Prematurity is related to high placental cortisol in preeclampsia

Fetal growth is compromised in animal models with high cortisol availability. In healthy pregnancies, the fetus is protected from high circulating cortisol levels by the placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which is reduced in preeclampsia. We hypothesized increased placental cortisol availability in preeclampsia as missing link to fetal growth restriction and prematurity. Placental tissue was obtained from 39 pregnant women dichotomized normotensive (n = 16) or preeclamptic (n = 23). Placental steroid hormone metabolites were analyzed by gas chromatography-mass spectrometry. Apparent 11beta-HSD2 enzyme activity was calculated as substrate to product ratio. Estradiol and pregnandiol positively correlated with gestational age. Cortisol was virtually absent in 93.8% of controls, yet detectable in 79.3% of preeclamptic samples resulting in an odds ratio (OR) of 0.019 (95% CI 0.002-0.185) for the presence of placental cortisol. Apparent 11beta-HSD2 activity directly correlated with birth weight (R2 = 0.16; p < 0.02) and gestational age (R2 = 0.11; p < 0.04) ensuing a reduced risk of premature delivery (OR 0.12; 95% CI 0.02-0.58). We conclude that normotensive pregnancies are characterized by an almost completely inactivated placental cortisol. In line with our hypothesis, reduced 11beta-HSD2 activity in preeclampsia is unable to abolish placental cortisol, a finding clearly associated with prematurity and low birth weight.

Call for a reference model of chronic hind limb ischemia to investigate therapeutic angiogenesis

A large number of studies utilize animal models to investigate therapeutic angiogenesis. However, the lack of a standardized experimental model leaves the comparison of different studies problematic. To establish a reference model of prolonged moderate tissue ischemia, we created unilateral hind limb ischemia in athymic rnu-rats by surgical excision of the femoral vessels. Blood flow of the limb was monitored for 60 days by laser Doppler imaging. Following a short postoperative period of substantially depressed perfusion, the animals showed a status of moderate hind limb ischemia from day 14 onwards. Thereafter, the perfusion remained at a constant level (55.5% of normal value) until the end of the observation period. Histopathological assessment of the ischemic musculature on postoperative days 28 and 60 showed essentially no inflammatory cell infiltrate or fibrosis. However, the mitochondrial activity and capillary-to-fiber ratio of the muscular tissue was reduced to 52.7% of normal, presenting with a significant weakness of the ischemic limb evidenced by a progressive decline in performance. Intramuscular injection of culture-expanded human endothelial progenitor cells (EPC) resulted in a significant increase in blood flow (82.0+/-3.5% of normal), capillary density (1.60+/-0.08/muscle fiber) and smooth muscle covered arterioles (8.0+/-0.6/high power field) in the ischemic hind limb as compared to controls (55.0+/-3.1%; 0.99+/-0.03; 5.0+/-0.2). In conclusion, chronic, moderate hind limb ischemia with consistently reduced perfusion levels persisting over a prolonged period can be established reliably in rnu athymic nude rats and is responsive to pro-angiogenic treatments such as EPC transplantation. This study provides a detailed protocol of a highly reproducible reference model to test novel therapeutic options for limb ischemia.

Maternal cholestasis during pregnancy programs metabolic disease in offspring

The intrauterine environment is a major contributor to increased rates of metabolic disease in adults. Intrahepatic cholestasis of pregnancy (ICP) is a liver disease of pregnancy that affects 0.5%-2% of pregnant women and is characterized by increased bile acid levels in the maternal serum. The influence of ICP on the metabolic health of offspring is unknown. We analyzed the Northern Finland birth cohort 1985-1986 database and found that 16-year-old children of mothers with ICP had altered lipid profiles. Males had increased BMI, and females exhibited increased waist and hip girth compared with the offspring of uncomplicated pregnancies. We further investigated the effect of maternal cholestasis on the metabolism of adult offspring in the mouse. Females from cholestatic mothers developed a severe obese, diabetic phenotype with hepatosteatosis following a Western diet, whereas matched mice not exposed to cholestasis in utero did not. Female littermates were susceptible to metabolic disease before dietary challenge. Human and mouse studies showed an accumulation of lipids in the fetoplacental unit and increased transplacental cholesterol transport in cholestatic pregnancy. We believe this is the first report showing that cholestatic pregnancy in the absence of altered maternal BMI or diabetes can program metabolic disease in the offspring.

Response to LIVint-15-00100

Although AST-to-platelet ratio index (APRI) and FIB-4 have been compared with liver biopsy in patients with hepatitis C virus (HCV), hepatitis B virus (HBV), HIV/HCV co-infection, and HIV/HBV co-infection, Johannessen and Lemoine stress that they have not been validated in HIV mono-infected populations in SSA. However, this is unlikely to occur because liver biopsy does not play a role in HIV management and the procedure carries its own risks for complication. Clinicians using APRI and FIB-4 in this setting should be aware of this limitation and should interpret test results in the context of each patient's clinical scenario. This article is protected by copyright. All rights reserved.

Feasible Dose Reduction in Routine Chest Computed Tomography Maintaining Constant Image Quality Using the Last Three Scanner Generations: From Filtered Back Projection to Sinogram-affirmed Iterative Reconstruction and Impact of the Novel Fully Integrated Detector Design Minimizing Electronic Noise

OBJECTIVE The aim of the present study was to evaluate a dose reduction in contrast-enhanced chest computed tomography (CT) by comparing the three latest generations of Siemens CT scanners used in clinical practice. We analyzed the amount of radiation used with filtered back projection (FBP) and an iterative reconstruction (IR) algorithm to yield the same image quality. Furthermore, the influence on the radiation dose of the most recent integrated circuit detector (ICD; Stellar detector, Siemens Healthcare, Erlangen, Germany) was investigated. MATERIALS AND METHODS 136 Patients were included. Scan parameters were set to a thorax routine: SOMATOM Sensation 64 (FBP), SOMATOM Definition Flash (IR), and SOMATOM Definition Edge (ICD and IR). Tube current was set constantly to the reference level of 100 mA automated tube current modulation using reference milliamperes. Care kV was used on the Flash and Edge scanner, while tube potential was individually selected between 100 and 140 kVp by the medical technologists at the SOMATOM Sensation. Quality assessment was performed on soft-tissue kernel reconstruction. Dose was represented by the dose length product. RESULTS Dose-length product (DLP) with FBP for the average chest CT was 308 mGy*cm ± 99.6. In contrast, the DLP for the chest CT with IR algorithm was 196.8 mGy*cm ± 68.8 (P = 0.0001). Further decline in dose can be noted with IR and the ICD: DLP: 166.4 mGy*cm ± 54.5 (P = 0.033). The dose reduction compared to FBP was 36.1% with IR and 45.6% with IR/ICD. Signal-to-noise ratio (SNR) was favorable in the aorta, bone, and soft tissue for IR/ICD in combination compared to FBP (the P values ranged from 0.003 to 0.048). Overall contrast-to-noise ratio (CNR) improved with declining DLP. CONCLUSION The most recent technical developments, namely IR in combination with integrated circuit detectors, can significantly lower radiation dose in chest CT examinations.

Positron emission tomography (PET) imaging of prostate cancer with a gastrin releasing peptide receptor antagonist - from mice to men

UNLABELLED Ex vivo studies have shown that the gastrin releasing peptide receptor (GRPr) is overexpressed on almost all primary prostate cancers, making it a promising target for prostate cancer imaging and targeted radiotherapy. METHODS Biodistribution, dosimetry and tumor uptake of the GRPr antagonist ⁶⁴Cu-CB-TE2A-AR06 [(⁶⁴Cu-4,11-bis(carboxymethyl)-1,4,8,11-tetraazabicyclo(6.6.2)hexadecane)-PEG₄-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-LeuNH₂] were studied by PET/CT in four patients with newly diagnosed prostate cancer (T1c-T2b, Gleason 6-7). RESULTS No adverse events were observed after injection of ⁶⁴Cu-CB-TE2A-AR06. Three of four tumors were visualized with high contrast [tumor-to-prostate ratio > 4 at 4 hours (h) post injection (p.i.)], one small tumor (T1c, < 5% tumor on biopsy specimens) showed moderate contrast (tumor-to-prostate ratio at 4 h: 1.9). Radioactivity was cleared by the kidneys and only the pancreas demonstrated significant accumulation of radioactivity, which rapidly decreased over time. CONCLUSION ⁶⁴Cu-CB-TE2A-AR06 shows very favorable characteristics for imaging prostate cancer. Future studies evaluating ⁶⁴Cu-CB-TE2A-AR06 PET/CT for prostate cancer detection, staging, active surveillance, and radiation treatment planning are necessary.

Imaging the Heliosphere using neutral Atoms from Solar Wind Energy down to 15 eV

We study the spatial and temporal distribution of hydrogen energetic neutral atoms (ENAs) from the heliosheath observed with the IBEX-Lo sensor of the Interstellar Boundary EXplorer (IBEX) from solar wind energies down to the lowest available energy (15 eV). All available IBEX-Lo data from 2009 January until 2013 June were included. The sky regions imaged when the spacecraft was outside of Earth's magnetosphere and when the Earth was moving toward the direction of observation offer a sufficient signal-to-noise ratio even at very low energies. We find that the ENA ribbon—a 20° wide region of high ENA intensities—is most prominent at solar wind energies whereas it fades at lower energies. The maximum emission in the ribbon is located near the poles for 2 keV and closer to the ecliptic plane for energies below 1 keV. This shift is an evidence that the ENA ribbon originates from the solar wind. Below 0.1 keV, the ribbon can no longer be identified against the globally distributed ENA signal. The ENA measurements in the downwind direction are affected by magnetospheric contamination below 0.5 keV, but a region of very low ENA intensities can be identified from 0.1 keV to 2 keV. The energy spectra of heliospheric ENAs follow a uniform power law down to 0.1 keV. Below this energy, they seem to become flatter, which is consistent with predictions. Due to the subtraction of local background, the ENA intensities measured with IBEX agree with the upper limit derived from Lyα observations.

Is the acetabular cup orientation after total hip arthroplasty on a two dimension or three dimension model accurate?

Purpose Malposition of the acetabular component in total hip arthroplasty (THA) is a common surgical problem that can lead to hip dislocation, reduced range of motion and may result in early loosening. The aim of this study is to validate the accuracy and reproducibility of a single x-ray image based 2D/3D reconstruction technique in determining cup inclination and anteversion against two different computer tomography (CT)-based measurement techniques. Methods Cup anteversion and inclination of 20 patients after cementless primary THA was measured on standard anteroposterior (AP) radiographs with the help of the single x-ray 2D/3D reconstruction program and compared with two different 3D CT-based analyses [Ground Truth (GT) and MeVis (MV) reconstruction model]. Results The measurements from the single x-ray 2D/3D reconstruction technique were strongly correlated with both types of CT image-processing protocols for both cup inclination [R²=0.69 (GT); R²=0.59 (MV)] and anteversion [R²=0.89 (GT); R²=0.80 (MV)]. Conclusions The single x-ray image based 2D/3D reconstruction technique is a feasible method to assess cup position on postoperative x-rays. CTscans remain the golden standard for a more complex biomechanical evaluation when a lower tolerance limit (+/-2 degrees) is required.

Optical Light Curve Observations to Determine Attitude States of Space Debris

The currently proposed space debris remediation measures include the active removal of large objects and “just in time” collision avoidance by deviating the objects using, e.g., ground-based lasers. Both techniques require precise knowledge of the attitude state and state changes of the target objects. In the former case, to devise methods to grapple the target by a tug spacecraft, in the latter, to precisely propagate the orbits of potential collision partners as disturbing forces like air drag and solar radiation pressure depend on the attitude of the objects. Non-resolving optical observations of the magnitude variations, so-called light curves, are a promising technique to determine rotation or tumbling rates and the orientations of the actual rotation axis of objects, as well as their temporal changes. The 1-meter telescope ZIMLAT of the Astronomical Institute of the University of Bern has been used to collect light curves of MEO and GEO objects for a considerable period of time. Recently, light curves of Low Earth Orbit (LEO) targets were acquired as well. We present different observation methods, including active tracking using a CCD subframe readout technique, and the use of a high-speed scientific CMOS camera. Technical challenges when tracking objects with poor orbit redictions, as well as different data reduction methods are addressed. Results from a survey of abandoned rocket upper stages in LEO, examples of abandoned payloads and observations of high area-to-mass ratio debris will be resented. Eventually, first results of the analysis of these light curves are provided.

Unearthing the roots of degradation of Quercus pyrenaica coppices: A root-to-shoot imbalance caused by historical management?

Slow growth, branch dieback and scarce acorn yield are visible symptoms of decay in abandoned Quercus pyrenaica coppices. A hypothetical root-to-shoot (R:S) imbalance provoked by historical coppicing is investigated as the underlying driver of stand degradation. After stem genotyping, 12 stems belonging to two clones covering 81 and 16 m2 were harvested and excavated to measure above- and below-ground biomass and nonstructural carbohydrate (NSC) pools. To study root system functionality, root connections and root longevity were assessed by radiocarbon analysis. Seasonality of NSC was monitored on five additional clones. NSC pools, R:S biomass ratio and fine roots-to-foliage ratio were higher in the large clone, whose centennial root system, estimated to be 550 years old, maintained large amounts of sapwood (51.8%) for NSC storage. 248 root connections were observed within the large clone, whereas the small clone showed comparatively simpler root structure (26 connections). NSC concentrations were higher in spring (before bud burst) and autumn (before leaf fall), and lower in summer (after complete leaf expansion); they were always higher in roots than in stems or twigs. The persistence of massive and highly inter-connected root systems after coppicing may lead to increasing R:S biomass ratios and root NSC pools over time. We highlight the need of surveying belowground organs to understand aboveground dynamics of Q. pyrenaica, and suggest that enhanced belowground NSC storage and consumption reflect a trade-off between clonal vegetative resilience and aboveground performance.