Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

Peer reviewedPublisher PD

Management of children's urinary tract infections in Dutch family practice: a cohort study

BACKGROUND: Optimal clinical management of childhood urinary tract infections (UTI) potentiates long-term positive health effects. Insight into the quality of care in Dutch family practices for UTIs was limited, particularly regarding observation periods of more than a year. Our aim was to describe the clinical management of young children's UTIs in Dutch primary care and to compare this to the national guideline recommendations. METHODS: In this cohort study, all 0 to 6-year-old children with a diagnosed UTI in 2001 were identified within the Netherlands Information Network of General Practitioners (LINH), which comprises 120 practices. From the Dutch guideline on urinary tract infections, seven indicators were derived, on prescription, follow-up, and referral. RESULTS: Of the 284 children with UTI who could be followed for three years, 183 (64%) were registered to have had one cystitis episode, 52 (18%) had two episodes, and 43 (15%) had three or more episodes. Another six children were registered to have had one or two episodes of acute pyelonephritis. Overall, antibiotics were prescribed for 66% of the children having had ≤ 3 cystitis episodes, two-thirds of whom received the antibiotics of first choice. About 30% of all episodes were followed up in general practice. Thirty-eight children were referred (14%), mostly to a paediatrician (76%). Less than one-third of the children who should have been referred was actually referred. CONCLUSION: Treatment of childhood UTIs in Dutch family practice should be improved with respect to prescription, follow-up, and referral. Quality improvement should address the low incidence of urinary tract infections in children in family practice

A randomised controlled trial of the effects of a web-based PSA decision aid, Prosdex. Protocol

Contains fulltext : 51771.pdf ( ) (Open Access)BACKGROUND: Informed decision making is the theoretical basis in the UK for men's decisions about Prostate Specific Antigen (PSA) testing for prostate cancer testing. The aim of this study is to evaluate the effect of a web-based PSA decision-aid, Prosdex, on informed decision making in men. The objective is to assess the effect of Prosdex on six specific outcomes: (i) knowledge of PSA and prostate cancer-related issues - the principal outcome of the study; (ii) attitudes to testing; (iii) decision conflict; (iv) anxiety; (v) intention to undergo PSA testing; (vi) uptake of PSA testing. In addition, a mathematical simulation model of the effects of Prosdex will be developed. METHODS: A randomised controlled trial with four groups: two intervention groups, one viewing Prosdex and the other receiving a paper version of the site; two control groups, the second controlling for the potential Hawthorn effect of the questionnaire used with the first control group. Men between the ages of 50 and 75, who have not previously had a PSA test, will be recruited from General Practitioners (GPs) in Wales, UK. The principal outcome, knowledge, and four other outcome measures - attitudes to testing, decision conflict, anxiety and intention to undergo testing - will be measured with an online questionnaire, used by men in three of the study groups. Six months later, PSA test uptake will be ascertained from GP records; the online questionnaire will then be repeated. These outcomes, and particularly PSA test uptake, will be used to develop a mathematical simulation model, specifically to consider the impact on health service resources

SFRP1 reduction results in an increased sensitivity to TGF-β signaling

Background Transforming growth factor (TGF)-β plays a dual role during mammary gland development and tumorigenesis and has been shown to stimulate epithelial-mesenchymal transition (EMT) as well as cellular migration. The Wnt/β-catenin pathway is also implicated in EMT and inappropriate activation of the Wnt/β-catenin signaling pathway leads to the development of several human cancers, including breast cancer. Secreted frizzled-related protein 1 (SFRP1) antagonizes this pathway and loss of SFRP1 expression is frequently observed in breast tumors and breast cancer cell lines. We previously showed that when SFRP1 is knocked down in immortalized non-malignant mammary epithelial cells, the cells (TERT-siSFRP1) acquire characteristics associated with breast tumor initiating cells. The phenotypic and genotypic changes that occur in response to SFRP1 loss are consistent with EMT, including a substantial increase in the expression of ZEB2. Considering that ZEB2 has been shown to interact with mediators of TGF-β signaling, we sought to determine whether TGF-β signaling is altered in TERT-siSFRP1 cells. Methods Luciferase reporter assays and real-time PCR analysis were employed to measure TGF-β transcriptional targets. Western blot analysis was used to evaluate TGF-β-mediated ERK1/2 phosphorylation. Migration chamber assays were utilized to quantify cellular migration. TERT-siSFRP1 cells were transfected with Stealth RNAi™ siRNA in order to knock-down the expression of ZEB2. Results TERT-siSFRP1 cells exhibit a significant increase in both TGF-β-mediated luciferase activity as well as TGF-β transcriptional targets, including Integrin β3 and PAI-1. Phosphorylation of ERK1/2 is increased in TERT-siSFRP1 cells in response to enhanced TGF-β signaling. Furthermore, when the TGF-β pathway is blocked with a TGF-βR antagonist (LY364947), cellular migration is significantly hindered. Finally, we found that when ZEB2 is knocked-down, there is a significant reduction in the expression of exogeneous and endogenous TGF-β transcriptional targets and cellular migration is impeded. Conclusions We demonstrate that down-regulation of SFRP1 renders mammary epithelial cells more sensitive to TGF-β signaling which can be partially ameliorated by blocking the expression of ZEB2

Localization and Functional Characterization of the Rat Oatp4c1 Transporter in an In Vitro Cell System and Rat Tissues

The organic anion transporting polypeptide 4c1 (Oatp4c1) was previously identified as a novel uptake transporter predominantly expressed at the basolateral membrane in the rat kidney proximal tubules. Its functional role was suggested to be a vectorial transport partner of an apically-expressed efflux transporter for the efficient translocation of physiological substrates into urine, some of which were suggested to be uremic toxins. However, our in vitro studies with MDCKII cells showed that upon transfection rat Oatp4c1 polarizes to the apical membrane. In this report, we validated the trafficking and function of Oatp4c1 in polarized cell systems as well as its subcellular localization in rat kidney. Using several complementary biochemical, molecular and proteomic methods as well as antibodies amenable to immunohistochemistry, immunofluorescence, and immunobloting we investigated the expression pattern of Oatp4c1 in polarized cell systems and in the rat kidney. Collectively, these data demonstrate that rat Oatp4c1 traffics to the apical cell surface of polarized epithelium and localizes primarily in the proximal straight tubules, the S3 fraction of the nephron. Drug uptake studies in Oatp4c1-overexpressing cells demonstrated that Oatp4c1-mediated estrone-3-sulfate (E3S) uptake was pH-dependent and ATP-independent. These data definitively demonstrate the subcellular localization and histological location of Oatp4c1 and provide additional functional evidence that reconciles expression-function reports found in the literature