It is often argued that the efficacy of herbal medicines is a result of the combined action of multiple constituents that work synergistically or additively. Determining the bioactive constituents in these mixtures poses a significant challenge. We have developed an approach to address this challenge, synergy directed fractionation, which combines comprehensive mass spectrometry profiling with synergy assays and natural products isolation. The applicability of synergy directed fractionation was demonstrated using the botanical medicine goldenseal (Hydrastis canadensis) as a case study. Three synergists from goldenseal were identified, sideroxylin (1), 8-desmethyl-sideroxylin (2), and 6-desmethyl-sideroxylin (3). These flavonoids synergistically enhance the antimicrobial activity of the alkaloid berberine (also a constituent of H. canadensis) against Staphylococcus aureus by inhibition of the NorA multidrug resistance pump. The flavonoids possess no inherent antimicrobial activity against S. aureus; therefore, they could have been missed using traditional bioactivity directed fractionation. The flavonoid synergists are present at higher concentration in extracts from H. canadensis leaves, while the antimicrobial alkaloid berberine is present at higher levels in H. canadensis roots. Thus, it may be possible to produce an extract with optimal activity against S. aureus using a combination of goldenseal roots and leaves.

Background Anterior cruciate ligament (ACL) injury prevention programmes have shown mixed results, which may be due to differing emphasis on training components. The purpose of this study was to (1) quantify the overall and relative duration of each training component encompassed within these programmes and (2) examine the effect of these durations on ACL injury rates. Methods A systematic review was completed and meta-analyses performed on eligible studies to produce a pooled OR estimate of the effectiveness of these programmes. Meta-regression was used to detect any relationship that programme duration and the duration of individual training components had on ACL injury rates.Results 13 studies were included for review. Results of the meta-analyses revealed a significant reduction of injuries after preventative training programmes for all ACL injuries ( pooled OR estimate of 0.612, 95% CI 0.44 to 0.85; p=0.004) and for non-contact ACL injuries (OR 0.351, 95% CI 0.23 to 0.54; p<0.001). Results of meta-regression analysis revealed that a greater duration of balance training was associated with a higher injury risk for ACL injury ( p=0.04), while greater durations of static stretching was associated with a lower injury risk for non-contact ACL injuries ( p=0.04). Conclusions While ACL prevention programmes are successful in reducing the risk of ACL injury, the ideal combination and emphasis of training components within these programmes remains unclear. Evidence indicates that greater emphases on balance training and static stretching may be associated with an increase and decrease in injury risk, respectively.

Delays in door-to-balloon time impact late survival in high-risk but not low-risk patients and in patients presenting early but not late after the onset of symptoms. These findings have implications for the triage of patients for primary PCI.

Adaptive phenotypic plasticity in thermally sensitive traits, that is, thermal acclimation, generally increases with increasing latitude and altitude. The presumed explanation is that high-latitude/altitude organisms have evolved greater acclimation ability because of exposure to greater temperature fluctuations. Using a conceptual model of the thermal environment during the reproductive season, we tested this hypothesis against an alternative that plasticity is greater because of increased exposure to specific temperatures that strongly select for thermal acclimation. We examined geographic variation in floral reflectance/color plasticity among 29 European populations of a widespread perennial herb, Plantago lanceolata. Individuals partially thermoregulate reproduction through temperature-sensitive plasticity in floral reflectance/color. Plasticity was positively correlated with latitude and altitude. Path analyses support the hypothesis that the thermal environment mediates these geographic effects. Plasticity declined as seasonal temperature range increased, and it increased as duration of the growing season shortened and as the proportion of time exposed to temperatures favoring thermoregulation increased. Data provide evidence that floral reflectance/color plasticity is adaptive and that it has evolved in response not to the magnitude of temperature variation during the reproductive season but rather to the relative exposure to low temperatures, which favor thermoregulation.

We propose a direct method of partitioning the particulate spectral scattering coefficient of the marine hydrosol based on the concurrent determination of the concentrations of particulate mineral and organic matter (the total mass of optically active scattering material exclusive of water) with the particulate spectral scattering coefficient. For this we derive a Model II multiple linear regression model. The multiple linear regression of the particulate spectral scattering coefficient against the independent variables, the concentrations of particulate inorganic matter and particulate organic matter, yields their massspecific spectral scattering cross sections. The mass-specific spectral scattering cross section is simply the particle scattering cross section normalized to the particle mass, a fundamental optical efficiency parameter for the attenuation of electromagnetic radiation [Absorption and Scattering of Light by Small Particles, (Wiley-Interscience, 1983), pp. 80-81, 289]. It is possible to infer the optical properties of the suspended matter from the mass-specific spectral scattering cross sections. From these cross sections we partition the particulate spectral scattering coefficient into its major components.