To mix or not to mix? A holistic approach to stratification-preserving and destratification aeration of drinking-water supply reservoirs.

Aeration is used globally as a remediation method for lakes and reservoirs with methods generally falling into two categories, those which preserve natural stratification (hypolimnetic aeration; HA) and those which destratify reservoirs through mixing of the water column (destratification aeration; DA). The United Kingdom and Australia largely focus on DA methods to manage harmful algal blooms and decrease trace metal concentrations, whereas the United States and Europe frequently focus on HA techniques to increase dissolved oxygen (DO) concentrations and decrease benthic nutrient and metal release from the sediment. A more holistic understanding of how the different techniques influence water quality in regard to raw water supply and ecosystem health should lead to more efficient treatment, reducing wasted energy and other costs during both reservoir management and the drinking-water treatment process. This study compares HA and DA on stratification, DO, and cyanobacteria concentrations in a single drinking-water supply reservoir during the 2016 summer stratification period. HA preserved stratification but could not maintain sufficient hypolimnetic DO past late April in this functionally eutrophic reservoir, establishing conditions favourable to cyanobacteria. An incipient cyanobacteria bloom formed that was subsequently dispersed after DA was initiated on May 05. Continuous monitoring revealed the formation of these issues in real-time and informed a switch from HA to DA, thereby allowing for a pro-active rather than reactive approach to reservoir management and subsequent drinking-water treatment. Both HA and DA are put forward as successful aeration strategies depending on management goals; however, performance is strongly site-specific. Such approaches are likely to become increasingly important as reservoir management tools to combat stratification-driven water quality issues under the pressing threats of anthropogenic activity and climate change.

Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review.

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma.

Maternal regulation of the vertebrate oocyte-to-embryo transition.

Maternally-loaded factors in the egg accumulate during oogenesis and are essential for the acquisition of oocyte and egg developmental competence to ensure the production of viable embryos. However, their molecular nature and functional importance remain poorly understood. Here, we present a collection of 9 recessive maternal-effect mutants identified in a zebrafish forward genetic screen that reveal unique molecular insights into the mechanisms controlling the vertebrate oocyte-to-embryo transition. Three genes, over easy, p33bjta, poached and black caviar, were found to control initial steps in yolk globule sizing and protein cleavage during oocyte maturation that act independently of nuclear maturation. The krang, kazukuram, p28tabj, and spotty genes play distinct roles in egg activation, including cortical granule biology, cytoplasmic segregation, the regulation of microtubule organizing center assembly and microtubule nucleation, and establishing the basic body plan. Furthermore, we cloned two of the mutant genes, identifying the over easy gene as a subunit of the Adaptor Protein complex 5, Ap5m1, which implicates it in regulating intracellular trafficking and yolk vesicle formation. The novel maternal protein Krang/Kiaa0513, highly conserved in metazoans, was discovered and linked to the function of cortical granules during egg activation. These mutant genes represent novel genetic entry points to decipher the molecular mechanisms functioning in the oocyte-to-embryo transition, fertility, and human disease. Additionally, our genetic adult screen not only contributes to the existing knowledge in the field but also sets the basis for future investigations. Thus, the identified maternal genes represent key players in the coordination and execution of events prior to fertilization.

Phenotype-Genotype Discordance and a Case of a Disorder of Sexual Differentiation.

Discordance between the genetic sex and phenotype seen on ultrasound can identify disorders of sexual development (DSD) that previously escaped detection until puberty. We describe a 46, XY disorder of sexual differentiation caused by a rare mutation in the SF1 gene (OMIM]184757, (NR5A1). The mutation (NR5A1)-c.205C > G (p. Arg69Gly) was discovered after a phenotype-genotype discrepancy was encountered during prenatal care. The baby with 46, XY DSD has female external genitalia but evidence of Y chromosome-related regression of Müllerian structures and the absence of palpable gonads. We discussed the literature on phenotype-genotype discrepancy and the importance of care coordination between the antenatal and postnatal teams to ensure a timely diagnosis of DSD.

Developing an initial programme theory for a model of social care in prisons and on release (empowered together): A realist synthesis approach.

Many people are living in prison with a range of social care needs, for example, requiring support with washing, eating, getting around safely, and/or maintaining relationships. However, social care for this vulnerable group is generally inadequate. There is uncertainty and confusion about who is legally responsible for this and how it can best be provided, and a lack of integration with healthcare. We used realist-informed approaches to develop an initial programme theory (IPT) for identifying/assessing social care needs of, and providing care to, male adults in prison and on release. IPT development was an iterative process involving (a) an initial scoping of the international prison literature; (b) scoping prison and community social care policy documents and guidelines; (c) full systematic search of the international prison social care literature; (d) insights from the community social care literature; (e) stakeholder workshops. Information from 189 documents/sources and stakeholder feedback informed the IPT, which recommended that models of prison social care should be: trauma-informed; well integrated with health, criminal justice, third-sector services and families; and person-centred involving service-users in all aspects including co-production of care plans, goals, and staff training/awareness programmes. Our IPT provides an initial gold standard model for social care provision for people in prison and on release. The model, named Empowered Together, will be evaluated in a future trial and will be of interest to those working in the criminal justice system, care providers and commissioners, local authorities, housing authorities, voluntary groups, and service-users and their families.

Physical health complications in children and young people with avoidant restrictive food intake disorder (ARFID): a systematic review and meta-analysis.

BACKGROUND: Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder with known acute and longstanding physical health complications in children and young people (CYP) and commonly presents to paediatricians. OBJECTIVE: To systematically review the published literature on physical health complications in CYP with ARFID using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: A systematic search of PubMed, Embase, Web of Science, PsycINFO and Cochrane Library was performed on 14 February 2024. Studies reporting physical health complications in CYP ≤25 years with ARFID were included. We pooled studies for meta-analysis comparing ARFID with healthy controls or anorexia nervosa (AN). RESULTS: Of 9058 studies found in searches, we included 132 studies. We found evidence for low weight, nutritional deficiencies and low bone mineral density. CYP with ARFID can present across the weight spectrum; however, the majority of CYP with ARFID were within the healthy weight to underweight range. Most studies reported normal range heart rates and blood pressures in ARFID, but some CYP with ARFID do experience bradycardia and hypotension. CYP with ARFID had higher heart rates than AN (weighted mean difference: 12.93 bpm; 95% CI: 8.65 to 17.21; n=685); heterogeneity was high (I2: 81.33%). CONCLUSION: There is a broad range of physical health complications associated with ARFID requiring clinical consideration. Many CYP with ARFID are not underweight yet still have complications. Less cardiovascular complications found in ARFID compared with AN may be related to chronicity. PROSPERO REGISTRATION NUMBER: CRD42022376866.

Comparing MRI and arthroscopic appearances of common knee pathologies: A pictorial review.

Knee pathology, including anterior cruciate ligament (ACL) tears, meniscal tears, articular cartilage lesions, and intra-articular masses or cysts are common clinical entities treated by orthopedic surgeons with arthroscopic surgery. Preoperatively, magnetic resonance imaging (MRI) is now standard in confirming knee pathology, particularly detecting pathology less evident with history and physical examination alone. The radiologist's MRI interpretation becomes essential in evaluating intra-articular knee structures. Typically, the radiologist that interprets the MRI does not have the opportunity to view the same pathology arthroscopically. Thus, the purpose of this article is to illustratively reconcile what the orthopedic surgeon sees arthroscopically with what the radiologist sees on magnetic resonance imaging when viewing the same pathology. Correlating virtual and actual images can help better understand pathology, resulting in more accurate MRI interpretations. In this article, we present and review a series of MR and correlating arthroscopic images of ACL tears, meniscal tears, chondral lesions, and intra-articular masses and cysts. Short teaching points are included to highlight the importance of radiological signs and pathological MRI appearance with significant clinical and arthroscopic findings.

Abundant hydrocarbons in the disk around a very-low-mass star.

Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI 147, a 0.11-solar-mass star. The inner disk has a carbon-rich chemistry; we identified emission from 13 carbon-bearing molecules, including ethane and benzene. The high column densities of hydrocarbons indicate that the observations probe deep into the disk. The high carbon-to-oxygen ratio indicates radial transport of material within the disk, which we predict would affect the bulk composition of any planets forming in the disk.

Analysis of Financial Barriers Experienced by Prospective Genetic Counseling Students.

PURPOSE: High costs of applying to genetic counseling graduate programs (GCGPs) are likely a barrier to workforce diversification. We sought to determine application costs and assess differences between individuals of historically underrepresented racial and ethnic backgrounds in medicine (hURM) and non-hURM applicants. METHODS: Applicants to GCGPs between 2005-2020 were surveyed about application history, related expenses, volunteer hours, and financial resources; 383 responses were analyzed. RESULTS: Median total application costs (MTAC) were $2,634, $4,762, and $5,607 (one, two, and three or more application cycles, respectively). Interview-related items (which includes travel) had the highest median cost (one application cycle: $879). Among those who applied to multiple cycles, hURM respondents had higher MTAC than those of non-hURM ($6,713 versus $4,762, p=0.03) and lower median total volunteer hours (246 versus 381, p=0.03). Parental education level differed by hURM status (p=0.04). Median financial contribution from parents with and without advanced degrees varied significantly (60% vs 2%, p=0.0009). CONCLUSION: Significant costs are incurred during the GCGP application process, but notable differences in costs and resources were observed between hURM and non-hURM applicants. Stakeholders within the profession should implement strategies to reduce financial barriers and the resulting inequities in the application process.

MiR-214-3p Regulates Piezo1, Lysyl Oxidases and Mitochondrial Function in Human Cardiac Fibroblasts.

Cardiac fibroblasts are pivotal regulators of cardiac homeostasis and are essential in the repair of the heart after myocardial infarction (MI), but their function can also become dysregulated, leading to adverse cardiac remodelling involving both fibrosis and hypertrophy. MicroRNAs (miRNAs) are noncoding RNAs that target mRNAs to prevent their translation, with specific miRNAs showing differential expression and regulation in cardiovascular disease. Here, we show that miR-214-3p is enriched in the fibroblast fraction of the murine heart, and its levels are increased with cardiac remodelling associated with heart failure, or in the acute phase after experimental MI. Tandem mass tagging proteomics and in-silico network analyses were used to explore protein targets regulated by miR-214-3p in cultured human cardiac fibroblasts from multiple donors. Overexpression of miR-214-3p by miRNA mimics resulted in decreased expression and activity of the Piezo1 mechanosensitive cation channel, increased expression of the entire lysyl oxidase (LOX) family of collagen cross-linking enzymes, and decreased expression of an array of mitochondrial proteins, including mitofusin-2 (MFN2), resulting in mitochondrial dysfunction, as measured by citrate synthase and Seahorse mitochondrial respiration assays. Collectively, our data suggest that miR-214-3p is an important regulator of cardiac fibroblast phenotypes and functions key to cardiac remodelling, and that this miRNA represents a potential therapeutic target in cardiovascular disease.

Weight Nadir and Long-Term Weight Outcomes After Laparoscopic Sleeve Gastrectomy in a Diverse Cohort of Adolescents and Young Adults.

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is currently the most common bariatric procedure performed in adolescents and young adults in the United States (USA), but there are limited data available on long-term postoperative weight outcomes in these patients. This single-institution US study follows longitudinal weight data in a diverse group of patients undergoing LSG at age 25 years or younger. METHODS: We retrospectively reviewed records of all patients 25 years or younger who underwent LSG at our institution between 2013 and 2020. All weight data documented in the medical record through January 2023 was included. We calculated weight change postoperatively as percent total weight loss (%TWL) relative to preoperative weight. RESULTS: One hundred forty-one patients underwent LSG, at a mean age of 23.1 years. Within this cohort, 56.1% identified as non-Hispanic Black or Hispanic, and 39.7% had private health insurance. The mean %TWL at weight nadir was 28.5% at a mean of 1.35 years postoperatively. The mean long-term %TWL (in patients with ≥ 4 years of follow-up) was 11.8% at a mean of 5.6 years postoperatively, with 43 of the 84 patients with long-term weight data (51%) within 10% of their preoperative weight at most recent follow-up. CONCLUSION: Adolescents and young adults undergoing LSG at our institution had weight nadir comparable to published results during the first 1 to 2 years postoperatively, but the majority developed significant weight recurrence over the ensuing years. Our findings highlight the need for adjuvant weight loss strategies to improve the durability of weight outcomes after LSG in this population.

Modeling transthyretin (TTR) amyloid diseases, from monomer to amyloid fibrils.

ATTR amyloidosis is caused by deposition of large, insoluble aggregates (amyloid fibrils) of cross-ß-sheet TTR protein molecules on the intercellular surfaces of tissues. The process of amyloid formation from monomeric TTR protein molecules to amyloid deposits has not been fully characterized and is therefore modeled in this paper. Two models are considered: 1) TTR monomers in the blood spontaneously fold into a ß-sheet conformation, aggregate into short proto-fibrils that then circulate in the blood until they find a complementary tissue where the proto-fibrils accumulate to form the large, insoluble amyloid fibrils found in affected tissues. 2) TTR monomers in the native or ß-sheet conformation circulate in the blood until they find a tissue binding site and deposit in the tissue or tissues forming amyloid deposits in situ. These models only differ on where the selection for ß-sheet complementarity occurs, in the blood where wt-wt, wt-v, and v-v interactions determine selectivity, or on the tissue surface where tissue-wt and tissure-v interactions also determine selectivity. Statistical modeling in both cases thus involves selectivity in fibril aggregation and tissue binding. Because binding of protein molecules into fibrils and binding of fibrils to tissues occurs through multiple weak non-covalent bonds, strong complementarity between ß-sheet molecules and between fibrils and tissues is required to explain the insolubility and tissue selectivity of ATTR amyloidosis. Observation of differing tissue selectivity and thence disease phenotypes from either pure wildtype TTR protein or a mix of wildtype and variant molecules in amyloid fibrils evidences the requirement for fibril-tissue complementarity. Understanding the process that forms fibrils and binds fibrils to tissues may lead to new possibilities for interrupting the process and preventing or curing ATTR amyloidosis.

Use of Patient-Reported Outcome Measures to Assess the Effectiveness of Hybrid Psychiatric Visits.

OBJECTIVE: Little empirical evidence exists to support the effectiveness of hybrid psychiatric care, defined as care delivered through a combination of telephone, videoconferencing, and in-person visits. The authors aimed to investigate the effectiveness of hybrid psychiatric care compared with outpatient waitlist groups, assessed with patient-reported outcome measures (PROMs). METHOD: Participants were recruited from an adult psychiatry clinic waitlist on which the most common primary diagnoses were unipolar depression, generalized anxiety disorder, and bipolar disorder. Patients (N=148) were randomly assigned to one of two waitlist groups that completed PROMs once or monthly before treatment initiation. PROMs were used to assess symptoms of depression (Patient Health Questionnaire-9 [PHQ-9]), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), and daily psychological functioning (Brief Adjustment Scale-6 [BASE-6]). Patient measures were summarized descriptively with means, medians, and SDs and then compared by using the Kruskal-Wallis test; associated effect sizes were calculated. PROM scores for patients who received hybrid psychiatric treatment during a different period (N=272) were compared with scores of the waitlist groups. RESULTS: PROM assessments of patients who engaged in hybrid care indicated significant improvements in symptom severity compared with the waitlist groups, regardless of the number of PROMs completed while patients were on the waitlist. Between the hybrid care and waitlist groups, the effect size for the PHQ-9 score was moderate (d=0.66); effect sizes were small for the GAD-7 (d=0.46) and BASE-6 (d=0.45) scores. CONCLUSIONS: The findings indicate the clinical effectiveness of hybrid care and that PROMs can be used to assess this effectiveness.

Combined Germline and Mosaic SDHA Mutation Is Associated With a Multicancer Syndrome Including Neuroblastoma, Renal Cancer, and Multifocal GI Tumor.

Highlighting here a patient case with neuroblastoma, renal cancer & GIST from germline SDHA.

Conceptus Estrogen and prostaglandins provide the maternal recognition of pregnancy signal to prevent Luteolysis during early pregnancy in the pig†.

Conceptus estrogens and prostaglandins have long been considered the primary signals for maternal recognition of pregnancy (MRP) in the pig. However, loss-of-function studies targeting conceptus aromatase genes (CYP19A1 and CYP19A2) and prostaglandin-endoperoxide synthase 2 (PTGS2) indicated that conceptuses can not only signal MRP without estrogens or prostaglandins but can maintain early pregnancy. However, complete loss of estrogen production leads to abortion after day 25 of gestation. Although neither conceptus estrogens nor prostaglandins had a significant effect on early maintenance of CL function alone, the two conceptus factors have a biological relationship. To investigate the role that both conceptus estrogens and prostaglandins have on MRP and maintenance of pregnancy, a triple loss-of function model (TKO) was generated for conceptus CYP19A1, CYP19A2 and PTGS2. In addition, a conceptus CYP19A2-/- model (A2KO) was established to determine the role of placental estrogen during later pregnancy. Estrogen and prostaglandin synthesis were greatly reduced in TKO conceptuses which resulted in a failure to inhibit luteolysis after day 15 of pregnancy despite the presence of conceptuses in the uterine lumen. However, A2KO placentae not only maintained functional CL but were able to maintain pregnancy to day 32 of gestation. Despite the loss of placental CYP19A2 expression, the allantois fluid content of estrogen was not affected as the placenta compensated by expressing CYP19A1 and CYP19A3, which are normally absent in controls. Results suggest conceptuses can signal MRP through production of conceptus PGE or stimulating PGE synthesis from the endometrium through conceptus estrogen. Failure of conceptuses to produce both factors results in failure of MRP and loss of pregnancy.

Video analysis of anterior cruciate ligament tears of professional basketball players in the National Basketball Association.

BACKGROUND: Anterior cruciate ligament (ACL) tears are devastating for elite athletes, including those in the National Basketball Association (NBA). The purpose of this study was to describe common in-game mechanisms of injury, playing situations, and anatomic positioning of players who sustained an ACL injury in the NBA. METHODS: ACL tears which occurred in NBA games during the previous 16 seasons (2007-2022) and had accessible video clips were identified through publicly available reports. RESULTS: Thirty-one ACL tears were identified with quality videos available. Nearly all players were on offense (93.5%, 29/31). Most ACL tears (29/31, 93.5%) did not involve direct contact to the injured extremity. The most common physical activity at the time of injury was landing from any type of jump (45.2%, 14/31). Anatomically, the knee was frequently in early flexion (58.8%, 10/17) and abducted (77.4%, 24/31); the foot was commonly abducted (87.1%, 27/31); and the hip was usually abducted (64.5%, 20/31) and flexed (80.6%, 25/31). Almost all players had another individual near them at the time of injury, with 90.3% (28/31) and 96.8% (30/31) having someone within 2ft and 5ft. CONCLUSIONS: Most ACL tears occurred inside the lane, regardless of mechanism of injury (26/31, 83.9%). ACL tears in the NBA were primarily not due to direct contact of the injured extremity but did have common anatomic patterns. The findings of this study can be used in the future to help reduce the risk of injury through the adaptation of current training activities.

Comparison of in-shoe plantar pressure between Korean combat boots and running shoes.

INTRODUCTION: Combat boots are special shoes designed for soldiers to wear during activities in rough terrain, such as long marches or military training. Combat boots have been known to cause high plantar pressure and increase the injury rate of the lower extremities. Therefore, this study aimed to compare the difference in in-shoe plantar pressure between Korean combat boots and running shoes. We hypothesised that the newest Korean combat boots would have comparable plantar pressure distribution with running shoes. METHODS: We prospectively recruited 30 asymptomatic male participants, who are candidates for military services, from the local area. Two types of shoes (the newly developed Korean combat boots and running shoes) were examined. Pedobarographic measurements were collected using the pedar-X in-shoe pressure measurement system. Peak pressure (PP), pressure time integral (PTI), contact area and contact time were analysed. RESULTS: Both PP and PTI at the region of central and lateral forefeet (FF) were significantly higher in combat boots. The contact area of combat boots was significantly lower at the region of the hallux, second-fifth toes, medial FF, central FF and midfoot. Contact time at the region of central FF and medial heel was significantly higher in combat boots. CONCLUSIONS: Understanding the plantar pressure distribution of combat boots can be helpful for developing combat boots and preventing injury. Based on the results of our study, the next-generation Korean combat boots should be developed to increase contact area and distribute impulse under the head of the metatarsal bone.

Evaluation of non-additive genetic effects on carcass and meat quality traits in Korean Hanwoo cattle using genomic models.

The traditional genetic evaluation methods generally consider additive genetic effects only and often ignore non-additive (dominance and epistasis) effects that may have contributed to genetic variation of complex traits of livestock species. The available dense single nucleotide polymorphisms (SNPs) panels offer to investigate the potential benefits of including non-additive genetic effects in the genomic evaluation models. Data from 16 971 genotyped (Illumina Bovine 50 K SNP chip) Korean Hanwoo cattle were used to estimate genetic variance components and prediction accuracy of genomic breeding values (GEBVs) for four carcass and meat quality traits: carcass weight (CWT), eye muscle area (EMA), back fat thickness (BFT) and marbling score (MS). Five different genetic models were evaluated through including additive, dominance and epistatic interactions (additive by additive, A × A; additive by dominance, A × D and dominance by dominance, D × D) successively in the models. The estimates of additive genetic variances and narrow sense heritabilities (ha2) were found similar across the evaluated models and traits except when additive interaction (A × A) was included. The dominance variance estimates relative to phenotypic variance ranged from 1.7-3.4% for CWT and MS traits, whereas, they were close to zero for EMA and BFT traits. The magnitude of A × A epistatic heritability (haa2) ranged between 14.8 and 27.7% in all traits. However, heritability estimates for A × D and D × D epistatic interactions (had2 and hdd2) were quite low compared to haa2 and were contributed only 0.0-9.7% of the total phenotypic variation. In general, broad sense heritability (hG2) estimates were almost twice (ranging between 0.54 and 0.68) the ha2 for all of the investigated traits. The inclusion of dominance effects did not improve the prediction accuracy of GEBV but improved 2.0-3.0% when epistatic effects were included in the model. More importantly, rank correlation revealed that partitioning of variance components considering dominance and epistatic effects in the model would enable to re-rank of top animals with better prediction of GEBV. The present result suggests that dominance and epistatic effects could be included in the genomic evaluation model for better estimates of variance components and more accurate prediction of GEBV for carcass and meat quality traits in Korean Hanwoo cattle.

Comparative toxicological assessment of 2 bisphenols using a systems approach: evaluation of the behavioral and transcriptomic responses of Danio rerio to bisphenol A and tetrabromobisphenol A.

The zebrafish (Danio rerio) is becoming a critical component of new approach methods (NAMs) in chemical risk assessment. As a whole organism in vitro NAM, the zebrafish model offers significant advantages over individual cell-line testing, including toxicokinetic and toxicodynamic competencies. A transcriptomic approach not only allows for insight into mechanism of action for both apical endpoints and unobservable adverse outcomes, but also changes in gene expression induced by lower, environmentally relevant concentrations. In this study, we used a larval zebrafish model to assess the behavioral and transcriptomic alterations caused by subphenotypic concentrations of 2 chemicals with the same structural backbone, the endocrine-disrupting chemicals bisphenol A and tetrabromobisphenol A. Following assessment of behavioral toxicity, we used a transcriptomic approach to identify molecular pathways associated with previously described phenotypes. We also determined the transcriptomic point of departure for each chemical by modeling gene expression changes as continuous systems which allows for the identification of a single concentration at which toxic effects can be predicted. This can then be investigated with confirmatory cell-based testing in an integrated approach to testing and assessment to determine risk to human health and the environment with greater confidence. This paper demonstrates the impact of using a multi-faceted approach for evaluating the physiological and neurotoxic effects of exposure to structurally related chemicals. By comparing phenotypic effects with transcriptomic outcomes, we were able to differentiate, characterize, and rank the toxicities of related bisphenols, which demonstrates methodological advantages unique to the larval zebrafish NAM.