Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-β knock-out mice

BACKGROUND: CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-β in the immunomodulatory effects of CpG-ODN is not known. OBJECTIVE: Here, we aimed to elucidate the role of IFN-β in the anti-allergic effect of CpG motifs. METHODS: We assessed the immune response in OVA-primed/OVA-challenged IFN-β knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs. RESULTS: Vaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-β-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-β(-)/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-β-/- mice. The ratio of IFN-γ/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-β(-)/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-γ, IL-2 and also IL-12 were significantly lower in IFN-β-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-β-/- mice. CONCLUSION: Our results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-β, while IFN-β is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination

A Model to Evaluate Pauwels Type III Femoral Neck Fractures

While many femoral neck fractures can be reliably treated with surgical intervention, Pauwels III femoral neck fractures in the young adult population continue to be a challenging injury, and there is no consensus on optimal treatment. As such, there are past and ongoing biomechanical studies to evaluate the fixation provided by different constructs for this inherently unstable fracture. While many investigations rely on cadavers to evaluate the biomechanical performance of a construct, significant inter-subject variability can confound the analysis. Biomechanical femur analogs are being used more frequently due to more consistent mechanical properties; however, they have not been stringently evaluated for morphology or suitability for instrumentation. This study sought to determine the variability among composite femoral analogs as well as consistently create a Pauwels III injury and instrument the analogs without the need for fluoroscopic guidance. In total, 24 fourth-generation composite femoral analogs were evaluated for femoral height, neck–shaft angle, anteversion, and cortical thickness. A method was developed to simulate a Pauwels III fracture and to prepare three different constructs: an inverted triangle of cannulated screws, a sliding hip screw, and a hybrid inverted triangle with cannulated screws and a sliding hip screw. Radiographs were utilized to evaluate the variation in implant position. All but one of the morphological parameters varied b

A Sliding Hip Screw Augmented with 2 Screws is Biomechanically Similar to an Inverted Triad of Cannulated Screws in Repair of a Pauwels Type-III Fracture

Objective Pauwels III femoral neck fractures are highly unstable. These fractures are commonly treated with three cannulated screws or sliding hip screw (SHS) implants, however high rates of non-union persist. A hybrid SHS construct has recently been proposed. The objective of the study was to compare this construct to the familiar inverted triad of cannulated screws and to a single SHS. Methods Fourth generation biomechanical femur analogs were used to create a highly repeatable injury model. The hybrid SHS construct contained a SHS with two superior cannulated screws in an inverted triangle configuration. Eight samples for each construct were biomechanically evaluated and the results compared using ANOVA (p \u3c 0.05). Results The cannulated triad and hybrid SHS provided similar stiffness and fracture gap motion. The single SHS exhibited significantly lower stiffness and larger fracture plane diastasis than either the inverted triangle of cannulated screws or hybrid SHS (p \u3c 0.05). None of the constructs exhibited catastrophic failure during cyclic loading nor under loading up to 2.5 times body weight. Conclusions The single SHS provided the least stable fracture fixation, while the inverted triad and hybrid SHS constructs were mechanically similar. The fracture repair simulated here illustrates how these repairs have the potential to return near pre-fracture strength in ideal conditions with young, healthy bone. However; in clinical situations where comminution impairs load transfer through the cortices the hybrid SHS may be the most favorable option