Severe Myasthenic Manifestation of Leptospirosis Associated with New Sequence Type of Leptospira interrogans

We report the rapid development of a myasthenic crisis as the first-time manifestation of myasthenia gravis. The symptoms developed in the course of acute leptospirosis associated with a new sequence type of Leptospira interrogans. Antibiotic treatment led to rapid amelioration of myasthenia

ERCC1 mutations impede DNA damage repair and cause liver and kidney dysfunction in patients

ERCC1-XPF is a multifunctional endonuclease involved in nucleotide excision repair (NER), interstrand cross-link (ICL) repair, and DNA double-strand break (DSB) repair. Only two patients with bi-allelic ERCC1 mutations have been reported, both of whom had features of Cockayne syndrome and died in infancy. Here, we describe two siblings with bi-allelic ERCC1 mutations in their teenage years. Genomic sequencing identified a deletion and a missense variant (R156W) within ERCC1 that disrupts a salt bridge below the XPA-binding pocket. Patient-derived fibroblasts and knock-in epithelial cells carrying the R156W substitution show dramatically reduced protein levels of ERCC1 and XPF. Moreover, mutant ERCC1 weakly interacts with NER and ICL repair proteins, resulting in diminished recruitment to DNA damage. Consequently, patient cells show strongly reduced NER activity and increased chromosome breakage induced by DNA cross-linkers, while DSB repair was relatively normal. We report a new case of ERCC1 deficiency that severely affects NER and considerably impacts ICL repair, which together result in a unique phenotype combining short stature, photosensitivity, and progressive liver and kidney dysfunction

Systematic review of rugby injuries in children and adolescents under 21 years

A systematic review of rugby union and league injuries among players under the age of 21 years was carried out to calculate probabilities of match injury for a player over a season and a pooled estimate of match injury incidence where studies were sufficiently similar. The probability of a player being injured over a season ranged from 6% to 90% for rugby union and 68% to 96% for rugby league. The pooled injury incidence estimate for rugby union was 26.7/1000 player-hours for injuries irrespective of need for medical attention or time-loss and 10.3/1000 player-hours for injuries requiring at least 7 days absence from games; equivalent to a 28.4% and 12.1% risk of being injured over a season. Study heterogeneity contributed to a wide variation in injury incidence. Public injury surveillance and prevention systems have been successful in reducing injury rates in other countries. No such system exists in the UK