In cystic fibrosis (CF) patients airways mucus shows an increased viscoelasticity due to the concentration of high molecular weight components. Such mucus thickening eventually leads to bacterial overgrowth and prevents mucus clearance. The altered rheological behavior of mucus results in chronic lung infection and inflammation, which causes most of the cases of morbidity and mortality, although the cystic fibrosis complications affect other organs as well. Here, we present a quantitative study on the correlation between cystic fibrosis mucus viscoelasticity and patients clinical status. In particular, a new diagnostic parameter based on the correlation between CF sputum viscoelastic properties and the severity of the disease, expressed in terms of FEV1 and bacterial colonization, was developed. By using principal component analysis, we show that the types of colonization and FEV1 classes are significantly correlated to the elastic modulus, and that the latter can be used for CF severity classification with a high predictive efficiency (88%). The data presented here show that the elastic modulus of airways mucus, given the high predictive efficiency, could be used as a new clinical parameter in the prognostic evaluation of cystic fibrosis.

Blood is a complex fluid with non-Newtonian characteristics and consists primarily of a concentrated suspension of red blood cells (RBCs) characterized by high deformability and aggregability. The majority of both research and clinical investigations on blood rheology is based on steady shear measurements aimed at determining blood viscosity as a function of shear rate. On the other hand, investigations of blood rheology in the linear viscoelastic regime are sparse in the literature and currently limited. In principle, small amplitude oscillatory flow is best suited to study blood microstructure and rheology under quasi-static conditions, which are relevant in a range of applications, from blood storage to blood aggregability testing. Here, we present the first systematic experimental investigation of blood rheological behavior in the linear viscoelastic regime, by performing oscillatory shear measurements by conventional bulk rheology. The storage (G′) and loss (G″) moduli of whole human blood have been measured over an extended range of frequencies [0.1–30 rad/s]. Data show that G″ predominates over G′ across the entire tested range of frequency. By comparing steady and oscillatory shear viscosity, it was found that the Cox-Merz rule is followed to a good approximation, with higher deviations at small shear rate/frequencies. The effects of RBC volume fraction and of aggregating media (i.e., dextran solution at two different concentrations) have been also investigated. Overall, our results are consistent with the behavior of a weakly attractive suspension, where RBCs form reversible aggregates that can be broken by the action of flow

Malaria is associated with significant microcirculation disorders, especially when the infection reaches its severe stage. This can lead to a range of fatal conditions, from cerebral malaria to multiple organ failure, of not fully understood pathogenesis. It has recently been proposed that a breakdown of the glycocalyx, the carbohydrate-rich layer lining the vascular endothelium, plays a key role in severe malaria, but direct evidence supporting this hypothesis is still lacking. Here, the interactions between Plasmodium falciparum infected red blood cells ( Pf RBCs) and endothelial glycocalyx are investigated by developing an in vitro , physiologically relevant model of human microcirculation based on microfluidics. Impairment of the glycocalyx is obtained by enzymatic removal of sialic acid residues, which, due to their terminal location and net negative charge, are implicated in the initial interactions with contacting cells. We show a more than twofold increase of Pf RBC adhesion to endothelial cells upon enzymatic treatment, relative to untreated endothelial cells. As a control, no effect of enzymatic treatment on healthy red blood cell adhesion is found. The increased adhesion of Pf RBCs is also associated with cell flipping and reduced velocity as compared to the untreated endothelium. Altogether, these results provide a compelling evidence of the increased cytoadherence of Pf RBCs to glycocalyx-impaired vascular endothelium, thus supporting the advocated role of glycocalyx disruption in the pathogenesis of this disease.

2 Dehydrated hereditary stomatocytosis (DHS) is an autosomal dominant hereditary hemolyticanemia characterized by erythrocyte dehydration due to loss of the cation content. Affected subjects exhibit highly variable clinical presentation, ranging from absence of clinical symptoms to lethal perinatal edema. They may present severe iron overload leading to hepatic transplantation, or life threatening thromboembolic disease after splenectomy, thus making the diagnosis of this condition very tricky.1 DHS results in two different forms: (i) DHS1, the most frequent, is caused by mutations in PIEZO1, encoding a cation selective channel activated by mechanical force; (ii) DHS2due to altered KCNN4 gene, encoding a Ca2+-sensitive (Gardos) channel. [2][3][4] Particularly, PIEZO1 is a large and highly polymorphic gene. Several electrophysiology studies demonstrated that the mutations cause a gain-of-function phenotype with delayed inactivation of the channel. 5-10We herein studied seven DHS patients from two unrelated families (A-B) showing highly variable clinical expressivity and carrying the same new PIEZO1 mutation. We demonstrated that the presence of an additional de novo PIEZO1 rare missense variant in one of the two probands accounts for a more severe phenotype.Case 1 from family A (A-I1) was a 42-year-old male form UK that suffered from hemolytic anemia for over 20 years. Four out his five children also suffered from anemia ( Figure 1A). He showed gallstones and splenomegaly. On complete blood count (CBC) decreased hemoglobin (Hb) levels, increased MCV, mean corpuscular hemoglobin concentration (MCHC) and reticulocytes count were observed (Table 1). He also exhibited high levels of bilirubin and LDH, as well as increased ferritin and transferrin saturation, indicating iron overload (negative for hemochromatosis) with normal liver function. Peripheral blood smear highlighted the presence of macrocytosis, polychromasia, schistocytes and few stomatocytes.Case 2 from family B (B-II2) was a 6-year-old child from Southern Italy ( Figure 1B). At birth, he presented jaundice treated with phototherapy. At 7 months, he was admitted to hospitalization for skin and scleral jaundice. During this hospitalization, severe normocytic anemia with reticulocytosis was observed. At 3 years, he experienced severe anemia (Hb 8.3 g/dl), with reticulocytosis (181764/ml -6.12%), high platelet count (662.000/ml), signs of hemolysis (high unconjugated bilirubin and low haptoglobin levels), splenomegaly (longitudinal diameter 10.5 cm). Iron balance was normal for age (transferrin saturation 18% -ferritin 64 ng/ml). He was hospitalized several times after 3 years, requiring frequent transfusions (2/3 per year) because of hemolytic crisis.Peripheral blood smear highlighted the presence of polychromasia, schistocytes and few stomatocytes.The father B-I1 was affected too, but he showed a well-compensated anemia with normal Hb (14.6 g/dl), macrocytosis (MCV 98.2 fl), reticulocytosis (453100/ml -11.53%), and splenomegaly and a lower Hb levels (8.7±0....

No abstract