Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6–12 years of age in Mexico City

Background Epidemiologic and animal-based studies have raised concern over the potential impact of fluoride exposure on neurobehavioral development as manifested by lower IQ and deficits in attention. To date, no prospective epidemiologic studies have examined the effects of prenatal fluoride exposure on behavioral outcomes using fluoride biomarkers and sensitive measures of attention. Objective We aimed to examine the association between prenatal fluoride exposure and symptoms associated with attention-deficit/hyperactivity disorder (ADHD). Method 213 Mexican mother-children pairs of the Early Life Exposures to Environmental Toxicants (ELEMENT) birth cohort study had available maternal urinary samples during pregnancy and child assessments of ADHD-like behaviors at age 6–12. We measured urinary fluoride levels adjusted for creatinine (MUFcr) in spot urine samples collected during pregnancy. The Conners' Rating Scales-Revised (CRS-R) was completed by mothers, and the Conners' Continuous Performance Test (CPT-II) was administered to the children. Results Mean MUFcr was 0.85 mg/L (SD = 0.33) and the Interquartile Range (IQR) was 0.46 mg/L. In multivariable adjusted models using gamma regression, a 0.5 mg/L higher MUFcr (approximately one IQR higher) corresponded with significantly higher scores on the CRS-R for DSM-IV Inattention (2.84 points, 95% CI: 0.84, 4.84) and DSM-IV ADHD Total Index (2.38 points, 95% CI: 0.42, 4.34), as well as the following symptom scales: Cognitive Problems and Inattention (2.54 points, 95% CI: 0.44, 4.63) and ADHD Index (2.47 points; 95% CI: 0.43, 4.50). The shape of the associations suggested a possible celling effect of the exposure. No significant associations were found with outcomes on the CPT-II or on symptom scales assessing hyperactivity. Conclusion Higher levels of fluoride exposure during pregnancy were associated with global measures of ADHD and more symptoms of inattention as measured by the CRS-R in the offspring

Extracellular vesicles shed by follicular lymphoma B cells promote the polarization of bone marrow stromal cell niche

International audienceFollicular Lymphoma (FL) originates in the lymph nodes (LN) and infiltrates bone marrow (BM) early in the course of the disease. BM FL B cells are characterized by a lower cytological grade, a decreased proliferation, and a specific phenotypic and subclonal profile. Mesenchymal stromal cells (MSC) obtained from FL BM display a specific gene expression profile (GEP), including enrichment for a lymphoid-stromal cell signature, and an increased capacity to sustain FL B-cell growth. However, the mechanisms triggering the formation of the medullar FL permissive stromal niche have not been yet identified. In the current work, we demonstrated that FL B cells produced extracellular vesicles (EVs) that could be internalized by BM-MSC, making them more efficient to support FL B-cell survival and quiescence. Accordingly, EVs purified from FL BM plasma activated TGF-b dependent and independent pathways in BM-MSC, modified their GEP, triggering an upregulation of factors classically associated with hematopoietic stem cell niche, including CXCL12 or angiopoietin-1. Moreover, we provided the first characterization of BM FL B-cell GEP, allowing the definition of the landscape of molecular interactions they could engage with EV-primed BM-MSC. This work identified FL-derived EVs as putative mediators of BM stroma polarization and supported further investigation of their clinical interest for targeting the crosstalk between BM-MSC and malignant B cells