Urinary calcium: a promising predictive biomarker for early recognition of environmental lead exposure in children

Background: In the continuous search for accessible, reliable and sensitive biomarkers for early detection of environmental lead exposure, authors determined the interaction between blood lead level (BLL), the conventional marker of lead exposure, and the indices of calcium and bone metabolism in children.Methods: This cross-sectional study involved 309 apparently healthy children from eight public primary schools in Ibadan, Nigeria who were classified as Elevated BLL (EBLL) and control based on standard cut-off for childhood BLL. BLL, serum Ca (tCa), phosphate, magnesium (Mg), 25-hydroxy-Vitamin D, alkaline phosphatase (ALP), urinary calcium (uCa) and urinary deoxypyridinoline (uDPD) were determined using AAS, HPLC and ELISA as appropriate. Bone-specific ALP (B-ALP) and ionized calcium (iCa) were calculated using standard formulae. Data analyses involved Student’s t-test, Pearson correlation and multivariate regression analysis. p0.05). BLL had significant positive correlation with uCa (r=0.176, p=0.002) (p0.05). BLL could be accounted for by uCa by applying the equation, BLL=0.329+0.324uCa.Conclusions: Urinary calcium could be a promising predictive biomarker for early recognition of significant environmental lead exposure in children

Perceptions of leadership effectiveness in schools for children who are blind or have low vision in Nigeria

This study used the standard-based essential behavioural leadership qualities (EBLQ) method of leadership assessment, to determine leadership effectiveness of the principals of the schools for children who are blind and have low vision in Nigeria, from the perspective of the teachers of these schools. The four-stage method of leadership assessment of the EBLQ method was used to analyze data (N = 271) collected through availability sampling, to determine leadership effectiveness of the principals relative to levels of essentiality of EBLQ items. Findings show a pattern of incongruence between rankings of essentialities and effectiveness of the principals on the EBLQ items. The principals were perceived most effective in having ˜excellent educational qualifications\u27 which was ranked fourth as essential for leadership effectiveness. The principals were also rated twentieth on ˜timely payment of salary\u27, which was ranked most essential for leadership effectiveness. Overall effectiveness of the principals, however, was described as exemplary. This study is expected to contribute to much-needed studies on leadership in the schools for the blind in Nigeria, as well as provide a coaching effect for the principals of these schools

Crizotinib and erlotinib inhibits growth of c-Met+/EGFRvIII+ primary human glioblastoma xenografts

Objectives: Receptor tyrosine kinases (RTK), such as c-Met and epidermal growth factor receptor (EGFR), are implicated in the malignant progression of glioblastoma. Studies show that RTK systems can co-modulate distinct and overlapping oncogenic downstream signaling pathways. EGFRvIII, a constitutively activated EGFR deletion mutant variant, leads to increased tumor growth and diminishes the tumor growth response to HGF: c-Met pathway inhibitor therapy. Conversely, activation of the c-Met pathway diminishes the tumor growth response to EGFR pathway inhibitors. Previously we reported that EGFRvIII and c-Met pathway inhibitors synergize to inhibit tumor growth in isogenic GBM cell lines engineered to express EGFRvIII. More recently, studies suggest that despite targeting RTK signaling in glioblastoma multiforme, a subpopulation of stem-like tumor-propagating cells can persist to replenish the tumor cell population leading to tumor recurrence. Patients and Methods: Mayo 39 and Mayo 59 xenograft lines were cultured and xenografts were maintained. Subcutaneous xenograft lines were serially passaged in nude mice to generate subcutaneous xenografts. Xenografts were implanted in 6–8 week old nude mice. Once tumors reached a substantial size (150 mm3), mice were randomly divided into 4 groups: 1) control vehicle, 2) Crizotinib (crizo), 3) Erlotinib (erlot), or 4) Crizotinib + Erlotinib, (n = 5 per group). Results: Crizotinib (c-Met pathway inhibitor) and Erlotinib (EGFR pathway inhibitor) in combination significantly inhibited tumor growth, phospho-EGFRvIII, phospho-Met, phospho-AKT, phospho-MAPK, and neurosphere growth in Mayo 39 and Mayo 59 primary GBM subcutaneous xenografts. The expression of the stem cell markers Nestin, Musashi, Olig 2 and Sox2 were also significantly down-regulated by c-Met inhibition, but no additive down-regulation was seen by co-treatment with Erlotinib. Conclusions: These results are consistent with and corroborate our previous findings demonstrating that targeting these two parallel pathways with c-Met and EGFR inhibitor therapy provides substantial anti-tumor activity in glioblastoma models