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Background: Muscle mitochondrial decline is associated with aging-related muscle weakness and insulin resistance. FoxO transcription factors are targets of insulin action and deletion of FoxOs improves mitochondrial function in diabetes. However, disruptions in proteostasis and autophagy are hallmarks of aging and the effect of chronic inhibition of FoxOs in aged muscle is unknown. This study investigated the role of FoxOs in regulating muscle strength and mitochondrial function with age., Methods: We measured muscle strength, cross-sectional area, muscle fibre-type, markers of protein synthesis/degradation, central nuclei, glucose/insulin tolerance, and mitochondrial bioenergetics in 4.5-month (Young) and 22-24-month-old (Aged) muscle-specific FoxO1/3/4 triple KO (TKO) and littermate control (Ctrl) mice., Results: Lean mass was increased in Aged TKO compared with both Aged Ctrl and younger groups by 26-33% (P < 0.01). Muscle strength, measured by max force of tibialis anterior (TA) contraction, was 20% lower in Aged Ctrl compared with Young Ctrls (P < 0.01) but was not decreased in Aged TKOs. Increased muscle strength in Young and Aged TKO was associated with 18-48% increased muscle weights compared with Ctrls (P < 0.01). Muscle cross-sectional analysis of TA, soleus, and plantaris revealed increases in fibre size distribution and a 2.5-10-fold increase in central nuclei in Young and Aged TKO mice, without histologic signs of muscle damage. Age-dependent increases in Gadd45a and Ube4a expression as well accumulation of K48 polyubiquitinated proteins were observed in quad and TA but were prevented by FoxO deletion. Young and Aged TKO muscle showed minimal changes in autophagy flux and no accumulation of autophagosomes compared with Ctrl groups. Increased strength in Young and Aged TKO was associated with a 10-20% increase in muscle mitochondrial respiration using glutamate/malate/succinate compared with controls (P < 0.05). OXPHOS subunit expression and complex I activity were decreased 16-34% in Aged Ctrl compared with Young Ctrl but were prevented in Aged TKO. Both Aged Ctrl and Aged TKO showed impaired glucose tolerance by 33% compared to young groups (P < 0.05) indicating improved strength and mitochondrial respiration are not due to improved glycemia., Conclusions: FoxO deletion increases muscle strength even during aging. Deletion of FoxOs maintains muscle strength in part by mild suppression of atrophic pathways, including inhibition of Gadd45a and Ube4a expression, without accumulation of autophagosomes in muscle. Deletion of FoxOs also improved mitochondrial function by maintenance of OXPHOS in both young and aged TKO., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Six different organizations participated in this interlaboratory study to quantify the variability in the tensile properties of Inconel 625 specimens manufactured using laser-powder-bed-fusion additive manufacturing machines. The tensile specimens were heat treated and tensile tests conducted until failure. The properties measured were yield strength, ultimate tensile strength, elastic modulus, and elongation. Statistical analysis revealed that between-participant variability for yield strength, ultimate tensile strength, and elastic modulus values were significantly higher (up to 4 times) than typical within-participant variations. Only between-participant and within-participant variability were both similar for elongation. A scanning electron microscope was used to examine one tensile specimen for fractography. The fracture surface does not have many secondary cracks or other features that would reduce the mechanical properties. In fact, the features largely consist of microvoid coalescence and are entirely consistent with ductile failure.

One way to improve confidence and encourage proliferation of additive manufacturing (AM) technologies and parts is by generating more high quality data describing the performance of AM processes and parts. Many in the AM community see round robin studies as a way to generate large data sets while distributing the cost among the participants, thereby reducing the cost to individual users. The National Institute of Standards and Technology (NIST) has conducted and participated in several of these AM round robin studies. While the results of these studies are interesting and informative, many of the lessons learned in conducting these studies concern the logistics and methods of the study and unique issues presented by AM. Existing standards for conducting interlaboratory studies of measurement methods, along with NIST's experience, form the basis for recommended protocols for conducting AM round robin studies. The role of round robin studies in AM qualification, some of the limitations of round robin studies, and the potential benefit of less formal collaborative experiments where multiple factors, AM machine being only one, are varied simultaneously are also discussed.

Bone tissue and geometry are constantly modified through modeling and remodeling at the periosteal, endosteal and intracortical envelopes. Results from several studies indicate that femoral bone geometry is a predictor of whole bone strength (e.g. femoral neck strength), however, it is not known whether there is a relationship between bone structural and material properties. Bone geometry can be determined from parameters based on plane X-ray radiogrammetry which are used to evaluate femoral bone quality for implant success. If there is a relationship between these parameters and tissue mechanical properties, this would have implications in the interpretation of such parameters for assessment of fracture risk and in further understanding of bone biology. Following measurement of radiogrammetric parameters from antero-posterior and medio-lateral X-rays (cortical thickness, bone diameter, bone area, moment of inertia, cortical index, Singh index), human femurs were machined into standard test specimens for assessment of tensile fracture toughness (GIc) of the tissue. Results indicated that tensile fracture toughness generally increased with increasing bone size. We also found that fracture toughness of the tissue was significantly related to radiogrammetric indices and that some of these indices explained a greater variability in toughness than porosity, age or gender., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Short and long duration tests were conducted on hollow femoral bone cylinders to study the circumferential (hoop) creep response of cortical bone subjected to an intramedullary radial load. It was hypothesized that there is a stress threshold above which nonlinear creep effects dominate the mechanical response and below which the response is primarily determined by linear viscoelastic material properties. The results indicate that a hoop stress threshold exists for cortical bone, where creep strain, creep strain rate and residual strain exhibited linear behavior at low hoop stress and nonlinear behavior above the hoop stress threshold. A power-law relationship was used to describe creep strain as a function of hoop stress and time and damage morphology was assessed.

The influence of in ovo administration of insulin-like growth factor-I (IGF-I) on long bone growth (tibiae and femora) of 42-d-old broiler chickens was investigated. Eggs were divided into three groups: uninjected control, vehicle-injected control, and recombinant human (rh) IGF-I. Eggs were injected once with 100 microL vehicle (10 mM acetic acid and 0.1% BSA) per embryo or vehicle containing 100 ng rh IGF-I/100 microL per embryo (n = 555 eggs total) on Days 1, 2, 3, or 4 of embryonic development. Males had greater bone length and moment of inertia than did females for the tibia and the femur (P < or = 0.01 for all). Although fracture load was significantly affected by gender (P < or = 0.02 and P < or = 0.006 for the femur and tibia, respectively), there was no treatment effect on these variables. However, when the fracture load was normalized with body weight of the animal, treatment and gender effects were found for femora (P < or = 0.04). Hydroxyproline concentrations of bones from male broilers were increased by the treatment (P < or = 0.02), whereas it had no effect on female broilers. There was no treatment effect on ash content, stiffness, yield load, yield deflection, and ultimate deflection and elastic, plastic, and total work for the femur or the tibia. We suggest that the effect of in ovo administration of IGF-I on bone mechanical properties was site-specific, and treated femora tended to have a lower fracture load relative to increased body weight.

The fracture toughness of the right femoral neck, femoral shaft, and tibial shaft of matched cadaveric bones, ages 50 to 90 years, was compared. Results of this study indicate that tensile (G(Ic)) and shear (G(IIc)) fracture toughness vary depending on bone location. The femoral neck has the greatest resistance to crack initiation for both tension and shear loading while the femoral shaft has the least. The relationship between age and the fracture toughness of the femoral neck and shaft was investigated. G(c) of the femoral shaft significantly decreased with age for mode I and was nearly significant for mode II. Fracture toughness of the femoral neck did not change with age for the later decades of life. Implications of these findings are discussed., (Copyright 2000 John Wiley & Sons, Inc.)

The relationship between microdamage accumulation and bone fragility is not well understood. Previous work has demonstrated a positive relationship between microdamage and age in human cortical bone. Prior investigations have also demonstrated that fracture toughness decreases with age in the same bone. Based on these findings, the objective of this study was to test the hypothesis that a decrease in fracture toughness can be attributed to an increase in microdamage density. Microdamage parameters (density, surface density, and average crack length) were measured from bone taken from the shaft of the human femur and tibia and correlated with results from fracture toughness tests of the same bone. Results indicated that there was a weak but significant inverse relationship between fracture toughness and microdamage parameters for tension loading of the femur. These findings suggest that in vivo microdamage observable at the transmitted light level (100x) plays a secondary role to other contributory factors to decreased fracture toughness with age. Results also indicate that this relationship depends on bone ductility that apparently differs between the femur and the tibia. This study, in addition to prior investigations, suggests that crack size (microscopic vs. submicroscopic) and crack origin or type (in vivo vs. stress induced de novo) may influence the relationship between microdamage and bone toughness.

The influence of wet and dry apparent density, apparent and real percentage of mineral, organic and water contents on the tension and shear fracture toughness, i.e., the mode I and mode II strain energy release rate (GIc and GIIc), respectively, was investigated for the human femur and the tibia. The results suggest that the water content, apparent density, and age were the best explanatory parameters for GIc and GIIc. Both GIc and GIIc significantly increase with increasing wet or dry apparent density. They also decrease with increasing water content; the decrease is nonsignificant for GIIc in the femur only. Mineral and organic percentage did not change in the bone with age, while the apparent percentages did change. Compositional parameters altogether can explain 35%-59% of the variation in fracture toughness. We conclude that bone composition and density have an important influence on fracture resistance of the cortical bone.

The influence of porosity, osteon density, osteonal area, osteonal lamellar area, osteon size, and haversian canal size on the tension and shear fracture toughness, that is, the mode I and mode II strain energy release rate (GIc and GIIc), respectively, were investigated for the human femur and the tibia. The results suggest that porosity and osteon density were the best explanatory morphological parameters for GIc and GIIc. Both GIc and GIIc significantly decrease with increasing porosity. They also increase with increasing osteon density, the increase being significant for the femur only. Morphological parameters, altogether, can explain 49%-68% of the variation in fracture toughness. We concluded that, although there must be other factors such as biochemical components and microdamage, osteon morphology has an important influence on fracture resistance of the cortical bone.