Vitamin D treatment prevents uremia-induced reductions in aortic microRNA-145 attenuating osteogenic differentiation despite hyperphosphatemia

In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis:rationale, design, and study protocol of a large-scale epidemiological study in Europe

BACKGROUND: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. METHODS: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. RESULTS: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. CONCLUSION: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

A survey for variable young stars with small telescopes: II - mapping a protoplanetary disc with stable structures at 0.15 au

The HOYS citizen science project conducts long term, multifilter, high cadence monitoring of large YSO samples with a wide variety of professional and amateur telescopes. We present the analysis of the light curve of V1490 Cyg in the Pelican Nebula. We show that colour terms in the diverse photometric data can be calibrated out to achieve a median photometric accuracy of 0.02 mag in broadband filters, allowing detailed investigations into a variety of variability amplitudes over timescales from hours to several years. Using Gaia DR2 we estimate the distance to the Pelican Nebula to be 870 +70 −55 pc. V1490 Cyg is a quasi-periodic dipper with a period of 31.447 ± 0.011 d. The obscuring dust has homogeneous properties, and grains larger than those typical in the ISM. Larger variability on short timescales is observed in U and Rc−Hα, with U-amplitudes reaching 3 mag on timescales of hours, indicating the source is accreting. The Hα equivalent width and NIR/MIR colours place V1490 Cyg between CTTS/WTTS and transition disk objects. The material responsible for the dipping is located in a warped inner disk, about 0.15 AU from the star. This mass reservoir can be filled and emptied on time scales shorter than the period at a rate of up to 10−10 M�/yr, consistent with low levels of accretion in other T Tauri stars. Most likely the warp at this separation from the star is induced by a protoplanet in the inner accretion disk. However, we cannot fully rule out the possibility of an AA Tau-like warp, or occultations by the Hill sphere around a forming planet