Identification of novel circulating microRNAs in advanced heart failure by next-generation sequencing

Abstract Aims Risk stratification in patients with advanced chronic heart failure (HF) is an unmet need. Circulating microRNA (miRNA) levels have been proposed as diagnostic and prognostic biomarkers in several diseases including HF. The aims of the present study were to characterize HF‐specific miRNA expression profiles and to identify miRNAs with prognostic value in HF patients. Methods and results We performed a global miRNome analysis using next‐generation sequencing in the plasma of 30 advanced chronic HF patients and of matched healthy controls. A small subset of miRNAs was validated by real‐time PCR (P < 0.0008). Pearson's correlation analysis was computed between miRNA expression levels and common HF markers. Multivariate prediction models were exploited to evaluate miRNA profiles' prognostic role. Thirty‐two miRNAs were found to be dysregulated between the two groups. Six miRNAs (miR‐210‐3p, miR‐22‐5p, miR‐22‐3p, miR‐21‐3p, miR‐339‐3p, and miR‐125a‐5p) significantly correlated with HF biomarkers, among which N‐terminal prohormone of brain natriuretic peptide. Inside the cohort of advanced HF population, we identified three miRNAs (miR‐125a‐5p, miR‐10b‐5p, and miR‐9‐5p) altered in HF patients experiencing the primary endpoint of cardiac death, heart transplantation, or mechanical circulatory support implantation when compared with those without clinical events. The three miRNAs added substantial prognostic power to Barcelona Bio‐HF score, a multiparametric and validated risk stratification tool for HF (from area under the curve = 0.72 to area under the curve = 0.82). Conclusions This discovery study has characterized, for the first time, the advanced chronic HF‐specific miRNA expression pattern. We identified a few miRNAs able to improve the prognostic stratification of HF patients based on common clinical and laboratory values. Further studies are needed to validate our results in larger populations

On singular Lagrangians affine in velocities

The properties of Lagrangians affine in velocities are analyzed in a geometric way. These systems are necessarily singular and exhibit, in general, gauge invariance. The analysis of constraint functions and gauge symmetry leads us to a complete classification of such Lagrangians.Comment: AMSTeX, 22 page

Sex- and age-related differences in the management and outcomes of chronic heart failure: an analysis of patients from the ESC HFA EORP Heart Failure Long-Term Registry

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P\ua0 64 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P\ua0=\ua00.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P\ua075 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF 6445%

Complementary use of in sacco and in vitro studies to investigate ruminal forage degradation in relation to gas production

International audienc

Supervivencia de Pseudomonas fluorescens en suelos con diferente contenido de materia orgánica Pseudomonas fluorescens survival in soils with different contents of organic matter

Pseudomonas fluorescens es una bacteria PGPR (plant growth promoting rhizobacteria), heterótrofa, capaz de combatir fitopatógenos edáficos. Su supervivencia podría estar favorecida por el elevado contenido de materia orgánica del suelo (MOS). Para probarlo, se inocularon, en condiciones de laboratorio, tres cepas de P. fluorescens: UP61, C7R12, y P190 (nativa de Balcarce, Buenos Aires) en suelos rizosféricos de tomate representativos de diferentes zonas de Argentina: suelo Argiudol (Balcarce, y Zavalla, Santa Fe) y suelo Torrifluvens (Cipolletti, Río Negro) (MOS %: 7,2; 4,3 y 2,6 respectivamente). Los resultados indicaron que la supervivencia de P. fluorescens en los suelos Argiudoles fue similar; aunque las pendientes de las curvas de supervivencia en el suelo de Zavalla fueron menores que las observadas en el suelo de Balcarce. La producción de CO2 fue superior en el suelo de Balcarce que en el suelo de Zavalla (4,3 y 2,8 mmol.g-1suelo), esta diferencia podría ser explicada por la existencia de una mayor presión competitiva por parte de la microflora nativa. La supervivencia en el suelo Torrifluvens resultó mínima, lo que sería atribuible a su elevada conductividad eléctrica más que al menor contenido de MOS. La cepa UP61 presentó en todos los casos la mejor supervivencia.<br>Pseudomonas fluorescens are plant growth promoting rhizobacteria (PGPR). The survival of this inoculated heterotrophic bacterium may be affected by soil organic matter content (SOM). To confirm this hypothesis, three strains of P. fluorescens: UP61, C7R12 y P190 (native of Balcarce, Buenos Aires) were inoculated, in laboratory conditions, into three argentine rhizospheric soils: two Argiudolls (Balcarce, and Zavalla, Santa Fe) and a Torrifluvens (Cipolletti, Río Negro) with different SOM: 7,2; 4,3; and 2,6%, respectibily. The results indicated that the all three isolates survival in general was not different. The slopes of the regression curves in Zavalla soil were very similars, while in the Balcarce soil the strains behaviour were very different. CO2 production was superior in the Balcarce than the Zavalla soil. These results suggest that the situations that affected the survival in the Balcarce soil may be associated with the presence of a larger number of functional microflora compared with Zavalla soil. The survival in the Cipolletti soil was the lowest; independently of the protective effect of the SOM in relation with the capability of survival of the inoculated bacteria, the scarcity of survival in this soil, specially after the great fall observed, is not attributable to the low SOM content, it might be related with its high electric conductivity. The UP61 had the best survival rate in all soils