Association between noninvasive fibrosis markers and cardio-vascular organ damage among adults with hepatic steatosis

Evidence suggests that advanced fibrosis, as determined by the noninvasive NAFLD fibrosis score (NFS), is a predictor of cardiovascular mortality in individuals with ultrasonography-diagnosed NAFLD. Whether the severity of histology (i.e., fibrosis stage) is associated with more pronounced cardiovascular organ damage is unsettled. In this study, we analyzed the clinical utility of NFS in assessing increased carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI). In this cross-sectional study NFS, cIMT and LVMI were assessed in 400 individuals with ultrasonography-diagnosed steatosis. As compared with individuals at low probability of liver fibrosis, individuals both at high and at intermediate probability of fibrosis showed an unfavorable cardio-metabolic risk profile having significantly higher values of waist circumference, insulin resistance, high sensitivity C-reactive protein (hsCRP), fibrinogen, cIMT, and LVMI, and lower insulin-like growth factor-1 (IGF-1) levels. The differences in cIMT and LVMI remained significant after adjustment for smoking and metabolic syndrome. In a logistic regression model adjusted for age, gender, smoking, and diagnosis of metabolic syndrome, individuals at high probability of fibrosis had a 3.9-fold increased risk of vascular atherosclerosis, defined as cIMT.0.9 mm, (OR 3.95, 95% CI 1.12–13.87) as compared with individuals at low probability of fibrosis. Individuals at high probability of fibrosis had a 3.5-fold increased risk of left ventricular hypertrophy (LVH) (OR 3.55, 95% CI 1.22–10.34) as compared with individuals at low probability of fibrosis. In conclusion, advanced fibrosis, determined by noninvasive fibrosis markers, is associated with cardiovascular organ damage independent of other known factors

Additive effect of non-alcoholic fatty liver disease on metabolic syndrome-related endothelial dysfunction in hypertensive patients

Metabolic syndrome (MS) is characterized by an increased risk of incident diabetes and cardiovascular (CV) events, identifying insulin resistance (IR) and endothelial dysfunction as key elements. Moreover, non-alcoholic fatty liver disease (NAFLD) is bidirectionally linked with MS as a consequence of metabolic and inflammatory abnormalities. We addressed the question if the evolution in NAFLD might worsen endothelium-dependent vasodilating response in MS hypertensives. We recruited 272 Caucasian newly-diagnosed never-treated hypertensive outpatients divided into three groups according to the presence/absence of MS alone or in combination with NAFLD. MS and NAFLD were defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and non-invasive fatty liver index, respectively. We determined IR by using the homeostasis model assessment (HOMA) index. Vascular function, as forearm blood flow (FBF), was determined through strain-gauge plethysmography after intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside. MS+NAFLD+ group showed worse metabolic, inflammatory and vascular profiles compared with MS-NAFLD- and MS+NAFLD-. HOMA resulted in being the strongest predictor of FBF both in the MS+NAFLD- and in the MS+NAFLD+ groups, accounting for 20.5% and 33.2% of its variation, respectively. In conclusion, we demonstrated that MS+NAFLD+ hypertensives show a worse endothelium-dependent vasodilation compared with MS+NAFLD-, allowing for consideration of NAFLD as an early marker of endothelial dysfunction in hypertensives

Immunity, Inflammation and Heart Failure: Their Role on Cardiac Function and Iron Status

Aims: Heart failure is a clinical syndrome characterized by subclinical systemic inflammation and immune system activation associated with iron deficiency. No data exist on the various activations of immune-mediated mechanisms of inflammation in heart failure patients with reduced/preserved ejection fraction. We aimed to (1) investigate possible differences in inflammatory parameters and oxidative stress, and (2) detect a different iron status between groups. Materials and Methods: We enrolled 50 consecutive Caucasian outpatients with heart failure. All patients underwent echocardiographic measurements, laboratory determinations, evaluation of iron status and Toll-like receptors, and NF-κB expression in peripheral blood mononuclear cells, as well as pro-inflammatory cytokines. All statistical calculations were made using SPSS for Mac version 21.0. Results: Patients with reduced ejection fraction showed significantly lower hemoglobin levels (12.3 ± 1.4 vs. 13.6 ± 1.4 g/dl), serum iron (61.4 ± 18.3 vs. 93.7 ± 33.7 mcg/dl), transferrin iron binding capacity (20.7 ± 8.4 vs. 31.1 ± 15.6 %), and e-GFR values (78.1 ± 36.1 vs. 118.1 ± 33.9 ml/min/1.73 m2) in comparison to patients with preserved ejection fraction, while unsaturated iron binding capacity (272.6 ± 74.9 vs. 221.7 ± 61.4 mcg/dl), hepcidin (4.61 ± 0.89 vs. 3.28 ± 0.69 ng/ml), and creatinine (1.34 ± 0.55 vs. 1.03 ± 0.25 mg/dl) were significantly higher in the same group. When considering inflammatory parameters, patients with reduced ejection fraction showed significantly higher expression of both Toll-like receptors-2 (1.90 ± 0.97 vs. 1.25 ± 0.76 MFI) and Toll-like receptors-4 (4.54 ± 1.32 vs. 3.38 ± 1.62 MFI), respectively, as well as a significantly higher activity of NF-κB (2.67 ± 0.60 vs. 1.07 ± 0.30). Furthermore, pro-inflammatory cytokines, interleukin-1, and interleukin-6, was significantly higher in patients with reduced ejection fraction, while the protective cytokine interleukin-10 was significantly lower in the same group. Correlational analyses demonstrated a significant and inverse relationship between left ventricular function and inflammatory parameters in patients with reduced ejection fraction, as well as a direct correlation between ferritin and inflammatory parameters. Conclusions: Our data demonstrate a different immune-mediated inflammatory burden in heart failure patients with reduced or preserved ejection fraction, as well as significant differences in iron status. These data contribute to further elucidate pathophysiologic mechanisms leading to cardiac dysfunction

Cybernetics, Fuzziness and Scientific Revolutions

Settimo Termini ​pioneered along with Aldo de Luca the concept of fuzziness measures in the sixties. Today he is a Full Professor of Theoretical Computer Science at the University of Palermo and an affiliated researcher at the European Center for Soft Computing, Mieres (Asturias), Spain. He has directed from 2002 to 2009 the Istituto di Cibernetica "Eduardo Caianiello" of CNR (National Research Council) in Italy. Among his scientific interests, the introduction and formal development of the theory of (entropy) measures of fuzziness; an analysis in innovative terms of the notion of vague predicate as it appears and is used in Information Sciences, Cybernetics and AI. Recently he has been interested also in the connections between scientific research and economic development and the conceptual foundations of Fuzzy Sets and Soft Computing. He is Fellow of the International Fuzzy Systems Association and of the Accademia Nazionale di Scienze, Lettere ed Arti of Palermo. In 2015 he will be 70, and we want to celebrate his birthday with the Soft Computing community with this interview where he discusses history of Cybernetics. The interview was conducted in Italian and translated by the authors

Ketogenic diet-induced weight loss is associated with an increase in vitamin d levels in obese adults

Vitamin D is an important micronutrient involved in several processes. Evidence has shown a strong association between hypovitaminosis D and cardio-metabolic diseases, including obesity. A ketogenic diet has proven to be very effective for weight loss, especially in reducing fat mass while preserving fat-free mass. The aim of this study was to investigate the effect of a ketogenic diet-induced weight loss on vitamin D status in a population of obese adults. We enrolled 56 obese outpatients, prescribed with either traditional standard hypocaloric Mediterranean diet (SHMD) or very low-calorie ketogenic diet (VLCKD). Serum 25(OH)D concentrations were measured by chemiluminescence. The mean value of serum 25-hydroxyvitamin D (25(OH)D) concentrations in the whole population at baseline was 17.8 +/- 5.6 ng/mL, without differences between groups. After 12 months of dietetic treatment, in VLCKD patients serum 25(OH)D concentrations increased from 18.4 +/- 5.9 to 29.3 +/- 6.8 ng/mL (p < 0.0001), vs 17.5 +/- 6.1 to 21.3 +/- 7.6 ng/mL (p = 0.067) in the SHMD group (for each kilogram of weight loss, 25(OH)D concentration increased 0.39 and 0.13 ng/mL in the VLCKD and in the SHMD groups, respectively). In the VLCKD group, the increase in serum 25(OH)D concentrations was strongly associated with body mass index, waist circumference, and fatty mass variation. In a multiple regression analysis, fatty mass was the strongest independent predictor of serum 25(OH)D concentration, explaining 15.6%, 3.3%, and 9.4% of its variation in the whole population, in SHMD, and VLCKD groups, respectively. We also observed a greater reduction of inflammation (evaluated by high-sensitivity C reactive protein (hsCRP) values) and a greater improvement in glucose homeostasis, confirmed by a reduction of HOMA values, in the VLCKD versus the SHMD group. Taken together, all these data suggest that a dietetic regimen, which implies a great reduction of fat mass, can improve vitamin D status in the obese

Foco en el significado y foco en las formas en la categorización de la entonación inglesa

This study investigated the categorisation of two nuclear pitch accents in English by River Plate Spanish speakers using two different listening modes: listening with a focus on intonational meaning or function and listening with a focus on intonational forms. Thirty-two participants listened to intonational minimal pairs differing in nuclear pitch accents, the forms H* L- L% and H* L- H%. In the first test, they were asked to decide between two pragmatic meanings conveyed by the speaker: making a statement/telling or asking/checking. In the second test, with the same stimuli, they had to decide if the nuclear pitch accent was either falling or falling-rising. The results showed that focus on form promoted a more successful categorisation of H* L- L% as statement, but hindered the categorisation of H* L- H% as question. On the other hand, a focus on forms facilitated the categorisation of the H* L- H% form as falling-rising, whereas it hindered the categorisation of H* L- L% as falling. In view of the L2LP model, it was concluded that a focus on forms promotes more accurate perception of the boundary tone H% within the new scenario., whereas it may lead to an erroneous cue weighting in the similar scenario. A focus on meaning promotes a more accurate categorisation of forms in the similar scenario, but not in the new scenario. Thus, a new L2 form becomes more or less readily accessible depending on the listening modality.Este estudio investigó la categorización de dos acentos tonales nucleares del inglés en hablantes de español rioplatense, según dos modalidades de escucha: con foco en el significado o función entonativa y con foco en la forma entonativa. Treinta y dos participantes escucharon una lista de oraciones dispuestas en pares mínimos entonativos, con igual lexis y sintaxis, pero distintos acentos tónicos, las formas H*L- H% y H* L- L%. En un primer test, los participantes debieron decidir si el hablante estaba afirmando o preguntando; en el segundo test, basado en los mismos estímulos, debieron decidir si el acento tonal nuclear era descendente o descendente-ascendente. Los resultados mostraron que el enfoque en la forma promovió una categorización más exitosa de H* L- L% como declarativa, pero dificultó la interpretación de H* L- H% como pregunta. Por otro lado, un enfoque en las formas facilitó la categorización de la forma H* L- H% como descendente-ascendente, mientras que obstaculizó la categorización de H* L- L% como descendente. A la luz del modelo L2LP, se concluyó que el enfoque en la forma facilita la categorización del tono de frontera H% dentro del nuevo escenario, mientras que puede conducir a una ponderación errónea de las pistas prosódicas dentro del escenario similar. Un enfoque en el significado promueve una categorización más precisa de las formas en el escenario similar, pero no en el nuevo escenario. Así, una nueva forma L2 se hace más o menos accesible dependiendo de la modalidad de escucha

Association between serum Mg2+ concentrations and cardiovascular organ damage in a cohort of adult subjects

Magnesium (Mg2+) levels are associated with insulin resistance, hypertension, atherosclerosis, and type 2 diabetes (T2DM). We evaluated the clinical utility of physiological Mg2+ in assessing subclinical cardiovascular organ damage including increased carotid artery intima-media thickness (c-IMT) and left ventricular mass index (LVMI) in a cohort of well-characterized adult non-diabetic individuals. Age-and gender-adjusted correlations between Mg2+ and metabolic parameters showed that Mg2+ circulating levels were correlated negatively with body mass index (BMI), fasting glucose, and 2h-oral glucose tolerance test (OGTT) glucose. Similarly, Mg2+ levels were significantly and negatively related to c-IMT and LVMI. A multivariate regression analysis revealed that age (β = 0.440; p < 0.0001), BMI (β = 0.225; p < 0.0001), and Mg2+ concentration (β = −0.122; p < 0.01) were independently associated with c-IMT. Age (β = 0.244; p = 0.012), Mg2+ (β = −0.177; p = 0.019), and diastolic blood pressure (β = 0.184; p = 0.038) were significantly associated with LVMI in women, while age (β = 0.211; p = 0.019), Mg2+ (β = −0.171; p = 0.038) and the homeostasis model assessment index of insulin resistance (HOMA-IR) (β = −0.211; p = 0.041) were the sole variables associated with LVMI in men. In conclusion, our data support the hypothesis that the assessment of Mg2+ as part of the initial work-up might help unravel the presence of subclinical organ damage in subjects at increased risk of cardiovascular complications

Endothelial dysfunction and C-reactive protein predict the incidence of heart failure in hypertensive patients

Aims: Endothelial dysfunction and heart failure are associated, but no prospective studies demonstrated that impaired endothelium-dependent vasodilation predicts incident heart failure. We designed this study to test whether endothelial dysfunction is associated with incident heart failure in a group of hypertensives. Methods and results: We enrolled 735 White never-treated hypertensive outpatients free from heart failure, diabetes, chronic kidney disease, and previous cardiovascular events. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. During the follow-up [median 114 months (range 26–206)], there were 208 new cases of heart failure (3.1 events/100 patient-years). Dividing the study population in progressors and non-progressors, we observed that progressors were older, showed a higher prevalence of being female, and had a higher baseline heart rate, glucose, insulin, Homeostatic Model Assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP) mean values, while estimated glomerular filtration rate and maximal acetylcholine-stimulated forearm blood flow were lower. In the multiple Cox regression analysis, female gender [hazard ratio (HR) = 1.454, 95% CI = 1.067–1.981], fasting glucose (HR = 1.186, 95% CI = 1.038–1.357), hs-CRP (HR = 1.162, 95% CI = 1.072–1.259), HOMA (HR = 1.124, 95% CI = 1.037–1.219), acetylcholine-stimulated forearm blood flow (HR = 0.779, 95% CI = 0.695–0.874), and estimated glomerular filtration rate (HR = 0.767, 95% CI = 0.693–0.849) maintained an independent association with the outcome. Successively, testing the interaction between forearm blood flow and hs-CRP, we observed that patients who have hs-CRP values above the median and forearm blood flow under the median show a higher risk of developing heart failure (HR = 7.699, 95% CI = 4.407–13.451). Conclusions: The present data demonstrate that an impaired endothelium-dependent vasodilation and hs-CRP predict development of incident heart failure in hypertensives

COPD significantly increases cerebral and cardiovascular events in hypertensives

Essential hypertension and chronic obstructive pulmonary disease often coexist in the same patient. The aim of this study was to evaluate whether the addition of chronic obstructive pulmonary disease modifies the risk of cardiovascular events in hypertensives. We enrolled 1728 hypertensives. Study outcomes included fatal and non-fatal cardiovascular stroke and myocardial infarction, and cardiovascular death. During a mean follow-up of 57 months there were 205 major adverse cardiovascular events (2.47 per 100 pts/yr): cardiac (n117; 1.41 per 100 pts/yr) and cerebrovascular (n = 77; 0.93 per 100 pts/yr). In hypertensives with chronic obstructive pulmonary disease we observed a greater number of cardiovascular events than in hypertensives without respiratory disease (133 [5.55 per 100 pts/yr) vs 72 [1.22 per 100 pts/yr], respectively. The addition of chronic obstructive pulmonary disease to hypertension increased the incidence of total and non-fatal stroke of more than nine- (2.42 vs 0.32 per 100 pts/yr) and 11-fold (2.09 vs 0.22 per 100 pts/yr), respectively. The same trend was observed for total (2.88 vs 0.81 per 100 pts/yr) and non-fatal (2.67 vs 0.79 per 100 pts/y) myocardial infarction. The presence of chronic obstructive pulmonary disease in hypertensives significantly increases the risk of stroke, myocardial infarction and major adverse cardiovascular events

Renal function is impaired in normotensive chronic HCV patients: role of insulin resistance

Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m2) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and HDL-cholesterol, triglyceride, creatinine, and HOMA to evaluate insulin sensitivity. HCV patients with respect to both healthy subjects and metabolic syndrome patients have a decreased e-GFR: 86.6 ± 16.1 vs 120.2 ± 23.1 mL/min/1.73 m2 (P < 0.0001) and 94.9 ± 22.6 mL/min/1.73 m2 (P = 0.003), respectively. Regarding biochemical variables, HCV patients, in comparison with healthy subjects, have a higher triglyceride level, creatinine, fasting insulin and HOMA (3.4 ± 1.4 vs 2.6 ± 1.3; P < 0.0001). At linear regression analysis, the correlation between e-GFR and HOMA is similar in the metabolic syndrome (r = -0.555, P < 0.0001) and HCV (r = -0.527, P < 0.0001) groups. At multiple regression analysis, HOMA is the major determinant of e-GFR in both groups, accounting for, respectively, 30.8 and 27.8 % of its variation in the metabolic syndrome and HCV. In conclusion, we demonstrate that HCV patients have a significant reduction of e-GFR and that insulin resistance is the major predictor of renal dysfunction