102 research outputs found

    Reliability of race assessment based on the race of the ascendants: a cross-sectional study

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    BACKGROUND: Race is commonly described in epidemiological surveys based on phenotypic characteristics. Training of interviewers to identify race is time-consuming and self identification of race might be difficult to interpret. The aim of this study was to determine the agreement between race definition based on the number of ascendants with black skin colour, with the self-assessment and observer's assessment of the skin colour. METHODS: In a cross-sectional study of 50 women aged 14 years or older, from an outpatient clinic of an University affiliated hospital, race was assessed through observation and the self-assignment of the colour of skin and by the number of black ascendants including parents and grandparents. Reliability was measured through Kappa coefficient. RESULTS: Agreement beyond chance between self-assigned and observed skin colour was excellent for white (0.75 95% CI 0.72–0.78) and black women (0.89 95% CI 0.71–0.79), but only good for participants with mixed colour (0.61 95% CI 0.58–0.64), resulting in a global kappa of 0.75 (95% CI 0.71–0.79). However, only a good agreement for mixed women was obtained. The presence of 3 or more black ascendants was highly associated with observed and self-assessed black skin colour. Most women self-assigned or observed as white had no black ascendants. CONCLUSIONS: The assessment of race based on the race of ascendants showed reasonable agreement with the ascertainment done by trained interviewers and with the self-report of race. This method may be considered for evaluation of race in epidemiological surveys, since it is less time-consuming than the evaluation by interviewers

    Examination of potential virulence factors of Candida tropicalis clinical isolates from hospitalized patients

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    Candida tropicalis has been reported to be one of the Candida species which is most likely to cause bloodstream and urinary tract infections in hospitalized patients. Accordingly, the aim of this study was to characterize the virulence of C. tropicalis by assessing antifungal susceptibility and comparing the expression of several virulence factors. This study was conducted with seven isolates of C. tropicalis from urine and blood cultures and from central venous catheter. C. tropicalis ATCC 750 was used as reference strain. Yeasts adhered (2 h) to epithelial cells and silicone and 24 h biofilm biomass were determined by crystal violet staining. Pseudohyphae formation ability was determined after growth in fetal bovine serum. Enzymes production (hemolysins, proteases, phospholipases) was assessed by halo formation on agar plates. Susceptibility to antifungal agents was determined by E-test. Regarding adhesion, it can be highlighted that C. tropicalis strains adhered significantly more to epithelium than to silicone. Furthermore, all C. tropicalis strains were able to form biofilms and to express total hemolytic activity. However, protease was only produced by two isolates from urine and by the isolates from catheter and blood. Moreover, only one C. tropicalis (from catheter) was phospholipase positive. All isolates were susceptible to voriconazole, fluconazole and amphotericin B. Four strains were susceptible-dose dependent to itraconazole and one clinical isolate was found to be resistant

    Control of bovine mastitis: old and recent therapeutic approaches

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    Mastitis is defined as the inflammatory response resulting of the infection of the udder tissue and it is reported in numerous species, namely in domestic dairy animals. This pathology is the most frequent disease of dairy cattle and can be potentially fatal. Mastitis is an economically important pathology associated with reduced milk production, changes in milk composition and quality, being considered one of the most costly to dairy industry. Therefore, the majority of research in the field has focused on control of bovine mastitis and many efforts are being made for the development of new and effective anti-mastitis drugs. Antibiotic treatment is an established component of mastitis control programs; however, the continuous search for new therapeutic alternatives, effective in the control and treatment of bovine mastitis, is urgent. This review will provide an overview of some conventional and emerging approaches in the management of bovine mastitis infections.F. Gomes acknowledge the financial support of the Portuguese Foundation for Science and Technology through the Grant SFRH/BPD/84488/2012 and for financial support to the CEB research center

    Chromosome copy number changes carry prognostic information independent of KIT/PDGFRA point mutations in gastrointestinal stromal tumors

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    <p>Abstract</p> <p>Background</p> <p>Oncogenic point mutations in <it>KIT </it>or <it>PDGFRA </it>are recognized as the primary events responsible for the pathogenesis of most gastrointestinal stromal tumors (GIST), but additional genomic alterations are frequent and presumably required for tumor progression. The relative contribution of such alterations for the biology and clinical behavior of GIST, however, remains elusive.</p> <p>Methods</p> <p>In the present study, somatic mutations in <it>KIT </it>and <it>PDGFRA </it>were evaluated by direct sequencing analysis in a consecutive series of 80 GIST patients. For a subset of 29 tumors, comparative genomic hybridization was additionally used to screen for chromosome copy number aberrations. Genotype and genomic findings were cross-tabulated and compared with available clinical and follow-up data.</p> <p>Results</p> <p>We report an overall mutation frequency of 87.5%, with 76.25% of the tumors showing alterations in <it>KIT </it>and 11.25% in <it>PDGFRA</it>. Secondary <it>KIT </it>mutations were additionally found in two of four samples obtained after imatinib treatment. Chromosomal imbalances were detected in 25 out of 29 tumors (86%), namely losses at 14q (88% of abnormal cases), 22q (44%), 1p (44%), and 15q (36%), and gains at 1q (16%) and 12q (20%). In addition to clinico-pathological high-risk groups, patients with <it>KIT </it>mutations, genomic complexity, genomic gains and deletions at either 1p or 22q showed a significantly shorter disease-free survival. Furthermore, genomic complexity was the best predictor of disease progression in multivariate analysis.</p> <p>Conclusions</p> <p>In addition to <it>KIT/PDGFRA </it>mutational status, our findings indicate that secondary chromosomal changes contribute significantly to tumor development and progression of GIST and that genomic complexity carries independent prognostic value that complements clinico-pathological and genotype information.</p

    Oral Administration of GW788388, an Inhibitor of Transforming Growth Factor Beta Signaling, Prevents Heart Fibrosis in Chagas Disease

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    Cardiac damage and dysfunction are prominent features in patients with chronic Chagas disease, which is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi) and affects 10–12 million individuals in South and Central America. Our group previously reported that transforming growth factor beta (TGFß) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. In the present work, we evaluated the therapeutic action of an oral inhibitor of TGFß signaling (GW788388) administered during the acute phase of experimental Chagas disease. GW788388 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that GW788388 treatment was effective in protecting the cardiac conduction system, preserving gap junction plaque distribution and avoiding the development of cardiac fibrosis. Inhibition of TGFß signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic tool for acute and chronic Chagas disease that warrants further pre-clinical exploration. Administration of TGFß inhibitors during chronic infection in mouse models should be further evaluated, and future clinical trials should be envisaged

    The Homeobox Transcription Factor Barx2 Regulates Plasticity of Young Primary Myofibers

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    Adult mammalian muscle retains incredible plasticity. Muscle growth and repair involves the activation of undifferentiated myogenic precursors called satellite cells. In some circumstances, it has been proposed that existing myofibers may also cleave and produce a pool of proliferative cells that can re-differentiate into new fibers. Such myofiber dedifferentiation has been observed in the salamander blastema where it may occur in parallel with satellite cell activation. Moreover, ectopic expression of the homeodomain transcription factor Msx1 in differentiated C2C12 myotubes has been shown to induce their dedifferentiation. While it remains unclear whether dedifferentiation and redifferentiaton occurs endogenously in mammalian muscle, there is considerable interest in induced dedifferentiation as a possible regenerative tool.We previously showed that the homeobox protein Barx2 promotes myoblast differentiation. Here we report that ectopic expression of Barx2 in young immature myotubes derived from cell lines and primary mouse myoblasts, caused cleavage of the syncytium and downregulation of differentiation markers. Microinjection of Barx2 cDNA into immature myotubes derived from primary cells led to cleavage and formation of mononucleated cells that were able to proliferate. However, injection of Barx2 cDNA into mature myotubes did not cause cleavage. Barx2 expression in C2C12 myotubes increased the expression of cyclin D1, which may promote cell cycle re-entry. We also observed differential muscle gene regulation by Barx2 at early and late stages of muscle differentiation which may be due to differential recruitment of transcriptional activator or repressor complexes to muscle specific genes by Barx2.We show that Barx2 regulates plasticity of immature myofibers and might act as a molecular switch controlling cell differentiation and proliferation

    Evolutionary Rate Covariation Identifies New Members of a Protein Network Required for Drosophila melanogaster Female Post-Mating Responses

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    Seminal fluid proteins transferred from males to females during copulation are required for full fertility and can exert dramatic effects on female physiology and behavior. In Drosophila melanogaster, the seminal protein sex peptide (SP) affects mated females by increasing egg production and decreasing receptivity to courtship. These behavioral changes persist for several days because SP binds to sperm that are stored in the female. SP is then gradually released, allowing it to interact with its female-expressed receptor. The binding of SP to sperm requires five additional seminal proteins, which act together in a network. Hundreds of uncharacterized male and female proteins have been identified in this species, but individually screening each protein for network function would present a logistical challenge. To prioritize the screening of these proteins for involvement in the SP network, we used a comparative genomic method to identify candidate proteins whose evolutionary rates across the Drosophila phylogeny co-vary with those of the SP network proteins. Subsequent functional testing of 18 co-varying candidates by RNA interference identified three male seminal proteins and three female reproductive tract proteins that are each required for the long-term persistence of SP responses in females. Molecular genetic analysis showed the three new male proteins are required for the transfer of other network proteins to females and for SP to become bound to sperm that are stored in mated females. The three female proteins, in contrast, act downstream of SP binding and sperm storage. These findings expand the number of seminal proteins required for SP's actions in the female and show that multiple female proteins are necessary for the SP response. Furthermore, our functional analyses demonstrate that evolutionary rate covariation is a valuable predictive tool for identifying candidate members of interacting protein networks. © 2014 Findlay et al
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