Analytical Interference by Contrast Agents in Biochemical Assays

Objective. To provide a clinically relevant overview of the analytical interference by contrast agents (CA) in laboratory blood test measurements. Materials and Methods. The effects of five CAs, gadobutrol, gadoterate meglumine, gadoxetate disodium, iodixanol, and iomeprol, were studied on the 29 most frequently performed biochemical assays. One-day-old plasma, serum, and whole blood were spiked with doses of each agent such that the gadolinium agents and the iodine agents reached concentrations of 0.5 mM and 12 mg iodine/mL, respectively. Subsequently, 12 assays were reexamined using 1/2 and 1/4 of these CA concentrations. The results were assessed statistically by a paired Student’s t-test. Results. Iodixanol produced a negative interference on the bicarbonate (p=0.011), lactate dehydrogenase (p<0.0001), and zinc (p=0.0034) assays and a positive interference on the albumin (p=0.0062), calcium (p<0.0001), ionized calcium (p=0.0086), iron (p<0.0001), and potassium (p=0.0003) assays. Iomeprol produced a negative interference on the bicarbonate (p=0.0057) and magnesium (p=0.0001) assays and a positive interference on the calcium (p<0.0001) and potassium (p=0.0012) assays. Gadoxetate disodium produced a negative interference on the iron (p<0.0001) and zinc (p<0.0001) assays and a positive interference on the sodium (p=0.032) assay. Conclusion. CAs cause analytical interference. Attention should be given to the above-mentioned analyte-CA combinations when assessing laboratory blood test results obtained after CA administration

Pathologic Correlation of PET-CT Based Auto Contouring for Radiation Planning in Lung Cancer

Purpose/Objective(s): Radiation therapy in lung cancer relies on CT and functional imaging (FDG-PET) to delineate tumor volumes. Semi-automatic contouring tools have been developed for PET to improve on the inter-observer bias of manual contouring and intrinsic differences in imaging equipment. A common method involves using a threshold at a given percentage of the max activity, which may be less accurate with smaller tumors and tumors with low source to background ratio. To overcome this deficiency, a gradient algorithm, which detects changes in image counts at the border of the tumor, has been developed. Few studies have correlated these methods to pathological specimens. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

The trans-activation domain of the sporulation response regulator Spo0A revealed by X-ray crystallography

Sporulation in Bacillus involves the induction of scores of genes in a temporally and spatially co-ordinated programme of cell development. Its initiation is under the control of an expanded two-component signal transduction system termed a phosphorelay. The master control element in the decision to sporulate is the response regulator, Spo0A, which comprises a receiver or phosphoacceptor domain and an effector or transcription activation domain. The receiver domain of Spo0A shares sequence similarity with numerous response regulators, and its structure has been determined in phosphorylated and unphosphorylated forms. However, the effector domain (C-Spo0A) has no detectable sequence similarity to any other protein, and this lack of structural information is an obstacle to understanding how DNA binding and transcription activation are controlled by phosphorylation in Spo0A. Here, we report the crystal structure of C-Spo0A from Bacillus stearothermophilus revealing a single alpha -helical domain comprising six alpha -helices in an unprecedented fold. The structure contains a helix-turn-helix as part of a three alpha -helical bundle reminiscent of the catabolite gene activator protein (CAP), suggesting a mechanism for DNA binding. The residues implicated in forming the sigma (A)-activating region clearly cluster in a flexible segment of the polypeptide on the opposite side of the structure from that predicted to interact with DNA. The structural results are discussed in the context of the rich array of existing mutational data

Simulated moult reduces flight performance but overlap with breeding does not affect breeding success in a long-distance migrant

1.Long-distance migrants are time-constrained as they need to incorporate many annual cycle stages within a year. Migratory passerines moult in the short interval between breeding and migration. To widen this interval, moult may start while still breeding, but this results in flying with moulting wings when food provisioning.2.We experimentally simulated wing gaps in breeding male pied flycatchers by plucking two primary feathers from both wings. We quantified the nest visitations of both parents, proportion of high-quality food brought to the nestlings and adults and nestlings condition. Differences in oxidative damage caused by a possible reduction in flight efficiency were measured in amounts of ROMs and OXY in the blood. We also measured how flight performance was affected with recordings of the male`s escape flight using high-speed cameras. Finally, we collected data on adult survival, clutch size and laying date in the following year.3.“Plucked” males travelled a 5% shorter distance per wingbeat, showing that our treatment reduced flight performance. In line with this, “plucked” males visited their nests less often. Females of “plucked” males, however, visited the nest more often than controls, and fully compensated their partner's reduced visitation rate. As a result, there were no differences between treatments in food quality brought to the nest, adult or chick mass or number of successfully fledged chicks. Males did not differ in their oxidative damage or local survival to the following year. In contrast, females paired with plucked males tended to return less often to breed in the next year in comparison to controls, but this difference was not significant. For the birds that did return, there were no effects on breeding.4.Our results reveal that wing gaps in male pied flycatchers reduce their flight performance, but when it occurs during breeding they prioritise their future reproduction by reducing parental care. As a result, there is no apparent detriment to their condition during breeding. Because non-moulting females are able to compensate their partner's reduced care, there is also no immediate cost to the offspring, but females may pay the cost suffering from a reduced survival

A quantum magnetic analogue to the critical point of water

At the familiar liquid-gas phase transition in water, the density jumps discontinuously at atmospheric pressure, but the line of these first-order transitions defined by increasing pressures terminates at the critical point, a concept ubiquitous in statistical thermodynamics. In correlated quantum materials, a critical point was predicted and measured terminating the line of Mott metal-insulator transitions, which are also first-order with a discontinuous charge density. In quantum spin systems, continuous quantum phase transitions (QPTs) have been investigated extensively, but discontinuous QPTs have received less attention. The frustrated quantum antiferromagnet SrCu$_2$(BO$_3$)$_2$ constitutes a near-exact realization of the paradigmatic Shastry-Sutherland model and displays exotic phenomena including magnetization plateaux, anomalous thermodynamics and discontinuous QPTs. We demonstrate by high-precision specific-heat measurements under pressure and applied magnetic field that, like water, the pressure-temperature phase diagram of SrCu$_2$(BO$_3$)$_2$ has an Ising critical point terminating a first-order transition line, which separates phases with different densities of magnetic particles (triplets). We achieve a quantitative explanation of our data by detailed numerical calculations using newly-developed finite-temperature tensor-network methods. These results open a new dimension in understanding the thermodynamics of quantum magnetic materials, where the anisotropic spin interactions producing topological properties for spintronic applications drive an increasing focus on first-order QPTs.Comment: 8+4 pages, 4+3 figure

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

Cadmium accumulation and interactions with zinc, copper, and manganese, analysed by ICP-MS in a long-term Caco-2 TC7 cell model

The influence of long-term exposure to cadmium (Cd) on essential minerals was investigated using a Caco-2 TC7 cells and a multi-analytical tool: microwave digestion and inductively coupled plasma mass spectrometry. Intracellular levels, effects on cadmium accumulation, distribution, and reference concentration ranges of the following elements were determined: Na, Mg, Ca, Cr, Fe, Mn, Co, Ni, Cu, Zn, Mo, and Cd. Results showed that Caco-2 TC7 cells incubated long-term with cadmium concentrations ranging from 0 to 10 lmol Cd/l for 5 weeks exhibited a significant increase in cadmium accumulation. Furthermore, this accumulation was more marked in cells exposed long-term to cadmium compared with controls, and that this exposure resulted in a significant accumulation of copper and zinc but not of the other elements measured. Interactions of Cd with three elements: zinc, copper, and manganese were particularly studied. Exposed to 30 lmol/l of the element, manganese showed the highest inhibition and copper the lowest on cadmium intracellular accumulation but Zn, Cu, and Mn behave differently in terms of their mutual competition with Cd. Indeed, increasing cadmium in the culture medium resulted in a gradual and significant increase in the accumulation of zinc. There was a significant decrease in manganese from 5 lmol Cd/l exposure, and no variation was observed with copper. Abbreviation: AAS – Atomic absorption spectrometry; CRM– Certified reference material; PBS – Phosphate buffered saline without calcium and magnesium; DMEM – Dubelcco’s modified Eagle’s medium