-
Children (Basel, Switzerland) Jun 2024Tooth eruption is an essential process for the development of the oral and maxillofacial system. Several inherited and acquired diseases might affect this tightly... (Review)
Review
Tooth eruption is an essential process for the development of the oral and maxillofacial system. Several inherited and acquired diseases might affect this tightly regulated process, resulting in premature, delayed, or even failed tooth eruption. The purpose of this article is to review the literature and the clinical parameters of metabolic bone diseases that affect tooth eruption. It examines the physiological aspects of tooth eruption and the pathophysiological changes induced by metabolic bone diseases, including changes in bone metabolism, density, and structure. The search strategy for this review included an electronic search in PubMed, Google Scholar, Medline, Scopus, and the Cochrane Library using the following keywords: "metabolic bone diseases", "tooth eruption", "delayed tooth eruption", and each reported disease in combination with "tooth eruption disorders", covering publications up to March 2024 and limited to English-language sources. Understanding the influence of metabolic bone diseases on tooth eruption is crucial for managing both dental and skeletal manifestations associated with these disorders. This review suggests that a multidisciplinary approach to treatment may significantly improve oral outcomes for patients suffering from such conditions. Clinicians should be aware of the specific dental abnormalities that may arise and consider comprehensive evaluations and individualized treatment plans. These findings underscore the need for further research into targeted therapies that address these abnormalities.
PubMed: 38929327
DOI: 10.3390/children11060748 -
Children (Basel, Switzerland) May 2024Recognized as one of the most serious musculoskeletal deformities, occurring in 1-2 per 1000 newborns, 80% of clubfeet are idiopathic while 20% present with associated...
BACKGROUND
Recognized as one of the most serious musculoskeletal deformities, occurring in 1-2 per 1000 newborns, 80% of clubfeet are idiopathic while 20% present with associated malformations. The etiopathogenesis of clubfoot is described as multifactorial, including both genetic and environmental risk factors. The aim of this study was to analyze possible genetic causes of isolated and syndromic clubfoot in Serbian children, as well as to correlate clinical and genetic characteristics that would provide insight into clubfoot etiopathogenesis and possibly contribute to global knowledge about clinical features of different genetically defined disorders.
METHODS
We evaluated 50 randomly selected, eligible children with clubfoot aged 3 to 16 years that were initially hospitalized and treated at University Children's Hospital between November 2006 and November 2022. The tested parameters were gender, age, dominant foot, affected foot, degree of deformity, treatment, neuromuscular disorders, positive family history, and maternal smoking. According to the presence of defined genetic mutation/s by whole exome sequencing (WES), patients were separated into two groups: positive (with genetic mutation/s) and negative (without genetic mutation/s).
RESULTS
Seven patients were found to be positive, i.e., with genetic mutation/s. A statistically significant difference between categorical variables was found for families with a history of clubfoot, where more than half (57.14%) of patients with confirmed genetic mutation/s also had a family history of genetic mutation/s ( = 0.023).
CONCLUSIONS
The results from this study further expand the genetic epidemiology of clubfoot. This study contributes to the establishment of genetic diagnostic strategies in pediatric patients with this condition, which can lead to more efficient genetic diagnosis.
PubMed: 38929227
DOI: 10.3390/children11060647 -
Biomolecules May 2024Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and...
Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose-Response Study.
Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice ( < 0.0001). Fasting blood glucose (FBG) increased by 40% ( < 0.0001), plasma insulin by 100% ( < 0.05), and HOMA-IR by 150% ( < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day ( < 0.0001) and 50% at 280 mg/kg/day ( < 0.005). HOMA-IR decreased by 45% at both doses ( < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups ( < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice ( < 0.001) and reduced by 20% with all hesperidin doses ( < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.
Topics: Animals; Hesperidin; Oxidative Stress; Insulin Resistance; Metabolic Syndrome; Male; Mice; Citrus; Mice, Inbred C57BL; Dietary Supplements; Disease Models, Animal; Dose-Response Relationship, Drug; Blood Glucose; Diet, High-Fat; Antioxidants
PubMed: 38927040
DOI: 10.3390/biom14060637 -
Nature Communications Jun 2024Idiopathic inflammatory myopathies (IIMs) are severe autoimmune diseases with poorly understood pathogenesis and unmet medical needs. Here, we examine the role of...
Idiopathic inflammatory myopathies (IIMs) are severe autoimmune diseases with poorly understood pathogenesis and unmet medical needs. Here, we examine the role of interferon γ (IFNγ) using NOD female mice deficient in the inducible T cell co-stimulator (Icos), which have previously been shown to develop spontaneous IFNγ-driven myositis mimicking human disease. Using muscle proteomic and spatial transcriptomic analyses we reveal profound myofiber metabolic dysregulation in these mice. In addition, we report muscle mitochondrial abnormalities and oxidative stress in diseased mice. Supporting a pathogenic role for oxidative stress, treatment with a reactive oxygen species (ROS) buffer compound alleviated myositis, preserved muscle mitochondrial ultrastructure and respiration, and reduced inflammation. Mitochondrial anomalies and oxidative stress were diminished following anti-IFNγ treatment. Further transcriptomic analysis in IIMs patients and human myoblast in vitro studies supported the link between IFNγ and mitochondrial dysfunction observed in mice. These results suggest that mitochondrial dysfunction, ROS and inflammation are interconnected in a self-maintenance loop, opening perspectives for mitochondria therapy and/or ROS targeting drugs in myositis.
Topics: Animals; Oxidative Stress; Interferon-gamma; Myositis; Humans; Female; Reactive Oxygen Species; Mice; Mice, Inbred NOD; Mitochondria; Muscle, Skeletal; Disease Models, Animal; Mitochondria, Muscle; Mice, Knockout; Myoblasts
PubMed: 38926363
DOI: 10.1038/s41467-024-49460-1 -
Journal of Orthopaedic Surgery and... Jun 2024Tuberculosis (TB) is one of the top ten causes of death worldwide, with approximately 10 million cases annually. Focus has been on pulmonary TB, while extrapulmonary TB... (Comparative Study)
Comparative Study
Comparing gene expression profiles of adults with isolated spinal tuberculosis to disseminated spinal tuberculosis identified by FDG-PET/CT at time of diagnosis, 6- and 12-months follow-up: classifying clinical stages of spinal tuberculosis and monitoring treatment response (Spinal TB X cohort...
BACKGROUND
Tuberculosis (TB) is one of the top ten causes of death worldwide, with approximately 10 million cases annually. Focus has been on pulmonary TB, while extrapulmonary TB (EPTB) has received little attention. Diagnosis of EPTB remains challenging due to the invasive procedures required for sample collection. Spinal TB (STB) accounts for 10% of EPTB and often leads to lifelong debilitating disease due to devastating spinal deformation and compression of neural structures. Little is known about the extent of disease, although both isolated STB and a disseminated form of STB have been described. In our Spinal TB X cohort study, we aim to describe the clinical phenotype of STB using whole-body FDG-PET/CT, identify a specific gene expression profile for different stages of dissemination and compare findings to previously described gene expression signatures for latent and active pulmonary TB.
METHODS
A single-centre, prospective cohort study will be established to describe the distributional pattern of STB detected by whole-body FDG-PET/CT and gene expression profile of patients with suspected STB on magnetic resonance imaging (MRI) at point of diagnosis, six months, and 12 months. Blood biobanking will be performed at these time points. Specimens for microbiology will be obtained from sputum/urine, from easily accessible sites of disease (e.g., lymph nodes, abscess) identified in the first FDG-PET/CT, from CT-guided biopsy and/or surgery. Clinical parameters and functional scores will be collected at every physical visit. Data will be entered into RedCap® database; data cleaning, validation and analysis will be performed by the study team. The University of Cape Town Ethics Committee approved the protocol (243/2022).
DISCUSSION
The Spinal TB X cohort study is the first prospective cohort study using whole-body 18FDG-PET/CT scans in patients with microbiologically confirmed spinal tuberculosis. Dual imaging techniques of the spine using FDG-PET/CT and magnetic resonance imaging as well as tissue diagnosis (microbiology and histopathology) will allow us to develop a virtual biopsy model. If successful, a distinct gene-expression profile will aid in blood-based diagnosis (point of care testing) as well as treatment monitoring and would lead to earlier diagnosis of this devastating disease.
TRIAL REGISTRATION
The study has been registered on ClinicalTrials.gov (NCT05610098).
Topics: Humans; Tuberculosis, Spinal; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Prospective Studies; Adult; Follow-Up Studies; Cohort Studies; Transcriptome; Time Factors; Treatment Outcome; Male; Radiopharmaceuticals; Gene Expression Profiling; Female
PubMed: 38918806
DOI: 10.1186/s13018-024-04840-7 -
Skeletal Radiology Jun 2024(I) Characterize the demographics and clinical features of patients with meniscal root tears (MRT); (II) analyze the morphology, extent, and grade of MRT on MRI; (III)...
PURPOSE
(I) Characterize the demographics and clinical features of patients with meniscal root tears (MRT); (II) analyze the morphology, extent, and grade of MRT on MRI; (III) evaluate associated abnormalities on imaging; and (IV) evaluate the associations between imaging findings, demographics, clinical features, and joint structural abnormalities.
MATERIAL AND METHODS
A search was performed to identify meniscal root tears. Age, sex, BMI, and pain were recorded. Knee radiographs and MRI were reviewed. Presence, grade and morphology of MRT, meniscal extrusion, insufficiency fractures, as well as joint structural abnormalities were scored. For goals (I), (II), and (III), tabulations for categorical variables and mean for continuous variables were computed. MRT findings variables were described using percentages. For goal (IV), adjusted linear and logistic regression were employed.
RESULTS
Ninety-six patients with a mean age of 56.6 years (69 females) and mean BMI of 28.9 kg/m were included; 88 of the MRT were located at the posterior horn of the medial meniscus (PHMM), and 82% were radial tear. The mean tear diameter was 3.8 mm, and 78/96 tears presented with meniscal extrusion. Nineteen patients presented with subchondral insufficiency fracture (SIF), which was significantly associated with the gap of the tear (p = 0.001) and grade of the meniscal root lesion (p = 0.005).
CONCLUSION
MRT typically found in middle-aged to older overweight and obese women. Lesions were mostly radial tears and located at PHMM and were frequently associated with meniscal extrusion and SIF. Moreover, the presence of SIF was significantly associated with the gap width and grade of root tear.
PubMed: 38916756
DOI: 10.1007/s00256-024-04724-1 -
The Journal of Foot and Ankle Surgery :... Jun 2024Hallux valgus is one of the most common surgically corrected forefoot deformities. Studies evaluating clinical outcomes of minimally invasive chevron and akin (MICA)...
Hallux valgus is one of the most common surgically corrected forefoot deformities. Studies evaluating clinical outcomes of minimally invasive chevron and akin (MICA) procedure have shown shorter operation time, faster recovery, and smaller scars compared to the open approach. Previous biomechanical cadaveric studies have largely focused on the open approach with minimal on MICA. To our knowledge, no studies have compared different proximal screw placements in MICA which can either be three-point fixation or intramedullary. This study aims to compare the biomechanical properties of fixation between these two techniques in MICA. Six matched pairs of human fresh frozen cadaveric feet were randomized to either three-point fixation or intramedullary groups. Both procedures were performed by a single fellowship-trained orthopaedic foot and ankle surgeon. Using a material testing machine, each specimen underwent 1000 cycles of plantar-to-dorsal uniaxial loads from 0 to 31 N in cantilever configuration while monitoring bending stiffness and distal fragment dorsal angulation. They were then subjected to load until failure at a compression rate of 10 mm/min. Specimens from both groups tolerated the walking fatigue test. Mean bending stiffness of three-point fixation was 84% higher than intramedullary constructs (P=0.002). Mean dorsal angulation of intramedullary was thrice that of three-point fixation constructs (P=0.008). Mean load to failure of three-point fixation was 30% higher than intramedullary constructs (P=0.001). Three-point fixation provide superior biomechanical stability compared to intramedullary proximal screw placement. The surgical technique using three-point proximal screw fixation can offer robust fixation and lead to better clinical outcomes. LEVEL OF CLINICAL EVIDENCE: 5.
PubMed: 38909965
DOI: 10.1053/j.jfas.2024.06.007 -
Journal of Physics. Condensed Matter :... Jun 2024The double-bag theory in modern anatomy suggests that structures with coatings are commonly found in human body at various length scales, such as osteocyte processes...
The double-bag theory in modern anatomy suggests that structures with coatings are commonly found in human body at various length scales, such as osteocyte processes covered by pericellular matrix and bones covered by muscle tissue. To understand the mechanical behaviors and physiological responses of such biological structures, we develop an analytical model to quantify surface effects on the deformation of a coated cylindrical compressible liquid inclusion in an elastic matrix subjected to remote loading. Our analytical solution reveals that coating can either amplify or attenuate the volumetric strain of the inclusion, depending on the relative elastic moduli of inclusion, coating, and matrix. For illustration, we utilize this solution to explore amplification/attenuation of volumetric strain in musculoskeletal systems, nerve cells, and vascular tissues. We demonstrate that coating often plays a crucial role in mechanical regulation of the development and repair of human tissues and cells. Our model provides qualitative analysis of cross-scale mechanical response of coated liquid inclusions, helpful for constructing mechanical microenvironment of cells.
Topics: Humans; Biomechanical Phenomena; Models, Biological; Stress, Mechanical; Elastic Modulus; Compressive Strength
PubMed: 38906135
DOI: 10.1088/1361-648X/ad5ace -
Gait & Posture Jun 2024Femoral deformities are highly prevalent in children with cerebral palsy (CP) and can have a severe impact on patients' gait abilities. While the mechanical stress...
INTRODUCTION
Femoral deformities are highly prevalent in children with cerebral palsy (CP) and can have a severe impact on patients' gait abilities. While the mechanical stress regime within the distal femoral growth plate remains underexplored, understanding it is crucial given bone's adaptive response to mechanical stimuli. We quantified stresses at the distal femoral growth plate to deepen our understanding of the relationship between healthy and pathological gait patterns, internal loading, and femoral growth patterns.
METHODS
This study included three-dimensional motion capture data and magnetic resonance images of 13 typically developing children and twelve participants with cerebral palsy. Employing a multi-scale mechanobiological approach, integrating musculoskeletal simulations and subject-specific finite element analysis, we investigated the orientation of the distal femoral growth plate and the stresses within it. Limbs of participants with CP were grouped depending on their knee flexion kinematics during stance phase as this potentially changes the stresses induced by knee and patellofemoral joint contact forces.
RESULTS
Despite similar growth plate orientation across groups, significant differences were observed in the shape and distribution of growth values. Higher growth rates were noted in the anterior compartment in CP limbs with high knee flexion while CP limbs with normal knee flexion showed high similarity to the group of healthy participants.
DISCUSSION
Results indicate that the knee flexion angle during the stance phase is of high relevance for typical bone growth at the distal femur. The evaluated growth rates reveal plausible results, as long-term promoted growth in the anterior compartment leads to anterior bending of the femur which was confirmed for the group with high knee flexion through analyses of the femoral geometry. The framework for these multi-scale simulations has been made accessible on GitHub, empowering peers to conduct similar mechanobiological studies. Advancing our understanding of femoral bone development could ultimately support clinical decision-making.
PubMed: 38905850
DOI: 10.1016/j.gaitpost.2024.06.012 -
Skeletal Radiology Jun 2024This article will provide a perspective review of the most extensively investigated deep learning (DL) applications for musculoskeletal disease detection that have the... (Review)
Review
This article will provide a perspective review of the most extensively investigated deep learning (DL) applications for musculoskeletal disease detection that have the best potential to translate into routine clinical practice over the next decade. Deep learning methods for detecting fractures, estimating pediatric bone age, calculating bone measurements such as lower extremity alignment and Cobb angle, and grading osteoarthritis on radiographs have been shown to have high diagnostic performance with many of these applications now commercially available for use in clinical practice. Many studies have also documented the feasibility of using DL methods for detecting joint pathology and characterizing bone tumors on magnetic resonance imaging (MRI). However, musculoskeletal disease detection on MRI is difficult as it requires multi-task, multi-class detection of complex abnormalities on multiple image slices with different tissue contrasts. The generalizability of DL methods for musculoskeletal disease detection on MRI is also challenging due to fluctuations in image quality caused by the wide variety of scanners and pulse sequences used in routine MRI protocols. The diagnostic performance of current DL methods for musculoskeletal disease detection must be further evaluated in well-designed prospective studies using large image datasets acquired at different institutions with different imaging parameters and imaging hardware before they can be fully implemented in clinical practice. Future studies must also investigate the true clinical benefits of current DL methods and determine whether they could enhance quality, reduce error rates, improve workflow, and decrease radiologist fatigue and burnout with all of this weighed against the costs.
PubMed: 38902420
DOI: 10.1007/s00256-024-04684-6