A General Iron-Catalyzed Decarboxylative Oxygenation of Aliphatic Carboxylic Acids.

We report an iron-catalyzed decarboxylative C(sp3)-O bond-forming reaction under mild, base-free conditions with visible light irradiation. The transformation uses readily available and structurally diverse carboxylic acids, iron photocatalyst, and 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) derivatives as oxygenation reagents. The process exhibits a broad scope in acids possessing a wide range of stereoelectronic properties and functional groups. The developed reaction was applied to late-stage oxygenation of a series of bio-active molecules. The reaction leverages the ability of iron complexes to generate carbon-centered radicals directly from carboxylic acids by photoinduced carboxylate-to-iron charge transfer. Kinetic, electrochemical, EPR, UV/Vis, HRMS, and DFT studies revealed that TEMPO has a triple role in the reaction: as an oxygenation reagent, an oxidant to turn over the Fe-catalyst, and an internal base for the carboxylic acid deprotonation. The obtained TEMPO adducts represent versatile synthetic intermediates that were further engaged in C-C and C-heteroatom bond-forming reactions using commercial organo-photocatalysts and nucleophilic reagents.

Time-resolved Fourier-transform infrared spectroscopy reveals the hidden bimolecular process of the ferrioxalate actinometer.

Step-scan Fourier-transform infrared spectroscopy was used to monitor the photochemical reactions following the 266 nm-photolysis of aqueous ferrioxalate solutions on microsecond-to-millisecond time scales. Together with most recent observations from ultrafast infrared spectroscopy the reported results finally disclose the full molecular-level mechanism of a photochemical system that is widely known as the Hatchard-Parker actinometer.

Dynamic VAD simulations: Performing accurate simulations of ventricular assist devices in interaction with the cardiovascular system.

Medical advancements, particularly in ventricular assist devices (VADs), have notably advanced heart failure (HF) treatment, improving patient outcomes. However, challenges such as adverse events (strokes, bleeding and thrombosis) persist. Computational fluid dynamics (CFD) simulations are instrumental in understanding VAD flow dynamics and the associated flow-induced adverse events resulting from non-physiological flow conditions in the VAD.This study aims to validate critical CFD simulation parameters for accurate VAD simulations interacting with the cardiovascular system, building upon the groundwork laid by Hahne et al. A bidirectional coupling technique was used to model dynamic (pulsatile) flow conditions of the VAD CFD interacting with the cardiovascular system. Mesh size, time steps and simulation method (URANS, LES) were systematically varied to evaluate their impact on the dynamic pump performance (dynamic H-Q curve) of the HeartMate 3, aiming to find the optimal simulation configuration for accurately reproduce the dynamic H-Q curve. The new Overlapping Ratio (OR) method was developed and applied to quantify dynamic H-Q curves.In particular, mesh and time step sizes were found to have the greatest influence on the calculated pump performance. Therefore, small time steps and large mesh sizes are recommended to obtain accurate dynamic H-Q curves. On the other hand, the influence of the simulation method was not significant in this study. This study contributes to advancing VAD simulations, ultimately enhancing clinical efficacy and patient outcomes.

Viscosity Modeling for Blood and Blood Analog Fluids in Narrow Gap and High Reynolds Numbers Flows.

For the optimization of ventricular assist devices (VADs), flow simulations are crucial. Typically, these simulations assume single-phase flow to represent blood flow. However, blood consists of plasma and blood cells, making it a multiphase flow. Cell migration in such flows leads to a heterogeneous cell distribution, significantly impacting flow dynamics, especially in narrow gaps of less than 300 µm found in VADs. In these areas, cells migrate away from the walls, forming a cell-free layer, a phenomenon not usually considered in current VAD simulations. This paper addresses this gap by introducing a viscosity model that accounts for cell migration in microchannels under VAD-relevant conditions. The model is based on local particle distributions measured in a microchannels with a blood analog fluid. We developed a local viscosity distribution for flows with particles/cells and a cell-free layer, applicable to both blood and analog fluids, with particle volume fractions of up to 5%, gap heights of 150 µm, and Reynolds numbers around 100. The model was validated by comparing simulation results with experimental data of blood and blood analog fluid flow on wall shear stresses and pressure losses, showing strong agreement. This model improves the accuracy of simulations by considering local viscosity changes rather than assuming a single-phase fluid. Future developments will extend the model to physiological volume fractions up to 40%.

Interaction of a Ventricular Assist Device With Patient-Specific Cardiovascular Systems: In-Silico Study With Bidirectional Coupling.

Ventricular assist devices (VADs) are used to assist the heart function of patients with advanced heart failure. Computational fluid dynamics in VADs are widely applied in the development and optimization, for example, to evaluate blood damage. For these simulations, the pulsating operating conditions, in which the VAD operates, should be included accurately. Therefore, this study aims to evaluate the flow in a VAD by interacting with patient-specific cardiovascular systems of heart failure patients. A numeric method will be presented, which includes a patient-specific cardiovascular system model that is bidirectionally coupled with a three-dimensional (3D) flow simulation of the HeartMate 3. The cardiovascular system is represented by a lumped parameter model. Three heart failure patients are considered, based on clinical data from end-stage heart failure patients. Various parameters of the cardiovascular system and the VAD are analyzed, for example, flow rates, pressures, VAD heads, and efficiencies. A further important parameter is the blood damage potential of the VAD, which varies significantly among different patients. Moreover, the predicted blood damage fluctuates within a single heartbeat. The increase in blood damage is evaluated based on the operating conditions. Both, overload and especially partial load conditions during the pulsating operation result in elevated blood damage.

Effect of Particle Migration on the Stress Field in Microfluidic Flows of Blood Analog Fluids at High Reynolds Numbers.

In the present paper, we investigate how the reductions in shear stresses and pressure losses in microfluidic gaps are directly linked to the local characteristics of cell-free layers (CFLs) at channel Reynolds numbers relevant to ventricular assist device (VAD) applications. For this, detailed studies of local particle distributions of a particulate blood analog fluid are combined with wall shear stress and pressure loss measurements in two complementary set-ups with identical flow geometry, bulk Reynolds numbers and particle Reynolds numbers. For all investigated particle volume fractions of up to 5%, reductions in the stress and pressure loss were measured in comparison to a flow of an equivalent homogeneous fluid (without particles). We could explain this due to the formation of a CFL ranging from 10 to 20 µm. Variations in the channel Reynolds number between Re = 50 and 150 did not lead to measurable changes in CFL heights or stress reductions for all investigated particle volume fractions. These measurements were used to describe the complete chain of how CFL formation leads to a stress reduction, which reduces the apparent viscosity of the suspension and results in the Fåhræus-Lindqvist effect. This chain of causes was investigated for the first time for flows with high Reynolds numbers (Re∼100), representing a flow regime which can be found in the narrow gaps of a VAD.

Efficient Prediction of Mole Fraction Related Vibrational Frequency Shifts.

While so far it has been possible to calculate vibrational spectra of mixtures at a particular composition, we present here a novel cluster approach for a fast and robust calculation of mole fraction dependent infrared and vibrational circular dichroism spectra at the example of acetonitrile/(R)-butan-2-ol mixtures. By assigning weights to a limited number of quantum chemically calculated clusters, vibrational spectra can be obtained at any desired composition by a weighted average of the single cluster spectra. In this way, peak positions carrying information about intermolecular interactions can be predicted. We show that mole fraction dependent peak shifts can be accurately modeled and, that experimentally recorded infrared spectra can be reproduced with high accuracy over the entire mixing range. Because only a very limited number of clusters is required, the presented approach is a valuable and computationally efficient tool to access mole fraction dependent spectra of mixtures on a routine basis.

Problematic Social Media Use and Lifestyle Behaviors in Adolescents: Cross-Sectional Questionnaire Study.

Background: The use of social media by adolescents has increased considerably in the past decade. With this increase in social media use in our daily lives, there has been a rapidly expanding awareness of the potential unhealthy lifestyle-related health effects arising from excessive, maladaptive, or addictive social media use. Objective: This study aims to assess the association between adolescents' social media use and health-related behaviors. Methods: We used a cross-sectional research approach and analyzed data from 96,919 adolescents at high schools throughout the Netherlands. A structured 43-item questionnaire was used to gather data on sociodemographics, dietary and lifestyle factors, and the degree of social media use based on the Compulsive Internet Use Scale. Logistic regression analyses were performed to assess the association between problematic social media use (PSMU) and lifestyle behaviors while adjusting for sociodemographic factors. Results: Of the 96,919 included adolescents, 7.4% (n=7022) were identified as at risk for PSMU. Furthermore, logistic regression results showed that adolescents who are at risk for PSMU were more likely to report alcohol consumption and smoking while simultaneously having significantly lower levels of health-promoting behavior such as healthy eating habits (eating fruits, vegetables, and breakfast regularly) and physical activity. Conclusions: This study confirms that adolescents at risk of PSMU were more likely to exhibit an unhealthy lifestyle. Being at risk for PSMU was a determinant of soft drug use, alcohol consumption, smoking, poor eating habits, and lower physical activity independent of the additional adjusted covariates including demographic variables and remaining lifestyle variables. Future research is needed to confirm this observation in an experimental setting.

Equivalent Scalar Stress Formulation Taking into Account Non-Resolved Turbulent Scales.

PURPOSE: Cardiovascular engineering includes flows with fluid-dynamical stresses as a parameter of interest. Mechanical stresses are high-risk factors for blood damage and can be assessed by computational fluid dynamics. By now, it is not described how to calculate an adequate scalar stress out of turbulent flow regimes when the whole share of turbulence is not resolved by the simulation method and how this impacts the stress calculation. METHODS: We conducted direct numerical simulations (DNS) of test cases (a turbulent channel flow and the FDA nozzle) in order to access all scales of flow movement. After validation of both DNS with literature und experimental data using magnetic resonance imaging, the mechanical stress is calculated as a baseline. Afterwards, same flows are calculated using state-of-the-art turbulence models. The stresses are computed for every result using our definition of an equivalent scalar stress, which includes the influence from respective turbulence model, by using the parameter dissipation. Afterwards, the results are compared with the baseline data. RESULTS: The results show a good agreement regarding the computed stress. Even when no turbulence is resolved by the simulation method, the results agree well with DNS data. When the influence of non-resolved motion is neglected in the stress calculation, it is underpredicted in all cases. CONCLUSION: With the used scalar stress formulation, it is possible to include information about the turbulence of the flow into the mechanical stress calculation even when the used simulation method does not resolve any turbulence.

Influence of turbulent shear stresses on the numerical blood damage prediction in a ventricular assist device.

The blood damage prediction in rotary blood pumps is an important procedure to evaluate the hemocompatibility of such systems. Blood damage is caused by shear stresses to the blood cells and their exposure times. The total impact of an equivalent shear stress can only be taken into account when turbulent stresses are included in the blood damage prediction. The aim of this article was to analyze the influence of the turbulent stresses on the damage prediction in a rotary blood pump's flow. Therefore, the flow in a research blood pump was computed using large eddy simulations. A highly turbulence-resolving setup was used in order to directly resolve most of the computed stresses. The simulations were performed at the design point and an operation point with lower flow rate. Blood damage was predicted using three damage models (volumetric analysis of exceeded stress thresholds, hemolysis transport equation, and hemolysis approximation via volume integral) and two shear stress definitions (with and without turbulent stresses). For both simulations, turbulent stresses are the dominant stresses away from the walls. Here, they act in a range between 9 and 50 Pa. Nonetheless, the mean stresses in the proximity of the walls reach levels, which are one order of magnitude higher. Due to this, the turbulent stresses have a small impact on the results of the hemolysis prediction. Yet, turbulent stresses should be included in the damage prediction, since they belong to the total equivalent stress definition and could impact the damage on proteins or platelets.

Large eddy simulation in a rotary blood pump: Viscous shear stress computation and comparison with unsteady Reynolds-averaged Navier-Stokes simulation.

PURPOSE:: Numerical flow analysis (computational fluid dynamics) in combination with the prediction of blood damage is an important procedure to investigate the hemocompatibility of a blood pump, since blood trauma due to shear stresses remains a problem in these devices. Today, the numerical damage prediction is conducted using unsteady Reynolds-averaged Navier-Stokes simulations. Investigations with large eddy simulations are rarely being performed for blood pumps. Hence, the aim of the study is to examine the viscous shear stresses of a large eddy simulation in a blood pump and compare the results with an unsteady Reynolds-averaged Navier-Stokes simulation. METHODS:: The simulations were carried out at two operation points of a blood pump. The flow was simulated on a 100M element mesh for the large eddy simulation and a 20M element mesh for the unsteady Reynolds-averaged Navier-Stokes simulation. As a first step, the large eddy simulation was verified by analyzing internal dissipative losses within the pump. Then, the pump characteristics and mean and turbulent viscous shear stresses were compared between the two simulation methods. RESULTS:: The verification showed that the large eddy simulation is able to reproduce the significant portion of dissipative losses, which is a global indication that the equivalent viscous shear stresses are adequately resolved. The comparison with the unsteady Reynolds-averaged Navier-Stokes simulation revealed that the hydraulic parameters were in agreement, but differences for the shear stresses were found. CONCLUSION:: The results show the potential of the large eddy simulation as a high-quality comparative case to check the suitability of a chosen Reynolds-averaged Navier-Stokes setup and turbulence model. Furthermore, the results lead to suggest that large eddy simulations are superior to unsteady Reynolds-averaged Navier-Stokes simulations when instantaneous stresses are applied for the blood damage prediction.

Ultrasound in acute internal medicine; time to set a European standard.

Nowadays point-of-care ultrasound (POCUS) is considered indispensable for critical care and emergency physicians. POCUS is a noninvasive tool, can be done at the bedside, leads to instant diagnostic information and is safe in terms of radiation. POCUS could also be very suitable for internists in the field of acute internal medicine. There are differences between European internists in the use of POCUS from no use at all to more outlined educational programs. In literature there are examples of comprehensive POCUS guidelines which could serve as an example for the European Federation of Internal Medicine (EFIM). In this review some aspects of POCUS are highlighted and the authors encourage EFIM to set European standards for this important development.

Uptake of functionalized, fluorescent-labeled polymeric particles in different cell lines and stem cells.

Labeling of cells with particles for in-vivo detection is interesting for various biomedical applications. The objective of this study was to evaluate the feasibility and efficiency labeling of cells with polymeric particles without the use of transfection agents. We hypothesized that surface charge would influence cellular uptake. The submicron particles were synthesized by the miniemulsion process. A fluorescent dye which served as reporter was embedded in these particles. The surface charge was varied by adjusting the amount of copolymerized monomer with amino group thus enabling to study the cellular uptake in correlation to the surface charge. Fluorescent-activated cell sorter (FACS) measurements were performed for detecting the uptake of the particles or attachment of particles in mesenchymal stem cells (MSC), and the three cell lines HeLa, Jurkat, and KG1a. These cell lines were chosen as they can serve as models for clinically interesting cellular targets. For these cell lines-with the exception of MSCs-a clear correlation of surface charge and fluorescence intensity could be shown. For an efficient uptake of the submicron particles, no transfection agents were needed. Confocal laser scanning microscopy and transmission electron microscopy (TEM) revealed differences in subcellular localization of the particles. In MSCs and HeLa particles were mostly located inside of cellular compartments resembling endosomes, while in Jurkat and KG1a, nanoparticles were predominantly located in clusters on the cell surface. Scanning electron microscopy showed microvilli to be involved in this process.