Multiscale modelling of intracranial aneurysm evolution: A novel Patient-specific Fluid-Solid-Growth (p-FSG) framework incorporating endothelial mechanobiology

IAs (intracranial aneurysms) affect 2-5% of the adult population with a high fatality rate upon rupture. However, the rupture rate is around 0.1%-1% per year which indicates most aneurysms are stable. This leads to a strong demand for clinicians to have a better understanding of the aneurysm stability for treatment planning. Aneurysm stability is thought to be linked to its mechanical environment from both the blood flow and the pulsatile pressure giving the mechanistic signals to vascular cells. A cascade of subsequently biological reactions through the routine of cellular mechanotransduction within the aneurysm tissue determine the development of aneurysms. It is envisaged that mechanistic modelling of biological processes that govern aneurysm growth may help to distinguish between vulnerable and stable aneurysms. We developed an integrated Patient-specific Fluid-Solid-Growth (p-FSG) framework for simulating the growth of existing intracranial aneurysms. An aneurysm and connected arteries are modelled as fibre-reinforced nonlinear elastic soft-tissue in the commercial software ANSYS. Computational Fluid Dynamics (CFD) simulation quantifies haemodynamic stimuli that act on endothelial cells. Here, we link the morphology of the cells (spindle, hexagonal) to a novel flow metric (Anisotropic Ratio, AR) that characterizes the oscillatory nature of the flow pattern. We then proposed a hypothesis that the endothelial permeability could be regarded as a function of the morphology of endothelial cells which is associated to the growth and remodelling of the aneurysmal tissue. Mass density of elastin and collagen decreases in the region of high endothelial permeability via the inflammatory pathway. Collagen growth (mass changes) is driven by stretch based stimuli of fibroblast cells. Collagen remodelling employs a stress-mediated method that restores the Cauchy stress on collagen fibres to homeostatic levels in the course of the aneurysm enlargement. Principal destructive and self-protective activities during the aneurysm evolution involving elastin, collagen fibres, endothelial cells and fibroblasts are mathematically represented by our p-FSG framework. Our research suggests that the collagen growth function is a vital mechanism for the stability of aneurysms. This is the first framework models the aneurysm evolution on the basis of the patient-specific aneurysm geometry. Also, we incorporated the functionality of endothelial cells quantified by a novel flow metric to the aneurysm growth and remodelling (G&R) model. This automatic p-FSG framework fully integrated into ANSYS engineering software provides a foundational platform for modelling the aneurysm growth and might become a practical tool in the estimation of aneurysm stability

The Influence of Hierarchical Masks on Masked Repetition Priming: Evidence From Event-Related Potential Investigation

The discussion about relationship between prime and target has contributed to the mechanism of priming effect and object recognition. Nevertheless, the role of relationship between mask and target in those cognitive processes remains unquestioned. In the present study, we aim to investigate how mask-target hierarchical relationship may affect word priming and familiarity, by using the masked repetition paradigm and manipulating three hierarchical relationship between mask and target. It is hypothesized that a closer hierarchical relationship between mask and target is associated with a higher mask target similarity, and thereby it leads to a worse recognition performance. Our behavioral results do not support this hypothesis by showing no effect of mask target hierarchical relationship on response time (RT) and accuracy. Event-related potentials (ERPs) indicated that highly similar mask-target triggered (i.e., the subordinate-subordinate-subordinate trials) larger N1 amplitudes, suggesting that it requires more cognitive resource to discriminate the stimuli. In addition, trials with highly similar mask-target hierarchical relationship induced smaller P2 (150–250 ms) and larger mid-frontal FN400 amplitudes than do trials with low mask-target similarity (i.e., the subordinate-basic-subordinate and the subordinate-superordinate-subordinate trials). Our results suggested that the similarity between mask and target may impede conceptual fluency to reduce word priming and familiarity effect

Production, purification and characterization of novel beta glucosidase from newly isolated Penicillium simplicissimum H-11 in submerged fermentation

β-Glucosidase is an important component of the cellulase complex. It not only hydrolyzes cellobiose and short-chain cellooligos accharides to glucose, but also removes the inhibitory effect of cellobiose on the β-1, 4-endoglucanase and exoglucanase, thereby increasing the overall rate of cellulose biodegradation. β-glucosidasefrom culture supernatant of a fungus Penicillium simplicissimum was purified to homogeneity, by using ammonium sulfate fraction, Sephadex G-100 chromatography, and its properties were studied. The molecular mass of the enzyme was about 126.0 kDa, as identified by 12% SDS-PAGE. The optimum pH and temperature were 4.4 ~ 5.2 and 60°C, respectively. The enzyme was stable in pH 5.2 ~ 6.4 and under 40°C. Metal profile of the enzyme showed that Mn2+ enhances its activity, while Cu2+, Co2+ and Fe3+ cause obvious inhibition. The Km and Vmax was 14.881 mg/ml and 0.364 mg ml/min against salicin as a Substrate. This enzyme had secondary protein structure as evidenced by FTIR spectrum

Effects of dispersed fibres in myocardial mechanics, Part I: passive response

It is widely acknowledged that an imbalanced biomechanical environment can have significant effects on myocardial pathology, leading to adverse remodelling of cardiac function if it persists. Accurate stress prediction essentially depends on the strain energy function which should have competent descriptive and predictive capabilities. Previous studies have focused on myofibre dispersion, but not on fibres along other directions. In this study, we will investigate how fibre dispersion affects myocardial biomechanical behaviours by taking into account both the myofibre dispersion and the sheet fibre dispersion, with a focus on the sheet fibre dispersion. Fibre dispersion is incorporated into a widely-used myocardial strain energy function using the discrete fibre bundle approach. We first study how different dispersion affects the descriptive capability of the strain energy function when fitting to ex vivo experimental data, and then the predictive capability in a human left ventricle during diastole. Our results show that the chosen strain energy function can achieve the best goodness-of-fit to the experimental data by including both fibre dispersion. Furthermore, noticeable differences in stress can be found in the LV model. Our results may suggest that it is necessary to include both dispersion for myofibres and the sheet fibres for the improved descriptive capability to the ex vivo experimental data and potentially more accurate stress prediction in cardiac mechanics

Health System Barriers and Facilitators to Delivering Additional Vaccines through the National Immunisation Programme in China: A Qualitative Study of Provider and Service-User Perspectives.

In China, there are two categories of vaccines available from the Chinese Center for Disease Control and associated public health agencies. Extended Program of Immunization (EPI) vaccines are government-funded and non-EPI vaccines are voluntary and paid for out-of-pocket. The government plans to transition some non-EPI vaccines to EPI in the coming years, which may burden public health system capacity, particularly in terms of budget, workforce, supply chains, and information systems. Our study explored vaccinator and caregiver perspectives on introducing non-EPI vaccines into routine immunization and perceived facilitators and barriers affecting this transition. We conducted a qualitative study from a realist perspective, analysing semi-structured interviews with 26 vaccination providers and 160 caregivers in three provinces, selected to represent regional socioeconomic disparities across Eastern, Central, and Western China. Data were analysed thematically, using deductive and inductive coding. Most participants were positive about adding vaccines to the national schedule. Candidate EPI vaccines most frequently recommended by participants were varicella, mumps vaccine, and hand-foot-mouth disease. Providers generally considered existing workspaces, cold-chain equipment, and funding sufficient, but described frontline staffing and vaccine information systems as requiring improvement. This is the first qualitative study to explore interest, barriers, and facilitators related to adding vaccines to China's national schedule from provider and caregiver perspectives. Findings can inform government efforts to introduce additional vaccines, by including efforts to retain and recruit vaccine programme staff and implement whole-process data management and health information systems that allow unified nationwide data collection and sharing

Preliminary Evaluation of the Sural Nerve Using 22-MHz Ultrasound: A New Approach for Evaluation of Diabetic Cutaneous Neuropathy

Background: The application of 22-MHz high-frequency ultrasound allows for visualization of the inner part of the sural nerve. The aim of this study was to evaluate the morphological changes of sural nerves in patients with type 2 diabetes mellitus using ultrasound. Materials and Methods: The thickness/width (T/W) ratio, the cross-sectional area (CSA) of the sural nerves and the maximum thickness (MT) of the nerve fascicles were measured in 100 patients with type 2 diabetes mellitus and 50 healthy volunteers using 22-MHz ultrasound. Receiver operating characteristic (ROC) curves were plotted to determine the optimal cut-off values as well as the sensitivities and specificities. All parameters were significantly different between the subject and control groups. The ROC curves demonstrated that the MT was the most predictive of diabetic cutaneous neuropathy, with an optimal cut-off value of 0.365 mm that yielded a sensitivity of 90.3 % and a specificity of 87.7%. Conclusions: The results of this study suggest that 22-MHz ultrasound may be a valuable tool for evaluating diabeti

On the Validation of a Multiple-Network Poroelastic Model Using Arterial Spin Labeling MRI Data

The Multiple-Network Poroelastic Theory (MPET) is a numerical model to characterize the transport of multiple fluid networks in the brain, which overcomes the problem of conducting separate analyses on individual fluid compartments and losing the interactions between tissue and fluids, in addition to the interaction between the different fluids themselves. In this paper, the blood perfusion results from MPET modeling are partially validated using cerebral blood flow (CBF) data obtained from arterial spin labeling (ASL) magnetic resonance imaging (MRI), which uses arterial blood water as an endogenous tracer to measure CBF. Two subjects—one healthy control and one patient with unilateral middle cerebral artery (MCA) stenosis are included in the validation test. The comparison shows several similarities between CBF data from ASL and blood perfusion results from MPET modeling, such as higher blood perfusion in the gray matter than in the white matter, higher perfusion in the periventricular region for both the healthy control and the patient, and asymmetric distribution of blood perfusion for the patient. Although the partial validation is mainly conducted in a qualitative way, it is one important step toward the full validation of the MPET model, which has the potential to be used as a testing bed for hypotheses and new theories in neuroscience research