Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis.

BACKGROUND AND AIMS: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to act as a negative regulator of T cell function and has been implicated in the regulation of T helper 1 (Th1)/Th2 development and the function of regulatory T cells. Tests were carried out to determine whether anti-CTLA-4 treatment would alter the polarisation of naive T cells in vivo. METHODS: Mice were treated with anti-CTLA-4 monoclonal antibody (mAb) (UC10-4F10) at the time of immunisation or colonic instillation of trinitrobenzene sulfonic acid (TNBS). The cytokines produced by lymph node cells after in vitro antigenic stimulation and the role of indoleamine 2,3 dioxygenase (IDO) and of interleukin-10 (IL-10) were tested, and the survival of mice was monitored. RESULTS: Injection of anti-CTLA-4 mAb in mice during priming induced the development of adaptive CD4(+) regulatory T cells which expressed high levels of ICOS (inducible co-stimulator), secreted IL-4 and IL-10. This treatment inhibited Th1 memory responses in vivo and repressed experimental intestinal inflammation. The anti-CTLA-4-induced amelioration of disease correlated with IDO expression and infiltration of ICOS(high) Foxp3(+) T cells in the intestine, suggesting that anti-CTLA-4 acted indirectly through the development of regulatory T cells producing IL-10 and inducing IDO. CONCLUSIONS: These observations emphasise the synergy between IL-10 and IDO as anti-inflammatory agents and highlight anti-CTLA-4 treatment as a potential novel immunotherapeutic approach for inducing adaptive regulatory T cells.

Estimating the magnitude of trastuzumab effects within patient subgroups in the HERA trial.

BACKGROUND: Trastuzumab (Herceptin(R)) improves disease-free survival (DFS) and overall survival for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We aimed to assess the magnitude of its clinical benefit for subpopulations defined by nodal and steroid hormone receptor status using data from the Herceptin Adjuvant (HERA) study. PATIENTS AND METHODS: HERA is an international multicenter randomized trial comparing 1 or 2 years of trastuzumab treatment with observation after standard chemotherapy in women with HER2-positive breast cancer. In total, 1703 women randomized to 1-year trastuzumab and 1698 women randomized to observation were included in these analyses. Median follow-up was 23.5 months. The primary endpoint was DFS. RESULTS: The overall hazard ratio (HR) for trastuzumab versus observation was 0.64 [95% confidence interval (CI) 0.54-0.76; P < 0.0001], ranging from 0.46 to 0.82 for subgroups. Estimated improvement in 3-year DFS in subgroups ranged from +11.3% to +0.6%. Patients with the best prognosis (those with node-negative disease and tumors 1.1-2.0 cm) had benefit similar to the overall cohort (HR 0.53, 95% CI 0.26-1.07; 3-year DFS improvement +4.6%, 95% CI -4.0% to 13.2%). CONCLUSIONS: Adjuvant trastuzumab therapy reduces the risk of relapse similarly across subgroups defined by nodal status and steroid hormone receptor status, even those at relatively low risk for relapse.

Discriminations à l’emploi à l’égard des personnes LGBT et estime de soi

info:eu-repo/semantics/nonPublished

Employment discrimination against transgender people and self-esteem.

The evocation of gender identity in company anti-discrimination policies is still very rare. This observation is also true forscientific studies. Very few researches have focused exclusively on transgender employees. Transgender are neither sick nor lesscompetent, and yet, the feeling of being strongly discriminated is shared by many transgender people. Such discrimination and thetype of causal attribution do not remain without any effect on the well-being of the concerned individuals. According to Crocker &Quinn (1998), the attribution of the discrimination to the existing prejudices may be a way to protect one-self from the negativeimpact on self-esteem. In this theoretical scope, the "rejection-identification" model (Branscombe, Schmitt & Harvey, 1999) has beenhighly mobilized. It emphasizes the importance of ingroup identification in the causal relationship between perceived discriminationsituation and well-being. Previous studies which did test this model show that the identification to a certain group can counteract thenegative effects on well-being. Following this theoretical frame, the presented study examines the impact of different types of causalattributions on self-esteem: internal causes (e.g. lack of skills), external causes (e.g. economic crisis), and gender identity relatedissues. For that purpose, an online survey has been created and fulfilled by 110 transgender people. Different scales were used to testthe model: the Rosenberg self-esteem scale, a causal attribution scale, the perceived discrimination of the transgender population inthe workplace scale and a group identification scale. The results show that transgender people feel still highly stigmatized today andattribute, significantly, the causes of their situation to the prejudices they are victim of. Also, in accordance with the “rejectionidentification”model, three links are observed: (1) a negative link between perceived discrimination and self-esteem; (2) a positivelink between perceived discrimination and ingroup identification; and (3) a positive link between ingroup identification and selfesteem.This situation reflects a lack in diversity considerations. Nevertheless, the attribution made to group stigmatization seems toplay a protective role towards transgender people self-esteem.

Health networks: Actors, professional relationships, and controversies

In recent years international policies have aimed to stimulate the use of information and communication technologies (ICT) in the field of health care. Belgium has also been affected by these developments and, for example, health electronic regional networks ("HNs") are established. Thanks to a qualitative case study we have explored the implementation of such innovations (HN) to better understand how health professionals collaborate through the HN and how the HN affect their relationships. Within the HNs studied a common good unites the actors: the continuity of care for a better quality of care. However behind this objective of continuity of care other individual motivations emerge. Some controversies need also to be resolved in order to achieve cooperative relationships. HNs have notably to take national developments into account. These developments raise the question of the control of medical knowledge and medical practice. Professional issues, and not only practical changes, are involved in these innovations. © 2008 The authors and IOS Press. All rights reserved.

Phenolic compounds, antioxidant and antibacterial activities of three Ericaceae from Algeria

Herbs of the Ericaceae family are commonly found in Algeria and used in traditional medicine as anti- septic, diuretic, astringent, depurative, and to treat scalds and wounds. The methanolic extracts of three species, Arbutus unedo L. (A. unedo, leaves), Erica arborea L. (E. arborea, flowered aerial parts), and Erica multiflora L. (E. multiflora, flowered aerial parts), were compared regarding their content in pheno- lic compounds, their antioxidant, and antibacterial activities. A. unedo harbors the highest content in total phenolics and flavonoids, followed by E. arborea E. multiflora. The contents in total phenolics and flavonoids showed a correlation with the measured antioxidant (hydrogen-donating) activities; this was particularly the case for flavonoids content. The A. unedo extract showed antibacterial activity against all the tested strains (Staphylococcus aureus ATCC 6538, S. aureus C100459, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 9027); however, the E. arborea and E. multiflora extracts showed antibacterial activity only against Gram positive bacteria. Some polyphenols were identified in the three herbs by thin-layer chromatography and high-performance liquid chromatography coupled with diode array and mass spectrometry detection; from these, caffeic acid, p-coumaric acid, naringin, quercetin and kaempferol are reported for the first time in E. multiflora.

Les discriminations au travail dues à l’orientation sexuelle et les identités de genre

info:eu-repo/semantics/published

Parliamentary party loyalty and party family: the missing link?

info:eu-repo/semantics/inPress