CCN1 expression in interleukin-6 deficient mouse kidney in experimental model of heart failure

Chronic heart failure often leads to worsening of the renal function. Mediators of this process include inflammatory and neuroendocrine factors. CCN1 (Cyr 61), a member of growth factor-inducible immediate early genes, which modulates inflammation and fibrogenesis, is excreted with urine in the early phase of acute renal injury and may be involved in the pathogenesis of the cardiorenal syndrome. The aim of the study was to evaluate CCN1 protein abundance and localization in the kidney of IL-6-deficient C57BL/6J (IL-6 KO) mice and respective wild-type (WT) animals in basal conditions and in animals with chronic heart failure twelve weeks after myocardial infarction. Age- and sex-matched mice from both strains subjected to sham operation served as controls. One group of WT animals subjected to myocardial infarction was treated with antagonist of AT1 receptor telmisartan over 12 weeks. Abundance and localization of CCN1 protein in kidney were assessed with Western blotting and immunohistochemistry, respectively. In all groups the strongest immunohistochemical reaction for CCN1 was observed in distal convoluted tubules and in smaller arteries, however, the total expression of CCN1 protein was lower in IL-6 KO mice in comparison to WT animals. The main difference in CCN1 distribution between the examined genotypes was lack of reaction in internal renal medulla and very weak reaction in proximal convoluted tubules in IL-6 KO mice. Experimental heart failure only slightly attenuated the expression of CCN1 protein in the kidney of WT mice and had no effect in IL-6 KO mice. Although, blockade of AT1 receptor did not alter CCN1 protein expression in kidneys of WT mice after myocardial infarction, it significantly changed its CCN1 distribution in the renal tubular system. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 84–91

A hunter-gatherer-farmer population model: Lie symmetries, exact solutions and their interpretation

The Lie symmetry classification of the known three-component reaction-diffusion system modelling the spread of an initially localized population of farmers into a region occupied by hunter-gatherers is derived. The Lie symmetries obtained for reducing the system in question to systems of ODEs and constructing exact solutions are applied. Several exact solutions of traveling front type are found, their properties are identified and biological interpretation is discussed

Subsequent Event Risk in Individuals with Established Coronary Heart Disease:Design and Rationale of the GENIUS-CHD Consortium

BACKGROUND: The "GENetIcs of sUbSequent Coronary Heart Disease" (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185,614 participants with either acute coronary syndrome, stable CHD or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with duration of follow up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (HR 1.15 95% CI 1.14-1.16) per 5-year increase, male sex (HR 1.17, 95% CI 1.13-1.21) and smoking (HR 1.43, 95% CI 1.35-1.51) with risk of subsequent CHD death or myocardial infarction, and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and non-genetic determinants of subsequent event risk in individuals with established CHD, in order to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators

ECG in the clinical and prognostic evaluation of patients with pulmonary arterial hypertension: an underestimated value

Background: Pulmonary arterial hypertension (PAH) is a rare disease leading to right ventricular (RV) failure and manifests in decreasing exercise tolerance. Our study aimed to assess the usefulness of electrocardiographic parameters reflecting right heart hypertrophy as predictors of clinical status in PAH. Methods: The retrospective analysis included 26 patients, mean 49 ± 17 years of age, diagnosed with PAH, and eligible to undergo cardiopulmonary exercise test (CPET). The relations between ECG values and parameters obtained in procedures such as six-minute walk test (6-MWT), echocardiography, right heart catheterization (RHC), and CPET were analyzed. Results: P-wave amplitude in lead II correlated positively with CPET parameter of respiratory response: minute ventilation to carbon dioxide production slope (VE/VCO 2 slope; r  = 0.436, p  = 0.029) and echocardiographic estimated RA pressure (RAP; r  = 0.504, p  = 0.02). RV Sokolow-Lyon index (RVSLI) positively correlated with echocardiographic parameters reflecting RV function, overload, and afterload–tricuspid regurgitation pressure gradient (TRPG; r  = 0.788, p  < 0.001), RV free wall thickness ( r  = 0.738, p  < 0.001), and mean pulmonary arterial pressure (mPAP ECHO ; r  = 0.62, p  = 0.0016), respectively, as well as VE/VCO 2 slope ( r  = 0.593, p  = 0.001) and mPAP assessed directly in RHC (mPAP RHC ; r  = 0.469, p  = 0.0497). R-wave in lead aVR correlated positively with TRPG ( r  = 0.719, p  < 0.001), mPAP ECHO ( r  = 0.446, p  = 0.033), and several hemodynamic criteria of PAH diagnosis: positively with mPAP RHC ( r  = 0.505, p  = 0.033) and pulmonary vascular resistance ( r  = 0.554, p  = 0.026) and negatively with pulmonary capillary wedge pressure ( r  = −0.646, p  = 0.004). QRS duration correlated positively with estimated RAP ( r  = 0.589, p  = 0.004), vena cava inferior diameter ( r  = 0.506, p  = 0.016), and RA area ( r  = 0.679, p  = 0.002) and negatively with parameters of exercise capacity: peak VO 2 ( r  = −0.486, p  = 0.012), CPET maximum load ( r  = − 0.439, p  = 0.025), and 6-MWT distance ( r  = −0.430, p  = 0.046). ROC curves to detect intermediate/high 1-year mortality risk (based on ESC criteria) indicate RVSLI (cut-off point: 1.57 mV, AUC: 0.771) and QRS duration (cut-off points: 0.09 s, AUC: 703 and 0.1 s, AUC: 0.759) as relevant predictors. Conclusion: Electrocardiography appears to be an important and underappreciated tool in PAH assessment. ECG corresponds with clinical parameters reflecting PAH severity

Oral Health-Related Quality of Life and Missing Teeth in an Adult Population: A Cross-Sectional Study from Poland

The aim of the study was to determine oral health–related quality of life (OHRQoL) using the measures Geriatric/General Oral Health Assessment (GOHAI) and Oral Health Impact Profile (OHIP-14) in relation to missing teeth in the Polish population aged 20–79. This was a cross-sectional study carried out among 1112 randomly selected participants. The mean age was 48.72 and mean number of teeth was 20.12. Altogether, in the GOHAI, the percentage that gave a positive response to each question ranged from 3.3% to 48.0%; in the OHIP-14, these answers ranged from 2.4% to 25.1%. The GOHAI measure was statistically significant, with more grouping variables than the OHIP-14 measure. Both measures showed significant associations with gender, age, dry mouth, education, professional status, number of teeth, and upper and lower total dentures. We detected a significant relationship between oral health–related quality of life and the factors influencing the presence or absence of dentition. Missing teeth were statistically associated with GOHAI, OHIP-14, advanced age, self-reported dry mouth, lower education, higher Body Mass Index (BMI), lower professional status, diabetes, myocardial infraction, and total dentures in upper or/and lower jaws. However, edentulous individuals had two times higher risk of having an OHIP-14 score above the median. This suggests that oral health practitioners should work to prevent oral diseases that lead to tooth loss in their patients, starting from an early age.publishedVersio

Polymorphism of 9p21.3 locus is associated with 5-year survival in high-risk patients with myocardial infarction.

OBJECTIVE: The rs1333049, rs10757278 and rs4977574 are single nucleotide polymorphisms (SNPs) of chromosome 9p21 locus that are associated with prevalence of acute coronary syndromes (ACS). The rs1333049 SNP was also associated with cardiac outcome 6 months post ACS. No data concerning their association with long term prognosis after myocardial infarction is available. The aim of our study was to investigate the association of the 9p21.3 locus with 5-year overall mortality in patients with ST-elevation myocardial infarction (STEMI) treated invasively. MATERIALS AND METHODS: We performed a retrospective analysis of data collected prospectively in a registry of consecutive patients with STEMI treated with primary PCI. Genotyping was performed with a TaqMan method. The analyzed end-point was total 5-year mortality. RESULTS: The study group comprised 589 patients: 25.3% of females (n = 149), mean age 62.4±11.9 years, total 5-year mortality 16.6% (n = 98). When all the study group was analyzed, no significant differences in mortality were found between the genotypes. However, in high-risk patients (Grace risk score ≥155 points, n = 238), low-risk homozygotes had significantly better 5-year survival compared to other genotypes. The hazard ratio associated with high-risk genotype (high-risk homozygote or heterozygote) was: HR = 2.9 (95%CI 1.4-6.1) for the rs4977574 polymorphism, HR = 2.6 (1.25-5.3) for the rs1333049 one and HR = 2.35 (1.2-4.6) for the rs10757278 one (Cox proportional hazards model). CONCLUSIONS: The 9p21.3 locus is associated with 5-year mortality in high-risk patients with STEMI. This finding, due to very high effect size, could potentially be applied into clinical practice, if appropriate methods are elaborated

A comparison of different machine-learning techniques for the selection of a panel of metabolites allowing early detection of brain tumors

Abstract Metabolomics combined with machine learning methods (MLMs), is a powerful tool for searching novel diagnostic panels. This study was intended to use targeted plasma metabolomics and advanced MLMs to develop strategies for diagnosing brain tumors. Measurement of 188 metabolites was performed on plasma samples collected from 95 patients with gliomas (grade I–IV), 70 with meningioma, and 71 healthy individuals as a control group. Four predictive models to diagnose glioma were prepared using 10 MLMs and a conventional approach. Based on the cross-validation results of the created models, the F1-scores were calculated, then obtained values were compared. Subsequently, the best algorithm was applied to perform five comparisons involving gliomas, meningiomas, and controls. The best results were obtained using the newly developed hybrid evolutionary heterogeneous decision tree (EvoHDTree) algorithm, which was validated using Leave-One-Out Cross-Validation, resulting in an F1-score for all comparisons in the range of 0.476–0.948 and the area under the ROC curves ranging from 0.660 to 0.873. Brain tumor diagnostic panels were constructed with unique metabolites, which reduces the likelihood of misdiagnosis. This study proposes a novel interdisciplinary method for brain tumor diagnosis based on metabolomics and EvoHDTree, exhibiting significant predictive coefficients

The rs4977574 polymorphism and 5-year survival.

<p>No significant differences were observed between the genotypes.</p

Baseline characteristics of the study group based on rs4977574 genotype (risk allele- G).

<p>eGFR- estimated GFR, mean values with standard deviations are given, unless otherwise specified.</p

Univariate and multivariate analysis for 5-year mortality in a subgroup of high-risk patients (Grace risk score ≥155).

<p>In the brackets values adjusted for severity of coronary artery disease (number of vessels with significant stenosis) are given.</p