3,198 research outputs found

    ‘Pizza every day – why?’: A survey to evaluate the impact of COVID‐19 guidelines on secondary school food provision in the UK

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    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

    Maximum Power Efficiency and Criticality in Random Boolean Networks

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    Random Boolean networks are models of disordered causal systems that can occur in cells and the biosphere. These are open thermodynamic systems exhibiting a flow of energy that is dissipated at a finite rate. Life does work to acquire more energy, then uses the available energy it has gained to perform more work. It is plausible that natural selection has optimized many biological systems for power efficiency: useful power generated per unit fuel. In this letter we begin to investigate these questions for random Boolean networks using Landauer's erasure principle, which defines a minimum entropy cost for bit erasure. We show that critical Boolean networks maximize available power efficiency, which requires that the system have a finite displacement from equilibrium. Our initial results may extend to more realistic models for cells and ecosystems.Comment: 4 pages RevTeX, 1 figure in .eps format. Comments welcome, v2: minor clarifications added, conclusions unchanged. v3: paper rewritten to clarify it; conclusions unchange

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

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    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 endotoxinand 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

    Fatal Outcome of Disseminated Strongyloidiasis despite Detectable Plasma and Cerebrospinal Levels of Orally Administered Ivermectin

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    Strongyloides stercoralis affects over 100 million people worldwide. Those people most susceptible to infection are those with an immunocompromising condition, such as cancer or human immunodeficiency virus (HIV). Local disease may spread throughout the body of the host, causing a condition termed disseminated strongyloidiasis. Standard treatment for Strongyloides stercoralis infection is oral ivermectin. We describe a patient with chronic lymphocytic leukemia diagnosed with disseminated strongyloidiasis two weeks after initial presentation. After repeated dosing of oral ivermectin with no clinical response, serum and cerebral spinal fluid (CSF) concentrations of ivermectin were measured to assess absorption. The peak serum concentration of 49.3 ng/mL correlated with a CSF concentration of 0.14 ng/mL. Despite these concentrations, the patient eventually succumbed to multi-system organ failure. We discuss the reasons for treatment failure and explore the utility of measuring ivermectin concentrations

    Multiple Exportins Influence Thyroid Hormone Receptor Localization

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    The thyroid hormone receptor (TR) undergoes nucleocytoplasmic shuttling and regulates target genes involved in metabolism and development. Previously, we showed that TR follows a CRM1/calreticulinmediated nuclear export pathway. However, two lines of evidence suggest TR also follows another pathway: export is only partially blocked by leptomycin B (LMB), a CRM1-specific inhibitor; and we identified nuclear export signals in TR that are LMB-resistant. To determine whether other exportins are involved in TR shuttling, we used RNA interference and fluorescence recovery after photobleaching shuttling assays in transfected cells. Knockdown of exportins 4, 5, and 7 altered TR shuttling dynamics, and when exportins 5 and 7 were overexpressed, TR distribution shifted towards the cytosol. To further assess the effects of exportin overexpression, we examined transactivation of a TR-responsive reporter gene. Our data indicate that multiple exportins influence TR localization, highlighting a fine balance of nuclear import, retention, and export that modulates TR function

    Relativistic mean field approximation to the analysis of 16O(e,e'p)15N data at |Q^2|\leq 0.4 (GeV/c)^2

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    We use the relativistic distorted wave impulse approximation to analyze data on 16O(e,e'p)15N at |Q^2|\leq 0.4 (GeV/c)^2 that were obtained by different groups and seemed controversial. Results for differential cross-sections, response functions and A_TL asymmetry are discussed and compared to different sets of experimental data for proton knockout from p_{1/2} and p_{3/2} shells in 16O. We compare with a nonrelativistic approach to better identify relativistic effects. The present relativistic approach is found to accommodate most of the discrepancy between data from different groups, smoothing a long standing controversy.Comment: 28 pages, 7 figures (eps). Major revision made. New figures added. To be published in Phys. Rev.

    DIFFERENTIAL REGULATION OF INDIVIDUAL SULFOTRANSFERASE ISOFORMS BY PHENOBARBITAL IN MALE RAT LIVER

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    This paper is available online at http://www.dmd.org ABSTRACT: Xenobiotics that induce the cytochromes P450 also produce changes in rat hepatic sulfotransferase (SULT) gene expression. In the present study, male Sprague-Dawley rats were treated for 3 consecutive days with doses of phenobarbital (PB) that induce cytochrome P450 2B1/2 expression. The effects of PB treatment on hepatic aryl SULT (SULT1) and hydroxysteroid SULT (SULT2) mRNA and immunoreactive protein levels and on mRNA expression of individual SULT1 and SULT2 enzyme isoforms were characterized. PB suppressed SULT1A1 mRNA levels, increased the expression of the SULT-Dopa/tyrosine isoform, and did not produce significant changes in SULT1C1 and SULT1E2 mRNA expression. In rats injected with the highest test dose of PB (100 mg/kg), hepatic SULT1A1 mRNA levels were decreased to ϳ42% of control levels and SULT-Dopa/tyrosine mRNA levels were increased to ϳ417% of vehicle-treated control levels. Like the SULT1 subfamily, individual members of the SULT2 gene subfamily were differentially affected by PB treatment. PB (35, 80, and 100 mg/kg) suppressed SULT20/21 mRNA expression to ϳ61, ϳ30, and ϳ41% of vehicle-treated control levels, respectively. In contrast, SULT60 mRNA levels were increased to ϳ162% of control levels and SULT40/41 mRNA levels were increased to ϳ416% of vehicletreated control levels in rats treated with 100 mg/kg PB. These studies support a complex role for PB-mediated effects on the SULT multigene family in rat liver. Because individual SULT1 and SULT2 enzyme isoforms are known to metabolize a variety of potentially toxic substrates, varied responses to PB among members of the SULT multigene family might have important implications for xenobiotic hepatotoxicity

    Peer Influence during Adolescence: The Moderating Role of Parental Support

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    Although many studies show that peers influence the development of adolescent internalizing and externalizing difficulties, few have considered both internalizing and externalizing difficulties in the same study, and fewer have considered the contributions of parents. Using a longitudinal sample of 385 adolescents, the contributions of best friends\u27 internalizing and externalizing difficulties (as assessed in Grade 6; G6: M(age) = 13.64 years; 53% female; 40% ethnic or racial minority) were examined as they predicted subsequent adolescent internalizing and externalizing difficulties (at G8); in addition, the moderating role of both maternal and paternal support (at G6) was explored. Structural equation modelling revealed that best friend internalizing difficulties predicted decreases, but that best friend externalizing difficulties predicted increases in adolescents\u27 externalizing difficulties over time. Significant interactions involving both maternal and paternal support revealed that the negative impact of a G6 best friend having internalizing problems on later G8 adolescent externalizing problems was stronger at low levels of maternal and paternal support. The findings highlight the complex, and interactive, influences of friends and parents on the development of internalizing and externalizing symptomatology during adolescence, and underscore the importance of targeting both sources of social influence in research and clinical work
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