Transcriptome signatures of wastewater effluent exposure in larval zebrafish vary with seasonal mixture composition in an effluent-dominated stream

Wastewater treatment plant (WWTP) effluent-dominated streams provide critical habitat for aquatic and terrestrial organisms but also continually expose them to complex mixtures of pharmaceuticals that can potentially impair growth, behavior, and reproduction. Currently, few biomarkers are available that relate to pharmaceutical-specific mechanisms of action. In the experiment reported in this paper, zebrafish (Danio rerio) embryos at two developmental stages were exposed to water samples from three sampling sites (0.1 km upstream of the outfall, at the effluent outfall, and 0.1 km below the outfall) during base-flow conditions from two months (January and May) of a temperate-region effluent-dominated stream containing a complex mixture of pharmaceuticals and other contaminants of emerging concern. RNA-sequencing identified potential biological impacts and biomarkers of WWTP effluent exposure that extend past traditional markers of endocrine disruption. Transcriptomics revealed changes to a wide range of biological functions and pathways including cardiac, neurological, visual, metabolic, and signaling pathways. These transcriptomic changes varied by developmental stage and displayed sensitivity to variable chemical composition and concentration of effluent, thus indicating a need for stage-specific biomarkers. Some transcripts are known to be associated with genes related to pharmaceuticals that were present in the collected samples. Although traditional biomarkers of endocrine disruption were not enriched in either month, a high estrogenicity signal was detected upstream in May and implicates the presence of unidentified chemical inputs not captured by the targeted chemical analysis. This work reveals associations between bioeffects of exposure, stage of development, and the composition of chemical mixtures in effluent-dominated surface water. The work underscores the importance of measuring effects beyond the endocrine system when assessing the impact of bioactive chemicals in WWTP effluent and identifies a need for non-targeted chemical analysis when bioeffects are not explained by the targeted analysis

A Genome Wide Association Scan of Bovine Tuberculosis Susceptibility in Holstein-Friesian Dairy Cattle

peer-reviewedBackground: Bovine tuberculosis is a significant veterinary and financial problem in many parts of the world. Although many factors influence infection and progression of the disease, there is a host genetic component and dissection of this may enlighten on the wider biology of host response to tuberculosis. However, a binary phenotype of presence/absence of infection presents a noisy signal for genomewide association study. Methodology/Principal Findings: We calculated a composite phenotype of genetic merit for TB susceptibility based on disease incidence in daughters of elite sires used for artificial insemination in the Irish dairy herd. This robust measure was compared with 44,426 SNP genotypes in the most informative 307 subjects in a genome wide association analysis. Three SNPs in a 65 kb genomic region on BTA 22 were associated (i.e. p,1025, peaking at position 59588069, p = 4.0261026) with tuberculosis susceptibility. Conclusions/Significance: A genomic region on BTA 22 was suggestively associated with tuberculosis susceptibility; it contains the taurine transporter gene SLC6A6, or TauT, which is known to function in the immune system but has not previously been investigated for its role in tuberculosis infection

Spleen transcriptome response to infection with avian pathogenic Escherichia coli in broiler chickens

<p>Abstract</p> <p>Background</p> <p>Avian pathogenic <it>Escherichia coli </it>(APEC) is detrimental to poultry health and its zoonotic potential is a food safety concern. Regulation of antimicrobials in food-production animals has put greater focus on enhancing host resistance to bacterial infections through genetics. To better define effective mechanism of host resistance, global gene expression in the spleen of chickens, harvested at two times post-infection (PI) with APEC, was measured using microarray technology, in a design that will enable investigation of effects of vaccination, challenge, and pathology level.</p> <p>Results</p> <p>There were 1,101 genes significantly differentially expressed between severely infected and non-infected groups on day 1 PI and 1,723 on day 5 PI. Very little difference was seen between mildly infected and non-infected groups on either time point. Between birds exhibiting mild and severe pathology, there were 2 significantly differentially expressed genes on day 1 PI and 799 on day 5 PI. Groups with greater pathology had more genes with increased expression than decreased expression levels. Several predominate immune pathways, Toll-like receptor, Jak-STAT, and cytokine signaling, were represented between challenged and non-challenged groups. Vaccination had, surprisingly, no detectible effect on gene expression, although it significantly protected the birds from observable gross lesions. Functional characterization of significantly expressed genes revealed unique gene ontology classifications during each time point, with many unique to a particular treatment or class contrast.</p> <p>Conclusions</p> <p>More severe pathology caused by APEC infection was associated with a high level of gene expression differences and increase in gene expression levels. Many of the significantly differentially expressed genes were unique to a particular treatment, pathology level or time point. The present study not only investigates the transcriptomic regulations of APEC infection, but also the degree of pathology associated with that infection. This study will allow for greater discovery into host mechanisms for disease resistance, providing targets for marker assisted selection and advanced drug development.</p

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Using intervention mapping in the systematic development of a behaviour change intervention to enhance exercise adherence among people with persistent musculoskeletal pain

Purpose: This article describes the first four steps of the intervention mapping framework used to design a programme aimed at increasing adherence to prescribed exercise by people with persistent musculoskeletal pain. Method: In Step 1, a systematic review and qualitative study was completed to inform Step 2 and the identification of the Health Action Process Approach as an appropriate theoretical framework for establishing two programme objectives: enhancing self-management and providing tailored and accessible exercise instructions. Step 3 encompassed the selection of the programme methods, and the programme is described in Step 4. The resulting programme provides virtually delivered motivational interviewing and an app-based exercise programme to support individuals’ adherence to exercise. Results: The resulting intervention was assessed in a proof-of-concept feasibility and acceptability study and was shown to be feasible and acceptable. Refinements to the programme included additional tailoring of the exercise app and modifying the motivational interviewing schedule. Conclusions: Using the intervention mapping approach enabled us to successfully develop an intervention aimed at supporting the development of self-management behaviours and addressing maladaptive beliefs as a means of enhancing individuals’ adherence to exercise. Evaluation and implementation of the intervention should now be carried out. Objectif : décrire les quatre premières étapes du cadre de modélisation d’une intervention, utilisé pour concevoir un programme visant à accroître l’adhésion à une prescription d’exercices chez les personnes souffrant de douleurs musculosquelettiques persistantes. Méthodologie : à la première étape, les chercheurs ont effectué une analyse systématique et une étude qualitative pour étayer la deuxième étape et déterminer le processus d’action en santé dans un cadre théorique approprié qui permettrait de formuler les deux objectifs du programme : améliorer l’autogestion et fournir des directives d’exercices adaptées et accessibles. L’étape trois englobait le choix de la méthodologie du programme, décrite à l’étape quatre. Le programme qui en découle comprend des entrevues motivationnelles virtuelles et un programme d’exercices fondé sur une application pour renforcer l’adhésion à l’exercice. Résultats : l’intervention obtenue, évaluée dans une étude de validation de la faisabilité et de l’acceptabilité, s’est révélée faisable et acceptable. Les améliorations au programme ont inclus de nouvelles adaptations à l’application d’exercices et des modifications au calendrier d’entrevues motivationnelles. Conclusion : grâce à la démarche de modélisation de l’intervention, il a été possible d’élaborer une intervention visant à promouvoir l’acquisition de comportements d’autogestion et à corriger des convictions mésadaptées pour accroître l’adhésion à l’exercice. Il reste maintenant à évaluer et à mettre en œuvre l’intervention

Towards a gaze-independent hybrid-BCI based on SSVEPs, alpha-band modulations and the P300

In recent years it has been shown to be possible to create a Brain Computer Interface (BCI) using non-invasive electroencephalographic (EEG) measurements of covert visual spatial attention. For example, that both Steady-State Visual Evoked Potentials (SSVEP) and parieto-occipital alpha band activity have been shown to be sensitive to covert attention and this has been exploited to provide simple communication control without the need for any physical movement. In this study, potential improvements in the speed and accuracy of such a BCI are investigated by exploring the possibility of incorporating a P300 task into an SSVEP covert attention paradigm. Should this be possible it would pave the way for a gaze-independent hybrid BCI based on three somewhat independent EEG signals. Within a well-established SSVEP-based attention paradigm we show that it is possible to make a binary classification of covert attention using just the P300 with an average accuracy of 71% across three subjects. We also validate previously published research by showing robust attention effects on the SSVEP and alpha band activity within this paradigm. In future work, it is hoped that by integrating the three signals into a hybrid BCI a significant improvement in performance will be forthcoming leading to an easily usable real time communication device for patients with severe disabilities such as Locked-In Syndrome (LIS)

Traumatic brain injury : integrated approaches to improve prevention, clinical care, and research

Rahul Raj on työryhmän InTBIR Participants Investigators jäsen.Peer reviewe