Frenchhenson5639

59; 95% CI, 2.98-7.07), stage III+IV (OR, 26.57; 95% CI, 13.52-52.22), prediagnosis SA 1-30 days (OR, 2.73; 95% CI, 1.30-5.70), prediagnosis SA >90 days (OR, 24.52; 95% CI, 12.25-49.08), and prediagnosis DP (OR, 659.97; 95% CI, 292.52->999.99). Conversely, adjusting for prediagnosis SA/DP and stage, sociodemographic factors were not associated with high levels of SA/DP. CONCLUSION After BC diagnosis, SA/DP increased significantly but then decreased. The absolute majority had no SA/DP during year 3. Advanced cancer stage and previous high SA/DP rendered the greatest risk for future high SA/DP. More knowledge is needed for applying the information in rehabilitation and return-to-work planning. © 2020 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.BACKGROUND AND PURPOSE Prolonged use of opioids causes analgesic tolerance and adverse effects including constipation and dependence. Evidence exists that molecules targeting imidazoline-2 receptors (I2Rs) potentiate opioid analgesia in rodents. We investigated whether combination with the I2R ligand CR4056 could improve efficacy and safety of morphine, and explored the mechanisms of CR4056-opioid interaction. EXPERIMENTAL APPROACH We used the complete Freund's adjuvant (CFA) model in rats to study the effects of treatments on hyperalgesia, morphine tolerance, and microglia activation as measured by immunofluorescence. Opioid-induced adverse effects were assessed in rodent models of morphine-induced constipation, sedation (open field, sedation rating scale, rotarod), physical dependence (naloxone-induced withdrawal), and abuse (conditioned place preference-associated reward). Chemiluminescence assays tested CR4056 as allosteric modulator of μ-opioid receptors. KEY RESULTS CR4056 (ED50=4.88 mg·kg-1 ) and morphine (ED50=2.07 mg·kg-1 ) synergised in reducing CFA-induced hyperalgesia (ED50=0.52 mg·kg-1 ; 11 combination). Consistently, low doses of CR4056 (1 mg·kg-1 ) spared one-third of the cumulative morphine dose administered during 4 days, and prevented/reversed the development of tolerance to morphine anti-hyperalgesia. These opioid-sparing effects were associated with a significant drop in microglia activation and were independent of CR4056 interactions on μ-opioid receptors. Importantly, the low doses of CR4056 and morphine that synergise in analgesia did not induce constipation, sedation, physical dependence, or place preference. CONCLUSIONS AND IMPLICATIONS Our study points towards a selective synergism CR4056-morphine in analgesia, with the potential for their combination to have an improved safety and abuse liability profile over morphine alone. These findings support CR4056 development as opioid-sparing drug in multimodal analgesia. This article is protected by copyright. All rights reserved.Many behaviours have differential fitness consequences across thermal and ecological contexts, indicating that both ecological shifts and warming temperatures induced by climatic change may alter how organisms behave. However, empirical evidence of temperature-driven behavioural selection in natural systems is lacking. We compared behaviours and behavioural syndromes related to activity, exploration, boldness and aggression in populations of largemouth bass (Micropterus salmoides) from ambient lakes to the those from artificially warmed, power plant cooling lakes to investigate changes in behaviours associated with warmer environments. Activity, exploration, boldness, and aggression of juvenile largemouth bass were assessed in laboratory conditions using a novel environment assay and a risky situation assay. We found that activity and exploratory behaviours were higher and decreased through first year ontogeny in populations from heated lakes, whereas these behaviours were lower and showed no relationship through ontogeny in populations from ambient lakes. We attribute these differences with the changes in food source availability in heated lakes associated with temperature driven ecological effects. Bold and aggressive behaviours tended to differ between populations, as did correlations between behaviours, but did not differ between ambient and heated lakes. The findings of this work identify that large ecological changes associated with warming environments, such as food availability, may drive changes in some aspects of behavioural expression in largemouth bass but that other aspects of behavioural expression may be driven by lake-specific factors not related to warming. This article is protected by copyright. All rights reserved. find more This article is protected by copyright. All rights reserved.BACKGROUND AND PURPOSE The synthetic vitamin D3 analog paricalcitol acts as a selective activator of vitamin D receptor (VDR). While there is evidence for cardioprotective effects of paricalcitol associated with the VDR pathway, less information is available about the structural and functional cardiac effects of paricalcitol on established heart failure (HF), and particularly its effects on associated electrophysiological or Ca2+ -handling remodelling. EXPERIMENTAL APPROACH We used a murine model of transverse aortic constriction (TAC) to study the effect of paricalcitol on established HF. Treatment was initiated 4 weeks after surgery over 5 consecutive weeks and mice were sacrificed 9 weeks after surgery. Cardiac magnetic resonance imaging (CMRI) was performed 4 and 9 weeks after surgery. Hearts were used for biochemical and histological studies and to isolate ventricular myocytes for electrophysiological and calcium imaging studies. KEY RESULTS CMRI analysis revealed that, compared with vehicle, paricalcitol treatment prevented the progression of ventricular dilation and hypertrophy after TAC and halted the corresponding decline in ejection fraction. These beneficial effects were related to the attenuation of intracellular Ca2+ -mishandling remodelling, antifibrotic and antihypertrophic effects, and potentially antiarrhythmic effects by preventing the reduction of K+ current density and the long QT, JT and TpTe intervals observed in HF animals. CONCLUSIONS AND IMPLICATIONS The results suggest that paricalcitol treatment in established HF hampers disease progression and improves adverse electrophysiological and Ca2+ handling remodelling, attenuating the vulnerability to HF-associated ventricular arrhythmias. Paricalcitol may emerge as a potential therapeutic option in the treatment of HF. This article is protected by copyright. All rights reserved.