Baseline neutrophil-to-lymphocyte ratio predicts response to corticosteroids and is associated with infection and renal dysfunction in alcoholic hepatitis

Background Treating severe alcoholic hepatitis involves the exposure of patients to corticosteroids for 7 days to assess “response”. Aim To assess the prognostic and therapeutic implications of baseline neutrophil‐to‐lymphocyte ratio (NLR) in patients with severe alcoholic hepatitis. Methods Patients recruited to the STOPAH trial and an independent validation group were analysed retrospectively. Area under the receiver operating curve (AUC) analysis was performed. Kaplan‐Meier analysis was used to assess survival. Log‐rank test and odds ratio (OR) were used for comparative analysis. Results Baseline NLR was available for 789 STOPAH patients. The AUC for NLR was modest for 90‐day outcome (0.660), but was associated with infection, acute kidney injury (AKI) and severity of alcoholic hepatitis. Ninety‐day survival was not affected by prednisolone treatment if NLR 8 but mortality was reduced with prednisolone treatment when the NLR was 5‐8 (21.0% cf. 34.5%; P = 0.012). Prednisolone treatment increased the chance of Lille response if the NLR was ≥ 5 (56.5% cf. 41.1%: P = 0.01; OR 1.86) but increased the risk of day 7 infection (17.3% cf. 7.4%: P = 0.006; OR 2.60) and AKI (20.8% cf. 7.0%: P = 0.008; OR 3.46) if the NLR was > 8. Incorporation of NLR into a modified Glasgow alcoholic hepatitis score (mGAHS) improved the AUC to 0.783 and 0.739 for 28‐day and 90‐day outcome, respectively. Conclusion The NLR is associated with AKI and infection in severe alcoholic hepatitis. The NLR identifies those most likely to benefit from corticosteroids at baseline (NLR 5‐8). The mGAHS has a good predictive value for 28‐ and 90‐day outcomes

Morphology shapes community dynamics in early animal ecosystems

Acknowledgements: Funding was provided by an School of Biological Sciences Balfour Studentship (PFAG/076) to N.P.S.; a Natural Environment Research Council C-CLEAR DTP studentship (LBAG/265.03.G10) to K.M.D.; Leverhulme Trust Funding (ECF-2018-542) and from the Isaac Newton Trust (INT18.08(h)) to C.G.K.; a Natural Environment Research Council Standard Grant (NE/P002412/1) and an Independent Research Fellowship (NE/S014756/1) to E.G.M. The Parks and Natural Areas Division, Department of Environment and Conservation, Government of Newfoundland and Labrador, provided permits to conduct research within the MPER in 2010, 2016–2018 and 2021–2023. Readers are advised that access to MPER is by scientific research permit only. Fossil surfaces in the Bonavista Peninsula and Bay Roberts area are protected under reg. 67/11, of the Historic Resources Act 2011 and their access is only allowed under permit from the Government of Newfoundland and Labrador. Fieldwork in the Discovery Geopark and the Bay Roberts area was conducted under permit from the Government of Newfoundland and Labrador. Bed B forms part of a designated Site of Special Scientific Interest, protected in law and administered by Natural England. Access to Bed B casts was facilitated by BGS and P. Wilby. We thank S. Pates and F. Dunn for discussions, B. Jewer for image processing and J. Durden for support with the methods. We thank E. Samson for everything she does to support us and our work.Funder: Independent Research Fellowship NE/S014756/1Funder: School of Biological Science Balfour StudentshipFunder: RCUK | Natural Environment Research Council (NERC); doi: https://doi.org/10.13039/501100000270Funder: ECF-2018-542, INT18.08(h)The driving forces behind the evolution of early metazoans are not well understood, but key insights into their ecology and evolution can be gained through ecological analyses of the in situ, sessile communities of the Avalon assemblage in the Ediacaran (~565 million years ago). Community structure in the Avalon is thought to be underpinned by epifaunal tiering and ecological succession, which we investigate in this study in 18 Avalon communities. Here we found that Avalon communities form four distinctive Community Types irrespective of succession processes, which are instead based on the dominance of morphologically distinct taxa, and that tiering is prevalent in three of these Community Types. Our results are consistent with emergent neutrality, whereby ecologically specialized morphologies evolve as a consequence of neutral (stochastic or reproductive) processes within niches, leading to generalization within the frond-dominated Community Type. Our results provide an ecological signature of the first origination and subsequent loss of disparate morphologies, probably as a consequence of community restructuring in response to ecological innovation. This restructuring led to the survival of non-tiered frondose generalists over tiered specialists, even into the youngest Ediacaran assemblages. Such frondose body plans also survive beyond the Ediacaran–Cambrian transition, perhaps due to the greater resilience afforded to them by their alternative ecological strategies

Morphology shapes community dynamics in early animal ecosystems

Acknowledgements: Funding was provided by an School of Biological Sciences Balfour Studentship (PFAG/076) to N.P.S.; a Natural Environment Research Council C-CLEAR DTP studentship (LBAG/265.03.G10) to K.M.D.; Leverhulme Trust Funding (ECF-2018-542) and from the Isaac Newton Trust (INT18.08(h)) to C.G.K.; a Natural Environment Research Council Standard Grant (NE/P002412/1) and an Independent Research Fellowship (NE/S014756/1) to E.G.M. The Parks and Natural Areas Division, Department of Environment and Conservation, Government of Newfoundland and Labrador, provided permits to conduct research within the MPER in 2010, 2016–2018 and 2021–2023. Readers are advised that access to MPER is by scientific research permit only. Fossil surfaces in the Bonavista Peninsula and Bay Roberts area are protected under reg. 67/11, of the Historic Resources Act 2011 and their access is only allowed under permit from the Government of Newfoundland and Labrador. Fieldwork in the Discovery Geopark and the Bay Roberts area was conducted under permit from the Government of Newfoundland and Labrador. Bed B forms part of a designated Site of Special Scientific Interest, protected in law and administered by Natural England. Access to Bed B casts was facilitated by BGS and P. Wilby. We thank S. Pates and F. Dunn for discussions, B. Jewer for image processing and J. Durden for support with the methods. We thank E. Samson for everything she does to support us and our work.Funder: Independent Research Fellowship NE/S014756/1Funder: School of Biological Science Balfour StudentshipFunder: RCUK | Natural Environment Research Council (NERC); doi: https://doi.org/10.13039/501100000270Funder: ECF-2018-542, INT18.08(h)The driving forces behind the evolution of early metazoans are not well understood, but key insights into their ecology and evolution can be gained through ecological analyses of the in situ, sessile communities of the Avalon assemblage in the Ediacaran (~565 million years ago). Community structure in the Avalon is thought to be underpinned by epifaunal tiering and ecological succession, which we investigate in this study in 18 Avalon communities. Here we found that Avalon communities form four distinctive Community Types irrespective of succession processes, which are instead based on the dominance of morphologically distinct taxa, and that tiering is prevalent in three of these Community Types. Our results are consistent with emergent neutrality, whereby ecologically specialized morphologies evolve as a consequence of neutral (stochastic or reproductive) processes within niches, leading to generalization within the frond-dominated Community Type. Our results provide an ecological signature of the first origination and subsequent loss of disparate morphologies, probably as a consequence of community restructuring in response to ecological innovation. This restructuring led to the survival of non-tiered frondose generalists over tiered specialists, even into the youngest Ediacaran assemblages. Such frondose body plans also survive beyond the Ediacaran–Cambrian transition, perhaps due to the greater resilience afforded to them by their alternative ecological strategies

Mannan-binding lectin and hepatitis C infection

Japanese patients with chronic hepatitis C infection unresponsive to treatment with interferon possessed genotypes disproportionately conferring low mannan-binding lectin (MBL) concentrations. Our aims were to confirm or refute this finding in European patients at the MBL protein level, and to investigate whether a low circulating concentration of MBL might influence susceptibility to, or disease progression from, hepatitis C viral infection. Serum samples obtained from 180 hepatitis C patients and 566 blood donors were assayed for MBL. MBL concentrations were related to disease characteristics retrieved from patients’ records. MBL concentrations were higher in hepatitis C patients (median 2·5 µg/ml versus 1·3; P < 0·0001) and the proportion of patients with very low (MBL-deficient) concentrations was similar to that of the healthy controls. There were no significant associations between patients with low serum MBL and the disease features studied, including response to antiviral therapy. Therefore, low circulating MBL does not increase susceptibility to hepatitis C infection, and MBL concentration does not have a major influence on the course of the disease or the response to antiviral therapy. MBL replacement therapy would therefore not be indicated for chronic hepatitis C patients who failed to respond fully to treatment with interferon and ribavirin

Response and predictors of response, to pegylated interferon and ribavirin for chronic hepatitis C patients in Scotland:alanine aminotransferase (ALT) and gamma glutamyl transferase (GGT) are valuable pre-treatment markers of an SVR in routine clinical practice

It is not clear what proportion of HCV (hepatitis C virus) patients attain a sustained viral response (SVR) when treated with pegylated interferon and ribavirin combination therapy outside randomised clinical trials (RCTs). Secondly, pre-treatment factors available in routine clinical settings that are predictive of SVR (the optimal treatment outcome) are not known. HCV clinical databases from nine Scottish treatment clinics were used to derive a retrospective cohort of 934 patients initiated on HCV treatment during 2000–2007. In our cohort, 39% (123/315, 95% CI 34% to 45%) of genotype (GT) 1, and 70% (414/594, 95% CI 66% to 73%) of genotype 2/3 (GT2/3) patients achieved a SVR; this compares with pooled estimates of 47% for GT1 (95% CI 41% to 52%), and 80% for GT2/3 (95% CI 75% to 85%) patients from RCTs. Pre-treatment factors significantly associated with SVR were: gamma glutamyl transferase (GGT) ≥55 IU/l (adjusted OR: 0.46, 95% CI 0.33 to 0.65), platelet count ≥150×109/l (1.92, 95% CI 1.26 to 2.93), ALT quotient ≥2.5 (for those GT1 infected: 2.66, 95% CI 1.46 to 4.84), GT2/3 (for those with ALT quotient <2.5: 4.05, 95% CI 2.82 to 5.80; and for those with ALT quotient ≥2.5: 1.91, 95% CI 1.01 to 3.61), age (per ten year increase) (0.84, 95% CI 0.72 to 0.99), ever HBV infection (0.67, 95% CI 0.45 to 0.98), and male gender (0.70, 95% CI 0.50 to 0.98). The principal conclusions are twofold: (1) the proportion of patients attaining a SVR in Scottish routine practice is marginally lower than in RCTs, and (2) in addition to genotype, GGT (in all patients) and ALT (in GT1 patients only) emerge as valuable predictors of an SVR in the routine clinical setting

A Unique Arabinose 5-Phosphate Isomerase Found within a Genomic Island Associated with the Uropathogenicity of Escherichia coli CFT073 ▿

Previous studies showed that deletion of genes c3405 to c3410 from PAI-metV, a genomic island from Escherichia coli CFT073, results in a strain that fails to compete with wild-type CFT073 after a transurethral cochallenge in mice and is deficient in the ability to independently colonize the mouse kidney. Our analysis of c3405 to c3410 suggests that these genes constitute an operon with a role in the internalization and utilization of an unknown carbohydrate. This operon is not found in E. coli K-12 but is present in a small number of pathogenic E. coli and Shigella boydii strains. One of the genes, c3406, encodes a protein with significant homology to the sugar isomerase domain of arabinose 5-phosphate isomerases but lacking the tandem cystathionine beta-synthase domains found in the other arabinose 5-phosphate isomerases of E. coli. We prepared recombinant c3406 protein, found it to possess arabinose 5-phosphate isomerase activity, and characterized this activity in detail. We also constructed a c3406 deletion mutant of E. coli CFT073 and demonstrated that this deletion mutant was still able to compete with wild-type CFT073 in a transurethral cochallenge in mice and could colonize the mouse kidney. These results demonstrate that the presence of c3406 is not essential for a pathogenic phenotype