Metacarpophalangeal joint loads during bonobo locomotion: model predictions vs. proxies

The analysis of internal trabecular and cortical bone has been an informative tool for drawing inferences about behaviour in extant and fossil primate taxa. Within the hand, metacarpal bone architecture has been shown to correlate well with primate locomotion; however, the extent of morphological differences across taxa is unexpectedly small given the variability in hand use. One explanation for this observation is that the activity-related differences in the joint loads acting on the bone are simply smaller than estimated based on commonly used proxies (i.e. external loading and joint posture), which neglect the influence of muscle forces. In this study, experimental data and a musculoskeletal finger model are used to test this hypothesis by comparing differences between climbing and knuckle-walking locomotion of captive bonobos (Pan paniscus) based on (i) joint load magnitude and direction predicted by the models and (ii) proxy estimations. The results showed that the activity-related differences in predicted joint loads are indeed much smaller than the proxies would suggest, with joint load magnitudes being almost identical between the two locomotor modes. Differences in joint load directions were smaller but still evident, indicating that joint load directions might be a more robust indicator of variation in hand use than joint load magnitudes. Overall, this study emphasizes the importance of including muscular forces in the interpretation of skeletal remains and promotes the use of musculoskeletal models for correct functional interpretations

Psychometric properties of the Centers for Disease Control and Prevention Health-Related Quality of Life (CDC HRQOL) items in adults with arthritis

BACKGROUND: Measuring health-related quality of life (HRQOL) is important in arthritis and the SF-36v2 is the current state-of-the-art. It is only emerging how well the Centers for Disease Control and Prevention (CDC) HRQOL measures HRQOL for people with arthritis. This study's purpose is to assess the psychometric properties of the 9-item CDC HRQOL (4-item Healthy Days Core Module and 5-item Healthy Days Symptoms Module) in an arthritis sample using the SF-36v2 as a comparison. METHODS: In Fall 2002, a cross-sectional study acquired survey data including the CDC HRQOL and SF-36v2 from 2 North Carolina populations of adult patients reporting osteoarthritis, rheumatoid arthritis, and fibromyalgia; 2182 (52%) responded. The first item of both the CDC HRQOL and the SF-36v2 was general health (GEN). All 8 other CDC HRQOL items ask for the number of days in the past 30 days that respondents experienced various aspects of HRQOL. Exploratory principal components analyses (PCA) were conducted on each sample and the combined samples of the CDC HRQOL. The multitrait-multimethod matrix (MTMM) was used to compute correlations between each trait (physical health and mental health) and between each method of measurement (CDC HRQOL and SF36v2). The relative contribution of the CDC HRQOL in predicting the physical component summary (PCS) and the mental component summary (MCS) was determined by regressing the CDC HRQOL items on the PCS and MCS scales. RESULTS: All 9 CDC HRQOL items loaded primarily onto 1 factor (explaining 57% of the item variance) representing a reasonable solution for capturing overall HRQOL. After rotation a 2 factor interpretation for the 9 items was clear, with 4 items capturing physical health (physical, activity, pain, and energy days) and 3 items capturing mental health (mental, depression, and anxiety days). All of the loadings for these two factors were greater than 0.70. The CDC HRQOL physical health factor correlated with PCS (r = -.78, p < 0.0001) and the mental health factor correlated with MCS (r = -.71, p < 0.0001). The relative contribution of the CDC HRQOL in predicting PCS was 73% (R(2 )= .73) when GEN was included in the CDC HRQOL score and 65% (R(2 )= .65) when GEN was removed. The relative contribution of the CDC HRQOL in predicting MCS was 56% (R(2 )= .56) when GEN was included and removed. CONCLUSION: The CDC HRQOL appears to have strong psychometric properties in individuals with arthritis in both community-based and subspecialty clinical settings. The 9 item CDC HRQOL is a reasonable measure for overall HRQOL and the two subscales, representing physical and mental health, are reasonable when the goal is to examine those aspects

Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach

[EN] In this work, explicit expressions to estimate all the transversely isotropic elastic constants of lamellar bone as a function of the volumetric bone mineral density (BMD) are provided. The methodology presented is based on the direct homogenization procedure using the finite element method, the continuum approach based on the Hill bounds, the least-square method and the mean field technique. Firstly, a detailed description of the volumetric content of the different components of bone is provided. The parameters defined in this step are related to the volumetric BMD considering that bone mineralization process occurs at the smallest scale length of the bone tissue. Then, a thorough description provides the details of the numerical models and the assumptions adopted to estimate the elastic behaviour of the forward scale lengths. The results highlight the noticeable influence of the BMD on the elastic modulus of lamellar bone. Power law regressions fit the Young's moduli, shear stiffness moduli and Poisson ratios. In addition, the explicit expressions obtained are applied to the estimation of the elastic constants of cortical bone. At this scale length, a representative unit cell of cortical bone is analysed including the fibril orientation pattern given by Wagermaier et al. (Biointerphases 1:1-5, 2006) and the BMD distributions observed by Granke et al. (PLoS One 8:e58043, 2012) for the osteon. Results confirm that fibril orientation arrangement governs the anisotropic behaviour of cortical bone instead of the BMD distribution. The novel explicit expressions obtained in this work can be used for improving the accuracy of bone fracture risk assessment.The authors acknowledge the Ministerio de Economia y Competitividad for the financial support received through the project DPI2013-46641-R and to the Generalitat Valenciana for Programme PROMETEO 2016/007. 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Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone

During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-β has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-β signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-β signaling on bone remain unclear. To examine the role of TGF-β in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-β type I receptor (TβRI) kinase on bone mass, architecture and material properties. Inhibition of TβRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TβRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TβRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineral concentration and material properties, that collectively increase bone fracture resistance. Therefore, TβRI inhibitors may be effective in treating conditions of skeletal fragility

Changes in elderly women's health-related quality of life following discontinuation of hormone replacement therapy

BACKGROUND: Many women have discontinued hormone replacement therapy (HRT) in view of recent findings. The goal of this study was to determine if HRT discontinuation is associated with changes in health-related quality of life (HRQOL) in elderly women. METHODS: We studied women enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) program, linking prescription claims with data from a longitudinal mail survey. HRQOL measures included the number of days out of the last 30 that physical health was not good and analogous measures for mental health, pain, and interference with activities, as well as a composite "healthy days" measure developed by CDC. Longitudinal analyses focused on 2,357 women who completed surveys in both 2002 and 2003, and who used HRT at baseline (mean age = 75.5, range = 65–102). Propensity scores were used to match HRT continuers and discontinuers according to HRT type, demographics, and baseline HRQOL. Analysis of covariance was used to compare HRQOL change in continuers and discontinuers. RESULTS: Between 2002 and 2003, 43% of HRT users discontinued therapy. Analysis of covariance to examine HRQOL change revealed complex interactions with age. Discontinuers aged 65–74 reported greater increases in days in which mental health was not good (p < .05), fewer "healthy days" (p < .05), more days in which health interfered with activities (p < .01), and more days with pain (p < .01). Among women aged 75–84, HRT discontinuers reported more days in which physical health was not good (p < .01); no other significant effects were observed in this group. Relative to HRT continuers, discontinuers aged 85 and older experienced apparent HRQOL improvements following cessation, with fewer days in which physical health was not good (p < .01), fewer days of poor mental health (p < .05), and more "healthy days" (p < .01). CONCLUSIONS: These results suggest that there are substantial age differences in response to HRT discontinuation. While women aged 65–74 experienced apparent declines in HRQOL following HRT cessation, women aged 85 and older experienced relative improvements. The HRQOL declines observed among younger women underscore the importance of communication between clinicians and patients throughout the discontinuation process. These results also demonstrate the value of HRQOL surveillance as a component of health program administration

Population growth of Mexican free-tailed bats (Tadarida brasiliensis mexicana) predates human agricultural activity

Background Human activities, such as agriculture, hunting, and habitat modification, exert a significant effect on native species. Although many species have suffered population declines, increased population fragmentation, or even extinction in connection with these human impacts, others seem to have benefitted from human modification of their habitat. Here we examine whether population growth in an insectivorous bat (Tadarida brasiliensis mexicana) can be attributed to the widespread expansion of agriculture in North America following European settlement. Colonies of T. b. mexicana are extremely large (~106 individuals) and, in the modern era, major agricultural insect pests form an important component of their food resource. It is thus hypothesized that the growth of these insectivorous bat populations was coupled to the expansion of agricultural land use in North America over the last few centuries. Results We sequenced one haploid and one autosomal locus to determine the rate and time of onset of population growth in T. b. mexicana. Using an approximate Maximum Likelihood method, we have determined that T. b. mexicana populations began to grow ~220 kya from a relatively small ancestral effective population size before reaching the large effective population size observed today. Conclusions Our analyses reject the hypothesis that T. b. mexicana populations grew in connection with the expansion of human agriculture in North America, and instead suggest that this growth commenced long before the arrival of humans. As T. brasiliensis is a subtropical species, we hypothesize that the observed signals of population growth may instead reflect range expansions of ancestral bat populations from southern glacial refugia during the tail end of the Pleistocene

More than one way of being a moa: differences in leg bone robustness map divergent evolutionary trajectories in Dinornithidae and Emeidae (Dinornithiformes).

The extinct moa of New Zealand included three families (Megalapterygidae; Dinornithidae; Emeidae) of flightless palaeognath bird, ranging in mass from 200 kg. They are perceived to have evolved extremely robust leg bones, yet current estimates of body mass have very wide confidence intervals. Without reliable estimators of mass, the extent to which dinornithid and emeid hindlimbs were more robust than modern species remains unclear. Using the convex hull volumetric-based method on CT-scanned skeletons, we estimate the mass of a female Dinornis robustus (Dinornithidae) at 196 kg (range 155-245 kg) and of a female Pachyornis australis (Emeidae) as 50 kg (range 33-68 kg). Finite element analysis of CT-scanned femora and tibiotarsi of two moa and six species of modern palaeognath showed that P. australis experienced the lowest values for stress under all loading conditions, confirming it to be highly robust. In contrast, stress values in the femur of D. robustus were similar to those of modern flightless birds, whereas the tibiotarsus experienced the highest level of stress of any palaeognath. We consider that these two families of Dinornithiformes diverged in their biomechanical responses to selection for robustness and mobility, and exaggerated hindlimb strength was not the only successful evolutionary pathway

Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis.

The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy. Intravital Förster resonance energy transfer imaging of a cyclin-dependent kinase 1 biosensor to monitor the efficacy of cytotoxic drugs revealed that priming improves pancreatic cancer response to gemcitabine/Abraxane at both primary and secondary sites. Transient priming also sensitized cells to shear stress and impaired colonization efficiency and fibrotic niche remodeling within the liver, three important features of cancer spread. Last, we demonstrate a graded response to priming in stratified patient-derived tumors, indicating that fine-tuned tissue manipulation before chemotherapy may offer opportunities in both primary and metastatic targeting of pancreatic cancer