A structural study of the interaction between the Dr haemagglutinin DraE and derivatives of chloramphenicol

The structures of two Dr adhesin (DraE) complexes with chloramphenicol derivatives, namely chloramphenicol succinate and bromamphenicol, have been solved. The structures reveal important functional groups for small-molecule binding and imply possible modifications to the molecule that would permit a more wide-ranging interaction without the toxic side effects associated with chloramphenicol

The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation

Time to arrest in donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischaemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following DCD SPK transplantation. Data were extracted from the UK transplant registry from 2014 to 2022. Predictors of graft loss were evaluated by a Cox proportional hazards model. Adjusted restricted cubic spline (RCS) models were generated to further delineate the relationship between TTD and outcome. Three-hundred-and-seventy-five DCD simultaneous kidney-pancreas transplant recipients were included. Increasing TTD was not associated with graft survival (aHR 0.98, 95% CI 0.68-1.41, P=0.901). Increasing asystolic time worsened graft survival (aHR 2.51, 95% CI 1.16-5.43, P=0.020). RCS modelling revealed a non-linear relationship was demonstrated between asystolic time and graft survival, and no relationship between TTD and graft survival. We found no evidence that TTD impacts on pancreas graft survival after DCD SPK transplantation, however increasing asystolic time was a significant predictor of graft loss. Procurement teams should attempt to minimise asystolic time to optimize pancreas graft survival rather than focus on the duration of TTD

Research to action to address inequities: the experience of the Cape Town Equity Gauge

© 2008 Scott et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Bacterial Signatures of Paediatric Respiratory Disease : An Individual Participant Data Meta-Analysis

Introduction: The airway microbiota has been linked to specific paediatric respiratory diseases, but studies are often small. It remains unclear whether particular bacteria are associated with a given disease, or if a more general, non-specific microbiota association with disease exists, as suggested for the gut. We investigated overarching patterns of bacterial association with acute and chronic paediatric respiratory disease in an individual participant data (IPD) meta-analysis of 16S rRNA gene sequences from published respiratory microbiota studies.Methods: We obtained raw microbiota data from public repositories or via communication with corresponding authors. Cross-sectional analyses of the paediatric (10 case subjects were included. Sequence data were processed using a uniform bioinformatics pipeline, removing a potentially substantial source of variation. Microbiota differences across diagnoses were assessed using alpha- and beta-diversity approaches, machine learning, and biomarker analyses.Results: We ultimately included 20 studies containing individual data from 2624 children. Disease was associated with lower bacterial diversity in nasal and lower airway samples and higher relative abundances of specific nasal taxa including Streptococcus and Haemophilus. Machine learning success in assigning samples to diagnostic groupings varied with anatomical site, with positive predictive value and sensitivity ranging from 43 to 100 and 8 to 99%, respectively.Conclusion: IPD meta-analysis of the respiratory microbiota across multiple diseases allowed identification of a non-specific disease association which cannot be recognised by studying a single disease. Whilst imperfect, machine learning offers promise as a potential additional tool to aid clinical diagnosis.Peer reviewe

Developing cancer warning statements for alcoholic beverages

Background: There is growing evidence of the increased cancer risk associated with alcohol consumption, but this is not well understood by the general public. This study investigated the acceptability among drinkers of cancer warning statements for alcoholic beverages. Methods: Six focus groups were conducted with Australian drinkers to develop a series of cancer-related warning statements for alcohol products. Eleven cancer warning statements and one general health warning statement were subsequently tested on 2,168 drinkers via an online survey. The statements varied by message frame (positive vs negative), cancer reference (general vs specific), and the way causality was communicated (‘increases risk of cancer’ vs ‘can cause cancer’). Results: Overall, responses to the cancer statements were neutral to favorable, indicating that they are unlikely to encounter high levels of negative reaction from the community if introduced on alcoholic beverages. Females, younger respondents, and those with higher levels of education generally found the statements to be more believable, convincing, and personally relevant. Positively framed messages, those referring to specific forms of cancer, and those using ‘increases risk of cancer’ performed better than negatively framed messages, those referring to cancer in general, and those using the term ‘can cause cancer’. Conclusion: Cancer warning statements on alcoholic beverages constitute a potential means of increasing awareness about the relationship between alcohol consumption and cancer risk

Polydendrocytes Display Large Lineage Plasticity following Focal Cerebral Ischemia

Polydendrocytes (also known as NG2 glial cells) constitute a fourth major glial cell type in the adult mammalian central nervous system (CNS) that is distinct from other cell types. Although much evidence suggests that these cells are multipotent in vitro, their differentiation potential in vivo under physiological or pathophysiological conditions is still controversial