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yield. The methodology is designed to be especially relevant to hypothesize on which microbial pathway variants should be most favored in microbial ecosystems under high selective pressure for efficient metabolic energy conservation. Syntrophic microbial oxidation of propionate to acetate has an extremely small quantity of available energy and requires an extremely high metabolic efficiency to sustain life. Our results bring mechanistic insights into the optimum pathway variants, other metabolic bottlenecks, and the impact of environmental conditions on the ATP yields. Additionally, our results conclude that, as previously reported, under specific conditions, IET mechanisms other than hydrogen must exist to simultaneously sustain the growth of both propionate oxidizers and hydrogenotrophic methanogens.Gut dysbiosis has been repeatedly reported in Parkinson’s disease (PD) but only once in idiopathic rapid-eye-movement sleep behavior disorder (iRBD) from Germany. Abnormal aggregation of α-synuclein fibrils causing PD possibly starts from the intestine, although this is still currently under debate. iRBD patients frequently develop PD. Early-stage gut dysbiosis that is causally associated with PD is thus expected to be observed in iRBD. We analyzed gut microbiota in 26 iRBD patients and 137 controls by 16S rRNA sequencing (16S rRNA-seq). Our iRBD data set was meta-analyzed with the German iRBD data set and was compared with gut microbiota in 223 PD patients. Unsupervised clustering of gut microbiota by LIGER, a topic model-based tool for single-cell RNA sequencing (RNA-seq) analysis, revealed four enterotypes in controls, iRBD, and PD. Short-chain fatty acid (SCFA)-producing bacteria were conserved in an enterotype observed in controls and iRBD, whereas they were less conserved in enterotypes observed in PD. ents, and may make the intestinal neural plexus exposed to oxidative stress, which can lead to abnormal aggregation of prion-like α-synuclein fibrils in the intestine. In contrast to PD, SCFA-producing bacteria were not decreased in iRBD. As SCFA induces regulatory T (Treg) cells, a decrease of SCFA-producing bacteria may be a prerequisite for the development of PD. We propose that prebiotic and/or probiotic therapeutic strategies to increase the intestinal mucin layer and to increase intestinal SCFA potentially retard the development of iRBD and PD.The BvgS/BvgA two-component system controls expression of ∼550 genes of Bordetella pertussis, of which, ∼245 virulence-related genes are positively regulated by the BvgS-phosphorylated transcriptional regulator protein BvgA (BvgA∼P). We found that a single G-to-T nucleotide transversion in the 5′-untranslated region (5′-UTR) of the rplN gene enhanced transcription of the ribosomal protein operon and of the rpoA gene and provoked global dysregulation of B. pertussis genome expression. This comprised overproduction of the alpha subunit (RpoA) of the DNA-dependent RNA polymerase, downregulated BvgA and BvgS protein production, and impaired production and secretion of virulence factors by the mutant. DB2313 Nonetheless, the mutant survived like the parental bacteria for >2 weeks inside infected primary human macrophages and persisted within infected mouse lungs for a longer period than wild-type B. pertussis These observations suggest that downregulation of virulence factor production by bacteria internalized into host cells may enable persistence of the whooping cough agent in the airways.IMPORTANCE We show that a spontaneous mutation that upregulates transcription of an operon encoding ribosomal proteins and causes overproduction of the downstream-encoded α subunit (RpoA) of RNA polymerase causes global effects on gene expression levels and proteome composition of Bordetella pertussis Nevertheless, the resulting important downregulation of the BvgAS-controlled expression of virulence factors of the whooping cough agent did not compromise its capacity to persist for prolonged periods inside primary human macrophage cells, and it even enhanced its capacity to persist in infected mouse lungs. These observations suggest that the modulation of BvgAS-controlled expression of virulence factors may occur also during natural infections of human airways by Bordetella pertussis and may possibly account for long-term persistence of the pathogen within infected cells of the airways.

As cases of COVID-19 infections surge, concerns have renewed about intensive care units (ICUs) being overwhelmed and the need for specific triage protocols over winter. This study aimed to help inform triage guidance by exploring the views of lay people about factors to include in triage decisions.

Online survey between 29th of May and 22nd of June 2020 based on hypothetical triage dilemmas. Participants recruited from existing market research panels, representative of the UK general population. Scenarios were presented in which a single ventilator is available, and two patients require ICU admission and ventilation. Patients differed in one of chance of survival, life expectancy, age, expected length of treatment, disability and degree of frailty. Respondents were given the option of choosing one patient to treat or tossing a coin to decide.

Seven hundred and sixty-three participated. A majority of respondents prioritised patients who would have a higher chance of survival (72%-93%), longer life expectto ICU triage in the face of overwhelming need. Survey respondents endorsed the relevance of patient factors currently included in triage guidance, but also factors not currently included. They supported the permissibility of reallocating treatment in a pandemic.

Research using the UK Biobank data has shown ethnic inequalities in hearing health; however, the hearing test used may exhibit a disadvantage for non-native language speakers.

To validate the results of the UK Biobank hearing test (Digit Triplet Test, DTT) against self-reported measures of hearing in the dataset and create classifications of hearing health. To observe if language proficiency and migration age have the same effect on hearing health classification as on the DTT in isolation. Our hypothesis is that language proficiency acts differently on the DTT, demonstrating that the DTT is biased for non-native speakers of English.

Latent classes representing profiles of hearing health were identified from the available hearing measures. Factors associated with class membership were tested using multinomial logistic regression models. Ethnicity was defined as (1) White, native English-speaking, (2) ethnic minority, arrived in the UK aged <12 or (3) ethnic minority, arrived aged >12.

The UK Biobank participants with valid hearing test results and associated covariates (N=151 268).