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Sudden cardiac death (SCD) prevention in cardiomyopathies such as hypertrophic (HCM), dilated (DCM), non-dilated left ventricular (NDLCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) remains a crucial but complex clinical challenge, especially among younger populations. Accurate risk stratification is hampered by the variability in phenotypic expression and genetic heterogeneity inherent in these conditions. This article explores the multifaceted strategies for preventing SCD across a spectrum of cardiomyopathies and emphasizes the integration of clinical evaluations, genetic insights, and advanced imaging techniques such as cardiac magnetic resonance (CMR) in assessing SCD risks. Advanced imaging, particularly CMR, not only enhances our understanding of myocardial architecture but also serves as a cornerstone for identifying at-risk patients. The integration of new research findings with current practices is essential for advancing patient care and improving survival rates among those at the highest risk of SCD. This review calls for ongoing research to refine risk stratification models and enhance the predictive accuracy of both clinical and imaging techniques in the management of cardiomyopathies.

Neuropathic pain is a type of pain that persists for a long time and becomes pathological. Additionally, the anxiodepressive disorders derived from neuropathic pain are difficult to palliate with the current treatments and need to be resolved. Then, using male mice with neuropathic pain provoked by chronic constriction of the sciatic nerve (CCI), we analyzed and compared the analgesic actions produced by three new heme oxygenase 1 (HO-1) inducers, 1m, 1b, and 1a, with those performed by dimethyl fumarate (DMF). Their impact on the anxiety- and depressive-like comportments and the expression of the inflammasome NLRP3, Nrf2, and some antioxidant enzymes in the dorsal root ganglia (DRG) and amygdala (AMG) were also investigated. Results revealed that the administration of 1m, 1b, and DMF given orally for four days inhibited the allodynia and hyperalgesia caused by CCI, while 1a merely reduced the mechanical allodynia. However, in the first two days of treatment, the antiallodynic effects produced by 1m were higher than those of 1a and DMF, and its antihyperalgesic actions were greater than those produced by 1b, 1a, and DMF, revealing that 1m was the most effective compound. At four days of treatment, all drugs exerted anxiolytic and antidepressant effects, decreased the NLRP3 levels, and increased/normalized the Nrf2, HO-1, and superoxide dismutase 1 levels in DRG and AMG. Data indicated that the dual modulation of the antioxidant and inflammatory pathways produced by these compounds, especially 1m, is a new promising therapeutic approach for neuropathic pain and related emotional illnesses.

Chronic pain caused by persistent inflammation is current in multiple diseases and has a strong negative impact on society. It is commonly associated with several mental illnesses, which can exert a negative influence on pain perception, and needs to be eradicated. Nevertheless, actual therapies are not sufficiently safe and effective. Recent reports demonstrate that the induction of heme oxygenase-1 (HO-1) enzyme produces analgesic effects in animals with osteoarthritis pain and reverses the grip strength loss caused by sciatic nerve crush. In this research, we evaluated the potential use of three new HO-1 inducers, 1m, 1a, and 1b, as well as dimethyl fumarate (DMF), for treating persistent inflammatory pain induced by the subplantar injection of complete Freud's adjuvant and the functional deficits and emotional sickness associated. The modulator role of these treatments on the inflammatory and antioxidant pathways were also assessed. Our findings revealed that repeated treatment, for four days, with 1m, 1a, 1b, or DMF inhibited inflammatory pain, reversed grip strength deficits, and reversed the linked anxious- and depressive-like behaviors, with 1m being the most effective. These treatments also suppressed the up-regulation of the inflammasome NLRP3 and activated the expression of the Nrf2 transcription factor and the HO-1 and superoxide dismutase 1 enzymes in the paw and/or amygdala, thus revealing the anti-inflammatory and antioxidant capacity of these compounds during inflammatory pain. Results suggest the use of 1m, 1a, 1b, and DMF, particularly 1m, as promising therapies for inflammatory pain and the accompanying functional disabilities and emotional diseases.

Attention Deficit/Hyperactivity Disorder (ADHD) is a neurobiological condition characterized by developmentally inadequate levels of inattention, hyperactivity, and impulsivity, and a neurobiological disruption in brain neurotransmitters and circuitry causing abnormal responses to rewards. Playing electronic games generates a biological response that activates the neuronal circuits linked to pleasure and reward, and there is a growing attention to this type of activity, which can also turn into a mental health condition. The existence and the boundaries between the functional and the dysfunctional are still a source of debate, with the recognition of 'Internet Gaming Disorder' (IGD) as a condition belonging to the broader area of addiction requiring more in-depth study with respect to the DSM-5, while 'Gaming Disorder' (GD) was officially recognized as a new diagnosis by the World Health Organization (WHO) in the updated revision of the International Classification of Diseases (ICD-11). Notwithstanding, the suggested criteria for the diagnosis of Gaming Disorder are still debated. Since ADHD has been reported as a risk factor for developing addictions, this narrative review aims to provide the current state-of-the art of the knowledge about the comorbidity between ADHD and Gaming Disorder. For this aim, a literature search was conducted using a combination of specific keywords and the results are discussed within the R-Do-C framework and dimensions, and implications for treatment are considered.

The stress and anxiety caused by the coronavirus pandemic (COVID-19) have exacerbated body image concerns. A society that perpetuates the attempt for a perfect and thin appearance represents a fertile ground for the development of exercise addiction (EA). This cross-sectional study aims to explore EA during the second wave of the pandemic (October−December 2020) and to examine the independent influence of both time spent on moderate and vigorous physical activities and body image variables (i.e., drive for leanness and sociocultural attitudes toward appearance) on EA. A sample of Italian sporty people (N = 194; 48.5% females; Mage = 25.91 ± 6.32) was surveyed using the Exercise Addiction Inventory, the Drive for Leanness Scale, the Sociocultural Attitudes Towards Appearance Questionnaire, and the Global Physical Activity Questionnaire. A total of 82% of the sample were symptomatic of and 11.3% were at risk of EA. Hierarchical regressions revealed an association between the time spent on vigorous physical activities and levels of EA (p < 0.05). Moreover, body image variables were positively related to EA, explaining an additional 11% of variance (p < 0.05). Results showed the importance of considering and addressing body image factors to investigate and dampen the risk of EA among sporty people.

Cardiomyopathy is a common complication in diabetic patients. Ventricular dysfunction without coronary atherosclerosis and hypertension is driven by hyperglycemia, hyperinsulinemia and impaired insulin signaling. Cardiomyocyte death, hypertrophy, fibrosis, and cell signaling defects underlie cardiomyopathy. Notably, detrimental effects of the diabetic milieu are not limited to cardiomyocytes and vascular cells. The diabetic heart acquires a senescent phenotype and also suffers from altered cellular homeostasis and the insufficient replacement of dying cells. Chronic inflammation, oxidative stress, and metabolic dysregulation damage the population of endogenous cardiac stem cells, which contribute to myocardial cell turnover and repair after injury. Therefore, deficient myocardial repair and the progressive senescence and dysfunction of stem cells in the diabetic heart can represent potential therapeutic targets. While our knowledge of the effects of diabetes on stem cells is growing, several strategies to preserve, activate or restore cardiac stem cell compartments await to be tested in diabetic cardiomyopathy.

Vaccine hesitancy (VH) may be significant in jeopardizing efforts to mass containment of COVID-19. A cross-sectional survey was carried out on a sample of 2667 Italian college students, before the COVID-19 vaccines became available for this age group (from 7 May to 31 May 2021). An online survey was created to obtain information about socio-demographic, health-related, and psychological factors linked to mRNA and viral vector COVID-19 vaccines. Statistically significant higher VH (30.4%) and vaccine resistance (12.2%) rates were found for viral vector than mRNA COVID-19 vaccines (7.2% and 1.0%, respectively; p < 0.001). Factors related to viral vector VH were partially different from those related to mRNA VH. Students with greater endorsement on conspiracy statements and negative attitudes toward the vaccine had higher odds of being vaccine-hesitant or -resistant. Students who had received a previous COVID-19 test and who scored higher on the agreeableness personality dimension had lower odds to be vaccine-hesitant or -resistant. The willingness to choose the vaccine was related to the viral vector but not to the mRNA VH. Taking into consideration the factors involved in vaccine hesitancy/resistance in college students could represent a key public health strategy to increase vaccine coverage and reduce viral spreading.

Background: Two-dimensional volumetric exercise stress echocardiography (ESE) provides an integrated view of left ventricular (LV) preload reserve through end-diastolic volume (EDV) and LV contractile reserve (LVCR) through end-systolic volume (ESV) changes., Purpose: To assess the dependence of cardiac reserve upon LVCR, EDV, and heart rate (HR) during ESE., Methods: We prospectively performed semi-supine bicycle or treadmill ESE in 1344 patients (age 59.8 ± 11.4 years; ejection fraction = 63 ± 8%) referred for known or suspected coronary artery disease. All patients had negative ESE by wall motion criteria. EDV and ESV were measured by biplane Simpson rule with 2-dimensional echocardiography. Cardiac index reserve was identified by peak-rest value. LVCR was the stress-rest ratio of force (systolic blood pressure by cuff sphygmomanometer/ESV, abnormal values ≤2.0). Preload reserve was defined by an increase in EDV. Cardiac index was calculated as stroke volume index * HR (by EKG). HR reserve (stress/rest ratio) <1.85 identified chronotropic incompetence., Results: Of the 1344 patients, 448 were in the lowest tertile of cardiac index reserve with stress. Of them, 303 (67.6%) achieved HR reserve <1.85; 252 (56.3%) had an abnormal LVCR and 341 (76.1%) a reduction of preload reserve, with 446 patients (99.6%) showing ≥1 abnormality. At binary logistic regression analysis, reduced preload reserve (odds ratio [OR]: 5.610; 95% confidence intervals [CI]: 4.025 to 7.821), chronotropic incompetence (OR: 3.923, 95% CI: 2.915 to 5.279), and abnormal LVCR (OR: 1.579; 95% CI: 1.105 to 2.259) were independently associated with lowest tertile of cardiac index reserve at peak stress., Conclusions: Heart rate assessment and volumetric echocardiography during ESE identify the heterogeneity of hemodynamic phenotypes of impaired chronotropic, preload or LVCR underlying a reduced cardiac reserve.

Over the years strong evidence has been accumulated showing that aerobic physical exercise exerts beneficial effects on the prevention and reduction of cardiovascular risk. Exercise in healthy subjects fosters physiological remodeling of the adult heart. Concurrently, physical training can significantly slow-down or even reverse the maladaptive pathologic cardiac remodeling in cardiac diseases, improving heart function. The underlying cellular and molecular mechanisms of the beneficial effects of physical exercise on the heart are still a subject of intensive study. Aerobic activity increases cardiovascular nitric oxide (NO) released mainly through nitric oxidase synthase 3 activity, promoting endothelium-dependent vasodilation, reducing vascular resistance, and lowering blood pressure. On the reverse, an imbalance between increasing free radical production and decreased NO generation characterizes pathologic remodeling, which has been termed the "nitroso-redox imbalance". Besides these classical evidence on the role of NO in cardiac physiology and pathology, accumulating data show that NO regulate different aspects of stem cell biology, including survival, proliferation, migration, differentiation, and secretion of pro-regenerative factors. Concurrently, it has been shown that physical exercise generates physiological remodeling while antagonizes pathologic remodeling also by fostering cardiac regeneration, including new cardiomyocyte formation. This review is therefore focused on the possible link between physical exercise, NO, and stem cell biology in the cardiac regenerative/reparative response to physiological or pathological load. Cellular and molecular mechanisms that generate an exercise-induced cardioprotective phenotype are discussed in regards with myocardial repair and regeneration. Aerobic training can benefit cells implicated in cardiovascular homeostasis and response to damage by NO-mediated pathways that protect stem cells in the hostile environment, enhance their activation and differentiation and, in turn, translate to more efficient myocardial tissue regeneration. Moreover, stem cell preconditioning by and/or local potentiation of NO signaling can be envisioned as promising approaches to improve the post-transplantation stem cell survival and the efficacy of cardiac stem cell therapy.

Glucose induces corneal epithelial dysfunctions characterized by delayed wound repair. Nuclear erythroid 2-related factor 2 (Nrf2) mediates cell protection mechanisms even through the Heme oxygenase-1 (HO-1) up-regulation. Here, we synthesized new HO-1 inducers by modifying dimethyl fumarate (DMF) and used docking studies to select VP13/126 as a promising compound with the best binding energy to Kelch-like ECH-associated protein 1 (keap1), which is the the regulator of Nrf2 nuclear translocation. We verified if VP13/126 protects SIRC cells from hyperglycemia compared to DMF. SIRC were cultured in normal (5 mM) or high glucose (25 mM, HG) in presence of DMF (1-25 μM) or VP13/126 (0.1-5 μM) with or without ERK1/2 inhibitor PD98059 (15 μM). VP13/126 was more effective than DMF in the prevention of HG-induced reduction of cell viability and proliferation. Reduction of wound closure induced by HG was similarly counteracted by 1 μM VP13/126 and 10 μM DMF. VP13/126 strongly increased phospho/total ERK1/2 and restored HO-1 protein in HG-treated SIRC; these effects are completely counteracted by PD98059. Moreover, high-content screening analysis showed a higher rate of Nrf2 nuclear translocation induced by VP13/126 than DMF in HG-stimulated SIRC. These data indicate that VP13/126 exerts remarkable pro-survival properties in HG-stimulated SIRC, promoting the Nrf2/HO-1 axis.