Pollution, Health and Life Expectancy: How Environmental Policy Can Promote Growth

This article investigates the influence of environmental policy on growth assuming that the channel of transmission relies on the link between pollution, health and the survival probability, in an overlapping generations model à la Blanchard (1985) where growth is driven by a mechanism à la Romer (1986). We demonstrate that environmental policy has an ambiguous effect on growth in the steady-state when the detrimental impact of pollution on health and lifetime is taken into account: for low levels of taxation, environmental policy promotes growth while it is harmful to growth for high levels. Furthermore, we show that the environmental policy is more likely to promote growth (i.e. it stimulates growth for a wider range of environmental taxes) when public expenditures in health and/or the impact of pollution on health are important. Finally, using numerical simulations, we find that for the value of parameters chosen the environmental policy will be more likely to harm growth when agents smooth consumption over time

P166 Inflammatory bowel disease: risk factors to disease activity during pregnancy and postpartum

Abstract Background The literature suggests that inflammatory bowel disease (IBD) activity during the periconceptional period is a risk factor for active disease during pregnancy. This study aims to evaluate if there is influence of IBD characteristics (type, classification, duration, activity in the periconceptional period, severity and treatment of disease) on the frequency of active disease during pregnancy and postpartum. Methods Retrospective study that included pregnant women followed in Maternal-Fetal Medicine department at Hospital de Santa Maria diagnosed with IBD, with information on ≥2 of the referred variables and delivery between March 2012 and July 2018 (n = 37; 24 Crohn’s disease, CD and 13 ulcerative colitis, UC). The statistical tests used were chi-square and Fisher’s exact test. Results There was no statistically significant difference between CD and CU in the activity of IBD during pregnancy and postpartum. Diagnosis &amp;gt;5 years and &amp;gt;10 years ago was associated with lower frequency of active disease during pregnancy (15% vs. 78.6%, p &amp;lt; 0.005 and 8.3% vs. 59.1%, p = 0.009, respectively), but did not influence postpartum activity. Age at diagnosis (≤16 years or 17–40 years) did not appear to influence IBD activity. IBD activity during the periconceptional period and pregnancy had a statistically significant association (72.7% with active disease during the periconceptional period and pregnancy and 26.1% with quiescent IBD at the time of conception but active during pregnancy, p = 0.023). There were 3 cases of IBD remission during pregnancy (2 CD and 1 UC). Of the 15 cases of active disease during pregnancy, 6 of them (40%; 4 with CD and 2 with UC) were reactivations. 3 women had active IBD during the postpartum period and all of them already had active disease during pregnancy. Regarding severity, all cases of active IBD were classified as mild disease. The type of therapy (biological, corticosteroids, thiopurines, salicylates, antibiotics or lack of therapy) was not related to disease activity during pregnancy or postpartum. Prior bowel surgery related to IBD (n = 7, all with CD) was associated with a lower frequency of active disease during pregnancy (0% vs. 51.7%, p = 0.027). Conclusion The diagnosis of IBD for more than 5 or 10 years and previous bowel surgery were associated with a lower frequency of active disease during pregnancy. There was a relationship between IBD activity in the periconceptional period and pregnancy, which reinforces the importance of pregnancy planning and prior disease control. </jats:sec

The Geroprotective Drug Candidate CMS121 Alleviates Diabetes, Liver Inflammation, and Renal Damage in db/db Leptin Receptor Deficient Mice

db/db mice, which lack leptin receptors and exhibit hyperphagia, show disturbances in energy metabolism and are a model of obesity and type 2 diabetes. The geroneuroprotector drug candidate CMS121 has been shown to be effective in animal models of Alzheimer&rsquo;s disease and aging through the modulation of metabolism. Thus, the hypothesis was that CMS121 could protect db/db mice from metabolic defects and thereby reduce liver inflammation and kidney damage. The mice were treated with CMS121 in their diet for 6 months. No changes were observed in food and oxygen consumption, body mass, or locomotor activity compared to control db/db mice, but a 5% reduction in body weight was noted. Improved glucose tolerance and reduced HbA1c and insulin levels were also seen. Blood and liver triglycerides and free fatty acids decreased. Improved metabolism was supported by lower levels of fatty acid metabolites in the urine. Markers of liver inflammation, including NF-&kappa;B, IL-18, caspase 3, and C reactive protein, were lowered by the CMS121 treatment. Urine markers of kidney damage were improved, as evidenced by lower urinary levels of NGAL, clusterin, and albumin. Urine metabolomics studies provided further evidence for kidney protection. Mitochondrial protein markers were elevated in db/db mice, but CMS121 restored the renal levels of NDUFB8, UQCRC2, and VDAC. Overall, long-term CMS121 treatment alleviated metabolic imbalances, liver inflammation, and reduced markers of kidney damage. Thus, this study provides promising evidence for the potential therapeutic use of CMS121 in treating metabolic disorders

Ferroptosis and Charcot&ndash;Marie&ndash;Tooth Disease 1A: Emerging Evidence for a Pathogenic Association

Charcot&ndash;Marie&ndash;Tooth disease (CMT) is the most common hereditary peripheral neuropathy worldwide, presenting clinically as muscle weakness that progresses to impaired ambulation or quadriplegia with age. CMT1A, the most common subtype, is caused by a duplication in PMP22, encoding an essential membrane protein for Schwann cell myelin integrity. While the mechanisms of peripheral neurodegeneration in CMT1A are poorly understood, excessive oxidative stress, particularly lipid peroxidation, is a known pathological feature, and antioxidant therapy has reversed the CMT1A phenotype in a mouse model. For the first time, we define the pathogenic link between CMT1A and ferroptosis, a form of regulated cell death caused by excessive lipid peroxidation and hindered antioxidant defenses. Human-derived CMT1A fibroblasts showed greater susceptibility to RSL3, a pro-ferroptosis agent, compared with controls, alongside several ferroptosis markers, including elevated lipid peroxides and depleted GPX4, a critical anti-ferroptosis repressor. Similarly, transcriptomic analysis of human iPSC-derived Schwann cells revealed elevated ferroptosis activation and cellular stress markers in CMT1A. We propose that chronic, sublethal ferroptotic stress, mediated by lipid peroxide accumulation, depletes antioxidant defenses in CMT1A Schwann cells, leading to decompensation with age, manifesting as symptomatic disease. These results emphasize ferroptosis as a driver of CMT1A pathology, potentially revealing a new therapeutic path

P645 Adalimumab drug monitoring is superior to empirical treatment adjustment in inflammatory bowel disease

Abstract Background Anti-TNF blockers are effective drugs in the treatment of inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) of Adalimumab (ADA) may potentially improve clinical outcomes in this setting, but data are still scarce. Methods To compare ADA TDM and empirical treatment adjustment (ETA) in patients with IBD. Outcomes were evaluated at 2 years and included hospitalisation, surgery, treatment discontinuation, endoscopic remission and treatment failure (any unfavourable event). Single-centre retrospective study, including patients under ADA therapy. Results 103 patients were included, 86 with Crohn’s disease and 17 with ulcerative colitis. 52.4% male, mean age 28.5 (18–72). 56 patients received ADA TDM and 47 ETA. At 2-years, rates of treatment escalation (57.1% vs. 21.3%, p &amp;lt;0.001), mucosal healing (69.6% vs. 48.9%, p =0.032) and treatment discontinuation (17.9% vs. 4.3%, p =0.032) favored the TDM group. For TDM and ETA respectively, there was no statistically significant difference regarding need for hospitalisation (12.5% vs. 21.3%, p = 0.232), surgery (5.4% vs. 14.9%, p =0.103) and treatment failure (26.7% vs. 34.5%, p =0.395). Conclusion Our results suggest a benefit of TDM in achieving higher rates of mucosal healing The higher rates of treatment discontinuation suggest that TDM improves drug selection as patients switched unhelpful treatment earlier. </jats:sec