A few upstream bifurcations drive the spatial distribution of red blood cells in model microfluidic networks

The physics of blood flow in small vessel networks is dominated by the interactions between Red Blood Cells (RBCs), plasma and blood vessel walls. The resulting couplings between the microvessel...

Clinical Reasoning: A 55-Year-Old Woman With Recurrent Episodes of Aphasia and Vision Changes

A 55-year-old woman presented with recurrent episodes of headache, vision changes and language disturbances. Brain MRI showed multifocal white matter lesions, microhemorrhages, and enlarged perivascular spaces. After an extensive and unrevealing workup, she underwent a biopsy of brain and meninges that revealed thick and hyalinized leptomeningeal and cortical vessel walls that were strongly positive for ß-amyloid by immunohistochemical staining, suggestive of cerebral amyloid angiopathy (CAA). CAA can present as a spectrum of inflammatory responses to the deposition of amyloid-ß in the vessel walls. Her clinical presentation, radiological and histopathological findings supported a diagnosis of probable CAA-related inflammation (CAA-ri). Although an uncommon entity, it is important to recognize it because most patients respond to immunosuppressive therapy.

Emerging Microfluidic Approaches for Platelet Mechanobiology and Interplay With Circulatory Systems

Understanding how platelets can sense and respond to hemodynamic forces in disturbed blood flow and complexed vasculature is crucial to the development of more effective and safer antithrombotic therapeutics. By incorporating diverse structural and functional designs, microfluidic technologies have emerged to mimic microvascular anatomies and hemodynamic microenvironments, which open the floodgates for fascinating platelet mechanobiology investigations. The latest endothelialized microfluidics can even recapitulate the crosstalk between platelets and the circulatory system, including the vessel walls and plasma proteins such as von Willebrand factor. Hereby, we highlight these exciting microfluidic applications to platelet mechanobiology and platelet–circulatory system interplay as implicated in thrombosis. Last but not least, we discuss the need for microfluidic standardization and summarize the commercially available microfluidic platforms for researchers to obtain reproducible and consistent results in the field.

Cherenkov probes and runaway electrons diagnostics

The beams of fast runaway electrons (RE), which are often produced during tokamak discharges, are particularly dangerous and can induce serious damages of the vacuum vessel and internal components of the machine. The proper and fast diagnostics of RE beams is essential for controlling the discharge, e.g., by early mitigation of disruptions and potentially dangerous RE beams. The diagnostics of RE beams is usually based on measurements of the radiation emitted either by these electrons, or as a result of their interactions with plasma and/or vessel walls. Such a radiation is usually recorded by the means of probes placed outside the vacuum vessel. The method developed by our team is based on the probe located inside the vacuum vessel. The probe can be used to detect highly localized RE bunches and to determine their spatial and temporal characteristics. During last few years, the NCBJ team have developed and used the RE diagnostics based on the Cherenkov effect observed in diamond radiators coupled with fast photomultipliers. During the investigated discharges, the probe was inserted into the vacuum vessel, and its head was placed at the plasma edge, where fast RE are expected. A correlation between signals recorded using our probes and other diagnostics, e.g., hard x-ray signals, was also studied. In this paper, we present recent results of the RE measurements by means of Cherenkov probes, which were performed in the COMPASS and TCV tokamaks.

Endothelial junctional membrane protrusions serve as hotspots for neutrophil transmigration

Upon inflammation, leukocytes rapidly transmigrate across the endothelium to enter the inflamed tissue. Evidence accumulates that leukocytes use preferred exit sites, though it is not yet clear how these hotspots in the endothelium are defined and how they are recognized by the leukocyte. Using lattice light sheet microscopy, we discovered that leukocytes prefer endothelial membrane protrusions at cell junctions for transmigration. Phenotypically, these junctional membrane protrusions are present in an asymmetric manner, meaning that one endothelial cell shows the protrusion and the adjacent one does not. Consequently, leukocytes cross the junction by migrating underneath the protruding endothelial cell. These protrusions depend on Rac1 activity and by using a photo-activatable Rac1 probe, we could artificially generate local exit-sites for leukocytes. Overall, we have discovered a new mechanism that uses local induced junctional membrane protrusions to facilitate/steer the leukocyte escape/exit from inflamed vessel walls.

A Microfluidic 3D Endothelium-on-a-Chip Model to Study Transendothelial Migration of T Cells in Health and Disease

The recruitment of T cells is a crucial component in the inflammatory cascade of the body. The process involves the transport of T cells through the vascular system and their stable arrest to vessel walls at the site of inflammation, followed by extravasation and subsequent infiltration into tissue. Here, we describe an assay to study 3D T cell dynamics under flow in real time using a high-throughput, artificial membrane-free microfluidic platform that allows unimpeded extravasation of T cells. We show that primary human T cells adhere to endothelial vessel walls upon perfusion of microvessels and can be stimulated to undergo transendothelial migration (TEM) by TNFα-mediated vascular inflammation and the presence of CXCL12 gradients or ECM-embedded melanoma cells. Notably, migratory behavior was found to differ depending on T cell activation states. The assay is unique in its comprehensiveness for modelling T cell trafficking, arrest, extravasation and migration, all in one system, combined with its throughput, quality of imaging and ease of use. We envision routine use of this assay to study immunological processes and expect it to spur research in the fields of immunological disorders, immuno-oncology and the development of novel immunotherapeutics.

At the Games

Hundreds of fragmentary glass cups preserve labeled representations of the empire’s leading sports stars, especially charioteers and gladiators. This mold-blown glassware illustrates how imagery common on popular terracotta plaques and lamps was adapted for upright translucent vessel walls. Comparing scenes reveals an important difference: whereas chariots are shown racing around the track’s monument-filled dividing line, gladiators compete without any indication of setting. When the cups are glimpsed at a utilitarian angle (45 degrees), they represent the events as they appeared from inclined stands and conjure the visual experience of spectacular entertainment. Most examples have been documented in the northwest provinces; in funerary, religious, and domestic contexts; and in places that did necessarily possess sports venues. Previously considered tools of Romanization or mementoes brought home from games, they were more likely commodities that found success in a competitive market for tableware by offering virtual experiences of the games in miniature.

Shape anisotropy-governed locomotion of surface microrollers on vessel-like microtopographies against physiological flows

Surface microrollers are promising microrobotic systems for controlled navigation in the circulatory system thanks to their fast speeds and decreased flow velocities at the vessel walls. While surface propulsion on the vessel walls helps minimize the effect of strong fluidic forces, three-dimensional (3D) surface microtopography, comparable to the size scale of a microrobot, due to cellular morphology and organization emerges as a major challenge. Here, we show that microroller shape anisotropy determines the surface locomotion capability of microrollers on vessel-like 3D surface microtopographies against physiological flow conditions. The isotropic (single, 8.5 µm diameter spherical particle) and anisotropic (doublet, two 4 µm diameter spherical particle chain) magnetic microrollers generated similar translational velocities on flat surfaces, whereas the isotropic microrollers failed to translate on most of the 3D-printed vessel-like microtopographies. The computational fluid dynamics analyses revealed larger flow fields generated around isotropic microrollers causing larger resistive forces near the microtopographies, in comparison to anisotropic microrollers, and impairing their translation. The superior surface-rolling capability of the anisotropic doublet microrollers on microtopographical surfaces against the fluid flow was further validated in a vessel-on-a-chip system mimicking microvasculature. The findings reported here establish the design principles of surface microrollers for robust locomotion on vessel walls against physiological flows.

Monoclonal gammopathy of renal significance (MGRS)-related AL amyloidosis complicated by amyloid myopathy: a case report

Background Lately, monoclonal gammopathy of renal significance (MGRS) has been defined as a group of renal disorders that are strongly associated with monoclonal protein, including amyloid immunoglobulin light chain (AL) amyloidosis. Amyloid myopathy is rare (1.5% of all patients with amyloidosis) and the prognosis is poor. Furthermore, only approximately 20% of patients with amyloid myopathy are reported to have renal involvement, indicating a lack of data in the literature. Case presentation Here, we report a rare case of MGRS-related AL amyloidosis complicated by amyloid myopathy that presented with muscle weakness in the upper and lower limbs, neck and fingers, and nephrotic syndrome. Blood, urine, and bone marrow examination revealed monoclonal gammopathy of undetermined significance (MGUS) (Bence Jones protein-lambda). Muscle biopsy of the vastus lateralis muscle demonstrated amyloid proteins in the sarcolemma and in the blood vessel walls on Congo red staining, suggesting amyloid myopathy, and tiny inclusions in fibers on modified Gomori trichrome stain. Although we thought they were reminiscent of nemaline bodies, we could not confirm the nature of this structure. Renal biopsy demonstrated amyloid proteins in the mesangial region, part of the capillary walls, and the blood vessel walls on direct fast scarlet staining. As these amyloid proteins were positive for p-component staining and negative for amyloid A staining, β2-microglobulin, and pre-albumin, and as lambda light chains were positive in the mesangial region, we diagnosed the patient with MGRS-related AL amyloidosis. Although he was treated with melphalan and dexamethasone, his symptoms did not improve. Conclusions AL amyloidosis involving the kidneys and muscles has a poor prognosis, and a delayed diagnosis of amyloid myopathy is common because of its rarity and frequent misdiagnosis, which increases organ function deterioration. Therefore, early detection, therapeutic intervention, and careful follow-up are crucial.