Search Results (308)

Although cranial growth has been extensively explored, forensic and biological anthropology lack a formal incorporation of how cranial growth processes impact the adult phenotype and downstream biological profile estimations. Objectives: This research uses an ontogenetic framework to identify when interlandmark distances (ILDs) stabilize during growth to reach adult levels of variation and to evaluate patterns of cranial sexual size dimorphism. Methods: Multivariate adaptive regression splines (MARS) were conducted on standardized cranial ILDs for 595 individuals from the Subadult Virtual Anthropology Database (SVAD) and the Forensic Data Bank (FDB) aged between birth and 25 years. Cross-Validated R-squared (CVRSq) values evaluated ILD variation explained by age while knot placements identified meaningful changes in ILD growth trajectories. Results: Results reveal the ages at which males and females reach craniometric maturity across splanchnocranium, neurocranium, basicranium and cross-regional ILDs. Changes in growth patterns observed here largely align with growth milestones of integrated soft tissue and skeletal structures as well as developmental milestones like puberty. Conclusions: Our findings highlight the variability in growth by sex and cranial region and move forensic anthropologists towards recognizing cranial growth as a mosaic, continuous process with overlap between subadults and adults rather than consistently approaching subadult and adult research separately. Full article

Human induced pluripotent stem cell-derived cardiomyocytes (iCMs) provide a powerful platform for investigating cardiac biology. However, structural, metabolic, and electrophysiological immaturity of iCMs limits their capacity to model adult cardiomyocytes. Currently, no universally accepted criteria or protocols for effective iCMs maturation exist. This study aimed to identify practical culture conditions that promote iCMs maturation, thereby generating more physiologically relevant in vitro cardiac models. We evaluated the effects of short- and long-term culture in media supplemented with various stimulatory compounds under 2D conditions, focusing on intracellular content and localization of slow skeletal troponin I (ssTnI) and cardiac troponin I (cTnI) isoforms. Our findings demonstrate that the multicomponent metabolic maturation medium (MM-1) effectively enhances the transition toward a more mature iCM phenotype, as evidenced by increased cTnI expression and formation of cross-striated myofibrils. iCMs cultured in MM-1 more closely resemble adult cardiomyocytes and are compatible with high-resolution single-cell techniques such as electron microscopy and patch-clamp electrophysiology. This work provides a practical and scalable approach for advancing the maturation of iPSC-derived cardiac models, with applications in disease modeling and drug screening. Full article

Background/Objectives: Surgical treatment is generally recommended for adolescent idiopathic scoliosis (AIS) when the Cobb angle exceeds 50 degrees even after skeletal maturity or 40 degrees with remaining growth potential. However, limited evidence exists regarding the natural history of curves between 40 and 50 degrees during the late stage of skeletal growth. This study aimed to evaluate the curve progression in AIS patients with a curve between 40 and 50 degrees at Risser stage IV or V. Methods: The inclusion criteria were as follows: (1) AIS patients at the late stage of skeletal growth (Risser IV or V) and a (2) curve between 40 and 50 degrees, with a minimum follow-up of 5 years. Sex, age, the magnitude of the curve, the location of the apex, Risser stage, height, and weight were measured at the baseline and the final follow-up. Curve progression was defined as an increase in the Cobb angle of ≥5 degrees. Patients were also categorized based on whether their final Cobb angle was <50 or ≥50 degrees to evaluate additional risk factors. Results: A total of 97 patients were included, with a mean follow-up of 97 months. Their mean age was 14.6 years at the baseline and 22.6 years at the final follow-up. The mean Cobb angle increased from 42.6 to 45.1 degrees, with a mean change of 2.7 degrees and an annual progression rate of 0.35 degrees. Curve progression was observed in 38 patients (39.2%), and 24 patients (24.7%) reached a final Cobb angle ≥ 50 degrees. Younger age (p = 0.004) and Risser stage IV (p = 0.014) were significantly associated with curve progression. In patients with a final Cobb angle ≥ 50 degrees, Risser stage IV (p = 0.050) and a larger baseline curve magnitude (p = 0.045) were also significant risk factors. Conclusions: In AIS patients at the late stage of skeletal growth, 39.2% experienced significant curve progression. A younger age and Risser stage IV were identified as risk factors for curve progression. A larger baseline curve magnitude and Risser stage IV were also associated with a final Cobb angle ≥ 50 degrees. Full article

Skeletal muscle regeneration requires a reliable source of myogenic progenitor cells capable of forming new fibers and creating a self-renewing satellite cell pool. Human induced pluripotent stem cell (hiPSC)-derived teratomas have emerged as a novel in vivo platform for generating skeletal myogenic progenitors, although in vivo studies to date have provided only an early single-time-point snapshot. In this study, we isolated a specific population of CD82⁺ ERBB3⁺ NGFR⁺ cells from human iPSC-derived teratomas and verified their long-term in vivo regenerative capacity following transplantation into NSG-mdx^4Cv mice. Transplanted cells engrafted, expanded, and generated human Dystrophin⁺ muscle fibers that increased in size over time and persisted stably long-term. A dynamic population of PAX7⁺ human satellite cells was established, initially expanding post-transplantation and declining moderately between 4 and 8 months as fibers matured. MyHC isoform analysis revealed a time-based shift from embryonic to neonatal and slow fiber types, indicating a slow progressive maturation of the graft. We further show that these progenitors can be cryopreserved and maintain their engraftment potential. Together, these findings give insight into the evolution of teratoma-derived human myogenic stem cell grafts, and highlight the long-term regenerative potential of teratoma-derived human skeletal myogenic progenitors. Full article

Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article

This study aimed to assess skeletal and upper airway modifications induced by the Twin Block appliance in patients with Class II malocclusion due to mandibular retrusion, using two-dimensional imaging techniques. A total of 11 patients (6 males, 5 females) were included and stratified into two groups (Pre-Peak and Peak) based on skeletal maturity evaluated through the cervical vertebral maturation (CVM) method. Lateral cephalometric radiographs were obtained at the beginning (T0) and end (T1) of treatment and analyzed using DeltaDent software. The appliance was worn full-time, except during meals and oral hygiene procedures, with monthly follow-ups. Significant changes were observed between T0 and T1 across the sample. Comparison between groups revealed statistically significant differences only in the H-C3a1 and vertical height (th) parameters (p < 0.05). In conclusion, the Twin Block appliance proved effective in enhancing mandibular and dental positioning, while also exerting a favorable influence on upper airway development. Full article

The thyroid gland plays a crucial role in regulating metabolism and supporting development through the production of the hormones T4 and T3. These hormones are essential during childhood for nervous system myelination, physical growth, puberty, skeletal and dental maturation, and overall metabolic balance. In early infancy, when the hypothalamic–pituitary–thyroid axis is still immature, thyroid dysfunction can result in a range of long-term complications. The metabolism and action of thyroid hormones depend not only on iodine but also on other vital micronutrients, particularly selenium (Se). This narrative review aims to comprehensively examine the role of selenium in maintaining thyroid health from fetal life through adolescence. Selenium is a key micronutrient involved in thyroid development, hormone synthesis, antioxidant defense, and immune regulation, especially during pregnancy and childhood. Inadequate selenium levels may contribute to the onset, progression, and clinical management of various thyroid disorders, particularly hypothyroidism and autoimmune thyroid diseases. Although scientific evidence supports selenium’s critical functions in hormone metabolism and antioxidant protection, public awareness and monitoring of selenium intake remain insufficient. Beyond the need for further research, there is an urgent call for integrated public health strategies, ranging from sustainable, food-based approaches to targeted clinical screening and educational programs. Promoting awareness of selenium’s importance and incorporating selenium status into maternal and pediatric care protocols could play a significant role in preventing deficiencies and supporting long-term endocrine and neurodevelopmental health. Full article

Background: Tooth agenesis, particularly hypodontia, poses a clinical and esthetic challenge in growing patients due to limitations in definitive implant placement before skeletal maturity. Traditional solutions such as removable prostheses or orthodontic space closure often fail to provide adequate long-term stability, function, and tissue preservation. In recent years, orthodontic mini-implants have emerged as a promising interim solution. This narrative review aims to synthesize current clinical evidence on the use of orthodontic mini-implants as temporary prosthetic abutments in children and adolescents with hypodontia or post-traumatic tooth loss. Methods: A literature search was conducted using PubMed and Google Scholar databases, covering studies published between January 2004 and March 2025. Inclusion criteria were clinical reports involving skeletally immature patients with congenital or traumatic tooth loss treated with mini-implants, with mandatory radiographic diagnostics and outcome data. Data extracted included patient demographics, etiology, implant site, imaging, follow-up, complications, and outcomes. A total of 17 studies comprising 42 cases were analyzed and summarized in tabular form. Results: Patients aged 6 to 16 years were treated primarily for agenesis of maxillary lateral or central incisors. The mean follow-up duration was 36.9 months. CBCT was used in 28.6% of cases. Mini-implants demonstrated high clinical success with stable soft tissue contours and preservation of alveolar volume. Complications were reported in 21.4% of cases and included crown debonding, minor infraocclusion, soft tissue irritation, and rare instances of osseointegration. Conclusions: Orthodontic mini-implants may provide a minimally invasive and reversible approach to interim tooth replacement in growing patients. Preliminary evidence suggests favorable outcomes in terms of stability, esthetics, and tissue preservation, but further prospective research is needed to validate their long-term effectiveness and standardize clinical application. Full article

Introduction: Celiac disease (CD) impairs bone development in children through inflammation and nutrient malabsorption. Osteoprotegerin (OPG), a decoy receptor for RANKL, plays a role in bone remodeling and is increasingly recognized as a potential biomarker of bone metabolism and inflammation. However, its clinical significance in pediatric CD remains unclear. Aim: To evaluate the relationship between OPG levels, growth parameters, and delayed bone age in children with CD, and to assess OPG’s potential as a biomarker of bone health and disease activity. Methods: This three-year case–control study included 146 children: 25 with newly diagnosed CD (Group A), 54 with established CD on a gluten-free diet (Group B), and 67 healthy controls (Group C). Participants underwent clinical, anthropometric, and laboratory assessments at baseline and after 6 months (Groups A and B). OPG and osteocalcin were measured, and bone age was assessed radiologically. Statistical analyses included ANOVA, Spearman’s correlations, and binomial logistic regression. Results: OPG levels were highest in newly diagnosed children (Group A), showing a non-significant decrease after gluten-free diet initiation. OPG correlated negatively with age and height in CD patients and controls, and positively with hemoglobin and iron in Group B. Logistic regression revealed no significant predictive value of OPG for delayed bone age, although a trend was observed in Group B (p = 0.091). Children in long-term remission exhibited bone maturation patterns similar to healthy peers. Conclusions: OPG levels reflect disease activity and growth delay in pediatric CD but lack predictive power for delayed bone age. While OPG may serve as a secondary marker of bone turnover and inflammatory status, it is not suitable as a standalone biomarker for skeletal maturation. These findings highlight the need for integrative biomarker panels to guide bone health monitoring in children with CD. Full article

Background/Objectives: Hypertension is a major contributor to cardiovascular diseases and is often intensified by psychological stress, which can also affect bone metabolism. Although both conditions independently compromise bone health, their combined impact—particularly under acute and chronic stress—remains unclear. This pilot study aimed to assess the effects of such stressors on bone structure in spontaneously hypertensive rats (SHRs). Methods: Forty male rats, both normotensive and SHRs, were randomly assigned to control, acute stress, or chronic stress groups. Acute stress involves a single 2 h physical restraint. Chronic stress was induced over 10 days using alternating stressors: agitation, forced swimming, physical restraint, cold exposure, and water deprivation. Tibial bones were analyzed by microcomputed tomography (micro-CT), and histology was performed using Hematoxylin and Eosin and Masson’s Trichrome stains. Results: Micro-CT showed increased trabecular bone volume in normotensive rats under chronic stress, whereas SHRs displayed impaired remodeling under both stress types. Histological analysis revealed preserved connective tissue overall but evident changes in growth plate structure among stressed rats. SHRs exhibited exacerbated trabecular formation and cartilage abnormalities, including necrotic zones. Conclusions: Both acute and chronic stress, especially in the context of hypertension, negatively affect bone remodeling and maturation. Despite the absence of overt inflammation, structural bone changes were evident, indicating potential long-term risks. These findings highlight the importance of further studies on stress–hypertension interactions in bone health as well as the exploration of therapeutic approaches to mitigate skeletal damage under such conditions. Full article

Background: Duchenne muscular dystrophy (DMD), which affects 1 in 3500 to 5000 newborn boys worldwide, is characterized by progressive skeletal muscle weakness and degeneration. The reduced muscle regeneration capacity presented by patients is associated with increased fibrosis. Satellite cells (SCs) are skeletal muscle stem cells that play an important role in adult muscle maintenance and regeneration. The absence or mutation of dystrophin in DMD is hypothesized to impair SC asymmetric division, leading to cell cycle arrest. Methods: To overcome the limited availability of biopsies from DMD patients, we used our 3D skeletal muscle organoid (SMO) system, which delivers a stable population of myogenic progenitors (MPs) in dormant, activated, and committed stages, to perform SMO cultures using three DMD patient-derived iPSC lines. Results: The results of scRNA-seq analysis of three DMD SMO cultures versus two healthy, non-isogenic, SMO cultures indicate reduced MP populations with constant activation and differentiation, trending toward embryonic and immature myotubes. Mapping our data onto the human myogenic reference atlas, together with primary SC scRNA-seq data, indicated a more immature developmental stage of DMD organoid-derived MPs. DMD fibro-adipogenic progenitors (FAPs) appear to be activated in SMOs. Conclusions: Our organoid system provides a promising model for studying muscular dystrophies in vitro, especially in the case of early developmental onset, and a methodology for overcoming the bottleneck of limited patient material for skeletal muscle disease modeling. Full article

Background: Vitamin D is increasingly recognized not only for its role in skeletal development but also for its immunomodulatory and gastrointestinal effects. Maternal and neonatal vitamin D deficiency (VDD) has been associated with alterations in gut microbiota, impaired intestinal barrier integrity, and increased susceptibility to inflammatory conditions in neonates. However, the exact mechanisms linking perinatal vitamin D status to neonatal gastrointestinal morbidity remain incompletely understood. Methods: This review synthesizes current evidence (2015–2024) from clinical studies, animal models, and mechanistic research on the impact of VDD during pregnancy and the neonatal period on gastrointestinal health. Databases such as PubMed, Scopus, and Web of Science were systematically searched using keywords, including “vitamin D”, “neonate”, “gut microbiome”, “intestinal barrier”, and “necrotizing enterocolitis”. Results: Emerging data suggest that VDD in utero and postnatally correlates with dysbiosis, increased intestinal permeability, and elevated inflammatory responses in neonates. Notably, low 25(OH)D levels in mothers and newborns have been linked with a higher incidence of necrotizing enterocolitis (NEC), delayed gut maturation, and altered mucosal immunity. Vitamin D appears to modulate the expression of tight junction proteins, regulate antimicrobial peptides, and maintain microbial diversity through the vitamin D receptor (VDR). Conclusions: Understanding the gastrointestinal implications of early-life VDD opens a potential window for preventive strategies in neonatal care. Timely maternal supplementation and targeted neonatal interventions may mitigate gut-related morbidities and improve early-life health outcomes. Further longitudinal and interventional studies are warranted to clarify causality and optimal intervention timing. Full article

Collagen II is a vital structural component in developing bones and mature cartilage. Mutations in this protein cause spondyloepiphyseal dysplasia, a disease characterized primarily by altered skeletal growth and manifesting with a range of phenotypes, from lethal to mild. This study examined transgenic mice harboring the R992C (p.R1124C) substitution in collagen II. Previous research demonstrated significant growth abnormalities and disorganized growth plate structure in these mice, and histological signs of osteoarthritic changes in the knee joints of 9-month-old mice with the R992C mutation. Our study focuses on detecting early structural changes in the articular cartilage that occur before histological signs become apparent. Through microscopic and spectroscopic analyses, we observed significant alterations in the distribution gradients of collagenous proteins and proteoglycans in the cartilage of R992C mutant mice. We propose that these early changes, eventually leading to articular cartilage degeneration in older mice, underscore the progressive nature of osteoarthritic changes linked to collagen II mutations. By identifying these early structural aberrations, our findings emphasize the importance of early detection of osteoarthritic changes, potentially facilitating timely, non-surgical interventions. Full article

Background/Objectives: Children with congenital adrenal hyperplasia (CAH) face significant risks of impaired growth and metabolic disturbances despite standard glucocorticoid therapy. This cross-sectional study aimed to evaluate growth outcomes, nutritional status, and associated factors among children with CAH treated in a Vietnamese tertiary pediatric center. Methods: We assessed 201 children aged 1.1–16.5 years in a tertiary pediatric center in Vietnam for anthropometric parameters, biochemical markers (calcium, phosphate, 25-hydroxyvitamin D), and clinical features. Growth status was evaluated using WHO standards, and bone age was assessed radiographically. Statistical analyses explored associations between growth outcomes and clinical, biochemical, and treatment-related factors. Results: Stunting was present in 16.4% of children, while 53.3% were overweight or obese. Bone age advancement occurred in 51.7% of cases. Vitamin D insufficiency or deficiency was detected in 85.6% of patients, and hypocalcemia was present in 85.1%. Overweight/obesity, vitamin D deficiency, and bone age advancement were associated with older age, prolonged corticosteroid therapy, higher androgen levels, and clinical features of treatment imbalance (e.g., Cushingoid appearance, hyperpigmentation). Female sex was significantly associated with higher rates of stunting. Conclusions: Growth impairment, nutritional deficiencies, and skeletal maturation disturbances are prevalent among children with CAH in Vietnam. Early identification of risk factors and the implementation of tailored management strategies that address both endocrine and nutritional health are crucial for optimizing long-term outcomes. Full article

Background/Aims: The aim of this study was to evaluate the effectiveness of large language model (LLM)-based chatbot systems in predicting bone age and identifying growth stages, and to explore their potential as practical, infrastructure-independent alternatives to conventional methods and convolutional neural network (CNN)-based deep learning models. Methods: This study evaluated the performance of three ChatGPT-based models (GPT-4o, GPT-o4-mini-high, and GPT-o1-pro) in predicting bone age and growth stage using 90 anonymized hand–wrist radiographs (30 from each growth stage—pre-peak, peak, and post-peak—with equal male and female distribution). Reference standards were ensured by expert orthodontists using Fishman’s Skeletal Maturity Indicators (SMI) system and the Greulich–Pyle Atlas, with each radiograph analyzed by three GPT models using standardized prompts. Model performances were evaluated through statistical analyses assessing agreement and prediction accuracy. Results: All models showed significant agreement with the reference values in bone age prediction (p < 0.001), with GPT-o1-pro having the highest concordance (Pearson r = 0.546). No statistically significant difference was observed in the mean absolute error (MAE) among the models (p > 0.05). The GPT-o4-mini-high model achieved an accuracy rate of 72.2% within a ±2 year deviation range for bone age prediction. The GPT-o1-pro and GPT-o4-mini-high models showed bias in the Bland–Altman analysis of bone age predictions; however, GPT-o1-pro yielded more reliable predictions with narrower limits of agreement. In terms of growth stage classification, the GPT-4o model achieved the highest agreement with the reference values (κ = 0.283, p < 0.001). Conclusions: This study shows that general-purpose GPT models can support bone age and growth stages prediction, with each model having distinct strengths. While GPT models do not replace clinical examination, their contextual reasoning and ability to perform preliminary assessments without domain-specific training make them promising tools, though further development is needed. Full article