Platelet-derived chemokines, PF-4 and RANTES, are significantly increased in hemodynamically significant degenerative aortic stenosis

Aortic valve stenosis (AoS) is the most common acquired valvular disorder found in developed countries, being present in 2% to 7% of adults over the age of 65 [1], [2] and [3]. Calcified AoS is a chronic progressive disease. The pathomechanisms leading to valve degeneration remain unknown. Valve disease shares many features with atherosclerosis. Platelet activation is an important constituent of the atherosclerotic process [4] and [5]. The study focused on two platelet-derived chemokines, which bridge three important components of atherogenesis: platelet activation, inflammation, and generation of atheroma. The study group was comprised of 124 consecutive patients being considered for aortic valve replacement for symptomatic degenerative trileaflet valvular AoS, and were undergoing cardiac catheterization in the Cardiocentre (Table 1) [6]. The exclusion criterion was the presence of an additional hemodynamically significant valve disease

Metabolic profile of methylazoxymethanol model of schizophrenia in rats and effects of three antipsychotics in long-acting formulation

Mortality in psychiatric patients with severe mental illnesses reaches a 2-3 times higher mortality rate compared to the general population, primarily due to somatic comorbidities. A high prevalence of cardiovascular morbidity can be attributed to the adverse metabolic effects of atypical antipsychotics (atypical APs), but also to metabolic dysregulation present in drug-naive patients. The metabolic aspects of neurodevelopmental schizophrenia-like models are understudied. This study evaluated the metabolic phenotype of a methylazoxymethanol (MAM) schizophrenia-like model together with the metabolic effects of three APs [olanzapine (OLA), risperidone (RIS) and haloperidol (HAL)] administered via long-acting formulations for 8 weeks in female rats. Body weight, feed efficiency, serum lipid profile, gastrointestinal and adipose tissue-derived hormones (leptin, ghrelin, glucagon and glucagon-like peptide 1) were determined. The lipid profile was assessed in APs-naive MAM and control cohorts of both sexes. Body weight was not altered by the MAM model, though cumulative food intake and feed efficiency was lowered in the MAM compared to CTR animals. The effect of the APs was also present; body weight gain was increased by OLA and RIS, while OLA induced lower weight gain in the MAM rats. Further, the MAM model showed lower abdominal adiposity, while OLA increased it. Serum lipid profile revealed MAM model-induced alterations in both sexes; total, HDL and LDL cholesterol levels were increased. The MAM model did not exert significant alterations in hormonal parameters except for elevation in leptin level. The results support intrinsic metabolic dysregulation in the MAM model in both sexes, but the MAM model did not manifest higher sensitivity to metabolic effects induced by antipsychotic treatment

Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans

OBJECTIVE—Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple beneficial effects on glucose homeostasis and insulin sensitivity in animal models. This study aimed to investigate the relationship between its serum levels and various cardiometabolic parameters in humans. RESEARCH DESIGN AND METHODS—A newly developed immunoassay was used to measure serum FGF21 levels in 232 Chinese subjects recruited from our previous cross-sectional studies. The mRNA expression levels of FGF21 in the liver and adipose tissues were quantified by real-time PCR. RESULTS—Serum FGF21 levels in overweight/obese subjects were significantly higher than in lean individuals. Serum FGF21 correlated positively with adiposity, fasting insulin, and triglycerides but negatively with HDL cholesterol, after adjusting for age and BMI. Logistic regression analysis demonstrated an independent association between serum FGF21 and the metabolic syndrome. Furthermore, the increased risk of the metabolic syndrome associated with high serum FGF21 was over and above the effects of individual components of the metabolic syndrome. Our in vitro study detected a differentiation-dependent expression of FGF21 in 3T3-L1 adipocytes and human adipocytes. In db/db obese mice, FGF21 mRNA expression was markedly increased in both the liver and adipose tissue compared with that in their lean littermates. Furthermore, FGF21 expression in subcutaneous fat correlated well with its circulating concentrations in humans. CONCLUSIONS—FGF21 is a novel adipokine associated with obesity-related metabolic complications in humans. The paradoxical increase of serum FGF21 in obese individuals, which may be explained by a compensatory response or resistance to FGF21, warrants further investigation

Chair/bedside diagnosis of oral and respiratory tract infections, and identification of antibiotic resistances for personalised monitoring and treatment

Global healthcare systems are struggling with the enormous burden associated with infectious diseases, as well as the incessant rise of antimicrobial resistance. In order to adequately address these issues, there is an urgent need for rapid and accurate infectious disease diagnostics. The H2020 project DIAGORAS aims at diagnosing oral and respiratory tract infections using a fully integrated, automated and user-friendly platform for physicians' offices, schools, elderly care units, community settings, etc. Oral diseases (periodontitis, dental caries) will be detected via multiplexed, quantitative analysis of salivary markers (bacterial DNA and host response proteins) for early prevention and personalised monitoring. Respiratory Tract Infections will be diagnosed by means of DNA/RNA differentiation so as to identify their bacterial or viral nature. Together with antibiotic resistance screening on the same platform, a more efficient treatment management is expected at the point-of-care. At the heart of DIAGORAS lies a centrifugal microfluidic platform (LabDisk and associated processing device) integrating all components and assays for a fully automated analysis. The project involves an interface with a clinical algorithm for the comprehensive presentation of results to end-users, thereby increasing the platform's clinical utility. DIAGORAS' performance will be validated at clinical settings and compared with gold standards