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Background: Hendra virus is an emerging virus with a geographically broad host reservoir. In humans, Hendra virus causes excessive inflammatory disease of the lung and nervous system. Our current understanding as to how Hendra virus or what factors induce inflammation is limited and as such, there are currently no therapeutic options available for patients who contract Hendra virus. Recent studies have identified viral aggregating proteins as drivers of inflammation in influenza A virus and SARS-CoV-2 virus. In this study, we sought to identify potential aggregating Hendra virus proteins as proof-of-concept that inflammasome activation may induce inflammation and contribute to disease pathology., Results: Here, we have identified that a peptide analogue of Hendra virus C protein (termed HeVc) forms aggregates and activates the NLRP3 inflammasome through phagocytic uptake into cells in vitro. Treatment of cells with the specific NLRP3 inhibitor MCC950 ameliorated IL-1β secretion responses in vitro. Critically, in vivo intranasal inoculation of mice with aggregated HeVc peptide induced pulmonary inflammation, suggesting HeVc may drive immunopathology during infection. Importantly, mice treated with MCC950 demonstrated reduced IL-1β secretion into the bronchoalveolar space, highlighting the role of NLRP3 in host HeV infections and a potential therapeutic strategy to reduce disease pathology., Conclusion: Taken together, these results identify Hendra virus C protein as a possible contributor to immunopathology during Hendra virus infections. Importantly, these studies highlight a potential role for NLRP3 in driving disease-associated inflammation, critically identifying a possible therapeutic strategy to alleviate disease-associated inflammation of infected patients through targeting of the NLRP3 inflammasome., (© 2023. The Author(s).)

National parks often serve as a cornerstone for a country's species and ecosystem conservation efforts. However, despite the protection these sites afford, climate change is expected to drive a substantial change in their bird assemblages. We used species distribution models to predict the change in environmental suitability (i.e., how well environmental conditions explain the presence of a species) of 49 Canadian national parks during summer and winter for 434 bird species under a 2°C warming scenario, anticipated to occur in Canada around the mid-21st century. We compared these to existing species distributions in the 2010s, and classified suitability projections for each species at each park as potential extirpation, worsening, stable, improving, or potential colonisation. Across all parks, and both seasons, 70% of the projections indicate change, including a 25% turnover in summer assemblages and 30% turnover in winter assemblages. The majority of parks are projected to have increases in species richness and functional traits in winter, compared to a mix of increases and decreases in both in summer. However, some changes are expected to vary by region, such as Arctic region parks being likely to experience the most potential colonisation, while some of the Mixedwood Plains and Atlantic Maritime region parks may experience the greatest turnover and potential extirpation in summer if management actions are not taken to mitigate some of these losses. Although uncertainty exists around the precise rate and impacts of climate change, our results indicate that conservation practices that assume stationarity of environmental conditions will become untenable. We propose general guidance to help managers adapt their conservation actions to consider the potentially substantive changes in bird assemblages that are projected, including managing for persistence and change., Competing Interests: The authors have declared that no competing interests exist.

Hill's thistle (Cirsium hillii (Canby) Fernald) is a perennial plant endemic to the Great Lakes region of North America. Hill's thistle is listed as threatened in Ontario and Canada where it is found in globally rare alvar habitats. The main objective of this study was ex-situ conservation of Hill's thistle using in vitro culture techniques and reintroduction of micropropagated plants back to their natural habitat in Bruce Peninsula National Park, Ontario, Canada. Two out of twenty-nine available seeds were successfully germinated under in vitro condition. An efficient micropropagation protocol was optimized with 100% survival during acclimatization of plantlets in the greenhouse. Three hundred micropropagated plants were reintroduced to twelve different sites within Bruce Peninsula National Park in June and July 2017. Plants were monitored for survival, rosette growth, and flowering on all sites from 2017-2019. After four months of planting, 67 to 99% of the plants were alive in different sites and 90 to 99% of them survived over winter. In the following years, shoot regeneration and flowering were observed on most sites. This study further confirms the benefit of plant tissue culture techniques to ensure revival of Hill's thistle ecological biodiversity through the reintroduction of micropropagated plants. This approach consisting of the components of conservation, propagation, and reintroduction (CPR) may potentially serve as a model for saving and enriching other species at risk., Competing Interests: The authors have declared that no competing interests exist.

Background: Benzodiazepine and z-hypnotic prescribing has slowly decreased over the past 20 years, however long-term chronic prescribing still occurs and is at odds with prescribing guidance., Objectives: To identify the pattern of benzodiazepine and z-hypnotic prescribing in psychiatric inpatients at discharge and 12 months post-discharge., Methods: Retrospective observational longitudinal cohort study of patients admitted to two adult psychiatric wards between June and November 2012 (inclusive) who were discharged with a prescription for a benzodiazepine or z-hypnotic drug. Routinely collected prescription data available from NHS Scotland Prescribing Information System was used to identify and follow community prescribing of benzodiazepine and z-hypnotics for a 12 month period post-discharge. Data were entered in Excel ® and further analysed using SPSS 23. Ethical approval was not required for this service evaluation however Caldicott Guardian approval was sought and granted., Results: Eighty patients were admitted during the study period however only those patients with a single admission were included for analysis (n=74). Thirty per cent (22/74) of patients were prescribed a benzodiazepine or z-hypnotics at discharge; 14 of whom received 'long-term' benzodiazepine and z-hypnotics i.e. continued use over the 12 month period. Seven patients received a combination of anxiolytics and hypnotics (e.g., diazepam plus temazepam or zopiclone). Long-term use was associated with a non-significant increase in median benzodiazepine or z-hypnotic dose, expressed as diazepam equivalents., Conclusions: One in three patients were prescribed a benzodiazepine or z-hypnotics at discharge with 1 in 5 receiving continuous long-term treatment (prescriptions) for 12 months post-discharge. As chronic long-term B-Z prescribing and use still remains an issue, future strategies using routine patient-level prescribing data may support prescribers to review and minimise inappropriate long-term prescribing., Competing Interests: CONFLICT OF INTEREST None.

Cutaneous mechanoreceptors in the anterior lower leg and foot dorsum provide important information about contact with objects and movement at the knee and ankle. This cutaneous feedback contributes to static and dynamic balance control. We conducted experiment 1 to determine the effects of ageing on anterior lower leg cutaneous feedback. We measured light touch (monofilament) perceptual thresholds (MPT) at seven skin sites across the anterior lower leg and foot dorsum in 12 young (5 male, aged 21-28) and 13 older adults (8 male, aged 73-92). Results showed that older adults had ~5.5× higher MPTs across these skin sites. We conducted experiment 2 to probe how different cutaneous mechanoreceptor subtypes are affected by ageing through measures of vibrotactile perceptual threshold (VPT) at 3, 15, and 40Hz at six skin sites across the anterior lower leg and foot dorsum in 10 young (5 male, aged 21-26) and 10 older adults (3 male, aged 75-85). In this group, we also assessed functional balance using the timed-up-and-go (TUG) and functional reach test (FRT). Older adults demonstrated significantly higher VPTs overall, and this effect was largest at 40Hz - a frequency primarily transmitted by fast adapting cutaneous afferents. Furthermore, higher thresholds at each frequency tended to correlate with poorer performance on the TUG within the older adult group (3Hz: r=0.550; 15Hz: r=0.689; 40Hz: r=0.663). These results suggest ageing influences cutaneous feedback from regions of the lower leg that provide important information about movement and contact., (Copyright © 2017 Elsevier Inc. All rights reserved.)