Prediagnostic toenail selenium and risk of bladder cancer

The association between several cancers and selenium status has been investigated in epidemiological studies. However, few results concerning bladder cancer have been reported thus far. The association between toenail selenium status and subsequent bladder cancer incidence was investigated in a prospective cohort study among 120,852 men and women aged 55-69 years at baseline (September 1986). The cohort members completed a questionnaire on risk factors for cancer and provided toenail clippings for determination of baseline selenium status. Follow-up for incident cancer was established by record linkage to cancer registries until December 1992. The multivariable case-cohort analysis was based on 431 bladder cancer cases and 2,459 subcohort members, for whom toenail selenium levels were available. The age-, sex- and smoking-adjusted rate ratios (95% confidence intervals) for increasing quintiles of toenail selenium were 1.00 (reference), 1.09 (0.80-1.48), 0.55 (0.38-0.79), 0.63 (0.43-0.91), and 0.67 (0.46-0.97), respectively (P-trend &lt; 0.01). Analyses with selenium as a continuous variable supported these findings. An inverse association between toenail selenium and bladder cancer risk was most pronounced among ex-smokers (P-trend &lt; 0.01); was similar for subjects with high versus low intakes of beta-carotene, vitamin C, and vitamin E; and was mainly confined to invasive transitional cell carcinomas of the urinary bladder, irrespective of tumor morphology. We conclude that the evidence is in favor of an inverse association between selenium and bladder cancer risk.<br/

The Role of the Expert Witness

In this chapter, we discuss general aspects of the role of the expert in court and issues faced by experts. The chapter is written largely from a Dutch perspective, so that references to the Court almost exclusively refer to a judge rather than a jury acting as a fact-finder. Notwithstanding this perspective of the authors, the concepts illustrated herein are widely applicable to issues relating to experts serving in courts outside of the Netherlands. Although the discussions in this chapter are intended to apply to experts in forensic epidemiology, we draw extensively from writings in Law and Economics, in part because so much has been published in this area on the topic of experts and expert testimony, and in part because these writings translate well to other disciplines

O impacto da terapêutica de ressincronização cardíaca nas células produtoras de IL-17 circulantes em doentes com insuficiência cardíaca avançada: efeito anti-inflamatório da terapêutica de ressincronização cardíaca

Provas públicas apresentadas à Escola Superior de Saúde Dr. Lopes Dias do Instituto Politécnico de Castelo Branco para o cumprimento dos requisitos necessários à obtenção do título de Especialista.OBJETIVO: As células produtoras de IL-17 circulantes têm sido implicadas no ambiente inflamatório da insuficiência cardíaca crónica (ICC) e associadas a um mau prognóstico da doença. O objetivo deste trabalho foi avaliar o impacto da terapêutica de ressincronização cardíaca (TRC) na frequência e atividade funcional das células Th17 e Tc17, assim como a expressão de mRNA de IL-17 em doentes com ICC. MÉTODOS: Foram incluídos neste estudo 28 doentes com ICC, avaliados antes da TRC (T0) e 6 meses após (T6), e 15 controlos saudáveis. As células Th17 e Tc17 do sangue periférico foram analisadas por citometria de fluxo e a quantificação do mRNA de IL17 por PCR em tempo-real. RESULTADOS: As células Tc17 tendem a estar mais elevadas nos doentes com ICC submetidos à TRC que nos controlos (0.92% (0.24-3.32) versus 0.60% (0.09-3.68), sem atingir significado estatístico. Depois da TRC, a frequência de células Tc17 diminui significativamente, chegando a níveis semelhantes aos encontrados no grupo controlo (HG) (0.92% (0.24-3.32) ao T0 versus 0.56% (0.21-4.20) ao T6, p<0.05), devido, maioritariamente, aos doentes que responderam à TRC. Além disto, a expressão do mRNA de IL-17 foi apenas detetada num pequeno número de doentes respondedores ao T0 (27%) e apenas detetado num doente respondedor ao T6 (7%). Inversamente, nos doentes não-respondedores, a expressão de mRNA de IL-17 aumenta da avaliação inicial (17%) para T6 (42%). Relativamente às células Th17 não foram encontradas diferenças significativas entre o HG e os doentes com ICC ao T0 e ao T6. CONCLUSÃO: A resposta inflamatória mediada pelas células produtoras de IL-17 do SP parece ser suprimida pela TRC, particularmente nos doentes respondedores.ABSTRACT: PURPOSE: IL-17-producing T cells have been implicated in the inflammatory milieu of chronic heart failure (CHF), which implies a dismal prognosis in affected patients. The aim of this study was to evaluate the impact of cardiac resynchronization therapy (CRT) on the frequency and functional activity of Th17 and Tc17 cells, as well as, on IL-17 mRNA expression in patients with CHF. METHODS: 28 patients with CHF, analysed before CRT (T0) and 6 months later (T6), and 15 healthy controls (HG) were enrolled in this study. Circulating Th17 and Tc17 cells were evaluated by flow cytometry. The quantification of IL-17A mRNA expression was performed by real-time PCR. RESULTS: Circulating Tc17 cells tended to be higher in CHF patients submitted to CRT than in HG (0.92% (0.24-3.32) versus 0.60% (0.09-3.68), although not reaching statistical significance. The frequency of Tc17 cells in CHF patients significantly decreases after CRT reaching levels similar to those of HG (0.92% (0.24-3.32) at T0 versus 0.56% (0.21-4.20) at T6, p<0.05), mainly due to responders to CRT. Additionally, the expression of IL-17 mRNA was detected in a few number of responder patients at T0 (27%) and only detected in one responder at T6 (7%). Conversely, in non-responders, the proportion of patients exhibiting IL-17 mRNA expression increases from baseline (17%) to T6 (42%). No significant differences were observed in Th17 cells between HG, CHF patients in T0 and patients in T6. CONCLUSION: The inflammatory response mediated by circulating IL-17 producing cells seems to be suppressed by CRT, particularly in responders.N/

A case-cohort study on prostate cancer risk in relation to family history of prostate cancer.

We investigated the risk of prostate cancer in relation to a family history of prostate cancer in 58,279 men ages 55-69 years. We found 704 incident cases after 6.3 years of follow-up. Rate ratios and 95% confidence intervals for having an affected vs nonaffected father and brother were, respectively 1.44 (0.80-2.58) and 5.57 (1.61-19.26). We found no evidence for an increasing risk with an increasing percentage of affected family members. The associations we observed were stronger for cases diagnosed before age 70 compared with cases diagnosed after age 70 and for advanced compared with localized tumors

A discrete choice experiment to identify the most efficient quality indicators for the supervision of psychiatric hospitals

Background: In the Netherlands, health care is regulated by the Health and Youth Care Inspectorate. Forty-six indicators are used to prioritize supervision of psychiatric hospitals. The objective of this study is to define a smaller set of weighted indicators which reflects a consensus among inspectors about which aspects are most important for risk assessment. Methods: The set of 46 indicators, complemented with missing information, was reduced to six indicators by means of interviews, group discussions and ranking among the inspectors. These indicators were used as attributes in a discrete choice experiment (DCE) to define their weights. Results: Twenty-six inspectors defined the top four indicators suitable for the risk assessment of psychiatric hospitals. These are: The policy on prevention of compulsory treatment; the policy on dysfunctional professionals; the quality of internal research after a serious incident; and the implementation of multidisciplinary guidelines on suicidal behaviour. These indicators share the same importance with regard to risk assessment. The screening of somatic symptoms and the policy on integrated care are important indicators too, but less relevant. Conclusion: Through a DCE, we reduced the amount of information for risk assessmen

Associations between maternal long-chain polyunsaturated fatty acid concentrations and child cognition at 7 years of age: The MEFAB birth cohort

Concentrations of the fish fatty acids EPA and DHA are low among Dutch women of reproductive age. As the human brain incorporates high concentrations of these fatty acids in utero, particularly during third trimester of gestation, these low EPA and DHA concentrations may have adverse consequences for fetal brain development and functioning. Analyses were conducted using longitudinal observational data of 292 mother-child pairs participating in the MEFAB cohort. Maternal AA, DHA, and EPA were determined in plasma phospholipids - obtained in three trimesters - by gas-liquid chromatography. Cognitive function was assessed at 7 years of age, using the Kaufman Assessment Battery for Children, resulting in three main outcome parameters: sequential processing (short-term memory), simultaneous processing (problem-solving skills), and the mental processing composite score. Spline regression and linear regression analyses were used to analyse the data, while adjusting for potential relevant covariates. Only 2% of the children performed more than one SD below the mental processing composite norm score. Children with lower test scores (<25%) were more likely to have a younger mother with a higher pre-gestational BMI, less likely to be breastfed, and more likely to be born with a lower birth weight, compared to children with higher test scores (≥25%). Fully-adjusted linear regression models did not show associations of maternal AA, DHA, or EPA status during any of the pregnancy trimesters with childhood sequential and simultaneous processing. Maternal fatty acid status during pregnancy was not associated with cognitive performance in Dutch children at age 7