| 1. |
- Codita, Alina, et al.
(författare)
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Effects of spatial and cognitive enrichment on activity pattern and learning performance in three strains of mice in the IntelliMaze.
- 2012
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Ingår i: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 42:3, s. 449-460
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Tidskriftsartikel (refereegranskat)abstract
- The IntelliMaze allows automated behavioral analysis of group housed laboratory mice while individually assigned protocols can be applied concomitantly for different operant conditioning components. Here we evaluate the effect of additional component availability (enrichment) on behavioral and cognitive performance of mice in the IntelliCage, by focusing on aspects that had previously been found to consistently differ between three strains, in four European laboratories. Enrichment decreased the activity level in the IntelliCages and enhanced spatial learning performance. However, it did not alter strain differences, except for activity during the initial experimental phase. Our results from non-enriched IntelliCages proved consistent between laboratories, but overall laboratory-consistency for data collected using different IntelliCage set-ups, did not hold for activity levels during the initial adaptation phase. Our results suggest that the multiple conditioning in spatially and cognitively enriched environments are feasible without affecting external validity for a specific task, provided animals have adapted to such an IntelliMaze.
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| 2. |
- Dudenhöffer-Pfeifer, Monika, et al.
(författare)
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Different Munc13 isoforms function as priming factors in lytic granule release from murine cytotoxic T lymphocytes.
- 2013
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Ingår i: Traffic. - : Wiley. - 1398-9219 .- 1600-0854. ; 14:7
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Tidskriftsartikel (refereegranskat)abstract
- In order to fuse lytic granules (LGs) with the plasma membrane at the immunological synapse, cytotoxic T lymphocytes (CTLs) have to render these LGs fusion-competent through the priming process. In secretory tissues such as brain and neuroendocrine glands, this process is mediated by members of the Munc13 protein family. In human CTLs, mutations in the Munc13-4 gene cause a severe loss in killing efficiency, resulting in familial hemophagocytic lymphohistiocytosis type 3, suggesting a similar role of other Munc13 isoforms in the immune system. Here, we investigate the contribution of different Munc13 isoforms to the priming process of murine CTLs at both the mRNA and protein level. We demonstrate that Munc13-1 and Munc13-4 are the only Munc13 isoforms present in mouse CTLs. Both isoforms rescue the drastical secretion defect of CTLs derived from Munc13-4-deficient Jinx mice. Mobility studies using total internal reflection fluorescence microscopy indicate that Munc13-4 and Munc13-1 are responsible for the priming process of LGs. Furthermore, the domains of the Munc13 protein, which is responsible for functional fusion, could be identified. We conclude from these data that both isoforms of the Munc13 family, Munc13-1 and Munc13-4, are functionally redundant in murine CTLs.
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| 3. |
- McEvoy, Peter M., et al.
(författare)
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Assessing the efficacy of imagery-enhanced cognitive behavioral group therapy for social anxiety disorder : Study protocol for a randomized controlled trial
- 2017
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Ingår i: Contemporary Clinical Trials. - : ELSEVIER SCIENCE INC. - 1551-7144 .- 1559-2030. ; 60, s. 34-41
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavior group therapy (CBGT) is effective for social anxiety disorder (SAD), but a substantial proportion of patients do not typically achieve normative functioning. Cognitive behavioral models of SAD emphasize negative self-imagery as an important maintaining factor, and evidence suggests that imagery is a powerful cognitive mode for facilitating affective change. This study will compare two group CBGT interventions, one that predominantly uses verbally-based strategies (VB-CBGT) and another that predominantly uses imagery-enhanced strategies (IE-CBGT), in terms of (a) efficacy, (b) mechanisms of change, and (c) cost-effectiveness. This study is a parallel groups (two-arm) single-blind randomized controlled trial. A minimum of 96 patients with SAD will be recruited within a public outpatient community mental health clinic in Perth, Australia. The primary outcomes will be self-reported symptom severity, caseness (SAD present: yes/no) based on a structured diagnostic interview, and clinician-rated severity and life impact. Secondary outcomes and mechanism measures include blind observer-rated use of safety behaviors, physiological activity (heart rate variability and skin conductance level) during a standardized speech task, negative self-beliefs, imagery suppression, fear of negative and positive evaluation, repetitive negative thinking, anxiety, depression, self-consciousness, use of safety behaviors, and the EQ-5D-5L and TiC-P for the health economic analysis. Homework completion, group cohesion, and working alliance will also be monitored. The outcomes of this trial will inform clinicians as to whether integrating imagery-based strategies in cognitive behavior therapy for SAD is likely to improve outcomes. Common and distinct mechanisms of change might be identified, along with relative cost-effectiveness of each intervention.
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| 4. |
- McEvoy, Peter M., et al.
(författare)
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Imagery-enhanced v. verbally-based group cognitive behavior therapy for social anxiety disorder : a randomized clinical trial
- 2022
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Ingår i: Psychological Medicine. - : Cambridge University Press. - 0033-2917 .- 1469-8978. ; 52:7, s. 1277-1286
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.MethodsA randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.ResultsIntention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09-2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).ConclusionsGroup IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.
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| 5. |
- McEvoy, Peter M., et al.
(författare)
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Impacts of imagery-enhanced versus verbally-based cognitive behavioral group therapy on psychophysiological parameters in social anxiety disorder : Results from a randomized-controlled trial
- 2022
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Ingår i: Behaviour Research and Therapy. - : Elsevier. - 0005-7967 .- 1873-622X. ; 155
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Tidskriftsartikel (refereegranskat)abstract
- Social anxiety disorder (SAD) is associated with marked physiological reactivity in social-evaluative situations. However, objective measurement of biomarkers is rarely evaluated in treatment trials, despite potential utility in clarifying disorder-specific physiological correlates. This randomized controlled trial sought to examine the differential impact of imagery-enhanced vs. verbal-based cognitive behavioral group therapy (IE-CBGT, n = 53; VB-CBGT, n = 54) on biomarkers of emotion regulation and arousal during social stress in people with SAD (pre and post-treatment differences in heart rate variability (HRV) and skin conductance). We acquired psycho physiological data from randomized participants across four social stress test phases (baseline, speech preparation, speech, interaction) at pre-treatment, and 1-and 6-months post-treatment. Analyses revealed that IECBGT selectively attenuated heart rate as indexed by increases in median heart rate interval (median-RR) compared to VB-CBGT at post-treatment, whereas one HRV index showed a larger increase in the VB-CBGT condition before but not after controlling for median-RR. Other psychophysiological indices did not differ between conditions. Lower sympathetic arousal in the IE-CBGT condition may have obviated the need for parasympathetic downregulation, whereas the opposite was true for VB-CBGT. These findings provide preliminary insights into the impact of imagery-enhanced and verbally-based psychotherapy for SAD on emotion regulation biomarkers.
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| 6. |
- Schunk, Stefan J., et al.
(författare)
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Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:18, s. 1742-1756
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Tidskriftsartikel (refereegranskat)abstract
- AimsInflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.Methods and resultsWe explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality.ConclusionThe NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.
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