Identification of Specific Language Impairment in Multilingual Contexts: Preliminary Validation of a Short Parental Bilingual Questionnaire in Lebanon

Assessing children with Specific language Impairment (SLI) in multilingual contexts is challenging for speech language therapists given that language patterns in bilinguals and in children with SLI are often reported to be remarkably similar and that screening language tests are not standardized on bilingual populations. The present study aims to validate the use of a parental questionnaire focusing on early language development, the languages spoken by the child, the use of languages in his/her environment, and information on linguistic difficulties within the family, as a complement to language assessment in multilingual contexts. Thirty-three Lebanese/French bilingual children (12 with SLI and 21 with typical development) and their parents participated in this study in Lebanon. The parents were interviewed via the questionnaire while the children were administered standardized language tests in each language. Data analysis showed that the parents’ answers to the questionnaire were coherent throughout and that some variables of the questionnaire strongly discriminated between the two groups of children, in particular the age of the first words and first sentences. Moreover, although significant correlations were found with language test scores, the answers to the questionnaire allowed us to refine the interpretation of the performance on the standardized tests, thus demonstrating the value of the parental questionnaire as a complementary tool to clinical evaluation

Tumour macrophages as potential targets of bisphosphonates

Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use

Zoledronic Acid Restores Doxorubicin Chemosensitivity and Immunogenic Cell Death in Multidrug-Resistant Human Cancer Cells

<div><p>Durable tumor cell eradication by chemotherapy is challenged by the development of multidrug-resistance (MDR) and the failure to induce immunogenic cell death. The aim of this work was to investigate whether MDR and immunogenic cell death share a common biochemical pathway eventually amenable to therapeutic intervention. We found that mevalonate pathway activity, Ras and RhoA protein isoprenylation, Ras- and RhoA-downstream signalling pathway activities, Hypoxia Inducible Factor-1alpha activation were significantly higher in MDR+ compared with MDR− human cancer cells, leading to increased P-glycoprotein expression, and protection from doxorubicin-induced cytotoxicity and immunogenic cell death. Zoledronic acid, a potent aminobisphosphonate targeting the mevalonate pathway, interrupted Ras- and RhoA-dependent downstream signalling pathways, abrogated the Hypoxia Inducible Factor-1alpha-driven P-glycoprotein expression, and restored doxorubicin-induced cytotoxicity and immunogenic cell death in MDR+ cells. Immunogenic cell death recovery was documented by the ability of dendritic cells to phagocytise MDR+ cells treated with zoledronic acid plus doxorubicin, and to recruit anti-tumor cytotoxic CD8+ T lymphocytes. These data indicate that MDR+ cells have an hyper-active mevalonate pathway which is targetable with zoledronic acid to antagonize their ability to withstand chemotherapy-induced cytotoxicity and escape immunogenic cell death.</p> </div