Measuring the association between the opening of a new multi-national restaurant with young people's eating behaviours.

Out-of-home eating (takeaway, take-out and fast-foods) is associated with intakes of higher energy and fat, and lower intakes of micronutrients, and is associated with excess weight gain. In 2017, a unique opportunity arose to measure the association between the opening of a new multi-national fast-food restaurant (McDonald's) and consumption of fast-food on young people aged 11-16. This study uses a repeated cross-sectional design to explore group level change over time with respect to out-of-home eating behaviours of young people. Two secondary schools in Redcar and Cleveland agreed to participate and facilitated the completion of a questionnaire on their pupils eating behaviours at three timepoints a) prior to the new restaurant opening, b) three months post-opening and c) nine months post opening. Reported frequency of visits to McDonald's showed a statistically significant increase in visits between 3 and 9 months of the restaurant opening. This research asks and explores the question of whether the introduction of a new multi-national fast-food restaurant influences eating habits of young people attending schools near the new outlet.

The Impact of Electronic Health Record Interventions on Patient Access to Post-Hospital Discharge Prescriptions.

Purpose: Assess the impact of electronic health record interventions on patient access to post-hospital discharge prescriptions. Methods: Five interventions were implemented in the electronic health record to improve patient access to prescriptions after discharge from hospital: electronic prior authorization, alternative medication suggestions, order sets, mail order pharmacy alerts, and medication interchange instructions. This was a retrospective cohort study of patient responses from discharges during 6 months before the first intervention implementation and 6 months after the last intervention implementation documented in the electronic health record and a transition-in-care platform. Primary endpoint was the proportion of discharges with patient-reported issues that would have been prevented by the studied interventions out of number of discharges with at least one prescription, analyzed using Chi-squared test (level of significance .05). Results: Discharges with patient-reported issues that would have been prevented by the studied interventions decreased from 1.68 to 1.07 out of 1000 discharges with prescriptions (P < .001). Conclusion: Interventions in the electronic health record reduced barriers faced by patients to picking up prescriptions post-discharge from hospital, potentially leading to improved patient satisfaction and improved health outcomes. Important factors to consider for electronic health record intervention implementation are workflow development and intrusiveness of clinical decision support. Multiple targeted electronic health record interventions can improve patients' access to prescriptions after discharge from hospital.

Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260.

NP260 was designed as a first-in-class selective antagonist of α4-subtype GABAA receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog>human>rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity.

A curated data resource to support safe carbon dioxide transport-route planning.

Supporting the national target of net-zero greenhouse gas emissions in the United States by 2050, the Bipartisan Infrastructure Law (BIL) authorized investments into carbon capture and storage (CCS), highlighting the need for the safe and sustainable transport of carbon dioxide (CO2). Curated to support CO2 pipeline route planning optimization and assess existing energy transport corridors, the CCS Pipeline Route Planning Database is a compilation of 47 publicly available, authoritative geospatial data resources, spanning the contiguous U.S., and some including Alaska and Hawaii. Key considerations were identified following comprehensive literature review, which included state legislation, known pipeline stressors, and energy, environmental, and social justice (EJSJ) considerations. Data layers were sorted into relevant categories (i.e., natural hazards, boundaries) and assigned preliminary weights representing potential social, environmental, and economic costs associated with routing pipelines. Version one of the CCS Pipeline Route Planning Database, made available on the Energy Data eXchange® (EDX), contains categorized vector features representing protected areas, public and energy infrastructure, EJSJ factors, potential risks, federal and state regulations and legislation, and natural features, along with associated metadata. This paper provides details on individual layers, methods used to identify data needs, acquire, and process the disparate data, as well as planned enhancements to future versions of this database.

Bioactivation and toxicity of acetaminophen in a rat hepatocyte micropatterned coculture system.

We have recently shown that primary rat hepatocytes organized in micropatterned cocultures with murine embryonic fibroblasts (HepatoPac™) maintain high levels of liver functions for at least 4 weeks. In this study, rat HepatoPac was assessed for its utility to study chemical bioactivation and associated hepatocellular toxicity. Treatment of HepatoPac cultures with acetaminophen (APAP) over a range of concentrations (0-15 mM) was initiated at 1, 2, 3, or 4 weeks followed by the assessment of morphological and functional endpoints. Consistent and reproducible concentration-dependent effects on hepatocyte structure, viability, and basic functions were observed over the 4-week period, and were exacerbated by depleting glutathione using buthionine sulfoximine or inducing CYP3A using dexamethasone, presumably due to increased reactive metabolite-induced stress and adduct formation. In conclusion, the results from this study demonstrate that rat HepatoPac represents a structurally and functionally stable hepatic model system to assess the long-term effects of bioactivated compounds.

Long-term stability of primary rat hepatocytes in micropatterned cocultures.

Primary hepatocytes display functional and structural instability in standard monoculture systems. We have previously developed a model in which primary hepatocytes are organized in domains of empirically optimized dimensions and surrounded by murine embryonic fibroblasts (HepatoPac™). Here, we assess the long-term phenotype of freshly isolated and cryopreserved rat hepatocytes in a 96-well HepatoPac format. The viability, cell polarity (actin microfilaments, bile canaliculi), and functions (albumin, urea, Phase I/II enzymes, transporters) of fresh and cryopreserved rat hepatocytes were retained in HepatoPac at similar levels for at least 4 weeks as opposed to rapidly declining over 5 days in collagen/Matrigel™ sandwich cultures. Pulse or continuous exposure of rat HepatoPac to GW-7647, a selective agonist of PPARα, caused reproducible induction of CYP4A1 and 3-hydroxy-3-methylglutaryl-CoA synthase over 4 weeks. In conclusion, rat HepatoPac in a 96-well format can be used for chronic dosing of highly functional hepatocytes and assessment of perturbed hepatocellular pathways.

Enhancing knowledge discovery from unstructured data using a deep learning approach to support subsurface modeling predictions.

Subsurface interpretations and models rely on knowledge from subject matter experts who utilize unstructured information from images, maps, cross sections, and other products to provide context to measured data (e. g., cores, well logs, seismic surveys). To enhance such knowledge discovery, we advanced the National Energy Technology Laboratory's (NETL) Subsurface Trend Analysis (STA) workflow with an artificial intelligence (AI) deep learning approach for image embedding. NETL's STA method offers a validated science-based approach of combining geologic systems knowledge, statistical modeling, and datasets to improve predictions of subsurface properties. The STA image embedding tool quickly extracts images from unstructured knowledge products like publications, maps, websites, and presentations; categorically labels the images; and creates a repository for geologic domain postulation. Via a case study on geographic and subsurface literature of the Gulf of Mexico (GOM), results show the STA image embedding tool extracts images and correctly labels them with ~90 to ~95% accuracy.

Healthy plant-based diets and their short-term effects on weight loss, nutrient intake and serum cholesterol levels.

Healthy plant-based diets (hPBD) are being promoted to reduce the risks of cardiovascular and associated diseases. This study investigates short-term adherence to a hPBD to examine whether these dietary changes impact weight and cardiovascular risk factors. A simple, uncontrolled, before and after design was used. Twenty women (mean BMI 31 ± 4 kg/m2 ) participated in a 6-week hPBD intervention. Participants completed a 3-week reset, eliminating all refined sugar, heavily processed foods, artificial sweeteners, alcohol, meat, fish, dairy and oil from their diets, which could then be reintroduced into their diet if the participant chose to do so. Participants had 1-h, weekly group support sessions. A weight loss of 4.4 kg, SD = 1.8 kg (n = 17, t = 10.2, p < 0.001) was observed after 6 weeks following the hPBD. BMI reduced from 31 to 29 kg/m2 (mean reduction = 1.38, SD = 0.76, n = 17, t = 7.49, p < 0.001). Reductions for waist circumference (mean reduction = 4.4 cm, SD = 5.22 cm, n = 8, t = 2.55, p = 0.034), LDL cholesterol (mean reduction = 0.600 mmol/L, SD = 0.828, n = 17, t = 2.81, p = 0.014) and total cholesterol (mean = 0.525 mmol/L, SD = 0.969, n = 17, t = 2.24, p = 0.040) were also observed. Body fat % was not significantly reduced (mean reduction = 2.3, SD = 6.6, n = 17, t = 1.49, p = 0.154). Dietary data were obtained from 17 participants at week 3 and from six participants at week 6. Energy intake at week 3 decreased compared with baseline (mean reduction = 1068 kcal/day, SD = 585 kcal, n = 17, t = 7.07, p < 0.001) and at week 6 (mean reduction = 715 kcal, SD = 645 kcal, n = 6, t = 2.72, p = 0.042). Protein, saturated fat and cholesterol intakes were also lower at weeks 3 and 6 compared with baseline. Fibre intake increased significantly from baseline to week 6 (mean increase = 11.3 g/day, SD = 8.9, n = 6, t = 3.11, p = 0.027) whilst sugar intake decreased from baseline to week 3 (mean reduction = 26.0 g/day, SD = 22.3, n = 17, t = 4.52, p < 0.001), but the reduction at week 6 was not significant. These results suggest that motivated participants can learn to adopt new dietary patterns for a few weeks at least with some support. This study demonstrated positive effects of a hPBD on weight reduction, cholesterol and BMI over a short time period, although the short- and long-term adherence to this diet requires further research.

A mixed-method systematic review and meta-analysis of the influences of food environments and food insecurity on obesity in high-income countries.

Obesity remains a serious public health concern in rich countries and the current obesogenic food environments and food insecurity are predictors of this disease. The impact of these variables on rising obesity trends is, however, mixed and inconsistent, due to measurement issues and cross-sectional study designs. To further the work in this area, this review aimed to summarize quantitative and qualitative data on the relationship between these variables, among adults and children across high-income countries. A mixed-method systematic review was conducted using 13 electronic databases, up to August 2021. Two authors independently extracted data and evaluated quality of publications. Random-effects meta-analysis was used to estimate the odds ratio (OR) for the association between food insecurity and obesity. Where statistical pooling for extracted statistics related to food environments was not possible due to heterogeneity, a narrative synthesis was performed. Meta-analysis of 36,113 adults and children showed statistically significant associations between food insecurity and obesity (OR: 1.503, 95% confidence interval: 1.432-1.577, p < .05). Narrative synthesis showed association between different types of food environments and obesity. Findings from qualitative studies regarding a reliance on energy-dense, nutrient-poor foods owing to their affordability and accessibility aligned with findings from quantitative studies. Results from both qualitative and quantitative studies regarding the potential links between increased body weight and participation in food assistance programs such as food banks were supportive of weight gain. To address obesity among individuals experiencing food insecurity, wide-reaching approaches are required, especially among those surrounded by unhealthy food environments which could potentially influence food choice.

A database and framework for carbon ore resources and associated supply chain data.

The Carbon Ore Resources Database (CORD) is a working collection of 399 data files associated with carbon ore resources in the United States. The collection includes spatial/non-spatial, filtered, processed, and secondary data files with original data acquisition efforts focused on domestic coal resources. All data were acquired via open-source, online sources from a combination of 18 national, state, and university entities. Datasets are categorized to represent aspects of carbon ore resources, to include: Geochemistry, Geology, Infrastructure, and Samples. Geospatial datasets are summarized and analyzed by record and dataset density or the number of records or datasets per 400 square kilometer grid cells. Additionally, the "CORD Platform," an ArcGIS Online geospatial dashboard web application, enables users to interact and query with CORD datasets. The CORD provides a single database and location for data-driven analytical needs associated with the utilization of carbon ore resources.

'Pizza every day - why?': A survey to evaluate the impact of COVID-19 guidelines on secondary school food provision in the UK.

The nutritional requirements of adolescence and the reported poor UK eating behaviours of young people are a significant public health concern. Schools are recognised as an effective 'place' setting to enable improvement to nutrition outcomes. The COVID-19 pandemic resulted in UK school closures from March 2020. In re-opening in September 2020, schools were required to meet guidelines to ensure the minimised impact of COVID-19 on the population (DfE 2020). We aimed to evaluate the impact of COVID-19 school guidelines on secondary and post-16 (16-18 years) food provision. An online survey was posted on 8th October to 1st December 2020, targeted at young people, parents and staff of secondary/post-16 education establishments in the UK. Two hundred and fifty-two responses were received, of which 91% reported a change in their school food provision, 77% reported time for lunch was shortened and 44% indicated the provision was perceived as less healthy during September 2020 (post-lockdown school return) compared with March 2020 (pre-lockdown). Analyses demonstrated that time, limited choice and healthiness impacted negatively upon young people's school food experience. The COVID-19 pandemic has presented a huge challenge to the delivery of healthy school food to young people. Therefore, schools require more support in following national food standards and incorporating nutrition education and behaviour change strategies within current guidelines.

The impact of, and views on, school food intervention and policy in young people aged 11-18 years in Europe: A mixed methods systematic review.

Understanding the social and environmental influencers of eating behaviours has the potential to improve health outcomes for young people. This review aims to explore the effectiveness of school nutrition interventions and the perceptions of young people experiencing a nutrition focused intervention or change in school food policy. A comprehensive systematic search identified studies published between 1 December 2007 to 20 February 2020. Twenty-seven studies were included: 22 quantitative studies of nutrition related outcomes and five qualitative studies reporting views and perceptions of young people (combined sample of 22,138 participants, mean ages 12-18 years). The primary outcome was nutrition knowledge/dietary behaviours, with secondary outcomes exploring body mass index (BMI) and wellbeing. Due to the heterogeneity of studies, a narrative results description is presented. The findings demonstrate that school nutrition programmes can be effective in reducing sugar, sugar sweetened beverages (SSB) and saturated fat and increasing fruit and vegetable (FV) intake. The lived experiences of young people in a school context provide valuable insights that should be considered in the development of effective school food policy and interventions. This review affirms the significant role that schools can play in supporting good nutrition in all young people and provides opportunities to inform the school food agenda.

Left atrial infarction: a case report and review of the literature.

The majority of cardiac related deaths are due to ischemic heart disease, with the most common clinical scenario being severe coronary artery atherosclerosis resulting in left ventricular myocardial infarction. However, infarction of other cardiac chambers does occur, and often has specific clinical associations. We report a case of a 70-year-old man who suffered from left atrial infarction that resulted in a transmural rupture of his left atrium. The patient had a history of rheumatic heart disease, mitral valve stenosis, and severe atherosclerotic coronary artery disease. Four days before death, he underwent mitral valve replacement and left circumflex coronary artery bypass. Two days later, he developed atrial fibrillation. On the day of death, he had decreased mental status, questionable seizure activity, hematemesis, ventricular tachycardia, and eventually asystole. At autopsy, he had significant hemopericardium with a fibrinous pericarditis and bilateral hemothoraces (total blood volume: 1250 mL). A 0.1 to 0.2 cm left atrial transmural defect was identified. The prosthetic mitral valve was free of vegetations, and completely intact. Similarly, the left circumflex artery bypass graft was completely patent and unremarkable. Severe calcific atherosclerosis was of his native left circumflex and left main coronary arteries. Microscopic examination revealed acute myocardial infarction of the left atrium at the rupture site. The anatomy of atrial circulation as well as the pathology and consequences of atrial infarction are discussed.

Development of a liquid chromatography/mass spectrometry-based drug accumulation assay in Pseudomonas aeruginosa.

Bacterial resistance to antibiotic therapy remains a worldwide problem. In Pseudomonasaeruginosa, rates of efflux confer inherent resistance to many antimicrobial agents, including fluoroquinolones, due to a high level of expression and a relatively high turnover number of the efflux pumps in gram-negative bacteria. To understand the roles of efflux pumps in both the influx and efflux of compounds in P. aeruginosa and to aid the chemistry compound design by bridging in vitro enzymatic binding data (IC(50) values) with whole cell results (MIC numbers), a collaborative effort was put forward to validate a series of bacterial penetration/accumulation assays for assessment of intracellular drug concentration. Initially, using 2-(4-dimethylaminostyryl)-1-ethylpyridinium cation (DMP) as the tracer, a 96-well fluorescence assay was established to measure the time-dependent accumulation of DMP in wild-type (PAO1), MexABOprM deletion (PAO200), and MexABOprM-MexCDOprJ-MexJKL:FRT deletion mutants (PAO314). At steady state, the order of DMP accumulation was PAO314>PAO200>PAO1. Subsequently, the established assay conditions were applied to a radiolabeled assay format using (3)H-labeled ciprofloxacin. At the concentration tested, the accumulation of [(3)H]ciprofloxacin approached a plateau after 15 min and the amount of accumulation in PAO314 was higher (~2- to 10-fold) than that in PAO1. Finally, with an additional step of cell lysis, a liquid chromatography/mass spectrometry-based assay was established with ciprofloxacin with (i) superior sensitivity (the detection limit can be as low as 0.24 ng/ml for ciprofloxacin) and (ii) the ability to monitor cold or nonfluorescent compounds in a drug discovery setting.

Hepatocyte-Derived Exosomes Promote Liver Immune Tolerance: Possible Implications for Idiosyncratic Drug-Induced Liver Injury.

Most idiosyncratic drug-induced liver injury appears to result from an adaptive immune attack on the liver. Recent evidence suggests that the T-cell response may be facilitated by the loss of immune tolerance. In this study, we explored the hypothesis that constitutively released hepatocyte-derived exosomes (HDE) are important for maintaining normal liver immune tolerance. Exosomes were isolated from the conditioned medium of primary human hepatocytes via polymer precipitation. Mock controls were prepared by processing fresh medium that was not hepatocyte exposed with precipitation reagent. THP-1 monocytes were then treated with HDE or an equivalent volume of mock control for 24 h, followed by a 6-h stimulation with LPS. HDE exposure resulted in a significant decrease in the LPS-induced media levels of interleukin-1ß and interleukin-8. Gene expression profiling performed in THP-1 cells just prior to LPS-induced stimulation identified a significant decrease among genes associated with innate immune response. MicroRNA (miRNA) profiling was performed on the HDE to identify exosome contents that may drive immune suppression. Many of the predicted mRNA target genes for the most abundant microRNAs in HDE were among the differentially expressed genes in THP-1 cells. Taken together, our data suggest that HDE play a role in maintaining normal liver immune tolerance. Future experiments will explore the possibility that drugs causing idiosyncratic liver injury promote the loss of homeostatic HDE signaling.

Nationwide satellite training for public health professionals: Web-based follow-up.

INTRODUCTION: Few studies have rigorously evaluated the effectiveness of health-related continuing education using satellite distribution. This study assessed participants' professional characteristics and their changes in knowledge, attitudes, and actions taken after viewing a public health preparedness training course on mass vaccination broadcast nationally by satellite. METHODS: A three-part survey design was used to evaluate training effectiveness. Paper-based questionnaires were distributed at a stratified sample of downlink facilities to collect knowledge and attitude responses before and after the broadcast. Six weeks later, willing participants were invited by e-mail to complete a Web-based follow-up questionnaire to assess actions taken as a result of viewing the broadcast. Paired t-tests and McNemar's chi-square were used to compare changes in attitude from before to after the broadcast, after the broadcast to follow-up, and before the broadcast to follow-up. RESULTS: A total of 544 paper-based questionnaires were received from 59 of 70 sampled sites. The pre- and post assessments administered the day of the broadcast demonstrated statistically significant knowledge gain (p < .001) and an increased belief immediately following the broadcast that mass vaccination clinics are important to their organizations' public health activities (p < .001). Of the 291 respondents who completed the follow-up online questionnaire, 44% (n = 128) reported they implemented or planned some form of action after the broadcast. Reported actions were higher among public health workers most likely to be directly involved in preparedness and immunization activities. DISCUSSION: This evaluation assessed (1) participants' professional characteristics, (2) knowledge gain, (3) self-reported actions taken following the broadcast, (4) program satisfaction, and (5) suggested improvements for future satellite broadcast programs. The study's methodology of using a Web-based survey for follow-up is a relatively economical tool for assessing longer-term continuing education program objectives.

Metabolism and transporter-mediated drug-drug interactions of the endothelin-A receptor antagonist CI-1034.

CI-1034, an endothelin-A receptor antagonist was being developed for pulmonary hypertension. Drug-drug interaction studies using human hepatic microsomes were conducted to assess CYP1A2, CYP2C9, CYP2C19, CYP3A4 and CYP2D6 inhibition potential; CYP3A4 induction potential was evaluated using primary human hepatocytes. CI-1034 moderately inhibited CYP2C9 (IC(50) 39.6 microM) and CYP3A4 activity (IC(50) 21.6 microM); CYP3A4 inhibition was metabolism-dependent. In human hepatocytes, no increase in CYP3A4 activity was observed in vitro, while mRNA was induced 15-fold, similar to rifampin, indicating that CI-1034 is both an inhibitor and inducer of CYP3A4. A 2-week clinical study was conducted to assess pharmacokinetics, pharmacodynamics and safety. No significant changes were observed in [formula: see text] between days 1 and 14. However, reversible elevations of serum liver enzymes were observed with a 50mg BID dose and the program was terminated. To further understand the interactions of CI-1034 in the liver and possible mechanisms of the observed hepatotoxicity, we evaluated the effect of CI-1034 on bile acid transport and previously reported that CI-1034 inhibited biliary efflux of taurocholate by 60%, in vitro. This indicated that inhibition of major hepatic transporters could be involved in the observed hepatotoxicity. We next evaluated the in vitro inhibition potential of CI-1034 with the major hepatic transporters OATP1B1, OATP1B3, OATP2B1, MDR1, MRP2 and OCT. CI-1034 inhibited OATP1B1 (K(i) 2 microM), OATP1B3 (K(i) 1.8 microM) and OATP2B1 activity (K(i) 3.3 microM) but not OCT, MDR1 or MRP2 mediated transport. Our data indicates that CI-1034 is an inhibitor of major hepatic transporters and inhibition of bile efflux may have contributed to the observed clinical hepatotoxicity. We recommend that in vitro drug-drug interaction panels include inhibition and induction studies with transporters and drug metabolizing enzymes, to more completely assess potential in vivo interactions or toxicity.

Co-culture of Hepatocytes and Kupffer Cells as an In Vitro Model of Inflammation and Drug-Induced Hepatotoxicity.

Immune-mediated drug-induced hepatotoxicity is often unrecognized as a potential mode of action due to the lack of appropriate in vitro models. We have established an in vitro rat donor-matched hepatocyte and Kupffer cell co-culture (HKCC) model to study immune-related responses to drug exposure. Optimal cell culture conditions were identified for the maintenance of co-cultures based on cell longevity, monolayer integrity, and cytokine response after lipopolysaccharide (LPS) exposure. Hepatocyte monocultures and HKCCs were then used to test a subset of compounds associated with hepatotoxic effects with or without LPS. Cytokine levels and metabolic activity (cytochrome P450 3A [Cyp3A]) were measured after a 48-h exposure to monitor endotoxin-induced changes in acute phase and functional end points. LPS-activated HKCCs, but not hepatocyte monocultures, treated with trovafloxacin or acetaminophen, compounds associated with immune-mediated hepatotoxicity, showed LPS-dependent decreases in interleukin-6 production with concomitant increases in Cyp3A activity. Differential endotoxin- and model-dependent alterations were observed in cytokine profiles and Cyp3A activity levels that corresponded to specific compounds. These results indicate the utility of the HKCC model system to discern compound-specific effects that may lead to enhanced or mitigate hepatocellular injury due to innate or adaptive immune responses.

Attention-deficit/hyperactivity disorder, medication treatment, and substance use patterns among adolescents and young adults.

OBJECTIVE: The aim of this study was to examine the relationship between current active attention-deficit/hyperactivity disorder (ADHD) symptoms, medication treatment, and substance use patterns among college students. METHOD: Three hundred and thirty-four students at a local college were surveyed for current ADHD symptoms and psychopharmacological treatment. The survey was conducted in conjunction with an annual national survey that probes students about their substance use patterns and attitudes. RESULTS: Participants with ADHD as ascertained by medication treatment of ADHD had greater past-year tobacco and marijuana use. Among those with ADHD, participants with active ADHD symptoms were more likely to have past-year tobacco and other drug (besides tobacco, alcohol, and marijuana) use as compared to those without active ADHD symptoms. In addition, participants with active ADHD symptoms were more likely to have past-month "other" drug use as compared to those without active ADHD symptoms. Among those prescribed medications for ADHD, 25% reported ever using their medication to "get high" and almost 29% reported ever giving or selling their medication to someone else. CONCLUSIONS: Results of our preliminary study indicated that ADHD symptom control may be important to protect against increased risk of substance use (particularly tobacco and drugs other than alcohol and marijuana) among college-age students with ADHD. Further studies of misuse/diversion of prescription stimulant medication among college students are needed.

Evaluation of hepatotoxic potential of drugs by inhibition of bile-acid transport in cultured primary human hepatocytes and intact rats.

Inhibition of canalicular bile acid efflux by medications is associated with clinical liver toxicity, sometimes in the absence of major liver effects in experimental species. To predict the hepatotoxic potential of compounds in vitro and in vivo, we investigated the effect of clinical cholestatic agents on [3H]taurocholic acid transport in regular and collagen-sandwich cultured human hepatocytes. Hepatocytes established a well-developed canalicular network with bile acid accumulating in the canalicular lumen within 15 min of addition to cells. Removing Ca2+ and Mg2+ from the incubation buffer destroyed canalicular junctions, resulting in bile acid efflux into the incubation buffer. Canalicular transport was calculated based on the difference between the amount of bile acid effluxed into the Ca/Mg2+-free and regular buffers with linear efflux up to 10 min. Hepatocytes cultured in the nonsandwich configuration also transported taurocholic acid, but at 50% the rate in sandwiched cultures. Cyclosporin A, bosentan, CI-1034, glyburide, erythromycin estolate, and troleandomycin inhibited efflux in a concentration-dependent manner. In contrast, new generation macrolide antibiotics with lower incidence of clinical hepatotoxicity were much less potent inhibitors of efflux. An in vivo study was conducted whereby glyburide or CI-1034, administered iv to male rats, produced a 2.4-fold increase in rat total serum bile acids. A synergistic 6.8-fold increase in serum total bile acids was found when both drugs were delivered together. These results provide methods to evaluate inhibitory effects of potentially cholestatic compounds on bile-acid transport, and to rank compounds according to their hepatotoxic potential.