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Toxicoepigenetics for Risk Assessment: Bridging the Gap Between Basic and Regulatory Science.

ABSTRACT: Toxicoepigenetics examines the health effects of environmental exposure associated with, or mediated by, changes in the epigenome. Despite high expectations, toxicoepigenomic data and methods have yet to become significantly utilized in chemical risk assessment. This article draws on a social science framework to highlight hitherto overlooked structural barriers to the incorporation of toxicoepigenetics in risk assessment and to propose ways forward. The present barriers stem not only from the lack of maturity of the field but also from differences in constraints and standards between the data produced by toxicoepigenetics and the regulatory science data that risk assessment processes require. Criteria and strategies that frame the validation of knowledge used for regulatory purposes limit the application of basic research in toxicoepigenetics toward risk assessment. First, the need in regulatory toxicology for standardized methods that form a consensus between regulatory agencies, basic research, and the industry conflicts with the wealth of heterogeneous data in toxicoepigenetics. Second, molecular epigenetic data do not readily translate into typical toxicological endpoints. Third, toxicoepigenetics investigates new forms of toxicity, in particular low-dose and long-term effects, that do not align well with the traditional framework of regulatory toxicology. We propose that increasing the usefulness of epigenetic data for risk assessment will require deliberate efforts on the part of the toxicoepigenetics community in 4 areas: fostering the understanding of epigenetics among risk assessors, developing knowledge infrastructure to demonstrate applicability, facilitating the normalization and exchange of data, and opening the field to other stakeholders.

SUBMITTER: Le Goff A

PROVIDER: S-EPMC9290111 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe past decades of research have seen an increase in statistical tools to explore the complex dynamics of mental health from patient data, yet the application of these tools in clinical practice remains uncommon. This is surprising, given that clinical reasoning, e.g., case conceptualizations, largely coincides with the dynamical system approach. We argue that the gap between statistical tools and clinical practice can partly be explained by the fact that current estimation techniques disregard theoretical and practical considerations relevant to psychotherapy. To address this issue, we propose that case conceptualizations should be formalized. We illustrate this approach by introducing a computational model of functional analysis, a framework commonly used by practitioners to formulate case conceptualizations and design patient-tailored treatment.MethodsWe outline the general approach of formalizing idiographic theories, drawing on the example of a functional analysis for a patient suffering from panic disorder. We specified the system using a series of differential equations and simulated different scenarios; first, we simulated data without intervening in the system to examine the effects of avoidant coping on the development of panic symptomatic. Second, we formalized two interventions commonly used in cognitive behavioral therapy (CBT; exposure and cognitive reappraisal) and subsequently simulated their effects on the system.ResultsThe first simulation showed that the specified system could recover several aspects of the phenomenon (panic disorder), however, also showed some incongruency with the nature of panic attacks (e.g., rapid decreases were not observed). The second simulation study illustrated differential effects of CBT interventions for this patient. All tested interventions could decrease panic levels in the system.ConclusionsFormalizing idiographic theories is promising in bridging the gap between complexity science and clinical practice and can help foster more rigorous scientific practices in psychotherapy, through enhancing theory development. More precise case conceptualizations could potentially improve intervention planning and treatment outcomes. We discuss applications in psychotherapy and future directions, amongst others barriers for systematic theory evaluation and extending the framework to incorporate interactions between individual systems, relevant for modeling social learning processes. With this report, we hope to stimulate future efforts in formalizing clinical frameworks.

Project description:Purpose/objectivesThe current study was undertaken to investigate whether self-assessment of clinical skills of undergraduate dental students could be bridged with faculty assessment by deliberate training over an extended period. A secondary aim was to explore students' perception of self-assessment and its effect on their learning and motivation. MATERIAL AND METHODS: A prospective pilot study was conducted at the Department of Restorative Dentistry at Damascus University. Sixteen students participated in the study, ranging in age between 22 and 23 years. A modified Direct Observation of Procedural Skills form with a grading rubric was used to register and guide students' self-assessment; both were pretested on four students before the study. In total, four clinical encounters were completed by each student. Students were trained on how to conduct proper self-assessment before and after each clinical encounter. A postcourse questionnaire was used to investigate students' perception of self-assessment.ResultsBias in self-assessment decreased consistently after each encounter, and the difference in bias between the first (bias = 0.77) and the last encounter (bias = 0.21) was significant with a medium effect size (p = .022, d = 0.64). The percentage of disconfirming performance dimensions decreased from 39.7% to 26.9%. Students' ability to exactly pinpoint strengths improved consistently and significantly. However, their ability to pinpoint areas of improvement was volatile and showed no significant difference. Bland-Altman graph plots showed higher levels of agreement between self-assessment and faculty assessment. Moreover, students' perception of self-assessment was very positive overall.ConclusionsThese findings suggest the possibility that the gap between self-assessment and faculty assessment could be bridged through deliberate training. Future longitudinal research using a larger sample size is still required to further explore whether self-assessment can be actively bridged with faculty assessment by deliberate training.

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Toxicoepigenetics for Risk Assessment: Bridging the Gap Between Basic and Regulatory Science.

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