Prevalence of tail biting in pigs and associations to carcass condemnations - a Finnish pilot study

The aim of this study was to investigate the prevalence of tail biting in Finland and the relationship between tail biting and carcass condemnation

First genome-wide association study on rocuronium dose requirements shows association with SLCO1A2

Background: Rocuronium, a common neuromuscular blocking agent, is mainly excreted unchanged in urine (10-25%) and bile ( 70%). Age, sex, liver blood flow, smoking, medical conditions, and ethnic background can affect its pharmacological actions. However, reasons for the wide variation in rocuronium requirements are mostly unknown. We hypothesised that pharmacogenetic factors might explain part of the variation. Methods: One thousand women undergoing surgery for breast cancer were studied. Anaesthesia was maintained with propofol (50-100 mg kg(-1) min(-1)) and remifentanil (0.05-0.25 mg kg(-1) min(-1)). Neuromuscular block was maintained with rocuronium to keep the train-of-four ratio at 0-10%. DNA was extracted from peripheral blood and genotyped with a next-generation genotyping array. The genome-wide association study (GWAS) was conducted using an additive linear regression model with PLINK software. The FINEMAP tool and data from the Genotype-Tissue Expression project v8 were utilised to study the locus further. Results: The final patient population comprised 918 individuals. Of the clinical variables tested, age, BMI, ASA physical status, and total dose of propofol correlated significantly (all P Conclusions: Genetic variation in the gene SLCO1A2, encoding OATP1A2, an uptake transporter, accounted for 4% of the variability in rocuronium consumption. The underlying mechanism remains unknown.Peer reviewe

Spared Nerve Injury Causes Sexually Dimorphic Mechanical Allodynia and Differential Gene Expression in Spinal Cords and Dorsal Root Ganglia in Rats

Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells (cd28, ctla4, cd274, cd4, prf1), other immunological responses (dpp4, c5a, cxcr2 and il1b), neuronal transmission (hrh3, thbs4, chrna4 and pdyn), plasticity (atf3, c1qc and reg3b), and others (bhlhe22, mcpt1l, trpv6). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.Peer reviewe

Systemic hypertonic saline enhances glymphatic spinal cord delivery of lumbar intrathecal morphine

The blood-brain barrier significantly limits effective drug delivery to central nervous system (CNS) targets. The recently characterized glymphatic system offers a perivascular highway for intrathecally (i.t.) administered drugs to reach deep brain structures. Although periarterial cerebrospinal fluid (CSF) influx and concomitant brain drug delivery can be enhanced by pharmacological or hyperosmotic interventions, their effects on drug delivery to the spinal cord, an important target for many drugs, have not been addressed. Hence, we studied in rats whether enhancement of periarterial flow by systemic hypertonic solution might be utilized to enhance spinal delivery and efficacy of i.t. morphine. We also studied whether the hyperosmolar intervention affects brain or cerebrospinal fluid drug concentrations after systemic administration. Periarterial CSF influx was enhanced by intraperitoneal injection of hypertonic saline (HTS, 5.8%, 20 ml/kg, 40 mOsm/kg). The antinociceptive effects of morphine were characterized, using tail flick, hot plate and paw pressure tests. Drug concentrations in serum, tissue and microdialysis samples were determined by liquid chromatography-tandem mass spectrometry. Compared with isotonic solution, HTS increased concentrations of spinal i.t. administered morphine by 240% at the administration level (T13-L1) at 60 min and increased the antinociceptive effect of morphine in tail flick, hot plate, and paw pressure tests. HTS also independently increased hot plate and paw pressure latencies but had no effect in the tail flick test. HTS transiently increased the penetration of intravenous morphine into the lateral ventricle, but not into the hippocampus. In conclusion, acute systemic hyperosmolality is a promising intervention for enhanced spinal delivery of i.t. administered morphine. The relevance of this intervention should be expanded to other i.t. drugs and brought to clinical trials.Peer reviewe

Effects of a dual CCR3 and H1-antagonist on symptoms and eosinophilic inflammation in allergic rhinitis

<p>Abstract</p> <p>Background</p> <p>The CC-chemokine receptor-3 (CCR3) has emerged as a target molecule for pharmacological intervention in allergic inflammation.</p> <p>Objective</p> <p>To examine whether a dual CCR3 and H₁-receptor antagonist (AZD3778) affects allergic inflammation and symptoms in allergic rhinitis.</p> <p>Methods</p> <p>Patients with seasonal allergic rhinitis were subjected to three seven days' allergen challenge series. Treatment with AZD3778 was given in a placebo and antihistamine-controlled design. Symptoms and nasal peak inspiratory flow (PIF) were monitored in the morning, ten minutes post challenge, and in the evening. Nasal lavages were carried out at the end of each challenge series and α₂-macroglobulin, ECP, and tryptase were monitored as indices of allergic inflammation.</p> <p>Results</p> <p>Plasma levels of AZD3778 were stable throughout the treatment series. AZD3778 and the antihistamine (loratadine) reduced rhinitis symptoms recorded ten minutes post challenge during this period. AZD3778, but not the anti-histamine, also improved nasal PIF ten minutes post challenge. Furthermore, scores for morning and evening nasal symptoms from the last five days of the allergen challenge series showed statistically significant reductions for AZD3778, but not for loratadine. ECP was reduced by AZD3778, but not by loratadine.</p> <p>Conclusions</p> <p>AZD3778 exerts anti-eosinophil and symptom-reducing effects in allergic rhinitis and part of this effect can likely be attributed to CCR3-antagonism. The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis.</p> <p>Trial registration</p> <p>EudraCT No: 2005-002805-21.</p

Study of Vibrations in a Short-Span Bridge Under Resonance Conditions Considering Train-Track Interaction

[EN] Resonance is a phenomenon of utmost importance in railways engineering, leading to vast damages both in track and vehicles. A short-span bridge has been modeled by means of a finite elements method model, calibrated and validated with real data, to study resonance vibrations induced by the passage of trains. Furthermore, the influence of vehicle speed and track damping on the vibrations registered on the rail, the sleeper and the bridge has been assessed. Different track and vehicle pathologies have been proposed and their effect on the resonance of the bridge has been evaluated.Ribes-Llario, F.; Velarte-González, JL.; Pérez-Garnes, JL.; Real Herráiz, JI. (2016). Study of Vibrations in a Short-Span Bridge Under Resonance Conditions Considering Train-Track Interaction. Latin American Journal of Solids and Structures. 13(7):1236-1249. doi:10.1590/1679-78252773S12361249137Ahlström, J., & Karlsson, B. (1999). Microstructural evaluation and interpretation of the mechanically and thermally affected zone under railway wheel flats. Wear, 232(1), 1-14. doi:10.1016/s0043-1648(99)00166-0Bian, X., Chao, C., Jin, W., & Chen, Y. (2011). A 2.5D finite element approach for predicting ground vibrations generated by vertical track irregularities. Journal of Zhejiang University-SCIENCE A, 12(12), 885-894. doi:10.1631/jzus.a11gt012Grassie, S. L., & Kalousek, J. (1993). Rail Corrugation: Characteristics, Causes and Treatments. Proceedings of the Institution of Mechanical Engineers, Part F: Journal of Rail and Rapid Transit, 207(1), 57-68. doi:10.1243/pime_proc_1993_207_227_02Gupta, A., & Singh Ahuja, A. (2014). Dynamic Analysis of Railway Bridges under High Speed Trains. Universal Journal of Mechanical Engineering, 2(6), 199-204. doi:10.13189/ujme.2014.020604Ju, S. H., & Lin, H. T. (2003). Resonance characteristics of high-speed trains passing simply supported bridges. Journal of Sound and Vibration, 267(5), 1127-1141. doi:10.1016/s0022-460x(02)01463-3Kwark, J. W., Choi, E. S., Kim, Y. J., Kim, B. S., & Kim, S. I. (2004). Dynamic behavior of two-span continuous concrete bridges under moving high-speed train. Computers & Structures, 82(4-5), 463-474. doi:10.1016/s0045-7949(03)00054-3Lu, Y., Mao, L., & Woodward, P. (2012). Frequency characteristics of railway bridge response to moving trains with consideration of train mass. Engineering Structures, 42, 9-22. doi:10.1016/j.engstruct.2012.04.007Makino, T., Yamamoto, M., & Fujimura, T. (2002). Effect of material on spalling properties of railroad wheels. Wear, 253(1-2), 284-290. doi:10.1016/s0043-1648(02)00117-5Mao, L., & Lu, Y. (2013). Critical Speed and Resonance Criteria of Railway Bridge Response to Moving Trains. Journal of Bridge Engineering, 18(2), 131-141. doi:10.1061/(asce)be.1943-5592.0000336Museros, P., Romero, M. ., Poy, A., & Alarcón, E. (2002). Advances in the analysis of short span railway bridges for high-speed lines. Computers & Structures, 80(27-30), 2121-2132. doi:10.1016/s0045-7949(02)00261-4Pal, S., Valente, C., Daniel, W., & Farjoo, M. (2012). Metallurgical and physical understanding of rail squat initiation and propagation. Wear, 284-285, 30-42. doi:10.1016/j.wear.2012.02.013Sheng, X., Jones, C. J. C., & Thompson, D. J. (2004). A theoretical model for ground vibration from trains generated by vertical track irregularities. Journal of Sound and Vibration, 272(3-5), 937-965. doi:10.1016/s0022-460x(03)00782-xSimon, S., Saulot, A., Dayot, C., Quost, X., & Berthier, Y. (2013). Tribological characterization of rail squat defects. Wear, 297(1-2), 926-942. doi:10.1016/j.wear.2012.11.011Wang, Y., Wei, Q., Shi, J., & Long, X. (2010). Resonance characteristics of two-span continuous beam under moving high speed trains. Latin American Journal of Solids and Structures, 7(2), 185-199. doi:10.1590/s1679-78252010000200005Xia, H., Zhang, N., & Guo, W. W. (2006). Analysis of resonance mechanism and conditions of train–bridge system. Journal of Sound and Vibration, 297(3-5), 810-822. doi:10.1016/j.jsv.2006.04.022Yang, Y. B., & Lin, C. W. (2005). Vehicle–bridge interaction dynamics and potential applications. Journal of Sound and Vibration, 284(1-2), 205-226. doi:10.1016/j.jsv.2004.06.03

Conformational and Structural Relaxations of Poly(ethylene oxide) and Poly(propylene oxide) Melts: Molecular Dynamics Study of Spatial Heterogeneity, Cooperativity, and Correlated Forward-Backward Motion

Performing molecular dynamics simulations for all-atom models, we characterize the conformational and structural relaxations of poly(ethylene oxide) and poly(propylene oxide) melts. The temperature dependence of these relaxation processes deviates from an Arrhenius law for both polymers. We demonstrate that mode-coupling theory captures some aspects of the glassy slowdown, but it does not enable a complete explanation of the dynamical behavior. When the temperature is decreased, spatially heterogeneous and cooperative translational dynamics are found to become more important for the structural relaxation. Moreover, the transitions between the conformational states cease to obey Poisson statistics. In particular, we show that, at sufficiently low temperatures, correlated forward-backward motion is an important aspect of the conformational relaxation, leading to strongly nonexponential distributions for the waiting times of the dihedrals in the various conformational statesComment: 13 pages, 13 figure

Evidence for a weakening relationship between interannual temperature variability and northern vegetation activity.

Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Satellite-derived Normalized Difference Vegetation Index (NDVI), a proxy of vegetation productivity, is known to be correlated with temperature in northern ecosystems. This relationship, however, may change over time following alternations in other environmental factors. Here we show that above 30°N, the strength of the relationship between the interannual variability of growing season NDVI and temperature (partial correlation coefficient RNDVI-GT) declined substantially between 1982 and 2011. This decrease in RNDVI-GT is mainly observed in temperate and arctic ecosystems, and is also partly reproduced by process-based ecosystem model results. In the temperate ecosystem, the decrease in RNDVI-GT coincides with an increase in drought. In the arctic ecosystem, it may be related to a nonlinear response of photosynthesis to temperature, increase of hot extreme days and shrub expansion over grass-dominated tundra. Our results caution the use of results from interannual time scales to constrain the decadal response of plants to ongoing warming.Strategic Priority Research Program (B) of the Chinese Academy of SciencesNational Basic Research Program of ChinaChinese Ministry of Environmental ProtectionNational Natural Science Foundation of China111 ProjectUS Department of Energy (DOE), Office of Science, Biological and Environmental Researc