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Background: Aspergillus fumigatus (Af) infection is associated with poor lung health in chronic suppurative lung diseases but often goes undetected. We hypothesised that inhibition of Af growth by Pseudomonas aeruginosa (Pa) increases the frequency of false-negative Af culture in co-infected people. Using a substantial group of cystic fibrosis (CF) airway samples, we assessed the relationship between Af and bacterial pathogens, additionally comparing fungal culture with next-generation sequencing., Methods: Frequency of co-culture was assessed for 44,554 sputum/BAL cultures, from 1,367 CF patients between the years 2010-2020. In a subgroup, Internal Transcribed Spacer-2 (ITS2) fungal sequencing was used to determine sequencing-positive, culture-negative (S+/C-) rates., Results: Pa+ samples were nearly 40% less likely (P<0.0001) than Pa- samples to culture Af, an effect that was also seen with some other Gram-negative isolates. This impact varied with Pa density and appeared to be moderated by Staphylococcus aureus co-infection. Sequencing identified Af-S+/C- for 40.1% of tested sputa. Samples with Pa had higher rates of Af-S+/C- (49.3%) than those without (35.7%; RR 1.38 [1.02-1.93], P<0.05). Af-S+/C- rate was not changed by other common bacterial infections. Pa did not affect the S+/C- rates of Candida, Exophiala or Scedosporium., Conclusions: Pa/ Af co-positive cultures are less common than expected in CF. Our findings suggest an Af-positive culture is less likely in the presence of Pa. Interpretation of negative cultures should be cautious, particularly in Pa-positive samples, and a companion molecular diagnostic could be useful. Further work investigating mechanisms, alternative detection techniques and other chronic suppurative lung diseases is needed., Competing Interests: Declaration of Competing Interest No authors declare competing interests directly relating to this manuscript. NS reports personal fees from Vertex, Chiesi, Gilead, Menarini, Pulmocide, Zambon and Roche. ML reports personal fees from Insmed, Astra Zeneca, and Grifols. JCD reports advisory roles with Algipharma AS, Bayer AG, Boehringer Ingelheim Pharma GmbH & Co. KG, Galapagos NV, ImevaX GmbH, Nivalis Therapeutics Inc., ProQR Therapeutics III B.V., Proteostasis Therapeutics Inc., Raptor Pharmaceuticals Inc., Vertex Pharmaceuticals (Europe) Limited, Enterprise, Novartis, Pulmocide, Flatley, and Teva., (Copyright © 2022. Published by Elsevier B.V.)

Background: Beneficial effects of nut supplementation on cognitive function have previously been demonstrated in young and older adults. Alterations to gut microbiota have also been shown following tree nut consumption. However, no data exists on the effects of nuts on cognition and intestinal microbial communities assessed within the same study., Objectives: The study aimed to examine the effects of daily consumption of tree nuts for 4 wk on cognitive function (primary outcome), mood, metabolomics, and gut microbial species (secondary outcomes) in healthy, nonelderly adults., Methods: This randomized, placebo-controlled, double-blind, counterbalanced crossover study assessed the effects of 4 wk of supplementation with 30 g/d mixed tree nuts versus placebo on cognition and mood in 79 healthy adults aged 18-49 y. Metabolic responses, gut bacterial community structure, and the potential for these to impact cognition were explored using a multi-omic approach. Bacterial community analysis was conducted in Quantitative Insights Into Microbial Ecology 2 (QIIME2)., Results: Mixed model analysis indicated that nut consumption led to significant improvements to accuracy (placebo M = 92.2% compared with NUTS M = 94.5%; P = 0.019) and speed of response (placebo M = 788 ms compared with NUTS M = 757 ms; P = 0.004) on a picture recognition task. No significant changes to bacterial community α or β diversity were observed when comparing nut consumption to the placebo arm. However, an unclassified Lachnospiraceae amplicon sequence variant (ASV) was significantly enriched in participants when supplemented with nuts (P = 0.015). No correlations were observed between the changes to picture recognition and the changes to the unclassified Lachnospiraceae ASV. There were no significant changes to the urinary metabolome., Conclusions: These findings indicate a positive effect of nut on cognition following only 4 wk of consumption in a healthy nonelderly sample, as well as upregulation of a microbial taxa associated with gut health. The effects appear to be independent of one another, but further exploration is required in those experiencing cognitive decline and/or gut dysbiosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objectives: This study aimed to compare discriminant validity evidence of 2 generic patient-reported outcome measures (PROMs), the Veterans RAND 12-Item Health Survey (VR-12) and level 5 of EQ-5D (EQ-5D-5L), for use in emergency departments (EDs)., Methods: Data were obtained via a cross-sectional survey of 5876 patients in British Columbia (Canada) who completed a questionnaire after visiting an ED in 2018. We compared the extent to which the VR-12 and the EQ-5D-5L distinguished among groups of ED patients with different levels of comorbidity burden and self-reported physical and mental or emotional health status. Multivariable logistic regression was used to evaluate the ability of the 2 PROMs to identify patients presenting with a mental health (MH) condition., Results: All the measures produced small effect sizes (ESs) for discriminating comorbidity levels (R 2 range: 0.00 [VR-12 mental component summary {MCS}] to 0.10 [VR-12 physical component summary score]). The EQ-5D visual analog scale offered the largest ES for discriminating self-reported physical health (R 2  = 0.48), whereas the MCS, the VR-12 MH domain, and the EQ-5D-5L anxiety/depression dimension had the largest ESs for discriminating self-reported mental or emotional health (R 2  = 0.42, 0.40, and 0.38, respectively). The MCS produced a medium ES (R 2  = 0.42) along with the VR-12 utility score (R 2  = 0.27) compared with the EQ-5D-5L index (R 2  = 0.19). Having a MH condition was predominantly identified by the MCS (Pratt index = 0.56)., Conclusions: The VR-12 PROM provides a more comprehensive measurement of MH than the EQ-5D-5L, which is important to inform healthcare service needs for patients who present in EDs with MH challenges., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To (1) estimate the relative value of older adults' healthcare experiences based on the Canadian Patient Experience Survey for Inpatient Care (CPES-IC) using an economic valuation technique, and (2) compare the results with those of a conventional key-driver analysis of healthcare experiences based on bivariate correlations., Study Design and Setting: An online survey of 1,074 Canadians aged 60 and older who had been hospitalized within five years. Participants completed the CPES-IC and a best-worst scaling (BWS) valuation task. BWS data were analyzed using a conditional logit model. These results were compared to a conventional key-driver analysis that estimates importance through Spearman's correlations between experiences and a global rating of overall experience., Results: The valuation approach found that the three experiences most valued by patients were: that staff seemed informed and up-to-date about their hospital care, doctors explained things in a way that they could understand, and that they got all the information they needed about their care and treatment. Three of the top five most valued experiences from the valuation approach were among the top five in the key driver analysis. However, there were noteworthy differences in rank order., Conclusion: The results of the valuation exercise can inform local and/or system level quality improvement efforts by identifying priorities from an economic evaluation point of view, which are different than those based on a conventional key-driver analysis. Given the degree of uncertainty in estimates both the rank order and confidence intervals should be used to guide decision-making., (Copyright © 2021. Published by Elsevier Inc.)

Background: The prevalence of fungal disease in cystic fibrosis (CF) and non-CF bronchiectasis is increasing and the clinical spectrum is widening. Poor sensitivity and a lack of standard diagnostic criteria renders interpretation of culture results challenging. In order to develop effective management strategies, a more accurate and comprehensive understanding of the airways fungal microbiome is required. The study aimed to use DNA sequences from sputum to assess the load and diversity of fungi in adults with CF and non-CF bronchiectasis., Methods: Next generation sequencing of the ITS2 region was used to examine fungal community composition (n = 176) by disease and underlying clinical subgroups including allergic bronchopulmonary aspergillosis, chronic necrotizing pulmonary aspergillosis, non-tuberculous mycobacteria, and fungal bronchitis. Patients with no known active fungal disease were included as disease controls., Results: ITS2 sequencing greatly increased the detection of fungi from sputum. In patients with CF fungal diversity was lower, while burden was higher than those with non-CF bronchiectasis. The most common operational taxonomic unit (OTU) in patients with CF was Candida parapsilosis (20.4%), whereas in non-CF bronchiectasis sputum Candida albicans (21.8%) was most common. CF patients with overt fungal bronchitis were dominated by Aspergillus spp., Exophiala spp., Candida parapsilosis or Scedosporium spp., Conclusion: This study provides a framework to more accurately characterize the extended spectrum of fungal airways diseases in adult suppurative lung diseases., Competing Interests: Declaration of Competing Interests The authors have no conflicts of interests to disclose., (Copyright © 2020. Published by Elsevier B.V.)

The 15th European Cystic Fibrosis Society (ECFS) Basic Science pre-conference Symposium focused on the topic of the microbiome, asking the question "The lung and gut microbiome: what has to be considered for cystic fibrosis (CF)?" This review gives an overview of the main points raised during the symposium, which dealt with the technical considerations, pathophysiology and clinical implications of the microbiome in CF., (Copyright © 2018 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: Best practice when performing culture-independent microbiological analysis of sputum samples involves their rapid freezing and storage at -80°C. However, accessing biobanked collections can mean that material has been passed through repeated freeze-thaw cycles. The aim of this study was to determine the impact of these cycles on microbial community profiles., Methods: Sputum was collected from eight adults with cystic fibrosis, and each sample was subjected to six freeze-thaw cycles. Following each cycle, an aliquot was removed and treated with propidium monoazide (PMA) prior to DNA extraction and 16S rRNA gene pyrosequencing., Results: The impact of freeze-thaw cycles was greatest on rare members of the microbiota, with variation beyond that detected with within-sample repeat analysis observed after three cycles., Conclusion: Four or more freeze thaw cycles result in a significant distortion of microbiota profiles from CF sputum., (Copyright © 2014. Published by Elsevier B.V.)

The ligands that interact with the vast majority of small-molecule binding transcription factors are unknown, a significant gap in our understanding of sensory perception by cells. TetR-family regulators (TFRs) are found in most prokaryotes and are involved in regulating virtually every aspect of prokaryotic life however only a few TFRs have been characterized. We report the application of phylogenomics to the identification of cognate ligands for TFRs. Using phylogenomics we identify a TFR, KijR, that responds to the antibiotic kijanimicin. We go on to show that KijR represses a gene, kijX, which confers resistance to kijanimicin. Finally we show that KijX inactivates kijanimicin by the hydrolytic removal of sugar residues. This is a demonstration of antibiotic resistance by deglycosylation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Finding ways to increase the biosynthesis of medically important microbial secondary metabolites is a challenge of microbial chemical biology. Lechner et al. (in this issue of Chemistry & Biology) show that transcriptional regulation can be manipulated to selectively increase the production of a desired metabolite., (Copyright © 2011 Elsevier Ltd. All rights reserved.)