Cardiac Glycosides Lower C-Reactive Protein Plasma Levels in Patients with Decompensated Heart Failure: Results from the Single-Center C-Reactive Protein-Digoxin Observational Study (C-DOS).

Recent randomized controlled multi-center trials JUPITER, CANTOS and COLCOT impressively demonstrated the effect of anti-inflammatory therapy on secondary prevention of cardiovascular events. These studies also rapidly re-vitalized the question of whether the C-reactive protein (CRP), the prototype human acute phase protein, is actively involved in atherosclerosis and its sequelae. Direct CRP inhibition may indeed improve the specificity and effectiveness of anti-inflammatory intervention. In the present paper, we report on the final results of our single-center C-reactive protein-Digoxin Observational Study (C-DOS). Methods and Results: Based on the experimental finding that cardiac glycosides potently inhibit hepatic CRP synthesis on the transcriptional level in vitro, 60 patients with decompensated heart failure, NYHA III−IV, severely reduced Left Ventricular Ejection Fraction (LVEF < 40%), and elevated CRP plasma levels were treated by either digoxin + conventional heart failure therapy (30 patients) or by conventional heart failure therapy alone (30 patients). Plasma CRP levels in both groups were assessed for 21 d. Plasma CRP levels on d1, d3 and d21 were compared by regression analysis. CRP levels d21−d1 significantly declined in both groups. Notably, comparative CRP reduction d21−d3 in digoxin versus the control group also revealed borderline significance (p = 0.051). Conclusions: This small observational trial provides the first piece of evidence that cardiac glycosides may inhibit CRP synthesis in humans. In case of further pharmacological developments, cardiac glycosides may emerge as lead compounds for chemical modification in order to improve the potency, selectivity and pharmacokinetics of CRP synthesis inhibition in cardiovascular disease.

Effect of pore diameter and length on electrochemical CO2 reduction reaction at nanoporous gold catalysts.

In this work, we employ differential electrochemical mass spectrometry (DEMS) to track the real-time evolution of CO at nanoporous gold (NpAu) catalysts with varying pore parameters (diameter and length) during the electrochemical CO2 reduction reaction (CO2RR). We show that due to the increase in the local pH with increasing catalyst roughness, NpAu catalysts suppress the bicarbonate-mediated hydrogen evolution reaction (HER) compared to a flat Au electrode. Additionally, the geometric current density for CO2RR increases with the roughness of NpAu catalysts, which we attribute to the increased availability of active sites at NpAu catalysts. Together, the enhancement of CO2RR and the suppression of competing HER results in a drastic increase in the faradaic selectivity for CO2RR with increasing pore length and decreasing pore diameter, reaching near 100% faradaic efficiency for CO in the most extreme case. Interestingly, unlike the geometric current density, the specific current density for CO2RR has a more complicated relation with the roughness of the NpAu catalysts. We show that this is due to the presence of ohmic drop effects along the length of the porous channels. These ohmic drop effects render the pores partially electrocatalytically inactive and hence, they play an important role in tuning the CO2RR activity on nanoporous catalysts.

No Difference in 30-Day Outcome and Quality of Life in Transradial Versus Transfemoral Access - Results From the German Austrian ABSORB Registry (GABI-R).

BACKGROUND: Radial (RA) instead of femoral access (FA) for coronary interventions has become a European Society of Cardiology Class-IA guideline recommendation. But when the decision on the access site is left to the discretion of the operator, differences in adverse event rates mitigate. METHODS: We compared the 30-day outcome for RA and FA in all patients recruited for the observational German Austrian ABSORB Registry (GABI-R) in regard to all-cause mortality, stroke, myocardial infarction (MI), TIMI major bleedings (TMB) and quality of life (QoL). All patients were treated with a bioresorbable vascular scaffold. Access site was left to the discretion of the operator. RESULTS: In total, 3137 patients included by 92 centers received percutaneous coronary interventions (PCI) for acute MI in 51.5% and non-acute settings in 48.5%. RA was performed in 47.8% and had a higher median radiation exposure (3896 vs. 3082 cGycm2, p < 0.001). There was no difference in the amount of contrast used. There was also no difference in all-cause mortality (0.53% vs. 0.49%, p = 0.86), the combination of death, MI and stroke (1.87% vs. 1.83%, p = 0.94), but a trend towards more TMB (0.47% vs. 1.04%, p = 0.07) with FA. These outcomes were consistent across the subgroups of patients with ST-elevation MI, non-ST-elevation-ACS and stable coronary artery disease. Finally, QoL did not differ between RA and FA. CONCLUSIONS: In this contemporary GABI-R cohort, in which access site was left to the discretion of the operator, both access routes were safe and equal concerning QoL (ClinicalTrials.gov; NCT02066623).

Direct and Broadband Plasmonic Charge Transfer to Enhance Water Oxidation on a Gold Electrode.

Plasmonic photocatalysis via hot charge carriers suffers from their short lifetime compared with the sluggish kinetics of most reactions. To increase lifetime, adsorbates on the surface of a plasmonic metal may create preferential states for electrons to be excited from. We demonstrate this effect with O adsorbates on a nanoporous gold electrode. Nanoporous gold is used to obtain a broadband optical response, to increase the obtained photocurrent, and to provide a SERS-active substrate. Only with adsorbates present, we observe significant photocurrents. Illumination also increases the adsorbate coverage above its dark potential-dependent equilibrium, as derived from a two-laser in situ SERS approach. Density functional theory calculations confirm the appearance of excitable states below the Fermi level. The photocurrent enhancement and broadband characteristics reveal the potential of the plasmonic approach to improve the efficiency of photoelectrochemical water splitting.

Suppression of Hydrogen Evolution in Acidic Electrolytes by Electrochemical CO2 Reduction.

In this article we investigate the electrochemical reduction of CO2 at gold electrodes under mildly acidic conditions. Differential electrochemical mass spectroscopy (DEMS) is used to quantify the amounts of formed hydrogen and carbon monoxide as well as the consumed amount of CO2. We investigate how the Faradaic efficiency of CO formation is affected by the CO2 partial pressure (0.1-0.5 bar) and the proton concentration (1-0.25 mM). Increasing the former enhances the rate of CO2 reduction and suppresses hydrogen evolution from proton reduction, leading to Faradaic efficiencies close to 100%. Hydrogen evolution is suppressed by CO2 reduction as all protons at the electrode surfaces are used to support the formation of water (CO2 + 2H+ + 2e- → CO + H2O). Under conditions of slow mass transport, this leaves no protons to support hydrogen evolution. On the basis of our results, we derive a general design principle for acid CO2 electrolyzers to suppress hydrogen evolution from proton reduction: the rate of CO/OH- formation must be high enough to match/compensate the mass transfer of protons to the electrode surface.

Two year efficacy and safety of small versus large ABSORB bioresorbable vascular scaffolds of ≤18 mm device length: A subgroup analysis of the German-Austrian ABSORB RegIstRy (GABI-R).

AIMS: The ABSORB bioresorbable vascular scaffold raised safety concerns due to higher rates of scaffold thrombosis (ScT) and adequate scaffold diameter and length for scaffold technology. Smaller scaffold diameter (SScD, 2.5 mm) was an infrequently quoted predictor of major adverse cardiac events (MACE). Therefore, we evaluated the impact of SScD compared to large scaffold diameter (LScD, ≥3 mm) of ≤18 mm device length on 2 year outcome in the all-comer real life GABI-R cohort. METHODS AND RESULTS: We compared patients with implanted LScD (1341 patients) vs. SScD (444 patients) of ≤18 mm device length. Patients with LScD more often presented with ST-elevation myocardial infarction (35.8% vs. 20.6%, p < 0.0001) and single-vessel disease (50.6% vs. 36.5% p < 0.0001). After a 24 months follow-up, there was no difference in regard of MACE (9.66% vs. 12.31%, p = 0.14) or definite/probable ST (2.47% vs. 2.82%, p = 0.71). Despite no difference in target lesion revascularisations (TLR) (5.81% vs. 7.71%, p = 0.18), there was a higher need for target vessel revascularisation (TVR) in the SScD-group (11.57% vs. 7.51%, p < 0.05). CONCLUSION: Compared to LScD, SScD of ≤18 mm device length demonstrated comparable safety in regard to MACE and ScT as well as efficacy in regard to TLR. Resorbable scaffold technology should not be restricted to large vessel diameters. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02066623.

Metamaterial emitter for thermophotovoltaics stable up to 1400 °C.

High temperature stable selective emitters can significantly increase efficiency and radiative power in thermophotovoltaic (TPV) systems. However, optical properties of structured emitters reported so far degrade at temperatures approaching 1200 °C due to various degradation mechanisms. We have realized a 1D structured emitter based on a sputtered W-HfO2 layered metamaterial and demonstrated desired band edge spectral properties at 1400 °C. To the best of our knowledge the temperature of 1400 °C is the highest reported for a structured emitter, so far. The spatial confinement and absence of edges stabilizes the W-HfO2 multilayer system to temperatures unprecedented for other nanoscaled W-structures. Only when this confinement is broken W starts to show the well-known self-diffusion behavior transforming to spherical shaped W-islands. We further show that the oxidation of W by atmospheric oxygen could be prevented by reducing the vacuum pressure below 10-5 mbar. When oxidation is mitigated we observe that the 20 nm spatially confined W films survive temperatures up to 1400 °C. The demonstrated thermal stability is limited by grain growth in HfO2, which leads to a rupture of the W-layers, thus, to a degradation of the multilayer system at 1450 °C.

[Temporary Pacemakers - Step by Step]. / Passagerer Herzschrittmacher.

Symptomatic bradycardia is usually caused by abnormalities of atrioventricular conduction or sinus node dysfunction. Reversible and irreversible causes must be considered.Temporary pacemakers are used in the emergency treatment in case of severe bradyarrhythmia.They help to bridge the acute phase until spontaneous restoration of atrioventricular or sinus node function or -if spontaneous restoration fails- until a permanent pacemaker system was implanted.In the following article we discuss the commonly used temporary pacemaker systems. We demonstrate their use and correct programming by an illustrated step by step explanation. For troubleshooting a flow chart was added.

Dealloying progress during nanoporous structure evolution analyzed by in situ resistometry.

The progress of dealloying, an electrochemical synthesis method capable of producing nanoporous structures with bulk outer dimensions, is studied by in situ resistometry. The resistance increases by three orders of magnitude while nanoporous gold or platinum is formed. Simultaneous monitoring of charge flow and electrical resistance increase proves to be an ideal combination for analyzing the etching progress, which in accordance with recent studies can be demonstrated to occur in two steps referred to as 'primary (or bulk) dealloying' and 'secondary (or ligament) dealloying'. A model is developed, which describes the resistance increase during etching as governed by the reduction of the master alloy backbone in favor of the nanoporous structure. This new approach allows an evaluation of the etching front propagation (primary dealloying) as well as the status of the already porous structure (secondary dealloying).

Electrocatalytic methanol oxidation with nanoporous gold: microstructure and selectivity.

The properties of Nanoporous Gold (NPG) obtained by the selective dissolution of Ag from an Au-Ag alloy can be tuned by the details of its fabrication, and specifically the residual Ag content is correlated to the ligament size of the material. We link this correlation to methanol electro-oxidation. Specifically, two different NPG types (obtained by potentiostatic dealloying) are compared with one obtained by free corrosion. They show remarkable differences in activity. Quantitative product analysis reveals that NPG shows nearly selective oxidation of CH3OH to HCOO- when NPG is used as an active electrode in contrast to planar Au. This trend can further be enhanced when applying finer nanoporous structures that are linked to a higher Ag content. X-ray photoelectron spectroscopy (XPS) reveals changes in the nature of residual Ag from which we conclude that Ag is not a passive component in the methanol oxidation process.

Takotsubo Syndrome After Cardiopulmonary Resuscitation During Emergency Cesarean Delivery.

BACKGROUND: Takotsubo syndrome is a rare, stress-related, and reversible form of acute heart failure primarily affecting postmenopausal women. It is characterized by left ventricular dysfunction with a classic apical and midventricular wall motion abnormality (apical ballooning). CASE: A 28-year-old woman, gravida 2 para 1, at 30 4/7 weeks of gestation was admitted with fetal bradycardia, a fully dilated cervix, and breech presentation. During emergency cesarean delivery, the patient had intraoperative cardiac arrest. Resuscitation was successful. Twelve hours postoperatively, after demonstrating symptoms of acute heart failure, she was diagnosed with Takotsubo syndrome. CONCLUSION: Peripartum Takotsubo syndrome must be differentiated from peripartum cardiomyopathy. Cesarean delivery and sympathomimetic medications can increase the risk of occurrence. Early recognition and interdisciplinary management are essential in the prevention of serious and potentially fatal complications.

Electrical Conductivity through a Single Atomic Step Measured with the Proximity-Induced Superconducting Pair Correlation.

Local disordered nanostructures in an atomically thick metallic layer on a semiconducting substrate play significant and decisive roles in transport properties of two-dimensional (2D) conductive systems. We measured the electrical conductivity through a step of monoatomic height in a truly microscopic manner by using as a signal the superconducting pair correlation induced by the proximity effect. The transport property across a step of a one-monolayer Pb surface metallic phase, formed on a Si(111) substrate, was evaluated by inducing the pair correlation around the local defect and measuring its response, i.e., the reduced density of states at the Fermi energy using scanning tunneling microscopy. We found that the step resistance has a significant contribution to the total resistance on a nominally flat surface. Our study also revealed that steps in the 2D metallic layer terminate the propagation of the pair correlation. Superconductivity is enhanced between the first surface step and the superconductor-normal-metal interface by reflectionless tunneling when the step is located within a coherence length.

Femoral insertion site in medial patellofemoral ligament reconstruction.

BACKGROUND: The optimal femoral insertion point in MPFL (medial patellofemoral ligament)-reconstruction still remains ambiguous. Three-dimensional knee simulations based on computerized tomography (CT) images acquired under physiological loading conditions give further insights to predict the optimal femoral insertion site of the MPFL. The hypothesis of the present study is that the optimal insertion point is not as reliable as thought and is dependent on subject-specific anatomical factors. METHODS: High-resolution 3D images of the knee were acquired in ten weight-bearing knees of healthy subjects in five flexion angles (0 to 120°). The distance between different femoral insertion points and two defined patellar points was computed in each position to quantify length of respective bundles and isometry of the femoral insertion site. RESULTS: The median length of both bundles was maximal in full extension (proximal bundle: 62.2mm and distal bundle: 59.9mm). The shortest ligament length was obtained in the flexion position 90° for bundle I (57.3mm) and 30° for bundle II (85.3mm). The calculated most isometric femoral attachment point showed a non-uniform distribution pattern related to anatomic landmarks. The radiographic landmark showed the worst isometric score value compared to virtually defined spots by surgeons and the computed most isometric point. CONCLUSIONS: This study provides results on the MPFL path length under physiological loading conditions using high-resolution bone geometry. The most important finding of this study was that the computed, best isometric femoral insertion point showed a variable anatomical distribution. This suggests that the optimal position for femoral MPFL-graft fixation is patient specific.

Computer algorithms for three-dimensional measurement of humeral anatomy: analysis of 140 paired humeri.

BACKGROUND: In the presence of severe osteoarthritis, osteonecrosis, or proximal humeral fracture, the contralateral humerus may serve as a template for the 3-dimensional (3D) preoperative planning of reconstructive surgery. The purpose of this study was to develop algorithms for performing 3D measurements of the humeral anatomy and further to assess side-to-side (bilateral) differences in humeral head retrotorsion, humeral head inclination, humeral length, and humeral head radius and height. METHODS: The 3D models of 140 paired humeri (70 cadavers) were extracted from computed tomographic data. Geometric characteristics quantifying the humeral anatomy in 3D were determined in a semiautomatic fashion using the developed computer algorithms. The results between the sides were compared for evaluating bilateral differences. RESULTS: The mean bilateral difference of the humeral retrotorsion angle was 6.7° (standard deviation [SD], 5.7°; range, -15.1° to 24.0°; P = .063); the mean side difference of the humeral head inclination angle was 2.3° (SD, 1.8°; range, -5.1° to 8.4°; P = .12). The side difference in humeral length (mean, 2.9 mm; SD, 2.5 mm; range, -8.7 mm to 10.1 mm; P = .04) was significant. The mean side difference in the head sphere radius was 0.5 mm (SD, 0.6 mm; range, -3.2 mm to 2.2 mm; P = .76), and the mean side difference in humeral head height was 0.8 mm (SD, 0.6 mm; range, -2.4 mm to 2.4 mm; P = .44). CONCLUSIONS: The contralateral anatomy may serve as a reliable reconstruction template for humeral length, humeral head radius, and humeral head height if it is analyzed with 3D algorithms. In contrast, determining humeral head retrotorsion and humeral head inclination from the contralateral anatomy may be more prone to error.

Three-dimensional postoperative accuracy of extra-articular forearm osteotomies using CT-scan based patient-specific surgical guides.

BACKGROUND: Computer assisted corrective osteotomy of the diaphyseal forearm and the distal radius based on computer simulation and patient-specific guides has been described as a promising technique for accurate reconstruction of forearm deformities. Thereby, the intraoperative use of patient-specific drill and cutting guides facilitate the transfer of the preoperative plan to the surgery. However, the difference between planned and performed reduction is difficult to assess with conventional radiographs. The aim of this study was to evaluate the accuracy of this surgical technique based on postoperative three-dimensional (3D) computed tomography (CT) data. METHODS: Fourteen patients (mean age 23.2 (range, 12-58) years) with an extra-articular deformity of the forearm had undergone computer assisted corrective osteotomy with the healthy anatomy of the contralateral uninjured side as a reconstruction template. 3D bone surface models of the pathological and contralateral side were created from CT data for the computer simulation. Patient-specific drill and cutting guides including the preoperative planned screw direction of the angular-stable locking plates and the osteotomy planes were used for the intraoperative realization of the preoperative plan. There were seven opening wedge osteotomies and nine closing wedge (or single-cut) osteotomies performed. Eight-ten weeks postoperatively CT scans were obtained to assess bony consolidation and additionally used to generate a 3D model of the forearm. The simulated osteotomies- preoperative bone models with simulated correction - and the performed osteotomies - postoperative bone models - were analyzed for residual differences in 3D alignment. RESULTS: On average, a significant higher residual rotational deformity was observed in opening wedge osteotomies (8.30° ± 5.35°) compared to closing wedge osteotomies (3.47° ± 1.09°). The average residual translation was comparable small in both groups, i.e., below 1.5 mm and 1.1 mm for opening and closing wedge osteotomies, respectively. CONCLUSIONS: The technique demonstrated high accuracy in performing closing wedge (or single-cut) osteotomies. However, for opening wedge osteotomies with extensive lengthening, probably due to the fact that precise reduction was difficult to achieve or maintain, the final corrections were less accurate.

Theory of nodal s ± -wave pairing symmetry in the Pu-based 115 superconductor family.

The spin-fluctuation mechanism of superconductivity usually results in the presence of gapless or nodal quasiparticle states in the excitation spectrum. Nodal quasiparticle states are well established in copper-oxide, and heavy-fermion superconductors, but not in iron-based superconductors. Here, we study the pairing symmetry and mechanism of a new class of plutonium-based high-Tc superconductors and predict the presence of a nodal s(±) wave pairing symmetry in this family. Starting from a density-functional theory (DFT) based electronic structure calculation we predict several three-dimensional (3D) Fermi surfaces in this 115 superconductor family. We identify the dominant Fermi surface "hot-spots" in the inter-band scattering channel, which are aligned along the wavevector Q = (π, π, π), where degeneracy could induce sign-reversal of the pairing symmetry. Our calculation demonstrates that the s(±) wave pairing strength is stronger than the previously thought d-wave pairing; and more importantly, this pairing state allows for the existence of nodal quasiparticles. Finally, we predict the shape of the momentum- and energy-dependent magnetic resonance spectrum for the identification of this pairing symmetry.

C-reactive protein in human atherogenesis: facts and fiction.

The role of C-reactive protein (CRP) in atherosclerosis is controversially discussed. Whereas initial experimental studies suggested a pathogenic role for CRP in atherogenesis, more recent genetic data from Mendelian randomization trials failed to provide evidence for a causative role of CRP in cardiovascular disease. Also, experimental results from laboratories all over the world were indeed contradictory, partly because of species differences in CRP biology and partly because data were not accurately evaluated. Here we summarize the published data from experimental work with mainly human material in order to avoid confusion based on species differences in CRP biology. Experimental work needs to be reevaluated after reconsideration of some traditional rules in research: (1) in order to understand a molecule's role in disease it may be helpful to be aware of its role in physiology; (2) it is necessary to define the disease entity that experimental CRP research deals with; (3) the scientific consensus is as follows: do not try to prove your hypothesis. Specific CRP inhibition followed by use of CRP inhibitors in controlled clinical trials may be the only way to prove or disprove a causative role for CRP in cardiovascular disease.

Automatic string generation for estimating in vivo length changes of the medial patellofemoral ligament during knee flexion.

Modeling ligaments as three-dimensional strings is a popular method for in vivo estimation of ligament length. The purpose of this study was to develop an algorithm for automated generation of non-penetrating strings between insertion points and to evaluate its feasibility for estimating length changes of the medial patellofemoral ligament during normal knee flexion. Three-dimensional knee models were generated from computed tomography (CT) scans of 10 healthy subjects. The knee joint under weight-bearing was acquired in four flexion positions (0°-120°). The path between insertion points was computed in each position to quantify string length and isometry. The average string length was maximal in 0° of flexion (64.5 ± 3.9 mm between femoral and proximal patellar point; 62.8 ± 4.0 mm between femoral and distal patellar point). It was minimal in 30° (60.0 ± 2.6 mm) for the proximal patellar string and in 120° (58.7 ± 4.3 mm) for the distal patellar string. The insertion points were considered to be isometric in 4 of the 10 subjects. The proposed algorithm appears to be feasible for estimating string lengths between insertion points in an automatic fashion. The length measurements based on CT images acquired under physiological loading conditions may give further insights into knee kinematics.

Role of the Fermi-surface anisotropy in angle-dependent magnetic-field oscillations for identifying the energy-gap anisotropy of A(y)Fe(2)Se(2) superconductors.

We present a numerical study of the field-angle resolved oscillations of the thermal conductivity and specific heat under a rotated magnetic field in the A(y)Fe(2-x)Se(2) [A = K, Rb, Cs, (Tl, K)] superconductors, using realistic two-band Fermi surface parametrization. Our key finding is that even for isotropic pairing on an anisotropic Fermi surface, the thermodynamic quantities exhibit substantial oscillatory behavior in the superconducting state, even much below the upper critical field. Furthermore, in multiband systems the competition of anisotropies between two Fermi surfaces can cause a double sign reversal of oscillations as a function of temperature, irrespective of gap anisotropy. Our findings put severe constraints on simple interpretations of field-angle resolved measurements widely used to identify the angular structure of the superconducting gap.

Spin fluctuations and the peak-dip-hump feature in the photoemission spectrum of actinides.

We present first-principles multiband spin susceptibility calculations within the random-phase approximation for four isostructural superconducting PuCoIn{5}, PuCoGa{5}, PuRhGa{5}, and nonsuperconducting UCoGa{5} actinides. The results show that a strong peak in the spin-fluctuation dressed self-energy is present around 0.5 eV in all materials, which is mostly created by 5f electrons. These fluctuations couple to the single-particle spectrum and give rise to a peak-dip-hump feature, characteristic of the coexistence of itinerant and localized electronic states. Results are in quantitative agreement with photoemission spectra. Finally, we show that the studied actinides can be understood within the rigid-band filling approach, in which the spin-fluctuation coupling constant follows the same materials dependence as the superconducting transition temperature T{c}.