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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/β-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., Competing Interests: IV, DC, KP, TV, DH, RG, ME, IT, PE, ED, MH, VK, GD, JR, MK, MH, TV, LH No competing interests declared, (© 2023, Vietor et al.)

Objective:  Criss-cross heart (CCH) is a rare congenital cardiac defect defined by crossing of ventricular inflow streams contributing to less than 0.1 % of all congenital heart anomalies. Due to its rarity and complexity, prenatal diagnosis in these patients remains challenging. We sought to describe prenatal findings and postnatal course in eight cases of prenatally diagnosed CCH., Methods:  This is a retrospective case series of prenatally diagnosed CCH in three centers between 2010-2017. We reviewed fetal echocardiograms as well as postnatal clinical charts and surgical reports., Results:  8 cases of CCH were included. The median gestational age at diagnosis was 27 weeks. 7 patients were found with situs solitus, one fetus with situs ambiguous. In all patients, the four-chamber view was abnormal. There was atrioventricular discordance in half of the patients, while all patients showed ventriculoarterial discordance. All patients were found with additional cardiac anomalies, including ventricular septal defect, double outlet right ventricle, right aortic arch, atrial septal defect and pulmonary stenosis. Three patients underwent amniocentesis without pathological findings. All patients were born alive at a median gestational age of 38 + 2 weeks and survived our median follow-up of 181 days., Conclusion:  CCH can be diagnosed prenatally by detailed fetal echocardiography when observing an abnormal four-chamber view with crossing of inflow streams into both ventricles and a lack of parallel orientation of the atrioventricular valve axis due to a clockwise or counterclockwise rotation of the ventricular mass along its axis. With the help of prenatal ultrasound, parental guidance and counselling as well as postnatal pediatric cardiac management can be warranted., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

We report on a thin-disk laser system with more than 10 kW of output power and a beam quality of M 2 =1.76 at an overall optical-to-optical efficiency of 51%. The system consists of two thin-disk laser oscillators and a thin-disk multi-pass amplifier system. To reach high output powers while maintaining good beam quality, the output beams of two identical laser oscillators are polarization-combined. Subsequently, the beam is amplified in a multi-pass system. To the best of our knowledge, this is the highest output power achieved for a thin-disk laser system with a beam quality close to fundamental mode.

Anaemia is frequently present in patients with acute myocardial infarction (AMI) and contributes to an adverse prognosis. We hypothesised that, besides reduced oxygen carrying capacity, anaemia is associated with (1) red blood cell (RBC) dysfunction and a reduced circulating nitric oxide (NO) pool, (2) compensatory enhancement of vascular and cardiac endothelial nitric oxide synthase (eNOS) activity, and (3) contribution of both, RBC dysfunction and reduced circulatory NO pool to left ventricular (LV) dysfunction and fatal outcome in AMI. In mouse models of subacute and chronic anaemia from repeated mild blood loss the circulating NO pool, RBC, cardiac and vascular function were analysed at baseline and in reperfused AMI. In anaemia, RBC function resulted in profound changes in membrane properties, enhanced turnover, haemolysis, dysregulation of intra-erythrocytotic redox state, and RBC-eNOS. RBC from anaemic mice and from anaemic patients with acute coronary syndrome impaired the recovery of contractile function of isolated mouse hearts following ischaemia/reperfusion. In anaemia, the circulating NO pool was reduced. The cardiac and vascular adaptation to anaemia was characterised by increased arterial eNOS expression and activity and an eNOS-dependent increase of end-diastolic left ventricular volume. Endothelial dysfunction induced through genetic or pharmacologic reduction of eNOS-activity abrogated the anaemia-induced cardio-circulatory compensation. Superimposed AMI was associated with decreased survival. In summary, moderate blood loss anaemia is associated with severe RBC dysfunction and reduced circulating NO pool. Vascular and cardiac eNOS are crucial for the cardio-circulatory adaptation to anaemia. RBC dysfunction together with eNOS dysfunction may contribute to adverse outcomes in AMI.

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 6 th 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., Competing Interests: Declaration of Interests J.H., N.G., and A.V. are employed by Nestlé Research. J.H., N.G., and A.V. have filed a patent on Methods of Modulating ALK (WO2019101490)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Information on the adaptation of bone structures during evolution is rare since histological data are limited. Micro- and nano-computed tomography of a fossilized vertebra from Champsosaurus sp., which has an estimated age of 70-73 million years, revealed lower porosity and higher bone density compared to modern Crocodylidae vertebrae. Mid-infrared reflectance and energy dispersive X-ray mapping excluded a petrification process, and demonstrated a typical carbonate apatite distribution, confirming histology in light- and electron microscopy of the preserved vertebra. As a consequence of this evolutionary process, the two vertebrae of modern Crocodylidae show reduced overall stiffness in the finite element analysis simulation compared to the fossilized Champsosaurus sp. vertebra, with predominant stiffness along the longitudinal z-axes., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Two-dimensional speckle tracking echocardiography (2D-STE)-based strain values of the left and the right ventricle have been established; however, less is known about atrial deformation. The aim of our study was to assess both atrial strain and ventricular strain using 2D-STE in a cardiac 4-chamber view and to investigate the effect of possible influencing factors such as gestational age., Methods: Fetal echocardiography was performed on a Toshiba Aplio 500 ultrasound system. Based on an apical or basal 4-chamber view of the fetal heart, left and right ventricular longitudinal peak systolic strain (LVLPSS and RVLPSS) as well as left and right atrial longitudinal peak systolic strain (LALPSS and RALPSS) were assessed by 2D-STE., Results: A total of 101 healthy fetuses were included. The mean gestational age (GA) was 26.0 ± 5.6 weeks. GA was significantly positively correlated (p < 0.05) with LVLPSS and RVLPSS and significantly negatively correlated (p < 0.05) with LALPSS and RALPSS. The mean values for LVLPSS and RVLPSS were -17.44 ± 2.29% and -16.89 ± 1.72%. The mean values for LALPSS and RALPSS were 34.09 ± 4.17% and 35.36 ± 2.90%., Conclusion: Ventricular and atrial deformation analysis in 2D-STE was technically feasible and showed comparable values to current data. For future research on myocardial function (MF) of the fetus, considering GA as an influencing factor for deformation analysis seems to be adequate. Especially, atrial deformation analysis allows the assessment of diastolic myocardial function. Further research needs to clarify the clinical meaning of these myocardial deformation indices in fetuses at risk., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Lichen secondary metabolites show important biological activities as well as pharmaceutical and chemotaxonomic potential. In order to utilize such substances of interest, detailed knowledge of their biosynthetic pathways is essential. 13 CO 2 -pulse/chase experiments using intact thalli of the lichen Usnea dasopoga resulted in multiple 13 C-labeled isotopologs in amino acids, but not in the dibenzofuran derivative usnic acid - one of the best-studied lichen metabolites, with considerable and renewed interest for pharmaceutical and lifestyle applications. Spraying an aqueous solution of [U- 13 C 6 ]glucose onto the thalli of U. dasopoga afforded a specific mixture of multiple 13 C-labeled isotopologs in usnic acid. One- and two-dimensional NMR analysis of the crude lichen extract corroborated the polyketide biosynthetic pathway via methylphloroacetophenone but not via phloroacetophenone. With usnic acid as an exemplar, we provide proof-of-principle experiments that can be used in general to study metabolic pathways and fluxes in intact lichens., (© 2019 The Authors. New Phytologist © 2019 New Phytologist Trust.)

Rationale: Chronic stress contributes to the pathogenesis of chronic pain. Yet, the role of close relationship stress in these pathways to pain is not fully understood., Objective: To delineate specific psychosocial pathways associated with chronic pain, specifically emphasizing close relationships for midlife adults. We tested whether relationship strain, relationship support, social integration, depression, anxiety, and pain severity predict chronic pain etiology and persistence over 10 years, highlighting specific associations for acute versus chronic pain., Method: Using data from the National Survey of Midlife in the U.S. (MIDUS 2 and 3, collected in 2004-2006 and 2013-2014, respectively), we used logistic regression to test the etiology of new chronic pain (n = 1591) and persistence of pain for adults with acute (n = 352) and chronic pain (n = 367) conditions at baseline., Results: Of participants who reported they did not have chronic pain at baseline, the development of chronic pain 10 years later was significantly associated with baseline family strain (OR = 1.38, p < .01). For participants with acute pain at baseline, the transition of this pain to chronic a decade later was significantly associated with initial reports of pain interference (OR = 1.24, p < .001), family support (OR = 0.60, p < .05), and depression (OR = 1.20, p < .05). Persistent chronic pain was solely associated with baseline pain interference (OR = 1.21, p < .01)., Conclusions: Family strain is an important part of the chronic stress profile associated with chronic pain etiology, whereas family support is associated with a reduced risk of acute pain transitioning to chronic pain over time. Prioritizing family relationships in treatment approaches to pain may be an indicated, innovative approach to preventing pain development and escalation and requires systems training in healthcare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Significance: Recent clinical evidence identified anemia to be correlated with severe complications of cardiovascular disease (CVD) such as bleeding, thromboembolic events, stroke, hypertension, arrhythmias, and inflammation, particularly in elderly patients. The underlying mechanisms of these complications are largely unidentified. Recent Advances: Previously, red blood cells (RBCs) were considered exclusively as transporters of oxygen and nutrients to the tissues. More recent experimental evidence indicates that RBCs are important interorgan communication systems with additional functions, including participation in control of systemic nitric oxide metabolism, redox regulation, blood rheology, and viscosity. In this article, we aim to revise and discuss the potential impact of these noncanonical functions of RBCs and their dysfunction in the cardiovascular system and in anemia., Critical Issues: The mechanistic links between changes of RBC functional properties and cardiovascular complications related to anemia have not been untangled so far., Future Directions: To allow a better understanding of the complications associated with anemia in CVD, basic and translational science studies should be focused on identifying the role of noncanonical functions of RBCs in the cardiovascular system and on defining intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718-742.

In this study different state-of-the-art visualization methods such as micro-computed tomography (micro-CT), mid-infrared (MIR) microscopic imaging and energy dispersive X-ray (EDS) mapping were evaluated to study human skeletal remains for the determination of the post-mortem interval (PMI). PMI specific features were identified and visualized by overlaying molecular imaging data and morphological tissue structures generated by radiological techniques and microscopic images gained from confocal microscopy (Infinite Focus (IFM)). In this way, a more distinct picture concerning processes during the PMI as well as a more realistic approximation of the PMI were achieved. It could be demonstrated that the gained result in combination with multivariate data analysis can be used to predict the Ca/C ratio and bone volume (BV) over total volume (TV) for PMI estimation. Statistical limitation of this study is the small sample size, and future work will be based on more specimens to develop a screening tool for PMI based on the outcome of this multidimensional approach.

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)., (© 2015 by The Mycological Society of America.)

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 β2. 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 β2-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., (Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.)

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., (© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Unlabelled: Whole vertebrae areal and volumetric bone mineral density (BMD) measurements are not ideal predictors of vertebral fractures. We introduce a technique which enables quantification of bone microstructural parameters at precisely defined anatomical locations. Results show that local assessment of bone volume fraction at the optimal location can substantially improve the prediction of vertebral strength., Introduction: Whole vertebrae areal and volumetric BMD measurements are not ideal predictors of vertebral osteoporotic fractures. Recent studies have shown that sampling bone microstructural parameters in smaller regions may permit better predictions. In such studies, however, the sampling location is described only in general anatomical terms. Here, we introduce a technique that enables the quantification of bone volume fraction and microstructural parameters at precisely defined anatomical locations. Specific goals of this study were to investigate at what anatomical location within the vertebrae local bone volume fraction best predicts vertebral-body strength, whether this prediction can be improved by adding microstructural parameters and to explore if this approach could better predict vertebral-body strength than whole bone volume fraction and finite element (FE) analyses., Methods: Eighteen T12 vertebrae were scanned in a micro-computed tomography (CT) system and FE meshes were made using a mesh-morphing tool. For each element, bone microstructural parameters were measured and correlated with vertebral compressive strength as measured experimentally. Whole bone volume fraction and FE-predicted vertebral strength were also compared to the experimental measurements., Results: A significant association between local bone volume fraction measured at a specific central region and vertebral-body strength was found that could explain up to 90% of the variation. When including all microstructural parameters in the regression, the predictive value of local measurements could be increased to 98%. Whole bone volume fraction could explain only 64% and FE analyses 76% of the variation in bone strength., Conclusions: A local assessment of volume fraction at the optimal location can substantially improve the prediction of bone strength. Local assessment of other microstructural parameters may further improve this prediction but is not clinically feasible using current technology.

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., (© 2013 Published by Elsevier Ltd.)

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., (© 2013 American Society for Bone and Mineral Research.)

Decreased expression of the microRNA miR-205 has been observed in multiple tumour types due to its role in the epithelial to mesenchymal transition, which promotes metastasis. We determined the expression of miR-205 in 111 archival samples of prostate carcinoma and found it to be strongly reduced in most samples, with a median expression level of 16% in comparison to benign tissue from the same patient. Lower miR-205 expression correlated significantly with tumour size and miR-205 levels decreased with increasing Gleason score from 7a=3+4 to 8=4+4. In addition, we describe the anti-apoptotic protein BCL2 as a target of miR-205, relevant for prostate cancer due to its role in prognosis of primary tumours and in the appearance of androgen independence. The repression of BCL2 by miR-205 was confirmed using reporter assays and western blotting. BCL2 mRNA expression in the same collective of prostate cancer tissue samples was associated with higher Gleason score and extracapsular extension of the tumour (pT3). Consistent with its anti-apoptotic target BCL2, miR-205 promoted apoptosis in prostate cancer cells in response to DNA damage by cisplatin and doxorubicin in the prostate cancer cell lines PC3 and LnCap. MiR-205 also inhibited proliferation in these cell lines.

Background: The development of new global health academic programs provides unique opportunities to create innovative educational approaches within and across universities. Recent evidence suggests that digital media technologies may provide feasible and cost-effective alternatives to traditional classroom instruction; yet, many emerging global health academic programs lag behind in the utilization of modern technologies., Objective: We created an inter-departmental University of Southern California (USC) collaboration to develop and implement a course focused on digital media and global health., Design: Course curriculum was based on core tenants of modern education: multi-disciplinary, technologically advanced, learner-centered, and professional application of knowledge. Student and university evaluations were reviewed to qualitatively assess course satisfaction and educational outcomes., Results: 'New Media for Global Health' ran for 18 weeks in the Spring 2012 semester with N=41 students (56.1% global health and 43.9% digital studies students). The course resulted in a number of high quality global health-related digital media products available at http://iml420.wordpress.com/. Challenges confronted at USC included administrative challenges related to co-teaching and frustration from students conditioned to a rigid system of teacher-led learning within a specific discipline. Quantitative and qualitative course evaluations reflected positive feedback for the course instructors and mixed reviews for the organization of the course., Conclusion: The development of innovative educational programs in global health requires on-going experimentation and information sharing across departments and universities. Digital media technologies may have implications for future efforts to improve global health education.

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.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We report for the first time, to the best of our knowledge, on a large mode area Er-doped photonic crystal fiber laser system. The fiber core had a diameter of 40 μm and NA of <0.04 leading to a mode field diameter of about 31 μm around 1550 nm wavelength. More than 70 W of single-frequency output power at 1556 nm could be extracted using a master-oscillator power-amplifier scheme. Near diffraction limited output beam quality has been verified by measuring the TEM(00) content with a nonconfocal scanning ring cavity., (© 2011 Optical Society of America)

We report on experiments performed with a cladding-pumped single-mode Er:Yb-codoped single-frequency fiber amplifier simultaneously seeded by a distributed-feedback diode at 1556 nm and a tunable external-cavity diode laser emitting at a wavelength of about 1 μm wavelength. The influence of the output wavelength of the external-cavity laser on amplification and reabsorption behavior of the Yb emission as well as the amplifier performance at a wavelength of 1556 nm is examined experimentally.

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.

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.

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.

To the best of our knowledge we report for the first time on an Yb-sensitized Er-doped cladding pumped fiber amplifier which is simultaneously seeded by two single-frequency lasers operating at 1556 nm and 1064 nm, respectively. This mode of operation ensures stable amplifier operation by reducing the gain around 1 microm wavelength to the large signal gain value, while having no significant effect on the slope efficiency of the amplification process at 1556 nm when pumping at 976 nm. We were able to demonstrate stable output power of 8.7 W at 1556 nm with an amplifier gain of > 22 dB, a co-propagating pumping scheme and the power limitation only being set by the available amount of pump power.

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.

This report describes studies in hyperlipidemic New Zealand White (NZW) rabbits investigating the impact of the liver-selective thyromimetic T-0681 on lipoprotein metabolism and the development of atherosclerosis. Prolonged treatment with T-0681 increased the hepatic expression of both LDL receptor and scavenger receptor class B, type I without affecting cholesteryl ester transfer protein activity. Upregulation of hepatic lipoprotein receptors was accompanied by a marked decrease of apolipoprotein B-containing lipoproteins, reflected by a 60% reduction of plasma cholesterol and a >70% reduction of plasma triglyceride levels. Most importantly, T-0681 reduced the development of atherosclerosis by 80% in NZW rabbits on high-cholesterol chow. Our data suggest that liver-selective thyromimetics, such as T-0681, may prove to be useful therapeutic agents against the development of atherosclerosis in humans.

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.

Bone mass predicts a high proportion of variability in bone failure strength but is known to overlap among subjects with and without fractures. Here, we tested the hypothesis that trabecular bone microstructure, determined with micro-computed tomography (microCT), can improve the prediction of experimental failure loads in the distal forearm compared with bone mass alone. The right forearm and left distal radius of 130 human specimens were examined. Bone mineral density (BMD) was measured with peripheral dual energy X-ray absorptiometry (DXA). The specimens were mechanically tested to failure in a fall configuration, with the hand, elbow, ligaments, and tendons intact. Cylindrical bone samples from the metaphysis of the contralateral distal radius were obtained adjacent to the subchondral bone plate and scanned with microCT. When analyzing the total sample, BMD of the distal radius displayed a correlation of r = 0.82 with mechanical failure loads. After excluding 21 specimens with no obvious radiological sign of fracture after the test, the correlation increased to r = 0.85. When only including 79 specimens with loco typico fractures, the correlation was r = 0.82. The microstructural parameters showed correlation coefficients with the failure loads of < or =0.55 and did not add significant information to DXA in predicting failure loads in multiple regression models. These findings suggest that, under experimental conditions of mechanically testing entire bones, measurement of bone microstructure does not improve the prediction of distal radius bone strength. Determination of bone microstructure may thus be less promising in improving the prediction of fractures than commonly assumed.

Although the correlation between decreased bone mineral density and increased incidence of distal radius fractures is widely acknowledged, the effect of osteoporosis on specific fracture types is seldom addressed. No classification system has been established for clinical use that has been validated for osteoporotic fractures or that includes parameters of the bone density or bone quality. So far, only one experimental study could report a clear correlation between bone properties and fracture patterns, and an additional clinical study assesses bone density in relation to displacement in Colles fractures. Further studies are needed to analyze the intra- and interobserver reproducibility of more simplified but nonetheless comprehensive classification systems that recognize the impact of osteoporosis on distal radius fracture and that specifically incorporate bone mineral density.

A solid and accurate proximal femur segmentation technique using the popular active shape model (ASM) is proposed. For generating an optimal shape prior, the minimum description length, based on 200 supervised manual segmented proximal femur shapes, is used. The segmentation is based on a coarse to fine scaling technique including a profile scale space method. The segmentation results are compared using an optimal defined initial pose and a pose based on a registration technique. Using ideal template initialization, 95% of the shapes have been recovered exactly (average point-to-point error approximately 13 pixels, average point-to-boundary error approximately 7 pixels). Using a template-based initialization based on a registration technique, a successful segmentation rate of approximately 89% is achieved, with an average point-to-point error approximately 12 pixels, and an average point-to-boundary error approximately 8 pixels. With an adequate template initialization and an improved ASM, this method seems to provide an accurate tool for segmentation of the proximal femur shapes on conventional hip overview x-ray images.

In this paper we present a knowledge-based femur detection algorithm. The algorithm uses femur corpus constraints, Canny edge detection and Hough lines. For optimal femur template placement in the local area we use cross-correlation. The segmentation itself is done with an optimized active shape modeling technique. Using the knowledge-based technique we have located 95% of the femur shapes of N=117 X-rays. From those 83% of the target femur shapes have been segmented successfully (point-to-point error: approximately 14 pixels, point-to-boundary error = approximately 9 pixels).

Unlabelled: Computerized analysis of the trabecular structure was used to test whether femur failure load can be estimated from radiographs. The study showed that combined analysis of trabecular bone structure and geometry predicts in vitro failure load with similar accuracy as DXA., Introduction: Since conventional radiography is widely available with low imaging cost, it is of considerable interest to discover how well bone mechanical competence can be determined using this technology. We tested the hypothesis that the mechanical strength of the femur can be estimated by the combined analysis of the bone trabecular structure and geometry., Methods: The sample consisted of 62 cadaver femurs (34 females, 28 males). After radiography and DXA, femora were mechanically tested in side impact configuration. Fracture patterns were classified as being cervical or trochanteric. Computerized image analysis was applied to obtain structure-related trabecular parameters (trabecular bone area, Euler number, homogeneity index, and trabecular main orientation), and set of geometrical variables (neck-shaft angle, medial calcar and femoral shaft cortex thicknesses, and femoral neck axis length). Multiple linear regression analysis was performed to identify the variables that best explain variation in BMD and failure load between subjects., Results: In cervical fracture cases, trabecular bone area and femoral neck axis length explained 64% of the variability in failure loads, while femoral neck BMD also explained 64%. In trochanteric fracture cases, Euler number and femoral cortex thickness explained 66% of the variability in failure load, while trochanteric BMD explained 72%., Conclusions: Structural parameters of trabecular bone and bone geometry predict in vitro failure loads of the proximal femur with similar accuracy as DXA, when using appropriate image analysis technology.

Background: College drinking is a significant public health problem. Although parental monitoring and supervision reduces the risk for alcohol consumption among younger adolescents, few studies have investigated the impact of earlier parental monitoring on later college drinking. This study examined whether parental monitoring indirectly exerts a protective effect on college drinking by reducing high school alcohol consumption., Methods: A longitudinal cohort of 1,253 male and female students, ages 17 to 19, attending a large, public, mid-Atlantic university was studied at two time points. First, data on high school parental monitoring and alcohol consumption were gathered via questionnaire during the summer prior to college entry. Second, during the first year of college, past-year alcohol consumption was measured via a personal interview. Multiple regression models tested the relationship between parental monitoring and past year alcohol use (i.e., number of drinks per drinking day)., Results: Holding constant demographics, SAT score, and religiosity, parental monitoring had a significant protective effect on both high school and college drinking level. However, the association between parental monitoring and college drinking level became non-significant once high school drinking level was held constant., Conclusion: While parental monitoring did not directly influence college alcohol consumption, evidence for mediation was observed, whereby parental monitoring had an indirect influence on college drinking through reductions in high school drinking. Initiatives that promote effective parenting might be an important strategy to curb high-risk drinking among older adolescents. More research is needed to understand the nature and degree of parent-child communication that is necessary to extend the protective influence of parents into the college years.

We report on an erbium-doped fiber oscillator mode-locked by nonlinear polarization evolution operating in the large normal dispersion regime. The setup produced highly chirped 10 nJ pulses at 37 MHz which can be compressed externally to below 75 fs. Hence, this simple and practical setup is capable of providing ultrashort pulses with a peak power of 140 kW. The pulse formation is indeed subject to intrapulse Raman-scattering but a clean and stable pulse train can be observed. The similarities as well as the differences of the output characteristics to the parabolic pulse and wave breaking-free regime are explicated.

Although the thumb saddle is one of the most common sites of degenerative osteoarthritis in the hand, little is known about the altered microstructure in osteoarthritic trapezial bones. External forces resulting from subluxation of the carpometacarpal joint of the thumb (CMC I) should provoke microstructural changes in the trapezium. The purpose of this study was to compare the regional differences of the microstructure between osteoarthritic and healthy trapezial bones. Fifteen trapezia harvested from female patients with radiologically and clinically diagnosed saddle joint osteoarthritis (OA) were compared with 15 unaffected controls. Microstructural parameters, such as bone volume ratio (BV/TV), three-dimensional connectivity (Conn.D), trabecular number (Tb.N), and trabecular thickness (Tb.Th) were studied using a microcomputed tomography (microCT) system. While the trapezial height in OA was 22% less, the sclerotic subchondral bone layer thickness was 50% higher in OA compared with the control group (p < 0.001). In the OA group there was a 42% higher bone volume ratio (p

Operative fixation is the treatment of choice for a rupture of the distal tendon of biceps. A variety of techniques have been described including transosseous sutures and suture anchors. The poor quality of the bone of the radial tuberosity might affect the load to failure of the tendon repair in early rehabilitation. The aim of this study was to determine the loads to failure of different techniques of fixation and to investigate their association with the bone mineral density of the radial tuberosity. Peripheral quantitative computed tomography was carried out to measure the trabecular and cortical bone mineral density of the radial tuberosity in 40 cadaver specimens. The loads to failure in four different techniques of fixation were determined. The Endobutton-based method showed the highest failure load at 270 N (sd 22) (p < 0.05). The mean failure load of the transosseous suture technique was 210 N (sd 66) and that of the TwinFix-QuickT 5.0 mm was 57 N (sd 22), significantly lower than those of all other repairs (p < 0.05). No significant correlation was seen between bone mineral density and loads to failure. The transosseous technique is an easy and cost-saving procedure for fixation of the distal biceps tendon. TwinFix-QuickT 5.0 mm had significantly lower failure loads, which might affect early rehabilitation, particularly in older patients.

Background: Surgical repair is the most favored treatment for a rupture of the distal biceps tendon. A variety of techniques have been described for distal biceps tendon reattachment, including transosseous sutures, suture anchors, interference screws, and an EndoButton-based technique., Hypothesis: EndoButton and suture anchor have initially stronger fixation strengths than do transosseous sutures, allowing early postoperative rehabilitation., Study Design: Controlled laboratory study., Methods: Single loads to failure and mode of failure of 13 different fixation techniques were determined using 130 human cadaveric elbows. Quantitative computer tomography was performed to exclude differences in bone mineral density as an affecting factor. Repeated-measures analysis of variance was used to assess differences in failure load between repair techniques., Results: The EndoButton-based technique showed a significantly higher failure load (259 +/- 28 N) than did all other techniques (P < .05). No significant differences were seen between the transosseous suture technique (210 +/- 29 N) and most other techniques (P > .05). Failure loads of the TwinFix-QuickT (57 +/- 29 N) and Biocuff screw (105 +/- 28 N) were significantly lower than those of all other repairs (P < .05)., Conclusion: Significant differences exist in failure loads and modes of failure for the different repair techniques after rupture of the distal biceps tendon., Clinical Relevance: The transosseous technique is still a sufficient and cost-saving procedure for repair of the distal biceps tendon. TwinFix-QuickT 5.0 mm and Biocuff screw 5.7 mm had significantly lower failure loads, which might affect early rehabilitation, particularly in patients with poor bone quality.

Unlabelled: In this study, we characterize bone microstructure, specifically sex differences, at multiple skeletal sites in 165 subjects >52 yr of age, using microCT technology in vitro. Significant sex differences are observed at the distal radius, femoral neck, and femoral trochanter, but not at the iliac crest, calcaneus, and lumbar vertebral body. Correlations in BV/TV between sites ranged from r = 0.13 to 0.56., Introduction: The goals of this study were (1) to assess potential sex differences of bone microstructure and their difference between skeletal sites and (2) to explore the relationship of trabecular microstructural properties between relevant skeletal sites., Materials and Methods: Trabecular bone microstructural properties were measured in vitro in 165 subjects 52-99 yr of age using microCT. Defined volumes of interest (cylinders with 6 mm diameter and 6 mm length) were scanned at a resolution of 26 microm (isotropic) in six different anatomical sites: distal radius, femoral neck and trochanter, iliac crest, calcaneus, and second lumbar vertebral body., Results: At the radius and femoral neck, trabecular bone displayed a more plate-like structure, thicker trabeculae, smaller separation/higher trabecular number, higher connectivity, and a higher degree of anisotropy in men than in women (p < 0.05). At the trochanter, men displayed more plate-like structure and thicker trabeculae (p < 0.05), but no differences in trabecular separation or other parameters compared with the women. At the calcaneus, iliac crest, and second lumbar vertebra none of the bone parameters displayed significant differences between sexes. The BV/TV at one site explained a range of only 2-32% of the variability at other sites., Conclusions: These results suggest that trabecular bone microstructural properties are remarkably heterogeneous throughout the skeleton. Significant differences between men and women are observed at some, but not at all, sites. The magnitude of sex differences in trabecular microstructure coincides with that of fracture incidence observed for some of the sites in epidemiological studies.

Objectives: We sought to compare the diagnostic performance of screen-film radiography, storage-phosphor radiography, and a flat-panel detector system in detecting forearm fractures and to classify distal radius fractures according to the Müller-AO and Frykman classifications compared with the true extent, depicted by anatomic preparation., Materials and Methods: A total of 71 cadaver arms were fractured in a material testing machine creating different fractures of the radius and ulna as well as of the carpal bones. Radiographs of the complete forearm were evaluated by 3 radiologists, and anatomic preparation was used as standard of reference in a receiver operating curve analysis., Results: The highest diagnostic performance was obtained for the detection of distal radius fractures with area under the receiver operating curve (AUC) values of 0.959 for screen-film radiography, 0.966 for storage-phosphor radiography, and 0.971 for the flat-panel detector system (P > 0.05). Exact classification was slightly better for the Frykman (kappa values of 0.457-0.478) compared with the Müller-AO classification (kappa values of 0.404-0.447), but agreement can be considered as moderate for both classifications., Conclusions: The 3 imaging systems showed a comparable diagnostic performance in detecting forearm fractures. A high diagnostic performance was demonstrated for distal radius fractures and conventional radiography can be routinely performed for fracture detection. However, compared with anatomic preparation, depiction of the true extent of distal radius fractures was limited and the severity of distal radius fractures tends to be underestimated.

Unlabelled: We experimentally studied the distribution of hip fracture types at different structural mechanical strength. Femoral neck fractures were dominant at the lowest structural strength levels, whereas trochanteric fractures were more common at high failure loads. The best predictor of fracture type across all failure loads and in both sexes was the neck-shaft angle., Introduction: Bone geometry has been shown to be a potential risk factor for osteoporotic fractures. Risk factors have been shown to differ between cervical and trochanteric hip fractures. However, the determinants of cervical and trochanteric fractures at different levels of structural mechanical strength are currently unknown. In addition, it is not known if the distribution of fracture types differs between sexes. The aim of this experimental study on excised femora was to investigate whether there exist differences in the distribution of cervical and trochanteric fractures between different structural mechanical strength levels and different sexes and to identify the geometric determinants that predict a fracture type., Materials and Methods: The sample was comprised of 140 cadavers (77 females: mean age, 81.7 years; 63 males: mean age, 79.1 years) from whom the left femora were excised for analysis. The bones were radiographed, and geometrical parameters were determined from the digitized X-rays. The femora were mechanically tested in a side impact configuration, simulating a sideways fall. After the mechanical test, the fracture patterns were classified into cervical and trochanteric., Results: The overall proportion of cervical fractures was higher in females (74%) than in males (49%) (p = 0.002). The fracture type distribution differed significantly across load quartiles in females (p = 0.025), but not in males (p = 0.205). At the lowest load quartiles, 94.7% of fractures in female and 62.5% in males were femoral neck fractures. At the highest quartiles, in contrast, only 52.6% of fractures in females and 33.3% in males were cervical fractures. Among geometric variables, the neck-shaft angle was the best predictor of fracture type, with higher values in subjects with cervical fractures. This finding was made in females (p < 0.001) and males (p = 0.02) and was consistent across all failure load quartiles., Conclusions: Femoral neck fractures predominate at the lowest structural mechanical strength levels, whereas trochanteric fractures are more common at high failure loads. Females are more susceptible to femoral neck fractures than males. The best predictor of fracture type across all structural strength levels and both sexes was the neck-shaft angle.

We tested the hypothesis that bone mineral density (BMD) and bone mineral content (BMC) in proximal human femur specimens in the upper neck region of interest (ROI) and femoral neck axis length (FNAL) provide a significantly better prediction of femoral bone strength than standard ROIs in vitro. BMD and BMC were measured in 110 proximal femur specimens using a standard dual-energy X-ray absorptiometry (DXA) scanner. The analysis included a new ROI in the upper neck as well as the standard ROIs. FNAL was obtained from the scan images. The specimens' failure-load was measured in a mechanical loading device, simulating a fall on the greater trochanter. For the standard ROIs, correlations between failure-load and BMD ranged from R2 = 0.64 (shaft ROI) to R2 = 0.70, p < 0.001 (femoral neck). Prediction of strength by BMD did not significantly differ from those of BMC (R2 ranging from 0.65 to 0.75, p < 0.001). In the upper neck ROI, for both BMD and BMC correlations with failure-load were higher (R2 = 0.76 and 0.81, respectively; p < 0.001). A lower, yet still significant, correlation was found between FNAL and bone strength (R2 = 0.23, p < 0.001). Normalization of failure-load with respect to FNAL did not significantly increase the correlations with densitometric measures. This study provides in vitro evidence indicating that among the ROIs of the proximal femur the newly defined upper neck ROI provides the best prediction of bone strength. Only a weak association was observed between failure load and FNAL.

High-resolution magnetic resonance imaging (hrMRI) has recently made it possible to evaluate trabecular bone structure in vivo. Despite obvious gender differences in fracture incidence at the distal radius, little is known about gender differences in trabecular bone microarchitecture and its relationship to the structural strength of the forearm. The aim of this study was to determine trabecular bone structure in the distal radius of elderly women and men and its correlation with failure loads of the distal radius as determined in a fall configuration. Specifically, we tested the hypotheses that structural indices differ between women and men and that they offer information that is independent from BMD for predicting structural strength. Intact right arms were obtained from 73 formalin-fixed cadavers (age 80+/-11 years, 43 women, 30 men). Trabecular structural indices (apparent bone volume fraction [app. BV/TV], trabecular number [app. Tb.N], trabecular separation [app. Tb.Sp], trabecular thickness [app. Tb.Th] and fractal dimension [Frac.Dim]) were assessed in the distal metaphysis, using hrMRI with 156 microm in-plane resolution and proprietary digital image analysis, while BMD was measured with dual X-ray absorptiometry (DXA). Women displayed significantly lower BMD (-29.8%, p <0.001), app. BV/TV (-8.2%, p <0.05) and app. Tb.Th (-10.2%, p <0.001) than men, whereas app. Tb.N, app. Tb.Sp. and fractal dimension did not differ significantly. Structural parameters differed between normal and osteopenic women (BV/TV: -11%, p <0.01; Tb.Th: -8%, p <0.001) and between normal and osteoporotic women BV/TV: -21%, p <0.001; Tb.Th: -16%, p <0.001). App. BV/TV, app. Tb.Th and fractal dimension provided information independent from BMD in the prediction of radial failure loads in multiple regression models. These findings imply that it should be of clinical interest to monitor both bone mass and trabecular microstructure for predicting osteoporotic fracture risk.

The objective of this study was to compare the value of multislice CT arthrography and MR arthrography in the assessment of cartilage lesions of the elbow joint. Twenty-six cadaveric elbow specimens were examined with the use of CT arthrography and MR arthrography prior to joint exploration and macroscopic inspection of articular cartilage. Findings at CT and MR arthrography were compared with macroscopic assessments in 104 cartilage areas. At macroscopic inspection, 45 cartilage lesions (six grade 2 lesions, 25 grade 3 lesions, 14 grade 4 lesions) and 59 areas of normal articular cartilage were observed. With macroscopic assessment as the gold standard CT and MR arthrography showed an overall sensitivity/specificity of 80/93% and 78/95% for the detection of cartilage lesions, respectively. Only two of six grade 2 lesions were detected by CT and MR arthrography. For the diagnosis of grade 3 and 4 lesions, the sensitivity/specificity was 87/94% with CT arthrography, and 85/95% with MR arthrography. In an experimental setting multislice CT arthrography and MR arthrography showed a similar performance in the detection of cartilage lesions. Both methods indicated limited value in the diagnosis of grade 2 articular cartilage lesions.

Bone transport applying the principle of distraction osteogenesis makes it possible to reconstruct long bone defects caused by trauma or resection of bone tumors. The method employing a central cable, developed in Munich, is especially suitable for such applications. The main bone fragments are stabilized by an external fixateur, and bone transport is effected with a single central cable fixed to the tip of the segment, and driven by an external, programmable motor. In 15 patients the tractive forces during the entire bone transport were measured with a strain gauge incorporated within the cable. On the basis of the force profiles characteristics normal bone transport (forces between 150-250 N) can be distinguished from a critical transport (forces > 250 N) with the risk of premature consolidation. There is some evidence that at a very high level of force, just before premature consolidation a very effective form of bone transport with good bone neoformation can be achieved. Transport systems employing a central cable allow this special form of distraction osteogenesis, since there is continuous force monitoring, and there is the option of employing the traction force as a control factor in a loop.