Artificial intelligence improves resident detection of pediatric and young adult upper extremity fractures.

PURPOSE: We wished to evaluate if an open-source artificial intelligence (AI) algorithm ( https://www.childfx.com ) could improve performance of (1) subspecialized musculoskeletal radiologists, (2) radiology residents, and (3) pediatric residents in detecting pediatric and young adult upper extremity fractures. MATERIALS AND METHODS: A set of evaluation radiographs drawn from throughout the upper extremity (elbow, hand/finger, humerus/shoulder/clavicle, wrist/forearm, and clavicle) from 240 unique patients at a single hospital was constructed (mean age 11.3 years, range 0-22 years, 37.9% female). Two fellowship-trained musculoskeletal radiologists, three radiology residents, and two pediatric residents were recruited as readers. Each reader interpreted each case initially without and then subsequently 3-4 weeks later with AI assistance and recorded if/where fracture was present. RESULTS: Access to AI significantly improved area under the receiver operator curve (AUC) of radiology residents (0.768 [0.730-0.806] without AI to 0.876 [0.845-0.908] with AI, P < 0.001) and pediatric residents (0.706 [0.659-0.753] without AI to 0.844 [0.805-0.883] with AI, P < 0.001) in identifying fracture, respectively. There was no evidence of improvement for subspecialized musculoskeletal radiology attendings in identifying fracture (AUC 0.867 [0.832-0.902] to 0.890 [0.856-0.924], P = 0.093). There was no evidence of difference between overall resident AUC with AI and subspecialist AUC without AI (resident with AI 0.863, attending without AI AUC 0.867, P = 0.856). Overall physician radiograph interpretation time was significantly lower with AI (38.9 s with AI vs. 52.1 s without AI, P = 0.030). CONCLUSION: An openly accessible AI model significantly improved radiology and pediatric resident accuracy in detecting pediatric upper extremity fractures.

A Scoping Review of Associations Between Cannabis Use and Anxiety in Adolescents and Young Adults.

Cannabis and anxiety are both rising issues that impact young people. This review seeks to explore the association between anxiety and cannabis in adolescents and young adults (AYA). A database search was run retrospectively from July 2020 through calendar year 2013. Articles had to present outcomes examining cannabis use and symptoms of anxiety, be written in English, contain samples with ≥ 50% who are age 25 or younger, and be published in a peer-reviewed journal. Forty-seven studies were identified that examined the relationship between anxiety and cannabis use. Twenty-three studies found a positive association that greater anxiety among AYA was associated with greater cannabis use. In contrast, seven studies found a negative association that greater anxiety was related to less cannabis use. And finally, 17 studies found no clear association between anxiety and cannabis use. Further research is needed to better understand the relationship between anxiety and cannabis use.

A randomized controlled efficacy trial of an electronic screening and brief intervention for alcohol misuse in adolescents and young adults vulnerable to HIV infection: step up, test up study protocol.

BACKGROUND: Young people account for more than a quarter of new HIV infections in the US, with the majority of cases among young men who have sex with men; young transgender women are also vulnerable to infection. Substance use, particularly alcohol misuse, is a driver of sexual transmission and a potential barrier to engagement in the HIV prevention and care continuum, however vulnerable youth are difficult to reach for substance use services due, in part, to complex social and structural factors and limited access to health care. The Community Prevention Services Task Force recommends electronic screening and brief intervention as an evidence-based intervention for the prevention of excessive alcohol consumption; however, no prior studies have extended this model to community-based populations of youth that are susceptible to HIV infection. This paper describes the study protocol for an electronic screening and brief intervention to reduce alcohol misuse among adolescents and young adults vulnerable to HIV infection in community-based settings. METHODS: This study, Step Up, Test Up, is a randomized controlled trial of an electronic alcohol screening and brief intervention among youth, ages 16-25, who are vulnerable to HIV infection. Individuals who present for HIV testing at one of three community-based locations are recruited for study participation. Eligibility includes those aged 16-25 years, HIV-negative or unknown HIV status, male or trans female with a history of sex with men, and English-speaking. Participants who screen at moderate to high risk for alcohol misuse on the Alcohol Use Disorders Identification Test (AUDIT) are randomized (1:1) to either an electronic brief intervention to reduce alcohol misuse or a time-and attention-matched control. The primary outcome is change in the frequency/quantity of recent alcohol use at 1, 3, 6 and 12-month follow-up. DISCUSSION: Testing of evidence-based interventions to reduce alcohol misuse among youth vulnerable to HIV infection are needed. This study will provide evidence to determine feasibility and efficacy of a brief electronically-delivered intervention to reduce alcohol misuse for this population. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02703116, registered March 9, 2016.

Assessing the safety of cosmetic chemicals: Consideration of a flux decision tree to predict dermally delivered systemic dose for comparison with oral TTC (Threshold of Toxicological Concern).

Threshold of Toxicological Concern (TTC) aids assessment of human health risks from exposure to low levels of chemicals when toxicity data are limited. The objective here was to explore the potential refinement of exposure for applying the oral TTC to chemicals found in cosmetic products, for which there are limited dermal absorption data. A decision tree was constructed to estimate the dermally absorbed amount of chemical, based on typical skin exposure scenarios. Dermal absorption was calculated using an established predictive algorithm to derive the maximum skin flux adjusted to the actual 'dose' applied. The predicted systemic availability (assuming no local metabolism), can then be ranked against the oral TTC for the relevant structural class. The predictive approach has been evaluated by deriving the experimental/prediction ratio for systemic availability for 22 cosmetic chemical exposure scenarios. These emphasise that estimation of skin penetration may be challenging for penetration enhancing formulations, short application times with incomplete rinse-off, or significant metabolism. While there were a few exceptions, the experiment-to-prediction ratios mostly fell within a factor of 10 of the ideal value of 1. It can be concluded therefore, that the approach is fit-for-purpose when used as a screening and prioritisation tool.

Complex Trauma Exposure and Placement Stability among Systems-Impacted Black and Latinx Youth: The Mediating Role of Multisystemic Strengths.

The purpose of this study is to investigate the mediating role of multisystemic strengths in the association between complex trauma (CT) exposure and placement stability among racialized youth using the Child and Adolescent Needs and Strength (CANS) assessment. Participants were 4022 Black and Latinx youth in the child welfare system in a midwestern state. Negative binomial regressions revealed a significant indirect effect of CT exposure on placement stability through interpersonal strengths (p < .01), coping skills (p < .001), optimism (p < .01), and talents/interests (p < .05). At the familial level, there was a significant indirect effect of CT exposure on placement stability through family strengths and relationship permanence (p < .001). At the community level, educational system supports, and community resources indirectly impacted the relationship between CT exposure and placement stability (p < .01). These findings suggest that early interventions aimed at identifying and developing multisystemic strengths in Black and Latinx youth in the child welfare system can help maximize placement stability.

New approaches build upon historical studies in dermal toxicology.

These are my personal reflections on the history of approaches to understanding dermal toxicology brought together for the Paton Prize Award. This is not a comprehensive account of all publications from in vivo studies in humans to development of in vitro and in silico approaches but highlghts important progress. I will consider what is needed now to influence approaches to understanding dermal exposure with the current development and use of NAMs (new approach methodologies).

Findings From the Step Up, Test Up Study of an Electronic Screening and Brief Intervention for Alcohol Misuse in Adolescents and Young Adults Presenting for HIV Testing: Randomized Controlled Efficacy Trial.

BACKGROUND: Substance use, particularly binge drinking of alcohol and noninjection substance use, is associated with increased risk for HIV infection among youth, but structured substance use screening and brief intervention are not often provided as part of HIV risk reduction. OBJECTIVE: The purpose of the study was to test the efficacy of a fully automated electronic screening and brief intervention, called Step Up, Test Up, to reduce alcohol misuse among adolescents and young adults presenting for HIV testing. Secondary objectives were reduction in sexual risk and uptake of pre-exposure prophylaxis (PrEP) for HIV prevention. METHODS: Youth aged 16 years to 25 years who presented for HIV testing at community-based locations were recruited for study participation. Those who screened at moderate to high risk on the Alcohol Use Disorders Identification Test were randomized (1:1) to either an electronic brief intervention or a time-attention control. The primary outcome was change in alcohol use at 1, 3, 6, and 12-month follow-ups. Negative binomial and log binomial regression analyses with generalized estimating equations were conducted to evaluate the intervention efficacy. RESULTS: Among a sample of 329 youth, there were no significant differences in alcohol use outcomes between conditions over time or at the 1, 3, 6, or 12-month time points. In terms of secondary outcomes, there was evidence of reduction in condomless insertive anal sex under the influence of alcohol and drugs at 12 months compared with 3 months in the intervention versus the attention control condition (incidence rate ratio=0.15, 95% CI 0.05-0.44); however, there were no other significant differences in sexual risk and no difference in PrEP engagement. CONCLUSIONS: We found no effect of electronic brief intervention to reduce alcohol use and some effect on sexual risk among youth aged 16 years to 25 years who present for HIV testing. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02703116; https://clinicaltrials.gov/ct2/show/NCT02703116. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-020-8154-6.

Universal masking to control healthcare-associated transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2).

OBJECTIVES: To assess extent of a healthcare-associated outbreak of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and to evaluate the effectiveness of infection control measures, including universal masking. DESIGN: Outbreak investigation including 4 large-scale point-prevalence surveys. SETTING: Integrated VA healthcare system with 2 facilities and 330 beds. PARTICIPANTS: Index patient and 250 exposed patients and staff. METHODS: We identified exposed patients and staff and classified them as probable and confirmed cases based on symptoms and testing. We performed a field investigation and an assessment of patient and staff interactions to develop probable transmission routes. Infection prevention interventions included droplet and contact precautions, employee quarantine, and universal masking with medical and cloth face masks. We conducted 4 point-prevalence surveys of patient and staff subsets using real-time reverse-transcriptase polymerase chain reaction for SARS-CoV-2. RESULTS: Among 250 potentially exposed patients and staff, 14 confirmed cases of coronavirus disease 2019 (COVID-19) were identified. Patient roommates and staff with prolonged patient contact were most likely to be infected. The last potential date of transmission from staff to patient was day 22, the day universal masking was implemented. Subsequent point-prevalence surveys in 126 patients and 234 staff identified 0 patient cases and 5 staff cases of COVID-19, without evidence of healthcare-associated transmission. CONCLUSIONS: Universal masking with medical face masks was effective in preventing further spread of SARS-CoV-2 in our facility in conjunction with other traditional infection prevention measures.

The 2008 ICOH Workshop on Skin Notation.

BACKGROUND: On 29 March 2008 the International Commission on Occupational Health (ICOH) Scientific Committee on Occupational and Environmental Dermatoses organized a Skin Notation Workshop hosted by the 11th International Percutaneous Penetration Perspectives Conference (La Grande Motte, France). Skin notation (S) was chosen as a topic for discussion because this is the only example of existing regulation in the field of dermal risk assessment. The issue was discussed in a previous workshop held in Siena, Italy in 2006 with the objective of focussing on the problems related to S, the different assignment criteria and the attempts to improve the S system made by various international and governmental agencies. A position paper was subsequently published. OBJECTIVES: The workshop in France was a continuation of this activity with the aim of evaluating how the different strategies can improve S. METHODS AND DISCUSSION: The Workshop was divided into two sessions. The first was dedicated to lectures focused on different aspects of S. In the second session participants discussed key issues with the aim of exploring the actions needed to improve international S. systems.

DNA damage in horticultural farmers: a pilot study showing an association with organophosphate pesticide exposure.

A study of horticultural farmers exposed to organophosphate pesticides (OPs) and controls investigated the relationships between OP exposure, DNA damage and oxidative stress. Blood acetylcholinesterase (AChE) and urinary dialkylphosphate (DAP) levels determined exposure and 8-hydroxy-29- deoxyguanosine (8OHdG) indicated oxidative stress status. The farmers had approximately 30% lower AChE activity and increased DAP levels compared with the controls, reflecting moderate OP exposure. They had higher DNA damage than the controls and there was a significant positive relationship between DAP and DNA damage with greater than 95% power. The farmers also had a significant positive relationship between urinary DAP and 8OHdG levels.

DNA damage, signalling and repair after exposure of cells to the sulphur mustard analogue 2-chloroethyl ethyl sulphide.

Sulphur mustard (SM) is a blistering agent that is directly toxic to the skin and mucosal surfaces of the eye and respiratory system. Symptoms take several hours to develop and the mechanism of action is poorly understood although SM is able to alkylate nucleic acids and proteins. The ability of SM to form adducts with DNA has been documented, although there are limited data demonstrating how cells respond to this insult to repair the damage. This study used the sulphur mustard surrogate 2-chloroethyl ethyl sulphide (CEES) to identify DNA damage repair pathways and signalling events that are activated after exposure to the agent. A dose-dependent increase in DNA damage was observed in TK6 lymphoblastoid cells, which was associated with a loss of cell viability. Using both model human lymphoblastoid cell lines and pharmacological inhibitors, it was found that DNA damage induced by CEES was repaired by base excision repair (BER) and nucleotide excision repair (NER) pathways. Finally, CEES was found to induce the phosphorylation of p53 and Chk2 and these events were mediated by both the ATM ataxia telangiectasia mutated and ATR (ATM and Rad-3 related) protein kinases.

A Longitudinally Extensive Spinal Cord Lesion Restricted to Gray Matter in an Adolescent Male.

Longitudinally extensive spinal cord lesions (LECL) restricted to gray matter are poorly understood as are their neurodevelopmental repercussions in children. We herein report the critical case of a 13-year-old male presenting with progressive quadriparesis found to have cervical LECL restricted to the anterior horns. Challenged with a rare diagnostic dilemma, the clinical team systematically worked through potential vascular, genetic, infectious, rheumatologic, and paraneoplastic diagnoses before assigning a working diagnosis of acute inflammatory myelopathy. Nuanced consideration of and workup for both potential ischemic causes (arterial dissection, fibrocartilaginous embolism, vascular malformation) and specific inflammatory conditions including Transverse Myelitis, Neuromyelitis Optica Spectrum Disorders (NMOSD), Multiple Sclerosis (MS), Acute Disseminated Encephalomyelitis (ADEM), and Acute Flaccid Myelitis (AFM) is explained in the context of a comprehensive systematic review of the literature on previous reports of gray matter-restricted longitudinally extensive cord lesions in children. Treatment strategy was ultimately based on additional literature review of treatment-refractory acute inflammatory neurological syndromes in children. A combination of high-dose steroids and plasmapheresis was employed with significant improvement in functional outcome, suggesting a potential benefit of combination immune-modulatory treatment in these patients. This case furthermore highlights quality clinical reasoning with respect to the elusive nature of diagnosis, nuances in neuroimaging, and multifocal treatment strategies in pediatric LECL.

Metabolism of butoxyethanol in excised human skin in vitro.

Glycol ethers are widely used in industrial and household applications because their chemical and physical properties make them versatile solvents, miscible with both water and organic media. Due to the ease with which the glycol ethers are absorbed through the skin and the potential for development of adverse health effects it is important to understand the extent to which local metabolism can contribute to local and systemic toxicity. Sections of previously frozen, full thickness excised human skin samples were placed on transwell supports and placed with the underside of the skin in contact with receptor fluid. The skin surface was dosed with 115.2 mg of neat butoxyethanol and the absorption and metabolism of butoxyethanol to butoxyacetic acid monitored over time. In total 64.94+/-0.04 mg of butoxyethanol or its metabolites were removed from the surface of the skin at 24h, representing the equivalent of 56% of the applied dose, the equivalent of 17.5% of the applied dose was recovered from the receiver fluid, 3% from within the skin and the remaining 23.5% of the dose was lost to the atmosphere through evaporation. After 24h a total of 31.5 microg of butoxyacetic acid had been produced representing approximately 0.03% of the applied dose. Therefore approximately 0.16% (31.5 microg as a percentage of the total amount of butoxyethanol reaching the receiver fluid (20.17 mg) of the absorbed butoxyethanol was metabolised to butoxyacetic acid during its passage through the skin. This suggested that, although enzyme activities capable of converting butoxyethanol to butoxyacetic acid are present in skin, metabolic conversion during percutaneous absorption was small and systemic exposure to the parent compound rather than the metabolite would occur following dermal exposure to butoxyethanol. This experiment demonstrates that it is possible to maintain metabolic activity in skin samples in an in vitro setup for short, but experimentally useful, periods.

DNA damage and repair proteins in cellular response to sulfur mustard in Iranian veterans more than two decades after exposure.

Delayed effects of sulfur mustard (SM) exposure on the levels of five important damage/repair proteins were investigated in 40 SM-exposed veterans of Iran-Iraq war and 35 unexposed controls. A major DNA damage biomarker protein - phosphorylated H2AX - along with four DNA repair proteins in cell response to the genome damage MRE11, NBS1, RAD51, and XPA were evaluated in blood lymphocytes from the veterans and controls using western blotting. Mean levels of XPA, MRE11, RAD51 and NBS1 were lower in SM-exposed patients and the decrease in NBS1 was significant. Even though the raised level of phosphor-H2AX in SM-poisoned group compared to the controls was not significant it was consistent with DNA damage findings confirming the severity of damage to the DNA after exposure to SM. There were correlations between the values of RAD51 and NBS1 proteins as well as XPA and MRE11 proteins. More than two decades after exposure to SM, there is still evidences of DNA damage as well as impaired repair mechanisms in cells of exposed individuals. Such disorders in cellular level may contribute to long term health problems of the SM veterans.

Inter-individual variability in esterases in human liver.

Human liver has numerous hydrolytic enzymes involved in metabolism of endogenous and exogenous esters. Of these enzymes, carboxylesterases (EC 3.1.1.1) form an important group which hydrolyses many diverse ester substrates, including pro-ester drugs. Carboxylesterase activity was investigated in liver subcellular fractions from 22 individuals using the general carboxylesterase substrate phenylvalerate and the homologous series of esters methyl-, ethyl-, propyl-, butyl- and benzylparaben. The intra- and inter-individual variation in phenylvalerate and paraben metabolism was compared. Rates of hydrolysis were higher in microsomal fractions than cytosolic fractions for all compounds. The rate of paraben hydrolysis varied depending on the size of the paraben alcohol leaving group, showing a decrease with increasing leaving group size. Comparisons showed that individuals with high rates of hydrolysis towards methyl paraben also showed high rates of hydrolysis to the other parabens and phenylvalerate. Phenylvalerate as a non-specific carboxylesterase substrate was hydrolysed mainly by hCE1 in human livers and there was good correlation with small alcohol leaving group parabens, suggesting hCE1 involvement. Lower correlations with larger alcohol leaving group parabens are consistent with more hCE2 involvement.

The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue.

Ciclesonide (CIC) is an inhaled glucocorticosteroid. This study aimed to identify esterases involved in the metabolism of CIC to the active metabolite desisobutyryl-ciclesonide (des-CIC), and to measure hydrolysis rates in human liver, lung and plasma and normal human bronchial epithelial (NHBE) cells in vitro. Ciclesonide (5 microM and 500 microM) was incubated with microsomal or cytosolic fractions from liver, lung and plasma (n=4 for each) and des-CIC formation was determined by reverse-phase high-performance liquid chromatography with U.V. detection. The roles of carboxylesterase, cholinesterase and A-esterase in CIC hydrolysis were determined using a range of inhibitors. Inhibitor concentrations for liver and NHBE cells were 100 microM and 5 microM, respectively. Liver tissue had a higher activity for 500 microM CIC hydrolysis (microsomes: 25.4; cytosol: 62.9 nmol/g tissue/min) than peripheral lung (microsomes: 0.089; cytosol: 0.915 nmol/g tissue/min) or plasma (0.001 nmol/mL plasma/min), corresponding with high levels of carboxylesterase and cholinesterase in the liver compared with the lung. CIC (5 microM) was rapidly hydrolyzed by NHBE cells (approximately 30% conversion at 4h), with almost complete conversion by 24h. In liver and NHBE cells, major involvement of cytosolic carboxylesterases, with some contribution by cholinesterases, was indicated. The highest level of conversion was found in the liver, the site of inactivation of des-CIC through rapid oxidation by cytochrome P450. Carboxylesterases in bronchial epithelial cells probably contribute significantly to the conversion to des-CIC in the target organ, whereas low systemic levels of des-CIC are a result of the high metabolic clearance by the liver following CIC inhalation.

The distribution of esterases in the skin of the minipig.

Skin esterases serve an important pharmacological function as they can be utilised for activation of topically applied ester prodrugs. Understanding the nature of these enzymes, with respect to their role and local activity, is essential to defining the efficacy of ester prodrugs. Minipigs are used as models to study the kinetics of absorption of topically applied drugs. Their skin has structural properties very similar to human skin. However, regional distribution differences in esterase activity from site-to-site could influence cross-species extrapolation. Investigation of the regional site variation of minipig skin esterase activity will facilitate standardization of topically applied drug studies. Furthermore, the characterization of regional skin variation, will aid in translation of minipig results to better predictions of human esterase activity. Here we report the variation in rates of hydrolysis by minipig skin taken from different regional sites, using the esterase-selective substrates: phenyl valerate (carboxylesterase), phenyl acetate (arylesterase) and p-nitrophenyl acetate (general esterase). Skin from ears and back of male minipig showed higher activity than female. Skin from minipig ears and the back showed the highest level of esterase activity and was similar to human breast skin used in vitro absorption studies. These results suggest that skin from the minipig back is an appropriate model for preclinical human skin studies, particularly breast skin. This study supports the use of the minipig, with topical application to the back, as a model for the investigation of pharmacokinetics and metabolism of ester prodrugs.

Analysis, interpretation, and extrapolation of dermal permeation data using diffusion-based mathematical models.

New dermal penetration data have been measured in both "infinite" and finite dose experiments on a range of compounds of varying lipophilicities. The data are analyzed, using parameter fitting, to determine the values of parameters governing the overall skin absorption processes. Two one-dimensional diffusion models are used. The first is novel, and well suited to the modeling of dermal uptake in occupational exposure scenarios. The second is an implementation of a model taken from the literature. The models are compared in a variety of exposure scenarios, and exhibit good mutual agreement. Both successfully reproduce expected features of the absorption process. Penetration parameters are determined by analyzing both infinite and finite dose data. Prediction of dermal absorption with finite dose scenarios is carried out and compared with experimental data obtained under these conditions. Parameters determined may also have an important role in improving the reliability of predictive QSARs used to estimate the extent of penetration of untested molecules.

Intestinal parasites from the 2nd-5th century AD latrine in the Roman Baths at Sagalassos (Turkey).

The aim of this research was to determine the species of intestinal parasite present in a Roman Imperial period population in Asia Minor, and to use this information to improve our understanding of health in the eastern Mediterranean region in Roman times. We analyzed five samples from the latrines of the Roman bath complex at Sagalassos, Turkey. Fecal biomarker analysis using 5ß-stanols has indicated the feces were of human origin. The eggs of roundworm (Ascaris) were identified in all five samples using microscopy, and the cysts of the protozoan Giardia duodenalis (which causes dysentery) were identified multiple times in one sample using ELISA. The positive G. duodenalis result at Sagalassos is particularly important as it represents the earliest reliable evidence for this parasite in the Old World (i.e. outside the Americas). As both these species of parasite are spread through the contamination of food and water by fecal material, their presence implies that Roman sanitation technologies such as latrines and public baths did not break the cycle of reinfection in this population. We then discuss the evidence for roundworm in the writings of the Roman physician Galen, who came from Pergamon, another town in western Asia Minor.

Hepatic effects of tartrazine (E 102) after systemic exposure are independent of oestrogen receptor interactions in the mouse.

Tartrazine is a food colour that activates the transcriptional function of the human oestrogen receptor alpha in an in vitro cell model. Since oestrogens are cholestatic, we hypothesised tartrazine will cause periportal injury to the liver in vivo. To test this hypothesis, tartrazine was initially administered systemically to mice resulting in a periportal recruitment of inflammatory cells, increased serum alkaline phosphatase activity and mild periportal fibrosis. To determine whether an oestrogenic effect may be a key event in this response, tartrazine, sulphonated metabolites and a food additive contaminant were screened for their ability to interact with murine oestrogen receptors. In all cases, there were no interactions as agonists or antagonists and further, no oestrogenicity was observed with tartrazine in an in vivo uterine growth assay. To examine the relevance of the hepatic effects of tartrazine to its use as a food additive, tartrazine was orally administered to transgenic NF-κB-Luc mice. Pre- and concurrent oral treatment with alcohol was incorporated given its potential to promote gut permeability and hepatic inflammation. Tartrazine alone induced NF- κB activities in the colon and liver but there was no periportal recruitment of inflammatory cells or fibrosis. Tartrazine, its sulphonated metabolites and the contaminant inhibited sulphotransferase activities in murine hepatic S9 extracts. Given the role of sulfotransferases in bile acid excretion, the initiating event giving rise to periportal inflammation and subsequent hepatic pathology through systemic tartrazine exposure is therefore potentially associated an inhibition of bile acid sulphation and excretion and not on oestrogen receptor-mediated transcriptional function. However, these effects were restricted to systemic exposures to tartrazine and did not occur to any significant effect after oral exposure.