Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3

The success of CD8+ T cell-based cancer immunotherapy emphasizes the importance of understanding the mechanisms of generation of MHC-I peptide ligands and the possible pathways of tumor cell escape from immunosurveillance. Recently, we showed that peptides generated in the nucleus during a pioneer round of mRNA translation (pioneer translation products, or PTPs) are an important source of tumor specific peptides which correlates with the aberrant splicing and transcription events associated with oncogenesis. Here we show that up-regulation of PSME3 proteasome activator in cancer cells results in increased destruction of PTP-derived peptides in the nucleus thus enabling cancer cell to subvert immunosurveillance. These findings unveil a previously unexpected role for PSME3 in antigen processing and identify PSME3 as a druggable target to improve the efficacy of cancer immunotherapy

Factors associated with early menarche: results from the French Health Behaviour in School-aged Children (HBSC) study

<p>Abstract</p> <p>Background</p> <p>Puberty is a transition period making physiological development a challenge adolescents have to face. Early pubertal development could be associated with higher risks of poor health. Our objective was to examine risk behaviours, physical and psychological determinants associated with early menarche (<11 years).</p> <p>Methods</p> <p>Early menarche was assessed in the Health Behaviour in School-aged Children French cross-sectional survey. Data were collected in 2006 by anonymous self-reported standardized questionnaire from a nationally representative sample of 1072 15 years old girls in school classrooms. Family environment, school experience, physical and psychological factors, risk behaviours (substance use and sexual initiation) were recorded. Logistic regression models were applied (analysing for crude and adjusted relationships between early menarche and risk behaviours controlled for family context).</p> <p>Results</p> <p>Median age at menarche was 13.0 years; 57 girls (5.3%) were early-matured. Controlled for familial environment, early menarche was associated with having had more than two life-drunkenness episodes (adjusted OR = 2.5 [1.3-4.6]), early sexual initiation (adjusted OR = 2.8 [1.3-6.0]) and overweight (adjusted OR = 7.3 [3.6-14.9]).</p> <p>Conclusion</p> <p>Early-maturing girls may affiliate with older adolescents, hence engage in risk behaviours linked to their appearance rather than their maturity level. Factors associated with early menarche highlight the need to focus attention on early-matured girls to prevent further health problems linked to risk behaviours.</p

Prevalence of emergency contraceptive pill use among Spanish adolescent girls and their family and psychological profiles

The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background:Adolescent girls’ family context and psychological characteristics play important roles in their sexual behavior, including the use of the emergency contraceptive pill (ECP). This study aims to (1) determine the prevalence of ECP use among girls who have had sexual intercourse and (2) comparatively analyze their family and psychological profiles according to whether they have used ECPs. Methods:The sample of 1735 Spanish girls aged 15 to 18 came from a representative sample of the 2014 edition of the Health Behaviour in School-aged Children (HBSC) study. Of this sample, 398 girls had sexual intercourse and reported their ECP use. Data collection for the HBSC study was performed through an online questionnaire to which adolescents responded anonymously in school. Data analyses were descriptive and bivariate and were performed with the statistical program IBM SPSS Statistics 23.Results:The results demonstrated that 30.65% of girls who had sexual intercourse used ECPs. Noticeable differences in paternal knowledge and communication with the father were observed between girls who used the ECP at least once and those who did not use it. In contrast, differences between girls who used the ECP once and those who used it twice or more were pronounced with regard to parental knowledge, communication with parents, maternal affection,life satisfaction, sense of coherence and depression. Conclusions:This work demonstrates a high prevalence of ECP use and a more positive family and psychological profile for girls who used ECP once compared with those who used it twice or more.Peer reviewedFinal Published versio

Use of emergency contraceptive pill by 15-year-old girls: results from the international health behaviour in school-aged children (hbsc) study

Objective To describe emergency contraceptive pill (ECP) use and variation across countries/regions; and to explore personal and contextual factors associated with ECP use and differences across countries/regions. Design Data were obtained from 11 countries/regions in the 2006 Health Behaviour in School-aged Children cross-sectional study. Setting Data were collected by self-report questionnaire in school classrooms. Population The analysis is based on 2118 sexually active 15-year-old girls. Methods Contraceptive behaviours were compared across countries/regions by chi-square tests. Individual factors related to ECP use were investigated with separate logistic regression models. Multilevel random-intercept models allowed the investigation of individual and contextual effects, by partitioning the variance into student, school and country/region levels. Main outcome measures ECP use at last sexual intercourse. Results ECP use rate varied significantly across countries/regions. Poor communication with at least one adult (odds ratio [OR] 1.62 [1.12-2.36], P = 0.011) and daily smoking (OR 1.46 [1.00-2.11], P = 0.048) were independently associated with ECP use in comparison with condom and/or birth-control pill use. Sexual initiation at 14 years or later (OR 2.02 [1.04-3.93], P = 0.039), good perceived academic achievement (OR 1.69 [1.04-2.75], P = 0.035) and daily smoking (OR 1.63 [1.01-2.64], P = 0.045) were associated with higher levels of ECP use in comparison with unprotected girls. The country-level variance remained significant in both comparisons. Conclusions These data document the large heterogeneity in rates of ECP use between countries/regions. These differences could not be explained by individual or contextual factors, and raise further questions in relation to ECP access for adolescents and their education in its appropriate use

Use of emergency contraceptive pill by 15-year-old girls: results from the international health behaviour in school-aged children (hbsc) study

Objective To describe emergency contraceptive pill (ECP) use and variation across countries/regions; and to explore personal and contextual factors associated with ECP use and differences across countries/regions. Design Data were obtained from 11 countries/regions in the 2006 Health Behaviour in School-aged Children cross-sectional study. Setting Data were collected by self-report questionnaire in school classrooms. Population The analysis is based on 2118 sexually active 15-year-old girls. Methods Contraceptive behaviours were compared across countries/regions by chi-square tests. Individual factors related to ECP use were investigated with separate logistic regression models. Multilevel random-intercept models allowed the investigation of individual and contextual effects, by partitioning the variance into student, school and country/region levels. Main outcome measures ECP use at last sexual intercourse. Results ECP use rate varied significantly across countries/regions. Poor communication with at least one adult (odds ratio [OR] 1.62 [1.12-2.36], P = 0.011) and daily smoking (OR 1.46 [1.00-2.11], P = 0.048) were independently associated with ECP use in comparison with condom and/or birth-control pill use. Sexual initiation at 14 years or later (OR 2.02 [1.04-3.93], P = 0.039), good perceived academic achievement (OR 1.69 [1.04-2.75], P = 0.035) and daily smoking (OR 1.63 [1.01-2.64], P = 0.045) were associated with higher levels of ECP use in comparison with unprotected girls. The country-level variance remained significant in both comparisons. Conclusions These data document the large heterogeneity in rates of ECP use between countries/regions. These differences could not be explained by individual or contextual factors, and raise further questions in relation to ECP access for adolescents and their education in its appropriate use

Supplementary Material for: Evaluation of the Utility of in utero Treatment of Twin Anemia-Polycythemia Sequence

<b><i>Objective:</i></b> The aim of this study is to evaluate the interest in the in utero treatment of twin anemia-polycythemia sequence (TAPS). <b><i>Methods:</i></b> The obstetrical and neonatal data on all cases of TAPS followed up in our institution between 2006 and 2013 were reviewed. Statistical analyses were conducted using Bayesian methods. <b><i>Results:</i></b> Twenty cases of TAPS were included. Laser therapy or intrauterine transfusion (IUT) was performed on the donor twin in 9 cases. Eleven cases were included in the ‘nontreated' group (managed expectantly or diagnosed at birth). The gestational age at diagnosis was lower in the group with treated TAPS [difference (diff) = -22.20 days (-57.13, 14.28), probability (Pr) (diff >0) = 10.6%]. The rate of preterm premature rupture of membranes was higher in the group with treated TAPS [diff = 22.5% (-14, 57), Pr (diff >0) = 89%], but overall mortality was similar. The interval between diagnosis and delivery was longer [diff = 44.37 days (9.41, 77.90), Pr (diff >0) = 99.2%], the TAPS resolution rate was higher [diff = 49.9% (12, 81), Pr (diff >0) = 99.4%], and the neonatal transfusion rate was lower [diff = -30.5% (-60, 0), Pr (diff >0) = 2.6%] in the treated group. <b><i>Conclusion:</i></b> In utero treatment for TAPS is associated with a higher resolution rate of TAPS and a longer time between diagnosis and birth, but overall mortality is the same as with expectant management