Microfluidic human physiomimetic liver model as a screening platform for drug induced liver injury.

The pre-clinical animal models often fail to predict intrinsic and idiosyncratic drug induced liver injury (DILI), thus contributing to drug failures in clinical trials, black box warnings and withdrawal of marketed drugs. This suggests a critical need for human-relevant in vitro models to predict diverse DILI phenotypes. In this study, a porcine liver extracellular matrix (ECM) based biomaterial ink with high printing fidelity, biocompatibility and tunable rheological and mechanical properties is formulated for supporting both parenchymal and non-parenchymal cells. Further, we applied 3D printing and microfluidic technology to bioengineer a human physiomimetic liver acinus model (HPLAM), recapitulating the radial hepatic cord-like structure with functional sinusoidal microvasculature network, biochemical and biophysical properties of native liver acinus. Intriguingly, the human derived hepatic cells incorporated HPLAM cultured under physiologically relevant microenvironment, acts as metabolic biofactories manifesting enhanced hepatic functionality, secretome levels and biomarkers expression over several weeks. We also report that the matured HPLAM reproduces dose- and time-dependent hepatotoxic response of human clinical relevance to drugs typically recognized for inducing diverse DILI phenotypes as compared to conventional static culture. Overall, the developed HPLAM emulates in vivo like functions and may provide a useful platform for DILI risk assessment to better determine safety and human risk.

Evaluation of mixing performance and validation of CFD simulations in baffled anaerobic digesters using radiotracer technique.

The anaerobic digesters find usage in treating the huge amount of waste such as trash, garbage, human waste and animal waste. The sustained performance of an anaerobic digester depends on the flow pattern and mixing behaviour in the digester. A cylindrical digester tank with vertical baffles can provide flow behaviour approaching that of a plug flow reactor. However, the presence of dead zones and recirculating regions cause non-ideal flow in the digester. In this work, the mixing behaviour in two scaled-down models of baffled digester tanks is characterized by measurement of residence time distribution (RTD) using a radioactive tracer. While the first design has three vertical baffles, the second design include horizontal static flaps on the baffles. The flow behaviour in the digester is also simulated using computational fluid dynamics (CFD) and RTD is obtained computationally. The comparison of RTD curves obtained from CFD simulations with those obtained from radiotracer experiments show good agreement between them. There appear to be only minor difference in the flow behaviour and the RTD curves in the two digester designs. Using the RTD curve data, two commonly used RTD models, tank-in-series and dispersion models, have been fitted and both models are able to predict the RTD in the digester qualitatively.

Flow and Particle Modelling of Dry Powder Inhalers: Methodologies, Recent Development and Emerging Applications.

Dry powder inhaler (DPI) is a device used to deliver a drug in dry powder form to the lungs. A wide range of DPI products is currently available, with the choice of DPI device largely depending on the dose, dosing frequency and powder properties of formulations. Computational fluid dynamics (CFD), together with various particle motion modelling tools, such as discrete particle methods (DPM) and discrete element methods (DEM), have been increasingly used to optimise DPI design by revealing the details of flow patterns, particle trajectories, de-agglomerations and depositions within the device and the delivery paths. This review article focuses on the development of the modelling methodologies of flow and particle behaviours in DPI devices and their applications to device design in several emerging fields. Various modelling methods, including the most recent multi-scale approaches, are covered and the latest simulation studies of different devices are summarised and critically assessed. The potential and effectiveness of the modelling tools in optimising designs of emerging DPI devices are specifically discussed, such as those with the features of high-dose, pediatric patient compatibility and independency of patients' inhalation manoeuvres. Lastly, we summarise the challenges that remain to be addressed in DPI-related fluid and particle modelling and provide our thoughts on future research direction in this field.

Effect of sinus size and position on hemodynamics during pulsatile flow in a carotid artery bifurcation.

BACKGROUND AND OBJECTIVES: Hemodynamics plays a crucial role in the progression of atherosclerosis and the treatment of arterial diseases. Stroke is one of the arterial diseases and a leading cause of death worldwide. Hemodynamics in the carotid artery plays a vital role in the stroke. The common carotid artery bifurcates into the internal carotid artery and the external carotid artery. Carotid sinus, a slightly dilated area, exists in the internal carotid artery just after the bifurcation and acts as a pressure receptor and regulator. The location and size of the sinus can vary in different people; the change in sinus size and location may affect the hemodynamics. It is necessary to study the shift in hemodynamics due to changes in sinus size and position on atherosclerosis. The change in flow behavior may suggest the probable sites of backflow and low wall shear stress, and therefore the sites prone to atherosclerosis. METHODS: The model of the carotid artery has been constructed using patient data. Transient computational fluid dynamics simulations have been performed using a finite volume method for the numerical solution in a three-dimensional computational domain using ANSYS Fluent 19.2. Pulsatile flow is specified at the inlet boundary. The coupled scheme is used for the pressure-velocity coupling. The second-order discretization scheme is used for pressure interpolation and second-order upwind scheme is used for the discretisation of momentum equation. The temporal term is discretized using the first-order implicit scheme. RESULTS: The effect of sinus size and location on the overall flow behavior, wall shear stress, and secondary flow are presented. Results show that the outer wall of bifurcation has low wall shear stress and bigger recirculation as compared with that on the inner wall of bifurcation. Numerical results obtained for varying sinus size and position are shown in graphs and contours, including wall shear stress, secondary flow, and velocity streamlines. CONCLUSION: Numerical results reveal that sinus away from bifurcation, and larger diameter sinus has more recirculation and low wall shear stress. Therefore, the person having sinus away from bifurcation and larger sinus diameter are more susceptible to plaque formation.

Effect of asymmetry on the flow behavior in an idealized arterial bifurcation.

Flow behavior at the arterial bifurcations has significant implications on the plaque formation. It depends on the vessel size, two bifurcation angles, i.e. angle between the mother and daughter vessels and their relative magnitudes. In this study, hemodynamics for steady and pulsatile flow of blood has been investigated in an idealized carotid artery bifurcation having all the vessels in the same plane for a range of bifurcation angles for symmetric and asymmetric bifurcation. The simulations reveal the presence of a pair of helical vortices, symmetric about the bifurcation plane, in each daughter tube near the bifurcation.

Errors, limitations, and pitfalls in the diagnosis of central and peripheral nervous system lesions in intraoperative cytology and frozen sections.

CONTEXT: Intraoperative cytology and frozen section play an important role in the diagnosis of neurosurgical specimens. There are limitations in both these procedures but understanding the errors and pitfalls may help in increasing the diagnostic yield. AIMS: To find the diagnostic accuracy of intraoperative cytology and frozen section for central and peripheral nervous system (PNS) lesions and analyze the errors, pitfalls, and limitations in these procedures. SETTINGS AND DESIGN: Eighty cases were included in this prospective study in a span of 1.5 years. MATERIALS AND METHODS: The crush preparations and the frozen sections were stained with hematoxylin and eosin method. The diagnosis of crush smears and the frozen sections were compared with the diagnosis in the paraffin section, which was considered as the gold standard. STATISTICAL ANALYSES USED: Diagnostic accuracy, sensitivity, and specificity. RESULTS: The diagnostic accuracy of crush smears was 91.25% with a sensitivity of 95.5% and specificity of 100%. In the frozen sections, the overall diagnostic accuracy was 95%, sensitivity was 96.8%, and specificity was 100%. The categories of pitfalls noted in this study were categorization of spindle cell lesions, differentiation of oligodendroglioma from astrocytoma in frozen sections, differentiation of coagulative tumor necrosis of glioblastoma multiforme (GBM) from the caseous necrosis of tuberculosis, grading of gliomas in frozen section, and differentiation of the normal granular cells of the cerebellum from the lymphocytes in cytological smears. CONCLUSIONS: Crush smear and frozen section are complimentary procedures. When both are used together, the diagnostic yield is substantially increased.

Gallbladder cancer presenting with brain and bone metastasis: case report.

Although gallbladder cancer is a rare disease worldwide, north India has one of the highest incidences of this disease. We report a case of asymptomatic gall bladder cancer with brain metastasis. The patient presented with a scalp lump as the sole presenting feature, with no symptoms attributable to abdominal malignancy. Previously, the lump had been incised by a local practitioner who had probably misdiagnosed it as an abscess.