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BackgroundA subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina's Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10-8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM.ResultsTop-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation.ConclusionsEpigenetic alterations provide a dynamic link between an individual's genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.

PURPOSE:To evaluate the relationship between the burden of chronic thromboembolic disease quantified via CT pulmonary angiography and pre-operative hemodynamics and post-operative hemodynamic improvement in CTEPH patients undergoing PTE. METHODS:CTEPH patients who underwent pulmonary thromboendarterectomy surgery (PTE) between December 2017 and August 2019 were retrospectively screened for having 1) preoperative CT pulmonary angiogram (CTPAs) with corresponding preoperative vascular annotations, 2) preoperative right heart catheterization, 3) bilateral level 2 surgical disease (defined from surgically resected thromboembolic specimen) and 4) recorded postoperative hemodynamics. Clot burden was quantified in preoperative CTPAs using the Qanadli score, which weights the location and severity of thromboembolic lesions into a per-patient score. Mean pulmonary artery pressure, pulmonary vascular resistance, and total pulmonary resistance were obtained from right heart catheterization preoperatively and then on the day of Swan-Ganz removal in the ICU postoperatively. Linear regression was performed between measured clot burden and hemodynamic variables. Continuous variables are presented as mean ± standard deviation. RESULTS:15 patients (7 females, age: 36 ± 13 years, BMI: 35.0 ± 6.7, preoperative mPAP: 40 ± 13 mmHg) met all inclusion criteria. Clot burden score ranged from 11 to 30, with a mean of 19 ± 6. Level of surgical disease seen on imaging matched surgical findings in 87% and 67% of cases (right and left lungs, respectively). Figure 1 illustrates the significant linear correlations between clot burden and preoperative mPAP (R2= 0.59), PVR (R2 = 0.69) and TPR (R2= 0.58), as well as post PTE improvement in PVR (R2 = 0.48) and TPR (R2 = 0.35). CONCLUSION:Pre-operative CT-based quantitative assessment of the pulmonary vasculature is associated with the hemodynamic severity of CTEPH and surgical improvement in PVR after PTE.

A perceived dissonance exists between the stated conservation mission of modern zoos and the composition of species in their care. A bias toward charismatic taxa over threatened ones has been demonstrated in several studies. However, these prior examinations have principally relied on species threat status derived from global lists, and threat status reported for species on national and subnational lists often differ from global assessments. It has been suggested that some globally non‐threatened species maintained in zoos might fulfill local conservation priorities. In this study, we compare local threat status and zoo population size for native bird, mammal, reptile and amphibian species in North American zoos to assess the representation of locally threatened taxa. We found that native locally threatened species were kept in North American zoos slightly less than would be expected by chance; however, of the species that were represented in zoos, those that were threatened in more of the subnational regions where they occurred averaged larger populations within zoos. This suggests that the direct contribution from zoo animals to the conservation of locally threatened species is relatively limited with respect to taxonomic coverage, but this contribution may be underestimated by strictly counting the threatened species kept in zoos. [ABSTRACT FROM AUTHOR]