Reliable and streamlined model setup for digital twin assessment of fracture healing.

In large animal models of bone fracture repair, postmortem torsional testing is commonly used to assess healing biomechanics. Bending and axial tests are physiologically relevant, but much less commonly performed. Virtual torsional testing using image-based finite element models has been validated to postmortem bench tests, but its predictive value for capturing whole-bone mechanics and fracture healing quality under other physiologically relevant loading modes has not yet been established.

Don't mind the gap: reframing the Perren strain rule for fracture healing using insights from virtual mechanical testing.

Aims: The "2 to 10% strain rule" for fracture healing has been widely interpreted to mean that interfragmentary strain greater than 10% predisposes a fracture to nonunion. This interpretation focuses on the gap-closing strain (axial micromotion divided by gap size), ignoring the region around the gap where osteogenesis typically initiates. The aim of this study was to measure gap-closing and 3D interfragmentary strains in plated ovine osteotomies and associate local strain conditions with callus mineralization.

Prognostic bone fracture healing simulations in an ovine tibia model validated with in vivo sensors.

Bone fracture healing is a complex physiological process influenced by biomechanical and biomolecular factors. Mechanical stability is crucial for successful healing, and disruptions can lead to delayed healing or nonunion. Bone commonly heals itself through secondary fracture healing, which is governed by the mechanical strain at the fracture site.

Adaptive Image Segmentation Reveals Substantial Cortical Bone Remodeling During Early Fracture Repair.

The goal of this study was to develop an image analysis algorithm for quantifying the effects of remodeling on cortical bone during early fracture healing. An adaptive thresholding technique with boundary curvature and tortuosity control was developed to automatically identify the endocortical and pericortical boundaries in the presence of high-gradient bone mineral density (BMD) near the healing zone. The algorithm successfully segmented more than 47,000 microCT images from 12 healing ovine osteotomies and intact contralateral tibiae.

Direct Spectroscopic Ferrochelatase Assay.

Ferrochelatases (E.C. 4.

Impact of Phosphorylation at Various Sites on the Active Pocket of Human Ferrochelatase: Insights from Molecular Dynamics Simulations.

Ferrochelatase (FECH) is the terminal enzyme in human heme biosynthesis, catalyzing the insertion of ferrous iron into protoporphyrin IX (PPIX) to form protoheme IX (Heme). Phosphorylation increases the activity of FECH, and it has been confirmed that the activity of FECH phosphorylated at T116 increases. However, it remains unclear whether the T116 site and other potential phosphorylation modification sites collaboratively regulate the activity of FECH.

D-CRSE: Diminishing chemotherapy-related side effects through patient education, a mixed-methods pilot study.

Objectives: Patient education materials regarding self-management of chemotherapy-related side effects are limited, which may result in patients using disreputable sources. We created a brochure that educates patients on common side effects, tools to address problems themselves, and guidance on when to contact their oncologist or seek emergency care. This mixed-methods study conducted at Penn State Cancer Institute evaluates the feasibility of using an educational brochure to improve patient outcomes through education.

The alternative coproporphyrinogen III oxidase (CgoN) catalyzes the oxygen-independent conversion of coproporphyrinogen III into coproporphyrin III.

Nature utilizes three distinct pathways to synthesize the essential enzyme cofactor heme. The coproporphyrin III-dependent pathway, predominantly present in , employs an oxygen-dependent coproporphyrinogen III oxidase (CgoX) that converts coproporphyrinogen III into coproporphyrin III. In this study, we report the bioinformatic-based identification of a gene called , encoding a putative oxygen-independent counterpart, which we propose to term CgoN, from () .

Torsion constants and virtual mechanical tests are valid image-based surrogate measures of ovine fracture healing.

In large animal studies, the mechanical reintegration of the bone fragments is measured using postmortem physical testing, but these assessments can only be performed once, after sacrifice. Image-based virtual mechanical testing is an attractive alternative because it could be used to monitor healing longitudinally. However, the procedures and software required to perform finite element analysis (FEA) on subject-specific models for virtual mechanical testing can be time consuming and costly.

Embracing ethical research: Implementing the 3R principles into fracture healing research for sustainable scientific progress.

As scientific advancements continue to reshape the world, it becomes increasingly crucial to uphold ethical standards and minimize the potentially adverse impact of research activities. In this context, the implementation of the 3R principles-Replacement, Reduction, and Refinement-has emerged as a prominent framework for promoting ethical research practices in the use of animals. This article aims to explore recent advances in integrating the 3R principles into fracture healing research, highlighting their potential to enhance animal welfare, scientific validity, and societal trust.

Exploiting Differences in Heme Biosynthesis between Bacterial Species to Screen for Novel Antimicrobials.

The final three steps of heme biogenesis exhibit notable differences between di- and mono-derm bacteria. The former employs the protoporphyrin-dependent (PPD) pathway, while the latter utilizes the more recently uncovered coproporphyrin-dependent (CPD) pathway. In order to devise a rapid screen for potential inhibitors that differentiate the two pathways, the genes associated with the protoporphyrin pathway in an YFP strain were replaced with those for the CPD pathway from (SA) through a sliding modular gene replacement recombineering strategy to generate the strain -CPD-YFP.

Combined electric and magnetic field therapy for bone repair and regeneration: an investigation in a 3-mm and an augmented 17-mm tibia osteotomy model in sheep.

Background: Therapies using electromagnetic field technology show evidence of enhanced bone regeneration at the fracture site, potentially preventing delayed or nonunions.

Methods: Combined electric and magnetic field (CEMF) treatment was evaluated in two standardized sheep tibia osteotomy models: a 3-mm non-critical size gap model and a 17-mm critical size defect model augmented with autologous bone grafts, both stabilized with locking compression plates. CEMF treatment was delivered across the fracture gap twice daily for 90 min, starting 4 days postoperatively (post-OP) until sacrifice (9 or 12 weeks post-OP, respectively).

Mechanical Biomarkers in Bone Using Image-Based Finite Element Analysis.

Purpose Of Review: The purpose of this review is to summarize insights gained by finite element (FE) model-based mechanical biomarkers of bone for in vivo assessment of bone development and adaptation, fracture risk, and fracture healing.

Recent Findings: Muscle-driven FE models have been used to establish correlations between prenatal strains and morphological development. Postnatal ontogenetic studies have identified potential origins of bone fracture risk and quantified the mechanical environment during stereotypical locomotion and in response to increased loading.

Evaluating Adequacy of VTE Prophylaxis Dosing with Enoxaparin for Overweight and Obese Patients on an Orthopedic-Medical Trauma Comanagement Service.

Objectives: Venous thromboembolism (VTE) is a common nosocomial condition, developing frequently in overweight and obese patients. VTE prophylaxis with weight-based enoxaparin dosing may be more effective than the standard dosing regimen for overweight and obese patients; however, weight-based dosing is not practiced routinely. In this pilot study we sought to evaluate prophylactic anticoagulation regimens used for VTE prevention in overweight and obese patients on the Orthopedic-Medical Trauma (OMT) service to inform the need for modification of dosing practices.

Proteomic Analysis of Ferrochelatase Interactome in Erythroid and Non-Erythroid Cells.

Heme is an essential cofactor for multiple cellular processes in most organisms. In developing erythroid cells, the demand for heme synthesis is high, but is significantly lower in non-erythroid cells. While the biosynthesis of heme in metazoans is well understood, the tissue-specific regulation of the pathway is less explored.

Rethinking the 10% strain rule in fracture healing: A distal femur fracture case series.

Since the 1970s, the 2%-10% rule has been used to describe the range of interfragmentary gap closure strains that are conducive for secondary bone healing. Interpreting the available evidence for the association between strain and bone healing remains challenging because interfragmentary strain is impossible to directly measure in vivo. The question of how much strain occurs within and around the fracture gap is also difficult to resolve using bench tests with osteotomy models because these do not reflect the complexity of injury patterns seen in the clinic.

Dual-zone material assignment method for correcting partial volume effects in image-based bone models.

In image-based finite element analysis of bone, partial volume effects (PVEs) arise from image blur at tissue boundaries and as a byproduct of geometric reconstruction and meshing during model creation. In this study, we developed and validated a material assignment approach to mitigate partial volume effects. Our validation data consisted of physical torsion testing of intact tibiae from  = 20 Swiss alpine sheep.

A primer on heme biosynthesis.

Heme (protoheme IX) is an essential cofactor for a large variety of proteins whose functions vary from one electron reactions to binding gases. While not ubiquitous, heme is found in the great majority of known life forms. Unlike most cofactors that are acquired from dietary sources, the vast majority of organisms that utilize heme possess a complete pathway to synthesize the compound.

New Avenues of Heme Synthesis Regulation.

During erythropoiesis, there is an enormous demand for the synthesis of the essential cofactor of hemoglobin, heme. Heme is synthesized de novo via an eight enzyme-catalyzed pathway within each developing erythroid cell. A large body of data exists to explain the transcriptional regulation of the heme biosynthesis enzymes, but until recently much less was known about alternate forms of regulation that would allow the massive production of heme without depleting cellular metabolites.

Enhanced cycling of nitrogen and metals during rapid infiltration: Implications for managed recharge.

We present results from a series of plot-scale field experiments to quantify physical infiltration dynamics and the influence of adding a carbon-rich, permeable reactive barrier (PRB) for the cycling of nitrogen and associated trace metals during rapid infiltration for managed aquifer recharge (MAR). Recent studies suggest that adding a bio-available carbon source to soils can enhance denitrification rates and associated N load reduction during moderate-to-rapid infiltration (≤1 m/day). We examined the potential for N removal during faster infiltration (>1 m/day), through coarse and carbon-poor soils, and how adding a carbon-rich PRB (wood chips) affects subsurface redox conditions and trace metal mobilization.

Ferrochelatase: Mapping the Intersection of Iron and Porphyrin Metabolism in the Mitochondria.

Porphyrin and iron are ubiquitous and essential for sustaining life in virtually all living organisms. Unlike iron, which exists in many forms, porphyrin macrocycles are mostly functional as metal complexes. The iron-containing porphyrin, heme, serves as a prosthetic group in a wide array of metabolic pathways; including respiratory cytochromes, hemoglobin, cytochrome P450s, catalases, and other hemoproteins.

Bone density and its relation to the development of acromial stress fracture following reverse total shoulder arthroplasty.

Background: Postoperative acromial stress fracture is a troublesome postoperative complication after reverse shoulder arthroplasty. Our study aims to utilize routinely performed preoperative computed tomography scans to identify differences in the material properties of the acromion in patients who did and did not develop a postoperative acromial stress fracture.

Methods: Treatment records and computed tomography scans for 99 reverse shoulder arthroplasties were collected.

Boundary Conditions Matter-Impact of Test Setup on Inferred Construct Mechanics in Plated Distal Femur Osteotomies.

The mechanics of distal femur fracture fixation has been widely studied in bench tests that employ a variety of approaches for holding and constraining femurs to apply loads. No standard test methods have been adopted for these tests and the impact of test setup on inferred construct mechanics has not been reported. Accordingly, the purpose of this study was to use finite element models to compare the mechanical performance of a supracondylar osteotomy with lateral plating under conditions that replicate several common bench test methods.

Biomechanical duality of fracture healing captured using virtual mechanical testing and validated in ovine bones.

Bone fractures commonly repair by forming a bridging structure called callus, which begins as soft tissue and gradually ossifies to restore rigidity to the bone. Virtual mechanical testing is a promising technique for image-based assessment of structural bone healing in both preclinical and clinical settings, but its accuracy depends on the validity of the material model used to assign tissue mechanical properties. The goal of this study was to develop a constitutive model for callus that captures the heterogeneity and biomechanical duality of the callus, which contains both soft tissue and woven bone.