the development of catecholamine and cocaine-induced cardiomyopathy, as such conditions may be frequently encountered in the clinical practice of cardiologists and ICU specialists.

Challenges and opportunities for science journalists in adopting new technologies: the case of Spain = Retos y oportunidades para los periodistas científicos en la adopción de las nuevas tecnologías: el caso de España

This paper analyses the adoption of new information and communication technologies (ICTs) by Spanish journalists specialising in science. Applying an ethnographic research model, this study was based on a wide sample of professionals, aiming to evaluate the extent by which science journalists have adopted the new media and changed the way they use information sources. In addition, interviewees were asked whether in their opinion the Web 2.0 has had an impact on the quality of the news. The integration of formats certainly implies a few issues for today’s newsrooms. Finally, with the purpose of improving the practice of science information dissemination, the authors put forward a few proposals, namely: Increasing the training of Spanish science journalists in the field of new technologies; Emphasising the accuracy of the information and the validation of sources; Rethinking the mandates and the tasks of information professionals.

French summaries of product characteristics: content in relation to therapeutic monitoring of psychotropic drugs.

The prescription information (summary of product characteristics, SPC) is compiled by the pharmaceutical industry as required by the national regulatory authorities. They vary in their content about the properties of drugs and about the usefulness of therapeutic drug monitoring (TDM) in the blood of patients. Based on a previous study carried out in Germany, the degree of agreement of French SPC for 59 psychotropic drugs with the existing medico-scientific evidence in the area of TDM was examined using a recently developed instrument. A summary score of SPC content (SPCC) related to TDM (SPCC(TDM)) has been calculated and compared with the level of recommendation of TDM of the AGNP-TDM expert group consensus guidelines for TDM in psychiatry [AGNP: Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (Association for neuropsychopharmacology and pharmacopsychiatry)]. Among the antidepressants, antipsychotics, tranquillizers/hypnotic agents and mood stabilizers, the highest SPCC(TDM) scores in the French SPC were reached for imipramine (16), haloperidol (6), clonazepam (8) and lithium (23), respectively. Results were similar to those obtained from the analysis of German SPC, and considerable disagreement was found between the information on TDM in SPC and existing medico-scientific evidence, albeit less in the case of mood stabilizers. Taking into account the recommendations of the AGNP-TDM expert group guidelines, there is a deficit in the French SPC concerning TDM-relevant information. An amelioration of this situation could help to improve the clinical practice of TDM of psychotropic drugs, as the SPC is a widely used tool.

Diurnal and exercise-related variability of haemoglobin and reticulocytes in athletes.

Haemoglobin (Hb) and Reticulocytes (Ret) are measured as indirect markers of doping in athletes. We studied the diurnal variation, the impact of exercise, fluid intake and ambient temperature in athletes on these parameters. Hourly venous blood samples were obtained from 36 male athletes of different disciplines (endurance (END) and non-endurance (NON-END)) over 12 h during a typical training day. Seven inactive subjects served as controls (CON). Hb and Ret were determined. A mixed model procedure was used to analyse the data. At baseline, Hb was similar for all groups, END showed lower Ret than NON-END and CON. Exercise showed a significant impact on Hb (+0.46 g/dl, p<0.001), the effect disappeared approximately 2 h after exercise. Hb decreased over the day by approximately 0.55 g/dl (p<0.01). There was no relevant effect on Ret. Fluid intake and ambient temperature had no significant effect. Hb shows significant diurnal- and exercise related variations. In an anti-doping context, most of these variations are in favour of the athlete. Blood samples taken after exercise might therefore provide reliable results and thus be used for the longitudinal monitoring of athletes if a timeframe for the re-equilibration of vascular volumes is respected.

May absorbable suture anchors increase the rate of recurrent dislocations after shoulder stabilization?

Introduction: Absorbable anchors are frequently used in shoulder surgery. Mechanisms of absorption induce a local inflammatory reaction. It is not clear if this process may disturb healing of the capsule and ligaments. The purpose of the study was to compare the rate of recurrent dislocation following open shoulder stabilization when using absorbable or non-absorbable suture anchors. Methods: Between 1999 and 2003, 83 open Bankart repairs were performed by the same surgeon. All patients had recurrent traumatic anterior shoulder instability. All had preoperative arthro-MRI or arthro-CT which did not reveal any significant bony Bankart lesion or rotatorcuff tear. Thirty-four patients were treated with absorbable anchors (Panalok®) and sutures (Panacryl®) and 49 with non-absorbable anchors (Mitek GII®) and sutures (Ethibond®). The same surgical technique and rehabilitation protocol were used. The incidence of sports ability and recurrent instability were recorded. We defined instability as true dislocation. Results: Five patients on 34 were lost to follow-up in the absorbable group and 7 on 49 in the non-absorbable group. The mean age of absorbable group was 25 years (range, 17-39 years). At a mean follow-up of 66 months (range, 54-76 months), 86% could resume sports activity. Five patients on 29 (17%) reported recurrent instability and two did need revision surgery. The mean age in non-absorbable group was 28 year (range, 18-47 years). At a mean follow-up of 78 months (range, 49-82 months), 93% could resume sports activity. Three patients on 42 (7%) reported recurrent instability and one did need revision surgery. Conclusion: This clinical study showed a clear tendency to a higher recurrence rate of dislocation when using absorbable suture anchors (17% in absorbable vs 7% in non-absorbable group). It is known that Panacryl® may be responsible for a major local inflammatory response. However, it is still unclear if this could be the failure etiology. Consequently, we prefer to use systematically non-absorbable sutureanchors for shoulder stabilization.

India in Translation through Hindi Literature. A Plurality of Voices

What role have translations from Hindi literary works played in shaping and transforming our knowledge about India? In this book, renowned scholars, translators and Hindi writers from India, Europe, and the United States offer their approaches to this question. Their articles deal with the political, cultural, and linguistic criteria germane to the selection and translation of Hindi works, the nature of the enduring links between India and Europe, and the reception of translated texts, particularly through the perspective of book history. More personal essays, both on the writing process itself or on the practice of translation, complete the volume and highlight the plurality of voices that are inherent to any translation. As the outcome of an international symposium held at the University of Lausanne, Switzerland, in 2008, India in Translation through Hindi Literature engages in the building of critical histories of the encounter between India and the «West», the use and impact of translations in this context, and Hindi literature and culture in connection to English (post)colonial power, literature and culture.

Wave-height hazard analysis in Eastern Coast of Spain : Bayesian approach using generalized Pareto distribution

Standard practice of wave-height hazard analysis often pays little attention to the uncertainty of assessed return periods and occurrence probabilities. This fact favors the opinion that, when large events happen, the hazard assessment should change accordingly. However, uncertainty of the hazard estimates is normally able to hide the effect of those large events. This is illustrated using data from the Mediterranean coast of Spain, where the last years have been extremely disastrous. Thus, it is possible to compare the hazard assessment based on data previous to those years with the analysis including them. With our approach, no significant change is detected when the statistical uncertainty is taken into account. The hazard analysis is carried out with a standard model. Time-occurrence of events is assumed Poisson distributed. The wave-height of each event is modelled as a random variable which upper tail follows a Generalized Pareto Distribution (GPD). Moreover, wave-heights are assumed independent from event to event and also independent of their occurrence in time. A threshold for excesses is assessed empirically. The other three parameters (Poisson rate, shape and scale parameters of GPD) are jointly estimated using Bayes' theorem. Prior distribution accounts for physical features of ocean waves in the Mediterranean sea and experience with these phenomena. Posterior distribution of the parameters allows to obtain posterior distributions of other derived parameters like occurrence probabilities and return periods. Predictives are also available. Computations are carried out using the program BGPE v2.0

Recovery of rotators strength after latarjet surgery.

The purposes of this study were to prospectively determine changes in rotator cuff strength before and after surgical shoulder stabilization by Bristow-Latarjet procedure and to better estimate time needed for rotator cuff strength recovery. 20 patients with recurrent anterior posttraumatic shoulder dislocation underwent internal (IR) and external (ER) rotator isokinetic evaluation before and 3, 6 and 21 months after Bristow-Latarjet surgery. In a seated position with 45° of shoulder abduction in the scapular plane, both shoulders were evaluated concentrically with a Con-Trex® isokinetic dynamometer at 180°∙s - 1, 120°∙s - 1 and 60°∙s - 1. 3 months post-surgery, IR and ER strength of the operated shoulder were significantly lower than before surgery ( - 28±20% for IR, - 17±17% for ER) (P<0.05). At 6 and 21 months post-surgery, IR and ER strength were comparable to strength before surgery; strength recovery is seen at 6 months post-surgery with long-term maintenance at 21 months. Given the weakness 3 months post-surgery, return to sports (including overhead and contact sports) should be discussed, and 6 months post-surgery may be a better point for an athlete to resume practicing sports. Isokinetic rotator cuff strength evaluation appears to be relevant in helping to determine the need of continuing strength rehabilitation. Pre-surgical evaluation contributes to the relevance of later comparisons.

Maintenance of Traffic for Innovative Geometric Design Work Zones, 2015

Currently there are no guidelines within the Manual on Uniform Traffic Control Devices (MUTCD) on construction phasing and maintenance of traffic (MOT) for retrofit construction and maintenance projects involving innovative geometric designs. The research presented in this report addressed this gap in existing knowledge by investigating the state of the practice of construction phasing and MOT for several types of innovative geometric designs including the roundabout, single point urban interchange (SPUI), diverging diamond interchange (DDI), restricted-crossing left turn (RCUT), median U-turn (MUT), and displaced left turn (DLT). This report provides guidelines for transportation practitioners in developing construction phasing and MOT plans for innovative geometric designs. This report includes MOT Phasing Diagrams to assist in the development of MOT strategies for innovative designs. The MOT Phasing Diagrams were developed through a review of literature, survey, interviews with practitioners, and review of plans from innovative geometric design projects. These diagrams are provided as a tool to assist in improving work zone safety and mobility through construction of projects with innovative geometric designs. The aforementioned synthesis of existing knowledge documented existing practices for these types of designs.

Stab wounds in a Swiss emergency department: a series of 80 consecutive cases.

Background: Interpersonal violence is a worldwide social reality which seems to increasingly affect even the safest of countries, such as Switzerland. In this country, road traffic accidents, as well as professional and recreational activities, are the main providers of trauma-related injuries. The incidence of penetrative trauma related to stab wounds seems to be regularly increasing in our ED. The question arises of whether our strategies in trauma management are adapted to deal efficiently with these injuries.Methods: To answer this question, the study analysed patients admitted for intentional penetrative injuries in a tertiary urban emergency department (ED) during a 23 month period. Demographics, conditions of the assault, injury type and treatments applied were analysed.Results: Eighty patients admitted due to an intentional penetrating trauma accounted for 0.2% of the surgical practice of our ED. The assault occurred equally in a public or a private context, mainly affecting young males during the night and the weekend. Sixty six patients (83%) were treated as out-patients. Only 10 patients needed surgery. None of them required damage control surgery. No patient died and the mean hospital stay was 5.5 days.Conclusions: The prevalence of stab wounds in Switzerland is low. These injuries rarely need complex, surgical procedures. Observational strategies should be considered according to the patient status.

Detection in urine of 4-methyl-2-hexaneamine, a doping agent.

Stimulants are banned in-competition for all categories of sports by the World Anti-Doping Agency. A simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay employing electrospray ionisation in positive mode was developed in that work for the quantification in urine specimens of 4-methyl-2-hexaneamine, a primary amine exhibiting sympathomimetic properties. Following a simple pretreatment procedure, the analyte was separated using a gradient mobile phase on reverse phase C8 column. Selected reaction monitoring m/z 116.2-->57.3 was specific for detection of 4-methyl-2-hexaneamine and the assay exhibited a linear dynamic range of 50-700 ng/mL. The validated method has been successfully applied to analyze the target compound in food supplements as well as in urine specimens. The administered drug (40 mg) was detected at the level of 350 ng/mL in the urine up to 4 days.

Accuracy of indirect estimation of power output from uphill performance in cycling.

PURPOSE: To use measurement by cycling power meters (Pmes) to evaluate the accuracy of commonly used models for estimating uphill cycling power (Pest). Experiments were designed to explore the influence of wind speed and steepness of climb on accuracy of Pest. The authors hypothesized that the random error in Pest would be largely influenced by the windy conditions, the bias would be diminished in steeper climbs, and windy conditions would induce larger bias in Pest. METHODS: Sixteen well-trained cyclists performed 15 uphill-cycling trials (range: length 1.3-6.3 km, slope 4.4-10.7%) in a random order. Trials included different riding position in a group (lead or follow) and different wind speeds. Pmes was quantified using a power meter, and Pest was calculated with a methodology used by journalists reporting on the Tour de France. RESULTS: Overall, the difference between Pmes and Pest was -0.95% (95%CI: -10.4%, +8.5%) for all trials and 0.24% (-6.1%, +6.6%) in conditions without wind (<2 m/s). The relationship between percent slope and the error between Pest and Pmes were considered trivial. CONCLUSIONS: Aerodynamic drag (affected by wind velocity and orientation, frontal area, drafting, and speed) is the most confounding factor. The mean estimated values are close to the power-output values measured by power meters, but the random error is between ±6% and ±10%. Moreover, at the power outputs (>400 W) produced by professional riders, this error is likely to be higher. This observation calls into question the validity of releasing individual values without reporting the range of random errors.

Effect of hip flexion angle on hamstring optimum length after a single set of concentric contractions.

The eccentric contraction mode was proposed to be the primary stimulus for optimum angle (angle at which peak torque occurs) shift. However, the training range of motion (or muscle excursion range) could be a stimulus as important. The aim of this study was to assess the influence of the training range of motion stimulus on the hamstring optimum length. It was hypothesised that performing a single set of concentric contractions beyond optimal length (seated at 80° of hip flexion) would lead to an immediate shift of the optimum angle to longer muscle length while performing it below (supine at 0° of hip flexion) would not provide any shift. Eleven male participants were assessed on an isokinetic dynamometer. In both positions, the test consisted of 30 consecutive knee flexions at 4.19 rad · s⁻¹. The optimum angle was significantly shifted by ∼15° in the direction of longer muscle length after the contractions at 80° of hip flexion, while a non-significant shift of 3° was found at 0°. The hamstring fatigability was not influenced by the hip position. It was concluded that the training range of motion seems to be a relevant stimulus for shifting the optimum angle to longer muscle length. Moreover, fatigue appears as a mechanism partly responsible for the observed shift.