Dose-Dependent Onset of Regenerative Program in Neutron Irradiated Mouse Skin

Background: Tissue response to irradiation is not easily recapitulated by cell culture studies. The objective of this investigation was to characterize, the transcriptional response and the onset of regenerative processes in mouse skin irradiated with different doses of fast neutrons. Methodology/Principal Findings: To monitor general response to irradiation and individual animal to animal variation, we performed gene and protein expression analysis with both pooled and individual mouse samples. A high-throughput gene expression analysis, by DNA oligonucleotide microarray was done with three months old C57Bl/6 mice irradiated with 0.2 and 1 Gy of mono-energetic 14 MeV neutron compared to sham irradiated controls. The results on 440 irradiation modulated genes, partially validated by quantitative real time RT-PCR, showed a dose-dependent up-regulation of a subclass of keratin and keratin associated proteins, and members of the S100 family of Ca2+-binding proteins. Immunohistochemistry confirmed mRNA expression data enabled mapping of protein expression. Interestingly, proteins up-regulated in thickening epidermis: keratin 6 and S100A8 showed the most significant up-regulation and the least mouse-to-mouse variation following 0.2 Gy irradiation, in a concerted effort toward skin tissue regeneration. Conversely, mice irradiated at 1 Gy showed most evidence of apoptosis (Caspase-3 and TUNEL staining) and most 8-oxo-G accumulation at 24 h post-irradiation. Moreover, no cell proliferation accompanied 1 Gy exposure as shown by Ki67 immunohistochemistry. Conclusions/Significance: The dose-dependent differential gene expression at the tissue level following in vivo exposure to neutron radiation is reminiscent of the onset of re-epithelialization and wound healing and depends on the proportion of cells carrying multiple chromosomal lesions in the entire tissue. Thus, this study presents in vivo evidence of a skin regenerative program exerted independently from DNA repair-associated pathways

The clinical outcome of the Metha short hip stem: a systematic scoping review

Introduction: Short femoral stems were designed to bridge the gap between conventional straight design stems and hip resurfacing prostheses in total hip arthroplasty (THA). A number of clinical trials have been recently conducted to assess the clinical and safety profile of the cementless, colarless, tapered Metha short hip stem in young or active middle-aged individuals. Methods: A systematic scoping review was conducted according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. 4 reviewers independently conducted the search using the MEDLINE/PubMed database and the Cochrane Database of Systematic Reviews. These databases were queried with the terms “short” AND “hip” AND “stem”. Results: From the initial 773 studies we finally chose 12 studies after applying our inclusion-exclusion criteria. The number of operated hips that were included in these studies was 5048 (mean BMI range: 22.7–35.2, mean age range: 44.4–60.4 years, mean follow-up range: 2–9 years). The mean modified Coleman methodology score was 52.3/100, while it ranged from 31/100 to 63/100. All mean clinical outcome scores that were used in the studies illustrated significant postoperative improvement when compared with the respective initial values. The revision rate of the Metha stem for component-related reasons was 2.5%, while the rate of major complications not requiring revision of the Metha stem was 2.8%. Conclusions: The Metha stem performs well in young or active middle-aged THA patients. Further studies are required for the assessment of the long-term results. © The Author(s) 2020

Mesenchymal stem cell-dependent formation of heterotopic tendon-bone insertions (osteotendinous junctions).

International audienc

Online learning with the Continuous Ranked Probability Score for ensemble forecasting

International audienceEnsemble forecasting resorts to multiple individual forecasts to produce a discrete probability distribution which accurately represents the uncertainties. Before every forecast, a weighted empirical distribution function is derived from the ensemble, so as to minimize the Continuous Ranked Probability Score (CRPS). We apply online learning techniques, which have previously been used for deterministic forecasting, and we adapt them for the minimization of the CRPS. The proposed method theoretically guarantees that the aggregated forecast competes, in terms of CRPS, against the best weighted empirical distribution function with weights constant in time. This is illustrated on synthetic data. Besides, our study improves the knowledge of the CRPS expectation for model mixtures. We generalize results on the bias of the CRPS computed with ensemble forecasts, and propose a new scheme to achieve fair CRPS minimization , without any assumption on the distributions