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Endometrial cancer is a common gynaeological malignancy: life time exposure to oestrogen is a key risk factor. Oestrogen action is mediated by receptors encoded by ESR1 (ERα) and ESR2 (ERβ): ERα plays a key role in regulating endometrial cell proliferation. A truncated splice variant isoform (ERβ5) encoded by ESR2 is highly expressed in cancers. This study explored whether ERβ5 alters oestrogen responsiveness of endometrial epithelial cells. Immunhistochemistry profiling of human endometrial cancer tissue biopsies identified epithelial cells co-expressing ERβ5 and ERα in stage I endometrial adenocarcinomas and post menopausal endometrium. Induced co-expression of ERβ5 in ERαpos endometrial cancer cells (Ishikawa) significantly increased ligand-dependent activation of an ERE-luciferase reporter stimulated by either E2 or the ERα-selective agonist 1,3,5-(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) compared to untransfected cells. Fluorescence recovery after photobleaching (FRAP) analysis of tagged yellow fluorescent protein (YFP)-ERβ5 transfected into Ishikawa cells revealed that incubation with E2 induced a transient reduction in intra-nuclear mobility characterised by punctate protein redistribution which phenocopied the behaviour of ERα following ligand activation with E2. In ERαneg MDA-MD-231 breast cancer cells, there was no E2-dependent change in mobility of YFP-ERβ5 and no activation of the ERE reporter in cells expressing ERβ5. In conclusion, we demonstrate that ERβ5 can act as heterodimeric partner to ERα in Ishikawa cells and increases their sensitivity to E2. We speculate that expression of ERβ5 in endometrial epithelial cells may increase the risk of malignant transformation and suggest that immunostaining for ERβ5 should be included in diagnostic assessment of women with early grade cancers. [ABSTRACT FROM AUTHOR]

Background: Predicting risk of adverse healthcare outcomes, among community dwelling older adults, is difficult. The Risk Instrument for Screening in the Community (RISC) is a short (2-5 min), global subjective assessment of risk created to identify patients' 1-year risk of three outcomes:institutionalisation, hospitalisation and death. Methods: We compared the accuracy and predictive ability of the RISC, scored by Public Health Nurses (PHN), to the Clinical Frailty Scale (CFS) in a prospective cohort study of community dwelling older adults (n = 803), in two Irish PHN sectors. The area under the curve (AUC), from receiver operating characteristic curves and binary logistic regression models, with odds ratios (OR), compared the discriminatory characteristics of the RISC and CFS. Results: Follow-up data were available for 801 patients. The 1-year incidence of institutionalisation, hospitalisation and death were 10.2, 17.7 and 15.6 % respectively. Patients scored maximum-risk (RISC score 3,4 or 5/5) at baseline had a significantly greater rate of institutionalisation (31.3 and 7.1 %, p < 0.001), hospitalisation (25.4 and 13.2 %, p < 0.001) and death (33.5 and 10.8 %, p < 0.001), than those scored minimum-risk (score 1 or 2/5). The RISC had comparable accuracy for 1-year risk of institutionalisation (AUC of 0.70 versus 0.63), hospitalisation (AUC 0.61 versus 0.55), and death (AUC 0.70 versus 0.67), to the CFS. The RISC significantly added to the predictive accuracy of the regression model for institutionalisation (OR 1.43, p = 0.01), hospitalisation (OR 1.28, p = 0.01), and death (OR 1.58, p = 0.001). Conclusion: Follow-up outcomes matched well with baseline risk. The RISC, a short global subjective assessment, demonstrated satisfactory validity compared with the CFS. [ABSTRACT FROM AUTHOR]

BackgroundLoneliness is a widespread and significant problem on college campuses. Prolonged loneliness in young adulthood is a risk factor for concurrent and future mental health problems and attrition, making college a critical time for support. Cognitive and behavioral interventions show promise for decreasing loneliness and can be widely disseminated through technology. ObjectiveThis pilot randomized controlled trial was conducted to examine the initial efficacy, feasibility, and desirability of a smartphone app, Nod, designed to deliver cognitive and behavioral skill-building exercises to reduce loneliness during the transition to college. MethodsFirst-year college students (N=221, mean age 18.7 years, 59% female) were recruited online during incoming student orientation, and randomized to either receive immediate access to Nod (experimental group, n=100) or access after 4 weeks (control group, n=121). The app delivered skills via fully automated (1) “social challenges,” suggested activities designed to build social connections; (2) reflections, brief cognitive reframing exercises; and (3) student testimonials that encouraged a growth mindset toward social connection building. Main intention-to-treat analyses were used to compare the conditions on self-assessed loneliness, depressive symptoms, and other mental health and college adjustment outcomes at week 4, controlling for baseline values on those variables. Analyses were also performed to test the hypothesis that the treatment benefits would be particularly pronounced for participants with heightened psychological vulnerability at baseline (ie, higher baseline depressive symptoms and loneliness). ResultsRetention was 97% at week 4, and participants viewed an average 36.7 pages of app content. There were no significant condition differences in loneliness at week 4 (F1, 211=0.05, P=.82; ηp2