Assessing venous thrombus in renal cell carcinoma: preliminary results for unenhanced 3D-SSFP MRI.

AIM: To test the potential of unenhanced cardiac- and respiratory-motion-corrected three-dimensional steady-state free precession (3D-SSFP) magnetic resonance imaging (MRI) for the assessment of inferior vena cava (IVC) thrombus in patients with clear-cell renal cell carcinoma (cRCC), compared to standard contrast-enhanced (CE)-MRI and CE-computed tomography (CT). MATERIALS AND METHODS: Eighteen patients with cRCC and IVC thrombus, who received CE-MRI and 3D-SSFP at 1.5 T between June 2015 and December 2017, were included. The diagnostic performance of 3D-SSFP in determining the level of thrombus extension, contrast-to-noise ratio (CNR), and image quality were compared with standard MRI/CT and validated against intraoperative and histopathology results. RESULTS: There was 100% agreement between 3D-SSFP, 83.3% agreement between CE-MRI, and 71.4% agreement between CE-CT and surgical findings regarding the level of IVC thrombus. In addition, 3D-SSFP showed a slightly superior estimate of pathological IVC volume. 3D-SSFP reached a significantly higher CNR in the supra- and infrarenal IVC compared to the morphological sequence T2-weighted half-Fourier axial single-shot fast spin-echo (T2-HASTE) and all phases of CE-MRI. More specifically, 3D-SSFP showed a significantly higher CNR in the infrarenal IVC (mean CNR of 10.09±5.74 versus 4.21±2.33 in the delayed phase, p≤0.001) and in the suprarenal IVC (mean CNR of 9.22±4.11 versus 4.84±5.74 in the late arterial phase, p=0.015). CE-CT also was significantly inferior to 3D-SSFP (p≤0.01) and slightly inferior to CE-MRI (p>0.05). The thrombus delineation score for 3D-SSFP (4.38±0.67) was higher compared to CE-MRI (3.76±0.56, p=0.005). CONCLUSION: This preliminary study indicates that 3D-SSFP can achieve an accurate assessment of IVC thrombus in cRCC patients without the need for contrast medium administration, being superior to standard MRI and CT.

Cold streams in early massive hot haloes as the main mode of galaxy formation.

Massive galaxies in the young Universe, ten billion years ago, formed stars at surprising intensities. Although this is commonly attributed to violent mergers, the properties of many of these galaxies are incompatible with such events, showing gas-rich, clumpy, extended rotating disks not dominated by spheroids. Cosmological simulations and clustering theory are used to explore how these galaxies acquired their gas. Here we report that they are 'stream-fed galaxies', formed from steady, narrow, cold gas streams that penetrate the shock-heated media of massive dark matter haloes. A comparison with the observed abundance of star-forming galaxies implies that most of the input gas must rapidly convert to stars. One-third of the stream mass is in gas clumps leading to mergers of mass ratio greater than 1:10, and the rest is in smoother flows. With a merger duty cycle of 0.1, three-quarters of the galaxies forming stars at a given rate are fed by smooth streams. The rarer, submillimetre galaxies that form stars even more intensely are largely merger-induced starbursts. Unlike destructive mergers, the streams are likely to keep the rotating disk configuration intact, although turbulent and broken into giant star-forming clumps that merge into a central spheroid. This stream-driven scenario for the formation of discs and spheroids is an alternative to the merger picture.

Towards quantification of vibronic coupling in photosynthetic antenna complexes.

Photosynthetic antenna complexes harvest sunlight and efficiently transport energy to the reaction center where charge separation powers biochemical energy storage. The discovery of existence of long lived quantum coherence during energy transfer has sparked the discussion on the role of quantum coherence on the energy transfer efficiency. Early works assigned observed coherences to electronic states, and theoretical studies showed that electronic coherences could affect energy transfer efficiency--by either enhancing or suppressing transfer. However, the nature of coherences has been fiercely debated as coherences only report the energy gap between the states that generate coherence signals. Recent works have suggested that either the coherences observed in photosynthetic antenna complexes arise from vibrational wave packets on the ground state or, alternatively, coherences arise from mixed electronic and vibrational states. Understanding origin of coherences is important for designing molecules for efficient light harvesting. Here, we give a direct experimental observation from a mutant of LH2, which does not have B800 chromophores, to distinguish between electronic, vibrational, and vibronic coherence. We also present a minimal theoretical model to characterize the coherences both in the two limiting cases of purely vibrational and purely electronic coherence as well as in the intermediate, vibronic regime.

Spin-orbit-coupled fractional oscillators and trapped Bose-Einstein condensates.

We study the ensemble of pseudo-spin 1/2 ultracold bosons, performing Lévy flights, confined in a parabolic potential. The (pseudo-) spin-orbit coupling (SOC) is additionally imposed on these particles. We consider the structure and dynamics of macroscopic pseudospin qubits based on Bose-Einstein condensates, obtained from the above "fractional" bosons. Under "fractional" we understand the substitution of the ordinary second derivative (kinetic energy term) in the Gross-Pitaevskii equation by a so-called fractional Laplacian, characterized by the Lévy index µ. We show that the joint action of interparticle interaction, SOC, and Zeeman splitting in a synthetic magnetic field makes the dynamics of corresponding qubit highly nontrivial with evident chaotic features at both strong interactions and Lévy indices µâ†’1 when the Lévy trajectories of bosons with long jumps dominated over those derived from ordinary Gaussian distribution, corresponding to µ=2. Using analytical and numerical arguments, we discuss the possibilities to control the above qubit using the synergy of SOC, interaction strength, and "fractionality," characterized by the Lévy index µ.

Implementation of the quality management system improves postoperative pain treatment: a prospective pre-/post-interventional questionnaire study.

BACKGROUND: An organizational approach is proposed as an immediate solution for improving postoperative pain (POP) management. The aim was to evaluate the clinical effectiveness of a quality management system (QMS), based on procedure-specific, multimodal analgesic protocols, modified to meet the individual patients' requirements. METHODS: Patients from the orthopaedic, gynaecological, visceral, and trauma surgery departments of the university hospital were involved in two prospective surveys. Survey 1 was performed at baseline and survey 2 was performed after the implementation of QMS within an interval of 1 year. The patients were asked to report pain intensity on the visual rating scale, incidence of analgesia-related side-effects, and incidence of pain interference with the items of life quality and their satisfaction with the treatment of POP. RESULTS: Patients from Survey 2 (n=251) reported 25-30% less pain than those from Survey 1 (n=269) (P<0.0001). Nausea was reported by 40% of the patients from Survey 1 vs 17% from Survey 2, vomiting by 25 vs 11% and fatigue by 76% in Survey 1 vs 30% in Survey 2 (P<0.0001). Life quality and patients' satisfaction improved in Survey 2 vs Survey 1 (P<0.001). CONCLUSIONS: The implementation of QMS allowed the reduction in POP intensity with a simultaneous decrease in analgesia-related side-effects. This has led to an increased quality of life and patient satisfaction.

Independent phasing of rephasing and non-rephasing 2D electronic spectra.

Assigning absolute phase to two-dimensional (2D) third-order nonlinear optical signals generally requires acquiring both the rephasing and the non-rephasing signals and comparing the sum of the two to spectrally resolved pump-probe spectra. To date, however, Gradient Assisted Photon Echo Spectroscopy (GRAPES) has only been able to acquire rephasing spectra. Such a constraint requires a new phasing protocol. Here, we analytically prove that the rephasing and non-rephasing spectra can be phased independently using pump-probe signal. We verify this result holds even for finite duration pulses by simulation. This relationship holds for all 2D spectroscopies, not only GRAPES. In addition, we present improvements to GRAPES that enable acquisition of rephasing and non-rephasing signals in different phase-matched directions. We employ our phasing protocol to phase the data for laser dye IR-144, leading to reconstruction of purely absorptive 2D spectrum.

Primates and primatologists: social contexts for interspecies pathogen transmission.

Humans and nonhuman primates (NHP) interact in a variety of contexts. The frequency, duration, and intensity of interspecies interaction influence the likelihood that contact results in cross-species transmission of infectious agents. In this study, we present results of a cross-sectional survey of attendees at a national conference of primatologists, characterizing their occupational exposures to NHP. Of 116 individuals who participated in the study, 68.1% reported having worked with NHP in a field setting, 68.1% in a laboratory setting, and 24.1% at a zoo or animal sanctuary. Most subjects (N=98, 84.5%) reported having worked with multiple NHP taxa, including 46 (39.7%) who had worked with more than five distinct taxa. Sixty-nine subjects (59.5%) recalled having been scratched by a NHP and 48 (41.1%) had been bitten; 32 subjects reporting being bitten more than once. Eleven subjects (9.5%) reported having been injured by a needle containing NHP tissue or body fluids. We conclude that primatologists are at high risk for exposure to NHP-borne infectious agents. Furthermore, primatologists' varied occupational activities often bring them into contact with multiple NHP species in diverse contexts and geographic areas, over extended periods of time, making them a unique population with respect to zoonotic and anthropozoonotic disease risk.

The need for a new medical model: a challenge for biomedicine.

The dominant model of disease today is biomedical, and it leaves no room within tis framework for the social, psychological, and behavioral dimensions of illness. A biopsychosocial model is proposed that provides a blueprint for research, a framework for teaching, and a design for action in the real world of health care.

Modeling the absorption behavior of solar thermal collector coatings utilizing graded alpha-C:H/TiC layers.

Wavelength selective coatings are of common use in order to enhance the efficiency of devices heated by radiation such as solar thermal collectors. The use of suitable materials and the optimization of coating layer thicknesses are advisable ways to maximize the absorption. Further improvement is achievable by embedding particles in certain layers in order to modify material properties. We focus on optimizing the absorption behavior of a solar collector setup using copper as substrate, a layer of amorphous hydrogenated carbon with embedded titanium carbide particles (a-C:H/TiC), and an antireflection coating of amorphous silicon dioxide (aSiO(2)). For the setup utilizing homogeneous particle distribution, a relative absorption of 90.98% was found, while inhomogeneous particle embedding yielded 98.29%. These results are particularly interesting since until now, absorption of more than 95% was found only by using embedded Cr but not by using the more biocompatible Ti.

Analysis of organo-silica interactions during valve formation in synchronously growing cells of the diatom Navicula pelliculosa.

Biologically formed silica is produced at ambient conditions under the control of molecular and physicochemical processes that are apparently integrated in biosilica morphogenesis, but the mechanisms are not yet fully understood. With the recent identification of small polypeptides and proteins that are encapsulated inside the biosilica and functional in silica polymerization in vitro, it is of importance to determine whether interactions between inorganic silica species and these organic compounds occur in vivo. A time-resolved analysis of valve formation in synchronously growing cells of the diatom species Navicula pelliculosa enabled us to characterize the relevant chemical bonds by attenuated total reflectance Fourier-transformed infrared (ATR-FTIR) spectroscopy. Typically, inorganic bonds of Si-O-Si (bands at 1058, 843 cm(-1)), Si-OH (3689 cm(-1)), and P=O (1239 cm(-1)) and organic bonds of proteinaceous matter (with the amide I and II bands at 1642 and 1543 cm(-1), respectively) were positively identified during one cycle of valve formation. The observed variations in FTIR band intensity and location represented specific interactions between organic and inorganic molecules during the major silicification event, during which stretching of the Si-O bonds was predominantly noticed. The experimentally obtained frequencies (nu) of the major bonds corresponded to those that were obtained by MM+ and PM3 FTIR simulations for organo-silica interactions based on biomolecules that are proposed to be involved in biosilica formation. The results indicated that hydrogen bonds originated from interactions, albeit weak, between organic phosphate or amine groups to the inorganic hydroxyl groups or oxygen atoms from the silicic acid and/or silica. The existence of covalent P-O-Si bonds and electrostatic interactions could not be excluded. These interactions clearly suggest that biomolecules actively contribute to the silica polymerization process during valve formation in N. pelliculosa, and also might act comparably in other diatoms species in which similar biomolecules have been identified.

The German Acromegaly Registry: description of the database and initial results.

UNLABELLED: Patient registries are valuable tools to study long-term morbidity and mortality of rare diseases. Acromegaly is rare (incidence 3-4/mill/year, prevalence 40-70/mill; approx. 300 new patients/yr and up to 5700 patients in Germany). Diagnostic and therapeutic possibilities have considerably improved, but treatment results remain often unsatisfactory. The main cause is residual disease activity after surgery, most importantly due to invasive macroadenomas. The German Acromegaly Registry is an initiative of the Pituitary Study Group of the German Endocrine Society (DGE). Formally established in January 2003 by the Board of the DGE, long-term financial support is guaranteed by an unrestricted grant from Novartis Pharma GmbH to the DGE. The registry cooperates closely with the United Kingdom and the Austrian registries. The aim of the German Acromegaly Registry is to establish a database of sufficient epidemiological strength in order to (1) document co-morbidity and mortality, (2) provide data on diagnostic and therapeutic procedures/effectiveness, (3) enable comparison of procedures in different national centres, (4) provide information for patient support groups/interaction with health care providers, (5) enable comparison with other national registries within Europe. The registry has at present 82 participating centres, and 42 have included patients (20 university clinics, 8 non-university hospitals, 14 centres in private practice). The database aims to include all acromegalic patients in Germany who are cared for and treated at present. Up to December 2005 1543 patients have been entered in a retrospective manner. Data collection is by external monitoring by highly trained study nurses who visit the individual centres. Inclusion is planned to continue at a rate of 500 per year. Starting in 2005 centres are revisited every 3 years at a rate of 500 per year (prospective phase of the registry). Quality of the data has been validated by an independent monitoring team which demonstrated high data concordance. CONCLUSIONS: Initial results of the German Acromegaly Registry show that it was possible to include a large number of patients within 3 years into the registry. Data quality has been validated and shown to be satisfactory. Therefore, the registry will be a useful tool to study long-term morbidity and mortality in a large series of patients.

Lack of c-jun expression in a transformed cell line isolated by glucocorticoid promotion of ras-transfected rat embryo fibroblasts.

Rat embryo fibroblasts (REFs) are inefficiently transformed by the T24-ras oncogene. A contributing factor to cellular resistance to transformation is the limited tolerance to p21-ras oncoprotein expression. Here we present data suggesting that long-term glucocorticoid treatment of ras oncogene-transfected REFs results in increased tolerance to p21-ras oncoproteins, leading to expression of the transformed phenotype. Stably transformed cell lines that expressed high levels of H-ras and could be maintained in the absence of hormone were isolated. In three out of four lines studied, the AP-1-dependent collagenase gene was expressed at a low level. In one of these lines, low collagenase expression was paralleled by lack of c-jun mRNA. Immunochemical analysis revealed that progression to hormone independence was not paralleled by mutations in the p53 gene. We propose that a decreased expression of AP-1-driven genes may result in increased tolerance to p21-ras oncoprotein.

Tumorigenic and metastatic properties of two ras-oncogene transfected rat fibrosarcoma cell lines defective in c-jun.

We here report the spontaneous loss of both homologues of the c-jun gene in two cell lines, isolated after transfection of rat embryo fibroblasts with single ras-oncogenes. These cells lines (designated A14 and B25) grow rapidly in vitro, have transformed morphologies and are invasive through reconstituted basal membranes. Both c-jun defective cell lines were found to be tumorigenic and metastatic in athymic mice. Loss of c-jun was paralleled by a dramatic decrease in interstitial collagenase expression, whereas stromelysin mRNA expression in c-jun- A14 and B25 cells was similar to that observed in c-jun+ transformed cell lines. Transient transfection experiments using reporter plasmids showed that stromelysin promoter activity in A14 cells was severely impaired by a point mutation in the -71 to -65 AP-1 motif, and was inhibited by a Jun dominant negative mutant. Gel mobility shift studies demonstrated the presence of a factor in A14 nuclear extracts capable of binding the stromelysin TRE. This factor bound JunB, JunD and Fos antibodies. Our findings suggest that c-Jun is not required for the tumorigenic and metastatic potential of ras-transformed fibrosarcoma cells, and that AP-1 protein(s) lacking c-Jun are capable of activating the stromelysin gene promoter.

Characterization of beta-adrenergic receptor subtypes in androgen-induced mouse kidney hypertrophy using a new high-affinity ligand, [125I]iodocyanopindolol.

In fully developed androgen-induced hypertrophy of female mouse kidney, beta-adrenergic receptors per unit membrane protein were increased approx. 2.5-fold, as measured by the binding of [125I]iodocyanopindolol, with no change in apparent dissociation constants (Kd range 20-25 pM). Membrane protein relative to total kidney protein, Na+/K+-dependent ATPase (EC 3.6.1.3) and 5'-nucleotidase (EC 3.1.3.5) activities and cholesterol content per unit membrane protein did not differ significantly in preparations from control and treated animals. The binding of iodocyanopindolol to kidney membranes was characterized with respect to association and dissociation kinetics, and also in regard to the less-specific contributions of other major catecholamine or indolamine receptors, using mixtures of the corresponding specific competitors. beta 1-selective drugs, practolol and metoprolol, and beta 2-selective agents, IPS-339 and zinterol, were competed with iodocyanopindolol to assess the receptor type specificity, and the ensuing binding profiles were dissected by a nonlinear regression analysis as described by Munson, P.J. and Rodbard, D. (Anal. Biochem. (1982) 107, 220-239). Most of the androgen-induced beta-adrenergic receptors had the binding properties corresponding to beta 2-subtype. No consistent increase in the density of beta 1-adrenergic receptors could be shown.

Controlled silica synthesis inspired by diatom silicon biomineralization.

Silica becomes increasingly used in chemical, pharmaceutical, and (nano)technological processes, resulting in an increased demand for well-defined silicas and silica-based materials. The production of highly structured silica from cheap starting materials and under ambient conditions, which is a target for many researchers, is already realized in the formation of diatom biosilica, producing highly hierarchical ordered meso- and macropores silica structures. This notion formed the starting point in our integrative biomolecular and biomimetic study on diatom silicon biomineralization in which we have analyzed silica transformations and structure-direction in polymer-mediated silica syntheses using a combination of (ultra)small-angle X-ray scattering and (cryo)electron microscopy. Using bio-analogous reaction conditions and reagents, such as waterglass and (combinations of) polyethylene oxide (PEO) based polymers, we demonstrate in this review the synthesis of tailor-made mesoporous silicas in which we can, as in biosilica synthesis, control the morphological features of the resulting materials on the nanometer level as well as on the micrometer level.

Acute tubular necrosis after inhalation exposure to methylene chloride. Report of a case.

Nephrotoxic reaction occurred after inhalation exposure to methylene chloride. This exposure is associated with acute renal failure, myoglobinuria, hypocomplementemia, and liver enzyme elevations. Pathologic specimens, both light and electron microscopic, demonstrate renal tubular damage. We conclude that methylene chloride may have potential as both a hepatotoxic and nephrotoxic agent when inhaled at high concentrations over an extended period of time.

Antipyrine as a probe for human oxidative drug metabolism: identification of the cytochrome P450 enzymes catalyzing 4-hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation.

BACKGROUND AND OBJECTIVE: Antipyrine has been widely used as a probe drug for human oxidative drug metabolism. To evaluate the role of antipyrine as a model drug, we have identified the cytochrome P450 enzymes involved in 4-hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation. METHODS: We used the following methods for this study: (1) determination of enzyme kinetics for antipyrine metabolite formation in human liver microsomes, (2) inhibition studies with antibodies and inhibitors, and (3) formation of metabolites by stable expressed human P450 enzymes. RESULTS: Antipyrine biotransformation could be described by Michaelis-Menten kinetics: norantipyrine: maximum rate of metabolite formation (Vmax), 0.91 +/- 0.04 nmol . mg-1 . min-1; Michaelis-Menten constant (Km), 19.0 +/- 0.8 mmol/L; 4-hydroxyantipyrine: Vmax, 1.54 +/- 0.08 nmol . mg-1 . min-1;Km,39.6 +/- 2.5 mmol/L. Antibodies against CYP3A4 inhibited the formation of 4-hydroxyantipyrine by 25% to 65%. LKM-2 antibodies (anti-CYP2C) caused a 75% to 100% inhibition of norantipyrine and a 58% to 80% inhibition of 3-hydroxymethylantipyrine formation. Sulfaphenazole inhibited the formation of 3-hydroxymethylantipyrine and norantipyrine by about 50%. Furafylline and fluvoxamine inhibited norantipyrine, 4-hydroxyantipyrine, and 3-hydroxymethylantipyrine formation by about 30%, 30%, and 50%, respectively. Ketoconazole reduced formation of norantipyrine, 3-hydroxymethylantipyrine, and 4-hydroxyantipyrine by up to 80%. Formation in stable expressed enzymes indicated involvement of CYP1A2, CYP2B6, CYP2C, and CYP3A4 in metabolite formation. CONCLUSION: Antipyrine metabolites are formed by at least six hepatic cytochrome P450 enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, and CYP3A4). 4-Hydroxylation is mainly catalyzed by CYP3A4 and, to a lesser extent, by CYP1A2. The CYP2C subfamily contains the predominant enzymes for norantipyrine formation, and CYP1A2 is also involved. Formation of 3-hydroxymethylantipyrine is mediated by CYP1A2 and CYP2C9. Because several cytochrome P450 enzymes are involved in the formation of each metabolite, antipyrine is not well suited as a probe for distinct human cytochrome P450 enzymes.

Structure of a genome region of the Lactobacillus gasseri temperate phage phiadh covering a repressor gene and cognate promoters.

By sequencing the DNA regions which flank the intG gene encoding integrase of the temperate Lactobacillus (Lb.) gasseri bacteriophage phiadh, a continuous sequence of 6590 bp was established. It encompasses five newly identified ORFs, of which four are located upstream, and one (orfC) downstream of intG. Proteins corresponding to the expected products of the intG upstream coding regions, orfA (33 kDa), orf2 (14 kDa), rad (12.1 kDa), and tec (7.9 kDa), were identified by in vitro expression of subcloned DNA fragments. Rad shares homology with transcription regulators, including SinR of Bacillus species and the repressor of phage phi105. The gporf2 is similar to predicted products of topologically equivalent coding regions of the Lactococcus lactis phage TP901-1 and the B. subtilis phage phi105. Promoters for the divergently oriented rad and tec genes were mapped within the 435-bp region between them and specify overlapping transcripts with extended 5'-untranslated sequences. As shown with lacZ fusions, Rad repressed transcription from the tec and rad promoters 20- and 5-fold, respectively. In Lb. gasseri, weak expression of cloned rad ws sufficient to mediate immunity towards phiadh.

The clinical application of the biopsychosocial model.

How physicians approach patients and the problems they present is much influenced by the conceptual models around which their knowledge is organized. In this paper the implications of the biopsychosocial model for the study and care of a patient with an acute myocardial infarction are presented and contrasted with approaches used by adherents of the more traditional biomedical model. A medical rather than psychiatric patient was selected to emphasize the unity of medicine and to help define the place of psychiatrists in the education of physicians of the future.