Global phylogenomic assessment of Leptoseris and Agaricia reveals substantial undescribed diversity at mesophotic depths.

BACKGROUND: Mesophotic coral communities are increasingly gaining attention for the unique biological diversity they host, exemplified by the numerous mesophotic fish species that continue to be discovered. In contrast, many of the photosynthetic scleractinian corals observed at mesophotic depths are assumed to be depth-generalists, with very few species characterised as mesophotic-specialists. This presumed lack of a specialised community remains largely untested, as phylogenetic studies on corals have rarely included mesophotic samples and have long suffered from resolution issues associated with traditional sequence markers. RESULTS: Here, we used reduced-representation genome sequencing to conduct a phylogenomic assessment of the two dominant mesophotic genera of plating corals in the Indo-Pacific and Western Atlantic, respectively, Leptoseris and Agaricia. While these genome-wide phylogenies broadly corroborated the morphological taxonomy, they also exposed deep divergences within the two genera and undescribed diversity across the current taxonomic species. Five of the eight focal species consisted of at least two sympatric and genetically distinct lineages, which were consistently detected across different methods. CONCLUSIONS: The repeated observation of genetically divergent lineages associated with mesophotic depths highlights that there may be many more mesophotic-specialist coral species than currently acknowledged and that an urgent assessment of this largely unstudied biological diversity is warranted.

Proportion of Tubal Factor Infertility due to Chlamydia: Finite Mixture Modeling of Serum Antibody Titers.

In this study, we examined whether the proportion of tubal factor infertility (TFI) that is attributable to Chlamydia trachomatis, the population excess fraction (PEF), can be estimated from serological data using finite mixture modeling. Whole-cell inclusion immunofluorescence serum antibody titers were recorded among infertile women seen at St. Michael's Hospital in Bristol, United Kingdom, during the period 1985-1995. Women were classified as TFI cases or controls based on laparoscopic examination. Finite mixture models were used to identify the number of component titer distributions and the proportion of serum samples in each, from which estimates of PEF were derived. Four titer distributions were identified. The component at the highest titer was found only in samples from women with TFI, but there was also an excess of the second-highest titer component in TFI cases. Minimum and maximum estimates of the PEF were 28.0% (95% credible interval: 6.9, 50.0) and 46.8% (95% credible interval: 23.2, 64.1). Equivalent estimates based on the standard PEF formula from case-control studies were 0% and over 65%. Finite mixture modeling can be applied to serological data to obtain estimates of the proportion of reproductive damage attributable to C. trachomatis Further studies using modern assays in contemporary, representative populations should be undertaken.

Comparison of the performance of HPV tests in women with abnormal cytology: results of a study within the NHS cervical screening programme.

OBJECTIVE: The use of testing for human papillomavirus (HPV) is now recognized as an efficient means of triaging women with low-grade cytological abnormalities to either immediate referral to colposcopy or return to routine recall. We aimed to determine the sensitivity and specificity of each of four newer tests for HPV relative to the Qiagen Hybrid Capture 2 (HC2) assay in order to determine whether they could be approved for use in triage in the NHS cervical screening programme. METHODS: We compared the performance of each of four different HPV assays (Abbott M2000, Roche Cobas, Hologic Cervista and Gen-Probe APTIMA) with that of HC2 in order to determine the sensitivity and specificity of each test relative to HC2 for the detection of cervical intraepithelial neoplasia (CIN) grade 2 or worse, using routine cytology samples reported as borderline (atypical squamous cells) or mild dyskaryosis (low-grade squamous intraepithelial lesion) from six laboratories in England. All women who were found to be HPV positive on any test were referred to colposcopy. RESULTS: Between 2072 and 4217 tests were performed with each assay. All four assays were shown to have a relative sensitivity of no worse than 95% compared with HC2 when a cut-off of 2 relative light units (RLU) was used. All assays had higher relative specificity than HC2 for both borderline and mild cytology referrals (1.06-1.61). CONCLUSIONS: All assays tested met the criteria required. Consequently, all have now been approved for use in HPV triage in the NHS cervical screening programme.

Deprivation and access to treatment for colorectal cancer in Southeast Scotland 2003-2009.

AIM: Socioeconomic deprivation is associated with poorer survival from colorectal cancer. We examined the association of deprivation with access to treatment, disease stage at presentation and choice of treatment for colorectal cancer within a regional managed clinical network. METHOD: We performed a retrospective analysis of data from the Southeast Scotland Cancer Network colorectal database for the period 2003-2009. Socioeconomic status was assigned into five categories using postcode of residence and the Scottish Index of Multiple Deprivation score. Outcomes were access to consultation and treatment, stage of disease at presentation and treatment factors (type of surgery, adjuvant radiotherapy and adjuvant chemotherapy). RESULTS: Of 4960 colorectal cancer patients, 4016 patients (81%) underwent operative treatment. Deprivation was not associated with age, gender, tumour site, disease stage, delay in treatment pathway or permanent stoma rate. Primary tumour resection (P = 0.006) and chemotherapy treatment (P = 0.018) were higher in the least deprived compared with the most deprived quintile. Socioeconomic status was associated with both primary tumour resection [odds ratio for the most affluent compared with the most deprived quintiles (OR) 1.34, 95% confidence interval (CI) 1.05-1.72, P = 0.018] and chemotherapy treatment (OR 1.44, 95% CI 1.15-1.80, P = 0.001). However, when health board of treatment was added to the model, only chemotherapy treatment was independently associated with deprivation (OR 1.46, 95% CI 1.16-1.83, P = 0.001). CONCLUSION: Deprivation is not associated with treatment delay or more advanced disease stage at presentation. An apparent association between deprivation and treatment choice may be explained by other differences between patients treated in different areas.

An example of governance for AI in health services from Aotearoa New Zealand.

Artificial Intelligence (AI) is undergoing rapid development, meaning that potential risks in application are not able to be fully understood. Multiple international principles and guidance documents have been published to guide the implementation of AI tools in various industries, including healthcare practice. In Aotearoa New Zealand (NZ) we recognised that the challenge went beyond simply adapting existing risk frameworks and governance guidance to our specific health service context and population. We also deemed prioritising the voice of Maori (the indigenous people of Aotearoa NZ) a necessary aspect of honouring Te Tiriti (the Treaty of Waitangi), as well as prioritising the needs of healthcare service users and their families. Here we report on the development and establishment of comprehensive and effective governance over the development and implementation of AI tools within a health service in Aotearoa NZ. The implementation of the framework in practice includes testing with real-world proposals and ongoing iteration and refinement of our processes.

Evolutionary dynamics and temporal/geographical correlates of recombination in the human enterovirus echovirus types 9, 11, and 30.

The relationship between virus evolution and recombination in species B human enteroviruses was investigated through large-scale genetic analysis of echovirus type 9 (E9) and E11 isolates (n = 85 and 116) from 16 European, African, and Asian countries between 1995 and 2008. Cluster 1 E9 isolates and genotype D5 and A E11 isolates showed evidence of frequent recombination between the VP1 and 3Dpol regions, the latter falling into 23 (E9) and 43 (E11) clades interspersed phylogenetically with 46 3Dpol clades of E30 and with those of other species B serotypes. Remarkably, only 2 of the 112 3Dpol clades were shared by more than one serotype (E11 and E30), demonstrating an extremely large and genetically heterogeneous recombination pool of species B nonstructural-region variants. The likelihood of recombination increased with geographical separation and time, and both were correlated with VP1 divergence, whose substitution rates allowed recombination half-lives of 1.3, 9.8, and 3.1 years, respectively, for E9, E11, and E30 to be calculated. These marked differences in recombination dynamics matched epidemiological patterns of periodic epidemic cycles of 2 to 3 (E9) and 5 to 6 (E30) years and the longer-term endemic pattern of E11 infections. Phylotemporal analysis using a Bayesian Markov chain Monte Carlo method, which placed recombination events within the evolutionary reconstruction of VP1, showed a close relationship with VP1 lineage expansion, with defined recombination events that correlated with their epidemiological periodicity. Whether recombination events contribute directly to changes in transmissibility that drive epidemic behavior or occur stochastically during periodic population bottlenecks is an unresolved issue vital to future understanding of enterovirus molecular epidemiology and pathogenesis.

Continued emergence and changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus, United Kingdom, winter 2010/11.

During the winter period 2010/11 27 epidemiologically unlinked, confirmed cases of oseltamivir-resistant influenza A(H1N1)2009 virus infection have been detected in multiple, geographically dispersed settings. Three of these cases were in community settings, with no known exposure to oseltamivir. This suggests possible onward transmission of resistant strains and could be an indication of a possibility of changing epidemiology of oseltamivir-resistant influenza A(H1N1)2009 virus.

Sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies.

Molecular mimicry between viral antigens and host proteins was often suggested to be involved in induction of autoimmune diseases. In type 1 diabetes where pancreatic beta cells are destroyed by autoimmune phenomena, a linear sequence homology between a major autoantigen, glutamate decarboxylase (GAD), and the 2C protein of coxsackie B4 was identified. In addition, a sequence homology between GAD and the mycobacterial heat shock protein 60 was described and the suggestions were made that molecular mimicry between GAD, coxsackievirus B4-2C protein, and/or heat shock protein 60 (hsp60) may be actively involved in an autoimmune reaction towards the pancreatic beta-cells. Our group was the first to isolate human monoclonal autoantibodies to GAD (MICA 1-6) from a patient with newly diagnosed type 1 diabetes. The MICA allowed a detailed characterization of the diabetes associated self-epitopes in GAD and represent a set of GAD autoantibodies present in sera from patients with type 1 diabetes. Using deletion mutants of GAD we demonstrated that the regions of GAD covering the homology sequences to coxsackievirus B4 and to the hsp60 were absolutely required for binding of the MICA to GAD. We now designed an antibody-based analysis to ask whether molecular mimicry between GAD and coxsackie B4-2C or hsp60 is relevant in type 1 diabetes. Since part of the MICA recognize conformational epitopes, they allow to test for conformational molecular mimicry in viruses that have been incriminated in the development of type 1 diabetes. Our data reveal no crossreactivity between the diabetes associated GAD epitopes defined by the MICA and hsp60, rubellavirus, cytomegalovirus, and coxsackie B1-B6 virus antigens. Neither coxsackie B4-specific antibodies in sera from normal individuals nor GAD-positive sera from patients with type 1 diabetes indicated a crossreactivity between coxsackie B4-2C and GAD. Although the regions in GAD homologous to coxsackie B4-2C and hsp60 represented parts of GAD indispensible for binding of diabetes associated autoantibodies they did not mediate a crossreactivity of autoantibodies between GAD and these two proteins. No evidence for molecular mimicry between GAD and a whole panel of foreign antigens was detected by autoantibodies in type 1 diabetes.

Pathologic fracture healing after femoral limb salvage in a dog.

BACKGROUND: Bone sarcomas are a significant cause of pain, disability, and mortality in dogs. A variety of surgical limb salvage options are available to preserve limb function with comparable prognosis to amputation. CASE REPORT: This report describes successful healing after plate fixation of an undifferentiated sarcoma pathologic femoral fracture in a dog. The fracture was treated surgically with curettage of the tumour site, placement of autogenous bone graft, and then stabilized using a locking plate rod construct. The patient regained excellent mobility after surgery and was managed with monthly pamidronate therapy. Serial radiographs demonstrate progressive healing of the pathologic fracture. Ultimately, the patient developed a maxillary fibrosarcoma and was euthanased 1 year after treatment of the femoral fracture. Postmortem histopathological evaluation of the pathologic fracture site demonstrated complete bone healing. CONCLUSION: This case highlights the possibilities of limb salvage by fracture stabilization and bone healing as a viable option in select patients.

Correlation between orthopaedic and radiographic examination findings and arthroscopic ligament fibre damage in dogs with cruciate ligament rupture.

OBJECTIVE: The objective is to study the correlations between physical examination and stifle radiography findings and severity of arthroscopic cranial cruciate ligament (CrCL) fibre damage in dogs with cruciate rupture (CR). DESIGN: Design Prospective clinical study. METHODS: Twenty-nine client-owned dogs with CR underwent physical examination, stifle radiography and arthroscopy, and the findings were recorded. Initial examination was repeated after sedation and after general anaesthesia. The Spearman rank correlations of examination variables with diagnostic imaging were examined. RESULTS: Overall, cranial tibial translation assessed by the tibial compression test in extension showed correlation with arthroscopic CrCL fibre damage (P < 0.05). Correlations between severity of cranial drawer laxity and arthroscopic CrCL fibre damage were not significant. Under general anaesthesia, stifle laxity tests were positively correlated with lameness severity grade (SR ≥ 0.41, P < 0.05). Meniscal damage was correlated with pain on the internal rotation of the tibia (SR = 0.42, P < 0.05) and severity of radiographic osteophytosis (SR = 0.53, P = 0.01). CONCLUSION: Detection and estimation of severity of cranial tibial translation enable the diagnosis of CR and also the inference of the severity of CrCL fibre rupture, particularly with the tibial compression test in extension. Severity of joint laxity is best assessed under general anaesthesia. Such knowledge should reduce the risk of misdiagnosis and may enhance early diagnosis and treatment of dogs with CR over time.

Exercise-induced metacarpophalangeal joint adaptation in the Thoroughbred racehorse.

Repetitive bone injury and development of stress fracture is a common problem in humans and animals. The Thoroughbred racehorse is a model in which adaptive failure and associated development of stress fracture is common. We performed a histologic study of the distal end of the third metacarpal bone in two groups of horses: young Thoroughbreds that were actively racing (n = 10) and a group of non-athletic horses (n = 8). The purpose of this study was to determine whether development of articular microcracks was associated with specific alterations to subchondral plate osteocytes. Morphometric measurements were made in five regions of the joint surface: lateral condyle, lateral condylar groove, sagittal ridge, medial condylar groove, and medial condyle. The following variables were quantified: hyaline cartilage width; calcified cartilage width; the number of tidemarks; microcrack density at the articular surface; blood vessel density entering articular cartilage; the presence of atypical bone matrix in the subchondral plate; bone volume fraction; and osteocyte density. Adaptation of articular cartilage was similar in both groups of horses. Vascularization of articular cartilage was increased in the group of non-athletic horses. Microcracks, which typically had an oblique orientation to the joint surface, were co-localized with blood vessels, and resorption spaces. Microcracking was increased in the condylar grooves of athletic horses compared with the other joint regions and was also increased compared with the condylar groove regions of non-athletic horses. Coalescence of microcracks also led to development of an intracortical articular condylar stress fracture in some joints and targeted remodeling of affected subchondral plate. The subchondral plate of the condyles in athletic horses was sclerotic, and contained atypically stained bone matrix with increased numbers of osteocytes with atypical morphology. However, osteocyte numbers were not significantly different between groups. We conclude that differences in site-specific microdamage accumulation and associated targeted remodeling between athletic and non-athletic horses are much greater than differences in subchondral osteocyte morphology. However, the presence of atypical subchondral bone matrix in athletic horses was associated with extensive osteocyte loss. Although osteocyte mechanotransduction is considered important for functional adaptation, in this model, adaptation is likely regulated by multiple mechanotransduction pathways.

Comparison of radiofrequency treatment and mechanical debridement of fibrillated cartilage in an equine model.

OBJECTIVE: To compare a radiofrequency energy (RFE) prototype probe to mechanical debridement (MD) and a commercially available RFE system used for chondroplasty in the treatment of an experimentally created partial thickness cartilage lesion in horses. The study design was experimental, randomized complete block, n=8, using fifteen mature ponies. METHODS: Grade 2 to 3 cartilage lesions were prepared in both patellae. After 10 months duration, the injuries were used to study the effects of MD, a commercially available bipolar RFE device (CoVac 50; ArthroCare Corporation) and a prototype monopolar RFE device (Smith & Nephew Endoscopy). Six months after treatment the patellae were examined for chondrocyte viability and cartilage structure. RESULTS: Mean depth of cell death was significantly different among groups (controls, MD

Expression of immune response genes in the stifle joint of dogs with oligoarthritis and degenerative cranial cruciate ligament rupture.

Dysregulation of immune responses within joints plays an important role in development of inflammatory arthritis. We determined expression of a panel of immune response and matrix turnover genes in synovial fluid collected from a group of dogs with stifle oligoarthritis and associated degenerative cranial cruciate ligament (CCL) rupture (n=27). We also studied synovial fluid gene expression in dogs affected with other forms of degenerative arthritis (n=9) and in the stifle joint of healthy dogs with intact CCL (n=14). After collection, synovial cells were pelleted and RNA was isolated. Relative expression of cathepsin K, cathepsin S, tartrate-resistant acid phosphatase (TRAP), matrix metalloproteinase-9 (MMP-9), invariant chain (li), toll-like receptor-2 (TLR-2), and TLR-9 was determined using real-time quantitative RT-PCR. Data were normalized to peripheral blood mononuclear cells (PBMC) as an internal control. Relative expression of cathepsin K, MMP-9, TRAP, and li was increased in the stifle synovial fluid of dogs with oligoarthritis, when compared with the stifles of healthy dogs (P<0.05). In contrast, relative expression of all of the genes-of-interest in synovial fluid from joints affected with other forms of arthritis was not significantly different from the stifles of healthy dogs. TRAP expression was also significantly increased in the stifle joints of dogs with oligoarthritis, when compared to joint expression of TRAP in dogs with other forms of degenerative arthritis (P<0.05). In the dogs with stifle oligoarthritis, expression of both matrix turnover and immune response genes was increased in stifle synovial fluid, when compared with the internal PBMC control, whereas in healthy dogs and dogs with other forms of arthritis, only expression of matrix turnover genes was increased in synovial fluid, when compared with the internal PBMC control (P<0.05). Taken together, these findings suggest that antigen-specific immune responses within the stifle joint may be involved in the pathogenesis of persistent synovitis and associated joint degradation in dogs with oligoarthritis and degenerative CCL rupture.

Role of endochondral ossification of articular cartilage and functional adaptation of the subchondral plate in the development of fatigue microcracking of joints.

The mechanisms that regulate functional adaptation of the articular ends of long bones are poorly understood. However, endochondral ossification of articular cartilage and modeling/remodeling of the subchondral plate and epiphyseal trabeculae are important components of the adaptive response. We performed a histologic study of the distal end of the third metacarpal/metatarsal bone of Thoroughbreds after bones were bulk-stained in basic fuchsin and calcified sections were prepared. The Thoroughbred racehorse is a model of an extreme athlete which experiences particularly high cyclic strains in distal limb bones. The following variables were quantified: microcrack boundary density in calcified cartilage (N.Cr/B.Bd); blood vessel boundary density in calcified cartilage (N.Ve/B.Bd); calcified cartilage width (Cl.Cg.Wi); duplication of the tidemark; and bone volume fraction of the subchondral plate (B.Ar/T.Ar). Measurements were made in five joint regions (lateral condyle and condylar groove; sagittal ridge; medial condylar and condylar groove). N.Cr/B.Bd was site-specific and was increased in the condylar groove region; this is the joint region from which parasagittal articular fatigue (condylar) fractures are typically propagated. Formation of resorption spaces in the subchondral plate was co-localized with microcracking. N.Ve/B.Bd was also site-specific. In the sagittal ridge region, N.Ve/B.Bd was increased, Cl.Cg.Wi was decreased, and B.Ar/T.Ar was decreased, when compared with the other joint regions. Multiple tidemarks were seen in all joint regions. Cumulative athletic activity was associated with a significant decrease in B.Ar/T.Ar in the condylar groove regions. N.Cr/B.Bd was positively correlated with B.Ar/T.Ar (P < 0.05, r(s) = 0.29) and N.Ve/B.Bd was negatively correlated with B.Ar/T.Ar (P < 0.005, r2 = 0.14) and Cl.Cg.Wi (P < 0.05, r2 = 0.07). We conclude that endochondral ossification of articular cartilage and modeling/remodeling of the subchondral plate promote initiation and propagation of site-specific fatigue microcracking of the joint surface, respectively, in this model. Microcracking of articular calcified cartilage likely represents mechanical failure of the joint surface. Propagation of microcracks into the subchondral plate is a critical factor in the pathogenesis of articular condylar fatigue (stress) fracture. Functional adaptation of the joint likely protects hyaline cartilage from injury in the short-term but may promote joint degeneration and osteoarthritis with ongoing athleticism.

Influence of overstory removal on growth of epiphytic mosses and lichens in western Oregon.

Will old-growth-associated epiphytes survive if the forest canopy is opened around them by thinning or partial harvest? If old-growth association is due to a species' environmental tolerances, it may not survive in the relatively open stands that result from such treatments. If, however, old-growth association is due to dispersal limitations rather than environmental tolerances, retention of host trees as refugia and sources of inoculum might carry populations of old-growth-associated epiphytes into young stands. We studied growth rates of lichen and moss transplants in a Douglas-fir (Pseudotsuga menziesii) forest (tree ages approximately 55 yr) in western Oregon for nine months before and 27 months after moderate thinning, creation of 0.4-ha patch cuts, and in control areas. We also assessed moss sporophyte production. We contrasted responses of one moss species, Isothecium myosuroides sensu lato, which is ubiquitous in forests of varying ages, with those of another moss, Antitrichia curtipendula, and a lichen, Lobaria oregana, which are both associated with old-growth forests. Both old-growth associates grew faster in thinned areas and patch cuts than in controls, while Isothecuim grew most slowly and produced fewest sporophytes in patch cuts. These species are likely to survive in remnants, assuming they can remain attached, and may be successful in young stands if they can disperse and establish there. Our results suggest that logging with green-tree retention and other silvicultural practices that preserve trees or shrubs hosting the species studied here are likely to encourage these species' development in managed forests.

2015 UK National Guideline on the management of non-gonococcal urethritis.

We present the updated British Association for Sexual Health and HIV guideline for the management of non-gonococcal urethritis in men. This document includes a review of the current literature on its aetiology, diagnosis and management. In particular it highlights the emerging evidence that azithromycin 1 g may result in the development of antimicrobial resistance in Mycoplasma genitalium and that neither azithromycin 1 g nor doxycycline 100 mg twice daily for seven days achieves a cure rate of >90% for this micro-organism. Evidence-based diagnostic and management strategies for men presenting with symptoms suggestive of urethritis, those confirmed to have non-gonococcal urethritis and those with persistent symptoms following first-line treatment are detailed.

Up-regulation of site-specific remodeling without accumulation of microcracking and loss of osteocytes.

Functional adaptation of bone normally protects the skeleton from fracture during daily activity. Accumulation of microcracking and loss of osteocytes have been implicated in the regulation and initiation of targeted (reparative) remodeling of bone and, in certain situations, the development of fatigue or stress fracture. We performed a histologic study of the dorsal cortex of the mid-diaphysis of the third metacarpal (Mc-III) bone of Thoroughbred racehorses after bones were bulk-stained in basic fuchsin and transverse calcified sections were prepared. The Thoroughbred racehorse is an extreme athlete whose Mc-III bone experiences particularly high cyclic strains during training and racing. A group of non-athletic horses was also included in the experiment. The following variables were quantified: activation frequency (Ac.f); bone formation rate (BFR); resorption space density (Rs.N/T.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar; Ot.N/B.Ar); and bone volume fraction (B.Ar/T.Ar). Ac.f and BFR were estimated using a mathematical algorithm. Using confocal microscopy, bones were examined for fine microcracks, diffuse matrix injury, and disruption of the osteocyte syncytium. Low values for Cr.Dn (#/mm2) were found in both groups (0.022+/-0.008 and 0.013+/-0.006 for racing Thoroughbreds and non-athletic horses, respectively). There was no significant relationship between Cr.Dn and Ot.N/T.Ar; Ot.N/B.Ar, B.Ar/T.Ar, and Ot.N/T.Ar; Ot.N/B.Ar, and remodeling (Ac.f, Rs.N/T.Ar) and Ot.N/T.Ar; Ot.N/B.Ar. Intense remodeling of the Mc-III dorsal cortex was found in the racing Thoroughbreds (Ac.f 12.8+/-7.4 #/mm2/year; BFR 31.5+/-15.6%; Rs.N/T.Ar 0.19+/-0.09 #/mm2) and was significantly increased compared with non-athletic horses. Overall, remodeling was weakly correlated with Cr.Dn (r2=0.15, P<0.05). Subtle matrix injury, not detectable by bright-field microscopy, was particularly evident adjacent to resorption spaces in Thoroughbred bone. In non-athletic horses, disruption of the dendritic cell processes of osteocytes associated with cement lines and interstitial fragments was more evident. Taken together, these findings suggest that site-specific (targeted) induction of remodeling during functional adaptation of bone in a high-strain skeletal site is not dependent on accumulation of microcracking or loss of osteocytes. We hypothesize that athleticism can directly influence bone turnover in this extreme athlete through pathways that do not involve classical linear microcracks.

The effects of depriving feed to facilitate transport and slaughter in sheep--a case study of cull ewes held off pasture for different periods.

AIM: To determine the ability of sheep to mobilise their body reserves after being deprived of feed prior to transport for slaughter. METHODS: A total of 240 3- and 4-year-old cull ewes were held off pasture for 0, 9, 18 or 30 hours (n=60 per group) then transported 1 hour by road, unloaded and washed, held in lairage for 3 hours then slaughtered. Blood samples were collected from a subsample of 60 unfasted ewes 1 week earlier, and from all ewes at exsanguination to determine concentrations of serum metabolites indicative of adaptation to fasting. In addition, several attributes of carcass quality were measured. RESULTS: At slaughter, increased time off pasture prior to transport resulted in no change in glucose concentrations in serum (p=0.140). There were differences (p<0.001) between the group fasted for 30 compared with 0 hours in mean concentrations of free fatty acids (0.98 (SD 0.32) vs. 0.58 (SD 0.23) mmol/L), ß-hydroxybutyrate (0.69 (SD 0.17) vs. 0.42 (SD 0.11) mmol/L), triglycerides (0.29 (min 0.13, max 0.83) vs. 0.22 (min 0.06, max 0.96) mmol/L) and urea (10.17 (SD 1.80) vs. 6.94 (SD 2.03) mmol/L). Different periods of feed deprivation had no effect (p>0.05) on carcass weights (mean 22.7, min 13.2, max 32.9 kg) or dressing out percentages (mean 40.9, min 27, max 49%). Meat ultimate pH was unaffected (p>0.05) by the period of feed deprivation but meat became darker (p<0.05) and had reduced redness (p<0.001) with increasing time off feed. CONCLUSIONS: The results suggest that sheep in variable body condition adapted to the periods of feed deprivation by mobilising their energy reserves without any evidence of metabolic depletion (e.g. depleted blood glucose or high meat pH). However, being deprived of feed they probably experience a degree of hunger.

Asymmetric adaptive modeling of central tarsal bones in racing greyhounds.

Fatigue fracture of the cuboidal bones of the foot, especially the navicular tarsal bone, is common in athletes and dancers. The racing greyhound is a naturally occurring animal model of this injury because both microcracking and complete fracture occur in the right central (navicular) tarsal bone (CTB). The right limb is on the outside when racing in a counter-clockwise direction on circular tracks, and is subjected to asymmetric cyclic compressive loading. We wished to study in more detail adaptive modeling in the right CTB in racing greyhounds. We hypothesized that cyclic asymmetric loading of a cuboidal bone induced by racing on a circular track would induce site-specific bone adaptation. We also hypothesized that such an adaptive response would be attenuated in greyhounds that were retired from racing and no longer subjected to cyclic asymmetric loading. Central tarsal bones from racing greyhounds (racing group, n = 6) and retired greyhounds being used for breeding (nonracing group, n = 4) were examined using quantitative computed tomography (CT). Bone mineral density (BMD) was determined in a 3-mm diameter region-of-interest (ROI) in six contiguous 1-mm-thick sagittal CT slices of each CTB. Bones were subsequently examined histomorphometrically and percentage bone area (B.Ar./T.Ar., %) was determined in 10 ROI from dorsal to plantar in a transverse plane, mid-way between the proximal and distal articular surfaces. The BMD of the right CTB was greater than the left in all greyhounds (p < 0. 001). In comparing ipsilateral limbs between groups, BMD of the racing group was greater than the nonracing group for each side (p < 0.005). In sagittal plane histologic sections, bone in the dorsal region of the right CTB had undergone adaptive modeling, through thickening and compaction of trabeculae. B.Ar./T.Ar., % in the right CTB of the racing group was greater than in the contralateral CTB (p < 0.001), and the ipsilateral CTB of the nonracing group (p < 0.001). In the nonracing group, B.Ar./T.Ar., % in the right CTB was not significantly different from left CTB (p > 0.8; power = 80% at Delta = 48%). It was concluded that greyhounds racing on circular tracks develop site-specific bone adaptation with compaction of trabecular bone and increase in BMD in the right CTB in particular, the most common site for fatigue fracture. Our data also suggested that partial reversal of this adaptive process occurred in retired, nonracing greyhounds, after cessation of asymmetric cyclic loading at racing speed. Racing greyhounds provide a model in which to study fatigue fracture and adaptation of cuboidal foot bones subjected to cyclic loading.

In vivo matrix microdamage in a naturally occurring canine fatigue fracture.

Greyhound central tarsal bone (CTB) from animals with (n = 11) and without CTB fatigue fracture (n = 15) was examined histologically for the presence, numerical density, and morphology of in vivo microdamage. Complete fracture of the right CTB is a common occurrence during dog racing, because this is the outside limb when running counterclockwise on a circular or oval track. The CTB consisted of both remodeled cortical bone and inner trabecular bone. Thickening and coalescence of trabeculae were observed, particularly dorsally and medially, causing reduction or elimination of the marrow void spaces. A band of tightly packed transverse osteons was also observed adjacent to the concave proximal joint surface. Typical linear microcracks were most often seen in remodeled cortical and trabecular bone and were often observed adjacent to vascular channels. In contrast, ultra-microcracking, represented by diffuse staining with basic fuchsin, was consistently observed in the plantar process around the attachment site for the plantar ligament complex. Dog status (fractured or intact) and side (left or right) both had a significant effect on microcrack density and microcrack surface density (p < 0.05). Microcrack density and microcrack surface density were increased in the right (fractured) CTB from greyhounds with CTB fracture. There was also a trend for side to have a significant effect on microcrack length, with microcrack lengths being higher in the right CTB of both intact and fractured dogs. These data support the general hypothesis that fatigue fracture occurs because of ongoing cyclic stresses after induction of reparative remodeling. Development of methods for biomechanical testing of small cuboidal bones should allow investigation of relationships between accumulation of loading cycles and bone weakening because of microdamage.