Background Joint injury is a major risk factor for osteoarthritis and provides an opportunity to prospectively examine early processes associated with osteoarthritis. We investigated whether predefined baseline demographic and clinical factors, and protein analytes in knee synovial fluid and in plasma or serum, were associated with clinically relevant outcomes at 2 years after knee injury.Methods This longitudinal cohort study recruited individuals aged 16-50 years between Nov 1, 2010, and Nov 28, 2014, across six hospitals and clinics in London, UK. Participants were recruited within 8 weeks of having a clinically significant acute knee injury (effusion and structural injury on MRI), which was typically treated surgically. We measured several predefined clinical variables at baseline (eg, time from injury to sampling, extent and type of joint injury, synovial fluid blood staining, presence of effusion, self-reported sex, age, and BMI), and measured 12 synovial fluid and four plasma or serum biomarkers by immunoassay at baseline and 3 months. The primary outcome was Knee Injury and Osteoarthritis Outcome Score (KOOS 4 ) at 2 years, adjusted for baseline score, assessed in all patients. Linear and logistic regression models adjusting for predefined covariates were used to assess associations between baseline variables and 2-year KOOS 4 . This study is registered with ClinicalTrials.gov, number NCT02667756. FindingsWe enrolled 150 patients at a median of 17 days (range 1-59, IQR 9-26) after knee injury. 123 (82%) were male, with a median age of 25 years (range 16-50, IQR 21-30). 98 (65%) of 150 participants completed a KOOS 4 at 2 (or 3) years after enrolment (50 participants were lost to follow-up and two were withdrawn due to adverse events unrelated to study participation); 77 (51%) participants had all necessary variables available and were included in the core variable adjusted analysis. In the 2-year dataset mean KOOS 4 improved from 38 (SD 18) at baseline to 79 (18) at 2 years. Baseline KOOS 4, medium-to-large knee effusion, and moderate-to-severe synovial blood staining and their interaction significantly predicted 2-year KOOS 4 (n=77; coefficient -20•5, 95% CI -34•8 to -6•18; p=0•0060). The only predefined biomarkers that showed independent associations with 2-year KOOS 4 were synovial fluid MCP-1 (n=77; -0•015, 0•027 to -0•004 per change in 1 pg/mL units; p=0•011) and IL-6 (n=77; -0•0005, -0•0009 to -0•0001 per change in 1 pg/mL units; p=0•017). These biomarkers, combined with the interaction of effusion and blood staining, accounted for 39% of outcome variability. Two adverse events occurred that were linked to study participation, both at the time of blood sampling (one presyncopal episode, one tenderness and pain at the site of venepuncture).Interpretation The combination of effusion and haemarthrosis was significantly associated with symptomatic outcomes after acute knee injury. The synovial fluid molecular protein response to acute knee injury (best represented by MCP-1 and IL-6) was independently as...

This is the first report of a complete mitochondrial genome sequence from a photosynthetic member of the stramenopiles, the chrysophyte alga Chrysodidymus synuroideus. The circular-mapping mitochondrial DNA (mtDNA) of 34 119 bp contains 58 densely packed genes (all without introns) and five unique open reading frames (ORFs). Protein genes code for components of respiratory chain complexes, ATP synthase and the mitoribosome, as well as one product of unknown function, encoded in many other protist mtDNAs (YMF16). In addition to small and large subunit ribosomal RNAs, 23 tRNAs are mtDNA-encoded, permitting translation of all codons present in protein-coding genes except ACN (Thr) and CGN (Arg). The missing tRNAs are assumed to be imported from the cytosol. Comparison of the C.SYNUROIDEUS: mtDNA with that of other stramenopiles allowed us to draw conclusions about mitochondrial genome organization, expression and evolution. First, we provide evidence that mitochondrial ORFs code for highly derived, unrecognizable versions of ribosomal or respiratory genes otherwise 'missing' in a particular mtDNA. Secondly, the observed constraints in mitochondrial genome rearrangements suggest operon-based, co-ordinated expression of genes functioning in common biological processes. Finally, stramenopile mtDNAs reveal an unexpectedly low variability in genome size and gene complement, testifying to substantial differences in the tempo of mtDNA evolution between major eukaryotic lineages.

In man, central sensitisation (CS) contributes to the pain of osteoarthritis (OA). Dogs with spontaneous OA may also exhibit CS. Electrophysiological reflex measurements are more objective than behavioural assessments and can be used to evaluate CS in preclinical and clinical studies. It was hypothesised that dogs suffering from OA would exhibit electrophysiological characteristics indicative of CS, associated with reduced diffuse noxious inhibitory controls (DNICs). One hundred and seventeen client-owned dogs were recruited to the study. Hind limb nociceptive withdrawal reflex thresholds, stimulus response, and temporal summation characteristics were recorded, during alfaxalone anaesthesia, from 46 OA dogs, 29 OA dogs receiving nonsteroidal anti-inflammatory drugs (OANSAIDs), and 27 breed- and weight-matched control dogs. Efficacy of DNIC was evaluated in 12 control and 11 of the OA dogs, by application of a mechanical conditioning stimulus to the contralateral forelimb. Nociceptive withdrawal reflex thresholds were higher in OA compared with control dogs (P = 0.02). Stimulus response characteristics demonstrated an augmented response in OANSAID dogs compared with OA (P < 0.001) and control (P < 0.001) dogs. Temporal summation demonstrated exaggerated C-fibre-mediated responses in both OA (P < 0.001) and OANSAID (P = 0.005) groups, compared with control animals. Conditioning stimulus application resulted in inhibition of test reflex responses in both OA and control animals (P < 0.001); control animals demonstrated greater inhibition compared with OA (P = 0.0499). These data provide evidence of neurophysiological changes consistent with CS in dogs with spontaneous OA and demonstrate that canine OA is associated with reduced DNIC.

This publication is a compilation of all Research Abstracts presented at the Ninth International Conference on Equine Exercise Physiology. Unlike previous ICEEP conferences there will not be a conference proceedings of full length manuscripts. These abstracts succinctly summarise a wide array of investigations relevant to the equine athlete, and will be useful to veterinarians and others involved in management of horses used for sport, work and competition. The abstracts encompass the topics of Applied Physiology; Biochemistry, Haematology, Endocrinology, and Thermoregulation; Cardiovascular and Respiratory; Muscle and Bone; Nutrition; Genomics, Proteomics, and Metabolomics; Biomechanics and Locomotion; as well as Physiotherapy, Rehabilitation, and Equitation science.The International Committee of ICEEP publishes these abstracts so that the most recent scientific information is available to a wide audience, including veterinarians, physiotherapists, trainers, owners and riders.The Introduction:The ability to accurately assess equine oxygen consumption (VO2) under field conditions has been limited by the need for unrestricted gas exchange.Methods: Two variations of a mask and an associated electronics control module (ECM) were designed to enable breath-by-breath measurement of airflows with two 8.0 cm diameter pneumotachometers located 7.5 cm in front of each narus and connected to differential pressure transducers mounted on the outside of the mask. The ECM was comprised of electronics for signal filtering to the flow transducers, an oxygen sensing cell, and an analog-to-digital converter all powered by a lithium-ion battery. The battery also powered a pump connected to gas sampling ports between the nares and pneumotachometers. Airflow and oxygen content of inspired and expired gases were recorded through the ECM and electronically transferred to a notebook. VO2 was determined from these recordings by an operator using a customized software analysis program. One mask encased the lower head (E). The other left the jaw free so horse could wear a bit and be ridden (R). Multiple treadmill exercise tests were undertaken by 6 horses to measure VO2max and blood gases. Each mask was worn twice and results compared to those from an open flow-through system (O) by 2-way RMANOVA (P<0.05). Utility of the system was evaluated using the intraclass correlation coefficient of 4 independent raters.Results: Blood gases and VO2max (152.0 ± 4.0 (mean ± SEM; O), 147.7 ± 4.3 (E), 150.7 ± 3.3 (R) ml/(kg.min) were not different between masks. VO2 measures were reproducible for each mask. Agreement between the 4 raters was excellent (intraclass correlation coefficient = 0.99). Conclusions:Masks capable of measuring VO2 during field exercise were developed, tested and found accurate by multiple users.Ethical Animal Research: Studies performed were approved by the Institution's Animal Care and Use Committee (protocol #3807). Sources of funding: Institutional sources. Competing interests: Washington State University has filed notice of i...

Objective To describe clinically relevant, physiological measurements collected during a 3hour duration alfaxalone total intravenous anaesthesia. Study design Case series.Animals A total of 112 client-owned middle aged or older dogs.Methods Dogs were premedicated with intramuscular acepromazine (0.03 mg kg -1 ).Anaesthesia was induced and subsequently maintained for up to 3 hours with alfaxalone administered intravenously. Dogs breathed 100% oxygen via an endotracheal tube. Heart rate, respiratory rate, and blood pressure were evaluated 30 minutes after administration of acepromazine and used as baseline values for comparisons of intra-anaesthetic data. Blood glucose was measured one week prior to anaesthesia and every hour during alfaxalone anaesthesia. Quality and duration of recovery were recorded. Mean data for physiological variables were compared over three time points; before induction of anaesthesia, forthe first hour of anaesthesia and from 60 minutes to discontinuation of anaesthesia.Results Mean induction dose of alfaxalone was 1.4 (95% CI 1.3 -1.5) mg kg -1 . Post induction apnoea for greater than 60 seconds occurred in 13 (11.6%) dogs. Mean alfaxalone infusion rate during the first 60 minutes of anaesthesia was 0.099 mg kg -1 minute -1 ; from 60 minutes until discontinuation of anaesthesia, mean infusion rate was 0.092 mg kg -1 minute -1 .Heart rate was well maintained; hypotension (mean arterial blood pressure < 60 mmHg) was encountered in 23 (21%) of dogs. Blood glucose levels did not alter during anaesthesia.Median time between discontinuation of alfaxalone infusion and extubation was 17 (7 -35 minutes), time to assuming sternal recumbency was 75 (58 -110 minutes), and time to standing was 109 (88 -140 minutes).Conclusions and clinical relevance. Alfaxalone infusion provided effective anaesthesia in this population. In a minority of cases respiratory and haemodynamic support of the patient was required.