The development of an automated, high-throughput fractionation procedure to prepare and analyze natural product libraries for drug discovery screening is described. Natural products obtained from plant materials worldwide were extracted and first prefractionated on polyamide solid-phase extraction cartridges to remove polyphenols, followed by high-throughput automated fractionation, drying, weighing, and reformatting for screening and storage. The analysis of fractions with UPLC coupled with MS, PDA and ELSD detectors provides information that facilitates characterization of compounds in active fractions. Screening of a portion of fractions yielded multiple assay-specific hits in several high-throughput cellular screening assays. This procedure modernizes the traditional natural product fractionation paradigm by seamlessly integrating automation, informatics, and multimodal analytical interrogation capabilities.Natural products are a vast resource of compounds with seemingly unlimited chemical and functional diversity, and have been a rich source for lead molecules in drug discovery programs. 1-4 Sixty percent of new drugs for cancer and 75% of those for infectious diseases have originated from natural sources. 5,6 Between 2001 and 2005, 23 natural product based drugs were launched in Europe, Japan, and the United States for treating various disorders such as cancer, diabetes, dyslipidemia, atopic dermatitis, Alzheimer's disease, bacterial and fungal infections, genetic diseases such as tyrosinemia, and Gaucher's disease. 7 However, during the last two decades, research efforts in the discovery of therapeutic natural products have waned because of the complications and significant time requirements inherent in compound isolation. Primary screening of crude plant extracts or microbial fermentations, followed by bioassay-guided fractionation, purification, and structure elucidation of novel bioactive compounds can take several months. 8 The required scale of isolation has been too large to be implemented effectively in an automated, high-throughput fashion. The combination of these and other factors has led to a lagging emphasis in natural product discovery. However, recent advances in high-throughput screening (HTS) technology have
In 2005, the Ontario Ministry of Educationimplemented the Daily Physical Activity (DPA) Policy to provide every elementary student with at least 20 minutes of sustained moderate to vigorous intensity physical activity each day. This exploratory research sought to understand the factors shaping DPA implementation in schools and classrooms, from the perspective of elementary school teachers and principals. Semi-structured interviews were conducted with Ontario grade 1-8 teachers (n=14) and elementary school principals (n=5) regarding DPA implementation, facilitators, barriers, perceived outcomes, and suggestions for change. The majority of participants stated that students were not meeting the requirements daily. However, participants shared activities and techniques for incorporating physical activity into instructional time. Facilitators and barriers to implementation were organized using the Analysis Grid for Environments Linked to Obesity (ANGELO) framework in order to identify factors acting at four environmental levels. The facilitators and barriers identified indicate that staff and resources within individual schools strongly influence implementation. Although many positive outcomes for students were identified, increased fitness was not mentioned, highlighting additional benefits above physical health. The findings suggest DPA is not being implemented as intended, as school staff are finding it difficult to meet the time and intensity requirements. Policy makers must consider the local school environment and the roles of school staff when designing school-based health policies.
The environments in which population health interventions occur shape both their implementation and outcomes. Hence, when evaluating these interventions, we must explore both intervention content and context. Mixed methods (integrating quantitative and qualitative methods) provide this opportunity. However, although criteria exist for establishing rigour in quantitative and qualitative research, there is poor consensus regarding rigour in mixed methods. Using the empirical example of school-based obesity interventions, this methodological review examined how mixed methods have been used and reported, and how rigour has been addressed. Twenty-three peer-reviewed mixed methods studies were identified through a systematic search of five databases and appraised using the guidelines for Good Reporting of a Mixed Methods Study. In general, more detailed description of data collection and analysis, integration, inferences and justifying the use of mixed methods is needed. Additionally, improved reporting of methodological rigour is required. This review calls for increased discussion of practical techniques for establishing rigour in mixed methods research, beyond those for quantitative and qualitative criteria individually. A guide for reporting mixed methods research in population health should be developed to improve the reporting quality of mixed methods studies. Through improved reporting, mixed methods can provide strong evidence to inform policy and practice.
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