La troponine T ultrasensible : un nouvel outil diagnostic pour le médecin sportif?

peer reviewedIntroduction : Le risque d’accidents cardiaques ou de mort subite après effort physique intense est bien connu. Ces évènements indésirables se produisent souvent chez des sujets présentant une maladie coronarienne asymptomatique et ignorée. Néanmoins, vu ce risque, l’American Heart Association recommande de réaliser un screening cardiovasculaire chez les athlètes de tout âge. Dans cette optique, le dosage de marqueurs cardiaques de nouvelle génération, plus sensibles, comme la troponine T ultrasensible (hsTnT) peut certainement apporter des informations très intéressantes par la détection de dommages myocardiques mêmes mineurs. Matériels et méthodes : Des 20 sujets masculins volontaires âgés de 22.36±2.02 années, sédentaires, 8 ont dû être exclus (abandon, malaise à l’effort...). La VO2max a été préalablement déterminée lors d’un test à l’effort sur cycloergomètre une semaine avant le test afin de ne pas interférer avec les résultats de l’effort physique intense (EPI) pour lequel les sujets ont couru sur tapis roulant durant 1 heure à 75% de la VO2max. Quatre échantillons sanguins de 5 ml (tube hépariné-lithium) ont été prélevés : juste avant (T1), directement après (T2), 4 heures après (T3) et 24 heures après l’EPI (T4). Le dosage de hsTnT (Modular de Roche Diagnostic®) est réalisé sur du plasma par une technique d’électrocheminiluminescence. Résultats : Une augmentation statistiquement significative des résultats à T3 (p<0.01) est observée. L’élévation de la hsTnT est progressive pour atteindre un pic maximum à T3 et revenir dans les normes à T4. Le seuil critique de 0.03 ng/mL a été retenu et 75% des sujets présentent un taux supérieur à ce dernier à T3 (moyenne : 0.053 ng/mL), alors que 100% des sujets se trouvent en dessous de ce seuil à T1 (0.0041 ng/mL). Discussion - Conclusions : Ces résultats, extrêmement intéressants, suggèrent que la libération de hsTnT serait due soit à un processus physiologique de remodelage, soit à un processus irréversible de lésions au niveau des cardiomyocytes (nécrose). Il est également possible que cette élévation des troponines soit due à une libération à partir du pool cytosolique mais aussi elle peut être la conséquence de dommages membranaires potentiellement induits par le stress oxydatif. A l’issue de cette étude, nous démontrons que la hsTnT peut être un nouvel outil diagnostic dans le domaine de la cardiologie du sport

Gait analysis using a wearable accelerometer system: Comparison between control subjects and patients with Parkinson’s disease

peer reviewe

Socially-marketed rapid diagnostic tests and ACT in the private sector: ten years of experience in Cambodia.

Whilst some populations have recently experienced dramatic declines in malaria, the majority of those most at risk of Plasmodium falciparum malaria still lack access to effective treatment with artemisinin combination therapy (ACT) and others are already facing parasites resistant to artemisinins.In this context, there is a crucial need to improve both access to and targeting of ACT through greater availability of good quality ACT and parasitological diagnosis. This is an issue of increasing urgency notably in the private commercial sector, which, in many countries, plays an important role in the provision of malaria treatment. The Affordable Medicines Facility for malaria (AMFm) is a recent initiative that aims to increase the provision of affordable ACT in public, private and NGO sectors through a manufacturer-level subsidy. However, to date, there is little documented experience in the programmatic implementation of subsidized ACT in the private sector. Cambodia is in the unique position of having more than 10 years of experience not only in implementing subsidized ACT, but also rapid diagnostic tests (RDT) as part of a nationwide social marketing programme. The programme includes behaviour change communication and the training of private providers as well as the sale and distribution of Malarine, the recommended ACT, and Malacheck, the RDT. This paper describes and evaluates this experience by drawing on the results of household and provider surveys conducted since the start of the programme. The available evidence suggests that providers' and consumers' awareness of Malarine increased rapidly, but that of Malacheck much less so. In addition, improvements in ACT and RDT availability and uptake were relatively slow, particularly in more remote areas.The lack of standardization in the survey methods and the gaps in the data highlight the importance of establishing a clear system for monitoring and evaluation for similar initiatives. Despite these limitations, a number of important lessons can still be learnt. These include the importance of a comprehensive communications strategy and of a sustained and reliable supply of products, with attention to the geographical reach of both. Other important challenges relate to the difficulty in incentivising providers and consumers not only to choose the recommended drug, but to precede this with a confirmatory blood test and ensure that providers adhere to the test results and patients to the treatment regime. In Cambodia, this is particularly complicated due to problems inherent to the drug itself and the emergence of artemisinin resistance

The propensity to adopt evidence-based practice among physical therapists

<p>Abstract</p> <p>Background</p> <p>Many authors, as well as the American Physical Therapy Association, advocate that physical therapists adopt practice patterns based on research evidence, known as evidence-based practice (EBP). At the same time, physical therapists should be capable of integrating EBP within the day-to-day practice of physical therapy. The purpose of this study was to determine the extent to which personal characteristics and the characteristics of the social system in the workplace influence the propensity of physical therapists to adopt EBP.</p> <p>Methods</p> <p>The study used a 69 item mailed self-completion questionnaire. The questionnaire had four major sections. The first three sections were each drawn from a different theoretical framework and from different authors' work. The instrument was developed to capture the propensity of physical therapists to adopt EBP, characteristics of the social system in the workplace of physical therapists, personal characteristics of physical therapists, and selected demographic variables of physical therapists. The eligible population consisted of 3,897 physical therapists licensed by the state of Georgia in the United States of America. A random sample of 1320 potential participants was drawn.</p> <p>Results</p> <p>939 questionnaires were returned for a response rate of 73%. 831 of the participants' questionnaires were useable and became the basis for the study. There was a moderate association between desire for learning (<it>r </it>= .36, <it>r</it>²= .13), highest degree held (<it>r </it>= .29, <it>r</it>²= .08), practicality (<it>r </it>= .27, <it>r</it>²= .07) and nonconformity (<it>r </it>= .24, <it>r</it>²= .06) and the propensity to adopt EBP. A negative correlation was found between age, years licensed and percentage of time in direct patient care. The findings demonstrated that the best three variables for predicting the propensity to adopt EBP in physical therapy were: desire for learning, highest degree held, and practicality.</p> <p>Conclusion</p> <p>The study confirms there is no single factor to facilitate research evidence into day-to-day practice. Multiple practice change strategies will be needed to facilitate change in practice.</p

Expanding the genetic spectrum of TUBB1-related thrombocytopenia

β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying 6 β1-tubulin variants, p.Cys12LeufsTer12, p.Thr107Pro, p.Gln423*, p.Arg359Trp, p.Gly109Glu, and p.Gly269Asp, the last of which novel. Segregation studies showed incomplete penetrance of these variants for platelet traits. Indeed, most carriers showed macrothrombocytopenia, some only increased platelet size, and a minority had no abnormalities. Moreover, only homozygous carriers of the p.Gly109Glu variant displayed macrothrombocytopenia, highlighting the importance of allele burden in the phenotypic expression of TUBB1-RT. The p.Arg359Trp, p.Gly269Asp, and p.Gly109Glu variants deranged β1-tubulin incorporation into the microtubular marginal ring in platelets but had a negligible effect on platelet activation, secretion, or spreading, suggesting that β1-tubulin is dispensable for these processes. Transfection of TUBB1 missense variants in CHO cells altered β1-tubulin incorporation into the microtubular network. In addition, TUBB1 variants markedly impaired proplatelet formation from peripheral blood CD34+ cell-derived megakaryocytes. Our study, using in vitro modeling, molecular characterization, and clinical investigations provides a deeper insight into the pathogenicity of rare TUBB1 variants. These novel data expand the genetic spectrum of TUBB1-RT and highlight a remarkable heterogeneity in its clinical presentation, indicating that allelic burden or combination with other genetic or environmental factors modulate the phenotypic impact of rare TUBB1 variants.This work was partially supported by grants from Instituto de Salud Carlos III (ISCIII) and Feder (PI17/01311, PI17/01966, PI20/00926 and CB15/00055), Fundacion Séneca (19873/ GERM/15), Gerencia Regional de Salud (GRS 2061A/19 and 1647/A/17), Fundacion Mutua Madrile´ña (AP172142019), and ~ Sociedad Espanola de Trombosis y Hemostasia (Premio L ~ opez Borrasca 2019 and Ayuda a Grupos de Trabajo en Patologıa Hemorragica). The authors’ research on inherited platelet disorders is conducted in accordance with the aims of the Functional and Molecular Characterization of Patients with Inherited Platelet Disorders Project, from Grupo Espanol de Alteraciones Plaqueta- ~ rias Congenitas, which is supported by the Spanish Society of Thrombosis and Haemostasis. V.P.-B. has a predoctoral contract from CIBERER. L.B. was supported by a fellowship from Fondazione Umberto Veronesi. M.E.d.l.M.-B. holds a postdoctoral fellowship from the University of Murcia. A.M.-Q. holds a predoctoral grant from the Junta de Castilla y Leon

The interpretation of low mood and worry by high users of secondary care with medically unexplained symptoms

DA - 20111021 IS - 1471-2296 (Electronic) IS - 1471-2296 (Linking) LA - eng PT - Journal Article SB - IMPeer reviewedPublisher PD

Trans-Translation in Helicobacter pylori: Essentiality of Ribosome Rescue and Requirement of Protein Tagging for Stress Resistance and Competence

BACKGROUND: The ubiquitous bacterial trans-translation is one of the most studied quality control mechanisms. Trans-translation requires two specific factors, a small RNA SsrA (tmRNA) and a protein co-factor SmpB, to promote the release of ribosomes stalled on defective mRNAs and to add a specific tag sequence to aberrant polypeptides to direct them to degradation pathways. Helicobacter pylori is a pathogen persistently colonizing a hostile niche, the stomach of humans. PRINCIPAL FINDINGS: We investigated the role of trans-translation in this bacterium well fitted to resist stressful conditions and found that both smpB and ssrA were essential genes. Five mutant versions of ssrA were generated in H. pylori in order to investigate the function of trans-translation in this organism. Mutation of the resume codon that allows the switch of template of the ribosome required for its release was essential in vivo, however a mutant in which this codon was followed by stop codons interrupting the tag sequence was viable. Therefore one round of translation is sufficient to promote the rescue of stalled ribosomes. A mutant expressing a truncated SsrA tag was viable in H. pylori, but affected in competence and tolerance to both oxidative and antibiotic stresses. This demonstrates that control of protein degradation through trans-translation is by itself central in the management of stress conditions and of competence and supports a regulatory role of trans-translation-dependent protein tagging. In addition, the expression of smpB and ssrA was found to be induced upon acid exposure of H. pylori. CONCLUSIONS: We conclude to a central role of trans-translation in H. pylori both for ribosome rescue possibly due to more severe stalling and for protein degradation to recover from stress conditions frequently encountered in the gastric environment. Finally, the essential trans-translation machinery of H. pylori is an excellent specific target for the development of novel antibiotics

Towards integration of general practitioner posts and accident and emergency departments: a case study of two integrated emergency posts in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Accident and emergency (A&E) departments and general practitioner (GP) posts are often used inappropriately, leading to overcrowding. In the Netherlands, increasingly more integrated emergency posts (IEPs) are being created, integrating the care provided by GP posts and A&E departments, in order to improve the provision of the emergency care.</p> <p>Methods</p> <p>This explorative study compares the efficiency and patient and employee satisfaction in IEPs with those in two GP posts and two A&E departments. To this end, information was retrieved from hospital and GP patient records for the first quarter of the year before and of the year after the creation of IEPs. Patients and employees were sent a questionnaire to measure their satisfaction. Lastly, groups of hospital doctors, GPs, GP assistants, and nurses were interviewed.</p> <p>Results</p> <p>After the creation of IEPs, there was a shift of more than fifteen percent from secondary care to primary care for emergency consultations and waiting/consultation times were shortened by more than ten percent. Compared with the control settings, patients were more satisfied about telephone contact with an IEP, but professionals working at the IEP were less satisfied with several aspects of their work.</p> <p>Conclusion</p> <p>IEPs could be a promising innovation to organize emergency care more efficiently; however, it might take time to convince professionals of the possible advantages. Studies involving more IEPs and longer follow-up times are needed to determine whether such integration should be stimulated.</p

Fibronectin III 13-14 Domains Induce Joint Damage via Toll-Like Receptor 4 Activation and Synergize with Interleukin-1 and Tumour Necrosis Factor

Cartilage loss is a feature of chronic arthritis. It results from degradation of the extracellular matrix which is composed predominantly of aggrecan and type II collagen. Extracellular matrix degradation is mediated by aggrecanases and matrix metalloproteinases (MMPs). Recently, a number of endogenous matrix molecules, including fibronectin (FN), have been implicated in mediating cartilage degradation. We were interested in studying the C-terminal heparin-binding region of FN since it mediates aggrecan and type II collagen breakdown in cartilage, but the specific FN domains responsible for proteolytic enzyme activity and their receptors in cartilage are unknown. In this study, the ability of recombinant FN domains to induce cartilage breakdown was tested. We found that the FN III 13-14 domains in the C-terminal heparin-binding region of FN are potent inducers of aggrecanase activity in articular cartilage. In murine studies, the FN III 13-14-induced aggrecanase activity was inhibited in Toll-like receptor 4 (TLR4) knockout mice but not wild-type mice. FN III 13-14 domains also synergized with the known catabolic cytokines interleukin-1α and tumour necrosis factor and induced secretion of MMP-1, MMP-3, gp38 and serum amyloid-like protein A in chondrocytes. Our studies provide a mechanistic link between the innate immune receptor TLR4 and sterile arthritis induced by the FN III 13-14 domains of the endogenous matrix molecule FN