4,048 research outputs found

    Leveraging the Country-of-Origin Image by managing it at different levels

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    The study aims to articulate the Country-of-Origin Image (COI) at different levels (country, industry and firm levels) by advancing the knowledge and exploring ways to manage the COI at different levels underpinned on corporate brand and brand architecture strategies. For that, a mixed-methods approach was conducted where a qualitative study—looking into the case of the Brazilian Machinery Solutions Programme (BMS)—was carried out in combination with a quantitative survey held with a specific target country (Colombia). Data for the quantitative study were collected with 89 Colombian industrial buyers using Brazil as a manufacturer-supplier and country of reference. Findings indicate the relevance of managing the COI at different levels and highlight the development of the COI at the industry level. This demonstrates that nation-branding and COI literature should be developed and articulated using strategic marketing programmes and brand architecture elements. The study advances the body of knowledge in the COI literature by analysing it within three different levels and offers a framework to manage the COI using corporate brand and brand architecture elements, which is beneficial to institutions, governments, trade agencies, industry associations and firms to leverage the COI by understanding aspects of it transferrable to industry and firm levels

    Measles-containing vaccines in Brazil: Coverage, homogeneity of coverage and associations with contextual factors at municipal level

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    We aimed to (i) describe both the coverage and the homogeneity of coverage of the first and second doses of measles-containing vaccines (MCV) in Brazil in 2017, and (ii) to investigate the potential influence of contextual factors at municipal level. All 5570 Brazilian municipalities were included. The North and Center-West regions presented the lowest coverages of the first and second doses of MCV, respectively. We found significant associations of both first and second doses of MCV with population size, coverage of Family Health Strategy (FHS) and other indicators of living conditions and inequalities. Monitoring the homogeneity of MCV coverage at national, regional and state levels is essential, as it allows identifying areas at higher risk of measles spread that should be targeted for vaccination. Targeting large cities i.e. 100,000 or more inhabitants, especially poor neighborhoods and areas with low FHS coverage, could lead to improvements in coverage homogeneity

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

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    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

    Chromosome analysis in Saccodon wagneri (Characiformes) and insights into the karyotype evolution of Parodontidae

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    Parodontidae is a relatively small group of Neotropical characiform fishes consisting of three genera (Apareiodon, Parodon, and Saccodon) with 32 valid species. A vast cytogenetic literature is available on Apareiodon and Parodon, but to date, there is no cytogenetic data about Saccodon, a genus that contains only three species with a trans-Andean distribution. In the present study the karyotype of S. wagneri was described, based on both conventional (Giemsa staining, Ag- NOR, C-bands) and molecular (repetitive DNA mapping by fluorescent in situ hybridization) methods. A diploid chromosome number of 2n = 54 was observed in both sexes, and the presence of heteromorphic sex chromosomes of the ZZ/ ZW type was detected. The W chromosome has a terminal heterochromatin band that occupies approximately half of the long arm, being this band approximately half the size of the Z chromosome. The FISH assay showed a synteny of the 18S-rDNA and 5S-rDNA genes in the chromosome pair 14, and the absence of interstitial telomeric sites. Our data reinforce the hypothesis of a conservative karyotype structure in Parodontidae and suggest an ancient origin of the sex chromosomes in the fishes of this family

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

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    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

    Brazilian gamma detection device for sentinel lymph node biopsy

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    OBJECTIVE: To test the effectiveness of an intra-operative gamma detection Brazilian device (IPEN) on sentinel lymph node biopsy (SLNB) procedures. METHODS: Forty melanoma or breast cancer patients with indication for undergoing SLNB were studied. Lymphoscintigraphy was done 2 to 24 hours prior to surgery. Lymphatic mapping with vital dye and gamma detection were performed intraoperatively. For gamma detection Neoprobe ® 1500 was used followed by IPEN (equipment under test) in the first 20 patients and for the remaining half IPEN was used first to verify its ability to locate the sentinel node (SN). Measurements were taken from the radiopharmaceutical product injection site, from SN (in vivo and ex vivo) and from background. It was recorded if the SN was stained or not and if it was found easily by surgeon. RESULTS: There were 33 (82.5%) breast cancer and 7 (17.5%) melanoma patients. Ages varied from 21 to 68 year-old (median age of 46). Sex distribution was 35 (87.5%) women and 5 (12.5%) men. Sentinel node was found in all but one patient. There was no statistical difference between the reasons ex vivo/ background obtained with the measures of both equipments (p=0, 2583-ns). The SN was easily found by the surgeon with both devices. CONCLUSION: The SLNB was successfully performed using either equipment. It was possible to do SLNB with the Brazilian device developed by IPEN without prejudice for the patient.OBJETIVO: Testar a eficácia de equipamento de detecção gama intra-operatória (DGI) desenvolvido pelo IPEN (Brasil), em procedimentos de biópsia de linfonodo sentinela (BLS) no melanoma e no câncer de mama. MÉTODOS: Foram estudados 40 pacientes portadores de melanoma ou câncer de mama com indicação para realização de BLS.Todos pacientes foram submetidos à linfocintilografia e a BLS ocorreu entre 2 a 24 horas após a mesma. Concomitantemente à DGI, realizou-se o mapeamento linfático com corante vital. Foram feitas leituras com o equipamento convencional Neoprobe® 1500 e com o equipamento em teste (IPEN) dos valores de captação do sítio de injeção do radiofármaco, do LS in vivo e ex vivo e da captação de fundo. Foi registrado se o LS estava corado e se o cirurgião teve facilidade para encontrá-lo. Nos primeiros 20 pacientes utilizou-se o equipamento convencional e depois o de teste; nos outros 20, utilizou-se primeiro o equipamento em teste, com objetivo de verificar se o mesmo identificava primariamente o LS. RESULTADOS: Dos quarenta pacientes, 33 eram portadores de tumor de mama e sete de melanoma cutâneo; variação da idade: 21 a 68 anos (mediana= 46 anos); 35 mulheres e 5 homens. Em apenas um paciente o LS não foi encontrado, nem pela DGI nem pelo corante vital. Não houve diferença estatística entre as razões ex vivo/fundo obtidas com os dois equipamentos (p=0, 2583-ns). CONCLUSÃO: É possível realizar o procedimento de BLS com o equipamento brasileiro desenvolvido pelo IPEN, com facilidade e sem prejuízo para o paciente.Hospital Israelita Albert EinsteinIPENUniversidade Federal de São Paulo (UNIFESP)Faculdade de Medicina Anhembi-MorumbiUNIFESPSciEL

    Physicochemical-guided design of cathelicidin-derived peptides generates membrane active variants with therapeutic potential.

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    The spread of multi-drug resistance and the slow pace at which antibiotics come onto the market are undermining our ability to treat human infections, leading to high mortality rates. Aiming to overcome this global crisis, antimicrobial peptides are considered promising alternatives to counter bacterial infections with multi-drug resistant bacteria. The cathelicidins comprise a well-studied class of AMPs whose members have been used as model molecules for sequence modifications, aiming at enhanced biological activities and stability, along with reduced toxic effects on mammalian cells. Here, we describe the antimicrobial activities, modes of action and structural characterization of two novel cathelicidin-like peptides, named BotrAMP14 and CrotAMP14, which were re-designed from snake batroxicidin and crotalicidin, respectively. BotrAMP14 and CrotAMP14 showed broad-spectrum antibacterial activity against susceptible microorganisms and clinical isolates with minimal inhibitory concentrations ranging from 2-35.1 μM. Moreover, both peptides had low cytotoxicity against Caco-2 cells in vitro. In addition, in vivo toxicity against Galleria mellonella moth larvae revealed that both peptides led to>76% larval survival after 144 h. Microscopy studies suggest that BotrAMP14 and CrotAMP14 destabilize E. coli membranes. Furthermore, circular dichroism and molecular dynamics simulations indicate that, in a membrane-like environment, both peptides adopt α-helical structures that interact with bilayer phospholipids through hydrogen bonds and electrostatic interaction. Thus, we concluded that BotrAMP14 and CrotAMP14 are helical membrane active peptides, with similar antibacterial properties but lower cytotoxicity than the larger parent peptides batroxicidin and crotalicidin, having advantages for drug development strategies
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