Gene Expression Profiling as an Initial Approach for Mechanistic Studies of Toxicity and Tumorigenicity of Herbal Plants and Herbal Dietary Supplements

Dietary supplements are consumed by more than 300 million people worldwide, and herbal dietary supplements represent the most rapidly growing portion of this industry. Even though adverse health effects of many herbal dietary supplements have been reported, safety assurances are not being addressed adequately. Toxicological data on the identification of genotoxic and tumorigenic ingredients in many raw herbs are also lacking. Currently, more than 30 herbal dietary supplements and active ingredients have been selected by the National Toxicology Program (NTP) for toxicity and tumorigenicity studies. Due to the complexity of the chemical components present in plant extracts, there are no established methodologies for determining the mechanisms of toxicity (particularly tumorigenicity) induced by herbs, such as Gingko biloba leaf extract (GBE) and other herbal plant extracts. Consequently, the understanding of toxicity of herbal dietary supplements remains limited.

We have proposed that application of DNA microarrays could be a highly practical initial approach for revealing biological pathways and networks associated with toxicity induced by herbal dietary supplements and the generation of hypotheses to address likely mechanisms. The changes in expression of subsets of genes of interest, such as the modulation of drug metabolizing genes, can be analyzed after treatment with an herbal dietary supplement. Although levels of gene expression do not represent fully the levels of protein activities, we propose that subsequent biochemical and genomic experiments based on these initial observations will enable elucidation of the mechanisms leading to toxicity, including tumorigenicity. This review summarizes the current practices of microarray analysis of gene expressions in animals treated with herbal dietary supplements and discusses perspectives for the proposed strategy.     

Applicability of consumer activity monitor data in marathon events: an exploratory study

Emerging opportunities to measure individual and population-level health data with activity monitors during recreational running activities may set the stage for new research possibilities in mass participation running events and marathon medicine. This study explores the applicability of consumer activity monitor data in a preliminary study for future marathon health research with a cohort of 12 (n?=?12) participants completing a 3.379?km walking or running course. This study explored the feasibility of collecting pace and distance data from Fitbit brand consumer activity monitors, from access to user data to reporting of data characteristics and data analysis. We show that a large percentage of participant data can be successfully retrieved from Fitbit consumer activity monitor devices for analysis in marathon health research, and that identifying variations in pace across participants is a practical possibility. We note a mean absolute percentage error of 13% over the true distance of 3.379?km, a higher error than that reported by other studies. We also observe a Pearson correlation coefficient between participant variation in pace and absolute distance error of 0.61. This study provides preliminary evidence to support the applicability of consumer activity monitor data in marathon health research.     

Identifying the “Active Ingredients” of a School-Based,Workplace Safety and Health Training Intervention

Young workers in many industrialized countries experience a higher rate of largely preventable occupation-related injuries compared with adults. Safety education and training are considered critical to the prevention of these incidents. This can be promoted by the dissemination and scale-out of an evidence-based, safety training programs in vocational education. The aim of this study was to identify the intervention core components that comprise the “active ingredients” of a safety training intervention for young workers and assess the impact on student outcomes of interest. Fidelity of implementation was operationalized using measures of adherence and quality of intervention delivery. For this study, data were collected through a school-based, cluster randomized trial conducted in 2015 in eight Finnish upper secondary-level vocational schools (n = 229 students in 22 groups, each with one teacher). Results indicate that the intervention core components (safety skills training, safety inoculation training, a positive atmosphere for safety learning, and active learning techniques) had differing associations with student outcomes. Adherence related to the acquisition of safety skills training was the strongest active ingredient in terms of positive effects. Furthermore, quality of delivery in terms of fostering positive learning atmosphere and utilizing active learning methods was associated especially with motivational outcomes. These findings indicate that different active ingredients complemented each other. Contrary to expectations, we found no statistically significant relationship between any of the core components and risk-taking attitudes. The current study advances prevention science by identifying the active ingredients of an evidence-based intervention, implemented in Finnish vocational school settings, that helps protect young workers from work-related morbidity and mortality.

     

Bursts and oscillations as independent properties of neural activity in the parkinsonian globus pallidus internus

Bursts and oscillatory modulations in firing rate are hallmark features of abnormal neuronal activity in the parkinsonian Globus Pallidus internus (GPi). Although often implicated together in the pathophysiology of parkinsonian signs, little is known about how burst discharges and oscillatory firing (OF) relate to each other. To investigate this question, extracellular single-unit neuronal activity was recorded from 132 GPi cells in 14 Parkinson's disease patients. We found that burst firing was equally prevalent in OF and non-oscillatory firing (NOF) cells (p > 0.5). More than half of the cells were characterized by either aperiodic bursty activity or OF, but not both. OF and NOF cells had statistically-indistinguishable levels of mean burstiness (p = 0.8). Even when bursting and OF co-existed in individual cells, levels of burstiness and oscillatory power were seldom correlated across time. Interestingly, however, the few OF cells with spectral peaks between 8–13 Hz (α-range) were substantially burstier than other cells (p < 0.01) and showed an unique burst morphology and stronger temporal correlations between oscillatory power and burstiness. We conclude that independent mechanisms may underlie the burst discharges and OF typical of most neurons in the parkinsonian GPi.