Endothelial cell-derived oxysterol ablation attenuates experimental autoimmune encephalomyelitis.

The vasculature is a key regulator of leukocyte trafficking into the central nervous system (CNS) during inflammatory diseases including multiple sclerosis (MS). However, the impact of endothelial-derived factors on CNS immune responses remains unknown. Bioactive lipids, in particular oxysterols downstream of Cholesterol-25-hydroxylase (Ch25h), promote neuroinflammation but their functions in the CNS are not well-understood. Using floxed-reporter Ch25h knock-in mice, we trace Ch25h expression to CNS endothelial cells (ECs) and myeloid cells and demonstrate that Ch25h ablation specifically from ECs attenuates experimental autoimmune encephalomyelitis (EAE). Mechanistically, inflamed Ch25h-deficient CNS ECs display altered lipid metabolism favoring polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) expansion, which suppresses encephalitogenic T lymphocyte proliferation. Additionally, endothelial Ch25h-deficiency combined with immature neutrophil mobilization into the blood circulation nearly completely protects mice from EAE. Our findings reveal a central role for CNS endothelial Ch25h in promoting neuroinflammation by inhibiting the expansion of immunosuppressive myeloid cell populations

Low fertility and the risk of type 2 diabetes in women

BACKGROUND: Fertility problems are frequently followed by early menopause, and early menopause has been associated with increased risk of type 2 diabetes (T2D). Thus far, it is unknown whether low fertility is independently associated with future T2D risk. METHODS: We assessed the association between measures of low fertility and T2D in the Prospect-European Prospective Investigation into Cancer and Nutrition (EPIC) cohort of 17 357 Dutch women, aged 49-70 years at baseline using Cox proportional hazards models, adjusted for various confounders. To investigate whether BMI and waist circumference influence the observed associations, analyses were additionally adjusted for these variables. RESULTS: At baseline, 332 women had T2D. During a mean follow-up of 9.1 +/- 3.6 years, 535 T2D cases occurred. Out of 15 707 Prospect-EPIC women who wanted to get pregnant, 1940 consulted a physician for fertility problems and 700 remained childless. No relation was found between consulting a physician for fertility problems or nulliparity and T2D risk. Of all women who wanted to get pregnant, 3946 (25.1%) had one or more miscarriages, with an average of 1.4 (+/- 0.9) miscarriages and a maximum of 10 miscarriages. Women who had one or more miscarriage showed the same risk for T2D as women who had no miscarriage. Also, none of the other measures of low fertility were associated with increased risk for T2D. CONCLUSIONS: Generally, measures of low fertility were not independently associated with a risk of T2D in a cohort of 17 357 Dutch women

Indocyanin Green (ICG) for Colonic Viability Assessment in Left Pancreatic Minimal Invasive Surgery (MIS)

Background: Large distal pancreatic tumors may involve the transverse or splenic flexure mesocolon. R0 resection of such lesions may be extended to the mesocolon. Interruption of the arc of Riolan may be difficult to assess especially in MIS. Case report: We report a case of a 17 years old male presenting epigastric pain. The CT scan showed two lesions of the distal pancreas of 7x8cm and 4x3.5cm with aspects compatible with a solid pseudopapillary tumor. The octreo PET showed no fixation of the two lesions. A laparoscopic distal pancreatectomy with splenic preservation was attempted. Transverse and splenic flexure mesocolon were involved by the lesions. The dissection of the mesocolon to release the tumors lead to probable interruption of arc of Riolan and to a doubt on colonic optimal vascularisation after the surgery. We therefore used ICG to assess the viability of the colonic splenic flexure. Discussion and Conclusion: This short video illustrates how ICG can be simply used in left pancreatic surgery when R0 resection requires removal of splenic flexure mesocolon and partial interruption of arc of Riolan. In this case, ICG confirms the adequate perfusion of the splenic flexure and its safe preservation without any need of colonic resection

The Relationship of Menstrual Irregularity to Type 2 Diabetes in Pima Indian Women

OBJECTIVE Menstrual irregularity is associated with hyperinsulinemia and hyperandrogenemia in nondiabetic Pima Indian women of child-bearing age. In this population-based study, we determined the relationship of menstrual irregularity to type 2 diabetes in Pima Indian women. RESEARCH DESIGN AND METHODS Participants for this cross-sectional analysis were 695 nonpregnant Pima Indian women, aged 18–44 years, involved in an ongoing epidemiologic study of diabetes among residents of the Gila River Indian Community of Arizona. Clinical data were collected by questionnaire and an examination that included a 75-g oral glucose tolerance test; diabetes was diagnosed by World Health Organization criteria. Menstrual irregularity was defined as an interval of 3 months or more between menses, when not pregnant, since age 18 years. RESULTS History of menstrual irregularity was significantly associated with a high prevalence of diabetes (37 vs. 13%; odds ratio = 4.2, 95% CI = 1.6–10.8) in the least obese women (BMI < 30 kg/m2), adjusted for the effects of age and overall obesity. This association was, in part, because of greater central obesity in women with irregular menses. In more obese women, there was little association with menstrual irregularity, and diabetes was frequent regardless of menstrual history. CONCLUSIONS Prevalence of type 2 diabetes is higher among Pima indian women with a history of menstrual irregularity. The difference is most pronounced among the least obese group of women. This association may be because of insulin resistance and hyperinsulinemia, which predict type 2 diabetes, also causing hyperandrogenism and menstrual irregularity. The findings reinforce the need to evaluate women with menstrual irregularity for hyperglycemia

Ecopocalyptic visions in Haitian and Mexican landscapes of exploitation

This chapter investigates Jacques Roumain’s Gouverneurs de la rosée (Masters of the Dew, 1944) and Homero Aridjis’s La Leyenda de los soles (The Legend of the Suns, 1993) and ¿En quién piensas cuando haces el amor? (Of Whom Do You Think When You Make Love?, 1995). Despite their various contextual differences, these novels converge in their depictions of ecopocalyptic visions and utopian impulses. By considering the novels through the theory of postcolonial environmental ethics and in relation to the broader notion of environmental ethics and its “moral extentionism,” this chapter discusses the contemporary human and environmental crises of "postcolonial" countries as necessarily correlated, rather than as separate consequences of years of colonial and (neo-)imperialist exploitation of lands and communities

Chitin-glucan supplementation improved postprandial metabolism and altered gut microbiota in subjects at cardiometabolic risk in a randomized trial

International audienceChitin-glucan (CG), an insoluble dietary fiber, has been shown to improve cardiometabolic disorders associated with obesity in mice. Its effects in healthy subjects has recently been studied, revealing its interaction with the gut microbiota. In this double-blind, randomized, cross-over, twice 3-week exploratory study, we investigated the impacts of CG on the cardiometabolic profile and gut microbiota composition and functions in 15 subjects at cardiometabolic risk. They consumed as a supplement 4.5 g of CG daily or maltodextrin as control. Before and after interventions, fasting and postprandial metabolic parameters and exhaled gases (hydrogen [H(2)] and methane [CH(4)]) were evaluated. Gut microbiota composition (16S rRNA gene sequencing analysis), fecal concentrations of bile acids, long- and short-chain fatty acids (LCFA, SCFA), zonulin, calprotectin and lipopolysaccharide binding protein (LBP) were analyzed. Compared to control, CG supplementation increased exhaled H(2) following an enriched-fiber breakfast ingestion and decreased postprandial glycemia and triglyceridemia response to a standardized test meal challenge served at lunch. Of note, the decrease in postprandial glycemia was only observed in subjects with higher exhaled H(2), assessed upon lactulose breath test performed at inclusion. CG decreased a family belonging to Actinobacteria phylum and increased 3 bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005 and Eubacterium ventriosum group. Fecal metabolites, inflammatory and intestinal permeability markers did not differ between groups. In conclusion, we showed that CG supplementation modified the gut microbiota composition and improved postprandial glycemic response, an early determinant of cardiometabolic risk. Our results also suggest breath H(2) production as a non-invasive parameter of interest for predicting the effectiveness of dietary fiber intervention