Carbon and nitrogen substrate utilization by archival Salmonella typhimurium LT2 cells

BACKGROUND: A collection of over 20,000 Salmonella typhimurium LT2 mutants, sealed for four decades in agar stabs, is a unique resource for study of genetic and evolutionary changes. Previously, we reported extensive diversity among descendants including diversity in RpoS and catalase synthesis, diversity in genome size, protein content, and reversion from auxotrophy to prototrophy. RESULTS: Extensive and variable losses and a few gains of catabolic functions were observed by this standardized method. Thus, 95 catabolic reactions were scored in each of three plates in wells containing specific carbon and nitrogen substrates. CONCLUSION: While the phenotype microarray did not reveal a distinct pattern of mutation among the archival isolates, the data did confirm that various isolates have used multiple strategies to survive in the archival environment. Data from the MacConkey plates verified the changes in carbohydrate metabolism observed in the Biolog™ system

"They just come, pick and go." The Acceptability of Integrated Medication Adherence Clubs for HIV and Non Communicable Disease (NCD) Patients in Kibera, Kenya

Introduction The number of people on antiretroviral therapy (ART) for the long-term management of HIV in low- and middle-income countries (LMICs) is continuing to increase, along with the prevalence of Non-Communicable Diseases (NCDs). The need to provide large volumes of HIV patients with ART has led to significant adaptations in how medication is delivered, but access to NCD care remains limited in many contexts. Medication Adherence Clubs (MACs) were established in Kibera, Kenya to address the large numbers of patients requiring chronic HIV and/or NCD care. Stable NCD and HIV patients can now collect their chronic medication every three months through a club, rather than through individual clinic appointments. METHODOLOGY: We conducted a qualitative research study to assess patient and health-care worker perceptions and experiences of MACs in the urban informal settlement of Kibera, Kenya. A total of 106 patients (with HIV and/or other NCDs) and health-care workers were purposively sampled and included in the study. Ten focus groups and 19 in-depth interviews were conducted and 15 sessions of participant observation were carried out at the clinic where the MACs took place. Thematic data analysis was conducted using NVivo software, and coding focussed on people's experiences of MACs, the challenges they faced and their perceptions about models of care for chronic conditions. RESULTS: MACs were considered acceptable to patients and health-care workers because they saved time, prevented unnecessary queues in the clinic and provided people with health education and group support whilst they collected their medication. Some patients and health-care workers felt that MACs reduced stigma for HIV positive patients by treating HIV as any other chronic condition. Staff and patients reported challenges recruiting patients into MACs, including patients not fully understanding the eligibility criteria for the clubs. There were also some practical challenges during the implementation of the clubs, but MACs have shown that it is possible to learn from ART provision and enable stable HIV and NCD patients to collect chronic medication together in a group. CONCLUSIONS: Extending models of care previously only offered to HIV-positive cohorts to NCD patients can help to de-stigmatise HIV, allow for the efficient clinical management of co-morbidities and enable patients to benefit from peer support. Through MACs, we have demonstrated that an integrated approach to providing medication for chronic diseases including HIV can be implemented in resource-poor settings and could thus be rolled out in other similar contexts

The prevalence and impact of adolescent hospitalization to adult psychiatric units.

BACKGROUND: With increasing psychiatric hospitalizations among adolescents and constrained hospital resources, there are times when youth are hospitalized in adult inpatient psychiatry units. Evidence on the prevalence of this practice and associated impacts is lacking. AIMS: We sought to explore the prevalence, determinants, and outcomes related to the hospitalization of adolescents aged 12-17 years on adult inpatient psychiatry units in Ontario. METHODS: Using health administrative data, we constructed a cohort of adolescents with an inpatient psychiatric admission in Ontario (2007-2011). We classified adolescents as having an admission to an adult psychiatry unit or to other inpatient units. Multivariable regression models were used to estimate prevalence ratios (PR) for factors associated with adult admission, as well as risk ratios (RR) for the impact of adult admission on length of stay, discharge against medical advice, and 30-day readmission. RESULTS: Over the study period, 22.6% of adolescents with a psychiatric hospitalization (n = 16 998) had an admission to an adult psychiatry unit. Older age (16 vs. 15 years: PR = 2.27, 95% CI = 2.07-2.48; 17 vs. 15 years: PR = 2.91, 95% CI = 2.66-3.18), rural residence (PR = 1.46, 95% CI = 1.38-1.55), psychotic (PR = 1.25, 95% CI = 1.15-1.36) or personality disorder (PR = 1.59, 95% CI = 1.41-1.80) diagnoses, and involuntary status (PR = 2.18, 95% CI = 2.05-2.31) were independently associated with adult admission. Adolescents admitted to adult units were more likely to be discharged against medical advice (RR = 1.77, 95% CI = 1.45-2.17). CONCLUSIONS: Nearly one in four adolescent psychiatric admissions occurs on an adult psychiatric unit. These findings help to fill gaps in the prior literature, and highlight the need for further research to inform policy decisions and resource allocation for adolescent inpatient psychiatric care

The migratory pathways of the cells that form the endocardium, dorsal aortae, and head vasculature in the mouse embryo

BACKGROUND: Vasculogenesis in amniotes is often viewed as two spatially and temporally distinct processes, occurring in the yolk sac and in the embryo. However, the spatial origins of the cells that form the primary intra-embryonic vasculature remain uncertain. In particular, do they obtain their haemato-endothelial cell fate in situ, or do they migrate from elsewhere? Recently developed imaging techniques, together with new Tal1 and existing Flk1 reporter mouse lines, have allowed us to investigate this question directly, by visualising cell trajectories live and in three dimensions. RESULTS: We describe the pathways that cells follow to form the primary embryonic circulatory system in the mouse embryo. In particular, we show that Tal1-positive cells migrate from within the yolk sac, at its distal border, to contribute to the endocardium, dorsal aortae and head vasculature. Other Tal1 positive cells, similarly activated within the yolk sac, contribute to the yolk sac vasculature. Using single-cell transcriptomics and our imaging, we identify VEGF and Apela as potential chemo-attractants that may regulate the migration into the embryo. The dorsal aortae and head vasculature are known sites of secondary haematopoiesis; given the common origins that we observe, we investigate whether this is also the case for the endocardium. We discover cells budding from the wall of the endocardium with high Tal1 expression and diminished Flk1 expression, indicative of an endothelial to haematopoietic transition. CONCLUSIONS: In contrast to the view that the yolk sac and embryonic circulatory systems form by two separate processes, our results indicate that Tal1-positive cells from the yolk sac contribute to both vascular systems. It may be that initial Tal1 activation in these cells is through a common mechanism

CRISPR-delivery particles targeting nuclear receptor-interacting protein 1 (Nrip1) in adipose cells to enhance energy expenditure

RNA-guided, engineered nucleases derived from the prokaryotic adaptive immune system CRISPR-Cas represent a powerful platform for gene deletion and editing. When used as a therapeutic approach, direct delivery of Cas9 protein and single-guide RNA (sgRNA) could circumvent the safety issues associated with plasmid delivery and therefore represents an attractive tool for precision genome engineering. Gene deletion or editing in adipose tissue to enhance its energy expenditure, fatty acid oxidation, and secretion of bioactive factors through a browning process presents a potential therapeutic strategy to alleviate metabolic disease. Here, we developed CRISPR-delivery particles, denoted CriPs, composed of nano-size complexes of Cas9 protein and sgRNA that are coated with an amphipathic peptide called Endo-Porter that mediates entry into cells. Efficient CRISPR-Cas9-mediated gene deletion of ectopically expressed GFP by CriPs was achieved in multiple cell types, including a macrophage cell line, primary macrophages, and primary pre-adipocytes. Significant GFP loss was also observed in peritoneal exudate cells with minimum systemic toxicity in GFP-expressing mice following intraperitoneal injection of CriPs containing Gfp-targeting sgRNA. Furthermore, disruption of a nuclear co-repressor of catabolism, the Nrip1 gene, in white adipocytes by CriPs enhanced adipocyte browning with a marked increase of uncoupling protein 1 (UCP1) expression. Of note, the CriP-mediated Nrip1 deletion did not produce detectable off-target effects. We conclude that CriPs offer an effective Cas9 and sgRNA delivery system for ablating targeted gene products in cultured cells and in vivo, providing a potential therapeutic strategy for metabolic disease

No measure for culture? Value in the new economy

This paper explores articulations of the value of investment in culture and the arts through a critical discourse analysis of policy documents, reports and academic commentary since 1997. It argues that in this period, discourses around the value of culture have moved from a focus on the direct economic contributions of the culture industries to their indirect economic benefits. These indirect benefits are discussed here under three main headings: creativity and innovation, employability, and social inclusion. These are in turn analysed in terms of three forms of capital: human, social and cultural. The paper concludes with an analysis of this discursive shift through the lens of autonomist Marxist concerns with the labour of social reproduction. It is our argument that, in contemporary policy discourses on culture and the arts, the government in the UK is increasingly concerned with the use of culture to form the social in the image of capital. As such, we must turn our attention beyond the walls of the factory in order to understand the contemporary capitalist production of value and resistance to it. </jats:p

Correlates of child mental health and substance use related emergency department visits in Ontario: A linked population survey and administrative health data study

Introduction Knowledge of the sociodemographic, behavioural, and clinical characteristics of children visiting emergency departments (EDs) for mental health or substance use concerns in Ontario, Canada is lacking. Objectives Using data from a population-based survey linked at the individual level to administrative health data, this study leverages a provincially representative sample and quasi-experimental design to strengthen inferences regarding the extent to which children's sociodemographic, behavioural, and clinical characteristics are associated with the risk of a mental health or substance use related ED visit. Methods 9,301 children aged 4-17 years participating in the 2014 Ontario Child Health Study were linked retrospectively (6 months) and prospectively (12 months) with administrative health data on ED visits from the National Ambulatory Care Reporting System. Modified Poisson regression was used to examine correlates of mental health and substance use related ED visits among children aged 4-17 years over a 12-month period following their survey completion date, adjusting for ED visits in the 6 months prior to their survey completion date. Subgroup analyses of youths aged 14-17 years who independently completed survey content related to peer victimisation, substance use, and suicidality were also conducted. Results Among children aged 4-17 years, older age, parental immigrant status, internalising problems, and perceived need for professional help were statistically significant correlates that increased the risk of a mental health or substance use related ED visit; low-income and suicidal ideation with attempt were statistically significant only among youths aged 14-17 years. Conclusions Knowledge of the sociodemographic, behavioural, and clinical characteristics of children visiting EDs for mental health and substance use related concerns is required to better understand patient needs to coordinate effective emergency mental health care that optimises child outcomes, and to inform the development and targeting of upstream interventions that have the potential to prevent avoidable ED visits. Highlights • Growing rates of child mental health and substance use related ED visits have been observed internationally. • A population-based survey linked at the individual level to administrative health data was used to examine the extent to which children’s sociodemographic, behavioural, and clinical characteristics are associated with the risk of a mental health or substance use related ED visit in Ontario, Canada. • Older age, low-income, parental immigrant status, perceived need for professional help, internalising problems, and suicidality increase the risk of an ED visit. • Knowledge of the characteristics of children visiting EDs can be used to coordinate effective emergency mental health care that optimises child outcomes, and to inform the development and targeting of upstream interventions that have the potential to prevent avoidable ED visits

Falling into LINE: school strategies for overcoming challenges associated with learning in natural environments (LINE)

peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=rett2