Sexual Minorities in England Have Poorer Health and Worse Health Care Experiences: A National Survey

This is the final published version. Available from Springer via the DOI in this record.BACKGROUND: The health and healthcare of sexual minorities have recently been identified as priorities for health research and policy. OBJECTIVE: To compare the health and healthcare experiences of sexual minorities with heterosexual people of the same gender, adjusting for age, race/ethnicity, and socioeconomic status. DESIGN: Multivariate analyses of observational data from the 2009/2010 English General Practice Patient Survey. PARTICIPANTS: The survey was mailed to 5.56 million randomly sampled adults registered with a National Health Service general practice (representing 99 % of England’s adult population). In all, 2,169,718 people responded (39 % response rate), including 27,497 people who described themselves as gay, lesbian, or bisexual. MAIN MEASURES: Two measures of health status (fair/poor overall self-rated health and self-reported presence of a longstanding psychological condition) and four measures of poor patient experiences (no trust or confidence in the doctor, poor/very poor doctor communication, poor/very poor nurse communication, fairly/very dissatisfied with care overall). KEY RESULTS: Sexual minorities were two to three times more likely to report having a longstanding psychological or emotional problem than heterosexual counterparts (age-adjusted for 5.2 % heterosexual, 10.9 % gay, 15.0 % bisexual for men; 6.0 % heterosexual, 12.3 % lesbian and 18.8 % bisexual for women; p < 0.001 for each). Sexual minorities were also more likely to report fair/poor health (adjusted 19.6 % heterosexual, 21.8 % gay, 26.4 % bisexual for men; 20.5 % heterosexual, 24.9 % lesbian and 31.6 % bisexual for women; p < 0.001 for each). Adjusted for sociodemographic characteristics and health status, sexual minorities were about one and one-half times more likely than heterosexual people to report unfavorable experiences with each of four aspects of primary care. Little of the overall disparity reflected concentration of sexual minorities in low-performing practices. CONCLUSIONS: Sexual minorities suffer both poorer health and worse healthcare experiences. Efforts should be made to recognize the needs and improve the experiences of sexual minorities. Examining patient experience disparities by sexual orientation can inform such efforts.The Department of Health (England

Integrating Signals from the T-Cell Receptor and the Interleukin-2 Receptor

T cells orchestrate the adaptive immune response, making them targets for immunotherapy. Although immunosuppressive therapies prevent disease progression, they also leave patients susceptible to opportunistic infections. To identify novel drug targets, we established a logical model describing T-cell receptor (TCR) signaling. However, to have a model that is able to predict new therapeutic approaches, the current drug targets must be included. Therefore, as a next step we generated the interleukin-2 receptor (IL-2R) signaling network and developed a tool to merge logical models. For IL-2R signaling, we show that STAT activation is independent of both Src- and PI3-kinases, while ERK activation depends upon both kinases and additionally requires novel PKCs. In addition, our merged model correctly predicted TCR-induced STAT activation. The combined network also allows information transfer from one receptor to add detail to another, thereby predicting that LAT mediates JNK activation in IL-2R signaling. In summary, the merged model not only enables us to unravel potential cross-talk, but it also suggests new experimental designs and provides a critical step towards designing strategies to reprogram T cells

A new model of development of the mammalian ovary and follicles

Ovarian follicular granulosa cells surround and nurture oocytes, and produce sex steroid hormones. It is believed that during development the ovarian surface epithelial cells penetrate into the ovary and develop into granulosa cells when associating with oogonia to form follicles. Using bovine fetal ovaries (n = 80) we identified a novel cell type, termed GREL for Gonadal Ridge Epithelial-Like. Using 26 markers for GREL and other cells and extracellular matrix we conducted immunohistochemistry and electron microscopy and chronologically tracked all somatic cell types during development. Before 70 days of gestation the gonadal ridge/ovarian primordium is formed by proliferation of GREL cells at the surface epithelium of the mesonephros. Primordial germ cells (PGCs) migrate into the ovarian primordium. After 70 days, stroma from the underlying mesonephros begins to penetrate the primordium, partitioning the developing ovary into irregularly-shaped ovigerous cords composed of GREL cells and PGCs/oogonia. Importantly we identified that the cords are always separated from the stroma by a basal lamina. Around 130 days of gestation the stroma expands laterally below the outermost layers of GREL cells forming a sub-epithelial basal lamina and establishing an epithelial-stromal interface. It is at this stage that a mature surface epithelium develops from the GREL cells on the surface of the ovary primordium. Expansion of the stroma continues to partition the ovigerous cords into smaller groups of cells eventually forming follicles containing an oogonium/oocyte surrounded by GREL cells, which become granulosa cells, all enclosed by a basal lamina. Thus in contrast to the prevailing theory, the ovarian surface epithelial cells do not penetrate into the ovary to form the granulosa cells of follicles, instead ovarian surface epithelial cells and granulosa cells have a common precursor, the GREL cell.Katja Hummitzsch, Helen F. Irving-Rodgers, Nicholas Hatzirodos, Wendy Bonner, Laetitia Sabatier, Dieter P. Reinhardt, Yoshikazu Sado, Yoshifumi Ninomiya, Dagmar Wilhelm and Raymond J. Rodger