Barriers, facilitators and solutions for active inclusive play for children with a physical disability in the Netherlands: a qualitative study.

BACKGROUND: Children with physical disabilities (PD) are less physically active than typically developing peers. The most important contributor to physical activity for primary school-aged children is outside play and therefore this should be part of every child's life. However, children with PD experience multiple barriers to participation in playgrounds. Despite recent improvements in the accessibility of Dutch playgrounds, the participation of children with PD has not increased. This study aims to explore facilitators, barriers and solutions influencing the participation of children with PD in Dutch outdoor playgrounds, from parents' and professionals' perspectives. METHODS: Twelve semi-structured interviews with parents of children with PD aged 2-12 years and five focus group meetings with professionals working with these children were conducted. To ensure data saturation, we performed three member-check meetings. Two independent researchers analyzed the data using an inductive thematic approach. RESULTS: Similar barriers, facilitators and solutions were mentioned by parents and professionals. Three main themes were identified: the emotional barrier versus the physical barrier, play as a part of an inclusive society and the role of professionals in facilitating active inclusive play. The most important personal factors were physical and social problems experienced when children with PD wanted to join outdoor play. Interestingly, parents and professionals believed the social barrier was far more important than the physical one. The most important environmental factor was that the Dutch society is not sufficiently inclusive. CONCLUSIONS: According to both parents and professionals, the most important barrier to active inclusive outdoor play was social, hindering the participation of children with PD in play with typically developing peers. To overcome such problems, professionals should take an active role in empowering children with PD and their parents. Furthermore, it is important to introduce outdoor active play early, so it becomes part of normal daily life. In addition, a change in the mindset of typically developing children and their parents seems essential to achieve true inclusive active play.

Wheelchair Mobility Confidence Scale for Dutch youth using a manual wheelchair.

Purpose: The objective of this study was to develop a questionnaire to assess confidence in wheelchair mobility in Dutch youth (WheelCon-Mobility Dutch Youth).Methods: (1) A forward-backward translation process was used to translate the original WheelCon-M from English to Dutch. (2) Items related to wheelchair mobility in Dutch youth were selected and adapted based on focus groups with youth, parents and health care professionals to create the WheelCon-Mobility Dutch Youth. (3) The WheelCon-Mobility Dutch Youth and the Utrecht Pediatric Wheelchair Mobility Skills Test 2.0 (UP-WMST 2.0) were administered to 62 participants to evaluate internal consistency and construct validity.Results: Translation and cultural adaptation led to general adaptations in instructions, sentence structure and response scale. At the item level, 24 items were included with (n = 17) and without (n = 7) adaptation, 10 items were deleted and 7 new items were included. The WheelCon-Mobility Dutch Youth had an excellent Cronbach's alpha of 0.924 and a significant correlation (r = 0.44, p < .001) with the UP-WMST 2.0.Conclusions: This study resulted in the adaptation of the WheelCon-M into the WheelCon-Mobility for Dutch youth using a manual wheelchair. Our study suggests there is evidence supporting the internal consistency and construct validity of the WheelCon-Mobility Dutch Youth.Implications for RehabilitationThe WheelCon-Mobility Dutch Youth is a newly developed tool for assessing confidence in wheelchair mobility in Dutch youth using a manual wheelchair.It is important to assess performance and confidence in wheelchair mobility in paediatric rehabilitation.

Novel IRF6 Mutations Detected in Orofacial Cleft Patients by Targeted Massively Parallel Sequencing.

Common variants in interferon regulatory factor 6 ( IRF6) have been associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) as well as with tooth agenesis (TA). These variants contribute a small risk towards the 2 congenital conditions and explain only a small percentage of heritability. On the other hand, many IRF6 mutations are known to be a monogenic cause of disease for syndromic orofacial clefting (OFC). We hypothesize that IRF6 mutations in some rare instances could also cause nonsyndromic OFC. To find novel rare variants in IRF6 responsible for nonsyndromic OFC and TA, we performed targeted multiplex sequencing using molecular inversion probes (MIPs) in 1,072 OFC patients, 67 TA patients, and 706 controls. We identified 3 potentially pathogenic de novo mutations in OFC patients. In addition, 3 rare missense variants were identified, for which pathogenicity could not unequivocally be shown, as all variants were either inherited from an unaffected parent or the parental DNA was not available. Retrospective investigation of the patients with these variants revealed the presence of lip pits in one of the patients with a de novo mutation suggesting a Van der Woude syndrome (VWS) phenotype, whereas, in other patients, no lip pits were identified.

Digital image analysis versus clinical assessment of wound epithelialization: a validation study.

To evaluate the progress in wound healing, wound assessment is mandatory. Epithelialization is traditionally assessed subjectively by the clinician. In a previous study, subjective assessment of epithelialization was shown to be reliable. In this study, reliability of epithelialization measured by digital image analysis was investigated and then, we validated the subjective evaluation by comparing this assessment to measurements with digital image analysis. Clinicians assessed epithelialization in 50 burn wounds that were treated with a split skin graft. Epithelialization of these wounds was also measured by three observers using digital image analysis. Reliability of digital image analysis was tested using the intraclass correlation (IC). To test validity, subjective clinical assessment was correlated with digital image analysis (IC). The results showed that interobserver reliability of epithelialization measured by digital image analysis was good (IC coefficient 0.74). Subjective clinical assessment of epithelialization showed a strong correlation with digital image analysis (IC coefficient 0.80). In conclusion, subjective clinical evaluation of wound epithelialization is as good as an objective measure, in this study digital image analysis. Since digital image analysis is more time-consuming, we recommend the use of the subjective evaluation for daily practice.

Reliability of subjective wound assessment.

INTRODUCTION: Assessment of the take of split-skin graft and the rate of epithelialisation are important parameters in burn surgery. Such parameters are normally estimated by the clinician in a bedside procedure. This study investigates whether this subjective assessment is reliable for graft take and wound epithelialisation. METHODS: Observers involved in the field of burns (experienced, medium-experienced and inexperienced observers), and dermatologists specialized in the field of wound healing evaluated the percentage graft take and epithelialisation in 50 photographic skin-grafted burn wounds. Reliability was tested using the intraclass correlation coefficient (ICC). RESULTS: Intra- and interobserver reliability of parameter graft take was highest within the experienced observers (ICC average > 0.91), followed by medium- and inexperienced observers (ICC average > 0.80 and ICC average > 0.68). Parameter epithelialisation showed the same pattern of intra- and interobserver ICC scores (experienced > medium > inexperienced). Interobserver ICC single scores of the experienced group were reasonable to good. Interobserver reliability of the dermatologists was similar to medium-experienced observers. CONCLUSIONS: Our data show that one experienced observer can obtain adequate reliable results by means of a single assessment of graft take and epithelialisation. Furthermore, experience of the observer results in an increase of reliability.

Predictors of outcome at 2 years of age after early intrauterine growth restriction.

OBJECTIVE: To examine the relative importance of antenatal and perinatal variables on short- and long-term outcome of preterm growth restricted fetuses with umbilical artery (UA) Doppler abnormalities. METHODS: This was a cohort study of 180 neonates with birth weight < 10(th) percentile, gestational age at delivery < 34 weeks and abnormal Doppler ultrasound examination of the UA. Various antenatal and perinatal variables were studied in relation to short- and long-term outcome. RESULTS: Neonatal and overall mortality (up to 2 years of age) were predicted by low gestational age at delivery. Neonatal mortality was additionally predicted by absent or reversed UA end-diastolic flow, while the presence of severe neonatal complications and placental villitis were additional predictors of both infant (between 28 days and 1 year of postnatal life) and overall mortality. Placental villitis was found to be the only predictor of necrotizing enterocolitis. Low gestational age at delivery, male sex, abnormal cardiotocography, absent or reversed UA end-diastolic flow and the HELLP syndrome predicted respiratory distress syndrome. Abnormal neurodevelopmental outcome at 2 years was predicted by low birth weight (< 2.3(rd) percentile), fetal acidosis (UA pH < 7.00), and placental villitis. CONCLUSION: Less advanced gestation at delivery remains an important predictor of short-term outcome in growth-restricted fetuses. In addition, the presence of placental villitis may aid neonatologists in the early identification of infants at increased risk of necrotizing enterocolitis, death and abnormal neurodevelopment at 2 years of age. Abnormal neurodevelopment was related to low weight and acidosis at birth, indicating that the severity of malnutrition and fetal acidosis affect long-term outcome.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in gingival crevicular fluid during orthodontic tooth movement.

Orthodontic tooth movement requires extensive re-modelling of the periodontium. Matrix metalloproteinases (MMPs) degrade the extracellular matrix during re-modelling, while their activity is regulated by the tissue inhibitors of metalloproteinases (TIMPs). The aim of this study was to investigate differences in MMP and TIMP levels in the gingival crevicular fluid (GCF) at the resorption and apposition sides of orthodontically moved teeth, and to compare these with control teeth. GCF samples were collected from eight orthodontic patients wearing fixed appliances with superelastic nickel-titanium coil springs. The samples were analysed by gelatin zymography, which allows detection of both active and latent MMPs, and reverse zymography for analysis of TIMPs. Western blotting was performed to confirm the identity of MMPs. The data were analysed using either the one-way analysis of variance or the Kruskal-Wallis test. In general, higher levels of MMPs and TIMPs were found at both the resorption and apposition sides compared with the control teeth. Remarkably, partially active MMP-1 was found in GCF from both the resorption and the apposition side but was barely present at the control teeth. TIMP-1 was strongly increased at the apposition side. Gelatinases were mainly present at the resorption side, while gelatinolytic fragments were exclusively detected at the apposition side. MMP-9, which is known to be involved in bone degradation, and a 48 kDa gelatinase were increased at the resorption side. The small increase in TIMP-1 at the resorption side might stimulate bone resorption, whereas the large increase at the apposition side reduces bone resorption. The analysis of MMPs and TIMPs may contribute to the improvement of orthodontic treatment regimens.

Matrix metalloproteinase inhibitors reduce collagen gel contraction and alpha-smooth muscle actin expression by periodontal ligament cells.

BACKGROUND AND OBJECTIVE: Orthodontic tooth movement requires remodeling of the periodontal tissues. The matrix metalloproteinases (MMPs) degrade the extracellular matrix components of the periodontal ligament, while the tissue inhibitors of metalloproteinases (TIMPs) control their activity. Synthetic MMP inhibitors have been developed to inhibit MMP activity. In this study, periodontal ligament cells in contracting collagen gels served as a model for enhanced periodontal remodeling. The effect of MMP inhibitors on gel contraction and on MMP and TIMP expression was analyzed. MATERIAL AND METHODS: Human periodontal ligament cells were cultured in three-dimensional collagen gels and incubated with the MMP inhibitors BB94, CMT-3, doxycycline and Ilomastat. Gel contraction was determined using consecutive photographs. The relative amounts of MMPs and TIMPs were analyzed using substrate zymography and mRNA expression using quantitative polyermase chain reaction. RESULTS: All MMP inhibitors reduced MMP activity to about 20% of the control activity. They all reduced contraction, but CMT-3 and doxycycline had the strongest effect. These inhibitors also reduced MMP-2, MMP-3 and alpha-smooth muscle actin mRNA expression. The expression of MMP-1 mRNA seemed to be increased by CMT-3. No effects were found on the amounts of MMPs and TIMPs. CONCLUSION: Synthetic MMP inhibitors strongly reduced gel contraction by periodontal ligament cells. This was primarily caused by an inhibitory effect on MMP activity, which reduces matrix remodeling. In addition, alpha-smooth muscle actin expression was reduced by CMT-3 and doxycycline, which limits the contractile activity of the fibroblasts.

Expression of the gene encoding the beta-amyloid precursor protein APP in Xenopus laevis.

The beta-amyloid precursor protein APP is generally accepted to be directly or indirectly involved in the neurodegenerative disorder Alzheimer's disease and has been extensively studied in a number of mammalian systems. Its normal function remains, however, still elusive. We have used the clawed toad, Xenopus laevis, to study the first non-mammalian APP protein. Screening of a Xenopus laevis intermediate pituitary cDNA library led to the identification of two structurally different APP gene transcripts presumably resulting from duplicated genes. Sequence comparison between the Xenopus and human APP proteins revealed at the amino acid sequence level an identity of 92%. Both Xenopus genes were found to be expressed in all tissues examined, but their expression levels differed among tissues. In addition, as in mammals, alternative splicing was observed and the alternatively spliced APP(695) mRNA variant was expressed predominantly in the brain and the oocyte, while the longer isoforms (APP(751-770)) were predominant in the other tissues examined. Of special interest is the finding that, like human but unlike mouse or rat beta-amyloid (Abeta), the Xenopus peptide contains all amino acid residues implicated in amyloidogenesis. We conclude that Xenopus APP mRNA is ubiquitously expressed and alternatively spliced, and that the highly conserved Xenopus APP protein contains an Abeta peptide with amyloidogenic potency.

Novel frameshift mutations near short simple repeats.

In patients with Alzheimer's disease or Down's syndrome, the cerebellar cortex exhibits protein deposits in neurofibrillary tangles and neuritic plaques. Recently, the deposits have been shown to contain protein fragments of ubiquitin-B and amyloid precursor protein (APP) with an aberrant carboxyl terminus resulting from frameshift mutations (dinucleotide deletions; DeltaGU or DeltaGA) in or adjacent to GAGAG motifs in their mRNAs, a process referred to as molecular misreading. We have now used a bacterial expression system with the green fluorescent protein as a reporter to screen gene transcripts from aged controls, Alzheimer's disease, and Down's syndrome for molecular misreading. Novel frameshift mutations at a number of locations in the transcripts of the ubiquitin-B and APP genes were discovered (DeltaGA, DeltaG, DeltaGU, DeltaGG, DeltaCA, DeltaAU, DeltaA, DeltaAA, DeltaC, DeltaU, and insertion of an A). Interestingly, most mutations were in close proximity of short simple repeats (GAGAG, GGUGGU, GAGACACACA, UCAUCAUCA, CAAACAAA, and GAAGAAGAA), demonstrating that the GAGAG motif does not constitute the only hot spot for transcriptional errors. Unlike the previously detected aberrant APP fragments, some of the novel ones have the potential to generate the neurotoxic peptide beta-amyloid. We conclude that during aging molecular misreading is a widespread phenomenon.

Homeobox proteins as signal transduction intermediates in regulation of NCAM expression by recombinant human bone morphogenetic protein-2 in osteoblast-like cells.

The role of homeobox genes in signaling of recombinant human bone morphogenetic protein-2 (rhBMP-2) was studied in osteoblast-like cells. Expression of several homeobox genes was decreased by rhBMP-2. The finding that this regulation of homeobox gene expression by rhBMP-2 was not dependent on protein synthesis suggests that homeobox proteins can act as direct intermediates in signal transduction of BMPs. Therefore, we studied the regulation of neural cell adhesion molecule (NCAM), which has previously been described as a target gene of both rhBMP-2 and homeobox proteins. We now show that in osteoblast-like cells, rhBMP-2 inhibits NCAM expression, while HOXC6 increases its expression, both acting via the same region of the promoter. As overexpression of HOXC6 could abolish effects of rhBMP-2 on NCAM promoter activity, these data show for the first time that members of the homeobox gene family may form direct functional intermediates in the signaling mechanism of the TGF-beta superfamily.