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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.

Ceramides and other related sphingolipids, important cellular components linked to metabolic homeostasis and cardiometabolic diseases, have been found to be involved in different steps of the SARS-CoV-2 life cycle. Hence, changes in their physiological levels are identified as predictors of COVID-19 severity and prognosis, as well as potential therapeutic targets. In this review, an overview of the SARS-CoV-2 life cycle is given, followed by a description of the sphingolipid metabolism and its role in viral infection, with a particular focus on those steps required to finalize the viral life cycle. Furthermore, the use and development of pharmaceutical strategies to target sphingolipids to prevent and treat severe and long-term symptoms of infectious diseases, particularly COVID-19, are reviewed herein. Finally, research perspectives and current challenges in this research field are highlighted. Although many aspects of sphingolipid metabolism are not fully known, this review aims to highlight how the discovery and use of molecules targeting sphingolipids with reliable and selective properties may offer new therapeutic alternatives to infectious and other diseases, including COVID-19.

Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic patients still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), in addition to the low hypoglycemic effect, exert multiple beneficial effects at a metabolic and cardiovascular level, through mechanisms other than antihyperglycemic agents. This review aims to discuss the effects of these new antidiabetic drugs, highlighting cardiovascular and metabolic benefits, through the description of their action mechanisms as well as available data by preclinical and clinical studies. Moreover, new innovative tools in the T2D field will be described which may help to advance towards a better targeted T2D personalized care in future.

Iron overload in beta transfusion-dependent thalassemia (β-TDT) may provoke oxidative stress and reduction of the antioxidant defenses, with serious consequences for the disease course and complications. The present study evaluated the oxidant/antioxidant status of β-TDT patients and its correlation with demographic, clinical, laboratory, and instrumental biomarkers. The OXY-adsorbent assay and the d-ROMs (Diacron, Grosseto, Italy) were evaluated in 58 β-TDT patients (mean age: 37.55 ± 7.83 years, 28 females) enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload was quantified with R2* magnetic resonance imaging. Mean OXY was 323.75 ± 113.19 μmol HClO/mL and 39 (67.2%) patients showed a decreased OXY-Adsorbent level (

Sphingolipids (SLs) influence several cellular pathways, while vitamin D exerts many extraskeletal effects in addition to its traditional biological functions, including the modulation of calcium homeostasis and bone health. Moreover, Vitamin D and SLs affect the regulation of each others’ metabolism; hence, this study aims to evaluate the relationship between the levels of 25(OH)D and ceramides in acute myocardial infarction (AMI). In particular, the blood abundance of eight ceramides and 25(OH)D was evaluated in 134 AMI patients (aged 68.4 ± 12.0 years, 72% males). A significant inverse correlation between 25(OH)D and both Cer(d18:1/16:0) and Cer(d18:1/18:0) was found; indeed, patients with severe hypovitaminosis D (t-Value −2, p ≤ 0.05) and Cer(d18:1/18:0) (−0.2, −2.2, p < 0.05). In light of these findings, the crosstalk between sphingolipids and vitamin D may unravel additional mechanisms by which these molecules can influence CV risk in AMI.

Objectives: To evaluate CV profiles, periprocedural complications, and in-hospital mortality in acute myocardial infarction (AMI) according to climate. Methods: Data from 2478 AMI patients (1779 men; mean age 67 ∓ 13 years; Pasquinucci Hospital ICU, Massa, Italy; 2007–2018) were retrospectively analyzed according to climate (LAMMA Consortium; Firenze, Italy) by using three approaches as follows: (1) annual warm (May–October) and cold (November–April) periods; (2) warm and cold extremes of the two periods; and (3) warm and cold extremes for each month of the two periods. Results: All approaches highlighted a higher percentage of AMI hospitalization for patients with adverse CV profiles in relation to low temperatures, or higher periprocedural complications and in-hospital deaths. In warmer times of the cold periods, there were fewer admissions of dyslipidemic patients. During warm periods, progressive heat anomalies were characterized by more smoker (approaches 2 and 3) and young AMI patient (approach 3) admissions, whereas cooler times (approach 3) evidenced a reduced hospitalization of diabetic and dyslipidemic patients. No significant effects were observed for the heat index and light circulation. Conclusions: Although largely overlapping, different approaches identify patient subgroups with different CV risk factors at higher AMI admission risk and adverse short-term outcomes. These data retain potential implications regarding pathophysiological mechanisms of AMI and its prevention.

Abstract Background In body-mind relationship field, eating disorders (ED) are considered disabling disorders that can alter physical health status, inducing profound alterations in psychosocial, cognitive and emotional dimensions. These disorders, characterized by a strong comorbidity with other diseases, usually begin during childhood or adolescence, and include anorexia nervosa, bulimia nervosa and binge eating. Aim of this study was to investigate the associations between eating disorders perception and dimensions of health-related quality of life (HRQoL) and well-being perception (WBP) in school-dropout adolescents. Methods Data were collected in 450 adolescents (19 ± 2 years, male 308), and HRQoL, WBP, and ED were assessed by means a battery of standardized questionnaire. Results EDs are more pronounced in females than in males (p

(1) Background: The systemic inflammatory response index (SIRI; neutrophil count × monocyte/lymphocyte count), and the systemic immune-inflammation index (SII; platelet count × neutrophil count/lymphocyte count) are recently proposed biomarkers to assess the immune and inflammatory status. However, data on SIRI and SII are still relatively lacking and do not definitively and exhaustively define their role as predictors of an adverse prognosis in acute myocardial infarction (AMI). The aim of the present study was to evaluate SII and SIRI determinants as well as to assess SIRI and SII prognostic power in ST-elevation myocardial infarction (STEMI). (2) Methods: A total of 105 STEMI patients (74 males, 70 ± 11 years) were studied (median follow-up 54 ± 25 months, 24 deaths). (3) Results: The main determinants of SIRI and SII were creatinine and brain natriuretic peptide (BNP) (multivariate regression). Patients with higher SIRI (>75th percentile, 4.9) and SII (>75th percentile, 1257.5) had lower survival rates than those in the low SIRI/SII group (Kaplan–Meier analysis). Univariate Cox regression revealed that high SIRI and SII were associated with mortality (HR: 2.6, 95% CI: 1.1–5.8, p < 0.05; 2.2, 1–4.9, p ≤ 0.05, respectively); however, these associations lost their significance after multivariate adjustment. (4) Conclusions: SIRI and SII association with mortality was significantly affected by confounding factors in our population, especially creatinine and BNP, which are associated with both the inflammatory indices and the outcome.

We evaluated the association of vitamin D and parathormone (PTH) levels with cardiac iron and function in beta-thalassemia major (β-TM) patients. Two-hundred and seventy-eight TM patients (39.04 ± 8.58 years, 56.8% females) underwent magnetic resonance imaging for the assessment of iron overload (T2* technique), biventricular function parameters (cine images), and replacement myocardial fibrosis (late gadolinium enhancement technique). Vitamin D levels were deficient (p < 0.0001). In TM, the periodic and regular assessment of vitamin D levels can be beneficial for the prevention of cardiac iron accumulation and subsequent overt dysfunction.

Cardiometabolic diseases (CMD) remains the major cause of morbidity and mortality in Western countries, with a marked increased in the last years [...]

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.

Sphingolipids (SLs) are structural, bioactive molecules with several key cellular roles, whereas 1,25-dihydroxyvitamin D (1,25(OH)D), the active form of vitamin D, is considered the major regulator of calcium homeostasis, although it also exerts other extraskeletal effects. Many studies reported the physiological connection between vitamin D and SLs, highlighting not only the effects of vitamin D on SL metabolism and signaling but also the influence of SLs on vitamin D levels and function, thus strongly suggesting a crosstalk between these molecules. After a brief description of 1,25(OH)D and SL metabolism, this review aims to discuss the preclinical and clinical evidence on the crosstalk between SLs and 1,25(OH)D, with a special focus on cardiometabolic diseases.

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.

From the very beginning, the coronavirus pandemic (COVID-19) has tested the healthcare systems, having unpredictable and extreme adverse impacts on acute care clinical settings [...]

Thyroid hormone (TH) signaling is strictly regulated by iodothyronine deiodinase activity, which both preserves the circulating levels of the biologically active triiodothyronine (T3) and regulates TH homeostasis at the local level, in a cell- and time-dependent manner. Three deiodinases have been identified—namely iodothyronine deiodinase 1 (DIO1), DIO2, and DIO3—that differ in their catalytic properties and tissue distribution. The deiodinases represent a dynamic system that changes in the different stages of life according to their functions and roles in various cell types and tissues. Deiodinase activity at the tissue level permits cell-targeted fine regulation of TH homeostasis, mediating the activation (DIO1 and DIO2) and inactivation (DIO3) of THs. Deiodinase homeostasis is the driving force that leads T3-target cells towards customized TH signaling, which takes into account both the hormonal circulating levels and the tissue-specific response. This review analyzes the complex role of deiodinases in physiological and pathological contexts, exploring new challenges and opportunities deriving from a deeper knowledge of the dynamics underlying their roles and functions.

Background: Frailty is highly common in older patients (pts) undergoing transcatheter aortic valve replacement (TAVR), and it is associated with poor outcomes. The selection of patients who can benefit from this procedure is necessary and challenging. The aim of the present study is to evaluate outcomes in older severe aortic valve stenosis (AS) pts, selected by a multidisciplinary approach for surgical, clinical, and geriatric risk and referred to treatment, according to frailty levels. Methods: A total of 109 pts (83 ± 5 years; females, 68%) with AS were classified by Fried’s score in pre-frail, early frail, and frail and underwent surgical aortic valve replacement SAVR/TAVR, balloon aortic valvuloplasty, or medical therapy. We evaluated geriatric, clinical, and surgical features and detected periprocedural complications. The outcome was all-cause mortality. Results: Increasing frailty was associated with the worst clinical, surgical, geriatric conditions. By using Kaplan–Meier analysis, the survival rate was higher in pre-frail and TAVR groups (p < 0.001) (median follow-up = 20 months). By using the Cox regression model, frailty (p = 0.004), heart failure (p = 0.007), EF% (p = 0.043), albumin (p = 0.018) were associated with all-cause mortality. Conclusions: According to tailored frailty management, elderly AS pts with early frailty levels seem to be the most suitable candidates for TAVR/SAVR for positive outcomes because advanced frailty would make each treatment futile or palliative.

Resveratrol (RSV) is a phenolic compound with strong antioxidant activity, which is generally associated with the beneficial effects of wine on human health. All resveratrol-mediated benefits exerted on different systems and pathophysiological conditions are possible through resveratrol’s interactions with different biological targets, along with its involvement in several key cellular pathways affecting cardiometabolic (CM) health. With regard to its role in oxidative stress, RSV exerts its antioxidant activity not only as a free radical scavenger but also by increasing the activity of antioxidant enzymes and regulating redox genes, nitric oxide bioavailability and mitochondrial function. Moreover, several studies have demonstrated that some RSV effects are mediated by changes in sphingolipids, a class of biolipids involved in a number of cellular functions (e.g., apoptosis, cell proliferation, oxidative stress and inflammation) that have attracted interest as emerging critical determinants of CM risk and disease. Accordingly, this review aimed to discuss the available data regarding the effects of RSV on sphingolipid metabolism and signaling in CM risk and disease, focusing on oxidative stress/inflammatory-related aspects, and the clinical implications of this relationship.

Beyond its key role in calcium homeostasis, vitamin D has been found to significantly affect the cardiovascular (CV) system. In fact, low vitamin D levels have been associated with increased CV risk, as well as increased CV morbidity and mortality. The majority of effects of this molecule are related directly or indirectly to its antioxidative and anti-inflammatory properties. Generally, vitamin D insufficiency is considered for 25-hydroxyvitamin D (25(OH)D) levels between 21–29 ng/mL (corresponding to 52.5–72.5 nmol/L), deficiency as 25(OH)D levels less than 20 ng/mL (

Lipoprotein(a)-Lp(a), which retains proatherogenic and prothrombotic properties, may be modified by hormonal and metabolic factors. However, few studies have focused on differences related to sex and cardiometabolic risk factors in the relationship between Lp(a) and cardiovascular disease, especially in terms of prognosis. This study aimed at evaluating the predictive value of Lp(a) (cut-off 30 mg/dL) for hard events (HEs: mortality and non-fatal myocardial infarction) according to sex and cardiometabolic risk factors in 2110 patients (1501 males, mean age: 68 ± 9 years) undergoing coronary angiography for known or suspected coronary artery disease. There were 211 events over a median follow-up period of 33 months. Lp(a) > 30 mg/dL did not confer a worse prognosis on the overall population. However, Kaplan–Meier subgroup analysis evidenced a worse prognosis in type 2 diabetes (T2D) females with elevated Lp(a) (log-rank test: p = 0.03) vs. T2D males and no-T2D patients, but not in other high-risk cardiovascular states (e.g., smoking, hypertension, reduced left ventricular ejection fraction or obesity). After Cox multivariate adjustment, Lp(a) remained an independent determinant for HEs in the T2D female subgroup, conferring an HR of 2.9 (95% CI 1.1–7.7, p < 0.05). Lp(a) is therefore a strong independent predictor of HR in T2D women, but not in T2D men, or in noT2D patients.

Ceramides have been associated with cardiometabolic disease (e.g., acute myocardial infarction (AMI) and type 2 diabetes (T2D)) and adverse outcomes. Acute admission hyperglycemia (AH) is a transient glucose alteration in response to stress. As glycated hemoglobin (HbA1c) reflects the glycemia over a longer period of time, its use may be helpful in distinguishing between the AH and hyperglycemia associated with T2D in the AMI setting. The aim was to assess the correlation of ceramides with both AH (defined as an admission glucose level ≥140 mg/dL in the absence of T2D) and HbA1c-T2D and other demographic, clinical, and inflammatory-related biomarkers in AMI. High-performance liquid chromatography–tandem mass spectrometry was used to identify nine ceramide species, and their three ratios, in 140 AMI patients (FTGM coronary unit, Massa, Italy). The ceramides did not correlate with stress hyperglycemia, but specific species were elevated in T2D-AMI. Moreover, some ceramides were associated with other cardiometabolic risk factors. Ceramides assessment may be helpful in better understanding the pathogenic molecular mechanisms underlying myocardial acute events and cardiometabolic risk, as a basis for the future evaluation of their role as prognostic predictors and therapeutic targets in T2D-AMI patients.

Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk.

Oxidative stress has a pivotal and widely described role in the onset and progression of atherosclerotic plaque and cardiovascular disease. Many oxidative stress-related biomarkers can be measured in biological samples; however, there are still many aspects that limit the adoption of oxidative stress assessment in clinical laboratory practice. Here, we report an overview of the different sources and main common oxidative stress biomarkers relevant for cardiovascular physiopathology, describing in detail a recently proposed lipidomic assay for ceramide assessment, as a promising future development in oxidative stress evaluation among the many available redox-related tests.

Abstract Background Limited number of studies examined the relationship between factors (lifestyle, social, emotional, cognitive) affecting adolescents’ health and well-being. The aims of this study were to identify the more important variables of the different components affecting adolescents’ health [lifestyle habits (LH); emotional status (ES); social context (SC); and cognitive abilities (CA)], and explore the relationship between the aforementioned components. Methods Data were collected between 2017 and 2018 from 756 eligible students, recruited from 5 Italian junior high school, by using KIDSCREEN-52 and cognitive processing using the Stroop Test. School engagement was estimated through questions concerning the scholastic achievement. Results Of 756 adolescents, 395 were boys with a mean (SD) age of 12.19 (0.81) years. Compared to International T-value of reference group for KIDSCREEN-52, autonomy, bullying, psychological well-being and mood were lower than the reference groups, while self-perception score was higher. For LH, the most important predictor was autonomy (p

BackgroundHealth and well-being promotions are key points of educational programs for adolescents within schools. There are several health education programs mainly based on lifestyle habit changes; however, social and emotional dimensions should be considered within these educational strategies. ObjectiveThis study aimed to (1) develop a new web-based school support system to assess and analyze individual, classroom, and scholastic institute data on lifestyle habits, social context, emotional status, and scholastic performance; (2) create a web tool for managing the well-being of adolescents through a dynamic and personalized interface that provides immediate feedback that allows the school to monitor progress; and (3) evaluate, in a pilot study, the feasibility of this web-based school support system in order to build health programs that are specific to the needs of the studied population. MethodsThe AVATAR (a new purpose for the promotion and evaluation of health and well-being among healthy teenagers) method consists of integrating the information coming from different questionnaires. In particular, to allow planning didactic and educational actions based on the results obtained, the AVATAR approach allows subdivision of the results of the different observed variables and the 4 components into the following 3 percentile categories: modify, improve, and maintain. The AVATAR web platform was designed to collect data on lifestyle, emotional status, and social context from junior high schools in terms of the fundamental aspects of adolescent daily life, with free use by the scholastic community (scholars, teachers, and parents). In this pilot/feasibility study, data from 331 students were acquired between 2018 and 2019 at the beginning of the scholastic year (pre) and at the end following the school-based program (post). ResultsPreliminary results showed that after school planning and specific program implementation, defined after AVATAR feedback, students reported better well-being perception characterized by higher perception in psychological well-being (P=.001), mood (P=.001), self-perception (P=.006), and autonomy (P=.001), and an increase in the perception of financial resources (P=.001), which helped in developing healthy lifestyle habits (P=.007). In the social context assessment, students reported stronger relationships with family (P=.02) and peers (P=.001), and a lower perception of bullying (P=.001). ConclusionsThe AVATAR web-based platform is a feasible and flexible tool for the health and well-being management of adolescents from epidemiological, preventive, and educational points of view. In particular, it can be used to (1) promote information campaigns aimed at modifying risk behaviors in the student population, (2) sensitize students and put them at the center of their growth path, (3) inform institutions about the health and well-being of the school population, (4) ensure health programs are acceptable and feasible to users before launching on a large scale, and (5) improve the relationship of users (school) and educational agencies with research groups.

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.

The role of lipids is essential in any phase of the atherosclerotic process, which is considered a chronic lipid-related and inflammatory condition. The traditional lipid profile (including the evaluation of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein) is a well-established tool to assess the risk of atherosclerosis and as such has been widely used as a pillar of cardiovascular disease prevention and as a target of pharmacological treatments in clinical practice over the last decades. However, other non-traditional lipids have emerged as possible alternative predictors of cardiometabolic risk in addition to traditional single or panel lipids, as they better reflect the overall interaction between lipid/lipoprotein fractions. Therefore, this review deals with the lipid involvement characterizing the pathophysiology of atherosclerosis, discussing some recently proposed non-traditional lipid indices and, in the light of available knowledge, their actual potential as new additive tools to better stratify cardiovascular risk in patients with hyperlipidemia as well as possible therapeutic targets in the clinical practice.

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.

The role of thyroid hormones (THs) in the cardiovascular (CV) system, through several direct and indirect effects is recognized. Even very small modification in TH levels (as those observed in subclinical hypothyroidism or hyperthyroidism, and low triiodothyronine syndrome) may adversely affect the CV system, whereas thyroid hormones benefit the CV system and improve the prognosis. There is also evidence of vitamin D effects on cardiometabolic disease (e.g., through modulation of endothelial and smooth muscle cell activity, renin-angiotensin-aldosterone system, nitric oxide, oxidative stress, and inflammatory response), as well as an association between vitamin D [25(OH)D] deficiency and autoimmune thyroid diseases or cancer, and a relationship between vitamin D concentration and titers of antibodies and thyroid autoimmunity replacement. Interestingly, experimental data indicate a direct effect of vitamin D on Type 2 deiodinase expression causing subsequential peripheral conversion of T4 into T3. However, the functional links among THs, vitamin D and the cardiovascular system, and clinical effects of coexisting abnormalities in this new troublesome triad, have not yet been reviewed. The main aim of this review is to discuss pathophysiology of this relationship, proposing new mechanistic insights involving vitamin D in the modulation of cardiometabolic disease and thyroid profile.

A relationship between the presence of clinical symptoms and gastrointestinal (GI) disturbances associated with nutritional deficiencies, including vitamin D (25(OH)D) deficiency, has been observed in autism spectrum disorder (ASD). The aim was to evaluate 25(OH)D levels according to the annual rhythm cycle, gender, the severity of autism, nutritional or clinical status, inflammatory and metabolic biomarkers, GI symptoms, and the clinical response to probiotic/placebo supplementation in preschooler children with ASD. Eighty-one ASD preschoolers (67 males) were assessed with standardized tools for ASD severity (ADOS score) and GI symptoms (by GI-Index at six-items and at nine-items, the latter defined as the Total GI-Index). The 25(OH)D levels were compared among different ASD subgroups according to metabolic and inflammatory biomarkers (leptin, insulin, resistin, PAI-1, MCP-1, TNF-alfa, and IL-6), gender, and the presence or absence of: (i) GI symptoms, (ii) the response to probiotic supplementation (the improvement of GI symptomatology), (iii) the response to probiotic supplementation (improvement of ASD severity). Only 25% of the ASD children presented an adequate 25(OH)D status (≥30 ng/mL according to the Endocrine Society guidelines). All the 25(OH)D levels falling in the severe deficiency range (p = 0.037). An inverse correlation was found between 25(OH)D levels and the GI Index 6-Items and Total GI-Index (R = −0.25, p = 0.026; −0.27, = 0.009) and a direct relationship with the probiotic response (R = 0.4, p = 0.05). The monitoring of 25(OH)D levels and the co-administration of 25(OH)D and probiotic supplementation could be considered in ASD from early ages.

Coronavirus disease 2019 (COVID-19) outbreak represented an experience of social isolation potentially leading to changes in the health quality of life. The aim of this study is to investigate the health-related quality of life during quarantine in early adolescents. Data were collected from 1,289 adolescents (mean age, 12.5; male, 622), at the beginning of the school year (September 2019, Standard Condition, SC) as part of the AVATAR project and during Phase 1 of the Italian lockdown (mid-late April 2020) (COVID-19 Quarantine, CQ) using an online questionnaire. In the CQ period, with respect to SC, adolescents showed lower perception in the dimensions, such as psychological (p = 0.001), physical well-being (p = 0.001), mood/emotion (p = 0.008), autonomy (p = 0.001), and financial resources (p = 0.018). Relationship with the family (p = 0.021) and peers (p = 0.001), as well as the perception of bullying (p = 0.001) were reduced. In lifestyle, adolescents developed higher adherence to the Mediterranean diet (p = 0.001). Adolescents living in the village had greater reduction in both autonomy (p = 0.002) and peer relationships (p = 0.002). Moreover, the perception of physical well-being was lower in those living in the city instead of those living in the countryside (p = 0.03), in an apartment instead of a detached house (p = 0.002), and in those who did not have green space (p = 0.001). Gender effect emerged for the psychological (p = 0.007) and physical well-being (p = 0.001), mood/emotion (p = 0.001), and self-perception (p = 0.001). The study showed that health-related quality of life during quarantine changed in its psychosocial dimensions, from mood and self-esteem to social relationships, helping to define the educational policies at multiple points in the promotion process of health.

Type 2 diabetes (T2D) is considered one of the largest global public-health concerns, affecting approximately more than 400 million individuals worldwide. The pathogenesis of T2D is very complex and, among the modifiable risk factors, selenium (Se) has recently emerged as a determinant of T2D pathogenesis and progression. Selenium is considered an essential element with antioxidant properties, and is incorporated into the selenoproteins involved in the antioxidant response. Furthermore, deiodinases, the enzymes responsible for homeostasis and for controlling the activity of thyroid hormones (THs), contain Se. Given the crucial action of oxidative stress in the onset of insulin resistance (IR) and T2D, and the close connection between THs and glucose metabolism, Se may be involved in these fundamental relationships; it may cover a dual role, both as a protective factor and as a risk factor of T2D, depending on its basal plasma concentration and the individual’s diet intake. In this review we discuss the current evidence (from experimental, observational and randomized clinical studies) on how Se is associated with the occurrence of T2D and its influence on the relationship between thyroid pathophysiology, IR and T2D.

Type 2 diabetes (T2D) is a public health burden associated with high healthcare and societal costs and elevated morbidity and mortality [...]

COVID-19 has overwhelmed healthcare systems and increased workload and distress in healthcare professionals (HCPs). The objective of this study was to evaluate baseline distress before and after the pandemic, and the effect of Mindfulness-Based Stress Reduction (MBSR) training on well-being (PGWBI), stress (PSS) and burnout (MBI) in Italian HCPs. Moreover, the “fear of COVID-19” (FCV-19S) questionnaire was administered to HCPs participating in the post-emergency MBSR program. Baseline distress results were moderate in all groups. No differences between baseline distress were observed between the groups of HCPs beginning the MBSR courses in the pre or post pandemic period. Total PGWBI lowered with aging. Additionally, FCV-19S positively correlated with age. MBSR was able to lower distress levels, except for depersonalization, which increased, while emotional exhaustion decreased in the group enrolled in the last post-pandemic MBSR course. Levels of fear of COVID-19 in HCPs significantly decreased after MBSR training. The lack of change in baseline distress over time indicates that it is more influenced by work-related distress than by the pandemic in our HCPs. In view of its beneficial effects on psycho-emotional status, MBSR training may represent an effective strategy to reduce distress in emergency periods as well as an essential part of HCPs’ general training.

Background: Ceramides, biologically active lipids correlated to oxidative stress and inflammation, have been associated with adverse outcomes in acute myocardial infarction (AMI). The purpose of this study was to assess the association between ceramides/ratios included in the CERT1 score and increased cardiovascular (CV) risk, inflammatory and left ventricular function parameters in AMI. Methods: high performance liquid chromatography-tandem mass spectrometry was used to identify Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) levels and their ratios to Cer(d18:1/24:0), in 123 AMI patients (FTGM coronary unit, Massa, Italy). Results: Cer(d18:1/16:0): higher in female patients (1.7; ≤0.05), and in those with multivessel disease (1.7, Conclusion: Distinct ceramide species are associated with CV risk, inflammation and disease severity in AMI. Thus, a detailed analysis of ceramides may help to better understand CV pathobiology and suggest these new biomarkers as possible risk predictors and pharmacological targets in AMI patients.

Ceramides, composed of a sphingosine and a fatty acid, are bioactive lipid molecules involved in many key cellular pathways (e.g., apoptosis, oxidative stress and inflammation). There is much evidence on the relationship between ceramide species and cardiometabolic disease, especially in relationship with the onset and development of diabetes and acute and chronic coronary artery disease. This review reports available evidence on ceramide structure and generation, and discusses their role in cardiometabolic disease, as well as current translational chances and difficulties for ceramide application in the cardiometabolic clinical settings.

Introduction Environmental pollution has been progressively becoming one of the main risk factors to human diseases. In particular, populations living in high-contaminated sites are particularly exposed to environmental toxicants, with consequent increased risks to human health. In Italy, there are currently ongoing three epidemiological etiological studies aimed at evaluating the association between exposure to inorganic and organic chemicals and presence of biological markers of early effects in population living in three National Priority Contaminated Sites (NPCSs). Specifically, the correlations concern preclinical indicators of liver disease in Priolo NPCS, thyroid diseases in Milazzo-Valle del Mela NPCS and cardiovascular risk and kidney damage in Crotone NPCS.Methods and analysis Overall, approximately 1300 subjects of both sexes will be enrolled in the three NPCSs according to specific inclusion criteria. For each subject, serum and urine specimens are collected, on which the determination of biological markers of exposure and early effects for the selected outcomes are performed. Individual information on environmental and occupational exposure, medical history, diet and life habits is obtained through questionnaires provided by web platform. In Milazzo-Valle del Mela and Crotone NPCSs, not invasive instrumental and imaging examinations are performed in order to evaluate further risk factors of thyroid carcinoma and cardiovascular disease, respectively.Ethics and dissemination The protocol studies have been approved by the Ethics Committees responsible for the three involved NPCSs: the Ethics Committee ‘Catania 2’ for the NPCS of Priolo (21 July 2017, n. 500/2017/CECT2), the Ethics Committee of the University Hospitals of Messina for the NPCS of Milazzo-Valle del Mela (19 February 2018, n.2/2018); the Ethics Committee of the Region of Calabria for the NPCS of Crotone (20 July 2017, n. 174). Results will be disseminated among policy-makers, citizens, stakeholders and scientific community through the organisation of conferences and events, and the publication on international peer/reviewed journals.

Adolescence is not only typically considered a time of good health but also characterized by an emergence of risk factors that may have long-term consequences for well-being that represents strong predictors of adverse health outcomes. The aim of the study is to assess adolescence well-being through the development of an integrated Well-Being Index (WBI) including variables of lifestyle habits, social context, emotional status, and mental skills. One thousand two hundred forty-eight healthy adolescents (Female 48%; Male 52%; mean age 13 years) were recruited from five Italian junior high schools, by KIDSCREEN-52 and cognitive processing using the Stroop Test. School performance was estimated by questions concerning the scholastic achievement. Social context was the most important predictor of perceived well-being (β = 0.972, SE = 0.014, p < 0.0001), with parent relation (p < 0.0001) as the most observed variable. Subsequently, WBI was strongly represented by lifestyle habits (β = 0.954, SE = 0.017, p < 0.000) with autonomy (p < 0.0001), and emotional status (β = 0.949, SE = 0.017, p < 0.000) with psychological well-being perception (p < 0.0001). Finally, mental skills (β= −0.1417, SE = 0.031, p < 0.0.00) was the least important predictor for the WBI index (p < 0.0001). Personalised (P) WBI was obtained by the sum of each centered and scaled WBI variable, weighted by the corresponding ratio between factor loading and residual variance. Social context was the more important predictor of WBI, followed by lifestyle, emotional factors, and lastly mental skills. PWBI provides an integrated and personalized perspective of adolescents' well-being, on the basis of a cooperation between school, family, and community with the common intent to promote and protect adolescent health.

Ischemic heart disease is the main cause of morbidity and mortality worldwide and is becoming more widespread with population aging. Cardioprotection is a dynamic process characterized by mechanisms related to myocardial damage and activation of protective factors. Targeting these processes could be attractive as a new therapeutic strategy in the evolution of post-ischemic heart failure (HF). In this context, the role of thyroid hormone (TH)-mediated cardioprotection is supported by a number of findings regarding the modulation of neuroendocrine systems, inflammatory and oxidative stress status, pro-survival intracellular pathways, and epigenetic factors, its effects on cardiac angiogenesis, structure, and function and on the preservation of mitochondrial function and morphology, and its beneficial effects on cell growth and redifferentiation. Moreover, the numerous effects of TH on the heart involve genomic mechanisms, which include cardiac differentiation during the perinatal period and non-genomic action, directed toward the maintenance of cardiovascular homeostasis. This evidence suggests that there is an opportunity to treat HF patients with TH. This review is mainly focused on the clinical evidence of the role of the thyroid system in the complex setting of HF.

The thyroid hormone receptors are the mediators of a multitude of actions by the thyroid hormones in cells. Most thyroid hormone activities require interaction with nuclear receptors to bind DNA and regulate the expression of target genes. In addition to genomic regulation, thyroid hormones function via activation of specific cytosolic pathways, bypassing interaction with nuclear DNA. In the present work, we reviewed the most recent literature on the characteristics and roles of different factors involved in thyroid hormone function in particular, we discuss the genomic activity of thyroid hormone receptors in the nucleus and the functions of different thyroid hormone receptor isoforms in the cytosol. Furthermore, we describe the integrin αvβ3-mediated thyroid hormone signaling pathway and its rapid nongenomic action in the cell. We furthermore reviewed the thyroid hormone transporters enabling the uptake of thyroid hormones in the cell, and we also include a paragraph on the proteins that mediate thyroid receptors’ shuttling from the nucleus to the cytosol.

Background and Aims: Vitamin D counteracts the reduction in the peripheral conversion of tiroxine (T4) into triiodothyronine (T3), which is the mechanism of low T3 syndrome (LT3) in acute myocardial infarction (AMI). The aim of this study was to assess the relationship between LT3 and hypovitaminosis D in AMI patients. Methods and Results: One hundred and twenty-four AMI patients were enrolled. Blood samples were taken at admission, and at 3, 12, 24, 48, and 72 h after admission. LT3 was defined as a value of fT3 ≤ 2.2 pg/mL, occurring within 3 days of hospital admission. Levels were defined as follows: sufficiency as a value of ±30 ng/mL, vitamin D insufficiency as 25-hydroxyvitamin D (25(OH)D) between 21 and 29 ng/mL, deficiency in 25(OH)D as below 20 ng/mL, and severe deficiency as values under 10 ng/mL. The percentage of subjects with severe 25(OH)D deficiency was significantly higher in the LT3 group (33% vs. 13%, p < 0.01). When LT3S was evaluated as a dependent variable, severe 25(OH)D deficiency (OR 2.6: 95%CI 1–6.7, p < 0.05) remained as an independent determinant after logistic multivariate adjustment together with age (>69 yrs, 50th percentile; OR 3.4, 95% CI 1.3–8.3, p < 0.01), but not female gender (OR 1.7, 95% CI 0.7–4.2, p = ns). Conclusions: This pilot study shows a relationship between hypovitaminosis D and LT3 in AMI patients. This association opens potential therapeutic challenges concerning the restoration of euthyroidism through vitamin D administration, together with the normalization of hypovitaminosis.

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).

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 endothelium controls vascular homeostasis through a delicate balance between secretion of vasodilators and vasoconstrictors. The loss of physiological homeostasis leads to endothelial dysfunction, for which inflammatory events represent critical determinants. In this context, therapeutic approaches targeting inflammation-related vascular injury may help for the treatment of cardiovascular disease and a multitude of other conditions related to endothelium dysfunction, including COVID-19. In recent years, within the complexity of the inflammatory scenario related to loss of vessel integrity, hydrogen sulfide (H2S) has aroused great interest due to its importance in different signaling pathways at the endothelial level. In this review, we discuss the effects of H2S, a molecule which has been reported to demonstrate anti-inflammatory activity, in addition to many other biological functions related to endothelium and sulfur-drugs as new possible therapeutic options in diseases involving vascular pathobiology, such as in SARS-CoV-2 infection.

The incidence and prevalence of type 2 diabetes have increased in the last decades and are expected to further grow in the coming years. Chronic hyperglycemia triggers free radical generation and causes increased oxidative stress, affecting a number of molecular mechanisms and cellular pathways, including the generation of advanced glycation end products, proinflammatory and procoagulant effects, induction of apoptosis, vascular smooth-muscle cell proliferation, endothelial and mitochondrial dysfunction, reduction of nitric oxide release, and activation of protein kinase C. Among type 2 diabetes determinants, many data have documented the adverse effects of environmental factors (e.g., air pollutants) through multiple exposure-induced mechanisms (e.g., systemic inflammation and oxidative stress, hypercoagulability, and endothelial and immune responses). Therefore, here we discuss the role of air pollution in oxidative stress-related damage to glycemic metabolism homeostasis, with a particular focus on its impact on health. In this context, the improvement of new advanced tools (e.g., omic techniques and the study of epigenetic changes) may provide a substantial contribution, helping in the evaluation of the individual in his biological totality, and offer a comprehensive assessment of the molecular, clinical, environmental, and epidemiological aspects.