Wilkinsonryberg7479

Inflammatory bowel disease (IBD) is linked to psychiatric morbidity, but few studies have assessed general population comparators. We aimed to investigate the risk of psychiatric morbidity and suicide in adult-onset IBD patients.

Nationwide population-based cohort study in Sweden (1973-2013). We studied the risk of psychiatric disorders and suicide in 69,865 adult-onset IBD patients (ulcerative colitis, UC n=43,557; Crohn's disease, CD n=21,245; and IBD-unclassified n=5063) compared to 3,472,913 general population references and 66,292 siblings.

During a median follow-up of 11 years, we found 7,465 (10.7%) first psychiatric disorders in IBD (incidence rate, IR/1000 person-years 8.4) and 306,911 (9.9%) in the general population (IR 6.6), resulting in 1.8 extra psychiatric morbidity per 100 patients followed-up for 10 years and a hazard ratio (HR) of 1.3 (95% confidence interval, 95%CI=1.2-1.3). The highest risk of overall psychiatric morbidity was seen in the first year after IBD diagnosis (HR=1.4, 95%CIis.

The Centre-Periphery Hypothesis posits that higher species performance is expected in geographic and ecological centres rather than in peripheral populations. However, this is not the commonly found pattern; therefore, alternative approaches, including the historical dimension of species geographical ranges should be explored. Morphological functional traits are fundamental determinants of species performance, commonly related to environmental stability and productivity. We tested whether or not historical processes may have shaped variations in tree and leaf traits of the Chaco tree Bulnesia sarmientoi.

Morphological variation patterns were analysed from three centre-periphery approaches geographical, ecological and historical. Tree (stem and canopy) and leaf (leaf size and specific leaf area) traits were measured in 24 populations across the species range. Ras inhibitor A Principal Component Analysis was performed on morphological traits to obtain synthetic variables. Linear Mixed-Effects Models were used to test whi traits variation, highlighting that centre-periphery delimitations should be based on a multi-approach framework.

The decoupled response between leaf and tree traits suggests that these sets of traits respond differently to processes occurring at different times. The geographical and historical approaches showed centres with extreme environments in relation to their respective peripheries, but the historical centre has also been a climatically stable area since the Last Glacial Maximum. link2 The historical approach allowed for the recovery of historical processes underlying tree traits variation, highlighting that centre-periphery delimitations should be based on a multi-approach framework.

Arteriovenous fistula (AVF) maturation failure remains a clinical dilemma, and its pathobiology is largely unclear. Secondary hyperparathyroidism is a complication of chronic renal failure that is associated with cardiovascular disease. While parathyroid hormone (PTH) has a prosclerotic effect on vascular smooth muscle cells (VSMCs), its role in AVF maturation failure remained unknown.

This work aimed to investigate the association between plasma PTH and AVF maturation.

Patients receiving AVF creation were enrolled retrospectively. A mouse model of secondary hyperparathyroidism and aortocaval AVF was used to investigate the effect of PTH on an AVF lesion. A cell model of VSMCs treated with PTH in a pressurized culture system was used to disclose the signaling pathway underlying the effect of PTH on an AVF lesion.

In patients receiving AVF creation, higher PTH was associated with an increased risk for maturation failure. In a mouse model, vascular wall thickness and myofibroblasts of AVF significantly increased with higher PTH. When the same mice were treated with cinacalcet, AVF lesions were attenuated by suppression of PTH. A cell model showed that PTH increased the marker of myofibroblasts, integrin β6 subunit (ITGB6), via the phosphorylated protein kinase B pathway. Finally, in the same model of mice AVF, higher PTH also increased the expression of ITGB6 in the smooth muscle layer of AVF, suggesting the transition to myofibroblast.

Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of VSMCs to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.

Overall, our results suggest that higher PTH increased the risk of AVF maturation failure through increasing the transition of VSMCs to myofibroblasts. Lowering PTH may be a strategy to enhance AVF maturation.

Delta like noncanonical notch ligand 1 (DLK1) is a paternally expressed imprinted gene that encodes an epidermal growth factor repeat-containing transmembrane protein. A bioactive, truncated DLK1 protein is present in the circulation and has roles in development and metabolism.

We sought to investigate links between maternal pregnancy circulating DLK1 concentrations and (1) maternal and fetal DLK1 genotypes, (2) maternal insulin resistance and secretion, and (3) offspring size at birth.

We measured third-trimester maternal serum DLK1 concentrations and examined their associations with parentally transmitted fetal and maternal DLK1 genotypes, indices of maternal insulin resistance and secretion derived from 75-g oral glucose tolerance tests performed around week 28 of pregnancy, and offspring size at birth in 613 pregnancies from the Cambridge Baby Growth Study.

Maternal DLK1 concentrations were associated with the paternally transmitted fetal DLK1 rs12147008 allele (P = 7.8 × 10-3) but not with maternnal circulating DLK1 concentrations, stimulation of maternal insulin resistance and compensatory hyperinsulinemia during pregnancy, and the promotion of fetal growth.Pathogenic missense variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified through linkage analysis in familial Parkinson disease (PD). Subsequently, other missense variants with lower effect sizes on PD risk have emerged, as well as non-coding polymorphisms (e.g. rs76904798) enriched in PD cases in genome-wide association studies. Here we leverage recent whole-genome sequences from the Accelerating Medicines Partnership-Parkinson's Disease (AMP-PD) and the Genome Aggregation (gnomAD) databases to characterize novel missense variants in LRRK2 and explore their relationships with known pathogenic and PD-linked missense variants. Using a computational prediction tool that successfully classifies known pathogenic LRRK2 missense variants, we describe an online web-based resource that catalogs characteristics of over 1200 LRRK2 missense variants of unknown significance. Novel high-pathogenicity scoring variants, some identified exclusively in PD cases, tightly cluster within the ROC-COR-Kinase domains. Structure-function predictions support that some of these variants exert gain-of-function effects with respect to LRRK2 kinase activity. link3 In AMP-PD participants, all p.R1441G carriers (N = 89) are also carriers of the more common PD-linked variant p.M1646T. In addition, nearly all carriers of the PD-linked p.N2081D missense variant are also carriers of the LRRK2 PD-risk variant rs76904798. These results provide a compendium of LRRK2 missense variants and how they associate with one another. While the pathogenic p.G2019S variant is by far the most frequent high-pathogenicity scoring variant, our results suggest that ultra-rare missense variants may have an important cumulative impact in increasing the number of individuals with LRRK2-linked PD.

To investigate the association between religious involvement and cognitive functioning at the intersections of race-ethnicity and gender among mid-life and older adults, and to determine if psychosocial factors help explain this relationship.

The sample included 14,037 adults aged 50+ from the Health and Retirement Study (HRS). We utilized measures from the HRS 2010 and 2012 Core interviews and Leave Behind questionnaires and estimated our models using linear regression.

Compared to individuals who frequently attended religious services, infrequent religious service attendance was related to poorer cognitive functioning. Religiosity was inversely associated with cognitive functioning at baseline, but the relationship varied by race/gender subgroup. Greater religiosity was associated with better cognitive functioning among Black women, but lower cognitive functioning among White men and women. Psychosocial factors did little to explain the inverse association between religiosity and cognitive functioning.

Results suggest the association between religious involvement and cognitive functioning is varied and complex, and largely dependent on important social identities. The findings have important implications for investigating health-protective factors, like religious involvement, using an intersectional perspective.

Results suggest the association between religious involvement and cognitive functioning is varied and complex, and largely dependent on important social identities. The findings have important implications for investigating health-protective factors, like religious involvement, using an intersectional perspective.Plastic is omnipresent in the oceans and serves as a surface for biofilm-forming microorganisms. Plastic debris comprises different polymers, which may influence microbial colonization; here, we evaluated whether polymer type affects bacterial biofilm formation. Quantifying the biofilm on polyethylene (PE), polypropylene (PP) or polystyrene (PS) pellets by six marine bacterial strains (Vibrio,Pseudoalteromonas,Phaeobacter) demonstrated that each strain had a unique colonization behavior with either a preference for PS or PP over the other polymer types or no preference for a specific plastic type. PE, PP and PS pellets were exposed to natural seawater microbiota using free-living or total communities as inoculum. Microbial assembly as determined by 16S rRNA (V4) amplicon sequencing was affected by the composition of the initial inoculum and also by the plastic type. Known polymer and hydrocarbon degraders such as Paraglaciecola, Oleibacter and Hydrogenophaga were found in the plastic biofilms. Thus, on a community level, bacterial colonization on plastic is influenced by the microorganisms as well as the polymer type, and also individual strains can demonstrate polymer-specific colonization.The 5-year survival rate of pancreatic ductal carcinoma (PDAC) patients is less then 10% despite progress in clinical medicine. Strategies to prevent development of PDAC are urgently required. The flavonoids Luteolin (Lut) and hesperetin (Hes) may be cancer-chemopreventive, but effects on pancreatic carcinogenesis in vivo have not been studied. Here, chemopreventive effects of Lut and Hes on pancreatic carcinogenesis are assessed in the BOP-induced hamster PDAC model. Lut but not Hes suppressed proliferation of pancreatic intraepithelial neoplasia (PanIN), and reduced the incidence and multiplicity of PDAC in this model. Lut also inhibited proliferation of hamster and human pancreatic cancer cells in vitro. Multi-blot and microarray assays revealed decreased phosphorylated STAT3 (pSTAT3) and dihydropyrimidine dehydrogenase (DPYD) on Lut exposure. To explore the relationship between DPYD and STAT3 activity, the former was silenced by RNAi or overexpressed using expression vectors, and the latter was inactivated by small molecule inhibitors or stimulated by IL6 in human PDAC cells.