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International audience; Osteocytes are the most frequent bone cells connected with each other through cell processes within tiny tubular-shaped canaliculi. The so-called osteocyte lacunar-canalicular network (LCN) plays a crucial role in bone remodeling and mineral homeostasis. Given the critical nature of these functions, it is herein hypothesized that the LCN must be structurally “overengineered” to provide network resilience. This hypothesis is tested by characterizing canalicular networks in human bone at the fundamental “building-block” level of LCN formed by two adjacent osteocytes. As the hierarchical micro- and macroscale structure of bone is influenced by anatomical location, subjected loads, and growth rate, three distinct tissue types are studied. These include femur, jaw, and heterotopic ossification (HO), a rapidly forming mineralized tissue found in soft tissue compartments following severe trauma. It is found that the LCNs at the fundamental level are composed of hundreds of canalicular segments but of only few separated groups of linked canaliculi (canalicular clusters), resulting in a strongly pronounced interconnectivity. Fluid permeability simulations on intact and artificially altered LCN suggest that the function of the LCN is not only to optimize rapid and efficient access to bone mineral, but also to maintain high permeability when inevitable local interruption of canaliculi occurs.

One of the earliest changes in osteoarthritis (OA) is a surface discontinuity of the articular cartilage (AC), and these surface changes become gradually more complex with OA progression. We recently developed a contrast enhanced micro‐computed tomography (μCT) method for visualizing AC surface in detail. The present study aims to introduce a μCT analysis technique to parameterize these complex AC surface features and to demonstrate the feasibility of using these parameters to quantify degenerated AC surface. Osteochondral plugs (n = 35) extracted from 19 patients undergoing joint surgery were stained with phosphotungstic acid and imaged using μCT. The surface micro‐topography of AC was analyzed with developed method. Standard root mean square roughness (Rq) was calculated as a reference, and the Area Under Curve (AUC) for receiver operating characteristic analysis was used to compare the acquired quantitative parameters with semi‐quantitative visual grading of μCT image stacks. The parameters quantifying the complex micro‐topography of AC surface exhibited good sensitivity and specificity in identifying surface continuity (AUC: 0.93, [0.80 0.99]), fissures (AUC: 0.94, [0.83 0.99]) and fibrillation (AUC: 0.98, [0.88 1.0]). Standard Rq was significantly smaller compared with the complex roughness (CRq) already with mild surface changes with all surface reference parameters − continuity, fibrillation, and fissure sum. Furthermore, only CRq showed a significant difference when comparing the intact surface with lowest fissure sum score. These results indicate that the presented method for evaluating complex AC surfaces exhibit potential to identify early OA changes in superficial AC and is dynamic throughout OA progression.

in English, text in Finnish The aim of the article is to generate comprehensive data on the basis of previous evidence on the outsourcing of healthcare services in Finland. The outsourced healthcare services specifically refer to those operations that were previously provided by municipalities as their own service, and which were subsequently transferred either to an external service provider, or provided as a partially or fully outsourced service. In this article, the term external service provider refers to an independent provider, such as a commercial enterprise, a private sector service provider, or a third sector service provider. The research questions are as follows: 1. Which scientific perspectives have previously been applied to the study of outsourcing, and what are the types of methodology that have been employed in such research efforts? 2. Which specific topics have been investigated, and what are their main research findings? A systematic literature review was carried out, which resulted in 16 publications meeting the acceptance criteria. The data were analysed by qualitative content analysis. The results benefit healthcare management for the purposes of planning outsourcing activities. The results can also further be applied to direct future research studies into related topics. In Finland, research focusing on the outsourcing activities of healthcare services has been studied from the perspectives of health sciences, administrative science, medicine, and social sciences. Both qualitative and quantitative approaches have been employed. The most common method of data collection concerned interviews and questionnaires, with the resulting evidence being analysed by diverse methods. For qualitative studies, the most common methods of data analysis were content analysis and frame analysis, while in quantitative studies, descriptive methods were used, which were supplemented by several statistical methods. The main results of the existing evidence emphasised both the views and expectancies of the officials and politicians with respect to the outsourced healthcare services. In this article, these findings are discussed in the context of a decision-making theme. In addition, two further themes were identified from the data, namely know-how and the personnel and client perspectives. In Finland, the effects of outsourcing of healthcare services has been studied in a comprehensive and multifaceted manner especially in light of decision-making. An abundance of evidence also exists on the effects of outsourcing on the wellbeing of personnel and the quality of working atmosphere. On the other hand, research evidence concerning other aspects of outsourcing of healthcare services is scarce, and subsequently.

International audience; Altered levels of trace elements are associated with increased oxidative stress that is eventually responsible for pathologic conditions. Oxidative stress has been proposed to be involved in eye diseases, including cataract formation. We visualized the distribution of metals and other trace elements in the eye of zebrafish embryos by micro X-ray fluorescence (mu-XRF) imaging. Many elements showed highest accumulation in the retinal pigment epithelium (RPE) of the zebrafish embryo. Knockdown of the zebrafish brown locus homologues tyrp1a/b eliminated accumulation of these elements in the RPE, indicating that they are bound by mature melanosomes. Furthermore, albino (slc45a2) mutants, which completely lack melanosomes, developed abnormal lens reflections similar to the congenital cataract caused by mutation of the myosin chaperon Unc45b, and an in situ spin trapping assay revealed increased oxidative stress in the lens of albino mutants. Finally transplanting a wildtype lens into an albino mutant background resulted in cataract formation. These data suggest that melanosomes in pigment epithelial cells protect the lens from oxidative stress during embryonic development, likely by buffering trace elements

International audience; Gesunder humaner Knochen unterliegt einem permanenten Umbau, um sich den mechanischen Anforderungen anzupassen, Mikrofrakturen zu reparieren und das Mineralgleichgewicht zu erhalten. Der Umbauprozess der extrazellulären Matrix wird durch Osteoblasten und Osteoklasten realisiert. Eine bedeutende Rolle bei der Regulierung der Osteoklasten- und Osteoblastenaktivität wird den Osteozyten zugesprochen, welche in einem komplexen Netzwerk von Zelllakunen und Kanalikuli die extrazelluläre Matrix durchsetzen. Auf Phasenkontrast basierende hochauflösende Nano-Computertomografie erlaubt erstmals, sowohl das Zellnetzwerk als auch die direkt angrenzende mineralisierte Matrix in Untersuchungsvolumen, die hinsichtlich ihrer Größe als repräsentativ angesehen werden können, im nativen Zustand (nicht demineralisiert, nicht eingebettet) zu untersuchen.; Healthy human bone tissue undergoes a continuous remodeling process to i) repair microdamages, ii) adapt to mechanical boundary conditions, and iii) maintain a constant serum calcium level. Bone remodeling is realized by specialized bone synthesizing and resorbing cells, i. e. osteoblasts and osteoclasts, respectively. Osteocytes play an important role in the regulation of osteoblast and osteoclast activities. Osteocytes are embedded in the extracellular matrix in a complex porous lacunar-canalicular network (LCN). Recently developed high-fidelity phase-contrast nanotomography with synchrotron radiation x-ray sources enabled for the first time the simultaneous assessment of both, LCN and the adjacent extracellular mineralized matrix in close-to-native sample conditions.

International audience

International audience

International audience

Background Wood combustion emissions have been studied previously either by in vitro or in vivo models using collected particles, yet most studies have neglected gaseous compounds. Furthermore, a more accurate and holistic view of the toxicity of aerosols can be gained with parallel in vitro and in vivo studies using direct exposure methods. Moreover, modern exposure techniques such as air-liquid interface (ALI) exposures enable better assessment of the toxicity of the applied aerosols than, for example, the previous state-of-the-art submerged cell exposure techniques. Methods We used three different ALI exposure systems in parallel to study the toxicological effects of spruce and pine combustion emissions in human alveolar epithelial (A549) and murine macrophage (RAW264.7) cell lines. A whole-body mouse inhalation system was also used to expose C57BL/6 J mice to aerosol emissions. Moreover, gaseous and particulate fractions were studied separately in one of the cell exposure systems. After exposure, the cells and animals were measured for various parameters of cytotoxicity, inflammation, genotoxicity, transcriptome and proteome. Results We found that diluted (1:15) exposure pine combustion emissions (PM1 mass 7.7 ± 6.5 mg m− 3, 41 mg MJ$^{Zahl}$) contained, on average, more PM and polycyclic aromatic hydrocarbons (PAHs) than spruce (PM1 mass 4.3 ± 5.1 mg m− 3, 26 mg MJ− 1) emissions, which instead showed a higher concentration of inorganic metals in the emission aerosol. Both A549 cells and mice exposed to these emissions showed low levels of inflammation but significantly increased genotoxicity. Gaseous emission compounds produced similar genotoxicity and a higher inflammatory response than the corresponding complete combustion emission in A549 cells. Systems biology approaches supported the findings, but we detected differing responses between in vivo and in vitro experiments. Conclusions Comprehensive in vitro and in vivo exposure studies with emission characterization and systems biology approaches revealed further information on the effects of combustion aerosol toxicity than could be achieved with either method alone. Interestingly, in vitro and in vivo exposures showed the opposite order of the highest DNA damage. In vitro measurements also indicated that the gaseous fraction of emission aerosols may be more important in causing adverse toxicological effects. Combustion aerosols of different wood species result in mild but aerosol specific in vitro and in vivo effects.

International audience; This study was approved by the local research ethics committee, and patient informed consent was obtained. The purpose of this study was to demonstrate that high-spatial-resolution low-dose analyzer-based x-ray computed tomography (CT) can substantially improve the radiographic contrast of breast tissue in vitro when compared with that attained by using diagnostic mammography and CT. An excised human breast tumor was examined by using analyzer-based x-ray imaging with synchrotron radiation. The correspondence between analyzer-based x-ray images and diagnostic mammograms, CT images, and histopathologic findings was determined. Calcifications and fine details of soft tissue, which are at the contrast detection limit on diagnostic mammograms, are clearly visible on planar analyzer-based x-ray images. Analyzer-based x-ray CT yields high contrast from smoothly varying internal structures, such as tumorous mass lesions, corresponding to information on actual structures seen at histopathologic analysis. The mean glandular dose of 1.9 mGy in analyzer-based x-ray CT is approximately equivalent to the dose administered during single-view screening mammography. The improved visibility of mammographically indistinguishable lesions in vitro suggests that analyzer-based x-ray CT may be a valuable method in radiographic evaluation of the breast, thereby justifying further investigations.

USAXS and SAXS patterns from cancer-bearing human breast tissue samples were recorded at beamline ID02 of the ESRF using a Bonse–Hart camera and a pinhole camera. The samples were classified as being ductal carcinoma, grade II, and ductal carcinoma in situ, partly invasive. The samples included areas of healthy collagen, invaded collagen, necrotic ducts with calcifications, and adipose tissue. The scattering patterns were analyzed in different ways to separate the scattering contribution and the direct beam from the observed rocking curve (RC) of the analyzer. It was found that USAXS from all tissues was weak, and the effects on the analyzer RC were observed only in the low-intensity tails of the patterns. The intrinsic RC was convolved with different model functions for the impulse response of the sample, and the best fit with experiment was obtained by the Pearson VII function. Significantly different distributions for the Pearson exponent m were obtained in benign and malignant regions of the samples. For a comparison with analyzer-based imaging (ABI) or diffraction enhanced imaging (DEI) a “long-slit” integration of the patterns was performed, and this emphasized the scattering contribution in the tails of the rocking curve. © 2008 Elsevier Ireland Ltd. All rights reserved.

International audience; A new algorithm is introduced for separation of the scattered and non-scattered parts of a monochromatic and well collimated synchrotron radiation beam transmitted through a sample and analyzed by reflection from a perfect crystal in the non-dispersive setting. The observed rocking curve is described by the Voigt function, which is a convolution of Lorentzian and Gaussian functions. For the actual fitting, pseudo-Voigtians are used. The fit yields the scaled integrated intensity (the effect of absorption), the center of the rocking curve (the effect of refraction), and the intensity of the transmitted beam is divided into the scattered and non-scattered parts. The algorithm is tested using samples that exhibit various degrees of refraction and scattering. Very close fits are achieved in an angular range that is 15 times the full width at half-maximum of the intrinsic rocking curve of the analyzer. The scattering part has long tails of Lorentzian shape owing to the ;long-slit geometry' of the set-up. Quantitative images of absorption, refraction and scattering are constructed and compared with results of earlier treatments. The portion of scattering and the second moment of the observed rocking curve both increase linearly with the sample thickness and yield identical maps of the effects of scattering. The effects of refraction are calculated using the geometrical optics approximation, and a good agreement with experiment is found. The fits with reduced number of data points (minimum number is five) yield closely the same results as fits to the full data set.