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Finally, we explored genomic biomarker candidates using kidneys isolated from gentamicin- and cisplatin-treated zebrafish using microarray analysis, and identified three candidate genes, egr1, atf3, and fos based on increased expression levels and biological implications. The expression of these genes was upregulated dose-dependently in cisplatin-treated groups and was > 25-fold higher in gentamicin-treated than in the control group. In conclusion, these results suggest that the adult zebrafish has 1) similar nephrotoxic response to those of mammals, 2) considerable feasibility as an experimental model for toxicity studies, and 3) applicability to pathological examination and genomic biomarker evaluation in drug-induced kidney injury. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email journals.permissions@oup.com.INTRODUCTION The impact and outcome of hip fractures are well described for people living in the community, but inpatient hip fracture (IHF) have not been extensively studied. In this study, we examine the patient characteristics, common falls risk factors and clinical outcomes of this condition. METHODS Between January 2016 and December 2017, we analysed all inpatient falls that resulted in hip fracture within Aneurin Bevan University Health Board (ABUHB) in Wales. RESULTS The overall falls rate was 8.7/1000 occupied bed days (OBD). selleck chemicals llc Over the 2 years, 118 patients sustained an IHF, giving a rate of 0.12/1000 OBD. The mean age was 81.8 ± 9.5 (range 49-97) years and 60% were women. Most patients (n = 112) were admitted from their own home. Mean Charlson Comorbidity Index and the number of medications on admission were 5.5 ± 1.9 and 8.5 ± 3.7, respectively.Fifty-three patients (45%) sustained the IHF following their first inpatient fall. Twenty-four IHF (20%) occurred within 72 h. Mean length of stay was 84.9 ± 55.8 days. Only 43% were discharged back to their original place of residence following an IHF; 27% were discharged to a care home (26 new care home discharges), and 30% died as an inpatient. One-year mortality was 54% (n = 64/118). The most common comorbidity was dementia (63%). CONCLUSION Mortality and need for care home placement are both much higher after IHF than following community hip fracture. Most people who suffer a hip fracture in hospital have already demonstrated their need for falls risk management by having fallen previously during the same admission. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email journals.permissions@oup.com.Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great potential for personalized cardiac safety prediction, particularly for that of drug-induced proarrhythmia. However, hiPSC-CMs fire spontaneously and the variable beat rates of cardiomyocytes can be a confounding factor that interferes with data interpretation. Controlling beat rates with pacing may reduce batch and assay variations, enable evaluation of rate-dependent drug effects and facilitate the comparison of results obtained from hiPSC-CMs with those from adult human cardiomyocytes. As electrical stimulation (E-pacing) of hiPSC-CMs has not been validated with high-throughput assays, herein, we compared the responses of hiPSC-CMs exposed to classic cardiac ion channel blockers under spontaneous beating and E-pacing conditions utilizing microelectrode array (MEA) technology. We found that compared to spontaneously beating hiPSC-CMs, E-pacing 1) reduced overall assay variabilities; 2) showed limited changes of field potential duration (FPD) to pacemaker channel block; 3) revealed reverse rate dependence of multiple ion channel blockers on FPD; 4) eliminated the effects of sodium channel block on depolarization spike amplitude and spike slope due to a software error in acquiring depolarization spike at cardiac pacing mode. MEA optogenetic pacing and current clamp recordings at various stimulation frequencies demonstrated rate-dependent block of sodium channels in hiPSC-CMs as reported in adult cardiomyocytes. In conclusion, pacing enabled more accurate rate- and concentration-dependent drug effect evaluations. Analyzing responses of hiPSC-CMs under both spontaneously beating and rate-controlled conditions may help better assess the effects of test compounds on cardiac electrophysiology and evaluate the value of the hiPSC-CM model. Published by Oxford University Press 2020.BACKGROUND Strategies are urgently needed to mitigate the risk of zoonotic disease emergence in southern China, where pathogens with zoonotic potential are known to circulate in wild animal populations. However, the risk factors leading to emergence are poorly understood, which presents a challenge in developing appropriate mitigation strategies for local communities. METHODS Residents in rural communities of Yunnan, Guangxi and Guangdong provinces were recruited and enrolled in this study. Data were collected through ethnographic interviews and field observations, and thematically coded and analysed to identify both risk and protective factors for zoonotic disease emergence at the individual, community and policy levels. RESULTS Eighty-eight ethnographic interviews and 55 field observations were conducted at nine selected sites. Frequent human-animal interactions and low levels of environmental biosecurity in local communities were identified as risks for zoonotic disease emergence. Policies and programmes existing in the communities provide opportunities for zoonotic risk mitigation. CONCLUSIONS This study explored the relationship among zoonotic risk and human behaviour, environment and policies in rural communities in southern China. It identifies key behavioural risk factors that can be targeted for development of tailored risk-mitigation strategies to reduce the threat of novel zoonoses. © The Author(s) 2020. Published by Oxford University Press.Tox21 and ToxCast are high-throughput in vitro screening (HTS) programmes coordinated by the U.S. National Toxicology Program and the U.S. Environmental Protection Agency, respectively, with the goal of forecasting biological effects in vivo based on bioactivity profiling. The present study investigated whether mechanistic insights in the biological targets of food-relevant chemicals can be obtained from ToxCast results, when the chemicals are grouped according to structural similarity. Starting from the 556 direct additives that have been identified in the ToxCast database by Karmaus et al. (2017), the results showed that, despite the limited number of assays in which the chemical groups have been tested, sufficient results are available within so-called “DNA binding” and “nuclear receptor” target families to profile the biological activities of the defined chemical groups for these targets. The most obvious activity identified was the estrogen receptor (ER)-mediated actions of the chemical group containing parabens and structurally related gallates, as well the chemical group containing genistein and daidzein (the latter particularly towards ERβ as potential health beneficial target).