The role of the school nurse in protecting children and young people from maltreatment: An integrative review of the literature

Objectives. This review aims to describe the role of the school nurse in protecting children and young people from maltreatment by examining the international literature. Child maltreatment is a prevalent issue in global society today and includes physical, emotional and sexual abuse, neglect and exploitation. School nurses are ideally placed to identify and work with children and young people who are at risk of maltreatment through their regular contact with the school community. Design. Integrative literature review incorporating thematic analysis. Data Sources. Electronic databases British Nursing Database, Cumulative Index of Nursing and Allied Health Literature, Medline, PsycInfo, Cochrane Library Database for Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL). Search Terms: Role, School Nurse, Child Maltreatment. Review Methods. Initial title and abstract review of 444 studies resulted in 78 studies for full text review. Additional search strategies identified one relevant study. Inclusion and exclusion criteria were employed as follows; (1) study published in the English language, (2) peer-reviewed, (3) primary research, (4) inclusion of school nurses (or equivalent role internationally) in the study sample, and (5) a focus on the role of school nurses in preventing child maltreatment. Studies were appraised using the Critical Appraisal Skills Programme tool for qualitative studies and the Strengthening the Reporting of Observational Studies in Epidemiology checklist for mixed-methods and quantitative studies. Findings from the studies were identified, summarised and organised into a summary table, before being analysed thematically. Results. 21 studies met inclusion and quality criteria and were included in the review. Key themes that emerged from the analysis were; supporting the child and family, detective work, working with other professionals, training and supervision, barriers to protecting children and young people from maltreatment and trust. Conclusion. International literature highlights the variety of activities that school nurses may undertake in daily practice to protect children and young people from maltreatment. Several challenges to this role are identified, including time management and building relationships with children and young people. Recommendations for practice and further research are made

Using a multi-omic approach to investigate the mechanism of 12-bis-THA activity against Burkholderia thailandensis

Burkholderia pseudomallei is the causative agent of the tropical disease, melioidosis. It is intrinsically resistant to many antimicrobials and treatment requires an onerous regimen of intravenous and orally administered drugs. Relapse of disease and high rates of mortality following treatment are common, demonstrating the need for new anti-Burkholderia agents. The cationic bola-amphiphile, 12,12′-(dodecane-1,12-diyl) bis (9-amino-1,2,3,4-tetrahydroacridinium), referred to as 12-bis-THA, is a molecule with the potential to treat Burkholderia infections. 12-bis-THA spontaneously forms cationic nanoparticles that bind anionic phospholipids in the prokaryotic membrane and are readily internalized. In this study, we examine the antimicrobial activity of 12-bis-THA against strains of Burkholderia thailandensis. As B. pseudomallei produces a polysaccharide capsule we first examined if this extra barrier influenced the activity of 12-bis-THA which is known to act on the bacterial envelope. Therefore two strains of B. thailandensis were selected for further testing, strain E264 which does not produce a capsule and strain E555 which does produce a capsule that is chemically similar to that found in B. pseudomallei. In this study no difference in the minimum inhibitory concentration (MIC) was observed when capsulated (E555) and unencapsulated (E264) strains of B. thailandensis were compared, however time-kill analysis showed that the unencapsulated strain was more susceptible to 12-bis-THA. The presence of the capsule did not affect the membrane permeation of 12-bis-THA at MIC concentrations. Proteomic and metabolomic analyses showed that 12-bis-THA causes a shift in central metabolism away from glycolysis and glyoxylate cycle, and suppressed the production of the F1 domain of ATP synthase. In summary, we provide insight into the molecular mechanisms underpinning the activity of 12-bis-THA against B. thailandensis and discuss its potential for further development

Drug screening to identify compounds to act as co-therapies for the treatment of Burkholderia species

Burkholderia pseudomallei is a soil-dwelling organism present throughout the tropics. It is the causative agent of melioidosis, a disease that is believed to kill 89,000 people per year. It is naturally resistant to many antibiotics, requiring at least two weeks of intravenous treatment with ceftazidime, imipenem or meropenem followed by 6 months of orally delivered co-trimoxazole. This places a large treatment burden on the predominantly middle-income nations where the majority of disease occurs. We have established a high-throughput assay for compounds that could be used as a co-therapy to potentiate the effect of ceftazidime, using the related non-pathogenic bacterium Burkholderia thailandensis as a surrogate. Optimization of the assay gave a Z' factor of 0.68. We screened a library of 61,250 compounds and identified 29 compounds with a pIC50 (-log10(IC50)) greater than five. Detailed investigation allowed us to down select to six "best in class" compounds, which included the licensed drug chloroxine. Co-treatment of B. thailandensis with ceftazidime and chloroxine reduced culturable cell numbers by two orders of magnitude over 48 hours, compared to treatment with ceftazidime alone. Hit expansion around chloroxine was performed using commercially available compounds. Minor modifications to the structure abolished activity, suggesting that chloroxine likely acts against a specific target. Finally, an initial study demonstrates the utility of chloroxine to act as a co-therapy to potentiate the effect of ceftazidime against B. pseudomallei. This approach successfully identified potential co-therapies for a recalcitrant Gram-negative bacterial species. Our assay could be used more widely to aid in chemotherapy to treat infections caused by these bacteria

Differences in the gut microbiota between Gurkhas and soldiers of British origin

Previous work indicated that the incidence of travellers’ diarrhoea (TD) is higher in soldiers of British origin, when compared to soldiers of Nepalese descent (Gurkhas). We hypothesise that the composition of the gut microbiota may be a contributing factor in the risk of developing TD in soldiers of British origin. This study aimed to characterise the gut microbial composition of Gurkha and non-Gurkha soldiers of the British Army. Recruitment of 38 soldiers (n = 22 Gurkhas, n = 16 non-Gurkhas) and subsequent stool collection, enabled shotgun metagenomic sequencing-based analysis of the gut microbiota. The microbiota of Gurkhas had significantly (P < 0.05) lower diversity, for both Shannon and Simpson diversity indices, using species level markers than the gut microbiota of non-Gurkha soldiers. Non-metric Multidimensional Scaling (NMDS) of the Bray-Curtis distance matrix revealed a significant difference in the composition of the gut microbiota between Gurkhas and non-Gurkha soldiers, at both the species level (P = 0.0178) and the genus level (P = 0.0483). We found three genera and eight species that were significantly enriched in the non-Gurkha group and one genus (Haemophilus) and one species (Haemophilus parainfluenzae) which were enriched in the Gurkha group. The difference in the microbiota composition between Gurkha soldiers and soldiers of British origin may contribute to higher colonization resistance against diarrhoeal pathogens in the former group. Our findings may enable further studies into interventions that modulate the gut microbiota of soldiers to prevent TD during deployment

Individual bacteria in structured environments rely on phenotypic resistance to phage

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: All relevant data are within the paper and its Supporting Information files.Bacteriophages represent an avenue to overcome the current antibiotic resistance crisis, but evolution of genetic resistance to phages remains a concern. In vitro, bacteria evolve genetic resistance, preventing phage adsorption or degrading phage DNA. In natural environments, evolved resistance is lower possibly because the spatial heterogeneity within biofilms, microcolonies, or wall populations favours phenotypic survival to lytic phages. However, it is also possible that the persistence of genetically sensitive bacteria is due to less efficient phage amplification in natural environments, the existence of refuges where bacteria can hide, and a reduced spread of resistant genotypes. Here, we monitor the interactions between individual planktonic bacteria in isolation in ephemeral refuges and bacteriophage by tracking the survival of individual cells. We find that in these transient spatial refuges, phenotypic resistance due to reduced expression of the phage receptor is a key determinant of bacterial survival. This survival strategy is in contrast with the emergence of genetic resistance in the absence of ephemeral refuges in well-mixed environments. Predictions generated via a mathematical modelling framework to track bacterial response to phages reveal that the presence of spatial refuges leads to fundamentally different population dynamics that should be considered in order to predict and manipulate the evolutionary and ecological dynamics of bacteria-phage interactions in naturally structured environments.Medical Research Council (MRC)Engineering and Physical Sciences Research Council (EPSRC)Gordon and Betty and Gordon Moore FoundationEuropean Research Council (ERC)Biotechnology and Biological Sciences Research Council (BBSRC)Natural Environment Research Council (NERC)Marie Skłodowska-Curie ActionsDefence Science and Technology Laboratory (Dstl)Royal Societ

Using a multi-omic approach to investigate the mechanism of 12-bis-THA activity against Burkholderia thailandensis

Burkholderia pseudomallei is the causative agent of the tropical disease, melioidosis. It is intrinsically resistant to many antimicrobials and treatment requires an onerous regimen of intravenous and orally administered drugs. Relapse of disease and high rates of mortality following treatment are common, demonstrating the need for new anti-Burkholderia agents. The cationic bola-amphiphile, 12,12′-(dodecane-1,12-diyl) bis (9-amino-1,2,3,4-tetrahydroacridinium), referred to as 12-bis-THA, is a molecule with the potential to treat Burkholderia infections. 12-bis-THA spontaneously forms cationic nanoparticles that bind anionic phospholipids in the prokaryotic membrane and are readily internalized. In this study, we examine the antimicrobial activity of 12-bis-THA against strains of Burkholderia thailandensis. As B. pseudomallei produces a polysaccharide capsule we first examined if this extra barrier influenced the activity of 12-bis-THA which is known to act on the bacterial envelope. Therefore two strains of B. thailandensis were selected for further testing, strain E264 which does not produce a capsule and strain E555 which does produce a capsule that is chemically similar to that found in B. pseudomallei. In this study no difference in the minimum inhibitory concentration (MIC) was observed when capsulated (E555) and unencapsulated (E264) strains of B. thailandensis were compared, however time-kill analysis showed that the unencapsulated strain was more susceptible to 12-bis-THA. The presence of the capsule did not affect the membrane permeation of 12-bis-THA at MIC concentrations. Proteomic and metabolomic analyses showed that 12-bis-THA causes a shift in central metabolism away from glycolysis and glyoxylate cycle, and suppressed the production of the F1 domain of ATP synthase. In summary, we provide insight into the molecular mechanisms underpinning the activity of 12-bis-THA against B. thailandensis and discuss its potential for further development

Arts-based interventions for people living with dementia: Measuring ‘in the moment’ wellbeing with the Canterbury Wellbeing Scales

Background: There is growing acknowledgement for the need to move beyond exclusive biomedical understandings of dementia and also focus on how to improve the lives and wellbeing of people living with dementia. A mounting body of research advocates for the benefits of arts-based interventions for this population. The purpose of this study was to explore the links between multiple components of arts-based interventions and subjective wellbeing in order to help assess if these activities might contribute to meaningful community-based dementia care initiatives. Methods: Using previously collected data across different intervention sites, a within- and between- participants design was used that assessed wellbeing through the Canterbury Wellbeing Scales (CWS) in people with mild-to-moderate dementias (N = 201) who participated in various community arts-based interventions (ABI). Data were analysed using non-parametric statistical analyses and bootstrapped moderation models. Results: Increases in subjective wellbeing were associated with all forms of ABI. Co-creative sessions significantly strengthened the relationship between number of sessions attended and overall wellbeing as well as optimism. No significant moderating effect was observed between number of sessions attended and carer presence. Conclusions: In the largest study of its kind to date to assess wellbeing using arts activities in a community-based dementia sample, findings support the use and acceptability of the CWS as a measurement tool for people with early-to-middle stages of dementia and suggest that the CWS can reliably measure wellbeing in this population. In addition, the positive effect of arts-based interactions on specific aspects of wellbeing were found, which provide a better understanding of the conditions under which these effects can be prolonged and sustained. Further research is needed to better understand the environmental, social, and psychological mechanisms through which these improvements operate [version 2; peer review: 1 approved

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

The Fluoroquinolone Finafloxacin Protects BALB/c Mice Against an Intranasal Infection With Francisella tularensis Strain SchuS4

The efficacy of the novel fluoroquinolone finafloxacin was evaluated as a potential therapeutic in vitro and in vivo, following an intranasal infection of Francisella tularensis strain SchuS4 in BALB/c mice. We demonstrated that short treatment courses of finafloxacin provide high levels of protection, with a single dose resulting in a significant increase in time to death when compared to ciprofloxacin. In addition, following investigation into the window of opportunity for treatment, we have shown that finafloxacin can provided protection when administered up to 96 h post-challenge. This is particularly encouraging since mice displayed severe signs of disease at this time point. In summary, finafloxacin may be a promising therapy for use in the event of exposure to F. tularensis, perhaps enabling the treatment regimen to be shortened or if therapy is delayed. The efficacy of finafloxacin against other biological threat agents also warrants investigation

Validation of the Consensus-Definition for Cancer Cachexia and evaluation of a classification model—a study based on data from an international multicentre project (EPCRC-CSA)

A cancer cachexia classification into stages is warranted in order to guide treatment decisions and clinical trial inclusion. Weight loss and BMI clearly discriminate between non-cachectic and cachectic patients both with regards to all the domains (Intake, Catabolism and Function) and survival. The precachexia stage might be better defined by additional factors in order to be discriminativ