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Regular, low-intensity physical activity is currently advocated for lowering the risk of developing many acute and especially chronic diseases. However, several lines of evidence attest that strenuous exercise may enhance inflammation and trigger the generation of free radical-mediated damage, thus overwhelming the undisputable benefits of regular, medium-intensity physical activity. Since reactive oxygen species are actively generated during high-intensity exercise, and these reactive compounds are known to impact DNA stability, we review here the current evidence about strenuous exercise and DNA injury. Despite the outcome of the various studies cannot be pooled due to considerable variation in design, sample population, outcome, and analytical techniques used to assess DNA damage, it seems reasonable to conclude that medium- to high-volume exercise triggers a certain amount of DNA injury, which appears to be transitory and directly proportional to exercise intensity. This damage, reasonably attributable to direct effect of free radicals on nucleic acids, is efficiently repaired in vivo within 24-72h. Therefore, physical exercise should not bear long-term consequences for athlete's health provided that an appropriate time of recovery between volumes of high-intensity exercise is set. Regular exertion, with a step-by-step increase of exercise load, also seems to be the most safe approach for eluding DNA instability.

Erectile dysfunction (ED) is a very common pathology, affecting over 150 million men worldwide. The pathogenesis is typically multifactorial, involving a kaleidoscope of organic, endocrine, and psychogenic factors. In general, ED is divided into organic and psychogenic impotence, but most men with organic etiologies have an associated psychogenic component. Given the high frequency of this pathology, the identification of biochemical and genetic correlates and/or markers is of pivotal interest not only for treating preciously these patients and preventing serious psychological consequences but also for the high risk for occult cardiovascular disease (CVD) that often accompanies or follows this pathology. A variety of cardiovascular risk factors have been associated with both the onset and the severity of ED, including markers of endothelial function, thrombosis, and especially dyslipidemia, so that their measurement should now be considered as an important part of the increased global cardiometabolic risk profile in patients with ED. While nitric oxide (NO), asymmetric dimethylarginine (ADMA), and endothelin (ET) hold some promises as biochemical markers of both CVD and ED, there are several technical and clinical drawbacks that make their measurement overall meaningless in the clinical practice. As regards genetic polymorphisms, controversial results have been provided so far. Although some genetic markers were consistently associated with ED, other studies failed to demonstrate significant associations, highlighting a substantial bias in standardization of methodologies and patient enrolment. Nevertheless, further research in this area should be encouraged, since the first promising evidence that gene therapy might be effective to restore the decline in ED has been provided in the animal model.

The Brugada Syndrome (BS) is a "channellopathy," characterized by ion (e.g., sodium, calcium, and potassium) channel dysfunction and typical ECG alterations, originally described by Osher and Wolff in 1953 and further elucidated by Josep and Pedro Brugada in 1991. BS is typically associated with a high risk for sudden cardiac death (SCD) in young and otherwise healthy adults. Although in several patients the heart is structurally normal, subtle structural abnormalities in the right ventricular outflow tract are increasingly been reported. The worldwide prevalence of this disorder is still uncertain, and there are some significant regional differences. The syndrome is characterized by a strong genetic basis, and several mutations have been identified in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as in genes involved in the trafficking or regulation of these channels. Accordingly, eight types of BS (from BS1 to BS8) have already been described, involving mutations in SCN5A, GPD1-L, CACNA1c, CACNB2b, SCN1B, KCNE3, SCN3B, and HCN4 genes. The vast majority (i.e., up to two-third) of BS patients is asymptomatic, whereas the leading clinical manifestation is polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation (VF) and SCD. The diagnosis is still challenging, and ECG abnormalities represent one component of the diagnostic criteria which also include clinical and demographic data. Although molecular genetic testing is effective in detecting mutations in 20-38% of BS patients, it represents an appealing option for stratifying the risk of adverse events as well as for prenatal testing.

The recent development and introduction into clinical and laboratory practice of the novel highly sensitive cardiac troponin assays has contributed to improve the diagnosis and risk stratification of patients presenting with suspected myocardial injury and acute coronary syndrome at the emergency department (ED). The enhanced ability to detect very low amount of troponin in blood with the novel tests has also raised the challenge of intercepting values above the 99th percentile of the reference population in apparently healthy subjects as well as several patients with comorbidities different from myocardial infarction. As such, the diagnostic approach and the triage of chest pain patients need to be readjusted and, most probably, the role of clinical judgment will assume greater importance than with the old generation immunoassays. In this perspective, a strategy based on the "delta biomarker approach" rather than that based on the traditional "peak" value might be more viable, since the observation of a dynamic pattern of troponin values might help discriminating the timing of injury as well as distinguishing acute from chronic etiologies and thereby increasing both the specificity and the positive predictive value (PPV) of the test. Nevertheless, this approach would require an accurate definition of the reference ranges as well as the identification of the magnitude of increase or decrease during serial sampling. We are thereby navigating between the Scylla (i.e., definition of appropriate 99th percentile of the reference population) and Charybdis (i.e., identification of a reliable delta threshold) of the novel highly sensitive immunoassays. The aim of this article is to provide an overview on the clinical impact of the highly sensitive cardiac troponin immunoassays in the differential diagnosis of patients presenting to ED with thoracic pain suggestive for acute coronary syndrome.

Despite the relatively low prevalence, ovarian cancer is the fifth leading cause of death from cancer among women. As such, an early diagnosis for establishing a timely surgical and/or chemotherapeutic treatment is essential for improving the outcome. The most reliable, but not always straightforward, approach to diagnose ovarian cancer relies on multiple, time-consuming and expensive investigative tools. These typically include clinical presentation (i.e., pelvic or abdominal pain, urinary frequency or urgency, increased abdominal size or bloating) with pelvic examination, transvaginal ultrasonography (US), and measurement of carbohydrate antigen 125 (CA125). Although the conventional pathway to develop and market a clinically useful biomarker is challenging, recent advances in genomic and proteomic technologies have led to the identification of previously unknown candidate markers of ovarian cancer. Some of these are currently under clinical validation. The human epididymis protein 4 (HE4) has recently been approved by the Food and Drug Administration for monitoring recurrence or progression of epithelial ovarian cancer. Nevertheless, reliable clinical evidence demonstrates that HE4, used alone or in combination with CA125, substantially improves the accuracy of screening and/or disease monitoring. This chapter will review the current knowledge on biologic and clinical applications of ovarian cancer biomarkers, with particular emphasis on the newly proposed marker, HE4.

1. Abstract Idiopathic thrombocytopenic purpura (ITP) is a common autoimmune disease mediated by autoantibodies against platelet glycoproteins. This hemorrhagic disorder may be primary or secondary to various illnesses, including lymphoproliferative, autoimmune, or infectious diseases. Among the latter causes, there is increasing laboratory and clinical evidence that documents a pathogenic role of Helicobacter pylori infection in ITP. The aim of this review is to analyze the current knowledge on the pathogenic, diagnostic, clinical, and therapeutic characteristics of H. pylori -associated ITP.