Hypermobility and musculoskeletal pain in children:a systematic review

Objective: To examine the evidence of an association between hypermobility and musculoskeletal pain in children. Methods: A systematic review of the literature was performed using the databases PubMed, EMBASE, NHS Evidence, and Medline. Inclusion criteria were observational studies investigating hypermobility and musculoskeletal pain in children. Exclusion criteria were studies conducted on specialist groups (i.e. dancers) or hospital referrals. Pooled odds ratios (ORs) were calculated using random effects models and heterogeneity was tested using ?(2)-tests. Study quality was assessed using the Newcastle-Ottawa Scale for case-control studies. Results: Of the 80 studies identified, 15 met the inclusion criteria and were included in the review. Of these, 13 were included in the statistical analyses. Analysing the data showed that the heterogeneity was too high to allow for interpretation of the meta-analysis (I(2) = 72%). Heterogeneity was much lower when the studies were divided into European (I(2) = 8%) and Afro-Asian subgroups (I(2) = 65%). Sensitivity analysis based on data from studies reporting from European and Afro-Asian regions showed no association in the European studies [OR 1.00, 95% confidence interval (CI) 0.79-1.26] but a marked relationship between hypermobility and joint pain in the Afro-Asian group (OR 2.01, 95% CI 1.45-2.77). Meta-regression showed a highly significant difference between subgroups in both meta-analyses (p <0.001). Conclusion: There seems to be no association between hypermobility and joint pain in Europeans. There does seem to be an association in Afro-Asians; however, there was a high heterogeneity. It is unclear whether this is due to differences in ethnicity, nourishment, climate or study design.

Compressive membrane action in composite floor slabs in the Cardington LBTF

This paper presents the results of an experimental study (the ultimate load capacity of composite metal decking/concrete floor slabs. Full-scale in situ testing of composite floor slabs was carried out in the Building Research Establishment's Large Building Test Facility (LBTF) at Cardington. A parallel laboratory test programme, which compared the behaviour of composite floor slabs strips, also carried out at Queen's University Belfast (QUB). Articular attention was paid to the contribution of compressive membrane action to the load carrying capacity. The results of both test programmes were compared with predictions by yield line theory and a theoretical prediction method in which the amount of horizontal restraint mid be assessed. The full-scale tests clearly demon-wed the significant contribution of compressive membrane effects to the load capacity of interior floor panels with a lesser contribution to edge/corner panels.

Influence of predominant patterns of coordination on the exploitation of interaction torques in a two-joint rhythmic arm movement

In this study we investigate the coordination between rhythmic flexion-extension (FE) and supination-pronation (SP) movements at the elbow joint-complex, while manipulating the intersegmental dynamics by means of a 2-degrees of freedom (df) robot arm. We hypothesized that constraints imposed by the structure of the neuromuscular-skeletal system would (1) result in predominant pattern(s) of coordination in the absence of interaction torques and (2) influence the capabilities of participants to exploit artificially induced interaction torques. Two experiments were conducted in which different conditions of interaction torques were applied on the SP-axis as a function of FE movements. These conditions promoted different patterns of coordination between the 2-df. Control trials conducted in the absence of interaction torques revealed that both the in-phase (supination synchronized with flexion) and the anti-phase (pronation synchronized with flexion) patterns were spontaneously established by participants. The predominance of these patterns of coordination is explained in terms of the mechanical action of bi-articular muscles acting at the elbow joint-complex, and in terms of the reflexes that link the activity of the muscles involved. Results obtained in the different conditions of interaction torques revealed that those neuromuscular-skeletal constraints either impede or favor the exploitation of intersegmental dynamics depending on the context. Interaction torques were indeed found to be exploited to a greater extent in conditions in which the profiles of interaction torques favored one of the two predominant patterns of coordination (i.e., in-phase or anti-phase) as opposed to other patterns of coordination (e.g., 90 degrees or 270 degrees). Those results are discussed in relation to recent studies reporting exploitation of interaction torques in the context of rhythmic movements.

Fabrication and Repair of Cartilage Defects with a Novel Acellular Cartilage Matrix Scaffold

The objectives of this study were to develop a three-dimensional acellular cartilage matrix (ACM) and investigate its possibility for use as a scaffold in cartilage tissue engineering. Bovine articular cartilage was decellularized sequentially with trypsin, nuclease solution, hypotonic buffer, and Triton x 100 solution; molded with freeze-drying process; and cross-linked by ultraviolet irradiation. Histological and biochemical analysis showed that the ACM was devoid of cells and still maintained the collagen and glycosaminoglycan components of cartilage. Scanning electronic microscopy and mercury intrusion porosimetry showed that the ACM had a sponge-like structure of high porosity. The ACM scaffold had good biocompatibility with cultured rabbit bone marrow mesenchymal stem cells with no indication of cytotoxicity both in contact and in extraction assays. The cartilage defects repair in rabbit knees with the mesenchymal stem cell-ACM constructs had a significant improvement of histological scores when compared to the control groups at 6 and 12 weeks. In summary, the ACM possessed the characteristics that afford it as a potential scaffold for cartilage tissue engineering.

The complex effects of the slow-releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cells

The role of hydrogen sulfide (H2 S) in inflammation remains unclear with both pro- and anti-inflammatory actions of this gas described. We have now assessed the effect of GYY4137 (a slow-releasing H2 S donor) on lipopolysaccharide (LPS)-evoked release of inflammatory mediators from human synoviocytes (HFLS) and articular chondrocytes (HAC) in vitro. We have also examined the effect of GYY4137 in a complete Freund's adjuvant (CFA) model of acute joint inflammation in the mouse. GYY4137 (0.1-0.5 mM) decreased LPS-induced production of nitrite (NO2 (-) ), PGE2 , TNF-a and IL-6 from HFLS and HAC, reduced the levels and catalytic activity of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and reduced LPS-induced NF-?B activation in vitro. Using recombinant human enzymes, GYY4137 inhibited the activity of COX-2, iNOS and TNF-a converting enzyme (TACE). In the CFA-treated mouse, GYY4137 (50 mg/kg, i.p.) injected 1 hr prior to CFA increased knee joint swelling while an anti-inflammatory effect, as demonstrated by reduced synovial fluid myeloperoxidase (MPO) and N-acetyl-ß-D-glucosaminidase (NAG) activity and decreased TNF-a, IL-1ß, IL-6 and IL-8 concentration, was apparent when GYY4137 was injected 6 hrs after CFA. GYY4137 was also anti-inflammatory when given 18 hrs after CFA. Thus, although GYY4137 consistently reduced the generation of pro-inflammatory mediators from human joint cells in vitro, its effect on acute joint inflammation in vivo depended on the timing of administration.

Effect of collagen turnover on the accumulation of advanced glycation end products

Collagen molecules in articular cartilage have an exceptionally long lifetime, which makes them susceptible to the accumulation of advanced glycation end products (AGEs). In fact, in comparison to other collagen-rich tissues, articular cartilage contains relatively high amounts of the AGE pentosidine. To test the hypothesis that this higher AGE accumulation is primarily the result of the slow turnover of cartilage collagen, AGE levels in cartilage and skin collagen were compared with the degree of racemization of aspartic acid (% d-Asp, a measure of the residence time of a protein). AGE (N(epsilon)-(carboxymethyl)lysine, N(epsilon)-(carboxyethyl)lysine, and pentosidine) and % d-Asp concentrations increased linearly with age in both cartilage and skin collagen (p <0.0001). The rate of increase in AGEs was greater in cartilage collagen than in skin collagen (p <0.0001). % d-Asp was also higher in cartilage collagen than in skin collagen (p <0.0001), indicating that cartilage collagen has a longer residence time in the tissue, and thus a slower turnover, than skin collagen. In both types of collagen, AGE concentrations increased linearly with % d-Asp (p <0.0005). Interestingly, the slopes of the curves of AGEs versus % d-Asp, i.e. the rates of accumulation of AGEs corrected for turnover, were identical for cartilage and skin collagen. The present study thus provides the first experimental evidence that protein turnover is a major determinant in AGE accumulation in different collagen types. From the age-related increases in % d-Asp the half-life of cartilage collagen was calculated to be 117 years and that of skin collagen 15 years, thereby providing the first reasonable estimates of the half-lives of these collagens.

Antimicrobial peptides and proinflammatory cytokines in periprosthetic joint infection

Background: Differentiation between septic and aseptic loosening of joint replacements is essential for successful revision surgery, but reliable markers for the diagnosis of low-grade infection are lacking. The present study was performed to assess intra-articular and systemic levels of antimicrobial peptides and proinflammatory cytokines as diagnostic markers for periprosthetic joint infection. Methods: Fifteen consecutive patients with staphylococcal periprosthetic joint infections and twenty control patients with aseptic loosening of total hip and knee replacements were included in this prospective, single-center, controlled clinical trial. Expression of the antimicrobial peptides human β-defensin-2 (HBD-2), human β-defensin-3 (HBD-3), and cathelicidin LL-37 (LL-37) was determined by ELISA (enzyme-linked immunosorbent assay) in serum and joint aspirates. Proinflammatory cytokines were assessed in serum and joint aspirates with use of cytometric bead arrays. C-reactive protein in serum, microbiology, and histopathology of periprosthetic tissue served as the “gold standard” for the diagnosis of infection. Results: The antimicrobial peptides HBD-3 and LL-37 were significantly elevated in joint aspirates from patients with periprosthetic joint infection compared with patients with aseptic loosening, and the area under the curve (AUC) in a receiver operating characteristic curve analysis was equal to 0.745 and 0.875, respectively. Additionally, significant local increases in the proinflammatory cytokines interleukin (IL)-1β, IL-4, IL-6, IL-17A, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were observed to be associated with infection. Logistic regression analysis indicated that the combination of an antimicrobial peptide with another synovial fluid biomarker improved diagnostic accuracy; the AUC value was 0.916 for LL-37 and IL-4, 0.895 for LL-37 and IL-6, 0.972 for HBD-3 and IL-4, and 0.849 for HBD-3 and IL-6. In contrast, the only antimicrobial peptides and cytokines in serum that showed a significant systemic increase in association with infection were HBD-2, IL-4, and IL-6 (all of which had an AUC value of <0.75). Conclusions: The present study showed promising results for the use of antimicrobial peptides and other biomarkers in synovial fluid for the diagnosis of periprosthetic joint infection, and analysis of the levels in synovial fluid was more accurate than analysis of serum.

Efficacy and Acceptability of Reduced Intensity Constraint-Induced Movement Therapy for Children Aged 9–11 years with Hemiplegic Cerebral Palsy: A Pilot Study

OBJECTIVE: Assess efficacy and acceptability of reduced intensity constraint-induced movement therapy (CIMT) in children with cerebral palsy (CP).

METHODS: Single-subject research design and semi-structured interviews. Children (9-11y) with hemiplegia underwent five baseline assessments followed by two weeks CIMT. Six further assessments were performed during treatment and follow-up phases. The primary outcome was the Melbourne Assessment of Unilateral Upper Limb Function (MUUL). Quantitative data were analysed using standard single-subject methods and qualitative data by thematic analysis.

RESULTS: Four of the seven participants demonstrated statistically significant improvements in MUUL (3-11%, p < .05). Two participants achieved significant improvements in active range of motion but strength and tone remained largely unchanged. Qualitative interviews highlighted limitations of the restraint, importance of family involvement, and coordination of treatment with education.

CONCLUSIONS: Reduced intensity CIMT may be effective for some children in this population; however it is not suitable for all children with hemiplegia.