Report of the Second International Symposium on Molecular Epidemiology in Childhood Leukaemia and Embryonal Tumours, Rio de Janeiro, Brazil

The recent International Symposium on Molecular epidemiology in Embryonal Tumours and Paediatric Leukaemia was held on 4–6 March 2008 in Rio de Janeiro, Brazil. It proved a very productive meeting in which studies relating to genetics, therapeutical trials, identification of risk factors in acute leukaemia neuroblastoma and Wilms’ tumours were presented. Over 120 participants gathered for three days of fruitful discussions, including representatives of paediatrics, haematology, laboratory, epidemiology and pathology. Debates were held about strategies of applications of important biomarkers for clinical trials. Highlights of each of the scientific presentations are summarized below

approach chemistry, functional and biological

Dithiocarbamates represent a class of compounds that were evaluated in different biomedical applications because of their chemical versatility. For this reason, several pharmacological activities have already been attributed to these compounds, such as antiparasitic, antiviral, antifungal activities, among others. Therefore, compounds that are based on dithiocarbamates have been evaluated in different in vivo and in vitro models as potential new antimicrobials. Thus, the purpose of this review is to present the possibilities of using dithiocarbamate compounds as potential new antitrypanosomatids-drugs, which could be used for the pharmacological control of Chagas disease, leishmaniasis, and African trypanosomiasis.publishersversionpublishe

A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report.

BACKGROUND: Chromosome translocations are a hallmark of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Additional genomic aberrations are also crucial in both BCP-ALL leukemogenesis and treatment management. Herein, we report the phenotypic and molecular cytogenetic characterization of an extremely rare case of BCP-ALL harboring two concomitant leukemia-associated chromosome translocations: t(1;19)(q23;q13.3) and t(9;17)(p13;q11.2). Of note, we described a new rearrangement between exon 6 of PAX5 and a 17q11.2 region, where intron 3 of SPECC1 is located. This rearrangement seems to disrupt PAX5 similarly to a PAX5 deletion. Furthermore, a distinct karyotype between diagnosis and relapse samples was observed, disclosing a complex clonal evolution during leukemia progression. CASE PRESENTATION: A 16-year-old boy was admitted febrile with abdominal and joint pain. At clinical investigation, he presented with anemia, splenomegaly, low white blood cell count and 92% lymphoblast. He was diagnosed with pre-B ALL and treated according to high risk GBTLI-ALL2009. Twelve months after complete remission, he developed a relapse in consequence of a high central nervous system and bone marrow infiltration, and unfortunately died. CONCLUSIONS: To our knowledge, this is the first report of a rearrangement between PAX5 and SPECC1. The presence of TCF3-PBX1 and PAX5-rearrangement at diagnosis and relapse indicates that both might have participated in the malignant transformation disease maintenance and dismal outcome

Strict protected areas are essential for the conservation of larger and threatened mammals in a priority region of the Brazilian Cerrado

ssessing protected area (PA) effectiveness is key to ensure the objectives of habitat protection are being achieved. There is strong evidence that legal protection reduces loss of natural vegetation, but biodiversity loss can still happen without significant changes in vegetation cover. Here we use data from a specifically designed camera trap survey to conduct a counterfactual assessment of PA effectiveness at safeguarding local biodiversity in the Brazilian Cerrado. We surveyed the mammal community in 517 locations at the Sertão Veredas-Peruaçu mosaic, distributed across five strict PAs (264 survey sites in five arrays) and two multiple-use PAs with low management levels (253 survey sites in four arrays). We adopted a multi-species occupancy framework to analyse our dataset while also controlling for confounding factors not directly related to protection. Of the 21 species assessed, nine had higher occupancy in strict PAs, one had higher occupancy in multiple-use PAs, and ten did not respond to protection level. Site species richness was nearly twice as large in areas under stricter protection, with even greater differences for species richness of globally threatened and larger mammals (>15 kg). Overall we demonstrated that the strict PAs surveyed support higher mammal diversity than similar areas under less restrictive management, with a particular strong effect on larger and threatened species. Given that strict PAs cover only 3% of the Cerrado, our results suggest that expanding the area under strict protection is likely to benefit iconic species of the Brazilian savanna, such as the maned wolf and giant anteater

Le Cinéma en Réalité Virtuelle :

Résumé Le cinéma en Réalité Virtuelle (V. R.) est une rencontre entre le cinéma et un type spécifique de technologie qui simule les environnements virtuels. Cependant, tous deux revendiquent ce qui leur appartient : le cinéma, avec son propre langage qui glisse sous ses formes d’expression artistique et la Réalité Virtuelle qui est polymorphe. Lors de cette rencontre, la diégèse cinématographique subit un changement et met le langage à l’affût de nouveaux modes de composition. Il induit d’autres façons de penser le cinéma, qui doit désormais être vécu de l’intérieur.Abstract : VR cinema is an interchange between cinema and a specific kind of technology that simulates virtual environments, but both claim what belongs to them, which is proper to the medium. The cinema has its own grammar that slips under its forms of narrative and does not keep so many secrets anymore and Virtual Reality is polymorphic. In this meeting, cinematic diegesis suffers a blow and puts language in wait for a new convention and infers other ways of thinking the cinema, which now, needs to be experienced from the inside

CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia.

CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in N/KRAS, NOTCH1, FBXW7 as well as STIL-TAL1 and TLX3 rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1-1272), T-ALL was relatively low, with MFI 43.2 (1.9-1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1aneg) had a lower CD44 expression, MFI 57.5 (2.7-866.3), whereas mCD3/TCRγδpos cases had higher expressions, MFI 99.9 (16.4-866.3). NOTCH1 mut and STIL-TAL1 were associated with low CD44 expression, whereas N/KRAS mut and FBXW7 mut cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (p = 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL

t(10;11)(p12;q23) KMT2A/NEBL

Review on t(10;11)(p12;q23) KMT2A/NEBL, with data on clinics, and the genes involved

Linhagem celular RC-IAL: sensibilidade de crescimento do vírus da rubéola

OBJECTIVE: The rapid growth of the rubella virus in RC-IAL² with development of cytopathic effect, in response to rubella virus infection, is described. For purposes of comparison, the rubella virus RA-27/3 strain was titered simultaneously in the RC-IAL, Vero, SIRC and RK13 cell lines. METHODS: Rubella virus RA-27/3 strain are inoculated in the RC-IAL cell line (rabbit Kidney, Institute Adolfo Lutz). Plates containing 1.5x10(5) cells/ml of RC-IAL line were inoculated with 0.1ml s RA-27/3 strain virus containing 1x 10(4)TCID50/0.1ml. A 25% cytopathic effect was observed after 48 hours and 100% after 96 hours. The results obtained were compared to those observed with the SIRC, Vero and RK13 cell lines. Rubella virus was detected by immunohistochemistry. RESULTS: With the results, it was possible to conclude that the RC-IAL cell line is a very good substrate for culturing rubella virus. The cells inoculated with rubella virus were examined by phase contrast microscopy and showed the characteristic rounded, bipolar and multipolar cells. The CPE in RC-IAL was observed in the first 48 hours and the curve of the increased infectivity was practically the same as observed in other cell lines. CONCLUSIONS: These findings are important since this is one the few cell lines described in the literature with a cytopathic effect. So it can be used for antigen preparation and serological testing for the diagnosis of specific rubella antibodies.OBJETIVO: Descreve-se o crescimento do vírus-padrão da rubéola RA-27/3 na linhagem celular RC-IAL, com desenvolvimento de efeito citopático em resposta à infecção viral. Para este propósito, o vírus-padrão foi titulado simultaneamente nas linhagens celulares Vero, SIRC e RK13. MÉTODOS: O vírus-padrão da rubéola RA-27/3 foi inoculado na linhagem celular RC-IAL (rim de coelho, Instituto Adolfo Lutz). Placas contendo 1,5x10(5) células/ml foram inoculadas com 0,1 ml do vírus contendo 1x10(4) DICT50/0,1 ml. O efeito citopático correspondente a 25% foi observado após 48 h e 100% após 96 h. Os resultados obtidos foram comparados com o crescimento do vírus nas linhagens celulares SIRC, Vero e RK13. O vírus da rubéola na linhagem celular RC-IAL foi detectado por imuno-histoquímica. RESULTADOS: As células inoculadas com o vírus da rubéola apresentaram efeito citopático nas primeiras 48h. As células apresentaram aspecto arredondado, com formação de alguns prolongamentos citoplasmáticos e sincícios, produzindo células multinucleadas. A curva do crescimento da infectividade do vírus foi praticamente a mesma que a observada nas outras linhagens celulares. CONCLUSÃO: Os resultados obtidos mostram que a linhagem celular RC-IAL é um ótimo substrato para crescimento do vírus da rubéola, pois poucas linhagens celulares descritas na literatura apresentam efeito citopático considerável e podem ser utilizadas para preparação de antígenos e nos testes de diagnóstico sorológico para o vírus da rubéola

Understanding the meaning of medications for patients: The medication experience

Objective: To understand and describe the meaning of medications for patients. Methods: A metasynthesis of three different, yet complementary qualitative research studies, was conducted by two researchers. The first study was a phenomenological study of patients’ medication experiences that used unstructured interviews. The second study was an ethnographic study of pharmaceutical care practice, which included participant observation, in-depth interviews and focus groups with patients of pharmaceutical care. The third was a phenomenological study of the chronic illness experience of medically uninsured individuals in the United States and included an explicit aim to understand the medication experience within that context. The two researchers who conducted these three qualitative studies that examined the medication experience performed the meta-synthesis. The process began with the researchers reviewing the themes of the medication experience for each study. The researchers then aggregated the themes to identify the overlapping and similar themes of the medication experience and which themes are sub-themes within another theme versus a unique theme of the medication experience. The researchers then used the analytic technique, “free imaginative variation” to determine the essential, structural themes of the medication experience. Results: The meaning of medications for patients was captured as four themes of the medication experience: a meaningful encounter; bodily effects; unremitting nature; and exerting control. The medication experience is an individual’s subjective experience of taking a medication in his daily life. It begins as an encounter with a medication. It is an encounter that is given meaning before it occurs. The experience may include positive or negative bodily effects. The unremitting nature of a chronic medication often causes an individual to question the need for the medication. Subsequently, the individual may exert control by altering the way he takes the medication and often in part because of the gained expertise with the medication in his own body. Conclusion: The medication experience is a practice concept that serves to understand patients’ experiences and to understand an individual patient’s medication experience and medication-taking behaviors in order to meet his or her medication-related needs