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This article is protected by copyright. All rights reserved.AIMS Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation. METHODS In a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 1001 (75 mg 0.75 mg; [morphine-naloxone 1001]) or 2001 (75 mg 0.375 mg; [morphine-naloxone 2001]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated. RESULTS Intravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 1001 > morphine-naloxone 2001) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P less then .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone. CONCLUSION Morphine-naloxone 1001 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 2001 does not appear to be appropriate to prevent intravenous morphine misuse. © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.AIMS AND OBJECTIVES To explore and describe nurses' role in the rehabilitation and care of patients in one subacute care facility in Melbourne, Australia. BACKGROUND The role of nurses in subacute care and within the rehabilitation team is evolving and remains unclear. DESIGN Mixed methods. METHODS Fourteen nurses from seven rehabilitation and geriatric evaluation and management wards in one subacute facility in Melbourne, Australia, were observed in practice for two hours and then interviewed. Activities were recorded electronically. GSK2110183 nmr Interviews were audio-recorded and transcribed. Data were analysed using content analysis. The study complied with the Consolidated Criteria for Reporting Qualitative Research (COREQ). RESULTS Three main themes are as follows (a) Nurses as rehabilitators; (b) Teamwork in rehabilitation; and (c) The changing context of subacute care. Nurses prioritised patient personal and clinical care above other responsibilities. They were largely excluded from team decision-making because cliinary team and to the rehabilitation of patients, is used and acknowledged to improve patient care. © 2020 John Wiley & Sons Ltd.Mouse dorsal coat hair types, guard, awl, auchene and zigzag, develop in three consecutive waves. To date, it is unclear if these hair types are determined genetically through expression of specific factors or can change based on their mesenchymal environment. We undertook a novel approach to this question by studying individual hair type in 67 Collaborative Cross (CC) mouse lines and found significant variation in the proportion of each type between strains. Variation in the proportion of zigzag, awl and auchene, but not guard hair, was largely due to germline genetic variation. We utilised this variation to map a quantitative trait locus (QTL) on chromosome 12 that appears to influence a decision point switch controlling the propensity for either second (awl and auchene) or third wave (zigzag) hairs to develop. This locus contains two strong candidates, Sostdc1 and Twist1, each of which carry several ENCODE regulatory variants, specific to the causal allele, that can influence gene expression, are expressed in the developing hair follicle, and have been previously reported to be involved in regulating human and murine hair behaviour, but not hair subtype determination. Both of these genes are likely to play a part in hair type determination via regulation of BMP and/or WNT signalling. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Development of the highly selective targeted tyrosine kinase inhibitors (TKIs) has expanded the therapeutic options for chronic myeloid leukemia (CML). Patients undergoing TKI therapy should be closely monitored to ensure that the best therapeutic response and quality of life are achieved, and to control suboptimal responses and adverse events. Despite the high rate of response using current first-line TKIs, treatment failure may still occur, and resistance is considered a challenge in the treatment of patients with CML. The third-generation TKI, ponatinib, is a potent orally bioavailable pan BCR-ABL inhibitor that inhibits both wild-type and mutant BCR-ABL1 kinase, including the "gatekeeper" T315I mutation, which is resistant to all other currently available TKIs. This paper reviews the effectiveness, feasibility, and safety of ponatinib in the real-life clinical management of CML. Potential prognostic factors in identifying patients most likely to benefit from ponatinib treatment will be discussed, and case presentations illustrating situations encountered in real-life clinical practice are described. Ponatinib is effective in patients who have received prior TKIs in clinical studies as well as under real-life conditions. Nevertheless, the risk/benefit balance must be evaluated for each patient, particularly considering disease state, mutational status, treatment line, intolerance/resistance to prior TKIs, age, frailty, and specific comorbidities. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.BACKGROUND Uveitis is a leading cause of blindness in horses. Little work has been undertaken to investigate whether donkeys are affected by a similar disease prevalence. OBJECTIVES To investigate the disease prevalence of uveitis in a population of donkeys in the UK. STUDY DESIGN Descriptive observational study. METHODS An ophthalmic examination was performed on each donkey, in a darkened stable. Each donkey underwent slit lamp biomicroscopy, and direct and/or indirect ophthalmoscopy. Fluorescein staining, STT1 and IOPs were measured when deemed clinically necessary. Pharmacological pupillary dilation was achieved using 1% tropicamide. RESULTS A total of 207 donkeys were examined-139 male (67.1%), and 68 female (32.9%). Age range was 2-37 years (median 17 years, inter-quartile range 9-25 years). Three donkeys (1.5%) were blind in one eye, and one was monocular at the time of examination. Signs consistent with either previous or current uveitis were identified in 8 eyes of 6 animals (2.9%). Clinical signs included miosis (n=1), corpora nigra atrophy (n=6), anterior lens capsule pigment (n=2), cataract (n=8), posterior synechiae (n=3), lens subluxation (n=1), vitreal changes (n=2), peripapillary scarring (n=3), and phthisis bulbi (n=1).