Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force

BACKGROUND: Recombinant atrial natriuretic peptide (ANP) is administered in patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy. OBJECTIVE: Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium. METHODS: Human neutrophils were perfused over endothelial monolayers in a microfluidic lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact area and β(2)-integrin focal bond formation. RESULTS: ANP inhibited neutrophil rolling and firm adhesion without influencing the upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity CD18 and shedding of L-selectin during neutrophil activation. Exposed to fluid shear, integrin mediated arrest was disrupted with ANP treatment, which elicited formation of long tethers and diminished cell spreading and contact. This correlated with a ~40% increase in neutrophil viscosity and a reduction in the adhesive footprint. CONCLUSIONS: A decrease in cell deformation and neutrophil flattening with ANP results in fewer integrin bond clusters, which translates to higher tensile forces and impaired adhesion strengthening and cell detachment

Relationship satisfaction in couples raising a child with autism spectrum disorder: A systematic review of the literature

Background: Couples raising a child with autism spectrum disorder (ASD) face challenges that may impact on their relationship. The purpose of this review was to compare relationship satisfaction in couples raising children with and without ASD and to identify factors associated with satisfaction in couples with a child with ASD. Methods: Thirteen databases were searched and studies were systematically screened against predetermined inclusion criteria. Twenty six articles, ranging from good to strong methodological quality, met the criteria for inclusion. Of these, seven were included in a meta-analysis comparing relationship satisfaction in couples raising a child with ASD with couples raising children without disabilities. Results: The meta-analysis showed that couples raising a child with ASD were found to experience less relationship satisfaction than couples raising a child without a disability (Hedges's g = 0.41, p < 0.001); however, evidence from the narrative synthesis was mixed when compared with couples raising children with other disabilities. The most consistent evidence implicated challenging child behaviours, parental stress and poor psychological wellbeing as risk factors, and positive cognitive appraisal and social support as protective factors. Conclusion Findings demonstrate that couples raising a child with ASD would benefit from support to assist them in maintaining satisfaction in their relationship with their partner. However, further studies are needed to gain a greater understanding of the risk and protective factors and how these co-vary with relationship satisfaction over time. A theoretical framework has been developed to scaffold future research

Hochstromanwendungen mit Hochtemperatursupraleitern - technische Leiterentwicklung und Bau von Funktionsmodellen. YBCO Plattenleiterfertigung und Bau von Strombegrenzermodellen bis zu 1 MVA Abschlussbericht

In terms of materials, the main focus of the work was on the manufacture of large-area YBCO plate-type conductors with homogeneous properties and maximum current densities of j_c&gt;1 MA/cm&quot;2. j_c values of better than 3 MA/cm&quot;2 were achieved reproducibly on sapphire substrates of 100 mm diameter and 10 x 20 cm&quot;2 in size with a homogeneity of 10%; on polycrystalline substrates of 10 x 20 cm&quot;2 in size, homogeneous j_c values of up to 2 MA/cm&quot;2 were also successfully demonstrated. Of the total of four methods of coating available at the start of the project, thermal co-evaporation (TCE) proved best for YBCO thin films and the IBAD method best for quasi single-crystal buffer films. The latter are necessary to achieve high j_c on polycrystalline substrates such as ZrO_2(Y), glass and Al_2O_3. Polycrystalline substrates are essential in order to make the HTS current limiter as a future product commercially feasible. The favoured solutions ZrO_2(Y) and glass have not come up to expectations, because present investigations into quench propagation are showing that, with this approach, the high values of power density required for the switching process (1600 VA/cm&quot;2) cannot be achieved. Towards the end of the project, polycrystalline Al_2O_3 began to be seen as a successful alternative; the work is being pursued further within the context of a follow-on project. The coating processes were stabilized successfully and, when combined with strict quality control, allowed the yield of tested, ready-to-use plate-type conductors to be improved to 85%. This success was an essential prerequisite for the building of a 3-phase, 1.2 MVA model (7.2 kV) comprising a total of sixty-three 100 mm plate-type conductors. At the Berlin factory the model has been successfully tested up to a prospective short-circuit current of 5 kV. This has demonstrated the basic suitability of HTS thin-film technology for use in current limiters. So far the model has been switched a total of 43 times without any problems at all. At present the model is the first resistive 3-phase HTS current limiter in the world. It has been installed in a factory-assembled container together with all the necessary supply and protection equipment for further long-term tests. However, it has taken several fresh starts to actually arrive at this milestone of development. The causes for this were initially the inadequate reproducibility of the coating process and subsequently new insights on the stresses that the plate-type conductors are exposed to during quenching, which only became apparent from the three-phase model tests. These unforeseen delays were also the reason why the 10 MVA model (that was planned at the beginning of the project) was not brought to fruition. (orig.)Available from TIB Hannover: F02B1638 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung, Berlin (Germany)DEGerman