Richard Read

The work mental health nurses undertake is widely acknowledged as being challenging. Stressors encountered in the workplace can negatively impact nurses' psychological wellbeing and contribute to issues with retaining nurses in the profession. There is limited interventional research that focuses on external factors that foster nurse wellbeing. This study aimed to evaluate a peer group intervention to promote nurse wellbeing. A longitudinal mixed-methods study with an equal status concurrent design was undertaken. Qualitative and quantitative data were collected via semi-structured interviews and surveys across three timepoints, baseline, mid-intervention, and post-intervention. Qualitative data were collected to explore interviewees' experiences of participating in the intervention, and quantitative data were obtained to assess for any measurable effect on wellbeing outcomes. Fifteen peer group participants completed semi-structured interviews. There were n = 28 responses to the baseline survey, n = 27 returned the mid-intervention survey, and n = 25 responded to the post-intervention survey. Qualitative data analysis identified four main themes: Attending Peer Group, Participating in Peer Group, Impact on the Individual, and Unrelated Workplace Change. Wellbeing scores were found to be significantly modified by the number of peer group sessions attended for depression (p = 0.006), stress (p = 0.004), and emotional exhaustion (p = 0.02) By the post-intervention survey, more favourable scores were significantly associated with higher attendance levels for all three measures. Integration of the qualitative findings and quantitative results demonstrated potential benefits of peer groups for nurse wellbeing. Given that greater exposure to the intervention was associated with better outcomes, facilitating attendance is essential to realise the benefits of peer groups.

Objective(s): Meniscectomy (MX) of sheep induces a well-established animal model of human osteoarthritis (OA). This study compared the clinical (lameness) and pathological outcomes of unilateral, complete medial MX vs two less traumatic and more easily performed meniscal destabilisation procedures. Methods: Four-year old wethers (n = 6/group) underwent sham operation, cranial pole release (CPR), mid-body transection (MBT) or total MX of the medial meniscus. Joints were assessed for gross pathology (cartilage erosion and osteophytes), histomorphometry, two histopathology scoring methods (modified Mankin-type and Pritzker score), and immunohistology for ADAMTS- and MMP-cleaved neoepitopes, at 12 weeks post-op. Ground reaction forces (GRFs) were determined by force plate in a subset (n = 4/group) at baseline, 2.5, 8, and 12 weeks post-op. Results: Gross pathology scores of operated groups differed significantly from sham animals (P < 0.05) but not from each other, though qualitative differences were noted: CPR sheep developed more cranial and focal lesions, while MBT and MX joints showed more widespread lesions and osteophyte formation. Similarly, histopathology scores were significantly elevated vs sham but did not differ between operated groups at P < 0.05, except for a trend for lower tibial cartilage histopathology in MBT consistent with the immunohistologic pattern of reduced aggrecanase-cleavage neoepitope in that model. CPR sheep developed less femoral subchondral sclerosis, suggesting some residual biomechanical effect from the destabilised but intact meniscus. Few significant differences were noted between operated groups in force plate analyses, though gait abnormalities appeared to be least in CPR sheep, and most persistent (>12 weeks) in MBT animals. Conclusion: The well-validated ovine MX model and the simpler meniscal destabilisation procedures resulted in broadly similar joint pathology and lameness. Meniscal CPR or MBT, as easier and more clinically relevant procedures, may represent preferred models for the induction of OA and evaluation of potential disease-modifying therapies.

Osteoarthritis (OA) is a highly prevalent joint disease. Its slow progressive nature and the correlation between pathological changes and clinical symptoms mean that OA is often well advanced by the time of diagnosis. In the absence of any specific pharmacological treatments, there is a pressing need to develop robust biomarkers for OA. We have adopted a nuclear magnetic resonance (NMR)-based metabolomic strategy to identify molecular responses to surgically induced OA in an animal model. Sheep underwent one of three types of surgical procedure (sham (control), meniscal destabilization, MD or anterior cruciate ligament transaction, ACLT), and for every animal a serum sample was collected both pre- and postoperatively, thus, affording two types of "control" data for comparison. 1D 1H NMR spectra were acquired from each sample at 800 MHz and the digitized spectral data were analyzed using principal components analysis and partial least-squares regression discriminant analysis. Our approach, combined with the study design, allowed us to separate the metabolic responses to surgical intervention from those associated with OA. We were able to identify dimethyl sulfone (DMSO 2) as being increased in MD after 4 weeks, while ACLT-induced OA exhibited increased 3-methylhistidine and decreased branched chain amino acids (BCAAs). The findings are discussed in the context of interpretation of metabolomic results in studies of human disease, and the selection of appropriate "control" data sets.

Objectives: To investigate the regulation of sclerostin (SOST) in osteoarthritis (OA) and its potential effects on articular cartilage degradation. Methods: SOST and other Wnt-β-catenin components were immuno-localised in osteochondral sections of surgically-induced OA in knees of sheep and mice, and human OA samples obtained at arthroplasty. Regulation of SOST mRNA and protein expression by ovine chondrocytes in response to interleukin-1α (IL-1α) or tumour necrosis factor-α (TNFα) was examined in explant cultures. The effect of 25 or 250. ng/ml recombinant SOST alone or in combination with IL-1α, on ovine articular cartilage explant aggrecan degradation, and chondrocyte gene expression of Wnt-β-catenin pathway proteins, metalloproteinases and their inhibitors, and cartilage matrix proteins was quantified. Results: Contrary to being an osteocyte-specific protein, SOST was expressed by articular chondrocytes, and mRNA levels were upregulated in vitro by IL-1α but not TNFα. Chondrocyte SOST staining was significantly increased only in the focal area of cartilage damage in surgically-induced OA in sheep and mice, as well as end-stage human OA. In contrast, osteocyte SOST was focally decreased in the subchondral bone in sheep OA in association with bone sclerosis. SOST was biologically active in chondrocytes, inhibiting Wnt-β-catenin signalling and catabolic metalloproteinase [matrix metalloproteinases (MMP) and distintegrin and metalloproteinase with thrombospndin repeats (ADAMTS)] expression, but also decreasing mRNA levels of aggrecan, collagen II and tissue inhibitors of metalloproteinaes (TIMPs). Despite this mixed effect, SOST dose-dependently inhibited IL-1α-stimulated cartilage aggrecanolysis in vitro. Conclusions: These results implicate SOST in regulating the OA disease processes, but suggest opposing effects by promoting disease-associated subchondral bone sclerosis while inhibiting degradation of cartilage.

Characterising the metabolic response to an intervention can be challenging due to the large inter-subject variation. Because traditional chemometric approaches such as OPLS -DA do not take into account the paired data structure in these studies, we have adopted multivariate paired data analysis (MVPDA) to enhance the recovery of metabolic biomarkers from sheep subjected to surgically-induced osteoarthritis (OA). Sheep underwent one of three types of surgical procedure (sham (control), meniscal destabilisation, MD or anterior cruciate ligament transaction, ACLT), and for every animal a serum sample was collected prior to being operated on and at sacrifice. 1D 1H NMR spectra were acquired from each sample at 800 MHz. Results from traditional chemometric techniques (PCA, OPLS-DA) were compared and contrasted with MVPDA, which displayed enhanced classification and interpretability. MVPDA showed all types of surgical procedure were associated with elevated lactate and deceased TMAO/betaine. Serum from sheep that underwent ACLT was additionally characterised by elevated branched-chain amino acids (BCAAs) and decreased histidine, consistent with previous findings. There was no observable change in BCAAs for the MD cohort indicating that different OA subtypes were associated with unique metabolic fingerprints. This study reinforces the utility of MVPDA for datasets with a paired structure, and offers new insights into the metabolic consequences of OA.

Objective: To describe signalment, clinical findings, imaging and treatment of intestinal sand impaction in the dog. Methods: Medical records of dogs with radiographic evidence of small intestinal sand impaction were reviewed. Results: Sand impaction resulting in small intestinal obstruction was diagnosed in eight dogs. All dogs presented with signs of vomiting. Other clinical signs included anorexia, lethargy and abdominal pain. Radiographs confirmed the presence of radio-opaque material consistent with sand causing distension of the terminal small intestine in all dogs. Four dogs were treated surgically for their impaction and four dogs were managed medically. Seven of the eight dogs survived. Clinical Significance: Both medical and surgical management of intestinal sand impaction in the dog can be effective and both afford a good prognosis for recovery.

Objective: Sheep and goats are commonly used large animal species for studying pathogenesis and treatment of osteoarthritis (OA). This review focuses on the macroscopic and microscopic criteria for assessing OA in sheep and goats and recommends particular assessment criteria to assist standardization in the conduct and reporting of preclinical trials of OA. Methods: A review was conducted of all published OA studies using sheep and goats and the most common macroscopic, microscopic, or ultrastructural scoring systems were summarised. General recommendations regarding methods of OA assessment in the sheep and goat have been made and a preliminary study of their reliability and utility was undertaken. Results: The modified Mankin scoring system is recommended for semiquantitative histological assessment of OA due to its already widespread adoption, ease of use, similarity to scoring systems used for OA in humans, and its achievable inter-rater reliability. Specific recommendations are also provided for histological scoring of synovitis and scoring of macroscopic lesions of OA. Conclusions: The proposed system for assessment of sheep and goat articular tissues appears to provide a useful versatile method to quantify OA change. It is hoped that by adopting more standardised quantitative outcome measures, better comparison between different studies and arthritis models will be possible. The suggested scoring systems can be modified in the future as our knowledge of disease pathophysiology advances.

The study design included a multidisciplinary examination of the mineral phase of ovine intervertebral disc calcifications. The objective of the study was to investigate the mineral phase and its mechanisms of formation/association with degeneration in a naturally occurring animal model of disc calcification. The aetiology of dystrophic disc calcification in adult humans is unknown, but occurs as a well-described clinical disorder with hydroxyapatite as the single mineral phase. Comparable but age-related pathology in the sheep could serve as a model for the human disorder. Lumbar intervertebral discs (n = 134) of adult sheep of age 6 years (n = 4), 8 years (n = 12) and 11 years (n = 2) were evaluated using radiography, morphology, scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray powder diffraction, histology, immunohistology and proteoglycan analysis. Half of the 6-year, 84% of the 8-year and 86% of the 11-year-old discs had calcific deposits. These were not well delineated by plain radiography. They were either: (a) punctate deposits in the outer annulus, (b) diffuse deposits in the transitional zone or inner annulus fibrosus with occasional deposits in the nucleus, or (c) large deposits in the transitional zone extending variably into the nucleus. Their maximal incidence was in the lower lumbar discs (L4/5-L6/7) with no calcification seen in the lumbosacral or lower thoracic discs. All deposits were hydroxyapatite with large crystallite sizes (800-1,300 Å) compared to cortical bone (300-600 Å). No type X-collagen, osteopontin or osteonectin were detected in calcific deposits, although positive staining for bone sialoprotein was evident. Calcified discs had less proteoglycan of smaller hydrodynamic size than non-calcified discs. Disc calcification in ageing sheep is due to hydroxyapatite deposition. The variable, but large, crystal size and lack of protein markers indicate that this does not occur by an endochondral ossification-like process. The decrease in disc proteoglycan content and size suggests that calcification may precede or predispose to disc degeneration in ageing sheep.

OBJECTIVES: Published scoring methods for quantifying synovitis focus on acute inflammatory parameters, and are unsuitable as outcome measures in experimental surgical models of osteoarthritis (OA). The aim of the present study was to define a modified histopathological scoring system for ovine synovium more suited to the chronic pathology induced by ovine meniscectomy, and to apply it to detect any therapeutic effects following intraarticular injection of hyaluronan (HA) (Hyalgan®). METHODS: OA was induced in 12 sheep by bilateral lateral meniscectomy, before weekly intraarticular injections of HA or saline vehicle from 16-20 weeks post-operatively, prior to sacrifice at 26 weeks. Six matched sheep were used as controls. Synovial sections were qualitatively scored for hyperplasia, inflammatory infiltrate, fibrosis, and hypervascularity; cell number, depth of fibrosis, and vessel number were also quantified using a graticule. RESULTS: OA synovia had significantly elevated scores for inflammatory cell infiltration, subintimal fibrosis, vascularity, and aggregate score relative to controls. HA-treated sheep had significantly lower vascularity score (p=0.015), aggregate score (p=0.007), depth of fibrosis (p=0.003) and vessel number (p=0.048) compared to saline-injected sheep. CONCLUSIONS: This study confirms the presence of a chronic synovitis in this OA model, characterised by subintimal fibrosis and hypervascularity (but only modest infiltrate and minimal intimal hyperplasia), which is partially ameliorated by intraarticular hyaluronate therapy.

Objective — To apply a novel technique and use the number and size (diameter and mean area) of vascular foramina to estimate potential blood supply in the metacarpophalangeal bones of dogs. Animals — 28 Greyhounds. Procedures — The forelimb sesamoid bones of 23 dogs were obtained after dogs were euthanized. Bones were isolated and examined by scanning electron microscopy. The number, diameter, and area of vascular foramina were determined by image analysis. Arterial distribution was assessed by use of resin injection in the sesamoid bones of 5 additional dogs. Results — Sesamoids 2 and 7 had significantly fewer foramina (mean ± SE, 38.9 ± 2.5) and lower total foramen area (0.55 ± 0.04 mm2), compared with values for other sesamoids (70.4 ± 3.3 foramina and 1.43 ± 0.06 mm2, respectively). Mean area and diameter of foramina of sesamoids 2 and 7 were also smaller in some regions. Comparison of the foramen distribution in dogs with sesamoid disease and clinically normal dogs revealed that for sesamoids 2 and 7, intact sesamoids from dogs with sesamoid disease had a significantly lower total foramen area (20 sesamoids from 9 dogs, 0.45 ± 0.04 mm2), compared with sesamoids in clinically normal dogs (59 sesamoids from 14 dogs, 0.58 ± 0.03 mm2). However, for sesamoids other than 2 and 7, dogs with sesamoid disease had a significantly greater foramen area. Conclusions and Clinical Relevance — The restriction of vascular foramina in sesamoids 2 and 7 appeared to mirror the disease distribution and disease risk for specific dogs.