Immunothérapie : une révolution dans la prise en charge du cancer de la vessie ? [Immunotherapy : a revolution in the management of urothelial bladder cancer ?]

The treatment of urothelial bladder cancer has changed very little in recent years, with high rates of disease recurrence and progression, even in low aggressive urothelial bladder cancer. Immunotherapy has already proven its effectiveness as a treatment for several types of cancer and has been used in high-grade non-muscle-invasive bladder cancer for decades. Recent findings on immune checkpoints inhibitors have opened up a new chapter for treatment of bladder cancer, offering interesting therapeutic perspectives that could revolutionize the management

Fault self-defection of automatic testing systems by means of aspect-oriented programming

An Aspect Oriented approach to implement fault detection in automatic measurement systems is proposed. Faults are handled by means of "aspects", a specific software unit to better modularize issues transversal to many modules ("crosscutting concerns"). In this way, maintainability and reusability of a measurement software are improved: indeed, once a modification of the fault detection policy occurs, only the related aspects have to be modified. As an experimental case study, this technique has been applied to the fault self-detection of a flexible framework for magnetic measurements, developed at the European Organization for Nuclear Research (CERN)

Mobile Robot Localization using Panoramic Vision and Combinations of Feature Region Detectors

IEEE International Conference on Robotics and Automation (ICRA 2008, Pasadena, California, May 19-23, 2008), pp. 538-543.This paper presents a vision-based approach for mobile robot localization. The environmental model is topological. The new approach uses a constellation of different types of affine covariant regions to characterize a place. This type of representation permits a reliable and distinctive environment modeling. The performance of the proposed approach is evaluated using a database of panoramic images from different rooms. Additionally, we compare different combinations of complementary feature region detectors to find the one that achieves the best results. Our experimental results show promising results for this new localization method. Additionally, similarly to what happens with single detectors, different combinations exhibit different strengths and weaknesses depending on the situation, suggesting that a context-aware method to combine the different detectors would improve the localization results.This work was partially supported by USC Women in Science and Engineering (WiSE), the FI grant from the Generalitat de Catalunya, the European Social Fund, and the MID-CBR project grant TIN2006-15140-C03-01 and FEDER funds and the grant 2005-SGR-00093

Association of Anticholinergic Burden with Cognitive and Functional Status in a Cohort of Hospitalized Elderly: Comparison of the Anticholinergic Cognitive Burden Scale and Anticholinergic Risk Scale

Abstract Background Drugs with anticholinergic effects are associated with adverse events such as delirium and falls as well as cognitive decline and loss of independence. Objective The aim of the study was to evaluate the association between anticholinergic burden and both cognitive and functional status, according to the hypothesis that the cumulative anticholinergic burden, as measured by the Anticholinergic Cognitive Burden (ACB) Scale and Anticholinergic Risk Scale (ARS), increases the risk of cognitive decline and impairs activities of daily living. Methods This cross-sectional, prospective study (3-month telephone follow-up) was conducted in 66 Italian internal medicine and geriatric wards participating in the Registry of Polytherapies SIMI (Societa` Italiana di Medicina Interna) (REPOSI) study during 2010. The sample included 1,380 inpatients aged 65 years or older. Cognitive status was rated with the Short Blessed Test (SBT) and physical function with the Barthel Index. Each patient’s anticholinergic burden was evaluated using the ACB and ARS scores. Results The mean SBT score for patients treated with anticholinergic drugs was higher than that for patients receiving no anticholinergic medications as also indicated by the ACB scale, even after adjustment for age, sex, education, stroke and transient ischaemic attack [9.2 (95 % CI 8.6–9.9) vs. 8.5 (95 % CI 7.8–9.2); p = 0.05]. There was a dose–response relationship between total ACB score and cognitive impairment. Patients identified by the ARS had more severe cognitive and physical impairment than patients identified by the ACB scale, and the dose–response relationship between this score and ability to perform activities of daily living was clear. No correlation was found with length of hospital stay. Conclusions Drugs with anticholinergic properties identified by the ACB scale and ARS are associated with worse cognitive and functional performance in elderly patients. The ACB scale might permit a rapid identification of drugs potentially associated with cognitive impairment in a dose–response pattern, but the ARS is better at rating activities of daily living

Crystal Structure of Crataeva tapia Bark Protein (CrataBL) and Its Effect in Human Prostate Cancer Cell Lines

A protein isolated from the bark of Crataeva tapia (CrataBL) is both a Kunitz-type plant protease inhibitor and a lectin. We have determined the amino acid sequence and three-dimensional structure of CrataBL, as well as characterized its selected biochemical and biological properties. We found two different isoforms of CrataBL isolated from the original source, differing in positions 31 (Pro/Leu); 92 (Ser/Leu); 93 (Ile/Thr); 95 (Arg/Gly) and 97 (Leu/Ser). CrataBL showed relatively weak inhibitory activity against trypsin (K-iapp = 43 mu M) and was more potent against Factor Xa (K-iapp = 8.6 mu M), but was not active against a number of other proteases. We have confirmed that CrataBL contains two glycosylation sites and forms a dimer at high concentration. The high-resolution crystal structures of two different crystal forms of isoform II verified the beta-trefoil fold of CrataBL and have shown the presence of dimers consisting of two almost identical molecules making extensive contacts (similar to 645 angstrom(2)). The structure differs from those of the most closely related proteins by the lack of the N-terminal beta-hairpin. In experiments aimed at investigating the biological properties of CrataBL, we have shown that addition of 40 mM of the protein for 48 h caused maximum growth inhibition in MTT assay (47% of DU145 cells and 43% of PC3 cells). The apoptosis of DU145 and PC3 cell lines was confirmed by flow cytometry using Annexin V/FITC and propidium iodide staining. Treatment with CrataBL resulted in the release of mitochondrial cytochrome c and in the activation of caspase-3 in DU145 and PC3 cells

Structure and mechanism of human DNA polymerase η

The variant form of the human syndrome xeroderma pigmentosum (XPV) is caused by a deficiency in DNA polymerase eta (Pol eta), a DNA polymerase that enables replication through ultraviolet-induced pyrimidine dimers. Here we report high-resolution crystal structures of human Pol eta at four consecutive steps during DNA synthesis through cis-syn cyclobutane thymine dimers. Pol eta acts like a 'molecular splint' to stabilize damaged DNA in a normal B-form conformation. An enlarged active site accommodates the thymine dimer with excellent stereochemistry for two-metal ion catalysis. Two residues conserved among Pol eta orthologues form specific hydrogen bonds with the lesion and the incoming nucleotide to assist translesion synthesis. On the basis of the structures, eight Pol eta missense mutations causing XPV can be rationalized as undermining the molecular splint or perturbing the active-site alignment. The structures also provide an insight into the role of Pol eta in replicating through D loop and DNA fragile sites

Fungal diversity associated to the olive moth, prays oleae Bernard : a survey for potential entomopathogenic fungi

Olive production is one of the main agricultural activities in Portugal. In the region of Trás-os-Montes this crop has been considerably affected by Prays oleae. In order to evaluate the diversity of fungi on P. oleae population of Trás-os-Montes olive orchards, larvae and pupae of the three annual generations (phyllophagous, antophagous and carpophagous) were collected and evaluated for fungal growth on their surface. From the 3828 larvae and pupae, a high percentage of individuals exhibited growth of a fungal agent (40.6%), particularly those from the phyllophagous generation. From all the moth generations, a total of 43 species from 24 genera were identified, but the diversity and abundance of fungal species differed between the three generations. Higher diversity was found in the carpophagous generation, followed by the antophagous and phyllophagous generations. The presence of fungi displaying entomopathogenic features was highest in the phyllophagous larvae and pupae, being B. bassiana the most abundant taxa. The first report of B. bassiana presence on P. oleae could open new strategies for the biocontrol of this major pest in olive groves, since the use of an already adapted species increases the guarantee of success of a biocontrol approach. The identification of antagonistic fungi able to control agents that cause major olive diseases, such as Verticillium dahliae, will benefit future biological control approaches for limiting this increasingly spreading pathogen.This work was supported by Science and Technology Foundation (Fundação para a Ciência e Tecnologia – FCT) project PTDC/AGR-AAM/102600/2008 “Entomopathogenic fungi associated to olive pests: isolation, characterization and selection for biological control”. The first author is grateful to the Science and Technology Foundation for the PhD grant SFRH/BD/44265/2008

Physiological quality, content and activity of antioxidants in soybean seeds artificially aged.

ABSTRACT - The objective of this study was to evaluate physiological quality, content, and activity of antioxidants, in soybean seeds subjected to accelerated aging during different periods. Seeds of cultivars BRS 258, BRS 262 and BRS 268, subjected to accelerated aging during 12, 24, 36 and 48 hours and non-aged seeds were used. After each aging period, the seed were evaluated by tests of: germination; first count and tetrazolium. The total of phenolic compounds, total flavonoides, total of isoflavones, and activity for eliminating ABTS°+ radicals were quantified. There were differences among cultivars according to vigor and viability only after seeds were aged. Cultivars BRS 158 and BRS 268 have shown better seed physiological quality in each aging period; however, not presenting higher amounts of isoflavones and efficiency in removing free radicals. For all cultivars, the values for total of phenolic compounds, as well as total of flavonoids have shown quadratic positive behavior; the values for isoflavones remained constant and the vigor and viability showed contrary trend to activity of antioxidant agents. RESUMO: Qualidade fisiológica, conteúdo e atividade de antioxidantes presentes em sementes de soja envelhecidas artificialmente. O objetivo deste trabalho foi avaliar a qualidade fisiológica, o conteúdo e a atividade de agentes antioxidantes presentes em sementes de soja envelhecidas durante diferentes períodos. Foram utilizadas sementes das cultivares BRS 258, BRS 262 e BRS 268, envelhecidas durante 12, 24, 36 e 48 h e sementes não envelhecidas. Após cada período de envelhecimento, as sementes foram avaliadas pelo testes de: germinação; primeira contagem e tetrazólio. Foram quantificados: compostos fenólicos totais; flavonóides totais; total de isoflavonas e atividade eliminadora do radical ABTS°+. Houve diferença entre as cultivares em relação ao vigor e viabilidade somente quando foram envelhecidas. BRS 158 e BRS 268 apresentaram melhor qualidade fisiológica de sementes em cada período de envelhecimento, porém, não apresentaram maior quantidade de isoflavonas e eficiência no sequestro dos radicais livres. Para todas as cultivares, os valores de compostos fenólicos totais, assim como os flavonóides totais, apresentaram comportamento quadrático positivo; os valores das isoflavonas permaneceram constantes e o vigor e a viabilidade apresentaram tendência contrária à atividade dos agentes antioxidantes