Extensive horizontal gene transfer during Staphylococcus aureus co-colonization in vivo.

Staphylococcus aureus is a commensal and major pathogen of humans and animals. Comparative genomics of S. aureus populations suggests that colonization of different host species is associated with carriage of mobile genetic elements (MGE), particularly bacteriophages and plasmids capable of encoding virulence, resistance, and immune evasion pathways. Antimicrobial-resistant S. aureus of livestock are a potential zoonotic threat to human health if they adapt to colonize humans efficiently. We utilized the technique of experimental evolution and co-colonized gnotobiotic piglets with both human- and pig-associated variants of the lineage clonal complex 398, and investigated growth and genetic changes over 16 days using whole genome sequencing. The human isolate survived co-colonization on piglets more efficiently than in vitro. During co-colonization, transfer of MGE from the pig to the human isolate was detected within 4 h. Extensive and repeated transfer of two bacteriophages and three plasmids resulted in colonization with isolates carrying a wide variety of mobilomes. Whole genome sequencing of progeny bacteria revealed no acquisition of core genome polymorphisms, highlighting the importance of MGE. Staphylococcus aureus bacteriophage recombination and integration into novel sites was detected experimentally for the first time. During colonization, clones coexisted and diversified rather than a single variant dominating. Unexpectedly, each piglet carried unique populations of bacterial variants, suggesting limited transmission of bacteria between piglets once colonized. Our data show that horizontal gene transfer occurs at very high frequency in vivo and significantly higher than that detectable in vitro

Opportunities for topical antimicrobial therapy: permeation of canine skin by fusidic acid

BACKGROUND: Staphylococcal infection of the canine epidermis and hair follicle is amongst the commonest reasons for antimicrobial prescribing in small animal veterinary practice. Topical therapy with fusidic acid (FA) is an attractive alternative to systemic therapy based on low minimum inhibitory concentrations (MICs, commonly <0.03 mg/l) documented in canine pathogenic staphylococci, including strains of MRSA and MRSP (methicillin-resistant Staphylococcus aureus and S. pseudintermedius). However, permeation of canine skin by FA has not been evaluated in detail. This study aimed to define the degree and extent of FA permeation in canine skin in vitro from two sites with different hair follicle density following application of a licensed ophthalmic formulation that shares the same vehicle as an FA-betamethasone combination product approved for dermal application in dogs. Topical FA application was modelled using skin held in Franz-type diffusion cells. Concentrations of FA in surface swabs, receptor fluid, and transverse skin sections of defined anatomical depth were determined using high-performance liquid chromatography and ultraviolet (HPLC-UV) analysis. RESULTS: The majority of FA was recovered by surface swabs after 24 h, as expected (mean ± SEM: 76.0 ± 17.0%). FA was detected within 424/470 (90%) groups of serial sections of transversely cryotomed skin containing follicular infundibula, but never in 48/48 (100%) groups of sections containing only deeper follicular structures, nor in receptor fluid, suggesting that FA does not permeate beyond the infundibulum. The FA concentration (mean ± SEM) in the most superficial 240 μm of skin was 2000 ± 815 μg/g. CONCLUSIONS: Topically applied FA can greatly exceed MICs for canine pathogenic staphylococci at the most common sites of infection. Topical FA therapy should now be evaluated using available formulations in vivo as an alternative to systemic therapy for canine superficial bacterial folliculitis.Peer reviewedFinal Published versio

Exploring the behavioural drivers of veterinary surgeon antibiotic prescribing: a qualitative study of companion animal veterinary surgeons in the UK

Background: Multi-drug resistant bacteria are an increasing concern in both human and veterinary medicine. Inappropriate prescribing and use of antibiotics within veterinary medicine may be a contributory factor to antimicrobial resistance (AMR). The ‘One Health’ Initiative aims to work across species and environments to reduce AMR, however; little is currently known about the factors which influence antibiotic prescribing among veterinary surgeons in companion animal practice. This paper reports on qualitative data analysis of interviews with veterinary surgeons whose practice partially or wholly focuses on companion animals (N = 16). The objective of the research was to explore the drivers of companion animal veterinary surgeons’ antibiotic prescribing behaviours. The veterinary surgeons interviewed were all practising within the UK (England (n = 4), Scotland (n = 11), Northern Ireland (n = 1)). A behavioural thematic analysis of the data was undertaken, which identified barriers and facilitators to specific prescribing-related behaviours. Results: Five components of prescribing behaviours were identified: 1) confirming clinical need for antibiotics; 2) responding to clients; 3) confirming diagnosis; 4) determining dose, duration and type of antibiotic; and 5) preventing infection around surgery (with attendant appropriate and inappropriate antibiotic prescribing behaviours). Barriers to appropriate prescribing identified include: business, diagnostic, fear, habitual practice and pharmaceutical factors. Facilitators include: AMR awareness, infection prevention, professional learning and regulation and government factors. Conclusion: This paper uses a behavioural lens to examine drivers which are an influence on veterinary surgeons’ prescribing behaviours. The paper contributes new understandings about factors which influence antibiotic prescribing behaviours among companion animal veterinary surgeons. This analysis provides evidence to inform future interventions, which are focused on changing prescribing behaviours, in order to address the pressing public health concern of AMR

Species-level functional profiling of metagenomes and metatranscriptomes.

Functional profiles of microbial communities are typically generated using comprehensive metagenomic or metatranscriptomic sequence read searches, which are time-consuming, prone to spurious mapping, and often limited to community-level quantification. We developed HUMAnN2, a tiered search strategy that enables fast, accurate, and species-resolved functional profiling of host-associated and environmental communities. HUMAnN2 identifies a community's known species, aligns reads to their pangenomes, performs translated search on unclassified reads, and finally quantifies gene families and pathways. Relative to pure translated search, HUMAnN2 is faster and produces more accurate gene family profiles. We applied HUMAnN2 to study clinal variation in marine metabolism, ecological contribution patterns among human microbiome pathways, variation in species' genomic versus transcriptional contributions, and strain profiling. Further, we introduce 'contributional diversity' to explain patterns of ecological assembly across different microbial community types

Planning ahead in public health? A qualitative study of the time horizons used in public health decision-making

<p>Abstract</p> <p>Background</p> <p>In order to better understand factors that influence decisions for public health, we undertook a qualitative study to explore issues relating to the time horizons used in decision-making.</p> <p>Methods</p> <p>Qualitative study using semi-structured interviews. 33 individuals involved in the decision making process around coronary heart disease were purposively sampled from the UK National Health Service (national, regional and local levels), academia and voluntary organizations. Analysis was based on the framework method using N-VIVO software. Interviews were transcribed, coded and emergent themes identified.</p> <p>Results</p> <p>Many participants suggested that the timescales for public health decision-making are too short. Commissioners and some practitioners working at the national level particularly felt constrained in terms of planning for the long-term. Furthermore respondents felt that longer term planning was needed to address the wider determinants of health and to achieve societal level changes. Three prominent 'systems' issues were identified as important drivers of short term thinking: the need to demonstrate impact within the 4 year political cycle; the requirement to 'balance the books' within the annual commissioning cycle and the disruption caused by frequent re-organisations within the health service. In addition respondents suggested that the tools and evidence base for longer term planning were not well established.</p> <p>Conclusion</p> <p>Many public health decision and policy makers feel that the timescales for decision-making are too short. Substantial systemic barriers to longer-term planning exist. Policy makers need to look beyond short-term targets and budget cycles to secure investment for long-term improvement in public health.</p

Good practice in social care: the views of people with severe and complex needs and those who support them

This paper reports findings drawn from a study of good practice in English social care for adults with disability and older people with severe and complex needs. People with severe and complex needs are a relatively small proportion of adult social care service users, but they are growing in numbers and have resource-intensive needs. The study involved qualitative research with adults with disability and older people with severe and complex needs, family carers and members of specialist organisations (n = 67), focusing on the features of social care services they considered to be good practice. Data were collected between August 2010 and June 2011. The approach to data collection was flexible, to accommodate participants' communication needs and preferences, including face-to-face and telephone interviews, Talking Mats(c) sessions and a focus group. Data were managed using Framework and analysed thematically. Features of good practice were considered at three levels: (i) everyday support, (ii) service organisation, and (iii) commissioning. Findings relating to the first two of these are presented here. Participants emphasised the importance of person-centred ways of working at all levels. Personalisation, as currently implemented in English social care, aims to shift power from professionals to service users through the allocation of personal budgets. This approach focuses very much on the role of the individual in directing his/her own support arrangements. However, participants in this study also stressed the importance of ongoing professional support, for example, from a specialist key worker or case manager to co-ordinate diverse services and ensure good practice at an organisational level. The paper argues that, despite the recent move to shift power from professionals to service users, people with the most complex needs still value support from professionals and appropriate organisational support. Without these, they risk being excluded from the benefits that personalisation, properly supported, could yield. Keywords : continuity of care; dementia; people with disability; qualitative research; service delivery and organisation

Functional diversity of marine ecosystems after the Late Permian mass extinction event

Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

Peer reviewedPublisher PD

The epidemiology of injuries across the weight-training sports

Background: Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Objectives: Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. Methods: We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Results: Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12–0.7 injuries per lifter per year; 0.24–1 injury per 1000 h), with strongman (4.5–6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. Conclusion: While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure

Association of liver enzymes with incident type 2 diabetes: A nested case control study in an Iranian population

<p>Abstract</p> <p>Background</p> <p>To investigate the association of Aspartate aminotransferase (AST), Alanin aminotranferase (ALT) and Gamma glutamyl transferase (GGT) with incident type 2 diabetes.</p> <p>Methods</p> <p>In a nested case-control study, AST, ALT, GGT as well as classic diabetes risk factors, insulin and C-reactive protein (CRP) were measured in 133 non-diabetic subjects at baseline of which 68 were cases and 65 were controls. Incident diabetes was defined by the WHO 1999 criteria. Conditional logistic regression was used to calculate the odds ratio (OR) of incident diabetes associated with different hepatic markers. We used factor analysis for clustering of classic diabetes risk factors.</p> <p>Results</p> <p>In Univariate analysis both ALT and GGT were associated with diabetes with ORs of 3.07(1.21–7.79) and 2.91(1.29–6.53) respectively. After adjustment for CRP and insulin, ALT and GGT were still predictive of incident diabetes. When the model was further adjusted for anthropometric, blood pressure and metabolic factors, only ALT was independently associated with diabetes [OR = 3.18 (1.02–9.86)]. No difference was found between the area under the receiver operating characteristic curves of the models with and without ALT (0.820 and 0.802 respectively, P = 0.4)</p> <p>Conclusion</p> <p>ALT is associated with incident type 2 diabetes independent of classic risk factors. However, its addition to the classic risk factors does not improve the prediction of diabetes.</p