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.

Associations between advanced glycation endproducts and matrix metalloproteinases and its inhibitor in individuals with type 1 diabetes.

AIMS: Advanced glycation endproducts (AGEs) and altered extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) are associated with vascular complications in type 1 diabetes. Experimental studies have shown that AGEs regulate the production of MMPs and/or TIMP-1. Therefore, we investigated associations between specific AGEs and MMP-1, -2, -3, -9, and -10, and TIMP-1 in individuals with type 1 diabetes. METHODS: In 670 type 1 diabetic individuals we determined serum levels of protein-bound AGEs Nε-(carboxymethyl)lysine (CML), Nε-(carboxyethyl)lysine (CEL), 5-hydro-5-methylimidazolone (MG-H1) and pentosidine, and MMP-1, -2, -3, -9, and -10, and TIMP-1. We performed linear regression analyses to investigate associations between AGEs and markers of the MMP-TIMP system. Analyses were adjusted for age, sex, HbA1c and duration of diabetes, and additionally for other potential confounders and presence of vascular complication. RESULTS: After full adjustment, levels of CML were positively associated with levels of MMP-2 and inversely with MMP-9. CEL was positively associated with MMP-3 and TIMP-1. MG-H1 was only associated with TIMP-1, whereas pentosidine was not associated with MMPs or TIMP-1. CONCLUSIONS: We showed independent associations between several AGEs and markers of the MMP-TIMP system, which indicate specific AGE-MMP/TIMP-1 interactions potentially contributing to vascular complications in patients with type 1 diabetes.

Plasma matrix metalloproteinases are associated with incident cardiovascular disease and all-cause mortality in patients with type 1 diabetes: a 12-year follow-up study.

BACKGROUND: Altered regulation of extracellular matrix remodeling by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP) may contribute to vascular complications in type 1 diabetes. We investigated associations between plasma MMP-1, -2, -3, -9, -10 and TIMP-1, and cardiovascular events and all-cause mortality in type 1 diabetic patients. METHODS: We prospectively followed 337 type 1 diabetic patients [mean age 41.4 years (9.6), 39% female], 170 with and 167 without diabetic nephropathy, with median follow-up of 12.3 years. Survival analyses were applied to investigate differences in plasma MMP-1, -2, -3, -9, -10, and TIMP-1-levels in patients with and without a cardiovascular event and in those who died vs survivors. All analyses were adjusted for age, sex, duration of diabetes, HbA1c, nephropathy and for other conventional cardiovascular risk factors. RESULTS: After adjustment for potential confounders, higher MMP-2 plasma levels were significantly associated with higher incidence of cardiovascular events [HR 1.49 (95% CI 1.11; 1.99)], and higher plasma levels of MMP-1 [1.38 (1.07; 1.78)], MMP-2 [1.60 (1.19; 2.15)] and MMP-3 [1.39 (1.05; 1.85)] were associated with all-cause mortality. All associations were independent of low-grade inflammation and endothelial dysfunction as estimated by plasma markers. Associations between MMP-2 and cardiovascular events and between MMP-3 and mortality were attenuated after further adjustment for eGFR and changes in eGFR. CONCLUSIONS: Higher levels of MMP-2 are associated with CVD and higher MMP-1, -2 and -3 with all-cause mortality. In addition, associations between MMP-2 and CVD, and MMP-3 and mortality were attenuated after adjustment for eGFR while both MMPs were associated with eGFR decline, indicating a possible mediating role of eGFR.

Do active design buildings change health behaviour and workplace perceptions?

BACKGROUND: Occupying new, active design office buildings designed for health promotion and connectivity provides an opportunity to evaluate indoor environment effects on healthy behaviour, sedentariness and workplace perceptions. AIMS: To determine if moving to a health-promoting building changed workplace physical activity, sedentary behaviour, workplace perceptions and productivity. METHODS: Participants from four locations at the University of Sydney, Australia, relocated into a new active design building. After consent, participants completed an online questionnaire 2 months before moving and 2 months after. Questions related to health behaviours (physical activity and sitting time), musculoskeletal issues, perceptions of the office environment, productivity and engagement. RESULTS: There were 34 participants (60% aged 25-45, 78% female, 84% employed full-time); 21 participants provided complete data. Results showed that after the move participants spent less work time sitting (83-70%; P < 0.01) and more time standing (9-21%; P < 0.01), while walking time remained unchanged. Participants reported less low back pain (P < 0.01). Sixty per cent of participants in the new workplace were in an open-plan office, compared to 16% before moving. Participants perceived the new work environment as more stimulating, better lit and ventilated, but noisier and providing less storage. No difference was reported in daily physical activity, number of stairs climbed or productivity. CONCLUSIONS: Moving to an active design building appeared to have physical health-promoting effects on workers, but workers' perceptions about the new work environment varied. These results will inform future studies in other new buildings.

Current therapeutic interventions in the glycation pathway: evidence from clinical studies.

The increased formation of advanced glycation endproducts (AGEs) constitutes a potential mechanism of hyperglycaemia-induced micro- and macrovascular disease in diabetes. In vitro and animal experiments have shown that various interventions can inhibit formation and/or actions of AGEs, in particular the specific AGE inhibitor aminoguanidine and the AGEs crosslink breaker alagebrium, and the B vitamins pyridoxamine and thiamine, and the latter's synthetic derivative, benfotiamine. The potential clinical value of these interventions, however, remains to be established. The present review provides, from the clinical point of view, an overview of current evidence on interventions in the glycation pathway relating to (i) the clinical benefits of specific AGE inhibitors and AGE breakers and (ii) the potential AGE-inhibiting effects of therapies developed for purposes unrelated to the glycation pathway. We found that safety and/or efficacy in clinical studies with the specific AGE inhibitor, aminoguanidine and the AGE breaker, alagebrium, appeared to be a concern. The clinical evidence on the potential AGE-inhibiting effects of B vitamins is still limited. Finally, current evidence for AGE inhibition by therapies developed for purposes unrelated to glycation is limited due to a large heterogeneity in study designs and/or measurement techniques, which have often been sub-optimal. We conclude that, clinical evidence on interventions to inhibit formation and/or action of AGEs is currently weak and unconvincing.

Is fat perception a thermal effect?

It has been generally assumed that fat is detected by its flavour and by its lubrication of the oral mucosa. A recent study reported a correlation of -.99 between perceived temperature of a product and its fat content. This was significantly higher than correlations of sensory scores for fat flavour, mouthfeel, and afterfeel. This suggested a third detection mechanism; fat may be detected via its effect on the thermal conductivity of the food. In 3 studies, thermal sensitivity in humans was investigated to verify whether oral thermal receptors are sufficiently rapid and accurate to play a role in the perception of fats. The thermal sensitivity of the lips and oral mucosa of the anterior and middle one-third of the tongue were assessed using a Peltier device. Subjects detected 0.5 Hz fluctuations in temperature of 0.08'C on the lower lip, 0.26 degrees C and 1.36 degrees C at the tip and dorsum of the tongue, demonstrating that the lips are sufficiently sensitive to detect small differences in temperature. In two further experiments subjects ingested custards and mayonnaises and then spat out samples after 5, 10, or 20 sec. The temperature of the food and oral mucosa was measured before and after spitting and the rates of heating were calculated. Results suggest assessment of thermal conductivity of food may be used to assess fat content.

Accuracy and precision of a densitometric tool for jaw bone.

OBJECTIVES: To develop a digital densitometric tool for jaw bone to analyse intraoral radiographs. To assess precision and accuracy for this tool and determine the minimal detection threshold for density changes. METHODS: Bone samples deriving from the premolar region of 47 human mandibles were selected for analysis. The samples were obtained from adult cadavers in the department of anatomy (Faculty of Medicine, KULeuven) with ethical approval. Digital radiography was performed on all bone samples. Direct volumetric measurements served as gold standard density values and allowed determination of accuracy. Dual-energy X-ray absorptiometry (DXA) scans were performed on all specimens. For all radiographs, density in mm Al eq was calculated using custom-made software, Osteop. Precision and intraobserver and interobserver reliability of this method were assessed. The bone specimens were progressively decalcified. At standard time intervals the percentage of decalcification was calculated. At each decalcification step, radiographs were taken and analysed. RESULTS: CV was always lower than 3%, which points to a good precision of the method. Correlation between the density measurements in mm Al eq and the DXA results was 0.9, for the density measurements in mm Al eq and the direct density measurements r was 0.5. The custom-made software was able to detect a change in bone mineralization of 6.6%. CONCLUSIONS: The present method for bone densitometric analysis offers potentials for clinical evaluation of bone density and minute bone density changes in the jaw bone.

Oral physiology and mastication.

Mastication is a sensory-motor activity aimed at the preparation of food for swallowing. It is a complex process involving activities of the facial, the elevator and suprahyoidal muscles, and the tongue. These activities result in patterns of rhythmic mandibular movements, food manipulation and the crushing of food between the teeth. Saliva facilitates mastication, moistens the food particles, makes a bolus, and assists swallowing. The movement of the jaw, and thus the neuromuscular control of chewing, plays an important role in the comminution of the food. Characteristics of the food, e.g. water and fat percentage and hardness, are known to influence the masticatory process. Food hardness is sensed during mastication and affects masticatory force, jaw muscle activity, and mandibular jaw movements. When we chew for instance a crispy food, the jaw decelerates and accelerates as a result of resistance and breakage of food particles. The characteristic breakage behaviour of food is essential for the sensory sensation. This study presents a short review of the influence of oral physiology characteristics and food characteristics on the masticatory process.

Increased FcgammaRII expression and aberrant tumour necrosis factor alpha production by mature dendritic cells from patients with active rheumatoid arthritis.

OBJECTIVES: To investigate potential differences in phenotype and behaviour of immature (iDC) and mature dendritic cells (mDC) from patients with RA and healthy subjects. METHODS: iDC and mDC were derived from blood monocytes of patients with RA and healthy controls following standardised protocols. FACS was used to analyse expression of FcgammaRI, II, and III and molecules to characterise DC. Discrimination between FcgammaRIIa and FcgammaRIIb was achieved by RT-PCR. Immunohistochemistry was performed on synovial biopsy specimens of three patients with RA and three healthy controls. TNFalpha production by iDC and mDC upon FcgammaR dependent stimulation was compared between patients with RA and controls by ELISA. RESULTS: iDC from patients with active RA but not from patients with inactive RA or healthy controls markedly up regulated FcgammaRII. mDC from patients with active RA also lacked the physiological down regulation of FcgammaRII that occurs upon maturation in both control groups. RT-PCR analysis confirmed the increased expression of FcgammaRII in RA-especially marked for FcgammaRIIb. FcgammaR dependent stimulation of DC using antigen-IgG immune complexes (IC) significantly increased TNFalpha production by DC from healthy subjects, but significantly decreased TNFalpha by DC from patients with RA. Overlapping expression patterns between FcgammaRII and DC-LAMP in the synovial tissue of patients with RA imply that in vivo, also, mature DC express increased levels of FcgammaRIIb. CONCLUSION: The presence and altered characteristics of DC during active RA suggest that DC help to modulate autoimmunity in RA. Further studies should elucidate the role of local factors in altering the function of DC in RA and in increasing expression of FcgammaRII.

Relationship between oral sensitivity and masticatory performance.

The size of a bolus determines how it will be manipulated in the mouth and swallowed. We hypothesized that mucosal sensitivity would be important for masticatory function. The accuracy of solid object size perception, spatial acuity, and food particle size reduction during mastication were measured in 22 healthy adults with/without topical anesthesia of their oral mucosa. Topical anesthesia had no effect on the perception of sphere sizes, but significantly reduced spatial sensitivity. Without anesthesia, there was a correlation between an individual's ability to perceive the sizes of steel spheres (diameter, 4-9 mm) and the sizes of food particles chewed for 15 cycles and at swallowing. There was no correlation between spatial sensitivity and food particle size. We suggest that the stimuli used to test two-point discrimination stimulates only superficial receptors, which involve light touch and are easily anesthetized, while the spheres might excite more deeply-set receptors. The latter appear to be more important for masticatory performance and swallowing.

The influence of density and material on oral perception of ball size with and without palatal coverage.

The size of a bolus determines how it will be manipulated in the mouth and swallowed. Ten healthy individuals assessed the size of ball bearings of five sizes (4-11 mm diameter) and four materials with different densities in order to investigate the effect of weight on oral size perception. To study the role of the tongue and palate, the experiment was performed with and without a custom-made plastic palate. The results revealed that size itself determines size perception, and that material and weight are negligible factors. An illusional effect in the direction of under-estimation was found for the ball bearings, especially for the small sizes up to 8 mm diameter. While wearing a plastic palate a significant improvement (P<0.05) occurred; the participants performed better and there was less under-estimation. An explanation for this could be that only a minor part of the total area of the ball bearing touches the palate and is hence detected, while the tongue alone is more compliant and thereby able to sense the ball's whole size.

The immune dysregulatory compound mercuric chloride induces integrin-mediated T-lymphocyte adhesion.

Exposure of Brown Norway rats to mercuric chloride induces systemic autoimmunity, involving T- and B-lymphocyte activation, (auto-)antibody production and multiorgan inflammation. Several divalent metal ions, such as Mg2+ and Mn2+, can activate binding of integrins to their ligands, thus causing lymphocyte adhesion. To test the hypothesis that Hg2+ acts in a similar way, we studied the effect of HgCl2 on integrin-mediated T-cell adhesion. HgCl2 induced cell-cell aggregation of human T lymphoblasts. Exposure of a human T-cell clone to HgCl2 for 1 hr enhanced, in a dose-dependent way, cell binding to fibronectin (FN) and to intercellular adhesion molecules (ICAM) -1, -2 and -3. Furthermore, HgCl2 induced strong binding of Jurkat T cells to FN. These effects of HgCl2 were of similar magnitude as the effects of phorbol 12-myristate 13-acetate (PMA) or MnCl2. Studies using blocking antibodies indicated the involvement of CD11a in binding to ICAMs, and of CD49d, CD49e, and CD29 in binding to FN. Adhesion to FN induced by HgCl2 or by PMA, but not by MnCl2, was dependent on temperature and on extracellular Ca2+ or Mg2+. Addition of cytochalasin B enhanced synergistically the FN adhesion induced by MnCl2, whereas the effects of PMA and HgCl2 were not modified. These results indicate that Hg2+ is a potent activator of T-cell adhesion, mediated by several integrins and ligands. In contrast to the effect of MnCl2, HgCl2-induced cell adhesion probably involves an intracellular pathway. Activation of integrins by HgCl2 may play an important role in activation and migration of leucocytes involved in HgCl2-induced immune dysregulation in vivo.

The renal cell carcinoma-associated antigen G250 encodes a human leukocyte antigen (HLA)-A2.1-restricted epitope recognized by cytotoxic T lymphocytes.

Evidence has accumulated that the immune system can play a significant role in the defense against tumors in humans. Especially melanoma and renal cell carcinoma (RCC) are considered immunogenic tumors. In contrast to melanoma, hardly any RCC-associated antigens have been identified as targets for RCC-reactive T cells. Here, we report the identification of a human leukocyte antigen (HLA)-A2.1-restricted T-cell epitope within the G250 antigen. This antigen is expressed in 85% of RCCs but not by neighboring normal kidney tissue and has recently been molecularly defined and shown to be identical to MN/CA IX. Computer-aided motif prediction revealed the presence of 60 potential HLA-A2.1-binding peptides within the G250 antigen. Subsequent binding analysis showed that 13 of these peptides bound to HLA-A2.1 with high-to-intermediate affinity. Analysis of their immunogenicity in HLA-A2.1Kb transgenic mice indicated that 4 of the 13 peptides gave rise to cytotoxic T lymphocytes (CTLs) capable of lysing peptide-loaded target cells. However, only the G250 peptide 254-262 induced CTLs that recognized target cells that endogenously expressed the G250 antigen. Similarly, we were also able to raise human CTLs against the G250 peptide 254-262, which lysed target cells that endogenously expressed the G250 antigen. These findings and the high prevalence of this antigen in RCC patients makes G250 a potential target for anti-RCC immunotherapy.

Monoclonal antibodies for epidermal population analysis.

Three keratin antibodies (RKSE 60, Clone 77, and a rabbit polyclonal) and 2 vimentin antibodies (Vim ab and a rabbit polyclonal) were investigated using frozen sections of normal and psoriatic skin. Of these, the monoclonals RKSE 60 and Vim ab were selected for quantitative population analysis of healthy epidermis, psoriatic uninvolved epidermis, and psoriatic lesions. Suspensions of isolated cells were prepared from biopsy specimens by trypsinization, and stained with RKSE 60 or Vim ab using an indirect immunofluorescence assay. Our results showed an increase in the germinative fraction from the normal value of 30% to almost 50% in the psoriatic lesion; in absolute terms this corresponds to a 6-fold increase in the size of the germinative compartment. More interesting, the germinative psoriatic uninvolved epidermis (38%) was also significantly higher than normal. The percentage of vimentin-positive cells (Langerhans cells and melanocytes) was nearly double that of normal in both the lesion and the uninvolved psoriatic epidermis. We conclude that, in contrast to statements frequently encountered in the literature, the "uninvolved" skin of the patient is morphologically and functionally different from that of the healthy individual.