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1.
Elife ; 122023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37603466

RESUMO

Delta-like homolog 1 (Dlk1), an inhibitor of adipogenesis, controls the cell fate of adipocyte progenitors. Experimental data presented here identify two independent regulatory mechanisms, transcriptional and translational, by which Ifrd1 (TIS7) and its orthologue Ifrd2 (SKMc15) regulate Dlk1 levels. Mice deficient in both Ifrd1 and Ifrd2 (dKO) had severely reduced adipose tissue and were resistant to high-fat diet-induced obesity. Wnt signaling, a negative regulator of adipocyte differentiation, was significantly upregulated in dKO mice. Elevated levels of the Wnt/ß-catenin target protein Dlk1 inhibited the expression of adipogenesis regulators Pparg and Cebpa, and fatty acid transporter Cd36. Although both Ifrd1 and Ifrd2 contributed to this phenotype, they utilized two different mechanisms. Ifrd1 acted by controlling Wnt signaling and thereby transcriptional regulation of Dlk1. On the other hand, distinctive experimental evidence showed that Ifrd2 acts as a general translational inhibitor significantly affecting Dlk1 protein levels. Novel mechanisms of Dlk1 regulation in adipocyte differentiation involving Ifrd1 and Ifrd2 are based on experimental data presented here.


Assuntos
Adipogenia , Proteínas de Ligação ao Cálcio , Proteínas Imediatamente Precoces , Proteínas de Membrana , Animais , Camundongos , Adipócitos , Adipogenia/genética , Tecido Adiposo , Proteínas de Ligação ao Cálcio/genética , Antígenos CD36 , Diferenciação Celular , Proteínas de Membrana/genética
2.
Biomedicines ; 9(9)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34572397

RESUMO

For the non-invasive assessment of pulmonary artery pressure (PAP), surrogates like pulse wave transit time (PWTT) have been proposed. The aim of this study was to invasively validate for which kind of PAP (systolic, mean, or diastolic) PWTT is the best surrogate parameter. To assess both PWTT and PAP in six healthy pigs, two pulmonary artery Mikro-Tip™ catheters were inserted into the pulmonary vasculature at a fixed distance: one in the pulmonary artery trunk, and a second one in a distal segment of the pulmonary artery. PAP was raised using the thromboxane A2 analogue U46619 (TXA) and by hypoxic vasoconstriction. There was a negative linear correlation between PWTT and systolic PAP (r = 0.742), mean PAP (r = 0.712) and diastolic PAP (r = 0.609) under TXA. During hypoxic vasoconstriction, the correlation coefficients for systolic, mean, and diastolic PAP were consistently higher than for TXA-induced pulmonary hypertension (r = 0.809, 0.778 and 0.734, respectively). Estimation of sPAP, mPAP, and dPAP using PWTT is feasible, nevertheless slightly better correlation coefficients were detected for sPAP compared to dPAP. In this study we establish the physiological basis for future methods to obtain PAP by non-invasively measured PWTT.

3.
Sensors (Basel) ; 21(8)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924650

RESUMO

In this work, four sensor fusion algorithms for inertial measurement unit data to determine the orientation of a device are assessed regarding their usability in a hardware restricted environment such as body-worn sensor nodes. The assessment is done for both the functional and the extra-functional properties in the context of human operated devices. The four algorithms are implemented in three data formats: 32-bit floating-point, 32-bit fixed-point and 16-bit fixed-point and compared regarding code size, computational effort, and fusion quality. Code size and computational effort are evaluated on an ARM Cortex M0+. For the assessment of the functional properties, the sensor fusion output is compared to a camera generated reference and analyzed in an extensive statistical analysis to determine how data format, algorithm, and human interaction influence the quality of the sensor fusion. Our experiments show that using fixed-point arithmetic can significantly decrease the computational complexity while still maintaining a high fusion quality and all four algorithms are applicable for applications with human interaction.


Assuntos
Algoritmos , Orientação , Humanos , Orientação Espacial
4.
Cell ; 181(6): 1246-1262.e22, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32442405

RESUMO

There is considerable inter-individual variability in susceptibility to weight gain despite an equally obesogenic environment in large parts of the world. Whereas many studies have focused on identifying the genetic susceptibility to obesity, we performed a GWAS on metabolically healthy thin individuals (lowest 6th percentile of the population-wide BMI spectrum) in a uniquely phenotyped Estonian cohort. We discovered anaplastic lymphoma kinase (ALK) as a candidate thinness gene. In Drosophila, RNAi mediated knockdown of Alk led to decreased triglyceride levels. In mice, genetic deletion of Alk resulted in thin animals with marked resistance to diet- and leptin-mutation-induced obesity. Mechanistically, we found that ALK expression in hypothalamic neurons controls energy expenditure via sympathetic control of adipose tissue lipolysis. Our genetic and mechanistic experiments identify ALK as a thinness gene, which is involved in the resistance to weight gain.


Assuntos
Quinase do Linfoma Anaplásico/genética , Magreza/genética , Tecido Adiposo/metabolismo , Adulto , Animais , Linhagem Celular , Estudos de Coortes , Drosophila/genética , Estônia , Feminino , Humanos , Leptina/genética , Lipólise/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/genética , Interferência de RNA/fisiologia , Adulto Jovem
5.
Water Environ Res ; 91(1): 54-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30301485

RESUMO

The aim of the study was to investigate the influence of moderate temperatures on the efficiency of a full-scale anaerobic treatment system consisting of a primary sedimentation unit (PST) and an anaerobic baffled reactor (ABR, approx. 10 m3 ). Therefore, two trials with different test setups in series were carried out (1st trial: continuous load; 2nd trial: diurnal variation load). The plant was fed with municipal wastewater and operated at temperatures between 8 and 24°C. The mean efficiency of the ABR was low, compared to the one of the PST. At 10°C, only 10% of the COD was removed. The COD (chemical oxygen demand) removal efficiency of the plant (PST + ABR) averaged 50%. At low temperatures, volatile fatty acids began to accumulate. In both trials, the contents of total suspended solids in the sludge bed differed distinctly and influenced the effort for desludging. PRACTITIONER POINTS: The operation of ABR in combined collection systems depends on the efficiency of the pretreatment unit. At cold temperatures, an ABR has no advantages compared to conventional pretreatment processes. For use under moderate conditions, the design must be adjusted.

6.
Mycologia ; 107(1): 227-38, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25376797

RESUMO

The potential of 3-D nondestructive imaging techniques such as micro-computed tomography (micro-CT) was evaluated to study morphological patterns of the potential medicinal fungus Hericium coralloides (Basidiomycota). Micro-CT results were correlated with histological information gained from scanning electron microscopy (SEM) and light microscopy (LM). It is demonstrated that the combination of these imaging methods results in a more distinct picture of the morphology of the edible and potentially medicinal Hericium coralloides basidiomata. In addition we have created 3-D reconstructions and visualizations based on micro-CT imagery from a randomly selected part of the upper region of a fresh H. coralloides basidioma: Analyses for the first time allowed an approximation of the evolutionary effectiveness of this bizarrely formed basidioma type in terms of the investment of tissue biomass and its reproductive output (production of basidiospores).


Assuntos
Basidiomycota/química , Basidiomycota/ultraestrutura , Imageamento Tridimensional , Microscopia Eletrônica de Varredura , Esporos Fúngicos/química , Esporos Fúngicos/ultraestrutura , Microtomografia por Raio-X
7.
Matrix Biol ; 38: 22-35, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25063231

RESUMO

OBJECTIVE: Sensory and sympathetic nerve fibers (SNF) innervate bone and epiphyseal growth plate. The role of neuronal signals for proper endochondral ossification during skeletal growth is mostly unknown. Here, we investigated the impact of the absence of sensory neurotransmitter substance P (SP) and the removal of SNF on callus differentiation, a model for endochondral ossification in adult animals, and on bone formation. METHODS: In order to generate callus, tibia fractures were set in the left hind leg of wild type (WT), tachykinin 1-deficient (Tac1-/-) mice (no SP) and animals without SNF. Locomotion was tested in healthy animals and touch sensibility was determined early after fracture. Callus tissue was prepared for immunofluorescence staining for SP, neurokinin1-receptor (NK1R), tyrosine-hydroxylase (TH) and adrenergic receptors α1, α2 and ß2. At the fracture site, osteoclasts were stained for TRAP, osteoblasts were stained for RUNX2, and histomorphometric analysis of callus tissue composition was performed. Primary murine bone marrow derived macrophages (BMM), osteoclasts, and osteoblasts were tested for differentiation, activity, proliferation and apoptosis in vitro. Femoral fractures were set in the left hind leg of all the three groups for mechanical testing and µCT-analysis. RESULTS: Callus cells stained positive for SP, NK1R, α1d- and α2b adrenoceptors and remained ß2-adrenoceptor and TH-negative. Absence of SP and SNF did not change the general locomotion but reduces touch sensitivity after fracture. In mice without SNF, we detected more mesenchymal callus tissue and less cartilaginous tissue 5 days after fracture. At day 13 past fracture, we observed a decrease of the area covered by hypertrophic chondrocytes in Tac1-/- mice and mice without SNF, a lower number of osteoblasts in Tac1-/- mice and an increase of osteoclasts in mineralized callus tissue in mice without SNF. Apoptosis rate and activity of osteoclasts and osteoblasts isolated from Tac1-/- and sympathectomized mice were partly altered in vitro. Mechanical testing of fractured- and contralateral legs 21 days after fracture, revealed an overall reduced mechanical bone quality in Tac1-/- mice and mice without SNF. µCT-analysis revealed clear structural alteration in contralateral and fractured legs proximal of the fracture site with respect to trabecular parameters, bone mass and connectivity density. Notably, structural parameters are altered in fractured legs when related to unfractured legs in WT but not in mice without SP and SNF. CONCLUSION: The absence of SP and SNF reduces pain sensitivity and mechanical stability of the bone in general. The micro-architecture of the bone is profoundly impaired in the absence of intact SNF with a less drastic effect in SP-deficient mice. Both sympathetic and sensory neurotransmitters are indispensable for proper callus differentiation. Importantly, the absence of SP reduces bone formation rate whereas the absence of SNF induces bone resorption rate. Notably, fracture chondrocytes produce SP and its receptor NK1 and are positive for α-adrenoceptors indicating an endogenous callus signaling loop. We propose that sensory and sympathetic neurotransmitters have crucial trophic effects which are essential for proper bone formation in addition to their classical neurological actions.


Assuntos
Calo Ósseo/fisiologia , Diferenciação Celular/fisiologia , Condrócitos/fisiologia , Osteogênese/fisiologia , Substância P/deficiência , Sistema Nervoso Simpático/patologia , Animais , Fenômenos Biomecânicos , Calo Ósseo/citologia , Imunofluorescência , Técnicas Histológicas , Camundongos , Camundongos Knockout
8.
J Orthop Res ; 32(9): 1198-207, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24888549

RESUMO

To study the behavior of bovine disc cells and changes in disc matrix following in vitro compression tests; to compare the findings to investigations on human intervertebral discs (IVD) after burst fracture of the cervical spine. Healthy IVDs (n = 21) from three bovine tails were studied at 6 and 12 h post-mortem, with 16 IVDs subjected to impact loading and five as unloaded controls. IVDs (n = 8) from patients with burst fractures were compared to the bovine compression group. Specimens were studied macroscopically, histologically, and ultrastructurally for healthy cells, balloon cells, and disc cell death (DCD). Annulus ruptures were seen in both post-trauma groups, with radial ruptures being present histologically in all loaded bovine discs. Balloon cells were found in some human IVDs and were induced in vitro in bovine loaded discs within a distinct range of absorbed energy. There was a positive correlation between DCD and absorbed energy in all compartments of bovine discs. Both species showed similar patterns of DCD in the different compartments. This study was able to show similarities between both species in cell morphologies and matrix damage. The survival of the disc after substantial compression trauma thus seems to remain highly questionable.


Assuntos
Disco Intervertebral/patologia , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/patologia , Ferimentos e Lesões/complicações , Adolescente , Adulto , Animais , Bovinos , Sobrevivência Celular , Feminino , Humanos , Técnicas In Vitro , Disco Intervertebral/ultraestrutura , Degeneração do Disco Intervertebral/etiologia , Degeneração do Disco Intervertebral/patologia , Masculino , Pessoa de Meia-Idade , Modelos Animais , Pressão , Suporte de Carga , Adulto Jovem
9.
J Biomech ; 47(2): 438-44, 2014 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-24290135

RESUMO

Finite element (FE) modelling has been proposed as a tool for estimating fracture risk and patient-specific FE models are commonly based on computed tomography (CT). Here, we present a novel method to automatically create personalised 3D models from standard 2D hip radiographs. A set of geometrical parameters of the femur were determined from seven a-p hip radiographs and compared to the 3D femoral shape obtained from CT as training material; the error in reconstructing the 3D model from the 2D radiographs was assessed. Using the geometry parameters as the input, the 3D shape of another 21 femora was built and meshed, separating a cortical and trabecular compartment. The material properties were derived from the homogeneity index assessed by texture analysis of the radiographs, with focus on the principal tensile and compressive trabecular systems. The ability of these FE models to predict failure load as determined by experimental biomechanical testing was evaluated and compared to the predictive ability of DXA. The average reconstruction error of the 3D models was 1.77 mm (±1.17 mm), with the error being smallest in the femoral head and neck, and greatest in the trochanter. The correlation of the FE predicted failure load with the experimental failure load was r(2)=64% for the reconstruction FE model, which was significantly better (p<0.05) than that for DXA (r(2)=24%). This novel method for automatically constructing a patient-specific 3D finite element model from standard 2D radiographs shows encouraging results in estimating patient-specific failure loads.


Assuntos
Cabeça do Fêmur/diagnóstico por imagem , Análise de Elementos Finitos , Imageamento Tridimensional/métodos , Modelos Biológicos , Módulo de Elasticidade/efeitos da radiação , Feminino , Fraturas Ósseas , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Mecânico , Tomografia Computadorizada por Raios X , Malha Trabecular/diagnóstico por imagem
10.
Water Sci Technol ; 68(1): 83-90, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23823543

RESUMO

This paper deals with adaption capacity of nitrifiers to allylthiourea (ATU) as a model inhibitor at two temperature levels. Nitrifying communities were developed at 15 (BM15) and 30 °C (BM30). The activity of the nitrifiers was determined by using short-time respiration (STR) tests, oxygen monitoring and in-situ measurements. The oxygen monitoring provided information about the temperature-dependent time delay between the dosage of NH4(+)-N or ATU and reaching its characteristic level of effect. The greatly scattered results from the STR tests for BM15 were thus explained by the time delay, which was two to three times higher than for BM30. Furthermore, combining the results of oxygen-monitoring and in-situ measurements it can be stated that an adaption to ATU at psychrophilic temperature conditions was not achieved, whereby up to 40% of nitrification was sustained for BM30 at an ATU-concentration over 7 mg/l. The nitrification by BM15 did not start until ATU was degraded to 1-2 mg/l, the typical inhibition concentration for ATU. Hence, the results indicate a population drift to adapted nitrifiers at mesophilic conditions and ATU-degrading microorganisms at psychrophilic temperature conditions, which can have a considerable influence on domestic wastewater treatment in cold climates receiving industrial effluents.


Assuntos
Temperatura , Eliminação de Resíduos Líquidos/métodos , Amônia/metabolismo , Reatores Biológicos/microbiologia , Nitritos/metabolismo
11.
J Bone Miner Res ; 28(12): 2584-91, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23677814

RESUMO

Radiographic texture analysis has been developed lately to improve the assessment of bone architecture as a determinant of bone quality. We validate here an algorithm for the evaluation of trabecular homogeneity index (HI) in the proximal femur from hip radiographs, with a focus on the impact of the principal compressive system of the trabecular bone, and evaluate its correlation with femoral strength, bone mineral density (BMD), and volumetric trabecular structure parameters. A semiautomatic custom-made algorithm was applied to calculate the HI in the femoral neck and trochanteric areas from radiographs of 178 femoral bone specimens (mean age 79.3 ± 10.4 years). Corresponding neck region was selected in CT scans to calculate volumetric parameters of trabecular structure. The site-specific BMDs were assessed from dual-energy X-ray absorptiometry (DXA), and the femoral strength was experimentally tested in side-impact configuration. Regression analysis was performed between the HI and biomechanical femoral strength, BMD, and volumetric parameters. The correlation between HI and failure load was R(2) = 0.50; this result was improved to R(2) = 0.58 for cervical fractures alone. The discrimination of bones with high risk of fractures (load <3000 N) was similar for HI and BMD (AUC = 0.87). Regression analysis between the HIs versus site-specific BMDs yielded R(2) = 0.66 in neck area, R(2) = 0.60 in trochanteric area, and an overall of R(2) = 0.66 for the total hip. Neck HI and BMD correlated significantly with volumetric structure parameters. We present here a method to assess HI that can explain 50% of an experimental failure load and determines bones with high fracture risk with similar accuracy as BMD. The HI also had good correlation with DXA and computed tomography-derived data.


Assuntos
Osso e Ossos/diagnóstico por imagem , Osso e Ossos/fisiologia , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/fisiologia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Pescoço/diagnóstico por imagem , Pescoço/fisiologia , Curva ROC , Análise de Regressão , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X
12.
J Clin Invest ; 123(2): 812-22, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23298834

RESUMO

Klotho is a potent regulator of 1,25-hydroxyvitamin D3 [1,25(OH)2D3] formation and calcium-phosphate metabolism. Klotho-hypomorphic mice (kl/kl mice) suffer from severe growth deficits, rapid aging, hyperphosphatemia, hyperaldosteronism, and extensive vascular and soft tissue calcification. Sequelae of klotho deficiency are similar to those of end-stage renal disease. We show here that the mineralocorticoid receptor antagonist spironolactone reduced vascular and soft tissue calcification and increased the life span of kl/kl mice, without significant effects on 1,25(OH)2D3, FGF23, calcium, and phosphate plasma concentrations. Spironolactone also reduced the expression of osteoinductive Pit1 and Tnfa mRNA, osteogenic transcription factors, and alkaline phosphatase (Alpl) in calcified tissues of kl/kl mice. In human aortic smooth muscle cells (HAoSMCs), aldosterone dose-dependently increased PIT1 mRNA expression, an effect paralleled by increased expression of osteogenic transcription factors and enhanced ALP activity. The effects of aldosterone were reversed by both spironolactone treatment and PIT1 silencing and were mitigated by FGF23 cotreatment in HAoSMCs. In conclusion, aldosterone contributes to vascular and soft tissue calcification, an effect due, at least in part, to stimulation of spironolactone-sensitive, PIT1-dependent osteoinductive signaling.


Assuntos
Glucuronidase/deficiência , Espironolactona/farmacologia , Fator de Transcrição Pit-1/metabolismo , Calcificação Vascular/prevenção & controle , Aldosterona/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/metabolismo , Glucuronidase/genética , Humanos , Proteínas Klotho , Camundongos , Camundongos Knockout , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteoblastos/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição Pit-1/genética , Calcificação Vascular/etiologia , Calcificação Vascular/metabolismo , Calcificação Vascular/patologia
13.
Bone ; 51(4): 737-40, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22796418

RESUMO

Highly accurate nonlinear finite element (FE) models have been presented to estimate bone fracture load. However, these complex models require high computational capacity, which restricts their clinical applicability. The objective of this experimental FE study was to assess the predictive value of a more simple cortical bone simulation model in the estimation of experimentally measured fracture load of the proximal femur. The prediction was compared with that of DXA, and with the prediction of our previous, more complex FE model including trabecular bone. Sixty-one formalin-fixed cadaver femora (from 41 women and 20 men, age 55-100 years) were scanned using a multi-detector CT and were mechanically tested for failure in a sideways fall loading configuration. Trabecular bone was completely removed from the FE models and only cortical bone was analyzed. The training set FE models (N=21) was used to establish the stress and strain thresholds for the element failure criteria. Bi-linear elastoplastic FE analysis was performed based on the CT images. The validation set (N=40) was used to estimate the fracture load. The estimated fracture load values were highly correlated with the experimental data (r(2)=0.73; p<0.001). The slope was 1.128, with an intercept of -360 N, which was not significantly different from 1 and 0, respectively. DXA-based BMD and BMC correlated moderately with the fracture load (r(2)=0.41 and r(2)=0.40, respectively). The study shows that the proximal femoral failure load in a sideways fall configuration can be estimated with reasonable accuracy by using the CT-based bi-linear elastoplastic cortical bone FE model. This model was more predictive for fracture load than DXA and only slightly less accurate than a full bone FE model including trabecular bone. The accuracy and calculation time of the model give promises for clinical use.


Assuntos
Fêmur/fisiopatologia , Análise de Elementos Finitos , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
14.
Otol Neurotol ; 33(3): 481-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22410732

RESUMO

OBJECTIVE: Currently, no large animal model exists for surgical-experimental exploratory analysis of implantable hearing devices. In a histomorphometric study, we sought to investigate whether sheep or pig cochleae are suitable for this purpose and whether device implantation is feasible. METHODS: Skulls of pig and sheep cadavers were examined using high-resolution 128-slice computed tomography (CT) to study anatomic relationships. A cochlear implant and an active middle ear implant could be successfully implanted into the sheep's inner and middle ear, respectively. Correct device placement was verified by CT and histology. The cochlear anatomy of the sheep was further studied by micro-CT and histology. RESULTS: Our investigations indicate that the sheep is a suitable animal model for implantation of implantable hearing devices. The implantation of the devices was successfully performed by access through a mastoidectomy. The histologic, morphologic, and micro-CT study of the sheep cochlea showed that it is highly similar to the human cochlea. The temporal bone of the pig was not suitable for these microsurgical procedures because the middle and inner ear were not accessible owing to distinct soft and fatty tissue coverage of the mastoid. CONCLUSION: The sheep is an appropriate large animal model for experimental studies with implantable hearing devices, whereas the pig is not.


Assuntos
Cadáver , Implantes Cocleares , Orelha Interna/anatomia & histologia , Orelha Média/anatomia & histologia , Ovinos/fisiologia , Animais , Cóclea/anatomia & histologia , Cóclea/diagnóstico por imagem , Implante Coclear , Orelha Interna/diagnóstico por imagem , Orelha Média/diagnóstico por imagem , Endoscopia , Estudos de Viabilidade , Processamento de Imagem Assistida por Computador , Bigorna/anatomia & histologia , Bigorna/cirurgia , Processo Mastoide/cirurgia , Janela da Cóclea/anatomia & histologia , Janela da Cóclea/cirurgia , Rampa do Tímpano/anatomia & histologia , Rampa do Tímpano/cirurgia , Crânio/anatomia & histologia , Especificidade da Espécie , Suínos , Osso Temporal/anatomia & histologia , Tomografia Computadorizada por Raios X
15.
Bone ; 50(4): 824-9, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22306697

RESUMO

The objective of this experimental finite element (FE) study was to assess the accuracy of a simulation model estimate of the experimentally measured fracture load of the proximal femur in a sideways fall. Sixty-one formalin-fixed cadaver femora (41 female and 20 male) aged 55-100 years (an average of 80 years) were scanned with a multi-detector CT scanner and were mechanically tested for failure in a sideways fall loading configuration. Twenty-one of these femurs were used for training purposes, and 40 femurs were used for validation purposes. The training set FE models were used to establish the strain threshold for the element failure criteria. Bi-linear elastoplastic FE analysis was performed based on the CT images. The validation set was used to estimate the fracture loads. The Drucker-Prager criterion was applied to determine the yielding and the maximum principal stress criteria and the minimum principal strain criteria for element failure in tension and in compression, respectively. The estimated fracture load values were highly correlated with the experimental data (r=0.931; p<0.001). The slope was 0.929, with an intercept of 258 N, which was not significantly different from 1 and 0, respectively. The study shows that it is possible to estimate the fracture load with relatively high accuracy in a sideways fall configuration by using the CT-based FE method. This method may therefore be applied for studying the biomechanical mechanisms of hip fractures.


Assuntos
Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia , Análise de Elementos Finitos , Estresse Mecânico , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Anatômicos , Reprodutibilidade dos Testes , Fatores de Tempo , Suporte de Carga
16.
Med Phys ; 37(6): 2560-71, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20632568

RESUMO

PURPOSE: Standard diagnostic techniques to quantify bone mineral density (BMD) include dual-energy x-ray absorptiometry (DXA) and quantitative computed tomography. However, BMD alone is not sufficient to predict the fracture risk for an individual patient. Therefore, the development of tools, which can assess the bone quality in order to predict individual biomechanics of a bone, would mean a significant improvement for the prevention of fragility fractures. In this study, a new approach to predict the fracture risk of proximal femora using a statistical appearance model will be presented. METHODS: 100 CT data sets of human femur cadaver specimens are used to create statistical appearance models for the prediction of the individual fracture load (FL). Calculating these models offers the possibility to use information about the inner structure of the proximal femur, as well as geometric properties of the femoral bone for FL prediction. By applying principal component analysis, statistical models have been calculated in different regions of interest. For each of these models, the individual model parameters for each single data set were calculated and used as predictor variables in a multilinear regression model. By this means, the best working region of interest for the prediction of FL was identified. The accuracy of the FL prediction was evaluated by using a leave-one-out cross validation scheme. Performance of DXA in predicting FL was used as a standard of comparison. RESULTS: The results of the evaluative tests demonstrate that significantly better results for FL prediction can be achieved by using the proposed model-based approach (R = 0.91) than using DXA-BMD (R = 0.81) for the prediction of fracture load. CONCLUSIONS: The results of the evaluation show that the presented model-based approach is very promising and also comparable to studies that partly used higher image resolutions for bone quality assessment and fracture risk prediction.


Assuntos
Algoritmos , Fraturas do Fêmur/diagnóstico por imagem , Reconhecimento Automatizado de Padrão/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Inteligência Artificial , Simulação por Computador , Interpretação Estatística de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Modelos Estatísticos , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes , Medição de Risco/métodos , Fatores de Risco , Sensibilidade e Especificidade
17.
Calcif Tissue Int ; 87(3): 203-10, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20556370

RESUMO

Experimental analysis with paired femurs provides the opportunity to study within-person differences in fracture type and associated structural side differences. We hypothesized that different fracture types in the hips of a subject are associated with structural asymmetry. Bone mineral density (BMD) and structural measurements of paired cadaver femurs (32 females, 24 males) were performed before mechanical testing in a side-impact configuration. Fractures were classified (cervical or trochanteric) and differences in structural parameters, BMD, and failure load were evaluated between the left and right hips as well as between experimental fracture types. We observed larger dimensions (P < 0.05-0.01), thicker cortices (P < 0.05-0.001), and a smaller femoral shaft diameter (FSD) (P < 0.01) in the left hip than in the right. Seventeen pairs (30.4%) had trochanteric fractures on one side and cervical on the contralateral side. The asymmetric trochanteric fracture side had a higher head/neck diameter ratio (HD/ND) (P < 0.05) and a trend toward a lower neck-shaft angle (NSA) (P = 0.066) than its collateral cervical side in females and a lower HD and higher FSD (P < 0.05) in males. In females, asymmetric fracture cases displayed lower NSA (P < 0.001) and HD/ND (P < 0.01) than symmetric cervical ones. In males, asymmetric fracture cases showed larger dimensions than the other groups (P < 0.05-0.01). BMD increased from symmetric cervical to asymmetric and then to symmetric trochanteric cases (P < 0.05-0.01), with the experimental failure load showing a similar trend. In conclusion, intrasubject structural asymmetry is associated with asymmetric fracture types. Asymmetry should be considered when using the opposite side as control in clinical studies.


Assuntos
Densidade Óssea , Lesões do Quadril/patologia , Quadril/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Quadril/diagnóstico por imagem , Humanos , Masculino , Radiografia , Projetos de Pesquisa , Fatores de Risco
18.
Med Biol Eng Comput ; 48(7): 711-7, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20490945

RESUMO

The objective of this experimental finite element (FE) study is to test the hypothesis that strain distributions coincide with the occurrence of cervical versus trochanteric hip fractures during loading conditions simulating a sideways fall, and that the cervical versus trochanteric principal strain ratio predicts different fracture patterns. Cadaver femora (female, 83 +/- 9 years) were CT scanned and mechanically tested simulating a fall. Thirteen cervical and 13 trochanteric fracture cases were selected for FE analysis. Principal strain distributions were analysed, and strain ratio epsilon(C)/epsilon(T) for strain patterns over the cervical and trochanteric regions was computed. The ratio epsilon(C)/epsilon(T) in the femora with cervical fractures (mean +/- SD 1.103 +/- 0.127) differed from that in trochanteric fractures (0.925 +/- 0.137) (p = 0.001). The significant difference in the strain ratio between fracture types remained after accounting for femoral neck and trochanteric BMD (p = 0.014), showing that it is independent of BMD. Area under the ROC curve was 0.858 in the discrimination of fracture types. The model predicted the experimental fracture type correctly in 22 of 26 cases. The cervical versus trochanteric region principal strain ratio differed significantly between femora with experimental cervical versus trochanteric fractures, and 85% agreement was achieved for the occurrence of hip fracture types using a simple FE model.


Assuntos
Fêmur/fisiopatologia , Fraturas do Quadril/fisiopatologia , Modelos Biológicos , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Colo Femoral/fisiopatologia , Análise de Elementos Finitos , Humanos , Estresse Mecânico
19.
Ann Biomed Eng ; 37(9): 1910-20, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19585240

RESUMO

Although it is known that long cortical bone structurally alter their area moment of inertia with age related bone loss maintaining their bending strength, the incidence of fragility fractures associated with cortical thinning still prevails. We hypothesize that cortical thinning with aging increases the local buckling susceptibility under abnormal or eccentric loads, and initiates fracture. The paper presents a series of 3D geometrical model derived from CT scans of a human femoral neck used to simulate age-related bone loss. The purpose of the model is to predict the susceptibility of local buckling at the femoral neck in falls by elderly folks. Geometric three-dimensional models of femoral neck cortices were developed from 7 human cadaver femurs (4 female, 3 male, 52-68 years). Three age related femoral neck models were simulated by either reducing (young age-related model) or increasing (old age-related model) the outer cortical surfaces in the radial-direction, by 1-mm. The control model was the middle-age related model. The inner cortex diameter was also adjusted to equilibrate the compressive stresses, based on the load-profile of a single-legged stance. Based on the old age related model, two additional "fragile" models were simulated by reducing the compressive load profile by 10 and 20% changing the inner cortex diameter, respectively. Using these models for each specimen, the consequence of a fall on the greater trochanter was evaluated. The Finite Strip Method (FSM) was used to investigate the association between local buckling at the femoral neck and the load to failure. Under constant loading, buckling progressively reduced the load to failure with aging, as seen in 2/7 of the middle age (by 9-15%) and 5/7 of the old age (by 7-32%) related models. In the fragile models, a 51% reduction in the load to failure was noted. Structural adaptation to age-related bone loss might preserves the bending strength under physiologic loads, but cortical thinning effects the buckling ratio reaching a critical threshold that would make the bone susceptible to local buckling at the femoral neck increasing the risk of fracture in a fall.


Assuntos
Envelhecimento , Colo do Fêmur/fisiopatologia , Imageamento Tridimensional , Modelos Biológicos , Osteoporose/fisiopatologia , Suporte de Carga , Idoso , Feminino , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/fisiopatologia , Colo do Fêmur/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos
20.
Artigo em Inglês | MEDLINE | ID: mdl-19168377

RESUMO

OBJECTIVES: This study evaluated a method for determining the density and distribution of bone of mandibular condyles using proprietary computerized tomography (CT) software. STUDY DESIGN: Thirty-eight condylar specimens were investigated with a high-resolution multislice CT. The density was determined by using bone density analysis algorithms available within the proprietary software. Apparent density was estimated over the total cross-sectional area, the total trabecular bone area apart from the cortical fraction, and on individually selected points. Color-coded pictures were created to demonstrate density differences. RESULTS: The cortical bone presented significantly higher densities than the trabecular bone. The anterior cortical bone had significantly higher densities than the posterior. The central anterior cortical and the central trabecular areas showed significantly higher densities than the medial and lateral areas. CONCLUSION: This technique proved to be a valuable method for determination of the differences in density in the mandibular condyle. It shows potential in providing clinicians with an imaging modality for specific clinical use.


Assuntos
Densidade Óssea , Côndilo Mandibular/anatomia & histologia , Côndilo Mandibular/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador , Software
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