A systematic evidence map and bibliometric analysis of the behavioural impacts of pesticide exposure on zebrafish.

Pesticides are indispensable in agriculture and have become ubiquitous in aquatic environments. Pesticides in natural environments can cause many negative impacts on aquatic species, ranging from mortality to sub-lethal physiological and behavioural changes. The complex sub-lethal impacts of pesticides are routinely tested on model species, with zebrafish (Danio rerio) being regularly used as a behavioural model. Although behavioural ecotoxicology research using zebrafish is increasing rapidly, we lack quantitative evidence to support which pesticides have been tested and how study designs are carried out. This shortcoming not only limits the deliberate planning for future primary studies to fill the knowledge gaps but also hinders evidence synthesis. To provide quantitative evidence of what pesticides are currently studied and what study designs are used, we combined a systematic evidence map approach and bibliometric analysis. This novel method has been coined research weaving and allows us to elicit gaps and clusters in our evidence base, whilst showing connections between authors and institutions. The methodology can be summarised in five primary steps: literature searching, screening, extraction, data analysis and bibliometric analysis. We identified four areas where research on the sub-lethal effects of pesticide exposure on zebrafish is lacking. First, some widely used pesticides, such as neonicotinoids, are understudied. Second, most studies do not report important elements of the study design, namely the sex and the life-stage of the zebrafish. Third, some behaviours, such as impacts of pesticide exposure on zebrafish cognition, are underexplored. And last, we revealed through the bibliometric analysis that most of the research is conducted in developed countries and there is limited cross country co-authorships. Upon identifying these gaps, we offer solutions for each limitation, emphasizing the importance of diverse global research output and cross-country co-authorships. Our systematic evidence map and bibliometric analysis provide valuable insights for helping to guide future research, which can be used to help support evidence-based policy decisions.

A meta-analytic review of fish antioxidant defense and biotransformation systems following pesticide exposure.

Pesticides reach aquatic ecosystems and interact with various targets in cells of fish and other living organisms. Toxicity originates during the metabolization process, which may produce toxic metabolites or reactive oxygen species (ROS). Ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), catalase (CAT), superoxide dismutase (SOD) activities, and levels of reduced glutathione (GSH) indicate toxicants interacted with drug-metabolizing and antioxidant systems, i.e., they are biomarkers of biotransformation and oxidative stress. We meta-analytically quantified the impact of pesticides on the mean response and variability of these biomarkers. Our goals were to verify (i) the overall effect of pesticides on oxidative stress and biotransformation, and how each biomarker respond to exposure; (ii) how the life stage of fish (juvenile and adult) influence biomarkers variability and mean activity; (iii) to what extent fish sex (male, female or mixed-sex groups) modify pesticides toxicity; (iv) how different classes of pesticides, and the combination of their concentration and time of exposure, affect each biomarker. Overall, pesticides induced oxidative stress and the biotransformation system. Regardless of life stage, EROD mean activity increased significantly. In exposed juveniles, CAT and GST variability decreased and increased, respectively. CAT mean activity was higher in females, while EROD and GST activities increased in males after pesticide exposure. Organophosphorus (OPs) and organochlorine insecticides, along with imidazole and triazole fungicides, affected biomarkers the most, however the combined effect of concentration and time of exposure of OPs was not detected. Notably, imidazoles and triazoles classes increased EROD by more than 100%. Additionally, we identified research gaps, such as the lack of effect estimates of relevant pesticides on EROD (e.g., pyrethroids and neonicotinoids) and the small number of studies evaluating GSH on female fish. Future researchers may use these gaps as a guide towards enhanced experimental designs and, consequently, a better understanding of pesticide toxic effects on fish.

Prevalence and psychological repercussion of phantom breast syndrome in women undergoing mastectomy: a systematic review

Breast cancer is the most common cancer among women in the world and the leading cause of death among Brazilian women. The presence of phantom breast syndrome (PBS) is one of the possible postoperative complications and may reach prevalences of up to 53% among mastectomized women. This study assessed the scientific evidence regarding the presence of PBS and its psychological repercussions in women undergoing mastectomy. This is a systematic review of observational studies based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. The methodological quality of the studies and the level of scientific evidence were assessed using the Newcastle-Ottawa Scale and the Grading of Recommendations Assessment, Development and Evaluation. A total of 95 articles were identified, but only 11 met the eligibility criteria. The outcomes of the presence of PBS and psychological repercussion were evaluated in 2,160 and 1,996 patients, respectively. It was found that the prevalence of PBS varies according to age, being on average 28% and reaching up to 50% in women under 80 years of age. This phenomenon can occur from three months to six years after amputation, tending to regress over time. Anxiety, depression, and sleep disorders are the most prevalent psychological effects (35.8%, 31.5%, and 29.2%, respectively). The studies presented strong scientific evidence of PBS and moderate evidence of psychological repercussions associated with this context.

Pesticide effects on fish cholinesterase variability and mean activity: A meta-analytic review.

Fish cholinesterases (ChEs) - like acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) - are common biomarkers of environmental contamination due to their sensitivity to a variety of toxicants. To understand pesticide effects on fish ChEs mean activity and variability, we conducted a systematic review and meta-analyses. Our goal was to verify (i) if brain and muscle ChEs responded differently to pesticide exposure; (ii) how fish size and life stage (i.e., juvenile and adult) influence ChEs variability and mean activity; (iii) what type of pesticides (i.e., herbicide, insecticide, and fungicide) has the strongest effect, and if the analytical-grade compounds differ from commercial formulations; (iv) if increasing concentrations combined with prolonged exposure leads to stronger ChEs inhibition; and (v) how each class of pesticide affects these enzymes. We validated ChEs reliability as biomarkers and identified factors influencing their response. Regardless of tissue, BChE response was more variable than AChE, and no difference between their average activity was detected. The size of juvenile fish is an important factor affecting ChEs mean activity and variability, whereas pesticide had no significant effect on adult fish ChEs. Insecticides were stronger inhibitors compared to herbicides and fungicides. Analytical-grade compounds decreased ChEs mean activity to a higher degree than commercial formulations. The combined effect of concentration and time was only significant for fungicides and insecticides. Among classes, organophosphorus insecticides had the strongest effect on ChEs, followed by carbamates, organochlorines, and pyrethroids. Organophosphorus herbicides and oxazolidinones were the only herbicides to decrease ChEs mean activity significantly, and their effects were similar from those of pyrethroids and organochlorines. Additionally, our results identified research gaps, such as the small number of studies on fungicides, neonicotinoids and other relevant pesticides. These findings suggest future directions, which might help researchers identify robust cause-effect relationships between fish ChEs and pesticides.

Biomarker responses in fish exposed to polycyclic aromatic hydrocarbons (PAHs): Systematic review and meta-analysis.

Biomarkers of antioxidant and biotransformation systems are commonly used to assess polycyclic aromatic hydrocarbons (PAHs) pollution in fish. Despite their extensive application of biomarkers, contradictory results are vastly reported in the literature, even for the same species in similar contamination scenarios. This study aims to verify response patterns of biomarkers in fish exposed to PAHs. Through systematic reviews and meta-analyses, we were able to evaluate: (i) overall magnitude of PAHs effects on biotransformation and oxidative stress biomarkers; (ii) patterns of response among experimental approaches (laboratory, field and active biomonitoring), environment (marine and freshwater) and fish habitat (pelagic, demersal, etc.); (iii) effects of exposure route, time and concentration of PAHs; and (iv) which biomarkers respond best to PAHs exposure. Overall, biomarker responses were significantly affected by PAHs exposure. The activities of ethoxyresorufin-O-deethylase (EROD), glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GPx) and levels of oxidized glutathione (GSSG) and lipid peroxide (LPO) significantly increased in fish exposed to PAHs, whereas catalase (CAT) and glutathione reductase (GR) activities and levels of reduced glutathione (GSH) were not affected. Amongst responsive biomarkers, EROD and GST activities significantly differed among approaches and between marine and freshwater environments, but were not affected by fish habitat. GSSG levels were higher in fish from laboratory bioassays compared to the field, but did not differ between environments nor habitats. Exposure route played a major role only for GST and GPx responses. Finally, increasing PAHs concentration and exposure time had a significant effect on all assessed biomarkers, except for CAT. We conclude that EROD and GST are robust biomarkers to assess PAHs effects in fish. Contrarily, CAT is an inadequate biomarker of PAHs exposure since no significant response was observed. Our study also highlighted some research gaps in PAHs contamination studies, such as a clear lack of active biomonitoring experiments.

Diffuse sources of contamination in freshwater fish: Detecting effects through active biomonitoring and multi-biomarker approaches.

Aquatic organisms are usually exposed to a mixture of xenobiotics that may exert a large effect even in low concentrations, and when information is obtained exclusively from chemical analyses the prediction of the deleterious effects is potentially hindered. Therefore, the application of complementary monitoring methods is a priority. Here, in addition to chemical analyses, an active biomonitoring study using multiple biomarker responses in Nile tilapia Oreochromis niloticus was conducted to assess the effects of a contamination gradient along four reservoirs in Iguaçu River. Chemical analysis in the muscle showed high levels of metals in fish from the reservoir closest to an industrialized and environmentally degraded area, however fish exposed to all studied reservoirs showed hepatic alterations (necrosis and inflammatory processes). Also, significant variations of biochemical biomarkers were observed with no clear indication of contamination gradient, since an indicative of higher impact was found in an intermediary reservoir, including high concentrations of biliary polycyclic aromatic hydrocarbons (PAHs). However, nuclear morphological alterations (NMA) were less frequent at the same reservoir. Thus, the multi-biomarker approach allied to active biomonitoring is a practical and important tool to assess deleterious effects of contamination in freshwater, providing data for monitoring and conservation protocols.