Frequency of cannabis and illicit opioid use among people who use drugs and report chronic pain: A longitudinal analysis.

BACKGROUND:Ecological research suggests that increased access to cannabis may facilitate reductions in opioid use and harms, and medical cannabis patients describe the substitution of opioids with cannabis for pain management. However, there is a lack of research using individual-level data to explore this question. We aimed to investigate the longitudinal association between frequency of cannabis use and illicit opioid use among people who use drugs (PWUD) experiencing chronic pain. METHODS AND FINDINGS:This study included data from people in 2 prospective cohorts of PWUD in Vancouver, Canada, who reported major or persistent pain from June 1, 2014, to December 1, 2017 (n = 1,152). We used descriptive statistics to examine reasons for cannabis use and a multivariable generalized linear mixed-effects model to estimate the relationship between daily (once or more per day) cannabis use and daily illicit opioid use. There were 424 (36.8%) women in the study, and the median age at baseline was 49.3 years (IQR 42.3-54.9). In total, 455 (40%) reported daily illicit opioid use, and 410 (36%) reported daily cannabis use during at least one 6-month follow-up period. The most commonly reported therapeutic reasons for cannabis use were pain (36%), sleep (35%), stress (31%), and nausea (30%). After adjusting for demographic characteristics, substance use, and health-related factors, daily cannabis use was associated with significantly lower odds of daily illicit opioid use (adjusted odds ratio 0.50, 95% CI 0.34-0.74, p < 0.001). Limitations of the study included self-reported measures of substance use and chronic pain, and a lack of data for cannabis preparations, dosages, and modes of administration. CONCLUSIONS:We observed an independent negative association between frequent cannabis use and frequent illicit opioid use among PWUD with chronic pain. These findings provide longitudinal observational evidence that cannabis may serve as an adjunct to or substitute for illicit opioid use among PWUD with chronic pain

PEX11β induces peroxisomal gene expression and alters peroxisome number during early Xenopus laevis development

<p>Abstract</p> <p>Background</p> <p>Peroxisomes are organelles whose roles in fatty acid metabolism and reactive oxygen species elimination have contributed much attention in understanding their origin and biogenesis. Many studies have shown that <it>de novo </it>peroxisome biogenesis is an important regulatory process, while yeast studies suggest that total peroxisome numbers are in part regulated by proteins such as Pex11, which can facilitate the division of existing peroxisomes. Although <it>de novo </it>biogenesis and divisions are likely important mechanisms, the regulation of peroxisome numbers during embryonic development is poorly understood. Peroxisome number and function are particularly crucial in oviparous animals such as frogs where large embryonic yolk and fatty acid stores must be quickly metabolized, and resulting reactive oxygen species eliminated. Here we elucidate the role of Pex11β in regulating peroxisomal gene expression and number in <it>Xenopus laevis </it>embryogenesis.</p> <p>Results</p> <p>Microinjecting haemagglutinin (HA) tagged Pex11β in early embryos resulted in increased RNA levels for peroxisome related genes PMP70 and catalase at developmental stages 10 and 20, versus uninjected embryos. Catalase and PMP70 proteins were found in punctate structures at stage 20 in control embryos, whereas the injection of ectopic HA-Pex11β induced their earlier localization in punctate structures at stage 10. Furthermore, the peroxisomal marker GFP-SKL, which was found localized as peroxisome-like structures at stage 20, was similarly found at stage 10 when co-microinjected with HA-Pex11β.</p> <p>Conclusions</p> <p>Overexpressed Pex11β altered peroxisomal gene levels and induced the early formation of peroxisomes-like structures during development, both of which demonstrate that Pex11β may be a key regulator of peroxisome number in early Xenopus embryos.</p

Automated Repair of Layout Cross Browser Issues Using Search-Based Techniques

A consistent cross-browser user experience is crucial for the success of a website. Layout Cross Browser Issues (XBIs) can severely undermine a website’s success by causing web pages to render incorrectly in certain browsers, thereby negatively impacting users’ impression of the quality and services that the web page delivers. Existing Cross Browser Testing (XBT) techniques can only detect XBIs in websites. Repairing them is, hitherto, a manual task that is labor intensive and requires significant expertise. Addressing this concern, our paper proposes a technique for automatically repairing layout XBIs in websites using guided search-based techniques. Our empirical evaluation showed that our approach was able to successfully fix 86% of layout XBIs reported for 15 different web pages studied, thereby improving their cross-browser consistency

Beneficial hemodynamic effects of intravenous and oral diltiazem in severe congestive heart failure

Concern persists about the potential negative inotropic effects of calcium channel blockers in patients with severely depressed myocardial function. Therefore, intravenous diltiazem (100 to 200 ltg/kg per min infusion) was administered for 40 minutes followed by oral diltiazem (90 to 120 mg/8 hours) for 24 hours to patients with advanced congestive heart failure (New York Heart Association class III to IV, mean ejection fraction 26 ± 4 [SD]). Intravenous diltiazem (eight patients) increased cardiac index 20% (2.05 ± 0.8 to 2.47 ± 0.8 liters/min per MZ, p < 0.01), stroke volume index 50% (22 ± 9 to 33 ± 12 MI/M2, p < 0.001) and stroke work index 27% (19 ± 10 to 24 ± 10 g-m/MZ, p < 0.05); while reducing heart rate 23% (97 ± 18 to 75 ± 11 beats/min, p < 0.01), mean arterial pressure 18% (95 ± 13 to 78 ± 7 mm Hg) and pulmonary wedge pressure 34% (29 ± 9 to 19 ± 7 mm Hg), without altering maximal first derivative of left ventricular pressure (dP/dtmax). Oral diltiazem (seven patients) produced equivalent hemodynamic effects. Transient junctional arrhythmias were observed in three of eight patients with intravenous diltiazem and one of seven patients with oral diltiazem.It is concluded that intravenous and short-term oral diltiazem improve left ventricular performance and reduce myocardial oxygen demand by heart rate and afterload reduction without significantly depressing contractile function in severe congestive heart failure. Caution should be exercised to avoid potential adverse, druginduced electrophysiologic effects in such patients

The gas-phase reaction of NH2 with formaldehyde (CH2O) is not a source of formamide (NH2CHO) in interstellar environments

The first experimental study of the low-temperature kinetics of the gas-phase reaction of NH2 with formaldehyde (CH2O) has been performed. This reaction has previously been suggested as a source of formamide (NH2CHO) in interstellar environments. A pulsed Laval nozzle equipped with laser-flash photolysis and laser-induced fluorescence spectroscopy was used to create and monitor the temporal decay of NH2 in the presence of CH2O. No loss of NH2 could be observed via reaction with CH2O and we place an upper-limit on the rate coefficient of <6x10-12 cm3 molecule-1 s-1 at 34K. Ab initio calculations of the potential energy surface were combined with RRKM calculations to predict a rate coefficient of 6.2x10-14 cm3 molecule-1 s-1 at 35K, consistent with the experimental results. The presence of a significant barrier, 18 kJ mol-1, for the formation of formamide as a product, means that only the H-abstraction channel producing NH3 + CHO, in which the transfer of an H-atom can occur by quantum mechanical tunnelling through a 23 kJ mol-1 barrier, is open at low temperatures. These results are in contrast with a recent theoretical study which suggested that the reaction could proceed without a barrier and was therefore a viable route to gas-phase formamide formation. The calculated rate coefficients were used in an astrochemical model which demonstrated that this reaction produces only negligible amounts of gas-phase formamide under interstellar and circumstellar conditions. The reaction of NH2 with CH2O is therefore not an important source of formamide at low temperatures in interstellar environments.Comment: Manuscript, 14 pages, 4 figures. Supporting Information, 8 pages, 2 figures. Accepted for publication in The Astrophysical Journal Letter

Genetic and biochemical characterization of a novel metallo-beta-lactamase, TMB-1, from an Achromobacter xylosoxidans strain isolated in Tripoli, Libya

An Achromobacter xylosoxidans strain from the Tripoli central hospital produced a unique metallo-β-lactamase, designated TMB-1, which is related to DIM-1 (62%) and GIM-1 (51%). bla was embedded in a class 1 integron and located on the chromosome. The TMB-1β-lactamase has lower k values than both DIM-1 and GIM-1 with cephalosporins and carbapenems. The K values were more similar to those of GIM-1 than those of DIM-1, with the overall k /K values being lower than those for GIM-1 and DIM-1. Copyrigh