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Fulltext Shiga toxin sub-type 2a increases the efficiency of Escherichia coli O157 transmission between animals and restricts epithelial regeneration in bovine enteroids

Fitzgerald SF, Beckett AE, Palarea-Albaladejo J, McAteer S, Shaaban S, Morgan J, et al.

PLoS Pathog, 2019 10;15(10):e1008003.
PMID: 31581229 DOI: 10.1371/journal.ppat.1008003

Specific Escherichia coli isolates lysogenised with prophages that express Shiga toxin (Stx) can be a threat to human health, with cattle being an important natural reservoir. In many countries the most severe pathology is associated with enterohaemorrhagic E. coli (EHEC) serogroups that express Stx subtype 2a. In the United Kingdom, phage type (PT) 21/28 O157 strains have emerged as the predominant cause of life-threatening EHEC infections and this phage type commonly encodes both Stx2a and Stx2c toxin types. PT21/28 is also epidemiologically linked to super-shedding (>103 cfu/g of faeces) which is significant for inter-animal transmission and human infection as demonstrated using modelling studies. We demonstrate that Stx2a is the main toxin produced by stx2a+/stx2c+ PT21/28 strains induced with mitomycin C and this is associated with more rapid induction of gene expression from the Stx2a-encoding prophage compared to that from the Stx2c-encoding prophage. Bacterial supernatants containing either Stx2a and/or Stx2c were demonstrated to restrict growth of bovine gastrointestinal organoids with no restriction when toxin production was not induced or prevented by mutation. Isogenic strains that differed in their capacity to produce Stx2a were selected for experimental oral colonisation of calves to assess the significance of Stx2a for both super-shedding and transmission between animals. Restoration of Stx2a expression in a PT21/28 background significantly increased animal-to-animal transmission and the number of sentinel animals that became super-shedders. We propose that while both Stx2a and Stx2c can restrict regeneration of the epithelium, it is the relatively rapid and higher levels of Stx2a induction, compared to Stx2c, that have contributed to the successful emergence of Stx2a+ E. coli isolates in cattle in the last 40 years. We propose a model in which Stx2a enhances E. coli O157 colonisation of in-contact animals by restricting regeneration and turnover of the colonised gastrointestinal epithelium.
Fulltext Gender Differences in HIV Risk Behaviors Among Persons Involved in the U.S. Criminal Justice System and Living with HIV or at Risk for HIV: A "Seek, Test, Treat, and Retain" Harmonization Consortium

Loeliger KB, Biggs ML, Young R, Seal DW, Beckwith CG, Kuo I, et al.

AIDS Behav, 2017 Oct;21(10):2945-2957.
PMID: 28188460 DOI: 10.1007/s10461-017-1722-9

The U.S. female criminal justice (CJ) population is rapidly growing, yet large-scale studies exploring gender-specific HIV risk behaviors in the CJ population are lacking. This analysis uses baseline data on adults with a CJ history from eight U.S. studies in an NIH-funded "Seek, Test, Treat, Retain" harmonization consortium. Data were collected using a standardized HIV risk behavior assessment tool and pooled across studies to describe participants' characteristics and risk behaviors. Multilevel mixed-effects logistic regression models were used to test for gender-based behavior differences. Among 784 HIV-positive (21.4% female) and 5521 HIV-negative (8.5% female) participants, HIV-positive women had higher odds than HIV-positive men of engaging in condomless sexual intercourse (AOR 1.84 [1.16-2.95]) with potentially sero-discordant partners (AOR 2.40 [1.41-4.09]) and of sharing injection equipment (AOR 3.36 [1.31-8.63]). HIV risk reduction interventions targeting CJ-involved women with HIV are urgently needed as this population may represent an under-recognized potential source of HIV transmission.
Fulltext Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Howson JMM, Zhao W, Barnes DR, Ho WK, Young R, Paul DS, et al.

Nat Genet, 2017 Jul;49(7):1113-1119.
PMID: 28530674 DOI: 10.1038/ng.3874

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10-8, in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.
Fulltext The Global Alliance for Infections in Surgery: defining a model for antimicrobial stewardship-results from an international cross-sectional survey

Sartelli M, Labricciosa FM, Barbadoro P, Pagani L, Ansaloni L, Brink AJ, et al.

World J Emerg Surg, 2017;12:34.
PMID: 28775763 DOI: 10.1186/s13017-017-0145-2

BACKGROUND: Antimicrobial Stewardship Programs (ASPs) have been promoted to optimize antimicrobial usage and patient outcomes, and to reduce the emergence of antimicrobial-resistant organisms. However, the best strategies for an ASP are not definitively established and are likely to vary based on local culture, policy, and routine clinical practice, and probably limited resources in middle-income countries. The aim of this study is to evaluate structures and resources of antimicrobial stewardship teams (ASTs) in surgical departments from different regions of the world.
METHODS: A cross-sectional web-based survey was conducted in 2016 on 173 physicians who participated in the AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections) project and on 658 international experts in the fields of ASPs, infection control, and infections in surgery.
RESULTS: The response rate was 19.4%. One hundred fifty-six (98.7%) participants stated their hospital had a multidisciplinary AST. The median number of physicians working inside the team was five [interquartile range 4-6]. An infectious disease specialist, a microbiologist and an infection control specialist were, respectively, present in 80.1, 76.3, and 67.9% of the ASTs. A surgeon was a component in 59.0% of cases and was significantly more likely to be present in university hospitals (89.5%, p