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Each of 4 male alcoholic subjects received 0.7 mg/kg calcium carbimide (CC) orally 12 hr before ingestion of 0.25 gm/kg ethanol on 3 separate occasions. The CC-ethanol interaction consisted of increased blood acetaldehyde level and elevated heart rate. For each individual there was small variability in the area under the curve (AUC) values of the blood ethanol level--time course profiles for the 3 experiments, indicating a consistent extent of ethanol absorption. For subjects 1, 2, and 3 there was appreciable intraindividual variability in the AUC and the peak blood acetaldehyde levels of the blood acetaldehyde level--time course curves; the variation in these parameters was small for subjects 4. The intraindividual variability in the peak heart rate response was small for subjects 1 and 2 and appreciable for subjects 3 and 4. Regression analysis of the blood acetaldehyde level--heart rate data for each of the 3 experiments conducted on the 4 subjects revealed that there were positive, linear correlations. There was appreciable intraindividual variability in the slope values for the 3 experiments. The results of this study, conducted on 4 male alcoholics, suggest that for other alcoholic subjects there could be appreciable intraindividual variability in the intensity of the CC-ethanol interaction.

Aims The aim of this study was to determine whether the sequential application of povidone iodine-alcohol (PVI) followed by chlorhexidine gluconate-alcohol (CHG) would reduce surgical wound contamination to a greater extent than PVI applied twice in patients undergoing spinal surgery. Patients and Methods A single-centre, interventional, two arm, parallel group randomised controlled trial was undertaken, involving 407 patients who underwent elective spinal surgery. For 203 patients, the skin was disinfected before surgery using PVI (10% [w/w (1% w/w available iodine)] in 95% industrial denatured alcohol, povidone iodine; Videne Alcoholic Tincture) twice, and for 204 patients using PVI once followed by CHG (2% [w/v] chlorhexidine gluconate in 70% [v/v] isopropyl alcohol; Chloraprep with tint). The primary outcome measure was contamination of the wound determined by aerobic and anaerobic bacterial growth from samples taken after disinfection. Results The detection of viable bacteria in any one of the samples taken after disinfection (culture-positive) was significantly lower in the group treated with both PVI and CHG than in the group treated with PVI alone (59 (29.1%) versus 85 (41.7%), p = 0.009; odds ratio 0.574; 95% confidence interval, 0.380 to 0.866). Conclusions Antisepsis of the skin with the sequential application of PVI and CHG more effectively reduces the contamination of a surgical wound than PVI alone. Cite this article: Bone Joint J 2017;99-B:1354–65.

Background and purpose:The contribution of endothelin‐1 (ET‐1) to vascular hyper‐reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated.Experimental approach:The biphasic haemodynamic responses to ET‐1 (0.01–0.1 nmol kg−1, i.v.) or to the selective ETB agonist, IRL1620 (0.001–1.0 nmol kg−1, i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp‐Dasp‐Pro‐Dval‐Leu)) at 1 and 2.5 mg kg−1 and BQ788 (N‐cis‐2,6‐dimethyl‐piperidinocarbonyl‐L‐γ‐methylleucyl1‐D‐1methoxycarbonyltryptophanyl‐D‐norleucine) at 0.25 mg kg−1, respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined.Key results:The initial hypotensive responses to ET‐1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET‐1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg−1 reduced the pressor responses to ET‐1 in ethanol‐treated rats. Conversely, BQ788 (0.25 mg kg−1) potentiated ET‐1‐induced increases in mean arterial blood pressure in control as well as in ethanol‐treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET‐1 at a dose of 0.025 mg kg−1 were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol.Conclusions and implications:Increased vascular reactivity to ET‐1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.British Journal of Pharmacology (2008) 154, 971–981; doi:10.1038/bjp.2008.157; published online 12 May 2008

AbstractBackground and aimsCannabis and alcohol are frequently detected in fatal and injury motor vehicle crashes. While epidemiological meta‐analyses of cannabis and alcohol have found associations with an increase in crash risk, convergent evidence from driving performance measures is insufficiently quantitatively characterized. Our objectives were to quantify the magnitude of the effect of cannabis and alcohol—alone and in combination—on driving performance and behaviour.MethodsSystematic review and meta‐analysis. We systematically searched Academic Search Complete, CINAHL, Embase, Scopus, Google Scholar, MEDLINE, PsycINFO, SPORTDiscus and TRID. Of the 616 studies that underwent full‐text review, this meta‐analysis represents 57 studies and 1725 participants. We extracted data for hazard response time, lateral position variability, lane deviations or excursions, time out of lane, driving speed, driving speed variability, speed violations, time speeding, headway, headway variability and crashes from experimental driving studies (i.e. driving simulator, closed‐course, on‐road) involving cannabis and/or alcohol administration. We reported meta‐analyses of effect sizes using Hedges’ g and r.ResultsCannabis alone was associated with impaired lateral control [e.g. g = 0.331, 95% confidence interval (CI) = 0.212–0.451 for lateral position variability; g = 0.198, 95% CI = 0.001–0.395 for lane excursions) and decreased driving speed (g = –0.176, 95% CI = –0.298 to –0.053]. The combination of cannabis and alcohol was associated with greater driving performance decrements than either drug in isolation [e.g. g = 0.480, 95% CI = 0.096–0.865 for lateral position variability (combination versus alcohol); g = 0.525, 95% CI = 0.049–1.002 for time out of lane (versus alcohol); g = 0.336, 95% CI = 0.036–0.636 for lateral position variability (combination versus cannabis; g = 0.475, 95% CI = 0.002–0.949 for time out of lane (combination versus cannabis)]. Subgroup analyses indicated that the effects of cannabis on driving performance measures were similar to low blood alcohol concentrations. A scarcity of data and study heterogeneity limited the interpretation of some measures.ConclusionsThis meta‐analysis indicates that cannabis, like alcohol, impairs driving, and the combination of the two drugs is more detrimental to driving performance than either in isolation.

Failure to successfully implement and sustain change over the long term continues to be a major problem in health and social care. Translating evidence into routine clinical practice is notoriously complex, and it is recognised that to implement new evidence-based interventions and sustain them over time, professional behaviour needs to change accordingly. A number of theories and frameworks have been developed to support behaviour change among health and social care professionals, and models of sustainability are emerging, but few have translated into valid and reliable interventions. The long-term success of healthcare professional behavioural change interventions is variable, and the characteristics of successful interventions unclear. Previous reviews have synthesised the evidence for behaviour change, but none have focused on sustainability. In addition, multiple overlapping reviews have reported inconsistent results, which do not aid translation of evidence into practice. Overviews of reviews can provide accessible succinct summaries of evidence and address barriers to evidence-based practice. We aim to compile an overview of reviews, identifying, appraising and synthesising evidence relating to sustained social and healthcare professional behaviour change.We will conduct a systematic review of Cochrane reviews (an Overview). We plan to systematically search the Cochrane Database of Systematic Reviews. We will include all systematic reviews of randomised controlled trials comparing a healthcare professional targeted behaviour change intervention to a standard care or no intervention control group. Two reviewers will independently assess the eligibility of the reviews and the methodological quality of included reviews using the ROBIS tool. The quality of evidence within each comparison in each review will be judged based on the GRADE criteria. Disagreements will be resolved through discussion. Effects of interventions will be systematically tabulated and the quality of evidence used to determine implications for clinical practice and make recommendations for future research.This overview will bring together the best available evidence relating to the sustainability of health professional behaviour change, thus supporting policy makers with decision-making in this field.

This study was designed to test the hypothesis that chronic prenatal ethanol exposure decreases basal and stimulated L-glutamate release in the hippocampus of young, postnatal guinea pigs. Timed, pregnant guinea pigs were randomly assigned to one of the following three chronic treatment groups: 4 g ethanol/kg maternal body weight/day, isocaloric-sucrose and pair-feeding to the ethanol group, and water. Each oral treatment was given daily throughout gestation. Spontaneous locomotor activity was increased on postnatal day (PD) 10, and brain and hippocampal weights were decreased on PD 12 in the offspring of the ethanol group compared with the isocaloric-sucrose/pair-fed and water groups. On PD 12, the 45 mM K(+)- and 10 microM veratridine-stimulated release of glutamate in transverse hippocampal slices was decreased in the ethanol group compared with the two control groups. This alteration in glutamate release produced by chronic prenatal ethanol exposure may decrease the efficiency of excitatory synaptic transmission in the hippocampus during postnatal life.

Alcoholism and alcohol abuse represent a significant medical and societal problem, and have been thoroughly investigated in humans as well as using animal models. A less well understood aspect of alcohol related disorders is the possible effect of this drug on offspring whose parents were exposed prior to conception. The zebrafish has been successfully employed in alcohol research, however, the effect of exposing the parents to alcohol before fertilization of the eggs on offspring has not been demonstrated in this species. In this proof of concept study, we attempt to address this hiatus. We exposed both adult male and female zebrafish to 0.0% (control) or 0.5% (vol/vol) alcohol chronically for 7 days, subsequently bred the fish within their respective treatment group, collected the fertilized eggs, allowed them to develop, and tested the behavior of free-swimming offspring at their age of 7-9 days post-fertilization. We conducted the analysis in two genetically distinct quasi-inbred strains of zebrafish, AB and TL. Although gross morphology and general activity of the fish appeared unaffected, we found significant behavioral alterations in offspring of alcohol exposed parents compared to offspring of control parents in both strains. These alterations included robustly increased duration and reduced frequency of immobility, increased turn angle, and increased intra-individual variance of turn angle in offspring of alcohol exposed parents in both strains. The mechanisms underlying these behavioral effects or whether the effects are due to exposure of the father, the mother, or both to alcohol are unknown. Nevertheless, our results now set the stage for future studies with zebrafish that will address these questions.

Miniaturization of electrochemical detection ofPseudomonas aeruginosaquorum sensing molecules at a liquid/liquid interface through facilitated proton transfer reactions.