Omnidirectional displacements for deformable surfaces

Deformable surface models are often represented as triangular meshes in image segmentation applications. For a fast and easily regularized deformation onto the target object boundary, the vertices of the mesh are commonly moved along line segments (typically surface normals). However, in case of high mesh curvature, these lines may not intersect with the target boundary at all. Consequently, certain deformations cannot be achieved. We propose omnidirectional displacements for deformable surfaces (ODDS) to overcome this limitation. ODDS allow each vertex to move not only along a line segment but within the volumetric inside of a surrounding sphere, and achieve globally optimal deformations subject to local regularization constraints. However, allowing a ball-shaped instead of a linear range of motion per vertex significantly increases runtime and memory. To alleviate this drawback, we propose a hybrid approach, fastODDS, with improved runtime and reduced memory requirements. Furthermore, fastODDS can also cope with simultaneous segmentation of multiple objects. We show the theoretical benefits of ODDS with experiments on synthetic data, and evaluate ODDS and fastODDS quantitatively on clinical image data of the mandible and the hip bones. There, we assess both the global segmentation accuracy as well as local accuracy in high curvature regions, such as the tip-shaped mandibular coronoid processes and the ridge-shaped acetabular rims of the hip bones.     

Immediate versus conventional loading of palatal implants in humans: a first report of a multicenter RCT

This study aims to analyze the clinical performance of two loading concepts on second-generation palatal implants (Orthosystem, Straumann, Basel, Switzerland) in a prospective multicenter randomized controlled clinical trial. At the time of this interim analysis, 41 patients have been randomized on a 1:1 basis to one of two treatment groups. Group 1 underwent conventional loading of palatal implants after a healing period of 12 weeks (gold standard) while group 2 underwent immediate implant loading within 1 week after implant insertion. We report initial results at 6 months after functional loading. The primary outcome parameter was implant success (no implant mobility, no implant loss). The implants in both groups were initially stable at the time of insertion, and all were eligible for randomization. Twenty-two patients (group 1) were subjected to conventional implant loading after 12 weeks while 19 patients (group 2) received immediate functional loading within the first week after insertion. Direct (e.g. distal jet appliances) as well as indirect forms of anchorage (conventional or modified transpalatal arch) were used. The magnitude of orthodontic forces ranged between 1 and 4 N for the immediate loading group and between 1 and 5 N for the conventional loading group. One implant in group 1 was lost during the healing phase. One dropout was registered in group 2. Thirty-nine implants were functionally loaded for over 6 months now. These preliminary data provide first evidence of the fact that immediate loading of palatal implants yields equivalent success rates as conventional loading to 4 N after 6 months.     

Use of a serum-free medium for long-term storage of human corneas. Influence on endothelial cell density and corneal metabolism

BACKGROUND: The success of long-term corneal organ culture is limited by the progressive loss of endothelial cells during culture and the use of culture medium supplemented with fetal calf serum as a possible source of contamination with infectious agents. In this study, we investigated the suitability of a serum-free medium (Endothelial-SFM) to improve preservation conditions for human donor corneas. METHODS: Six pairs of corneas were stored in Minimum Essential Medium (MEM) supplemented with 2% fetal calf serum (FCS) for 8-14 days. One cornea of each pair was then further cultivated in Endothelial-SFM supplemented with 2% FCS or in MEM with 2% FCS, respectively. In a second series of experiments, the endothelial cell density of seven pairs of freshly isolated donor corneas was determined during cultivation in Endothelial-SFM with 2% FCS or serum-free Endothelial-SFM. RESULTS: After precultivation in conventional medium, the endothelial cell density of corneas allocated to cultivation in Endothelial-SFM was 1000-1950 cells/mm2 and that of those subsequently cultured in MEM 1200-2000 cells/mm2. At 9 weeks, cell densities of 900-1500 cells/mm2 were found after cultivation in Endothelial-SFM compared with a total cell loss in MEM. Freshly isolated corneas cultured in Endothelial-SFM with or without FCS supplementation showed a decrease of endothelial cell density of about 20% within the first 2 weeks of storage. During further cultivation cell density remained constant without statistically significant differences between the groups. Glucose consumption of the corneas was higher in Endothelial-SFM than in MEM. Corneas stored in Endothelial-SFM with 2% FCS showed a higher glucose consumption than those preserved in serum-free Endothelial-SFM. CONCLUSION: Organ culture of human donor corneas using the serum-free basal medium Endothelial-SFM is superior to conventional culture conditions because the decrease in endothelial cell density can be ameliorated, the culture period can be prolonged and the risk of transmitting infectious agents via serum can be minimised.     

Interleukin-1beta converting enzyme (caspase-1) in intestinal inflammation

An imbalance of T helper cell type 1 (Th1) versus type 2 (Th2) polarization in favor of Th1 cell subsets appears to be a key pathogenic mechanism in chronic inflammatory bowel disease (IBD), in particular in Crohn's disease. The interferon gamma-inducing factor interleukin (IL)-18 acts in strong synergism with the Th1 polarizing cytokine IL-12. Recent studies provide evidence for the participation of IL-18 in the pathogenesis of IBD: IL-18 expression is increased in inflamed lesions of Crohn's disease patients and neutralization of IL-18 in different models of experimental colitis resulted in a dramatic amelioration of disease severity. IL-18 and IL-1beta are cleaved and thereby activated by the interleukin-1beta converting enzyme (ICE). Activation of ICE also occurs during different types of infectious colitis, and ICE expression and subsequent release of IL-1beta and IL-18 significantly contribute to intestinal inflammation. ICE knockout mice as well as mice treated with the ICE inhibitor pralnacasan are protected against experimental mucosal inflammation. Thus, inhibition of ICE represents an intriguing new target that requires further investigation in animal models.     

Viral antigen-specific CD8+ T-cell responses are impaired in multiple myeloma

Multiple myeloma (MM) is associated with defects of humoral and cellular immunity, however, little is known about the frequency and function of antigen-specific CD8+ T cells. Such information might be critical for the development of immunotherapy for MM patients. As a model, we assessed the frequency and proliferation of CD8+ T cells specific for HLA-A*0201-restricted immunodominant epitopes from influenza A (Inf A) and Epstein-Barr virus (EBV). Experiments in identical twins demonstrated reduced numbers of antigen-specific T cells after ex-vivo antigenic challenge in the MM twin when compared with the healthy twin. Similarly, the proliferation and frequency of EBV- and Inf A-specific T cells was also significantly reduced in a cohort of 24 previously untreated or conventionally treated MM patients when compared with 19 healthy individuals. In contrast, MM patients studied after receiving an autologous stem cell transplantation showed strikingly higher frequencies of EBV-specific T cells with potential to proliferate ex vivo, suggesting that EBV-specific T cells are readily expandable under these circumstances. These data identify an impaired response of CD8+ T cells in MM patients, which might in part explain the relatively limited success of anti-MM immunisations. Prospective studies will determine whether such immune assessment strategies may identify patients more likely to benefit from cancer immunotherapy.