Erythrophagocytosis occurring in the spleen is a critical process for removing senescent and diseased red blood cells (RBCs) from the microcirculation. Although some progress has been made in understanding how the biological signaling pathways mediate the phagocytic processes, the role of the biophysical interaction between RBCs and macrophages, particularly under pathological conditions such as sickle cell disease, has not been adequately studied. Here, we combine computational simulations with microfluidic experiments to quantify RBC-macrophage adhesion dynamics under flow conditions comparable to those in the red pulp of the spleen. We also investigate the RBC-macrophage interaction under normoxic and hypoxic conditions. First, we calibrate key model parameters in the adhesion model using microfluidic experiments for normal and sickle RBCs under normoxia and hypoxia. We then study the adhesion dynamics between the RBC and the macrophage. Our simulation illustrates three typical adhesion states, each characterized by a distinct dynamic motion of the RBCs, namely firm adhesion, flipping adhesion, and no adhesion (either due to no contact with macrophages or detachment from the macrophages). We also track the number of bonds formed when RBCs and macrophages are in contact, as well as the contact area between the two interacting cells, providing mechanistic explanations for the three adhesion states observed in the simulations and microfluidic experiments. Furthermore, we quantify, for the first time to our knowledge, the adhesive forces between RBCs (normal and sickle) and macrophages under different oxygenated conditions. Our results show that the adhesive forces between normal cells and macrophages under normoxia are in the range of 33-58 pN and 53-92 pN for sickle cells under normoxia and 155-170 pN for sickle cells under hypoxia. Taken together, our microfluidic and simulation results improve our understanding of the biophysical interaction between RBCs and macrophages in sickle cell disease and provide a solid foundation for investigating the filtration function of the splenic macrophages under physiological and pathological conditions.

Microplastics (MPs) are critical emerging pollutants found in the environment worldwide; however, its toxicity in aquatic in amphibians, is poorly known. Thus, the aim of the present study is to assess the toxicological potential of polyethylene microplastics (PE MPs) in Physalaemus cuvieri tadpoles. According to the results, tadpoles\' exposure to MP PE at concentration 60 mg/L for 7 days led to mutagenic effects, which were evidenced by the increased number of abnormalities observed in nuclear erythrocytes. The small size of erythrocytes and their nuclei area, perimeter, width, length, and radius, as well as the lower nucleus/cytoplasm ratio observed in tadpoles exposed to PE MPs confirmed its cytotoxicity. External morphological changes observed in the animal models included reduced ratio between total length and mouth-cloaca distance, caudal length, ocular area, mouth area, among others. PE MPs increased the number of melanophores in the skin and pigmentation rate in the assessed areas. Finally, PE MPs were found in gills, gastrointestinal tract, liver, muscle tissues of the tail and in the blood, a fact that confirmed MP accumulation by tadpoles. Therefore, the present study pioneering evidenced how MPs can affect the health of amphibians.

An improved red blood cell (RBC) membrane model is developed based on the bilayer coupling model (BCM) to accurately predict the complete sequence of stomatocyte-discocyte-echinocyte (SDE) transformation of a RBC. The coarse-grained (CG)-RBC membrane model is proposed to predict the minimum energy configuration of the RBC from the competition between lipid-bilayer bending resistance and cytoskeletal shear resistance under given reference constraints. In addition to the conventional membrane surface area, cell volume and bilayer-leaflet-area-difference constraints, a new constraint: total-membrane-curvature is proposed in the model to better predict RBC shapes in agreement with experimental observations. A quantitative evaluation of several cellular measurements including length, thickness and shape factor, is performed for the first time, between CG-RBC model predicted and three-dimensional (3D) confocal microscopy imaging generated RBC shapes at equivalent reference constraints. The validated CG-RBC membrane model is then employed to investigate the effect of reduced cell volume and elastic length scale on SDE transformation, to evaluate the RBC deformability during SDE transformation, and to identify the most probable RBC cytoskeletal reference state. The CG-RBC membrane model can predict the SDE shape behaviour under diverse shape-transforming scenarios, in-vitro RBC storage, microvascular circulation and flow through microfluidic devices.

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UNASSIGNED: High prevalence of certain polymorphic alleles of erythrocytes in malaria endemic area has been linked to the resistance provided by these alleles against parasitic infestations. Numerous studies undertaken to demonstrate this correlation have generated conflicting results. This study was undertaken to investigate the abilities of various polymorphic erythrocytes to support in vitro growth of Plasmodium falciparum parasites.
UNASSIGNED: In this study under in vitro condition the ability of P. falciparum parasites to grow was assessed in the erythrocytes obtained from a total of 40 patients with various haemoglobinopathies, such as β-thalassaemia (β-Thal), sickle cell anaemia, erythroenzymopathy-like glucose-6-phosphate dehydrogenase deficiency and membranopathy-like hereditary spherocytosis.
UNASSIGNED: Significantly reduced in vitro invasion and growth of parasites was seen in the cultures containing abnormal erythrocytes than in control cultures containing normal erythrocytes (P< 0.05). The mean per cent parasitaemia comparison was also carried out among the three polymorphic erythrocyte groups, i.e. β-Thal, sickle cell anaemia and enzyme-membranopathies.
UNASSIGNED: Erythroenzymopathies and membranopathies were found to provide a more hostile environment for parasites, as the least parasitaemia was observed in these erythrocytes. The present in vitro study showed that P. falciparum did not grow well and did not invade well in erythrocytes obtained from common inherited red cell disorders.

BACKGROUND: Various studies confirm the biocompatibility and efficacy of clips for certain target tissues, but without any comparative analysis of hematological parameters. Therefore, we conducted a study to assess the possible association of the implantation of titanium and plastic clips in the neurocranium with possible morphological changes in the blood cells of experimental animals.
METHODS: As a control, the peripheral blood smears were taken before surgery from 12 adult dogs that were divided into two experimental groups. After placing titanium and plastic clips in the neurocranium, the peripheral blood of the first group was analyzed on the seventh postoperative day, while the peripheral blood of the second group was analyzed on the sixtieth day. By microscopy of the blood smears, the following parameters were analyzed: the presence of poikilocytosis of the red blood cells, degenerative changes in the leukocytes and leukogram.
RESULTS: There were no statistically significant differences between the mean values of the groups. Monocytosis was detected (first group 22.83 % and second 16.30 %), as well as neutropenia (46.80 %, in the second group). Degenerative changes to neutrophils and the occurrence of atypical lymphocytes were observed in the second experimental group (60th postoperative day).
CONCLUSIONS: A mild adverse effect from the biomaterials present in the neurocranium of dogs was detected, affecting the majority of leukocytic cells. A chronic recurrent inflammatory process was caused by the presence of the plastic and titanium clips in the brain tissue. No adverse effect of biomaterials on erythrocytes in the neurocranium was detected in the dogs studied. Further studies are necessary to explain the occurrence of degenerative changes in the neutrophils and lymphocytes.

Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K+ permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S-Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K+ was markedly abnormal with elevated activities of Psickle , Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca2+ entry and Mg2+ loss via Psickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K+ transporters also correlated with the level of HbS-Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS-Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S-Oman genotype.

BACKGROUND: While the presence of disseminated intravascular coagulation (DIC) has been implicated in worse clinical outcome in acute leukemia, the relationship between different subtypes of acute leukemia and the clinicopathologic features of DIC has not been systematically well studied.
METHODS: In this study, we retrospectively reviewed 149 cases of newly diagnosed acute leukemia and assessed the utility of evaluating red blood cell morphologic features, and coagulation parameters in determining the presence of DIC as well as differentiating subtypes of acute leukemia.
RESULTS: Review of our cohort demonstrates a novel finding, that elevated D-dimer concentrations ≥19 000 ng/mL fibrinogen equivalent units (FEU) are a sensitive diagnostic indicator of acute promyelocytic leukemia (APL) with moderate specificity, sensitivity 96%, specificity 92% in acute leukemia subtyping. Similar to other studies, APL showed an increased incidence of DIC (P < 0.01) compared to other subtypes of acute leukemia. Surprisingly, the presence of schistocytes on the peripheral blood smear was not a statistically significant indicator of DIC, sensitivity of 36% and specificity of 89%. Finally, the presence of DIC was not a significant indicator of poorer prognosis amongst all patients with AML.
CONCLUSIONS: Overall we identify elevated D-dimer concentrations ≥19 000 ng/mL FEU are a sensitive indicator of acute promyelocytic leukemia (APL), with a sensitivity of 96% and specificity of 92% in the subtyping of acute leukemias, and that the presence of schistocytes in peripheral blood smears is not a diagnostically sensitive screening test for DIC with a sensitivity of 36%.

The usefulness of the complete blood count (CBC) during the first week of life in infants with Down syndrome (DS) has been recognized; however, studies are limited and have evaluated only some of the parameters of the CBC. Here, we report a prospective study of 135 infants with cytogenetically confirmed DS and a reference group of 226 infants without birth defects all born during the period 2009-2015 at the Dr. Juan I. Menchaca Civil Hospital of Guadalajara (Guadalajara, Mexico). The goal was to evaluate hematological findings in the CBC during the first 7 days of life, interpreted according to gestational and postnatal age. Data were analyzed using multivariate logistic regression analysis expressed as adjusted odds ratio (aORs) with 95% confidence intervals (95% CIs). Infants with DS had a significantly higher risk for polycythemia (aOR = 12.4, 95% CI: 4.6-33.3), macrocytosis (aOR = 15.9, 95% CI: 1.8-143.4), high values of mean corpuscular hemoglobin (aOR = 36.4, 95% CI: 4.5-294.9), anisocytosis (red blood cells of unequal size) (aOR = 3.9, 95% CI: 2.1-7.6), thrombocytopenia (aOR = 32.4, 95% CI: 15.2-68.9), white blood cell (WBC) count ≥30 × 103 /µl (aOR = 19.4, 95% CI: 4.1-91.5), lymphocytosis (aOR = 73.3, 95% CI: 9.5-565.4), and basophilia (aOR = 16.8, 95% CI: 1.9-151.5). Overall, 74% of infants with DS in our study had polycythemia, thrombocytopenia, WBC count >30 × 103 /µl, or lymphocytosis (aOR = 35.6, 95% CI: 18.8-79.2). Compared with those in other studies, our infants with DS had distinctive hematological findings including a lower frequency of thrombocytopenia, infrequent neutrophilia, and frequent lymphocytosis and neutropenia. This suggests ethnic, socioeconomic, or nutritional differences. © 2017 Wiley Periodicals, Inc.

BACKGROUND: Anemia results in increased morbidity and mortality, underscoring the need to better understand its pathophysiology amongst HIV-exposed and infected children in sub-Saharan Africa, the region where most infant HIV exposure and infections occur.
METHODS: This analysis used samples obtained from children in the Kisumu Breastfeeding Study (KiBS). KiBS was a longitudinal phase IIB, open-label, one-arm clinical trial, designed to investigate the safety, tolerability and effectiveness of a maternal triple-antiretroviral (ARV) regimen for prevention of mother-to-child transmission (PMTCT) of HIV, during late pregnancy and early infancy while breastfeeding. Blood samples from 482 children were obtained at birth, 2, 6, 10 and 14 weeks and 6, 9, 12, 18 and 24 months. Severity of anemia was graded using the NIH Division of AIDS (DAIDS) toxicity tables. We describe the proportion of children with anemia and anomalies in red blood cell parameters at various time points over 24 months and compare rates of anemia between HIV-infected and HIV-uninfected children and by mothers\' ARV regimen and infant malaria infection.
RESULTS: The proportion of children with anemia significantly increased after the breastfeeding period in both HIV-infected and HIV-uninfected children with higher proportion among HIV-infected children compared to HIV-uninfected children (RR: 1.72; CI: 1.22-2.44, p = 0.002). Maternal triple-antiretroviral regimen was not associated with infant anemia (p = 0.11). There was no significant difference in mean hemoglobin between HIV-uninfected children with and without malaria at each time point except at 24 months.
CONCLUSIONS: A relatively lower proportion of children with severe anemia during the breastfeeding period suggest that exposure to mother\'s triple antiretroviral combinations through breast milk, posed minimal risk of hematologic toxicity.