We numerically studied localized elastic distortions in curved, effectively two-dimensional nematic shells. We used a mesoscopic Landau-de Gennes-type approach, in which the orientational order is theoretically considered by introducing the appropriate tensor nematic order parameter, while the three-dimensional shell shape is described by the curvature tensor. We limited our theoretical consideration to axially symmetric shapes of nematic shells. It was shown that in the surface regions of stomatocyte-class nematic shell shapes with large enough magnitudes of extrinsic (deviatoric) curvature, the direction of the in-plane orientational ordering can be mutually perpendicular above and below the narrow neck region. We demonstrate that such line-like nematic distortion configurations may run along the parallels (i.e., along the circular lines of constant latitude) located in the narrow neck regions of stomatocyte-like nematic shells. It was shown that nematic distortions are enabled by the order reconstruction mechanism. We propose that the regions of nematic shells that are strongly elastically deformed, i.e., topological defects and line-like distortions, may attract appropriately surface-decorated nanoparticles (NPs), which could potentially be useful for the controlled assembly of NPs.

BACKGROUND: Overhydrated hereditary stomatocytosis (OHSt) is a rare disorder characterized by abnormalities in erythrocytic volume homeostasis. Early and accurate diagnosis is essential for appropriate management and genetic counseling.
METHODS: We present the case of a child with beta-thalassemia and a history of multiple blood transfusions. Clinical presentation, laboratory findings, and genetic testing were reviewed. Peripheral blood smear examination and genetic analysis were performed.
RESULTS: The patient was admitted with severe anemia, and peripheral blood smear examination revealed the presence of up to 50% stomatocytes. Laboratory investigations showed abnormalities in red blood cell parameters, including decreased hemoglobin levels and increased mean corpuscular volume. Genetic testing identified a heterozygous mutation in the RHAG gene, confirming the diagnosis of OHSt. The presence of stomatocytes in the peripheral blood smear was transient, correlating with episodes of hemolysis and its control.

In this study, the potential toxicity of non-functionalized polystyrene nanoparticles (PS-NPs) in human erythrocytes has been assessed. The effect of PS-NPs with different diameters (∼30 nm, ∼45 nm, ∼70 nm) on fluidity of erythrocytes membrane, red blood cells shape, as well as haemolysis of these cells has been investigated. Erythrocytes were incubated for 24 h with non-functionalized PS-NPs in concentrations ranging from 0.001 to 200 μg/mL in order to study haemolysis and from 0.001 to 10 μg/mL to determine other parameters. Fluidity was estimated by electron paramagnetic resonance (EPR) and the fluorimetric method. It has been shown that PS-NPs induced haemolysis, caused changes in the fluidity of red blood cells membrane, and altered their shape. Non-functionalized PS-NPs increased the membrane stiffness in the hydrophobic region of hydrocarbon chains of fatty acids. The observed changes in haemolysis and morphology were dependent on the size of the nanoparticles. The smallest PS-NPs of ∼30 nm (with the smallest absolute value of the negative zeta potential -29.68 mV) induced the greatest haemolysis, while the largest PS-NPs of ∼70 nm (with the highest absolute value of the negative zeta potential -42.00 mV) caused the greatest changes in erythrocyte shape and stomatocytes formation.

In this work, a numerical model that enables simulation of the deformation and flow behaviour of differently aged Red Blood Cells (RBCs) is developed. Such cells change shape and decrease in deformability as they age, thus impacting their ability to pass through the narrow capillaries in the body. While the body filters unviable cells from the blood naturally, cell aging poses key challenges for blood stored for transfusions. Therefore, understanding the influence RBC morphology and deformability have on their flow is vital. While several existing models represent young Discocyte RBC shapes well, a limited number of numerical models are developed to model aged RBC morphologies like Stomatocytes and Echinocytes. The existing models are also limited to shear and stretching simulations. Flow characteristics of these morphologies are yet to be investigated. This paper aims to develop a new membrane formulation for the numerical modelling of Stomatocyte, Discocytes and Echinocyte RBC morphologies to investigate their deformation and flow behaviour. The model used represents blood plasma using the Lattice Boltzmann Method (LBM) and the RBC membrane using the discrete element method (DEM). The membrane and the plasma are coupled by the Immersed Boundary Method (IBM). Previous LBM-IBM-DEM formulations represent RBC membrane response based on forces generated from changes in the local area, local length, local bending, and cell volume. In this new model, two new force terms are added: the local area difference force and the local curvature force, which are specially incorporated to model the flow and deformation behaviour of Stomatocytes and Echinocytes. To verify the developed model, the deformation behaviour of the three types of RBC morphologies are compared to well-characterised stretching and shear experiments. The flow modelling capabilities of the method are then demonstrated by modelling the flow of each cell through a narrow capillary. The developed model is found to be as accurate as benchmark Smoothed Particle Hydrodynamics (SPH) approaches while being significantly more computationally efficient.

BACKGROUND: Canine stomatocytosis is a well-recognized rare erythrocyte disorder characterized by nonsyndromic forms with selective erythroid involvement, syndromic forms with extra-hematologic disease, and acquired forms.
OBJECTIVE: We describe serial clinicopathologic changes in two dogs with stomatocytosis of breeds that are different from those previously reported.
METHODS: Blood samples were obtained from a 12-year-old female neutered Australian Cattle Dog and a 12-year-old male neutered Beagle for hematologic and biochemical analyses, including a morphologic examination of peripheral blood films. Serial clinicopathologic data were reviewed, including CBCs performed by the referring veterinary surgeons.
RESULTS: Serial CBC data in both cases reported a variable decrease in RBC numbers commonly associated with a normal hematocrit, macrocytosis, hypochromasia, changes in red cell distribution width parameters including marked histogram abnormalities in volume distribution of the RBC population, and mildly increased or normal reticulocyte counts. Morphologic examination of peripheral blood films identified variable numbers of stomatocytes, knizocytes (Case 1, Day 1, Day 4), mild anisocytosis, mild macrocytosis, and mild polychromasia.
CONCLUSIONS: In both cases, the changes exhibited in the erythrogram raise suspicion for an RBC membrane disorder with cell volume dysregulation and stomatocytosis, although they did not appear to cause clinically relevant hemolysis.

Sitosterolemia is a rare autosomal recessively inherited lipid metabolic disorder that is characterized by hyper absorption of plant sterols from the intestinal mucosa leading to toxic levels in the blood. Four patients of age ranging from 11 to 29 years presented to the outpatient department with clinical features of hemolytic anemia. There were no features of hypercholesterolemia in any of the patients. Peripheral smear examination of all four patients showed stomatocytes and macrothrombocytopenia. Qualitative testing for plant sterols was performed in one case. Next generation sequencing revealed a compound heterozygous mutation in ABCG5 gene (c.1222C>T and c.1255C>T) in one case and homozygous mutations in ABCG5 gene (c.727C>T), (c.332G>A (p.G111E)), (c.1222C>T) in the other three cases. Ezetimibe (10 mg/day) was administered in one case, with complete resolution of symptoms. All patients were advised a low plant sterol diet and regular monitoring of hemoglobin and lipid profile. Our cases highlight a rare but important cause of hemolytic anemia that can be suspected from careful peripheral blood examination but only conclusively established by molecular genetic diagnosis.

In nature, dynamic processes are ubiquitous and often characterized by adaptive, transient behavior. Herein, we present the development of a transient bowl-shaped nanoreactor system, or stomatocyte, the properties of which are mediated by molecular interactions. In a stepwise fashion, we couple motility to a dynamic process, which is maintained by transient events; namely, binding and unbinding of adenosine triphosphate (ATP). The surface of the nanosystem is decorated with polylysine (PLL), and regulation is achieved by addition of ATP. The dynamic interaction between PLL and ATP leads to an increase in the hydrophobicity of the PLL-ATP complex and subsequently to a collapse of the polymer; this causes a narrowing of the opening of the stomatocytes. The presence of the apyrase, which hydrolyzes ATP, leads to a decrease of the ATP concentration, decomplexation of PLL, and reopening of the stomatocyte. The competition between ATP input and consumption gives rise to a transient state that is controlled by the out-of-equilibrium process.

Morphologically discrete nanoarchitectures, which mimic the structural complexity of biological systems, are an increasingly popular design paradigm in the development of new nanomedical technologies. Herein, engineered polymeric stomatocytes are presented as a structural and functional mimic of red blood cells (RBCs) with multifunctional therapeutic features. Stomatocytes, comprising biodegradable poly(ethylene glycol)-block-poly(D,L-lactide), possess an oblate-like morphology reminiscent of RBCs. This unique dual-compartmentalized structure is augmented via encapsulation of multifunctional cargo (oxygen-binding hemoglobin and the photosensitizer chlorin e6). Furthermore, stomatocytes are decorated with a cell membrane isolated from erythrocytes to ensure that the surface characteristics matched those of RBCs. In vivo biodistribution data reveal that both the uncoated and coated nano-RBCs have long circulation times in mice, with the membrane-coated ones outperforming the uncoated stomatoctyes. The capacity of nano-RBCs to transport oxygen and create oxygen radicals upon exposure to light is effectively explored toward photodynamic therapy, using 2D and 3D tumor models; addressing the challenge presented by cancer-induced hypoxia. The morphological and functional control demonstrated by this synthetic nanosystem, coupled with indications of therapeutic efficacy, constitutes a highly promising platform for future clinical application.

Hemodiafiltration (HDF) is a renal replacement therapy that is based on the principles of diffusion and convection for the elimination of uremic toxins. A significant and increasing number of end-stage renal disease (ESRD) patients are treated with HDF, even in the absence of definite and conclusive survival and anemia treatment data. However, its effects on red blood cell (RBC) physiological features have not been examined in depth. In this study, ESRD patients under regular HDF or conventional hemodialysis (cHD) treatment were examined for RBC-related parameters, including anemia, hemolysis, cell shape, redox status, removal signaling, membrane protein composition, and microvesiculation, in repeated paired measurements accomplished before and right after each dialysis session. The HDF group was characterized by better redox potential and suppressed exovesiculation of blood cells compared with the cHD group pre-dialysis. However, HDF was associated with a temporary but acute, oxidative-stress-driven increase in hemolysis, RBC removal signaling, and stomatocytosis, probably associated with the effective clearance of dialyzable natural antioxidant components, including uric acid, from the uremic plasma. The nature of these adverse short-term effects of HDF on post-dialysis plasma and RBCs strongly suggests the use of a parallel antioxidant therapy during the HDF session.

Self-powered artificial nanomotors are currently attracting increased interest as mimics of biological motors but also as potential components of nanomachinery, robotics, and sensing devices. We have recently described the controlled shape transformation of polymersomes into bowl-shaped stomatocytes and the assembly of platinum-driven nanomotors. However, the platinum encapsulation inside the structures was low; only 50% of the structures contained the catalyst and required both high fuel concentrations for the propelling of the nanomotors and harsh conditions for the shape transformation. Application of the nanomotors in a biological setting requires the nanomotors to be efficiently propelled by a naturally available energy source and at biological relevant concentrations. Here we report a strategy for enzyme entrapment and nanomotor assembly via controlled and reversible folding of polymersomes into stomatocytes under mild conditions, allowing the encapsulation of the proteins inside the stomach with almost 100% efficiency and retention of activity. The resulting enzyme-driven nanomotors are capable of propelling these structures at low fuel concentrations (hydrogen peroxide or glucose) via a one-enzyme or two-enzyme system. The confinement of the enzymes inside the stomach does not hinder their activity and in fact facilitates the transfer of the substrates, while protecting them from the deactivating influences of the media. This is particularly important for future applications of nanomotors in biological settings especially for systems where fast autonomous movement occurs at physiological concentrations of fuel.