Reduction of severe wrist injuries in snowboarding by an optimized wrist protection device: a prospective randomized trial

BACKGROUND: The benefits of sport are well recognized, but many activities carry a sport-specific injury risk. Snowboarding has become an increasingly popular winter sport in Austria in recent years, with an estimated 900,000 participants annually. Roughly 6,000 of these suffer from injury and up to 2,000 sustain moderate or severe wrist injuries (mainly fractures of the distal radius and epiphysiolyses). METHODS: We conducted a prospective, randomized, controlled trial to test the protective effect of a wrist protector, which differs in position, stiffness, length, and fixation from conventional protectors. Seven hundred twenty-one snowboarders were randomized into two groups. The risk factors and the injuries that occurred were registered by questionnaires and, in case of medical treatment, by medical reports. Time until injury (in half-days) was compared by the proportional hazards model. RESULTS: Nine severe wrist injuries were sustained in the unprotected control group and only one in the protected group (hazard ratio, 0.13; 95% confidence limits, 0.02, 1.04). Twelve snowboarders of the protector group secretly discarded their protectors during the trial (including the snowboarder who suffered the one and only severe wrist injury of this group). A per-protocol analysis was therefore performed, which demonstrated a more accentuated result (p = 0.003). There was no statistically significant increase in the incidence of other types of injury. Experience was shown to be a further protective factor. CONCLUSION: We recommend the use of a wrist protector, particularly for novices participating in this sport. As in other domains of medicine, preventive measures can decrease morbidity also in terms of sport injuries.     

Functional characterization of a BRAF insertion mutant associated with pilocytic astrocytoma

Pilocytic astrocytoma (PA) is emerging as a tumor entity with dysregulated Ras/Raf/MEK/ERK signaling. Common genetic lesions observed in PA, which are linked to aberrant ERK pathway activity, include either NF1 inactivation, KRAS or BRAF gain-of-function mutations. To investigate the mutation spectrum within the proto-oncogene encoding the Ser/Thr-kinase B-Raf in more detail, we analyzed 64 primary tumor samples from children with PA including two patients with neurofibromatosis type 1 (NF1). The well-known BRAF(V600E) mutation was found in 6/64 (9.38%) of our samples. For the first time, we report concomitant presence of a somatic BRAF(V600E) mutation in an NF1 patient indicating that more than one Ras/ERK pathway component can be affected in PA. Furthermore, 2/64 (3.13%) of our samples carried a 3-bp insertion in BRAF resulting in the duplication of threonine 599. This conserved residue is located within the activation segment and, if phosphorylated in a Ras-dependent manner, plays a key role in Raf activation. Here, we demonstrate that this mutant (B-Raf(insT) ) and another B-Raf mutant, which carries two additional threonine residues at this position, display an in vitro kinase activity and cellular MEK/ERK activation potential comparable to those of B-Raf(V600E) . Notably, replacement of threonines by valine residues had similar effects on B-Raf activity, suggesting that the distortion of the peptide backbone by additional amino acids rather than the insertion of additional, potential phosphorylation sites destabilizes the inactive conformation of the kinase domain. We also demonstrate that B-Raf(insT) and B-Raf(V600E) , but not B-Raf(wt) , provoke drastic morphological alterations in human astrocytes.