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The triad formed by thyroid dysfunction, metabolic syndrome (MetS), and cardiovascular (CV) risk forms a network with many connections that aggravates health outcomes. Thyroid hormones (THs) play an important role in glucose and lipid metabolism and hemodynamic regulation at the molecular level. It is noteworthy that a bidirectional association between THs and MetS and their components likely exists as MetS leads to thyroid dysfunction, whereas thyroid alterations may cause a higher incidence of MetS. Thyroid dysfunction increases insulin resistance, the circulating levels of lipids, in particular LDL-C, VLDL-C, and triglycerides, and induces endothelial dysfunction. Furthermore, THs are important regulators of both white and brown adipose tissue. Moreover, the pathophysiological relationship between MetS and TH dysfunction is made even tighter considering that these conditions are usually associated with inflammatory activation and increased oxidative stress. Therefore, the role of THs takes place starting from the molecular level, then manifesting itself at the clinical level, through an increased risk of CV events in the general population as well as in patients with heart failure or acute myocardial infarction. Thus, MetS is frequently associated with thyroid dysfunction, which supports the need to assess thyroid function in this group, and when clinically indicated, to correct it to maintain euthyroidism. However, there are still several critical points to be further investigated both at the molecular and clinical level, in particular considering the need to treat subclinical dysthyroidism in MetS patients.

The thyroid–heart relationship has a long and articulated history of its own, a history that encompasses physiological and pathophysiological knowledge. In recent years, molecular biology studies, in an experimental context, have highlighted the extraordinary dialogue that exists among the two systems in the field of cardioprotection, which is an extremely important area for the treatment of cardiac diseases in both acute and chronic phases. In addition, in the last few years, several studies have been carried out on the prognostic impact of alterations in thyroid function, including subclinical ones, in heart disease, in particular in heart failure and acute myocardial infarction, with evidence of a negative prognostic impact of these and, therefore, with the suggestion to treat these alterations in order to prevent cardiac events, such as death. This review provides a comprehensive summary of the heart–thyroid relationship.

Transitioning from childhood into adolescence is an extraordinary time of life, associated with major physical, emotional, cognitive, and social changes and characterized by dynamic development in which interaction with the environment modulates the individual resources responsible for well-being and health. This sensitive period is the time when, in addition to hormonal, metabolic, and neural changes, certain behavioral strategies begin to take shape that will shortly go on to define the emotional, social, and cultural identity of the individual. This narrative review aimed to uncover the crucial processes underlying the transition by identifying processes that are responsible for cognitive, psychosocial, and emotional development, in the absence of disease. For this aim, we highlight (1) the physical, psychological, and social determinants during the transition from childhood to adolescence; (2) the role of health-related variables in resilience or vulnerability mechanisms; and (3) recent school-based strategies to promote health and well-being. Recognizing that health and well-being are the result of the interaction of many biological, psychological, social, cultural, and physical factors will lead to comprehensive health promotion involving all actors joining the growth process, from health professionals and the educational community to parents and community. Furthermore, it is important that psychosocial dimensions are strengthened already during childhood to prevent the onset of frailty and illness in adolescence.

Transient left ventricular dysfunction (TLVD), a temporary condition marked by reversible impairment of ventricular function, remains an underdiagnosed yet significant contributor to morbidity and mortality in clinical practice. Unlike the well-explored atherosclerotic disease of the epicardial coronary arteries, the diverse etiologies of TLVD require greater attention for proper diagnosis and management. The spectrum of disorders associated with TLVD includes stress-induced cardiomyopathy, central nervous system injuries, histaminergic syndromes, various inflammatory diseases, pregnancy-related conditions, and genetically determined syndromes. Furthermore, myocardial infarction with non-obstructive coronary arteries (MINOCA) origins such as coronary artery spasm, coronary thromboembolism, and spontaneous coronary artery dissection (SCAD) may also manifest as TLVD, eventually showing recovery. This review highlights the range of ischemic and non-ischemic clinical situations that lead to TLVD, gathering conditions like Tako-Tsubo Syndrome (TTS), Kounis syndrome (KS), Myocarditis, Peripartum Cardiomyopathy (PPCM), and Tachycardia-induced cardiomyopathy (TIC). Differentiation amongst these causes is crucial, as they involve distinct clinical, instrumental, and genetic predictors that bode different outcomes and recovery potential for left ventricular function. The purpose of this review is to improve everyday clinical approaches to treating these diseases by providing an extensive survey of conditions linked with TLVD and the elements impacting prognosis and outcomes.

Magnetic resonance (MR) with sodium (23Na) is a noninvasive tool providing quantitative biochemical information regarding physiology, cellular metabolism, and viability, with the potential to extend MR beyond anatomical proton imaging. However, when using clinical scanners, the low detectable 23Na signal and the low 23Na gyromagnetic ratio require the design of dedicated radiofrequency (RF) coils tuned to the 23Na Larmor frequency and sequences, as well as the development of dedicated phantoms for testing the image quality, and an MR scanner with multinuclear spectroscopy (MNS) capabilities. In this work, we propose a hardware and software setup for evaluating the potential of 23Na magnetic resonance imaging (MRI) with a clinical scanner. In particular, the reliability of the proposed setup and the reproducibility of the measurements were verified by multiple acquisitions from a 3T MR scanner using a homebuilt RF volume coil and a dedicated sequence for the imaging of a phantom specifically designed for evaluating the accuracy of the technique. The final goal of this study is to propose a setup for standardizing clinical and research 23Na MRI protocols.

The prenatal diagnosis of congenital heart disease (CHD) represents, for both parents, a particularly stressful and traumatic life event from a psychological point of view. The present review sought to summarize the findings of the most relevant literature on the psychological impact of prenatal diagnosis of CHD on parents, describing the most common mechanisms employed in order to face this unexpected finding. We also highlight the importance of counseling and the current gaps in the effects of psychological support on this population.

Introduction: Adolescents experience rapid physical, cognitive, and psychosocial growth with different factors contributing to health and well-being. In this view, an important role is played by body weight and related perceptions. The purpose was to determine, in a sample of Italian high school students, whether health-related quality of life (HRQoL) is associated with the different weight status categories (underweight, normal weight, overweight, obese), even considering sex differences. Material and methods: Data were collected from 1826 adolescents (n = 735 males). HRQOL was analyzed using the Italian version of KIDSCREEN-52. Results: Overweight adolescents showed reductions in psychological well-being (p < 0.05) and self-perception (p < 0.05) compared with individuals in other BMI categories. Subjects with obesity reported increased bullying victimization (p < 0.05) and reductions in self-perception and eating disorders (p < 0.001), while underweight individuals were characterized by altered adherence to the Mediterranean diet (p < 0.001), eating disorders (p < 0.001), and problematic use of social media (p < 0.05). No sex differences were found, except for socio-economic status perceptions, where underweight girls reported higher economic well-being than boys (p < 0.05). Conclusions: Our findings may suggest that there is an association between weight status categories and HRQoL that is more pronounced in underweight and overweight adolescents. The association between BMI categories and psychosocial dimensions opens the need to define specific domains on which such preventive interventions should focus, always through a personalized perspective.

Background: Bullying is a hostile behavior repeated over a time period, affecting children and adolescents in different social settings, mainly small and stable ones like school, with negative effects on mental and physical health. In this study, we aimed to provide the degree of impairment of different variables related to health and well-being in bullying conditions, with attention to sex differences. Methods: Data were obtained from 5390 adolescents (mean age 13.08 ± 1.89; male 2729), and health-related quality of life (HRQoL) was assessed using the KIDSCREEN-52 questionnaire. Results: In all students, mood and emotion, self-perception, and parental relationships are the dimensions more compromised in bullying conditions, while lifestyle habit is the variable less involved. Bullied girls show a significant impairment of all HRQoL variables both with respect to the socially accepted counterpart and to the male population. Conclusions: Our study highlights the strict association between bullying and emotional and social dimensions, suggesting that enhancing them preventively could facilitate earlier detection of problems, thereby reducing health risks.

Background and Objectives: Roughly 10% of cancer patients experience an episode of bleeding. The bleeding severity can range from occasional trivial bleeds to major bleeding. The treatment for the bleeding may vary, depending on the clinical condition and anatomical site, and may include various strategies, among which TAE is a cornerstone of major bleeding management. However, the existing literature on tumor hemorrhages is inconsistent. The objective of this multicenter retrospective cohort study was to evaluate the effectiveness and safety of arterial embolization in the treatment of tumor hemorrhages in patients with solid cancers. Materials and Methods: The data for patients with solid cancers undergoing TAE for the management of tumor hemorrhages from January 2020 to May 2023 were gathered. Results: A total of 92 patients with cancer-related bleeding were treated between January 2020 and May 2023. No bleeding was detected by X-ray angiography (XA) in 12 (13%) cases; therefore, a blind embolization was performed. The most common bleeding site was the liver (21.7%). A total of 66 tumor hemorrhages were spontaneous. The most commonly used embolic agent was polyvinyl alcohol (PVA) particles (30.4%). Technical success was achieved in 82 (89.1%) cases, with an 84.8% clinical success rate related to 14 cases of rebleeding. Proximal embolization was performed for 19 (20.7%) patients. Complications were recorded for 10 (10.9%) patients. The 30-day bleeding-related mortality was 15.2%. The technical success, clinical success, proximal embolization rate, and 30-day rebleeding were worse in the subset of patients undergoing TAE with coils. Conclusions: Transcatheter arterial embolization (TAE) represents a viable and potentially life-saving therapeutic approach in the management of tumor hemorrhages, demonstrating a notable effectiveness and safety. The TAE of bleeding tumors using coils resulted in a higher rate of non-superselective proximal embolization, with a trend toward lower clinical success rates and higher rebleeding episodes.

The incidence of heart valve disease (HVD) has been rising over the last few decades, mainly due to the increasing average age of the general population, and mitral valve (MV) disease is the second most prevalent HVD after calcific aortic stenosis, but MV disease is a heterogeneous group of different pathophysiological diseases. It is widely proven that regular physical activity reduces all-cause mortality rates, and exercise prescription is part of the medical recommendations for patients affected by cardiovascular diseases. However, changes in hemodynamic balance during physical exercise (including the increase in heart rate, preload, or afterload) could favor the progression of the MV disease and potentially trigger major cardiac events. In young patients with HVD, it is therefore important to define criteria for allowing competitive sport or exercise prescription, balancing the positive effects as well as the potential risks. This review focuses on mitral valve disease pathophysiology, diagnosis, risk stratification, exercise prescription, and competitive sport participation selection, and offers an overview of the principal mitral valve diseases with the aim of encouraging physicians to embody exercise in their daily practice when appropriate.

Background and Objectives: Transcatheter arterial embolization (TAE) is part of the daily practice of most interventional radiologists worldwide. The ideal liquid embolic agent is far from being identified. Non-adhesive liquid embolic agents (NALEA) harden from the outside to the inside, resulting in deep penetration, known as “magma-like” progression, which permits a more distal embolization with good control of the embolic material. This multicenter retrospective cohort study aims to assess the efficacy, feasibility and safety of transcatheter arterial embolization (TAE) with ethylene-vinyl alcohol (EVOH)-based NALEAs (Onyx and Squid) in acute bleeding outside of the neurovascular area. Materials and Methods: This study is a multicenter analysis of retrospectively collected data of consecutive patients who had undergone, from January 2015 to December 2022, transcatheter arterial embolization with non-adhesive EVOH-based agents in the setting of acute non-neurovascular bleeding. Results: Fifty-three patients underwent transcatheter arterial embolization for acute non-neurovascular bleeding. Eight (15.1%) procedures were performed in patients with coagulopathy. The most used concentration of EVOH-based NALEAs was 34 (i.e., 8%), with a mean dose of 0.5 (±0.3) mL. The mean CT-to-groin time, the mean procedure time, the mean CT-to-embolization time and the mean fluoroscopy time were 22.9 (±12.4) min, 27.5 (±7) min, 50.3 (±13.1) min and 7.5 (±2.8) min, respectively. Technical success was achieved in all cases with a 96.2% clinical success rate. Complications were recorded in six (11.3%) patients. No statistically significant differences were observed between the group of patients with coagulopathy and the group of patients without coagulopathy in terms of efficacy and safety endpoints. Conclusions: Transcatheter arterial embolization (TAE) performed with non-adhesive EVOH-based embolic agents is an effective, feasible and safe strategy for the management of acute non-neurovascular bleeding, even in the subgroup of patients with coagulopathy.

Obesity is a serious public health issue and associated with an increased risk of cardiovascular disease events and mortality. The risk of cardiovascular complications is directly related to excess body fat mass and ectopic fat deposition, but also other obesity-related complications such as pre-type 2 diabetes, obstructive sleep apnoea, and non-alcoholic fatty liver diseases. Body mass index and waist circumference are used to classify a patient as overweight or obese and to stratify cardiovascular risk. Physical activity and diet, despite being key points in preventing adverse events and reducing cardiovascular risk, are not always successful strategies. Pharmacological treatments for weight reduction are promising strategies, but are restricted by possible safety issues and cost. Nonetheless, these treatments are associated with improvements in cardiovascular risk factors, and studies are ongoing to better evaluate cardiovascular outcomes. Bariatric surgery is effective in reducing the incidence of death and cardiovascular events such as myocardial infarction and stroke. Cardiac rehabilitation programs in obese patients improve cardiovascular disease risk factors, quality of life, and exercise capacity. The aim of this review was to critically analyze the current role and future aspects of lifestyle changes, medical and surgical treatments, and cardiac rehabilitation in obese patients, to reduce cardiovascular disease risk and mortality, and to highlight the need for a multidisciplinary approach to improving cardiovascular outcomes.

Background: Oxidative stress and impaired autophagy are directly and indirectly implicated in exercise-mediated muscle injury. Trehalose, spermidine, nicotinamide, and polyphenols possess pro-autophagic and antioxidant properties, and could therefore reduce exercise-induced damage to skeletal muscle. The aim of this study was to investigate whether a mixture of these compounds was able to improve muscle injury biomarkers in endurance athletes through the modulation of oxidative stress and autophagic machinery. Methods and Results: sNOX2-dp; H2O2 production; H2O2 breakdown activity (HBA); ATG5 and p62 levels, both markers of autophagic process; and muscle injury biomarkers were evaluated in five endurance athletes who were allocated in a crossover design study to daily administration of 10.5 g of an experimental mixture or no treatment, with evaluations conducted at baseline and after 30 days of mixture consumption. Compared to baseline, the mixture intake led to a remarkable reduction of oxidative stress and positively modulated autophagy. Finally, after the 30-day supplementation period, a significant decrease in muscle injury biomarkers was found. Conclusion: Supplementation with this mixture positively affected redox state and autophagy and improved muscle injury biomarkers in athletes, allowing for better muscle recovery. Moreover, it is speculated that this mixture could also benefit patients suffering from muscle injuries, such as cancer or cardiovascular patients, or elderly subjects.

Nonalcoholic fatty liver disease (NAFLD)-associated liver fibrosis is likely related to coronary artery disease (CAD) by the mediation of systemic inflammation. This study aimed at evaluating the predictive value of neutrophil-to-lymphocyte-ratio (NLR) and fibrosis-4 index (FIB-4), indices of inflammation and fibrosis, respectively, on CAD mortality. Data from 1460 CAD patients (1151 males, age: 68 ± 10 years, mean ± SD) were retrospectively analyzed. Over a median follow-up of 26 months (interquartile range (IQR) 12–45), 94 deaths were recorded. Kaplan–Meier survival analysis revealed worse outcomes in patients with elevation of one or both biomarkers (FIB-4 > 3.25 or/and NLR > 2.04, log-rank p-value < 0.001). In multivariate Cox regression analysis, the elevation of one biomarker (NLR or FIB-4) still confers a significant independent risk for mortality (hazard ratio (HR) = 1.7, 95% confidence interval (95% CI): 1.1–2.7, p = 0.023), whereas an increase in both biomarkers confers a risk corresponding to HR = 3.5 (95% CI: 1.6–7.8, p = 0.002). Categorization of patients with elevated FIB-4/NLR could provide valuable information for risk stratification and reduction of residual risk in CAD patients.

Oxidative stress and inflammation are key factors in cardiometabolic diseases. We set out to evaluate the relationship between serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) with cardiometabolic risk factors in coronary artery disease (CAD) patients, and their additive and multiplicative interactive effects on outcomes (cardiac death/CD and hard events (HE)—death plus reinfarction). A total of 2712 patients (67 ± 11 years, 1960 males) who underwent coronary angiography was retrospectively analyzed and categorized into no-CAD patients (n = 806), stable-CAD patients (n = 1545), and patients with acute myocardial infarction (AMI) (n = 361). UA and NLR were reciprocally correlated and associated with cardiometabolic risk factors. During a mean follow-up period of 27 ± 20 months, 99 ± 3.6% deaths, and 213 ± 7.8% HE were registered. The Kaplan–Meier survival estimates showed significantly worse outcomes in patients with elevated UA or NLR levels. Multivariate Cox regression analysis demonstrated that NLR independently predicted CD and HE. There was no multiplicative interaction between UA and NLR; however, the use of measures of additive interaction evidenced a positive additive interaction between UA and NLR for CD and HE. Although it is clear that correlation does not imply causation, the coexistence of NRL and UA appears to have a synergistic effect, providing further information for the risk stratification of CAD patients.

Sodium–glucose co-transporter-2 inhibitors or gliflozins, the newest anti-hyperglycemic class, induce cardioprotective benefits in patients with type 2 diabetes (T2D). As platelet activation and oxidative stress play a key role in atherothrombotic-related complications, we hypothesized that gliflozins might modulate oxidative stress, platelet activation and thrombus formation. We performed an interventional open-label single-arm before-after study in 32 T2D patients on top of their ongoing metformin therapy. The population was divided into two groups: treatment with GLP-1 receptor agonists (GLP-1RA, Group A) and gliflozins (Group B). Oxidative stress, platelet activation and thrombus growth were assessed before and after 15 days of treatment. Compared to the baseline, gliflozins treatment significantly decreased sNOX2-dp (−45.2%, p < 0.001), H2O2 production (−53.4%, p < 0.001), TxB2 (−33.1%, p < 0.001), sP-selectin (−49.3%, p < 0.001) and sCD40L levels (−62.3%, p < 0.001) as well as thrombus formation (−32%, p < 0.001), whereas it potentiated anti-oxidant power (HBA, +30.8%, p < 0.001). Moreover, a significant difference in oxidative stress, platelet activation and thrombus formation across groups A and B was found. In addition, an in vitro study on stimulated platelets treated with gliflozins (10–30 μM) showed a reduction in oxidative stress, platelet activation and thrombus growth. Our results showed that gliflozins have antiplatelet and antithrombic activity related to an NOX2 down-regulation, suggesting a new mechanism responsible for cardiovascular protection.

Trehalose, spermidine, nicotinamide, and polyphenols have been shown to display pro-autophagic and antioxidant properties, eventually reducing cardiovascular and ischemic complications. This study aimed to investigate whether a mixture of these components improves maximal walking distance (MWD) in peripheral artery disease (PAD) patients. Nitrite/nitrate (NOx), endothelin-1, sNOX2-dp, H2O2 production, H2O2 break-down activity (HBA), ATG5 and P62 levels, flow-mediated dilation (FMD), and MWD were evaluated in 20 PAD patients randomly allocated to 10.5 g of mixture or no-treatment in a single-blind study. The above variables were assessed at baseline and 60 days after mixture ingestion. Compared with baseline, mixture intake significantly increased MWD (+91%; p < 0.01) and serum NOx (+96%; p < 0.001), whereas it significantly reduced endothelin-1 levels (−30%, p < 0.01). Moreover, mixture intake led to a remarkable reduction in sNOX2dp (−31%, p < 0.05) and H2O2 (−40%, p < 0.001) and potentiated antioxidant power (+110%, p < 0.001). Finally, mixture ingestion restored autophagy by increasing ATG5 (+43%, p < 0.01) and decreasing P62 (−29%, p < 0.05). No changes in the above-mentioned variables were observed in the no-treatment group. The treatment with a mixture of trehalose, spermidine, nicotinamide, and polyphenols improves MWD in PAD patients, with a mechanism possibly related to NOX2-mediated oxidative stress downregulation and autophagic flux upregulation. Clinical Trial Registration unique identifier: NCT04061070.

(1) Background: here is a growing need for integrated and multidimensional approaches to health, especially in a particular category of populations, school-dropout (SD) adolescents, who are traditionally more prone to risky behavior. This study aimed to describe the association between possible risk factors (substance use, eating disorders, social addiction) and well-being perception through the application of a personalized well-being index (PWBI) in SD youths. (2) Methods: Data were collected in 450 school-dropout adolescents (19 ± 2 years, male 308); the health-related quality of life (HRQoL) and risk behaviors were assessed by means of a battery of standardized questions. (3) Results: The results revealed an altered perception of well-being in association with eating disorders (p < 0.001), the use of psychotropic drugs (p < 0.001), and the amount of their consumption (p < 0.05). In particular, there was a decrease in emotional state (p < 0.001) and PWBI (p < 0.001) in the presence of eating disorders, and an impairment in all PWBI components, emotional states (p < 0.001), lifestyle habits (p < 0.05), and social contexts (p < 0.001) when taking psychotropic drugs. (4) Conclusions: risk or unhealthy behaviors significantly worsen individual well-being. This study highlights the change of paradigm from a disease-oriented model to an educationally strength-based model when monitoring psychosocial well-being in order to define preventive and health promotion strategies in a vulnerable category of the population.

Compositional closure, spurious negative correlations in data sets of a fixed sum (e.g., fractions and percent), is often encountered in geostatistical analyses, particularly in mineralogy, petrology, and geochemistry. Techniques to minimize the effects of closure (e.g., log-ratio transformations) can provide consistent geostatistical results. However, such approaches do not remove these effects because closure does not result from mathematical operations but is an inherent property of the physical systems under study. The natural world causes physical closure; mathematics simply describes that closure and cannot alter it by manipulations. Here, we examine the distinct types of geologic systems and samples to determine in which situations closure (physical and mathematical) does or does not ensue and the reasons therefor. We parse compositional systems based on (1) types of components under study, immutable (e.g., elements) or reactive (minerals), and (2) whether the system is open or closed to component transfer. Further, open systems can be (1) displacive in which addition of a component physically crowds out others, or (2) accommodative in which addition or subtraction of components does not affect the others. Only displacive systems are subject to compositional closure. Accommodative systems, even with components expressed as percent or fractions, are not closed physically or, therefore, mathematically.

Selenium (Se), a microelement essential for life, is critical for homeostasis of several critical functions, such as those related to immune–endocrine function and signaling transduction pathways. In particular, Se is critical for the function of the thyroid, and it is particularly abundant in this gland. Unfortunately, Se deficiency is a very common condition worldwide. Supplementation is possible, but as Se has a narrow safety level, toxic levels are close to those normally required for a correct need. Thus, whether the obtaining of optimal selenium concentration is desirable, the risk of dangerous concentrations must be equally excluded. This review addressed the contribution by environment and food intake on Se circulating levels (e.g., geographical factors, such as soil concentration and climate, and different quantities in food, such as nuts, cereals, eggs, meat and fish) and effects related to its deficiency or excess, together with the role of selenium and selenoproteins in the thyroid pathophysiology (e.g., Hashimoto’s thyroiditis and Graves’ disease).

Paediatric chronic diseases (CD) are characterised by their ongoing duration and the fact that they are often managed throughout the lifespan, with the need to adjust lifestyle and expectations with the limitations coming from the CD. The aim of the PENSAMI study is to not only cure the disease, but to also care for the person from a clinical and psychosocial perspective. Data will be collected from 150 paediatric patients affected by heart disease, diabetes, and asthma admitted during in-hospital stay or outpatient visits, and from 200 healthy control subjects. The protocol will consist of two phases. The first one will aim at elaborating the predictive model by detecting (clinical, anthropometric at birth, environmental, lifestyle, social context, emotional state, and mental abilities) in order to develop a model predictive of the events considered: (1) re-hospitalisation; (2) severity and progression of the disease; (3) adherence to therapy; (4) HRQoL; (5) obesity and metabolic syndrome; (6) illness-stress related; (7) school drop-out; (8) school performance. The second one will address validating the previous predictive model. This model will aim to: (1) understand, prevent, and halt the progression of childhood CD; (2) develop new and improved diagnostic tools; (3) pave the way for innovative treatments and additional therapies to traditional clinical practice; and (4) create truly personalised therapeutic and preventive strategies in various sectors, such as cardiology, diabetes, and respiratory diseases.

Ceramides are a family of lipid molecules, composed of sphingosine and a fatty acid, and transported by lipoproteins (primarily by low-density lipoproteins) in the bloodstream. They are not only structural lipids, but multifunctional and bioactive molecules with key roles in many important cellular pathways, such as inflammatory processes and apoptosis, representing potential biomarkers of cardiometabolic diseases as well as pharmacological targets. Recent data reported ceramide modulation by diet and aerobic exercise, suggesting nutrients and exercise-targeting sphingolipid pathways as a countermeasure, also in combination with other therapies, for risk and progression of chronic disease prevention and health maintenance. In this review, we focus on the available data regarding remarks on ceramide structure and metabolism, their pathophysiologic roles, and the effect of dietary habit and aerobic exercise on ceramide levels. Moreover, advancements and limitations of lipidomic techniques and simplification attempts to overcome difficulties of interpretation and to facilitate practical applications, such as the proposal of scores, are also discussed.

The benefit of an antibiotic prophylaxis for most oral surgical procedures is controversial. The aim of this study was to collect information on the prescribing habits of a sample of Italian dentists with respect to the role of antibiotic prophylaxis in preventing surgical site infections (SSI). An anonymous questionnaire was prepared and made accessible online by sharing a Google Forms link. General anagraphic data and educational background information were collected to obtain a profile of the participants. Different clinical scenarios were then proposed, with the participants asked to choose whether they would prescribe an antibiotic prophylaxis and with which dosage regimens. In total, 169 dentists participated in the questionnaire and the obtained data were assessed through a percentage report. The results showed a substantial agreement in antibiotics prescription, but only in a limited number of clinical scenarios, such as deciduous teeth extraction or simple extractions in healthy adult patients. Discordant responses were found for several clinical cases, particularly for cases of comorbidities, surgical or multiple extractions, implant placement and abscess drainage. The answers obtained from the survey sample were notably heterogeneous, indicating that the choice to prescribe an antibiotic prophylaxis to prevent SSIs is often discretionary. Moreover, the dosage regimen of prophylaxis is also controversial. The results of this study demonstrate the need for specific guidelines on antibiotics in dentistry and, specifically, on antibiotic prophylaxis in oral surgery. Such guidelines would help to avoid unnecessary prescriptions.

Congenital heart disease, the most frequent malformation at birth, is usually not fatal but leads to multiple hospitalisations and outpatient visits, with negative impact on the quality of life and psychological profile not only of children but also of their families. In this paper, we describe the entire architecture of a system for remotely monitoring paediatric/neonatal patients with congenital heart disease, with the final aim of improving quality of life of the whole family and reducing hospital admissions. The interesting vital parameters for the disease are ECG, heart rate, oxygen saturation, body temperature and body weight. They are collected at home using some biomedical sensors specifically selected and calibrated for the paediatric field. These data are then sent to the smart hub, which proceeds with the synchronisation to the remote e-Health care center. Here, the doctors can log and evaluate the patient’s parameters. Preliminary results underline the sensor suitability for children and infants and good usability and data management of the smart-hub technology (E@syCare). In the clinical trial, some patients from the U.O.C. Paediatric and Adult Congenital Cardiology- Monasterio Foundation are enrolled. They receive a home monitoring kit according to the group they belong to. The trial aims to evaluate the effects of the system on quality of life. Psychological data are collected through questionnaires filled in by parents/caregivers in self-administration via the gateway at the beginning and at the end of the study. Results highlight an overall improvement in well-being and sleep quality, with a consequent reduction in anxious and stressful situations during daily life thanks to telemonitoring. At the same time, users reported a good level of usability, ease of data transmission and management of the devices.

Background: Exercise may affect lipid profile which in turn is related to inflammation, although changes of ceramides, diacylglycerols-DAG and sphingomyelin-SM and their relationship with inflammatory parameters following a half-marathon have never been examined. Methods: Ceramides, DAG and SM, and markers of inflammation (soluble fractalkine-CX3CL1, vascular endothelial growth factor-VEGF, interleukin6-IL-6 and tumor necrosis factorα-TNFα) were evaluated in trained half-marathoners before, post-race (withdrawal within 20 min after the race end) and 24 h after. Results: IL-6 and CX3CL1 increased immediately after the race, returning to baseline after 24 h. Total ceramides and total DAG significantly decreased post-race. Several ceramide classes decreased after exercise, while only one of the DAG (36:3) changed significantly. Total SM and specific species did not significantly change. Conclusion: Some inflammatory parameters (IL-6 and CX3CL1) transiently increased after the race, and, being reversible, these changes might represent a physiological response to acute exercise rather than a damage-related response. The decrease of specific lipid classes, i.e., DAGs and ceramides, and the lack of their relationship with inflammatory parameters, suggest their involvement in beneficial training effects, opening promising research perspectives to identify additional mechanisms of aerobic exercise adaptation.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are emerging worldwide epidemics, projected to become the leading cause of liver transplants. The strongest genetic risk factor for NAFLD/NASH susceptibility and progression is a single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 gene (PNPLA3), rs738409, encoding the missense mutation I148M. This aminoacidic substitution interferes with the normal remodeling of lipid droplets in hepatocytes. It is also thought to play a key role in promoting liver fibrosis by inhibiting the release of retinol from hepatic stellate cells. Reducing PNPLA3 levels in individuals homozygous for 148M may be an effective treatment for the entire spectrum of NAFLD, based on gene dosage analysis in the human population, as well as the protective effect of another naturally occurring SNP (rs2294918) in PNPLA3 which, when co-inherited, reduces PNPLA3 mRNA levels to 50% and counteracts disease risk. By screening a clinical compound library targeting specific signaling pathways active in primary human hepatocytes, we identified momelotinib, a drug evaluated in clinical trials to treat myelofibrosis, as a potent down-regulator of PNPLA3 expression, across all genotypes. We found that momelotinib treatment yielded >80% reduction in PNPLA3 mRNA in human primary hepatocytes and stellate cells, as well as in vivo via acute and chronic treatment of WT mice. Using a human multilineage 3D spheroid model of NASH homozygous for the PNPLA3 mutant protein, we additionally show that it decreases PNPLA3 mRNA as well as intracellular lipid content. Furthermore, we show that the effects on PNPLA3 coincide with changes in chromatin accessibility within regulatory regions of the PNPLA3 locus, consistent with inhibition occurring at the level of transcription. In addition to its primary reported targets, the JAK kinases, momelotinib inhibits several non-JAK kinases, including ACVR1. Using a combination of targeted siRNA knockdowns and signaling pathway perturbations, we show that momelotinib reduces the expression of the PNPLA3 gene largely through the inhibition of BMP signaling rather than the JAK/STAT pathway. Overall, our work identified momelotinib as a potential NASH therapeutic and uncovered previously unrecognized connections between signaling pathways and PNPLA3. These pathways may be exploited by drug modalities to “tune down” the level of gene expression, and therefore offer a potential therapeutic benefit to a high at-risk subset of NAFLD/NASH patients.

Oxidative stress has been suggested to affect age-associated physiological dysfunction. Therefore, it is speculated that antioxidant supplements could have a potential role in preventing age-related diseases and death. Among different dietary habits, the highly antioxidant Mediterranean dietary pattern, which includes high vegetable and fruit intake, consumption of legumes, cereals, and fish, low intake of meat and dairy derivatives, moderate red wine consumption, and use of extra-virgin olive oil, is characterized by other aspects than food, such as conviviality, sensory stimulation, socialization, biodiversity, and seasonality that can reinforce the Mediterranean diet’s (MeD) beneficial effects on wellbeing, quality of life, and healthy aging. The present review aims to discuss available data on the relationship between oxidative stress and aging, biomarkers of oxidative stress status, protective effects of the MeD, and the adoption of the Mediterranean lifestyle as a non-pharmacological and natural tool to cope with oxidative stress damage for a longer life span, and—even more important—healthy aging beyond the biological, psychological, and social challenges that old age entails.

Background: Oxidative stress is crucial in the pathogenesis of atherosclerosis and acute myocardial infarction (AMI). Under the generic terms “oxidative stress” (OS), many biomarkers belonging to different pathways have been proposed. Aim: To compare the levels of recently proposed OS-related parameters in acute coronary syndromes (ACS) and stable coronary artery disease (CAD), to evaluate their effectiveness as additive risk or illness indicators of stable and acute ischemic events, and their response over time during the course of AMI. Methods: 76 ACS, 77 CAD patients, and 63 controls were enrolled in the study. Different OS-related biomarkers, including reactive oxygen metabolites (ROM), the total antioxidant capacity (OXY), nitrite/nitrate (final nitric oxide products, NOx), and Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), were evaluated. Moreover, time response during AMI course (admission, and 6, 12, 18, 24, 36, and 48 hours after, T0-T6, respectively) and correlation with traditional cardiovascular (CV) risk factors (age, gender, hypertension, diabetes mellitus, dyslipidemia, smoking habit) were also assessed. Results: Over time, ROM progressively increased while OXY and NOx decreased. Kinetics of LOX-1 during AMI shows that this biomarker boosts early during the acute event (T1 and T2) and then progressively decreases, being significantly lower from T0 to T6. Different OS-related biomarkers were differentially associated with CV risk factors and CAD or ACS presence. Conclusion: Differences in OS-related biomarkers (between groups, according to the response over time during AMI, and to the presence of CV risk factors) confirmed OS involvement in the transition from healthy status to stable CAD and ACS, although evidencing the heterogeneous nature of redox processes. In future, a multi-marker panel including different biomarkers and pathways of oxidative stress could be evaluated as an additive tool to be used in the CV prevention, diagnosis, patient stratification, and treatment.

In this study, two capsaicin analogues, N-eicosapentaenoyl vanillylamine (EPVA) and N-docosahexaenoyl vanillylamine (DHVA), were enzymatically synthesized from their corresponding n-3 long chain polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both dietary relevant components. The compounds significantly reduced the production of some lipopolysaccharide (LPS)-induced inflammatory mediators, including nitric oxide (NO), macrophage-inflammatory protein-3α (CCL20) and monocyte chemoattractant protein-1 (MCP-1 or CCL2), by RAW264.7 macrophages. Next to this, only EPVA increased insulin secretion by pancreatic INS-1 832/13 β-cells, while raising intracellular Ca2+ and ATP concentrations. This suggests that the stimulation of insulin release occurs through an increase in the intracellular ATP/ADP ratio in the first phase, while is calcium-mediated in the second phase. Although it is not yet known whether EPVA is endogenously produced, its potential therapeutic value for diabetes treatment merits further investigation.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in western countries. Despite the high prevalence of NAFLD, the underlying biology of the disease progression is not clear, and there are no approved drugs to treat non-alcoholic steatohepatitis (NASH), the most advanced form of the disease. Thus, there is an urgent need for developing advanced in vitro human cellular systems to study disease mechanisms and drug responses. We attempted to create an organoid system genetically predisposed to NAFLD and to induce steatosis and fibrosis in it by adding free fatty acids. We used multilineage 3D spheroids composed by hepatocytes (HepG2) and hepatic stellate cells (LX-2) with a physiological ratio (24:1). HepG2 and LX-2 cells are homozygotes for the PNPLA3 I148M sequence variant, the strongest genetic determinant of NAFLD. We demonstrate that hepatic stellate cells facilitate the compactness of 3D spheroids. Then, we show that the spheroids develop accumulations of fat and collagen upon exposure to free fatty acids. Finally, this accumulation was rescued by incubating spheroids with liraglutide or elafibranor, drugs that are in clinical trials for the treatment of NASH. In conclusion, we have established a simple, easy to handle, in vitro model of genetically induced NAFLD consisting of multilineage 3D spheroids. This tool may be used to understand molecular mechanisms involved in the early stages of fibrogenesis induced by lipid accumulation. Moreover, it may be used to identify new compounds to treat NASH using high-throughput drug screening.

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The primary prevention of cardiovascular (CV) disease depends on the capacity to identify subjects at higher risk long before the occurrence of CV clinical manifestations. Traditional risk factors do not cover fully prediction of individual risk. Moreover, there is an area of gray for patients at intermediate CV risk, which offers wide margins of improvement. These observations highlight the need for new additive tools for a more accurate risk stratification. An increasing number of candidate biomarkers have been identified to predict CV risk and events, although they generally give only a moderate increase when added to currently available predictive scores. The approach utilizing a relative small number of biomarkers in multiple combinations, but only weakly related to each other or unrelated, thus belonging to independent-pathways, and so able to catch the multidimensional characteristic of atherosclerosis, appears promising. We discuss vitamin D and bone turnover biomarkers, hepatitis C virus, and psycho-emotional factors that may reflect alternative pathways over those generally considered for atherosclerosis (e.g., aspects directly related to inflammation and thrombosis). These new biomarkers could facilitate a more accurate assessment of CV risk stratification if incorporated in the current risk assessment algorithms.

The human plasma membrane transporter ASCT2 is responsible for mediating Na- dependent antiport of neutral amino acids. New insights into structure/function relationships were unveiled by a combined approach of recombinant over-expression, site-directed mutagenesis, transport assays in proteoliposomes and bioinformatics. WT and Cys mutants of hASCT2 were produced in P. pastoris and purified for functional assay. The reactivity towards SH reducing and oxidizing agents of WT protein was investigated and opposite effects were revealed; transport activity increased upon treatment with the Cys reducing agent DTE, i.e., when Cys residues were in thiol (reduced) state. Methyl-Hg, which binds to SH groups, was able to inhibit WT and seven out of eight Cys to Ala mutants. On the contrary, C467A loses the sensitivity to both DTE activation and Methyl-Hg inhibition. The C467A mutant showed a Km for Gln one order of magnitude higher than that of WT. Moreover, the C467 residue is localized in the substrate binding region of the protein, as suggested by bioinformatics on the basis of the EAAT1 structure comparison. Taken together, the experimental data allowed identifying C467 residue as crucial for substrate binding and for transport activity modulation of hASCT2.

Purpose/Introduction: Osteoporosis (OP) and cardiovascular (CV) disease emerge as closely related conditions, showing common risk factors and/or pathophysiological mechanisms. The aim of this study was to evaluate the association between bone health markers (BHM) and individual CV risk factors and overall CV risk (FRAMINGHAM-FRS, and PROCAM scores) in a general adult population. Methods: In 103 subjects (21 males; age: 56 ± 12 years), vitamin D (25(OH)D), osteocalcin (OC), bone alkaline phospatase (BALP), procollagen I aminoterminal propeptide (P1NP), CTx-telopeptide, as well clinical history and life style were evaluated. Results: Aging (p < 0.001) and glycemia (p < 0.05) emerged as independent 25(OH)D predictors. Aging (p < 0.001), male sex (p < 0.05), and obesity (p < 0.05) represented independent OC determinants. Aging (p < 0.05) was the only independent BALP determinant. After multivariate adjustment, low 25(OH)D (75th percentile-16.6 ng/mL) (6.7 (1.9–23.8) p < 0.01) were found to be significant FRS predictors, while subjects with elevated OC and/or BALP (>75th percentile-9.8 μg/L) showed a higher CV risk as estimated by PROCAM (3.6 (1.2–10.7) p < 0.05). CTx and P1NP did not significantly correlate with CV risk factors or scores. Conclusion: As we go further into bone and CV physiology, it is evident that a close relationship exists between these diseases. Further studies are needed to investigate mechanisms by which bone turnover markers are related to metabolic risk and could modulate CV risk. This knowledge may help to develop possible multiple-purpose strategies for both CV disease and OP prevention and treatment.

The increased life expectancy, urbanization, and unhealthy lifestyle characterized by a shift towards a sedentary lifestyle and decreased energy expenditure are considered the main drivers of epidemiological transition. In particular, developing countries are facing a double burden caused by coexisting under- and over-nutrition, which causes a change in the disease profile from infectious diseases to a chronic degenerative pattern. This review discusses the under- and over-nutrition context in Mauritania and India, two countries that are experiencing a nutritional transition, and where we began a collaboration with local medical staff to integrate interventional and diagnostic guidelines. If many studies about diet and its relationship to non-communicable diseases are available for India, very few nutrition and cardiovascular risk studies have been conducted in Mauritania. Presently, with the exponential increase of nutrition-related diseases, targeted approaches are needed to provide balanced diets in parallel with the development of national preventive health systems and screening programs adapted to local needs. In this context, the measurement of oxidative stress biomarkers could be promising as an additive tool to assess cardiovascular (CV) risk in general population, and ameliorating prevention in patients at CV risk or with overt CV disease. Moreover, the possibility of improving the outcome by the direct employment of antioxidant remains plausible. Moreover, studies on the content of antioxidant in different foods may be helpful to develop a balanced diet, and achieve the maximal nutritional and functional properties of cultivars with benefits for human health.

Water-saturation porosity and dye-penetration permeability measurements of Round Top Mountain rhyolite confirm that a ½-inch (13-mm) crush size would permit efficient acid heap leaching of yttrium and heavy rare earth elements (YHREEs) hosted in yttrofluorite, a YHREE-substituted variety of fluorite. Laboratory acid leaching has extracted up to 90% of the YHREEs. The bulk insoluble gangue mineralogy of the rhyolite, 90% to 95% quartz and feldspars, assures low acid consumption. Different crush sizes were weighed, soaked in water, and reweighed over time to determine water-penetration estimated porosity. Typical porosities were 1% to 2% for gray and 3% to 8% for pink varieties of Round Top rhyolite. The same samples were re-tested after soaking in dilute sulfuric to simulate heap leaching effects. Post-leach porosity favorably increased 15% in pink and 50% in gray varieties, due to internal mineral dissolution. Next, drops of water-based writing ink were placed on rhyolite slabs up to ~10 mm thick, and monitored over time for visual dye breakthrough to the lower side. Ink penetration through 0.5 to 2.5-mm-thick slabs was rapid, with breakthrough in minutes to a few hours. Pink rhyolite breakthrough was faster than gray. Thicker slabs, 4 to 10 mm, took hours to three days for breakthrough. Porosity and permeability of the Round Top rhyolite and acid solubility of the yttrofluorite host should permit liberation of YHREEs from the bulk rock by inexpensive heap leaching at a coarse and inexpensive nominal ½-inch (13-mm) crush size. The rate-limiting step in heap leach extraction would be diffusion of acid into, and back-diffusion of dissolution products out of, the crushed particles. The exceptional porosity and permeability that we document at Round Top suggest that there may be other crystalline rock deposits that economically can be exploited by a coarse-crush bulk heap leach approach.