A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease☆

Glucose-6-phosphate dehydrogenase deficiency is a genetic disorder that occurs almost exclusively in males. This condition mainly affects red blood cells, which carry oxygen from the lungs to tissues throughout the body. In affected individuals, a defect in an enzyme called glucose-6-phosphate dehydrogenase causes red blood cells to break down prematurely. This destruction of red blood cells is called hemolysis.

Glucose-6-phosphate dehydrogenase deficiency.

Dialkylbiaryl phosphines are a valuable class of ligand for Pd-catalyzed amination reactions and have been applied in a range of contexts. This perspective attempts to aid the reader in the selection of the best choice of reaction conditions and ligand of this class for the most commonly encountered and practically important substrate combinations.

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

The generation of polymer brushes by surface-initiated controlled radical polymerization (SI-CRP) techniques has become a powerful approach to tailor the chemical and physical properties of interfaces and has given rise to great advances in surface and interface engineering. Polymer brushes are defined as thin polymer films in which the individual polymer chains are tethered by one chain end to a solid interface. Significant advances have been made over the past years in the field of polymer brushes. This includes novel developments in SI-CRP, as well as the emergence of novel applications such as catalysis, electronics, nanomaterial synthesis and biosensing. Additionally, polymer brushes prepared via SI-CRP have been utilized to modify the surface of novel substrates such as natural fibers, polymer nanofibers, mesoporous materials, graphene, viruses and protein nanoparticles. The last years have also seen exciting advances in the chemical and physical characterization of polymer brushes, as well as an ev...

Surface-Initiated Controlled Radical Polymerization: State-of-the-Art, Opportunities, and Challenges in Surface and Interface Engineering with Polymer Brushes

This article reviews the application of electric circuit methods for the analysis of pressure-driven microfluidic networks with an emphasis on concentration- and flow-dependent systems. The application of circuit methods to microfluidics is based on the analogous behaviour of hydraulic and electric circuits with correlations of pressure to voltage, volumetric flow rate to current, and hydraulic to electric resistance. Circuit analysis enables rapid predictions of pressure-driven laminar flow in microchannels and is very useful for designing complex microfluidic networks in advance of fabrication. This article provides a comprehensive overview of the physics of pressure-driven laminar flow, the formal analogy between electric and hydraulic circuits, applications of circuit theory to microfluidic network-based devices, recent development and applications of concentration- and flow-dependent microfluidic networks, and promising future applications. The lab-on-a-chip (LOC) and microfluidics community will gain insightful ideas and practical design strategies for developing unique microfluidic network-based devices to address a broad range of biological, chemical, pharmaceutical, and other scientific and technical challenges.

Design of pressure-driven microfluidic networks using electric circuit analogy

Red blood cells (RBCs) possess a unique capacity for undergoing cellular deformation to navigate across various human microcirculation vessels, enabling them to pass through capillaries that are smaller than their diameter and to carry out their role as gas carriers between blood and tissues. Since there is growing evidence that red blood cell deformability is impaired in some pathological conditions, measurement of RBC deformability has been the focus of numerous studies over the past decades. Nevertheless, reports on healthy and pathological RBCs are currently limited and, in many cases, are not expressed in terms of well-defined cell membrane parameters such as elasticity and viscosity. Hence, it is often difficult to integrate these results into the basic understanding of RBC behaviour, as well as into clinical applications. The aim of this review is to summarize currently available reports on RBC deformability and to highlight its association with various human diseases such as hereditary disorders (e.g., spherocytosis, elliptocytosis, ovalocytosis, and stomatocytosis), metabolic disorders (e.g., diabetes, hypercholesterolemia, obesity), adenosine triphosphate-induced membrane changes, oxidative stress, and paroxysmal nocturnal hemoglobinuria. Microfluidic techniques have been identified as the key to develop state-of-the-art dynamic experimental models for elucidating the significance of RBC membrane alterations in pathological conditions and the role that such alterations play in the microvasculature flow dynamics.

Biomechanical properties of red blood cells in health and disease towards microfluidics.

In this work, we report on a systematic fluidodynamic investigation of red blood cell (RBC) suspensions flowing in microcapillaries with diameters comparable to the cell size in vitro. By using high-speed video microscopy and image analysis, we provide the first simultaneous determination of both cell velocity and shape parameters related to RBC membrane deformability over an extended range of pressure drops, and the first quantitative comparison with theoretical results from the literature. Good agreement was found with the predicted axisymmetric shapes tending towards an apparent bullet-like asymptotic configuration at increasing cell velocity. A potential application of this work is in the design of flow-based devices to study the pathological conditions affecting cell deformability, thus allowing us to overcome the limits of classical static methods, such as micropipette aspiration, which are not suitable for handling a large number of cells.

Red blood cell deformation in microconfined flow

In this work, a microfluidic system to investigate the flow behavior of red blood cells in a microcirculation-mimicking network of PDMS microchannels with thickness comparable to cell size is presented. We provide the first quantitative description of cell velocity and shape as a function of the applied pressure drop in such devices. Based on these results, a novel methodology to measure cell membrane viscoelastic properties in converging/diverging flow is developed, and the results are in good agreement with data from the literature. In particular, in the diverging channel the effect of RBC surface viscosity is dominant with respect to shear elasticity. Possible applications include measurements of cell deformability in pathological samples, where reliable methods are still lacking.

Microfluidics analysis of red blood cell membrane viscoelasticity

Mutations in more than 70 genes cause hereditary anemias (HA), a highly heterogeneous group of rare/low frequency disorders in which we included: hyporegenerative anemias, as congenital dyserythropoietic anemia (CDA) and Diamond-Blackfan anemia; hemolytic anemias due to erythrocyte membrane defects, as hereditary spherocytosis and stomatocytosis; hemolytic anemias due to enzymatic defects. The study describes the diagnostic workflow for HA, based on the development of two consecutive versions of a targeted-NGS panel, including 34 and 71 genes, respectively. Seventy-four probands from 62 unrelated families were investigated. Our study includes the most comprehensive gene set for these anemias and the largest cohort of patients described so far. We obtained an overall diagnostic yield of 64.9%. Despite 54.2% of cases showed conclusive diagnosis fitting well to the clinical suspicion, the multi-gene analysis modified the original clinical diagnosis in 45.8% of patients (nonmatched phenotype-genotype). Of note, 81.8% of nonmatched patients were clinically suspected to suffer from CDA. Particularly, 45.5% of the probands originally classified as CDA exhibited a conclusive diagnosis of chronic anemia due to enzymatic defects, mainly due to mutations in PKLR gene. Interestingly, we also identified a syndromic CDA patient with mild anemia and epilepsy, showing a homozygous mutation in CAD gene, recently associated to early infantile epileptic encephalopathy-50 and CDA-like anemia. Finally, we described a patient showing marked iron overload due to the coinheritance of PIEZO1 and SEC23B mutations, demonstrating that the multi-gene approach is valuable not only for achieving a correct and definitive diagnosis, but also for guiding treatment.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.25058

Giovanna Tomaiuolo

Papers

Biomechanical properties of red blood cells in health and disease towards microfluidics.

Red blood cell deformation in microconfined flow

Microfluidics analysis of red blood cell membrane viscoelasticity

Multi-gene panel testing improves diagnosis and management of patients with hereditary anemias.

Emulsions in porous media: From single droplet behavior to applications for oil recovery