Sudden cardiac death in young athletes: Literature review of molecular basis

Intense athletic training and competition can rarely result in sudden cardiac death (SCD). Despite the introduction of pre-participation cardiovascular screening, especially among young competitive athletes, sport-related SCD remains a debated issue among medical personnel, sports communities and laypersons alike, and generates significant media attention. The most frequent cause of SCD is a hidden inherited cardiomyopathy, the athletes may not even be aware of. Predictive medicine, by searching the presence of pathogenic alterations in cardiac genes, may be an integrative tool, besides the conventional ones used in cardiology (mainly electro and echocardiogram), to reach a definitive diagnosis in athletes showing signs/symptoms, even borderline, of inherited cardiomyopathy/ channelopathy, and in athletes presenting family history of SCD and/or of hereditary cardiac disease. In this review, we revised the molecular basis of the major cardiac diseases associated to sudden cardiac death and the clinical molecular biology approach that can be used to perform risk assessment at DNA level of sudden cardiac death, contributing to the early implementation of adequate therapy. Alterations can occur in ion channel genes, in genes encoding desmosomal and junctional proteins, sarcomeric and Z-disc proteins, proteins for the cytoskeleton and the nuclear envelope. The advent of next generation sequencing (NGS) technology has provided the means to search for mutations in all these genes, at the same time. Therefore, this molecular approach should be the preferred methodology for the aforementioned purpose

Vaccination Confidence among Healthcare Workers: Results from Two Anamnestic Questionnaires Adopted in the COVID-19 and Influenza Campaign

Background: Following the announcement of the development of COVID-19 vaccines, hesitancy about the safety of vaccinations and their side effects have spread, despite having the approval of international drug agencies. The aim of this study was to test the hypothesis that concern about side effects may have led people to fill out the COVID-19 anamnestic vaccine questionnaire with greater attention compared to the similar instrument used for the influenza vaccination. Methods: We analyzed vaccination questionnaires of 218 healthcare workers (HCWs) who underwent both COVID-19 and influenza vaccines in 2020/2021. Outcomes included self-reported allergies, chronic pharmacological treatments, and chronic diseases. We tested the difference in prevalence, analyzed differences using the kappa statistics and concordance correlation, and explored factors associated with differences in reporting. Results: HCWs reported more allergies to substances other than drugs and a higher prevalence of chronic drug intake in the COVID-19 questionnaires than in the influenza ones. Technical staff reported more drug allergies than physicians, and other HCWs reported more outcomes than physicians in the COVID-19 questionnaire. Conclusions: We found that this population of HCWs reported higher conditions during the 2020 COVID-19 vaccination campaign compared to that of the influenza vaccine. The identification of socio-demographic characteristics of the less vaccine-confident HCWs could help in planning targeted interventions to enhance vaccine adherence

Molecular Epidemiology of Mitochondrial Cardiomyopathy: A Search Among Mitochondrial and Nuclear Genes

Mitochondrial Cardiomyopathy (MCM) is a common manifestation of multi-organ Mitochondrial Diseases (MDs), occasionally present in non-syndromic cases. Diagnosis of MCM is complex because of wide clinical and genetic heterogeneity and requires medical, laboratory, and neuroimaging investigations. Currently, the molecular screening for MCM is fundamental part of MDs management and allows achieving the definitive diagnosis. In this article, we review the current genetic knowledge associated with MDs, focusing on diagnosis of MCM and MDs showing cardiac involvement. We searched for publications on mitochondrial and nuclear genes involved in MCM, mainly focusing on genetic screening based on targeted gene panels for the molecular diagnosis of the MCM, by using Next Generation Sequencing. Here we report twelve case reports, four case-control studies, eleven retrospective studies, and two prospective studies, for a total of twenty-nine papers concerning the evaluation of cardiac manifestations in mitochondrial diseases. From the analysis of published causal mutations, we identified 130 genes to be associated with mitochondrial heart diseases. A large proportion of these genes (34.3%) encode for key proteins involved in the oxidative phosphorylation system (OXPHOS), either as directly OXPHOS subunits (22.8%), and as OXPHOS assembly factors (11.5%). Mutations in several mitochondrial tRNA genes have been also reported in multi-organ or isolated MCM (15.3%). This review highlights the main disease-genes, identified by extensive genetic analysis, which could be included as target genes in next generation panels for the molecular diagnosis of patients with clinical suspect of mitochondrial cardiomyopathies

Enhanced Uptake and Phototoxicity of C60@albumin Hybrids by Folate Bioconjugation

Fullerenes are considered excellent photosensitizers, being highly suitable for photodynamic therapy (PDT). A lack of water solubility and low biocompatibility are, in many instances, still hampering the full exploitation of their potential in nanomedicine. Here, we used human serum albumin (HSA) to disperse fullerenes by binding up to five fullerene cages inside the hydrophobic cavities. Albumin was bioconjugated with folic acid to specifically address the folate receptors that are usually overexpressed in several solid tumors. Concurrently, tetramethylrhodamine isothiocyanate, TRITC, a tag for imaging, was conjugated to C-60@HSA in order to build an effective phototheranostic platform. The in vitro experiments demonstrated that: (i) HSA disperses C-60 molecules in a physiological environment, (ii) HSA, upon C-60 binding, maintains its biological identity and biocompatibility, (iii) the C-60@HSA complex shows a significant visible-light-induced production of reactive oxygen species, and (iv) folate bioconjugation improves both the internalization and the PDT-induced phototoxicity of the C-60@HSA complex in HeLa cells

Active elderly and health-can moderate exercise improve health and wellbeing in older adults? Protocol for a randomized controlled trial

Abstract Background: Aging is marked by a progressive rise in chronic diseases with an impact on social and healthcare costs. Physical activity (PA) may soothe the inconveniences related to chronic diseases, has positive effects on the quality of life and biological rhythms, and can prevent the decline in motor functions and the consequent falls, which are associated with early death and disability in older adults. Methods: We randomized 120 over-65 males and females into groups of similar size and timing and will give each either moderate physical activity or cultural and recreational activities. Being younger than 65 years, inability to participate in physical activity for any medical reason, and involvement in a massive program of physical exercise are the exclusion criteria. The primary outcome measures are quality of life, walking speed, and postural sway. Participants are tested at baseline, post-treatment, and 6-month (24 weeks) and 12-month (48 weeks) follow-ups. Discussion: This study aims at improving the quality of life, wellness, and cognitive functioning in the elderly through a low-cost affordable program of moderate physical activity. Given the growing aging of the world population and the social and economic burden of disability in the elderly, our results might have a major impact on future practices

Early Naso-Gastric Feeding and Outcomes of Anorexia Nervosa Patients

Nutritional rehabilitation with weight restoration is an important step in patients hospitalised for anorexia nervosa (AN). Naso-gastric feeding (NGF) should be considered when oral nutrition (OF) and oral nutritional supplementation (ONS) are insufficient. We evaluated the role of NGF on short- and long-term outcomes, considering weight gain, the length of hospitalisation (LOS) and the time to relapse. We report on the characteristics of patients under 18 years of age with AN admitted to the Department of Emergency and Acceptance of the Bambino Gesù Children’s Hospital, IRCCS, Rome, between March 2019 and August 2022. Three hundred and fifteen patients were enrolled. We compared patients treated with NGF (group A) and patients without NGF (group B). Group A was characterised by a significantly lower BMI on admission and discharge, more frequent use of inpatient psychotropic therapy (IPDT) and longer hospital stay. The time to relapse was significantly longer in group A compared to group B. An early NGF setting correlates with a longer time to relapse and may be associated with a shorter LOS. A high caloric intake with a balanced nutritional formula provided by NGF allows an earlier recovery. The main advantages of this approach could be the rapid discharge of patients and a more effective psychological and social recovery

The Hidden Fragility in the Heart of the Athletes: A Review of Genetic Biomarkers

Sudden cardiac death (SCD) is a devastating event which can also affect people in apparent good health, such as young athletes. It is known that intense and continuous exercise along with a genetic background that predisposes a person to the risk of fatal arrhythmias is a trigger for SCD. Therefore, knowledge of the athlete’s genetic conditions underlying the onset of SCD must be extended, in order to develop new effective prevention and/or therapeutic strategies. Arrhythmic features occur across a broad spectrum of cardiac diseases, sometimes presenting with overlapping phenotypes. The genetic basis of arrhythmogenic disorders has been greatly highlighted in the last 30 years, and has shown marked heterogeneity. The advent of next-generation sequencing has constantly updated our understanding of the genetic basis of arrhythmogenic diseases and is laying the foundation for precision medicine. With the exception of a few clinical cases involving a single athlete showing a highly suspected phenotype for the presence of a heart disease, there are few studies to date that analysed the applicability of genetic testing on cohorts of athletes. This evidence shows that genetic testing can contribute to the diagnosis of up to 13% of athletes; however, the presence of clinical markers is essential. This review aims to provide a reference collection on current knowledge of the genetic basis of sudden cardiac death in athletes and to review updated evidence on the effectiveness of genetic testing in early identification of athletes at risk for SCD