STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn\u27s Disease

Crohn\u27s disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in a cell-specific, cytokine-dependent manner, involving multiple immune responses. This study proposes the positive correlation between the prevalence of STAT3 rs744166 risky allele A with the severity of disease in a cohort of 94 CD patients. In addition, the results suggest an increased STAT3 activity in the inflamed ileum of CD patients, compared to unaffected ileum sections. Notably, IL-23 triggers the differentiation of CD117+NKp44- ILC3s and induces the activation of STAT3 in both CD117+NKp44- and CD117-NKp44- ILC subsets, implying the involvement of STAT3 in the initiation of ILC plasticity. Moreover, carriage of STAT3 A risk allele exhibited a higher basal level of STAT3 tyrosine phosphorylation, and an increased IL-23 triggered the pSTAT3 level. We also demonstrated that there was no delayed dephosphorylation of STAT3 in ILCs of both A/A and G/G donors. Overall, the results of this study suggest that IL-23-induced activation of STAT3 in the CD117-NKp44- ILC1s involves in ILC1-to-ILC3 plasticity and a potential regulatory role of ILC1 function. Those genetically susceptible individuals carried STAT3 rs744166 risky allele appear to have higher basal and cytokine-stimulated activation of STAT3 signal, leading to prolonged inflammation and chronic relapse

A systematic review of chronic disease management

Worldwide, chronic disease is on the rise, placing an increasing burden on those affected, their carers and the health system. In Australia many chronic diseases are predominantly managed in primary health care (PHC) and there is a need to understand how to do this more effectively. A systematic review was conducted on chronic disease management in primary health care using the Chronic Care Model (CCM) as the conceptual framework.The research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research, Evaluation and Development Strategy

Second-generation nitazoxanide derivatives: thiazolides are effective inhibitors of the influenza A virus

Aim: The only small molecule drugs currently available for treatment of influenza A virus (IAV) are M2 ion channel blockers and sialidase inhibitors. The prototype thiazolide, nitazoxanide, has successfully completed Phase III clinical trials against acute uncomplicated influenza. Results: We report the activity of seventeen thiazolide analogs against A/PuertoRico/8/1934(H1N1), a laboratory-adapted strain of the H1N1 subtype of IAV, in a cell culture-based assay. A total of eight analogs showed IC50s in the range of 0.14–5.0 μM. Additionally a quantitative structure–property relationship study showed high correlation between experimental and predicted activity based on a molecular descriptor set. Conclusion: A range of thiazolides show useful activity against an H1N1 strain of IAV. Further evaluation of these molecules as potential new small molecule therapies is justified

Multiple mycotoxins in rice : occurrence and health risk assessment in children and adults of Punjab, Pakistan

Mycotoxin contamination in rice can create a health risk for the consumers. In this study, the measurement of 23 mycotoxins in rice samples (n = 180) was performed using a validated LC-MS/MS method. A food frequency questionnaire was used to get rice consumption data for the assessment of mycotoxin dietary exposure, before calculating the health risk in adults and children of north and south regions of the Pakistani Punjab province. The prevalence of aflatoxin B-1 (56%), aflatoxin B-2 (48%), nivalenol (28%), diacetoxyscirpenol (23%), fumonisin B-1 (42%), zearalenone (15%), HT-2 toxin (10%), deoxynivalenol (8%), and ochratoxin A (6%) was estimated in samples with a mean concentration range between 0.61 and 22.98 mu g/kg. Aflatoxin degradation by traditional Pakistani cooking recipes was evaluated and observed to be 41-63%. The dietary exposure to aflatoxins exceeded the tolerable daily intake at all levels, and ochratoxin A and zearalenone posed health risk at high contamination and high consumption levels. The margin of aflatoxin B-1 exposure ranged between 10 and 69 in adults and 10 and 62 in children. The mean cancer risk by aflatoxin B-1 exposure was 0.070 (adults) and 0.071 (children) cases/year/100,000 people in South Punjab population, and 0.122 (adults) and 0.127 (children) cases/year/100,000 people in North Punjab population. This study will provide new insights for the planning and management of mycotoxins in Pakistan

Analysis of resolvins in fish cultured cells challenged with docosahexaenoic acid by liquid chromatography triple quadrupole mass spectrometry.

Master's Thesis in Quality in the Analytical LaboratoryQAL399BJMAMN-QAL

Translating knowledge for action against stroke – using 5-minute videos for stroke survivors and caregivers to improve post-stroke outcomes: study protocol for a randomized controlled trial (Movies4Stroke)

Participant timeline. (DOCX 48 kb

Optimising skill-mix in the primary health care workforce for the care of older Australians: a systematic review

Australia has an ageing population resulting in demand for extensive and comprehensive care of chronic disease. This demand has required new thinking about primary health care workforce re-modelling to meet the health care needs of community dwelling older Australians. Sibbald and others have developed a model of skill-mix change to discuss workforce redesign. We conducted a systematic literature review to identify skill-mix changes needed in the primary health care workforce to successfully meet the health care needs of older Australians. Sibbald's concept that skill-mix changes could be obtained through task substitution, enhancement, delegation and innovation formed the conceptual framework for the review.The research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research, Evaluation and Development Strategy

The contact zone and dialogical positionalities in ‘non-normative’ childhoods: How children who language broker manage conflict

This paper examines the processes by which different dialogical positionalities are taken in the contact zone (Hermans, 2001a, 2003; Pratt, 1991). The contact zone provides a framework for the consideration of potential confrontations and uncertainties during intercultural contacts between migrant children, their family and another adult. The other adult is usually someone in a position of authority. For young people who language broker, managing the uncertainties and confrontations of conflictual situations highlighted three positionalities: (i) ‘conflict avoider’, (ii), ‘the neutral or passive broker’, (iii) the ‘active broker’. The contact zone was a sphere of experience that opened up possibilities for agentic action as well as constraints. The contact zone had the potential to foreground different aspects of their status such as ‘the child,’ ‘the immigrant’ or the second-language speaker. Equally, the young people took opportunities to utilise these statuses as part of their dialogical positionalities to get the best outcome for them and/or their families. We argue that further exploration of the contact zone within the framing of dialogical positionalities can enable better understanding of critical-cultural-development childhoods

Examining conviviality and cultural mediation in arts-based workshops with child language brokers: Narrations of identity and (un)belonging

The concept of conviviality has usually been applied to contexts such as urban neighbourhoods of diversity (Gidley 2013; Lapiņa 2016; Valluvan 2016), and refers to what Gidley (2013) would term the ‘convivial turn’, or the notion of living together or coexisting in our daily social interactions (Wise and Velayutham 2013). The application of conviviality explored in this chapter concerns everyday encounters (Fincher et al. 2014), or what Amin (2002, 959) calls ‘the micropublics of everyday social contact’. ‘Micropublics’ are sites of (sometimes compulsory) conviviality, such as workplaces, schools (Neal et al. 2016), youth centres and community groups (Neal et al. 2015). In this vein, our lens of focus in this paper is on what Neal et al. (2016, 465) would describe as ‘extended encounters’, namely a series of arts-based workshops with students in a culturally and linguistically diverse school in London. The substantive focus of the research study on which this paper is based explored feelings of identity, belonging and cultural mediation among child language brokers. Child language brokers are children and young people who linguistically and culturally mediate between family members and officialdom (Antonini 2010). The arts-based workshops with our child language brokers, and their subsequent outputs, are the centre point for what Illich (1973) might term ‘tools for conviviality’. Our analytic endeavours explore the ‘autonomous and creative intercourse among persons’ (Illich 1973, 11), namely the young people taking part in the workshops, wherein there were possibilities to share, connect and interact. In exploring one of the arts-based workshops for this paper we ask, what role did the artist delivering the workshop have on the output, and how did that unfolding process reflect our research objectives

Knowledge, attitudes and practices regarding dengue fever among adults of high and low socioeconomic groups

OBJECTIVE: To ascertain the knowledge, attitudes and practices of selected adult population in Pakistan regarding Dengue Fever.METHODS: A cross sectional survey was conducted among selected communities with different socio-economic backgrounds in Karachi, Pakistan. A sample size of 440 adults (aged 18 years and above) were interviewed using a pre-tested questionnaire regarding their knowledge, attitude and practices about dengue fever. A composite scoring system, based on the answers given in the questionnaire, was used to establish the level of awareness in the population. The division of the higher and lower socio-economic groups was based on their income and locality; both these variables were determined as a part of our survey.RESULTS: Data from 400 respondents (244 males, 156 females) was used for primary analysis. About thirty five percent of the sample had adequate knowledge about dengue fever and its vector. Knowledge had significant associations with education (p = 0.004) and socioeconomic status (p = 0.02). The high socioeconomic group showed better preventive practices.CONCLUSION: Knowledge of dengue is inadequate in the low socioeconomic class. Better preventive practices against the vector are prevalent in the high socioeconomic group. Hence, a greater focus should be accorded to the low socioeconomic areas in future health campaigns