ABSTRACT
In human pose estimation methods based on graph convolutional architectures, the human skeleton is usually modeled as an undirected graph whose nodes are body joints and edges are connections between neighboring joints. However, most of these methods tend to focus on learning relationships between body joints of the skeleton using first-order neighbors, ignoring higher-order neighbors and hence limiting their ability to exploit relationships between distant joints. In this paper, we introduce a higher-order regular splitting graph network (RS-Net) for 2D-to-3D human pose estimation using matrix splitting in conjunction with weight and adjacency modulation. The core idea is to capture long-range dependencies between body joints using multi-hop neighborhoods and also to learn different modulation vectors for different body joints as well as a modulation matrix added to the adjacency matrix associated to the skeleton. This learnable modulation matrix helps adjust the graph structure by adding extra graph edges in an effort to learn additional connections between body joints. Instead of using a shared weight matrix for all neighboring body joints, the proposed RS-Net model applies weight unsharing before aggregating the feature vectors associated to the joints in order to capture the different relations between them. Experiments and ablations studies performed on two benchmark datasets demonstrate the effectiveness of our model, achieving superior performance over recent state-of-the-art methods for 3D human pose estimation.
Subject(s)
Benchmarking , Learning , Posture , Humans , Skeleton/diagnostic imagingABSTRACT
During a recent collection expedition to the Rio Negro, in the state of Amazonas, Brazil, eight individuals of an unknown species were collected, with a combination of characteristics that placed the species in the genus Rhadinoloricaria. Furthermore, the presence of two autapomorphic characteristics, including numerous elongated papillae on the lower lip and unbranched barbelets on the margin of lower lip, suggests that it is a new species. From morphological and phylogenetic analyses, including the sequencing of specific genes to calculate the maximum likelihood analyses, coupled with osteological computed tomography (CT) scan analyses, the authors corroborated that the specimens represent a new species of Rhadinoloricaria, described in the present study.
Subject(s)
Catfishes , Animals , Brazil , Catfishes/anatomy & histology , Catfishes/genetics , Phylogeny , Tomography, X-Ray Computed , Skeleton/diagnostic imagingABSTRACT
The human skeleton of a young adult male with marked asymmetry of the bilateral upper extremities was excavated from the Mashiki-Azamabaru site (3000-2000 BCE) on the main island of Okinawa in the southwestern archipelago of Japan. The skeleton was buried alone in a corner of the cemetery. In this study, morphological and radiographic observations were made on this skeleton, and the pathogenesis of the bone growth disorder observed in the left upper limb was discussed. The maximum diameter of the midshaft of the humerus was 13.8 mm on the left and 21.2 mm on the right. The long bones comprising the left upper extremity lost the structure of the muscle attachments except for the deltoid tubercle of the humerus. The bone morphology of the right upper extremity and the bilateral lower extremities was maintained and was close to the mean value of females from the Ohtomo site in northwestern Kyushu, Japan, during the Yayoi period. It is assumed that the anomalous bone morphology confined to the left upper extremity was secondary to the prolonged loss of function of the muscles attached to left extremity bones. In this case, birth palsy, brachial plexus injury in childhood, and acute grey matter myelitis were diagnosed. It was suggested that this person had survived into young adulthood with severe paralysis of the left upper extremity due to injury or disease at an early age.
Subject(s)
Fossils/pathology , Bone Diseases, Developmental/history , Bone Diseases, Developmental/pathology , Brachial Plexus Neuropathies/history , Brachial Plexus Neuropathies/pathology , Diagnosis, Differential , Fossils/diagnostic imaging , Fossils/history , History, Ancient , Humans , Japan , Male , Multidetector Computed Tomography , Paleopathology , Skeleton/diagnostic imaging , Skeleton/pathology , Upper Extremity/diagnostic imaging , Upper Extremity/injuries , Upper Extremity/pathology , Young AdultABSTRACT
Transforming growth factor ß (TGFß) signaling plays an important role in skeletal development. We previously demonstrated that the loss of TGFß receptor II (Tgfbr2) in Osterix-Cre-expressing mesenchyme results in defects in bones and teeth due to reduced proliferation and differentiation in pre-osteoblasts and pre-odontoblasts. These Osterix-Cre;Tgfbr2f/f mice typically die within approximately four weeks for unknown reasons. To investigate the cause of death, we performed extensive pathological analysis on Osterix-Cre- (Cre-), Osterix-Cre+;Tgfbr2f/wt (HET), and Osterix-Cre+;Tgfbr2f/f (CKO) mice. We also crossed Osterix-Cre mice with the ROSA26mTmG reporter line to identify potential off-target Cre expression. The findings recapitulated published skeletal and tooth abnormalities and revealed previously unreported osteochondral dysplasia throughout both the appendicular and axial skeletons in the CKO mice, including the calvaria. Alterations to the nasal area and teeth suggest a potentially reduced capacity to sense and process food, while off-target Cre expression in the gastrointestinal tract may indicate an inability to absorb nutrients. Additionally, altered nasal passages and unexplained changes in diaphragmatic muscle support the possibility of hypoxia. We conclude that these mice likely died due to a combination of breathing difficulties, malnutrition, and starvation resulting primarily from skeletal deformities that decreased their ability to sense, gather, and process food.
Subject(s)
Osteogenesis/genetics , Receptor, Transforming Growth Factor-beta Type II/genetics , Skeleton/abnormalities , Sp7 Transcription Factor/genetics , Animals , Bone and Bones/abnormalities , Bone and Bones/physiopathology , Cell Differentiation/genetics , Disease Models, Animal , Gene Expression Regulation, Developmental/genetics , Humans , Integrases/genetics , Mesoderm/growth & development , Mesoderm/metabolism , Mice , Osteoblasts/metabolism , Osteoblasts/pathology , Signal Transduction/genetics , Skeleton/diagnostic imaging , Skeleton/metabolism , Skeleton/physiopathologyABSTRACT
To develop an artificial intelligence (AI)-based method for the detection of focal skeleton/bone marrow uptake (BMU) in patients with Hodgkin's lymphoma (HL) undergoing staging with FDG-PET/CT. The results of the AI in a separate test group were compared to the interpretations of independent physicians. The skeleton and bone marrow were segmented using a convolutional neural network. The training of AI was based on 153 un-treated patients. Bone uptake significantly higher than the mean BMU was marked as abnormal, and an index, based on the total squared abnormal uptake, was computed to identify the focal uptake. Patients with an index above a predefined threshold were interpreted as having focal uptake. As the test group, 48 un-treated patients who had undergone a staging FDG-PET/CT between 2017-2018 with biopsy-proven HL were retrospectively included. Ten physicians classified the 48 cases regarding focal skeleton/BMU. The majority of the physicians agreed with the AI in 39/48 cases (81%) regarding focal skeleton/bone marrow involvement. Inter-observer agreement between the physicians was moderate, Kappa 0.51 (range 0.25-0.80). An AI-based method can be developed to highlight suspicious focal skeleton/BMU in HL patients staged with FDG-PET/CT. Inter-observer agreement regarding focal BMU is moderate among nuclear medicine physicians.
Subject(s)
Artificial Intelligence , Bone Marrow/metabolism , Hodgkin Disease/diagnosis , Skeleton/diagnostic imaging , Adolescent , Adult , Aged , Aged, 80 and over , Biological Transport/genetics , Biopsy , Bone Marrow/diagnostic imaging , Child , Female , Fluorodeoxyglucose F18/administration & dosage , Hodgkin Disease/diagnostic imaging , Hodgkin Disease/metabolism , Hodgkin Disease/pathology , Humans , Male , Middle Aged , Multimodal Imaging , Musculoskeletal System/diagnostic imaging , Musculoskeletal System/metabolism , Neural Networks, Computer , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals/administration & dosage , Skeleton/metabolism , Skeleton/pathology , Young AdultABSTRACT
PURPOSE: To compare the agreement between whole-body (WB) magnetic resonance (MR) imaging, 18F-FDG PET/CT, and skeletal survey (SS) in patients with multiple myeloma (MM) for diagnosis, initial staging, response evaluation, and early detection of complications. METHODS: This is a retrospective cohort study including MM patients who were diagnosed, treated, and followed in 2 institutions. These patients were studied with SS, WB-MR, and/or 18F-FDG PET/CT. We studied bone lesions by anatomical locations and analyzed the concordance between SS and a tomographic technique (WB-MR or 18F-FDG PET/CT) and between both tomographic techniques (WB-MR and PET/CT). RESULTS: Forty-four MM patients with a mean age of 62.6 years (range, 38-85 years) were included from January 2012 to February 2016. Whole-body MR and 18F-FDG PET/CT found more lesions than SS in every location except in the skull. Concordance between WB-MR and 18F-FDG PET/CT was either good or excellent in most of the locations and in plasmacytoma studies. However, WB-MR was better than 18F-FDG PET/CT in the study of complications (medullar compression and vascular necrosis). CONCLUSIONS: Our results suggest the study of MM patients should include WB-MR and/or 18F-FDG PET/CT, whereas SS is only useful for the skull. Whole-body MR and 18F-FDG PET/CT are complementary techniques, because both of them show good concordance in almost every location. It is still necessary to individualize the indication of each technique according to patient characteristics.
Subject(s)
Fluorodeoxyglucose F18 , Magnetic Resonance Imaging , Multiple Myeloma/pathology , Multiple Myeloma/therapy , Positron Emission Tomography Computed Tomography , Skeleton/diagnostic imaging , Whole Body Imaging , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Multiple Myeloma/diagnostic imaging , Retrospective Studies , Treatment OutcomeABSTRACT
Recently, skeleton-based human action recognition has attracted a lot of research attention in the field of computer vision. Graph convolutional networks (GCNs), which model the human body skeletons as spatial-temporal graphs, have shown excellent results. However, the existing methods only focus on the local physical connection between the joints, and ignore the non-physical dependencies among joints. To address this issue, we propose a hypergraph neural network (Hyper-GNN) to capture both spatial-temporal information and high-order dependencies for skeleton-based action recognition. In particular, to overcome the influence of noise caused by unrelated joints, we design the Hyper-GNN to extract the local and global structure information via the hyperedge (i.e., non-physical connection) constructions. In addition, the hypergraph attention mechanism and improved residual module are induced to further obtain the discriminative feature representations. Finally, a three-stream Hyper-GNN fusion architecture is adopted in the whole framework for action recognition. The experimental results performed on two benchmark datasets demonstrate that our proposed method can achieve the best performance when compared with the state-of-the-art skeleton-based methods.
Subject(s)
Imaging, Three-Dimensional/methods , Neural Networks, Computer , Skeleton , Algorithms , Human Activities , Humans , Movement/physiology , Skeleton/diagnostic imaging , Skeleton/physiologyABSTRACT
Primary Sjögren's syndrome (pSS) is a chronic slowly progressive autoimmune disease characterised by lymphocytic infiltration of salivary and lacrimal glands with varying degree of systemic involvement. Renal involvement, a recognised extraglandular manifestation of pSS, is commonly related to tubular dysfunction and generally manifests as distal renal tubular acidosis (RTA), proximal RTA, tubular proteinuria and nephrogenic diabetes insipidus. Untreated long-standing RTA is known to cause metabolic bone disease. Here, we present the report of a patient with sclerotic metabolic bone disease related to pSS with combined distal and proximal RTA and negative workup for other causes of sclerotic bone disease. A significant clinical and biochemical improvement, including recovery of proximal tubular dysfunction, was noted with alkali therapy. This case suggests the need to consider pSS in the diagnostic algorithm of a patient presenting with sclerotic bone disease.
Subject(s)
Acidosis, Renal Tubular/diagnosis , Back Pain/immunology , Bone Diseases, Metabolic/diagnosis , Sjogren's Syndrome/diagnosis , Absorptiometry, Photon , Acidosis, Renal Tubular/blood , Acidosis, Renal Tubular/drug therapy , Acidosis, Renal Tubular/immunology , Adult , Alkaline Phosphatase/blood , Back Pain/blood , Bone Density/immunology , Bone Diseases, Metabolic/blood , Bone Diseases, Metabolic/drug therapy , Bone Diseases, Metabolic/immunology , Female , Humans , Potassium Citrate/therapeutic use , Radionuclide Imaging , Sjogren's Syndrome/blood , Sjogren's Syndrome/complications , Sjogren's Syndrome/immunology , Skeleton/diagnostic imaging , Sodium Bicarbonate/therapeutic useABSTRACT
The purpose of this study was to estimate the phenotypic associations between residual food intake (RFI) and carcass traits, evaluated by ultrasonography, of young Nellore bulls. Information about 53 young Nelore bulls, pure origin (PO), participants in the Individual Performance Test of Nelore Bulls, carried out at the Capim Branco experimental farm of the Federal University of Uberlândia (UFU) were used for this purpose. It was evaluated the characteristics of residual feed intake (RFI), rib eye area (REA), marbling (MAR) and fat thickness (FT). In order to estimate the Spearman and Pearson correlation coefficients, the SAS program was used. Regarding the influence of the RFI classes (low RFI, medium RFI and high RFI) on carcass traits, an out analysis of variance was carried out using the least squares method. It was verified that there was no phenotypic association between RFI and the characteristics of REA and MAR, but the relation between FT and the phenotypic association revealed a medium magnitude. However, when evaluating the RFI classes, it was observed that there were no significant differences of the RFI classes with the carcass traits (REA, FT and MAR). It is recommended that new studies are carried out to verify if the selection for RFI does not result in damages to the finishing of carcass in Nelore cattle.
Subject(s)
Phenotype , Skeleton/diagnostic imaging , Cattle , EatingABSTRACT
Despite descending from heavily calcified ancestors, the holothuroid skeleton is fully internal and composed of microscopic ossicles and a ring of plates bound by connective tissue, the calcareous ring. The calcareous ring exhibits a complex and poorly understood morphology; as a result, establishing unambiguous homology statements about its macrostructure has been challenging and phylogenetic studies have had to simplify this important structure. Here, we provide the first broad comparative study of Dendrochirotida calcareous rings using micro-computed tomography (µCT). A detailed description of the three-dimensional macrostructure of the calcareous ring of 10 sea cucumber species, including rare and type specimens, is presented. The structures observed were highly variable at the subfamily level, especially at the point of tissue attachment. The relationship between the calcareous ring and its associated organs, and their functional morphology are discussed. To aid future phylogenetic studies, we listed 22 characters and performed a preliminary cladistic analysis. The topology obtained supports the idea that the simple, cucumariid ring is ancestral to the mosaic-like phyllophorid ring; however, it did not support the monophyly of the cucumariids. It also did not support the family Sclerodactylidae, which was described based on the ring morphology. Differently from the dermal ossicles, which are highly homoplastic, the general homoplasy index of the calcareous ring characters was relatively low. This result highlights the importance of this structure for phylogenetic inference. Unfortunately, time since collection, rough collection methods and fixation can damage the skeleton, and the calcareous ring is often overlooked in taxonomic descriptions. The data presented here will improve our understanding of holothuroid relationships and facilitate studies on holothuroid functional morphology and biomechanics.
Subject(s)
Sea Cucumbers/anatomy & histology , Skeleton/diagnostic imaging , Animals , Phylogeny , Skeleton/anatomy & histology , X-Ray MicrotomographyABSTRACT
Literature describes different patterns of calcaneal facets for the talus in terms of whether some calcaneal facets are connected or separated from each other or completely absent. The aim of this study was to establish the patterns of calcaneal facets for the talus, to calculate their total area, and to analyse the data with respect to gender. The study involved 59 calcanei which were photographed. The patterns of calcaneal facets noted in this study were compared with the patterns from the literature. ImageJ program was used to measure different parameters on calcanei. The pattern 1 was the most commonly found in the study sample (45.76%), then the pattern 2 (40.68%), and finally the pattern 3 (13.56%). That order of frequencies is the same in both sexes. The patterns 1 and 2 have a larger contact surface for the talus in comparison to the pattern 3. Male bones have a larger contact surface for the talus than female bones. The sum of the pattern 1 and pattern 3 frequencies was high. Knowing the frequency of different patterns of calcaneal facets for the talus in a certain population is important for orthopaedic surgeons when performing foot osteotomy.
Subject(s)
Arthritis/diagnostic imaging , Calcaneus/diagnostic imaging , Talus/diagnostic imaging , Zygapophyseal Joint/diagnostic imaging , Arthritis/physiopathology , Calcaneus/physiopathology , Calcaneus/surgery , Female , Humans , Male , Orthopedic Procedures , Pakistan/epidemiology , Serbia/epidemiology , Skeleton/diagnostic imaging , Skeleton/physiopathology , Skeleton/surgery , Talus/physiopathology , Talus/surgery , Zygapophyseal Joint/physiopathology , Zygapophyseal Joint/surgeryABSTRACT
Two analytical methods based on the neutrons high penetrability, i.e. neutron diffraction (ND) and neutron computed tomography (NCT) were used to investigate the structure of the aragonitic skeleton of an exemplar/sample of Dipastraea pallida (Dana 1846), a modern hermatypic coral. ND was used to reconstruct the orientation distribution function (ODF) of the crystalline fibrils which compose the coral skeleton. Accordingly, 684 ND spectra were analyzed using the Rietveld method. The result confirmed the aragonite as the sole mineral component of coral skeleton, allowing to recalculate the ODF of aragonite fibrils and to represent it by means of (100), (010) and (001) crystallographic planes pole figures (PF). Experimental PF showed a remarkable similarity with PF recalculated by considering that all aragonite fibrils are oriented either along the growth axis of polyp cups or perpendicular to this direction. This result confirmed the previous observations based on optical microscopy, proving at the same time the availability of ND for such types of investigations. In turn, NCT evidenced the individual polyp cups, their interlocked 3D rigid porous structure as well as a periodic variation of density which could be attributed to a seasonal influence of the marine environment. Different from the classical X-ray computed tomography, the NCT, in view of neutron high cross-section for hydrogen, demonstrated the presence of a small amount of organic matter, otherwise transparent for X- and gamma rays.
Subject(s)
Anthozoa/metabolism , Anthozoa/physiology , Calcification, Physiologic , Calcium Carbonate/metabolism , Neutron Diffraction/methods , Neutrons , Skeleton/diagnostic imaging , Skeleton/metabolism , Tomography, X-Ray Computed/methods , Animals , CrystallographyABSTRACT
La mucopolisacaridosis tipo IV (MPS-IV) también conocida como enfermedad de Morquio en recuerdo del pediatra uruguayo Luis Morquio que la describió por primera vez, es una enfermedad congénita causada por la deficiencia de la enzima N-acetilgalactosamina 6 sulfatasa o de la enzima B-Galactosidasa. Estas anomalías enzimáticas tienen como consecuencia que se acumulen en diferentes tejidos del organismo cantidades elevadas de mucopolisacaridos. En la bibliografía se describe con detalle los defectos del esmalte que presentan los pacientes diagnosticados del síndrome de Morquio. Estos defectos son una característica aparentemente constante en la enfermedad y, por lo tanto, hace necesaria las visitas al odontólogo para su control evitándose problemas mayores. Dichos defectos consisten en un esmalte anormalmente delgado, que es áspero debido a los numerosos hoyos diminutos y a una superficie irregular. La delgadez del esmalte da como resultado una forma alterada y decoloración de los dientes que, añadido a los diastemas interdentales, provocan alteraciones en la oclusión. Aparte de estos defectos, el esmalte es histológicamente normal y tiene una du-reza y radiodensidad normales. El trata-miento odontológico de los pacientes con MPS-IV requiere colaboración multidisciplinar, debido a que las manifestaciones orales de la enfermedad pueden aparecer a cualquier edad, resultando en ocasiones tedioso para el paciente y complicado para el profesional. Especial mención merecen las terapias utilizadas como trata-miento sintomático de la enfermedad, así como el manejo de la vía aérea en el caso de intervenciones bajo anestesia general o sedación para tratar ciertas patologías del territorio bucomaxilodental
Mucopolysaccharidosis type IV (MPS-IV) also known as Morquios disease in memory of the Uruguayan pediatrician Luis Morquio who described it for the first time, is a congenital disease caused by the deficiency of the enzyme N-acetylgalactosamine 6 sulfatase or enzyme B -Galactosidase. These enzymatic anomalies result in high amounts of mucopolysaccharides accumulating in different tissues of the organism. The enamel defects presented by patients diagnosed with Morquio syndrome are described in detail in the bibliography. These defects are an apparently constant feature in the disease and, therefore, make visits to the dentist necessary for their control, avoiding major problems. These defects consist of an abnormally thin enamel that is rough due to numerous tiny holes and an irregular surface. The thinness of the enamel results in an altered form and discoloration of the teeth, which added to the interdental diastemas, cause alterations in the occlusion. Apart from these defects, the enamel is histologically normal and has a normal hardness and radiodensity.Dental treatment of patients with MPS-IV requires multidisciplinary collaboration, because the oral manifestations of the disease can appear at any age, being sometimes tedious for the patient and complicated for the professional. Special mention should be made of the therapies used as a symptomatic treatment of the disease, as well as the management of the airway in the case of interventions under general anesthesia or sedation to treat certain pathologies of the bucomaxillodental territory
Subject(s)
Humans , Tooth Abnormalities/etiology , Tooth Abnormalities/pathology , Mucopolysaccharidoses/genetics , Mucopolysaccharidoses/physiopathology , Tooth Abnormalities/therapy , Mucopolysaccharidoses/classification , Mucopolysaccharidoses/etiology , Visual Acuity , Rib Cage/diagnostic imaging , Rib Cage/physiopathology , Skeleton/abnormalities , Skeleton/diagnostic imaging , Dental Enamel/abnormalitiesABSTRACT
Spaceflight is a unique environment that includes at least two factors which can negatively impact skeletal health: microgravity and ionizing radiation. We have previously shown that a diet supplemented with dried plum powder (DP) prevented radiation-induced bone loss in mice. In this study, we investigated the capacity of the DP diet to prevent bone loss in mice following exposure to simulated spaceflight, combining microgravity (by hindlimb unloading) and radiation exposure. The DP diet was effective at preventing most decrements in bone micro-architectural and mechanical properties due to hindlimb unloading alone and simulated spaceflight. Furthermore, we show that the DP diet can protect osteoprogenitors from impairments resulting from simulated microgravity. Based on our findings, a dietary supplementation with DP could be an effective countermeasure against the skeletal deficits observed in astronauts during spaceflight.
Subject(s)
Bone Diseases, Metabolic/prevention & control , Cosmic Radiation/adverse effects , Hindlimb Suspension/adverse effects , Prunus domestica , Space Flight , Animals , Bone Density/physiology , Bone Density/radiation effects , Bone Diseases, Metabolic/diagnosis , Bone Diseases, Metabolic/etiology , Bone Diseases, Metabolic/physiopathology , Disease Models, Animal , Food, Preserved , Hindlimb Suspension/physiology , Humans , Male , Mice , Skeleton/diagnostic imaging , Skeleton/physiopathology , Skeleton/radiation effects , X-Ray MicrotomographyABSTRACT
BACKGROUND: TSC1-related signaling plays a pivotal role in intramembranous and endochondral ossification processes during skeletogenesis. This study was aimed at determining the significance of the TSC1 gene at different stages of spinal development. Materials and Methods. TSC1-floxed mice (TSC1flox/flox) were crossed with Prrx1-Cre or BGLAP-Cre transgenic mice or mesenchymal stem cell- and osteoblast-specific TSC1-deficient mice, respectively. Somatic and vertebral differences between WT and Prrx1-TSC1 null mice were examined at 4 weeks after birth. RESULTS: No apparent body size abnormalities were apparent in newborn and 4-week- to 2-month-old mice with BGLAP-Cre driver-depleted TSC1. Vertebral and intervertebral discs displayed strong dysplasia in Prrx1-TSC1 null mice. In contrast, vertebrae were only slightly affected, and intervertebral discs from skeletal preparations displayed no apparent changes in BGLAP-TSC1 null mice. CONCLUSION: Our data suggest that the TSC1 gene is crucial for endochondral ossification during postnatal spine development but plays discriminative roles at different stages. Mesenchymal stem cell-specific ablation of TSC1 led to severe spinal dysplasia at early stages of endochondral ossification while osteoblast-specific deletion of TSC1 affected vertebrae slightly and had no detectable effects on intervertebral discs.
Subject(s)
Mesenchymal Stem Cells/metabolism , Osteoblasts/metabolism , Osteogenesis/genetics , Osteogenesis/physiology , Tuberous Sclerosis Complex 1 Protein/genetics , Tuberous Sclerosis Complex 1 Protein/metabolism , Animals , Bone Density , Bone Development/genetics , Bone Development/physiology , Gene Expression Regulation, Developmental , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Intervertebral Disc , Mice , Mice, Knockout , Mice, Transgenic , Osteoblasts/pathology , Osteocalcin/genetics , Osteocalcin/metabolism , Signal Transduction , Skeleton/diagnostic imaging , Skeleton/pathologyABSTRACT
Desbuquois dysplasia (DD) type 1 is a rare skeletal dysplasia characterized by a short stature, round face, progressive scoliosis, and joint laxity. The causative gene has been identified as calcium-activated nucleotidase 1 (CANT1), which encodes a nucleotidase that preferentially hydrolyzes UDP to UMP and phosphate. In this study, we generated Cant1 KO mice using CRISPR/Cas9-mediated genome editing. All F0 mice possessing frameshift deletions at both Cant1 alleles exhibited a dwarf phenotype. Germline transmission of the edited allele was confirmed in an F0 heterozygous mouse, and KO mice were generated by crossing of the heterozygous breeding pairs. Cant1 KO mice exhibited skeletal defects, including short stature, thoracic kyphosis, and delta phalanx, all of which are observed in DD type 1 patients. The glycosaminoglycan (GAG) content and extracellular matrix space were reduced in the growth plate cartilage of mutants, and proliferating chondrocytes lost their typical flat shape and became round. Chondrocyte differentiation, especially terminal differentiation to hypertrophic chondrocytes, was impaired in Cant1 KO mice. These findings indicate that CANT1 is involved in the synthesis of GAG and regulation of chondrocyte differentiation in the cartilage and contribute to a better understanding of the pathogenesis of DD type 1.
Subject(s)
Acid Anhydride Hydrolases/deficiency , Craniofacial Abnormalities/genetics , Dwarfism/genetics , Growth Plate/pathology , Joint Instability/genetics , Ossification, Heterotopic/genetics , Polydactyly/genetics , Acid Anhydride Hydrolases/genetics , Animals , Cell Differentiation/genetics , Chondrocytes/pathology , Craniofacial Abnormalities/diagnosis , Craniofacial Abnormalities/pathology , Disease Models, Animal , Dwarfism/diagnosis , Dwarfism/pathology , Female , Glycosaminoglycans/biosynthesis , Growth Plate/cytology , Growth Plate/growth & development , Humans , Joint Instability/diagnosis , Joint Instability/pathology , Male , Mice , Mice, Knockout , Ossification, Heterotopic/diagnosis , Ossification, Heterotopic/pathology , Polydactyly/diagnosis , Polydactyly/pathology , Skeleton/diagnostic imaging , Skeleton/growth & developmentABSTRACT
BACKGROUND: Axial and extra-axial deceleration in function and progressive joint pain with subsequent development of antalgic gait associated with swellings, and stiffness of the joints with loss of the physiological spine biomechanics were the natural history in this group of patients. Clinical and radiological phenotypes have been analysed carefully to further understand the aetiology behind. METHODS: Seven patients (three children around the age of 9-11 and one child of 17 years old). Three adults aging 25, 30, 33 and 40 years old were seen and examined. The paediatric group of patients were initially diagnosed with myopathy followed later by juvenile rheumatoid arthritis in other institutions. Clinical and imaging documentation were collected in our departments, followed by mutation screening, was carried out by bidirectional sequencing of the WISP3 gene. RESULTS: Clinical and radiological phenotypic studies confirmed the diagnosis of progressive pseudorheumatoid chondrodysplasia. A constellation of abnormalities such as early senile hyperostosis of the spine (Forestier disease), osteoarthritis of the hips showed progressive diminution and irregularities of the hip joint spaces associated with progressive capital femoral epiphyseal dysplasia and coxa vara have been encountered. Loss-of-function homozygous mutations (c.667T>G, p.Cys223Gly) and (c.170C>A, p.Ser57*) in the WISP3 gene were identified in our patients. CONCLUSION: The definite diagnosis was not defined via vigorous myopathic and rheumatologic investigations. Detailed clinical examination and skeletal survey, followed by genotypic confirmation, were our fundamental pointers to rule out the false diagnosis of juvenile rheumatoid arthritis and rheumatoid polyarthritis in the adult group of patients. We wish to stress that the clinical/radiological phenotype is the baseline tool to establish a definite diagnosis and to guide the geneticist toward proper genotype.Key Pointsâ¢Joint pain and difficulties in walking/climbing the stairs are characteristic features encountered in early childhood. False diagnosis of juvenile rheumatoid arthritis can be made at this point.â¢False positive-like muscular wasting resembling myopathy results in ensuing vigorous troublesome investigations.â¢Flattened vertebral bodies associated with defective ossification of the anterior end plates are characteristic features of progressive pseudorheumatoid chondrodysplasia.â¢Joint expansions, which are usually accompanied by narrowing of the articular ends of the appendicular skeletal system, show a clear radiological phenotype of pseudorheumatoid chondrodysplasia.
Subject(s)
Bone Morphogenetic Proteins/metabolism , CCN Intercellular Signaling Proteins/genetics , Joint Diseases/congenital , Skeleton/diagnostic imaging , Wnt Signaling Pathway , Adolescent , Adult , Child , Humans , Joint Diseases/diagnostic imaging , Joint Diseases/genetics , Joint Diseases/metabolism , Phenotype , Radiography , Retrospective StudiesABSTRACT
Peer-reviewed abstracts presented at the 2019 Society of Skeletal Radiology (SSR) Annual Meeting were reviewed following oral presentation. Topics felt to be of potential interest to musculoskeletal (MSK) investigators and practicing clinicians are highlighted in this compilation and analysis of the meeting. New concepts regarding MSK imaging and intervention, MSK protocols and techniques, and quality improvement are included. ePoster highlights are also presented.
Subject(s)
Bone Diseases/diagnostic imaging , Skeleton/diagnostic imaging , HumansABSTRACT
Accurate age estimation in wildlife conservation is an important diagnostic tool in the interpretation of biological data, necropsy examination, reproductive status and population demographics. The most frequently utilized methods to age bottlenose dolphins (Tursiops truncatus) include tooth extraction; counting dental growth layer groups and dental radiography. These methods are inaccurate in dolphins > 13 years old, due to overlapping of the growth layer groups in dolphins and worn teeth. Establishing a non-invasive method of accurately aging bottlenose dolphins across the entire age range is important to long term conservation efforts to understand health status, lifespan, reproduction and survivability. A database of 126 radiographs from 94 dolphins of known chronological age was utilized to establish the stages of skeletal ossification over time. A numerical score from -1 to 8 was assigned to 16 anatomic locations on the pectoral radiograph, to create a formula to estimate age. The most informative areas to evaluate morphologically were the metaphyseal regions of the radius and ulna, and the proximal and distal epiphysis of metacarpals II and III. Third order polynomial regression calculated separate age predictor formulas for male and female dolphins, with females reaching sexual maturity earlier than males. Completion of epiphyseal closure of the long bones correlated with average sexual maturity. Managed care dolphin ages could be properly estimated with decreasing precision from within 3 months in animals < 5 years old, to within 5 years in animals > 30 years old. This diagnostic tool could also be applied to diagnose atypical ossification patterns consistent with nutritional, developmental or growth abnormalities, and identifying subclinical health issues. In conclusion, knowledge of the lifespan and the onset of sexual maturity for each species will allow this model to be applied to other cetaceans, facilitating age estimation via pectoral radiography in future research.