Caratterizzazione clinica, metabolica e infiammatoria di una popolazione di coronaropatici senza apparenti disturbi del metabolismo glicidico: studio MIDIAB

Objective: patients with a previous Myocardial Infarction (MI) and Type 2 diabetes (DM) have the highest risk for cardiovascular mortality, but T2DM is often undiagnosed. We tried to identify which among inflammatory and metabolic markers is the best predictor of T2DM in our population. Methods and Results: glucose tolerance status in patients with a previous MI and no diagnosis of diabetes was correlated to severity of coronary artery disease and pro- and anti-inflammatory markers (high sensitivity C-Reactive Protein, TNF-alfa, Adiponectin). In non diabetic CAD patients, upon OGTT, we observed that 20% of the patients were affected by T2DM, 37% by impaired glucose tolerance (IGT), and only the 43% were really normoglycemic (NGT). The number of disease affected vessels was correlated to 2h-post load glucose value (Spearman’s ñ=0.3, p<0.01). Interestingly, we found that while at univariate analysis the 2h-post load glucose level was positively correlated with TNF-alfa (r =0.257, p<0.01) and inversely with Adiponectin (r =-203, p<0.05), the multivariate analysis showed that only Adiponectin was an independent predictor of defects in glucose tolerance in CAD patients. Treatment of CAD/IGT patients (n=13) with Pioglitazone for 12 weeks determined an increase in Adiponectin associated to an improved endothelial function and insulin sensitivity. Conclusions: Our study shows that adiponectin is decreased in CAD patients with undiagnosed impaired glucose metabolism independently from other risk factors for altered glucose tolerance, suggesting a potential role for Adiponectin/TNF-alfa axis in impairing glucose tolerance in patients with severe coronary atherosclerosi

Low molecular weight Adiponectin increases the mortality risk in very old patients

Despite its beneficial role on insulin resistance and atherosclerosis, adiponectin has been frequently reported as an independent positive predictor of cardiovascular mortality. Very few information is available regarding adiponectin isoforms and mortality, in particular in advanced aging. Baseline serum levels of Total Adiponectin and its circulating isoforms (HMW-, MMW-, LMW-Adiponectin) were measured in 97 old patients (mean age: 79 years). Patients were followed up for all-cause mortality (study end-point) for an average of 76.4 ±37.3 months. A positive association was observed for LMW-Ad and all-cause mortality (HR: 1.13, 95% CI: 1.05-1,22, p: 0.002). After multivariate adjustment for age, sex and a previous history of myocardial infarction, higher levels of LMW-Ad were significantly associated with all-cause mortality (HR: 1.11, 95% CI: 1.02-1.21; p: 0.017). Interestingly neither total adiponectin neither the other two circulating isoforms (MMW- and HMW-Ad) showed any significant association with the study end-point. Our data suggest that the association between high serum adiponectin levels and increased mortality rate in elderly is contingent to an unbalanced circulating levels of adiponectin isoforms. The present results support the hypothesis that high levels of Low Molecular Weight adiponectin are a biomarker for mortality risk in very old patients

C-peptide: a predictor of cardiovascular mortality in subjects with established atherosclerotic disease

Aim: Insulin resistance and type 2 diabetes are independent risk factors for cardiovascular diseases. Levels of C-peptide are increased in these patients and its role in the atherosclerosis progression was studied in vitro and in vivo over the past years. To evaluate the possible use of C-peptide as cardiovascular biomarkers, we designed an observational study in which we enrolled patients with mono- or poly-vascular atherosclerotic disease. Methods: We recruited 431 patients with stable atherosclerosis and performed a yearly follow-up to estimate the cardiovascular and total mortality and cardiovascular events. Results: We performed a mean follow-up of 56months on 268 patients. A multivariate Cox analysis showed that C-peptide significantly increased the risk of cardiovascular mortality [Hazard Ratio: 1.29 (95% confidence interval: 1.02-1.65, p<0.03513)] after adjustment for age, sex, diabetes treatment, estimated glomerular filtration rate and known diabetes status. Furthermore, levels of C-peptide were significantly correlated with metabolic parameters and atherogenic factors. Conclusion: C-peptide was associated with cardiovascular mortality independently of known diabetes status in a cohort of patients with chronic atherosclerotic disease. Future studies using C-peptide into a reclassification approach might be undertaken to consider its potential as a cardiovascular disease biomarker

Relationship between the night shift work and thyroid disorders: A systematic review and meta-analysis

AbstractObjectives. The night shift workers were reported to have health consequences, ranging from mild, as cluster headache, to severe, as heart attacks and hormonal irregularities. This study is aimed to perform a systematic review and meta-analyze of the association between the night shift work and the thyroid disorders.Methods. We comprehensively searched eight databases, including PubMed and Google Scholar for the relevant articles. This systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement.Results. We finally included six papers involving 4074 participants. Four papers were eligible for meta-analysis involving 1864 night shift workers and 2017 day shift workers. We against found that thyroid stimulating hormone (TSH) is significantly higher in the night shift group compared to the day shift group.Conclusions. The higher TSH among the night shift workers is attributed to disruption of the circadian rhythm and sleep/wake cycle, with subsequent eating disorders. We proposed that more attention should be paid to the working pattern and the related health consequences

Modeling the Cerebellar Microcircuit: New Strategies for a Long-Standing Issue

The cerebellar microcircuit has been the work bench for theoretical and computational modeling since the beginning of neuroscientific research. The regular neural architecture of the cerebellum inspired different solutions to the long-standing issue of how its circuitry could control motor learning and coordination. Originally, the cerebellar network was modeled using a statistical-topological approach that was later extended by considering the geometrical organization of local microcircuits. However, with the advancement in anatomical and physiological investigations, new discoveries have revealed an unexpected richness of connections, neuronal dynamics and plasticity, calling for a change in modeling strategies, so as to include the multitude of elementary aspects of the network into an integrated and easily updatable computational framework. Recently, biophysically accurate realistic models using a bottom-up strategy accounted for both detailed connectivity and neuronal non-linear membrane dynamics. In this perspective review, we will consider the state of the art and discuss how these initial efforts could be further improved. Moreover, we will consider how embodied neurorobotic models including spiking cerebellar networks could help explaining the role and interplay of distributed forms of plasticity. We envisage that realistic modeling, combined with closed-loop simulations, will help to capture the essence of cerebellar computations and could eventually be applied to neurological diseases and neurorobotic control systems

Influence of involvement of anterior leaflet versus posterior leaflet on residual regurgitation as assessed by transesophageal echocardiography in patients undergoing valve repair for mitral regurgitation due to mitral valve prolapse

<p>Abstract</p> <p>Background</p> <p>Repair of anterior leaflet prolapse is technically more challenging and this might influence outcomes as compared to the repair of posterior leaflet prolapse in patients undergoing surgical correction of mitral regurgitation. We investigated the association of anterior leaflet prolapse with minor residual mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) who underwent valve repair.</p> <p>Methods</p> <p>Eligible for this study were consecutive patients with severe MR due to MVP, who underwent mitral valve repair with residual MR by postpump transesophageal echocardiography ≤2+ during a 20-month period at Pasquinucci Hospital, Massa. Patients undergoing other cardiovascular surgical interventions were excluded. Two groups were defined according to the involvement of mitral valve leaflets: group 1, consisting of patients with anterior leaflet prolapse (isolated or not); and group 2, consisting of patients with isolated posterior leaflet prolapse.</p> <p>Results</p> <p>A total of 70 patients (18 in group 1 and 52 in group 2) were analyzed. Patients in group 2 were younger than those in group 1, but the difference was not significant (P = 0.052). There were no significant differences between the 2 study groups with respect to other variables. The proportion of patients with residual MR 1+/2+ was higher in group 1 than in group 2 (61.1% vs. 32.7%, respectively; P = 0.034). In a logistic regression model, anterior leaflet prolapse was an independent predictor of residual MR 1+/2+ (odds ratio, 4.0; 95% confidence interval, 1.14 to 14.04; P = 0.03).</p> <p>Conclusion</p> <p>In our study population, patients with anterior leaflet prolapse had a higher proportion of residual MR 1+/2+ as compared to those with posterior leaflet prolapse after repair of mitral valve.</p