Epithelial argininosuccinate synthetase is dispensable for intestinal regeneration and tumorigenesis

The epithelial signaling pathways involved in damage and regeneration, and neoplastic transformation are known to be similar. We noted upregulation of argininosuccinate synthetase (ASS1) in hyperproliferative intestinal epithelium. Since ASS1 leads to de novo synthesis of arginine, an important amino acid for the growth of intestinal epithelial cells, its upregulation can contribute to epithelial proliferation necessary to be sustained during oncogenic transformation and regeneration. Here we investigated the function of ASS1 in the gut epithelium during tissue regeneration and tumorigenesis, using intestinal epithelial conditional Ass1 knockout mice and organoids, and tissue specimens from colorectal cancer patients. We demonstrate that ASS1 is strongly expressed in the regenerating and Apc-mutated intestinal epithelium. Furthermore, we observe an arrest in amino acid flux of the urea cycle, which leads to an accumulation of intracellular arginine. However, loss of epithelial Ass1 does not lead to a reduction in proliferation or increase in apoptosis in vivo, also in mice fed an arginine-free diet. Epithelial loss of Ass1 seems to be compensated by altered arginine metabolism in other cell types and the liver.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Achieving diabetes treatment targets in people with registered mental illness is similar or improved compared with those without: Analyses of linked observational datasets

Aims To determine the association between registered mental illness and type 2 diabetes mellitus treatment targets, while taking into account the effects of health expenditure and social determinants of health. Methods This observational cross-sectional study was based on routine primary care data, linked to socio-economic and medical claims data. The main outcomes, analysed by multivariate logistic regression, were achieving primary care guideline treatment targets for HbA(1c), systolic blood pressure (SBP) and LDL-cholesterol in 2017. We examined the association with diagnosed mental illness registered by the general practitioner (GP) or treated via specialist' mental healthcare between 2016 and 2018, adjusting for, medication use, body mass index, co-morbidity, smoking, and additionally examining effect-modification of healthcare expenditures, migration status, income and demographics. Results Overall (N = 2862), 64.0% of participants achieved their treatment targets for HbA(1c), 65.1% for SBP and 53.0% for LDL-cholesterol. Adjusted for migrant background, income and care expenditures, individuals <65 years of age with mental illness achieved their HbA(1c) treatment target more often than those without (OR (95% CI)): treatment by GP: 1.46 (1.01, 2.11), specialist care: 1.61 (1.11, 2.34), as did men with mental illness for SBP: GP OR 1.61 (1.09, 2.40), specialist care OR 1.59 (1.09, 2.45). LDL-cholesterol target was not associated with mental illness. A migrant background or low income lowered the likelihood of reaching HbA(1c) targets. Conclusions People with registered mental illness appear comparable or better able to achieve diabetes treatment targets than those without. Achieving HbA(1c) targets is influenced by social disadvantage.Public Health and primary carePrevention, Population and Disease management (PrePoD

Achieving diabetes treatment targets in people with registered mental illness is similar or improved compared with those without: Analyses of linked observational datasets

Aims To determine the association between registered mental illness and type 2 diabetes mellitus treatment targets, while taking into account the effects of health expenditure and social determinants of health. Methods This observational cross-sectional study was based on routine primary care data, linked to socio-economic and medical claims data. The main outcomes, analysed by multivariate logistic regression, were achieving primary care guideline treatment targets for HbA(1c), systolic blood pressure (SBP) and LDL-cholesterol in 2017. We examined the association with diagnosed mental illness registered by the general practitioner (GP) or treated via specialist' mental healthcare between 2016 and 2018, adjusting for, medication use, body mass index, co-morbidity, smoking, and additionally examining effect-modification of healthcare expenditures, migration status, income and demographics. Results Overall (N = 2862), 64.0% of participants achieved their treatment targets for HbA(1c), 65.1% for SBP and 53.0% for LDL-cholesterol. Adjusted for migrant background, income and care expenditures, individuals <65 years of age with mental illness achieved their HbA(1c) treatment target more often than those without (OR (95% CI)): treatment by GP: 1.46 (1.01, 2.11), specialist care: 1.61 (1.11, 2.34), as did men with mental illness for SBP: GP OR 1.61 (1.09, 2.40), specialist care OR 1.59 (1.09, 2.45). LDL-cholesterol target was not associated with mental illness. A migrant background or low income lowered the likelihood of reaching HbA(1c) targets. Conclusions People with registered mental illness appear comparable or better able to achieve diabetes treatment targets than those without. Achieving HbA(1c) targets is influenced by social disadvantage