Modeling Ozonation and Chlorination in potable Water Treatment

This article presents SimOx, the new simulator being currently developed by Anjou Recherche / ENSCR for oxidation steps in potable water treatment works. Whereas designing this new prediction engine was originally motivated by difficulties encountered when simulating a plant under on-site conditions, an increasingly stringent legal context and the emergence of micropolluants of concern clearly confirmed the need for a performing and innovative tool. The experience gained with the development of previous simulators is of advantage and opens interesting possibilities, in particular calculation capabilities upon which SimOx partly bases. Nevertheless, given the very characteristics of the new simulator SimOx (capacity to deal with sparse on-site data under changing water matrixes and hydrodynamic conditions), special modelling and calculation procedures are being implemented

The stress of starvation: glucocorticoid restraint of beta cell development

Developmental insults during gestation, such as under-nutrition, are known to restrict the number of beta cells that form in the fetal pancreas and are maintained in adulthood, leading to increased risk of type 2 diabetes. There are now substantial data indicating that glucocorticoids mediate this effect of under-nutrition on beta cell mass and that even at physiological levels they restrain fetal beta cell development in utero. There are emerging clues that this occurs downstream of endocrine commitment by neurogenin 3 but prior to terminal beta cell differentiation. Deciphering the precise mechanism will be important as it might unveil new pathways by which to manipulate beta cell mass that could be exploited as novel therapies for patients with diabetes

Postnatal Pancreatic Islet β Cell Function and Insulin Sensitivity at Different Stages of Lifetime in Rats Born with Intrauterine Growth Retardation

Epidemiological studies have linked intrauterine growth retardation (IUGR) to the metabolic diseases, consisting of insulin resistance, type 2 diabetes, obesity and coronary artery disease, during adult life. To determine the internal relationship between IUGR and islet β cell function and insulin sensitivity, we established the IUGR model by maternal nutrition restriction during mid- to late-gestation. Glucose tolerance test and insulin tolerance test(ITT) in vivo and glucose stimulated insulin secretion(GSIS) test in vitro were performed at different stages in IUGR and normal groups. Body weight, pancreas weight and pancreas/body weight of IUGR rats were much lower than those in normal group before 3 weeks of age. While the growth of IUGR rats accelerated after 3 weeks, pancreas weight and pancreas/body weight remained lower till 15 weeks of age. In the newborns, the fasting glucose and insulin levels of IUGR rats were both lower than those of controls, whereas glucose levels at 120 and 180 min after glucose load were significantly higher in IUGR group. Between 3 and 15 weeks of age, both the fasting glucose and insulin levels were elevated and the glucose tolerance was impaired with time in IUGR rats. At age 15 weeks, the area under curve of insulin(AUCi) after glucose load in IUGR rats elevated markedly. Meanwhile, the stimulating index of islets in IUGR group during GSIS test at age 15 weeks was significantly lower than that of controls. ITT showed no significant difference in two groups before 7 weeks of age. However, in 15-week-old IUGR rats, there was a markedly blunted glycemic response to insulin load compared with normal group. These findings demonstrate that IUGR rats had both impaired pancreatic development and deteriorated glucose tolerance and insulin sensitivity, which would be the internal causes why they were prone to develop type 2 diabetes

Long-term kidney function recovery and mortality after COVID-19-associated acute kidney injury: An international multi-centre observational cohort study

Background: While acute kidney injury (AKI) is a common complication in COVID-19, data on post-AKI kidney function recovery and the clinical factors associated with poor kidney function recovery is lacking. Methods: A retrospective multi-centre observational cohort study comprising 12,891 hospitalized patients aged 18 years or older with a diagnosis of SARS-CoV-2 infection confirmed by polymerase chain reaction from 1 January 2020 to 10 September 2020, and with at least one serum creatinine value 1–365 days prior to admission. Mortality and serum creatinine values were obtained up to 10 September 2021. Findings: Advanced age (HR 2.77, 95%CI 2.53–3.04, p < 0.0001), severe COVID-19 (HR 2.91, 95%CI 2.03–4.17, p < 0.0001), severe AKI (KDIGO stage 3: HR 4.22, 95%CI 3.55–5.00, p < 0.0001), and ischemic heart disease (HR 1.26, 95%CI 1.14–1.39, p < 0.0001) were associated with worse mortality outcomes. AKI severity (KDIGO stage 3: HR 0.41, 95%CI 0.37–0.46, p < 0.0001) was associated with worse kidney function recovery, whereas remdesivir use (HR 1.34, 95%CI 1.17–1.54, p < 0.0001) was associated with better kidney function recovery. In a subset of patients without chronic kidney disease, advanced age (HR 1.38, 95%CI 1.20–1.58, p < 0.0001), male sex (HR 1.67, 95%CI 1.45–1.93, p < 0.0001), severe AKI (KDIGO stage 3: HR 11.68, 95%CI 9.80–13.91, p < 0.0001), and hypertension (HR 1.22, 95%CI 1.10–1.36, p = 0.0002) were associated with post-AKI kidney function impairment. Furthermore, patients with COVID-19-associated AKI had significant and persistent elevations of baseline serum creatinine 125% or more at 180 days (RR 1.49, 95%CI 1.32–1.67) and 365 days (RR 1.54, 95%CI 1.21–1.96) compared to COVID-19 patients with no AKI. Interpretation: COVID-19-associated AKI was associated with higher mortality, and severe COVID-19-associated AKI was associated with worse long-term post-AKI kidney function recovery. Funding: Authors are supported by various funders, with full details stated in the acknowledgement section

Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet.

AIMS/HYPOTHESIS: Adverse events during intra-uterine life may programme organ growth and favour disease later in life. In animals, protein or energy restriction during gestation alters the development of the endocrine pancreas, even though the duration of malnutrition is different. Here, we evaluate the specific effects of both diets during different periods of gestation and the mechanisms underlying the decreased beta cell mass. METHODS: Pregnant Wistar rats were fed either a low-protein or a low-energy diet during the last week of gestation or throughout gestation. Fetuses and their pancreases were analysed at days 15 and 21 of gestation. RESULTS: The low-energy diet reduced the beta cell mass from 21-day-old fetuses by 33 or 56% when administered during the last week or throughout gestation, respectively. Fetal corticosterone levels were increased. At 15 days of fetal age, the number of cells producing neurogenin 3 (NEUROG3) or pancreatic and duodenal homeobox gene 1 (PDX-1) was reduced. Neither islet vascularisation nor beta cell proliferation was affected. The low-protein diet, in contrast, was more efficient in decreasing the fetal beta cell mass when given during the last week of gestation (-53%) rather than throughout gestation (-33%). Beta cell proliferation was decreased by 50% by the low-protein diet, independently of its duration, and islet vascularisation was reduced. This diet did not affect NEUROG3- or PDX-1-positive cell numbers. CONCLUSION/INTERPRETATION: Although both diets reduced the fetal beta cell mass, the cellular mechanisms and the sensitivity windows were different. Early alteration of neogenesis due to elevated corticosterone levels is likely to be responsible for the decreased beta cell mass in low-energy fetuses, whereas impaired beta cell proliferation and islet vascularisation at later stages are implicated in low-protein fetuses