Search Results (261)

Long bone formation in vertebrates proceeds via endochondral ossification, a sequential process that begins with mesenchymal condensation, advances through cartilage anlage formation, and culminates in its replacement by mineralized bone. Recent advances in inducible lineage tracing and single-cell genomics have revealed that, rather than being a uniform event, mesenchymal condensation rapidly segregates into progenitor pools with distinct fates. Centrally located Sox9⁺/Fgfr3⁺ chondroprogenitors expand into the growth plate and metaphyseal stroma, peripheral Hes1⁺ boundary cells refine condensation via asymmetric division, and outer-layer Dlx5⁺ perichondrial cells generate the bone collar and cortical bone. Concurrently, dorsoventral polarity established by Wnt7a–Lmx1b and En1 ensures that dorsal progenitors retain positional identity throughout development. These lineage divergences integrate with signaling networks, including the Ihh–PTHrP, FGF, BMPs, and WNT/β-catenin networks, which impose temporal control over chondrocyte proliferation, hypertrophy, and vascular invasion. Perturbations in these programs, exemplified by mutations in Fgfr3, Sox9, and Dlx5, underlie region-specific skeletal dysplasias, such as achondroplasia, campomelic dysplasia, and split-hand/foot malformation, demonstrating the lasting impacts of embryonic patterning errors. Based on these insights, regenerative strategies are increasingly drawing upon developmental principles, with organoid cultures recapitulating ossification centers, biomimetic hydrogels engineered for spatiotemporal morphogen delivery, and stem cell- or exosome-based therapies harnessing developmental microRNA networks. By bridging developmental biology with biomaterials science, these approaches provide both a roadmap to unravel skeletal disorders and a blueprint for next-generation therapies to reconstruct functional bones with the precision of the embryonic blueprint. Full article

Total hip arthroplasty (THA) is a widely performed procedure that significantly enhances patients’ quality of life. However, nerve injury remains a concerning complication, with an incidence ranging from 0.6% to 3.7%, depending on patient and surgical variables. This narrative review provides a comprehensive overview of nerve injuries associated with THA, focusing on etiology, risk factors, clinical manifestations, prevention, and treatment strategies. The most affected nerves include the sciatic, femoral, lateral femoral cutaneous (LFCN), superior gluteal, and obturator nerves. Anatomical factors such as developmental hip dysplasia (DDH), limb length discrepancy, and aberrant nerve courses, along with patient-specific conditions like female sex, obesity, and pre-existing spinal disorders, increase the risk of nerve damage. Surgical complexity, revision procedures, and surgeon experience also influence injury likelihood. Clinical manifestations range from sensory disturbances to motor deficits including foot drop, Trendelenburg gait, or impaired knee extension, depending on the nerve involved. Diagnosis is primarily clinical, supported by electrophysiological studies and imaging when needed. Prevention hinges on careful preoperative planning, appropriate surgical approach selection, meticulous intraoperative technique, and attention to limb positioning. Treatment is typically conservative, involving pain control, physical therapy, and neurostimulation. In refractory or severe cases, interventions such as nerve decompression, repair, or tendon transfer may be considered. Pharmacological agents including vitamin B12, tacrolimus, and melatonin show potential in promoting nerve regeneration. Although most nerve injuries resolve spontaneously or with conservative measures, some cases may result in long-term deficits. Understanding the mechanisms, risk factors, and management strategies is essential to mitigating complications and optimizing functional outcomes in patients undergoing THA. Full article

Functional electrical stimulation (FES) is widely used to improve gait in individuals with neurological impairments; however, early responses in adults with congenital conditions, such as cerebral palsy, who are newly exposed to FES, remain poorly understood. This study investigated the orthotic and therapeutic effects of FES in short- and long-term users using standardized three-dimensional gait analysis. In this longitudinal study, short-term users (G1; n = 13; mean age 31.7 ± 18.1 years) were evaluated both without and with FES and followed over a 4–12-week insurance-covered trial period. Long-term users (G2; n = 11; mean age 32.2 ± 11.0 years), who had used FES for at least one year, were reassessed over a standardized 12-week interval. Linear mixed-effects models assessed the effects of FES and time, with subjects included as random effects to account for inter-individual variability. G1 showed significant therapeutic adaptations, including increased walking speed and step length and reduced step width, accompanied by decreased dorsiflexion during stance and swing, while no significant orthotic effects were observed. G2 demonstrated clear orthotic responses, such as increased dorsiflexion at heel strike and during swing and improved walking speed and step length, with minimal evidence of additional therapeutic adaptation. The initial reduction in dorsiflexion in G1 warrants further investigation. These findings suggest that evaluation timelines may need to be extended and that outcome measures beyond foot clearance should be considered, particularly given the heterogeneity and severity of congenital neurological conditions. Full article

Working equids are at high risk of musculoskeletal disorders due to strenuous labor, repetitive tasks, and harsh environmental conditions. This retrospective study describes the distribution of radiographically detected musculoskeletal findings in working equids presented to four Society for the Protection of Animals Abroad (SPANA) centers in Morocco, based on 498 animals and 1125 radiographs collected between 2015 and 2022. The study population was mainly composed of horses (78.1%), followed by donkeys (15.3%) and mules (6.6%). Most were males (65.7%), and the majority were between 5 and 15 years old (60.4%). The distal limb (foot, pastern, and fetlock) was the most frequently examined region (62.7%). Among the animals reviewed, 381 (76.5%) exhibited at least one radiographically detected abnormality, while 117 (23.5%) showed no visible osseous change. The most frequent findings included foot-related changes (36.2%), defined as non-fracture podiatric abnormalities, fractures (29.7%), and periosteal new bone formation (22%). Less frequent findings were degenerative joint disease (8.1%), joint subluxation or luxation (1.6%), epiphyseal abnormalities (1.6%), and angular deformities (0.8%). These results provide an overview of radiographically detected osseous changes in working equids under field conditions. They highlight the diagnostic value of radiography in low-resource environments and provide a basis for future field-based studies. Full article

Background/Objectives: Pes planus is characterized by loss of medial longitudinal foot arch, resulting potentially in dysfunction in balance. Chronic ankle instability (CAI) is related to sensorimotor control deficits. Both of these two musculoskeletal disorders have a diminishing effect on joint proprioception. The present study examined the impact of flatfoot on balance in individuals with CAI. Methods: A total of 28 students (15 men, 13 women; 18–23 years, M = 20.46, SD = 1.07) were assigned to CAI with pes planus (n = 15) or CAI only (n = 13). Balance was assessed using the Y-balance test (YBT) and modified star excursion balance test (mSEBT) in three directions (anterior, posteromedial, and posterolateral), alongside the Cumberland ankle instability tool (CAIT). Group differences were analyzed with independent t tests or Mann–Whitney U tests (α = 0.05). Results: The findings of the study did not show statistically significant differences between the two groups in the balance variable [mSEBT/anterior left foot (t = 0.239, p = 0.865); mSEBT/posteromedial left foot (t = −0.048, p = 0.562); mSEBT/posterolateral left foot (t = 0.164, p = 0.258); mSEBT/anterior right foot (t = −0.433, p = 0.748); mSEBT/posteromedial right foot (t = 0.745, p = 0.606); mSEBT/posterolateral right foot (t = 0.263, p = 0.680); YBT/anterior left foot (U = 96.00, p = 0.93); YBT/posteromedial left foot (U = 94.50, p = 0.87); YBT/posterolateral left foot (U = 96.00, p = 0.93); YBT/anterior right foot (U = 95.50, p = 0.92); YBT/posterolateral right foot (U = 82.50, p = 0.45)]. However, a trend towards significance was found as patients with flatfeet had a weaker performance in balance tests [posteromedial direction of the YBT for the right foot (U = 70.00, p = 0.12)]. Conclusions: Although pes planus did not seem to affect the balance ability of individuals with CAI, future studies should confirm the relationship of pes planus and CAI with a larger group, including variables such as ankle range of motion, muscle strength, and functional activity level. A better understanding of the above relationship may lead to more precise diagnostic processes and more efficient therapies in CAI. Full article

Parkinson’s Disease (PD) is a neurodegenerative disorder in which gait abnormalities serve as key indicators of motor impairment and disease progression. Although wearable sensor-based gait analysis has advanced, existing methods still face challenges in modeling multi-sensor spatial relationships, extracting adaptive multi-scale temporal features, and effectively integrating time–frequency information. To address these issues, this paper proposes a multi-sensor gait neural network that integrates biomechanical priors with time–frequency collaborative learning for the automatic assessment of PD gait severity. The framework consists of three core modules: (1) BGS-GAT (Biomechanics-Guided Graph Attention Network), which constructs a sensor graph based on plantar anatomy and explicitly models inter-regional force dependencies via graph attention; (2) AMS-Inception1D (Adaptive Multi-Scale Inception-1D), which employs dilated convolutions and channel attention to extract multi-scale temporal features adaptively; and (3) TF-Branch (Time–Frequency Branch), which applies Real-valued Fast Fourier Transform (RFFT) and frequency-domain convolution to capture rhythmic and high-frequency components, enabling complementary time–frequency representation. Experiments on the PhysioNet multi-channel foot pressure dataset demonstrate that the proposed model achieves 0.930 in accuracy and 0.925 in F1-score for four-class severity classification, outperforming state-of-the-art deep learning models. Full article

Background/Objectives: The Fibroblast Growth Factor Receptor 1 (FGFR1, MIM*136350) is a protein member of the fibroblast growth factor receptor (FGFR) family, with various biological functions, such as the normal development control. It contains an extracellular site for the ligand (three Ig-like domains, IgI, IgII, IgIII), a single transmembrane and a cytoplasmic protein tyrosine kinase (TK) domain. Variants in this gene have been associated with a wide spectrum of genetic disorders, including the clinical entity known as FGFR1-related Hartsfield or Hartsfield syndrome (HRTFDS, MIM#615465), which is an autosomal dominant or recessive disorder characterized by the clinical association of split-hand/foot malformation (SHFM) and holoprosencephaly (HPE). Dysmorphic facies, including cleft/lip palate, genitourinary anomalies, cardiovascular defects and intellectual disability/developmental delay (ID/DD) can also be a part of the clinical picture. Methods: The malformation phenotype of HRTFDS has been reviewed in 26 previously reported patients in terms of single congenital defects, mutational spectrum, impacted protein domains and inheritance. Molecular basis, clinical management, main differential diagnoses and genetic counseling were also illustrated. Results: SHFM was identified in every patient. The other main associated features included craniofacial defects, skeletal malformation identified at radiography, genitourinary anomalies, HPE and cardiovascular disorders. FGFR1 causative variants mainly impact the TK domain and have a smaller impact on other protein sites (IgII, IgIII). Conclusions: This study extensively recapitulates the malformation phenotype associated with HRTFDS and the underlying molecular perturbations. A multidisciplinary clinical approach is fundamental, in which genetic counseling can have an important role. However, our results are partial and refer to a restricted number of patients, pointing out the necessity of other descriptions and similar research. Additional studies will expand clinical and molecular knowledge as well as further clarify the biological mechanisms. Full article

Background: Atherosclerosis is the pathological basis for lethal cardio-cerebral vascular diseases, such as coronary artery disease and stroke. Fructus Choerospondiatis (FC) has demonstrated cardiac protective effects in multiple ethnomedicine. Whether these protective effects are attributed to the prevention of vascular atherosclerosis, however, remains unknown. We aim to examine the anti-atherosclerotic effect of FC aqueous extract and elucidate the underlying mechanism. Methods: FC was separated into peel and pulp, and the aqueous extract was obtained separately by boiling in water to mimic decocting. Atherosclerosis model was established in ApoE^−/− mice fed with a high-fat diet, and histological analysis were utilized to evaluate the development of atherosclerosis. Various inflammatory models were constructed in mice to evaluate the anti-inflammatory effect of FC extract systemically, including acute local inflammation induced by traumatic injury (ear/foot swelling), acute systemic inflammation triggered by pathogenic infection (LPS- and POLY (I:C)-induced), as well as chronic inflammatory conditions associated with oxidative stress (D-galactose-induced), metabolic disorder (db/db mice), and aging. LC-MS and network pharmacology identified bioactive components and targets. Western blotting, ELISA, qPCR, and immunofluorescence were utilized to analyze the key genes involved in the mechanisms. Results: FC peel extract reduced serum IL-6 level, atherosclerotic plaque area, and macrophage content in the plaque, while pulp extract showed no protective effects. Peel extract exhibits anti-inflammatory effects in all models. The integrative application of LC-MS and network pharmacology identified ellagic acid as the major bioactive component and AKT as its target protein. Mechanistically, FC peel extract inhibits AKT phosphorylation, suppresses c-FOS expression and nuclear translocation, reduces IL-6 transcription and inflammation, and thus alleviates atherosclerosis. Conclusions: FC peel aqueous extract exerts anti-atherosclerotic effect by inhibiting inflammation through AKT/c-FOS/IL-6 axis. This study provides novel insights into the protective effects against atherosclerosis of FC peel and highlights its potential application in the prevention and treatment of coronary artery diseases. Full article

Type 2 diabetes mellitus (T2DM) is a widespread metabolic disorder characterized by insulin resistance and pancreatic β-cell dysfunction, posing a substantial global health challenge. This review systematically summarizes the therapeutic potential of berberine, a natural isoquinoline alkaloid, in the management of T2DM. Berberine’s pharmacological activities are discussed from multiple perspectives, including enhancing insulin sensitivity and regulating glucose metabolism—encompassing glycogen synthesis, gluconeogenesis, and glucose transport. The review also highlights berberine’s anti-inflammatory, antioxidant, and epigenetic enzyme-targeting actions and its involvement in key T2DM-related signaling pathways such as AKT, AMPK, and GLUTs. These findings collectively elucidate the multi-targeted and multi-pathway molecular mechanisms underlying berberine’s efficacy against T2DM. Additionally, the review covers the pharmacological activities and molecular mechanisms of berberine in treating T2DM complications—including diabetic nephropathy, retinopathy, cardiomyopathy, neuropathy, and diabetic foot ulcers—as well as its clinical and preclinical applications and the synergistic benefits of combination therapy with agents such as metformin, ginsenoside Rb1, and probiotics. By systematically reviewing the literature retrieved from PubMed and Web of Science up to 2025, this article provides a comprehensive summary of current research, offering a theoretical foundation for the clinical use of berberine in T2DM therapy. Full article

Central sensitization of pain (CSP) is defined as the “increased responsiveness of nociceptive neurons in the central nervous system (CNS) to normal or subthreshold afferent input” The primary objective of this study is to compare the prevalence of CSP between patients presenting with foot and ankle conditions and those presenting with low back pain. Materials and Methods: A cross-sectional study was conducted comparing a cohort of patients with a first consultation for foot and ankle disorders to another cohort with a first consultation for lumbar spine pain at the same institution. Demographic variables, pain duration, main diagnosis, and a series of questionnaires assessing pain and disability were collected. The Central Sensitization Inventory (CSI) was administered to determine the presence of CSP within the groups. Statistical analyses were performed using STATA. Results: A total of 195 patients presenting with foot/ankle conditions and 252 patients with low back pain were included. Among the foot/ankle cohort, 16.4% (95% CI, 10.92–21.9%) were classified as having CSP, compared to 22.2% (95% CI, 16.85–27.6%) in the lumbar pain cohort. The difference in CSP prevalence between groups was not statistically significant (difference 5.79%, Chi² = 2.357, p = 0.125). However, the difference in mean scores on Part A of the CSI was statistically significant (31.82 ± 13.88 vs. 25.20 ± 14.31, z = 4.237, p < 0.001). Among foot/ankle pathologies, plantar fasciitis showed the highest prevalence of CSP (21.9%), followed by hallux valgus (18.8%). A significant association was observed between CSP and higher levels of pain and disability. Female patients demonstrated a higher prevalence of CSP. Conclusions: Patients with low back pain exhibited higher CSI scores and a greater prevalence of central sensitization compared with those with foot and ankle disorders. Recognizing these mechanisms may help clinicians tailor more effective, multidisciplinary treatment strategies. Full article

Background: Accurate assessment of pediatric foot biomechanics is challenging due to growth-related variability and limited quantitative tools. The supination and pronation angles of the ankle are critical for understanding lower limb alignment and pathological gait patterns. Objectives: This study introduces a novel digital pedoscopic system designed to enhance the quantitative evaluation of foot alignment and to demonstrate its clinical utility through clustering analysis of pediatric ankle angles. Methods: Thirty-five pediatric patients (mean age = 6.17 ± 4.54 years) with neurological or developmental disorders were evaluated using a semi-automated digital pedoscopic system to obtain quantitative measurements of ankle alignment. Key anatomical landmarks, including the heel, calf, and knee centers, were manually identified from posterior images, and the system automatically calculated ankle pronation and supination angles. K-means clustering analysis was applied to classify participants based on their biomechanical profiles. Results: A total of thirty-five pediatric patients were assessed, and the revised abstract now explicitly reports this sample size to improve clarity. Data-driven k-means clustering of bilateral rearfoot angles identified three clearly defined alignment subgroups—neutral, pronated, and supinated—each exhibiting characteristic distribution patterns and degrees of inter-individual variability. These findings highlight the system’s ability to quantitatively distinguish biomechanical phenotypes within a heterogeneous pediatric population. Visualization through scatter, box, and violin plots demonstrated distinct cluster-specific distributions and inter-individual variability in rearfoot alignment, demonstrating the feasibility of objective biomechanical stratification in pediatric populations. Conclusions: The digital pedoscopic imaging system provides a reliable and reproducible approach for quantitative assessment of foot alignment in children. Clustering analysis enables stratification of biomechanical subtypes, supporting individualized rehabilitation strategies and longitudinal monitoring in pediatric clinical practice. Full article

Background: Cavus foot, defined by an increased medial longitudinal arch and often forefoot plantarflexion, alters biomechanics and increases peak plantar pressures, raising the risk of musculoskeletal disorders such as metatarsalgia, Achilles tendinopathy, and gait instability. Custom foot orthoses are the preferred conservative treatment, offering plantar support, pressure redistribution, and reduction in compensatory muscle activity. This study evaluated the medium- and long-term effectiveness of custom orthoses in 71 patients with cavus feet using surface electromyography (sEMG) and the same shoes. Methods: Muscle activity of the peroneus longus, peroneus brevis, and gastrocnemius was recorded during treadmill gait after one and four months of orthotic use. Results: Significant reductions in muscles were observed, especially after four months, confirming greater long-term effectiveness. No residual benefits were found when participants walked without orthoses. Conclusions: These findings support the clinical value of insoles in reducing the compensatory muscle activity in cavus feet and emphasize the importance of investigating their long-term role in biomechanics and potential pathology risk reduction. Full article

Background: Hallux limitus (HL) is a restriction of first metatarsophalangeal joint dorsiflexion, commonly linked to foot biomechanics-related disorders or trauma, increasing sports injury risk. It involves plantar fascia tension, compensations, and tendon adaptations. Rehabilitative ultrasound imaging (RUSI) accurately assesses musculoskeletal changes, supporting physiotherapy evaluation and the study of HL-related structural adaptations. Objectives: Comparing the thickness and cross-sectional area (CSA) of flexor hallucis brevis (FHB), flexor digitorum brevis (FDB), abductor hallucis (AbH), and quadratus plantae (QP) muscles, as well as the thickness of the plantar fascia (PF), Achilles tendon (AT), and plantar calcaneal fat pad (CFP), between participants with and without HL. Methods: Case–control study included 80 basketball players recruited from semi-professional teams by consecutive non-probabilistic sampling. Participants were divided into two groups: an HL group (n = 40) and a healthy group (n = 40). Musculotendinous parameters were assessed using RUSI. Results: The FDB, FHB, AB, and QP showed significant reductions in thickness and CSA at rest and at contraction in the HL group. PF thickness increased in participants with HL, while CFP thickness decreased significantly. Significance was established at (p < 0.05). Conclusions: HL participants exhibited reduced muscle size and CSA, increased PF, and lower CFP thicknesses, indicating adaptive tissue alterations. Full article

Background: Childhood obesity is a growing global concern associated with early-onset orthopedic complications that may persist into adulthood. Among the anthropometric indicators, abdominal adiposity plays a key role in assessing health risks during pediatric evaluations. However, the relationship between abdominal fat distribution and biomechanical alterations, such as changes in posture and foot support, remains poorly understood. Ultrasonography (US) is a validated, noninvasive imaging method capable of distinguishing preperitoneal and intraperitoneal fat in children. Despite its diagnostic advantages, no study to date has directly examined ultrasound-measured abdominal adiposity-predicted pronated foot posture in children. Objective: We aimed to verify the impact of abdominal adiposity on foot support and its association with obese, overweight, and eutrophic schoolchildren. Methods: This is a cross-sectional study. Sixty-five pupils (aged 6–9 years) from a public school in São Paulo, Brazil, were divided into three groups according to nutritional status: obese (n = 25), overweight (n = 20), and eutrophic (n = 20). Anthropometric measurements and foot posture, assessed using the Foot Posture Index (FPI), were collected during the initial evaluation. Abdominal adiposity was determined by ultrasonography, measuring subcutaneous, preperitoneal, and intraperitoneal fat thickness. Statistical Analysis: Analyses compared group differences and relations between abdominal fat and foot posture, with significance set at p < 0.05. Results: Obese and overweight schoolchildren showed pronated foot posture when compared to eutrophic children, on both sides of the feet. Abdominal adiposity was a good predictor of a more pronated footrest for the right and left feet, showing a high-to-moderate association. Conclusions: Ultrasound-measured abdominal adiposity was identified as a significant predictor of pronated foot posture in schoolchildren. These findings highlight the importance of monitoring abdominal fat accumulation during pediatric evaluations, as excessive adiposity may increase the risk of musculoskeletal dysfunctions and pain in the lower limbs. Early detection of these alterations may help prevent postural and musculoskeletal disorders in overweight and obese children. Full article

The anatomical structure of the foot can be assessed by examining the plantar footprint for orthopedic intervention. In fact, there is a relationship between a specific type of foot and multiple musculoskeletal disorders, which are among the main ailments affecting the lower extremities, where its accurate classification is essential for early diagnosis. This work aims to develop a method for accurately classifying the plantar footprint and hindfoot, specifically concerning the sagittal plane. A custom image dataset was created, comprising 603 RGB plantar images that were modified and augmented. Six state-of-the-art models have been trained and evaluated: swin_tiny_patch4_window7_224, convnextv2_tiny, deit3_base_patch16_224, xception41, inception-v4, and efficientnet_b0. Among them, the swin_tiny_patch4_window7_224 model achieved 98.013% accuracy, demonstrating its potential as a reliable and low-cost tool for clinical screening and diagnosis of foot-related conditions. Full article