Effect of remote ischemic conditioning on atrial fibrillation and outcome after coronary artery bypass grafting (RICO-trial)

Background: Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC). Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF) is one of the most common complications after coronary artery bypass graft surgery (CABG), affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome.Methods/design: This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1) control, 2) remote ischemic preconditioning, 3) remote ischemic postconditioning, or 4) remote ischemic pre- and postconditioning. Remote conditio

Natriuretic peptides and integrated risk assessment for cardiovascular disease: an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention. FUNDING: British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7

Low‐Temperature Synthesis of Oxides in Ionic Liquids: Ozone‐Mediated Formation of Co 3 O 4 Nanoparticles Monitored by In Situ Infrared Spectroscopy

For most functional oxides, structure‐selective synthesis is the key for the task‐specific production of nanomaterials. Herein, the low‐temperature synthesis in ionic liquids (ILs) is an attractive strategy to produce nanomaterials which are not accessible otherwise is described. In this study, a bench‐scale synthesis route toward Co3O4 by applying O3 on the molecular precursor Co2(CO)8 in IL medium is reported. The Co3O4 nanoparticles (NPs) are characterized by infrared (IR) spectroscopy, X‐ray diffraction (XRD), and transmission electron microscopy (TEM). This protocol yields Co3O4 with good crystallinity and narrow size distribution. In addition to conventional materials characterization, a new experimental approach is described in which the material synthesis in situ by IR reflection absorption spectroscopy (IRAS) (in situ IRAS) is followed. The in situ approach provides additional information on the growth mechanisms and kinetics and confirms that O3 treatment of Co2(CO)8 in IL exclusively yields pure Co3O4 without the formation of byproducts or intermediates

Operando DRIFTS and DFT Study of Propane Dehydrogenation over Solid- and Liquid-Supported GaxPty Catalysts

Supported catalytically active liquid metal solutions (SCALMS) represent a class of catalytic materials that have only recently been developed, but have already proven to be highly active, e.g., for dehydrogenation reactions. Previous studies attributed the catalytic activity to isolated noble metal atoms at the surface of a liquid and inert Ga matrix. In this study, we apply diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) with CO as a probe molecule to Ga/Al2O3, Pt/Al2O3, and Ga37Pt/Al2O3 catalysts, to investigate in detail the nature of the active Pt species. Comparison of CO adsorption on Pt/Al2O3 and Ga37Pt/Al2O3 shows that isolated Pt atoms are, indeed, present at the surface of the liquid SCALMS. Combining DRIFTS with online gas chromatography (GC), we investigated the Ga/Al2O3, Pt/Al2O3, and Ga37Pt/Al2O3 systems under operando conditions during propane dehydrogenation in CO/propane and in Ar/propane. We find that the Pt/Al2O3 sample is rapidly poisoned by CO adsorption and coke, whereas propane dehydrogenation over Ga37Pt/Al2O3 SCALMS leads to higher conversion with no indication of poisoning effects. We show under operando conditions that isolated Pt atoms are present at the surface of SCALMS during the dehydrogenation reaction. IR spectra and density-functional theory (DFT) suggest that both the Ga matrix and the presence of coadsorbates alter the electronic properties of the surface Pt species.Fil: Bauer, Tanja. Universitat Erlangen-Nuremberg; AlemaniaFil: Maisel, Sven. Universitat Erlangen-Nuremberg; AlemaniaFil: Blaumeiser, Dominik. Universitat Erlangen-Nuremberg; AlemaniaFil: Vecchietti, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Taccardi, Nicola. Universitat Erlangen-Nuremberg; AlemaniaFil: Wasserscheid, Peter. Universitat Erlangen-Nuremberg; AlemaniaFil: Bonivardi, Adrian Lionel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Görling, Andreas. Universitat Erlangen-Nuremberg; AlemaniaFil: Libuda, Jörg. Universitat Erlangen-Nuremberg; Alemani

Highly Effective Propane Dehydrogenation Using Ga–Rh Supported Catalytically Active Liquid Metal Solutions

Our contribution demonstrates that rhodium, an element that has barely been reported as an active metal for selective dehydrogenation of alkanes becomes a very active, selective, and robust dehydrogenation catalyst when exposed to propane in the form of single atoms at the interface of a solid-supported, highly dynamic liquid Ga–Rh mixture. We demonstrate that the transition to a fully liquid supported alloy droplet at Ga/Rh ratios above 80, results in a drastic increase in catalyst activity with high propylene selectivity. The combining results from catalytic studies, X-ray photoelectron spectroscopy, IR-spectroscopy under reaction conditions, microscopy, and density-functional theory calculations, we obtained a comprehensive microscopy picture of the working principle of the Ga–Rh supported catalytically active liquid metal solution

Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011

Background Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Methods Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. Results The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%). Conclusions No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.

Genetic Correction of a LRRK2 Mutation in Human iPSCs Links Parkinsonian Neurodegeneration to ERK-Dependent Changes in Gene Expression

The LRRK2 mutation G2019S is the most common genetic cause of Parkinson’s disease (PD). To better understand the link between mutant LRRK2 and PD pathology, we derived induced pluripotent stem cells from PD patients harboring LRRK2 G2019S and then specifically corrected the mutant LRRK2 allele. We demonstrate that gene correction resulted in phenotypic rescue in differentiated neurons and uncovered expression changes associated with LRRK2 G2019S. We found that LRRK2 G2019S induced dysregulation of CPNE8, MAP7, UHRF2, ANXA1, and CADPS2. Knockdown experiments demonstrated that four of these genes contribute to dopaminergic neurodegeneration. LRRK2 G2019S induced increased extracellular-signal-regulated kinase 1/2 (ERK) phosphorylation. Transcriptional dysregulation of CADPS2, CPNE8, and UHRF2 was dependent on ERK activity. We show that multiple PD-associated phenotypes were ameliorated by inhibition of ERK. Therefore, our results provide mechanistic insight into the pathogenesis induced by mutant LRRK2 and pointers for the development of potential new therapeutics