637 research outputs found

    Iguais ou diferentes? Cuidados de saúde materno-infantil a uma população de imigrantes

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    Os concelhos de Amadora e Sintra constituem um território de fortes características de identidade na Área Metropolitana de Lisboa que resultam, entre outros aspectos, da elevada densidade populacional (sobretudo Amadora), do marcado crescimento na última década (sobr etudo Sintra, onde a população residente aumentou cerca de 40% entre 1991 e 2001) e, principalmente, da sua diversidade social, cultural e étnica. D e facto, a proporção de imigrantes nestes concelhos atinge um dos v alores mais elevados do país. A equidade na pr estação de cuidados tem sido demonstrada como factor de r edução das disparidades na saúde que determina a morbilidade e a mortalidade decorrentes da assimetria das populações. Na Unidade de Saúde D (Hospital Fernando Fonseca e 9 Centr os de Saúde da Amadora e Sintra), não tinha ainda sido desenvolvida uma investigação científica estruturada sobre os níveis de saúde e o acesso e utilização dos serviços e que sustentem políticas ajustadas às vulnerabilidades deste grupo. Este conhecimento possibilita a reorganização dos serviços de cuidados de saúde e é fundamental para (r e)pensar processos de planeamento e modelos de inter venção que culminem numa integração de sucesso para o século XXI.info:eu-repo/semantics/publishedVersio

    BR-BCSC Signature: The Cancer Stem Cell Profile Enriched in Brain Metastases that Predicts a Worse Prognosis in Lymph Node-Positive Breast Cancer

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    Brain metastases remain an unmet clinical need in breast oncology, being frequently found in HER2-overexpressing and triple-negative carcinomas. These tumors were reported to be highly cancer stem-like cell-enriched, suggesting that brain metastases probably arise by the seeding of cancer cells with stem features. Accordingly, we found that brain-tropic breast cancer cells show increased stem cell activity and tumorigenic capacity in the chick embryo choriallantoic membrane when compared to the parental cell line. These observations were supported by a significant increase in their stem cell frequency and by the enrichment for the breast cancer stem cell (BCSC) phenotype CD44+CD24-/low. Based on this data, the expression of BCSC markers (CD44, CD49f, P-cadherin, EpCAM, and ALDH1) was determined and found to be significantly enriched in breast cancer brain metastases when compared to primary tumors. Therefore, a brain (BR)-BCSC signature was defined (3-5 BCSC markers), which showed to be associated with decreased brain metastases-free and overall survival. Interestingly, this signature significantly predicted a worse prognosis in lymph node-positive patients, acting as an independent prognostic factor. Thus, an enrichment of a BCSC signature was found in brain metastases, which can be used as a new prognostic factor in clinically challenging breast cancer patients.This work was funded by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by FCT (Fundação para a Ciência e a Tecnologia) Ministério da Ciência, Tecnologia e Ensino Superior under the projects Pest-C/SAU/LA0003/2013, NORTE-01-0145-FEDER-000029, SAICTPAC/0022/2015 POCI—01-0145-FEDER-016390, and FCT/02/SAICT/2017/030625. A Novartis Oncology grant also funded part of the work, namely, the characterization of the Portuguese series of human brain metastases. FCT funded the research grant of R.C. (SFRH/BD/135831/2018). IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274)

    Clues from nearby galaxies to a better theory of cosmic evolution

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    The great advances in the network of cosmological tests show that the relativistic Big Bang theory is a good description of our expanding universe. But the properties of nearby galaxies that can be observed in greatest detail suggest a still better theory would more rapidly gather matter into galaxies and groups of galaxies. This happens in theoretical ideas now under discussion.Comment: published in Natur

    Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

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    To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11)) and MSRA (WC, P = 8.9x10(-9)). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8)). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity

    Bar-Driven Evolution and 2D Spectroscopy of Bulges

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    A multi-faceted approach is described to constrain the importance of bar-driven evolution in disk galaxies, particularly bulge formation. N-body simulations are used to construct stellar kinematic bar diagnostics for edge-on systems and to quantify the expected vertical structure of bars, and they are compared to observations of 30 edge-on spirals, most with a boxy bulge. Long-slit spectra of the galaxies show characteristic double-hump rotation curves, dispersion profiles with secondary peaks and/or flat maxima, and correlated h3 and V profiles, indicating that most of them harbor edge-on bars. The presence of cold, quasi-axisymmetric central stellar disks is also suggested, presumably formed through bar-driven gaseous inflow and star formation. K-band imaging of the same galaxies spectacularly highlights radial variations of the bars' scaleheights, as expected from vertical disk instabilities. The light profiles also vary radially in shape but never approach a classic de Vaucouleurs law. Filtering of the images further isolates the specific orbit families at the origin of the boxy structure, which can be directly related to periodic orbit calculations in 3D barred potentials. Bars are thus shown to contribute substantially to the formation of both large-scale triaxial bulges and embedded central disks. Relevant results from the SAURON survey of the stellar/ionized-gas kinematics and stellar populations of spheroids are also described. Examples are used to illustrate the potential of coupling stellar kinematics and linestrengths (age and metallicity), here specifically to unravel the dynamical evolution and related chemical enrichment history of bars and bulges. [Abridged]Comment: 10 pages, including 4 figures (LaTeX, kapproc.cls, procps.sty). To appear in "Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuning Fork Strikes a New Note", eds. D.L. Block, K.C. Freeman, I. Puerari, & R. Groess (Kluwer: Dordrecht). A version with full resolution PostScript figures is available at http://www.astro.columbia.edu/~bureau/Publications/peanut_sa_04.ps.g

    Associations of ATR and CHEK1 Single Nucleotide Polymorphisms with Breast Cancer

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    DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP) approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls) using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS). The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6x10-5) and rs2155388 in CHEK1 (p=3.1x10-6), but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12%) and breast cancer risk, with a summary odds ratio (confidence interval) of 0.90 (0.83-0.98) [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes
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