Evaluation of results and costs of high precision radiotherapy (VMAT) compared with conventional radiotherapy (3D) in the treatment of cancer patients with spinal cord compression of metastatic origin

BackgroundThe aim of this study was to evaluate the results and economic costs of using volumetric modulated arc therapy (VMAT) (5 fr × 5 Gy), compared with other conventional 3D radiotherapy schemes such as “5 × 4 Gy” and “10 × 3 Gy”.Materials and methodsThe data about the direct costs for the public health system was obtained from the Economic Information “Management per Patient” System available at the Integrated Health Organization Ezkerraldea Enkarterri Cruces. It is a model of real costs per patient which uses a bottom-up methodology which connects all sources of information generated in clinical practice, integrating healthcare information with economic information. This system presents the real cost per individualized patient, and shows the traceability of all clinical care. The costs of “typical patients” requiring hospital admission were identified for each of the three radiotherapy schemes based on the clinical activity and the material and human resources that were used.ResultsThe 5 × 5 Gy scheme has a cost of EUR 4,801.48, which is 1.64% higher (EUR 77) than the “5 × 4 Gy” scheme (EUR 4,724.05). The “10 × 3 Gy” scheme has a cost of EUR 8,394.61, which is 74.8% higher (EUR 3,593) than the “5 × 5 Gy” scheme. The main cost factor in the “10 × 3 Gy” scheme is hospitalization, since patients are at hospital for 2 weeks compared with 1 week in the “5 × 5 Gy” scheme.ConclusionsThe cost per patient of the VMAT “5 × 5 Gy” radiotherapy scheme is notably lower than that of the “10 × 3 Gy” scheme (conventional 3D radiotherapy), with the advantage of being administered in half the time. In relation to the scheme with 5 Gy × 4 sessions, the cost is similar to that of the “5 × 5 Gy” scheme.     

Intramolecular transposition of IS102

It has been postulated that deletions mediated by transposable elements are intramolecular transposition events. An implication of this hypothesis is that the deleted fragment may be recovered if it is capable of autonomous replication. We report here the characterization of the products of intramolecular transposition of the element IS102 in bireplicons. We show that when two origins (ori's) (of pSC101 and R6-5) generate the same copy numbers, two dissociated replicons are recovered as well as the inversions. On the contrary, when two ori's (of pSC101 and pBR322) have different copy numbers, intramolecular transposition results essentially in inversions. However, the very low frequency (5 X 10(-8)) at which intramolecular transpositions in the bireplicons occurs, as compared to the single replicon (10(-4)), suggests that a complete transposition reaction may not be necessary to generate deletions.     

Sir2 is induced by oxidative stress in a yeast model of Huntington disease and its activation reduces protein aggregation

Huntington disease (HD) is a neurodegenerative disorder caused by expansion of CAG trinucleotide repeats, leading to an elongated polyglutamine sequence (polyQ) in the huntingtin protein. Misfolding of mutant polyQ proteins with expanded tracts results in aggregation, causing cytotoxicity. Oxidative stress in HD has been documented in humans as important to disease progression. Using yeast cells as a model of HD, we report that when grown at high glucose concentration, cells expressing mutant polyQ do not show apparent oxidative stress. At higher cell densities, when glucose becomes limiting and cells are metabolically shifting from fermentation to respiration, protein oxidation and catalase activity increases in relation to the length of the polyQ tract. Oxidative stress, either endogenous as a result of mutant polyQ expression or exogenously generated, increases Sir2 levels. Δ sir2 cells expressing expanded polyQ lengths show signs of oxidative stress even at the early exponential phase. In a wild-type background, isonicotinamide, a Sir2 activator, decreases mutant polyQ aggregation and the stress generated by expanded polyQ. Taken together, these results describe mutant polyQ proteins as being more toxic in respiring cells, causing oxidative stress and an increase in Sir2 levels. Activation of Sir2 would play a protective role against this toxicity.     

Ultrastructure of compatible and incompatible interactions in phloem sieve elements during the stylet penetration by cotton aphids in melon

Resistance of the melon line TGR‐1551 to the aphid Aphis gossypii is based on preventing aphids from ingesting phloem sap. In electrical penetration graphs (EPGs), this resistance has been characterized with A. gossypii showing unusually long phloem salivation periods (waveform E1) mostly followed by pathway activities (waveform C) or if followed by phloem ingestion (waveform E2), ingestion was not sustained for more than 10 min. Stylectomy with aphids on susceptible and resistant plants was performed during EPG recording while the stylet tips were phloem inserted. This was followed by dissection of the penetrated leaf section, plant tissue fixation, resin embedding, and ultrathin sectioning for transmission electron microscopic observation in order to study the resistance mechanism in the TGR. The most obvious aspect appeared to be the coagulation of phloem proteins inside the stylet canals and the punctured sieve elements. Stylets of 5 aphids per genotype were amputated during sieve element (SE) salivation (E1) and SE ingestion (E2). Cross‐sections of stylet bundles in susceptible melon plants showed that the contents of the stylet canals were totally clear and also, no coagulated phloem proteins occurred in their punctured sieve elements. In contrast, electron‐dense coagulations were found in both locations in the resistant plants. Due to calcium binding, aphid saliva has been hypothesized to play an essential role in preventing/suppressing such coagulations that cause occlusion of sieves plate and in the food canal of the aphid's stylets. Doubts about this role of E1 salivation are discussed on the basis of our results.     

G Protein-coupled receptor kinase 2 (GRK2): A novel modulator of insulin resistance

G protein-coupled receptor kinase 2 (GRK2) is emerging as a key, integrative node in many signalling pathways. Besides its canonical role in the modulation of the signalling mediated by many G protein-coupled receptors (GPCR), this protein can display a very complex network of functional interactions with a variety of signal transduction partners, in a stimulus, cell type, or context-specific way. We review herein recent data showing that GRK2 can regulate insulin-triggered transduction cascades at different levels and that this protein plays a relevant role in insulin resistance and obesity in vivo, what uncovers GRK2 as a potential therapeutic target in the treatment of these disorders.     

Moth species richness,abundance and diversity in fragmented urban woodlands: implications for conservation and management strategies

Urban expansion threatens global biodiversity through the destruction of natural and semi-natural habitats and increased levels of disturbance. Whilst woodlands in urban areas may reduce the impact of urbanisation on biodiversity, they are often subject to under or over-management and consist of small, fragmented patches which may be isolated. Effective management strategies for urban woodland require an understanding of the ecology and habitat requirements of all relevant taxa. Yet, little is known of how invertebrate, and in particular moth, assemblages utilise urban woodland despite being commonly found within the urban landscape. Here we show that the abundance, species richness, and species diversity of moth assemblages found within urban woodlands are determined by woodland vegetation character, patch configuration and the surrounding landscape. In general, mature broadleaved woodlands supported the highest abundance and diversity of moths. Large compact woodlands with proportionally less edge exposed to the surrounding matrix were associated with higher moth abundance than small complex woodlands. Woodland vegetation characteristics were more important than the surrounding landscape, suggesting that management at a local scale to ensure provision of good quality habitat may be relatively more important for moth populations than improving habitat connectivity across the urban matrix. Our results show that the planting of broadleaved woodlands, retaining mature trees and minimising woodland fragmentation will be beneficial for moth assemblages.     

Microphytobenthos and chironomid larvae attenuate nutrient recycling in shallow‐water sediments

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Transport of galectin-3 between the nucleus and cytoplasm. I. Conditions and signals for nuclear import

Galectin-3, a factor involved in the splicing of pre-mRNA, shuttles between the nucleus and the cytoplasm. We have engineered a vector that expresses the fusion protein containing the following: (a) green fluorescent protein as a reporter of localization, (b) bacterial maltose-binding protein to increase the size of the reporter polypeptide, and (c) galectin-3, whose sequence we wished to dissect in search of amino acid residues vital for nuclear localization. In mouse 3T3 fibroblasts transfected with this expression construct, the full-length galectin-3 (residues 1-263) fusion protein was localized predominantly in the nucleus. Mutants of this construct, containing truncations of the galectin-3 polypeptide from the amino terminus, retained nuclear localization through residue 128; thus, the amino-terminal half was dispensable for nuclear import. Mutants of the same construct, containing truncations from the carboxyl terminus, showed loss of nuclear localization. This effect was observed beginning with truncation at residue 259, and the full effect was seen with truncation at residue 253. Site-directed mutagenesis of the sequence ITLT (residues 253-256) suggested that nuclear import was dependent on the IXLT type of nuclear localization sequence, first discovered in the Drosophila protein Dsh (dishevelled). In the galectin-3 polypeptide, the activity of this nuclear localization sequence is modulated by a neighboring leucine-rich nuclear export signal.