The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma

We are grateful to Paulo Vieira, Cecília Leão, Manuel T. Silva, Nuno Sousa, Jorge Correia- Pinto, Joana Palha, Margarida Correia-Neves, Margarida Lima and Matthew Berry for all their input throughout these studies and critical reading of the manuscript. We are grateful to the patients who joint this study as well as to all members of the Life and Health Sciences Research Institute and School of Health Sciences, University of Minho, who contributed in any way to the development of this workNon-Hodgkin lymphoma (NHL) has been associated with immunological defects, chronic inflammatory and autoimmune conditions. Given the link between immune dysfunction and NHL, genetic variants in toll-like receptors (TLRs) have been regarded as potential predictive factors of susceptibility to NHL. Adequate anti-tumoral responses are known to depend on TLR9 function, such that the use of its synthetic ligand is being targeted as a therapeutic strategy. We investigated the association between the functional rs5743836 polymorphism in the TLR9 promoter and risk for B-cell NHL and its major subtypes in three independent case-control association studies from Portugal (1160 controls, 797 patients), Italy (468 controls, 494 patients) and the US (972 controls, 868 patients). We found that the rs5743836 polymorphism was significantly overtransmitted in both Portuguese (odds ratio (OR), 1.85; P=7.3E-9) and Italian (OR, 1.84; P=6.0E-5) and not in the US cohort of NHL patients. Moreover, the increased transcriptional activity of TLR9 in mononuclear cells from patients harboring rs5743836 further supports a functional effect of this polymorphism on NHL susceptibility in a population-dependent manner.AC, NSO, MTC, and AJA were financially supported by a fellowship from Fundação para a Ciência e Tecnologia, Portugal. MS is a Ciência 2007 fellow. This study was supported by Fundação para a Ciência e Tecnologia, Portugal (PIC/IC/83313/2007) and by Fundação Calouste Gulbenkian, Serviço de Saúde e Desenvolvimento Humano, Portugal (Grant Number:Proc/60666-MM/734). CFS, PB and LC were supported by National Institutes of Health (NIH) grants CA122663 and CA104682, and PB also by NIH grants CA45614 and CA89745

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

The impacts of oral health on quality of life in working adults

This study investigated the impacts of oral health-related quality of life (OHRQoL) on daily activities and work productivity in adults. A cross-sectional study was conducted in a supermarket chain in the state of São Paulo, which included 386 workers, age-range 20 – 64 years. Participants were examined for oral disease following WHO recommendations, and the oral health impact profile (OHIP) assessment was used to determine OHRQoL. Demographic, socio-economic, use of dental services, and OHRQoL data were obtained. Answers to the OHIP were dichotomized into no impact and some impact, and the relationship to OHRQoL was determined. Poisson regression with robust variance was performed using SPSS version 17.0. Dimensions with highest OHIP scores were physical pain and psychological discomfort. Sex (male: PR = 0 .55, 9 5% C I 0 .38 – 0.80), lower family i ncome (PR = 1.49, 95% CI 1.04 – 2.12), visiting a dentist due to pain (PR = 2.14, 95% CI 1.57 – 3.43), tooth loss (PR = 1.59, 95% CI 1.09 – 2.32), and needing treatment for caries (PR = 1.59, 95% CI 1.09 – 2.32) were most likely to impact OHRQoL. Therefore, socioeconomic and demographic status and use of dental services impacted OHRQoL. These results indicate that oral health promotion strategies should be included in work environments

Desigualdades na autoavaliacao da saude bucal em adultos

OBJETIVO Analisar a associação entre autoavaliação da saúde bucal em adultos e desigualdades sociodemográficas. MÉTODOS Estudo transversal com 2.016 adultos de 20 a 59 anos de idade, de Florianópolis, SC, em 2009. A amostra foi obtida por duplo estágio (setores censitários e domicílios). Os dados foram coletados por entrevistas domiciliares face a face. O desfecho foi autoavaliação da saúde bucal. As variáveis exploratórias foram caracterizadas em blocos demográficos, socioeconômicos, de utilização de serviços e de condições bucais autorreferidas. Foi realizada análise de regressão multivariável de Poisson e estimadas as razões de prevalências e respectivos intervalos de 95% de confiança. RESULTADOS A prevalência de autoavaliação negativa da saúde bucal foi de 33,2% (IC95% 29,8;36,6). Idade avançada, referir-se como pardo, possuir menor escolaridade, ter consultado o dentista há três anos ou mais, ter realizado a última consulta em consultório público, possuir menos de dez dentes naturais presentes em pelo menos um arco, perceber necessidade de tratamento odontológico, apresentar sensação de boca seca e dificuldade de alimentação em virtude dos dentes foram associados à autoavaliação negativa da saúde bucal na análise ajustada. CONCLUSÕES A autoavaliação da saúde bucal reflete as desigualdades em saúde e está relacionada às piores condições socioeconômicas, menor uso de serviços de saúde e pior condição bucal autorreferida

Mesenchymal Stem Cells Promote Mammosphere Formation and Decrease E-Cadherin in Normal and Malignant Breast Cells

Normal and malignant breast tissue contains a rare population of multi-potent cells with the capacity to self-renew, referred to as stem cells, or tumor initiating cells (TIC). These cells can be enriched by growth as "mammospheres" in three-dimensional cultures.We tested the hypothesis that human bone-marrow derived mesenchymal stem cells (MSC), which are known to support tumor growth and metastasis, increase mammosphere formation.We found that MSC increased human mammary epithelial cell (HMEC) mammosphere formation in a dose-dependent manner. A similar increase in sphere formation was seen in human inflammatory (SUM149) and non-inflammatory breast cancer cell lines (MCF-7) but not in primary inflammatory breast cancer cells (MDA-IBC-3). We determined that increased mammosphere formation can be mediated by secreted factors as MSC conditioned media from MSC spheroids significantly increased HMEC, MCF-7 and SUM149 mammosphere formation by 6.4 to 21-fold. Mammospheres grown in MSC conditioned media had lower levels of the cell adhesion protein, E-cadherin, and increased expression of N-cadherin in SUM149 and HMEC cells, characteristic of a pro-invasive mesenchymal phenotype. Co-injection with MSC in vivo resulted in a reduced latency time to develop detectable MCF-7 and MDA-IBC-3 tumors and increased the growth of MDA-IBC-3 tumors. Furthermore, E-cadherin expression was decreased in MDA-IBC-3 xenografts with co-injection of MSC.MSC increase the efficiency of primary mammosphere formation in normal and malignant breast cells and decrease E-cadherin expression, a biologic event associated with breast cancer progression and resistance to therapy

Interaction of β-Sheet Folds with a Gold Surface

The adsorption of proteins on inorganic surfaces is of fundamental biological importance. Further, biomedical and nanotechnological applications increasingly use interfaces between inorganic material and polypeptides. Yet, the underlying adsorption mechanism of polypeptides on surfaces is not well understood and experimentally difficult to analyze. Therefore, we investigate here the interactions of polypeptides with a gold(111) surface using computational molecular dynamics (MD) simulations with a polarizable gold model in explicit water. Our focus in this paper is the investigation of the interaction of polypeptides with β-sheet folds. First, we concentrate on a β-sheet forming model peptide. Second, we investigate the interactions of two domains with high β-sheet content of the biologically important extracellular matrix protein fibronectin (FN). We find that adsorption occurs in a stepwise mechanism both for the model peptide and the protein. The positively charged amino acid Arg facilitates the initial contact formation between protein and gold surface. Our results suggest that an effective gold-binding surface patch is overall uncharged, but contains Arg for contact initiation. The polypeptides do not unfold on the gold surface within the simulation time. However, for the two FN domains, the relative domain-domain orientation changes. The observation of a very fast and strong adsorption indicates that in a biological matrix, no bare gold surfaces will be present. Hence, the bioactivity of gold surfaces (like bare gold nanoparticles) will critically depend on the history of particle administration and the proteins present during initial contact between gold and biological material. Further, gold particles may act as seeds for protein aggregation. Structural re-organization and protein aggregation are potentially of immunological importance