Thrombosis and Thrombotic Risk in Athletes.

The hemostatic system is characterized by a delicate balance between pro- and anticoagulant forces, and the smallest alteration can cause serious events such as hemorrhages or thrombosis. Although exercise has been shown to play a protective role in athletes, several factors may increase the risk of developing venous thromboembolism (VTE), including hemoconcentration induced by exertion, immobilization following sports injuries, frequent long-distance flights, dehydration, and the use of oral contraceptives in female athletes. Biomarkers such as D-dimer, Factor VIII, thrombin generation, inflammatory cytokines, and leukocyte count are involved in the diagnosis of deep vein thrombosis (DVT), although their interpretation is complex and may indicate the presence of other conditions such as infections, inflammation, and heart disease. Therefore, the identification of biomarkers with high sensitivity and specificity is needed for the screening and early diagnosis of thromboembolism. Recent evidence about the correlation between the intensity of physical activity and VTE is divergent, whereas the repeated gestures in sports such as baseball, hockey, volleyball, swimming, wrestling, or, on the other hand, soccer players, runners, and martial art training represent a risk factor predisposing to the onset of upper and lower DVT. Anticoagulant therapy is the gold standard, reducing the risk of serious complications such as pulmonary embolism. The aim of this review is to provide a general overview about the interplay between physical exercise and the risk of thromboembolism in athletes, focusing on the main causes of thrombosis in professional athletes and underlying the need to identify new markers and therapies that can represent a valid tool for safeguarding the athlete's health.

The Third-Generation Sequencing Challenge: Novel Insights for the Omic Sciences.

The understanding of the human genome has been greatly improved by the advent of next-generation sequencing technologies (NGS). Despite the undeniable advantages responsible for their widespread diffusion, these methods have some constraints, mainly related to short read length and the need for PCR amplification. As a consequence, long-read sequencers, called third-generation sequencing (TGS), have been developed, promising to overcome NGS. Starting from the first prototype, TGS has progressively ameliorated its chemistries by improving both read length and base-calling accuracy, as well as simultaneously reducing the costs/base. Based on these premises, TGS is showing its potential in many fields, including the analysis of difficult-to-sequence genomic regions, structural variations detection, RNA expression profiling, DNA methylation study, and metagenomic analyses. Protocol standardization and the development of easy-to-use pipelines for data analysis will enhance TGS use, also opening the way for their routine applications in diagnostic contexts.

Integrated Approach to Highlighting the Molecular Bases of a Deep Vein Thrombosis Event in an Elite Basketball Athlete.

Acute or intense exercise can result in metabolic imbalances, muscle injuries, or reveal hidden disorders. Laboratory medicine in sports is playing an increasingly crucial role in monitoring athletes' health conditions. In this study, we designed an integrated approach to explore the causes of a deep venous thrombosis event in an elite basketball player. Since the complete blood count revealed a marked platelet count (838 × 103 µL), and thrombophilia screening tests did not reveal any significant alteration, we evaluated the thrombin generation, which highlights a state of hypercoagulability. First-level haemostasis exams showed only a slight prolongation of the activated Partial Thromboplastin Time (aPTT). Thus, screening tests for von Willebrand Disease showed a reduction in vWF parameters. Therefore, we directed our hypothesis towards a diagnosis of acquired von Willebrand disease secondary to Essential Thrombocythemia (ET). To confirm this hypothesis and highlight the molecular mechanism underlying the observed phenotype, molecular tests were performed to evaluate the presence of the most common mutations associated with ET, revealing a 52-bp deletion in the coding region of CALR exon 9. This case report highlights the importance of an integrated approach to monitoring the athletes' health status to personalise training and treatments, thus avoiding the appearance of diseases and injuries that, if underestimated, can undermine the athlete's life.

The Potential Usefulness of the Expanded Carrier Screening to Identify Hereditary Genetic Diseases: A Case Report from Real-World Data.

Expanded carrier screening (ECS) means a comprehensive genetic analysis to evaluate an individual's carrier status. ECS is becoming more frequently used, thanks to the availability of techniques such as next generation sequencing (NGS) and array comparative genomic hybridization (aCGH), allowing for extensive genome-scale analyses. Here, we report the case of a couple who underwent ECS for a case of autism spectrum disorder in the male partner family. aCGH and whole-exome sequencing (WES) were performed in the couple. aCGH analysis identified in the female partner two deletions involving genes associated to behavioral and neurodevelopment disorders. No clinically relevant alterations were identified in the husband. Interestingly, WES analysis identified in the male partner a pathogenic variant in the LPL gene that is emerging as a novel candidate gene for autism. This case shows that ECS may be useful in clinical contexts, especially when both the partners are analyzed before conception, thus allowing the estimation of their risk to transmit an inherited condition. On the other side, there are several concerns related to possible incidental findings and difficult-to-interpret results. Once these limits are defined by the establishment of specific guidelines, ECS may have a greater diffusion.

Relevance of arginine residues in Cu(II)-induced DNA breakage and Proteinase K resistance of H1 histones.

This work analyzes the involvement of arginines in copper/H2O2-induced DNA breakage. Copper is a highly redox active metal which has been demonstrated to form compounds with arginines. For this aim we used mixtures of pGEM3 DNA plasmid and two types of H1 histones which differ only in their arginine content. The sperm H1 histone from the annelid worm Chaetopterus variopedatus (arginine content 12.6 mol% K/R ratio 2) and the somatic H1 histone from calf thymus (arginine content 1.8 mol% and K/R ratio 15). Copper/H2O2-induced DNA breakage was observed only in presence of sperm H1 histones, but it was more relevant for the native molecule than for the deguanidinated derivative (K/R ratio 14), in which 80% of arginine residues were converted to ornithine. Further, copper induced proteinase K resistance and increase of DNA binding affinity on native sperm H1 histones. These observations are consistent with a copper induced reorganization of the side-chains of arginine residues. Copper, instead, did not affect DNA binding affinity of somatic and deguanidinated H1 histones, which show similar K/R ratio and DNA binding mode. These results indicate that arginine residues could affect these H1 histones properties and provide new insights into copper toxicity mechanisms.