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

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

Morphine-3-glucuronide causes antinociceptive cross-tolerance to morphine and increases spinal substance P expression

Morphine-3-glucuronide (M3G), the main metabolite of morphine, has been implicated in the development of tolerance and of opioid-induced hyperalgesia, both limiting the analgesic use of morphine. We evaluated the acute and chronic effects of M3G and morphine as well as development of antinociceptive cross-tolerance between morphine and M3G after intrathecal administration and assessed the expression of pain-associated neurotransmitter substance P in the spinal cord. Sprague-Dawley rats received intrathecal M3G or morphine twice daily for 6 days. Nociception and tactile allodynia were measured with von Frey filaments after acute and chronic treatments. Substance P levels in the dorsal horn of the spinal cord were determined by immunohistochemistry after 4-day treatments. Acute morphine caused antinociception as expected, whereas acute M3G caused tactile allodynia, as did both chronic M3G and morphine. Chronic M3G also induced antinociceptive cross-tolerance to morphine. M3G and morphine increased substance P levels similarly in the nociceptive laminae of the spinal cord. This study shows that chronic intrathecal M3G sensitises animals to mechanical stimulation and elevates substance P levels in the nociceptive laminae of the spinal cord. Chronic M3G also induces antinociceptive cross-tolerance to morphine. Thus, chronic M3G exposure might contribute to morphine-induced tolerance and opioid-induced hyperalgesia.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

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

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

Study protocol for locoregional precision treatment of hepatocellular carcinoma with transarterial chemoembolisation (TACTida), a clinical study:idarubicin dose selection, tissue response and survival

INTRODUCTION: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death, often detected in the intermediate stage. The standard of care for intermediate-stage HCC is transarterial chemoembolisation (TACE), where idarubicin (IDA) is a promising drug. Despite the fact that TACE has been used for several decades, treatment success is unpredictable. This clinical trial has been designed believing that further improvement might be achieved by increasing the understanding of interactions between local pharmacology, tumour targeting, HCC pathophysiology, metabolomics and molecular mechanisms of drug resistance. METHODS AND ANALYSIS: The study population of this single-centre clinical trial consists of adults with intermediate-stage HCC. Each tumour site will receive TACE with two different IDA doses, 10 and 15 mg, on separate occasions. Before and after each patient's first TACE blood samples, tissue and liquid biopsies, and positron emission tomography (PET)/MRI will be performed. Blood samples will be used for pharmacokinetics (PK) and liver function evaluation. Tissue biopsies will be used for histopathology analyses, and culturing of primary organoids of tumour and non-tumour tissue to measure cell viability, drug response, multiomics and gene expression. Multiomics analyses will also be performed on liquid biopsies. PET/MRI will be used to evaluate tumour viability and liver metabolism. The two doses of IDA will be compared regarding PK, antitumour effects and safety. Imaging, molecular biology and multiomics data will be used to identify HCC phenotypes and their relation to drug uptake and metabolism, treatment response and survival. ETHICS AND DISSEMINATION: Participants give informed consent. Personal data are deidentified. A patient will be withdrawn from the study if considered medically necessary, or if it is the wish of the patient. The study has been approved by the Swedish Ethical Review Authority (Dnr. 2021-01928) and by the Medical Product Agency, Uppsala, Sweden. TRIAL REGISTRATION NUMBER: EudraCT number: 2021-001257-31

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

International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective