Discontinuities in the endothelium of epiphyseal cartilage canals and relevance to joint disease in foals

Cartilage canals have been shown to contain discontinuous blood vessels that enable circulating bacteria to bind to cartilage matrix, leading to vascular occlusion and associated pathological changes in pigs and chickens. It is also inconsistently reported that cartilage canals are surrounded by a cellular or acellular wall that may influence whether bacterial binding can occur. It is not known whether equine cartilage canals contain discontinuous endothelium or are surrounded by a wall. This study aimed to examine whether there were discontinuities in the endothelium of cartilage canal vessels, and whether canals had a cellular or acellular wall, in the epiphyseal growth cartilage of foals. Epiphyseal growth cartilage from the proximal third of the medial trochlear ridge of the distal femur from six healthy foals that were 1, 24, 35, 47, 118 and 122 days old and of different breeds and sexes was examined by light microscopy (LM), transmission electron microscopy (TEM) and immunohistochemistry. The majority of patent cartilage canals contained blood vessels that were lined by a thin layer of continuous endothelium. Fenestrations were found in two locations in one venule in a patent cartilage canal located deep in the growth cartilage and close to the ossification front in the 118-day-old foal. Chondrifying cartilage canals in all TEM-examined foals contained degenerated endothelial cells that were detached from the basement membrane, resulting in gap formation. Thirty-three percent of all canals were surrounded by a hypercellular rim that was interpreted as contribution of chondrocytes to growth cartilage. On LM, 69% of all cartilage canals were surrounded by a ring of matrix that stained intensely eosinophilic and consisted of collagen fibres on TEM that were confirmed to be collagen type I by immunohistochemistry. In summary, two types of discontinuity were observed in the endothelium of equine epiphyseal cartilage canal vessels: fenestrations were observed in a patent cartilage canal in the 118-day-old foal; and gaps were observed in chondrifying cartilage canals in all TEM-examined foals. Canals were not surrounded by any cellular wall, but a large proportion was surrounded by an acellular wall consisting of collagen type I. Bacterial binding can therefore probably occur in horses by mechanisms that are similar to those previously demonstrated in pigs and chickens

Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin

Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently used proximal V, D and J genes in complete IGH gene rearrangements, despite normal Ig locus contraction. Fewer N-nucleotides were added in IGH gene rearrangements in the context of low TdT and XRCC4 expression. Moreover, fetal progenitor-B cells expressed lower levels of IL7Rα than their pediatric counterparts. Analysis of progenitor-B cells from IL7Rα-deficient patients revealed that TdT expression and N-nucleotides additions in Dh-Jh junctions were dependent on functional IL7Rα. Thus, IL7Rα affects TdT expression, and decreased expression of this receptor underlies at least in part the skewed Ig repertoire formation in fetal B-cell precursors. These new insights provide a better understanding of the formation of adaptive immunity in the developing fetus

Osteochondrosis in the central and third tarsal bones of young horses

Recently, the central and third tarsal bones of 23 equine fetuses and foals were examined using micro-computed tomography. Radiological changes, including incomplete ossification and focal ossification defects interpreted as osteochondrosis, were detected in 16 of 23 cases. The geometry of the osteochondrosis defects suggested they were the result of vascular failure, but this requires histological confirmation. The study aim was to examine central and third tarsal bones from the 16 cases and to describe the tissues present, cartilage canals, and lesions, including suspected osteochondrosis lesions. Cases included 9 males and 7 females from 0 to 150 days of age, comprising 11 Icelandic horses, 2 standardbred horses, 2 warmblood riding horses, and 1 coldblooded trotting horse. Until 4 days of age, all aspects of the bones were covered by growth cartilage, but from 105 days, the dorsal and plantar aspects were covered by fibrous tissue undergoing intramembranous ossification. Cartilage canal vessels gradually decreased but were present in most cases up to 122 days and were absent in the next available case at 150 days. Radiological osteochondrosis defects were confirmed in histological sections from 3 cases and consisted of necrotic vessels surrounded by ischemic chondronecrosis (articular osteochondrosis) and areas of retained, morphologically viable hypertrophic chondrocytes (physeal osteochondrosis). The central and third tarsal bones formed by both endochondral and intramembranous ossification. The blood supply to the growth cartilage of the central and third tarsal bones regressed between 122 and 150 days of age. Radiological osteochondrosis defects represented vascular failure, with chondrocyte necrosis and retention, or a combination of articular and physeal osteochondrosis

Alterskapet fra Aure kirke. Undersøkelse og dokumentasjon

Utført på oppdrag av Riksantikvaren

Quantifying the hydroxyapatite orientation near the ossification front in a piglet femoral condyle using X-ray diffraction tensor tomography

While a detailed knowledge of the hierarchical structure and morphology of the extracellular matrix is considered crucial for understanding the physiological and mechanical properties of bone and cartilage, the orientation of collagen fibres and carbonated hydroxyapatite (HA) crystallites remains a debated topic. Conventional microscopy techniques for orientational imaging require destructive sample sectioning, which both precludes further studies of the intact sample and potentially changes the microstructure. In this work, we use X-ray diffraction tensor tomography to image non-destructively in 3D the HA orientation in a medial femoral condyle of a piglet. By exploiting the anisotropic HA diffraction signal, 3D maps showing systematic local variations of the HA crystallite orientation in the growing subchondral bone and in the adjacent mineralized growth cartilage are obtained. Orientation maps of HA crystallites over a large field of view (~ 3 7 3 7 3 mm3) close to the ossification (bone-growth) front are compared with high-resolution X-ray propagation phase-contrast computed tomography images. The HA crystallites are found to predominantly orient with their crystallite c-axis directed towards the ossification front. Distinct patterns of HA preferred orientation are found in the vicinity of cartilage canals protruding from the subchondral bone. The demonstrated ability of retrieving 3D orientation maps of bone-cartilage structures is expected to give a better understanding of the physiological properties of bones, including their propensity for bone-cartilage diseases

Osteochondrosis in the central and third tarsal bones of young horses

Publisher Copyright: © The Author(s) 2023.Recently, the central and third tarsal bones of 23 equine fetuses and foals were examined using micro-computed tomography. Radiological changes, including incomplete ossification and focal ossification defects interpreted as osteochondrosis, were detected in 16 of 23 cases. The geometry of the osteochondrosis defects suggested they were the result of vascular failure, but this requires histological confirmation. The study aim was to examine central and third tarsal bones from the 16 cases and to describe the tissues present, cartilage canals, and lesions, including suspected osteochondrosis lesions. Cases included 9 males and 7 females from 0 to 150 days of age, comprising 11 Icelandic horses, 2 standardbred horses, 2 warmblood riding horses, and 1 coldblooded trotting horse. Until 4 days of age, all aspects of the bones were covered by growth cartilage, but from 105 days, the dorsal and plantar aspects were covered by fibrous tissue undergoing intramembranous ossification. Cartilage canal vessels gradually decreased but were present in most cases up to 122 days and were absent in the next available case at 150 days. Radiological osteochondrosis defects were confirmed in histological sections from 3 cases and consisted of necrotic vessels surrounded by ischemic chondronecrosis (articular osteochondrosis) and areas of retained, morphologically viable hypertrophic chondrocytes (physeal osteochondrosis). The central and third tarsal bones formed by both endochondral and intramembranous ossification. The blood supply to the growth cartilage of the central and third tarsal bones regressed between 122 and 150 days of age. Radiological osteochondrosis defects represented vascular failure, with chondrocyte necrosis and retention, or a combination of articular and physeal osteochondrosis.Peer reviewe

Performance of an Artificial Intelligence System for Breast Cancer Detection on Screening Mammograms from BreastScreen Norway

A commercially available artificial intelligence system showed high performance in detecting breast cancers within 2 years of screening mammography and may help triage low-risk mammograms to reduce radiologist workload. Purpose - To explore the stand-alone breast cancer detection performance, at different risk score thresholds, of a commercially available artificial intelligence (AI) system. Materials and Methods - This retrospective study included information from 661 695 digital mammographic examinations performed among 242 629 female individuals screened as a part of BreastScreen Norway, 2004–2018. The study sample included 3807 screen-detected cancers and 1110 interval breast cancers. A continuous examination-level risk score by the AI system was used to measure performance as the area under the receiver operating characteristic curve (AUC) with 95% CIs and cancer detection at different AI risk score thresholds. Results - The AUC of the AI system was 0.93 (95% CI: 0.92, 0.93) for screen-detected cancers and interval breast cancers combined and 0.97 (95% CI: 0.97, 0.97) for screen-detected cancers. In a setting where 10% of the examinations with the highest AI risk scores were defined as positive and 90% with the lowest scores as negative, 92.0% (3502 of 3807) of the screen-detected cancers and 44.6% (495 of 1110) of the interval breast cancers were identified with AI. In this scenario, 68.5% (10 987 of 16 040) of false-positive screening results (negative recall assessment) were considered negative by AI. When 50% was used as the cutoff, 99.3% (3781 of 3807) of the screen-detected cancers and 85.2% (946 of 1110) of the interval breast cancers were identified as positive by AI, whereas 17.0% (2725 of 16 040) of the false-positive results were considered negative. Conclusion - The AI system showed high performance in detecting breast cancers within 2 years of screening mammography and a potential for use to triage low-risk mammograms to reduce radiologist workload

Cartilage canals in the pathogenesis of osteochondrosis in horses

Avhandling utgitt ved Norwegian School of Veterinary Science, Department of Companion Animal Clinical Sciences. Section for Equine Medicine and SurgeryOsteochondrosis (OC) is a common disease that arises in the developing joints of people, horses, pigs, dogs and other species. OC is defined as a disturbance in enchondral ossification, and in horses, the disturbance is due to primary disease of growth cartilage. At the epiphyseal growth cartilage, the disturbance tends to occur at specific predilection sites, and can lead to the formation of partially or completely detached fragments, or subchondral bone cysts, at these sites. The fragments consist of cartilage with or without bone. Whereas articular cartilage is avascular, growth cartilage has a rich blood supply during the early phases of development through so-called cartilage canals. Cartilage canals have been implicated in the pathogenesis of OC in pigs and horses.Osteochondrose (OC) er en vanlig sykdom som oppstår under utviklingen av ledd hos mennesker, hester, griser, hunder og andre arter. OC er definert som en forstyrrelse i den enchondrale forbeiningsprosessen, og hos hester oppstår denne forstyrrelsen som en følge av patologiske forandringer i vekstbrusken. I den epifyseale vekstbrusken oppstår forstyrrelsen på spesifikke, såkalte predileksjonssteder, og kan føre til helt eller delvis løse fragmenter (osteochondrosis dissecans, OCD), eller subchondrale bencyster, på disse stedene i leddet. Fragmentene består av brusk med eller uten benvev. Leddbrusk er avaskulær, mens vekstbrusk har en rikelig blodforsyning under de tidlige fasene av vekst gjennom såkalte karkanaler. Karkanaler har vært assosiert med patogenesen for OC hos griser og hester.submittedVersio