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Stopping smoking is crucial for public health and especially for individuals with diabetes. Combustion-free nicotine alternatives like e-cigarettes and heated tobacco products are increasingly being used as substitutes for conventional cigarettes, contributing to the decline in smoking prevalence. However, there is limited information about the long-term health impact of those products in patients with diabetes. This randomized controlled trial aims to investigate whether switching from conventional cigarettes to combustion-free nicotine alternatives will lead to a measurable improvement in cardiovascular risk factors and metabolic parameters over a period of 2 years in smokers with type 2 diabetes. The multicenter study will be conducted in seven sites across four countries. A total of 576 smokers with type 2 diabetes will be randomly assigned (1:2 ratio) to either standard of care with brief cessation advice (Control Arm) or combustion-free nicotine alternatives use (Intervention Arm). The primary end point is the change in the proportion of patients with metabolic syndrome between baseline and the 2-year follow-up. Additionally, the study will analyze the absolute change in the sum of the individual factors of metabolic syndrome at each study time point. Patient recruitment has started in September 2021 and enrollment is expected to be completed by December 2023. Results will be reported in 2026. This study may provide valuable insights into cardiovascular and metabolic health benefits or risks associated with using combustion-free nicotine alternatives for individuals with type 2 diabetes who are seeking alternatives to tobacco cigarette smoking. The study protocol, informed consent forms, and relevant documents were approved by seven ethical review boards. Study results will be disseminated through articles published in high-quality, peer-reviewed journals and presentations at conferences. [ABSTRACT FROM AUTHOR]

Background: Sudden cardiac death (SCD) may rarely occur among asymptomatic patients with Wolff-Parkinson-White (WPW) pattern. Risk stratification is based on electrophysiological study (EPS). We aimed to evaluate long-term efficacy of such a strategy in preventing SCD.Methods: Retrospective analysis of asymptomatic children with WPW who underwent EPS using isoproterenol. Patients considered at risk had inducible sustained atrial fibrillation or atrioventricular reentry tachycardia (AVRT) associated with the following: (1) accessory pathway (AP) effective refractory period or (2) 1:1 shortest cycle length along the AP or (3) shortest pre-excited R-R interval during AF ≤ 250 ms.Results: Fifty-one consecutive cases (7-18 years, 12 ± 3) were identified, 40 (78%) with right and 11 (22%) with left AP. Twenty-eight (55%) were classified as high risk (HI) and 23 (45%) as low risk (LO), with no significant differences in demographic characteristics and AP locations. Ablation was performed in 20/28 HI and 11/23 LO patients (p 0.08), with no significant differences in acute success (20/20 versus 10/11, p 0.17) or recurrence (1/20 versus 2/10, p 0.15). Follow-up (46 ± 27 months): ablated patients remained asymptomatic; among the 23 non-ablated, 18 (78%) remained asymptomatic, 5 (22%) were successfully ablated, and 5 (22%) presented events (4 AVRT, 1 SCD). Arrhythmic events did not differ significantly between non-ablated HR and LR (2/8 versus 3/15, p 0.29) and the SCD was in the LO group.Conclusions: More than 50% asymptomatic WPW children present high-risk AP properties. EPS-based risk stratification using isoproterenol was not able to identify increased risk of future events or SCD. [ABSTRACT FROM AUTHOR]

Using Italian data from the Time Use Survey (Istat) on the time devoted by Italian women to housework tasks, in this study we analyze how much individual ability of a woman employed in the market influences her housework time. To this aim we estimate a two-regime Endogenous-Switching model for both employed and not employed women. As a novelty, a ML estimation of this model provides also the point-estimation of the across-regime correlation parameter, that allows us to evaluate the individual skill effect on the time devoted to housework tasks by a woman and to calculate the probability of choosing one of the two regimes, corrected for the endogeneity of the choice. The estimation framework allows us to identify the role of individual skills of the Italian women in household decision-making. [ABSTRACT FROM AUTHOR]

Aims: Subjects with familial hypercholesterolemia (FH) are characterized by an increased amount of low-density lipoprotein cholesterol (LDL-C) that promotes a continuous inflammatory stimulus. Our aim was to evaluate the effect of PCSK9-i on inflammatory biomarkers, neutrophil-to-lymphocyte ratio, monocyte-to-high-density lipoprotein ratio (MHR), and on early atherosclerosis damage analyzed by pulse wave velocity (PWV) in a cohort of FH subjects. Methods: In this prospective observational study, we evaluated 56 FH subjects on high-intensity statins plus ezetimibe and with an off-target LDL-C. All subjects were placed on PCSK9-i therapy and obtained biochemical analysis as well as PWV evaluation at baseline and after six months of PCSK9-i therapy. Results: After six months of add-on PCSK9-i therapy, only 42.9% of FH subjects attained LDL-C targets. As expected, a significant reduction of LDL-C (− 49.61%, p < 0.001) was observed after PCSK9-i therapy. Neutrophil count (NC) and MHR were reduced by PCSK9-i (-13.82% and -10.47%, respectively, p value for both < 0.05) and PWV significantly decreased after PCSK9-i therapy (− 20.4%, p < 0.05). Finally, simple regression analyses showed that ∆ PWV was significantly associated with ∆ LDL-C (p < 0.01), ∆ NC and ∆ MHR (p value for both < 0.05). Conclusions: In conclusion, PCSK9-i therapy significantly improved lipid and inflammatory profiles and PWV values in FH subjects; our results support the positive effect of PCSK9-i in clinical practice. [ABSTRACT FROM AUTHOR]

Using Italian data on the Use of Time, in this study we analysed the influence of the bargaining process between partners on the allocation of intra-household labour after the retirement of the male partner. Adopting an appropriate procedure to identify the effect of women's bargaining power, we found that men's propensity to retire increased if women had strong bargaining power in labour division. This implies an overstatement of the effect of a man's retirement on the housework of a woman with higher bargaining power and, conversely, an understatement of the effect of the man's retirement on the housework time of a woman with lower bargaining power. To correct this selectivity effect, we estimated the effect of a man's retirement on the paid and domestic work of both partners by comparing couples in which the woman had high bargaining power and couples in which the woman had low bargaining power. [ABSTRACT FROM AUTHOR]

The results of previous studies on the effect of childbearing on both parents' paid and unpaid work suffer from the difficulty related to the specification of latent variables that influence the relationship between reproductive behaviour of the couple and working activity. The aim of this study is to estimate the effect of transition to parenthood on the partners' division of labour by accounting for latent variables, such as the bargaining process between partners and endogenous fertility decisions. In particular, this is the first time that our specific estimation strategy has been applied to determine the impact of childbearing on the division of household labour between partners taking into account the reverse causality effect between labour and fertility decisions. We use longitudinal data on married or cohabiting Italian couples provided by the Italian panel survey of the Generation and Gender Program. Our results are consistent with previous studies, and show that the birth of a child affects a woman's unpaid labour strongly and positively and her paid labour negatively, while men's work is mostly unaffected. Moreover, when partners hold traditional attitudes regarding gender roles and the family, the female partner is even more strongly affected by childbearing in terms of total amount of labour (paid plus unpaid). However, our sensitivity analysis shows that these results appear only when our correction strategy for the misspecification of latent variables is applied. [ABSTRACT FROM AUTHOR]

Aims: Inflammation is a key regulatory process that links hypercholesterolemia and immune mechanisms promoting atherosclerosis. Inflammatory biomarkers may be helpful to better define the atherosclerotic burden in patients with high cholesterol levels such as familial hypercholesterolemia (FH). Our aim was to evaluate the concentration of S100A12 protein in FH patients and its association with pulse wave velocity (PWV). Methods: We measured glucose and lipid profile, S100A12, sRAGE, esRAGE and PWV in 39 patients with a genetically confirmed diagnosis of FH and 39 hypercholesterolemic subjects without a clinical diagnosis of FH (Dutch score ≤ 3). All subjects were on statin treatment at the time of the enrollment. Results: No difference of glucose and lipid profile was found in the two groups. FH patients had higher S100A12 plasma levels than non-FH subjects (12.87 ± 4.82 vs. 8.57 ± 4.87 ng/mL, p < 0.01). No difference of hs-CRP, sRAGE and esRAGE was found between the two groups. Also, PWV was higher in FH patients than non-FH subjects (8.63 ± 0.92 vs. 6.68 ± 0.73 m/s, p < 0.05). Finally, S100A12 was independently correlated with age (p < 0.01), genetic mutation (p < 0.01) and PWV (p < 0.001). Conclusions: FH patients exhibited higher S100A12 levels than non-FH subjects. A novel vascular inflammation pathway, other than hs-CRP, might be useful to better characterize cardiovascular risk profile. [ABSTRACT FROM AUTHOR]

Objective: The presence of periodontal disease (PD) in subjects affected by the metabolic syndrome (MetS) may affect their risk of developing cardiovascular disease. The aim of this cross-sectional study was to investigate the systemic impact of PD in MetS, by assessing measures of sub-clinical atherosclerosis and left ventricular mass and geometry. Materials and methods: A total of 103 patients undergoing treatment for MetS were examined for confirmation of diagnosis, blood sampling, and measures of pulse wave velocity (PWV), carotid intima-media thickness (c-IMT), left ventricular mass index (LVM), and relative wall thickness (RWT). All subjects underwent a detailed dental assessment, including measurements of DMFT (decayed-missing-filled teeth) and periodontal parameters. Results: Ten patients (10%) were diagnosed with healthy-mild periodontitis, 38 patients (37%) were diagnosed in the moderate periodontitis group, and 55 (53%) had severe periodontitis. A total of 37% of subjects were affected by dental caries. Linear regression analysis revealed that patients with severe PD had increased average ventricular RWT (adjusted p = 0.032). Average full mouth probing pocket depth (PPD) was also associated with RWT (adjusted p = 0.006). No associations between PD and c-IMT, PWV, and LVM were detected after adjusted analyses. Conclusion: This study suggests that periodontitis may be associated with concentric left ventricular remodeling, a predictive index of cardiovascular events. Clinical relevance: The presence of periodontitis in patients with MetS might have an effect on left ventricular geometry. These findings stress the importance of prevention, diagnosis, and management of periodontitis in patients with MetS. Trail registration: NCT03297749 [ABSTRACT FROM AUTHOR]

Several studies indicate that the manner in which children spend their time affects their cognitive and social development. But, the time that a child dedicates to compulsory and extra-curricular activities depends on a set of key factors such as family demographic and economic characteristics, social and behavioral norms, and how parents allocate their time. Although these studies focus on the impact of parental investments (time and resources) on child cognitive development, minimal information regarding children's use of time is available. Our empirical approach is based on the assumption that attitudes and behavioral norms may be considered as latent factors related to how both mothers and children allocate their time. Therefore, focusing on the strict connection between time, parental and child resources and attitudes, we estimated in a Seemingly Unrelated Regression Estimation model how children and mothers spend their time. Data come from the National Time Use Survey 2008–2009 carried out by the Italian National Statistics Office. The use of a simultaneous-equation model to estimate all activities, taking into account the unobservable components included in the error terms, provides an innovative method for analyzing children's time allocation, by identifying the influence of latent variables common to mother and child's use of time. In particular, the estimated correlations between the error terms confirm that parental activities affect the children's allocation of time even through unobservable factors, such as subjective attitudes. The main results support the thesis that the mother's level of education plays an important role in the positive child outcomes. In addition, we found that the same trend that exists between Italian men and women also exists between boys and girls; and that girls spend more time in domestic activities and reading for pleasure and less time in leisure activities. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

Aims: The association of overweight status and cardiovascular disease is not clear. In this study we aimed to investigate coronary atherosclerotic disease, evaluated as coronary artery calcium score (CACs), in overweight patients with or without abdominal obesity as defined by waist-to-hip ratio (WHR).Methods: We enrolled 276 patients aged between 40 and 70 years, with a body mass index of 25-29.9 kg/m2 and at least one cardiovascular risk factor. Exclusion criteria were history of diabetes, cardiovascular or renal disease. Patients were stratified in high WHR (H-WHR) or low WHR (L-WHR) group according to WHR (≥ 0.85 for women and ≥ 0.90 for men) and underwent multi-detector computed tomography for CACs. Mean carotid intima-media thickness (IMT) and plaque presence were equally assessed.Results: CACs was higher in the H-WHR group compared to L-WHR (9.05 [0.0-83.48] vs 0.0 [0.0-64.7] AU, p < 0.01); the prevalence of CACs > 0 in the H-WHR group was significantly higher than subjects with L-WHR (59.6% vs 38.5%, p < 0.001). Moreover, H-WHR group had higher mean IMT (0.64 [0.56-0.72] vs 0.59 [0.55-0.67] mm, p < 0.05) and higher carotid plaque prevalence (63.7% vs 50.8%, p < 0.05) compared to subjects with L-WHR. Logistic regression showed that H-WHR was associated with presence of CACs and carotid plaque (p < 0.01). In a multiple linear regression, WHR was positively associated with CACs and IMT (p < 0.01).Conclusions: H-WHR is a marker of coronary and peripheral atherosclerotic burden in overweight patients. [ABSTRACT FROM AUTHOR]

Statins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study demonstrates, for the first time, that atorvastatin (lipophilic) but not pravastatin (hydrophilic) affected insulin release and mitochondrial metabolism due to the suppression of antioxidant defense system and induction of ROS production in pancreatic β-cell models. Mevalonate addition and treatment with a specific antioxidant (N-AcetylCysteine) effectively reversed the observed defects. These data demonstrate that mitochondrial oxidative stress is a key element in the pathogenesis of statin-related diabetes and may have clinical relevance to design strategies for prevention or reduction of statin induced β-cell dysfunction and diabetes in patients treated with lipophilic statins. [ABSTRACT FROM AUTHOR]

New recommendations for the use of glycated haemoglobin A1c (HbA1c) to diagnose prediabetes and type 2 diabetes have changed the constitution of the two populations. We aimed to investigate the pathophysiological characteristics of individuals with HbA1c-defined prediabetes and type 2 diabetes, respectively. Ten subjects with HbA1c-defined prediabetes, i.e. HbA1c from 5.7 to 6.4 % (39-46 mmol/mol), eight newly diagnosed patients with HbA1c-defined type 2 diabetes [HbA1c ≥6.5 % (≥48 mmol/mol)], and ten controls with HbA1c lower than 5.7 % (<39 mmol/mol), were studied. Blood was sampled over 4 h on two separate days after a 75 g-oral glucose tolerance test and an isoglycaemic intravenous glucose infusion, respectively. Blood was analysed for glucose, insulin, C-peptide, glucagon, and incretin hormones. Insulinogenic index, disposition index, glucagon suppression, and incretin effect were evaluated. Subjects with HbA1c-defined prediabetes showed significantly lower insulinogenic index ( P = 0.02), disposition index ( P = 0.001), and glucagon suppression compared with controls; and similar ( P = NS) insulinogenic index and glucagon suppression and higher disposition index ( P = 0.02) compared to HbA1c-diagnosed type 2 diabetic patients. The patients with type 2 diabetes showed lower insulinogenic index ( P = 0.0003), disposition index ( P < 0.0001), and glucagon suppression compared with the controls. The incretin effect was significantly ( P < 0.05) reduced in patients with HbA1c-defined type 2 diabetes compared to subjects with HbA1c-defined prediabetes and controls. Plasma levels of incretin hormones were similar across the three groups. HbA1c associated negatively with insulinogenic index, disposition index, and incretin effect. Our findings show clear alpha- and beta-cell dysfunction in HbA1c-defined type 2 diabetes compatible with the previously described pathophysiology of plasma glucose-defined type 2 diabetes. Furthermore, in HbA1c-defined prediabetes, we show defective insulin response in combination with inappropriate suppression of glucagon, which may constitute new targets for pharmacological interventions. [ABSTRACT FROM AUTHOR]

Dyslipidemias represent a variety of quantitative and/or qualitative lipoprotein abnormalities. According to etiology, we distinguish primary dyslipidemias with strictly genetic background and secondary ones with their origin in other disease or pathological states. Diabetic dyslipidemia is a type of secondary dyslipidemia and plays an important role in determining the cardiovascular risk of subjects with type 2 diabetes. In these patients, insulin resistance is responsible for overproduction and secretion of atherogenic very low density lipoprotein. In addition, insulin resistance promotes the production of small dense low-density lipoprotein (LDL) and reduces high-density lipoprotein (HDL) production. Cardiovascular disease remains a leading cause of morbidity and mortality in diabetic patients. Previous results support the role for small, dense LDL particles in the etiology of atherosclerosis and their association with coronary artery disease. Moreover, lowering LDL cholesterol reduces the risk of cardiovascular death. Therefore, the European guidelines for the management of dyslipidemias recommend an LDL cholesterol goal < 100 mg/dL in diabetic subjects without cardiovascular events. Moreover, if triglycerides (TG) are elevated (> 400 mg/dL), they recommend a non-HDL cholesterol goal < 130 mg/dL in diabetic individuals without cardiovascular events. Statins are the first line of LDL-lowering therapy in diabetic patients and combined therapy with ezetimibe and statins could be useful in very high cardiovascular risk diabetic subjects. Furthermore, the effect of a fibrate as an add-on treatment to a statin could improve the lipid profile in diabetic individuals with high TG and low HDL cholesterol. Regarding new therapies, recent data from phase III trials show that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors considerably decrease LDL cholesterol. Thus, they may be useful in diabetic patients with concomitant diseases such as familial dyslipidemia, recurrent cardiovascular events, and elevated LDL cholesterol after second drug administration in addition to maximal statin dose or statin intolerance. [ABSTRACT FROM AUTHOR]