[Navicular bone fractures in horses: Prognosis after conservative and surgical treatment]. / Strahlbein-Frakturen beim Pferd: Prognose nach konservativer und chirurgischer Therapie.

INTRODUCTION: The aim of this retrospective study is to describe and compare conservative and surgical treatment of navicular fractures in horses. An attempt is made to identify critical points that can favorably influence the prognosis of this orthopedic disease. All horses treated for a navicular fracture at the Equine Clinic, Vetsuisse Faculty, University of Zurich between 2005 and 2017 were included in this study. The severity of lameness at initial examination, radiographic assessment, hoof conformation, treatment (conservative or surgical), complications and outcome were determined from the medical records. Conservative and surgical treatment consisted of stable rest, a controlled exercise program and therapeutic orthopedic shoeing. During surgical treatment, fracture reduction was also carried out with a cortical screw. Computer assisted surgery were used in five horses and computer tomography in three horses. Follow-up examinations included clinical and radiographic examinations. The outcome was divided into three categories: 1 = very good; 2 = good; 3 = poor. Twelve horses met the inclusion criteria; Four horses were treated conservatively and eight were treated surgically. After conservative treatment, two horses (50 %) had a very good outcome and two (50 %) had a good outcome. After surgical treatment, four horses (50 %) had a very good outcome and four (50 %) had a poor outcome. Overall, 67 % of horses had a very good or good outcome, although radiographic signs of bone healing was not present in any of these cases. Various complications were identified, such as the fracture of a screw, the fragmentation of the small navicular bone fragment, the development of osteoarthrosis in the coffin joint and progressive podotrochosis. This study shows that the prognosis of navicular fractures is generally cautious and that degenerative changes to the navicular apparatus worsen the prognosis. In the present study, surgical treatment did not improve the prognosis of navicular fractures despite the intrasurgical use of three-dimensional imaging. However, technical advances could reduce the complication rate in the future.

INTRODUCTION: Le but de cette étude rétrospective était de décrire et de comparer le traitement conservateur et chirurgical des fractures de l'os naviculaires chez le cheval. Une tentative est faite pour identifier les points critiques qui peuvent influencer favorablement le pronostic de cette maladie orthopédique. Tous les chevaux traités pour une fracture de l'os naviculaire à la Clinique équine de la Faculté Vetsuisse de l'Université de Zurich entre 2005 et 2017 ont été inclus dans cette étude. La gravité de la boiterie lors de l'examen initial, l'évaluation radiographique, la conformation du sabot, le traitement (conservateur ou chirurgical), les complications et le résultat ont été déterminés à partir des dossiers médicaux. Le traitement conservateur et chirurgical consistait en un repos au box, un programme d'exercice contrôlé et un ferrage orthopédique thérapeutique. Au cours du traitement chirurgical, une réduction de la fracture a également été effectuée à l'aide d'une vis corticale. La chirurgie assistée par ordinateur a été utilisée sur cinq chevaux et la tomographie assistée par ordinateur sur trois chevaux. Les examens de suivi comprenaient des examens cliniques et radiographiques. Les résultats ont été divisés en trois catégories: 1 = très bon; 2 = bon; 3 = mauvais. Douze chevaux répondaient aux critères d'inclusion ; quatre chevaux ont été traités de manière conservatrice et huit ont été traités chirurgicalement. Après un traitement conservateur, deux chevaux (50 %) ont eu un très bon résultat et deux (50 %) un bon résultat. Après le traitement chirurgical, quatre chevaux (50 %) ont eu un très bon résultat et quatre (50 %) un mauvais résultat. Dans l'ensemble, 67 % des chevaux ont eu un très bon ou un bon résultat, bien que les signes radiographiques de guérison osseuse n'aient été présents dans aucun de ces cas. Diverses complications ont été identifiées, telles que la fracture d'une vis, la fragmentation du petit fragment de l'os naviculaire, le développement d'une arthrose dans l'articulation interphalangienne distale et une podotrochlose progressive. Cette étude montre que le pronostic des fractures de l'os naviculaire est généralement réservé et que les modifications dégénératives de l'appareil naviculaire aggravent le pronostic. Dans la présente étude, le traitement chirurgical n'a pas amélioré le pronostic des fractures du naviculaire malgré l'utilisation intra-chirurgicale de l'imagerie tridimensionnelle. Cependant, les progrès techniques pourraient réduire le taux de complications dans le futur.

The prevalence of equine odontoclastic tooth resorption and hypercementosis and the role of interincisal angulation in disease severity in a representative cohort of horses in Switzerland.

INTRODUCTION: Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is an increasingly diagnosed degenerative dental disease in aged horses. The primary aim of this retrospective study was to determine the prevalence of EOTRH in horses admitted to the Equine Hospital, University of Zurich, for dental procedures from 2004 to 2017. A secondary goal was to measure and compare interincisal angles on two-dimensional radiographs of horses with EOTRH to determine whether the interincisal angle is associated with age and severity of the disease. Radiographs were assessed for the presence of lysis and/or hypercementosis, and the number and position of the teeth affected were determined. Each tooth was also evaluated using the modified classification system introduced by Rehrl et al. (2018), in which stage 0 indicates no radiographic abnormalities and stage 3 denotes severe abnormalities. The overall stage was defined by the tooth with the most severe lesions. The interincisal angle was determined in horses that had suitable radiographs. The medical records of 838 horses admitted for dental procedures were evaluated, and 85 (10,1 %) had clinical evidence of EOTRH. The mean interincisal angle was 136,06 ° in horses with mild to moderate EOTRH and 135,10 ° (SD = 11,90 °) in severely affected patients. In conclusion, the angle measurements on lateral radiographs were highly reproducible. However, the interincisal angle was not associated with age or the severity of EOTRH. The interincisal angle and the disease pattern were not correlated.

INTRODUCTION: La résorption et l'hypercémentose odontoclastique des dents chez le cheval (EOTRH) est une maladie dentaire dégénérative de plus en plus diagnostiquée chez les animaux âgés. L'objectif principal de cette étude rétrospective était de déterminer la prévalence de l'EOTRH chez les chevaux admis à l'Hôpital équin de l'Université de Zurich pour des interventions dentaires entre 2014 et 2017. Un objectif secondaire était de mesurer et de comparer les angles inter-incisifs sur des radiographies bidimensionnelles de chevaux atteints d'EOTRH afin de déterminer si cet angle est associé à l'âge et à la gravité de la maladie. Les radiographies ont été évaluées pour la présence de lyse et/ou d'hypercémentose, et le nombre et la position des dents affectées ont été déterminés. Chaque dent a également été évaluée à l'aide du système de classification modifié introduit par Rehrl et al. (2018), dans lequel le stade 0 indique l'absence d'anomalies radiographiques et le stade 3 indique des anomalies graves. Le stade global a été défini par la dent présentant les lésions les plus sévères. L'angle inter-incisif a été déterminé chez les chevaux qui avaient des radiographies appropriées. Les dossiers médicaux de 838 chevaux admis pour des interventions dentaires ont été évalués et 85 (10,1 %) présentaient des signes cliniques d'EOTRH. L'angle inter-incisif moyen était de 136,06° chez les chevaux présentant une EOTRH légère à modérée et de 135,10° (écart-type = 11,90°) chez les patients gravement atteints. En conclusion, les mesures d'angle sur les radiographies latérales étaient très reproductibles. Cependant, l'angle inter-incisif n'était pas associé à l'âge ou à la sévérité de l'EOTRH. L'angle inter-incisif et le profil de la maladie n'étaient pas corrélés.

Changes in Depression and Anxiety Among Children and Adolescents From Before to During the COVID-19 Pandemic: A Systematic Review and Meta-analysis.

Importance: There is a growing body of high-quality cohort-based research that has examined changes in child and adolescent mental health during the COVID-19 pandemic vs before the pandemic. Some studies have found that child and adolescent depression and anxiety symptoms have increased, while others have found these symptoms to have remained stable or decreased. Objective: To synthesize the available longitudinal cohort-based research evidence to estimate the direction and magnitude of changes in depression and anxiety symptoms in children and adolescents assessed before and during the pandemic. Data Sources: Medline, Embase, and PsycInfo were searched for studies published between January 1, 2020, and May 17, 2022. Study Selection: Included studies reported on depression and/or anxiety symptoms, had cohort data comparing prepandemic to pandemic estimates, included a sample of children and/or adolescents younger than 19 years, and were published in English in a peer-reviewed journal. Data Extraction and Synthesis: In total, 53 longitudinal cohort studies from 12 countries with 87 study estimates representing 40 807 children and adolescents were included. Main Outcomes and Measures: Standardized mean changes (SMC) in depression and anxiety symptoms from before to during the pandemic. Results: The analysis included 40 807 children and adolescents represented in pre-COVID-19 studies and 33 682 represented in during-COVID-19 studies. There was good evidence of an increase in depression symptoms (SMC, 0.26; 95% CI, 0.19 to 0.33). Changes in depression symptoms were most conclusive for study estimates among female individuals (SMC, 0.32; 95% CI, 0.21 to 0.42), study estimates with mid to high income (SMC, 0.35; 95% CI, 0.07 to 0.63), and study estimates sourced from North America (SMC, 0.25; 95% CI, 0.15 to 0.36) and Europe (SMC, 0.35; 95% CI, 0.17 to 0.53). There was strong evidence that anxiety symptoms increased slightly during the pandemic (SMC, 0.10; 95% CI, 0.04 to 0.16), and there was some evidence of an increase in study estimates with mid to high income. Conclusions: This systematic review and meta-analysis of longitudinal studies including children and adolescents found an increase in depression symptoms during the COVID-19 pandemic, particularly among female individuals and those from relatively higher-income backgrounds.

Comparison of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation before and during the COVID-19 pandemic: a systematic review and meta-analysis.

BACKGROUND: There is a lack of consensus about the effect of the COVID-19 pandemic on the mental health of children and adolescents. We aimed to compare rates of paediatric emergency department visits for attempted suicide, self-harm, and suicidal ideation during the pandemic with those before the pandemic. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies published between Jan 1, 2020, and Dec 19, 2022. Studies published in English with data on paediatric (ie, those aged <19 years) emergency department visits before and during the COVID-19 pandemic were included. Case studies and qualitative analyses were excluded. Changes in attempted suicide, self-harm, suicidal ideation, and other mental-illness indicators (eg, anxiety, depression, and psychosis) were expressed as ratios of the rates of emergency department visits during the pandemic compared with those before the pandemic, and we analysed these with a random-effects meta-analysis. This study was registered with PROSPERO, CRD42022341897. FINDINGS: 10 360 non-duplicate records were retrieved, which yielded 42 relevant studies (with 130 sample-estimates) representing 11·1 million emergency department visits for all indications of children and adolescents across 18 countries. The mean age of the samples of children and adolescents across studies was 11·7 years (SD 3·1, range 5·5-16·3), and there were on average 57·6% girls and 43·4% boys as a proportion of emergency department visits for any health reasons (ie, physical and mental). Only one study had data related to race or ethnicity. There was good evidence of an increase in emergency department visits for attempted suicide during the pandemic (rate ratio 1·22, 90% CI 1·08-1·37), modest evidence of an increase in emergency department visits for suicidal ideation (1·08, 0·93-1·25), and good evidence for only a slight change in self-harm (0·96, 0·89-1·04). Rates of emergency department visits for other mental-illness indications showed very good evidence of a decline (0·81, 0·74-0·89), and paediatric visits for all health indications showed strong evidence of a reduction (0·68, 0·62-0·75). When rates for attempted suicide and suicidal ideation were combined as a single measure, there was good evidence of an increase in emergency department visits among girls (1·39, 1·04-1·88) and only modest evidence of an increase among boys (1·06, 0·92-1·24). Self-harm among older children (mean age 16·3 years, range 13·0-16·3) showed good evidence of an increase (1·18, 1·00-1·39), but among younger children (mean age 9·0 years, range 5·5-12·0) there was modest evidence of a decrease (0·85, 0·70-1·05). INTERPRETATION: The integration of mental health support within community health and the education system-including promotion, prevention, early intervention, and treatment-is urgently needed to increase the reach of mental health support that can mitigate child and adolescent mental distress. In future pandemics, increased resourcing in some emergency department settings would help to address their expected increase in visits for acute mental distress among children and adolescents. FUNDING: None.

Influence of Gender and Self-Perceived Competence on Psychological Well-Being in Adolescent and Young Adult Cancer Survivors.

Elucidating factors associated with mental health and well-being among adolescent and young adult cancer survivors (AYAs) is increasingly important as this population continues to grow. Adolescence and young adulthood are critical times for developing self-perceived competencies (SPCs), which may be shaped by the cancer experience and may have different consequences based on the person's gender. We assessed whether gender moderated the association between perceived competencies and mental health in 61 AYAs (51% males; 11-20 years old; diagnosed between 0.33 and 17.33 years old). Gender moderated the association of SPC in close friendship, job, and scholastic domains with depression, anxiety, and optimism.

Investigating pathological narcissism and loneliness, and the link with life satisfaction.

Loneliness is a significant health concern that may be influenced by dispositional features. Pathological narcissism may elevate loneliness through aversive interpersonal behaviors and negative social appraisals. The present study examined two dimensions of pathological narcissism, along with five-factor personality traits, in relation to loneliness among 120 young adults. Loneliness was also examined as a mediator between pathological narcissism and satisfaction with life. Narcissistic grandiosity and narcissistic vulnerability were both significantly associated with loneliness. Multiple regression analysis, including five-factor traits, revealed narcissistic vulnerability to be uniquely associated with loneliness, along with neuroticism. Mediation analysis also found an indirect effect of narcissistic vulnerability on reduced satisfaction with life, through loneliness as a mediator. These preliminary findings point to future research needs and potential clinical consideration of narcissistic vulnerability as a dispositional risk factor for loneliness.

Molecular basis for the production of cyclic peptides by plant asparaginyl endopeptidases.

Asparaginyl endopeptidases (AEPs) are proteases that have crucial roles in plant defense and seed storage protein maturation. Select plant AEPs, however, do not function as proteases but as transpeptidases (ligases) catalyzing the intra-molecular ligation of peptide termini, which leads to peptide cyclization. These ligase-type AEPs have potential biotechnological applications ranging from in vitro peptide engineering to plant molecular farming, but the structural features enabling these enzymes to catalyze peptide ligation/cyclization rather than proteolysis are currently unknown. Here, we compare the sequences, structures, and functions of diverse plant AEPs by combining molecular modeling, sequence space analysis, and functional testing in planta. We find that changes within the substrate-binding pocket and an adjacent loop, here named the "marker of ligase activity", together play a key role for AEP ligase efficiency. Identification of these structural determinants may facilitate the discovery of more ligase-type AEPs and the engineering of AEPs with tailored catalytic properties.

Epidemiology of fractures: The role of kick injuries in equine fractures.

BACKGROUND: Fractures occur commonly in equids and often are associated with complications and a poor outcome. There are no reports on the epidemiology of fractures in a heterogeneous equine population. OBJECTIVES: To study the epidemiology of fractures in a heterogeneous equine population, focusing on differences between fractures resulting from a kick and fractures, resulting from other causes and investigating predictors for recovery. STUDY DESIGN: Retrospective case series. METHODS: Data of all equids presented to the Equine Department, Vetsuisse Faculty, University of Zurich between 1990 and 2014 and diagnosed with a fracture were reviewed and those with a known cause were included in this study. Mann-Whitney and chi-squared tests were used to compare recovery rates of fractures resulting from a kick and fractures resulting from other causes, and a logistic regression was carried out for multivariate analysis of the most important factors affecting recovery. RESULTS: Here, 1144 cases fulfilled the inclusion criteria. Of all fractures (with a known cause), 43.6% were the result of a kick from another equid. Kicks often produced open fractures (44.7%) that involved bones of the limbs (85.6%). Overall recovery was 70.1%. Logistic regression showed that high-grade lameness accompanying the fracture and severe comminution negatively affected recovery. MAIN LIMITATIONS: The equids in this study were drawn from a referred population, which likely precluded the inclusion of both minor fractures and catastrophic fractures that necessitated immediate euthanasia. Moreover, many cases were excluded because the cause of the fracture could not be determined from the patient record. CONCLUSIONS: Kicks are the most common cause of fractures in a heterogeneous equine population and measures to reduce the incidence of kicks are necessary in group-housing systems.

Nitrogen sources affect productivity, desiccation tolerance and storage stability of Beauveria bassiana blastospores.

AIMS: Nitrogen is a critical element in industrial fermentation media. This study investigated the influence of various nitrogen sources on blastospore production, desiccation tolerance and storage stability using two strains of the cosmopolitan insect-pathogenic fungus Beauveria bassiana. METHODS AND RESULTS: Complex organic sources of nitrogen such as soy flour, autolysed yeast and cottonseed flour induced great numbers of blastospores after 2-3 days of fermentation, which also survived drying and remained viable (32-56% survival) after 9 months storage at 4°C, although variations were found between strains. Nitrogen availability in the form of free amino acids directly influenced blastospore production and resistance to desiccation. Increasing glucose and nitrogen concentrations up to 120 and 30 g l-1 , respectively, did not improve blastospore production but enhanced desiccation tolerance. Cell viability after drying and upon fast-rehydration was increased when ≥25 g acid-hydrolysed casein per litre was supplemented in the liquid culture medium. CONCLUSIONS: These findings indicate that low-cost complex nitrogen compounds are suitable to enhance yeast-like growth by B. bassiana with good desiccation tolerance and therefore support its further scale-up production as a mycoinsecticide. SIGNIFICANCE AND IMPACT OF THE STUDY: Nitrogen is the most expensive nutrient in liquid media composition, but this study underscores the feasibility of using low-cost nitrogen compounds composed mainly of agro-industrial by-products for rapid production of desiccation-tolerant B. bassiana blastospores by liquid culture fermentation.

Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain.

BACKGROUND: Cross-sectional studies suggest that the microbes in the human gut have a role in obesity by influencing the human body's ability to extract and store calories. The aim of this study was to assess if there is a correlation between change in body weight over time and gut microbiome composition. METHODS: We analysed 16S ribosomal RNA gene sequence data derived from the faecal samples of 1632 healthy females from TwinsUK to investigate the association between gut microbiome measured cross-sectionally and longitudinal weight gain (adjusted for caloric intake and baseline body mass index). Dietary fibre intake was investigated as a possible modifier. RESULTS: Less than half of the variation in long-term weight change was found to be heritable (h2=0.41 (0.31, 0.47)). Gut microbiota diversity was negatively associated with long-term weight gain, whereas it was positively correlated with fibre intake. Nine bacterial operational taxonomic units (OTUs) were significantly associated with weight gain after adjusting for covariates, family relatedness and multiple testing (false discovery rate <0.05). OTUs associated with lower long-term weight gain included those assigned to Ruminococcaceae (associated in mice with improved energy metabolism) and Lachnospiraceae. A Bacterioides species OTU was associated with increased risk of weight gain but this appears to be driven by its correlation with lower levels of diversity. CONCLUSIONS: High gut microbiome diversity, high-fibre intake and OTUs implicated in animal models of improved energy metabolism are all correlated with lower term weight gain in humans independently of calorie intake and other confounders.

Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling.

BACKGROUND/OBJECTIVES: Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence visceral fat (VF) development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM. SUBJECTS/METHODS: In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the 'VFM diet score' in the remainder of the sample. Using linear regression (adjusted for covariates, including body mass index and total fat mass), we investigated associations between the VFM diet score, the blood metabolomics profile and the fecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (⩾1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence. RESULTS: Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (beta (s.e.): 0.281 (0.091); P=0.002), butyrylcarnitine (0.199 (0.087); P=0.023) and hippurate (-0.297 (0.095); P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042 (0.011), P=8.47 × 10-5), VFM (0.057 (0.019), P=2.73 × 10-3) and hippurate (-0.075 (0.032), P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016 (0.004), P=9.82x10-6). CONCLUSIONS: We linked a dietary VFM score and VFM to E. dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM.

Effect of inoculum age and physical parameters on in vitro culture of the entomopathogenic nematode Steinernema feltiae.

Entomopathogenic nematodes (EPNs) of the families Steinernematidae and Heterorhabditidae have a symbiotic association with bacteria which makes them virulent against insects. EPNs have been mass produced using in vivo and in vitro methods, including both solid and liquid fermentation. This study assessed the effect of nematode inoculum age on the production of Steinernema feltiae in liquid, solid and biphasic processes. Several physical parameters were also assessed: the effect of medium viscosity, flask size and aeration speed on the recovery and yield of infective juveniles (IJs). Inoculum age treatments included inoculum liquid cultures that were 7, 14, 21 and 28 days old. Nematodes from the same inoculum were added to one liquid medium (liquid culture), one solid medium with bacteria previously grown in sponge (solid culture) and a variation of the solid medium (a biphasic culture), in which the bacteria were first grown in liquid and, then, soaked into the sponges, with the purpose of providing a more homogeneous bacterial culture before nematode inoculation. Experiments were conducted in Erlenmeyer flasks. Eight treatments were established involving combinations of three variables: two media (with and without 0.2% agar), two flask sizes (250 and 150 ml) and two agitation speeds (180 and 280 rpm). The study showed increases in nematode yield for liquid cultures, but not for solid or biphasic cultures, with the advance of the inoculum age up to 28 days of growth. Furthermore, the addition of 0.2% agar to the liquid medium and increasing the aeration rate by using larger flasks with higher agitation speed may increase nematode recovery and final yield. The experiments were conducted using shake flasks but the results may also be applicable for bioreactors.

A phantom-based forward projection approach in support of model-based iterative reconstructions for HAADF-STEM tomography.

We introduce a forward model for the computation of high angle annular dark field (HAADF) images of nano-crystalline spherical particles and apply it to image simulations for assemblies of nano-spheres of Al, Cu, and Au with a range of sizes, as well as an artificial bi-sphere, consisting of solid hemispheres of Al and Cu or Al and Au. Comparison of computed intensity profiles with experimental observations on Al spheres at different microscope accelerating voltages provides confidence in the forward model. Simulated tomographic tilt series for both HAADF and bright field (BF) images are then used to illustrate that the model-based iterative reconstruction (MBIR) approach is capable of reconstructing sphere configurations of mixed atomic number, with the correct relative reconstructed intensity ratio proportional to the square of the atomic number ratio.

Musculoskeletal injury rates in Thoroughbred racehorses following local corticosteroid injection.

A retrospective cohort study was performed to compare the rates of musculoskeletal injury (MSI) in horses receiving local corticosteroid injection (LCI) with those that were untreated and those prior to treatment. Of the 1911 study horses, 392 had been treated. A LCI was defined as any injection of corticosteroid into or adjacent to a synovial structure, muscle, or tendon/ligament. A MSI was defined as any limb injury identified by a veterinarian, following which the horse did not race for at least 6 months, or was retired. Hazard ratios (HR) comparing hazard of injury following injection to that in non-injected horses and prior to injection were calculated using Cox proportional hazards models. At least one LCI was administered to 392 horses (20.5%; median 2, range 1-16). Most LCIs were performed bilaterally (70.9%) and intra-articularly into the carpal (49.7%) or fore fetlock (29.3%) joints. There were 219 MSIs of which carpal injuries (47%), fore fetlock (22%) and forelimb tendon injuries (16%) were the most common. The incidence rate of MSI in untreated horses and those prior to injection was 1.22 (95% CI 1.04-1.44) injuries/100 horse-months, and following LCI the hazard of MSI was greater (HR 4.83, 3.54-6.61, P<0.001). The hazard ratio returned to levels indistinguishable from before treatment after 49 days. The hazard of MSI in horses following second and subsequent LCIs in the data collection period was greater than in horses following their first LCI (HR 2.10, 1.31-3.36, P=0.002). There was a positive association between LCI and subsequent musculoskeletal injury rates which was most likely due to progression of the musculoskeletal condition which prompted treatment. Assuming horses that received LCI were at increased risk of MSI subsequently, any beneficial effects of the LCI were insufficient to counter this increased risk for at least 49 days after the injection.

An assessment of intra- and interobserver agreement of reporting orthopaedic findings on presale radiographs of Thoroughbred yearlings.

REASONS FOR PERFORMING STUDY: Radiography is commonly used in clinical practice but agreement of reporting of radiographically detected orthopaedic findings in horses has rarely been studied. OBJECTIVES: To assess agreement within and between observers for reporting of orthopaedic findings on presale radiographs of Thoroughbred yearlings. STUDY DESIGN: Retrospective analysis of archived radiographs. METHODS: Four veterinary radiology specialists each twice examined 167 sets of radiographs for orthopaedic findings in the fore feet, fore and hind fetlocks, carpi, tarsi and stifles. There were 27 findings analysed for agreement. Kappa statistic (κ), percentage of positive agreement (Ppos) and percentage of negative agreement are reported. RESULTS: An excellent percentage of negative agreement was observed for all findings, with the exception of regular vascular channels of the proximal sesamoid bones. Ppos and κ results were variable. The presence of extra carpal bones, osseous cyst-like lesions of the ulnar carpal bone, sagittal ridge defects of the third metacarpus, fracture of the fore and hind proximal sesamoid bones, regular vascular channels in the hind proximal sesamoids, osteochondrosis lesions of the distal intermediate ridge and/or medial malleoli of the tibia, and osseous cyst-like lesions in the medial femoral condyle was consistently observed with an intra- and interagreement κ≥0.5 and Ppos≥50%. Lucency within the proximal sesamoids consistently had an observed intra- and interagreement κ<0.4 and Ppos<40%. CONCLUSIONS: Observation of orthopaedic findings on yearling repository radiographs showed generally excellent agreement on the absence of findings, but variable agreement on the presence of findings. Agreement was good for larger and easy to categorise radiographic findings. More accurate definitions and training need to be developed to improve agreement within and between observers for orthopaedic findings with poor or fair to good agreement.

Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats.

Estrogen deficiency results in accelerated bone turnover with a net increase in bone resorption. Subcutaneous administration of leptin attenuates bone loss in ovariectomized (ovx) rats by reducing bone resorption. However, in addition to its direct beneficial effects, leptin has been reported to have indirect (central nervous system-mediated) antiosteogenic effects on bone, which may limit the efficacy of elevated serum leptin to prevent estrogen deficiency-associated bone loss. The present study evaluated the long-term effects of increased hypothalamic leptin transgene expression, using recombinant adeno-associated virus-leptin (rAAV-Lep) gene therapy, on bone mass, architecture, and cellular endpoints in sexually mature ovx Sprague-Dawley rats. Ovx rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either rAAV-Lep or rAAV-GFP (control vector encoding green fluorescent protein) and maintained for 10 weeks. Additional controls consisted of ovary-intact rats and ovx rats pair-fed to rAAV-Lep rats. Lumbar vertebrae were analyzed by micro-computed tomography and tibiae by histomorphometry. Cancellous bone volume was lower and osteoclast perimeter, osteoblast perimeter, and bone marrow adipocyte density were greater in ovx rats compared to ovary-intact controls. In contrast, differences among ovx groups were not detected for any endpoint evaluated. In conclusion, whereas estrogen deficiency resulted in marked cancellous osteopenia, increased bone turnover and marrow adiposity, increasing hypothalamic leptin transgene expression in ovx rats had neither detrimental nor beneficial effects on bone mass, architecture, or cellular endpoints. These findings demonstrate that the antiresorptive effects of subcutaneous leptin administration in ovx rats are mediated through leptin targets in the periphery.

Risk factors for exercise-induced pulmonary haemorrhage in Thoroughbred racehorses.

REASONS FOR PERFORMING STUDY: Risk factors for occult exercise-induced pulmonary haemorrhage (EIPH) are poorly defined or quantified. OBJECTIVES: To investigate the importance of putative risk factors for EIPH amongst Thoroughbred racehorses in Australia. METHODS: Tracheobronchoscopy was used to determine EIPH status of 744 Thoroughbred racehorses after flat racing in Melbourne, Australia. Horses were identified for study before racing, and over 50% of horses racing during the study period were examined. Statistical analysis included use of bivariate and multivariate logistic regression analysis to account for simultaneous effects of a large number of variables. RESULTS: The only risk factor identified as associated with both EIPH ≥ 1 or ≥ 2 was ambient temperature, with horses racing at temperatures <20 °C being at ∼ 2 times risk of occult EIPH. There was no association of EIPH with age, sex, weight carried, track hardness, speed of racing, or air quality. CONCLUSIONS: There do not appear to be individual risk factors, amongst those examined in this study, that are strongly associated with EIPH. POTENTIAL RELEVANCE: The risk of developing EIPH cannot be readily determined from a combination of age, race speed, race distance, track hardness or air quality. This study does not provide support for the hypotheses that racing on hard surfaces or in polluted air contributes to the development of EIPH.

Genetic pathways and mutation profiles of human cancers: site- and exposure-specific patterns.

Cancer is a complex disease that involves the accumulation of both genetic and epigenetic alterations of numerous genes. Data in the Genetic Alterations in Cancer database for gene mutations and allelic loss [loss of heterozygosity (LOH)] in human tumors (e.g. lung, oral, esophagus, stomach and colon/rectum) were reviewed. Results for the genes and pathways implicated in tumor development at these sites are presented. Mutation incidence, spectra and codon specificity are described for lung, larynx and oral tumors. LOH occurred more frequently than gene mutations in tumors from all sites examined. The cell cycle gene, TP53 (all sites), and cell signaling gene, APC (colorectal and gastric cancers), were the only genes with similar incidences of LOH and mutation. Alterations of one or more cell cycle and cell signaling genes were reported for tumors from each site. Site-specific activation was apparent in the cell signaling mitogen-activated protein kinase oncogenes (KRAS in lung, HRAS in oral cancers and BRAF in esophageal and colorectal cancers). Analysis of genetic changes in lung tumors showed that the incidence of mutations in the TP53 and KRAS genes and the incidence of LOH in the FHIT gene were significantly greater in smokers versus non-smokers (P < 0.01). In lung and oral cancers, the TP53 GC --> TA transversion frequency increased with tobacco smoke exposure (P < 0.05). Furthermore, the TP53 mutational hot spots for lung and laryngeal cancers from smokers included codons 157, 245 and 273, whereas for oral tumors included codons 280 and 281.

Prevalence of pharyngeal and laryngeal abnormalities in Thoroughbreds racing in Australia, and their association with performance.

REASONS FOR PERFORMING STUDY: Little information is available regarding the prevalence of abnormalities of the upper airway and their association with performance in the general population of Thoroughbred racehorses. OBJECTIVES: To describe the prevalence of selected abnormalities of the upper airway and their association with performance in Thoroughbred racehorses in Australia. HYPOTHESIS: That abnormalities of the upper airway of Thoroughbred racehorses are associated with poor race performance. METHODS: Rhinolaryngoscopy was performed after racing and presence and characteristics of abnormalities of the larynx and pharynx were recorded in a prospective cross-sectional study of Thoroughbred horses racing in Victoria, Australia. RESULTS: Rhinolaryngoscopy was performed once on each of 744 horses over 35 months. Fifty abnormalities of the upper airway were detected in 47 horses (6.3%, 95% confidence interval [CI] 4.7-83%). Epiglottic entrapment was detected in 7 horses (0.9%, 95% CI 0.4-1.9%) and was significantly (P = 0.015) associated with superior performance. Grade 2 asymmetry (4 grade scale) of the left arytenoid cartilage was detected in 9 horses (1.2%, 95% CI 0.5-2.4%) and was also associated with superior performance (P<0.001). Ulceration or erosion of the mucosa of the axial surface of one or both arytenoids was detected in 18 horses (2.4%, 95% CI 13-3.8%) and was not associated with alterations in exercise performance (P = 0.31). CONCLUSIONS: Epiglottic entrapment, Grade 2 laryngeal asymmetry and mucosal erosions detected in Thoroughbred racehorses were not associated with impaired performance; therefore, surgical correction and concern over laryngeal function in horses with Grade 2 asymmetry may not be necessary in individuals performing to expectation.

Urban Jamaican children's exposure to community violence.

Exposure to violence in childhood is associated with aggression in adulthood. The high level of community violence in Jamaica is likely to expose Jamaican children to violence. There has been no detailed study of the exposure of Jamaican children to violence in their daily lives. Some 1674 urban 11-12-year-old children, previously part of a national birth cohort study, completed a questionnaire detailing their exposure to violence as witnesses, victims and aggressors. Their parents completed a socio-economic questionnaire. Jamaican children had high levels of exposure to physical violence. A quarter of the children had witnessed severe acts of physical violence such as robbery, shooting and gang wars, a fifth had been victims of serious threats or robbery and one in every twelve had been stabbed. Children reported being least exposed to sexual violence and to being shot at. Robbery was an almost universal experience affecting children from all schools and socio-economic groups. The single commonest experience as a victim of violence was the loss of a family member or close friend to murder, affecting 36.8% of children. Children's experiences of witnessing violence occurred chiefly in their communities but their personal experiences of violence occurred at school. Boys and children attending primary school had greater exposure to violence as witnesses and victims. Socio-economic status discriminated exposure to physical violence as witnesses but not as victims. Intervention strategies to reduce children's exposure to violence should include community education on the impact of exposure to violence on children, particularly the loss of a significant person, and the development of a range of school-based violence prevention programmes.