Can environment or allergy explain international variation in prevalence of wheeze in childhood?

Asthma prevalence in children varies substantially around the world, but the contribution of known risk factors to this international variation is uncertain. The International Study of Asthma and Allergies in Childhood (ISAAC) Phase Two studied 8–12 year old children in 30 centres worldwide with parent-completed symptom and risk factor questionnaires and aeroallergen skin prick testing. We used multilevel logistic regression modelling to investigate the effect of adjustment for individual and ecological risk factors on the between-centre variation in prevalence of recent wheeze. Adjustment for single individual-level risk factors changed the centre-level variation from a reduction of up to 8.4% (and 8.5% for atopy) to an increase of up to 6.8%. Modelling the 11 most influential environmental factors among all children simultaneously, the centre-level variation changed little overall (2.4% increase). Modelling only factors that decreased the variance, the 6 most influential factors (synthetic and feather quilt, mother’s smoking, heating stoves, dampness and foam pillows) in combination resulted in a 21% reduction in variance. Ecological (centre-level) risk factors generally explained higher proportions of the variation than did individual risk factors. Single environmental factors and aeroallergen sensitisation measured at the individual (child) level did not explain much of the between-centre variation in wheeze prevalence

Dynamic reorganization and enzymatic remodeling of type IV collagen at cell-biomaterial interface

Vascular basement membrane remodeling involves assembly and degradation of its main constituents, type IV collagen (Col IV) and laminin, which is critical during development, angiogenesis, and tissue repair. Remodeling can also occur at cell–biomaterials interface altering significantly the biocompatibility of implants. Here we describe the fate of adsorbed Col IV in contact with endothelial cells adhering on positively charged NH2 or hydrophobic CH3 substrata, both based on self-assembly monolayers (SAMs) and studied alone or mixed in different proportions. AFM studies revealed distinct pattern of adsorbed Col IV, varying from single molecular deposition on pure NH2 to network-like assembly on mixed SAMs, turning to big globular aggregates on bare CH3. Human umbilical endothelial cells (HUVECs) interact better with Col IV adsorbed as single molecules on NH2 surface and readily rearrange it in fibril-like pattern that coincide with secreted fibronectin fibrils. The cells show flattened morphology and well-developed focal adhesion complexes that are rich on phosphorylated FAK while expressing markedly low pericellular proteolytic activity. Conversely, on hydrophobic CH3 substrata HUVECs showed abrogated spreading and FAK phosphorylation, combined with less reorganization of the aggregated Col IV and significantly increased proteolytic activity. The later involves both MMP-2 and MMP-9, as measured by zymography and FITC-Col IV release. The mixed SAMs support intermediate remodeling activity. Taken together these results show that chemical functionalization combined with Col IV preadsorption provides a tool for guiding the endothelial cells behavior and pericellular proteolytic activity, events that strongly affect the fate of cardiovascular implants

Material-based strategies to engineer fibronectin matrices for regenerative medicine

Engineering biomaterials for regenerative medicine involves a myriad of aspects to be considered for the successful design, interaction with cells and integration with living tissues (i.e. pore size, mechanical properties, degradation rate, biological activity). Among different technologies used to functionalise synthetic biomaterials and promote cell adhesion, cell growth and cell differentiation, this review focuses on strategies to organise extracellular matrix (ECM) proteins in a biomimetic way, as cells do in natural tissues in vivo (the ECM is a mesh of proteins that surrounds cells, and therefore, constitutes the scaffolding of a tissue), but using functional materials instead of living cells. The authors critically review material-based strategies to organise fibronectin (FN), a core component in the ECM of many tissues, and engineer microenvironments that recapitulate the structure and properties of the ECM. Material-driven organisation of FN in analogy with their natural cell-mediated assembly is a powerful route to engineer the network structure and biological activity of FN fibrillar matrices, seeking to develop biomimetic scaffolds for regenerative medicine. Here, the authors discuss different routes to promote the cell-free formation of FN fibrils as well as the biological impact of these engineered cellular microenvironments

Nanoscale surface cues and cell behaviour

Nanotopographical cues are used to stimulate and manipulate cell responses. Hence, the development of understanding in this area will allow for the engineering of novel biomaterial and tissue engineering scaffolds. In this chapter we describe a range of material surface manufacturing techniques covering surface chemistry, topography, and mechanics in the form of switchable chemical surfaces and growth factor tethering on polymers. It is clear that these cues have large effects on cell response, for example, stem cells

Fibronectin adsorption and cell response on electroactive poly(vinylidene fluoride)films

Due to the large potential of electroactive materials in novel tissue engineering strategies, the aim of this work is to determine if the crystalline phase and/or the surface electrical charge of electroactive poly(vinylidene fluoride), PVDF, have influence on the biological response in monolayer cell culture. Non-polar α-PVDF and electroactive β-PVDF were prepared. The β-PVDF films were poled by corona discharge to show negative or positive electrical surface charge density. It has been concluded that hydrophilicity of the PVDF substrates depends significantly on crystalline phase and polarity. Furthermore, by means of atomic force microscopy and an enzyme-linked immunosorbent assay test, it has been shown that positive or negative poling strongly influences the behavior of β-PVDF supports with respect to fibronectin (FN) adsorption, varying the exhibition of adhesion ligands of adsorbed FN. Culture of MC3T3-E1 pre-osteoeblasts proved that cell proliferation depends on surface polarity as well. These results open the viability of cell culture stimulation by mechanical deformation of a piezoelectric substrate that results in varying electrical charge densities on the substrate surface

Prospective Cohort Study of Infective Endocarditis in People Who Inject Drugs

Background: Infective endocarditis (IE) in people who inject drugs (PWID) is an emergent public health problem. Objectives: The purpose of this study was to investigate IE in PWID and compare it with IE in non-PWID patients. Methods: Two prospective cohort studies (ICE-PCS and ICE-Plus databases, encompassing 8,112 IE episodes from 2000 to 2006 and 2008 to 2012, with 64 and 34 sites and 28 and 18 countries, respectively). Outcomes were compared between PWID and non-PWID patients with IE. Logistic regression analyses were performed to investigate risk factors for 6-month mortality and relapses amongst PWID. Results: A total of 7,616 patients (591 PWID and 7,025 non-PWID) were included. PWID patients were significantly younger (median 37.0 years [interquartile range: 29.5 to 44.2 years] vs. 63.3 years [interquartile range: 49.3 to 74.0 years]; p < 0.001), male (72.5% vs. 67.4%; p = 0.007), and presented lower rates of comorbidities except for human immunodeficiency virus, liver disease, and higher rates of prior IE. Amongst IE cases in PWID, 313 (53%) episodes involved left-side valves and 204 (34.5%) were purely left-sided IE. PWID presented a larger proportion of native IE (90.2% vs. 64.4%; p < 0.001), whereas prosthetic-IE and cardiovascular implantable electronic device-IE were more frequent in non-PWID (9.3% vs. 27.0% and 0.5% vs. 8.6%; both p < 0.001). Staphylococcus aureus caused 65.9% and 26.8% of cases in PWID and non-PWID, respectively (p < 0.001). PWID presented higher rates of systemic emboli (51.1% vs. 22.5%; p < 0.001) and persistent bacteremia (14.7% vs. 9.3%; p < 0.001). Cardiac surgery was less frequently performed (39.5% vs. 47.8%; p < 0.001), and in-hospital and 6-month mortality were lower in PWID (10.8% vs. 18.2% and 14.4% vs. 22.2%; both p < 0.001), whereas relapses were more frequent in PWID (9.5% vs. 2.8%; p < 0.001). Prior IE, left-sided IE, polymicrobial etiology, intracardiac complications, and stroke were risk factors for 6-month mortality, whereas cardiac surgery was associated with lower mortality in the PWID population. Conclusions: A notable proportion of cases in PWID involve left-sided valves, prosthetic valves, or are caused by microorganisms other than S. aureus

Materials-driven Fibronectin Assembly on Nanoscale Topography Enhances Mesenchymal Stem Cell Adhesion, Protecting Cells from Bacterial Virulence Factors and Preventing Biofilm Formation

Post-operative infection is a major complication in patients recovering from orthopaedic surgery. As such, there is a clinical need to develop biomaterials for use in regenerative surgery that can promote mesenchymal stem cell (MSC) osteospecific differentiation and that can prevent infection caused by biofilm-forming pathogens. Nanotopographical approaches to pathogen control are being identified, including in orthopaedic materials such as titanium and its alloys. These topographies use high aspect ratio nanospikes or nanowires to prevent bacterial adhesion but these features also significantly reduce MSC adhesion and activity. Here, we use a poly (ethyl acrylate) (PEA) polymer coating on titanium nanowires to spontaneously organise fibronectin (FN) and to deliver bone morphogenetic protein 2 (BMP2) to enhance MSC adhesion and osteospecific signalling. Using a novel MSC–Pseudomonas aeruginosa co-culture, we show that the coated nanotopographies protect MSCs from cytotoxic quorum sensing and signalling molecules, enhance MSC adhesion and osteoblast differentiation and reduce biofilm formation. We conclude that the PEA polymer-coated nanotopography can both support MSCs and prevent pathogens from adhering to a biomaterial surface, thus protecting from biofilm formation and bacterial infection, and supporting osteogenic repair