Significance of adverse outcome pathways in biomarker-based environmental risk assessment in aquatic organisms

In environmental risk assessments（ERA）, biomarkers have been widely used as an early warning signal of environmental contamination. However, biomarker responses have limitation due to its low relevance to adverse outcomes（e.g., fluctuations in community structure, decreases in population size, and other similar ecobiologically relevant indicators of community structure and function）. To mitigate these limitations, the concept of adverse outcome pathways（AOPs） was developed. An AOP is an analytical, sequentially progressive pathway that links a molecular initiating event（MIE） to an adverse outcome. Recently, AOPs have been recognized as a potential informational tool by which the implications of molecular biomarkers in ERA can be better understood. To demonstrate the utility of AOPs in biomarker-based ERA, here we discuss a series of three different biological repercussions caused by exposure to benzo（a）pyrene（Ba P）, silver nanoparticles（Ag NPs）, and selenium（Se）. Using mainly aquatic invertebrates and selected vertebrates as model species, we focus on the development of the AOP concept. Aquatic organisms are suitable bioindicator species whose entire lifespans can be observed over a short period; moreover, these species can be studied on the molecular and population levels.Also, interspecific differences between aquatic organisms are important to consider in an AOP framework, since these differences are an integral part of the natural environment.The development of an environmental pollutant-mediated AOP may enable a better understanding of the effects of environmental pollutants in different scenarios in the diverse community of an ecosystem.

Assessment of slow pathway function after successful radiofrequency modification in patients with typical AV nodal reentry tachycardia by the use of the maximal AH interval

Background Persistence of slow pathway (SP) function after SP modification is not uncommon after successful rediofrequency (RF) ablation of typical AV nodal reentry tachycardia (AVNRT). Methods and results We compared two methods (maximal AH interval during decremental atrial stimlation vs occurrence of AV nodal echos or dual AV nodal physiology (DAVNP): ≥50 msec increment in AH interval with a 10 msec decrement in A1A2) for the assessment of SP function immediately and 40 minutes after successful RF modification of SP. In 31 consecutive patients (age: 51±16 years, 18 women, 13 men) with typical AVNRT, SP modification was performed using a combined anatomic and electrogram guided approach. Immediately after successful SP modification, AV nodal function was assessed. This was repeated 40 minutes later. RF modification of SP was successful in all 31 patients. There was no recurrance during a 5±3 month follow up period. There was no significant difference between the electrophysiological parameters immediately and University of Frankfurt, Germany (Li YG, Bogun F, Grnefeld G, Hohnloser SH and Goethe JW)40 min after successful SP modification. There was evidence of SP function in 14 patients (6 with DAVNP+AV nodal echoes, 8 with either DAVNP or AV nodal echos) immehiately after SP modification. These patients could be differentiated from the patients without remaining SP function by maximal AH interval (298±102 msec vs 198±72 msec, P=0.004). 40 minutes after the suucessful SP modification, 11 patients displayed SP function (4 patients with DAVNP+AV nodal echos, 7 patients with either DAVNP or AV nodal echos). These patients could also be differentiated from the remaining patients with the use of the maximal AH interval (294±89 msec vs 189±50 msec, P<0.001).[BHDFG3,WK9ZQ,WK6,WK10*2,WK5W]Befroe SP modificationImmediately after RF40 min after RF[BHDZG1*2,WK9ZQ,WK6,WK10*2,WK5W]AVNERP (msec)258±44310±116316±114AVBCL (msec)330±55384±113376±110VABCL (msec)306±67306± 66311±54Max AH (msec)337±96247±100233±86 Conclusion SP function assessed immediately and 40 minutes after a successful SP modification remains stable. SP function can be assessed reliable by maximal AH interval during decremental atrial stimulation.