H-F cross-polarization magic angle spinning dynamic nuclear polarization NMR investigation of advanced pharmaceutical formulations.

A new 3.2 mm H-F-X magic angle spinning dynamic nuclear polarization NMR (MAS DNP-NMR) probe was developed with a unique coil design with separate radiofrequency channels for H excitation and C or F detection to enable acquisition of H-F cross-polarization (CP) MAS experiments, direct-detected F spectra with proton decoupling, and acquisition on C with simultaneous double decoupling on the H and 19F channels as well as H-F-C double-CP experiments under low temperature MAS DNP conditions. We use these sequences to study AZD2811, which is an active pharmaceutical ingredient (API), in its pure dry state as well as in its corresponding drug delivery formulation consisting of drug-loaded polymeric nanoparticles (PNPs).

Efficient DNP at high fields and fast MAS with antenna-sensitized dinitroxides.

Dynamic Nuclear Polarization (DNP) can significantly enhance the sensitivity of solid-state NMR. In DNP, microwave irradiation induces polarization transfer from unpaired electron spins to H nuclear spins hyperfine couplings and spin-diffusion. The structure of the polarizing agents that host the electron spins is key for DNP efficiency.

Prognostic Impact of High-Molecular-Weight von Willebrand Factor Multimer Ratio in Classical Low-Flow Low-Gradient Aortic Stenosis.

Introduction: High-molecular-weight (HMW) von Willebrand factor (VWF) multimer deficiency occurs in classical low-flow, low-gradient (LF/LG) aortic stenosis (AS) due to shear force-induced proteolysis. The prognostic value of HMW VWF multimer deficiency is unknown. Therefore, we sought to evaluate the impact of HMW VWF multimer deficiency on clinical outcome.

Radiological Parameters for the Detection of Pulmonary Hypertension in Severe Aortic Valve Stenosis and Their Influence on Mortality: Does Sex Matter?

Echocardiography has long been established as the primary noninvasive method for diagnosing pulmonary hypertension (PH) prior to transcatheter aortic valve replacement (TAVR) in patients with severe aortic valve stenosis (AS). In recent years, radiological methods for diagnosing PH have been investigated. Measurements such as the computed tomography angiography (CTA)-derived pulmonary artery (PA) diameter and PA diameter/body surface area (PA/BSA) have shown promising results regarding their diagnostic strength.

Sustainable and cost-effective MAS DNP-NMR at 30 K with cryogenic sample exchange.

We report here instrumental developments to achieve sustainable, cost-effective cryogenic Helium sample spinning in order to conduct dynamic nuclear polarisation (DNP) and solid-state NMR (ssNMR) at ultra-low temperatures (<30 K). More specifically, we describe an efficient closed-loop helium system composed of a powerful heat exchanger (95% efficient), a single cryocooler, and a single helium compressor to power the sample spinning and cooling. The system is integrated with a newly designed triple-channel NMR probe that minimizes thermal losses without compromising the radio frequency (RF) performance and spinning stability (±0.

Chemical and biological differences between original and mimetic pentosan polysulfates.

Pentosan polysulfate sodium (PPS) is a semi-synthetic, heparin-like polysaccharide with manifold therapeutic actions. It is approved for treatment of bladder pain syndrome / interstitial cystitis in humans and treatment of musculoskeletal diseases in animals. PPS is produced by a complex procedure using beech wood as starting material.

Impact of pacing mode and different echocardiographic parameters on cardiac output (PADIAC).

Introduction: The extent of the hemodynamic benefit from AV-synchronous pacing in patients with sinus rhythm and AV block is not completely understood. Thus, we systematically investigated the association of an array of echocardiographic and epidemiological parameters with the change in cardiac output depending on the stimulation mode (AV-synchronous or AV-asynchronous pacing).

Methods: Patients in sinus rhythm after previous dual chamber pacemaker implantation underwent a thorough basic echocardiographic assessment of diastolic and systolic left ventricular function, and atrial function (26 echo parameters, including novel speckle tracking strain measurements).

The Presence of Ascending Aortic Dilatation in Patients Undergoing Transcatheter Aortic Valve Replacement Is Negatively Correlated with the Presence of Diabetes Mellitus and Does Not Impair Post-Procedural Outcomes.

Unlabelled: Both relevant aortic valve stenosis (AS) and aortic valve insufficiency significantly contribute to structural changes in the ascending aorta (AA) and thus to its dilatation. In patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), survival data regarding aortic changes and laboratory biomarker analyses are scarce.

Methods: A total of 179 patients with severe AS and an available computed tomography were included in this retrospective study.

NT-pro-BNP as a Predictor for Recurrence of Atrial Fibrillation after Primary Cryoballoon Pulmonary Vein Isolation.

NT-pro-BNP is produced in the cardiac atria and ventricles in response to increased wall stress. It may be a marker of both AF disease progression and co-morbidities that affect success after pulmonary vein isolation (PVI). This single-center retrospective study analyzed the association between pre-procedural NT-pro-BNP serum levels and the long-term outcome after a first-ever PVI in cryo-technique.

On the authenticity of Beethoven's skull fragments from the estate of Prof. Dr. Romeo Seligmann.

On the occasion of the reburial of Beethoven's mortal remains in 1863, skull fragments are said to have come into the possession of Prof. Dr. Seligmann, who was present at that time and had conducted scientific investigations.

Comparability between Computed Tomography Morphological Vascular Parameters and Echocardiography for the Assessment of Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis-Results of a Multi-Center Study.

Background: Computed tomography (CT) of the aorta and cardiac vessels, which is performed in patients with severe aortic valve stenosis (AS) before transcatheter aortic valve replacement (TAVR), offers the possibility of non-invasive detection of pulmonary hypertension (PH), for example, by determining the diameter of the main pulmonary artery (PA), the right pulmonary artery (RPA) or the left pulmonary artery (LPA). An improvement of the significance of these radiological parameters is often achieved by indexing to the body surface area (BSA). The aim of this study was to compare different echocardiographic systolic pulmonary artery pressure (sPAP) values with radiological data in order to define potential clinical cut-off values for the presence or absence of PH.

CT-Diagnosed Sarcopenia and Cardiovascular Biomarkers in Patients Undergoing Transcatheter Aortic Valve Replacement: Is It Possible to Predict Muscle Loss Based on Laboratory Tests?-A Multicentric Retrospective Analysis.

Background: Patients with severe aortic valve stenosis (AS) often present with heart failure and sarcopenia. Sarcopenia, described as progressive degradation of skeletal muscle mass, has frequently been implicated as a cause of increased mortality, prolonged hospitalization and generalized poor outcome after transcatheter aortic valve replacement (TAVR). At present, sarcopenia is defined by the European Working Group on Sarcopenia in Older People (EWGSOP) based on clinical examination criteria and radiological imaging.

Empagliflozin in acute myocardial infarction: the EMMY trial.

Aims: Sodium-glucose co-transporter 2 inhibition reduces the risk of hospitalization for heart failure and for death in patients with symptomatic heart failure. However, trials investigating the effects of this drug class in patients following acute myocardial infarction are lacking.

Methods And Results: In this academic, multicentre, double-blind trial, patients (n = 476) with acute myocardial infarction accompanied by a large creatine kinase elevation (>800 IU/L) were randomly assigned to empagliflozin 10 mg or matching placebo once daily within 72 h of percutaneous coronary intervention.

Main pulmonary artery diameter in combination with cardiovascular biomarkers: new possibilities to identify pulmonary hypertension in patients with severe aortic valve stenosis.

Background: Echocardiography is currently the noninvasive method of choice to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). However, radiological options are also available by determining the main pulmonary artery (MPA) diameter in the setting of CT angiography. The aim of the present study was to compare cardiovascular biomarkers with the MPA diameter to allow other ways of detecting PH in patients with severe AS.

Systolic Pulmonary Artery Pressure and Cardiovascular Biomarkers-New Non-Invasive Ways to Detect Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis Undergoing TAVR?

Background: Patients with severe aortic valve stenosis (AS) frequently present with pulmonary hypertension (PH). The gold standard for detection of pulmonary hypertension is right heart catheterization, which is not routinely performed as a preoperative standard in cardiology centers today, neither before surgical valve replacement nor before transcatheter aortic valve replacement (TAVR) procedure. Echocardiographic determination of systolic pulmonary artery pressure (sPAP) provides an opportunity to assess the presence or absence of PH.

Pentosan Polysulfate Inhibits Attachment and Infection by SARS-CoV-2 In Vitro: Insights into Structural Requirements for Binding.

Two years since the outbreak of the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, there remain few clinically effective drugs to complement vaccines. One is the anticoagulant, heparin, which in 2004 was found able to inhibit invasion of SARS-CoV (CoV-1) and which has been employed during the current pandemic to prevent thromboembolic complications and moderate potentially damaging inflammation. Heparin has also been shown experimentally to inhibit SARS-CoV-2 attachment and infection in susceptible cells.

Delayed Total Atrioventricular Block After Transcatheter Aortic Valve Replacement Assessed by Implantable Loop Recorders.

Objectives: The aims of this study were to evaluate the rate and time course of delayed total atrioventricular block (DT-AVB) after transcatheter aortic valve replacement (TAVR) using continuous electrocardiographic monitoring by implantable loop recorders and to identify potential predictors.

Background: DT-AVB has been defined as onset more than 2 days after TAVR or after hospital discharge and is reported in 10% to 15% of patients at 30-day follow-up. To date, there is no standardized diagnostic and therapeutic algorithm to manage TAVR patients at risk for DT-AVB.

Tumor necrosis factor alpha-an underestimated risk predictor in patients undergoing transcatheter aortic valve replacement (TAVR)?

Background: Systemic inflammation has been identified as a major cardiovascular risk factor in patients undergoing transcatheter aortic valve replacement (TAVR), yet currently, it is not adequately portrayed in scores for pre-interventional risk assessment. The aim of this study was to investigate the predictive ability of TNF-α in TAVR.

Methods: A total of 431 patients undergoing transfemoral TAVR were enrolled in this study.

Beethoven's death-the result of medical malpractice?

Two different strands of hair taken from Beethoven's head after his death were examined for heavy metals using scanning electron microscopy (SEM) and laser ablation-ICP-MS (inductively coupled plasma-mass spectroscopy). The results revealed the presence of small lead particles on the surface of Beethoven's hairs and fluctuating lead levels in hair medulla along the length of the hair due to alternating lead exposure, with an average lead exposure of 100 times the normal value. The time-line attached to the peaks of these fluctuating values correlate with the pneumonia treatment and the paracenteses performed, including the subsequent treatment of the procedure wounds.

Remote ischemic preconditioning does not induce activation of Akt and STAT5 in the rat heart.

Remote ischemic preconditioning (RIPC) is hypothesized to be a promising cardioprotective strategy to protect hearts against ischemia and reperfusion (I/R) injury; however, the current understanding of the underlying signal transduction pathways involved remains unclear. It has been previously demonstrated that protein kinase B/AKT, which is a crucial protein of the reperfusion injury salvage kinases pathway, and STAT5, which is a member of the survivor activating factor enhancement pathway, serve a pivotal role in cardioprotection. However, whether and at what time-points (TPs) RIPC leads to the activation of AKT and STAT5 in a rat model of RIPC and I/R injury remains to be determined.

Intraprocedural dynamics of cardiac conduction during transcatheter aortic valve implantation: Assessment by simultaneous electrophysiological testing.

Background: Transcatheter aortic valve implantation (TAVI) is an established treatment for patients with severe aortic stenosis and high to intermediate surgical risk. However, the proximity of the conduction system to the prosthesis landing zone bears the risk of atrioventricular conduction disorders. The underlying pathophysiology is not fully understood.

Cardiac Computed Tomography-Derived Left Atrial Volume Index as a Predictor of Long-Term Success of Cryo-Ablation in Patients With Atrial Fibrillation.

Patients with symptomatic, drug-refractory atrial fibrillation (AF) are frequently treated with catheter ablation. Cryo-ablation has been established as an alternative to radiofrequency ablation but long-term outcome data are still limited. This study aimed at elucidating the influence of the left atrial volume index (LAVI), derived from cardiac computed tomography (cCT) data, on the long-term outcome of ablation-naïve AF patients, after their first cryo-ablation.

Dynamic Nuclear Polarization Enhancement of 200 at 21.15 T Enabled by 65 kHz Magic Angle Spinning.

Solid-state nuclear magnetic resonance under magic angle spinning (MAS) enhanced with dynamic nuclear polarization (DNP) is a powerful approach to characterize many important classes of materials, allowing access to previously inaccessible structural and dynamic parameters. Here, we present the first DNP MAS experiments using a 0.7 mm MAS probe, which allows us to reach spinning frequencies of 65 kHz, with microwave irradiation, at 100 K.