Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament.

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We tested the hypothesis that continuous intraopera-tive infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery. Thirty adolescents were randomly assigned to receive an intra-operative analgesic regimen consisting of continuous remifentanil infusion or intermittent morphine alone. Postoperative analgesic consumption was assessed with a patient-controlled analgesia device that was used to self-administer morphine. Cumulative postop-erative morphine consumption, pain scores, and sedation scores were recorded by a blinded investigator every hour for the first 4 h postoperatively and then every 4 h for a total of 24 h. Cumulative morphine consumption in the remifentanil group was significantly more than that in the morphine group at each time point in the initial 24 h after surgery (P 0.0001). At 24 h after surgery, cumulative morphine consumption was 30% greater in the remifentanil group (1.65 0.41 mg/kg) than in the morphine group (1.27 0.32 mg/ kg) (95% confidence interval for the difference, 0.11 to 0.65 mg/kg). Differences in pain and sedation scores were not statistically significant. These data suggest that intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery.

BACKGROUND. Body checking is the predominant mechanism of youth ice hockey injuries. The Canadian Hockey Association has allowed body checking from ages 12 to 13 (peewee level) and up. One Canadian province (Ontario) introduced body checking at ages 10 to 11 (atom level) in the competitive leagues, whereas in Quebec body checking has only been allowed at ages 14 to 15 (bantam Level). The purpose of this study was to compare body-checking injuries, fractures, and concussions in boys' minor hockey between jurisdictions in which checking is allowed and jurisdictions in which body checking is not allowed. METHODS. Data from the Canadian Hospitals Injury Reporting and Prevention Program (CHIRPP) were used to characterize children's ice hockey injuries from September 1995 to the end of August 2002. Children treated at CHIRPP hospitals in areas in which checking was allowed were compared with children in areas in which checking was not allowed. RESULTS. Of the 4736 hockey injuries, 3006 (63%) were in Ontario and 1730 (37%) were in Quebec. Most of the injuries occurred in areas in which checking was allowed (2824 [59.6%]). At ages 10 to 13, players had significantly greater odds of suffering a checking injury where checking was allowed (odds ratio [OR]: 1.86; 95% confidence interval [CI]: 1.6–2.11). Players in this age group were also more likely to suffer a concussion (OR: 1.42; 95% CI: 0.98–2.05) or fracture (OR: 1.25; 95% CI: 1.06–1.47) where checking was allowed. Among older players, when checking was allowed in both provinces, there were higher odds (OR: 1.90; 95% CI: 1.36–2.66) of receiving a checking injury in the province that had introduced checking at a younger age, suggesting that there is no protective effect from learning to check earlier. CONCLUSIONS. Increased injuries attributable to checking were observed where checking was allowed. This study supports policies that disallow body checking to reduce ice hockey injuries in children.

Secreted protein, acidic, cysteine-rich (SPARC) is a glycoprotein that binds to collagen type I and other proteins in the extracellular matrix. Using whole-exome sequencing to identify the molecular defect in two unrelated girls with severe bone fragility and a clinical diagnosis of osteogenesis imperfecta type IV, we identified two homozygous variants in SPARC (GenBank: NM_003118.3; c.497G>A [p.Arg166His] in individual 1; c.787G>A [p.Glu263Lys] in individual 2). Published modeling and site-directed mutagenesis studies had previously shown that the residues substituted by these mutations form an intramolecular salt bridge in SPARC and are essential for the binding of SPARC to collagen type I. The amount of SPARC secreted by skin fibroblasts was reduced in individual 1 but appeared normal in individual 2. The migration of collagen type I alpha chains produced by these fibroblasts was mildly delayed on SDS-PAGE gel, suggesting some overmodification of collagen during triple helical formation. Pulse-chase experiments showed that collagen type I secretion was mildly delayed in skin fibroblasts from both individuals. Analysis of an iliac bone sample from individual 2 showed that trabecular bone was hypermineralized on the material level. In conclusion, these observations show that homozygous mutations in SPARC can give rise to severe bone fragility in humans.

This is the first large observational study examining school travel mode and the environment. Walking proportions were higher than those previously reported in Toronto, with large variability. Associations between population density and several roadway design features and walking were confirmed. School crossing guards may override the influence of roadway features on walking. Results have important implications for policies regarding walking promotion.

These data do not support the use of intraoperative low-dose ketamine to prevent the development of remifentanil-induced acute opioid tolerance and/or hyperalgesia during pediatric scoliosis surgery.

Radiographic and physical measures of deformity do not correlate well with patients' and parents' perceptions of appearance. Patients and parents do not strongly agree on the cosmetic outcome of AIS surgery. Therefore, given that the adolescents themselves undergo the surgery, patients' assessments of their deformity, rather than radiographic measures or parents' assessments, should play a major role in the evaluation of surgical success.