αSMA Osteoprogenitor Cells Contribute to the Increase in Osteoblast Numbers in Response to Mechanical Loading.

Bone is a dynamic tissue that site-specifically adapts to the load that it experiences. In response to increasing load, the cortical bone area is increased, mainly through enhanced periosteal bone formation. This increase in area is associated with an increase in the number of bone-forming osteoblasts; however, the origin of the cells involved remains unclear. Alpha-smooth muscle actin (αSMA) is a marker of early osteoprogenitor cells in the periosteum, and we hypothesized that the new osteoblasts that are activated by loading could originate from αSMA-expressing cells. Therefore, we used an in vivo fate-mapping approach in an established axial loading model to investigate the role of αSMA-expressing cells in the load-induced increase in osteoblasts. Histomorphometric analysis was applied to measure the number of cells of different origin on the periosteal surface in the most load-responsive region of the mouse tibia. A single loading session failed to increase the number of periosteal αSMA-expressing cells and osteoblasts. However, in response to multiple episodes of loading, the caudal, but not the cranial, periosteal surface was lined with an increased number of osteoblasts originating from αSMA-expressing cells 5 days after the initial loading session. The proportion of osteoblasts derived from αSMA-labeled progenitors increased by 70% (p < 0.05), and the proportion of αSMA-labeled cells that had differentiated into osteoblasts was doubled. We conclude that αSMA-expressing osteoprogenitors can differentiate and contribute to the increase in periosteal osteoblasts induced by mechanical loading in a site-specific manner.

Transport of chloride and deuterated water in peat: The role of anion exclusion, diffusion, and anion adsorption in a dual porosity organic media.

The dual-porosity structure of peat and the extremely high organic matter content give rise to a complex medium that typically generates prolonged tailing and early 50% concentration breakthrough in the breakthrough curves (BTCs) of chloride (Cl-) and other anions. Untangling whether these observations are due to rate-limited (physical) diffusion into inactive pores, (chemical) adsorption or anion exclusion remains a critical question in peat hydrogeochemistry. This study aimed to elucidate whether Cl- is truly conservative in peat, as usually assumed, and whether the prolonged tailing and early 50% concentration breakthrough of Cl- observed is due to diffusion, adsorption, anion exclusion or a combination of all three. The mobile-immobile (MiM) dual-porosity model was fit to BTCs of Cl- and deuterated water measured on undisturbed cores of the same peat soils, and equilibrium Cl- adsorption batch experiments were conducted. Adsorption of Cl- to undecomposed and decomposed peat samples in batch experiments followed Freundlich isotherms but did not exhibit any trends with the degree of peat decomposition and sorption became negligible below aqueous Cl- concentrations of ~310 mg L-1. The dispersivity determined by fitting the Cl- BTCs whether assuming adsorption or no adsorption were significantly different than determined by the deuterated water (p < .0001). However, no statistical differences in dispersivity (p = .27) or immobile water content (p = .97) was observed between deuterated water and Cl- when accounting for anion exclusion. A higher degree of decomposition significantly increased anion exclusion (p < .0001) but did not influence the diffusion of either tracer into the immobile porosity. Contrary to previous assumptions, Cl- is not truly conservative in peat due to anion exclusion, and adsorption at higher aqueous concentrations, but the overall effect of anion exclusion on transport is likely minimal.

PEAT-CLSM: A Specific Treatment of Peatland Hydrology in the NASA Catchment Land Surface Model.

Peatlands are poorly represented in global Earth system modeling frameworks. Here we add a peatland-specific land surface hydrology module (PEAT-CLSM) to the Catchment Land Surface Model (CLSM) of the NASA Goddard Earth Observing System (GEOS) framework. The amended TOPMODEL approach of the original CLSM that uses topography characteristics to model catchment processes is discarded, and a peatland-specific model concept is realized in its place. To facilitate its utilization in operational GEOS efforts, PEAT-CLSM uses the basic structure of CLSM and the same global input data. Parameters used in PEAT-CLSM are based on literature data. A suite of CLSM and PEAT-CLSM simulations for peatland areas between 40°N and 75°N is presented and evaluated against a newly compiled data set of groundwater table depth and eddy covariance observations of latent and sensible heat fluxes in natural and seminatural peatlands. CLSM's simulated groundwater tables are too deep and variable, whereas PEAT-CLSM simulates a mean groundwater table depth of -0.20 m (snow-free unfrozen period) with moderate temporal fluctuations (standard deviation of 0.10 m), in significantly better agreement with in situ observations. Relative to an operational CLSM version that simply includes peat as a soil class, the temporal correlation coefficient is increased on average by 0.16 and reaches 0.64 for bogs and 0.66 for fens when driven with global atmospheric forcing data. In PEAT-CLSM, runoff is increased on average by 38% and evapotranspiration is reduced by 19%. The evapotranspiration reduction constitutes a significant improvement relative to eddy covariance measurements.

Nutrient and mercury transport in a sub-arctic ladder fen peatland subjected to simulated wastewater discharges.

Safely treating wastewater in remote communities and mining operations in sub-arctic Canada is critical to protecting the surrounding aquatic ecosystems. Undisturbed fen peatlands have been used to minimize the release of contaminants to the aquatic ecosystems; however, there is a limited understanding of wastewater transport or polishing in undisturbed fen peatlands. To elucidate these processes, a small (9800m2, ~250m long) ladder fen was continuously injected with a wastewater surrogate derived from a custom fertilizer blend and 38m3day-1 of water for 51days. The simulated wastewater included sulphate (27.2mgL-1), nitrate (7.6mgL-1), ammonium (9.1mgL-1), phosphate (7.4mgL-1), and chloride (47.2mgL-1). Major ion, total mercury (THg) and methylmercury (MeHg) pore water concentrations were measured throughout the study period. No wastewater contaminants were detected in the site outlet (~250m down-gradient) and most wastewater contaminants, except for SO42- and Cl-, remained relatively immobile. Within the SO42- plume, MeHg and THg concentrations became highly elevated relative to background (up to 10ngL-1, ~ three to five-fold increase) and MeHg comprised 60-100% of dissolved THg in the pore water. No MeHg or THg was exported at the outflow. The large increase in THg cannot be solely accounted for by the increase in MeHg and was likely due to enhanced decomposition of the peat substrate by increased microbial activity due to electron acceptor loading. Since the added nutrients were effectively transformed, sequestered or otherwise removed from pore waters in this experimental system, it appears that fen peatlands have a large capacity to safely treat residential wastewater nutrients; however, the inadvertent increases in THg and MeHg require further investigation and potential management.

Cost-consequence analysis of two different active flowable hemostatic matrices in spine surgery patients.

OBJECTIVES: A recently published retrospective analysis comparing two different active flowable hemostatic matrices (FLOSEAL and SURGIFLO Kit with Thrombin) showed significantly increased resource use and complications (surgery time, risk of blood product transfusion, and amount of matrix used) with SURGIFLO use compared to FLOSEAL in major spine surgery, and also significantly increased surgical time with SURGIFLO use in severe spine surgery. This analysis was developed as a follow-up to this prior analysis, to evaluate the cost-consequence of using FLOSEAL vs SURGIFLO in major and severe spine surgery. METHODS: A cost consequence model was constructed from a US hospital provider perspective. Model parameters combined clinical inputs from the published retrospective analysis with supplemental analyses on annual spine surgery volume using the 2012 National Inpatient Sample (NIS) database. Cost of hemostatic matrices, blood product transfusion, and operating room time were identified from published literature. Various one-way and probabilistic sensitivity analyses were performed. RESULTS: The base case for a medium volume hospital showed that, compared to SURGIFLO, patients receiving FLOSEAL required three fewer blood product transfusions and saved 27 h of OR time, resulting in annual savings of $151 per major and $574 per severe spine surgery. Additional scenarios for high and low volume hospitals supported cost savings in the base case. Probabilistic sensitivity analysis revealed FLOSEAL was cost-saving in 76% of simulations in major spine and 97% of iterations in severe spine surgery. CONCLUSIONS: This economic analysis indicates that use of FLOSEAL instead of SURGIFLO hemostatic matrices to induce hemostasis in both major and severe spine surgery could potentially lead to sizable cost savings in US hospitals, regardless of spinal surgery case-mix.

Disuse rescues the age-impaired adaptive response to external loading in mice.

UNLABELLED: We aimed to determine whether aged bone's diminished response to mechanical loading could be rescued by modulating habitual activity. By reducing background loading, aged bone's response to loading increased to a level no different to young mice. This suggests, given the right stimulus, that ageing bone can respond to mechanical loading. INTRODUCTION: Age-related decline in bone mass has been suggested to represent an impaired ability of bone to adapt to its mechanical environment. In young mice, the tibia's response to external mechanical loading has been shown to increase when habitual activity is reduced by sciatic neurectomy. Here we investigate if neurectomy can rescue bone's response to loading in old mice. METHODS: The effect of tibial disuse, induced by unilateral sciatic neurectomy (SN), on the adaptive response to a single peak magnitude of dynamic load-engendered mechanical strain was assessed in 19-month-old (aged) mice. In a second experiment, a range of peak loads was used to assess the load magnitude-related effects of loading on a background of disuse in young adult and aged mice. Bone architecture was analysed using micro-computed tomography (µCT) and dynamic histomorphometry. RESULTS: In the first experiment, SN in aged mice was associated with a significant periosteal osteogenic response to loading not observed in sham-operated mice (7.98 ± 1.7 vs 1.02 ± 2.2 % increase in periosteally enclosed area, p < 0.05). In the second experiment, SN abrogated the expected age-related difference in the bones' osteogenic response to peak strain magnitude (p > 0.05). CONCLUSIONS: These data suggest that bones' age-related decline in osteogenic responsiveness to loading does not originate in bone cells to either assess, or appropriately respond to strain, but rather is likely to be due to inhibitory "averaging" effects derived from the habitual strains to which the bone is already adapted. If such "strain averaging" is applicable to humans, it suggests that gentle exercise may degrade the beneficially osteogenic effects of short periods of more vigorous activity.

Polymorphisms in TNC and COL5A1 genes are associated with risk of superficial digital flexor tendinopathy in National Hunt Thoroughbred racehorses.

REASONS FOR PERFORMING THE STUDY: To explore whether genetic susceptibility is a potential risk factor for superficial digital flexor (SDF) tendinopathy in Thoroughbred (TB) racehorses. OBJECTIVES: To identify informative single nucleotide polymorphisms (SNPs) that capture genetic diversity across a range of candidate genes and to investigate, in a case-control study, their association with SDF tendinopathy in UK National Hunt TB racehorses in training. STUDY DESIGN: Case-control candidate gene association study. METHODS: This study used in silico gene assembly and DNA sequencing to screen candidate genes for SNPs. Seven candidate genes were selected using a hypothesis-driven approach: tenascin-C (TNC), collagen, type 1, α 1 (COL1A1), collagen, type 5, α 1 (COL5A1), matrix metalloproteinase type 3 (MMP3), matrix metalloproteinase type 13 (MMP13), fibromodulin (FMOD) and cartilage oligomeric matrix protein (COMP). The SNPs were validated in DNA isolated from 48 TB racehorses and used to genotype 270 racehorses with SDF tendinopathy and 270 yard-matched controls. Genotyping of cases and controls was performed using SNaPshot™. RESULTS: Racehorses heterozygous for the TNC BIEC2-696469 polymorphism were less likely to have SDF tendinopathy than racehorses homozygous for the wild-type allele (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.36-0.85, P = 0.01). This finding remained significant after adjustment for age and racing background (OR 0.57, 95% CI 0.36-0.92, P = 0.03). Racehorses homozygous for the novel COL5A1 COL5A1_01 variant allele were nearly 3 times more likely to have SDF tendinopathy than those homozygous for the wild-type allele (OR 2.82, 95% CI 1.25-6.35, P = 0.01); this association remained significant after adjustment for age and racing background (OR 2.77, 95% CI 1.18-6.53, P = 0.03). CONCLUSIONS: Results suggest that sequence variants in TNC and COL5A1 genes are associated with SDF tendinopathy in TB racehorses. In future genetic markers may be used to identify horses at risk of SDF tendinopathy.

The cyclooxygenase-2 selective inhibitor NS-398 does not influence trabecular or cortical bone gain resulting from repeated mechanical loading in female mice.

UNLABELLED: A single injection of the cyclooxygenase-2 (COX-2) selective inhibitor NS-398 reduces bone's osteogenic response to a single period of mechanical loading in female rats, while women taking COX-2 selective inhibitors do not have lower bone mass. We show that daily NS-398 injection does not influence bone gain from repeated loading in female mice. INTRODUCTION: Prostaglandins are mediators of bone cells' early response to mechanical stimulation. COX-2 expression is up-regulated by exposure of these cells to mechanical strain or fluid flow, and the osteogenic response to a single loading period is reduced by COX-2 inhibition. This study determined, in female mice in vivo, the effect of longer term COX-2 inhibition on adaptive (re)modelling of cortical and trabecular bone in response to repeated loading. METHODS: Nineteen-week-old female C57BL/6 mice were injected with vehicle or NS-398 (5 mg/kg/day) 5 days a week for 2 weeks. On three alternate days each week, the right tibiae/fibulae were axially loaded [40 cycles (7 min)/day] three hours after injection. Left limbs acted as internal controls. Changes in three-dimensional bone architecture were analysed by high-resolution micro-computed tomography. RESULTS: In control limbs NS-398 was associated with reduced trabecular number but had no influence on cortical bone. In loaded limbs trabecular thickness and cortical periosteally enclosed volume increased. NS-398 showed no effect on this response. CONCLUSION: Pharmacological inhibition of COX-2 by NS-398 does not affect trabecular or cortical bone's response to repeated mechanical loading in female mice and thus would not be expected to impair the functional adaptation of bone to physical activity in women.

Descriptive epidemiology of joint injuries in Thoroughbred racehorses in training.

REASONS FOR PERFORMING STUDY: No large scale epidemiological studies have previously quantified the occurrence of carpal, metacarpo- and metatarsophalangeal (MCP/MTP) joint injuries in Thoroughbred racehorses. OBJECTIVES: To develop an objective classification system for carpal and MCP/MTP joint injuries and estimate the incidence of these injuries in young Thoroughbreds in flat race training. METHODS: In a prospective cohort study, data on daily exercise and veterinary-diagnosed carpal and MCP/MTP joint injuries were collected from Thoroughbreds monitored since starting training as yearlings, for up to 2 years. Cases were classified in one of 4 categories: 1) localised to a carpal or MCP/MTP joint based on clinical examination and/or diagnostic analgesia; no diagnostic imaging performed; 2) localised to a carpal or MCP/MTP joint based on clinical examination and/or diagnostic analgesia; radiographs taken but no abnormalities detected; 3) evidence of abnormality of subchondral bone and/or articular margin(s) on diagnostic imaging and 4) evidence of discontinuity of the articular surface on diagnostic imaging. Incidence rates and rate ratios were estimated using Poisson regression, adjusting for trainer-level clustering. RESULTS: A total of 647 horses from 13 trainers throughout England contributed 7785 months at risk of joint injury. One-hundred-and-eighty-four cases of carpal (n = 82) or MCP/MTP (n = 102) joint injury were reported in 165 horses and classified in Category 1 (n = 21), Category 2 (n = 21), Category 3 (n = 72) or Category 4 (n = 70). The overall joint injury rate was 1.8 per 100 horse months (95% CI = 1.2, 2.8); rates did not differ significantly between 2- and 3-year-olds but females sustained Category 1 injuries at triple the rate of males (P = 0.03). Joint injury rates differed significantly between trainers (P<0.001) and there was trainer variation in anatomical site and severity of injury. CONCLUSIONS AND POTENTIAL RELEVANCE: Carpal and MCP/MTP joint injuries are an important cause of morbidity in Thoroughbred racehorses. Identification of modifiable risk factors for these injuries may reduce their incidence.

Mechanical loading-related changes in osteocyte sclerostin expression in mice are more closely associated with the subsequent osteogenic response than the peak strains engendered.

UNLABELLED: Osteocyte sclerostin is regulated by loading and disuse in mouse tibiae but is more closely related to subsequent local osteogenesis than the peak strains engendered. INTRODUCTION: The purpose of this study was to assess the relationship between loading-related change in osteocyte sclerostin expression, local strain magnitude, and local bone modeling/remodeling. METHODS: The right tibiae of 19-week-old female C57BL/6 mice were subjected to non-invasive, dynamic axial loading and/or to sciatic neurectomy-induced disuse. The sclerostin status of osteocytes was evaluated immunohistochemically, changes in bone mass by micro-computed tomography, new bone formation by histomorphometry, and loading-induced strain by strain gauges and finite element analysis. RESULTS: In cortical bone of the tibial shaft, loading engendered strains of similar peak magnitude proximally and distally. Proximally, sclerostin-positive osteocytes decreased and new bone formation increased. Distally, there was neither decrease in sclerostin-positive osteocytes nor increased osteogenesis. In trabecular bone of the proximal secondary spongiosa, loading decreased sclerostin-positive osteocytes and increased bone volume. Neither occurred in the primary spongiosa. Disuse increased sclerostin-positive osteocytes and decreased bone volume at all four sites. Loading reversed this sclerostin upregulation to a level below baseline in the proximal cortex and secondary spongiosa. CONCLUSION: Loading-related sclerostin downregulation in osteocytes of the mouse tibia is associated preferentially with regions where new bone formation is stimulated rather than where high peak strains are engendered. The mechanisms involved remain unclear, but could relate to peak surface strains not accurately reflecting the strain-related osteogenic stimulus or that sclerostin regulation occurs after sufficient signal processing to distinguish between local osteogenic and non-osteogenic responses.

The effect of exercise regimens on racing performance in National Hunt racehorses.

REASONS FOR PERFORMING STUDY: A previous study has identified exercise undertaken during training to be associated with racing performance in flat racehorses. However, no such studies have been conducted in National Hunt (NH) horses. AIM: To determine whether exercise undertaken during training is associated with racing performance in NH racehorses. METHODS: Data were collected as part of a larger study investigating injury occurrence in NH racehorses. Race records and daily exercise data were obtained from NH racehorses at 14 training yards. Canter, gallop and race distances accumulated in the 30 days preceding a 'case race' were calculated. Associations between exercise-, horse- and race-level variables and the odds of winning, winning prize money, being pulled up and falling were identified using mixed effects logistic regression. RESULTS: Data from 4444 races run by 858 horses were included in analyses. Horses accumulating longer canter distances in the preceding 30 days were more likely to win or win prize money and less likely to be pulled-up. Horses accumulating longer race distances in a 30 day period were more likely to win, whilst those accumulating longer gallop distances in a 30 day period were more likely to win prize money. Horses that had jump-schooled in the preceding 30 days were more likely to fall during the race than those that had not. Trainer and horse were associated with racing performance after adjusting for exercise. CONCLUSIONS: Results from this study suggest that NH race performance may be improved through modification of exercise regimens. After controlling for the abilities of individual trainers and horses and conditions of the case race, horses accumulating longer exercise distances in the 30 days preceding a race were more likely to be successful. However, horses that had jump-schooled in the 30 days preceding a race were more likely to fall.

Ultrasonographic assessment of the superficial digital flexor tendons of National Hunt racehorses in training over two racing seasons.

REASONS FOR PERFORMING STUDY: It is important to ascertain the prevalence of superficial digital flexor tendon (SDFT) injuries and to improve methods of predicting injury in National Hunt (NH) racehorses. OBJECTIVES: To establish: 1) the prevalence of SDFT tendinopathy in NH horses; 2) whether routine ultrasonography can be used to predict SDFT injuries; 3) whether previous tendinopathy predisposes to reinjury; 4) a normal range for the SDFT cross-sectional area (CSA); and 5) the effects of gender, age, background (ex-flat or ex-store), limb, training and rest periods on SDFT CSA. METHODS: Routine ultrasound assessment of the palmar metacarpal soft tissues of 263 NH racehorses was performed on up to 6 occasions over 2 NH racing seasons. RESULTS: The prevalence of SDFT pathology detected using ultrasonography was 24% (n = 148), with a nonsignificant variation between yards of 10-40%. No changes in SDFT CSA or ultrasonographic appearance were detected prior to injury. Older horses had a significantly higher prevalence of SDFT pathology compared to younger horses, and horses with tendinopathy were more likely to suffer an acute injury compared to horses with no evidence of pathology. A reference range for normal CSA measurements was established as 77-139 mm2 at level 4, from 142 horses with no ultrasonographic evidence of SDFT pathology. The CSA of normal horses did not vary significantly with age, limb or over 2 racing seasons, but did with sex and background. CONCLUSIONS: The study confirms that SDFT tendinopathy is common in NH horses, with substantial variation between training yards. Ultrasonography at 3 month intervals did not seem to predict acute SDFT injuries. POTENTIAL RELEVANCE: Variation in the prevalence of tendinopathy between yards suggests that training methods may influence injury rate. It was not possible to predict injury using routine ultrasonography and therefore other methods must be identified. A normal reference range for SDFT CSA is provided.

Descriptive epidemiology of fracture, tendon and suspensory ligament injuries in National Hunt racehorses in training.

REASONS FOR PERFORMING STUDY: While fractures and tendon injuries are known to be important diseases in National Hunt (NH) racehorses during racing, there are no accurate estimates of their incidence in NH training yards. OBJECTIVES: To estimate the incidence of fractures and tendon and suspensory ligament injuries (TLIs) in NH racehorses in training; to describe the injuries incurred and to compare injury incidence rates by horse age, trainer, gender and background (ex-flat vs. ex-store horses). METHODS: Cohort data were collected from 14 UK NH training yards for 2 racing seasons. Daily exercise regimens and details of fractures and TLIs occurring in study horses were recorded. RESULTS: Data were gathered from 1223 horses that spent 9466 months at risk of injury. The fracture incidence rate was 1.1/100 horse months and varied significantly by trainer (P<0.001) but not by gender, age or background. The pelvis and third metacarpal bone (MCIII) were the most common fracture sites, although this varied between racing and training. The TLI incidence rate was 1.9/100 horse months and varied significantly by trainer (P = 0.05) and age (P<0.001) but not by gender or background. However, ex-store horses were significantly more likely to have a TLI on the racecourse than ex-flat horses (P = 0.01). Superficial digital flexor injuries accounted for 89% of all TLIs, the remainder being suspensory ligament injuries. CONCLUSIONS AND POTENTIAL RELEVANCE: Fractures and TLIs are important causes of morbidity and mortality in NH racehorses in training in England. This study provides accurate estimates of their incidence in this population and provides a baseline against which to monitor the effect of future interventions.

Bone biomarkers and risk of fracture in two- and three-year-old Thoroughbreds.

The aim of this study was to determine whether bone biomarkers (osteocalcin, PICP, ICTP and CTX-I) could be used to identify 2- and 3-year-olds at increased risk of fracture in the subsequent flat racing season. It was concluded that these bone biomarkers cannot be used to identify 2- and 3-year-olds that sustain a fracture. Whether bone biomarkers have better predictive value in older horses or when measured serially in the same animal remains to be determined.

Identifying early osteoclastic resorptive lesions in feline teeth: a model for understanding the origin of multiple idiopathic root resorption.

BACKGROUND AND OBJECTIVE: Domestic cats commonly suffer from external osteoclastic tooth resorption, a disease with many similarities to human multiple idiopathic root resorption. In both diseases, it is unclear whether anatomical features of the tooth surface are associated with a predisposition for resorptive lesions. The aim of the present study was to investigate the origin and progression of early feline osteoclastic resorptive lesions in teeth exhibiting no clinical signs of disease. MATERIAL AND METHODS: The entire surfaces of 138 teeth from 13 adult cats were analysed using back-scattered electron microscopy. The distribution of lesions was assessed by tooth type, location and between individuals. RESULTS: Seventy-three (53%) teeth showed at least one resorptive lesion. Eleven (85%) cats had lesions, and there was a significant association between increasing age and incidence of resorptive lesions. The highest frequency occurred in mandibular molars (82%). On average, there were 3.5 lesions per tooth. Fifty-two (38%) teeth featured resorptive lesions at the cemento-enamel junction. Twenty-three per cent of teeth with resorptive lesions showed evidence of repair of lesions that was limited to the root surface. There was no evidence of repair of resorptive lesions at the cemento-enamel junction. CONCLUSION: Resorption is prevalent without evidence of clinical disease, and occurred at younger ages than previously reported. It can initiate anywhere on the root surface, but lack of repair of lesions at the cemento-enamel junction indicates that mechanisms of replacement are absent or compromised in this region. Whereas resorption of the root may undergo repair, resorption at the cervix may progress to clinically evident lesions.

Methicillin-resistant Staphylococcus aureus infections among healthy full-term newborns.

OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged in the community, causing disease among healthy people lacking traditional risk factors for MRSA infection. This article describes an outbreak of MRSA among healthy full-term newborns. DESIGN: Cases were identified and corresponding medical information collected. Telephone interviews were conducted with mothers of cases and surveillance cultures from mothers and newborns were performed. MRSA isolates were genotyped. SETTING: Hospital in Chicago, Illinois, USA. PARTICIPANTS: Newborns, their mothers and hospital healthcare workers. INTERVENTION: Nursery infection control practices were enhanced. The MRSA-colonised healthcare workers received intranasal mupirocin. MAIN OUTCOME: Within 4-23 days of birth, 11 newborns were identified with pustules, vesicles or blisters located on the head, groin, perineum, ears, legs, chin and trunk. All received antimicrobials and recovered without incident. RESULTS: None of 432 peripartum women, one of 399 newborns, and two of 135 healthcare workers were nasal MRSA carriers. Available isolates from six patients, two healthcare workers, and one from an MRSA-colonised newborn were similar by pulsed-field gel electrophoresis. Other than contact with the hospital, no common exposures of MRSA transmission were identified. CONCLUSIONS: MRSA strains that initially emerged in the community are now causing disease in healthcare settings. Providers should be aware that MRSA can cause skin infections among healthy newborns. Adherence to standard infection control practices is important to prevent transmission of MRSA in nurseries.

Days lost from training by two- and three-year-old Thoroughbred horses: a survey of seven UK training yards.

REASONS FOR PERFORMING STUDY: The first major epidemiological study of injury incidence in the UK flat racing Thoroughbred (TB), published in 1985, found lameness to be the single largest reason for days when horses failed to train. It was considered advisable to ascertain if progress has been made in reducing the problem of musculoskeletal injuries in the intervening period. OBJECTIVE: To quantify injury incidence and days lost from training by 2- and 3-year-old TBs in UK training yards during 2002 and 2003. METHODS: One-hundred-and-eighty-two yearling TBs were recruited at the end of 2001 and daily training and injury records maintained over the following 2 training and racing seasons. Days were defined as lost from training when a horse failed to train at a slow canter speed or faster, and could be assigned to one of 4 categories: lameness, medical, traumatic and unknown. The incidence and number of days lost due to specific injuries and medical conditions was determined by further subdividing the lameness and medical categories. RESULTS: The study period provided a total of 52,601 2-year-old and 29,369 3-year-old days available for training, with 2-year-olds failing to train on a significantly greater proportion of days available than 3-year-olds. Lameness was the most important condition causing horses to miss training, with stress fractures being the most important cause of lameness. Medical conditions were a relatively minor cause of days lost from training, accounting for approximately 5% of untrained days in the 2 age groups. CONCLUSIONS: In UK flat racehorses there has been little change in the proportion of days lost from training due to lameness over the last 20 years. POTENTIAL RELEVANCE: This study highlights the need for further efforts to reduce the problem of lameness in the racing TB.

Analysis of the surface characteristics and mineralization status of feline teeth using scanning electron microscopy.

External resorption of teeth by odontoclasts is a common condition of unknown origin affecting domestic cats. Odontoclastic resorptive lesions involve the enamel cementum junction (ECJ, cervix) and root surface, leading to extensive loss of enamel, dentine and cementum. This study was undertaken in order to determine whether features of the surface anatomy and mineralization of feline teeth could explain why odontoclastic resorptive lesions are so prevalent in this species. Backscattered electron scanning electron microscopy was used to study enamel, cementum and dentine in non-resorbed, undemineralized teeth from adult cats. Analysis of the ECJ revealed thin enamel and cementum and exposed dentine at this site. Furthermore, enamel mineralization decreased from the crown tip to the ECJ, and dentine mineralization was lowest at the ECJ and cervical root. Analysis of cementum revealed variations in the organization and composition of fibres between the cervical, mid- and apical root although no significant differences in mineralization of cementum were detected between different regions of the root. Reparative patches associated with resorption of cementum by odontoclasts and repair by cementoblasts were present on the root surface. In conclusion, results suggest that the ECJ and cervical dentine could be at a greater risk of destruction by odontoclasts compared with other regions of the tooth. The relationship of these features to the development and progression of resorption now requires further examination.

Hypoxia induces giant osteoclast formation and extensive bone resorption in the cat.

Dental disease due to osteoclast (OC) overactivity reaches epidemic proportions in older domestic cats and has also been reported in wild cats. Feline odontoclastic resorptive lesions (FORL) involve extensive resorption of the tooth, leaving it liable to root fracture and subsequent loss. The etiopathogenesis of FORL remains unclear. Here, we explore the hypothesis that FORL is associated with hypoxia in the oral microenvironment, leading to increased OC activity. To investigate this, we developed a method of generating OCs from cat blood. Reducing O2 from 20% to 2% increased the mean area of OC eightfold from 0.01 to 0.08 mm2. In hypoxic cultures, very large OCs containing several hundred nuclei were evident (reaching a maximum size of approximately 14 mm2). Cultures exposed to 2% O2 exhibited an increase of approximately 13-fold in the area of bone slices covered by resorption lacunae. In line with this finding, there was a significant increase in cells differentiating under hypoxic conditions, reflected in increased expression of cathepsin K and proton pump enzymes. In conclusion, these results demonstrate that oxygen tension is a major regulator of OC formation in the cat. However, in this species, hypoxia induces the formation of "giant" OCs, which can be so large as to be visible with the naked eye and yet also actively resorb. This suggests that local hypoxia is likely to play a key role in the pathogenesis of FORL and other inflammatory conditions that are associated with bone resorption in cats.

Nature's answer to breaching the skin barrier: an innovative development for amputees.

The human body has evolved to maintain homeostasis through the covering of skin and mucous membranes, which separate the internal environment from the harsh and variable external milieu. Few structures naturally penetrate these coverings, and teeth are the only exception in human beings. Attempts to breach these barriers, to develop skin- penetrating, bone-anchored amputation prostheses, can lead to opportunist invasion by microorganisms and subsequent infection, which can jeopardize the life of the individual. There are only a few fascinating examples where the integument of other species is interrupted without such dire consequences, and the deer antler is one such case. Deer antlers are cephalic bony appendages arising from the frontal bones of the skull of the males of most deer species, and are true transient skin-penetrating structures. Antlers are subject to extreme loading during the rutting season and yet the skin-bone barrier remains intact. Here we show how deer antlers can be used as natural analogues for the successful development of specialized orthopaedic amputation prosthetics. We have used quantitative and qualitative findings from a study of the morphology of deer antlers to develop a device that mimics their structure, which creates a tight seal between the implant and the host tissues, for use in amputation prosthetics.