Cell migration is a dynamic process that is central to a variety of physiological functions as well as disease pathogenesis. The modulation of cell migration by p27 has been reported, but the exact mechanism(s) whereby p27 intersects with downstream effectors that control cell migration have not been elucidated. By systematically comparing p27+/+ MEFs with genetically ablated p27−/− MEFs using wound healing, transwell and time-lapse microscopic analyses, we provide direct evidence demonstrating that p27 inhibits both directional and random cell migration. Identical results were obtained with normal and cancer epithelial cells using complementary knockdown and overexpression approaches. Additional studies revealed that overexpression of manganese superoxide dismutase (MnSOD) and reduced intracellular oxidation played a key role in increased cell migration in p27-deficient cells. Furthermore, we identified signal transducer and activator of transcription 3 (STAT3) as the transcription factor responsible for p27-regulated MnSOD expression which was further mediated by ERKs/ATF1-dependent transactivation of CRE within the stat3 promoter. Collectively, our data strongly indicate that p27 plays a crucially negative role in cell migration by inhibiting MnSOD expression in a STAT-3 dependent manner.

Objectives: There is a paucity of data on postoperative infections after endoscopic sinus surgery and associated risk factors. Our objective was to evaluate a cohort of patients undergoing endoscopic sinus surgery (ESS) for chronic rhinosinusitis to determine which perioperative factors may be associated with infection in the 30-day postoperative period. Methods: A retrospective cohort study of adults who underwent ESS at a tertiary academic medical center from 2015 to 2018 was performed. The primary outcome was incidence of postoperative infection, defined by identification of sinus purulence on nasal endoscopy necessitating antibiotics within 30 days of surgery. Independent variables collated included the result of postoperative cultures and use of perioperative antibiotics, oral corticosteroids, packing, and steroid-eluting stents. Statistical analysis involved bivariate analysis to identify variables that correlated with postoperative infection and subsequent multivariate logistic regression to identify independent risk factors. Results: Three hundred seventy-eight unique ESS cases performed in 356 patients were reviewed. The mean age was 46 years (range, 18-87). The most common indication for surgery was chronic rhinosinusitis without nasal polyposis. The postoperative infection rate was 10.1%. The most commonly cultured pathogen was Staphylococcus aureus. Multivariate logistic regression analysis showed that postoperative systemic corticosteroid use was the only risk factor independently associated with infection (OR 3.47 [95% CI 1.23-9.76], P = .018). Conclusion: The incidence of postoperative infection following ESS was 10.1%. The use of postoperative systemic corticosteroids independently increased the risk of infection by 3.47-fold.

Dynamic cervical spine loading can produce facet capsule injury. Despite a large proportion of neck pain being attributable to the C2/C3 facet capsule, potential mechanisms are not understood. This study replicated low-speed frontal and rear-end traffic collisions in occiput-C3 human cadaveric cervical spine specimens and used kinematic and full-field strain analyses to assess injury. Specimens were loaded quasi-statically in flexion and extension before and after dynamic rotation of C3 at 100 deg/s. Global kinematics in the sagittal plane were tracked at 1 kHz, and C2/C3 facet capsule full-field strains were measured. Dynamic loading did not alter the kinematics from those during quasi-static (QS) loading, but maximum principal strain (MPS) and shear strain (SS) were significantly higher (p = 0.028) in dynamic flexion than for the same quasi-static conditions. The full-field strain analysis demonstrated that capsule strain was inhomogeneous, and that the peak MPS generally occurred in the anterior aspect and along the line of the C2/C3 facet joint. The strain magnitude in dynamic flexion continued to rise after the rotation of C3 had stopped, with a peak MPS of 12.52 ± 4.59% and a maximum SS of 5.34 ± 1.60%. The peak MPS in loading representative of rear-end collisions approached magnitudes previously shown to induce pain in vivo, whereas strain analysis using linear approaches across the facet joint was lower and may underestimate injury risk compared to full-field analysis. The time at which peak MPS occurred suggests that the deceleration following a collision is critical in relation to the production of injurious strains within the facet capsule.

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