Characterization of iodothyronine sulfatase activities in human and rat liver and placenta

In conditions associated with high serum iodothyronine sulfate concentrations, e.g. during fetal development, desulfation of these conjugates may be important in the regulation of thyroid hormone homeostasis. However, little is known about which sulfatases are involved in this process. Therefore, we investigated the hydrolysis of iodothyronine sulfates by homogenates of V79 cells expressing the human arylsulfatases A (ARSA), B (ARSB), or C (ARSC; steroid sulfatase), as well as tissue fractions of human and rat liver and placenta. We found that only the microsomal fraction from liver and placenta hydrolyzed iodothyronine sulfates. Among the recombinant enzymes only the endoplasmic reticulum-associated ARSC showed activity toward iodothyronine sulfates; the soluble lysosomal ARSA and ARSB were inactive. Recombinant ARSC as well as human placenta microsomes hydrolyzed iodothyronine sulfates with a substrate preference for 3,3'-diiodothyronine sulfate (3,3'-T(2)S) approximately T(3) sulfate (T(3)S) >> rT(3)S approximately T(4)S, whereas human and rat liver microsomes showed a preference for 3,3'-T(2)S > T(3)S >> rT(3)S approximately T(4)S. ARSC and the tissue microsomal sulfatases were all characterized by high apparent K(m) values (>50 microM) for 3,3'-T(2)S and T(3)S. Iodothyronine sulfatase activity determined using 3,3'-T(2)S as a substrate was much higher in human liver microsomes than in human placenta microsomes, although ARSC is expressed at higher levels in human placenta than in human liver. The ratio of estrone sulfate to T(2)S hydrolysis in human liver microsomes (0.2) differed largely from that in ARSC homogenate (80) and human placenta microsomes (150). These results suggest that ARSC accounts for the relatively low iodothyronine sulfatase activity of human placenta, and that additional arylsulfatase(s) contributes to the high iodothyronine sulfatase activity in human liver. Further research is needed to identify these iodothyronine sulfatases, and to study the physiological importance of the reversible sulfation of iodothyronines in thyroid hormone metabolism

Geodesics and Newton's Law in Brane Backgrounds

In brane world models our universe is considered as a brane imbedded into a higher dimensional space. We discuss the behaviour of geodesics in the Randall-Sundrum background and point out that free massive particles cannot move along the brane only. The brane is repulsive, and matter will be expelled from the brane into the extra dimension. This is rather undesirable, and hence we study an alternative model with a non-compact extra dimension, but with an attractive brane embedded into the higher dimensional space. We study the linearized gravity equations and show that Newton's gravitational law is valid on the brane also in the alternative background.Comment: 14 page

Scalar kinks and fermion localisation in warped spacetimes

Scalar kinks propagating along the bulk in warped spacetimes provide a thick brane realisation of the braneworld. We consider here, a class of such exact solutions of the full Einstein-scalar system with a sine-Gordon potential and a negative cosmological constant. In the background of the kink and the corresponding warped geometry, we discuss the issue of localisation of spin half fermions (with emphasis on massive ones) on the brane in the presence of different types of kink-fermion Yukawa couplings. We analyse the possibility of quasi-bound states for large values of the Yukawa coupling parameter $\gamma_F$ (with $\nu$, the warp factor parameter kept fixed) using appropriate, recently developed, approximation methods. In particular, the spectrum of the low--lying states and their lifetimes are obtained, with the latter being exponentially enhanced for large $\nu \gamma_F$. Our results indicate quantitatively, within this model, that it is possible to tune the nature of warping and the strength and form of the Yukawa interaction to obtain trapped massive fermion states on the brane, which, however, do have a finite (but very small) probability of escaping into the bulk.Comment: 22 pages, 4 figures, RevTex

Validation of the Dutch Version of the Breakthrough Pain Assessment Tool in Patients With Cancer

Context: Essential for adequate management of breakthrough cancer pain is a combination of accurate (re-)assessment and a personalized treatment plan. The Breakthrough Pain Assessment Tool (BAT) has been proven to be a brief, multidimensional, reliable, and valid questionnaire for the assessment of breakthrough cancer pain. Objectives: The aim of this study was to examine the validity and reliability of the Dutch Language version of the BAT (BAT-DL) in patients with cancer. Methods: The BAT was forward-backward translated into the Dutch language. Thereafter, the psychometric properties of the BAT-DL were tested, that is factor structure, reliability (internal consistency and test-retest reliability), validity (content validity and construct validity), and the responsiveness to change. Results: The BAT-DL confirmed the two-factor structure in 170 patients with cancer: pain severity/impact factor and pain duration/medication efficacy factor. The Cronbach's alpha coefficient was 0.72, and the intraclass correlation for the test-retest reliability was 0.81. The BAT-DL showed to be able to differentiate between different group of patients and correlated significantly with the Brief Pain Inventory. In addition, the BAT-DL was capable to detect clinically important changes over time. Conclusion: The BAT-DL is a valid and reliable questionnaire to assess breakthrough pain in Dutch patients with cancer and is a relevant questionnaire for daily practice

Ultrasound markers for prediction of complex gastroschisis and adverse outcome: longitudinal prospective nationwide cohort study

Objectives: To identify antenatal ultrasound markers that can differentiate between simple and complex gastroschisis and assess their predictive value. Methods: This was a prospective nationwide study of pregnancies with isolated fetal gastroschisis that underwent serial longitudinal ultrasound examination at regular specified intervals between 20 and 37 weeks' gestation. The primary outcome was simple or complex (i.e. involving bowel atresia, volvulus, perforation or necrosis) gastroschisis at birth. Fetal biometry (abdominal circumference and estimated fetal weight), the occurrence of polyhydramnios, intra- and extra-abdominal bowel diameters and the pulsatility index (PI) of the superior mesenteric artery (SMA) were assessed. Linear mixed modeling was used to compare the individual trajectories of cases with simple and those with complex gastroschisis, and logistic regression analysis was used to estimate the strength of association between the ultrasound parameters and outcome. Results: Of 104 pregnancies with isolated fetal gastroschisis included, four ended in intrauterine death. Eighty-one (81%) liveborn infants with simple and 19 (19%) with complex gastroschisis were included in the analysis. We found no relationship between fetal biometric variables and complex gastroschisis. The SMA-PI was significantly lower in fetuses with gastroschisis than in healthy controls, but did not differentiate between simple and complex gastroschisis. Both intra- and extra-abdominal bowel diameters were larger in cases with complex, compared to those with simple, gastroschisis (P < 0.001 and P < 0.005, respectively). The presence of intra-abdominal bowel diameter ≥ 97.7th percentile on at least three occasions, not necessarily on successive examinations, was associated with an increased risk of the fetus having complex gastroschisis (relative risk, 1.56 (95% CI, 1.02–2.10); P = 0.006; positive predictive value, 50.0%; negative predictive value, 81.4%). Conclusions: This large prospective longitudinal study found that intra-abdominal bowel dilatation when present repeatedly during fetal development can differentiate between simple and complex gastroschisis; however, the positive predictive value is low, and therefore the clinical usefulness of this marker is limited

A review on substances and processes relevant for optical remote sensing of extremely turbid marine areas, with a focus on the Wadden Sea

The interpretation of optical remote sensing data of estuaries and tidal flat areas is hampered by optical complexity and often extreme turbidity. Extremely high concentrations of suspended matter, chlorophyll and dissolved organic matter, local differences, seasonal and tidal variations and resuspension are important factors influencing the optical properties in such areas. This review gives an overview of the processes in estuaries and tidal flat areas and the implications of these for remote sensing in such areas, using the Wadden Sea as a case study area. Results show that remote sensing research in extremely turbid estuaries and tidal areas is possible. However, this requires sensors with a large ground resolution, algorithms tuned for high concentrations of various substances and the local specific optical properties of these substances, a simultaneous detection of water colour and land-water boundaries, a very short time lag between acquisition of remote sensing and in situ data used for validation and sufficient geophysical and ecological knowledge of the area. © 2010 The Author(s)

Water vapor toward starless cores: the Herschel view

SWAS and Odin provided stringent upper limits on the gas phase water abundance of dark clouds (x(H2O) < 7x10^-9). We investigate the chemistry of water vapor in starless cores beyond the previous upper limits using the highly improved angular resolution and sensitivity of Herschel and measure the abundance of water vapor during evolutionary stages just preceding star formation. High spectral resolution observations of the fundamental ortho water (o-H2O) transition (557 GHz) were carried out with Herschel HIFI toward two starless cores: B68, a Bok globule, and L1544, a prestellar core embedded in the Taurus molecular cloud complex. The rms in the brightness temperature measured for the B68 and L1544 spectra is 2.0 and 2.2 mK, respectively, in a velocity bin of 0.59 km s^-1. The continuum level is 3.5+/-0.2 mK in B68 and 11.4+/-0.4 mK in L1544. No significant feature is detected in B68 and the 3 sigma upper limit is consistent with a column density of o-H2O N(o-H2O) < 2.5x10^13 cm^-2, or a fractional abundance x(o-H2O) < 1.3x10^-9, more than an order of magnitude lower than the SWAS upper limit on this source. The L1544 spectrum shows an absorption feature at a 5 sigma level from which we obtain the first value of the o-H2O column density ever measured in dark clouds: N(o-H2O) = (8+/-4)x10^12 cm^-2. The corresponding fractional abundance is x(o-H2O) ~ 5x10^-9 at radii > 7000 AU and ~2x10^-10 toward the center. The radiative transfer analysis shows that this is consistent with a x(o-H2O) profile peaking at ~10^-8, 0.1 pc away from the core center, where both freeze-out and photodissociation are negligible. Herschel has provided the first measurement of water vapor in dark regions. Prestellar cores such as L1544 (with their high central densities, strong continuum, and large envelopes) are very promising tools to finally shed light on the solid/vapor balance of water in molecular clouds.Comment: Accepted for publication in Astronomy and Astrophysics (HIFI first results issue

Observer variability of absolute and relative thrombus density measurements in patients with acute ischemic stroke

Introduction: Thrombus density may be a predictor for acute ischemic stroke treatment success. However, only limited data on observer variability for thrombus density measurements exist. This study assesses the variability and bias of four common thrombus density measurement methods by expert and non-expert observers. Methods: For 132 consecutive patients with acute ischemic stroke, three experts and two trained observers determined thrombus density by placing three standardized regions of interest (ROIs) in the thrombus and corresponding contralateral arterial segment. Subsequently, absolute and relative thrombus densities were determined using either one or three ROIs. Intraclass correlation coefficient (ICC) was determined, and Bland–Altman analysis was performed to evaluate interobserver and intermethod agreement. Accuracy of the trained observer was evaluated with a reference expert observer using the same statistical analysis. Results: The highest interobserver agreement was obtained for absolute thrombus measurements using three ROIs (ICCs ranging from 0.54 to 0.91). In general, interobserver agreement was lower for relative measurements, and for using one instead of three ROIs. Interobserver agreement of trained non-experts and experts was similar. Accuracy of the trained observer measurements was comparable to the expert interobserver agreement and was better for absolute measurements and with three ROIs. The agreement between the one ROI and three ROI methods was good. Conclusion: Absolute thrombus density measurement has superior interobserver agreement compared to relative density measurement. Interobserver variation is smaller when multiple ROIs are used. Trained non-expert observers can accurately and reproducibly assess absolute thrombus densities using three ROIs