Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

BACKGROUND: It has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression. METHODS: We initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3) and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells. RESULTS: Lymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium), although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating endothelial cells, and the cross sectional area of vessel profiles were significantly increased in response to VEGF-D in comparison to control tumor cells. In contrast, no significant changes were noted in myometrial blood vessels. In addition, examples of invading cells or tumor emboli were observed in mice receiving VEGF-D expressing 293EBNA cells. CONCLUSIONS: These results illustrate that VEGF-D over-expression has differential effects on the uterine vasculature. These effects may facilitate VEGF-D's ability to promote endometrial cancer metastasis and disease progression

Dilated Thin-Walled Blood and Lymphatic Vessels in Human Endometrium: A Potential Role for VEGF-D in Progestin-Induced Break-Through Bleeding

Progestins provide safe, effective and cheap options for contraception as well as the treatment of a variety of gynaecological disorders. Episodes of irregular endometrial bleeding or breakthrough bleeding (BTB) are a major unwanted side effect of progestin treatment, such that BTB is the leading cause for discontinued use of an otherwise effective and popular medication. The cellular mechanisms leading to BTB are poorly understood. In this study, we make the novel finding that the large, dilated, thin walled vessels characteristic of human progestin-treated endometrium include both blood and lymphatic vessels. Increased blood and lymphatic vessel diameter are features of VEGF-D action in other tissues and we show by immunolocalisation and Western blotting that stromal cell decidualisation results in a significant increase in VEGF-D protein production, particularly of the proteolytically processed 21 kD form. Using a NOD/scid mouse model with xenografted human endometrium we were able to show that progestin treatment causes decidualisation, VEGF-D production and endometrial vessel dilation. Our results lead to a novel hypothesis to explain BTB, with stromal cell decidualisation rather than progestin treatment per se being the proposed causative event, and VEGF-D being the proposed effector agent

Baby Business: a randomised controlled trial of a universal parenting program that aims to prevent early infant sleep and cry problems and associated parental depression

<p>Abstract</p> <p>Background</p> <p>Infant crying and sleep problems (e.g. frequent night waking, difficulties settling to sleep) each affect up to 30% of infants and often co-exist. They are costly to manage and associated with adverse outcomes including postnatal depression symptoms, early weaning from breast milk, and later child behaviour problems. Preventing such problems could improve these adverse outcomes and reduce costs to families and the health care system. Anticipatory guidance-i.e. providing parents with information about normal infant sleep and cry patterns, ways to encourage self-settling in infants, and ways to develop feeding and settling routines <it>before </it>the onset of problems-could prevent such problems. This paper outlines the protocol for our study which aims to test an anticipatory guidance approach.</p> <p>Methods/Design</p> <p>750 families from four Local Government Areas in Melbourne, Australia have been randomised to receive the <it>Baby Business </it>program (intervention group) or usual care (control group) offered by health services. The <it>Baby Business </it>program provides parents with information about infant sleep and crying via a DVD and booklet (mailed soon after birth), telephone consultation (at infant age 6-8 weeks) and parent group session (at infant age 12 weeks). All English speaking parents of healthy newborn infants born at > 32 weeks gestation and referred by their maternal and child health nurse at their first post partum home visit (day 7-10 postpartum), are eligible. The primary outcome is parent report of infant night time sleep as a problem at four months of age and secondary outcomes include parent report of infant daytime sleep or crying as a problem, mean duration of infant sleep and crying/24 hours, parental depression symptoms, parent sleep quality and quantity and health service use. Data will be collected at two weeks (baseline), four months and six months of age. An economic evaluation using a cost-consequences approach will, from a societal perspective, compare costs and health outcomes between the intervention and control groups.</p> <p>Discussion</p> <p>To our knowledge this is the first randomised controlled trial of a program which aims to prevent both infant sleeping and crying problems and associated postnatal depression symptoms. If effective, it could offer an important public health prevention approach to these common, distressing problems.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN63834603">ISRCTN63834603</a></p

"The Truth lies in Black and White." The Language of Truth and the Search for Coloured Identity in Zoe Wicomb’s David’s Story

Cet article analyse la manière dont Zoe Wicomb explore les procédés de construction identitaire et les notions d’inaccessibilité et de multiplicité de la vérité. Ancré dans l’Afrique du Sud peu après la chute de l’apartheid, ce roman reflète les difficultés intrinsèques à un pays en pleine mutation et soulève des questions importantes quant à la (re)construction de l’identité. Par le biais de jeux narratifs et langagiers, Wicomb problématise la notion de vérité et, créant au sein de ce roman des relations intertextuelles avec des textes sud-africains et internationaux, interroge la notion de l’hybridité, proposant ainsi une vision anti-essentialiste de la "Nouvelle" Afrique du Su

Histoire et histoires dans la fiction d'Yvonne Vera et de Zoë Wicomb (palimpsestes, identités, hybridité)

C est dans un contexte d incertitude épistémologique et ontologique que les deux écrivaines qui font l objet de cette thèse, Zoe Wicomb (sud-africaine) et Yvonne Vera (zimbabwéenne), écrivirent et publièrent leurs romans et leurs recueils de nouvelles. L euphorie qui régna dans un premier temps après l effondrement des régimes opprimants de leurs pays respectifs fut rapidement remplacée par des doutes et des craintes à l égard de l avenir, et le potentiel positif d une interrogation de l Histoire dite officielle donna lieu à un révisionnisme parfois problématique. Nous nous attachons ici à une analyse des procédés thématiques, structuraux, linguistiques et narratologiques déployés par ces auteures dans un effort de rendre compte de la relation entre l Histoire et les histoires dans leurs œuvres fictionnelles. En analysant l intertextualité, la représentation de la mémoire, la construction et la déconstruction identitaire, l hybridité, la porosité des frontières entre la vérité et le mensonge, et la représentation de la femme, nous révélons la complexité de la relation entre l Histoire et les histoires, telle qu elle est mise en avant dans la fiction de ces auteures. L interrogation quant à une convergence potentielle ou éventuelle entre le postcolonial et le postmoderne dans ces ouvrages est sous-jacente à cette analyse de l enchâssement de l Histoire et les histoires. En nous appuyant sur des théories critiques récentes, nous nous demandons si nous pouvons constater cette convergence dans les ouvrages étudiés, ou si la fiction de ces écrivaines réfutent de telles étiquettes qui se révèlent parfois totalisantes.It is within a context of epistemologial and ontological uncertainty that the two authors on whom this thesis concentrates, Zoë Wicomb (South African) and Yvonne Vera (Zimbabwean), wrote and published their novels and collections of short stories. The euphoria which reigned initially after the collapse of the oppressive regimes of their respective countries was rapidly replaced by uncertainty and fear regarding the future, and the positive potential of a questioning of official history, gave way to a sometimes problematic revisionism. An analysis of the thematic, structural, linguistic and narratological devices used by these authors in an effort to reveal the relationship between History and stories in their fiction is the central focus of this thesis. Analysing the use of intertextuality, the representation of memory, the construction and deconstruction of identity, hybridity, the blurred boundaries between truth and falsehood and the representation of women, the complexity of the relationship between History and stories, as it is underlined in the fiction of these authors, is shown. The question of whether one can pinpoint a potential convergence of the postcolonial and the postmodern in these texts underlies this analysis of the interlinking of History and stories. With the help of recent critical theory, we reveal whether this convergence can be found in the works studied, or whether the fiction of these writers refutes such labels which sometimes turn out to be problematic and totalisingPARIS3-BU (751052102) / SudocSudocFranceF

The Power of School Conditions: Individual, Relational, and Organizational Influences on Educator Wellbeing.

Wellbeing in schools is often focused at the individual level, exploring students' or teachers' individual traits, habits, or actions that influence wellbeing. However, studies rarely take a whole-school approach that includes staff wellbeing, and frequently ignore relational and organizational level variables. We take a systems informed positive psychology approach and argue that it is essential to build greater understanding about organizational and relational influences on wellbeing in order for schools to support educator wellbeing. Our study evaluated the relative contributions of individual, relational, and organizational factors to educator wellbeing. Our measure of wellbeing focused on the life satisfaction and flourishing of 559 educators in 12 New Zealand schools. We used a social network analysis approach to capture educators' relational ties, and demographic data and psychometric scales to capture individual and organizational level variables. Results of hierarchical blockwise regressions showed that individual, relational, and organizational factors were all significantly associated with educator wellbeing; however, it was educators' perceptions of trusting and collaborative school conditions that were most strongly associated with their wellbeing. The number of relational ties educators had explained the least amount of variance in wellbeing. Educators were more likely to experience high levels of support when their close contacts also experienced high levels of support. However, for many educators, there was a negative association between their most frequent relational ties and their reported levels of support. Our results suggest that attending to the organizational factors that influence wellbeing, through creating trusting and collaborative school conditions, may be one of the most influential approaches to enhancing educator wellbeing. We call for whole-school approaches to wellbeing that not only consider how to support and enhance the wellbeing of school staff as well as students, but also view the conditions created within a school as a key driver of wellbeing within schools

Visitors and Residents: mapping student attitudes to academic use of social networks

The Visitors and Residents model of internet use suggests a continuum of modes of engagement with the online world, ranging from tool use to social spaces. In this paper, we examine evidence derived from a large cohort of students to assess whether this idea can be validated by experimental evidence. We find statistically significant differences between individuals displaying ‘Visitor’ or ‘Resident’ attitudes, suggesting that the Visitors and Residents model is a useful typology for approaching and understanding online behaviour. From our limited sample, we have been able to produce evidence that the Visitors and Residents labels are statistically robust. This demonstrates that the Visitors and Residents approach provides a valuable framework for those considering the use of social tools in educational contexts