Clinical evaluation of a low-cost and high-fidelity animal model for palpable and nonpalpable implant removal.

This study aims to investigate the impact of partial blood volume FLASH irradiation on immune system in a mouse leg model. The right hind limbs of C57BL/6 N mice were irradiated in a single fraction with an electron beam using either 50 Gy/s (2 Gy, 5 Gy, 10 Gy, 20 Gy, delivery time 0.04 –0.4 s) or 10 Gy/s (5 Gy, 10 Gy, 15 Gy, 20 Gy, delivery time 0.5 –1.5 s). A total of 90 mice were used in the experiment, with five mice per dose/time group. T lymphocyte subsets (CD3+, CD4+, CD8+, naïve CD4+, and naïve CD8+) were analyzed in peripheral blood and spleen 1 and 4 days post-irradiation by flow cytometry. The dose response curves for the subset reduction can be well described by a sigmoid curve for subsets in both peripheral blood and spleen 1 day post-irradiation. Generally, higher dose rate (50 Gy/s) irradiation induced much less subsets depletion than lower dose rate (10 Gy/s) in peripheral blood, consistent with the simulation result that local FLASH radiotherapy may preserve immune cells in peripheral blood. Interestingly, the non-irradiated spleen also displayed substantial subset depletions with an opposite dose rate-dependent behavior. We speculate that radiation-induced red blood cell senescent may be responsible for this interesting phenomenon. The opposing dose rate–dependent responses in peripheral blood and splenic lymphocyte depletion highlight a dual effect of local FLASH irradiation: higher dose rates may protect circulating immune cells, yet may also potentially enhance damage to the lymphocytes in the spleen.

Purpose: Radiotherapy is a widely used cancer treatment, and radiation-induced fibrosis is a frequent late effect that can significantly reduce patients’ quality of life. Many approaches for evaluating and grading radiation late damage, such as fibrosis, are based on semi-quantitative methods. This study aimed to characterize the histopathological changes associated with late radiation damage in mice after exposure to proton and photon irradiation, and to evaluate the applicability of stereological methods for quantitative assessment of these changes. Materials and Methods: A mouse leg model was used to evaluate and compare the potential radiation-induced functionality impairments with histopathological changes. Mice (n = 32) were subjected to a single high dose of photon (n = 18) or proton (n = 14) irradiation on the right foot, while the left, unirradiated leg served as a control. Late damage was assessed using a leg contracture assay, while histopathological changes were quantified using stereological point counting. Results: Proton- and photon-irradiated legs histologically showed a dose-dependent increase in connective tissue and epidermal thickness and reduced adipose tissue. Adipose tissue was replaced with connective tissue, adnexal structures disappeared, and the epidermis was altered. An association was found between leg contracture in the living mice and histopathological connective tissue changes, suggesting that fibrosis contributes to impaired joint mobility. However, discrepancies between histological findings and the leg contracture assay indicate that factors other than connective tissue changes, such as tendon damage and experimental uncertainties, influence joint movement. Conclusions: This study provides a quantitative approach for associating radiation effects in normal tissue with histopathological changes, offering a valuable model for investigating late radiation-induced damage. The study highlights the need for larger studies to fully elucidate the late side effects of proton and photon irradiation.

To simulate the structure of living tissues and find alternatives with similar properties, and to reduce the differences between orthopedic and hip implants, functional grading is used to fabricate artificial replacements for a part of the knee joint, study their mechanical properties, and analyze the results using the finite element method. Functionally graded blends (10%-50% wt. PLA)/ (90%-50% wt. UHMWPE)/ 50% wt. PVA) are used. A porous implant is chosen instead of a solid one to reduce the stress-shielding effect. Finite element analysis (FEA) is used to analyze the stress-shielding effect of FGB under the loads acting on porous hip implants as an alternative to dense stems. Hardness and tensile tests are performed to analyze the behavior of functionally graded blend samples and a functionally graded porous hip implant model under critical loads, and are analyzed using a digital microscope to determine the count and average pore size. The implant design is found to be sensitive to the functional grading factor . Under tensile conditions, when the prosthetic leg model (PFGBs) structure takes a gradient according to stiffness values from the lowest (39.08) to the highest (46.9), dislocation and loosening are observed at the maximum tensile force at a displacement of (50 mm) for the highest total deformation of (16.564 mm) and the maximum von Mises stress of (12.736 MPa). While the prosthetic leg model under tension, when the (PFGBs) structure takes a gradient according to stiffness values from the highest (46.9) to the lowest (39.08), dislocation and loosening occur at the maximum tensile force and at the point of contact of the ball head with the leg under tensile loading conditions at a displacement of (50 mm) for the highest total deformation of (18.904 mm) and the maximum von Mises stress of (22.559 MPa).

Speed-dependent modulation of swing leg rest length during human walking.

Abstract This study draws inspiration from straw folding patterns to develop an innovative straw energy-absorbing block and a novel straw bumper system for pedestrian protection. The study employs the THUMS 4.0 dummy leg model coupled with a detailed finite element model of vehicle front-end structures to simulate pedestrian leg impact scenarios. Key design parameters of the straw structure were meticulously optimized according to the specific morphological and dimensional requirements of automotive front crash beams and exterior panels. The implemented solution features connecting plates that enable precise alignment along the vehicle’s crash beam profile. This redesigned straw energy absorbing blocks (SEB) system replaces conventional foam energy absorbers at vehicle front ends, facilitating comprehensive investigation of pedestrian leg injury mechanisms and dynamic responses during collision events. A systematic parametric study evaluates the protective efficacy of straw tube configurations, examining critical variables including layer quantity with particular focus on 4.5-layer and 7.5-layer arrangements, cytosolic small diameters, and row alignment patterns. Three distinct bumper prototypes incorporating varied straw tube geometries were developed for comparative performance analysis. Experimental results demonstrate substantial injury mitigation, with SEB implementations achieving stress reduction of 58.1% in femur and 9.0% in tibia compared to baseline foam absorbers. Building upon these findings, the research culminated in the development of an enhanced Straw Front Bumper system demonstrating remarkable protective capabilities. Quantitative analysis revealed significant stress reduction metrics, achieving 66.6% decrease in femoral stress and 15.2% reduction in tibial stress when compared with traditional bumper designs. Through systematic evaluation of three distinct SEB row configurations, this study yields critical engineering insights for advancing vehicle safety systems. The results conclusively validate straw-derived energy-absorbing architectures as biomechanically optimized solutions, thereby introducing transformative design frameworks for next-generation pedestrian protection technologies in automotive engineering.

Semantic typology in lexical systems reveals how languages categorise reality through patterned semantic relations, with meronymy (part–whole structuring) providing a productive domain for examining bodily terminology. This study investigates divergences in the meronymic encoding of kaki ‘leg/foot’ in Indonesian and Acehnese—two geographically proximate and genealogically related Austronesian languages—by examining the processes shaping meronymized lexis, formulating principles of meronymic relatedness, and identifying distinguishing features of the Acehnese partonym kaki. Using a descriptive qualitative design, the study analyses 32 Indonesian and 25 Acehnese foot-related meronyms drawn from KBBI and regional dictionaries, applying an inductive semantic-componential procedure to map hierarchical part–whole configurations. Results show that both languages display well-formed branching meronymic hierarchies but do not converge on a single unified model of the human leg. Indonesian exhibits a more fine-grained hierarchy (e.g., betis ‘calf’, telapak kaki ‘sole’, tumit ‘heel’, punggung kaki ‘instep’), whereas several of these—especially ‘instep’ and ‘calf’—lack fully lexicalised equivalents in Acehnese and are instead expressed through broader or descriptive forms. These differences align with functional salience and perceptual prominence, whereby experientially significant parts receive denser lexical encoding. The study concludes that Indonesians and Acehnese share universal principles of meronymic organisation yet differ markedly in semantic granularity, reflecting cultural perceptions of bodily segmentation. The findings support typological models of partonomy and underscore the need to expand Acehnese lexicographic documentation with native-speaker validation and future analyses across other body regions, including computational corpus-based extraction of meronymic structures.

Patients with lower limb lymphedema experience lymphatic fluid accumulation and swelling, which can progress to fibrosis and fat deposition in the soft tissues, impacting patients physically, socially, and psychologically. Compression therapy is one of the main treatments for lymphedema, but its effects on lymphedematous soft tissues are not yet fully understood. In this study, we developed a finite element model of a lymphedematous leg including subcutaneous and muscle tissues, as well as skin and fascia cruris, to investigate the hydrostatic pressure distribution resulting from the interface pressure applied by a compression stocking. The results highlight the significant influence of the leg's external geometry on the interface pressure, and demonstrate the importance of modeling skin to accurately predict hydrostatic pressure distribution in the subcutaneous tissue, with a 3.5% reduction in leg volume observed after compression. The outcomes improve the understanding of the effects of compression therapy on lower limbs affected by lymphedema and support the development of adapted treatment strategies for patients.

Objective.While FLASH radiotherapy is known to reduce skin damagein vivofrom ultra-high dose rate (UHDR) irradiation relative to conventional dose rates (CDR), it is not clear whether this sparing is preserved when delivered as fractionated. This study was designed to directly assess whether three daily fractions would maintain the sparing effects in murine leg models and preserve the murine skin sparing with single fraction treatments.Approach.C57Bl/6j female mice were irradiated with 9 MeV UHDR and CDR beams from a FLASH-capable Mobetron system, in a dose escalation study with doses ranging from single dose 22-30 Gy in a single fraction to three daily fractions of 10-16 Gy. The biological responses were scored by a visual skin damage response rubric using up to 5 blinded observers, and a leg contracture assay as a secondary measure of damage.Main results.There was a monotonic dose response in all treatment groups with irradiation dose, with skin damage onset at 9-10 d. In the single dose group a significant FLASH sparing was seen with a FLASH modifying factor (FMF) of approximately 0.73. Similarly in the single dose groups there were significant leg contracture differences between UHDR and CDR groups after 12-15 d. In comparison, there was no significant skin damage sparing between UHDR and CDR in the three daily fraction dose groups, and reduced sparing in the leg contracture assay.Significance.The results of this murine study show a significant reduction of the FLASH effect when the dose is split into three fractions of 10-16 Gy each, whereas there were substantial FLASH sparing effects noted for the single fractions of 22-30 Gy, showing a FMF of ∼0.73. These observations provide the data needed to optimize FLASH sparing experiments in further translational studies.

Motion Patterns and Kinematic Modeling of Backswimmer Hind Legs

The measurement of passive muscle-tendon parameters (PMPs) is crucial for understanding and analyzing human movement. However, the common methods for measuring PMPs are inconsistent or involve invasive procedures. We propose a novel noninvasive method for estimating PMPs using a direct collocated optimal control algorithm. The optimal control algorithm was employed to determine PMPs of a fully in silico musculoskeletal simulation, of a mechanical analogue, and of human subjects in vivo. To eliminate the confounding effects of force-velocity and active muscle contraction, a quasi-static knee flexion and ankle plantar flexion protocol was used for these evaluations. The simulation-based assessment resulted in predictions of muscle stiffness and tendon slack length with less than 3.5% error and tendon stiffness with less than 6% error. Secondly, using an analogue mechanical model of the human leg, we found maximum estimation errors in spring stiffness to be 9%. Lastly, in the in vivo validation method, we compared forward dynamic simulations of models with the predicted PMPs against experimental data. The average root mean square error (RMSE) for motion was found to be less than 0.56 , while the RMSE for torque was 0.012 Nm/kg. These results demonstrate the effectiveness and precision of our noninvasive method for estimating PMPs in knee flexors/extensors. This approach has the potential to provide valuable insights into the biomechanics of human movement and contribute to advancements in rehabilitation strategies, sports performance optimization, and injury prevention.

Basic anatomical education is essential for training healthcare professionals, but most first-year students have limited prior knowledge. The complexity of anatomical terminology across multiple languages presents a major barrier to learning. Therefore, developing hands-on educational materials that enhance student engagement and motivation is crucial.In this study, a practice-based anatomy curriculum was developed and applied to 32 first-year students majoring in Medical Engineering at a specialized health science university in the metropolitan area. The practice utilized life-size, disassembled human skeleton models (AK130, Inchemodel.com), and eight sets of arm and leg models were distributed to groups of four for hands-on learning. Using a practical guide that included anatomical diagrams and tables for each joint region, students observed skeletal structures, inferred anatomical names, and engaged in group discussions and online searches to deepen their understanding. Through this skeletal model practice, students were able to gain a three-dimensional understanding of anatomical knowledge. They clearly identified unfamiliar anatomical terms and structures by comparing them with actual models, which enhanced both teamwork and learning motivation. Based on the outcomes, this curriculum is proposed as a standard educational guideline for aptitude training in healthcare-related high school and early undergraduate programs.

Background: Congenital talipes equinovarus (clubfoot) affects 1–2 per 1000 newborns worldwide. The Ponseti method, based on staged manipulations and casting, is the gold standard for correction. However, the biomechanical processes underlying these corrections remain poorly understood, as infants rarely undergo imaging. Computational modeling may offer a non-invasive approach to studying correction pathways and exploring novel applications, such as customized casts. Methods: We developed a proof-of-concept framework using iterative finite element analysis (iFEA) to approximate the surface-level geometric corrections targeted in Ponseti treatment. A 3D surface model of a training clubfoot foot was scanned, meshed, and deformed stepwise under applied computational loads. The model was assumed to be homogeneous and hyperelastic, and correction was quantified using Cavus, Adductus, Varus, Equinus, and Derotation angles. We also introduced a secondary adult leg 3D surface model to assess whether model simplification influences correction outcomes, by comparing a homogeneous soft tissue model with a non-homogeneous model incorporating bone structure. Results: In the training model, iFEA generated progressive deformations consistent with Ponseti correction, with mean angular deviations of ±3.2°. In the adult leg model, homogeneous and non-homogeneous versions produced comparable correction geometries, differing by <2° in outcomes. The homogeneous model required less computation, supporting its use for feasibility testing. Applied loads were computational drivers, not physiological forces. Conclusions: This feasibility study shows that iFEA can reproduce surface-level geometric changes consistent with Ponseti correction, independent of model homogeneity. While not replicating clinical biomechanics, this framework lays the groundwork for future work that incorporates clinician-applied forces, pediatric tissue properties, and patient-specific geometries, with potential applications in customized 3D-printed casts.

The FLASH effect, where ultra-high dose rate elicits a favourable normal tissue-sparing, has been shown in several preclinical studies. Study setup differences, for example fixation methods that affect blood flow, can influence radiation response but are unexplored for FLASH. This study compared FLASH's acute skin-sparing effect with two fixation methods: a glued fixation (no blood flow restriction) and taped fixation (slight blood flow restriction). Patient/material and methods: Female CDF1 mice were irradiated on their hind foot using a glue-fixation or tape-fixation method. Glue-fixated mice were only taped during the glueing procedure and had a 10-min unrestricted period afterwards before irradiation, while tape-fixated mice were taped shortly before and throughout irradiation. Mice received single-dose irradiation (19-58 Gy) with either conventional dose rate (CONV, protons 0.06 Gy/s, electrons 0.16 Gy/s) or FLASH (electrons, 223-233 Gy/s). Differences in skin toxicity were analysed. CONV-treated tape-fixated mice required a 16-17% higher dose to induce skin toxicity relative to glued mice for both protons and electrons. Meanwhile, the fixation method did not affect FLASH-treated mice. The resulting electron FLASH-sparing effect was reduced by 18% due to the shift in radiosensitivity for CONV-treated mice. CONV-treated tape-fixated mice were more radioresistant than the glue-fixated mice, consistent with the expected response to mild hypoxia. FLASH-treated mice were unaffected. These findings demonstrate the impact of fixation and, in turn, oxygen level on the differential CONV versus FLASH skin response. The results highlight the importance of minimal systemic influence on animals during FLASH studies.

Passive implanted devices are commonly contraindicated at ultra-high field MRI due to the risk of radiofrequency heating. Mitigation of this risk has come in many forms, such as modifying implant materials or creating novel radiofrequency coils. These methods require substantial involvement from manufacturers and may not benefit patients with existing implants. In this study, a tailored metasurface design is demonstrated to improve implant safety at 7T by shielding the local B1+ field. A prototype metasurface was designed and implemented with a unit cell size of 15mm using discrete capacitors of 30pF values. Phantom and human body model simulations were used to validate differences in the SAR distribution with and without the metasurface. Fiber optic temperature probes were used to measure temperature increase across two representative orthopedic screws placed inside a tissue mimicking phantom during a high-SAR sequence. Phantom and in-vivo imaging were performed to assess the metasurface effect on image quality. With the metasurface, an average maximum temperature decrease of 0.50°C or 34.9% near the implant was observed. RF field simulations yielded similar decreases in SAR for the phantom (40.7%) and substantial decreases for the in-vivo leg model (97%). Phantom image SNR showed a global 8.5% decrease with the metasurface while in-vivo images showed a 4.8% decrease in SNR, with the region in its immediate vicinity experiencing substantial signal drop. These results demonstrate the feasibility of a metasurface designed to substantially reduce local RF induced heating with only minor degradation of image quality. Future work will focus on refinement of the metasurface design and further in-vivo testing.

Background. Given the shortcomings of conservative treatment, especially in young patients with multifragment fractures, the surgical method is the priority direction. Internal fixation can be achieved through a variety of designs, both single screws and plates, to provide absolute stability to support the articular surface. Double plate fixation is considered the gold standard, but recent studies using single and double plates have not found significant differences between groups. In addition, the overall rate of postoperative complications with double fixation, according to various authors, is about 11.4 %. Objective: to investigate the stress-strain state of a model with different variants of osteosynthesis of the lower leg with a multifragment fracture of the proximal end of the tibia under the influence of a bending load in the frontal plane. Materials and ­methods. A basic finite element model of the lower leg was developed, which included the tibia and fibula. A multifragment fracture was modeled at the proximal end of the tibia by dividing it into different planes. Three variants of osteosynthesis with bone plates were studied: on the medial, lateral side, and 2 plates on both sides. The models were investigated under the influence of bending load in the frontal plane. Results. Under the influence of bending loads in the frontal plane, osteosynthesis with two plates provides the lowest level of stresses in the bone elements of the model. The exception is the bone fragments in the fracture zone, in which the stresses around the screws from the lateral side have the highest values. As for models with unilateral fixation of fragments, the fundamental differences are also determined in the level of stresses on the bone fragments around the fixing screws, where they differ almost 8 times not in favor of the lateral location of the plate. Conclusions. Under the influence of bending load in the frontal plane, osteosynthesis with two plates provides minimal stress in both the bone elements of the model and the elements of the metal structure, except for stresses in the bone fragments around the screws from the lateral side in the metaphyseal zone. The stresses in models with unilateral fixation of fragments fundamentally differ only in the level of stresses on the bone fragments around the fixing screws, where they differ almost 8 times in favor of the medial location of the plate.

A constant relative biological effectiveness (RBE) of 1.1 is used in clinical proton therapy (PT) to convert prescribed photon doses into isoeffective proton doses. However, the RBE is not constant; it is a dynamic parameter highly influenced by factors such as linear energy transfer, tissue type, biological endpoint, and dose/fraction. Preclinical in vivo proton RBE studies using fractionated doses and late damage endpoints are almost nonexistent. The aim is to test the hypotheses that the RBE varies between single and fractionated doses and that the late damage development differs between proton and photon irradiation using a 6 MV linac as a reference modality in a murine leg model. The right hindlimb of unanesthetized mice was irradiated with single or four fractions of protons or 6 MV photons. Over one year after treatment, the mice were analyzed every fourteenth day using a joint contracture assay to investigate severe radiation-induced late damage. The results indicated a higher RBE for severe late damage endpoint of 1.25±0.06 (1.13-1.36) for fractionated doses than single doses, exhibiting an RBE of 1.16±0.08 (1.00-1.31). The onset of late damage is earlier for protons than photons for doses higher than 47Gy and fractionated doses above 50Gy (12.5Gy per fraction). The findings demonstrate that fractionated doses enhance the RBE for a late damage endpoint and lead to an earlier onset of severe late effects than its photon counterpart in vivo.

Improper compression bandage application can result in ineffective edema management, leading to pain and decreased patient adherence to treatment. The successful application depends on the operator’s experience, bandage overlap, and applied tension. In addition, the bandages’ structural properties are essential for sustained compression. This study investigates how compression bandage structure influences slippage, leg conformity, and therapeutic pressure application. It focuses on the effect of intermeshing, stiffness, and design for pressure consistency, comparing a dual compression system (DCS) with a traditional two-layer bandage (TLB). The DCS includes visual indicators to help practitioners achieve target pressure through proper extension and overlap. Methods involved a bench test, photographic microscopy, and a preliminary nonclinical study. The bench test evaluated bandage slippage and subbandage pressure using a leg model, photographic microscopy examined bandage intermeshing, and the nonclinical study assessed the effectiveness of the visual indicators in assisting nurses in achieving a target pressure of 40 ± 10 mmHg. Results showed that the TLB did not conform to the leg model after a 4 cm circumference reduction and significantly decreased stiffness after a 2 cm reduction ( P &lt; 0.05). In contrast, the DCS maintained its stiffness and conformed to the simulated leg despite the reduction in circumference. The nonclinical study revealed that nurses with no prior experience performed more effectively with the DCS after online training, while an experienced TLB nurse demonstrated proficiency with the DCS following both online and in-person training. This study emphasizes the importance of understanding bandage stretch properties to achieve the appropriate pressure levels, thus optimizing compression effectiveness.

Deuterium (2H) MRI is an emerging tool for noninvasive imaging. We explore the integration of 2H MRI with deuterated multifunctional nanopolymers for deuterated particle imaging (DPI). To this end, amine-terminated G5-polyamidoamine (PAMAM) dendrimers were labeled with deuterated acetyl surface groups, leading to highly 2H-loaded bioparticles, making them ideal for imaging studies. The accumulation of ∼5 nm PAMAM dendrimers in the kidneys could then be seen by 2H MRI with high submillimeter resolution. The natural abundance HDO signal provided an internal concentration reference to these measurements, leading to quantitative dynamic maps showing distinct nanopolymer uptakes within the renal compartments. Further, these nanopolymers allowed us to obtain in vivo maps of activity in the lymph nodes in an inflammatory rodent leg model, demonstrating these deuterated nanopolymers' potential as a novel class of contrast agents for the quantitative mapping of physiological processes.

ObjectiveDrug coated balloons (DCBs) are used to treat peripheral artery disease (PAD) but concerns about their efficacy and safety persist. Current evaluation methods, relying on benchtop studies and animal models, do not replicate the complexity of human PAD lesions. This study aimed to develop a novel methodology to assess paclitaxel delivery from DCBs to human peripheral arteries with complex plaque morphologies using scanning electron microscopy (SEM) with the purpose of examining how plaque morphology and vessel preparation affect drug transfer in human cadaveric legs.MethodsAn amputated leg model from patients with PAD and standardised vessel preparation, imaging, and quantification methods was used. Arteries were treated with plain balloon angioplasty, cutting balloon angioplasty, or no preparation before DCB treatment. Vessels were imaged with high vacuum SEM, and drug coverage was quantified with ImageJ. Lesions were classified as nodular or smooth based on magnetic resonance imaging. Drug distribution was analysed at 300×300 μm field of view (FOV), categorised as minimal, moderate, good, or excellent.ResultsSEM was effective at imaging paclitaxel crystals transferred to the vessel wall. Plaque morphology affected the amount of drug transferred with smooth plaques exhibiting greater drug coverage than nodular plaques. In nodular plaques, drug was concentrated on the protruding portions of the plaque and not in the recesses, while smooth plaques showed more uniform distribution. Excellent coverage was seen in 38.31% of FOVs of smooth plaques vs. 10.58% of nodular plaques. Drug transfer was more consistent in smooth vessels, regardless of vessel preparation method. Cutting balloons enhanced drug delivery when grooves were formed.ConclusionThis SEM based method effectively evaluated drug transfer in human PAD lesions, revealing greater drug delivery in smooth lesions and the impact of vessel preparation. This novel analytic model offers a platform for optimising DCB strategies to improve PAD patient outcomes.