Variations in radioiodine ablation: decision-making after total thyroidectomy.

BACKGROUND: The role of radioiodine treatment following total thyroidectomy for differentiated thyroid cancer is changing. The last major revision of the American Thyroid Association (ATA) Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer in 2015 changed treatment recommendations dramatically in comparison with the European Association of Nuclear Medicine (EANM) 2008 guidelines. We hypothesised that there is marked variability between the different treatment regimens used today. METHODS: We analysed decision-making in all Swiss hospitals offering radioiodine treatment to map current practice within the community and identify consensus and discrepancies. RESULTS AND CONCLUSION: We demonstrated that for low-risk DTC patients after thyroidectomy, some institutions offered only follow-up, while RIT with significant activities is recommended in others. For intermediate- and high-risk patients, radioiodine treatment is generally recommended. Dosing and treatment preparation (recombinant human thyroid stimulation hormone (rhTSH) vs. thyroid hormone withdrawal (THW)) vary significantly among centres.

Pluto's Interaction With Energetic Heliospheric Ions.

Pluto energies of a few kiloelectron volts and suprathermal ions with tens of kiloelectron volts and above. We measure this population using the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument on board the New Horizons spacecraft that flew by Pluto in 2015. Even though the measured ions have gyroradii larger than the size of Pluto and the cross section of its magnetosphere, we find that the boundary of the magnetosphere is depleting the energetic ion intensities by about an order of magnitude close to Pluto. The intensity is increasing exponentially with distance to Pluto and reaches nominal levels of the interplanetary medium at about 190R P distance. Inside the wake of Pluto, we observe oscillations of the ion intensities with a periodicity of about 0.2 hr. We show that these can be quantitatively explained by the electric field of an ultralow-frequency wave and discuss possible physical drivers for such a field. We find no evidence for the presence of plutogenic ions in the considered energy range.

Multicenter validation of cancer gene panel-based next-generation sequencing for translational research and molecular diagnostics.

The simultaneous detection of multiple somatic mutations in the context of molecular diagnostics of cancer is frequently performed by means of amplicon-based targeted next-generation sequencing (NGS). However, only few studies are available comparing multicenter testing of different NGS platforms and gene panels. Therefore, seven partner sites of the German Cancer Consortium (DKTK) performed a multicenter interlaboratory trial for targeted NGS using the same formalin-fixed, paraffin-embedded (FFPE) specimen of molecularly pre-characterized tumors (n = 15; each n = 5 cases of Breast, Lung, and Colon carcinoma) and a colorectal cancer cell line DNA dilution series. Detailed information regarding pre-characterized mutations was not disclosed to the partners. Commercially available and custom-designed cancer gene panels were used for library preparation and subsequent sequencing on several devices of two NGS different platforms. For every case, centrally extracted DNA and FFPE tissue sections for local processing were delivered to each partner site to be sequenced with the commercial gene panel and local bioinformatics. For cancer-specific panel-based sequencing, only centrally extracted DNA was analyzed at seven sequencing sites. Subsequently, local data were compiled and bioinformatics was performed centrally. We were able to demonstrate that all pre-characterized mutations were re-identified correctly, irrespective of NGS platform or gene panel used. However, locally processed FFPE tissue sections disclosed that the DNA extraction method can affect the detection of mutations with a trend in favor of magnetic bead-based DNA extraction methods. In conclusion, targeted NGS is a very robust method for simultaneous detection of various mutations in FFPE tissue specimens if certain pre-analytical conditions are carefully considered.

A consolidated analysis of the physiologic and molecular responses induced under acid stress in the legume-symbiont model-soil bacterium Sinorhizobium meliloti.

Abiotic stresses in general and extracellular acidity in particular disturb and limit nitrogen-fixing symbioses between rhizobia and their host legumes. Except for valuable molecular-biological studies on different rhizobia, no consolidated models have been formulated to describe the central physiologic changes that occur in acid-stressed bacteria. We present here an integrated analysis entailing the main cultural, metabolic, and molecular responses of the model bacterium Sinorhizobium meliloti growing under controlled acid stress in a chemostat. A stepwise extracellular acidification of the culture medium had indicated that S. meliloti stopped growing at ca. pH 6.0-6.1. Under such stress the rhizobia increased the O2 consumption per cell by more than 5-fold. This phenotype, together with an increase in the transcripts for several membrane cytochromes, entails a higher aerobic-respiration rate in the acid-stressed rhizobia. Multivariate analysis of global metabolome data served to unequivocally correlate specific-metabolite profiles with the extracellular pH, showing that at low pH the pentose-phosphate pathway exhibited increases in several transcripts, enzymes, and metabolites. Further analyses should be focused on the time course of the observed changes, its associated intracellular signaling, and on the comparison with the changes that operate during the sub lethal acid-adaptive response (ATR) in rhizobia.

Pluto's interaction with its space environment: Solar wind, energetic particles, and dust.

The New Horizons spacecraft carried three instruments that measured the space environment near Pluto as it flew by on 14 July 2015. The Solar Wind Around Pluto (SWAP) instrument revealed an interaction region confined sunward of Pluto to within about 6 Pluto radii. The region's surprisingly small size is consistent with a reduced atmospheric escape rate, as well as a particularly high solar wind flux. Observations from the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument suggest that ions are accelerated and/or deflected around Pluto. In the wake of the interaction region, PEPSSI observed suprathermal particle fluxes equal to about 1/10 of the flux in the interplanetary medium and increasing with distance downstream. The Venetia Burney Student Dust Counter, which measures grains with radii larger than 1.4 micrometers, detected one candidate impact in ±5 days around New Horizons' closest approach, indicating an upper limit of <4.6 kilometers(-3) for the dust density in the Pluto system.

The effects of cold stress on the phenolic compounds and antioxidant capacity of grapevine (Vitis vinifera L.) leaves.

According to some estimates, a 70% increase in crop yield could be achieved if the environmental conditions were close to the optimum ones for a given plant, which is why the identification and control of adverse environmental effects is a top priority in many countries worldwide. This paper contains a discussion of the changes in selected elements of the secondary metabolism in the leaves of two grapevine varieties (Vitis vinifera L.) with a different degree of tolerance to cold stress during prolonged and constant low temperature stress. The analyses have shown that the more-tolerant variety was characterized by a higher content of phenolic compounds, better radical-scavenging capacity and stronger reducing power. However, the cold stress caused a decrease in the concentration of the phenolics and decreased the scavenging capacity in the leaves of both varieties. Four phenolic acids have been identified in the extracts from the leaves of both grapevines: caffeic acid, p-coumaric acid, ferulic acid and a caffeic acid derivative. Caffeic acid appeared in the highest concentrations in all the leaf extracts. Additionally, it has been noted that in the leaves of the varieties susceptible and tolerant to cold stress, the prolonged exposure to low temperature caused a considerable reduction of the content of all identified phenolic acids. The results of the analyses have demonstrated large differences in the functioning of the secondary metabolism in response to the same stressor.

Improved analysis of ultra-high molecular mass polystyrenes in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using DCTB matrix and caesium salts.

RATIONALE: The ionization of polystyrenes in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is typically achieved by the use of silver salts. Since silver salts can cause severe problems, such as cluster formation, fragmentation of polymer chains and end group cleavage, their substitution by alkali salts is highly desirable. METHODS: The influence of various cations (Ag(+), Cs(+) and Rb(+)) on the MALDI process of polystyrene (PS) mixtures and high mass polystyrenes was examined. The sample preparation was kept as straightforward as possible. Consequently, no recrystallization or other cleaning procedures were applied. RESULTS: The investigation of a polystyrene mixture showed that higher molecular polystyrenes could be more easily ionized using caesium, rather than rubidium or silver salts. In combination with the use of DCTB as matrix a high-mass polymer analysis could be achieved, which was demonstrated by the detection of a 1.1 MDa PS. CONCLUSIONS: A fast, simple and robust MALDI sample preparation method for the analysis of ultra-high molecular weight polystyrenes based on the use of DCTB and caesium salts has been presented. The suitability of the presented method has been validated by using different mass spectrometers and detectors.

An integrated time-of-flight versus residual energy subsystem for a compact dual ion composition experiment for space plasmas.

We have developed a novel concept for a Compact Dual Ion Composition Experiment (CoDICE) that simultaneously provides high quality plasma and energetic ion composition measurements over 6 decades in ion energy in a wide variety of space plasma environments. CoDICE measures the two critical ion populations in space plasmas: (1) mass and ionic charge state composition and 3D velocity and angular distributions of ∼10 eV/q-40 keV/q plasma ions­CoDICE-Lo and (2) mass composition, energy spectra, and angular distributions of ∼30 keV-10 MeV energetic ions­CoDICE-Hi. CoDICE uses a common, integrated Time-of-Flight (TOF) versus residual energy (E) subsystem for measuring the two distinct ion populations. This paper describes the CoDICE design concept, and presents results of the laboratory tests of the TOF portion of the TOF vs. E subsystem, focusing specifically on (1) investigation of spill-over and contamination rates on the start and stop microchannel plate (MCP) anodes vs. secondary electron steering and focusing voltages, scanned around their corresponding model-optimized values, (2) TOF measurements and resolution and angular resolution, and (3) cross-contamination of the start and stop MCPs' singles rates from CoDICE-Lo and -Hi, and (4) energy resolution of avalanche photodiodes near the lower end of the CoDICE-Lo energy range. We also discuss physical effects that could impact the performance of the TOF vs. E subsystem in a flight instrument. Finally, we discuss advantages of the CoDICE design concept by comparing with capabilities and resources of existing flight instruments.

MR anatomy of salivary glands in the dog.

This retrospective analysis documented the magnetic resonance imaging (MRI) appearance of normal salivary glands based on 101 studies in dogs with no detectable disease in the splanchnocranium. Surface, signal intensity, homogeneity, structure, symmetry and the relationship of glands to surrounding tissues were noted, and gland topography was assessed with E12 plastinated embedded sections. Signal intensity of salivary glands was isointense (7-40%) to hyperintense (60-90%) to muscle tissue on T1- and hyperintense on T2-weighted images. Salivary glands had an increased T1 signal after contrast medium was applied. Salivary gland structure appeared homogeneous in mandibular and major sublingual glands and heterogeneous in zygomatic and parotid glands. Consistent landmarks were the external auditory canal for parotid glands, the digastric muscle for mandibular and major sublingual glands, and the pterygopalatine fossa for zygomatic glands. The minor sublingual and ventral buccal glands could not be localized with low-field MRI.

CT sialography in the dog - a cadaver study.

To document computed tomographic topography of salivary glands and their ducts in dogs, a retrograde filling with methylcellulose and iodinated contrast medium was performed in three cadavers. Demarcation of the parotid, mandibular and zygomatic glands was achieved. Surrounding structures were imaged without beam hardening artefacts. Landmarks for the parotid, mandibular and zygomatic glands were the external acoustic canal, the mandibular angle and the pterygopalatine fossa, respectively. Sialograms of the parotid, mandibular and zygomatic ducts were achieved, whereas neither the sublingual glands nor their ducts could be contrasted. The images provide a three-dimensional visualization of the salivary glands and their ducts.

Training of attention and memory deficits in children with acquired brain injury.

UNLABELLED: This pilot study concerns cognitive rehabilitation of children with acquired brain injury (ABI). AIM: The aim is threefold; to determine (1) whether the Amsterdam Memory and Attention Training for Children (AMAT-C) programme for children with ABI can be integrated in the child's school, (2) whether supervision in the school-setting maintains the child's motivation throughout the training programme and (3) whether positive changes in memory, attention and executive functions are found with this implementation of the training method. METHODS: Seven children with memory and/or attention deficits after ABI were trained with AMAT-C. Measures used were programme evaluation questions, neuropsychological tests and a questionnaire concerning executive functions. RESULTS: Overall, children, parents and trainers were satisfied with the programme and the children were motivated throughout the programme. The children showed significant improvements in neuropsychological subtests, primarily in tests of learning and memory. No overall change in executive functions was noted. CONCLUSION: Provision of AMAT-C training and supervision at the child's school appears to ensure (1) satisfaction with the programme, (2) sustaining of motivation and (3) improvements in learning and memory.

The complete sequence of the 1,683-kb pSymB megaplasmid from the N2-fixing endosymbiont Sinorhizobium meliloti.

Analysis of the 1,683,333-nt sequence of the pSymB megaplasmid from the symbiotic N(2)-fixing bacterium Sinorhizobium meliloti revealed that the replicon has a high gene density with a total of 1,570 protein-coding regions, with few insertion elements and regions duplicated elsewhere in the genome. The only copies of an essential arg-tRNA gene and the minCDE genes are located on pSymB. Almost 20% of the pSymB sequence carries genes encoding solute uptake systems, most of which were of the ATP-binding cassette family. Many previously unsuspected genes involved in polysaccharide biosynthesis were identified and these, together with the two known distinct exopolysaccharide synthesis gene clusters, show that 14% of the pSymB sequence is dedicated to polysaccharide synthesis. Other recognizable gene clusters include many involved in catabolic activities such as protocatechuate utilization and phosphonate degradation. The functions of these genes are consistent with the notion that pSymB plays a major role in the saprophytic competence of the bacteria in the soil environment.

Analysis of the chromosome sequence of the legume symbiont Sinorhizobium meliloti strain 1021.

Sinorhizobium meliloti is an alpha-proteobacterium that forms agronomically important N(2)-fixing root nodules in legumes. We report here the complete sequence of the largest constituent of its genome, a 62.7% GC-rich 3,654,135-bp circular chromosome. Annotation allowed assignment of a function to 59% of the 3,341 predicted protein-coding ORFs, the rest exhibiting partial, weak, or no similarity with any known sequence. Unexpectedly, the level of reiteration within this replicon is low, with only two genes duplicated with more than 90% nucleotide sequence identity, transposon elements accounting for 2.2% of the sequence, and a few hundred short repeated palindromic motifs (RIME1, RIME2, and C) widespread over the chromosome. Three regions with a significantly lower GC content are most likely of external origin. Detailed annotation revealed that this replicon contains all housekeeping genes except two essential genes that are located on pSymB. Amino acid/peptide transport and degradation and sugar metabolism appear as two major features of the S. meliloti chromosome. The presence in this replicon of a large number of nucleotide cyclases with a peculiar structure, as well as of genes homologous to virulence determinants of animal and plant pathogens, opens perspectives in the study of this bacterium both as a free-living soil microorganism and as a plant symbiont.

Antineutrophil cytoplasmic antibodies induce human monocytes to produce oxygen radicals in vitro.

OBJECTIVE: Antineutrophil cytoplasmic antibodies (ANCA) are believed to play a pathogenetic role in necrotizing small-vessel vasculitis. While the involvement of neutrophils in this disease has been extensively studied in vitro, we undertook to analyze thoroughly the contribution of monocytes to tissue destruction in systemic vasculitis. METHODS: Monocytes obtained from normal human individuals were stimulated by ANCA isolated from patients with active vasculitis. The formation of oxygen radicals was measured by a fluorometric assay using 2',7'-dichlorofluorescin diacetate. RESULTS: ANCA induced monocytes to produce oxygen radicals, resulting in a mean 43% increase (range 21-84%) in oxygen radical formation compared with normal IgG. The formation of reactive oxygen species was time and concentration dependent and was also induced by ANCA F(ab')2 fragments. Normal nonspecific IgG or their corresponding F(ab')2 fragments induced no release or very little release of oxygen radicals. Preincubation of monocytes with the Fcy receptor type II-blocking monoclonal antibody IV.3 before addition of ANCA greatly reduced formation of oxygen radicals. Using ligand affinity chromatography with proteinase 3 (PR3) and myeloperoxidase (MPO), ANCA were further purified by depletion of patient IgG. The stimulation of monocytes with these pure PR3- and MPO-ANCA confirmed that cellular activation was specifically induced by ANCA. CONCLUSION: These results show that ANCA induce the formation of reactive oxygen species in human monocytes. These findings support the notion that ANCA specifically activate monocytes by several mechanisms to participate in the inflammatory process of ANCA-associated vasculitis.

Metallocyclodextrins as building blocks in noncovalent assemblies of photoactive units for the study of photoinduced intercomponent processes.

Cyclodextrin cups have been employed to build supramolecular systems consisting of metal and organic photoactive/redox-active components; the photoinduced communication between redox-active units assembled in water via noncovalent interactions is established. The functionalization of a beta-cyclodextrin with a terpyridine unit, ttp-beta-CD, is achieved by protection of all but one of the hydroxyl groups by methylation and attachment of the ttp unit on the free primary hydroxyl group. The metalloreceptors [(beta-CD-ttp)Ru(ttp)][PF(6)](2), [(beta-CD-ttp)Ru(tpy)][PF(6)](2), and [Ru(beta-CD-ttp)(2)][PF(6)](2) are synthesized and fully characterized. The [(beta-CD-ttp)Ru(ttp)][PF(6)](2) metalloreceptor exhibits luminescence in water, centered at 640 nm, from the (3)MLCT state with a lifetime of 1.9 ns and a quantum yield of Phi = 4.1 x 10(-)(5). Addition of redox-active quinone guests AQS, AQC, and BQ to an aqueous solution of [(beta-CD-ttp)Ru(ttp)](2+) results in quenching of the luminescence up to 40%, 20%, and 25%, respectively. Measurement of the binding strength indicates that, in saturation conditions, 85% for AQS and 77% for AQC are bound. The luminescence quenching is attributed to an intercomponent electron transfer from the appended ruthenium center to the quinone guest inside the cavity. Control experiments demonstrate no bimolecular quenching at these conditions. A photoactive osmium metalloguest, [Os(biptpy)(tpy)][PF(6)], is designed with a biphenyl hydrophobic tail for insertion in the cyclodextrin cavity. The complex is luminescent at room temperature with an emission band maximum at 730 nm and a lifetime of 116 ns. The osmium(III) species are formed for the study of photoinduced electron transfer upon their assembly with the ruthenium cyclodextrin, [(beta-CD-ttp)Ru(ttp)](2+). Time-resolved spectroscopy studies show a short component of 10 ps, attributed to electron transfer from Ru(II) to Os(III) giving an electron transfer rate 9.5 x 10(9) s(-)(1).

Phylogenetic Analysis of Bacterial Communities Associated with Leaves of the Seagrass Halophila stipulacea by a Culture-Independent Small-Subunit rRNA Gene Approach.

The phylogenetic diversity of the bacterial community associated with leaves of the marine plant Halophila stipulacea in the northern Gulf of Elat was examined by 16S rRNA gene (rDNA) sequence analyses of a clone library. For 59 clones corresponding to 51 ARDRA (amplified rDNA restriction analysis) groups, the sequence of approximately 1 kb was determined, and the fraction of the corresponding ARDRA groups of the leaf library was calculated. The class Proteobacteria was represented by 62.6% of the clone sequences. Most sequences originated from members of the gamma-subclass (27.3%), affiliated with members of the genera Pseudomonas, Vibrio, Marinomonas, Oceanospirillum, and other marine groups. Affiliation to the alpha-subclass was determined for 24.2% of the sequences. They were related to the genera Hyphomonas, Roseobacter, Ruegeria, and Rhizobiaceae. Several alpha-proteobacterial sequences were distantly related to known sequences. Only 4% of the clone sequences were related to beta-Proteobacteria. Additionally, 7.1% of the sequences possibly belonged to the class Proteobacteria, but branched deeply from known subclasses. Several sequences were affiliated to members of the orders Verrucomicrobiales and Planctomycetales, the Holophaga/Acidobacterium phylum, and chloroplasts of marine diatoms.

Participation of the tightly-bound (putative cytoskeleton-bound) polysomes in translation during germination of dormant and non-dormant cereal caryopses.

Research was done on dormant and non-dormant barley cv. Ars caryopses and triticale cv. Grado caryopses treated and non-treated with abscisic acid (ABA). During germination higher participation of populations of so-called tightly-bound polysomes (TBP) in embryos of dormant barley caryopses was observed, as well as their high metabolic activity. In embryos of triticale caryopses of which dormancy was imposed in an artificial way by ABA (100 microM), the strongest incorporation of 14C-amino acids into nascent polypeptide chains in vivo was found in population of TBP, as well as the highest participation among three of the studied fractions (free polysomes, membrane-bound polysomes and tightly-bound polysomes). These results may indicate the significant role of TBP (putative cytoskeleton-bound polysomes--CBP) in maintaining dormancy during imbibition of cereal caryopses.

[Effect of diclofenac on human osteoblasts and their stromal precursors in vitro in relation to arthroplasty]. / Wirkung von Diclofenac auf humane Osteoblasten und stromale Knochenmarkzellen in vitro in bezug auf die Endoprothetik.

INTRODUCTION: Results of animal experiments have demonstrated that the osseous integration of non-cemented prostheses can, at the very least temporarily, be impaired by the application of non-steroidal antiphlogistic agents (such as diclofenac). It is the objective of this study to examine whether there is a direct influence of diclofenac used in usual clinical dosages (3 times 50 mg daily) on bone cells and their progenitor cells which would explain the observed slow integration of the prostheses. METHODS: To investigate this, cultivated human in vitro osteoblasts and stromal bone marrow cells were incubated with increasing doses of the medications. Our study focused on the effect of diclofenac application on proliferation and functional metabolism in both cell lines. The measurable maximal plasma concentration 2 h after the application of one tablet Voltaren 50 reached 1.6 micrograms/ml. This correlated with diclofenac concentrations between 1 and 10 ml found in our experiments. The detected values were correlated to the control group (0 microgram/ml diclofenac). RESULTS: The drug effect upon osteoblasts was higher than on progenitor cells. The proliferation of in vitro stromal bone marrow cells, compared to untreated cells, was found to be decreased. We observed a decrease to 82% at a diclofenac concentration of 1 microgram/ml, Osteoblasts exhibited a decrease to 97.5% at the same concentration. The DNA synthesis increased to 118% in stromal bone marrow cells, in osteoblasts to 144%. In contrast, we detected a neglectible decrease to 92% in the collagen synthesis of osteoblasts compared to untreated cells. The synthesis of osteocalcin by osteoblasts increased to 119%. The alkaline phosphatase activity was found to be decreased to 88% in stromal bone marrow cells and increased in osteoblasts to 111%. CONCLUSION: Temporary inhibiting effects on osseous integration in non-cemented prosthesis by diclofenac could be caused by a disturbance in the anabolic bone metabolism, exhibited by an increase of osteoblastic osteocalcin expression. Osteocalcin as a known negative regulator of the osteoneogenesis is most likely inhibiting the collagen matrix deposition.