Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of ...mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development. In addition, we found distinct alterations of hematopoiesis-regulating factors such as Kit-ligand and Jagged1 accompanied by a significantly diminished ability to support CD34+ hematopoietic stem and progenitor cells in long-term culture-initiating cells (LTC-ICs) assays. This deficient osteogenic differentiation and insufficient stromal support was reversible and correlated with disease status as indicated by Osteocalcin serum levels and LTC-IC frequencies returning to normal values at remission. In line with this, cultivation of healthy MSC in conditioned medium from four AML cell lines resulted in decreased proliferation and osteogenic differentiation. Taken together, AML-derived MSC are molecularly and functionally altered and contribute to hematopoietic insufficiency. Inverse correlation with disease status and adoption of an AML-like phenotype after exposure to leukemic conditions suggests an instructive role of leukemic cells on bone marrow microenvironment.
We introduce the concept of a liquid compound refractive X-ray zoom lens. The lens is generated by pumping a suitable liquid lens material like water, alcohol or heated lithium through a line of ...nozzles each forming a jet with the cross section of lens elements. The system is housed, so there is a liquid-circulation. This lens can be used in white beam at high brilliance synchrotron sources, as radiation damages are cured by the continuous reformation of the lens. The focal length can be varied by closing nozzles, thus reducing the number of lens elements in the beam.
Background
Surgical treatment and clinical management of foot pathology requires accurate, reliable assessment of foot deformities. Foot and ankle deformities are multi‐planar and therefore difficult ...to quantify by standard radiographs. Three‐dimensional (3D) imaging modalities have been used to define bone orientations using inertial axes based on bone shape, but these inertial axes can fail to mimic established bone angles used in orthopaedics and clinical biomechanics. To provide improved clinical relevance of 3D bone angles, we developed techniques to define bone axes using landmarks on quantitative computed tomography (QCT) bone surface meshes. We aimed to assess measurement precision of landmark‐based, 3D bone‐to‐bone orientations of hind foot and lesser tarsal bones for expert raters and a template‐based automated method.
Methods
Two raters completed two repetitions each for twenty feet (10 right, 10 left), placing anatomic landmarks on the surfaces of calcaneus, talus, cuboid, and navicular. Landmarks were also recorded using the automated, template‐based method. For each method, 3D bone axes were computed from landmark positions, and Cardan sequences produced sagittal, frontal, and transverse plane angles of bone‐to‐bone orientations. Angular reliability was assessed using intraclass correlation coefficients (ICCs) and the root mean square standard deviation (RMS‐SD) for intra‐rater and inter‐rater precision, and rater versus automated agreement.
Results
Intra‐ and inter‐rater ICCs were generally high (≥ 0.80), and the ICCs for each rater compared to the automated method were similarly high. RMS‐SD intra‐rater precision ranged from 1.4 to 3.6° and 2.4 to 6.1°, respectively, for the two raters, which compares favorably to uni‐planar radiographic precision. Greatest variability was in Navicular: Talus sagittal plane angle and Cuboid: Calcaneus frontal plane angle. Precision of the automated, atlas‐based template method versus the raters was comparable to each rater's internal precision.
Conclusions
Intra‐ and inter‐rater precision suggest that the landmark‐based methods have adequate test‐retest reliability for 3D assessment of foot deformities. Agreement of the automated, atlas‐based method with the expert raters suggests that the automated method is a valid, time‐saving technique for foot deformity assessment. These methods have the potential to improve diagnosis of foot and ankle pathologies by allowing multi‐planar quantification of deformities.
Various physical demands are placed on soldiers, whose effectiveness and survivability depend on their combat-specific physical fitness. Because sport training programs involving weight-based ...training have proven effective, this study examined the value of such a program for short-term military training using combat-relevant tests. A male weight-based training (WBT) group (n = 15; mean +/- SD: 27.0 +/- 4.7 years, 173.8 +/- 5.8 cm, 80.9 +/- 12.7 kg) performed full-body weight-based training workouts, 3.2-km runs, interval training, agility training, and progressively loaded 8-km backpack hikes. A male Army Standardized Physical Training (SPT) group (n = 17; mean +/- SD: 29.0 +/- 4.6 years, 179.7 +/- 8.2 cm, 84.5 +/- 10.4 kg) followed the new Army Standardized Physical Training program of stretching, varied calisthenics, movement drills, sprint intervals, shuttle running, and distance runs. Both groups exercised for 1.5 hours a day, 5 days a week for 8 weeks. The following training-induced changes were statistically significant (P < 0.05) for both training groups: 3.2-km run or walk with 32-kg load (minutes), 24.5 +/- 3.2 to 21.0 +/- 2.8 (SPT) and 24.9 +/- 2.8 to 21.1 +/- 2.2 (WBT); 400-m run with 18-kg load (seconds), 94.5 +/- 14.2 to 84.4 +/- 11.9 (SPT) and 100.1 +/- 16.1 to 84.0 +/- 8.4 (WBT); obstacle course with 18-kg load (seconds), 73.3 +/- 10.1 to 61.6 +/- 7.7 (SPT) and 66.8 +/- 10.0 to 60.1 +/- 8.7 (WBT); 5 30-m sprints to prone (seconds), 63.5 +/- 4.8 to 59.8 +/- 4.1 (SPT) and 60.4 +/- 4.2 to 58.9 +/- 2.7 (WBT); and 80-kg casualty rescue from 50 m (seconds), 65.8 +/- 40.0 to 42.1 +/- 9.9 (SPT) and 57.6 +/- 22.0 to 44.2 +/- 8.8 (WBT). Of these tests, only the obstacle course showed significant difference in improvement between the two training groups. Thus, for short-term (i.e., 8-week) training of relatively untrained men, the Army's new Standardized Physical Training program and a weight-based training experimental program can produce similar, significant, and meaningful improvements in military physical performance. Further research would be needed to determine whether weight-based training provides an advantage over a longer training period.
Abstract We investigated the capacity of bone quantity and bone geometric strength indices to predict ultimate force in the human second metatarsal (Met2) and third metatarsal (Met3). Intact lower ...extremity cadaver samples were measured using clinical, volumetric quantitative computed tomography (vQCT) with positioning and parameters applicable to in vivo scanning. During processing, raw voxel data (0.4 mm isotropic voxels) were converted from Hounsfield units to apparent bone mineral density (BMD) using hydroxyapatite calibration phantoms to allow direct volumetric assessment of whole-bone and subregional metatarsal BMD. Voxel data were realigned to produce cross-sectional slices perpendicular to the longitudinal axes of the metatarsals. Average mid-diaphyseal BMD, bone thickness, and buckling ratio were measured using an optimized threshold to distinguish bone from non-bone material. Minimum and maximum moments of inertia and section moduli were measured in the mid-diaphysis region using both a binary threshold for areal, unit-density measures and a novel technique for density-weighted measures. BMD and geometric strength indices were strongly correlated to ultimate force measured by ex vivo 3-point bending. Geometric indices were more highly correlated to ultimate force than was BMD; bone thickness and density-weighted minimum section modulus had the highest individual correlations to ultimate force. Density-weighted geometric indices explained more variance than their binary analogs. Multiple regression analyses defined models that predicted 85–89% of variance in ultimate force in Met2 and Met3 using bone thickness and minimum section modulus in the mid-diaphysis. These results have implications for future in vivo imaging to non-invasively assess bone strength and metatarsal fracture risk.
Neuropathic foot impairments treated with immobilization and off-loading result in osteolysis. In order to prescribe and optimize rehabilitation programs after immobilization we need to understand ...the magnitude of pedal osteolysis after immobilization and the time course for recovery.
To determine differences in a) foot skin temperature; b) calcaneal bone mineral density (BMD) after immobilization; c) calcaneal BMD after 33–53weeks of recovery; and d) percent of feet classified as osteopenic or osteoporotic after recovery in participants with neuropathic plantar ulcers (NPU) compared to Charcot neuroarthropathy (CNA).
Fifty-five participants with peripheral neuropathy were studied. Twenty-eight participants had NPU and 27 participants had CNA. Bilateral foot skin temperature was assessed before immobilization and bilateral calcaneal BMD was assessed before immobilization, after immobilization and after recovery using quantitative ultrasonometry.
Before immobilization, skin temperature differences in CNA between their index and contralateral foot were markedly higher than NPU feet (3.0 degree C versus 0.7 degree C, respectively, p<0.01); BMD in NPU immobilized feet averaged 486±136mg/cm2, and CNA immobilized feet averaged 456±138mg/cm2, p>0.05). After immobilization, index NPU feet lost 27mg/cm2; CNA feet lost 47mg/cm2 of BMD, p<0.05. After recovery, 61% of NPU index feet and 84% of CNA index feet were classified as osteopenic or osteoporotic.
There was a greater osteolysis after immobilization with an attenuated recovery in CNA feet compared to NPU feet. The attenuated recovery of pedal BMD in CNA feet resulted in a greater percentage of feet classified as osteoporotic and osteopenic.
•Before immobilization, foot temperature in Charcot neuroarthropathy subjects were higher than plantar ulcer subjects.•Before immobilization, calcaneal BMD in NPU feet averaged 486±136mg/cm2 and CNA feet averaged 456±138mg/cm2, p>0.05).•After 14-16weeks of cast immobilization, NPU feet lost 3mg/cm2; CNA feet lost 48mg/cm2 of BMD, p<0.05.•After 33-53weeks of recovery, calcaneal BMD is blunted in CNA feet compared to NPU feet.•After recovery, 61% of NPU index feet and 84% of CNA index feet were classified as osteopenic or osteoporotic, p<0.05.
This study investigated the effects on metabolic cost and gait biomechanics of using a prototype lower-body exoskeleton (EXO) to carry loads. Nine US Army participants walked at 1.34 m/s on a 0% ...grade for 8 min carrying military loads of 20 kg, 40 kg and 55 kg with and without the EXO. Mean oxygen consumption (VO
2
) scaled to body mass and scaled to total mass were significantly higher, by 60% and 41% respectively, when the EXO was worn, compared with the control condition. Mean VdotO
2
and mean VdotO
2
scaled to body mass significantly increased with load. The kinematic and kinetic data revealed significant differences between EXO and control conditions, such as walking with a more flexed posture and braking with higher ground reaction force at heel strike when wearing the EXO. Study findings demonstrate that the EXO increased users' metabolic cost while carrying various loads and altered their gait biomechanics compared with conventional load carriage.
Statement of Relevance: An EXO designed to assist in load bearing was found to raise energy expenditure substantially when tested by soldiers carrying military loads. EXO weight, weight distribution and design elements that altered users' walking biomechanics contributed to the high energy cost. To realise the potential of EXOs, focus on the user must accompany engineering advances.
Abstract Background Elevated plantar loading has been implicated in the etiology of plantar ulceration in individuals with diabetes mellitus and peripheral neuropathy. Total contact casts and cast ...walker boots are common off-loading strategies to facilitate ulcer healing and prevent re-ulceration. The purpose of this study was to compare off-loading capabilities of these strategies with respect to plantar loading during barefoot walking. Methods Twenty-three individuals with diabetes, peripheral neuropathy, and plantar ulceration were randomly assigned to total contact cast (n = 11) or removable cast walker boot (n = 12). Each subject underwent plantar loading assessment walking barefoot and wearing the off-loading device. Analysis of covariance was used to compare loading patterns in the off-loading devices for the whole foot, hindfoot, midfoot, and forefoot while accounting for walking speed and barefoot loading. Findings For the foot as a whole, there were no differences in off-loading between the two techniques. Subjects wearing cast walker boots had greater reductions in forefoot peak pressure, pressure-time integral, maximum force, and force-time integral with respect to barefoot walking. Healing times were similar between groups, but a greater proportion of ulcers healed in total contact casting compared to cast walker boots. Interpretation In subjects with diabetes, peripheral neuropathy, and plantar ulceration, cast walker boots provided greater load reduction in the forefoot, the most frequent site of diabetic ulceration, though a greater proportion of subjects wearing total contact casts experienced ulcer healing. Taken together, the less effective ulcer healing in cast walker boots despite superior forefoot off-loading suggests an important role for patient compliance in ulcer healing.
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