Violence prevention climate in general adult inpatient mental health units : validation study of the VPC‐14

Ward social climate is an important contributor to patient outcomes in inpatient mental health services. Best understood as the general ‘vibe’ or ‘atmosphere’ on the unit, social climate has been subject to a significant research aimed at its quantification. One aspect of social climate, the violence prevention climate, describes the extent to which the ward is perceived as safe and protective against the occurrence of aggression by both the patients and the staff. The violence prevention climate scale (VPC‐14), developed in a UK forensic setting, was used in this study in a test of its validity in an Australian general mental health setting. The VPC‐14 was administered across eleven wards of one metropolitan Local Health District in Sydney, NSW. N = 213 valid responses from nursing staff and patients were returned (response rates 23.4 and 24.3%, respectively). The VPC‐14 demonstrated good internal reliability, and convergent validity was evidenced through moderate correlations with the WAS's anger and aggression subscale and the GMI total score. Concurrent validity was demonstrated by expected staff–patient differences in VPC‐14 rating and by correlations between incidents of conflict and containment on wards and the VPC‐14 ratings of staff and patients from those wards. Rasch analysis suggested that future tool development should focus on identifying ways to discriminate between ratings at the high end of the scale. The VPC‐14 supplies valid and useful information about the violence prevention climate in general adult mental health wards

The callipyge mutation and other genes that affect muscle hypertrophy in sheep

Genetic strategies to improve the profitability of sheep operations have generally focused on traits for reproduction. However, natural mutations exist in sheep that affect muscle growth and development, and the exploitation of these mutations in breeding strategies has the potential to significantly improve lamb-meat quality. The best-documented mutation for muscle development in sheep is callipyge (CLPG), which causes a postnatal muscle hypertrophy that is localized to the pelvic limbs and loin. Enhanced skeletal muscle growth is also observed in animals with the Carwell (or rib-eye muscling) mutation, and a double-muscling phenotype has been documented for animals of the Texel sheep breed. However, the actual mutations responsible for these muscular hypertrophy phenotypes in sheep have yet to be identified, and further characterization of the genetic basis for these phenotypes will provide insight into the biological control of muscle growth and body composition

A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development

Background: The developmental transition between the late fetus and a newborn animal is associated with profound changes in skeletal muscle function as it adapts to the new physiological demands of locomotion and postural support against gravity. The mechanisms underpinning this adaption process are unclear but are likely to be initiated by changes in hormone levels. We tested the hypothesis that this developmental transition is associated with large coordinated changes in the transcription of skeletal muscle genes.Results: Using an ovine model, transcriptional profiling was performed on Longissimus dorsi skeletal muscle taken at three fetal developmental time points (80, 100 and 120 d of fetal development) and two postnatal time points, one approximately 3 days postpartum and a second at 3 months of age. The developmental time course was dominated by large changes in expression of 2,471 genes during the interval between late fetal development (120 d fetal development) and 1-3 days postpartum. Analysis of the functions of genes that were uniquely up-regulated in this interval showed strong enrichment for oxidative metabolism and the tricarboxylic acid cycle indicating enhanced mitochondrial activity. Histological examination of tissues from these developmental time points directly confirmed a marked increase in mitochondrial activity between the late fetal and early postnatal samples. The promoters of genes that were up-regulated during this fetal to neonatal transition were enriched for estrogen receptor 1 and estrogen related receptor alpha cis-regulatory motifs. The genes down-regulated during this interval highlighted de-emphasis of an array of functions including Wnt signaling, cell adhesion and differentiation. There were also changes in gene expression prior to this late fetal - postnatal transition and between the two postnatal time points. The former genes were enriched for functions involving the extracellular matrix and immune response while the latter principally involved functions associated with transcriptional regulation of metabolic processes.Conclusions: It is concluded that during late skeletal muscle development there are substantial and coordinated changes in the transcription of a large number of genes many of which are probably triggered by increased estrogen levels. These changes probably underpin the adaption of muscle to new physiological demands in the postnatal environment

Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings.

An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.This work was supported by the Wellcome Trust. We would like to thank the members of the Pathogen Informatics Team and the core sequencing teams at the Wellcome Trust Sanger Institute (Cambridge, UK). We are grateful to D. Harris for work in managing the sequence data

Impacts of the Callipyge Mutation on Ovine Plasma Metabolites and Muscle Fibre Type

<div><p>The ovine Callipyge mutation causes postnatal muscle hypertrophy localized to the pelvic limbs and torso, as well as body leanness. The mechanism underpinning enhanced muscle mass is unclear, as is the systemic impact of the mutation. Using muscle fibre typing immunohistochemistry, we confirmed muscle specific effects and demonstrated that affected muscles had greater prevalence and hypertrophy of type 2X fast twitch glycolytic fibres and decreased representation of types 1, 2C, 2A and/or 2AX fibres. To investigate potential systemic effects of the mutation, proton NMR spectra of plasma taken from lambs at 8 and 12 weeks of age were measured. Multivariate statistical analysis of plasma metabolite profiles demonstrated effects of development and genotype but not gender. Plasma from Callipyge lambs at 12 weeks of age, but not 8 weeks, was characterized by a metabolic profile consistent with contributions from the affected hypertrophic fast twitch glycolytic muscle fibres. Microarray analysis of the perirenal adipose tissue depot did not reveal a transcriptional effect of the mutation in this tissue. We conclude that there is an indirect systemic effect of the Callipyge mutation in skeletal muscle in the form of changes of blood metabolites, which may contribute to secondary phenotypes such as body leanness.</p></div

Metabolic pathway analysis.

<p>The metabolic pathways are represented as circles according to their scores from enrichment (vertical axis) and topology analyses (pathway impact, horizontal axis) using MetaboAnalyst 2.0 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone.0099726-Xia1" target="_blank">[56]</a>. Darker circle colors indicate more significant changes of metabolites in the corresponding pathway. The size of the circle corresponds to the pathway impact score and is correlated with the centrality of the involved metabolites. The metabolic pathways involved in age differences are shown in panels A and B, and the pathways perturbed due to the Callipyge mutation are summarized in panels C and D. Panels A and C were generated using the <i>Homo sapiens</i> library, while the <i>Bos taurus</i> library was selected for production of panels B and D, respectively. Pathways were annotated by numbering when the <i>P</i> values calculated from the enrichment analysis were <0.05. The annotated pathways include: 1, Aminoacyl-tRNA biosynthesis; 2, Arginine and proline metabolism; 3, Biotin metabolism; 4, Cyanoamino acid metabolism; 5, D-Glutamine and D-glutamate metabolism; 6, Galactose metabolism; 7, Glycine, serine and threonine metabolism; 8, Lysine degradation; 9, Methane metabolism; 10, Nitrogen metabolism; 11, Synthesis and degradation of ketone bodies. The color of each metabolic pathway is related to the <i>P</i> value obtained from enrichment analysis and its size represents the fold enrichment score <i>i.e.</i> −ln(<i>P</i>).</p

Metabolic pathways involved in postnatal lamb development.

<p>Metabolites indentified in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone-0099726-t002" target="_blank">Table 2</a> are summarized according to their occurrence in metabolic pathways as annotated by KEGG metabolic pathways. ↓, metabolites decreasing with age (blue); ↑, metabolites increasing with age (red). TMAO, trimethylamine N-oxide; HCHO, formaldehyde; CH₄, methane. The reactions contained in the boxed section are likely to be derived from rumen microbial metabolism, except for reactions denoted by **, which occur in mammalian tissues <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone.0099726-Asatoor1" target="_blank">[63]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone.0099726-Yeung1" target="_blank">[84]</a>, and reactions denoted by *, which can occur both in mammalian tissues or the gut microbiome <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone.0099726-Zhang1" target="_blank">[85]</a>. This representation of the data recognises that plasma metabolites report the combined metabolic activities of all major tissues as well as the rumen microbiome.</p

Myofibre characteristics of muscle affected (<i>semimembranosus</i> and <i>semitendinosus</i>) and not affected (<i>supraspinatus</i>) by the Callipyge mutation, determined using myosin heavy chain (MHC) immunohistochemistry in normal (N^matN^pat) and Callipyge (N^matC^pat) lambs at 11 weeks of age.

a<p>Significant <i>P</i> values (<i>P</i><0.05) are labeled as *.</p>b<p>CSA, cross-sectional area.</p>c<p>Type 1, type 1 myosin heavy chain (MHC) slow twitch oxidative fibres; Type 2A, type 2A MHC fast oxidative-glycolytic fibres; Type 2X, type 2X MHC fast twitch glycolytic fibres; Type 2C, type 1–type 2A intermediate fibres; Type 2AX, type 2A–type 2X intermediate fibres.</p

Orthogonal partial least squares – discriminant analysis (OPLS–DA) of lamb plasma metabolic profiles.

<p>Panel A: Scores plot of the comparison of plasma samples at 8 weeks (red dots) and 12 weeks (black dots) of age. Samples are separated by their age in dimension t<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone.0099726-Jackson1" target="_blank">[1]</a>, while the first orthogonal dimension to<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone.0099726-Jackson1" target="_blank">[1]</a> contains orthogonal intra-group variation unrelated to age. Panel C: Scores plot of the comparison of plasma samples from N^matN^pat (triangles) and N^matC^pat (open triangles) lambs at 12 weeks of age. Samples are separated by genotype in dimension t<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone.0099726-Jackson1" target="_blank">[1]</a>, while the first orthogonal dimension to<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099726#pone.0099726-Jackson1" target="_blank">[1]</a> contains intra-group variation unrelated to genotype. Panels B and D: corresponding 1D back-scaled loadings plots (0.5–5.1 ppm) for panels A and C, respectively, with the identity of several metabolites annotated. Weights of variables are shown by the colour scale. 3HB, 3-hydroxybutyrate; NAC, N-acetyl glycoproteins; TMAO, trimethylamine N-oxide; U3/U4, unknown metabolites 3/4.</p