Bioincompatible Impact of Different Peritoneal Dialysis Fluid Components and Therapeutic Interventions as Tested in a Rat Peritoneal Dialysis Model

Peritoneal dialysis (PD) is associated with functional and structural changes of the peritoneal membrane. In this paper, we describe the impact of different factors contributing to peritoneal incompatibility of PD fluid installation including presence of a catheter, volume loading, and the PD fluid components itself. These factors initiate recruitment and activation of peritoneal immune cells such as macrophages and mast cells, as well as activation of peritoneal cells as mesothelial cells in situ. We provide an overview of PD-associated changes as seen in our rat PD-exposure model. Since these changes are partly reversible, we finally discuss therapeutic strategies in the rat PD model with possible consequences of long-term PD in the relevant human setting

Submillimeter galaxies behind the Bullet Cluster (1E 0657-56)

Clusters of galaxies are effective gravitational lenses able to magnify background galaxies and making it possible to probe the fainter part of the galaxy population. Submillimeter galaxies, which are believed to be star-forming galaxies at typical redshifts of 2 to 3, are a major contaminant to the extended Sunyaev-Zeldovich (SZ) signal of galaxy clusters. For a proper quantification of the SZ signal the contribution of submillimeter galaxies needs to be quantified. The aims of this study are to identify submillimeter sources in the field of the Bullet Cluster (1E 0657-56), a massive cluster of galaxies at z~0.3, measure their flux densities at 870 micron, and search for counterparts at other wavelengths to constrain their properties. We carried out deep observations of the submillimeter continuum emission at 870 micron using the Large APEX BOlometer CAmera (LABOCA) on the Atacama Pathfinder EXperiment (APEX) telescope. Several numerical techniques were used to quantify the noise properties of the data and extract sources. In total, seventeen sources were found. Thirteen of them lie in the central 10 arcminutes of the map, which has a pixel sensitivity of 1.2 mJy per 22 arcsec beam. After correction for flux boosting and gravitational lensing, the number counts are consistent with published submm measurements. Nine of the sources have infrared counterparts in Spitzer maps. The strongest submm detection coincides with a source previously reported at other wavelengths, at an estimated redshift z~2.7. If the submm flux arises from two images of a galaxy magnified by a total factor of 75, as models have suggested, its intrinsic flux would be around 0.6 mJy, consistent with an intrinsic luminosity below 10^12 L_sun.Comment: Accepted by A&A, 15 pages, 11 figure

Recruitment, augmentation and apoptosis of rat osteoclasts in 1,25-(OH)2D3 response to short-term treatment with 1,25-dihydroxyvitamin D3in vivo

Background Although much is known about the regulation of osteoclast (OC) formation and activity, little is known about OC senescence. In particular, the fate of of OC seen after 1,25-(OH)2D3 administration in vivo is unclear. There is evidence that the normal fate of OC is to undergo apoptosis (programmed cell death). We have investigated the effect of short-term application of high dose 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on OC apoptosis in an experimental rat model. Methods OC recruitment, augmentation and apoptosis was visualised and quantitated by staining histochemically for tartrate resistant acid phosphatase (TRAP), double staining for TRAP/ED1 or TRAP/DAPI, in situ DNA fragmentation end labelling and histomorphometric analysis. Results Short-term treatment with high-dose 1,25-(OH)2D3 increased the recruitment of OC precursors in the bone marrow resulting in a short-lived increase in OC numbers. This was rapidly followed by an increase in the number of apoptotic OC and their subsequent removal. The response of OC to 1,25-(OH)2D3 treatment was dose and site dependent; higher doses producing stronger, more rapid responses and the response in the tibiae being consistently stronger and more rapid than in the vertebrae. Conclusions This study demonstrates that (1) after recruitment, OC are removed from the resorption site by apoptosis (2) the combined use of TRAP and ED1 can be used to identify OC and their precursors in vivo (3) double staining for TRAP and DAPI or in situ DNA fragmentation end labelling can be used to identify apoptotic OC in vivo

The Herschel Multi-tiered Extragalactic Survey: HerMES

The Herschel Multi-tiered Extragalactic Survey, HerMES, is a legacy program designed to map a set of nested fields totalling ~380 deg^2. Fields range in size from 0.01 to ~20 deg^2, using Herschel-SPIRE (at 250, 350 and 500 \mu m), and Herschel-PACS (at 100 and 160 \mu m), with an additional wider component of 270 deg^2 with SPIRE alone. These bands cover the peak of the redshifted thermal spectral energy distribution from interstellar dust and thus capture the re-processed optical and ultra-violet radiation from star formation that has been absorbed by dust, and are critical for forming a complete multi-wavelength understanding of galaxy formation and evolution. The survey will detect of order 100,000 galaxies at 5\sigma in some of the best studied fields in the sky. Additionally, HerMES is closely coordinated with the PACS Evolutionary Probe survey. Making maximum use of the full spectrum of ancillary data, from radio to X-ray wavelengths, it is designed to: facilitate redshift determination; rapidly identify unusual objects; and understand the relationships between thermal emission from dust and other processes. Scientific questions HerMES will be used to answer include: the total infrared emission of galaxies; the evolution of the luminosity function; the clustering properties of dusty galaxies; and the properties of populations of galaxies which lie below the confusion limit through lensing and statistical techniques. This paper defines the survey observations and data products, outlines the primary scientific goals of the HerMES team, and reviews some of the early results.Comment: 23 pages, 17 figures, 9 Tables, MNRAS accepte

[18F]FDG and [18F]FES PET/CT Imaging as a Biomarker for Therapy Effect in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant

PURPOSE: Positron emission tomography (PET) with 16α-[18F]-fluoro-17β-estradiol ([18F]FES) allows assessment of whole body estrogen receptor (ER) expression. The aim of this study was to investigate [18F]fluorodeoxyglucose ([18F]FDG) and [18F]FES PET/CT imaging for response prediction and monitoring of drug activity in patients with metastatic ER+ breast cancer undergoing treatment with the selective estrogen receptor downregulator (SERD) rintodestrant.PATIENTS AND METHODS: In this trial (NCT03455270), PET/CT imaging was performed at baseline ([18F]FDG and [18F]FES), during treatment and at time of progression (only [18F]FES). Visual, quantitative and mutational analysis was performed to derive a heterogeneity score (HS) and assess tracer uptake in lesions, in relation to the mutation profile. The primary outcome was progression-free survival (PFS).RESULTS: The HS and PFS in the entire group did not correlate (n=16, Spearman's rho, P=0.06), but patients with a low HS (&lt;25.0%, n=4) had a PFS of &gt;5 months whereas patients with no [18F]FES uptake (HS 100.0%, n =3) had a PFS of &lt;2 months. [18F]FES uptake was not affected by ESR1 mutations. On-treatment [18F]FES PET/CT scans showed no [18F]FES uptake in any of the baseline [18F]FES positive lesions. At progression, [18F]FES uptake remained blocked in patients scanned ≤1-2 half-lives of rintodestrant whereas it restored in patients scanned ≥5 days after end of treatment.CONCLUSION: Absence of ER expression on [18F]FES PET is a predictor for no response to rintodestrant. [18F]FES uptake during treatment and at time of progression is useful to monitor the (reversible) effect of therapy and continued mode of action of SERDs.</p

A Novel Rat Model of Vitamin D Deficiency: Safe and Rapid Induction of Vitamin D and Calcitriol Deficiency without Hyperparathyroidism

Vitamin D deficiency is associated with a range of clinical disorders. To study the mechanisms involved and improve treatments, animal models are tremendously useful. Current vitamin D deficient rat models have important practical limitations, including time requirements when using, exclusively, a vitamin D deficient diet. More importantly, induction of hypovitaminosis D causes significant fluctuations in parathyroid hormone (PTH) and mineral levels, complicating the interpretation of study results. To overcome these shortcomings, we report the successful induction of vitamin D deficiency within three weeks, with stable serum PTH and minerals levels, in Wistar rats. We incorporated two additional manoeuvres compared to a conventional diet. Firstly, the vitamin D depleted diet is calcium (Ca) enriched, to attenuate the development of secondary hyperparathyroidism. Secondly, six intraperitoneal injections of paricalcitol during the first two weeks are given to induce the rapid degradation of circulating vitamin D metabolites. After three weeks, serum 25-hydroxyvitamin D 3 (25D) and 1,25-dihydroxyvitamin D 3 (1,25D) levels had dropped below detection limits, with unchanged serum PTH, Ca, and phosphate (P) levels. Therefore, this model provides a useful tool to examine the sole effect of hypovitaminosis D, in a wide range of research settings, without confounding changes in PTH, Ca, and P