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OBJECTIVE: Skeletal stress fracture of the lower limbs remains a significant problem for the military. The objective of this study was to develop a subject-specific 3D reconstruction of the tibia using only a few CT images for the prediction of peak stresses and locations. METHODS: Full bilateral tibial CT scans were recorded for 63 healthy college male participants. A 3D finite element (FE) model of the tibia for each subject was generated from standard CT cross-section data (i.e., 4%, 14%, 38%, and 66% of the tibial length) via a transformation matrix. The final reconstructed FE models were used to calculate peak stress and location on the tibia due to a simulated walking load (3,700 N), and compared to the raw models. RESULTS: The density-weighted, spatially-normalized errors between the raw and reconstructed CT models were small. The mean percent difference between the raw and reconstructed models for peak stress (0.62%) and location (-0.88%) was negligible. CONCLUSIONS: Subject-specific tibia models can provide even great insights into the mechanisms of stress fracture injury, which are common in military and athletic settings. Rapid development of 3D tibia models allows for the future work of determining peak stress-related injury correlates to stress fracture outcomes.

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Bacterial laccases are now known to be abundant in soil and to function outside of the cell facilitating the bacterial degradation of lignin. In this study we wanted to test the hypotheses that: i) Such enzymes can be identified readily in stratified paleosols using metagenomics approaches, ii) The distribution of these genes as potential 'public good' proteins in soil is a function of the soil environment, iii) Such laccase genes can be readily retrieved and expressed in E. coli cloning systems to demonstrate that de novo assembly processes can be used to obtain similar metagenome-derived enzyme activities. To test these hypotheses, in silico gene-targeted assembly was employed to identify genes encoding novel type B two-domain bacterial laccases from alpine soil metagenomes sequenced on an Illumina MiSeq sequencer. The genes obtained from different strata were heterologously cloned, expressed and the gene products were shown to be active against two classical laccase substrates. The use of a metagenome-driven pipeline to obtain such active biocatalysts has demonstrated the potential for gene mining to be applied systematically for the discovery of such enzymes. These data ultimately further demonstrate the application of soil pedology methods to environmental enzyme discovery. As an interdisciplinary effort, we can now establish that paleosols can serve as a useful source of novel biocatalytic enzymes for various applications. We also, for the first time, link soil stratigraphy to enzyme profiling for widespread functional gene activity in paleosols.

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There is remarkable potential for research at the interface between the earth sciences and environmental microbiology that may lead to advances in our understanding of the role of bacterial communities in the surface or subsurface environment of our planet. One mainstay of sedimentary classification is the concept of differential soil and/or paleosol horizons being the result of primarily physical and chemical weathering, with relatively little understanding of how microbial communities between these stratified horizons differ, if at all. In this study we evaluate the differences in microbial community taxonomy and biogeochemical functional potential between stratified soil horizons in an alpine paleosol environment using next-generation sequencing (NGS) shotgun sequencing. Paleosols represent a unique environment to study the effect of differences soil horizon environments on the microbial community due to their relative isolation, and the fact that three distinct stratified soil horizons can be identified within the top 30 cm of the soil. This enables us to assess variation in microbial community composition that will be relatively distinct from variation due to distance alone. We test the hypothesis that variation in soil community composition is linked to variation in the physical and chemical parameters that define stratigraphy. Multivariate statistical analysis of sequencing reads from soil horizons across five sampling sites revealed that 1223 microbial genera vary significantly and consistently in abundance across stratified soil horizons at class level. Specifically Ktedonobacter, Bacilli and Betaproteobacteria responded most strongly to soil depth. Alpha diversity showed a positive correlation with soil depth. Beta diversity, however, did not differ significantly between horizons. Genes involved in carbohydrate and nitrogen metabolism were found to be more abundant in Ah horizon samples. Closer inspection of carbohydrate metabolism genes revealed that genes involved in CO2 fixation, fermentation and saccharide metabolism decreased in abundance with depth while one­carbon metabolism increased down profile.

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A draft genome sequence of Halobacteriovorax sp. strain JY17 was assembled from a metagenomic data set. The 3.47-Mbp genome of this unusual predatory bacterium contains 3,263 protein-coding sequences, 33 tRNAs, and 2 copies each of the 16S, 23S, and 5S rRNA genes. This is only the third sequenced representative of this genus.

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According to the Substance Abuse and Mental Health Services Administration, 2.4 million individuals have an opioid use disorder (OUD). Yet, nearly 80 percent of them-more than 1.9 million people-do not receive treatment. Medication-assisted treatment (MAT), specifically with buprenorphine, has proven to be effective in treating patients with OUDs while also reducing costs to the healthcare system, criminal justice system, and workforce. Despite its effectiveness, barriers to MAT continue to exist. Consequently, many individuals must wait months, if not years, to receive treatment. This article analyzes the US Department of Health and Human Services' final rule (Final Rule) on MAT, common barriers to treatment, and the cost-benefit of treatment in light of the current opioid abuse epidemic. The article finds that while the Final Rule was a step in the right direction, it does not go far enough to adequately address the epidemic. Finally, the article proposes practical recommendations for increasing patient access to treatment for OUDs, including increasing the patient limit for highly qualified addiction treatment providers so that they can practice addiction medicine on a full-time basis and exempting buprenorphine products labeled by the US Food and Drug Administration for direct administration from the practitioner's patient limit.

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The morphogenetic process of cardiac looping transforms the straight heart tube into a curved tube that resembles the shape of the future four-chambered heart. Although great progress has been made in identifying the molecular and genetic factors involved in looping, the physical mechanisms that drive this process have remained poorly understood. Recent work, however, has shed new light on this complicated problem. After briefly reviewing the current state of knowledge, we propose a relatively comprehensive hypothesis for the mechanics of the first phase of looping, termed c-looping, as the straight heart tube deforms into a c-shaped tube. According to this hypothesis, differential hypertrophic growth in the myocardium supplies the main forces that cause the heart tube to bend ventrally, while regional growth and cytoskeletal contraction in the omphalomesenteric veins (primitive atria) and compressive loads exerted by the splanchnopleuric membrane drive rightward torsion. A computational model based on realistic embryonic heart geometry is used to test the physical plausibility of this hypothesis. The behavior of the model is in reasonable agreement with available experimental data from control and perturbed embryos, offering support for our hypothesis. The results also suggest, however, that several other mechanisms contribute secondarily to normal looping, and we speculate that these mechanisms play backup roles when looping is perturbed. Finally, some outstanding questions are discussed for future study.

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A novel, empirical, macroscopic model is developed to describe the release of a model anticancer drug, Mitoxantrone, from native and chemically modified porous Si (PSi) thin films. Drug release from these carriers results from a combination of two mechanisms, i.e. out-diffusion of the drug molecules and erosion of the Si scaffold. Thus, the proposed mathematical model adapts the Crank model to lump the effects of temporal changes in molecular interactions and carrier scaffold erosion into a comprehensive model of hindered drug diffusion from nanoscale porous systems. Careful characterization of pore size, porosity, surface area, drug loading, as well as Si scaffold degradation profiles, measured over the same time-scale as drug release, are incorporated into the model parameter estimation. A comparison of the experimental and model results shows accurate representation of the data, emphasizing the reliability of the model. The proposed model shows that drug diffusivity values significantly vary with time for the two studied carriers, which are ascribed to the distinctive role of the prevailing physical mechanisms in each system. Finally, secondary validation of the proposed model is demonstrated by showing adequate fit to published data of the release of dexamethasone from similar mesoporous Si carriers.

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Accurate material properties of developing embryonic tissues are a crucial factor in studies of the mechanics of morphogenesis. In the present work, we characterize the viscoelastic material properties of the looping heart tube in the chick embryo through nonlinear finite element modeling and microindentation experiments. Both hysteresis and ramp-hold experiments were performed on the intact heart and isolated cardiac jelly (extracellular matrix). An inverse computational method was used to determine the constitutive relations for the myocardium and cardiac jelly. With both layers assumed to be quasilinear viscoelastic, material coefficients for an Ogden type strain-energy density function combined with Prony series of two terms or less were determined by fitting numerical results from a simplified model of a heart segment to experimental data. The experimental and modeling techniques can be applied generally for determining viscoelastic material properties of embryonic tissues.

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Tone regulation in coronary microvessels has largely been studied in isolated vessels in the absence of myocardial tethering. Here, the potential effect of radial tethering and interstitial space connective tissue (ISCT) between coronary microvessels and the surrounding myocardium was studied. We hypothesized that rigid tethering between microvessels and the myocardium would constrain the active contraction of arterioles and is not compatible with the observed tone regulation. The ISCT between coronary microvessels and myocardium in five swine was found to increase exponentially from 0.22 ± 0.02 µm in capillaries (modified Strahler order 0) of the endocardium to 34.9 ± 7.1 µm in epicardial vessels (order 10). Microvessels with both soft tethering and ISCT gap were capable of significant changes in vessel resistance (up to an ∼1,600% increase), consistent with experimental measurements of high coronary flow reserve. Additionally, the mechanical energy required for myogenic contraction was estimated. The results indicate that rigid tethering requires up to four times more mechanical energy than soft tethering in the absence of a gap. Hence, the experimental measurements and model predictions suggest that effectiveness and efficiency in tone regulation can be achieved only if the vessel is both softly tethered to and separated from the myocardium in accordance with the experimental findings of ISCT gap. These results have fundamental implications on future simulations of coronary circulation.

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The analysis of the biomechanics of growth and remodeling in soft tissues requires the formulation of specialized pseudoelastic constitutive relations. The nonlinear finite element analysis package ABAQUS allows the user to implement such specialized material responses through the coding of a user material subroutine called UMAT. However, hand coding UMAT subroutines is a challenge even for simple pseudoelastic materials and requires substantial time to debug and test the code. To resolve this issue, we develop an automatic UMAT code generation procedure for pseudoelastic materials using the symbolic mathematics package MATHEMATICA and extend the UMAT generator to include continuum growth. The performance of the automatically coded UMAT is tested by simulating the stress-stretch response of a material defined by a Fung-orthotropic strain energy function, subject to uniaxial stretching, equibiaxial stretching, and simple shear in ABAQUS. The MATHEMATICA UMAT generator is then extended to include continuum growth by adding a growth subroutine to the automatically generated UMAT. The MATHEMATICA UMAT generator correctly derives the variables required in the UMAT code, quickly providing a ready-to-use UMAT. In turn, the UMAT accurately simulates the pseudoelastic response. In order to test the growth UMAT, we simulate the growth-based bending of a bilayered bar with differing fiber directions in a nongrowing passive layer. The anisotropic passive layer, being topologically tied to the growing isotropic layer, causes the bending bar to twist laterally. The results of simulations demonstrate the validity of the automatically coded UMAT, used in both standardized tests of hyperelastic materials and for a biomechanical growth analysis.

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