20 research outputs found

    The Renin Angiotensin System (RAS) mediates bifunctional growth regulation in melanoma and is a novel target for therapeutic intervention

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    Despite emergence of new systemic therapies, metastatic melanoma remains a challenging and often fatal form of skin cancer. The renin–angiotensin system (RAS) is a major physiological regulatory pathway controlling salt–water equilibrium, intravascular volume and blood pressure. Biological effects of the RAS are mediated by the vasoactive hormone angiotensin II (AngII) via two receptor subtypes, AT1R (encoded by AGTR1) and AT2R (encoded by AGTR2). We report decreasing expression and increasing CpG island methylation of AGTR1 in metastatic versus primary melanoma and detection in serum of methylated genomic DNA from the AGTR1 CpG island in metastatic melanoma implying that AGTR1 encodes a tumour suppressor function in melanoma. Consistent with this hypothesis, antagonism of AT1R using losartan or shRNA-mediated knockdown in melanoma cell lines expressing AGTR1 resulted in acquisition of the ability to proliferate in serum-free conditions. Conversely, ectopic expression of AGTR1 in cell lines lacking endogenous expression inhibits proliferation irrespective of the presence of AngII implying a ligand-independent suppressor function for AT1R. Treatment of melanoma cell lines expressing endogenous AT2R with either AngII or the AT2R-selective agonist Y6AII induces proliferation in serum-free conditions whereas the AT2R-specific antagonists PD123319 and EMA401 inhibit melanoma growth and angiogenesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations. Our results demonstrate that the RAS has both oncogenic and tumour suppressor functions in melanoma. Pharmacological inhibition of AT2R may provide therapeutic opportunities in melanomas expressing this receptor and AGTR1 CpG island methylation in serum may serve as a novel biomarker of metastatic melanoma

    Food Sources of Fiber and Micronutrients of Concern in Infants and Children in the United Arab Emirates: Findings from the Feeding Infants and Toddlers Study (FITS) and the Kids Nutrition and Health Survey (KNHS) 2020

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    We estimated the usual intakes of fiber, iron, zinc, calcium, folate, vitamin D, and vitamin A and the top foods that contribute to them among children in the UAE. Dietary intake was assessed using 24 h recalls among 5 age groups of infants and children. Foods were clustered into 54 food groups and ranked by their percentage contribution to the nutrients of interest in this study. The percentage achieving the adequate intake (AI) of fiber was negligible among all children. The top source of fiber was vegetables among children under 4 years, and white breads among those over 4 years. Only 45% of infants achieved iron adequacy, but iron standards were met by most children beyond the age of 1. The main contributors to iron intake were infant/young child formula and baby cereal in children under 4 years, while children over 4 years obtained it primarily from grains (fortified) and meat/fish. Vitamin D was inadequate across all age groups, with the percentage achieving adequacy ranging from 0 to 19% among pre-adolescents and toddlers, respectively. The top sources of vitamin D were fortified milks. Overall, nutrient inadequacies in fiber, calcium, and vitamin D highlight the need for greater intakes of whole grains and fortified dairy products in the UAE

    Total Usual Nutrient Intakes and Nutritional Status of United Arab Emirates Children (4 Years–12.9 Years): Findings from the Kids Nutrition and Health Survey (KNHS) 2021

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    This study aims at investigating the anthropometric status and food consumption patterns of children in the United Arab Emirates (UAE) and assessing their adherence to nutrient and dietary recommendations. It is a population-based cross-sectional survey of 690 children (4–12.9 years), from 3 major Emirates. Socio-demographic and anthropometric characteristics were collected. Dietary intakes were assessed using the 24-hour recall approach. Of the total sample, 4% were stunted, 8% were wasted and 28% were overweight/obese. A third of participating children consumed above the Estimated Energy Requirement, while the majority’s intakes carbohydrate, total fat, and protein were within the recommendations; whereas over 70% and 90% of participants consumed above the WHO daily limits of free sugars and saturated fats, respectively. Inadequate intakes of linoleic acid (36% of children), alpha-linolenic acid (91%) and dietary fiber (100%) were observed. All children failed to meet the recommendation for vitamin D and considerable proportions had inadequate intakes of vitamin A, calcium, zinc, folate, and magnesium. Compared with the American Heart Association/American Academy of Pediatrics recommendations, low dietary adherence was noted for fruits (9%), vegetables (4%), and milk/dairy (14%). These findings may be used in the development of nutritional policies aimed at improving the diets of children in the UAE

    Exploring the effects of a universal classroom management training programme on teacher and child behaviour: A group randomised controlled trial and cost analysis

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    Teachers frequently struggle to cope with conduct problems in the classroom. The aim of this study was to assess the effectiveness of the Incredible Years Teacher Classroom Management Training Programme for improving teacher competencies and child adjustment. The study involved a group randomised controlled trial which included 22 teachers and 217 children (102 boys and 115 girls). The average age of children included in the study was 5.3 years (standard deviation = 0.89). Teachers were randomly allocated to an intervention group (n = 11 teachers; 110 children) or a waiting-list control group (n = 11; 107 children). The sample also included 63 ‘high-risk’ children (33 intervention; 30 control), who scored above the cut-off (>12) on the Strengths and Difficulties Questionnaire for abnormal socioemotional and behavioural difficulties. Teacher and child behaviours were assessed at baseline and 6 months later using psychometric and observational measures. Programme delivery costs were also analysed. Results showed positive changes in teachers’ self-reported use of positive classroom management strategies (effect size = 0.56), as well as negative classroom management strategies (effect size = −0.43). Teacher reports also highlight improvements in the classroom behaviour of the high-risk group of children, while the estimated cost of delivering the Incredible Years Teacher Classroom Management Training Programme was modest. However, analyses of teacher and child observations were largely non-significant. A need for further research exploring the effectiveness and cost-effectiveness of the Incredible Years Teacher Classroom Management Training Programme is indicated

    Addressing equity in interventions to reduce air pollution in urban areas: a systematic review.

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    International audienceWe did a systematic review to assess quantitative studies investigating the association between interventions aiming to reduce air pollution, health benefits and equity effects. Three databases were searched for studies investigating the association between evaluated interventions aiming to reduce air pollution and heath-related benefits. We designed a two-stage selection process to judge how equity was assessed and we systematically determined if there was a heterogeneous effect of the intervention between subgroups or subareas. Of 145 identified articles, 54 were reviewed in-depth with eight satisfying the inclusion criteria. This systematic review showed that interventions aiming to reduce air pollution in urban areas have a positive impact on air quality and on mortality rates, but the documented effect on equity is less straightforward. Integration of equity in evidence-based public health is a great challenge nowadays. In this review we draw attention to the importance of considering equity in air pollution interventions. We also propose further methodological and theoretical challenges when assessing equity in interventions to reduce air pollution and we present opportunities to develop this research area
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