Inflammation drives atherosclerosis. Both immune and resident vascular cell types are involved in the development of atherosclerotic lesions. The phenotype and function of these cells are key in determining the development of lesions. Toll-like receptors are the most characterised innate immune receptors and are responsible for the recognition of exogenous conserved motifs on pathogens, and, potentially, some endogenous molecules. Both endogenous and exogenous TLR agonists may be present in atherosclerotic plaques. Engagement of toll-like receptors on immune and resident vascular cells can affect atherogenesis as signalling downstream of these receptors can elicit proinflammatory cytokine release, lipid uptake, and foam cell formation and activate cells of the adaptive immune system. In this paper, we will describe the expression of TLRs on immune and resident vascular cells, highlight the TLR ligands that may act through TLRs on these cells, and discuss the consequences of TLR activation in atherosclerosis.

Srdjan Saso clinical research fellow 1 , Jayanta Chatterjee clinical research fellow 1 , Ektoras Georgiou clinical research fellow 2 , Anthony M Ditri general practitioner 3 , J Richard Smith gynaecological surgeon 4 , Sadaf Ghaem-Maghami senior lecturer and honorary consultant in gynaecological oncology 5The International Agency for Research on Cancer recently estimated that endometrial carcinoma is the commonest gynaecological cancer in the developed world, 1 with a rising incidence in postmenopausal women. In 2007, 7536 new endometrial cancers were diagnosed in the UK, making it the fourth most common cancer in women after breast, lung, and colorectal cancers. 2 Cancer of the endometrium is the commonest cancer of the uterine corpus (about 92%, the remainder being uterine carcinosarcomas and sarcomas), according to the Surveillance, Epidemiology and End Results programme of the US National Cancer Institute, which has collected data on cancer from various locations and sources since 1973. 3 Cure is possible and the overall five year survival rate for all stages is currently around 80%. Most women present early in the course of the disease when cure is more likely, so primary care practitioners need to be vigilant for potential indicators. We discuss the epidemiology, diagnosis, and treatment of endometrial cancer on the basis of a review of observational research, randomised trials, reviews, and meta-analyses. Summary pointsEndometrial cancer is the most common gynaecological cancer in more developed countries and its incidence is increasing in postmenopausal women Postmenopausal bleeding is the hallmark symptomThe main risk factors for the development of endometrioid endometrial carcinoma are obesity and chronic unopposed oestrogen stimulation of the endometrium All women with suspected endometrial cancer require transvaginal ultrasonography and most will undergo endometrial biopsy; more sophisticated radiological examinations are required for accurate preoperative staging.Treatment is usually surgical, comprising total hysterectomy and bilateral salpingo-oophorectomy.Adjuvant therapy with radiotherapy, chemotherapy, or hormonal therapy is considered in more advanced or high risk disease Sources and selection criteriaWe searched PubMed to identify peer reviewed original research articles, meta-analyses, and reviews. Search terms were endometrial cancer, cancer of the endometrium, endometrial adenocarcinoma, neoplasm and endometrium, and endometrial neoplasm. Only papers written in English were considered.

External cephalic version can safely be performed with most breech presentations.

Progesterone is widely used to prolong gestation in women at risk of preterm labour (PTL), and acts at least in part via the inhibition of inflammatory cytokine-induced prostaglandin synthesis. This study investigates the mechanisms responsible for this inhibition in human myometrial cells. We used reporter constructs to demonstrate that interleukin 1beta (IL-1β) inhibits progesterone driven PRE activation via p65 activation and that IL-1β reduced progesterone driven gene expression (FKBP5). Conversely, we found that the activity of a p65-driven NFκB reporter construct was reduced by overexpression of progesterone receptor B (PRB) alone and that this was enhanced by the addition of MPA and that both MPA and progesterone suppressed IL-1β-driven cyclo-oxygenase-2 (COX-2) expression. We found that over-expressed Halo-tagged PRB, but not PRA, bound to p65 and that in IL-1β-treated cells, with no overexpression of either PR or p65, activated p65 bound to PR. However, we found that the ability of MPA to repress IL-1β-driven COX-2 expression was not enhanced by overexpression of either PRB or PRA and that although the combined PR and GR antagonist Ru486 blocked the effects of progesterone and MPA, the specific PR antagonist, Org31710, did not, suggesting that progesterone and MPA act via GR and not PR. Knockdown using siRNA confirmed that both MPA and progesterone acted via GR and not PR or AR to repress IL-1β-driven COX-2 expression. We conclude that progesterone acts via GR to repress IL-1β-driven COX-2 activation and that although the interaction between p65 and PRB may be involved in the repression of progesterone driven gene expression it does not seem to be responsible for progesterone repression of IL-1β-induced COX-2 expression.