Intraoperative radiation therapy opportunities for clinical practice normalization: Data recording and innovative development

Background

Intraoperative radiotherapy (IORT) refers to the delivery of a high dose of radiation at the time of surgery.

Aim

To analyze clinical and research-oriented innovative activities developed in a 17-year period using intraoperative electron-radiation therapy (IOeRT) as a component of treatment in a multidisciplinary approach for cancer management.

Materials and methods

From 01/1995 to 03/2012 IOeRT procedures were registered in a specific Hospital-based database. Research and developments in imaging and recording for treatment planning implementation are active since 2006.

Results

1004 patients were treated and 1036 IORT procedures completed. Median age of patients was 61 (range 5 months to 94 years). Gender distribution was male in 54% of cases and female in 46%. Disease status at the time of IORT was 796 (77%) primary and 240 (23%) recurrent. Cancer type distribution included: 62% gastrointestinal, 18% sarcoma, 5% pancreas, 2% paediatric, 3% breast, 77 7% oligotopic recurrences, 2% other. IORT technical characteristics were: Applicator size 5 cm 22%, 6 cm 21%, 7 cm 21%, 8 cm 15%, 9 cm 6%, 10 cm 7% 12 cm 5% 15 cm 3%. Electron energies: 6 MeV 19%, 8 MeV 15%, 10 MeV 15%, 12 MeV 23%, 15 MeV 19%, 18 MeV 6%, other 3%. Multiple fields: 108 (11%). Dose: 7.5 Gy 3%, 10 Gy 35%, 12 Gy 3%, 12.5 Gy 49%, 15 Gy 5%, other 5%.

Conclusion

An IORT programme developed in an Academic Hospital based on practice-oriented medical decisions is an attractive interdisciplinary oncology initiative proven to be able to generate an intensive clinical activity for cancer patient quality care and a competitive source of scientific patient-oriented research, development and innovation.     

Cross-Checking Different Sources of Mobility Information

The pervasive use of new mobile devices has allowed a better characterization in space and time of human concentrations and mobility in general. Besides its theoretical interest, describing mobility is of great importance for a number of practical applications ranging from the forecast of disease spreading to the design of new spaces in urban environments. While classical data sources, such as surveys or census, have a limited level of geographical resolution (e.g., districts, municipalities, counties are typically used) or are restricted to generic workdays or weekends, the data coming from mobile devices can be precisely located both in time and space. Most previous works have used a single data source to study human mobility patterns. Here we perform instead a cross-check analysis by comparing results obtained with data collected from three different sources: Twitter, census, and cell phones. The analysis is focused on the urban areas of Barcelona and Madrid, for which data of the three types is available. We assess the correlation between the datasets on different aspects: the spatial distribution of people concentration, the temporal evolution of people density, and the mobility patterns of individuals. Our results show that the three data sources are providing comparable information. Even though the representativeness of Twitter geolocated data is lower than that of mobile phone and census data, the correlations between the population density profiles and mobility patterns detected by the three datasets are close to one in a grid with cells of 2×2 and 1×1 square kilometers. This level of correlation supports the feasibility of interchanging the three data sources at the spatio-temporal scales considered.     

Synthesis and antitumoral evaluation of indole alkaloid analogues containing an hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole skeleton

The scope of acid-mediated cyclative additions of electrophiles to tryptophan-derived alpha-amino nitriles for the synthesis of 10b-substituted-1,2,4,5,10b,10c-hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indoles analogues of indole alkaloids has been studied. The results demonstrate the high potential of the methodology for the synthesis of 10b-bromo-derivatives, by bromination with NBS, 10b-allyl-derivatives, by bromo-allyl exchange, and 10b-prenyl-derivatives, by reaction with prenyl bromide in the presence of Mg(NO(3))(2).6H(2)0. Some of the new pyrroloimidazoindole derivatives displayed moderate microM cytotoxicities in human cancer cell lines and at 10 microg/mL inhibited more than 50% EGFR or HIF-1alpha.     

Secondary old‐field succession in an ecosystem with restrictive soils: does time from abandonment matter?

Question: Our knowledge of secondary old‐field succession in Mediterranean environments is extremely poor and is non‐existent for restrictive soil conditions. How these ecosystems, such as those on semi‐arid gypsum outcrops, recover seems a priority for managing change and for ensuring conservation of specialized and endangered biota. We tested whether reinstallation of gypsum vegetation after cropland abandonment requires: (1) soil physical restructuring and (2) chemical readjustment to enable growth and survival of specialized gypsophilous vegetation, and more specifically how time from abandonment drives such environmental change. Location: We sampled a complete set of old fields on gypsum soils (1–60 yr since abandonment) in Villarrubia de Santiago (Toledo, Spain). Methods: Generalized linear models and model comparisons were used to analyse the effect of several environmental parameters on species abundance and richness. Ordination methods (canonical correspondence analyses and partial canonical correspondence analyses) were undertaken to evaluate compositional variation among the sampled fields. Results: Secondary old‐field succession on semi‐arid Mediterranean gypsum soils was controlled by a complex set of factors acting relatively independently. Surprisingly, time since abandonment explains only a small proportion of compositional variation (3%). Conversely, soil chemical features independently from time since abandonment are important for explaining differences found in old‐field composition. Conclusions: Secondary succession on specialized Mediterranean soils does not follow the widely described “amelioration” process in which soil features and composition are closely related over time. Restrictive soil conditions control both structure and functioning of mature communities and also secondary succession.     

The miRNA machinery targets Mei‐P26 and regulates Myc protein levels in the Drosophila wing

MicroRNAs (miRNAs) have been implicated in cell‐cycle regulation and in some cases shown to have a role in tissue growth control. Depletion of miRNAs was found to have an effect on tissue growth rates in the wing primordium of Drosophila, a highly proliferative epithelium. Dicer‐1 (Dcr‐1) is a double‐stranded RNAseIII essential for miRNA biogenesis. Adult cells lacking dcr‐1, or with reduced dcr‐1 activity, were smaller than normal cells and gave rise to smaller wings. dcr‐1 mutant cells showed evidence of being susceptible to competition by faster growing cells in vivo and the miRNA machinery was shown to promote G₁–S transition. We present evidence that Dcr‐1 acts by regulating the TRIM‐NHL protein Mei‐P26, which in turn regulates dMyc protein levels. Mei‐P26 is a direct target of miRNAs, including the growth‐promoting bantam miRNA. Thus, regulation of tissue growth by the miRNA pathway involves a double repression mechanism to control dMyc protein levels in a highly proliferative and growing epithelium.     

Facultative nest-parasitism among Iberian shrubsteppe passerines

This paper analyses intra- and interspecific facultative nest parasitism of shrubsteppe passerines on the Iberian peninsula through 4 seasons, from 1991–94. Daily frequency of nest parasitism was very low (f = 3.9 × 10^-3 during laying and f = 2.8 × 10^-4 during incubation). Observation of the 3 examples found in the field of 2 intraspecific and one interspecific instances revealed that the eggs were accepted and, in the latter case, that the parasitic chick was viable. The experimental tests in the field of placing 1 additional egg that was similar to (n = 57) or clearly different from the host (n = 50), in order to simulate both intra and interspecific parasitism revealed: (i) higher rejection rates in areas with higher risk of predation and (ii) similar rejection rates for both types of eggs. The experimental addition of nestlings of other species (n = 6) revealed that in 67% of the cases studied, the parasitic chick had a normal growth rate. It is suggested that nest parasitism among these species is an occasional behaviour pattern, caused by high nest predation rates in Iberian shrubsteppe habitats.     

Low-temperature 1H-NMR evidence of the folding of isolated ribonuclease S-peptide

The temperature (-7 degrees C to 45 degrees C, pH 5.4) and pH (0 degrees C) dependence of 1H chemical shifts of ribonuclease S-peptide (5 mM, 1 M NaCl) has been measured at 360 MHz. The observed variations evidence the formation of a partial helical structure, involving the fragment Thr-3-Met-13. Two salt-bridges stabilize the helix: those formed by Glu-9- ...His-12+ and Glu-2- ...Arg-10+. The structural features deduced from the 1H-NMR at low temperature for the isolated S-peptide are compatible with the structure shown by the same molecule in the ribonuclease S crystal.     

Sequential 1H-NMR assignment and solution structure of bovine pancreatic ribonuclease A

Assignments for 1H-NMR resonances of most of the residues of bovine pancreatic ribonuclease (RNase A) have been obtained by sequence-specific methods. Identification and classification of spin systems have been carried out by two-dimensional phase-sensitive correlated spectroscopy (360 MHz) and single relayed coherence transfer spectroscopy. Sequence-specific assignments have been achieved by phase-sensitive two-dimensional nuclear Overhauser effect spectroscopy. To overcome the problem of spectral overlap use has been made of (a) an exhaustive analysis of partly exchanged RNase A (spectra in D2O), (b) a comparison with the subtilisin-modified enzyme (RNase S) and (c) small spectral perturbations caused by changes in pH and temperature. The secondary structure elements have been identified from the observed sequential, medium and long-range nuclear Overhauser effects together with data from amide-exchange rates. All information collected leads to the conclusion that the crystal and the solution structures are closely similar.     

In vitro and in vivo characterization of neural stem cells

Neural stem cells are defined as clonogenic cells with self-renewal capacity and the ability to generate all neural lineages (multipotentiality). Cells with these characteristics have been isolated from the embryonic and adult central nervous system. Under specific conditions, these cells can differentiate into neurons, glia, and non-neural cell types, or proliferate in long-term cultures as cell clusters termed neurospheres. These cultures represent a useful model for neurodevelopmental studies and a potential cell source for cell replacement therapy. Because no specific markers are available to unequivocally identify neural stem cells, their functional characteristics (self-renewal and multipotentiality) provide the main features for their identification. Here, we review the experimental and ultrastructural studies aimed at identifying the morphological characteristics and the antigenic markers of neural stem cells for their in vitro and in vivo identification.