Menstrual and reproductive factors and risk of breast cancer: A case-control study in the Fez region, Morocco

Breast cancer is the most common cancer in women worldwide. In the Moroccan context, the role of well-known reproductive factors in breast cancer remains poorly documented. The aim of this study was to explore the relationship between menstrual and reproductive factors and breast cancer risk in Moroccan women in the Fez region. Methods A case-control study was conducted at the Hassan II University Hospital of Fez between January 2014 and April 2015. A total of 237 cases of breast cancer and 237 age-matched controls were included. Information on sociodemographic characteristics, menstrual and reproductive history, family history of breast cancer, and lifestyle factors was obtained through a structured questionnaire. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals for breast cancer by menstrual and reproductive factors adjusted for potential confounders. Results Early menarche (OR = 1.60, 95% CI: 1.08-2.38) and nulliparity (OR = 3.77, 95% CI: 1.98-7.30) were significantly related to an increased risk of breast cancer, whereas an early age at first full-term pregnancy was associated with a decreased risk of breast cancer (OR = 0.41, 95% CI: 0.25-0.65). Conclusion The results of this study confirm the role of established reproductive factors for breast cancer in Moroccan women. It identified some susceptible groups at high risk of breast cancer. Preventive interventions and screening should focus on these groups as a priority. These results should be confirmed in a larger, multicenter study

Evolution of coastal zone vulnerability to marine inundation in a global change context. Application to Languedoc Roussillon (France)

The coastal system is likely to suffer increasing costal risk in a global change context. Its management implies to consider those risks in a holistic approach of the different vulnerability components of the coastal zone, by improving knowledge of hazard and exposure as well as analyzing and quantifying present day and future territory vulnerability. The ANR/VMC2007/MISEEVA project (2008-2011) has applied this approach on Languedoc Roussillon region in France. MISEEVA approach relies on several scenarios for 2030 and 2100, in terms of meteorology (driver of coastal hazard), sea level rise, and also considering further trends in demography and economy, and possible adaption strategies Hazard has been modeled (SWAN, MARS and SURFWB), on the base of the presentday situation, sea level rise hypotheses, and existing or modeled data, of extreme meteorological driving f. It allowed to assess the possible surges ranges and map coastal zone exposure to: - a permanent inundation (considering sea level rise in 2030 and 2100, - a recurrent inundation (considering sea level rise and extreme tidal range) - an exceptional inundation (adding extreme storm surge to sea level rise and tidal range). In 2030, exposure will be comparable to present day exposure. In 2100, extreme condition will affect a larger zone. Present days social and economic components of the coastal zone have been analyzed in terms of vulnerability and potential damaging. Adaptation capacity was approached by public inquiries and interviews of stakeholders and policy makers, based on existing planning documents The knowledge of the present day system is then compared to the possible management strategies that could be chosen in the future, so to imagine what would be the evolution of vulnerability to marine inundation, in regards to these possible strategies

Exploitation of Herpesvirus Immune Evasion Strategies to Modify the Immunogenicity of Human Mesenchymal Stem Cell Transplants

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent cells residing in the connective tissue of many organs and holding great potential for tissue repair. In culture, human MSCs (hMSCs) are capable of extensive proliferation without showing chromosomal aberrations. Large numbers of hMSCs can thus be acquired from small samples of easily obtainable tissues like fat and bone marrow. MSCs can contribute to regeneration indirectly by secretion of cytokines or directly by differentiation into specialized cell types. The latter mechanism requires their long-term acceptance by the recipient. Although MSCs do not elicit immune responses in vitro, animal studies have revealed that allogeneic and xenogeneic MSCs are rejected. METHODOLOGY/PRINCIPAL FINDINGS: We aim to overcome MSC immune rejection through permanent down-regulation of major histocompatibility complex (MHC) class I proteins on the surface of these MHC class II-negative cells through the use of viral immune evasion proteins. Transduction of hMSCs with a retroviral vector encoding the human cytomegalovirus US11 protein resulted in strong inhibition of MHC class I surface expression. When transplanted into immunocompetent mice, persistence of the US11-expressing and HLA-ABC-negative hMSCs at levels resembling those found in immunodeficient (i.e., NOD/SCID) mice could be attained provided that recipients' natural killer (NK) cells were depleted prior to cell transplantation. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate the potential utility of herpesviral immunoevasins to prevent rejection of xenogeneic MSCs. The observation that down-regulation of MHC class I surface expression renders hMSCs vulnerable to NK cell recognition and cytolysis implies that multiple viral immune evasion proteins are likely required to make hMSCs non-immunogenic and thereby universally transplantable

Etude biochimique & moléculaire de b-D-Glucoside hydrolases de la baie de raisin (Vitis vinifera L.)

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine.

Pharmacological effects of amantadine on dopaminergic transmission are proposed to result from an uncompetitive antagonism at glutamate N-methyl-D-aspartate (NMDA) receptors. However, our previous studies examining amantadine-mediated dopamine receptor regulation in the rat striatum revealed a discrepancy from a direct interference with glutamate transmission. Preliminary in vitro binding data from the literature suggested the interaction of amantadine with the sigma1 receptor. Therefore, we have now further characterized the pharmacological properties of amantadine and memantine at this receptor and investigated its involvement in the modulation of striatal dopaminergic transmission. Our binding studies using [3H]-(+)SKF-10,047 indicated that amantadine and memantine behave as ligands of the sigma(1) receptor in rat forebrain homogenates (Ki values of 7.44 +/- 0.82 and 2.60 +/- 0.62 microm, respectively). In NG108-15 neuroblastoma cells, both drugs (amantadine (100 microm) and memantine (10 microm)) potentiated the bradykinin-induced mobilization of intracellular Ca2+, mimicking the effect of the sigma1 receptor agonist PRE-084 (1 microm). Finally, we previously showed that in striatal membranes from amantadine-treated rats, the functional coupling of dopamine receptors with G-proteins was enhanced. Similarly, PRE-084 dose-dependently increased the [35S]GTPgammaS binding induced by dopamine (Emax 28 and 26% of basal, 0.3 and 1 mg/kg PRE-084, respectively). By contrast, BD1047, which is without effect on its own, antagonized the effects of amantadine and PRE-084. Together, these data demonstrate that aminoadamantanes behave as sigma1 receptor agonists, and confirm an involvement of this receptor in modulating dopamine receptors exerted by therapeutically relevant concentrations of amantadine

Sensitivity of beach morphodynamics to climate variability. Application to truc vert beach (France)

International audienceCoastal systems should be vulnerable to climate change/variability. The present paper investigates the sensitivity of Truc Vert beach to present day climate conditions as well as possible climate change in the near future. A modeling approach is used, based on three numerical morphodynamic models (MORPHODYN, MARSOUIN, TELEMAC). The first results show an important sensitivity to present day wave classes. Some first indications on the potential influence of wave climate changes are also given, investigating variations of wave classes characteristics. The present work also illustrates the need to go on improving and developing these models

Circulating follicular helper T cells exhibit reduced ICOS expression and impaired function in narcolepsy type 1 patients

International audienceDespite genetic and epidemiological evidence strongly supporting an autoimmune basis for narcolepsy type 1, the mechanisms involved have remained largely unknown. Here, we aimed to investigate whether the frequency and function of circulating follicular helper and follicular regulatory T cells are altered in narcolepsy type 1. Peripheral blood mononuclear cells were collected from 32 patients with narcolepsy type 1, including 11 who developed disease after Pandemrix® vaccination, and 32 age-, sex-, and HLA-DQB1*06:02-matched healthy individuals. The frequency and phenotype of the different circulating B cell and follicular T cell subsets were examined by flow cytometry. The function of follicular helper T cells was evaluated by assessing the differentiation of naïve and memory B cells in a co-culture assay. We revealed a notable increase in the frequency of circulating B cells and CD4+CXCR5+ follicular T cells in narcolepsy patients compared to age-, sex- and HLA-matched healthy controls. However, the inducible T-cell costimulator molecule, ICOS, was selectively down-regulated on follicular T cells from patients. Reduced frequency of activated ICOS+ and PD1high blood follicular T cells was also observed in the narcolepsy group. Importantly, follicular T cells isolated from patients with narcolepsy type 1 had a reduced capacity to drive the proliferation/survival and differentiation of memory B cells. Our results provide novel insights into the potential involvement of T cell-dependent B cell responses in the pathogenesis of narcolepsy type 1 in which down-regulation of ICOS expression on follicular helper T cells correlates with their reduced function. We hypothesize that these changes contribute to regulation of the deleterious autoimmune process after disease onset

Prognostic impact of the inclusion of uPA/PAI-1 tumor levels in the current adjuvant treatment decision-making for early breast cancer

International audienceAIMS: Following the introduction of new adjuvant therapies we wanted to reappraise the prognostic and predictive value of uPA/PAI-1 in early breast cancer. PATIENTS & METHODS: This monocentric retrospective study included 652 patients who had curative surgery between 2006 and 2011 and adjuvant treatment decision-making, taking into account uPA/PAI-1 tumor levels. RESULTS: uPA and PAI-1 levels were associated with classical clinicopathological parameters and adjuvant chemotherapy decision, but not with peritumoral vascular invasion (PVI; also known as peritumoral vascular emboli). HER2 overexpression, PVI and uPA/PAI-1 levels were not significantly associated with relapse-free survival in univariate analysis. In multivariate analysis, T stage, N stage and progesterone receptors were the only independent relapse-free survival predictive factors. CONCLUSION: The absence of an association between uPA/PAI-1 and PVI allows their concomitant consideration in adjuvant treatment discussion. The overall good prognosis of patients with high uPA/PAI-1 levels might be linked to the uPA/PAI-1 predictive value and the inclusion of these parameters in adjuvant guidelines