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991.
992.
Janmaat S Akwa Y Doulazmi M Bakouche J Gautheron V Liere P Eychenne B Pianos A Luiten P Groothuis T Baulieu EE Mariani J Sherrard RM Frédéric F 《Age (Dordrecht, Netherlands)》2011,33(4):565-578
A major problem of ageing is progressive impairment of neuronal function and ultimately cell death. Since sex steroids are neuroprotective, their decrease with age may underlie age-related neuronal degeneration. To test this, we examined Purkinje cell numbers, plasma sex steroids and cerebellar neurosteroid concentrations during normal ageing (wild-type mice, WT), in our model of precocious ageing (Rora(+/sg), heterozygous staggerer mice in which expression of the neuroprotective factor RORα is disrupted) and after long-term hormone insufficiency (WT post-gonadectomy). During normal ageing (WT), circulating sex steroids declined prior to or in parallel with Purkinje cell loss, which began at 18 months of age. Although Purkinje cell death was advanced in WT long-term steroid deficiency, this premature neuronal loss did not begin until 9 months, indicating that vulnerability to sex steroid deficiency is a phenomenon of ageing Purkinje neurons. In precocious ageing (Rora(+/sg)), circulating sex steroids decreased prematurely, in conjunction with marked Purkinje cell death from 9 months. Although Rora(+/sg) Purkinje cells are vulnerable through their RORα haplo-insufficiency, it is only as they age (after 9 months) that sex steroid failure becomes critical. Finally, cerebellar neurosteroids did not decrease with age in either genotype or gender; but were profoundly reduced by 3 months in male Rora(+/sg) cerebella, which may contribute to the fragility of their Purkinje neurons. These data suggest that ageing Purkinje cells are maintained by circulating sex steroids, rather than local neurosteroids, and that in Rora(+/sg) their age-related death is advanced by premature sex steroid loss induced by RORα haplo-insufficiency. 相似文献
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Raymond S Saliou A Nicot F Delobel P Dubois M Cazabat M Sandres-Sauné K Marchou B Massip P Izopet J 《AIDS (London, England)》2011,25(13):1668-1670
We used ultra-deep pyrosequencing and the Toulouse Tropism Test phenotypic assay to determine the prevalence of CXCR4-using viruses in 21 patients with primary HIV-1 infections. We found X4-containing virus populations in 9% of patients by ultra-deep pyrosequencing using position-specific scoring matrices (PSSM(X4/R5)) or geno2pheno(5.75) and in 14% using the combined 11/25 and net charge rule. The phenotypic assay identified 9% of CXCR4-using viruses. This confirms that R5 viruses are predominant in primary HIV-1 infections. 相似文献
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Susan M. O'Brien John C. Byrd Peter Hillmen Steven Coutre Jennifer R. Brown Paul M. Barr Jacqueline C. Barrientos Stephen Devereux Tadeusz Robak Nishitha M. Reddy Thomas J. Kipps Alessandra Tedeschi Florence Cymbalista Paolo Ghia Stephen Chang Joi Ninomoto Danelle F. James Jan A. Burger 《American journal of hematology》2019,94(5):554-562
The efficacy of ibrutinib has been demonstrated in patients with chronic lymphocytic leukemia (CLL), including as first-line therapy. However, outcomes after ibrutinib discontinuation have previously been limited to higher-risk populations with relapsed/refractory (R/R) disease. The objective of this study was to evaluate outcomes of ibrutinib-treated patients based on prior lines of therapy, including after ibrutinib discontinuation. Data were analyzed from two multicenter phase 3 studies of single-agent ibrutinib: RESONATE (PCYC-1112) in patients with R/R CLL and RESONATE-2 (PCYC-1115) in patients with treatment-naive (TN) CLL without del(17p). This integrated analysis included 271 ibrutinib-treated non-del(17p) patients with CLL (136 TN and 135 R/R). Median progression-free survival (PFS) was not reached for subgroups with 0 and 1/2 prior therapies but was 40.6 months for patients with ≥3 therapies (median follow-up: TN, 36 months; R/R, 44 months). Median overall survival (OS) was not reached in any subgroup. Overall response rate (ORR) was 92% in TN and 92% in R/R, with depth of response increasing over time. Adverse events (AEs) and ibrutinib discontinuation due to AEs were similar between patient groups. Most patients (64%) remain on treatment. OS following discontinuation was 9.3 months in R/R patients (median follow-up 18 months, n = 51) and was not reached in TN patients (median follow-up 10 months, n = 30). In this integrated analysis, ibrutinib was associated with favorable PFS and OS, and high ORR regardless of prior therapies in patients with CLL. The best outcomes following ibrutinib discontinuation were for patients receiving ibrutinib in earlier lines of therapy. 相似文献
996.
Morgane Nudel Fanny Baran-Marszak Jean-Baptiste Bossard Romain Dubois Héloïse Dapvril Jehan Dupuis Kamel Laribi Jacques-Olivier Bay Cécile Tomowiak Brigitte Dreyfus Stéphane Lepretre Hélène Demarquette Frédéric Wallyn Lidwine Wemeau Mathieu Wemeau Stéphanie Poulain Franck Morschhauser Florence Cymbalista Charles Herbaux 《British journal of haematology》2019,186(5):e126-e130
997.
Gender and sexual vulnerability of young women in Africa: experiences of young girls in secondary schools in Uganda 总被引:1,自引:0,他引:1
Muhanguzi FK 《Culture, health & sexuality》2011,13(6):713-725
Sexuality is part and parcel of students' experiences of schooling manifested in personal friendships, relations and social interaction. These encounters constitute sites within which sexual identities are developed, practiced and actively produced through processes of negotiation. Drawing on qualitative research conducted in 14 selected secondary schools in Central and Western Uganda, the study illuminates gendered sexual vulnerability within patterns of social interaction and young girls gendered experiences and negotiation of their sexuality. The study reveals that through social and discursive practices, students construct complex gendered relations of domination and subordination that position boys and girls differently, often creating gender inequalities and sexual vulnerability for those gendered as girls. Girls' vulnerability is characterised by confusing and traumatic experiences fraught with double standards and silences. Typical of these experiences are complex tensions and contradictions surrounding constructions of sexuality that are predicated upon unequal power and gender relations characterised by homophobia, misogyny, control of female sexuality and sexual abuse and exploitation, all which work against girls' expression of sexuality. Gender sensitive sexuality education is identified as a valuable site of intervention to address such vulnerabilities and promote gender equality and equity in society. 相似文献
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The purpose of promoting "use of self" or "self-disclosures" as a teaching strategy in teaching the P.A.T.H.S. curriculum is to create an interactive environment between teachers and students which can enhance the interactions between both parties. This article focuses on three major consequences of utilizing self-disclosures in the education settings, including humanizing the classroom, encouraging students' openness, and promoting teachers' awareness and reflective practice. Positive feedback of the participants of the Secondary 3 P.A.T.H.S. training programs show that participants were moved by the training instructors, who demonstrated the power of "use of self" in a humanistic manner. To retain a humanized and open classroom atmosphere depends greatly on the relational exchanges between teachers and students. This revelation should be purposeful and intentional, with appropriate boundaries and frequencies. Acknowledging the issues to consider in using "use of self" as a teaching strategy, teachers should focus attention on the process of connecting students with them. Guidelines for worker's self-disclosure are also discussed. 相似文献