On the propagation of pressure and flow waves through the patient specific arterial system

For pre-operative decision making in cardiovascular surgery, patient-specific physiological data are needed. These data (e.g. pressure, flow and wall shear stress) can be obtained using a computational model of the arterial system. Because of the high computational costs involved with fully three-dimensional models of the total arterial tree, one-dimensional wave propagation models are more suited to provide clinically relevant information. Current models of the arterial system are based on assumptions concerning the frictional and convection forces in the one-dimensional momentum balance that yield an inaccurate representation of the physiological situation. Moreover, the constitutive law, relating the local pressure to the local cross-sectional area, is usually based on purely elastic material properties of the arterial wall, whereas arteries are known to possess viscoelastic properties as well. Furthermore, standard one-dimensional wave propagation methods are based on the assumption of fluid flow through straight or slightly tapered vessels where the velocity component in the radial direction is negligibly small with respect to its axial counterpart. In pathological regions such as stenoses and aneurysms these assumption do not hold. In the current study, a one-dimensional wave propagation model is developed, using an approximate velocity profile function to provide an estimate for the frictional forces and the non-linear term. The resulting wall shear stress and convection forces are compared to the analytical solution for pulsatile flow in a rigid tube showing good agreement. With respect to the arterial wall, a constitutive law, based on the viscoelastic behaviour of the standard linear solid model is introduced, that relates the local cross-sectional area of the vessel lumen to the local blood pressure. The resulting one-dimensional wave propagation model is validated by a comparison to data obtained from an experimental setup, modelling fluid flow through straight and tapered polyurethane vessels. In order to apply the one-dimensional wave propagation model to patient-specific arterial systems, a bifurcation model is implemented to relate the pressure and flow of the parent artery to the pressure and flow of the child arteries. Also, terminal impedances based on a three-element Windkessel model are introduced to obtain appropriate boundary conditions at the truncated ends of the arterial network. Furthermore, to accurately model the fluid dynamics near pathological regions, such as stenoses and aneurysms, relations between the pressure drop and flow characteristics as a function of the local geometry are developed. These relations are based on the results of a computational study of blood flow through two-dimensional axisymmetric stenoses and aneurysm models. The final model is applied to an idealised arterial network known from literature to investigate the influence of the different model assumptions made on the pressure, the flow and on the wall shear stress. The pressure and flow waves computed using the approximate velocity profile function, show only moderate changes with respect to those obtained using Poiseuille profiles. The resulting wall shear stress, however, does differ significantly. The introduced viscoelastic properties of the arterial wall are shown to significantly contribute to the pressure and flow wave attenuation and the influence of a femoral stenoses and an abdominal aortic aneurysms has been demonstrated. In conclusion, the resulting one-dimensional wave propagation model can be used to obtain clinically relevant information that may be crucial in surgical planning

NQO2 is a reactive oxygen species generating off-target for acetaminophen

[Image: see text] The analgesic and antipyretic compound acetaminophen (paracetamol) is one of the most used drugs worldwide. Acetaminophen overdose is also the most common cause for acute liver toxicity. Here we show that acetaminophen and many structurally related compounds bind quinone reductase 2 (NQO2) in vitro and in live cells, establishing NQO2 as a novel off-target. NQO2 modulates the levels of acetaminophen derived reactive oxygen species, more specifically superoxide anions, in cultured cells. In humans, NQO2 is highly expressed in liver and kidney, the main sites of acetaminophen toxicity. We suggest that NQO2 mediated superoxide production may function as a novel mechanism augmenting acetaminophen toxicity

Citrulline supplementation improves organ perfusion and arginine availability under conditions with enhanced arginase activity

Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues

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Spectroscopic and biochemical correlations during the course of human lens aging

BACKGROUND: With age, the human lens accumulates variety of substances that absorbs and fluorescence, which explains the color of yellow, brunescent and nigrescent cataract in terms of aging. The aim of this study was to assess lens fluorophores with properties comparable to those of advanced glycated end products (AGEs) in relation to age in human lenses. These fluorescent compounds are believed to be involved in the development of cataract. METHODS: Spectroscopic (UV-Vis-NIR) and fluorescence photography (CCD-Digital based image analysis) studies were carried out in randomly selected intact human lenses (2–85 years). AGE-like fluorophores were also measured in water soluble and insoluble (alkali soluble) fractions of human lenses (20–80 years). RESULTS: Our experimental findings suggest that there was a progressive shift in the absorbance characteristic of intact lens in the range of λ(210 nm)-λ(470 nm). A relative increase in the absorptivity at λ((511–520 nm)), with age, was also observed. In addition, the ratio of absorptivity at λ((511–520 nm)) versus the maximum absorbance recorded at blue-end cut-off (210–470 nm) was also found to increase, with age. The fluorescent intensity in the intact lens at both UV-B (λ(Ex312 nm)) and UV-A (λ(Ex365 nm)) were found to be positively correlated (r(2 )= 0.91 & 0.94, respectively; Confidence interval 95%) upto 50 years of age. In addition, a concomitant changes in AGE- like fluorophores were also observed in the processed lens samples (soluble and insoluble fractions) along the age. A significant increase in the concentration of AGE- like fluorophores, both in intact and processed lens was observed during the period of 40 – 50 years. CONCLUSION: Based on the present investigation, it was concluded that significant changes do occur in the AGE-like fluorophores of human lenses during the period of 40–50 years

Approaches to mixture risk assessment of PFASs in the European population based on human hazard and biomonitoring data

Per- and polyfluoroalkyl substances (PFASs) are a highly persistent, mobile, and bioaccumulative class of chemicals, of which emissions into the environment result in long-lasting contamination with high probability for causing adverse effects to human health and the environment. Within the European Biomonitoring Initiative HBM4EU, samples and data were collected in a harmonized way from human biomonitoring (HBM) studies in Europe to derive current exposure data across a geographic spread. We performed mixture risk assessments based on recent internal exposure data of PFASs in European teenagers generated in the HBM4EU Aligned Studies (dataset with N = 1957, sampling years 2014-2021). Mixture risk assessments were performed based on three hazard-based approaches: the Hazard Index (HI) approach, the sum value approach as used by the European Food Safety Authority (EFSA) and the Relative Potency Factor (RPF) approach. The HI approach resulted in the highest risk estimates, followed by the RPF approach and the sum value approach. The assessments indicate that PFAS exposure may result in a health risk in a considerable fraction of individuals in the HBM4EU teenager study sample, thereby confirming the conclusion drawn in the recent EFSA scientific opinion. This study underlines that HBM data are of added value in assessing the health risks of aggregate and cumulative exposure to PFASs, as such data are able to reflect exposure from different sources and via different routes.This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 733032 HBM4EU (www.HBM4EU.eu), and received co-funding from the au thors’ organizations. The Norwegian Institute of Public Health (NIPH) has contributed to funding of the Norwegian Environmental Biobank (NEB), and the laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465). The PCB cohort (follow-up) received additional funding from the Ministry of Health of the Slovak Republic (program 07B0103).S

Appreciation and implementation of the Krachtvoer healthy diet promotion programme for 12- to 14- year-old students of prevocational schools

<p>Abstract</p> <p>Background</p> <p>Krachtvoer is a school-based healthy diet programme, developed in 2001 and revised in 2007 to meet the needs of particular segments of the target population as well as a wider target group. The main aims of the present process evaluation of the revised programme were to examine student and teacher appreciation of the programme, completeness of and adherence to its implementation, and relations between appreciation and completeness of implementation.</p> <p>Methods</p> <p>Data were collected among 22 teachers and 1117 students of 13 schools, using student evaluation forms, teacher logbooks, telephone interviews, and classroom observations.</p> <p>Results</p> <p>Results indicate favourable levels of teacher and student appreciation for the programme in general and the revised elements. Girls, first-year students and students with more favourable dietary intakes particularly appreciated individual programme elements. Levels of completeness of implementation were high, but several teachers did not adhere to the intended implementation period. Some moderately strong relations were found between teacher appreciation and completeness of implementation scores.</p> <p>Conclusion</p> <p>We conclude that the revisions have resulted in a programme that was appreciated well, also by the extended target group, and was implemented with a high degree of completeness. Teacher appreciation proved potentially important for completeness of implementation. We identified several aspects requiring improvement, indicating the importance of continued programme updates and repeated evaluation.</p