Kinetics of plasma cell‐free DNA and creatine kinase in a canine model of tissue injury

Background: Cell‐free DNA (cfDNA) comprises short, double‐stranded circulating DNA sequences released from damaged cells. In people, cfDNA concentrations correlate well with disease severity and tissue damage. No reports are available regarding cfDNA kinetics in dogs. Objectives/Hypothesis: Cell‐free DNA will have a short biological half‐life and would be able to stratify mild, moderate, and severe tissue injury. Our study aims were to determine the kinetics and biological half‐life of cfDNA and to contrast them with those of creatine kinase (CK). Animals: Three groups of 10 dogs undergoing open ovariohysterectomy, surgery for cranial cruciate ligament rupture (CCLR), or hemilaminectomy. Methods: Plasma for cfDNA and CK analysis was collected at admission, at induction of anesthesia, postsurgery (time 0) and at 6, 12, 24, 36, 48, 60, and 72 hours after surgery. Results: The biological half‐life of plasma cfDNA and CK were 5.64 hours (95% confidence interval [CI 95], 4.36–7.98 hours) and 28.7 hours (CI95, 25.3–33.3 hours), respectively. In the hemilaminectomy group, cfDNA concentrations differed significantly from admission at 6–12 hours after surgery. Creatine kinase activity differed among the surgical groups and reached a peak 6 hours after surgery. In the ovariohysterectomy and CCLR groups, plasma CK activity 72 hours after surgery did not differ from admission activity of the ovariohysterectomy group. In contrast, in the hemilaminectomy group, plasma CK activity after 72 hours did not return to the ovariohysterectomy group admission activity. Conclusions and Clinical Importance: Plasma CK activity has a longer biological half‐life than previously thought. In contrast to plasma CK activity, cfDNA has a short half‐life and could be a useful marker for peracute severe tissue injury

The Inherent Tracer Fingerprint of Captured CO2.

Carbon capture and storage (CCS) is the only currently available technology that can directly reduce anthropogenic CO2 emissions arising from fossil fuel combustion. Monitoring and verification of CO2 stored in geological reservoirs will be a regulatory requirement and so the development of reliable monitoring techniques is essential. The isotopic and trace gas composition - the inherent fingerprint - of captured CO2 streams is a potentially powerful, low cost geochemical technique for tracking the fate of injected gas in CCS projects; carbon and oxygen isotopes, in particular, have been used as geochemical tracers in a number of pilot CO2 storage sites, and noble gases are known to be powerful tracers of natural CO2 migration. However, the inherent tracer fingerprint in captured CO2 streams has yet to be robustly investigated and documented and key questions remain, including how consistent is the fingerprint, what controls it, and will it be retained en route to and within the storage reservoir? Here we present the first systematic measurements of the carbon and oxygen isotopes and the trace noble gas composition of anthropogenic CO2 captured from combustion power stations and fertiliser plants. The analysed CO2 is derived from coal, biomass and natural gas feedstocks, using amine capture, oxyfuel and gasification processes, from six different CO2 capture plants spanning four different countries. We find that δ13C values are primarily controlled by the δ13C of the feedstock while δ18O values are predominantly similar to atmospheric O2. Noble gases are of low concentration and exhibit relative element abundances different to expected reservoir baselines and air, with isotopic compositions that are similar to air or fractionated air. The use of inherent tracers for monitoring and verification was provisionally assessed by analysing CO2 samples produced from two field storage sites after CO2 injection. These experiments at Otway, Australia, and Aquistore, Canada, highlight the need for reliable baseline data. Noble gas data indicates noble gas stripping of the formation water and entrainment of Kr and Xe from an earlier injection experiment at Otway, and inheritance of a distinctive crustal radiogenic noble gas fingerprint at Aquistore. This fingerprint can be used to identify unplanned migration of the CO2 to the shallow subsurface or surface

Adaptive host manipulation by Toxoplasma gondii: fact or fiction?

It is widely accepted that behavioural changes induced by Toxoplasma gondii are an adaptation of the parasite to enhance transmission to its cat definitive host. In our opinion, this explanation requires a rethink. We argue that the experimental evidence that observed behavioural changes will enhance transmission to cats is not convincing. We also argue that cats and sexual reproduction may not be essential for transmission and maintenance of this parasite. Thus, the selection pressure to infect a cat may not be sufficiently strong for the evolution of adaptive host manipulation to have occurred in order to enhance predation by cats

PDBLIG: classification of small molecular protein binding in the Protein Data Bank

It is known that proteins can adopt different folds while sharing similar features for recognition of similar substrates or ligands, for example, in the binding sites of enzyme cofactors such as ATP. On the other hand, proteins that have highly flexible binding sites or belong to large and diverse protein families can bind structurally dissimilar ligands, as, for example, in the case of the matrix metalloprotease family. We have developed a database, PDBLIG, that classifies protein domains and ligands. The information stored includes each protein's function, domain class(es), which ligand(s) it binds, and so on. The database can provide valuable knowledge for drug discovery, supporting the answering of questions such as whether the same drug molecule can bind different target protein families and whether these families are related functionally or structurally, which ligand classes (such as metabolites or organic molecules) bind to a particular protein family and whether the ligands are druglike, and which target families bind a wide variety of ligands and whether different ligands are associated with different subfamilies

Impact of an Integrated Antibiotic Allergy Testing Program on Antimicrobial Stewardship: A Multicenter Evaluation

Background. Despite the high prevalence of patient-reported antibiotic allergy (so-called antibiotic allergy labels [AALs]) and their impact on antibiotic prescribing, incorporation of antibiotic allergy testing (AAT) into antimicrobial stewardship (AMS) programs (AAT-AMS) is not widespread. We aimed to evaluate the impact of an AAT-AMS program on AAL prevalence, antibiotic usage, and appropriateness of prescribing. Methods. AAT-AMS was implemented at two large Australian hospitals during a 14-month period beginning May 2015. Baseline demographics, AAL history, age-adjusted Charlson comorbidity index, infection history, and antibiotic usage for 12 months prior to testing (pre-AAT-AMS) and 3 months following testing (post-AAT-AMS) were recorded for each participant. Study outcomes included the proportion of patients who were "de-labeled" of their AAL, spectrum of antibiotic courses pre- and post-AAT-AMS, and antibiotic appropriateness (using standard definitions). Results. From the 118 antibiotic allergy-tested patients, 226 AALs were reported (mean, 1.91/patient), with 53.6% involving 1 or more penicillin class drug. AAT-AMS allowed AAL de-labeling in 98 (83%) patients-56% (55/98) with all AALs removed. Post-AAT, prescribing of narrow-spectrum penicillins was more likely (adjusted odds ratio [aOR], 2.81, 95% confidence interval [CI], 1.45-5.42), as was narrow-spectrum beta-lactams (aOR, 3.54; 95% CI, 1.98-6.33), and appropriate antibiotics (aOR, 12.27; 95% CI, 5.00-30.09); and less likely for restricted antibiotics (aOR, 0.16; 95% CI,.09-.29), after adjusting for indication, Charlson comorbidity index, and care setting. Conclusions. An integrated AAT-AMS program was effective in both de-labeling of AALs and promotion of improved antibiotic usage and appropriateness, supporting the routine incorporation of AAT into AMS programs

Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells

10.1038/ncomms12175Nature Communications71217

Perpetration of violence by female sex workers in Papua New Guinea: 'we will crush their bones'

There is a small but important body of literature on female sex workers' (FSWs) violence towards others, but little of that focused on low- and middle-income countries. Drawn from a larger biobehavioural study of FSWs in three cities in Papua New Guinea, we analyse the interviews from 19 FSWs who reported having perpetrated physical violence towards four major groups: (1) ex-husbands; (2) clients; (3) other sex workers and (4) other people (mainly women). Our study demonstrates that FSWs' use of violence arises from a complex set of social, material and gendered circumstances and cannot be addressed in isolation from other aspects of their lives