Biological ageing and colorectal cancer: fetuin A, sirtuins and telomeres at the interface between inflammation, metabolism and cancer

Colorectal cancer is a common, age-associated disease with significant comorbidity and mortality. Biomarkers of ageing may have prognostic or predictive value in colorectal cancer. Fetuin A, members of the sirtuin family of proteins and telomeres have shown promise as potential biomarkers of ageing. AIM: To evaluate these potential biomarkers in the context of colorectal cancer. METHODS: Two cohorts of patients were used. Telomere length was measured in peripheral blood leukocytes (PBL), and for a subset of patients, in normal colorectal and colorectal tumour tissue. Serum fetuin A was measured for these patients and data on clinico-pathological factors of accepted significance in colorectal cancer was collected prospectively. Telomere length in the matched samples of leukocytes, normal colorectal and colorectal tumour tissue was compared. Associations between telomere length in the different tissues, serum fetuin A and clinico-pathological factors of accepted significance in colorectal cancer were evaluated. A systematic review of the literature was performed to examine the evidence for correlation between telomere length in different tissues in humans. Tissue from colorectal tumours from the second cohort patients was mounted in a tissue microarray (TMA) and stained for sirtuin proteins (SIRT2-SIRT7). This TMA also contained tissue from a subset of matched samples of adjacent normal colorectal mucosa. Staining of normal colorectal and colorectal tumour tissue was evaluated by the weighted Histoscore method and compared. The effect of staining in tumour tissue on cancer-specific survival was examined. Associations between Histoscores and clinico-pathological factors of accepted significance in colorectal cancer were assessed. RESULTS: Systematic review of the literature did not show robust evidence of correlation between telomere length in different tissues in humans. Telomere length in peripheral blood leukocytes did not show correlation with telomere length in normal colorectal mucosa, or in colorectal tumour tissue. PBL telomere length was potentially related to the presence of distant metastases. Fetuin A was inversely associated with markers of systemic inflammation and with T stage. Novel nuclear localisation was described for SIRT4 and SIRT5. Protein expression of the sirtuins was reduced in tumour tissue in comparison to normal colorectal mucosa, apart from SIRT3 cytoplasmic and nuclear and SIRT6 nuclear stainng. Lowest and highest quartile SIRT2 expression was associated with worse survival. Sirtuin protein expression levels and localisation correlate with increased systemic inflammation and pathological markers of poor prognosis in tumour tissue. Intercorrelations between sirtuin expression levels in normal tissue are not seen in tumour tissue, possibly indicating a breakdown of signalling and control.

Investigating problem-based learning in Saudi Arabian mathematics education: a TIMSS-related study

The aim of this study is to investigate the effectiveness of problem-based learning (PBL) on students’ mathematical performance. This includes mathematics achievement and students’ attitudes towards mathematics for third and eighth grade students in Saudi Arabia. Mathematics achievement includes, knowing, applying, and reasoning domains, while students’ attitudes towards mathematics covers, ‘Like learning mathematics’, ‘value mathematics’, and ‘a confidence to learn mathematics’. This study goes deeper to examine the interaction of a PBL teaching strategy, with trained face-to-face and self-directed learning teachers, on students’ performance (mathematics achievement and attitudes towards mathematics). It also examines the interaction between different ability levels of students (high and low levels) with a PBL teaching strategy (with trained face-to-face or self-directed learning teachers) on students’ performance. It draws upon findings and techniques of the TIMSS international benchmarking studies. Mixed methods are used to analyse the quasi-experimental study data. One -way ANOVA, Mixed ANOVA, and paired t-tests models are used to analyse quantitative data, while a semi-structured interview with teachers, and author’s observations are used to enrich understanding of PBL and mathematical performance. The findings show that the PBL teaching strategy significantly improves students’ knowledge application, and is better than the traditional teaching methods among third grade students. This improvement, however, occurred only with the trained face-to-face teacher’s group. Furthermore, there is robust evidence that using a PBL teaching strategy could raise significantly students’ liking of learning mathematics, and confidence to learn mathematics, more than traditional teaching methods among third grade students. Howe ver, there was no evidence that PBL could improve students’ performance (mathematics achievement and attitudes towards mathematics), more than traditional teaching methods, among eighth grade students. In 8th grade, the findings for low achieving students show significant improvement compared to high achieving students, whether PBL is applied or not. However, for 3th grade students, no significant difference in mathematical achievement between high and low achieving students was found. The results were not expected for high achieving students and this is also discussed. The implications of these findings for mathematics education in Saudi Arabia are considered.