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Osteochondrosis ( OC) is the most prevalent developmental orthopaedic disease in the horse. It is a complex disorder because of the interplay of factors that influence the formation of lesions and the ensuing natural healing process, the end result of which determines clinical outcome. The early pathogenetic mechanism of OC has long remained elusive, but recent research has provided compelling evidence for vascular disturbances leading to areas of ischaemic necrosis in the subarticular growth cartilage as the primary event. The aetiological factors that influence the process of the development of lesions are many and comprise both genetic and environmental factors. The genetic background of OC (dissecans) is highly complex with quantitative trait loci associated with some form of OC found on not fewer than 22 of the 33 chromosomes of the horse, and different manifestations and locations of OC having probably different genetic backgrounds. The environmental factors can be divided into nutritional factors and factors influencing the biomechanical loading of joints. Feeding large quantities of easily digestible carbohydrates is a clear risk factor and also the availability of sufficient copper for mares in the last part of pregnancy is important. Factors influencing the biomechanical loading of joints include the exercise regimen of foals, paddock size and roughness of terrain, and conformation. Equine OC is rarely a life-threatening disease and the prognosis of (surgical) treatment is good to very good. However, the impact on economics of the equine industry and on horse welfare is large. This impact can only be lessened by the judicious management of both horse breeding and horse husbandry. Some of the measures that would alleviate the burden of OC conflict with (commercial) pressures from the industry and a balance between human-imposed breeding and performance goals and the interest of the animal itself should be sought. [ABSTRACT FROM AUTHOR]

Osteochondrosis arises as a result of focal failure of the blood supply to growth cartilage. The current aim was to examine the pathogenesis of pseudocysts and true cysts in subchondral bone following failure of the blood supply to the articular-epiphyseal cartilage complex in horses. Cases were recruited based on identification of lesions (n = 17) that were considered likely to progress to or to represent pseudocysts or true cysts in epiphyseal bone in histological sections and included 10 horses ranging in age from 48 days to 5 years old. Cases comprised 3 warmbloods, 3 Standardbreds, 1 Quarter horse and 1 Arabian with spontaneous lesions and 2 Fjord ponies with experimentally induced lesions. Seven lesions consisted of areas of ischemic chondronecrosis and were compatible with pseudocysts. Two lesions were located at intermediate depth in epiphyseal growth cartilage, 2 lesions were located in the ossification front, 2 lesions were located in epiphyseal bone and 1 lesion was located in the metaphyseal growth plate (physis). Ten lesions contained dilated blood vessels and were compatible with true cysts. In 2 lesions the dilated blood vessels were located within the lumina of failed cartilage canals. In the 8 remaining lesions areas of ischemic chondronecrosis were associated with granulation tissue in the subjacent bone and dilated vessels were located within this granulation tissue. Failure of the blood supply and ischemic chondronecrosis can lead to formation of pseudocysts or dilatation of blood vessels and formation of true cysts in the epiphyseal bone of horses. [ABSTRACT FROM AUTHOR]

Tracking individual variation in the dynamics of parasite infections in wild populations is often complicated by lack of knowledge of the epidemiological history of hosts. Whereas the dynamics and development of Gyrodactylus salaris Malmberg, 1957, on Atlantic salmon, Salmo salar L., are known from laboratory studies, knowledge about infection development on individual wild fishes is currently sparse. In this study, the dynamics of an infection of G. salaris on individually marked Atlantic salmon parr was followed in a section of a natural stream. During the 6-week experiment, the prevalence increased from 3.3 to 60.0%, with an average increase in intensity of 4.1% day−1. Survival analyses showed an initially high probability (93.6%) of staying uninfected by G. salaris, decreasing significantly to 37% after 6 weeks. The results showed that even at subarctic water temperatures and with an initially low risk of infection, the parasite spread rapidly in the Atlantic salmon population, with the capacity to reach 100% prevalence within a short summer season. The study thus track individual infection trajectories of Atlantic salmon living under near-natural conditions, providing an integration of key population parameters from controlled experiments with the dynamics of the epizootic observed in free-living living populations. [ABSTRACT FROM AUTHOR]

Reasons for performing study: To increase understanding of why the prevalence of clinical/radiographic osteochond rosis (OC) dissecans is high in horses and low in ponies. Objectives: To investigate whether the clinical difference in OC occurrence between horses and ponies could partly be explained by a difference in: 1) number of patent vessels in the epiphyseal growth cartilage; 2) duration of the presence of patent cartilage canals; or 3) growth cartilage thickness at predilection sites for OC. The hypothesis was that pony foals would have fewer cartilage canals, shorter duration of blood supply and thinner growth cartilage than horse foals. Study design: Observational, cross-sectional study. Methods: Nine Standardbred foals (horse group) 1-49 days old and 11 Norwegian Fjord foals (pony group) 1-62 days old were included. A total of 15 anatomical locations in the tarsocrural and metatarsophalangeal joints were examined by one or more of the following techniques: arterial perfusion; photography of cleared specimens; microcomputed tomography; radiography; and histology. The number of cartilage canals was counted. Cartilage thickness was measured. Duration of blood supply was assessed in histological sections. Results: Of the 3 common predilection sites for OC investigated, there were significantly fewer vessels (P = 0.003) and thinner cartilage (P = 0.002) at the distal lateral trochlear ridge of the talus in the pony group. There was no difference in the duration of presence of cartilage canals between the groups. Conclusion: The hypothesis that pony foals would have fewer cartilage canals and thinner growth cartilage than horse foals was confirmed for the lateral trochlear ridge of the talus. The current results may contribute towards an explanation for the low prevalence of OC at the distal lateral trochlear ridge of the talus in pony foals. [ABSTRACT FROM AUTHOR]

Atlantic salmon, Salmo salar L. parr (age 1+), infected by the monogenean ectoparasite Gyrodactylus salaris ( Malmberg, 1957), were exposed to chlorine ( Cl)-enriched water at three different concentrations: Cllow (0-5 μg Cl L−1), Clmedium (18 μg Cl L−1) and Clhigh (50 μg Cl L−1). There was a negative correlation between G. salaris infections and the hypochlorite concentrations added. The parasite infection was eliminated by day 6-8 and day 2-4 in the groups Clmedium and Clhigh, respectively, while inhibition of G. salaris population growth was observed in the Cllow group. An important note to this matter, however, is that the G. salaris specimens observed at day 6 in Clmedium and at day 2 in Clhigh were all considered dead by subjective judgement. No mortality in the salmon parr was observed during the first 8 days of the experiment, demonstrating that Cl has a stronger effect on G. salaris than on the salmonid host. The differences in sensitivity between the parasite and the Atlantic salmon indicate that hypochlorite has a potential use as a parasiticide with a therapeutic margin. The low-dose sensitivity may imply that Cl pollution in urban areas may pose a greater risk towards biodiversity than previously assumed. [ABSTRACT FROM AUTHOR]

Being able to image the microstructure of growth cartilage is important for understanding the onset and progression of diseases such as osteochondrosis and osteoarthritis, as well as for developing new treatments and implants. Studies of cartilage using conventional optical brightfield microscopy rely heavily on histological staining, where the added chemicals provide tissue-specific colours. Other microscopy contrast mechanisms include polarization, phase- and scattering contrast, enabling non-stained or 'label-free' imaging that significantly simplifies the sample preparation, thereby also reducing the risk of artefacts. Traditional high-performance microscopes tend to be both bulky and expensive. Computational imaging denotes a range of techniques where computers with dedicated algorithms are used as an integral part of the image formation process. Computational imaging offers many advantages like 3D measurements, aberration correction and quantitative phase contrast, often combined with comparably cheap and compact hardware. X-ray microscopy is also progressing rapidly, in certain ways trailing the development of optical microscopy. In this study, we first briefly review the structures of growth cartilage and relevant microscopy characterization techniques, with an emphasis on Fourier ptychographic microscopy (FPM) and advanced x-ray microscopies. We next demonstrate with our own results computational imaging through FPM and compare the images with hematoxylin eosin and saffron (HES)-stained histology. Zernike phase contrast, and the nonlinear optical microscopy techniques of second harmonic generation (SHG) and two-photon excitation fluorescence (TPEF) are explored. Furthermore, X-ray attenuation-, phase- and diffraction-contrast computed tomography (CT) images of the very same sample are presented for comparisons. Future perspectives on the links to artificial intelligence, dynamic studies and in vivo possibilities conclude the article., (Creative Commons Attribution license.)

Background: The neuro-central synchondrosis (NCS) is a physis responsible for the growth of the dorsal third of the vertebral body and neural arches. When the NCS of pigs is tethered to model scoliosis, stenosis also ensues. It is necessary to describe the NCS for future evaluation of its potential role in equine spinal cord compression and ataxia (wobbler syndrome)., Objectives: To describe the NCS, including when it and other physes closed in computed tomographic (CT) scans of the cervical spine of foals, due to its potential role in vertebral stenosis., Study Design: Post-mortem cohort study., Methods: The cervical spine of 35 cases, comprising both sexes and miscellaneous breeds from 153 gestational days to 438 days old, was examined with CT and physes scored from 6: fully open to 0: fully closed. The dorsal physis, physis of the dens and mid-NCS were scored separately, whereas the cranial and caudal NCS portions were scored together with the respective cranial and caudal vertebral body physes., Results: The NCS was a pair of thin physes located in a predominantly dorsal plane between the vertebral body and neural arches. The mid-NCS was closed in C1 from 115 days of age, and in C2-C7 from 38 days of age. The dorsal physis closed later than the NCS in C1, and earlier than the NCS in C2-C7. The dens physis was closed from 227 days of age. The cranial and caudal physes were closing, but not closed from different ages in the different vertebrae of the oldest cases., Main Limitations: Hospital population., Conclusions: The NCS was a thin physis that contributed mainly to height-wise growth, but also width- and length-wise growth of the vertebral body and neural arches. The mid-NCS was closed in all cervical vertebrae from 115 days of age. The NCS warrants further investigation in the pathogenesis of vertebral stenosis., (© 2024 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Developmental trauma has a profound effect on people's lives. There are few studies of the perceived difficulties and treatment needs of adolescents with developmental trauma. More studies are called for to explore the perspectives and experiences of these patients, especially adolescents., Method: Semi-structured interviews were conducted with eight adolescents with developmental trauma aged 14-18 years in a Child and Adolescent Mental Health Service, Outpatient Unit. The interviews were analyzed using systematic text condensation., Results: A main finding in this study regards the participants' understanding of why they needed therapy: symptom alleviation and coping tools. They expressed a need for talking with a safe and reliable adult who understood their situation. Their stories of daily functioning and bodily sensations align mainly with symptoms described for adolescents with developmental trauma. The study also shows that the participants' experiences of trauma affected their lives to a greater or lesser extent, in the form of ambivalence, avoidance, regulation, and coping strategies. They also described various physical problems, especially insomnia and inner restlessness. Their subjective stories revealed insights into their experiences., Conclusion: Based on the results, we recommend that adolescents with developmental trauma be allowed to express their understandings of their difficulties and their treatment expectations at an early stage of their therapy. An emphasis on patient involvement and the therapeutic relationship can increase their autonomy and control over their own lives and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Olstad, Sørensen, Lien and Danbolt.)

The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.

Background: Osteochondrosis is a major cause of leg weakness in pigs. Selection against osteochondrosis is currently based on manual scoring of computed tomographic (CT) scans for the presence of osteochondrosis manifesta lesions. It would be advantageous if osteochondrosis could be diagnosed automatically, through artificial intelligence methods using machine learning. The aim of this study was to describe a method for labelling articular osteochondrosis lesions in CT scans of four pig joints to guide development of future machine learning algorithms, and to report new observations made during the labelling process. The shoulder, elbow, stifle and hock joints were evaluated in CT scans of 201 pigs., Results: Six thousand two hundred fifty osteochondrosis manifesta and cyst-like lesions were labelled in 201 pigs representing a total volume of 211,721.83 mm 3 . The per-joint prevalence of osteochondrosis ranged from 64.7% in the hock to 100% in the stifle joint. The lowest number of lesions was found in the hock joint at 208 lesions, and the highest number of lesions was found in the stifle joint at 4306 lesions. The mean volume per lesion ranged from 26.21 mm 3 in the shoulder to 42.06 mm 3 in the elbow joint. Pigs with the highest number of lesions had small lesions, whereas pigs with few lesions frequently had large lesions, that have the potential to become clinically significant. In the stifle joint, lesion number had a moderate negative correlation with mean lesion volume at r = - 0.54, p < 0.001., Conclusions: The described labelling method is an important step towards developing a machine learning algorithm that will enable automated diagnosis of osteochondrosis manifesta and cyst-like lesions. Both lesion number and volume should be considered during breeding selection. The apparent inverse relationship between lesion number and volume warrants further investigation., (© 2022. The Author(s).)

Background: Meaning in life is important to achieve quality of life, psychological well-being and good mental health. Existential issues such as meaning in life have limited attention in mental health care and treatment for children and young people in Norway. People in crisis often ponder existential questions. We find little research on this topic in relation to therapists who work with adolescents with developmental trauma. The purpose of this study was to examine how meaning in life is understood and addressed from the perspectives of therapists working with adolescents struggling with trauma., Method: The study has a qualitative design, based on focus groups with therapists in mental health care for children and adolescents. The interviews were transcribed and analyzed using systematic text condensation., Results: Therapists had limited professional experience and competence to address and explore meaning as a topic in therapy. Yet there was interest in the topic and they thought that young people with trauma experience may benefit from the incorporation of meaning perspectives into therapy., Conclusion: Therapists at a mental health outpatient clinic for children and adolescents found the topic of meaning important but challenging to involve in the treatment of adolescents with developmental trauma. There is a need for more research to enhance understanding of what it means to include meaning as a topic in child and adolescent psychiatry, and what may be the specific benefit and challenges involved., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Olstad, Lien, Leonhardt, Sørensen and Danbolt.)

Background: Computed tomography (CT) is used to evaluate body composition and limb osteochondrosis in selection of breeding boars. Pigs also develop heritably predisposed abnormal curvature of the spine including juvenile kyphosis. It has been suggested that osteochondrosis-like changes cause vertebral wedging and kyphosis, both of which are identifiable by CT. The aim of the current study was to examine the spine from occiput to sacrum to map changes and evaluate relationships, especially whether osteochondrosis caused juvenile kyphosis, in which case CT could be used in selection against it. Whole-body CT scans were collected retrospectively from 37 Landrace or Duroc boars with poor back conformation scores. Spine curvature and vertebral shape were evaluated, and all inter-vertebral, articular process and rib joints from the occiput to the sacrum were assessed for osteochondrosis and other lesions., Results: Twenty-seven of the 37 (73%) pigs had normal spine curvature, whereas 10/37 (27%) pigs had abnormal curvature and all of them had wedge vertebrae. The 37 pigs had 875 focal lesions in articular process and rib joints, 98.5% of which represented stages of osteochondrosis. Five of the 37 pigs had focal lesions in other parts of vertebrae, mainly consisting of vertebral body osteochondrosis. The 10 pigs with abnormal curvature had 21 wedge vertebrae, comprising 10 vertebrae without focal lesions, six ventral wedge vertebrae with ventral osteochondrosis lesions and five dorsal wedge vertebrae with lesions in the neuro-central synchondrosis, articular process or rib joints., Conclusions: Computed tomography was suited for identification of wedge vertebrae, and kyphosis was due to ventral wedge vertebrae compatible with heritably predisposed vertebral body osteochondrosis. Articular process and rib joint osteochondrosis may represent incidental findings in wedge vertebrae. The role of the neuro-central synchondrosis in the pathogenesis of vertebral wedging warrants further investigation., (© 2022. The Author(s).)

Background: Osteochondrosis occurs due to failure of the blood supply to growth cartilage. Osteochondrosis lesions have been identified in small tarsal bones and suggested to cause distal tarsal osteoarthritis; however, it has not been determined whether distal tarsal osteochondrosis lesions were the result of vascular failure., Objectives: To perform post-mortem arterial perfusion and micro-computed tomography (CT) of the central (CTB) and third tarsal bones (TIII) of fetuses and foals up to 5 months old, to describe tarsal development and any lesions detected., Study Design: Descriptive, nonconsecutive case series., Methods: Twenty-three animals that died or were euthanased from 228 days of gestation to 5 months old were collected, comprising two fetuses and nine foals of miscellaneous breeds and 12 Icelandic Horse foals, a breed with high prevalence of distal tarsal osteoarthritis. One hindlimb from each foal was perfused arterially with barium, and the CTB and TIII were examined with micro-CT., Results: Perfusion yielded partial information from 41% of the animals. The CTB and TIII were supplied by nutrient arteries and perichondrial vessels with vertical, transverse and circumferential configurations. Fourteen of the 23 (61%) animals had focal defects in the ossification front, that is, radiological osteochondrosis. The majority of lesions matched the configuration and development of vertical vessels. Additionally, full-thickness, cylindrical defects matched transverse vessels, and the long axes of some dorsal lesions matched circumferential vessels., Main Limitations: Lack of histological validation., Conclusions: Post-mortem perfusion was poor for examination of the blood supply to the growth cartilage of the CTB and TIII. Radiological osteochondrosis lesions were compatible with vascular failure because they were focal, and because lesion geometry matched vessel configuration. The relationship between osteochondrosis and distal tarsal osteoarthritis warrants further investigation., (© 2021 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

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 × 3 × 3 mm 3 ) 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.

Background: Growth cartilage is found in the articular-epiphyseal cartilage complex (AECC) and the physis. It has a temporary blood supply organised as end arteries. Vascular failure is associated with osteochondrosis, but infection can also obstruct vessels. The location of bacteria was recently compared to arterial perfusion, and the results indicated that they were located in the distal tips of AECC end arteries. Systematic perfusion studies were not available for comparison to the infected physes. Further studies may improve our understanding of infections and other pathologies., Objectives: To describe development of the blood supply to the growth cartilage of the medial femoral condyle in fetuses and foals from 228 days of gestation to 62 days old., Study Design: Ex vivo arterial perfusion study., Methods: The left medial femoral condyle of 10 Norwegian Fjord Pony fetuses and foals (228 days of gestation to 62 days old) and one Norwegian-Swedish Coldblooded Trotter foal (10 days old) was arterially perfused with barium and underwent micro-computed tomography, qualitative and quantitative description of vessels., Results: In the fetus, the physis was supplied by metaphyseal-origin arteries. In 1-10 day-old foals, the physis was supplied by a mixture of metaphyseal- and epiphyseal-origin arteries, and from 15 days of age by epiphyseal-origin arteries only. The number of vessels increased before it decreased in both the AECC and the physis postnatally. Vessels in the cartilage showed a monopodial branching pattern, whereas vessels in epiphyseal and metaphyseal bone showed both monopodial and dichotomous branching., Main Limitations: Foals with confirmed pathologies were not examined., Conclusions: The blood supply to growth cartilage changed with age, including the physeal supply that changed from metaphyseal- to epiphyseal-origin arteries. The number of vessels increased before it decreased postnatally, and two different branching patterns were observed. These results may improve our understanding of growth cartilage vascular failure and osteomyelitis., (© The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Introduction: The majority of new HIV infections occur through mucosal transmission. The availability of readily applicable and accessible platforms for anti-retroviral (ARV) delivery is critical for the prevention of HIV acquisition through sexual transmission in both women and men. There is a compelling need for developing new topical delivery systems that have advantages over the pills, gels and rings, which currently fail to guarantee protection against mucosal viral transmission in vulnerable populations due to lack of user compliance. The silk fibroin (SF) platform offers another option that may be better suited to individual circumstances and preferences to increase efficacy through user compliance. The objective of this study was to test safety and efficacy of SF for anti-HIV drug delivery to mucosal sites and for viral prevention., Methods: We formulated a potent HIV inhibitor Griffithsin (Grft) in a mucoadhesive silk fibroin (SF) drug delivery platform and tested the application in a non-human primate model in vivo and a pre-clinical human cervical and colorectal tissue explant model. Both vaginal and rectal compartments were assessed in rhesus macaques (Mucaca mulatta) that received SF (n = 4), no SF (n = 7) and SF-Grft (n = 11). In this study, we evaluated the composition of local microbiota, inflammatory cytokine production, histopathological changes in the vaginal and rectal compartments and mucosal protection after ex vivo SHIV challenge., Results: Effective Grft release and retention in mucosal tissues from the SF-Grft platform resulted in protection against HIV in human cervical and colorectal tissue as well as against SHIV challenge in both rhesus macaque vaginal and rectal tissues. Mucoadhesion of SF-Grft inserts did not cause any inflammatory responses or changes in local microbiota., Conclusions: We demonstrated that in vivo delivery of SF-Grft in rhesus macaques fully protects against SHIV challenge ex vivo after two hours of application and is safe to use in both the vaginal and rectal compartments. Our study provides support for the development of silk fibroin as a highly promising, user-friendly HIV prevention modality to address the global disparity in HIV infection., (© 2020 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Articular osteochondrosis follows a dynamic development pattern. Lesions arise, in incidence peaks compatible with failure of cartilage canal vessels during incorporation into bone, and can also resolve. Lesions that resolve before examination at a single time point will constitute false-negative diagnoses. The aim of the study was to identify physeal osteochondrosis lesions in pigs and monitor their development by computed tomography (CT), to determine if they follow a similar dynamic development pattern to articular osteochondrosis., Results: Thirteen physes were evaluated bilaterally in up to eight biweekly CT scans from 18 male Landrace pigs age 70-180 days (total: 112 scans), generating 2912 scores. There were 1754 (60%) lesion-negative scores and 1158 (40%) lesion-positive scores. Positive scores comprised 138 lesions present at the start and 235 lesions that developed during the study, from 4 to 32 lesions per physis (median: 15 lesions). There were 1-2 peaks in the incidence curves for 12/13 examined physes, the exception being the proximal humerus. Positive scores also included 785 times that lesions persisted, from 1.3-4.8 examination intervals per lesion (median: 2.8 intervals). Negative scores included 190 times that lesions resolved, from 19 to 100% of lesions per physis (median: 65%). Lesions resolved by filling with bone from marginal sclerosis and reparative ossification centres. In the distal scapula and distal fibula, perichondrial new bone formation occurred that led to permanent enlargement of physeal regions. Angular limb deformity was not identified in any pig., Conclusions: Physeal osteochondrosis followed a similar dynamic development pattern to articular osteochondrosis. There were peaks in the incidence curves, compatible with failure of vessels during incorporation into bone. In some physes, osteochondrosis led to permanent enlargement, potentially relevant for decubital ulcers. The relationship between physeal osteochondrosis and angular limb deformity must be examined further in pigs over 6 months old in future.

Articular osteochondrosis (OC) arises due to vascular failure and ischemic chondronecrosis. The aim of the study was to describe the histological and computed tomographic (CT) characteristics of changes in the distal femoral physis of pigs, to determine if they represented OC lesions and if the pathogenesis was the same as for articular OC. The material included 19 male Landrace pigs bred for predisposition to OC. One or 2 pigs were euthanized and CT-scanned at 2-week intervals from 82 to 180 days of age. Material from 10 pigs was available for histological validation. The CT scans revealed 31 lesions confirmed in 3 planes and 1 additional macroscopically visible lesion confirmed in 2 CT planes. Twelve of the lesions were histologically validated. All lesions were compatible with OC. Cartilage canal and eosinophilic streak morphological changes corresponded to failure of end arteries coursing from the epiphysis, toward the metaphysis. The location of lesions was compatible with failure at the point of vessel incorporation into bone. Vascular failure was associated with retention of viable hypertrophic chondrocytes and delayed ossification but not cartilage necrosis. Lesion width ranged from 1.1% to 45.6% of the physis. Several lesions were expected to resolve due to small size and evidence of CT-identifiable, reparative ossification. Angular limb deformity was not detected in any pig. The pathogenesis of physeal OC started with vascular failure that was morphologically identical to articular OC. The heritable predisposition may therefore be the same. The association between lesions and limb deformity should be studied further in older pigs in future.

Pancreatic islet cell tumours are rare in non-human primates. The majority of reported cases are benign islet cell adenomas in rhesus macaques (Macaca mullata). Here we describe a pancreatic tumour composed of both exocrine and endocrine cells known as a mixed acinar-neuroendocrine carcinoma in a captive rhesus macaque. A diagnosis of a mixed tumour requires intermingling of neoplastic exocrine and neuroendocrine cells and must be differentiated from ductal adenocarcinomas in which only the ductal component is neoplastic with interspersed normal neuroendocrine cells. Immunohistochemistry, including antibodies against cytokeratin 7 and chromogranin A, was used to demonstrate that both exocrine and endocrine neoplastic cells exhibited cellular atypia, invasion into the adjacent parenchyma and intraparenchymal metastasis consistent with a mixed malignant tumour. Expression of multiple hormones such as gastrin, insulin, pancreatic polypeptide and somatostatin was also observed throughout the neoplastic cell population, while the endocrine component of the neoplasm was predominantly positive for glucagon., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Young Standardbred horses frequently develop fragments in joints. Some fragments represent osteochondrosis; others are considered developmental, but it is uncertain whether they result from preceding osteochondrosis. Osteochondrosis occurs as a consequence of failure of the cartilage canal blood supply and ischaemic chondronecrosis. In heritably predisposed foals, failure was associated with incorporation of vessels into bone. However, bacterial vascular failure was also recently documented in foals suffering spontaneous infections, proving that bacteria can cause osteochondral lesions in foals up to 150 days old. The aim was to determine prevalence of fetlock and hock lesions at screening age in Standardbred horses that survived infections before 6 months of age, and compare this to prevalence reported in the literature., Methods: The material consisted of 28 Standardbred horses; 17 males and 11 females that presented and were diagnosed clinically with bacterial infections from 1 to 150 days of age (average: 41.3 days). A screening set of 8 radiographic projections was available from all 28 horses at 7-85 months of age (average: 23.6 months). Lesion prevalence was compared to three previously reported Standardbred cohorts., Results: Osteochondral lesions were detected in one or more joints of 19/28 horses (67.9%); in the fetlock joint of 14/28 horses (50%) and the hock joint of 11/28 horses (39.3%). These prevalences were ≥ 2 x higher than the corresponding prevalences in the comparison cohorts, and statistically significantly so in 5:6 comparisons (p-values from < 0.00001 to 0.01). In the sepsis cohort, there were an average of 2.3 affected joints and 2.5 lesions per affected horse, whereas there in the one comparable literature cohort were an average of 1.5 affected joints and 1.7 lesions per affected horse., Conclusions: Standardbred horses that survived bacterial infections before 6 months of age had more osteochondral lesions than literature comparison cohorts at screening age. The implication was that some of the lesions in this group were caused by bacteria. It may become necessary to develop methods for differentiating between acquired, septic and aseptic, heritably predisposed lesions.