69 research outputs found
Paediatric and adolescent athletes in Switzerland: age-adapted proposals for pre-participation cardiovascular evaluation
High-level sports competition is popular among Swiss youth. Even though preparticipation evaluation for competitive athletes is widespread, screening strategies for diseases responsible for sudden death during sport are highly variable. Hence, we sought to develop age-specific preparticipation cardiovascular evaluation (PPCE) proposals for Swiss paediatric and adolescent athletes (under 18 years of age). We recommend that all athletes practising in a squad with a training load of at least 6 hours per week should undergo PPCE based on medical history and physical examination from the age of 12 years on. Prior to 12 years, individual judgement of athletic performance is required. We suggest the inclusion of a standard 12-lead electrocardiogram (ECG) evaluation for all post-pubertal athletes (or older than 15 years) with analysis in accordance with the International Criteria for ECG Interpretation in Athletes. Echocardiography should not be a first-line screening tool but rather serve for the investigation of abnormalities detected by the above strategies. We recommend regular follow-up examinations, even for those having normal history, physical examination and ECG findings. Athletes with an abnormal history (including family history), physical examination and/or ECG should be further investigated and pathological findings discussed with a paediatric cardiologist. Importantly, the recommendations provided in this document are not intended for use among patients with congenital heart disease who require individualised care according to current guidelines
Synthetic prions generated in vitro are similar to a newly identified subpopulation of PrPSc from sporadic Creutzfeldt-Jakob disease
In recent studies, the amyloid form of recombinant prion protein (PrP) encompassing residues 89â230 (rPrP 89-230) produced in vitro induced transmissible prion disease in mice. These studies showed that unlike âclassicalâ PrPSc produced in vivo, the amyloid fibrils generated in vitro were more proteinase-K sensitive. Here we demonstrate that the amyloid form contains a proteinase K-resistant core composed only of residues 152/153â230 and 162â230. The PK-resistant fragments of the amyloid form are similar to those observed upon PK digestion of a minor subpopulation of PrPSc recently identified in patients with sporadic Creutzfeldt-Jakob disease (CJD). Remarkably, this core is sufficient for self-propagating activity in vitro and preserves a ÎČ-sheet-rich fibrillar structure. Full-length recombinant PrP 23-230, however, generates two subpopulations of amyloid in vitro: One is similar to the minor subpopulation of PrPSc, and the other to classical PrPSc. Since no cellular factors or templates were used for generation of the amyloid fibrils in vitro, we speculate that formation of the subpopulation of PrPSc with a short PK-resistant C-terminal region reflects an intrinsic property of PrP rather than the influence of cellular environments and/or cofactors. Our work significantly increases our understanding of the biochemical nature of prion infectious agents and provides a fundamental insight into the mechanisms of prions biogenesis
Diagnostic yield and cost analysis of electrocardiographic screening in Swiss paediatric athletes
OBJECTIVES
Athletes performing sports on high level are at increased risk for sudden cardiac death. This includes paediatric athletes, even though data on screening strategies in this age group remain scarce. This study aimed to assess electrocardiogram interpretation criteria in paediatric athletes and to evaluate the cost of screening.
METHODS
National, multicentre, retrospective, observational study on 891 athletes of paediatric age (<18âŻyears) evaluated by history, physical examination and 12-lead electrocardiogram. The primary outcome measure was abnormal electrocardiogram findings according to the International Recommendations for Electrographic Interpretation in Athletes. The secondary outcome measure was cost of screening.
RESULTS
19 athletes (2.1%) presented abnormal electrocardiogram findings requiring further investigations, mainly abnormal T-wave inversion. These 19 athletes were predominantly males, performing endurance sports with a mean volume of 10 weekly hours for a mean duration of 6âŻyears of training. Further investigations did not identify any relevant pathology. All athletes were cleared for competition with regular follow-up. Total costs of the screening were 108,860 USD (122 USD per athlete).
CONCLUSIONS
Our study using the International Recommendations for Electrographic Interpretation in Athletes identified a low count of abnormal findings in paediatric athletes, yet raising substantially the cost of screening. Hence, the utility of electrocardiogram-inclusive screening of paediatric athletes remains to be elucidated by longitudinal data
Propagation of RML Prions in Mice Expressing PrP Devoid of GPI Anchor Leads to Formation of a Novel, Stable Prion Strain
PrPC, a host protein which in prion-infected animals is converted to PrPSc, is linked to the cell membrane by a GPI anchor. Mice expressing PrPC without GPI anchor (tgGPI- mice), are susceptible to prion infection but accumulate anchorless PrPSc extra-, rather than intracellularly. We investigated whether tgGPIâ mice could faithfully propagate prion strains despite the deviant structure and location of anchorless PrPSc. We found that RML and ME7, but not 22L prions propagated in tgGPIâ brain developed novel cell tropisms, as determined by the Cell Panel Assay (CPA). Surprisingly, the levels of proteinase K-resistant PrPSc (PrPres) in RML- or ME7-infected tgGPIâ brain were 25â50 times higher than in wild-type brain. When returned to wild-type brain, ME7 prions recovered their original properties, however RML prions had given rise to a novel prion strain, designated SFL, which remained unchanged even after three passages in wild-type mice. Because both RML PrPSc and SFL PrPSc are stably propagated in wild-type mice we propose that the two conformations are separated by a high activation energy barrier which is abrogated in tgGPIâ mice
Ligand Binding and Hydration in Protein Misfolding: Insights from Studies of Prion and p53 Tumor Suppressor Proteinsâ
Protein misfolding has been implicated in a large number of diseases termed protein- folding disorders (PFDs), which include Alzheimerâs disease, Parkinsonâs disease, transmissible spongiform encephalopathies, familial amyloid polyneuropathy, Huntingtonâs disease, and type II diabetes. In these diseases, large quantities of incorrectly folded proteins undergo aggregation, destroying brain cells and other tissues
Short-term heparin kinetics during catheter ablation of atrial fibrillation
CONTEXTE: L'ablation percutanĂ©e par cathĂ©ter de la fibrillation auriculaire (AC-FA) est une option de traitement pour les patients souffrant de fibrillation auriculaire (FA) symptomatique rĂ©fractaire au traitement mĂ©dicamenteux. L'AC-FA comporte un risque de complications thromboemboliques qui a Ă©tĂ© rĂ©duit par l'utilisation de l'hĂ©parine non fractionnĂ©e (HNF) intraveineuse durant la procĂ©dure. L'administration optimale de l'HNF ainsi que sa cinĂ©tique ne sont pas bien Ă©tablies et nĂ©cessitent d'ĂȘtre dĂ©terminĂ©es avec prĂ©cision.
MĂTHODES ET RĂSULTATS: Cette Ă©tude a inclus 102 patients consĂ©cutifs atteints de FA symptomatique, rĂ©fractaire au traitement mĂ©dicamenteux, rĂ©fĂ©rĂ©s pour une AC-FA. L'Ăąge moyen Ă©tait de 61 ± 10 ans. AprĂšs une ponction transseptale de la fosse ovale, une injection intraveineuse de HNF ajustĂ©e au poids (100 U / kg) a Ă©tĂ© administrĂ©. Une augmentation significative du temps de coagulation activĂ© (ACT) a Ă©tĂ© observĂ©e passant d'une valeur de base moyenne de 100 ± 27 secondes, Ă 355 ± 94 secondes Ă 10 minutes (T10) et Ă 375 ± 90 secondes Ă 20 minutes (T20). 24 patients n'ont pas atteint la valeur visĂ©e d'ACT > 300 secondes Ă T10 et plus de la moitiĂ© de ce collectif est restĂ© avec les valeurs d'ACT infrathĂ©rapeutiques Ă T20. Ce sous-ensemble de patients avait des caractĂ©ristiques cliniques similaires et avait reçu des doses similaires d'HNF, mais s'Ă©tait plus frĂ©quemment fait prescrire de la vitamine Kl prĂ©-procĂ©durale que le reste de la population de l'Ă©tude.
CONCLUSION: Au cours d'une intervention standard, l'HNF montre, de maniÚre inattendue, une cinétique d'anticoagulation lente dans une proportion significative des procédures et ceci jusqu'à 20 minutes aprÚs l'administration. Ces résultats soutiennent l'importance d'une administration d'HNF avant la ponction transseptale ou tout cathétérisme gauche avec des mesures précoces et répétées d'ACT afin d'identifier les patients avec une cinétique retardée. Ils sont en ligne avec les directives récentes proposant d'effectuer l'AC-FA sous anticoagulation thérapeutique
CĆur et sport [Heart and sport]
Physical activity is beneficial for health and the cardiovascular risk profile. However, it can be dangerous in people with cardiac disease that might be asymptomatic. Individuals of all ages and all levels engage in sporting activities. The medical approach is different whether one evaluates a young competitive athlete, a sedentary adult who wants to start a recreational sport or a patient with heart disease who wishes to engage in sport. This article summarizes the various recommendations on the subject
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