An approach to testing undiluted e-cigarette aerosol in vitro using 3D reconstituted human airway epithelium.

The data presented here show that to provide an estimate of the relative cytotoxicity and therefore potency of e-cigarettes, undiluted aerosol techniques can be used. With the emergence of electronic nicotine delivery systems, fit-for-purpose in vitro screening methods are required. Reconstituted 3D human airway epithelium, was exposed to undiluted aerosols at the air-liquid interface, using a Vitrocell VC 10. TEER, cilia beat frequency and cytotoxic responses were assessed. Using two smoking regimes (ISO and HCI) a 3R4F reference cigarette, produced IC50s of 5.2 and 2.1 min, 1458 ng/mL and 1640 ng/mL nicotine respectively. Using an open tank e-cigarette device, a full cytotoxicity dose-response curve was obtained giving an IC50 of 30 min with corresponding nicotine of 10,957 ng/mL, 6-14 times less cytotoxic than cigarette smoke. A commonly used e-liquid flavourant cinnamaldehyde and known skin sensitizer was added to the standard e-liquid formulation and used as an aerosolised positive control, at 0.1, 0.025, 0.01 and 0%, demonstrating a full dose response. The delivery of undiluted aerosols in vitro has resulted in increased method sensitivity, throughput and quantitative e-cigarette comparisons. A positive control aerosol generated from a 'safe' e-liquid benchmark can inform risk assessments on supportable levels of flavour ingredients.

High-intensity interval training for improving health-related fitness in adolescents: a systematic review and meta-analysis.

BACKGROUND: High-intensity interval training (HIIT) may be a feasible and efficacious strategy for improving health-related fitness in young people. The objective of this systematic review and meta-analysis was to evaluate the utility of HIIT to improve health-related fitness in adolescents and to identify potential moderators of training effects. METHODS: Studies were considered eligible if they: (1) examined adolescents (13-18 years); (2) examined health-related fitness outcomes; (3) involved an intervention of ≥4 weeks in duration; (4) included a control or moderate intensity comparison group; and (5) prescribed high-intensity activity for the HIIT condition. Meta-analyses were conducted to determine the effect of HIIT on health-related fitness components using Comprehensive Meta-analysis software and potential moderators were explored (ie, study duration, risk of bias and type of comparison group). RESULTS: The effects of HIIT on cardiorespiratory fitness and body composition were large, and medium, respectively. Study duration was a moderator for the effect of HIIT on body fat percentage. Intervention effects for waist circumference and muscular fitness were not statistically significant. CONCLUSIONS: HIIT is a feasible and time-efficient approach for improving cardiorespiratory fitness and body composition in adolescent populations.

An approach to ingredient screening and toxicological risk assessment of flavours in e-liquids.

Flavour ingredients are an essential part of e-liquids. Their responsible selection and inclusion levels in e-liquids must be guided by toxicological principles. We propose an approach to the screening and toxicological risk assessment of flavour ingredients for e-liquids. The screening involves purity requirements and avoiding ingredients that are carcinogenic, mutagenic or toxic to reproduction. Additionally, owing to the uncertainties involved in potency determination and the derivation of a tolerable level for respiratory sensitisation, we propose excluding respiratory sensitisers. After screening, toxicological data on the ingredients should be reviewed. Inhalation-specific toxicological issues, for which no reliable safe levels can currently be derived, can lead to further ingredient exclusions. We discuss the use of toxicological thresholds of concern for flavours that lack inhalation data suitable for quantitative risk assessment. Higher toxicological thresholds of concern are suggested for flavour ingredients (170 or 980µg/day) than for contaminant assessment (1.5µg/day). Analytical detection limits for measurements of potential reaction and thermal breakdown products in vaping aerosol, should be informed by the contaminant threshold. This principle leads us to recommend 5ng/puff as an appropriate limit of detection for untargeted aerosol measurements.

Preliminary efficacy and feasibility of embedding high intensity interval training into the school day: A pilot randomized controlled trial.

Current physical activity and fitness levels among adolescents are low, increasing the risk of chronic disease. Although the efficacy of high intensity interval training (HIIT) for improving metabolic health is now well established, it is not known if this type of activity can be effective to improve adolescent health. The primary aim of this study is to assess the effectiveness and feasibility of embedding HIIT into the school day. A 3-arm pilot randomized controlled trial was conducted in one secondary school in Newcastle, Australia. Participants (n = 65; mean age = 15.8(0.6) years) were randomized into one of three conditions: aerobic exercise program (AEP) (n = 21), resistance and aerobic exercise program (RAP) (n = 22) and control (n = 22). The 8-week intervention consisted of three HIIT sessions per week (8-10 min/session), delivered during physical education (PE) lessons or at lunchtime. Assessments were conducted at baseline and post-intervention to detect changes in cardiorespiratory fitness (multi-stage shuttle-run), muscular fitness (push-up, standing long jump tests), body composition (Body Mass Index (BMI), BMI-z scores, waist circumference) and physical activity motivation (questionnaire), by researchers blinded to treatment allocation. Intervention effects for outcomes were examined using linear mixed models, and Cohen's d effect sizes were reported. Participants in the AEP and RAP groups had moderate intervention effects for waist circumference (p = 0.024), BMI-z (p = 0.037) and BMI (not significant) in comparison to the control group. A small intervention effect was also evident for cardiorespiratory fitness in the RAP group.

Science into policy: preparing for pandemic influenza.

Authoratative government pandemic preparedness requires an evidence-based approach. The scientific advisory process that has informed the current UK pandemic preparedness plans is described. The final endorsed scientific papers are now publicly available.

Estimations of lipid bilayer geometry in fluid lamellar phases.

The excess water bilayer thickness, d(l,0), and molecular area, A(0), of lipid amphiphiles in the fluid lamellar phases of dioleoylphosphatidylcholine (DOPC) and dipalmitoleoylphosphatidylcholine (DPolPC) have been estimated between 15 and 50 degrees C and for dimyristoylphosphatidylcholine (DMPC) between 25 and 50 degrees C. These determinations have been made from X-ray measurements on samples of known water composition. With respect to temperature, T, d(l,0) and A(0) are well fitted to a linear equation. We find d(l,0) (A)=(35.68+/-0.02)-(0.0333+/-0.0006)T (degrees C) and A(0) (A(2))=(70.97+/-0.05)+(0.136+/-0.001)T (degrees C) for DOPC, d(l,0) (A)=(35.2+/-0.1)-(0.068+/-0.003)T (degrees C) and A(0) (A(2))=(59.7+/-0.2)+(0.210+/-0.006)T (degrees C) for DMPC, and d(l,0) (A)=(34.54+/-0.03)-(0.0531+/-0.0009)T (degrees C) and A(0) (A(2))=(67.12+/-0.09)+(0.173+/-0.003)T (degrees C) for DPolPC. The accuracy of these estimates depends largely on how accurately the excess water point is determined. Ideally, reliable X-ray and compositional data will be available around the excess water and it may be found by simple inspection, but this is the exception rather than the rule, since samples close to water excess normally sequester sizeable amounts of water in defects, which lead to an underestimate of d(l,0). and overestimate of A(0). In this paper, we report a methodology for identifying and removing such data points and fitting the remaining data in order to determine the excess water point.

Dural puncture: the patients' perspective. A patient survey of cases at a DGH maternity unit 1983-1993.

BACKGROUND: This study was designed to investigate the patient experience following accidental dural puncture complicating obstetric epidural analgesia. METHODS: Sixty-three patients who had suffered from accidental dural puncture during obstetric epidural analgesia over a ten-year period were sent a questionnaire enquiring about their experiences. 68% responded. RESULTS: Headache was the most severe symptom, occurring in 86% of this group; it lasted for a median of eight days and recurred after discharge in 47%. Backache occurred in 70% and 58% suffered with backache following discharge. Headache was considered to be the worst aspect by 49% of responders, backache by 19% and bedrest by 33%. Bed rest was frequently voluntary (as opposed to being enforced on medical orders) since many patients only gained relief from their headache when supine. Twenty patients (47%) received a blood patch, which was effective in relieving headache in 14 patients; however, the headache recurred after discharge in 10 of these 14 patients. Only 8 patients (19%) stated that they were aware of the risk of dural puncture prior to their epidural, three of whom were members of paramedical professions. CONCLUSIONS: Headache and backache are both common following dural puncture with a 16 G needle and both frequently recur after discharge from hospital. It was the strongly expressed opinion of this selected group that all mothers should be warned of the risk of dural puncture before undergoing epidural analgesia.

Photoregulation of beta-Tubulin mRNA Abundance in Etiolated Oat and Barley Seedlings.

The effect of light on the abundance of beta-tubulin mRNA was measured in etiolated Avena sativa L. and Hordeum vulgare L. seedlings. Slot blot analysis employing an oat beta-tubulin cDNA clone was used to measure beta-tubulin mRNA levels. White light induced a 45% decrease in oat beta-tubulin mRNA abundance by 2 hours after transfer. A saturating red light pulse induced 40 and 55% decreases in beta-tubulin mRNA levels in oats and barley, respectively. Recovery of beta-tubulin mRNA levels was observed after a red light pulse but not after transfer to continuous white light. The red light induced decrease in oat beta-tubulin mRNA abundance was not reversible by a subsequent far-red light treatment. The mesocotyl portion of etiolated oat seedlings exhibited a more dramatic decrease in beta-tubulin mRNA abundance in response to red light than did the coleoptile portion. The results indicate that the well-documented effects of red light on the growth of etiolated seedlings are accompanied by changes in the expression of the beta-tubulin genes.