Effect of preparation design on fracture strength of compromised molars restored with lithium disilicate inlay and overlay restorations: An in vitro and in silico study

PURPOSE: The objective of this study was to determine the influence of different preparation designs on the fracture strength, failure type, repairability, formation of polymerization-induced cracks, and tooth deformation of structurally compromised molars restored with lithium disilicate inlays and overlays in combination with Immediate Dentin Sealing (IDS). MATERIAL AND METHODS: Human molars (N = 64) were randomly assigned to four different preparation designs: Undermined Inlay (UI), Extended Inlay (EI), Restricted Overlay (RO), and Extended Overlay (EO). The teeth were restored using lithium disilicate partial restorations and subjected to thermomechanical fatigue in a chewing simulator (1,2 × 10 (Mondelli et al., 2007) cycles on 50 N, 8000x 5-55 °C), followed by load to failure testing. In silico finite element analysis was conducted to assess tooth deformation. Polymerization-induced cracks were evaluated using optical microscopy and transillumination. Fracture strengths were statistically analyzed using a Kruskal-Wallis test, while the failure mode, repairability, and polymerization cracks were analyzed using Fisher exact test. RESULTS: The propagation of polymerization-induced cracks did not significantly differ among preparation designs. All specimens withstood chewing simulator fatigue, with no visible cracks in teeth or restorations. Fracture strength was significantly influenced by preparation design, with restricted overlay (RO) showing higher fracture strength compared to extended inlay (EI) (p = .042). Tooth deformation and fracture resistance correlated between in vitro and in silico analyses). UI exhibited a statistically less destructive failure pattern than EO (p < .01) and RO (p = .036). No statistically significant influence of the preparation design on repairability was observed. Groups with higher repairability rates experienced increased tooth deformation, leading to less catastrophic failures. CONCLUSIONS: The preparation design affected the fracture strength of compromised molars restored with lithium disilicate inlays and overlays, with significantly lower fracture strength for an extended inlay. The failure pattern of lithium disilicate overlays is significantly more destructive than that of undermined and extended inlays. The finite element analysis showed more tooth deformation in the inlay restorations, with lower forces in the roots, leading to less destructive fractures. Since cusp coverage restorations fracture in a more destructive manner, this study suggests the undermined inlay preparation design as a viable option for restoring weakened cusps

Immune activation correlates with and predicts CXCR4 co-receptor tropism switch in HIV-1 infection

HIV-1 cell entry is mediated by binding to the CD4-receptor and chemokine co-receptors CCR5 (R5) or CXCR4 (X4). R5-tropic viruses are predominantly detected during early infection. A switch to X4-tropism often occurs during the course of infection. X4-tropism switching is strongly associated with accelerated disease progression and jeopardizes CCR5-based HIV-1 cure strategies. It is unclear whether host immunological factors play a causative role in tropism switching. We investigated the relationship between immunological factors and X4-tropism in a cross-sectional study in HIV-1 subtype C (HIV-1C)-infected patients and in a longitudinal HIV-1 subtype B (HIV-1B) seroconverter cohort. Principal component analysis identified a cluster of immunological markers (%HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD4+ T-cells, %CD38+HLA-DR+ CD8+ T-cells, %CD70+ CD4+ T-cells, %CD169+ monocytes, and absolute CD4+ T-cell count) in HIV-1C patients that was independently associated with X4-tropism (aOR 1.044, 95% CI 1.003–1.087, p = 0.0392). Analysis of individual cluster contributors revealed strong correlations of two markers of T-cell activation (%HLA-DR+ CD4+ T-cells, %HLA-DR+CD38+ CD4+ T-cells) with X4-tropism, both in HIV-1C patients (p = 0.01;p = 0.03) and HIV-1B patients (p = 0.0003;p = 0.0001). Follow-up data from HIV-1B patients subsequently revealed that T-cell activation precedes and independently predicts X4-tropism switching (aHR 1.186, 95% CI 1.065–1.321, p = 0.002), providing novel insights into HIV-1 pathogenesis and CCR5-based curative strategies