Predicting Substance Use Treatment Failure with Transfer Learning.

Transfer learning, which involves repurposing a trained model on a related task, may allow for better predictions with substance use data than models that are trained using the target data alone. This approach may also be useful for small clinical datasets. The current study examined a method of classifying substance use treatment success using transfer learning. Transfer learning was used to classify data from a nationwide database. We trained a convolutional neural network on a heroin use treatment dataset, then trained and tested on a smaller opioid use treatment dataset. We compared this model with a baseline model that did not benefit from transfer learning, and a tuned random forest (RF). The goal was to see if model weights transfer across related substances and from large to small datasets. The transfer model outperformed the RF model and baseline model. These findings suggest leveraging the power of large datasets for transfer learning may be an effective approach in predicting substance use disorder (SUD) treatment outcomes. It is possible to achieve a score that performs better than RF using transfer learning.

An enriched network motif family regulates multistep cell fate transitions with restricted reversibility.

Multistep cell fate transitions with stepwise changes of transcriptional profiles are common to many developmental, regenerative and pathological processes. The multiple intermediate cell lineage states can serve as differentiation checkpoints or branching points for channeling cells to more than one lineages. However, mechanisms underlying these transitions remain elusive. Here, we explored gene regulatory circuits that can generate multiple intermediate cellular states with stepwise modulations of transcription factors. With unbiased searching in the network topology space, we found a motif family containing a large set of networks can give rise to four attractors with the stepwise regulations of transcription factors, which limit the reversibility of three consecutive steps of the lineage transition. We found that there is an enrichment of these motifs in a transcriptional network controlling the early T cell development, and a mathematical model based on this network recapitulates multistep transitions in the early T cell lineage commitment. By calculating the energy landscape and minimum action paths for the T cell model, we quantified the stochastic dynamics of the critical factors in response to the differentiation signal with fluctuations. These results are in good agreement with experimental observations and they suggest the stable characteristics of the intermediate states in the T cell differentiation. These dynamical features may help to direct the cells to correct lineages during development. Our findings provide general design principles for multistep cell linage transitions and new insights into the early T cell development. The network motifs containing a large family of topologies can be useful for analyzing diverse biological systems with multistep transitions.

The Use of Stimulus Preference Assessments for Persons with Neurocognitive Disorder: A Literature Review.

Objectives: Stimulus preference assessments are a systematic, observation-based approach for identifying preferences among individuals with impaired communication skills. The purpose of this paper is to provide a review of the existing empirical literature that has utilized these methods with persons who have neurocognitive disorder (NCD).Methods: Studies were identified by searching online databases using a variety of search terms. Articles were included in the review if they were peer-reviewed, in English, were empirical in nature, and conducted a stimulus preference assessment with older adults diagnosed with NCD.Results: Eleven articles met the search criteria. Results revealed that data from stimulus preference assessments could increase activity engagement, increase requests for preferred items, identify reinforcers, and reduce behavioral and psychological symptoms.Conclusions: A small body of empirical literature suggests that data derived from stimulus preference assessments can be used to improve the lives of persons with NCD and their caregivers. Additional research is needed, however, to determine how effectively these procedures can be implemented into everyday practice in long-term care facilities.Clinical Implications: Stimulus preference assessments may provide a clinically useful means for efficiently identifying preferences in persons with severe NCD who cannot verbalize their needs.

Preferential potentiation of AMPA-mediated currents in brainstem hypoglossal motoneurons by subchronic exposure of mice expressing the human superoxide dismutase 1 G93A gene mutation to neurotoxicant methylmercury in vivo.

The exact causes of Amyotrophic lateral sclerosis (ALS), a progressive and fatal neurological disorder due to loss of upper and/or lower motoneurons, remain elusive. Gene-environment interactions are believed to be an important factor in the development of ALS. We previously showed that in vivo exposure of mice overexpressing the human superoxide dismutase 1 (hSOD1) gene mutation (hSOD1G93A; G93A), a mouse model for ALS, to environmental neurotoxicant methylmercury (MeHg) accelerated the onset of ALS-like phenotype. Here we examined the time-course of effects of MeHg on AMPA receptor (AMPAR)-mediated currents in hypoglossal motoneurons in brainstem slices prepared from G93A, hSOD1wild-type (hWT) and non-carrier WT mice following in vivo exposure to MeHg. Mice were exposed daily to 3 ppm (approximately 0.7 mg/kg/day) MeHg via drinking water beginning at postnatal day 28 (P28) and continued until P47, 64 or 84, then acute brainstem slices were prepared, and spontaneous excitatory postsynaptic currents (sEPSCs) or AMPA-evoked currents were examined using whole cell patch-clamp recording technique. Brainstem slices of untreated littermates were prepared at the same time points to serve as control. MeHg exposure had no significant effect on either sEPSCs or AMPA-evoked currents in slices from hWT or WT mice during any of those exposure time periods under our experimental conditions. MeHg also did not cause any significant effect on sEPSCs or AMPA-currents in G93A hypoglossal motoneurons at P47 and P64. However, at P84, MeHg significantly increased amplitudes of both sEPSCs and AMPA-evoked currents in hypoglossal motineurons from G93A mice (p < 0.05), but not the sEPSC frequency, suggesting a postsynaptic action on AMPARs. MeHg exposure did not cause any significant effect on GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs). Therefore, MeHg exposure in vivo caused differential effects on AMPARs in hypoglossal motoneurons from mice with different genetic backgrounds. MeHg appears to preferentially stimulate the AMPAR-mediated currents in G93A hypoglossal motoneurons in an exposure time-dependent manner, which may contribute to the AMPAR-mediated motoneuron excitotoxicity, thereby facilitating development of ALS-like phenotype.

Hover fly (Diptera: Syrphidae) diversity and seasonality in North Georgia apple and peach orchards.

Crop pollination and natural biological control provided by beneficial insects have an economic worth of hundreds of billions of dollars annually. Apple and peach production in North Georgia are economically important industries that benefit from these ecological services. Hover flies are dual ecosystem service providers that have been relatively understudied in orchard ecosystems. We investigated the diversity and seasonal activity of hover flies in apple and peach orchards at 2 sites in North Georgia from March to October 2020 and 2021. Bowl traps were used to sample hover flies in orchard edge and interior habitats. The aphidophagous species Toxomerus geminatus (Say) (Diptera: Syrphidae) and Toxomerus marginatus (Say) (Diptera: Syrphidae) comprised 86.6% of the total hover flies collected. Apple orchards yielded the greatest hover fly presence, species richness, and Toxomerus spp. abundance. Hover fly richness and diversity were greatest during postbloom, but Toxomerus spp. abundance was greatest during the bloom period. No differences in presence, richness, diversity, or Toxomerus spp. abundance were found between edge and interior habitats. Toxomerus geminatus and T. marginatus were dominant from March through August, with T. geminatus being more abundant than T. marginatus in March, early April, and August. October sampling produced the greatest hover fly richness. Our results suggest that hover flies are abundant in North Georgia orchards and exhibit substantial spatial and temporal variation in richness and diversity. Expanded studies incorporating additional sampling efforts and methods are needed to further characterize the hover fly fauna and their impact on North Georgia apple and peach orchards.

Zebrafish model systems for developmental neurobehavioral toxicology.

Zebrafish offer many advantages that complement classic mammalian models for the study of normal development as well as for the teratogenic effects of exposure to hazardous compounds. The clear chorion and embryo of the zebrafish allow for continuous visualization of the anatomical changes associated with development, which, along with short maturation times and the capability of complex behavior, makes this model particularly useful for measuring changes to the developing nervous system. Moreover, the rich array of developmental, behavioral, and molecular benefits offered by the zebrafish have contributed to an increasing demand for the use of zebrafish in behavioral teratology. Essential for this endeavor has been the development of a battery of tests to evaluate a spectrum of behavior in zebrafish. Measures of sensorimotor plasticity, emotional function, cognition and social interaction have been used to characterize the persisting adverse effects of developmental exposure to a variety of chemicals including therapeutic drugs, drugs of abuse and environmental toxicants. In this review, we present and discuss such tests and data from a range of developmental neurobehavioral toxicology studies using zebrafish as a model. Zebrafish provide a key intermediate model between high throughput in vitro screens and the classic mammalian models as they have the accessibility of in vitro models and the complex functional capabilities of mammalian models.

Toward a Data-based Approach to the Selection of Applied Behavior Analysis Program Characteristics.

There is a paucity of data that describe how program characteristics relate to program outcome goals. This gap limits the use of data to guide and support decisions concerning the selection of applied behavior analysis (ABA) program characteristics. Therefore, the purpose of the present study was to describe a methodology for the evaluation of the relationships between program characteristics and program outcome goals in the context of identifying the ideal program characteristics to propose for a new master of science in ABA program at Franciscan Missionaries of Our Lady University (FranU). For FranU, 11 program characteristics, enrollment, and the 2019 board certified behavior analyst (BCBA) pass rates were selected as variables. We provide a description of the procedures, data analysis and a general overview of our findings. The utility of the methodology for future research is also discussed.

Immune response to COVID-19 vaccination in a population with a history of elevated exposure to per- and polyfluoroalkyl substances (PFAS) through drinking water.

BACKGROUND: Exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to lower vaccine-induced antibody concentrations in children, while data from adults remains limited and equivocal. Characteristics of PFAS exposure and age at vaccination may modify such effects. OBJECTIVE: We used the mass administration of novel COVID-19 vaccines to test the hypothesis that prior exposure to environmentally-relevant concentrations of PFAS affect antibody response to vaccines in adolescents and adults. METHODS: Between April and June 2021, 226 participants aged 12-90 years with a history of exposure to PFAS in drinking water and who received an mRNA COVID-19 vaccine participated in our prospective cohort study. SARS-CoV-2 anti-spike and anti-nucleocapsid antibodies (IgG) were quantified before the first and second vaccine doses and again at two follow-ups in the following months (up to 103 days post dose 1). Serum PFAS concentrations (n = 39 individual PFAS) were measured once for each participant during baseline, before their first vaccination. The association between PFAS exposure and immune response to vaccination was investigated using linear regression and generalized estimating equation (GEE) models with adjustment for covariates that affect antibody response. PFAS mixture effects were assessed using weighted quantile sum and Bayesian kernel machine regression methods. RESULTS: The geometric mean (standard deviation) of perfluorooctane sulfonate and perfluorooctanoic acid serum concentrations in this population was 10.49 (3.22) and 3.90 (4.90) µg/L, respectively. PFAS concentrations were not associated with peak anti-spike antibody response, the initial increase in anti-spike antibody response following vaccination, or the waning over time of the anti-spike antibody response. Neither individual PFAS concentrations nor their evaluation as a mixture was associated with antibody response to mRNA vaccination against COVID-19. IMPACT STATEMENT: Given the importance of understanding vaccine response among populations exposed to environmental contaminants and the current gaps in understanding this relationship outside of early life/childhood vaccinations, our manuscript contributes meaningful data from an adolescent and adult population receiving a novel vaccination.

Tutorial: Artificial neural networks to analyze single-case experimental designs.

Since the start of the 21st century, few advances have had as far-reaching impact in science as the widespread adoption of artificial neural networks in fields as diverse as fundamental physics, clinical medicine, and psychology. In research methods, one promising area for the adoption of artificial neural networks involves the analysis of single-case experimental designs. Given that these types of networks are not generally part of training in the psychological sciences, the purpose of our article is to provide a step-by-step introduction to using artificial neural networks to analyze single-case designs. To this end, we trained a new model using data from a Monte Carlo simulation to analyze multiple baseline graphs and compared its outcomes with traditional methods of analysis. In addition to showing that artificial neural networks may produce less error than other methods, this tutorial provides information to facilitate the replication and extension of this line of work to other designs and datasets. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Building More Resilient Culture Collections: A Call for Increased Deposits of Plant-Associated Bacteria.

Biological collections preserve our past, while helping protect our future and increase future knowledge. Plant bacterial culture collections are our security for domestic and global biosecurity. This feature article will provide an introduction to the global position of plant bacterial collections. The role of collections in monitoring plant pathogenic bacteria will be explored through the presentation of five cases studies. These case studies demonstrate why culture collections were imperative for the outcome in each situation. We discuss what we believe should be the best practices to improve microbial preservation and accessioning rates, and why plant bacterial culture collections must increase deposits to be prepared for future emerging pathogens. This is not only the case for global culture collections, but on a much bigger scale, our future scientific successes, our biosecurity decisions and responses, and our knowledge are contingent upon preserving our valuable bacterial strains. It is hoped that once you read this article, you will see the need to deposit your strains in registered public collections and make a concerted effort to build better bacterial culture collections with us.

Prevalence, incidence, and years-lived with disability due to oral disorders in Brazil: an analysis of the Global Burden of Disease Study 2019.

INTRODUCTION: Epidemiological surveys revealed that Brazil has a high burden of oral diseases. However, no prior study has reported estimates of untreated dental caries, periodontitis, and edentulism over a three-decade period. The objective of this study is to report the trends of prevalence, incidence, and years-lived with disability (YLDs) due to untreated dental caries in primary and permanent teeth, periodontitis, and edentulism in Brazil between 1990 and 2019. METHODS: Estimates of prevalence, incidence, and YLDs due to dental caries in primary and permanent teeth, periodontitis, and edentulism were produced for Brazil, by sex and age, between 1990 and 2019, using Dismod-MR 2.1, as part of the Global Burden of Disease Study 2019 (GBD 2019). Trends of oral disorders were analyzed using generalized linear regression models applying the Prais-Winsten method. RESULTS: Almost 100 million Brazilians presented at least one oral disorder in 2019, which was equivalent to a prevalence of 45.3%. All oral diseases combined ranked eighth among all causes of disability, causing more than 970,000 YLDs. Untreated dental caries in primary teeth were estimated to affect 13.5 million children, and untreated dental caries in permanent teeth affected more than 52 million people. Periodontitis affected 29.5 million people, and edentulism affected almost 22 million. The generalized linear regression models revealed a trend of stability of oral disorders between 1990 and 2019. CONCLUSIONS: The burden of oral diseases in Brazil is extremely high. Oral disorders, edentulism in particular, caused disability at levels that are comparable to other important chronic diseases.

Machine Learning for Supplementing Behavioral Assessment.

The Questions About Behavioral Function (QABF) has a high degree of convergent validity, but there is still a lack of agreement between the results of the assessment and the results of experimental function analysis. Machine learning (ML) may improve the validity of assessments by using data to build a mathematical model for more accurate predictions. We used published QABF and subsequent functional analyses to train ML models to identify the function of behavior. With ML models, predictions can be made from indirect assessment results based on learning from results of past experimental functional analyses. In Experiment 1, we compared the results of five algorithms to the QABF criteria using a leave-one-out cross-validation approach. All five outperformed the QABF assessment on multilabel accuracy (i.e., percentage of predictions with the presence or absence of each function indicated correctly), but false negatives remained an issue. In Experiment 2, we augmented the data with 1,000 artificial samples to train and test an artificial neural network. The artificial network outperformed other models on all measures of accuracy. The results indicated that ML could be used to inform conditions that should be present in a functional analysis. Therefore, this study represents a proof-of-concept for the application of machine learning to functional assessment.

Facilitating engagement of persons with opioid use disorder in treatment for hepatitis C virus infection via telemedicine: Stories of onsite case managers.

Although hepatitis C virus (HCV) infection has high prevalence and incidence in persons with opioid use disorder (PWOUD), their engagement in HCV care has been limited due to a variety of factors. In an ongoing multisite study at 12 opioid treatment programs (OTPs) throughout New York State (NYS), we have been evaluating telemedicine accompanied by onsite administration of direct acting antiviral (DAA) medications compared with usual care including offsite referral to a liver specialist for HCV management. Each site has a case manager (CM) who is responsible for all study-related activities including participant recruitment, facilitating telemedicine interactions, retention in care, and data collection. Our overall objective is to analyze CM experiences of clients' stories and events to understand how the telemedicine model facilitates HCV treatment. Hermeneutic phenomenology was used to interpret and to explicate common meanings and shared practices of the phenomena of case management, and a focus group with CMs was conducted to reinforce and expand on key themes identified from the CMs' stories. We identified three themes: (1) building trust, (2) identification of multiple competing priorities, and (3) development of personalized care approaches. Our results illustrate that trust is a fundamental pillar on which the telemedicine system can be based. Participants' experiences at the OTP can reinforce trust. Understanding the specific competing priorities and routinizing dedicated personalized approaches to overcome them are key to increasing participation in HCV care among PWOUD.

Zebrafish show long-term behavioral impairments resulting from developmental vitamin D deficiency.

Vitamin D has been shown in a wide variety of species to play critical roles in neurodevelopment. Vitamin D deficiency disrupts development of the brain and can cause lasting behavioral dysfunction. Zebrafish have become an important model for the study of development in general and neurodevelopment in particular. Zebrafish were used in the current study to characterize the effects of developmental vitamin D deficiency on behavioral function. Adult zebrafish that had been chronically fed a vitamin D deficient or replete diets were bred and the offspring were continued on those diets. The offspring were behaviorally tested as adults. In the novel tank diving test the vitamin D deficient diet significantly lowered the vertical position of fish indicative of more anxiety-like behavior. In the novel tank diving test swimming activity was also significantly decreased by vitamin D deficiency. Startle response was increased by developmental vitamin D deficiency during the early part of the test. No significant effects of vitamin D deficiency were seen with social affiliation and predatory stimulus avoidance tests. These results indicate a phenotype of vitamin D deficiency characterized by more anxiety-like behavior. This result was relatively specific inasmuch as few or no behavioral effects were seen in other behavioral tests.

Australia: A Continent Without Native Powdery Mildews? The First Comprehensive Catalog Indicates Recent Introductions and Multiple Host Range Expansion Events, and Leads to the Re-discovery of Salmonomyces as a New Lineage of the Erysiphales.

In contrast to Eurasia and North America, powdery mildews (Ascomycota, Erysiphales) are understudied in Australia. There are over 900 species known globally, with fewer than currently 60 recorded from Australia. Some of the Australian records are doubtful as the identifications were presumptive, being based on host plant-pathogen lists from overseas. The goal of this study was to provide the first comprehensive catalog of all powdery mildew species present in Australia. The project resulted in (i) an up-to-date list of all the taxa that have been identified in Australia based on published DNA barcode sequences prior to this study; (ii) the precise identification of 117 specimens freshly collected from across the country; and (iii) the precise identification of 30 herbarium specimens collected between 1975 and 2013. This study confirmed 42 species representing 10 genera, including two genera and 13 species recorded for the first time in Australia. In Eurasia and North America, the number of powdery mildew species is much higher. Phylogenetic analyses of powdery mildews collected from Acalypha spp. resulted in the transfer of Erysiphe acalyphae to Salmonomyces, a resurrected genus. Salmonomyces acalyphae comb. nov. represents a newly discovered lineage of the Erysiphales. Another taxonomic change is the transfer of Oidium ixodiae to Golovinomyces. Powdery mildew infections have been confirmed on 13 native Australian plant species in the genera Acacia, Acalypha, Cephalotus, Convolvulus, Eucalyptus, Hardenbergia, Ixodia, Jagera, Senecio, and Trema. Most of the causal agents were polyphagous species that infect many other host plants both overseas and in Australia. All powdery mildews infecting native plants in Australia were phylogenetically closely related to species known overseas. The data indicate that Australia is a continent without native powdery mildews, and most, if not all, species have been introduced since the European colonization of the continent.

Evaluating a Gene-Environment Interaction in Amyotrophic Lateral Sclerosis: Methylmercury Exposure and Mutated SOD1.

PURPOSE OF REVIEW: Gene-environment (GxE) interactions likely contribute to numerous diseases, but are often difficult to model in the laboratory. Such interactions have been widely hypothesized for amyotrophic lateral sclerosis (ALS); recent controlled laboratory studies are discussed here and hypotheses related to possible mechanisms of action are offered. Using methylmercury exposure and mutated SOD1 to model the impacts of such an interaction, we interpret evidence about their respective mechanisms of toxicity to interrogate the possibility of additive (or synergistic) effects when combined. RECENT FINDINGS: Recent work has converged on mechanisms of calcium-mediated glutamate excitotoxicity as a likely contributor in one model of a gene-environment interaction affecting the onset and progression of ALS-like phenotype. The current experimental literature on mechanisms of metal-induced neuronal injury and their relevant interactions with genetic contributions in ALS is sparse, but we describe those studies here and offer several integrative hypotheses about the likely mechanisms involved.

Exposure to a PBDE/OH-BDE mixture alters juvenile zebrafish (Danio rerio) development.

Polybrominated diphenyl ethers (PBDEs) and their metabolites (e.g., hydroxylated BDEs [OH-BDEs]) are contaminants frequently detected together in human tissues and are structurally similar to thyroid hormones. Thyroid hormones partially mediate metamorphic transitions between life stages in zebrafish, making this a critical developmental window that may be vulnerable to chemicals disrupting thyroid signaling. In the present study, zebrafish were exposed to 6-OH-BDE-47 (30 nM; 15 µg/L) alone, or to a low-dose (30 µg/L) or high-dose (600 µg/L) mixture of PentaBDEs, 6-OH-BDE-47 (0.5-6 µg/L), and 2,4,6-tribromophenol (5-100 µg/L) during juvenile development (9-23 d postfertilization) and evaluated for developmental endpoints mediated by thyroid hormone signaling. Fish were sampled at 3 time points and examined for developmental and skeletal morphology, apical thyroid and skeletal gene markers, and modifications in swimming behavior (as adults). Exposure to the high-dose mixture resulted in >85% mortality within 1 wk of exposure, despite being below reported acute toxicity thresholds for individual congeners. The low-dose mixture and 6-OH-BDE-47 groups exhibited reductions in body length and delayed maturation, specifically relating to swim bladder, fin, and pigmentation development. Reduced skeletal ossification was also observed in 6-OH-BDE-47-treated fish. Assessment of thyroid and osteochondral gene regulatory networks demonstrated significantly increased expression of genes that regulate skeletal development and thyroid hormones. Overall, these results indicate that exposures to PBDE/OH-BDE mixtures adversely impact zebrafish maturation during metamorphosis. Environ Toxicol Chem 2017;36:36-48. © 2016 SETAC.

Prevalence, incidence, and years-lived with disability due to oral disorders in Brazil: an analysis of the Global Burden of Disease Study 2019

Abstract INTRODUCTION Epidemiological surveys revealed that Brazil has a high burden of oral diseases. However, no prior study has reported estimates of untreated dental caries, periodontitis, and edentulism over a three-decade period. The objective of this study is to report the trends of prevalence, incidence, and years-lived with disability (YLDs) due to untreated dental caries in primary and permanent teeth, periodontitis, and edentulism in Brazil between 1990 and 2019. METHODS Estimates of prevalence, incidence, and YLDs due to dental caries in primary and permanent teeth, periodontitis, and edentulism were produced for Brazil, by sex and age, between 1990 and 2019, using Dismod-MR 2.1, as part of the Global Burden of Disease Study 2019 (GBD 2019). Trends of oral disorders were analyzed using generalized linear regression models applying the Prais-Winsten method. RESULTS Almost 100 million Brazilians presented at least one oral disorder in 2019, which was equivalent to a prevalence of 45.3%. All oral diseases combined ranked eighth among all causes of disability, causing more than 970,000 YLDs. Untreated dental caries in primary teeth were estimated to affect 13.5 million children, and untreated dental caries in permanent teeth affected more than 52 million people. Periodontitis affected 29.5 million people, and edentulism affected almost 22 million. The generalized linear regression models revealed a trend of stability of oral disorders between 1990 and 2019. CONCLUSIONS The burden of oral diseases in Brazil is extremely high. Oral disorders, edentulism in particular, caused disability at levels that are comparable to other important chronic diseases.

Persistent behavioral effects following early life exposure to retinoic acid or valproic acid in zebrafish.

BACKGROUND: Moderate to severe dysregulation in retinoid signaling during early development is associated with a constellation of physical malformations and/or neural tube defects, including spina bifida. It is thought that more subtle dysregulation of this system, which might be achievable via dietary (i.e. hypervitaminosis A) or pharmacological (i.e. valproic acid) exposure in humans, will manifest on behavioral domains including sociability, without overt physical abnormalities. METHODS: During early life, zebrafish were exposed to low doses of two chemicals that disrupt retinoid signaling. From 0 to 5dpf, larvae were reared in aqueous solutions containing retinoic acid (0, 0.02, 0.2 or 2nM) or valproic acid (0, 0.5, 5.0 or 50µM). One cohort of zebrafish was assessed using a locomotor activity screen at 6-dpf; another was reared to adulthood and assessed using a neurobehavioral test battery (startle habituation, novel tank exploration, shoaling, and predator escape/avoidance). RESULTS: There was no significant increase in the incidence of physical malformation among exposed fish compared to controls. Both retinoic acid and valproic acid exposures during development disrupted larval activity with persisting behavioral alterations later in life, primarily manifesting as decreased social affiliation. CONCLUSIONS: Social behavior and some aspects of motor function were altered in exposed fish; the importance of examining emotional or psychological consequences of early life exposure to retinoid acting chemicals is discussed.

Pharmacological analyses of learning and memory in zebrafish (Danio rerio).

Over the last decade, zebrafish (Danio rerio) have become valuable as a complementary model in behavioral pharmacology, opening a new avenue for understanding the relationships between drug action and behavior. This species offers a useful intermediate approach bridging the gap between in vitro studies and traditional mammalian models. Zebrafish offer great advantages of economy compared to their rodent counterparts, their complex brains and behavioral repertoire offer great translational potential relative to in vitro models. The development and validation of a variety of tests to measure behavior, including cognition, in zebrafish have set the stage for the use of this animal for behavioral pharmacology studies. This has led to research into the basic mechanisms of cognitive function as well as screening for potential cognition-improving drug therapies, among other lines of research. As with all models, zebrafish have limitations, which span pharmacokinetic challenges to difficulties quantifying behavior. The use, efficacy and limitations associated with a zebrafish model of cognitive function are discussed in this review, within the context of behavioral pharmacology.