Systems Biology and Biomechanical Model of Heart Failure

Heart failure is seen as a complex disease caused by a combination of a mechanical disorder, cardiac remodeling and neurohormonal activation. To define heart failure the systems biology approach integrates genes and molecules, interprets the relationship of the molecular networks with modular functional units, and explains the interaction between mechanical dysfunction and cardiac remodeling. The biomechanical model of heart failure explains satisfactorily the progression of myocardial dysfunction and the development of clinical phenotypes. The earliest mechanical changes and stresses applied in myocardial cells and/or myocardial loss or dysfunction activate left ventricular cavity remodeling and other neurohormonal regulatory mechanisms such as early release of natriuretic peptides followed by SAS and RAAS mobilization. Eventually the neurohormonal activation and the left ventricular remodeling process are leading to clinical deterioration of heart failure towards a multi-organic damage. It is hypothesized that approaching heart failure with the methodology of systems biology we promote the elucidation of its complex pathophysiology and most probably we can invent new therapeutic strategies.     

Home blood pressure monitoring in children: how many measurements are needed?

OBJECTIVE: To investigate the minimum schedule of blood pressure (BP) measurements necessary to provide a reliable assessment of home BP (HBP) in children and adolescents. METHODS: Subjects aged 6-18 years referred for elevated BP were assessed with HBP monitoring (6 workdays, duplicate morning and evening measurements) and 24-h ambulatory BP monitoring (ABP). Criteria for HBP reliability were its reproducibility (test-retest correlations and SD of differences (SDDs) between repeated measurements), its stability (average home BP of an increasing number of readings and its SD), and its relationship with ABP. RESULTS: Data from 100 subjects were analyzed (mean age 13 +/- 2.8 (SD) years, 61 boys). The reproducibility of 3-day HBP (r 0.88/0.79, SDDs 5.1/4.9, systolic/diastolic) was superior to that of a single (r 0.79/0.65, SDDs 7.6/7.1) or 2-day HBP (r 0.85/0.72, SDDs 6.1/5.4). By averaging up to 12 readings (3 days), there was a progressive decline in average HBP, with no further decline thereafter. The SD of average HBP was also progressively reduced, with little change after day 3. The association of HBP with ABP was improved by averaging more readings up to 12, with no further improvement when more readings were averaged. The exclusion of first-day measurements slightly increased the SD of average HBP and weakened the correlation with ABP, probably due to reduced number of readings. CONCLUSIONS: In children and adolescents, 3-day monitoring with duplicate morning and evening measurements appears to be the minimum schedule for the reliable assessment of HBP.     

Attitudes regarding occupational vaccines and vaccination coverage against vaccine-preventable diseases among healthcare workers working in pediatric departments in Greece

We studied the attitudes with regard to occupational vaccines and vaccination coverage among healthcare workers in pediatric departments. Completed vaccination rates were 33%, 33%, 41.7%, 3%, 5.8%, 69.2% and 36.3% against measles, mumps, rubella, varicella, hepatitis A, hepatitis B and tetanus-diphtheria, respectively. Susceptibility rates were 14.2%, 15.7%, 14.6%, 7.6%, 87.4%, 22.6% and 61.8% for measles, mumps, rubella, varicella, hepatitis A, hepatitis B and tetanus-diphtheria, respectively. Mandatory vaccinations were supported by 70.6% of healthcare workers, with considerable differences by target disease.     

Association of Daily Physical Activity and Sedentary Behaviour with Protein Intake Patterns in Older Adults: A Multi-Study Analysis across Five Countries

Physical activity and protein intake are associated with ageing-related outcomes, including loss of muscle strength and functional decline, so may contribute to strategies to improve healthy ageing. We investigated the cross-sectional associations between physical activity or sedentary behaviour and protein intake patterns in community-dwelling older adults across five countries. Self-reported physical activity and dietary intake data were obtained from two cohort studies (Newcastle 85+ Study, UK; LiLACS, New Zealand Māori and Non-Māori) and three national food consumption surveys (DNFCS, The Netherlands; FINDIET, Finland; INRAN-SCAI, Italy). Associations between physical activity and total protein intake, number of eating occasions providing protein, number of meals with specified protein thresholds, and protein intake distribution over the day (calculated as a coefficient of variance) were assessed by regression and repeated measures ANOVA models adjusting for covariates. Greater physical activity was associated with higher total protein intake and more eating occasions containing protein, although associations were mostly explained by higher energy intake. Comparable associations were observed for sedentary behaviour in older adults in Italy. Evidence for older people with higher physical activity or less sedentary behaviour achieving more meals with specified protein levels was mixed across the five countries. A skewed protein distribution was observed, with most protein consumed at midday and evening meals without significant differences between physical activity or sedentary behaviour levels. Findings from this multi-study analysis indicate there is little evidence that total protein and protein intake patterns, irrespective of energy intake, differ by physical activity or sedentary behaviour levels in older adults.     

Lack of association between carotid intima-media thickness and PAF-acetylhydrolase mass and activity in patients with primary hyperlipidemia

Carotid intima media thickness (IMT), represents an important clinical indicator of early atherosclerosis. Human plasma platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme primarily associated with low-density lipoprotein (LDL) while a small proportion of enzymatic activity is also associated with high-density lipoprotein (HDL). Plasma paraoxonase 1 (PON1) is an esterase exclusively associated with HDL. The authors investigated the possible relationship between carotid IMT and the plasma levels of PAF-AH mass and activity as well as the PON1 activity in hyperlipidemic patients. One hundred unrelated patients with primary hyperlipidemia and 67 age-and sex-matched normolipidemic apparently healthy volunteers participated in the study. The PAF-AH activity in total plasma and in HDL-rich plasma (HDL-PAF-AH activity), the plasma PAF-AH mass, and the serum PON1 activities toward paraoxon and phenyl acetate were determined. The plasma PAF-AH mass and activity were higher in hyperlipidemic patients compared to controls, whereas the HDL-PAF-AH activity, as well as the serum PON1 activities were not significantly different between the studied groups. When hyperlipidemic patients were divided into 2 subgroups according to their IMT values (IMT <0.7 mm and IMT > or =0.7 mm) patients with IMT > or =0.7 mm had significantly higher age, and serum triglyceride concentrations, whereas no difference was found in the plasma PAF-AH mass and activity as well as in the HDL-PAF-AH activity between the 2 studied subgroups. The same phenomenon was observed for serum PON1 activities. In a multivariate analysis, only the age was significantly correlated with IMT values (p<0.05). Neither the total plasma PAF-AH mass and activity nor the HDL-PAF-AH activity are associated with early carotid atherosclerosis.     

Acute nateglinide administration in subjects with type 2 diabetes: effects on postprandial metabolism, coagulation, and fibrinolysis

BACKGROUND AND AIM: Postprandial glycaemia and lipaemia are known risk factors for atherosclerosis in type 2 diabetes. Coagulation activation in the postprandial state also contributes to acceleration of atherosclerosis. Nateglinide is effective in reducing postprandial glycaemia. Its effect on glycaemia may also be beneficial in postprandial lipaemia and coagulation. The aim of this study was to examine the potential effect of a single dose of nateglinide on postprandial triglyceridaemia, coagulation, and fibrinolysis in patients with type 2 diabetes. METHODS AND RESULTS: Ten subjects with type 2 diabetes, treated with diet alone were recruited in a crossover randomized study. In the morning, after a 12- to 14-h fast, each subject received a standard mixed meal (total energy 783 kcal), preceded by one tablet of 120 mg nateglinide or placebo. Venous blood samples were drawn prior to meal consumption and 6h afterwards for the measurement of plasma glucose, insulin, and C-peptide, lipids, coagulation, and fibrinolysis factors. As expected, there was a significant reduction in postprandial glycaemia after nateglinide administration compared to placebo (P<0.001). Plasma insulin levels were significantly higher after nateglinide than after placebo (P=0.002). Nateglinide administration resulted in a lower overall postprandial reduction of tissue-plasminogen activator than placebo (-2.9+/-1.3 vs. -8.3+/-3.7 ng/ml h, P=0.003). In addition, a significant reduction of postprandial plasminogen activator inhibitor-1 was observed in comparison with the baseline values after nateglinide (P=0.001), although the overall response was not significantly different after nateglinide and placebo (P=0.31). Plasma concentrations of C-peptide, lipids and the remaining coagulation parameters studied were not different between nateglinide and placebo. CONCLUSIONS: Acute nateglinide administration improves postprandial glycaemia and fibrinolytic activity in patients with type 2 diabetes. This combined effect, if confirmed by a long-treatment study, might reduce cardiovascular risk in type 2 diabetes.