Hospital usage of TOXBASE in Great Britain:Temporal trends in accesses 2008 to 2015

Aim: Examining temporal trends in accesses to the UK's National Poison Information Service's TOXBASE database in Britain. Methods: Generalised additive models were used to examine trends in daily numbers of accesses to TOXBASE from British emergency departments between January 2008 and December 2015. Day-of-the-week, seasonality and long term trends were analysed at national and regional levels (Wales, Scotland and the 9 English Government Office Regions). Results: The long-term trend in daily accesses increases from 2.8 (95% CI:2.6, 3.0) per user on 1st January 2008 to 4.6 (95% CI:4.3, 4.9) on 31st December 2015, with small but significant differences in population-corrected accesses by region (p<0.001). There are statistically significant seasonal and day of the week patterns (p<0.001) across all regions. Accesses are 18 % (95% CI:14%, 22%) higher in summer than in January and at the weekend compared to weekdays in all regions; there is a 7.5% (95% CI:6.1%, 8.9%) increase between Friday and Sunday. Conclusions: There are consistent in-year patterns in access to TOXBASE indicating potential seasonal patterns in poisonings in Britain, with location-dependant rates of usage. This novel descriptive work lays the basis for future work on the interaction of TOXBASE use with emergency admission of patients into hospital

Effect of Stretch Orientation and Rolling Orientation on the Mechanical Properties of 2195 Al-Cu-Li Alloy

Sheets of 2195 aluminum-lithium alloy were solution-treated at 507 A degrees C for 30 min. One set was stretched to 3-5% in the 0A degrees, 45A degrees, and 90A degrees angle with respect to the original rolling direction. Two other sets were rolled 6% reduction in thickness and 24% reduction in thickness in the 0A degrees, 45A degrees, and 90A degrees angle with respect to the original rolling direction. All specimens were aged at 143 A degrees C for 36 h. A second group of samples was rolled at 24 and 50% reduction in thickness after a solution treatment of 507 A degrees C for 1 h prior to aging at 190 A degrees C for 24 h. Tensile specimens were machined from each sheet at 0A degrees, 45A degrees, and 90A degrees angles to the original grain orientation. Tensile testing was used to determine the mechanical properties and anisotropic behavior of each condition. Rolling 6% reduction in thickness in the 45A degrees orientation yielded anisotropy of 7.6% in the yield strength

Cocaethylene: A neuropharmacologically active metabolite assciated with concurrent cocaine-ethanol ingestion

High concentrations of cocaethylene (EC), the ethyl ester of benzoylecgonine, were measured in the blood of individuals who had concurrently used cocaine and ethanol. Since the powerful reinforcing effects of cocaine appear to be dependent on inhibition of dopamine reuptake in brain, we compared the effects of EC on the dopamine uptake system and its behavioral effects with those of cocaine. EC was equipotent to cocaine with respect to inhibition of binding of [3H]GBR 12395 to the dopamine reuptake complex, inhibition of [3H]dopamine uptake into synaptosomes and in its ability to increase extracellular dopamine concentration in the nucleus accumbens following its systemic administration to rats. Moreover, in rats, EC and cocaine each increased locomotor activity and rearing to the same extent following i.p. administration. In self-administration studies in primates, EC was approximately equipotent to cocaine in maintaining responding. The in vivo formation of this active, transesterified ethyl homolog of cocaine may contribute to the effects and consequences of combined cocaine and ethanol abuse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29671/1/0000760.pd

Adsorption Isotherms of Hydrogen: The Role of Thermal Fluctuations

It is shown that experimentally obtained isotherms of adsorption on solid substrates may be completely reconciled with Lifshitz theory when thermal fluctuations are taken into account. This is achieved within the framework of a solid-on-solid model which is solved numerically. Analysis of the fluctuation contributions observed for hydrogen adsorption onto gold substrates allows to determine the surface tension of the free hydrogen film as a function of film thickness. It is found to decrease sharply for film thicknesses below seven atomic layers.Comment: RevTeX manuscript (3 pages output), 3 figure

Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials

BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802

Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions

xposing animal models of mental illness to addictive drugs provides an approach to understanding the neural etiology of dual diagnosis disorders. Previous studies have shown that neonatal ventral hippocampal lesions (NVHL) in rats produce features of both schizophrenia and addiction vulnerability. Objective This study investigated ventral and dorsal striatal dopamine (DA) efflux in NVHL rats combined with behavioral sensitization to cocaine. Methods Adult NVHL vs. SHAM-operated rats underwent a 5-day injection series of cocaine (15 mg/kg/day) vs. saline. One week later, rats were cannulated in nucleus accumbens SHELL, CORE, or caudate–putamen. Another week later, in vivo microdialysis sampled DA during locomotor testing in which a single cocaine injection (15 mg/kg) was delivered. Results NVHLs and cocaine history significantly increased behavioral activation approximately 2-fold over SHAM-saline history rats. DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient. However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.Conclusion Differences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history. These findings suggest other neurotransmitter systems, and alterations in striatal network function post-synaptic to DA transmission are more important to understanding the interactive effects of addictive drugs and mental illness

Differential serotonin transport is linked to the rh5-HTTLPR in peripheral blood cells

The human serotonin transporter (SERT) gene possesses a 43-base pair (bp) insertion-deletion promoter polymorphism, the h5-HTTLPR. Genotype at this locus correlates with variation in anxiety-related personality traits and risk for major depressive disorder in many studies. Yet, the complex effects of the h5-HTTLPR, in combination with closely associated single-nucleotide polymorphisms (SNPs), continue to be debated. Moreover, although SERT is of high clinical significance, transporter function in vivo remains difficult to assess. Rhesus express a promoter polymorphism related to the h5-HTTLPR. The rh5-HTTLPR has been linked to differences in stress-related behavior and cognitive flexibility, although allelic variations in serotonin uptake have not been investigated. We studied the serotonin system as it relates to the 5-HTTLPR in rhesus peripheral blood cells. Sequencing of the rh5-HTTLPR revealed a 23-bp insertion, which is somewhat longer than originally reported. Consistent with previous reports, no SNPs in the rh5-HTTLPR and surrounding genomic regions were detected in the individuals studied. Reductions in serotonin uptake rates, cell surface SERT binding, and 5-hydroxyindoleacetic acid/serotonin ratios, but not SERT mRNA levels, were associated with the rh5-HTTLPR short allele. Thus, serotonin uptake rates are differentiable with respect to the 5-HTTLPR in an easily accessible native peripheral tissue. In light of these findings, we foresee that primary blood cells, in combination with high sensitivity functional measurements enabled by chronoamperometry, will be important for investigating alterations in serotonin uptake associated with genetic variability and antidepressant responsiveness in humans