Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments

Return to Play and Player Performance After Foot Fracture in UEFA Soccer Players

Background: There is a paucity of information on rate and time to return to play (RTP) in elite-level soccer players who have sustained foot fractures. Purpose: To (1) determine the rate and timing of RTP after foot fracture (eg, tarsal, metatarsal, or phalangeal), (2) investigate foot fracture reinjury incidence after RTP, and (3) evaluate performance after foot fracture as compared with matched, uninjured controls. Study Design: Descriptive epidemiology study. Methods: Athletes sustaining foot fractures were identified across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A) between 2000 and 2016. Injured athletes were matched to controls (1:1) using demographic characteristics and performance metrics from 1 season before injury. The authors recorded RTP rate, reinjury incidence, player characteristics associated with RTP within 2 seasons of injury, player availability, field time, and performance metrics during the 4 seasons after injury. Results: A total of 192 elite soccer players sustaining a foot fracture were identified; 40 players (20.8%) underwent operative treatment. Athletes missed an average of 69.41 ± 59.43 days and 5.15 ± 23.28 games. In the 4 seasons after injury, 80% of players returned to play, with 72% returning to play within 1 season of injury. Nine players (5%) sustained a subsequent foot fracture. Athletes with a foot fracture demonstrated significantly longer league retention compared with uninjured controls ( P &lt; .001). Elite soccer players older than 30 years of age were less likely to RTP (odds ratio, 0.67; P = .002), whereas career experience, field position, and baseline performance showed no significant association with RTP rates. Injured athletes demonstrated similar performance to controls during the 4 years after injury, and there were no position-dependent differences on subgroup analysis. The players who underwent operative treatment had more assists per 90 minutes and more team points per game during the first season after injury compared with athletes treated nonoperatively. Conclusion: Foot fractures in elite soccer players resulted in moderate loss of play time (69.41 days). RTP rates were high at 80%, although players older than 30 years of age were less likely to RTP. On RTP, athletes who sustained a foot fracture maintained performance similar to preinjury levels and to uninjured controls. </jats:sec