Jamessteele5245

Studies exploring mediators of socioeconomic inequalities in excess weight gain in early-life and subsequent overweight/obesity (OW/OB) among youth are limited. Thus, this study examined the mediating role of prenatal and early postnatal factors and child energy balance-related behaviours (EBRB) in the effects of parental education on (i) excess weight gain from birth to 2 years and (ii) OW/OB at 5, 8 and 14 years. The Norwegian Mother, Father and Child Cohort Study was used to include participants at the ages of 2 (n = 59,597), 5 (n = 27,134), 8 (n = 28,285) and 14 (n = 11,278) years. Causal mediation analyses using the inverse odds weighting approach were conducted. Children of low-educated parents had a higher conditional excess weight gain at 2 years compared to children of high-educated parents (total effect, RRTE = 1.06; 95% CI 1.01, 1.10). The joint mediation effects of the prenatal and early postnatal factors explained most of the total effect of low education on conditional excess weight gain at 2 years. Children of low-educated parents had a higher risk of OW/OB at 5, 8 and 14 years compared to children of high-educated parents. The mediators jointly explained 63.7%, 67% and 88.9% of the total effect of parental education on OW/OB among 5, 8 and 14 year-old-children, respectively. Of the total mediated effects at 5, 8 and 14 years, the prenatal and early postnatal mediators explained 59.2%, 61.7% and 73.7%, whereas the child EBRB explained 10.3%, 15.8.0%% and 34.8%. The mediators included were found to have a considerable mediating effect in the associations explored, in particular the prenatal and early postnatal factors. If truly causal, the findings could indicate potential targets for interventions to tackle socioeconomic inequalities in OW/OB from birth to adolescence.

Glucagon-like peptide-1 receptor agonists (GLP-1ra) are increasingly used in treating type 2 diabetes and obesity. Exendin-4 (Ex-4), a long acting GLP-1ra, was previously reported to decrease oxidative stress in hepatocytes, adipocytes and skeletal muscle cells in obese nondiabetic fa/fa Zucker rats (ZFR), thereby improving insulin resistance.

We aimed first to identify Ex-4-induced changes in the transcriptome of skeletal muscle cells in ZFR.

Ontology analysis of differentially expressed genes (DEGs) in ZFR versus lean animals (LR) showed that the extracellular matrix (ECM) is the first most affected cellular compartment, followed by myofibrils and endoplasmic reticulum (ER). Interestingly, among 15 genes regulated in ZFR versus LR, 14 of them were inversely regulated by Ex-4, as further confirmed by RT-qPCR. Picro-Sirius red histological staining showed that decreased ECM fiber area in ZFR is partially restored by Ex-4. Ontology analysis of the myofibril compartment revealed that decreased muscle contractile function in ZFR is partially restored by Ex-4, as confirmed by Phalloidin histological staining that showed a partial restoration by Ex-4 of altered contractile apparatus in ZFR. Ontology analysis of ER DEGs in ZFR versus LR showed that some of them are related to the AMP-activated protein kinase (AMPK) signaling pathway. Phosphorylated AMPK levels were strongly increased in Ex-4-treated ZFR.

Altogether, our results suggest that GLP-1ra strongly restructure ECM and reinforce contractile capabilities in ZFR, while optimizing the cellular metabolism through AMPK.

Altogether, our results suggest that GLP-1ra strongly restructure ECM and reinforce contractile capabilities in ZFR, while optimizing the cellular metabolism through AMPK.Pathologic diabetic wound healing is caused by sequential and progressive deterioration of hemostasis, inflammation, proliferation, and resolution/remodeling. Cellular senescence promotes wound healing; however, diabetic wounds exhibit low levels of senescent factors and accumulate senescent cells, which impair the healing process. Here we show that the number of p15INK4B + PDGFRα + senescent mesenchymal cells in adipose tissue increases transiently during early phases of wound healing in both non-diabetic mice and humans. Transplantation of adipose tissue from diabetic mice into non-diabetic mice results in impaired wound healing and an altered cellular senescence-associated secretory phenotype (SASP), suggesting that insufficient induction of adipose tissue senescence after injury is a pathological mechanism of diabetic wound healing. These results provide insight into how regulation of senescence in adipose tissue contributes to wound healing and could constitute a basis for developing therapeutic treatment for wound healing impairment in diabetes.Successful treatment of chronic inflammatory diseases integrates both the cessation of inflammation and the induction of adequate tissue repair processes. Strikingly, targeting a single proinflammatory cytokine, tumor necrosis factor (TNF), induces both processes in a relevant cohort of inflammatory bowel disease (IBD) patients. However, the molecular mechanisms underlying intestinal repair following TNF blockade during IBD remain elusive. Using a novel humanized model of experimental colitis, we demonstrate that TNF interfered with the tissue repair program via induction of a soluble natural antagonist of IL-22 (IL-22Ra2; IL-22BP) in the colon and abrogated IL-22/STAT3-mediated mucosal repair during colitis. Furthermore, membrane-bound TNF expressed by T cells perpetuated colonic inflammation, while soluble TNF produced by epithelial cells (IECs) induced IL-22BP expression in colonic dendritic cells (DCs) and dampened IL-22-driven restitution of colonic epithelial functions. Finally, TNF induced IL-22BP expression in human monocyte-derived DCs and levels of IL22-BP correlated with TNF in sera of IBD patients. Thus, our data can explain how anti-TNF therapy induces mucosal healing by increasing IL-22 availability and implicates new therapeutic opportunities for IBD.Despite the clinical importance of glaucoma surgery, studies on its prevalence and risk factors are limited. We analyzed a database comprising approximately 1,000,000 Korean residents to investigate the prevalence and risk factors for undergoing glaucoma surgery within 5 years of diagnosis with open-angle glaucoma. Of the 4,303 patients evaluated, 226 (5.3%) underwent glaucoma surgery. Factors associated with the likelihood of glaucoma surgery included the use of two or more eye drops (odds ratio [OR], 30.30; 95% confidence interval [CI], 10.95-83.84), intake of oral carbonic anhydrase inhibitor (OR, 1.79; 95% CI, 1.23-2.61), age > 55 years (55-65 years OR, 1.71; 95% CI, 1.06-2.76; > 65 years OR 1.72; 95% CI, 1.10-2.70), female sex (OR, 1.46; 95% CI, 1.10-1.94), middle- and high-income (OR, 2.36; 95% CI, 1.30-4.28, OR, 1.86; 95% CI, 1.03-3.35, respectively), and metropolitan residence (OR, 1.61; 95% CI, 1.14-2.26). Our nomogram for predicting the likelihood of glaucoma surgery showed an acceptable result. In conclusion, older age, female sex, and the intensity of intraocular pressure lowering treatment increased the likelihood of undergoing glaucoma surgery. Our findings indicated that a lower socioeconomic status may forestall receiving this necessary surgery, which requires further attention.Although 23% of Thailand's land is in protected areas, these are vulnerable to climate change. We used spatial distribution modelling for 866 vertebrate and 591 plant species to understand potential climate change impacts on species in protected areas. Most mammals, birds, and plants were projected to decline by 2070, but most amphibians and reptiles were projected to increase. By 2070 under RCP8.5, 54% of modeled species will be threatened and 11 nationally extinct. However, SDMs are sensitive to truncation of the climate space currently occupied by habitat loss and hunting, and apparent truncation by data limitations. In Thailand, lowland forest clearance has biased records for forest-dependent species to cooler uplands (> 250 m a.s.l.) and hunting has confined larger vertebrates to well-protected areas. In contrast, available data is biased towards lowland non-forest taxa for amphibians and reptiles. Niche truncation may therefore have resulted in overestimation of vulnerability for some mammal and plant species, while data limitations have likely led to underestimation of the threat to forest-dependent amphibians and reptiles. In view of the certainty of climate change but the many uncertainties regarding biological responses, we recommend regular, long-term monitoring of species and communities to detect early signals of climate change impacts.The salutogenic effects of green exercise are widely recognised, yet many individuals do not engage in this health-related behaviour. Using a convergent mixed methods approach, this study explored the impact of experiencing nature through Virtual Reality (VR) on the decision-making process relating to green exercise. Leptomycin B in vivo Three experimental trials were conducted (overall n = 136), in which healthy adults were exposed to different VR scenarios reproducing a virtual walk in an existing urban green area. Participants reported medium-high rating of intent to visit the location. Significant pre-to-post increments in future green exercise intention were observed after the VR exposure, though a significance difference was not achieved in comparison with a control condition. Qualitative analysis revealed the impact of the VR experience on behaviour regulation, and highlighted the pivotal role of anticipated emotional benefits. Despite scepticism, the VR experience was effective in arousing curiosity to explore natural environments, which was associated with environmental perceptions as well as nostalgic and socio-cultural perspectives.

Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown.

Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infants <29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers.

Of the 2414 eligible twin infants <29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59).. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality.