Atmospheric pressure non-equilibriumplasma for the production of composite materials

In the evolving field of tissue engineering, continuous advances are required to improve scaffold design and fabrication to obtain biomimetic supports for cell adhesion, proliferation, penetration and differentiation. Both electrospun fibrous scaffolds and hydrogels are used in this field since they well reproduce the structure of the extracellular matrix (ECM) of many biological tissues. Limitations of these two types of materials can be overcome through their combination, by developing composite structures combining enhanced mechanical properties (provided by the fibrous components) and improved cell penetration (provided by the gel phase) in a superior ability to mimic natural ECM that is constituted by both a fibrous protein network and a hydrogel matrix. Here we develop new composite materials made of electrospun PLLA scaffolds and poly(amidoamine) hydrogels with different degrees of crosslinking. To promote compatibilization and good adhesion between the two materials, surface chemical reactions between hydrogels and PLLA mats are induced by inserting amino functional groups on electrospun PLLA mats by means of atmospheric pressure non-thermal plasma. Results will be presented concerning the exposure of PLLA substrates to the plasma region generated by a Dielectric Barrier Discharge at atmospheric pressure, driven by a HV Amplifier connected to a function generator operating with a microsecond rise time and operated in N2. Surface and solid-state thermo-mechanical characterizations of plasma treated substrates and of resulting composite materials at different crosslinking degrees are presented. Results of mechanical tests show a high adhesion between hydrogel and plasma treated PLLA electrospun mats, underlining the opportunity to use atmospheric non-thermal plasmas to fabricate a composite starting from two materials otherwise physically incompatible. Potential effects of nanofibrous-hydrogel were evaluated by investigating pluripotent stem cells response

Interfacing Graphene-Based Materials With Neural Cells

The scientific community has witnessed an exponential increase in the applications of graphene and graphene-based materials in a wide range of fields, from engineering to electronics to biotechnologies and biomedical applications. For what concerns neuroscience, the interest raised by these materials is two-fold. On one side, nanosheets made of graphene or graphene derivatives (graphene oxide, or its reduced form) can be used as carriers for drug delivery. Here, an important aspect is to evaluate their toxicity, which strongly depends on flake composition, chemical functionalization and dimensions. On the other side, graphene can be exploited as a substrate for tissue engineering. In this case, conductivity is probably the most relevant amongst the various properties of the different graphene materials, as it may allow to instruct and interrogate neural networks, as well as to drive neural growth and differentiation, which holds a great potential in regenerative medicine. In this review, we try to give a comprehensive view of the accomplishments and new challenges of the field, as well as which in our view are the most exciting directions to take in the immediate future. These include the need to engineer multifunctional nanoparticles (NPs) able to cross the blood-brain-barrier to reach neural cells, and to achieve on-demand delivery of specific drugs. We describe the state-of-the-art in the use of graphene materials to engineer three-dimensional scaffolds to drive neuronal growth and regeneration in vivo, and the possibility of using graphene as a component of hybrid composites/multi-layer organic electronics devices. Last but not least, we address the need of an accurate theoretical modeling of the interface between graphene and biological material, by modeling the interaction of graphene with proteins and cell membranes at the nanoscale, and describing the physical mechanism(s) of charge transfer by which the various graphene materials can influence the excitability and physiology of neural cells

A Semi-Lagrangian scheme for a modified version of the Hughes model for pedestrian flow

In this paper we present a Semi-Lagrangian scheme for a regularized version of the Hughes model for pedestrian flow. Hughes originally proposed a coupled nonlinear PDE system describing the evolution of a large pedestrian group trying to exit a domain as fast as possible. The original model corresponds to a system of a conservation law for the pedestrian density and an Eikonal equation to determine the weighted distance to the exit. We consider this model in presence of small diffusion and discuss the numerical analysis of the proposed Semi-Lagrangian scheme. Furthermore we illustrate the effect of small diffusion on the exit time with various numerical experiments

Airway cellularity, lipid laden macrophages and microbiology of gastric juice and airways in children with reflux oesophagitis

BACKGROUND: Gastroesophageal reflux disease (GORD) can cause respiratory disease in children from recurrent aspiration of gastric contents. GORD can be defined in several ways and one of the most common method is presence of reflux oesophagitis. In children with GORD and respiratory disease, airway neutrophilia has been described. However, there are no prospective studies that have examined airway cellularity in children with GORD but without respiratory disease. The aims of the study were to compare (1) BAL cellularity and lipid laden macrophage index (LLMI) and, (2) microbiology of BAL and gastric juices of children with GORD (G+) to those without (G-). METHODS: In 150 children aged <14-years, gastric aspirates and bronchoscopic airway lavage (BAL) were obtained during elective flexible upper endoscopy. GORD was defined as presence of reflux oesophagitis on distal oesophageal biopsies. RESULTS: BAL neutrophil% in G- group (n = 63) was marginally but significantly higher than that in the G+ group (n = 77), (median of 7.5 and 5 respectively, p = 0.002). Lipid laden macrophage index (LLMI), BAL percentages of lymphocyte, eosinophil and macrophage were similar between groups. Viral studies were negative in all, bacterial cultures positive in 20.7% of BALs and in 5.3% of gastric aspirates. BAL cultures did not reflect gastric aspirate cultures in all but one child. CONCLUSION: In children without respiratory disease, GORD defined by presence of reflux oesophagitis, is not associated with BAL cellular profile or LLMI abnormality. Abnormal microbiology of the airways, when present, is not related to reflux oesophagitis and does not reflect that of gastric juices

Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes

Objectives: To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. Methods: Twenty‐five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio‐Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes  3 mL/min/1.73m2/year, respectively), and albumin‐creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource. Results: In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor‐3, cystatin C, and beta‐2 microglobulin (B2M) (B coefficient[95%CI]: −0.19 [−0.27, −0.12], P = 7.0 × 10−7; −0.18 [−0.26, −0.11], P = 5.1 × 10−6; −0.12 [−0.20, −0.05], P = 1.6 × 10−3), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (−0.21 [−0.28, −0.14], P = 2.3 × 10−8) and cystatin C (−0.16 [−0.22, −0.09], P = 1.6 × 10−6). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10−6), whereas rapid increaser phenotype was associated with fibroblast growth factor‐23 (FGF‐23) (1.59 [1.23, 2.04], P = 2.6 × 10−4). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR. Conclusions: In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF‐23 was associated with eGFR increases, whereas trefoil factor‐3, cystatin C, and B2M were associated with baseline eGFR

Recruitment of regulatory T cells is correlated with hypoxia-induced CXCR4 expression, and is associated with poor prognosis in basal-like breast cancers

Introduction: Basal-like breast cancers behave more aggressively despite the presence of a dense lymphoid infiltrate. We hypothesised that immune suppression in this subtype may be due to T regulatory cells (Treg) recruitment driven by hypoxia-induced up-regulation of CXCR4 in Treg.Methods: Immunoperoxidase staining for FOXP3 and CXCL12 was performed on tissue microarrays from 491 breast cancers. The hypoxia-associated marker carbonic anhydrase IX (CA9) and double FOXP3/CXCR4 staining were performed on sections from a subset of these cancers including 10 basal-like and 11 luminal cancers matched for tumour grade.Results: High Treg infiltration correlated with tumour CXCL12 positivity (OR 1.89, 95% CI 1.22 to 2.94, P = 0.004) and basal phenotype (OR 3.14, 95% CI 1.08 to 9.17, P = 0.004) in univariate and multivariate analyses. CXCL12 positivity correlated with improved survival (P = 0.005), whereas high Treg correlated with shorter survival for all breast cancers (P = 0.001), luminal cancers (P &lt; 0.001) and basal-like cancers (P = 0.040) that were confirmed in a multivariate analysis (OR 1.61, 95% CI 1.02 to 2.53, P = 0.042). In patients treated with hormone therapy, high Treg were associated with a shorter survival in a multivariate analysis (OR 1.78, 95% CI 1.01 to 3.15, P = 0.040). There was a tendency for luminal cancers to show CXCL12 expression (102/138, 74%) compared to basal-like cancers (16/27, 59%), which verged on statistical significance (P = 0.050). Up-regulation of CXCR4 in Treg correlated with the basal-like phenotype (P = 0.029) and tumour hypoxia, as indicated by CA9 expression (P = 0.049).Conclusions: Our data show that in the setting of hypoxia and CXCR4 up-regulation in Treg, CXCL12 expression may have the negative consequence of enhancing Treg recruitment and suppressing the anti-tumour immune response. © 2011 Yan et al.; licensee BioMed Central Ltd