361 research outputs found
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Pilot study: Improving attention bias modification of alcohol cues through concealed gaze-contingent feedback in alcohol dependence.
In an attempt to improve attention bias modification (ABM), we tested whether an attentional training protocol which featured monetary operant conditioning of eye-gaze to avoid alcohol stimuli in alcohol-dependent patients could reduce attention, craving and relapse to alcohol. We employed a pilot randomized control trial (RCT) with 21 detoxified alcohol dependent patients (48.9âŻÂąâŻ10âŻyears of age, 9 male) from an inpatient and outpatient treatment centre. The novel concealed operant conditioning paradigm provided monetary reinforcements or punishments respective to eye-gaze patterns towards neutral or towards alcohol stimuli along with an 80% probability of a to-be-detected probe appearing following neutral stimuli (ET-ABM group). Patients in the control-group received random monetary feedback and a 50/50 ABM contingency. We compared AB on trained and untrained stimuli and addiction severity measures of obsessive thoughts and desires to alcohol following training. We further assessed addiction severity and relapse outcome at a 3-month follow-up. Results indicate that this attentional retraining only worked for the trained stimuli and did not generalize to untrained stimuli or to addiction severity measures or relapse outcome. Potential explanations for lack of generalization include the low sample size and imbalances on important prognostic variables between the active-group and control-group. We discuss progress and challenges for further research on cognitive training using gaze-contingent feedback
Widespread erosion on high plateaus during recent glaciations in Scandinavia
Glaciers create some of Earthâs steepest topography; yet, many areas that were repeatedly overridden by ice sheets in the last few million years include extensive plateaus. The distinct geomorphic contrast between plateaus and the glacial troughs that dissect them has sustained two long-held hypotheses: first, that ice sheets perform insignificant erosion beyond glacial troughs, and, second, that the plateaus represent ancient pre-glacial landforms bearing information of tectonic and geomorphic history prior to PlioceneâPleistocene global cooling (~3.5âMyr ago). Here we show that the Fennoscandian ice sheets drove widespread erosion across plateaus far beyond glacial troughs. We apply inverse modelling to 118 new cosmogenic 10Be and 26Al measurements to quantify ice sheet erosion on the plateaus fringing the Sognefjorden glacial trough in western Norway. Our findings demonstrate substantial modification of the pre-glacial landscape during the Quaternary, and that glacial erosion of plateaus is important when estimating the global sediment flux to the oceans
Opioid use is associated with increased out-of-hospital cardiac arrest risk among 40,000-cases across two countries
AIMS: Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and outâofâhospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCAârisk of opioids in the community. METHODS: We conducted 2 populationâbased caseâcontrol studies separately in the Netherlands (2009â2018) and Denmark (2001â2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to 5 nonâOHCAâcontrols according to age, sex and OHCAâdate. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 5473 OHCAâcases matched with 21â866 nonâOHCAâcontrols in the Netherlands, and 35â017 OHCAâcases matched with 175â085 nonâOHCAâcontrols in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCAârisk in both regions (the Netherlands: OR 2.1 [95% CI 1.8â2.5]; Denmark: OR 1.8 [95% CI 1.5â2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95% CI 1.5â2.1]; Denmark: OR 1.6 [95% CI 1.5â1.7]) or without (the Netherlands: OR 3.4 [95% CI: 2.4â4.8], P (interaction)Â <â.0001; Denmark: OR 2.3 [95% CI: 2.0â2.5], P (interaction)Â <â.0001). CONCLUSION: Use of opioids is associated with increased OHCAârisk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids
Risk of out-of-hospital cardiac arrest in antidepressant drug users
Conflicting results have been reported regarding the association between antidepressant use and outâofâhospital cardiac arrest (OHCA) risk. We investigated whether the use of antidepressants is associated with OHCA. METHODS: We conducted a nationwide nested caseâcontrol study to assess the association of individual antidepressant drugs within drug classes with the hazard of OHCA. Cases were defined as OHCA from presumed cardiac causes. Cox regression with timeâdependent exposure and timeâdependent covariates was conducted to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) overall and in subgroups defined by established cardiac disease and cardiovascular risk factors. Also, we studied antidepressants with and without sodium channel blocking or potassium channel blocking properties separately. RESULTS: During the study period from 2001 to 2015 we observed 10â987 OHCA cases, and found increased OHCA rate for highâdose citalopram (>20âmg) and highâdose escitalopram (>10âmg; HR:1.46 [95% CI:1.27â1.69], HR:1.43 [95% CI:1.16â1.75], respectively) among selective serotonin reuptake inhibitors (reference drug sertraline), and for highâdose mirtazapine (>30; HR:1.59 [95% CI:1.18â2.14]) among the serotoninânorepinephrine reuptake inhibitors or noradrenergic and specific serotonergic antidepressants (reference drug duloxetine). Among tricyclic antidepressants (reference drug amitriptyline), no drug was associated with significantly increased OHCA rate. Increased OHCA rate was found for antidepressants with known potassium channel blocking properties (HR:1.14 [95% CI:1.05â1.23]), but for not those with sodium channel blocking properties. Citalopram, although not statistically significant, and mirtazapine were associated with increased OHCA rate in patients without cardiac disease and cardiovascular risk factors. CONCLUSION: Our findings indicate that careful titration of citalopram, escitalopram and mirtazapine dose may have to be considered due to drug safety issues
Effort-reward imbalance at work and risk of type 2 diabetes in a national sample of 50,552 workers in Denmark : A prospective study linking survey and register data
Objective: To examine the prospective relation between effort-reward imbalance at work and risk of type 2 diabetes. Methods: We included 50,552 individuals from a national survey of the working population in Denmark, aged 30-64 years and diabetes-free at baseline. Effort-reward imbalance was defined, in accordance with the literature, as a mismatch between high efforts at work (e.g. high work pace, time pressure), and low rewards received in return (e.g. low recognition, job insecurity) and assessed as a continuous and a categorical variable. Incident type 2 diabetes was identified in national health registers. Using Cox regression we calculated hazard ratios (HR) and 95% confidence intervals (95% CI) for estimating the association between effort-reward imbalance at baseline and risk of onset of type 2 diabetes during follow-up, adjusted for sex, age, socioeconomic status, cohabitation, children at home, migration background, survey year and sample method. Results: During 136,239 person-years of follow-up (mean = 2.7 years) we identified 347 type 2 diabetes cases (25.5 cases per 10,000 person-years). For each one standard deviation increase of the effort-reward imbalance score at baseline, the fully adjusted risk of type 2 diabetes during follow-up increased by 9% (HR: 1.09, 95% CI: 0.98-1.21). When we used effort-reward imbalance as a dichotomous variable, exposure to effort-reward imbalance was associated with an increased risk of type 2 diabetes with a HR of 1.27 (95% CI: 1.02-1.58). Conclusion The results of this nationwide study of the Danish workforce suggest that effort-reward imbalance at work may be a risk factor for type 2 diabetes.Peer reviewe
Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis
<p>Abstract</p> <p>Background</p> <p>Approximately half of all human genes use alternative transcription start sites (TSSs) to control mRNA levels and broaden the transcriptional output in healthy tissues. Aberrant expression patterns promoting carcinogenesis, however, may arise from alternative promoter usage.</p> <p>Results</p> <p>By profiling 108 colorectal samples using exon arrays, we identified nine genes (<it>TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5</it>, and <it>SCIN</it>) showing tumor-specific alternative TSS usage in both adenoma and cancer samples relative to normal mucosa. Analysis of independent exon array data sets corroborated these findings. Additionally, we confirmed the observed patterns for selected mRNAs using quantitative real-time reverse-transcription PCR. Interestingly, for some of the genes, the tumor-specific TSS usage was not restricted to colorectal cancer. A comprehensive survey of the nine genes in lung, bladder, liver, prostate, gastric, and brain cancer revealed significantly altered mRNA isoform ratios for <it>CHEK1, OSBPL1A</it>, and <it>TCF12 </it>in a subset of these cancer types.</p> <p>To identify the mechanism responsible for the shift in alternative TSS usage, we antagonized the Wnt-signaling pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably led to a shift in the preferred TSS for both <it>OSBPL1A </it>and <it>TRAK1</it>. This indicated a regulatory role of the Wnt pathway in selecting TSS, possibly also involving TP53 and SOX9, as their transcription binding sites were enriched in the promoters of the tumor preferred isoforms together with their mRNA levels being increased in tumor samples.</p> <p>Finally, to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry was used to show deregulation of the total protein levels of both TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore, the level of nuclear TCF12 had a significant correlation to progression free survival in a cohort of 248 stage II colorectal cancer samples.</p> <p>Conclusions</p> <p>Alternative TSS usage in colorectal adenoma and cancer samples has been shown for nine genes, and <it>OSBPL1A </it>and <it>TRAK1 </it>were found to be regulated <it>in vitro </it>by Wnt signaling. TCF12 protein expression was upregulated in cancer samples and correlated with progression free survival.</p
Contacts With the Health Care System Before Out-of-Hospital Cardiac Arrest
BACKGROUND: It remains challenging to identify patients at risk of outâofâhospital cardiac arrest (OHCA). We aimed to examine health care contacts in patients before OHCA compared with the general population that did not experience an OHCA. METHODS AND RESULTS: Patients with OHCA with a presumed cardiac cause were identified from the Danish Cardiac Arrest Registry (2001â2014) and their health care contacts (general practitioner [GP]/hospital) were examined up to 1Â year before OHCA. In a caseâcontrol study (1:9), OHCA contacts were compared with an ageâ and sexâmatched background population. Separately, patients with OHCA were examined by the contact type (GP/hospital/both/no contact) within 2Â weeks before OHCA. We included 28Â 955 patients with OHCA. The weekly percentages of patient contacts with GP the year before OHCA were constant (25%) until 1Â week before OHCA when they markedly increased (42%). Weekly percentages of patient contacts with hospitals the year before OHCA gradually increased during the last 6Â months (3.5%â6.6%), peaking at the second week (6.8%) before OHCA; mostly attributable to cardiovascular diseases (21%). In comparison, there were fewer weekly contacts among controls with 13% for GP and 2% for hospital contacts (P<0.001). Within 2Â weeks before OHCA, 57.8% of patients with OHCA had a health care contact, and these patients had more contacts with GP (odds ratio [OR], 3.17; 95% CI, 3.09â3.26) and hospital (OR, 2.32; 95% CI, 2.21â2.43) compared with controls. CONCLUSIONS: The health care contacts of patients with OHCA nearly doubled leading up to the OHCA event, with more than half of patients having health care contacts within 2Â weeks before arrest. This could have implications for future preventive strategies
Whole-genome amplified DNA from stored dried blood spots is reliable in high resolution melting curve and sequencing analysis
<p>Abstract</p> <p>Background</p> <p>The use of dried blood spots (DBS) samples in genomic workup has been limited by the relative low amounts of genomic DNA (gDNA) they contain. It remains to be proven that whole genome amplified DNA (wgaDNA) from stored DBS samples, constitutes a reliable alternative to gDNA.</p> <p>We wanted to compare melting curves and sequencing results from wgaDNA derived from DBS samples with gDNA derived from whole blood.</p> <p>Methods</p> <p>gDNA was extracted from whole blood obtained from 10 patients with lone atrial fibrillation (mean age 22.3 years). From their newborn DBS samples, stored at -24°C, genomic DNA was extracted and whole-genome amplified in triplicates. Using high resolution melting curve analysis and direct sequencing in both wgaDNA and gDNA samples, all coding regions and adjacent intron regions of the genes <it>SCN5A </it>and <it>KCNA5 </it>were investigated.</p> <p>Results</p> <p>Altered melting curves was present in 85 of wgaDNA samples and 81 of gDNA samples. Sequence analysis identified a total of 31 variants in the 10 wgaDNA samples. The same 31 variants were found in the exact same pattern of samples in the gDNA group. There was no false positive or negative sequence variation in the wgaDNA group.</p> <p>Conclusions</p> <p>The use of DNA amplified in triplicates from DBS samples is reliable and can be used both for high resolution curve melting analysis as well as direct sequence analysis. DBS samples therefore can serve as an alternative to whole blood in sequence analysis.</p
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