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Summary Reasons for performing study To identify pain-related behaviour in working donkeys in order to assist their owners and veterinarians to recognise and manage pain. Objectives To identify general and specific behaviours associated with pain or its relief using a trial with the nonsteroidal anti-inflammatory drug meloxicam (Metacam). Study design Observer-blinded, placebo-controlled trial. Methods Forty adult male working donkeys with common clinical abnormalities were randomly assigned to receive either a single loading dose of meloxicam (1.2 mg/kg bwt per os; n = 20) or a placebo (30 mg honey/250 ml water per os; n = 20). Observation of postural and event behaviours was undertaken at 2 pretreatment time points followed by 4 post treatment time points, using scan (instantaneous) and focal sampling. Results In comparison to pretreatment baselines, donkeys receiving meloxicam were more alert post treatment than the placebo group. They were observed lying down less frequently (P = 0.007), with their eyes closed less frequently (P = 0.04) and having a high head carriage more frequently (P = 0.02). Dozing behaviour decreased after meloxicam compared with the pretreatment baseline (P = 0.03). Donkeys given meloxicam also showed more interest in their environment, turning to look at environmental stimuli more frequently (P = 0.05) than those in the placebo group post treatment. Neither the meloxicam nor the placebo group showed a significant post treatment improvement in lameness scores. Conclusions Working donkeys receiving meloxicam were more active and alert compared with their pretreatment behaviour, confirming the potential value of nonsteroidal anti-inflammatory drugs in identifying behaviours indicative of pain in working donkeys. Behavioural assessment of pain in working donkeys in field clinic conditions will enable veterinary staff and owners to identify welfare issues promptly and monitor response to analgesia. The Summary is available in Chinese – see Supporting information.

To determine whether lame broilers are in pain it is necessary to compare measures of lameness and mobility before and after analgesic treatment. Such measures should not be unduly affected by other bird characteristics. This study assessed the performance of lame (gait score, GS 3-4) and non-lame (GS 0-1) broilers using two mobility tests: (i) a novel test to assess broiler ability to access resources when housed in groups (Group Obstacle test); and (ii) a Latency-to-Lie (LTL) test. Outcome test measures included number of obstacle crossings, latency to cross an obstacle, and time taken to sit in shallow water. Associations between outcome test measures and other bird characteristics (established lameness risk-factors), including strain, sex, age, mass, contact dermatitis and pathology, were also investigated. The performance of high-GS and low-GS broilers differed in both mobility tests and no other bird characteristics were as consistent a predictor as lameness. This demonstrates that mobility impairments are closely related to lameness assessed using GS, and that there is a component of lameness that cannot be explained by other bird characteristics (eg being male and heavy). This component may represent pain or discomfort. Both mobility tests are suitable for further application with analgesic testing to classify lameness-associated pain in broilers.

Pain associated with poultry lameness is poorly understood. The anti-nociceptive properties of two non- steroidal anti-inflammatory drugs (NSAIDs) were evaluated using threshold testing in combination with an acute inflammatory arthropathy model. Broilers were tested in six groups (n = 8 per group). Each group underwent a treatment (saline, meloxicam (3 or 5 mg/kg) or carprofen (15 or 25 mg/kg)) and a pro- cedure (Induced (arthropathy-induction) or sham (sham-handling)) prior to testing. Induced groups had Freund's complete adjuvant injected intra-articularly into the left intertarsal joint (hock). A ramped ther- mal stimulus (1 C/s) was applied to the skin of the left metatarsal. Data were analysed using random- intercept multi-level models. Saline-induced birds had a significantly higher skin temperature (± SD) than saline-sham birds (37.6 ± 0.8 C vs. 36.5 ± 0.5 C; Z = 3.47, P < 0.001), consistent with an inflammatory response. Saline was associated with significantly lower thermal thresholds (TT) than analgesic treatment (meloxicam: Z = 2.72, P = 0.007; carprofen: Z = 2.58, P = 0.010) in induced birds. Saline-induced birds also had signifi- cantly lower TT than saline-sham birds (Z = 2.17, P = 0.030). This study found direct evidence of an asso- ciation between inflammatory arthropathies and thermal hyperalgesia, and showed that NSAID treatment maintained baseline thermal sensitivity (via anti-nociception). Quantification of nociceptive responsiveness in a predictable broiler pain model identified thermal anti-hyperalgesic properties of two NSAIDs, which suggested that therapeutically effective treatment was provided at the doses admin- istered. Such validation of analgesic strategies will increase the understanding of pain associated with specific natural broiler lameness types.

Behavioural signs of pain are difficult to quantify and interpret in animals. Nociceptive threshold testing is therefore a useful method for examining the perception and processing of noxious stimuli underlying pain states. Devices were developed to measure response thresholds to quantified, ramped mechanical and thermal nociceptive stimuli applied to the leg or keel of unrestrained birds. Up to 9N mechanical force was delivered via a single round-ended 2mm pin using a pneumatic actuator at 0.4Ns(-1). Heat was applied through a small copper element at 0.8°Cs(-1) to a maximum of 50°C. The repeatability and reliability of threshold measures were validated using 10-12 broiler chickens (aged 49-66 days) per site and modality. Mechanical threshold, or skin and threshold temperature, were recorded over three sessions across a 36h period. Both stimulus types elicited clear, reproducible behavioural responses. Mechanical threshold means and 95% confidence intervals were 3.0 (2.8-3.2)N for keel and 2.0 (1.8-2.1)N for leg sites. Keel thermal tests gave a mean skin temperature of 39.3 (39.1-39.5)°C, and threshold of 46.8 (46.6-47.1)°C. Leg skin temperature was 35.7 (35.6-35.9)°C and threshold 42.5 (42.2-42.8)°C. Threshold measures were consistent within and across sessions and birds showed individual repeatability across tests within sessions. Individual birds' mechanical keel thresholds were also repeatable across sessions. The apparatus gave reliable, reproducible measurements of thresholds to noxious mechanical and thermal stimuli. The range recorded was comparable with previously published nociceptor thresholds in dissected chicken nerve filament fibres, and the method appears suitable for studying nociceptive processes in broiler chickens.

Objective To investigate whether events that may be stressful to young lambs, including simulated infection or social isolation, modulate pain experienced by lambs following castration and tail docking (C/D). Study design Randomised, controlled, prospective study. Animals Fifty male lambs born to 46 second-parity Mule ewes. Methods Lambs were allocated randomly to one of four groups, experiencing either a potential stressor or handling on day 2 after birth, followed by C/D or handling only on day 3. Quantitative sensory testing (QST) data [mechanical nociceptive thresholds (MNT), Semmes Weinstein filaments (SW), response to cold] and serum cortisol concentration were measured at time points after application of treatments to lambs on days 2 and 3 after birth. The treatment groups were LPS, injection of bacterial lipopolysaccharide IV on day 2, C/D on day 3; ISOL, isolation from the dam for 10 minutes on day 2, C/D on day 3; CAST, handling only on day 2, C/D on day 3; CONT, handled only on days 2 and 3. Results Castration and tail docking caused transient hypoalgesia as measured by MNT and SW. Simulated infection and isolation caused hyperalgesia 3 hours after application, indicated by a reduction in MNT, however they did not alter the pain response to C/D compared to lambs in the CAST group. Injection of LPS and C/D caused increased serum cortisol concentration. The magnitude of the cortisol response to C/D was not altered by prior exposure to either LPS or isolation. Conclusions and clinical relevance LPS and isolation did not modulate the response to C/D but did cause hyperalgesia. This highlights the importance of flock health management and husbandry techniques to reduce the incidence of either systemic infection or psychological stressors in young lambs.

A T-to-C missense mutation at nucleotide position 9,185 in the protein-coding ATP6 gene of the mitochondrial genome was present at high heteroplasmy in members of a Canadian family with Leigh syndrome with predominant ataxia and peripheral neuropathy. This mutation results in the substitution of a proline residue for an evolutionary-conserved leucine at position of amino acid 220 near the carboxyl terminus of the mitochondrial protein. The index patient and brother, who had an identical clinical presentation, had >90% mutant mtDNA in cultured skin fibroblasts, lymphocytes, and whole blood. Their mother and a maternal uncle, symptomatic with a peripheral neuropathy alone, had 86% and 85% heteroplasmy, respectively. Symptomatic maternal cousins with early onset revealed 90% and 91% mutant mtDNA in all tissues analyzed. Studies of lymphoblasts from the asymptomatic maternal grandmother and eldest brother of the proband were heteroplasmic for mutant mtDNA with 56% and 17%, respectively. Biochemical analysis demonstrated normal respiratory chain enzyme activity in muscle and fibroblasts, normal ATP synthesis, but reduced oligomycin-sensitive H(+)ATPase in cultured lymphoblast mitochondria. We propose that the 9,185T > C mtDNA mutation is pathogenic even though the initial phenotype is mild and the biochemical phenotype not easily detectable.

Thirty-six female dogs undergoing ovariohysterectomy were randomly allocated into three groups in this assessor-blinded study. The control group received no ketamine, the preketamine group were given ketamine (2.5 mg kg(-1)i.m.) at anaesthetic induction (in addition to the induction agents), the post-ketamine group received ketamine (2.5 mg kg(-1)i.m.) at extubation. Mechanical nociceptive thresholds and visual analogue scale (VAS) scores were measured before premedication and post-operatively at 20 minutes, 1, 2, 4, 8 and 18 hours after extubation. Dogs in the control group required more rescue analgesics than those in the other two groups (significantly more than the preketamine group), they also had consistently higher VAS pain scores throughout the post-operative period. Administration of ketamine post-operatively delayed the onset of post-operative wound hyperalgesia; dogs in the control group had the greatest amount of post-operative wound hyperalgesia. A single subanaesthetic dose of ketamine provided effective but short acting analgesia and preoperative administration may confer some benefits over administration post-operatively.

To determine what effect the timing of carprofen administration has on the severity of postoperative pain in dogs undergoing ovariohysterectomy and to investigate the pharmacokinetics of carprofen under these conditions.A prospective, randomized, double-blind, clinical trial.Sixty-two adult bitches weighing between 10 and 25 kgs, undergoing elective ovariohysterectomy.Examinations were performed for 20 hours postoperatively using subjective visual assessment scoring systems (DIVAS) and objective mechanical nociceptive threshold measurements. Forty dogs were assigned to one of three groups: (1) preoperative carprofen; (2) postoperative carprofen; and (3) no analgesics (saline injections). The dose of carprofen was 4.0 mg/kg subcutaneously. In another 22 bitches, the pharmacokinetics of carprofen given preoperatively or postoperatively at the same dose were examined.The dogs given carprofen preoperatively had lower pain scores than the other groups, significantly so at 2 hours postextubation (P.01 and P.05, Kruskal-Wallis and post hoc Dunn's). Mechanical pain thresholds measured at the distal tibia showed the development of hyperalgesia at 12 and 20 hours postextubation; this was prevented by both the preoperative (P.05 at 12 and 20 hours, Kruskal-Wallis) and postoperative (P.05 at 20 hours, Kruskal-Wallis) administration of carprofen. Mechanical pain threshold testing at the wound showed a significant analgesic effect of carprofen. Plasma concentrations of carprofen were not directly related to analgesia; maximum plasma concentration, the area under the curve to the last data point, and area under the first moment curve up to the last data point were all significantly higher in the dogs given carprofen postoperatively (P.05, Mann-Whitney).Preoperative administration of carprofen has a greater analgesic effect than postoperative administration in the early postoperative period in dogs undergoing ovariohysterectomy. Plasma levels of carprofen are not related to the degree of analgesia achieved.Carprofen provides effective analgesia after canine ovariohysterectomy. The timing of analgesic administration is important to optimize the control of postoperative pain.

BackgroundThe donkey has a reputation for stoicism and its behavioural repertoire in clinical contexts is under-reported. Lack of understanding of the norms of donkey behaviour and how it may vary over time can compromise use of behavioural measures as indicators of pain or emotional state. The objective of this study was to find out whether the behaviour of working donkeys was influenced by gender, the time of day or differed between days with a view to assessing how robust these measures are for inclusion in a working donkey ethogram.Methodology/principal findingsFrequency and consistency of postural and event behaviours were measured in 21 adult working donkeys (12 females; 9 males). Instantaneous (scan) and focal sampling were used to measure maintenance, lying, ingestive and investigative behaviours at hourly intervals for ten sessions on each of two consecutive days. High head carriage and biting were seen more frequently in male donkeys than females (PConclusions/significanceAll donkeys expressed an extensive behavioural repertoire, although some differences in behaviour were evident between genders. While most behaviours were consistent over time, some behaviours were influenced by time of day. Few behaviours differed between the two test days. The findings can be used to inform the development of a robust, evidence-based ethogram for working donkeys.

This is the first time that gait characteristics of broiler (meat) chickens have been compared with their progenitor, jungle fowl, and the first kinematic study to report a link between broiler gait parameters and defined lameness scores. A commercial motion-capturing system recorded three-dimensional temporospatial information during walking. The hypothesis was that the gait characteristics of non-lame broilers (n = 10) would be intermediate to those of lame broilers (n = 12) and jungle fowl (n = 10, tested at two ages: immature and adult). Data analysed using multi-level models, to define an extensive range of baseline gait parameters, revealed inter-group similarities and differences. Natural selection is likely to have made jungle fowl walking gait highly efficient. Modern broiler chickens possess an unbalanced body conformation due to intense genetic selection for additional breast muscle (pectoral hypertrophy) and whole body mass. Together with rapid growth, this promotes compensatory gait adaptations to minimise energy expenditure and triggers high lameness prevalence within commercial flocks; lameness creating further disruption to the gait cycle and being an important welfare issue. Clear differences were observed between the two lines (short stance phase, little double-support, low leg lift, and little back displacement in adult jungle fowl; much double-support, high leg lift, and substantial vertical back movement in sound broilers) presumably related to mass and body conformation. Similarities included stride length and duration. Additional modifications were also identified in lame broilers (short stride length and duration, substantial lateral back movement, reduced velocity) presumably linked to musculo-skeletal abnormalities. Reduced walking velocity suggests an attempt to minimise skeletal stress and/or discomfort, while a shorter stride length and time, together with longer stance and double-support phases, are associated with instability. We envisage a key future role for this highly quantitative methodology in pain assessment (associated with broiler lameness) including experimental examination of therapeutic agent efficacy.

Neuronal intranuclear hyaline inclusion disease is a progressive, fatal neurologic condition characterized by eosinophilic inclusions in neurons of the central, autonomic, and peripheral nervous systems. The clinical and pathologic findings of a 4-year-old boy who presented with a rapidly progressive cerebellar ataxia and seizure disorder that had begun 2 years earlier are described. Although intraneuronal inclusions were identified in neurons of cortex, basal ganglia, brainstem, cerebellum, and spinal cord, clinical signs were restricted to cerebellar ataxia, internuclear ophthalmoplegia, and cognitive delay. Predominant cerebellar atrophy, early age of onset, and short clinical course distinguishes it from previously reported patients.

To assess the effectiveness of an environmental falls prevention intervention delivered by qualified occupational therapists or unqualified trained assessors.A pilot three-armed randomized controlled trial.Airedale National Health Service Trust catchment, North and West Yorkshire, England.Two hundred thirty-eight community-dwelling adults aged 70 and older with a history of falls in the previous year.Assessment and modification of the home environment of people at greater risk of falls.Fear of falling was the primary outcome measure, and an analysis of covariance was conducted on the area under the curve at 12 months. As a secondary outcome, falls were analysed using negative binomial regression. Quality of life and independence in activities of daily living (ADLs) were also measured.The intervention had no effect on fear of falling (P=.63). The occupational therapy group had significantly fewer falls than controls 12 months after the assessment (incidence rate ratio (IRR)=0.54, 95% confidence interval (CI)=0.36-0.83, P=.005). There was no significant effect on falls in the trained assessor group (IRR=0.78, 95% CI=0.51-1.21, P=.34).Environmental assessment had no effect on fear of falling. Environmental assessment prescribed by an occupational therapist significantly reduced the number of falls in high-risk individuals whereas that prescribed by a trained assessor did not. Further research in other settings is needed to confirm this, to explore the mechanisms, and to estimate cost-effectiveness.

Cycloaddition reactions of functionalised Δ 1 -pyrroline- N -oxides have been used to prepare the hydroxylated pyrrolizidines 11 and 22 , the indolizidine 16 , and the iminoheptitol 12 .

International audience; In France, crack users are particularly exposed to hepatitis C transmission, through the use of glass pipes, which are responsible for a lot of burns and cracks on users’ lips and hands. They also represent transmission pathways for infectious agents. Todate, the main political measures in the harm reduction field remain focused on injection practises, without considering exposure to this specific risk. This situation led the French Institute for Public Health Surveillance (InVS) and CERMES3 to conductan exploratory cross-sectional study to better know the needs of this population in France, and to assess the impact of thedelivery of such a tool on the crack users’ health. This action research is carried out through an active process of collaborativework between harm reduction associations and drug users.; Les auteurs présentent les résultats d'une enquête épidémiologique exploratoire à visée descriptive ayant pour objectif de mieux connaître les besoins des usagers de crack et d'évaluer l'impact d'un nouvel outil de réduction des risques sur leur santé.

Copolymers of acrylonitrile with a furfuryl alcohol resin have been prepared by a free radical reaction, and have been characterized by n.m.r. and i.r. spectroscopy. Their t.g.a. has been performed in air and in a nitrogen atmosphere, to permit the recognition of a number of stages in the weight loss process. D.s.c., also in air and in nitrogen, has identified a number of exothermic and one endothermic process in the copolymers. Solid state cross-polarization/magic angle spinning 13C n.m.r. spectroscopy and i.r. spectroscopy has been used to obtain some insight into the chemistry of the various chemical changes, which in air are completed by combustion and in nitrogen leave a carbon.

Twenty-eight dogs were randomly allocated into two groups. They were premedicated with either 10 or 20 microg/kg buprenorphine and 0.05 mg/kg acepromazine administered intramuscularly, and then anaesthetised with intravenous thiopentone to effect and maintained with isoflurane in 100 per cent oxygen. The dogs underwent routine castration, and a second dose of 10 microg/kg buprenorphine was administered four hours after the first or 20 microg/kg six hours after the first dose. Levels of pain and sedation were scored on a visual analogue scale and in terms of the dogs' requirement for rescue analgesia, and mechanical nociceptive thresholds were measured at the hock and wound at premedication and one, two, three, four, five, six, seven, 10 and 21 to 22 hours later. Pain scores were low in both groups, with a trend for lower scores in the high dose group; administration of the second dose of buprenorphine further decreased the pain scores. Buprenorphine produced good preoperative sedation and the level of sedation decreased over time after surgery. Administration of the second high dose of buprenorphine did not increase the level of sedation. Both doses of buprenorphine prevented hyperalgesia at the wound and hock postoperatively. Three dogs given the low dose and one dog given the high dose required rescue analgesia with carprofen.