703 research outputs found
Effect of live yeast culture supplementation on fibrolytic and saccharolytic bacterial populations in the feces of horses fed a high-fiber or high-starch diet
The objective of this study was to assess the effect of live yeast (Saccharomyces cerevisiae) supplementation on the populations of specific cellulolytic (Fibrobacter succinogenes and Ruminococcus flavefaciens) and saccharolytic (Streptococcus equinus and Streptococcus bovis) bacteria in the feces of horses fed high-starch and high-fiber diets. Four horses were each fed diets consisting of high fiber with no yeast (HF), high fiber with yeast (HFY), high starch with no yeast (HS), and high starch with yeast (HSY) in a 4 Ă— 4 Latin-square design study. Fresh fecal samples were collected on the last 3 days of each 31-day experimental period and were then assessed, using semiquantitative real-time PCR, for total bacterial load and levels of target bacterial species, relative to the total bacterial load. The most abundant of the target species was F. succinogenes, and the HSY diet resulted in a significant (P = .045) reduction in relative levels of this bacterium. No significant effect (P = .224) of diet was observed in relation to abundance of R. flavefaciens. Results show that diet did not have a significant (P = .068) effect on relative quantities of S. equinus, although there appeared to be a trend for increased levels of this bacterium during feeding of high-starch diets. Numbers of S. bovis were higher (P < .001) when horses were fed HS and HSY diets than when fed the HF and HFY diets. Significant variation in levels of S. equinus (P = .024) and S. bovis (P = .049) was observed between individual horses
Singing for people with aphasia (SPA): a protocol for a pilot randomised controlled trial of a group singing intervention to improve well-being
Introduction: The singing for people with aphasia (SPA) intervention aims to improve quality of life and well-being for people with poststroke aphasia. A definitive randomised controlled trial (RCT) is required to assess the clinical and cost effectiveness of SPA. The purpose of this pilot study is to assess the feasibility of such a definitive trial and inform its design.
Methods and analysis: A two-group, assessor-blinded, randomised controlled external pilot trial with parallel mixed methods process evaluation and economic evaluation. Forty-eight participants discharged from clinical speech and language therapy will be individually randomised 1:1 to SPA (10 group sessions plus a resource booklet) or control (resource booklet only). Outcome assessment at baseline, 3 and 6 months postrandomisation include: ICEpop CAPability measure for adults, Stroke and Aphasia Quality of Life, EQ-5D-5L, modified Reintegration into Normal Living Index, Communication Outcome After Stroke, Very Short Version of the Minnesota Aphasia Test, Service Receipt Inventory and Care Related Quality of Life. Feasibility, acceptability and process outcomes include recruitment and retention rates, with measurement burden and trial experiences being explored in qualitative interviews (15 participants, 2 music facilitators and 2 music champions). Analyses include: descriptive statistics, with 95% CIs where appropriate; qualitative themes; intervention fidelity from videos and session checklists; rehearsal of health economic analysis.
Ethics and dissemination: NHS National Research Ethics Service and the Health Research Authority confirmed approval in April 2017; recruitment commenced in June 2017. Outputs will include: pilot data to inform whether to proceed to a definitive RCT and support a funding application; finalised intervention manual for multicentre replication of SPA; presentations at conferences, public involvement events; internationally recognised peer reviewed journal publications, open access sources and media releases
Promoting Respectful Maternity Care: A training guide for facility-based workshops—Participant\u27s guide
This guide was produced as part of the Respectful Maternity Care (RMC) Resource Package. The Resource Package was designed to support health facility managers, health care providers, and communities in confronting disrespect and abuse (D&A) during facility-based childbirth and to promote respectful maternity care. The Resource Package includes a facilitator’s guide (facility-based workshops), facilitator’s guide (community-based workshops), participant’s guide, community flipchart, tools, and program briefs. Workshop objectives outlined in the Participant’s Guide: Outline current status of maternal and neonatal health in relation to respectful care. Discuss key RMC concepts, terminology, legal and rights-based approaches related to respectful maternity care and the RMC Resource Package. Demonstrate knowledge and use of VCAT theory and practice. Discuss selected evidence-based strategies that reduce D&A. Discuss participants’ role in promoting RMC. Develop action plans to support the implementation of RMC interventions at various levels of health (e.g., policy, program, regional/county, subcounty, facility, and community)
Promoting Respectful Maternity Care: A training guide for community-based workshops—Community facilitator\u27s guide
This guide was produced as part of the Respectful Maternity Care (RMC) Resource Package. The Resource Package was designed to support health facility managers, health care providers, and communities in confronting disrespect and abuse (D&A) during facility-based childbirth and to promote respectful maternity care. The Resource Package includes a facilitator’s guide (facility-based workshops), facilitator’s guide (community-based workshops), participant’s guide, community flipchart, tools, and program briefs. The Community Facilitator’s Guide, designed to be used by facilitators to promote respectful maternity care at the community level, can be adapted to educate a variety of stakeholders in community settings (i.e., Community Health Extension Workers, Community Health Workers, society leaders, legal aid officers). The Guide highlights key practical points to enable participants to act as resource persons regarding the rights and obligations of childbearing women, and as advocates of respectful maternity care including how to conduct an Alternative Dispute Resolution mechanism
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Clades of huge phages from across Earth's ecosystems.
Bacteriophages typically have small genomes1 and depend on their bacterial hosts for replication2. Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is-to our knowledge-the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR-Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR-Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR-Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth's ecosystems
Singing for people with aphasia (SPA): results of a pilot feasibility randomised controlled trial of a group singing intervention investigating acceptability and feasibility
Objectives: Pilot feasibility randomised controlled trial (RCT) for the singing groups for people with aphasia (SPA) intervention to assess: (1) the acceptability and feasibility of participant recruitment, randomisation and allocation concealment; (2) retention rates; (3) variance of continuous outcome measures; (4) outcome measure completion and participant burden; (5) fidelity of intervention delivery; (6) SPA intervention costs; (7) acceptability and feasibility of trial and intervention to participants and others involved.
Design: A two-group, assessor-blinded, randomised controlled external pilot trial with parallel mixed methods process evaluation and economic evaluation.
Setting: Three community-based cohorts in the South-West of England.
Participants: Eligible participants with post-stroke aphasia were randomised 1:1 to SPA or control.
Intervention: The manualised SPA intervention was delivered over 10 weekly singing group sessions, led by a music facilitator and assisted by an individual with post-stroke aphasia. The intervention was developed using the Information-Motivation-Behavioural skills model of behaviour change and targeted psychosocial outcomes. Control and intervention participants all received an aphasia information resource pack.
Outcome measures: Collected at baseline, 3 and 6 months post-randomisation, candidate primary outcomes were measured (well-being, quality of life and social participation) as well as additional clinical outcomes. Feasibility, acceptability and process outcomes included recruitment and retention rates, and measurement burden; and trial experiences were explored in qualitative interviews.
Results: Of 87 individuals screened, 42 participants were recruited and 41 randomised (SPA=20, control=21); 36 participants (SPA=17, control=19) completed 3-month follow-up, 34 (SPA=18, control=16) completed 6-month follow-up. Recruitment and retention (83%) were acceptable for a definitive RCT, and participants did not find the study requirements burdensome. High fidelity of the intervention delivery was shown by high attendance rates and facilitator adherence to the manual, and participants found SPA acceptable. Sample size estimates for a definitive RCT and primary/secondary outcomes were identified.
Conclusions: The SPA pilot RCT fulfilled its objectives, and demonstrated that a definitive RCT of the intervention would be both feasible and acceptable.
Trial registration number: NCT03076736
Metabolic imaging across scales reveals distinct prostate cancer phenotypes
Hyperpolarised magnetic resonance imaging (HP-13C-MRI) has shown promise as a clinical tool for detecting and characterising prostate cancer. Here we use a range of spatially resolved histological techniques to identify the biological mechanisms underpinning differential [1-13C]lactate labelling between benign and malignant prostate, as well as in tumours containing cribriform and non-cribriform Gleason pattern 4 disease. Here we show that elevated hyperpolarised [1-13C]lactate signal in prostate cancer compared to the benign prostate is primarily driven by increased tumour epithelial cell density and vascularity, rather than differences in epithelial lactate concentration between tumour and normal. We also demonstrate that some tumours of the cribriform subtype may lack [1-13C]lactate labelling, which is explained by lower epithelial lactate dehydrogenase expression, higher mitochondrial pyruvate carrier density, and increased lipid abundance compared to lactate-rich non-cribriform lesions. These findings highlight the potential of combining spatial metabolic imaging tools across scales to identify clinically significant metabolic phenotypes in prostate cancer
VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever
Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-Îł CD4+ T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models
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