The fast multi-frame X-ray diffraction detector at the Dynamic Compression Sector.

A multi-frame, X-ray diffraction (XRD) detector system has been developed for use in time-resolved XRD measurements during single-event experiments at the Dynamic Compression Sector (DCS) at the Advanced Photon Source (APS). The system is capable of collecting four sequential XRD patterns separated by 153 ns, the period of the APS storage ring in the 24-bunch mode. This capability allows an examination of the temporal evolution of material dynamics in single-event experiments, such as plate impact experiments, explosive detonations, and split-Hopkinson pressure bar experiments. This system is available for all user experiments at the DCS. Here, the system description and measured performance parameters (detective quantum efficiency, spatial and temporal resolution, and dynamic range) are presented along with procedures for synchronization and image post-processing.

Player position in American football influences the magnitude of mechanical strains produced in the location of chronic traumatic encephalopathy pathology: A computational modelling study.

American football players are frequently exposed to head impacts, which can cause concussions and may lead to neurodegenerative diseases such as chronic traumatic encephalopathy (CTE). Player position appears to influence the risk of concussion but there is limited work on its effect on the risk of CTE. Computational modelling has shown that large brain deformations during head impacts co-localise with CTE pathology in sulci. Here we test whether player position has an effect on brain deformation within the sulci, a possible biomechanical trigger for CTE. We physically reconstructed 148 head impact events from video footage of American Football games. Players were separated into 3 different position profiles based on the magnitude and frequency of impacts. A detailed finite element model of TBI was then used to predict Green-Lagrange strain and strain rate across the brain and in sulci. Using a one-way ANOVA, we found that in positions where players were exposed to large magnitude and low frequency impacts (e.g. defensive back and wide receiver), strain and strain rate across the brain and in sulci were highest. We also found that rotational head motion is a key determinant in producing large strains and strain rates in the sulci. Our results suggest that player position has a significant effect on impact kinematics, influencing the magnitude of deformations within sulci, which spatially corresponds to where CTE pathology is observed. This work can inform future studies investigating different player-position risks for concussion and CTE and guide design of prevention systems.

Comparative safety profile of chloral hydrate versus other sedatives for procedural sedation in hospitalized infants.

BACKGROUND: Given the limited available evidence on chloral hydrate safety in neonatal populations and the discrepancy in chloral hydrate acceptance between the US and other countries, we sought to clarify the safety profile of chloral hydrate compared to other sedatives in hospitalized infants. METHODS: We included all infants <120 days of life who underwent a minor procedure and were administered chloral hydrate, clonidine, clonazepam, dexmedetomidine, diazepam, ketamine, lorazepam, midazolam, propofol, or pentobarbital on the day of the procedure. We characterized the distribution of infant characteristics and evaluated the relationship between drug administration and any adverse event. We performed propensity score matching, regression adjustment (RA), and inverse probability weighting (IPW) to ensure comparison of similar infants and to account for confounding by indication and residual bias. Results were assessed for robustness to analytical technique by reanalyzing the main outcomes with multivariate logistic regression, a doubly robust IPW with RA model, and a doubly robust augmented IPW model with bias-correction. RESULTS: Of 650 infants, 497 (76%) received chloral hydrate, 79 (12%) received midazolam, 54 (8%) received lorazepam, and 15 (2%) received pentobarbital. Adverse events occurred in 41 (6%) infants. Using propensity score matching, chloral hydrate was associated with a decreased risk of an adverse event compared to other sedatives, risk difference (95% confidence interval) of -12.79 (-18.61, -6.98), p <  0.001. All other statistical methods resulted in similar findings. CONCLUSION: Administration of chloral hydrate to hospitalized infants undergoing minor procedures is associated with a lower risk for adverse events compared to other sedatives.

Paradoxical aortic stiffening and subsequent cardiac dysfunction in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome (HGPS) is an ultra-rare disorder with devastating sequelae resulting in early death, presently thought to stem primarily from cardiovascular events. We analyse novel longitudinal cardiovascular data from a mouse model of HGPS (LmnaG609G/G609G) using allometric scaling, biomechanical phenotyping, and advanced computational modelling and show that late-stage diastolic dysfunction, with preserved systolic function, emerges with an increase in the pulse wave velocity and an associated loss of aortic function, independent of sex. Specifically, there is a dramatic late-stage loss of smooth muscle function and cells and an excessive accumulation of proteoglycans along the aorta, which result in a loss of biomechanical function (contractility and elastic energy storage) and a marked structural stiffening despite a distinctly low intrinsic material stiffness that is consistent with the lack of functional lamin A. Importantly, the vascular function appears to arise normally from the low-stress environment of development, only to succumb progressively to pressure-related effects of the lamin A mutation and become extreme in the peri-morbid period. Because the dramatic life-threatening aortic phenotype manifests during the last third of life there may be a therapeutic window in maturity that could alleviate concerns with therapies administered during early periods of arterial development.

Genetic and pharmacologic modulation of cementogenesis via pyrophosphate regulators.

Pyrophosphate (PPi) serves as a potent and physiologically important regulator of mineralization, with systemic and local concentrations determined by several key regulators, including: tissue-nonspecific alkaline phosphatase (ALPL gene; TNAP protein), the progressive ankylosis protein (ANKH; ANK), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1; ENPP1). Results to date have indicated important roles for PPi in cementum formation, and we addressed several gaps in knowledge by employing genetically edited mouse models where PPi metabolism was disrupted and pharmacologically modulating PPi in a PPi-deficient mouse model. We demonstrate that acellular cementum growth is inversely proportional to PPi levels, with reduced cementum in Alpl KO (increased PPi levels) mice and excess cementum in Ank KO mice (decreased PPi levels). Moreover, simultaneous ablation of Alpl and Ank results in reestablishment of functional cementum in dKO mice. Additional reduction of PPi by dual deletion of Ank and Enpp1 does not further increase cementogenesis, and PDL space is maintained in part through bone modeling/remodeling by osteoclasts. Our results provide insights into cementum formation and expand our knowledge of how PPi regulates cementum. We also demonstrate for the first time that pharmacologic manipulation of PPi through an ENPP1-Fc fusion protein can regulate cementum growth, supporting therapeutic interventions targeting PPi metabolism.

[Comparison of anatomic and functional results between Z6 femtosecond laser assisted and manual trephination in deep anterior lamellar keratoplasty for advanced keratoconus [French version]]. / Comparaison des résultats anatomiques et fonctionnels à 12 mois d'une série de kératoplasties lamellaires profondes assistées au laser femtoseconde Z6 versus trépanation manuelle pour kératocônes sévères.

The management of severe keratoconus requires corneal transplantation, for which the gold standard is deep anterior lamellar keratoplasty (DALK), preserving the healthy Descemet's membrane and endothelium. The safety and reproducibility of corneal cuts have been improved by the evolution of femtosecond lasers in refractive surgery, and femtosecond laser in DALK would seem to provide the same advantages over the manual method. In our retrospective study, we compare functional and anatomical results of femtosecond assisted DALK versus manual trephination DALK in patients with keratoconus in stage 4 of the Krumeich classification. It is a retrospective study including all patients with stage 4 keratoconus who underwent femtosecond laser assisted DALK between November 2012 and November 2015 in Nantes hospital. We compared those patients to a group of patients who underwent manual DALK in the same period, paired by age and maximal keratometry. We assessed visual acuity, pachymetry, endothelial cell density (specular microscopy), and keratometry before surgery and at 4, 8 and 12 months of follow-up. Laser settings and intraoperative complications were recorded. Nineteen patients underwent surgery by femtosecond assisted DALK, 6 women and 12 men with average age 30.2±10.8 years at transplantation. They were paired with a group of 17 patients who underwent manual DALK in order to compare results. Before surgery, mean visual acuity in the femtosecond group was 0.90 logMAR versus 0.89 logMAR in the manual group, showing no statistically significant difference (P=0.96). Both groups were similar in terms of preoperative age, mean keratometry, pachymetry and endothelial cell density. Average visual acuity post-surgery was 0.27, 0.26; and 0.14 logMAR for femtosecond DALK versus 0.27, 0.17 et 0.25 for manual DALK at 4, 8 and 12 months follow-up, respectively showing no statistically significant difference. After surgery, at 4, 8 and 12 months, mean pachymetry was similar in both groups, and average endothelial cell density was 2390 cells/mm2 in femtoDALK versus 2531 cells/mm2 in manual DALK at 12 months of follow-up, showing no statistically significant difference (P=0.5726). The rate of Descemet's membrane microperforations during the procedure was low and similar for both groups. Our study allows for a 12 month follow-up, with assessment of visual recovery, anatomical result and endothelial safety in a sample of 19 femtosecond laser assisted DALK with no statistical significant difference versus the manual trephination group. Femtosecond laser allows for increased reproducibility of the DALK procedure without reducing adverse effects during surgery. Femtosecond laser seems to improve the technique of the DALK procedure, and future developments could improve the reproducibility of DALK even further. A medical economics study would be necessary to determine the cost effectiveness of femtosecond laser assisted DALK.

Comparison of 12-month anatomic and functional results between Z6 femtosecond laser-assisted and manual trephination in deep anterior lamellar keratoplasty for advanced keratoconus.

The management of severe keratoconus requires corneal transplantation, for which the gold standard is deep anterior lamellar keratoplasty (DALK), preserving the healthy Descemet's membrane and endothelium. The safety and reproducibility of corneal cuts have been improved by the evolution of femtosecond lasers in refractive surgery, and femtosecond laser in DALK would seem to provide the same advantages over the manual method. In our retrospective study, we compare functional and anatomical results of femtosecond-assisted DALK versus manual trephination DALK in patients with keratoconus in stage 4 of the Krumeich classification. It is a retrospective study including all patients with stage 4 keratoconus who underwent femtosecond laser-assisted DALK between November 2012 and November 2015 in Nantes university medical center. We compared those patients to a group of patients who underwent manual DALK in the same period, paired by age and maximal keratometry. We assessed visual acuity, pachymetry, endothelial cell density (specular microscopy), and keratometry before surgery and at 4, 8 and 12 months of follow-up. Laser settings and intraoperative complications were recorded. Nineteen patients underwent surgery by femtosecond-assisted DALK, 6 women and 12 men with average age 30.2±10.8 years at transplantation. They were paired with a group of 17 patients who underwent manual DALK in order to compare results. Before surgery, mean visual acuity in the femtosecond group was 0.90 logMAR versus 0.89 logMAR in the manual group, showing no statistically significant difference (P=0.96). Both groups were similar in terms of preoperative age, mean keratometry, pachymetry and endothelial cell density. Average visual acuity post-surgery was 0.27; 0.26; and 0.14 logMAR for femtosecond DALK versus 0.27; 0.17 et 0.25 for manual DALK at 4, 8 and 12 months follow-up respectively, showing no statistically significant difference. After surgery, at 4, 8 and 12 months, mean pachymetry was similar in both groups, and average endothelial cell density was 2390 cells/mm2 for femto DALK versus 2531 cells/mm2 for manual DALK at 12 months of follow-up, showing no statistically significant difference (P=0.5726). The rate of Descemet's membrane microperforations during the procedure was low and similar for both groups. Our study allows for a 12-month follow-up, with assessment of visual recovery, anatomic result and endothelial safety in a series of 19 femtosecond laser-assisted DALK with no statistical significant difference versus the manual trephination group. Femtosecond laser allows for increased reproducibility of the DALK procedure without reducing adverse effects during surgery. Femtosecond laser seems to improve the technique of the DALK procedure, and future developments could improve the reproducibility of DALK even further. A medical economics study would be necessary to determine the cost-effectiveness of femtosecond laser-assisted DALK.

Beyond animals and plants: dynamic maternal effects in the fungus Neurospora crassa.

Maternal effects are widely documented in animals and plants, but not in fungi or other eukaryotes. A principal cause of maternal effects is asymmetrical parental investment in a zygote, creating greater maternal vs. paternal influence on offspring phenotypes. Asymmetrical investments are not limited to animals and plants, but are also prevalent in fungi and groups including apicomplexans, dinoflagellates and red algae. Evidence suggesting maternal effects among fungi is sparse and anecdotal. In an experiment designed to test for maternal effects across sexual reproduction in the model fungus Neurospora crassa, we measured offspring phenotypes from crosses of all possible pairs of 22 individuals. Crosses encompassed reciprocals of 11 mating-type 'A' and 11 mating-type 'a' wild strains. After controlling for the genetic and geographic distances between strains in any individual cross, we found strong evidence for maternal control of perithecia (sporocarp) production, as well as maternal effects on spore numbers and spore germination. However, both parents exert equal influence on the percentage of spores that are pigmented and size of pigmented spores. We propose a model linking the stage-specific presence or absence of maternal effects to cellular developmental processes: effects appear to be mediated primarily through the maternal cytoplasm, and, after spore cell walls form, maternal influence on spore development is limited. Maternal effects in fungi, thus far largely ignored, are likely to shape species' evolution and ecologies. Moreover, the association of anisogamy and maternal effects in a fungus suggests maternal effects may also influence the biology of other anisogamous eukaryotes.

Selection of pairings reaching evenly across the data (SPREAD): A simple algorithm to design maximally informative fully crossed mating experiments.

We present a novel algorithm for the design of crossing experiments. The algorithm identifies a set of individuals (a 'crossing-set') from a larger pool of potential crossing-sets by maximizing the diversity of traits of interest, for example, maximizing the range of genetic and geographic distances between individuals included in the crossing-set. To calculate diversity, we use the mean nearest neighbor distance of crosses plotted in trait space. We implement our algorithm on a real dataset of Neurospora crassa strains, using the genetic and geographic distances between potential crosses as a two-dimensional trait space. In simulated mating experiments, crossing-sets selected by our algorithm provide better estimates of underlying parameter values than randomly chosen crossing-sets.

Histopathologic variation between liver lobes in dogs.

BACKGROUND: Biopsy of the liver evaluates a small portion of tissue, with inferences made to the entire organ. The method and number of biopsies obtained are tempered by consideration of the risks and benefits. Recommendations often include biopsy of more than one liver lobe, although the consistency of histopathology among lobes in dogs is unknown. HYPOTHESIS/OBJECTIVES: To describe the distribution of histopathologic abnormalities between liver lobes. We hypothesized that discordant results would be evenly distributed among all liver lobes. ANIMALS: Seventy dogs undergoing necropsy. METHODS: Prospective study. Liver samples were obtained from all lobes. A primary diagnosis was assigned to each liver sample based on the predominant histopathologic abnormality. RESULTS: In this population of dogs, biopsy of at least 2 liver lobes identified the predominant histologic abnormality in 98.6% of the cases. Ten (14%) of the dogs had ≤ 3 lobes in agreement and could not be assigned a predominant diagnosis. The same diagnosis was present in 6/6 lobes in 39 (56.5%) dogs, 5/6 lobes in 10 (14.5%) dogs, 4/6 lobes in 10 (14.5%) dogs, 3/6 lobes in 7 (10.1%) dogs, and 2/6 in 3 (4.3%) dogs. The number of discordant results did not differ between the liver lobes. CONCLUSION AND CLINICAL IMPORTANCE: The likelihood of obtaining a sample that is reflective of the predominant histologic abnormality in the liver is increased when multiple liver lobes are biopsied.

A comparison of liver sampling techniques in dogs.

BACKGROUND: The liver sampling technique in dogs that consistently provides samples adequate for accurate histopathologic interpretation is not known. HYPOTHESIS/OBJECTIVES: To compare histopathologic results of liver samples obtained by punch, cup, and 14 gauge needle to large wedge samples collected at necropsy. ANIMALS: Seventy dogs undergoing necropsy. METHODS: Prospective study. Liver specimens were obtained from the left lateral liver lobe with an 8 mm punch, a 5 mm cup, and a 14 gauge needle. After sample acquisition, two larger tissue samples were collected near the center of the left lateral lobe to be used as a histologic standard for comparison. Histopathologic features and numbers of portal triads in each sample were recorded. RESULTS: The mean number of portal triads obtained by each sampling method were 2.9 in needle samples, 3.4 in cup samples, 12 in punch samples, and 30.7 in the necropsy samples. The diagnoses in 66% of needle samples, 60% of cup samples, and 69% of punch samples were in agreement with the necropsy samples, and these proportions were not significantly different from each other. The corresponding kappa coefficients were 0.59 for needle biopsies, 0.52 for cup biopsies, and 0.62 for punch biopsies. CONCLUSION AND CLINICAL IMPORTANCE: The histopathologic interpretation of a liver sample in the dog is unlikely to vary if the liver biopsy specimen contains at least 3-12 portal triads. However, in comparison large necropsy samples, the accuracy of all tested methods was relatively low.

Cardiac biomarkers in hyperthyroid cats.

BACKGROUND: Hyperthyroidism has substantial effects on the circulatory system. The cardiac biomarkers NT-proBNP and troponin I (cTNI) have proven useful in identifying cats with myocardial disease but have not been extensively investigated in hyperthyroidism. HYPOTHESIS: Plasma NT-proBNP and cTNI concentrations are higher in cats with primary myocardial disease than in cats with hyperthyroidism and higher in cats with hyperthyroidism than in healthy control cats. ANIMALS: Twenty-three hyperthyroid cats, 17 cats with subclinical hypertrophic cardiomyopathy (HCM), and 19 euthyroid, normotensive healthy cats ≥8 years of age. Fourteen of the hyperthyroid cats were re-evaluated 3 months after administration of radioiodine ((131)I). METHODS: Complete history, physical examination, complete blood count, serum biochemistries, urinalysis, blood pressure measurement, serum T4 concentration, plasma concentrations of NT-proBNP and cTNI, and echocardiogram were obtained prospectively from each cat. RESULTS: Hyperthyroid cats and cats with HCM had plasma NT-proBNP and cTNI concentrations that were significantly higher than those of healthy cats, but there was no significant difference between hyperthyroid cats and cats with HCM with respect to the concentration of either biomarker. In hyperthyroid cats that were re-evaluated 3 months after (131) I treatment, plasma NT-proBNP and cTNI concentrations as well as ventricular wall thickness had decreased significantly. CONCLUSIONS AND CLINICAL IMPORTANCE: Although there may be a role for NT-proBNP in monitoring the cardiac response to treatment of hyperthyroidism, neither NT-proBNP nor cTNI distinguish hypertrophy associated with hyperthyroidism from primary HCM. Therefore, the thyroid status of older cats should be ascertained before interpreting NT-proBNP and cTNI concentrations.

Intramedullary spinal cord neoplasia in 53 dogs (1990-2010): distribution, clinicopathologic characteristics, and clinical behavior.

BACKGROUND: Intramedullary neoplasms of the canine spinal cord are infrequently reported. OBJECTIVE: To describe distribution, clinicopathologic characteristics, radiographic findings, and clinical features of canine intramedullary spinal tumors. METHODS: Retrospective series of histologically confirmed canine intramedullary spinal tumors. Contingency tables were generated for categorical variables (breed, sex, treatment, pain, chief complaint, localization, histology, imaging, and site). Associations were assessed by Fisher's exact, Wilcoxon rank sum test, t-test, and one-way ANOVA. RESULTS: Intramedullary spinal cord tumors comprised 16% (53/331) of all tumors of the spinal cord. Primary tumors were diagnosed in 66% (35/53) of cases, with neuroepithelial-origin tumors comprising 51% (18/35) of all primary neoplasms. Intraparenchymal metastases of transitional cell carcinoma and hemangiosarcoma accounted for 66% (6/18 each) of all secondary tumors. Primary tumors were more likely to affect younger dogs. Dogs with intramedullary metastases were most commonly presented for primary myelopathic signs (8/18, 44%). The majority of all tumors (52.8%) occurred in the T3-L3 spinal cord segments. All dogs with cervical neurolocalization had primary tumors. Dogs with metastatic lesions had a shorter duration of clinical signs before presentation, but there was no difference in survival time between dogs with primary as compared with secondary tumors. CONCLUSIONS: Intramedullary spinal cord tumors are uncommon. Primary intramedullary spinal cord tumors are more common than secondary intramedullary spinal cord tumors and tend to occur in the cervical spinal cord of younger dogs. Intramedullary metastases occur in older dogs, are rarely asymptomatic, and neurologic dysfunction is a common clinical presentation. Dogs with primary tumors may have a protracted clinical course compared with those with intramedullary metastases.

Concentrations of noncortisol adrenal steroids in response to ACTH in dogs with adrenal-dependent hyperadrenocorticism, pituitary-dependent hyperadrenocorticism, and nonadrenal illness.

BACKGROUND: Increases of adrenal hormone concentrations other than cortisol have been reported in dogs with hyperadrenocorticism (HAC). HYPOTHESIS/OBJECTIVES: Measuring noncortisol adrenal hormone concentrations will help identify HAC in dogs. The objective was to determine plasma cortisol, androstenedione, estradiol, progesterone, testosterone, and 17-hydroxyprogesterone concentrations during ACTH stimulation testing of dogs with clinical signs of HAC to ascertain their utility in diagnosis of the disease. ANIMALS: Ninety dogs with clinical findings consistent with HAC had ACTH stimulation tests performed. Results from 29 dogs were excluded from analysis because diagnoses were inconclusive for a variety of reasons. Results from 32 dogs with HAC and 29 dogs with disease other than HAC were analyzed. METHODS: Prospective observational study. Concentrations of adrenocortical hormones were determined before and 1 hour after injecting 5 µg/kg ACTH IM. Diagnoses were determined by response to therapy, histopathology or both. RESULTS: Post-ACTH cortisol (P < .001), progesterone (P = .001), and 17-hydroxyprogesterone (P < .001) concentrations were associated with a diagnosis of HAC. Sensitivity and specificity, respectively, for diagnosing HAC for post-ACTH cortisol were 84 and 59%, progesterone 88 and 55%, and 17-hydroxyprogesterone 91 and 59%, and for post-ACTH cortisol, progesterone and 17-hydroxyprogesterone combined were 88 and 55%. Of 5 dogs with HAC and normal post-ACTH cortisol concentrations, 5 had increased progesterone and 4 had increased 17-hydroxyprogesterone. CONCLUSIONS AND CLINICAL IMPORTANCE: Serum progesterone and 17-hydroxyprogesterone concentrations were useful to diagnose HAC in this study, but were not more sensitive or specific than cortisol concentration.

Real-time, high-resolution x-ray diffraction measurements on shocked crystals at a synchrotron facility.

The Advanced Photon Source (APS) at Argonne National Laboratory was used to obtain real-time, high-resolution x-ray diffraction measurements to determine the microscopic response of shock-compressed single crystals. Disk shaped samples were subjected to plane shock wave compression by impacting them with half-inch diameter, flat-faced projectiles. The projectiles were accelerated to velocities ranging between 300 and 1200 m/s using a compact powder gun designed specifically for use at a synchrotron facility. The experiments were designed to keep the sample probed volume under uniaxial strain and constant stress for a duration longer than the 153.4 ns spacing between x-ray bunches. X-rays from a single pulse (<100 ps duration) out of the periodic x-ray pulses emitted by the synchrotron were used for the diffraction measurements. A synchronization and x-ray detection technique was developed to ensure that the measured signal was obtained unambiguously from the desired x-ray pulse incident on the sample while the sample was in a constant uniaxial strain state. The synchronization and x-ray detection techniques described can be used for a variety of x-ray measurements on shock compressed solids and liquids at the APS. Detailed procedures for applying the Bragg-Brentano parafocusing approach to single crystals at the APS are presented. Analytic developments to determine the effects of crystal substructure and non-ideal geometry on the diffraction pattern position and shape are presented. Representative real-time x-ray diffraction data, indicating shock-induced microstructural changes, are presented for a shock-compressed Al(111) sample. The experimental developments presented here provided, in part, the impetus for the Dynamic Compression Sector (DCS) currently under development at the APS. Both the synchronization∕x-ray detection methods and the analysis equations for high-resolution single crystal x-ray diffraction can be used at the DCS.

High spectral resolution, real-time, Raman spectroscopy in shock compression experiments.

The use of Raman measurements to examine molecular changes associated with shock-induced structural and chemical changes in condensed materials often poses two challenging requirements: high spectral resolution and significantly reduced background light. Here, we describe an experimental method that addresses these requirements and provides better quality data than the time resolved approach used previously. Representative measurements are presented for shock compression of two energetic crystals: pentaerythritol tetranitrate and cyclotrimethylene trinitramine. The high spectral resolution data have provided insight into molecular changes that could not be obtained from lower-resolution, time-resolved methods.

Cyclooxygenase-2 (COX-2) expression in canine intracranial meningiomas.

Meningiomas are the most common canine intracranial tumour. Neurologic disability and death from treatment failure remain problematic despite current surgical and radiotherapeutic treatments for canine intracranial meningiomas. Cyclooxygenase-2 (COX-2) over-expression has been demonstrated in multiple canine malignancies, and COX-2 inhibitory treatment strategies have been shown to have both preventative and therapeutic effects in spontaneous and experimental models of cancer. The purpose of this study was to evaluate COX-2 expression in canine intracranial meningiomas. Immunohistochemical and Western blot (WB) analyses showed COX-2 expression in multiple tissues of the normal canine brain, and 87% (21/24) of intracranial meningiomas studied were immunoreactive to COX-2. No significant associations between COX-2 immunoreactivity and tumour grade were identified. Further studies are required to elucidate the physiologic roles of constitutive COX-2 expression in the central nervous system as well as its participation in meningioma tumourigenesis.

Neurological effects of acute uranium exposure with and without stress.

Circulating uranium rapidly enters the brain and may cause adverse effects on the nervous system that are potentially modulated by stress. In this study, the neurological effects of a single intramuscular injection of 0, 0.1, 0.3, or 1 mg uranium/kg (as uranyl acetate, UA) in rats were examined in the presence and absence of stress. Treatment with UA produced time and dose-dependent increases in serum and regional brain uranium levels. While serum levels returned to control levels by day 30, brain levels remained elevated. Application of stress did not affect the distribution or retention of uranium. Exposure to 1 mg U/kg significantly decreased ambulatory activity, weight gain, forelimb grip strength and transiently impaired working memory. Effects on grip strength and memory were prevented by application of stress prior to uranium exposure. Striatal dopamine content was reduced by 30% 3 days after treatment with 1mg/kg (59+/-6 nmol/mg tissue versus 41+/-5 nmol/mg tissue), but levels returned to control 7 days after uranium exposure. The effect on dopamine was ameliorated by prior application of stress. Exposure to UA did not alter 3,4 dihydroxyphenylacetic acid (DOPAC) levels or numbers of D2 receptors in the striatum. No effect of uranium or stress was observed on levels of GABA, serotonin, norepinephrine, or glutathione (GSH) in the striatum, hippocampus, cerebellum, or cortex. These results indicate that single intramuscular exposures to uranium produce sustained elevation of brain uranium levels and at doses above 0.3 mg/kg can have adverse neurological effects. Application of stress prior to uranium administration modulates neurological effects, but the mechanism is not due to effects on uranium distribution. Uranium exposure also produced renal toxicity which must be considered to accurately assess the effects of uranium on neurological function.

Intestinal carriage of Campylobacter jejuni and Campylobacter coli among cattle from south-western Norway and comparative genotyping of bovine and human isolates by amplified-fragment length polymorphism.

In a survey conducted in 1999-2001, the carriage of thermotolerant Campylobacters in cattle was investigated, and the genetic diversity of C. jejuni within one herd was examined and compared with human isolates. C. jejuni, C. coli and other thermotolerant Campylobacter spp. were isolated from intestinal contents from 26%, 3% and 2% of 804 cattle, respectively. The carriage rate was higher in calves (46%) than in adults (29%). Twenty-nine C. jejuni isolates from one herd and 31 human isolates from the study area were genotyped with amplified-fragment length polymorphism (AFLP). Eighty-three % of the bovine isolates fell into three distinct clusters with 95-100% similarity, persistent in the herd for 5-10 months. Among human isolates, 58% showed >90% similarity with bovine isolates. The results show that cattle are a significant and stable reservoir for C. jejuni in the study area. Transmission between individuals within the herd may be sufficient to maintain a steady C. jejuni population independent of environmental influx. The results of this study have provided new information on C. jejuni and C. coli transmission, and also on the carriage in cattle, genotypes stability and similarity between bovine and human isolates.