A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Environmental determinants of islet autoimmunity (ENDIA): a pregnancy to early life cohort study in children at-risk of type 1 diabetes

Members of ENDIA Study Group: Peter Baghurst, Simon Barry, Jodie Dodd, Maria Makrides for the University of Adelaide.BACKGROUND The incidence of type 1 diabetes has increased worldwide, particularly in younger children and those with lower genetic susceptibility. These observations suggest factors in the modern environment promote pancreatic islet autoimmunity and destruction of insulin-producing beta cells. The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is investigating candidate environmental exposures and gene-environment interactions that may contribute to the development of islet autoimmunity and type 1 diabetes. METHODS/DESIGN ENDIA is the only prospective pregnancy/birth cohort study in the Southern Hemisphere investigating the determinants of type 1 diabetes in at-risk children. The study will recruit 1,400 unborn infants or infants less than six months of age with a first-degree relative (i.e. mother, father or sibling) with type 1 diabetes, across five Australian states. Pregnant mothers/infants will be followed prospectively from early pregnancy through childhood to investigate relationships between genotype, the development of islet autoimmunity (and subsequently type 1 diabetes), and prenatal and postnatal environmental factors. ENDIA will evaluate the microbiome, nutrition, bodyweight/composition, metabolome-lipidome, insulin resistance, innate and adaptive immune function and viral infections. A systems biology approach will be used to integrate these data. Investigation will be by 3-monthly assessments of the mother during pregnancy, then 3-monthly assessments of the child until 24 months of age and 6-monthly thereafter. The primary outcome measure is persistent islet autoimmunity, defined as the presence of autoantibodies to one or more islet autoantigens on consecutive tests. DISCUSSION Defining gene-environment interactions that initiate and/or promote destruction of the insulin-producing beta cells in early life will inform approaches to primary prevention of type 1 diabetes. The strength of ENDIA is the prospective, comprehensive and frequent systems-wide profiling from early pregnancy through to early childhood, to capture dynamic environmental exposures that may shape the development of islet autoimmunity. TRIAL REGISTRATION Australia New Zealand Clinical Trials Registry ACTRN12613000794707.Megan AS Penno, Jennifer J Couper, Maria E Craig, Peter G Colman, William D Rawlinson, Andrew M Cotterill, Timothy W Jones, Leonard C Harrison and ENDIA Study Grou

Enhancing motivation and psychological wellbeing in the workplace through conscious physical activity: Suggestions from a qualitative study examining workers' experience

Introduction: After COVID-19 restrictions, hybrid solutions were established that combined smart working and work in presence. Workplace conditions significantly impact employees' lives, particularly in terms of meeting their needs and promoting their wellbeing. Based on a socio-ecological and multilevel methodology, the UP150 concept (Proactive Office 150) represents a possible innovative solution to meet employees' needs and valorize flexible work. It encourages physical exercise and active breaks during the typical workday by using particular architectural modifications, a dedicated App, and physical activity professionals as wellness coaches. The present study is the last step of the preliminary actions planned to check the benefits of the UP150 concept and aims to explore the workers' perceptions after experiencing this project. Methods: The qualitative analysis of a preliminary survey (concerning information about the company structure and workers' habits) performed before conducting a randomized controlled trial intervention study and the analysis of the semi-structured interviews after 8 weeks of a UP150 experience served as datasets for this study and have been examined and discussed. Results: In the preliminary survey, the young (under 40) and generally active (57% of the workers) reported being motivated to exercise but inhibited by a lack of time and a heavy workload. After 8 weeks at a modified workplace designed in accordance with the motive behind the UP150, the workers displayed noticeable positive perceptions and appreciation. Discussion: The qualitative analysis confirmed and supported the effectiveness of the UP150 concept that previous research had already found in quantitative parameters related to employees' motor efficiency, psychophysical status, and amount of physical activity. Participants reported beneficial perceived effects on their wellness and psychophysical status following a UP150 experience. Moreover, the concept improved social relationships and increased motivation. In conclusion, the UP150 concept efficiently fostered a positive perception of physical exercise and directed the employees toward the assumption of healthy behaviors fitting the physical literacy paradigm

Circadian transcriptome analysis in human fibroblasts from Hunter syndrome and impact of iduronate-2-sulfatase treatment

Background: Hunter syndrome (HS) is a lysosomal storage disease caused by iduronate-2-sulfatase (IDS) deficiency and loss of ability to break down and recycle the glycosaminoglycans, heparan and dermatan sulfate, leading to impairment of cellular processes and cell death. Cell activities and functioning of intracellular organelles are controlled by the clock genes (CGs), driving the rhythmic expression of clock controlled genes (CCGs). We aimed to evaluate the expression of CGs and downstream CCGs in HS, before and after enzyme replacement treatment with IDS. Methods: The expression levels of CGs and CCGs were evaluated by a whole transcriptome analysis through Next Generation Sequencing in normal primary human fibroblasts and fibroblasts of patients affected by HS before and 24 h/144 h after IDS treatment. The time related expression of CGs after synchronization by serum shock was also evaluated by qRT-PCR before and after 24 hours of IDS treatment. Results: In HS fibroblasts we found altered expression of several CGs and CCGs, with dynamic changes 24 h and 144 h after IDS treatment. A semantic hypergraph-based analysis highlighted five gene clusters significantly associated to important biological processes or pathways, and five genes, AHR, HIF1A, CRY1, ITGA5 and EIF2B3, proven to be central players in these pathways. After synchronization by serum shock and 24 h treatment with IDS the expression of ARNTL2 at 10 h (p = 0.036), PER1 at 4 h (p = 0.019), PER2 at 10 h (p = 0.041) and 16 h (p = 0.043) changed in HS fibroblasts. Conclusion: CG and CCG expression is altered in HS fibroblasts and IDS treatment determines dynamic modifications, suggesting a direct involvement of the CG machinery in the physiopathology of cellular derangements that characterize HS