Mapping cardiac remodeling in chronic kidney disease

Patients with advanced chronic kidney disease (CKD) mostly die from sudden cardiac death and recurrent heart failure. The mechanisms of cardiac remodeling are largely unclear. To dissect molecular and cellular mechanisms of cardiac remodeling in CKD in an unbiased fashion, we performed left ventricular single-nuclear RNA sequencing in two mouse models of CKD. Our data showed a hypertrophic response trajectory of cardiomyocytes with stress signaling and metabolic changes driven by soluble uremia-related factors. We mapped fibroblast to myofibroblast differentiation in this process and identified notable changes in the cardiac vasculature, suggesting inflammation and dysfunction. An integrated analysis of cardiac cellular responses to uremic toxins pointed toward endothelin-1 and methylglyoxal being involved in capillary dysfunction and TNFα driving cardiomyocyte hypertrophy in CKD, which was validated in vitro and in vivo. TNFα inhibition in vivo ameliorated the cardiac phenotype in CKD. Thus, interventional approaches directed against uremic toxins, such as TNFα, hold promise to ameliorate cardiac remodeling in CKD.</p

Budget impact analysis of medicines : updated systematic review and implications

This evaluation determines whether published studies to date meet the key characteristics identified for budget impact analyses (BIA) for medicines, accomplished through a systematic review and assessment against identified key characteristics. Studies from 2001 to 2015 on "budget impact analysis" with "drug" interventions were assessed, selected based on their titles/abstracts and full texts, with their characteristics checked according to key criteria. Out of 1984 studies, 92 were identified. Of these, 95% were published in Europe and the USA. 2012 saw the largest number of publications (16%) with a decline thereafter. 48% met up to 6 or 7 out of the 9 key characteristics. Only 22% stated no conflict of interest. The results indicate low adherence to the key characteristics that should be considered for BIAs and strong conflict of interest. This is an issue since BIAs can be of fundamental importance in managing the entry of new medicines including reimbursement decisions

State of the art of the meiofauna of Brazilian Sandy Beaches

Abstract In Brazil, meiofauna studies began in the middle of last century, but they adopted a purely taxonomical approach, describing species from various zoological groups. After this first step, this benthic group was largely neglected until the end of the 20th century when ecological studies began. We here provide a brief review of present knowledge of the meiofauna found on Brazilian sandy beaches to provide information for ReBentos (Coastal Benthic Habitats Monitoring Network). Our methodology consisted of a bibliographic survey undertaken using different datasets (Web of ScienceTM, SCOPUS, Google Scholar and Lattes Plataform). For the survey, we considered only those studies published till early 2015. Our analysis showed that the number of meiofauna studies has increased over the last two decades, though they are mainly still concentrated on the Southeast of Brazil. These studies aim to explain the distribution pattern of the meiofauna of the intertidal region of sandy beaches. Based on the results, we presented a discussion of three main topics, i.e., (a) current knowledge of Brazilian sandy beach meiofauna, (b) sampling strategies for monitoring of the meiofauna, and (c) use of the meiofauna as a tool to assess climate change. We trust that this brief review will be useful as a starting point for the delineation of further climate change investigations into sandy beach meiofauna

Contractile effects of angiotensin and endothelin in failing and non-failing human hearts

Background: Angiotensin 11 (Ang 11) and endothelin-1 (ET-1) share their effects on growth of myocardial cells but have been shown to elicit different effects on myocardial function. However, these effects vary markedly among species, cardiac regions (atrium or ventricle) and failing or non-failing myocardium. We therefore investigated the effects of both peptides on contractile function of isolated human myocytes from failing and non-failing hearts. Methods and results: Cardiomyocytes were enzymatically isolated and electrically stimulated (15 V, 0.2 Hz). Ang 11 elicited a positive inotropic effect (PIE) mediated by activation of protein kinase C (PKC) in atrial but no effect in ventricular myocytes. ET-I (10(-8) M) increased cell-shortening by 146 +/- 9.3% (p < 0.05) in atrial myocytes, by 99.1 +/- 16.5% (p < 0.05) in non-failing ventricular but only by 40.5 +/- 6.4% (p < 0.05) in failing ventricular myocytes. The PIE of ET-1 in failing myocytes was more pronounced at low extracellular pH (+112.6 +/- 27% at pH 7.0 vs. + 40.5 +/- 6.4% at pH 7.4, p < 0.05). Amiloride, a sodium-hydrogen-exchange inhibitor, inhibited two thirds of the PIE of ET-I in failing myocytes. The PKC-inhibitor decreased the PIE by 50% from 113% to 64% in ventricular myocytes under acidotic conditions. Conclusion: Ang 11 and ET-I elicited PIE in atrial myocytes, whereas in ventricular myocytes Ang 11 did not induce PIE in contrast to ET-1. The PIE of ET-I was markedly attenuated in failing myocytes. Under acidotic conditions, the PIE of ET-I was more pronounced in failing myocytes, indicating that ET-I may activate signaling processes in failing myocytes, which are not activated in normal myocytes. (c) 2006 Elsevier Ireland Ltd. All rights reserved

Spatial and temporal density dependence regulates the condition of central Baltic Sea clupeids: compelling evidence using an extensive international acoustic survey

For the first time an international acoustic survey dataset covering three decades was used to investigate the factors shaping the spatial and temporal patterns in the condition of sprat and herring in the Baltic Proper. Generalized additive models showed that the spatial and temporal fluctuations in sprat density have been the main drivers of the spatio-temporal changes of both sprat and herring condition, evidencing intra- and inter-specific density dependence mediated by the size and distribution of the sprat population. Salinity was also an important predictor of herring condition, whereas temperature explained only a minor part of sprat model deviance. Herring density was an additional albeit weak significant predictor for herring condition, evidencing also intra-specific density dependence within the herring population. For both species, condition was high and similar in all areas of the Baltic Proper until the early 1990s, coincident with low sprat densities. Afterwards, a drop in condition occurred and a clear south-north pattern emerged. The drop in condition after the early 1990s was stronger in the northern areas, where sprat population increased the most. We suggest that the increase in sprat density in the northern areas, and the consequent spatial differentiation in clupeid condition, have been triggered by the almost total disappearance of the predator cod from the northern Baltic Proper. This study provides a step forward in understanding clupeid condition in the Baltic Sea, presenting evidence that density-dependent mechanisms also operate at the spatial scale within stock units. This stresses the importance of spatio-temporal considerations in the management of exploited fish

Interventional therapy for AV valve disease-focus onmitral valve regurgitation. Position paper of the German Cardiac Society

Mitral and tricuspid valve regurgitation remain among the most prevalent valvular defects. The treatment strategy critically depends on the etiology of disease and differs with respect to the role of medical therapy, the timing of intervention, the strategy of whether to replace or repair, and the use of a transcatheter approach. Here, we summarize currently approved transcatheter therapies for the treatment of mitral and tricuspid regurgitation. Given the prevalence of disease and the high and increasing number of transcatheter procedures in particular for mitral valve regurgitation, the German Cardiac Society herewith publishes criteria for centers for transcatheter mitral valve therapy