New approaches build upon historical studies in dermal toxicology

\ua9 2023 Royal Society of Chemistry. All rights reserved.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)

Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay

Background: Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) is a common reactive oxygen intermediate generated by various forms of oxidative stress. Aim: The aim of this study was to investigate the DNA damage capacity of H<sub>2</sub>O<sub>2</sub> in HepG2 cells. Methods: Cells were treated with H<sub>2</sub>O<sub>2</sub> at concentrations of 25 mM or 50 mM for 5 min, 30 min, 40 min, 1 h, or 24 h in parallel. The extent of DNA damage was assessed by the comet assay. Results: Compared to the control, DNA damage by 25 and 50 mM H<sub>2</sub>O<sub>2</sub> increased significantly with increasing incubation time up to 1 h, but it was not increased at 24 h. Conclusions: Our findings confirm that H<sub>2</sub>O<sub>2</sub> is a typical DNA damage-inducing agent and thus is a good model system to study the effects of oxidative stress. DNA damage in HepG2 cells increased significantly with H<sub>2</sub>O<sub>2</sub> concentration and time of incubation but later decreased likely due to DNA repair mechanisms and antioxidant enzymes.Keywords: DNA damage; hydrogen peroxide; HepG2 cells; comet assa

Ultrasonic NDT Prototype for the Inspection of Ducted Post Stressing Tendons in Concrete Beams

There is worldwide concern about concrete bridges which derive their strength from post stressed steel tendons in grouted ducts. Problems arise when grouting has not been carried out properly, since the combination of voided regions and moisture penetration can cause corrosion of the tendon and catastrophic failure of the structure [1]. Post tensioned bridges built during the middle of this century are particularly susceptible and there is a pressing need for a cost effective non destructive means of assessing the condition of the embedded ducts and tendons. In response to this problem, a track mounted ultrasonic scanning system ‘CANDI’ (Cable Analysis by Non Destructive Inspection) is currently under development in UMIST, and this work describes the CANDI prototype and results obtained

Draft genome sequence of Enterobacter sp. strain EA-1, an electrochemically active microorganism isolated from tropical sediment

© 2018 Doyle et al. Enterobacter sp. strain EA-1 is an electrochemically active bacterium isolated from tropical sediment in Singapore. Here, the annotated draft genome assembly of the bacterium is reported. Whole-genome comparison indicates that Enterobacter sp. EA-1, along with a previously sequenced Enterobacter isolate from East Asia, forms a distinct clade within the Enterobacter genus

Risk prediction models for colorectal cancer in people with symptoms: a systematic review.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related death in Europe and the United States. Detecting the disease at an early stage improves outcomes. Risk prediction models which combine multiple risk factors and symptoms have the potential to improve timely diagnosis. The aim of this review is to systematically identify and compare the performance of models that predict the risk of primary CRC among symptomatic individuals. We searched Medline and EMBASE to identify primary research studies reporting, validating or assessing the impact of models. For inclusion, models needed to assess a combination of risk factors that included symptoms, present data on model performance, and be applicable to the general population. Screening of studies for inclusion and data extraction were completed independently by at least two researchers. Twelve thousand eight hundred eight papers were identified from the literature search and three through citation searching. 18 papers describing 15 risk models were included. Nine were developed in primary care populations and six in secondary care. Four had good discrimination (AUROC > 0.8) in external validation studies, and sensitivity and specificity ranged from 0.25 and 0.99 to 0.99 and 0.46 depending on the cut-off chosen. Models with good discrimination have been developed in both primary and secondary care populations. Most contain variables that are easily obtainable in a single consultation, but further research is needed to assess clinical utility before they are incorporated into practice.JUS is funded by a National Institute of Health Research (NIHR) Clinica

Serum aspirin esterase is strongly associated with glucose and lipids in healthy subjects: different association patterns in subjects with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Aspirin esterase (AE) activity can account for part of aspirin pharmacokinetics in the circulation, possibly being associated with the impairment of aspirin effectiveness as an inhibitor of platelet aggregation.</p> <p>Aims</p> <p>The study was aimed at investigating the correlations of serum AE activity with cholinesterase (ChE) and metabolic variables in healthy subjects in comparison to subjects with type 2 diabetes mellitus (T2DM).</p> <p>Methods</p> <p>In cardiovascular disease-free T2DM subjects and healthy controls, the AE activity levels and/or the correlation patterns between AE and the other variables were analyzed.</p> <p>Results</p> <p>Neither AE nor ChE activities were higher in the subjects with T2DM. Serum AE activity strongly correlated with ChE as well as glucose/lipids variables such as total cholesterol and triglyceride in healthy subjects, while the correlations between AE and glucose/lipids variables were not present in T2DM subjects.</p> <p>Conclusions</p> <p>These data may reflect the pathophysiological changes between healthy and T2DM subjects. Our data may thus provide the basis for future studies to unravel the mechanisms.</p

The effect of distance on reaction time in aiming movements

Target distance affects movement duration in aiming tasks but its effect on reaction time (RT) is poorly documented. RT is a function of both preparation and initiation. Experiment 1 pre-cued movement (allowing advanced preparation) and found no influence of distance on RT. Thus, target distance does not affect initiation time. Experiment 2 removed pre-cue information and found that preparing a movement of increased distance lengthens RT. Experiment 3 explored movements to targets of cued size at non-cued distances and found size altered peak speed and movement duration but RT was influenced by distance alone. Thus, amplitude influences preparation time (for reasons other than altered duration) but not initiation time. We hypothesise that the RT distance effect might be due to the increased number of possible trajectories associated with further targets: a hypothesis that can be tested in future experiments

Advances in prevention and therapy of neonatal dairy calf diarrhoea : a systematical review with emphasis on colostrum management and fluid therapy

Neonatal calf diarrhoea remains the most common cause of morbidity and mortality in preweaned dairy calves worldwide. This complex disease can be triggered by both infectious and non-infectious causes. The four most important enteropathogens leading to neonatal dairy calf diarrhoea are Escherichia coli, rota-and coronavirus, and Cryptosporidium parvum. Besides treating diarrhoeic neonatal dairy calves, the veterinarian is the most obvious person to advise the dairy farmer on prevention and treatment of this disease. This review deals with prevention and treatment of neonatal dairy calf diarrhoea focusing on the importance of a good colostrum management and a correct fluid therapy

Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile

Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox

This article discusses three statistical paradoxes that pervade epidemiological research: Simpson's paradox, Lord's paradox, and suppression. These paradoxes have important implications for the interpretation of evidence from observational studies. This article uses hypothetical scenarios to illustrate how the three paradoxes are different manifestations of one phenomenon – the reversal paradox – depending on whether the outcome and explanatory variables are categorical, continuous or a combination of both; this renders the issues and remedies for any one to be similar for all three. Although the three statistical paradoxes occur in different types of variables, they share the same characteristic: the association between two variables can be reversed, diminished, or enhanced when another variable is statistically controlled for. Understanding the concepts and theory behind these paradoxes provides insights into some controversial or contradictory research findings. These paradoxes show that prior knowledge and underlying causal theory play an important role in the statistical modelling of epidemiological data, where incorrect use of statistical models might produce consistent, replicable, yet erroneous results