Preexisting Rotator Cuff Tears as a Predictor of Outcomes in National Football League Athletes.

BACKGROUND: A preexisting rotator cuff tear may affect the draft status and career performance of National Football League (NFL) players. HYPOTHESIS: Preexisting rotator cuff tears decrease a player's draft status, performance, and longevity in the NFL. STUDY DESIGN: Retrospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: Medical reports of prospective NFL players during the NFL Scouting Combine from 2003 to 2011 were evaluated to identify players with a previous rotator cuff tear. Athletes were matched to control draftees without documented shoulder pathology by age, position, year drafted, and round drafted. Career statistics and performance scores were calculated. RESULTS: Between 2003 and 2011, 2965 consecutive athletes were evaluated. Forty-nine athletes had preexisting rotator cuff tears: 22 athletes underwent surgical intervention for their tear and 27 were treated nonoperatively. Those with a rotator cuff tear were significantly less likely to be drafted than those without a previous injury (55.1% vs 77.5%, P = 0.002). The 27 drafted athletes with preexisting rotator cuff tears started significantly fewer games (23.7 vs 43.0, P = 0.02) and played significantly fewer years (4.3 vs 5.7, P = 0.04) and significantly fewer games (47.1 vs 68.4, P = 0.04) than matched control athletes without rotator cuff tears. CONCLUSION: Athletes with a preexisting rotator cuff tear were less likely to be drafted and had decreased career longevity.

Catalytic site amino acids of PKGI-alpha influence allosteric cGMP binding.

Ser-64, an autophosphorylation site in the autoinhibitory subdomain of cGMP-dependent protein kinase type I-alpha (PKGI-alpha), lowers affinity for cGMP and suppresses catalytic activity (1). Using the structure of homologous cAMP-dependent protein kinase as a model, three conserved residues (Gln-401, His-404, Cys-518) in the PKGI-alpha catalytic site are predicted to be juxtaposed to Ser-64 (2). Individual point mutants (Q401A, H404A and C518A) and a double mutant (S64A/H404A) have been generated. cGMP or cAMP affinities (K(a)) of each mutant protein for phosphotransferase activation and allosteric (3H)cGMP-binding affinity (K(D)) of each mutant protein are significantly improved over those of wild-type (WT) PKGI-alpha. However, affinities (K(m)) of the mutant PKGs for peptide substrates or ATP are unaltered. Kinase activity ratio (-GMP/+cGMP) of H404A is greater than that for WT, Q401A, or C518A, and similar to that for S64A and S64A/H404A. These results reveal a unique mechanism whereby catalytic domain residues predicted to be spatially close to Ser-64 of the regulatory domain weaken the intrinsically high affinity of PKGI-alpha for cGMP and provide for autoinhibition of catalytic activity.

Host response signature to Staphylococcus aureus alpha-hemolysin implicates pulmonary Th17 response.

Staphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lungs to define the host response to wild-type S. aureus compared with the response to an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at 4 and at 24 h postinfection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting staphylococci was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent Th17 response to the wild-type pathogen. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary Th17 response to the secretion of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease.