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The brain endocannabinoid system is believed to play significant roles in anti-nociception, fear response, anxiety, and stress. This study investigated the effects of rat inguinal surgery on the levels of endocannabinoids in the cerebral cortex.
The aim of this study was to investigate the effects of acute post-surgical pain on the levels of endocannabinoids in the cerebral cortex.
Quantitation of endocannabinoids in the rat cerebral cortex was performed by liquid chromatography–tandem mass spectrometry.
There was no significant difference in the cerebral cortical levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) between the sham and surgery experimental groups. However, there were lateralized differences in the levels of these endocannabinoids between the right and left cerebral cortices irrespective of the two groups. The concentrations of AEA and 2-AG were significantly higher in the right cerebral cortex compared to the contralateral cerebral cortex.
Acute post-surgical pain did not induce significant alterations in the cerebral cortical levels of endocannabinoids in this study, but the phenomenon of lateralization of the cerebral cortical AEA and 2-AG levels was observed; this latter finding may be related to the role played by endocannabinoids in fear conditioning.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
The study examined (a) whether alcohol use subgroups could be identified among African Americans assessed from adolescence through early adulthood, and (b) whether subgroup membership was associated with the interaction between internalizing symptoms and antisocial behavior polygenic risk scores (PRSs) and environmental characteristics (i.e., parental monitoring, community disadvantage). Participants (N = 436) were initially recruited for an elementary school-based prevention trial in a Mid-Atlantic city. Youths reported on the frequency of their past year alcohol use from ages 14–26. DNA was obtained from participants at age 21. Internalizing symptoms and antisocial behavior PRSs were created based on a genome-wide association study (GWAS) conducted by Benke et al. (2014) and Tielbeek et al. (2017), respectively. Parental monitoring and community disadvantage were assessed at age 12. Four classes of past year alcohol use were identified: (a) early-onset, increasing; (b) late-onset, moderate use; (c) low steady; and (d) early-onset, decreasing. In high community disadvantaged settings, participants with a higher internalizing symptoms PRS were more likely to be in the early-onset, decreasing class than the low steady class. When exposed to elevated community disadvantage, participants with a higher antisocial behavior PRS were more likely to be in the early-onset, increasing class than the early-onset, decreasing and late-onset, moderate use classes.
In this cohort of Escherichia coli and Klebsiella spp hospital-onset bacteremia, isolated fluoroquinolone resistance had a larger relative impact on mortality than other phenotypic resistance patterns. This finding may support stewardship efforts targeting unnecessary fluoroquinolone use and increased attention from infection prevention and control departments.
Species distribution models (SDMs) are statistical tools used to develop continuous predictions of species occurrence. ‘Integrated SDMs’ (ISDMs) are an elaboration of this approach with potential advantages that allow for the dual use of opportunistically collected presence-only data and site-occupancy data from planned surveys. These models also account for survey bias and imperfect detection through the use of a hierarchical modelling framework that separately estimates the species–environment response and detection process. This is particularly helpful for conservation applications and predictions for rare species, where data are often limited and prediction errors may have significant management consequences. Despite this potential importance, ISDMs remain largely untested under a variety of scenarios. We performed an exploration of key modelling decisions and assumptions on an ISDM using the endangered Baird’s tapir (Tapirus bairdii) as a test species. We found that site area had the strongest effect on the magnitude of population estimates and underlying intensity surface and was driven by estimates of model intercepts. Selecting a site area that accounted for the individual movements of the species within an average home range led to population estimates that coincided with expert estimates. ISDMs that do not account for the individual movements of species will likely lead to less accurate estimates of species intensity (number of individuals per unit area) and thus overall population estimates. This bias could be severe and highly detrimental to conservation actions if uninformed ISDMs are used to estimate global populations of threatened and data-deficient species, particularly those that lack natural history and movement information. However, the ISDM was consistently the most accurate model compared to other approaches, which demonstrates the importance of this new modelling framework and the ability to combine opportunistic data with systematic survey data. Thus, we recommend researchers use ISDMs with conservative movement information when estimating population sizes of rare and data-deficient species. ISDMs could be improved by using a similar parameterization to spatial capture–recapture models that explicitly incorporate animal movement as a model parameter, which would further remove the need for spatial subsampling prior to implementation.
Advance care planning (ACP) is identified as being an important process for people with dementia. However, its efficacy for improving outcomes relevant for the individual, carers and the health system has yet to be established.
We conducted a systematic review with the aims of testing the efficacy of ACP for people with dementia and describing the settings and population in which it has been evaluated.
A search was completed of electronic databases in August 2016. Articles were included if they described interventions aimed at increasing planning for future care of people with dementia, delivered to the person with dementia, their carers and/or health professionals.
Of 4,772 articles returned by searches, 30 met the inclusion criteria, testing interventions in nursing home (n= 16) community (n = 10) and acute care (n = 4) settings. Only 18 interventions directly involved the person with dementia, with the remainder focusing on surrogate decision-makers. In all settings, interventions were found effective in increasing ACP practice. In nursing homes, ACP was found to influence care and increase the concordance between end of life wishes and care provided. Interventions in the community were found to improve patient quality of life but were not shown to influence concordance.
Future research should focus on ways to involve people with dementia in decision-making through supported means.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Background: Although previous research has suggested that patients with incidentally discovered low-grade gliomas (iLGG) who undergo surgery prior to the appearance of symptoms have improved outcomes compared to those who are symptomatic, an ideal approach to managing iLGG is not well-established. The purpose of this systematic review is to identify all cases of iLGG in the literature and characterize the effect of the timing of surgery on survival. Methods: We searched EMBASE, MEDLINE, and PubMed for articles related to iLGG. After duplicates were removed, the articles were then screened based on strict inclusion and exclusion criteria. Results: We retrieved 24/1377 unique articles with a total of 175 patients who underwent surgery for iLGG prior to symptoms appearing. The average age was 29.1yrs (range 1-62) and the mean follow-up period was 56 months (range 1-234months). Unfortunately, only 6/24 articles reported progression-free survival (average 32.4months) and only 1/24 reported 10-year survival. Conclusions: The articles we identified favored an early intervention for iLGG, however, there was a considerable lack of long-term follow-up and survival data to justify such a claim. Further studies need to be performed with adequate follow-up data in order to determine the optimal timing of surgical intervention for these patients.
Introduction: Influenza is a preventable infectious disease that causes a yearly burden to Canada. While an influenza vaccine is available free of charge in most provinces, uptake is below target rates. 15% of Canadians who did not get the influenza vaccine reported that they “didn't get around to it”; this presents an opportunity to combine the task of influenza prevention with the logistical issue of another health system challenge: escalating emergency department (ED) wait times. At the Queen Elizabeth II Health Sciences Centre (QEII) in Halifax, NS, average wait time is 4.6 hours. Offering the influenza vaccine during this time could increase convenient access to health services, and ultimately, improve vaccination rates. Methods: This observational, cross-sectional design study is currently in progress. It aims to gauge public interest, health care provider (HCP) support, perceived barriers and perceived facilitators to influenza vaccine availability at the QEII ED. Data is being collected via short, anonymous, close-ended questionnaires over a 7-week period, set to end Dec 14, 2018. Client participants are a convenience sample of low-acuity (Canadian Triage and Acuity Scale score 4/5), adult clients who use the QEII ED during the study period, anticipated n = 150. Client questionnaires are completed, with the help of a research assistant, on an iPad that inputs data directly into a secure online data collection tool. The HCP group is a convenience sample of nurses, physicians and paramedics currently working in the QEII ED, anticipated n = 80. Questionnaires are available to HCPs either on paper outside the staff lounge, or online. Data is being collected via short, anonymous, close-ended questionnaires over a 7-week period, set to end Dec 14, 2018. Client participants are a convenience sample of low-acuity (Canadian Triage and Acuity Scale score 4/5), adult clients who use the QEII ED during the study period, anticipated n = 150. Client questionnaires are completed, with the help of a research assistant, on an iPad that inputs data directly into a secure online data collection tool. The HCP group is a convenience sample of nurses, physicians and paramedics currently working in the QEII ED, anticipated n = 80. Questionnaires are available to HCPs either on paper outside the staff lounge, or online. Results: Following completion of data collection, descriptive statistics, such as the frequency of support for ED influenza vaccination and the proportion of unvaccinated clients willing to receive the vaccine if available in the ED, will be calculated using IBM SPSS Statistics 25. This will provide meaningful data that can be used by the QEII to inform future program planning (i.e. should the influenza vaccine be made available in the ED). Conclusion: An ED vaccination program could add value to the hours clients spend waiting to be seen, and make ED care more cohesive. It is essential that clients and ED staff are approached prior to any new initiative; this study is one way we can lay the necessary groundwork for a public health program that would utilize patient “wait time” more effectively.
Synthetic biology has a huge potential to produce the next generation of advanced materials by accessing previously unreachable (bio)chemical space. In this prospective review, we take a snapshot of current activity in this rapidly developing area, focusing on prominent examples for high-performance applications such as those required for protective materials and the aerospace sector. The continued growth of this emerging field will be facilitated by the convergence of expertise from a range of diverse disciplines, including molecular biology, polymer chemistry, materials science, and process engineering. This review highlights the most significant recent advances and addresses the cross-disciplinary challenges currently being faced.
Background: Safety behaviours are ubiquitous across anxiety disorders and are associated with the aetiology, maintenance and exacerbation of anxiety. Cognitive behavioural models posit that beliefs about safety behaviours directly influence their use. Therefore, beliefs about safety behaviours may be an important component in decreasing safety behaviour use. Unfortunately, little empirical research has evaluated this theorized relationship.
Aims: The present study aimed to examine the predictive relationship between beliefs about safety behaviours and safety behaviour use while controlling for anxiety severity.
Method: Adults with clinically elevated levels of social anxiety (n = 145) and anxiety sensitivity (n = 109) completed an online survey that included established measures of safety behaviour use, quality of life, and anxiety severity. Participants also completed the Safety Behaviour Scale (SBS), a measure created for the current study which includes a transdiagnostic checklist of safety behaviours, as well as questions related to safety behaviour use and beliefs about safety behaviours.
Results: Within both the social anxiety and anxiety sensitivity groups, positive beliefs about safety behaviours predicted greater safety behaviour use, even when controlling for anxiety severity. Certain beliefs were particularly relevant in predicting safety behaviour use within each of the clinical analogue groups.
Conclusions: Findings suggest that efforts to decrease safety behaviour use during anxiety treatment may benefit from identifying and modifying positive beliefs about safety behaviours.
Lithium-treated patients with polyuria are at increased risk of lithium toxicity. We aimed to describe the clinical benefits and risks of different management strategies for polyuria in community lithium-treated patients.
This is a naturalistic, observational, prospective 12-month cohort study of lithium-treated patients with polyuria attending a community mental health service in Dublin, Ireland. When polyuria was detected, management changed in one of four ways: (a) no pharmacological change; (b) lithium dose decrease; (c) lithium substitution; or (d) addition of amiloride.
Thirty-four participants were diagnosed with polyuria and completed prospective data over 12 months. Mean 24-hour urine volume decreased from 4852 to 4344 ml (p = 0.038). Mean early morning urine osmolality decreased from 343 to 338 mOsm/kg (p = 0.823). Mean 24-hour urine volume decreased with each type of intervention but did not attain statistical significance for any individual intervention group. Mean early morning urine osmolality decreased in participants with no pharmacological change and increased in participants who received a change in medication but these changes did not attain statistical significance. Only participants who discontinued lithium demonstrated potentially clinically significant changes in urine volume (mean decrease 747 ml in 24 hours) and early morning urine osmolality (mean increase 31 mOsm/kg) although this was not definitively proven, possibly owing to power issues.
Managing polyuria by decreasing lithium dose does not appear to substantially improve objective measures of renal tubular dysfunction, whereas substituting lithium may do so. Studies with larger numbers and longer follow-up would clarify these relationships.
This narrative review addresses vascular access device choice from peripheral intravenous catheters through central venous catheters, including the evolving use of midline catheters. The review incorporates best practices, published algorithms, and complications extending beyond CLABSI and phlebitis to assist clinicians in navigating complex vascular access decisions.
The measurement of residual stress, using X-ray diffraction techniques, is based on the change in diffraction angle determined for the Intensity maximum of some suitable reflection from the sample when this is placed consecutively with its surface at two different angles to the diffracting planes. These diffraction angles may be obtained in a variety of ways, but are most often calculated from measurements of three X-ray diffraction intensities at angles selected in the immediate vicinity of the peak maximum at each sample angle and fitting each set of data to a parabolic curve. A simple mathematical expression may be derived relating the diffraction angles, and hence the residual stress, to the measured X-ray intensities; there will, however, be statistical errors in the calculated diffraction angles due to random counting errors in the measurement of the X-ray diffraction intensities. From the expression relating the residual stress to the X-ray intensities an equation has been derived giving the standard deviation in the residual stress due to random counting errors. In addition, a simple approximation has been obtained from this equation showing that the standard deviation is decreased by increasing the number of counts accumulated for each X-ray intensity measurement and by increasing the size of the angular increments between the data points. It will also be shown that, using the approximation, it is possible to estimate in advance the number of accumulated counts at each point necessary to attain a desired standard deviation in a residual stress measurement.
The angular dependent factors which affect the intensities of X-ray diffraction line profiles, as observed on a Standard X-ray diffractometer, are well established. They are the Lorentz factor, the polarization factor, the atomic scattering factor, and the temperature factor. For residual stress analysis, in which measurements are made at non-zero omega (psi) angles, an absorption factor must be added to this list. It is usual, however, in residual stress analysis, to omit two of these factors: the atomic scattering factor and the temperature factor. The omission of these two factors appreciably alters the change in the combined correction factor with change of diffraction angle. The proper angular dependent corrections are in the opposite sense to those customarily employed. The effect of the additional factors on measurements of residual stress are discussed.
An X-ray fluorescence analysis unit has been automated with a multi-position sample changer, a stepping motor to position the spectrometer, and computer addressable switches to control the selection of crystal, detector, collimator, and beam filter. The unit can be controlled off-line through a Teletype or on-line with a computer. This computer utilizes a multi-user program for the simultaneous operation of the fluorescence analysis unit and two diffractometers. Programming the system for any desired analytical or research procedure is accomplished using an expanded version of BASIC.