Temporal and spatial changes in wall shear stress during atherosclerotic plaque progression in mice

Wall shear stress (WSS) is involved in atherosclerotic plaque initiation, yet its role in plaque progression remains unclear. We aimed to study (i) the temporal and spatial changes in WSS over a growing plaque and (ii) the correlation between WSS and plaque composition, using animal-specific data in an atherosclerotic mouse model. Tapered casts were placed around the right common carotid arteries (RCCA) of ApoE−/− mice. At 5, 7 and 9 weeks after cast placement, RCCA geometry was reconstructed using contrast-enhanced micro-CT. Lumen narrowing was observed in all mice, indicating the progression of a lumen intruding plaque. Next, we determined the flow rate in the RCCA of each mouse using Doppler Ultrasound and computed WSS at all time points. Over time, as the plaque developed and further intruded into the lumen, absolute WSS significantly decreased. Finally at week 9, plaque composition was histologically characterized. The proximal part of the plaque was small and eccentric, exposed to relatively lower WSS. Close to the cast a larger and concentric plaque was present, exposed to relatively higher WSS. Lower WSS was significantly correlated to the accumulation of macrophages in the eccentric plaque. When pooling data of all animals, correlation between WSS and plaque composition was weak and no longer statistically significant. In conclusion, our data showed that in our mouse model absolute WSS strikingly decreased during disease progression, which was significantly correlated to plaque area and macrophage content. Besides, our study demonstrates the necessity to analyse individual animals and plaques when studying correlations between WSS and plaque composition

Contrast-enhanced micro-CT imaging in murine carotid arteries: A new protocol for computing wall shear stress

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 atheroscleroti

Defects in Thick Composites and Some Methods to Locate Them

Nondestructive evaluation (NDE) of thick composites is a difficult task. If ultrasonic techniques are used, such factors as attenuation (preferentially high frequencies); dispersion which causes the ultrasonic wave to change shape as it propagates in the composite; anisotropy (sound velocity a function of direction); material variation (inhomogeneities in composition); and transducer beam spread must be taken into account. Radiographic techniques depend on density differences to produce images. However, in many instances, the density differences produced by defects in composites are not great with the result that many defects go unnoticed. Thermography and shearography are two relatively new NDE techniques but heat flow considerations (for thermography) and stressing a large-thick composite structure sufficiently (for shearography) limit the application of these methods. Regardless of the technique used, the two principal aspects of NDE in a manufacturing environment are defect location and defect sizing.</p

The scaling infrared DSE solution as a critical end-point for the family of decoupling ones

Both regular (the zero-momentum ghost dressing function not diverging), also named decoupling, and critical (diverging), also named scaling, Yang-Mills propagators solutions can be obtained by analyzing the low-momentum behaviour of the ghost propagator Dyson-Schwinger equation (DSE) in Landau gauge. The asymptotic expression obtained for the regular or decoupling ghost dressing function up to the order ${\cal O}(q^2)$ fits pretty well the low-momentum ghost propagator obtained through the numerical integration of the coupled gluon and ghost DSE in the PT-BFM scheme. Furthermore, when the size of the coupling renormalized at some scale approaches some critical value, the PT-BFM results seems to tend to the the scaling solution as a limiting case.Comment: Presented in QCSHS09; Madrid (Spain), 30 Aug. 201

The effect of the heart rate lowering drug Ivabradine on hemodynamics in atherosclerotic mice

The heart rate lowering drug Ivabradine was shown to improve cardiac outcome in patients with previous heart failure. However, in patients without heart failure, no beneficial effect of Ivabradine was observed. Animal studies suggested a preventive effect of Ivabradine on atherosclerosis which was due to an increase in wall shear stress (WSS), the blood flow-induced frictional force exerted on the endothelium, triggering anti-inflammatory responses. However, data on the effect of Ivabradine on WSS is sparse. We aim to study the effect of Ivabradine on (i) the 3D WSS distribution over a growing plaque and (ii) plaque composition. We induced atherosclerosis in ApoE−/− mice by placing a tapered cast around the right common carotid artery (RCCA). Five weeks after cast placement, Ivabradine was administered via drinking water (15 mg/kg/day) for 2 weeks, after which the RCCA was excised for histology analyses. Before and after Ivabradine treatment, animals were imaged with Doppler Ultrasound to measure blood velocity. Vessel geometry was obtained using contrast-enhanced micro-CT. Time-averaged WSS during systole, diastole and peak WSS was subsequently computed. Ivabradine significantly decreased heart rate (459 ± 28 bpm vs. 567 ± 32 bpm, p < 0.001). Normalized peak flow significantly increased in the Ivabradine group (124.2% ± 40.5% vs. 87.3% ± 25.4%, p < 0.05), reflected by an increased normalized WSS level during systole (110.7% ± 18.4% vs. 75.4% ± 24.6%, p < 0.05). However, plaque size or composition including plaque area, relative necrotic core area and macrophage content were not altered in mice treated with Ivabradine compared to controls. We conclude that increased WSS in response to Ivabradine treatment did not affect plaque progression in a murine model

Imaging of atherosclerosis, targeting LFA-1 on inflammatory cells with 111In-DANBIRT

Background: 111In-DOTA-butylamino-NorBIRT (DANBIRT) is a novel radioligand which binds to Leukocyte Function-associated Antigen-1 (LFA-1), expressed on inflammatory cells. This study evaluated 111In-DANBIRT for the visualization of atherosclerotic plaque inflammation in mice. Methods and Results: ApoE−/− mice, fed an atherogenic diet up to 20 weeks (n = 10), were imaged by SPECT/CT 3 hours post injection of 111In-DANBIRT (~ 200 pmol, ~ 40 MBq). Focal spots of 111In-DANBIRT were visible in the aortic arch of all animals, with an average Target-to-Background Ratio (TBR) of 1.7 ± 0.5. In vivo imaging results were validated by ex vivo SPECT/CT imaging, with a TBR up to 11.5 (range 2.6 to 11.5). Plaques, identified by Oil Red O lipid-staining on excised arteries, co-localized with 111In-DANBIRT uptake as determined by ex vivo autoradiography. Subsequent histological processing and in vitro autoradiography confirmed 111In-DANBIRT uptake at plaque areas containing CD68 expressing macrophages and LFA-1 expressing inflammatory cells. Ex vivo incubation of a human carotid endarterectomy specimen with 111In-DANBIRT (~ 950 nmol, ~ 190 MBq) for 2 hours showed heterogeneous plaque uptake on SPECT/CT, after which immunohistochemical analysis demonstrated co-localization of 111In-DANBIRT uptake and CD68 and LFA-1 expressing cells. Conclusions: Our results indicate the potential of radiolabeled DANBIRT as a relevant imaging radioligand for non-invasive evaluation of atherosclerotic inflammation

Characteristics and health outcomes associated with activation for self-management in patients with non-specific low back pain: A cross-sectional study

Background: Research has shown that the course of non-specific low back pain (LBP) is influenced by, among other factors, patients' self-management abilities. Therefore, clinical guidelines recommend stimulation of self-management. Enhancing patients' self-management potentially can improve patients’ health outcomes and reduce future healthcare costs for non-specific LBP. Objectives: Which characteristics and health outcomes are associated with activation for self-management in patients with non-specific LBP? Design: Cross-sectional study. Method: Patients with non-specific LBP applying for primary care physiotherapy were asked to participate. Multivariable linear regression analysis was performed to analyze the multivariable relationship between activation for self-management (Patient Activation Measure, range 0–100) and a range of characteristics, e.g., age, gender, and health outcomes, e.g., self-efficacy, pain catastrophizing. Results: The median activation for self-management score of the patients with non-specific LBP (N = 208) was 63.10 (IQR = 19.30) points. The multivariable linear regression analysis revealed that higher self-efficacy scores (B = 0.54), female gender (B = 3.64), and a middle educational level compared with a high educational level (B = −5.47) were associated with better activation for self-management in patients with non-specific LBP. The goodness-of-fit of the model was 17.24% (R2 = 0.17). Conclusions: Patients with better activation for self-management had better self-efficacy, had a higher educational level, and were more often female. However, given the explained variance better understanding of the factors that influence the complex construct of self-management behaviour in patients who are not doing well might be needed to identify possible barriers to engage in self-management

Psychosocial developmental milestones of young adult survivors of childhood cancer

Purpose: The study aimed to compare the psychosocial development of young adult survivors of childhood cancer (YACCS) with a norm group of young adults from the general population. Methods: From 2017 to 2020, 558 YACCS (18–30 years, 51% female, 10.9% CNS cancer) who participated in the Dutch Childhood Cancer Survivor Study (DCCSS) LATER cohort (diagnosed 1963–2001) part 2 completed the Course of Life Questionnaire (CoLQ), assessing the achievement of milestones. Items were grouped into the scales autonomy, psychosexual, and social development. Differences between YACCS and norm group were examined with ANOVA and Cohen’s d (CoLQ scales) and with logistic regression analysis and odds ratio (OR) (CoLQ items), for the total group and YACCS of CNS cancer. Results: The total group of YACCS did not report a less favorable psychosocial development than the norm group. YACCS of CNS cancer scored lower than the norm group (p < 0.001) on the scales autonomy (d = − 0.36) and psychosexual (d = − 0.46). Additionally, on half of the items of autonomy (0.25 ≤ OR ≤ 0.34), psychosexual (0.30 ≤ OR ≤ 0.48), and social (0.23 ≤ OR ≤ 0.47) development, YACCS of CNS cancer were less likely (p < 0.01) than the norm group to have achieved the milestones. Conclusion: Overall, psychosocial development of YACCS was as favorable as the norm, but YACCS of CNS cancer were at risk of an unfavorable psychosocial development in all domains. Monitoring psychosocial development should be included in the standards of psychosocial care, especially for CNS cancer patients and survivors, to be able to trace delay. Personalized interventions should be offered to improve the psychosocial development in an early stage