Scientific examination of the heart of Blessed Pauline Jaricot-a French missionary figure-was carried out in 2022. As tandem mass spectrometry proteotyping has proven to be valuable to obtain the ...broad taxonomic repertoire of a given sample without any a priori information, we aimed at exploring the conditions of preservation of the relics and possible conditions of death. Metaproteomics and high-resolution microtomography imaging approaches were combined. A dataset comprising 6731 high-resolution MS/MS spectra was acquired and 968 of these spectra could be assigned to specific peptidic biomolecules. Based on the taxonomical information encompassed by the identified peptide sequences, 5 phyla were identified amongst eukaryota (94% of the biomass): Ascomycota (55%), with the species
,
and
, corresponding to expected cadaverous fungal flora; Chordata (42%), represented by a unique species,
; Streptophyta (3%); and Arthropoda (traces). Bacteria (6% of the biomass) were poorly represented. No trace of embalming substance could be retrieved, nor any pathogens. Imaging evidenced no heart defect nor embalming traces. No evidence that was inconsistent with natural and spontaneous conservation could be retrieved. This study prefigures the power of modern molecular techniques such as paleoproteotyping coupled to microtomography to gain insight into historical relics.
X-linked hypophosphataemia (XLH) is the most frequent cause of hypophosphataemia-associated rickets of genetic origin and is associated with high levels of the phosphaturic hormone fibroblast growth ...factor 23 (FGF23). In addition to rickets and osteomalacia, patients with XLH have a heavy disease burden with enthesopathies, osteoarthritis, pseudofractures and dental complications, all of which contribute to reduced quality of life. This Consensus Statement presents the outcomes of a working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, and provides robust clinical evidence on management in XLH, with an emphasis on patients' experiences and needs. During growth, conventional treatment with phosphate supplements and active vitamin D metabolites (such as calcitriol) improves growth, ameliorates leg deformities and dental manifestations, and reduces pain. The continuation of conventional treatment in symptom-free adults is still debated. A novel therapeutic approach is the monoclonal anti-FGF23 antibody burosumab. Although promising, further studies are required to clarify its long-term efficacy, particularly in adults. Given the diversity of symptoms and complications, an interdisciplinary approach to management is of paramount importance. The focus of treatment should be not only on the physical manifestations and challenges associated with XLH and other FGF23-mediated hypophosphataemia syndromes, but also on the major psychological and social impact of the disease.
The craniofacial area is prone to trauma or pathologies often resulting in large bone damages. One potential treatment option is the grafting of a tissue‐engineered construct seeded with adult ...mesenchymal stem cells (MSCs). The dental pulp appears as a relevant source of MSCs, as dental pulp stem cells display strong osteogenic properties and are efficient at bone formation and repair. Fibroblast growth factor‐2 (FGF‐2) and/or hypoxia primings were shown to boost the angiogenesis potential of dental pulp stem cells from human exfoliated deciduous teeth (SHED). Based on these findings, we hypothesized here that these primings would also improve bone formation in the context of craniofacial bone repair. We found that both hypoxic and FGF‐2 primings enhanced SHED proliferation and osteogenic differentiation into plastically compressed collagen hydrogels, with a much stronger effect observed with the FGF‐2 priming. After implantation in immunodeficient mice, the tissue‐engineered constructs seeded with FGF‐2 primed SHED mediated faster intramembranous bone formation into critical size calvarial defects than the other groups (no priming and hypoxia priming). The results of this study highlight the interest of FGF‐2 priming in tissue engineering for craniofacial bone repair. Stem Cells Translational Medicine 2019;8:844&857
Priming stem cells from human exfoliated deciduous teeth with fibroblast growth factor‐2 within plastically compressed collagen hydrogels improves osteoformation in vivo in the context of craniofacial bone repair with a faster intramembranous bone formation into calvarial bone critical size defects when compared with either of the 2 other groups (no priming and hypoxia priming) that produced smaller amounts of new bone.
Biomedical research seeks to generate experimental results for translation to clinical settings. In order to improve the transition from bench to bedside, researchers must draw justifiable ...conclusions based on data from an appropriate model. Animal testing, as a prerequisite to human clinical exposure, is performed in a range of species, from laboratory mice to larger animals (such as dogs or non-human primates). Minipigs appear to be the animal of choice for studying bone surgery around intraoral dental implants. Dog models, well-known in the field of dental implant research, tend now to be used for studies conducted under compromised oral conditions (biofilm). Regarding small animal models, research studies mostly use rodents, with interest in rabbit models declining. Mouse models remain a reference for genetic studies. On the other hand, over the last decade, scientific advances and government guidelines have led to the replacement, reduction, and refinement of the use of all animal models in dental implant research. In new development strategies, some in vivo experiments are being progressively replaced by in vitro or biomaterial approaches. In this review, we summarize the key information on the animal models currently available for dental implant research and highlight (i) the pros and cons of each type, (ii) new levels of decisional procedures regarding study objectives, and (iii) the outlook for animal research, discussing possible non-animal options.
Cone beam CT (CBCT) for dentomaxillofacial paediatric assessment has been widely used despite the uncertainties of the risks of the low-dose radiation exposures. The aim of this work was to ...investigate the clinical performance of different CBCT acquisition protocols towards the optimization of paediatric exposures. Custom-made anthropomorphic phantoms were scanned using a CBCT unit in six protocols. CT slices were blinded, randomized and presented to three observers, who scored the image quality using a 4-point scale along with their level of confidence. Sharpness level was also measured using a test object containing an air/PMMA e,dge. The effective dose was calculated by means of a customized Monte Carlo (MC) framework using previously validated paediatric voxels models. The results have shown that the protocols set with smaller voxel size (180 µm), even when decreasing exposure parameters (kVp and mAs), showed high image quality scores and increased sharpness. The MC analysis showed a gradual decrease in effective dose when exposures parameters were reduced, with an emphasis on an average reduction of 45% for the protocol that combined 70 kVp, 16 mAs and 180 µm voxel size. In contrast, both "ultra-low dose" protocols that combined a larger voxel size (400 µm) with lower mAs (7.4 mAs) demonstrated the lowest scores with high levels of confidence unsuitable for an anatomical approach. In conclusion, a significant decrease in the effective dose can be achieved while maintaining the image quality required for paediatric CBCT.
Despite optimal conventional treatment (oral phosphate supplements and active vitamin D analogs), about 40-50% of children with well-controlled X-linked hypophosphatemia (XLH) show linear growth ...failure, making them less likely to achieve an acceptable final height. Here, we studied the hypothesis that rhGH treatment improves final height in children with XLH and growth failure.
Two cohorts of children with XLH were included in this retrospective longitudinal analysis: (1) a cohort treated with rhGH for short stature (n = 34) and (2) a cohort not treated with rhGH (n = 29). The mean duration of rhGH treatment was 4.4 ± 2.9 years. We collected the auxological parameters at various time points during follow-up until final height.
In rhGH-treated children, 2 years of rhGH therapy was associated with a significant increase in height from - 2.4 ± 0.9 to - 1.5 ± 0.7 SDS (p < 0.001). Their mean height at rhGH discontinuation was - 1.2 ± 0.9 SDS and at final height was - 1.3 ± 0.9 SDS corresponding to 165.5 ± 6.4 cm in boys and 155.5 ± 6.3 cm in girls. Notably, the two groups had similar final heights; i.e., the final height in children not treated with rhGH being - 1.2 ± 1.1 SDS (165.4 ± 6.8 cm in boys and 153.7 ± 7.8 cm in girls), p = 0.7.
Treatment with rhGH permits to improve final height in children with XLH and growth failure, despite optimal conventional treatment. We propose therefore that rhGH therapy could be considered as an option for short stature in the context of XLH.
X-linked hypophosphatemia (XLH) is a dento-osseous disorder caused by inactivating mutations in the PHEX gene, leading to renal phosphate wasting and hypophosphatemia, and impaired mineralization of ...bones and teeth. In the oral cavity, recent reports suggest a higher susceptibility of XLH patients to periodontitis, where patients present with impaired tooth cementum – a bone-like tissue involved in tooth attachment to the jaw bones and post-eruption tooth positioning – and a higher frequency of intrabony defects. In the present study, the pathobiology of alveolar bone and tooth cementum was investigated in the Hyp mouse, the murine analog of XLH. PHEX deficiency in XLH/Hyp dramatically alters the periodontal phenotype, with hypoplasia of tooth root cementum associated with a lack of periodontal ligament attachment and the presence of an immature apatitic mineral phase of all periodontal mineralized tissues. Challenging the Hyp periodontium in two surgical experimental models – ligature-induced periodontal breakdown and repair, and a model of tooth movement adaptation inducing cementum formation – we show that bone and cementum formation, and their healing, are altered. Bone and cementum mineralization appear similarly disturbed, where hypomineralized pericellular matrix surrounds cells, and where the protein osteopontin (OPN, a mineralization inhibitor) accumulates in a tissue-specific manner, most notably in the perilacunar matrix surrounding osteocytes. Although the pathobiology is different between XLH/Hyp bone and cementum, our results show a major XLH phenotype in oral mineralized tissues consistent with variations in patient susceptibility to periodontal disorders.
•A biological explanation is proposed for the higher susceptibility of XLH patients to develop periodontitis.•PHEX deficiency severely affects periodontal tissues, resulting in an altered tooth attachment complex.•Hyp mouse oral bone is less capable of repair.•Hyp tooth cementum is less able to adapt to tooth movement.•Although mineralization appears similarly disturbed in Hyp bone and cementum, osteopontin accumulation is tissue-specific.
PDF
