Measuring social participation in children with chronic health conditions: validation and reference values of the child and adolescent scale of participation (CASP) in the German context

Background: While ICF-CY-based models of care are promising avenues for improving participation of children with chronic health conditions, feasible and valid instruments to assess participation as an outcome in routine are still needed. We aimed to validate a German parent-report version of the Child and Adolescent Scale of Participation (CASP) in children with chronic health conditions of different severity. Methods: Cross-sectional data were collected in 327 children (mean age 7.8 years, 55% boys) from two paediatric centres (n = 112) and one population-based sample (n = 215). Cronbach’s alpha, factor analyses, face validity assessments, correlation analyses, receiver operating characteristics (ROC) curves, and parent-reported health-related quality of life (HRQoL: KINDL) were used to examine internal consistency, test-retest reliability, and capacity to differentiate between disease severity groups. Disease severity was operationalized according to ICD-diagnosis groups and/or parent-reports on health problems, medical and educational support, and medication. A newly developed item “overall perceived participation” was added to the CASP and evaluated. Results: We found good to excellent content validity, excellent internal consistency, and good-to-excellent test-retest reliability of the instrument. While children with mild disease had a significantly greater extent of participation (higher CASP scores) than children with severe disease, they did not differ from healthy children. Children with mild compared to severe disease much more differed in participation as measured by the CASP compared to the KINDL (area under the ROC curve: 0.92 vs. 0.75). In addition, the item “overall perceived participation” was highly correlated (r = 0.86) with the CASP total score, indicating the potential value of this specific single item. Finally, we provided preliminary reference values for the CASP obtained in a population-based sample of children without chronic health conditions. Conclusions: The German version of the CASP and the new item are efficient, valid and reliable measures of social participation in childhood. The CASP-measured participation focuses more on attendance than on involvement into social circumstances of everyday life. To detect children with a high burden of disease on everyday life, the CASP may be more accurate than HRQoL instruments such as the KINDL. As outcome measurement, the CASP may facilitate the implementation of patient-centred paediatric health care

Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia

Hereditary spastic paraplegias are a group of inherited motor neuron diseases characterized by progressive paraparesis and spasticity. Mutations in the spastic paraplegia gene SPG11, encoding spatacsin, cause an autosomal-recessive disease trait; however, the precise knowledge about the role of spatacsin in neurons is very limited. We for the first time analyzed the expression and function of spatacsin in human forebrain neurons derived from human pluripotent stem cells including lines from two SPG11 patients and two controls. SPG11 patients'-derived neurons exhibited downregulation of specific axonal-related genes, decreased neurite complexity and accumulation of membranous bodies within axonal processes. Altogether, these data point towards axonal pathologies in human neurons with SPG11 mutations. To further corroborate spatacsin function, we investigated human pluripotent stem cell-derived neurons and mouse cortical neurons. In these cells, spatacsin was located in axons and dendrites. It colocalized with cytoskeletal and synaptic vesicle (SV) markers and was present in synaptosomes. Knockdown of spatacsin in mouse cortical neurons evidenced that the loss of function of spatacsin leads to axonal instability by downregulation of acetylated tubulin. Finally, time-lapse assays performed in SPG11 patients'-derived neurons and spatacsin-silenced mouse neurons highlighted a reduction in the anterograde vesicle trafficking indicative of impaired axonal transport. By employing SPG11 patient-derived forebrain neurons and mouse cortical neurons, this study provides the first evidence that SPG11 is implicated in axonal maintenance and cargo trafficking. Understanding the cellular functions of spatacsin will allow deciphering mechanisms of motor cortex dysfunction in autosomal-recessive hereditary spastic paraplegia

Is the Concept of a Green Economy a Useful Way of Framing Policy Discussions and Policymaking to Promote Sustainable Development?

In this article, the authors discuss the use of green economy to promote sustainable development. Research and Partnerships Unit Head Sheng Fulai states that sustainable development is composed of economic, social and environmental development. Furthermore, it features Research and Partnerships associate Gary Flomenhoft who believes that green economy is useful when it deals with factors such as distribution of wealth and throughput of materials and energy

Dashboard aimed at decision-makers and citizens in place managmenent, within SD principles

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Effect of vagotomy and atropine on plasma somatostatin response to a meal in conscious dogs

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Crystal Structures of Archaemetzincin Reveal a Moldable Substrate-Binding Site

<div><h3>Background</h3><p>Archaemetzincins are metalloproteases occurring in archaea and some mammalia. They are distinct from all the other metzincins by their extended active site consensus sequence HEXXHXXGXXHCX₄CXMX₁₇CXXC featuring four conserved cysteine residues. Very little is known about their biological importance and structure-function relationships.</p> <h3>Principal Findings</h3><p>Here we present three crystal structures of the archaemetzincin <em>Af</em>AmzA (Uniprot O29917) from <em>Archaeoglobus fulgidus</em>, revealing a metzincin architecture featuring a zinc finger-like structural element involving the conserved cysteines of the consensus motif. The active sites in all three structures are occluded to different extents rendering the enzymes proteolytically inactive against a large variety of tested substrates. Owing to the different ligand binding there are significant differences in active site architecture, revealing a large flexibility of the loops covering the active site cleft.</p> <h3>Conclusions</h3><p>The crystal structures of <em>Af</em>AmzA provide the structural basis for the lack of activity in standard proteolytic assays and imply a triggered activity onset upon opening of the active site cleft.</p> </div

Structural alignment of archaemetzincins and metzincins.

<p>(A) Superposition of the three known AmzA structures <i>Af</i>AmzA (yellow), <i>Mk</i>AmzA (green) and <i>Ml</i>AmzA (slate). (B) Close-up view of the Cys₄ zinc finger domains of all three AmzA structures from (A). (D) Superposition of <i>Af</i>AmzA (yellow) with selected metzincins Bap1 (orange), H2-proteinase (grey), acutolysin A (red) and ADAM33 (blue). In place of a Cys₄ zinc finger found in <i>Af</i>AmzA (yellow), the superposed metzincins exhibit two disulfide bonds as shown in (C) using the example of Bap1 (orange). Individual cysteine residues are labeled in accordance with the amino acid sequence of <i>Af</i>AmzA (yellow) in (B) and Bap1 (orange) in (C), respectively. Important secondary structure elements are labeled.</p

Structure of <i>Af</i>AmzA.

<p>Overall structure of <i>Af</i>AmzA in cartoon representation. The N-terminal domain (NTD) is colored in slate, the active site helix α2 in orange and the C-terminal domain (CTD) in green. The N- and C-termini, the edge strand β4 (cyan), the backing helix α1, the S-loop (yellow), the bulge edge segment (red), the S1′-wall forming segment (magenta) and the specificity loop (purple) are labeled. The residues involved in zinc ion binding, the catalytic base and the structurally important methionine are shown as sticks and the zinc ions as spheres.</p

Multiple sequence alignment of the amino acid sequences of <i>Af</i>AmzA with other archaemetzincins and metzincins.

<p>Archaemetzincins from <i>M. kandleri</i> (AMZA_METKA), <i>M. labreanum</i> (AMZA_METLZ), <i>H. sapiens</i> (AMZ2_HUMAN), non-catalytic archaemetzincin from <i>M. xanthus</i> (Q50888_MYXXA) and metzincins <i>H. sapiens</i> ADAM33 (ADA33_HUMAN), <i>P. flavoviridis</i> H2-proteinase (VMHR2_PROFL), <i>B. asper</i> Bap1 (VMBP1_BOTAS) and <i>A. acutus</i> acutolysin A (VMACA_DEIAC). Sequences were aligned using Chimera <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043863#pone.0043863-Meng1" target="_blank">[38]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043863#pone.0043863-Pettersen1" target="_blank">[39]</a> and visualized with ESPript <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043863#pone.0043863-Gouet1" target="_blank">[40]</a>. 3₁₀-Helices are indicated by η, β-turns by TT. Conserved residues in all sequences are highlighted in red. Similar sequences are in red letters, orange color indicates residues similar in each group (1, 2 or 3) but significantly different from the other groups.</p