983 resultados para Bone technology
Resumo:
The use of areal bone mineral density (aBMD) for fracture prediction may be enhanced by considering bone microarchitectural deterioration. Trabecular bone score (TBS) helped in redefining a significant subset of non-osteoporotic women as a higher risk group. INTRODUCTION: TBS is an index of bone microarchitecture. Our goal was to assess the ability of TBS to predict incident fracture. METHODS: TBS was assessed in 560 postmenopausal women from the Os des Femmes de Lyon cohort, who had a lumbar spine (LS) DXA scan (QDR 4500A, Hologic) between years 2000 and 2001. During a mean follow-up of 7.8 ± 1.3 years, 94 women sustained 112 fragility fractures. RESULTS: At the time of baseline DXA scan, women with incident fracture were significantly older (70 ± 9 vs. 65 ± 8 years) and had a lower LS_aBMD and LS_TBS (both -0.4SD, p < 0.001) than women without fracture. The magnitude of fracture prediction was similar for LS_aBMD and LS_TBS (odds ratio [95 % confidence interval] = 1.4 [1.2;1.7] and 1.6 [1.2;2.0]). After adjustment for age and prevalent fracture, LS_TBS remained predictive of an increased risk of fracture. Yet, its addition to age, prevalent fracture, and LS_aBMD did not reach the level of significance to improve the fracture prediction. When using the WHO classification, 39 % of fractures occurred in osteoporotic women, 46 % in osteopenic women, and 15 % in women with T-score > -1. Thirty-seven percent of fractures occurred in the lowest quartile of LS_TBS, regardless of BMD. Moreover, 35 % of fractures that occurred in osteopenic women were classified below this LS_TBS threshold. CONCLUSION: In conclusion, LS_aBMD and LS_TBS predicted fractures equally well. In our cohort, the addition of LS_TBS to age and LS_aBMD added only limited information on fracture risk prediction. However, using the lowest quartile of LS_TBS helped in redefining a significant subset of non-osteoporotic women as a higher risk group which is important for patient management.
Resumo:
OBJECTIVE: To evaluate the effect of strenuous exercise on bone metabolism and related hormones in elderly subjects. METHODS: Twenty one active elderly subjects (11 men and 10 women; mean age 73.3 years) showing a mean theoretical Vo2max of 151.4% participated. Concentrations of plasma ionised calcium (iCa), serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D (25(OH)D), and 1.25-dihydroxy-vitamin D3 (1.25(OH)2D3), as well as the bone biochemical markers type I collagen C-telopeptide for bone resorption and osteocalcin and bone alkaline phosphatase for bone formation, were analysed before and after a maximal incremental exercise test. RESULTS: At basal level, iPTH was positively correlated with age (r = 0.56, p < 0.01) and negatively correlated with 25(OH)D (r = -0.50; p < 0.01) and 1.25(OH)2D3 (r = -0.47; p < 0.05). Moreover, 25(OH)D and 1.25(OH)2D3 levels were negatively correlated with age (r = -0.50, p < 0.01 and r = -0.53, p < 0.01, respectively). After exercise, iCa and 25(OH)D decreased (p < 0.001 and p = 0.01, respectively) while iPTH increased (p < 0.001). The levels of 1.25(OH)2D3, bone biochemical markers, haematocrit, and haemoglobin were unchanged. The variations in iCa and 25(OH)D were not related to age and/or sex. The iPTH variation was directly related to basal iPTH levels (p < 0.01) and indirectly related to age. CONCLUSIONS: In active elderly subjects, strenuous exercise disturbed calcium homeostasis and bone related hormones without immediate measurable effect on bone turnover. Although an increase in iPTH could have an anabolic action on bone tissue, our findings from our short term study did not allow us to conclude that such action occurred.
Resumo:
Malnutrition, a risk factor for osteoporotic fractures, is frequent in elderly people and, is underdiagnosed and undertreated. There are only few studies on the nutritional status of elderly people in Europe. The Mini Nutritional Assessment (MNA) is a non invasive and validated questionnaire to evaluate nutritional status in elderly people, classified in three groups: 1 degree score < 17: malnourished, 2 degrees score >17 and < 24: at risk of malnutrition, 3 degrees score >24: well-nourished, with a maximum of 30 points. Quantitative ultrasound of bone (QUS) is a method for assessing quality of bone which can be easily performed in nursing homes. Therefore, these two tests allowed to study the relationships between nutritional status and ultrasonic parameters of bone in 78 institutionalized women aged 86 +/- 6 years, living in 11 nursing homes around Lausanne (Switzerland). All were assessed by the MNA, had a measurement of the tricipital skin fold and of the grip strength. Functional status was evaluated by the scale "Activity of Daily Living" (ADL), and serum albumin level was measured when permitted. All had QUS of the calcaneus (with an Achilles, GE Lunar). The measured parameters are the Broadband Ultrasound Attenuation (BUA), attenuation of a band of ultrasonic frequencies through the medium, expressed in dB/MHz, and the Speed of Sound (SOS), speed of the ultrasounds through the medium, expressed in m/s. A third parameter, the stiffness index (SI), expressed as a percentage of the values obtained by the manufacturer in a young population and derived from BUA and SOS, was calculated automatically : SI = (0.67xBUA) + (0.28xSOS) - 420, expressed in percent compared to a young adult population (%YA). Fifteen percent of the women were undernourished and 58% were at risk of malnutrition. As expected, compared with the well-nourished minority, undernourished subjects had significant lower body mass index (BMI), tricipital skin fold (TSF), ADL score and albumin level (p < 0,01). The subjects "at risk of malnutrition" had significant lower BMI, ADL score (p < 0.01), tricipital skin fold and serum albumin (p < 0.05). Ultrasound parameters were low independently of the nutritional status. MNA score correlated significantly with tricipital skin fold (r = 0.508, p < 0.01), ADL (r = 0.538, p < 0.01) and albumin serum level (r = 0.409, p = 0.01). There was a trend for a correlation between the MNA and the ultrasound parameter BUA (r = 0.207, p = 0.07), whereas no correlation was found with SOS and SI. A multivariate analysis showed that tricipital skin fold and ADL explained 61% of the variance of the MNA. In conclusion, using simple and non invasive methods, this study showed that malnutrition and osteoporosis are frequent in institutionalized elderly persons in our country, and the ultrasound parameters are influenced by many others factors in addition to nutrition, especially at this age and in elderly residents of nursing homes.
Resumo:
The decision to publish educational materials openly and under free licenses brings up the challenge of doing it in a sustainable way. Some lessons can be learned from the business models for production, maintenance and distribution of Free and Open Source Software. The Free Technology Academy (FTA) has taken on these challenges and has implemented some of these models. We briefly review the FTA educational programme, methodologies and organisation, and see to which extent these models are proving successful in the case of the FTA.
Resumo:
The place of technology in the development of coherent educational responses to environmental and socio-economic disruption is here placed under scrutiny. One emerging area of interest is the role of technology in addressing more complex learning futures, and more especially in facilitating individual and social resilience, or the ability to manage and overcome disruption. However, the extent to which higher education practitioners can utilise technology to this end is framed by their approaches to the curriculum, and the socio-cultural practices within which they are located. This paper discusses how open education might enable learners to engage with uncertainty through social action within a form of higher education that is more resilient to economic, environmental and energy-related disruption. It asks whether open higher education can be (re)claimed by users and communities within specific contexts and curricula, in order to engage with an uncertain world.
Resumo:
La televisió està en crisi. Les noves tecnologies i els dispositius han fragmentat les audiències de televisió en segments més petits. En aquest informe, Marissa Gluck i Meritxell Roca Sales examinen l'explosió dels mitjans de comunicació que han impulsat aquesta fragmentació.
Resumo:
Résumé Le but final de ce projet est d'utiliser des cellules T ou des cellules souches mésenchymateuses modifiées génétiquement afin de surexprimer localement les deux chémokines CXCL13 et CCL2 ensemble ou chacune séparément à l'intérieur d'une tumeur solide. CXCL13 est supposé induire des structures lymphoïdes ectopiques. Un niveau élevé de CCL2 est présumé initier une inflammation aiguë. La combinaison des deux effets amène à un nouveau modèle d'étude des mécanismes régulateur de la tolérance périphérique et de l'immunité tumorale. Les connaissances acquises grâce à ce modèle pourraient permettre le développement ou l'amélioration des thérapies immunes du cancer. Le but premier de ce travail a été l'établissement d'un modèle génétique de la souris permettant d'exprimer spécifiquement dans la tumeur les deux chémokines d'intérêt à des niveaux élevés. Pour accomplir cette tâche, qui est en fait une thérapie génétique de tumeurs solides, deux types de cellules porteuses potentielles ont été évaluées. Des cellules CD8+ T et des cellules mésenchymateuses de la moelle osseuse transférées dans des receveurs portant une tumeur. Si on pouvait répondre aux besoins de la thérapie génétique, indépendamment de la thérapie immune envisagée, on posséderait là un outil précieux pour bien d'autres approches thérapeutiques. Plusieurs lignées de souris transgéniques ont été générées comme source de cellules CD8+ T modifiées afin d'exprimer les chémokines d'intérêt. Dans une approche doublement transgénique les propriétés de deux promoteurs spécifiques de cellules T ont été combinées en utilisant la technologie Cre-loxP. Le promoteur de granzyme B confère une dépendance d'activation et le promoteur distal de lck assure une forte expression constitutive dès que les cellules CD8+ T ont été activées. Les transgènes construits ont montré une bonne performance in vivo et des souris qui expriment CCL2 dans des cellules CD8+ T activées ont été obtenues. Ces cellules peuvent maintenant être utilisées avec différents protocoles pour transférer des cellules T cytotoxiques (CTL) dans des receveurs porteur d'une tumeur, permettant ainsi d'évaluer leur capacité en tant que porteuse de chémokine d'infiltrer la tumeur. L'établissement de souris transgéniques, qui expriment pareillement CXCL13 est prévu dans un avenir proche. L'évaluation de cellules mésenchymateuses de la moelle osseuse a démontré que ces cellules se greffent efficacement dans le stroma tumoral suite à la co-injection avec des cellules tumorales. Cela représente un outil précieux pour la recherche, vu qu'il permet d'introduire des cellules manipulées dans un modèle tumoral. Les résultats confirment partiellement d'autres résultats rapportés dans un modèle amélioré. Cependant, l'efficacité et la spécificité suggérées de la migration systémique de cellules mésenchymateuses de la moelle osseuse dans une tumeur n'ont pas été observées dans notre modèle, ce qui indique, que ces cellules ne se prêtent pas à une utilisation thérapeutique. Un autre résultat majeur de ce travail est l'établissement de cultures de cellules mésenchymateuses de la moelle osseuse in vitro conditionnées par des tumeurs, ce qui a permis à ces cellules de s'étendre plus rapidement en gardant leur capacité de migration et de greffe. Cela offre un autre outil précieux, vu que la culture in vitro est un pas nécessaire pour une manipulation thérapeutique. Abstract The ultimate aim of the presented project is to use genetically modified T cells or mesenchymal stem cells to locally overexpress the two chemokines CXCL13 and CCL2 together or each one alone inside a solid tumor. CXCL13 is supposed to induce ectopic lymphoid structures and a high level of CCL2 is intended to trigger acute inflamation. The combination of these two effects represents a new model for studying mechanisms that regulate peripheral tolerance and tumor immunity. Gained insights may help developing or improving immunotherapy of cancer. The primary goal of the executed work was the establishment of a genetic mouse model that allows tumor-specific expression of high levels of the two chemokines of interest. For accomplishing this task, which represents gene therapy of solid tumors, two types of potentially useful carrier cells were evaluated. CD8+ T cells and mesenchymal bone marrow cells to be used in adoptive cell transfers into tumor-bearing mice. Irrespectively of the envisaged immunotherapy, satisfaction of so far unmet needs of gene therapy would be a highly valuable tool that may be employed by many other therapeutic approaches, too. Several transgenic mouse lines were generated as a source of CD8+ T cells modified to express the chemokines of interest. In a double transgenic approach the properties of two T cell-specific promoters were combined using Cre-loxP technology. The granzyme B promoter confers activation-dependency and the lck distal promoter assures strong constitutive expression once the CD8+ T cell has been activated. The constructed transgenes showed a good performance in vivo and mice expressing CCL2 in activated CD8+ T cells were obtained. These cells can now be used with different protocols for adoptively transferring cytotoxic T cells (CTL) into tumor-bearing recipients, thus allowing to study their capacity as tumor-infiltrating chemokine carrier. The establishment of transgenic mice likewisely expressing CXCL13 is expected in the near future. In addition, T cells from generated single transgenic mice that have high expression of an EGFP reporter in both CD4+ and CD8+ cells can be easily traced in vivo when setting up adoptive transfer conditions. The evaluation of mesenchymal bone marrow cells demonstrated that these cells can efficiently engraft into tumor stroma upon local coinjection with tumor cells. This represents a valuable tool for research purposes as it allows to introduce manipulated stromal cells into a tumor model. Therefore, the established engraftment model is suited for studying the envisaged immunotherapy. These results confirm to some extend previously reported results in an improved model, however, the suggested systemic tumor homing efficiency and specificity of mesenchymal bone marrow cells was not observed in our model indicating that these cells may not be suited for therapeutic use. Another major result of the presented work is the establishment oftumor-conditioned in vitro culture of mesenchymal bone marrow cells, which allowed to more rapidly expand these cells while maintaining their tumor homing and engrafting capacities. This offers another valuable tool as in vitro culture is a necessary step for therapeutic manipulations.
Resumo:
The development of markets for technology has eased the acquisition of technology and reshaped the innovation strategies of firms that we classify as producers of innovations or as imitators. Innovative activities of firms include research, acquisition of technology and downstream activities. Within an industry, firms producing innovations tend to conduct more research and downstream activities than those imitating innovations. Acquisition of technology is equally important for both. To implement innovation strategies, firms producing innovations require both the capability to scan the external environment for technology and the capability to integrate new technology. Firms producing innovations require both, while firms imitating innovations require scan capabilities only
Resumo:
Hematogones are normal B-lymphoid precursors that multiply in the bone marrow of small children and of adults with ferropenic anaemia, neuroblastoma or idiopathic thrombocytopenic purpura. They are not normally found in peripheral blood, and the immunophenotype is virtually indistinguishable from that of B lymphoblasts. We discuss the case of a 3-month infant with an active cytomegalovirus infection, with hepatitis and pancytopenia associated with 13% hematogones in the bone marrow
Resumo:
BACKGROUND: Intracoronary administration of autologous bone marrow-derived mononuclear cells (BM-MNC) may improve remodeling of the left ventricle (LV) after acute myocardial infarction. The optimal time point of administration of BM-MNC is still uncertain and has rarely been addressed prospectively in randomized clinical trials. METHODS AND RESULTS: In a multicenter study, we randomized 200 patients with large, successfully reperfused ST-segment elevation myocardial infarction in a 1:1:1 pattern into an open-labeled control and 2 BM-MNC treatment groups. In the BM-MNC groups, cells were administered either early (ie, 5 to 7 days) or late (ie, 3 to 4 weeks) after acute myocardial infarction. Cardiac magnetic resonance imaging was performed at baseline and after 4 months. The primary end point was the change from baseline to 4 months in global LV ejection fraction between the 2 treatment groups and the control group. The absolute change in LV ejection fraction from baseline to 4 months was -0.4±8.8% (mean±SD; P=0.74 versus baseline) in the control group, 1.8±8.4% (P=0.12 versus baseline) in the early group, and 0.8±7.6% (P=0.45 versus baseline) in the late group. The treatment effect of BM-MNC as estimated by ANCOVA was 1.25 (95% confidence interval, -1.83 to 4.32; P=0.42) for the early therapy group and 0.55 (95% confidence interval, -2.61 to 3.71; P=0.73) for the late therapy group. CONCLUSIONS: Among patients with ST-segment elevation myocardial infarction and LV dysfunction after successful reperfusion, intracoronary infusion of BM-MNC at either 5 to 7 days or 3 to 4 weeks after acute myocardial infarction did not improve LV function at 4-month follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186.
Resumo:
In the last decade, both regenerative medicine and nanotechnology have been broadly developed leading important advances in biomedical research as well as in clinical practice. The manipulation on the molecular level and the use of several functionalized nanoscaled materials has application in various fields of regenerative medicine including tissue engineering, cell therapy, diagnosis and drug and gene delivery. The themes covered in this review include nanoparticle systems for tracking transplanted stem cells, self-assembling peptides, nanoparticles for gene delivery into stem cells and biomimetic scaffolds useful for 2D and 3D tissue cell cultures, transplantation and clinical application.
Resumo:
CONTEXT: Cirrhosis after viral hepatitis has been identified as a risk factor for osteoporosis in men. However, in postmenopausal women, most studies have evaluated the effect of primary biliary cirrhosis, but little is known about the effect of viral cirrhosis on bone mass [bone mineral density (BMD)] and bone metabolism. OBJECTIVE: Our objective was to assess the effect of viral cirrhosis on BMD and bone metabolism in postmenopausal women. DESIGN: We conducted a cross-sectional descriptive study. SETTING AND PATIENTS: We studied 84 postmenopausal female outpatients with viral cirrhosis and 96 healthy postmenopausal women from the general community. BMD was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN). RESULTS: The percentage with osteoporosis did not significantly differ between patients (LS, 43.1%; FN, 32.2%) and controls (LS, 41.2%; FN, 29.4%), and there was no difference in BMD (z-score) between groups. Serum concentrations of soluble TNF receptors, estradiol, and osteoprotegerin (OPG) were significantly higher in patients vs. controls (P < 0.001, P < 0.05, and P < 0.05, respectively). No significant difference was observed in urinary deoxypyridinoline. Serum OPG levels were positively correlated with soluble TNF receptors (r = 0.35; P < 0.02) and deoxypyridinoline (r = 0.37; P < 0.05). CONCLUSIONS: This study shows that bone mass and bone resorption rates do not differ between postmenopausal women with viral cirrhosis and healthy postmenopausal controls and suggests that viral cirrhosis does not appear to increase the risk of osteoporosis in these women. High serum estradiol and OPG concentrations may contribute to preventing the bone loss associated with viral cirrhosis in postmenopausal women.
Resumo:
Background: Local antibiotics may significantly improve the treatmentoutcome in bone infection without systemic toxicity. For impregnationof polymethylmethacrylate (PMMA), gentamicin, vancomycin and/orclindamycin are currently used. A new lipopeptid antibiotic,daptomycin, is a promising candidate for local treatment due to itsspectrum against staphylococci and enterococci (including multiresistantstrains), and concentration-dependent rapid bactericidalactivity. We investigated activity of antibiotic-loaded PMMA againstStaphylococcus epidermidis biofilms using an ultra-sensitive bacterialheat detection method (microcalorimetry).Methods: Staphylococcus epidermidis (strain RP62A, susceptibleto daptomycin, vancomycin and gentamicin) at concentration 106bacteria/ml was incubated with 2 g-PMMA block (Palacos, HeraeusMedical, Hanau, Germany) in 25 ml tryptic soy broth (TSB)supplemented with calcium. PMMA blocks were preloaded withdaptomycin, vancomycin and gentamicin each at 2 g/40 mg (= 100 mg/block) PMMA. After 72 h-incubation at 35 °C under static conditions,PMMA blocks were rinsed in phosphate-buffered solution (PBS) 5times and transferred in 4 ml-microcalorimetry ampoule filled with 1 mlTSB. Bacterial heat production, which is proportional to the quantityof biofilm on PMMA surface, was measured by isothermalmicrocalorimetry. The detection time was calculated as the time untilthe heat flow reached 20 microwatt.Results: Biomechanical properties did not differ between antibioticloadedand non-loaded PMMA blocks. The mean detection time (±standard deviation) of bacterial heat was 6.5 ± 0.4 h for PMMA withoutantibiotics (negative control), 13.5 ± 4.6 h for PMMA with daptomycin,14.0 ± 4.1 h for PMMA with vancomycin and 5.0 ± 0.4 h for PMMAwith gentamicin.Conclusion: Our data indicates that antibiotics at 2 g/40 mg PMMAdid not change the biomechanical properties of bone cement. Daptomycinand vancomycin were more active than gentamicin against S.epidermidis biofilms when all tested at 2 g/40 mg PMMA. In the nextstep, higher concentrations of daptomycin and their elution kineticneeds to be determined to optimize its antibiofilm activity before usingin the clinical setting.
Resumo:
The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.
Resumo:
Background: Specific physical loading leads to enhanced bone development during childhood. A general physical activity program mimicking a real-life situation was successful at increasing general physical health in children. Yet, it is not clear whether it can equally increase bone mineral mass. We performed a cluster-randomized controlled trial in children of both gender and different pubertal stages to determine whether a school-based physical activity (PA) program during one school-year influences bone mineral content (BMC) and density (BMD), irrespective of gender.Methods: Twenty-eight 1st and 5th grade (6-7 and 11-12 year-old) classes were cluster randomized to an intervention (INT, 16 classes, n = 297) and control (CON; 12 classes, n = 205) group. The intervention consisted of a multi-component PA intervention including daily physical education with at least 10 min of jumping or strength training exercises of various intensities. Measurements included anthropometry, and BMC and BMD of total body, femoral neck, total hip and lumbar spine using dual-energy X-ray absorptiometry (DXA). PA was assessed by accelerometers and Tanner stages by questionnaires. Analyses were performed by a regression model adjusted for gender, baseline height and weight, baseline PA, post-intervention pubertal stage, baseline BMC, and cluster.Results: 275 (72%) of 380 children who initially agreed to have DXA measurements had also post-intervention DXA and PA data. Mean age of prepubertal and pubertal children at baseline was 8.7 +/- 2.1 and 11.1 +/- 0.6 years, respectively. Compared to CON, children in INT showed statistically significant increases in BMC of total body, femoral neck, and lumbar spine by 5.5%, 5.4% and 4.7% (all p < 0.05), respectively, and BMD of total body and lumbar spine by 8.4% and 7.3% (both p < 0.01), respectively. There was no gender*group, but a pubertal stage*group interaction consistently favoring prepubertal children.Conclusion: A general school-based PA intervention can increase bone health in elementary school children of both genders, particularly before puberty. (C) 2010 Elsevier Inc. All rights reserved.