Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

BACKGROUND: Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. METHODS: We evaluated obesity and longitudinal growth among children (1-18 years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥ + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. RESULTS: We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. CONCLUSIONS: Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.

Investigating the anti-bioadhesion properties of short, medium chain length, and amphiphilic polyhydroxyalkanoate films.

Silicone materials are widely used in fouling release coatings, but developing eco-friendly protection via biosourced coatings, such as polyhydroxyalcanoates (PHA) presents a major challenge. Anti-bioadhesion properties of medium chain length PHA and short chain length PHA films are studied and compared with a reference Polydimethylsiloxane coating. The results highlight the best capability of the soft and low-roughness PHA-mcl films to resist bacteria or diatoms adsorption as compared to neat PDMS and PHBHV coatings. These parameters are insufficient to explain all the results and other properties related to PHA crystallinity are discussed. Moreover, the addition of a low amount of PEG copolymers within the coatings, to create amphiphilic coatings, boosts their anti-adhesive properties. This work reveals the importance of the physical or chemical ambiguity of surfaces in their anti-adhesive effectiveness and highlights the potential of PHA-mcl film to resist the primary adhesion of microorganisms.

Straightforward Way to Provide Antibacterial Properties to Healthcare Textiles through N-2-Hydroxypropyltrimethylammonium Chloride Chitosan Crosslinking.

A straightforward and cost-effective way to coat polypropylene fibers, designed for healthcare textiles, was developed through chitosan crosslinking for antibacterial purposes. As polypropylene is an inert material, the goal was to physically trap the inert fibers through a network of crosslinked chitosan or a quaternized derivative (to enhance the antibacterial action). First, chitosan or its quaternized derivative was physically deposited by impregnation or spraying. Then, chitosan was crosslinked in glutaraldehyde solution followed by its quaternized derivative with a diisocyanate. Coated fabrics were characterized by infrared spectroscopy (IR), weight gain measurements, and scanning electron microscopy (SEM) coupled with energy dispersive X-ray (EDX). This led us to conclude that spraying provides uniform deposition while maintaining the fabric's porosity. Acidic washing allowed us to prove that chitosan and its quaternized derivative were successfully immobilized on the fabric. Biological assays were conducted against two major strains of bacteria responsible for nosocomial infections: Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative). Chitosan-crosslinked samples did not show significant antibacterial activity, but the quaternized derivative allowed a significant decrease in S. aureus colonization. This study presents a simple and scalable process to coat inert fabrics with a polymer containing reactive functions potentially available to graft various additional antimicrobial agents.

Green Physical Modification of Polypropylene Fabrics by Cross-Linking Chitosan with Tannic Acid and Postmodification by Quaternary Ammonium Grafting to Improve Antibacterial Activity.

A green cross-linking and straightforward method to physically trap inert fibers in a network of chitosan was implemented. The cross-linking reaction involved a biosourced and biocompatible cross-linker [tannic acid (TA)] and mild conditions in water (pH = 8.5, O2 bubbling, 60 °C, 3 h). The steric hindrance of TA led to a low but effective cross-linking rate leaving parts of primary amines of chitosan available for postmodification such as the grafting of quaternary ammoniums for antibacterial purposes. Fabric's coatings were characterized by scanning electron microscopy coupled with energy-dispersive X-ray, infrared spectroscopy, and weight gain measurements. This allowed the optimization of process conditions. No significant antioxidant activity was observed on fabrics coated with chitosan cross-linked with TA, confirming the low cross-linking rate. This low cross-linking rate allowed grafting of quaternary ammoniums for antibacterial purposes, but it is possible to consider grafting other active molecules. Biological assays were conducted on this coating to assess its antibacterial properties. Reduction of bacterial colonization on both Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative), two of the major strains responsible for nosocomial infections, confirmed the potential of the coating for antibacterial purposes. This study displays a simple and ecofriendly process to coat inert fabrics with a chitosan network containing reactive functions (primary amines) available for grafting active molecules for various purposes.

The State of Cognitive Control in Language Processing.

Understanding language requires readers and listeners to cull meaning from fast-unfolding messages that often contain conflicting cues pointing to incompatible ways of interpreting the input (e.g., "The cat was chased by the mouse"). This article reviews mounting evidence from multiple methods demonstrating that cognitive control plays an essential role in resolving conflict during language comprehension. How does cognitive control accomplish this task? Psycholinguistic proposals have conspicuously failed to address this question. We introduce an account in which cognitive control aids language processing when cues conflict by sending top-down biasing signals that strengthen the interpretation supported by the most reliable evidence available. We also provide a computationally plausible model that solves the critical problem of how cognitive control "knows" which way to direct its biasing signal by allowing linguistic knowledge itself to issue crucial guidance. Such a mental architecture can explain a range of experimental findings, including how moment-to-moment shifts in cognitive-control state-its level of activity within a person-directly impact how quickly and successfully language comprehension is achieved.

Thyroid axis participates in high-temperature-induced male sex reversal through its activation by the stress response.

Environmental changes alter the sex fate in about 15% of vertebrate orders, mainly in ectotherms such as fish and reptiles. However, the effects of temperature changes on the endocrine and molecular processes controlling gonadal sex determination are not fully understood. Here, we provide evidence that thyroid hormones (THs) act as co-players in heat-induced masculinization through interactions with the stress axis to promote testicular development. We first demonstrated that the thyroid axis (through thyroid-related genes and T3 levels) is highly active in males during the gonadal development in medaka (Oryzias latipes). Similarly, T3 treatments promoted female-to-male sex reversal in XX embryos. Subsequently, embryonic exposure to temperature-induced stress up-regulated the genes related to the thyroid and stress axes with a final increase in T3 levels. In this context, we show that blocking the stress axis response by the loss of function of the corticotropin-releasing hormone receptors suppresses thyroid-stimulating hormone expression, therefore, heat-induced activation of the thyroid axis. Thus, our data showed that early activation of the stress axis and, in consequence, the TH axis, too, leaves us with that both being important endocrine players in inducing female-to-male reversal, which can help predict possible upcoming physiological impacts of global warming on fish populations.

Meeting report: The first soil viral workshop 2022.

Soil viral ecology is a growing research field; however, the state of knowledge still lags behind that of aquatic systems. Therefore, to facilitate progress, the first Soil Viral Workshop was held to encourage international scientific discussion and collaboration, suggest guidelines for future research, and establish soil viral research as a concrete research area. The workshop took place at Søminestationen, Denmark, between 15 and 17th of June 2022. The meeting was primarily held in person, but the sessions were also streamed online. The workshop was attended by 23 researchers from ten different countries and from a wide range of subfields and career stages. Eleven talks were presented, followed by discussions revolving around three major topics: viral genomics, virus-host interactions, and viruses in the soil food web. The main take-home messages and suggestions from the discussions are summarized in this report.

Hydrogel Based on Polyhydroxyalkanoate Sulfonate: Control of the Swelling Rate by the Ionic Group Content.

Hydrogels based on poly(3-hydroxyalkanoate) (PHA) sulfonate and poly(ethylene glycol) diacrylate, PEGDA, are prepared. First, PHA sulfonate is synthesized from unsaturated PHA by a thiol-ene reaction in the presence of sodium-3-mercapto-1-ethanesulfonate. The hydrophilicity of PHAs is considerably increased by adding sulfonate functions, and three amphiphilic PHAs are synthesized, containing 10, 22, or 29% sulfonate functions. Then, hydrogels are formed in the presence of PEGDA having different molar masses, that is, 575 or 2000 g mol-1. The hydrogels show fibrillar and porous structures observed in cryo-MEB with pore sizes that vary according to the content of sulfonated groups (10 to 29 mol %) ranging from 50 to more than 150 nm. Furthermore, depending on the proportions of the two polymers, a variable rigidity is observed from 2 to 40 Pa. In fact, the evaluation of the dynamic mechanical properties of the hydrogel determined by DMA reveals that the less rigid hydrogels hinder the adhesion of Pseudomonas aeruginosa PaO1 bacteria. Finally, these hydrogels swelling up to 5000% are noncytotoxic, allowing the adhesion and amplification of immortalized C2C12 cells, and they are therefore seen as promising materials both for repelling PaO1 bacteria and for amplifying myogenic cells.

A Tale of Two Seasons: Distinct Seasonal Viral Communities in a Thermokarst Lake.

Thermokarst lakes are important features of subarctic landscapes and are a substantial source of greenhouse gases, although the extent of gas produced varies seasonally. Microbial communities are responsible for the production of methane and CO2 but the "top down" forces that influence microbial dynamics (i.e., grazers and viruses) and how they vary temporally within these lakes are still poorly understood. The aim of this study was to examine viral diversity over time to elucidate the seasonal structure of the viral communities in thermokarst lakes. We produced virus-enriched metagenomes from a subarctic peatland thermokarst lake in the summer and winter over three years. The vast majority of vOTUs assigned to viral families belonged to Caudovirales (Caudoviricetes), notably the morphological groups myovirus, siphovirus and podovirus. We identified two distinct communities: a dynamic, seasonal community in the oxygenated surface layer during the summer and a stable community found in the anoxic water layer at the bottom of the lake in summer and throughout much of the water column in winter. Comparison with other permafrost and northern lake metagenomes highlighted the distinct composition of viral communities in this permafrost thaw lake ecosystem.

Isotopic and microbial evidence for biodegradation of diluted bitumen in the unsaturated zone.

The oil sands region in Western Canada is one of the world's largest proven oil reserves. To facilitate pipeline transport, highly viscous oil sands bitumen is blended with lighter hydrocarbon fractions to produce diluted bitumen (dilbit). Anticipated increases in dilbit production and transport raise the risk of inland spills. To understand the behaviour of dilbit in the unsaturated or vadose zone following a surface spill, we ran parallel dilbit and conventional heavy crude exposures, along with an untreated control, using large soil-filled columns over 104 days. Phospholipid fatty acids (PLFAs), biomarkers for the active microbial population, were extracted from column soil cores. Stable carbon isotope contents (δ13C) of individual PLFAs and radiocarbon contents (Δ14C) of bulk PLFAs were characterized over the course of the experiment. The Δ14CPLFA values in soils impacted by dilbit (-221.1 to -54.7‰) and conventional heavy crude (-259.4 to -97.9‰) indicated similar levels of microbial uptake of fossil carbon. In contrast, Δ14CPLFA values in the control column (-46.1 to +53.7‰) reflected assimilation of more recently fixed organic carbon. Sequencing of 16S ribosomal RNA genes extracted from soil cores revealed a significant increase in the relative abundance of Polaromonas, a known hydrocarbon-degrader, following exposure to both types of oil. This study demonstrates that in the first several months following a surface spill, dilbit has a similar potential for biodegradation by a native shallow subsurface microbial community as conventional heavy crude oil.

Early developmental toxicity of Atlantic salmon exposed to conventional and unconventional oils.

Atlantic salmon is an important species for Canadian culture and economy and its importance extends beyond Canada to Scandinavia and Western Europe. However, it is a vulnerable species facing decline due to habitat contamination and destruction. Existing and new Canadian pipeline projects pose a threat to salmonid habitat. The effects of diluted bitumen (dilbit), the main oil circulating in pipelines, are less studied than those of conventional oils, especially during the critical early embryonic developmental stage occurring in freshwater ecosystems. Therefore, this study aimed to compare the effects of water-accommodated fractions (WAF) of the Clearwater McMurray dilbit and the Lloydminster Heavy conventional oil on Atlantic salmon embryos exposed either from fertilization or from eyed stage. The dilbit contained the highest concentrations of low molecular weight (LMW) compounds (including BTEX and C6-C10), while the conventional oil contained the highest concentrations of PAHs. The Clearwater dilbit caused a higher percentage of mortality and malformations than the conventional oil at similar WAF concentrations. In addition, the embryos exposed from fertilization suffered a higher mortality rate, more developmental delays, and malformations than embryos exposed from the eyed stage, suggesting that early development is the most sensitive developmental stage to oil exposure. Gene expression and enzymatic activity of the detoxification phase I and II enzymes (CYP1A and GST) were measured. Data showed increases in both cyp1a expression and GST activity with increasing WAF concentrations, while gst expression was not affected by the exposures. Also, gene expression of proteins involved in the biotransformation of vitamin A and DNA damage repair were modified by the oil exposures. Overall, this study indicates that Atlantic salmon is mostly affected by oil exposure at the beginning of its development, during which embryos accumulate deformities that may impact their survival at later life stages.

Biocompatible Semi-Interpenetrating Materials Based on Poly(3-hydroxyalkanoate)s and Poly(ethyleneglycol) Diacrylate.

Biocompatible gels based on poly(3-hydroxyalkanoate)s (PHAs) were developed by radical polymerization in the presence of poly(ethylene glycol) diacrylate (PEGDA). In order to elaborate cross-linked networks based on PEGDA and PHAs, several PHAs were tested; saturated PHAs, such as poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) or poly(3-hydroxyoctanoate) (PHO), and an unsaturated PHA, poly(3-hydroxyoctanoate-co-3-hydroxyundecenoate) PHOU. The PHAxPEGDA1-x networks obtained in this work were studied by FTIR, Raman spectroscopy, DSC, TGA and NMR. The microscopic structure varied according to the mass proportions between the two polymers. Time Domain 1H DQ NMR measurements demonstrated that in the case of the unsaturated PHA, it was chemically crosslinked with PEGDA, due to the presence of double bonds in the lateral groups. The organogels were able to swell in organic solvents, such as THF, up to 2000% and in water up to 86%. It was observed by rheological analysis that the stiffness of the networks was dependent on the content of PHA and on the degree of cross-linking. The biocompatible characters of PHOU and PEGDA were not affected by the formation of the networks and these networks had the advantage of being non-cytotoxic to immortalized C2C12 myoblast cells.

Phenology of the transcriptome coincides with the physiology of double-crested cormorant embryonic development.

The rigorous timing of the dynamic transcriptome within the embryo has to be well orchestrated for normal development. Identifying the phenology of the transcriptome along with the physiology of embryonic development in birds may suggest periods of increased sensitivity to contaminant exposure depending on the contaminant's mechanism of action. Double-crested cormorants (Nannopterum auritum, formerly Phalacrocorax auritus) are commonly used in ecotoxicological studies, but relatively little is known about their functional transcriptome profile in early development. In this study, we tracked the phenology of the transcriptome during N. auritum embryogenesis. Fresh eggs were collected from a reference site and artificially incubated from collection until four days prior to hatching. Embryos were periodically sampled throughout incubation for a total of seven time points. A custom microarray was designed for cormorants (over 14,000 probes) and used for transcriptome analysis in whole body (days 5, 8) and liver tissue (days 12, 14, 16, 20, 24). Three main developmental periods (early, mid, and late incubation) were identified with differentially expressed genes, gene sets, and pathways within and between each developmental transition. Overall, the timing of differentially expressed genes and enriched pathways corresponded to previously documented changes in morphology, neurology, or physiology during avian embryonic development. Targeted investigation of a subset of genes involved in endogenous and xenobiotic metabolism (e.g., cytochrome P450 cyp1a, cyp1b1, superoxide dismutase 1 sod1) were expressed in a pattern similar to reported endogenous compound levels. These data can provide insights on normal embryonic development in an ecologically relevant species without any environmental contaminant exposure.

Longitudinal Changes in Cardiac Structure and Function in Pediatric Kidney Transplant Recipients.

BACKGROUND: Cardiovascular disease results in increased morbidity and mortality in pediatric kidney transplant recipients. Longitudinal changes in cardiac structure and function and the association with blood pressure control over time in pediatric kidney transplant recipients are unknown. METHODS: To determine the influence of blood pressure control on cardiac changes following pediatric kidney transplant, we conducted a retrospective cohort study of children who received their first kidney transplant at the Hospital for Sick Children from 2004 to 2015. Children were followed until transfer to adult care or censoring in July 2018. Cardiac structure and function parameters were collected from clinical echocardiograms and assessed using standardized scores. Blood pressure control was determined by systolic blood pressure Z scores (above or below the 90th percentile) in combination with antihypertensive medications. A segmented mixed-effects model assessed Z scores of interventricular septum thickness, left ventricular end-diastolic dimension, and left ventricular posterior wall dimension. RESULTS: Of 142 children included, 58% were men, mean age at transplant was 11 (±4.5) years, and average follow-up time was 4 (±3) years. All cardiac structural Z scores improved during follow-up. Interventricular septum thickness normalized at 4.0 years post-transplant. Left ventricular end-diastolic dimension normalized at 1.5 years post-transplant. Left ventricular posterior wall dimension normalized at 6.3 years post-transplant. Left ventricular mass index showed sustained improvement up to 12 years post-transplant. Individuals with uncontrolled blood pressure had increased left ventricular mass (ß=2.97 [95% CI, 0.77-5.16]). CONCLUSIONS: Cardiac structural abnormalities improve following kidney transplantation and normalize within 7 years, especially with controlled blood pressure. Strict blood pressure control is critical after pediatric kidney transplantation.

Improved Processability and Antioxidant Behavior of Poly(3-hydroxybutyrate) in Presence of Ferulic Acid-Based Additives.

Poly(3-hydroxybutyrate), PHB, has gathered a lot of attention for its promising properties-in particular its biobased nature and high biodegradability. Although PHB is prime candidate for the packaging industry, the applications are still limited by a narrow processing window and thermal degradation during melt processing. In this work, three novel additives based on ferulic acid esterified with butanediol, pentanediol, and glycerol (BDF, PDF, and GTF, respectively) were used as plasticizers and antioxidative additives to improve mechanical properties of PHB. Elongation at break up to 270% was obtained in presence of BDF and the processing window was improved nearly 10-fold. The Pawley method was used to identify the monoclinic space group P2 of the BDF. The estimated crystallite size (71 nm) agrees with a crystalline additive. With PHB70BDF30 blends, even higher elongations at break were obtained though dwindled with time. However, these properties could be recovered after thermal treatment. The high thermal stability of this additive leads to an increase in the fire retardancy property of the material, and the phenolic structure induced antioxidant properties to the samples as demonstrated by radical scavenging tests, further highlighting the possibilities of the PHB/additive blends for packaging applications.

Resilience of larval wood frogs (Rana sylvatica) to hydrocarbons and other compounds released from naturally weathered diluted bitumen in a boreal lake.

The risks to aquatic wildlife from spills of diluted bitumen (dilbit) into inland waters are poorly understood. In this paper, we describe the response of larval wood frogs (Rana sylvatica) to hydrocarbons and other compounds released from experimental spills of dilbit in a temperate boreal lake. To simulate a wide range of environmentally relevant oil spill scenarios, different volumes of Cold Lake Winter Blend dilbit (0, 1.5, 2.9, 5.5, 18, 42, 82, and 180 L) were added to 10 m diameter in-lake limnocorrals. Larvae (n = 360) were reared (from Gosner Stage (GS) 25 to ∼42) in land-based aquatic microcosms, where they were first exposed to clean water during a 2-week baseline phase, and then (at GS ∼30), to contaminated water withdrawn from the limnocorrals for 3 weeks. We observed no statistically significant trends in survival, growth, or development of larvae as a consequence of exposure to the chemical compounds released from naturally weathered dilbit. Likewise, neither cytochrome P450 1A biomarkers nor levels of thyroid hormones in wood frogs near metamorphic climax were significantly related to volume of the oil spills. However, there was a modest statistically significant decrease in larval activity (up to 8.7% relative to the control), but no change in other behavioral metrics (i.e., sociality or space use). Our work adds to the limited body of literature on the effects of unconventional oils on aquatic wildlife and helps to inform risk assessments regarding pipeline projects.

A comprehensive review on current technologies for removal of endocrine disrupting chemicals from wastewaters.

In the recent years, endocrine disrupting compounds (EDCs) has received increasing attention due to their significant toxic effects on human beings and wildlife by affecting their endocrine systems. As an important group of emerging pollutant, EDCs have been detected in various aquatic environments, including surface waters, groundwater, wastewater, runoff, and landfill leachates. Their removal from water resources has also been an emerging concern considering growing population as well as reducing access to fresh water resources. EDC removal from wastewaters is highly dependent on physicochemical properties of the given EDCs present in each wastewater types as well as various aquatic environments. Due to chemical, physical and physicochemical diversities in these parameters, variety of technologies consisting of physical, biological, electrochemical, and chemical processes have been developed for their removal. This review highlights that the effectiveness of EDC removal is highly dependent of selecting the appropriate technology; which decision is made upon a full wastewater chemical characterization. This review aims to provide a comprehensive perspective about all the current technologies used for EDCs removal from various aquatic matrices along with rising challenges such as the antimicrobial resistance gene transfer during EDC treatment.

Comparative toxicity of conventional and unconventional oils during rainbow trout (Oncorhynchus mykiss) embryonic development: From molecular to health consequences.

Canadian freshwater ecosystems are vulnerable to oil spills from pipelines, which contain mostly diluted bitumen. This study aimed to compare the toxicity of a dilbit and a conventional oil on developing rainbow trout. A total of five exposure scenarios were performed, from 10 to 43 days, using water-accommodated fraction (WAF) with an initial loading of 1:9 oil to water ratio (w/v) in a range of dilutions from 0.32 to 32% WAF, respectively, with TPAH and VOC concentrations from 2.41 to 17.5 µg/L and 7.94-660.99 µg/L, and with or without a recovery period. Following the five exposures, several endpoints were examined, including survivorship, morphometrics, gene expression, and enzymatic activity. Significant mortality rates were measured for the highest WAF concentration of the dilbit in all five exposures (60-100% mortality at 32% WAF). In comparison, the highest WAF concentration of the conventional oil induced significant mortality in three out of the five exposure (from 35 to 100% mortality at 32% WAF). Hatching delays were noted in embryos exposed to both oils. Developmental delays were observed in dilbit-exposed embryos and are suspected to be an indicator of reduced survivorship after hatching. The induced expression of cyp1a remained a reliable biomarker of exposure and of fish malformations, though it did not always predict mortality. Using CYP1A activity in combination with cyp1a may bring more insights in studies of oil risk assessment. This study demonstrates that dilbits are more toxic to early life stages compared to conventional oils and highlights the need to consider the most sensitive stage of development when performing risk assessment studies on oils.

Disruption by stealth - Interference of endocrine disrupting chemicals on hormonal crosstalk with thyroid axis function in humans and other animals.

Thyroid hormones (THs) are important regulators of growth, development, and homeostasis of all vertebrates. There are many environmental contaminants that are known to disrupt TH action, yet their mechanisms are only partially understood. While the effects of Endocrine Disrupting Chemicals (EDCs) are mostly studied as "hormone system silos", the present critical review highlights the complexity of EDCs interfering with TH function through their interactions with other hormonal axes involved in reproduction, stress, and energy metabolism. The impact of EDCs on components that are shared between hormone signaling pathways or intersect between pathways can thus extend beyond the molecular ramifications to cellular, physiological, behavioral, and whole-body consequences for exposed organisms. The comparatively more extensive studies conducted in mammalian models provides encouraging support for expanded investigation and highlight the paucity of data generated in other non-mammalian vertebrate classes. As greater genomics-based resources become available across vertebrate classes, better identification and delineation of EDC effects, modes of action, and identification of effective biomarkers suitable for HPT disruption is possible. EDC-derived effects are likely to cascade into a plurality of physiological effects far more complex than the few variables tested within any research studies. The field should move towards understanding a system of hormonal systems' interactions rather than maintaining hormone system silos.

Towards regulation of Endocrine Disrupting chemicals (EDCs) in water resources using bioassays - A guide to developing a testing strategy.

Endocrine disrupting chemicals (EDCs) are found in every environmental medium and are chemically diverse. Their presence in water resources can negatively impact the health of both human and wildlife. Currently, there are no mandatory screening mandates or regulations for EDC levels in complex water samples globally. Bioassays, which allow quantifying in vivo or in vitro biological effects of chemicals are used commonly to assess acute toxicity in water. The existing OECD framework to identify single-compound EDCs offers a set of bioassays that are validated for the Estrogen-, Androgen-, and Thyroid hormones, and for Steroidogenesis pathways (EATS). In this review, we discussed bioassays that could be potentially used to screen EDCs in water resources, including in vivo and in vitro bioassays using invertebrates, fish, amphibians, and/or mammalians species. Strengths and weaknesses of samples preparation for complex water samples are discussed. We also review how to calculate the Effect-Based Trigger values, which could serve as thresholds to determine if a given water sample poses a risk based on existing quality standards. This work aims to assist governments and regulatory agencies in developing a testing strategy towards regulation of EDCs in water resources worldwide. The main recommendations include 1) opting for internationally validated cell reporter in vitro bioassays to reduce animal use & cost; 2) testing for cell viability (a critical parameter) when using in vitro bioassays; and 3) evaluating the recovery of the water sample preparation method selected. This review also highlights future research avenues for the EDC screening revolution (e.g., 3D tissue culture, transgenic animals, OMICs, and Adverse Outcome Pathways (AOPs)).