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Introduction: Recently, a mouse model was developed showing spontaneous plaque rupture leading to stroke (ApoE−/−Fbn1C1039G+/− mouse). However, a longitudinal follow-up of these mice was hampered by the lack of an accurate in vivo method to visualize the cerebral vasculature. Methods: In this feasibility study, a female ApoE−/−Fbn1C1039G+/− and an ApoE−/− (control) mouse (stable plaques) were fed a western-type diet for up to 20 weeks. At week 10, 15 and 20 after the start of the diet CT-scans were performed before and after injection of a gold-nanoparticle contrast agent (Aurovist®, Nanoprobes, New York, USA). Image reconstruction was based on the iterative maximum-likelihood polychromatic algorithm, to reconstruct high quality images at 50-μm. Post- and pre- contrast injection images were co-registered and subtracted, using 3Dslicer, resulting in angiographic images. These images were segmented by executing a Frangi vesselness filtering, an isosurface extraction and a geodesic evolution step in VMTK. Results: It was feasible to obtain a 3D-visualisation of the mouse cerebral vasculature (see figures for the ApoE−/−Fbn1C1039G+/−mouse) up to vessels of 0.15 mm diameter. Interestingly, at week 15 and 20 contrast agent from previous injections was still present in plaques (presumably taken up by macrophages), allowing us to determine plaque position and progression over time. More severe stenosis was observed in the ApoE−/−Fbn1C1039G+/−mouse compared to the control mouse. Conclusions: The described in vivo method enabled us to generate detailed 3D reconstructions of the mouse cerebral vasculature, including presence of atherosclerotic plaques. Future work will include numerical models of the blood flow.

Background: Advancements in tomographic medical imaging have revolutionized diagnostics and treatment monitoring by offering detailed 3D visualization of internal structures. Despite the significant value of computed tomography (CT), challenges such as high radiation dosage and cost barriers limit its accessibility, especially in low- and middle-income countries. Recognizing the potential of radiographic imaging in reconstructing CT images, this scoping review aims to explore the emerging field of synthesizing 3D CT-like images from 2D radiographs by examining the current methodologies., Methods: A scoping review was carried out following PRISMA-SR guidelines. Eligibility criteria for the articles included full-text articles published up to September 9, 2024, studying methodologies for the synthesis of 3D CT images from 2D biplanar or four-projection x-ray images. Eligible articles were sourced from PubMed MEDLINE, Embase, and arXiv., Results: 76 studies were included. The majority (50.8 %, n = 30) were published between 2010 and 2020 (38.2 %, n = 29) and from 2020 onwards (36.8 %, n = 28), with European (40.8 %, n = 31), North American (26.3 %, n = 20), and Asian (32.9 %, n = 25) institutions being primary contributors. Anatomical regions varied, with 17.1 % (n = 13) of studies not using clinical data. Further, studies focused on the chest (25 %, n = 19), spine and vertebrae (17.1 %, n = 13), coronary arteries (10.5 %, n = 8), and cranial structures (10.5 %, n = 8), among other anatomical regions. Convolutional neural networks (CNN) (19.7 %, n = 15), generative adversarial networks (21.1 %, n = 16) and statistical shape models (15.8 %, n = 12) emerged as the most applied methodologies. A limited number of studies included explored the use of conditional diffusion models, iterative reconstruction algorithms, statistical shape models, and digital tomosynthesis., Conclusion: This scoping review summarizes current strategies and challenges in synthetic imaging generation. The development of 3D CT-like imaging from 2D radiographs could reduce radiation risk while simultaneously addressing financial and logistical obstacles that impede global access to CT imaging. Despite initial promising results, the field encounters challenges with varied methodologies and frequent lack of proper validation, requiring further research to define synthetic imaging's clinical role., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Background/objectives: Detailed morphometric analysis of an aneurysm and the related vascular bifurcation are critical factors when determining rupture risk and planning treatment for unruptured intracranial aneurysms (UIAs). The standard visualization of digital subtraction angiography (DSA) and its 3D reconstruction on a 2D monitor provide precise measurements but are subject to variability based on the rater. Visualization using virtual (VR) and augmented reality platforms can overcome those limitations. It is, however, unclear whether accurate measurements of the aneurysm and adjacent arterial branches can be obtained on VR models. This study aimed to assess interrater reliability and compare measurements between 3D VR, standard 2D DSA, and 3D DSA reconstructions, evaluating the reliability and accuracy of 3D VR as a measurement tool., Methods: A pool of five neurosurgeons performed three individual analyses on each of the ten UIA cases, measuring them in completely immersed 3D VR and the standard on-screen format (2D DSA and 3D reconstruction). This resulted in three independent measurements per modality for each case. Interrater reliability of measurements and morphology characterization, comparative differences, measurement duration, and VR user experience were assessed., Results: Interrater reliability for 3D VR measurements was significantly higher than for 3D DSA measurements (3D VR mean intraclass correlation coefficient [ICC]: 0.69 ± 0.22 vs. 3D DSA mean ICC: 0.36 ± 0.37, p = 0.042). No significant difference was observed between 3D VR and 2D DSA (3D VR mean ICC: 0.69 ± 0.22 vs. 2D DSA mean ICC: 0.43 ± 0.31, p = 0.12). A linear mixed-effects model showed no effect of 3D VR and 3D DSA (95% CI = -0.26-0.28, p = 0.96) or 3D VR and 2D DSA (95% CI = -0.02-0.53, p = 0.066) on absolute measurements of the aneurysm in the anteroposterior, mediolateral, and craniocaudal dimensions., Conclusions: 3D VR technology allows for reproducible, accurate, and reliable measurements comparable to measurements performed on a 2D screen. It may also potentially improve precision for measurements of non-planar aneurysm dimensions.

Stillbirth is a tragedy that can leave parents feeling powerless and vulnerable. Respectful and supportive bereavement care is essential to reducing adverse psychosocial impact. Initiatives of the Australian Centre of Research Excellence in Stillbirth are designed to improve care after stillbirth. At their heart are the voices of perinatally bereaved parents and support organisations and shared decision making between parents and health care providers. Priorities in future perinatal bereavement care research include ensuring appropriate care for population groups who experience higher rates of stillbirth and addressing implementation challenges to best practice in respectful and supportive bereavement care within our health systems., (Copyright © 2020 Australian College of Midwives. All rights reserved.)

The aim was to compare the effectiveness of dual-task training (DTT) compared to single mobility training (SMT) on dual-task walking, mobility and cognition, in persons with Multiple Sclerosis (pwMS). Forty pwMS were randomly assigned to the DTT or SMT groups. The DTT-group performed dual-task exercises using an interactive tablet-based application, while the SMT-group received conventional walking and balance exercises. Both interventions were supervised and identical in weeks (8) and sessions (20). Nine cognitive-motor dual-task conditions were assessed at baseline, after intervention and at 4-weeks follow-up (FU). The dual-task cost (DTC), percentage change of dual-task performance compared to single-task performance, was the primary outcome. Mobility and cognition were secondarily assessed. Mixed model analyses were done with group, time and the interaction between group and time as fixed factors and participants as random factors. Significant time by group interactions were found for the digit-span walk and subtraction walk dual-task conditions, with a reduction in DTC (gait speed) for the DTT maintained at FU. Further, absolute dual-task gait speed during walking over obstacles only improved after the DTT. Significant improvements were found for both groups in various motor and cognitive measures. However, the DTT led to better dual-task walking compared to the SMT.

Background: Wall shear stress (WSS) is involved in the pathophysiology of atherosclerosis. The correlation between WSS and atherosclerosis can be investigated over time using a WSS-manipulated atherosclerotic mouse model. To determine WSS in vivo, detailed 3D geometry of the vessel network is required. However, a protocol to reconstruct 3D murine vasculature using this animal model is lacking. In this project, we evaluated the adequacy of eXIA 160, a small animal contrast agent, for assessing murine vascular network on micro-CT. Also, a protocol was established for vessel geometry segmentation and WSS analysis., Methods: A tapering cast was placed around the right common carotid artery (RCCA) of ApoE -/- mice (n = 8). Contrast-enhanced micro-CT was performed using eXIA 160. An innovative local threshold-based segmentation procedure was implemented to reconstruct 3D geometry of the RCCA. The reconstructed RCCA was compared to the vessel geometry using a global threshold-based segmentation method. Computational fluid dynamics was applied to compute the velocity field and WSS distribution along the RCCA., Results: eXIA 160-enhanced micro-CT allowed clear visualization and assessment of the RCCA in all eight animals. No adverse biological effects were observed from the use of eXIA 160. Segmentation using local threshold values generated more accurate RCCA geometry than the global threshold-based approach. Mouse-specific velocity data and the RCCA geometry generated 3D WSS maps with high resolution, enabling quantitative analysis of WSS. In all animals, we observed low WSS upstream of the cast. Downstream of the cast, asymmetric WSS patterns were revealed with variation in size and location between animals., Conclusions: eXIA 160 provided good contrast to reconstruct 3D vessel geometry and determine WSS patterns in the RCCA of the atherosclerotic mouse model. We established a novel local threshold-based segmentation protocol for RCCA reconstruction and WSS computation. The observed differences between animals indicate the necessity to use mouse-specific data for WSS analysis. For our future work, our protocol makes it possible to study in vivo WSS longitudinally over a growing plaque.

Background: Low and oscillatory wall shear stresses (WSS) near aortic bifurcations have been linked to the onset of atherosclerosis. In previous work, we calculated detailed WSS patterns in the carotid bifurcation of mice using a Fluid-structure interaction (FSI) approach. We subsequently fed the animals a high-fat diet and linked the results of the FSI simulations to those of atherosclerotic plaque location on a within-subject basis. However, these simulations were based on boundary conditions measured under anesthesia, while active mice might experience different hemodynamics. Moreover, the FSI technique for mouse-specific simulations is both time- and labor-intensive, and might be replaced by simpler and easier Computational Fluid Dynamics (CFD) simulations. The goal of the current work was (i) to compare WSS patterns based on anesthesia conditions to those representing active resting and exercising conditions; and (ii) to compare WSS patterns based on FSI simulations to those based on steady-state and transient CFD simulations., Methods: For each of the 3 computational techniques (steady state CFD, transient CFD, FSI) we performed 5 simulations: 1 for anesthesia, 2 for conscious resting conditions and 2 more for conscious active conditions. The inflow, pressure and heart rate were scaled according to representative in vivo measurements obtained from literature., Results: When normalized by the maximal shear stress value, shear stress patterns were similar for the 3 computational techniques. For all activity levels, steady state CFD led to an overestimation of WSS values, while FSI simulations yielded a clear increase in WSS reversal at the outer side of the sinus of the external carotid artery that was not visible in transient CFD-simulations. Furthermore, the FSI simulations in the highest locomotor activity state showed a flow recirculation zone in the external carotid artery that was not present under anesthesia. This recirculation went hand in hand with locally increased WSS reversal., Conclusions: Our data show that FSI simulations are not necessary to obtain normalized WSS patterns, but indispensable to assess the oscillatory behavior of the WSS in mice. Flow recirculation and WSS reversal at the external carotid artery may occur during high locomotor activity while they are not present under anesthesia. These phenomena might thus influence plaque formation to a larger extent than what was previously assumed., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

It is generally accepted that low and oscillatory wall shear stress favors the initiation and development of atherosclerosis. However, a quantitative analysis of the association between shear stress metrics at baseline and lesion prevalence at a later stage is challenging to perform in vivo on a within-subject basis. In this study, we assessed carotid hemodynamics and derived hemodynamic wall parameters from subject-specific fluid-structure interaction simulations in the left and right carotid arteries of 4 ApoE(-/-) mice prior to disease development. We then applied a point-by-point quantitative association (surrogate sample data analysis) between various established and more recent shear related parameters and the extent of macrophage infiltration at a later stage. We conclude that, for the atherosclerotic murine carotid bifurcation, (i) there is an association between hemodynamics and macrophage infiltration; (ii) this correlation is most apparent when assessed at the level of the entire carotid bifurcation; (iii) the strongest spatial correlation between hemodynamics and atherosclerosis development was found for the time averaged wall shear stress (negative correlation) and the relative residence time (positive correlation); (iv) aggregating the data leads to an overestimation of the correlation.

The ApoE(-)(/)(-) mouse is a common small animal model to study atherosclerosis, an inflammatory disease of the large and medium sized arteries such as the carotid artery. It is generally accepted that the wall shear stress, induced by the blood flow, plays a key role in the onset of this disease. Wall shear stress, however, is difficult to derive from direct in vivo measurements, particularly in mice. In this study, we integrated in vivo imaging (micro-Computed Tomography-µCT and ultrasound) and fluid-structure interaction (FSI) modeling for the mouse-specific assessment of carotid hemodynamics and wall shear stress. Results were provided for 8 carotid bifurcations of 4 ApoE(-)(/)(-) mice. We demonstrated that accounting for the carotid elasticity leads to more realistic flow waveforms over the complete domain of the model due to volume buffering capacity in systole. The 8 simulated cases showed fairly consistent spatial distribution maps of time-averaged wall shear stress (TAWSS) and relative residence time (RRT). Zones with reduced TAWSS and elevated RRT, potential indicators of atherosclerosis-prone regions, were located mainly at the outer sinus of the external carotid artery. In contrast to human carotid hemodynamics, no flow recirculation could be observed in the carotid bifurcation region., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Recently, an apolipoprotein E-deficient (ApoE-/-) mouse model with a mutation (C1039G+/-) in the fibrillin-1 (Fbn1) gene (ApoE-/-Fbn1C1039G+/- mouse model) was developed showing vulnerable atherosclerotic plaques, prone to rupture, in contrast to the ApoE-/- mouse model, where mainly stable plaques are present. One indicator of plaque vulnerability is the level of macrophage infiltration. Therefore, this study aimed to measure and quantify in vivo the macrophage infiltration related to plaque development and progression. For this purpose, 5-weekly consecutive gold nanoparticle-enhanced micro-computed tomography (microCT) scans were acquired. Histology confirmed that the presence of contrast agent coincided with the presence of macrophages. Based on the microCT scans, regions of the artery wall with contrast agent present were calculated and visualized in three dimensions. From this information, the contrast-enhanced area and contrast-enhanced centerline length were calculated for the branches of the carotid bifurcation (common, external, and internal carotid arteries). Statistical analysis showed a more rapid development and a larger extent of plaques in the ApoE-/-Fbn1C1039G+/- compared to the ApoE-/- mice. Regional differences between the branches were also observable and quantifiable. We developed and applied a methodology based on gold particle-enhanced microCT to visualize the presence of macrophages in atherosclerotic plaques in vivo.

: Microbial fermentations are of major importance in the field of biotechnology. The range of applications is rather extensive, for example, the production of vaccines, recombinant proteins, and plasmids. During the past decades single-use bioreactors have become widely accepted in the biopharmaceutical industry. This acceptance is due to the several advantages these bioreactors offer, such as reduced operational and investment costs. Although this technology is attractive for microbial applications, its usage is rarely found. The main limitations are a relatively low oxygen transfer rate and cooling capacity. The aim of this study was to examine a stirred single-use bioreactor for its microbial suitability. Therefore, the important process engineering parameters volumetric mass transfer coefficient (k L a), mixing time, and the heat transfer coefficient were determined. Based on the k L a characteristics a mathematical model was established that was used with the other process engineering parameters to create a control space. For a further verification of the control space for microbial suitability, Escherichia coli and Pichia pastoris high cell density fermentations were carried out. The achieved cell density for the E. coli fermentation was OD600 = 175 (DCW = 60.8 g/L). For the P. pastoris cultivation a wet cell weight of 381 g/L was reached. The achieved cell densities were comparable to fermentations in stainless steel bioreactors. Furthermore, the expression of recombinant proteins with titers up to 9 g/L was guaranteed.

Due to the growing shortage of donor livers, more patients are waiting for transplantation. Living donor liver transplantation may help expanding the donor pool, but is often confronted with the small-for-size syndrome. Since the hemodynamic effects of partial hepatectomy are not fully understood, we developed an electrical rat liver model to compare normal with resected liver hemodynamics. Detailed geometrical data and 3-D reconstructions of the liver vasculature of two rats were gathered by combining vascular corrosion casting, micro-CT scanning, and image processing. Data extrapolations allowed obtaining a total liver pressure- and flow-driven electrical analog. Subsequently, virtual resections led to 70%, 80%, or 90% partial hepatectomy models. Results demonstrated hyperperfusion effects such as portal hypertension and elevated lobe-specific portal venous flows (11, 12, and 24 mmHg, and 1.0-3.0, 1.8-3.5, and 7.4 ml/min for 70%, 80%, and 90% hepatectomy, respectively). Comparison of two 90% resection techniques demonstrated different total arterial flows (0.28 ml/min versus 0.61 ml/min), portal (24 mmHg versus 21 mmHg), and sinusoidal pressures (14 mmHg versus 9.5-12 mmHg), probably leading to better survival for lower portal and sinusoidal pressures. Toward the future, the models may be extrapolated to human livers and help us to optimize hepatectomy planning.

The present study investigates the validity of one of the key assumptions underlying the general plate height model of chromatography, i.e., the presumed independency of the individual band broadening contributions. More precisely, it is investigated under which conditions the mass transfer inside the stationary zone (e.g., porous pillars) is independent from the axial transport of species outside this zone, and how strongly any such dependency would affect the validity of the general plate height model of chromatography. For this purpose, detailed calculations of the species concentration distribution inside and outside the porous pillars of a computer-mimic of a porous pillar array column have been made. These simulations revealed a clear interplay between the mass transfer inside and outside the pillars, manifesting itself as an asymmetry of the species concentration distribution inside the pillars. The latter is in disagreement with the basic assumption used to calculate the value of the C(s)-term of the general plate height model. The asymmetry-effect is largest at low reduced velocities, high retention factors and high intra-pillar diffusion coefficients. Fortunately, these are conditions where the C(s)-term is relatively small, which might explain why the general plate height model of chromatography (and based on the symmetry assumption) can represent the band broadening in a porous pillar array within an accuracy on the order of some 1-2%., (Copyright 2010 Elsevier B.V. All rights reserved.)

The band broadening that can be expected in perfectly ordered cylindrical pillar arrays has been calculated for a wide range of intra-particle diffusion coefficients (D(sz)) and zone retention factors (0

Stem cells derived from midguts of the caterpillar, Spodoptera littoralis, can be induced to multiply and differentiate in vitro. Ecdysone (E) and 20-hydroxyecdysone (20E) had a concentration-dependent effect: E was more active in cell proliferation and 20E in differentiation. Ecdysteroid receptors in midgut stem cell nuclei were stained with the antibody 9B9. In addition, alpha-arylphorin and four midgut differentiation factors (MDF) specifically stimulated proliferation and differentiation of stem cells, respectively. The activity of a panel of peptide growth factors and hormones on growth and metamorphosis of the insect midgut is discussed.

Pheochromocytomas produce, store and secrete catecholamines. Diagnosis is often suspected in young patients with severe hypertension. We present the case of a 47-year-old woman without a previous history of hypertension, whose initial presentation was cardiovascular shock. Despite early diagnosis of the disease, the fulminant evolution of the pheochromocytoma crisis was fatal a few hours after admission. Only a few therapeutic options remain when haemodynamic collapse is catecholamine induced.

The utility of a new target gene (fem-3) is described for investigating the molecular nature of mutagenesis in the nematode Caenorhabditis elegans. As a principal attribute, this system allows for the selection, maintenance and molecular analysis of any type of mutation that disrupts the gene, including deletions. In this study, 86 mutant strains were isolated, of which 79 proved to have mutations in fem-3. Twenty of these originally tested as homozygous inviable. Homozygous inviability was expected, as Stewart and coworkers had previously observed that, unlike in other organisms, most UV radiation-induced mutations in C. elegans are chromosomal rearrangements of deficiencies (Mutat. Res. 249, 37-54, 1991). However, additional data, including Southern blot analyses on 48 of the strains, indicated that most of the UV radiation-induced fem-3 mutations were not deficiencies, as originally inferred from their homozygous inviability. Instead, the lethals were most likely "coincident mutations" in linked, essential genes that were concomitantly induced. As such, they were lost owing to genetic recombination during stock maintenance. As in mammalian cells, yeast and bacteria, the frequency of coincident mutations was much higher than would be predicted by chance.