Investigation of in Silico Modelling to Predict the Human Health Effects of Cosmetics Ingredients

Animal experiments have been the standard method to assess the safety of chemicals used in cosmetic products for decades. However, public opinion has continued to demand that in vivo hazard identification methods conducted on animals are replaced with alternative methods. Research on alternative methods to replace in vivo toxicity testing continually increased over the past few decades with different alternatives developed, such as in vitro, in chemico and in silico approaches. Although different alternative techniques can be employed, no single technique can solely replace the complexity and an in vivo test, especially for chronic effects. Therefore, integrated testing strategies that can utilise the information from all available alternative testing approaches have been developed. Within the Adverse Outcome Pathway (AOP) paradigm, the molecular initiating event(s) MIE can be induced by several chemical key features which can be captured by structural alerts. When structural alerts for a MIE are compiled and supported by mechanistic and toxicity information confirming the induction of the same MIE, then they can be considered as an in silico profiler. The overall aim of the work presented in this thesis was to assess the current in silico profilers for carcinogenicity (both genotoxic and non-genotoxic), mutagenicity and skin sensitisation through assessment using multiple high-quality experimental databases. The research presented herein demonstrates the ability to assess the positive predictivity of two types of structural alert, mechanism- and chemistry-based that pertain to the endpoints and proposes ways to improve the overall accuracy of these profilers. In this context, this study has given an insight to those alerts that may be found equally in endpoint-positive or negative compounds, and those which may be more effectively utilised to form groups of analogues for read across predictions. A detailed analysis of positive predictivity of the available mutagenicity, carcinogenicity and skin sensitisation structural alerts and profilers Page 3 within the OECD QSAR Toolbox against experimental data is presented. This investigation showed the structural alerts that are accurate as such, and those that may need further refinement, or their use may need to be reconsidered. In addition, the relationship between scaffolds of a range of diverse compounds and carcinogenicity showed that a total of 17 carcinogenicity scaffolds could be identified from the available databases and could be used as a base for an in silico profiler. This work has also determined the need for further in-depth research in this area to study the suitability and merits of each of the alerts within the profilers currently included in the OECD QSAR Toolbox, and other in silico toxicity platforms, to identify the possibilities for improvement in their performance. This will, by implication, also improve the reliability of chemical read-across and grouping/categorisation for classification, labelling and risk assessment for regulatory use of the in silico methods

Saudi Arabian science and mathematics teachers’ attitudes toward integrating STEM in teaching before and after participating in a professional development program

For the advancement of current and future economic and overall well-being to occur, STEM professionals are highly needed. STEM education is an approach that integrates science, technology, engineering and mathematics curricula into one interdisciplinary curriculum. In the context of STEM education, learners acquire deep and critical thinking abilities, which help them become creative and analytic thinkers, and hence innovators in their careers. For this to happen, the teacher must be trained to successfully design and effectively teach an integrated STEM curriculum. The purpose of this study was to analyze Saudi Arabian science and mathematics teachers’ attitudes toward integrating Science, Technology, Engineering and Mathematics (STEM) in teaching before and after they participated in a short professional development program focused on STEM integration in a specific middle school science and mathematics content. The participants were 48 Saudi Arabian science and mathematics teachers, who participated in a 6-day program held in Riyadh, Saudi Arabia. The research methodology was a pretest–posttest one group (pre-experimental) design. The primary data source was the Instrument for Teachers’ Attitudes Toward Teaching Integrated STEM. The results indicate that Saudi Arabian science and mathematics teachers’ perceptions of difficulties decreased due to their participation in the professional development program on integrated STEM. Meanwhile, the teachers’ self-efficacy improved following their participation in the STEM professional development (PD) program. However, no perceived effect was found for the teachers’ perceptions of the relevance of or their anxiety about or enjoyment of Integrated STEM teaching due to their participation in the 6-day PD program. We argue that Engaging teachers in integrated STEM professional development may improve their attitudes toward and increase their interest in teaching this approach. To improve teachers’ attitudes toward, it is suggested that future PD programs should be long and continuous, and focus on training science and mathematics teachers to teach integrated STEM subjects

Characterization of carbapenemases, ESBLs, and plasmid-mediated quinolone determinants in carbapenem-insensitive Escherichia coli and Klebsiella pneumoniae in Riyadh hospitals

The main objective of this work was to characterize carbapenemases, extended-spectrum β-lactamases (ESBLs), and plasmid-mediated quinolone resistance (PMQR) among carbapenem-insensitive Klebsiella pneumoniae and Escherichia coli clinical isolates which were isolated from three hospitals in Riyadh. Thirty-one carbapenem-insensitive isolates (21 K. pneumoniae and 10 E. coli) were recovered from March 2014 to May 2014. Susceptibility testing and phenotypic detection tests were used to characterize the classes of β-lactamases. PCR assays were performed for the detection of the genes encoding ESBL (blaCTX-M, blaTEM, blaSHV, and blaOXA-1), carbapenemase (blaKPC, blaGES, blaVIM, blaIMP, blaNDM, and blaOXA-48), and PMQR (qnrA, qnrB, qnrS, aac(6)-Ib-cr, qepA, oqxA, and oqxB) genes. All carbapenem-insensitive isolates were carbapenemase producers, with 41.9% and 58.1% being class B carbapenemases class D OXA-48, respectively. While the prevalence of ESBL producers was 80.6%. The following resistance genes were detected; OXA-48-like (58.1%), NDM-type (41.9%), CTX-M-1-like (77.4%), CTX-M-9-like (9.6%), TEM-1 (74.2%), OXA-1 (54.8%), SHV-1 (4.4%), qnrS (58.1%), qnrB (3.2%), and aac(6)-Ib-cr (51.6%). The predominant carbapenemases in the isolates that had carbapenem MIC ≤ 4 μg/ml and MIC ≥ 12 μg/ml were blaOXA-48-type and blaNDM-type respectively. CTX-M-1-like and qnrS were the dominant ESBL and PMQR genes, respectively. This is the first report in which qnrS was described in the isolates from Saudi Arabia. Keywords: OXA-48, NDM, Carbapenem resistance, Saudi Arabi