Publications by authors named "I J Blix"

34 Publications

Host Modulation and Treatment of Periodontal Disease.

J Dent Res 2021 Mar 3:22034521995157. Epub 2021 Mar 3.

Center for Clinical and Translational Research, Forsyth Institute, Cambridge, MA, USA.

Periodontitis is the sixth-most prevalent disease in the world and the first cause for tooth loss in adults. With focus shifted to the inflammatory/immune response in the pathogenesis of periodontitis, there is a critical need to evaluate host modulatory agents. Synthetic and biological disease-modifying antirheumatic drugs are a cornerstone for the treatment of inflammatory diseases. Recent prospective cohort studies showed that synthetic disease-modifying antirheumatic drugs improved periodontal clinical parameters following nonsurgical periodontal treatment in patients with rheumatoid arthritis. Treatment with recombinant humanized monoclonal antibodies against CD20 (rituximab) and IL-6 receptor (tocilizumab), the latter also in clinical trials for the treatment of COVID-19 pneumonia, resulted in decreased periodontal inflammation and improved periodontal status. Studies on the effect of TNF-α inhibitors in patients with periodontitis yielded inconsistent results. Recent data suggest that probiotics provide anti-inflammatory clinical benefit, as do nutritional supplements, such as n-3 fatty acids, when combined with periodontal therapy. Probiotics reduce the production of proinflammatory cytokines/chemokines by suppressing NF-κB pathways and promote the accumulation of T regulatory cells. Statins, like aspirin, have been shown to exhibit anti-inflammatory and bone-preserving actions by upregulating production of Specialized Proresolving Mediators (SPMs). Currently, there is insufficient scientific support for the topical delivery of statins or bisphosphonates as adjuncts to periodontal therapy. Here, we present a critical review of the most recent host modulatory agents applied in humans and the key immune pathways that they target. Emerging evidence from novel drug candidates, including SPMs and complement inhibitors as previously studied in animal models and currently in human clinical trials, suggests future availability of adjunctive therapeutic strategies for the management of periodontitis.
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http://dx.doi.org/10.1177/0022034521995157DOI Listing
March 2021

Trauma in the third decade: Ruminative coping, social relationships and posttraumatic stress symptoms.

J Affect Disord 2021 Jan 28;278:601-606. Epub 2020 Sep 28.

Norwegian Centre for Violence and Traumatic Stress Studies (NKVTS), 181 Nydalen, 0409 Oslo, Norway.

Background: Previous research suggest that rumination and poor social relationships contribute to the maintenance of posttraumatic stress symptoms (PTSS) after traumatic events. Less is known about how these factors work together. The aim of this study was to assess the association between ruminative coping style and long-term PTSS, and to determine whether perceived social support and loneliness can attenuate or potentiate this association, respectively.

Methods: This study used cross-sectional data from survivors and bereaved (n = 185) collected 26 years after the 1990 fire on the Scandinavian Star ferry.

Results: Ruminative coping style, perceived social support, and loneliness were all uniquely associated with PTSS. Social support, but not loneliness, moderated the association between ruminative coping style and PTSS.

Limitations: The 26-year interval between the traumatic event and the data collection mean that we cannot infer how a ruminative coping style, perceived social support, and loneliness could affect PTSS in the early aftermath of disaster.

Conclusions: The results suggest that perceived social support and loneliness play different roles in long-term maintenance of PTSS. Whereas loneliness seem to have a direct association with PTSS, high social support may also protect against the negative effects of a ruminative coping style on PTSS. Social relationships may play a crucial role in recovery from trauma, particularly in individuals with a ruminative coping style.
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http://dx.doi.org/10.1016/j.jad.2020.09.095DOI Listing
January 2021

Long-term mental health and social support in victims of disaster: comparison with a general population sample.

BJPsych Open 2019 Jan;5(1):e2

Senior Researcher,Norwegian Centre for Violence and Traumatic Stress Studies,Norway.

Background: Trauma and traumatic bereavement have well-known consequences for mental health, but little is known about long-term adjustment, particularly with respect to health-protective factors.AimsTo assess the levels of anxiety/depression and perceived social support among the survivors and the bereaved 26 years after the Scandinavian Star ferry disaster compared with expected levels from the general population.

Method: Anxiety/depression and social support were assessed in face-to-face interviews with the survivors and the bereaved (N = 165, response rate 58%). Expected scores were calculated for each participant based on the means and proportions for each age and gender combination from a general population sample. We computed the ratio between expected and observed scores, standardised mean differences with 95% confidence intervals and standardised effect sizes.

Results: We found an elevated level of anxiety/depression symptoms in the victims (Mdiff = 0.28, 95% CI 0.18, 0.38; effect size 0.43, 95% CI 0.31, 0.55) and a significant excess of individuals with a clinically significant level of symptoms. The observed level of perceived social support was significantly lower than that expected (Mdiff = -0.57, 95% CI -0.70, -0.44; effect size -0.73, 95% CI -0.89, -0.57). This was the case for both survivors and those who were bereaved and for both men and women.

Conclusions: This study reveals that disaster survivors and the bereaved reported elevated levels of anxiety and depression symptoms 26 years after the event. They also reported a markedly reduced level of social support. Traumas and post-traumatic responses may thus cause lasting harm to interpersonal relationships.Declaration of interestNone.
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http://dx.doi.org/10.1192/bjo.2018.74DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343115PMC
January 2019

Loss of Trust May Never Heal. Institutional Trust in Disaster Victims in a Long-Term Perspective: Associations With Social Support and Mental Health.

Front Psychol 2018 16;9:1204. Epub 2018 Jul 16.

Norwegian Centre for Violence and Traumatic Stress Studies, Oslo, Norway.

Natural disasters, technological disasters, and terrorist attacks have an extensive aftermath, often involving society's institutions such as the legal system and the police. Victims' perceptions of institutional trustworthiness may impact their potential for healing. This cross-sectional study investigates institutional trust, health, and social support in victims of a disaster that occurred in 1990. We conducted face-to-face interviews with 184 survivors and bereaved, with a 60% response rate 26 years after the disaster. Levels of trust in the police and in the justice system were compared with general population data. We assessed the relationships between institutional trust and current psychological distress, social support, and life satisfaction. The levels of trust in the police and in the justice system were notably lower in survivors and bereaved than in the general population. Among the victims, low institutional trust was associated with more mental health problems, poorer social support, more barriers to seeking social support, and a lower life satisfaction. Lost trust in the aftermath of a disaster may perhaps never be restored and the lack of trust may act to strengthen or maintain health problems. An exclusively individualistic approach to trauma and disaster may miss out on the opportunities for promoting health and well-being that lies within the larger societal structures. Decision-makers should take this information into account, and acknowledge the potential long-term consequences of institutional performance in the aftermath of a disaster.
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http://dx.doi.org/10.3389/fpsyg.2018.01204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055587PMC
July 2018

Imagining What Could Have Happened: Types and Vividness of Counterfactual Thoughts and the Relationship With Post-traumatic Stress Reactions.

Front Psychol 2018 20;9:515. Epub 2018 Apr 20.

Norwegian Centre for Violence and Traumatic Stress Studies, Oslo, Norway.

A growing body of research suggests that counterfactual thinking after traumatic events is associated with post-traumatic stress reactions. In this study we explored frequency of upward and downward counterfactuals in trauma-exposed individuals, and how trauma-related counterfactuals were represented in terms of vividness. We examined the relationships between vividness and frequency of counterfactual thoughts and post-traumatic stress reactions in two groups who had experienced different types of traumatic exposure, namely survivors and bereaved from the fire on the ferry Scandinavian Star in 1990. Even after 26 years, both survivors and bereaved reported that they currently entertained thoughts about what could have happened during the fire on Scandinavian Star. Survivors reported more downward counterfactuals than the bereaved, whereas the bereaved reported more upward counterfactuals than the survivors did. Vividness of counterfactual thoughts, as well as reported frequency of upward and downward counterfactuals, were associated with post-traumatic stress reactions. Our results suggest that both upward and downward counterfactuals can be harmful, and that vivid counterfactuals about a traumatic event might play a similar role in post-traumatic stress as trauma memories. Therefore, traumatized individuals who entertain counterfactual thoughts may benefit from interventions that target these thoughts specifically.
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http://dx.doi.org/10.3389/fpsyg.2018.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920021PMC
April 2018

Gender Differences in Posttraumatic Stress Symptoms after a Terrorist Attack: A Network Approach.

Front Psychol 2017 1;8:2091. Epub 2017 Dec 1.

Norwegian Centre for Violence and Traumatic Stress Studies, Oslo, Norway.

Posttraumatic stress symptoms are more prevalent in women than in men. To improve our understanding of gender differences in PTSD, detailed knowledge about the underlying symptom networks and gender specific symptom profiles is needed. We aimed to describe the gender differences in levels of individual posttraumatic stress symptoms after a terrorist attack, as well as identify possible gender differences in associations between posttraumatic stress symptoms. This study used survey data from ministerial employees directly ( = 190) and indirectly ( = 1,615) exposed to the 2011 Oslo bombing. Data was collected approximately 10 months after the event. In order to investigate gender differences in levels of symptoms, we used bootstrapped means and standard deviations. Network analyses were conducted to identify gender differences in the associations between posttraumatic stress symptoms. Women reported higher levels of all symptoms, and the strongest effect sizes were found for symptoms of re-experiencing, and anxious and dysphoric arousal. Among individuals with considerable levels of posttraumatic stress symptoms, women reported higher levels of physiological cue activity and exaggerated startle response. No significant gender differences in the networks of posttraumatic stress were found. The present results find no indication that the gender difference in prevalence of PTSD can be explained by differences in associations between symptoms. In order to determine if this finding can be applied to other participants and circumstances, future studies should seek to replicate this study in both community and clinical samples.
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http://dx.doi.org/10.3389/fpsyg.2017.02091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717368PMC
December 2017

The Regulatory Role of the Oral Commensal Streptococcus mitis on Human Monocytes.

Scand J Immunol 2018 Feb 19;87(2):80-87. Epub 2017 Dec 19.

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

Streptococcus mitis colonizes all niches of the human oral cavity from early infancy and throughout life. Monocytes patrol blood vessels, lymphoid and non-lymphoid tissues and migrate into infected tissue where they participate in the inflammatory cascade and immune regulation. Here, we studied the effect of S. mitis on monocytes. Transcriptome analysis of monocytes exposed to S. mitis (SmMo) revealed increased transcription of chemotactic factors (CCL2, CCL3, CCL20, CXCL1, CXCL2) and cytokines (IL1A, IL1B, IL6, IL23, IL36G, TNF), indicating that S. mitis may trigger recruitment of leucocytes and initiate inflammation. Increased transcription in SmMo of IL1B, IL6 and IL23 indicated that S. mitis may participate in the induction of Th17 responses and agreed with our earlier findings of S. mitis-mediated memory Th17 reactivity. Furthermore, S. mitis inhibited tetanus toxoid-specific CD4 T cell proliferation. This can be due to the increased secretion of IL-10 and expression of PD-L1 that was observed in SmMo. PGE2 can modulate IL-10 and PD-L1 expression, concomitant with that of CCR7, IL-12 and IL-23 that also were changed. This, along with increased SmMo transcription of PTGS2 (COX2) and PTGER4 (EP4), pointed to a role of PGE2. Measurement of PGE2 secretion by SmMo showed indeed a marked increase, and chemical inhibition of PGE2 production lowered the PD-L1 expression on SmMo. In conclusion, our findings show that S. mitis may trigger immune modulation by recruiting immune cells to the site of infection, while at the same time dampening the severity of the response through expression of IL-10, PGE2 and PD-L1.
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http://dx.doi.org/10.1111/sji.12636DOI Listing
February 2018

Prevalence and Course of Symptom-Defined PTSD in Individuals Directly or Indirectly Exposed to Terror: A Longitudinal Study.

Psychiatry 2017 ;80(2):171-183

Objective: It is well established that direct exposure to terrorism can result in posttraumatic stress disorder (PTSD). However, individuals indirectly exposed to terrorism may also develop symptoms of PTSD. This study examined the prevalence and course of symptom-defined PTSD in employees who were present and not present at the site of a workplace terror attack.

Methods: Survey data from ministerial employees were collected 10, 22, and 34 months after the 2011 bombing in the government district of Oslo. A total of 3,520 employees were initially invited to the study. Response rates of eligible participants were 56% (N = 1,974) at T1, 55% (N = 1,780) at T2, and 54% (N = 1,578) at T3. PTSD was measured using the Post-traumatic Stress Disorder Checklist-Specific (PCL-S). Symptom-defined PTSD was specified as meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), B, C, and D criteria.

Results: Our findings showed a low and declining prevalence of symptom-defined PTSD in employees indirectly exposed to a workplace terror attack (4%, 3%, and 2% at the three respective times). In employees present at the site of the explosion, PTSD was six- to eightfold more prevalent (24%, 17%, and 17%).

Conclusions: Individuals indirectly exposed to terrorism may develop long-lasting posttraumatic stress reactions fulfilling PTSD symptom criteria. Due to the large number of individuals that may be indirectly exposed to terrorism, even a low risk of PTSD may result in high numbers of individuals with substantial posttraumatic stress. Our findings have implications for the planning and implementation of health care services beyond those directly exposed after large-scale terror events.
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http://dx.doi.org/10.1080/00332747.2016.1230983DOI Listing
April 2018

The oral commensal Streptococcus mitis activates the aryl hydrocarbon receptor in human oral epithelial cells.

Int J Oral Sci 2017 09 16;9(3):145-150. Epub 2017 Jun 16.

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

Streptococcus mitis (S. mitis) is a pioneer commensal bacterial species colonizing many of the surfaces of the oral cavity in healthy individuals. Yet, not much information is available regarding its interaction with the host. We used examination of its transcriptional regulation in oral keratinocytes to elucidate some of its potential roles in the oral cavity. Transcription factor analysis of oral keratinocytes predicted S. mitis-mediated activation of aryl hydrocarbon receptor (AhR). Activation and functionality of AhR was confirmed through nuclear translocation determined by immunofluorescence microscopy and real-time polymerase chain reaction with reverse transcription analysis of CYP1A1, the hallmark gene for AhR activation. Addition of Streptococcus mutans or Streptococcus gordonii did not induce CYP1A1 transcription in the keratinocyte cultures. Introduction of an AhR-specific inhibitor revealed that S. mitis-mediated transcription of CXCL2 and CXCL8 was regulated by AhR. Elevated levels of prostaglandin E2 (enzyme-linked immunosorbent assay) in supernatants from S. mitis-treated oral epithelial cells were also attenuated by inhibition of AhR activity. The observed AhR-regulated activities point to a contribution of S. mitis in the regulation of inflammatory responses and thereby to wound healing in the oral cavity. The concept that the oral commensal microbiota can induce AhR activation is important, also in view of the role that AhR has in modulation of T-cell differentiation and as an anti-inflammatory factor in macrophages.
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http://dx.doi.org/10.1038/ijos.2017.17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709542PMC
September 2017

Lysophosphatidic acid induces expression of genes in human oral keratinocytes involved in wound healing.

Arch Oral Biol 2017 Aug 13;80:153-159. Epub 2017 Apr 13.

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway; Department of Periodontology, Faculty of Dentistry, University of Oslo, Norway.

Objective: Epithelial cells participate in wound healing by covering wounds, but also as important mediators of wound healing processes. Topical application of the phospholipid growth factor lysophosphatidic acid (LPA) accelerates dermal wound healing and we hypothesized that LPA can play a role in human oral wound healing through its effects on human oral keratinocytes (HOK).

Design: HOK were isolated from gingival biopsies and exposed to LPA. The LPA receptor profile, signal transduction pathways, gene expression and secretion of selected cytokines were analyzed.

Results: HOK expressed the receptors LPA, LPA and LPA and LPA activated the ERK1/2, JNK and p38 intracellular pathways, substantiated by secretion of IL-6 and IL-8. The early (2h) and intermediate (6h) gene expression profiles of HOK after LPA treatment showed a wide array of regulated genes. The majority of the strongest upregulated genes were related to chemotaxis and inflammation, and became downregulated after 6h. At 6h, genes coding for factors involved in extracellular matrix remodeling and re-epithelialization became highly expressed. IL-36γ, not earlier known to be regulated by LPA, was strongly transcribed and translated but not secreted.

Conclusions: After stimulation with LPA, HOK responded by regulating factors and genes that are essential in wound healing processes. As LPA is found in saliva and is released by activated cells after wounding, our results indicate that LPA has a favorable physiological role in oral wound healing. This may further point towards a beneficial role for application of LPA on oral surgical or chronic wounds.
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http://dx.doi.org/10.1016/j.archoralbio.2017.04.008DOI Listing
August 2017

For Whom Does Time Heal Wounds? Individual Differences in Stability and Change in Posttraumatic Stress After the 2011 Oslo Bombing.

J Trauma Stress 2017 02 19;30(1):19-26. Epub 2017 Jan 19.

Norwegian Centre for Violence and Traumatic Stress Studies, Oslo, Norway.

Prospective studies describing and predicting individual differences in the course of posttraumatic stress symptoms (PTSS) after disasters are scarce. The present study aimed to describe and predict individual differences in both the level and the rate of change in PTSS after the 2011 Oslo bombing, a terrorist attack directed at the Norwegian government. Survey data from ministerial employees (N = 256) were collected 10, 22, and 34 months after the bombing. We used latent growth modeling to examine the development of PTSS, and to identify the strength of predictor variables. High exposure, female sex, and high levels of neuroticism were associated with higher levels of PTSS 10 months after the traumatic event (β ranged from .25 to .30, p < .001), whereas social support was associated with lower levels of PTSS (β = -.30, p < .001). The combination of being female and high in neuroticism was associated with a faster decline in PTSS (β range: -.20 to -.39, p = .010 < .05). High exposure seemed to have a lasting influence by maintaining high levels of PTSS. Our findings suggested that being female, being highly exposed, and having low levels of social support were risk markers for enduring PTSS.
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http://dx.doi.org/10.1002/jts.22158DOI Listing
February 2017

Towards an exposure-dependent model of post-traumatic stress: longitudinal course of post-traumatic stress symptomatology and functional impairment after the 2011 Oslo bombing.

Psychol Med 2016 11 9;46(15):3241-3254. Epub 2016 Sep 9.

Norwegian Centre for Violence and Traumatic Stress Studies,Oslo,Norway.

Background: Our understanding of the dynamics of post-traumatic stress symptomatology and its link to functional impairment over time is limited.

Method: Post-traumatic stress symptomatology (Post-traumatic Checklist, PCL) was assessed three times in 1-year increments (T1, T2, T3) following the Oslo bombing of 22 July, 2011, in directly (n = 257) and indirectly exposed (n = 2223) government employees, together with demographics, measures of exposure and work and social adjustment. The dynamics of post-traumatic stress disorder symptom cluster interplay were examined within a structural equation modelling framework using a cross-lagged autoregressive panel model.

Results: Intrusions at T1 played a prominent role in predicting all symptom clusters at T2 for the directly exposed group, exhibiting especially strong cross-lagged relationships with avoidance and anxious arousal. For the indirectly exposed group, dysphoric arousal at T1 played the most prominent role in predicting all symptom clusters at T2, exhibiting a strong relationship with emotional numbing. Emotional numbing seemed to be the main driver behind prolonged stress at T3 for both groups. Functional impairment was predominately associated with dysphoric arousal and emotional numbing in both groups.

Conclusions: For directly exposed individuals, memories of the traumatic incident and the following intrusions seem to drive their post-traumatic stress symptomatology. However, as these memories lose their potency over time, a sequela of dysphoric arousal and emotional numbing similar to the one reported by the indirectly exposed individuals seems to be the main driver for prolonged post-traumatic stress and functional impairment. Findings are discussed using contemporary models within an exposure-dependent perspective of post-traumatic stress.
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http://dx.doi.org/10.1017/S0033291716001860DOI Listing
November 2016

Does optimism act as a buffer against posttraumatic stress over time? A longitudinal study of the protective role of optimism after the 2011 Oslo bombing.

Psychol Trauma 2017 03 19;9(2):207-213. Epub 2016 Sep 19.

Norwegian Centre for Violence and Traumatic Stress Studies.

Objective: Cross-sectional studies have revealed that high levels of optimism can protect against high levels of posttraumatic stress after exposure to trauma. However, this is the first study to explore (a) the protective role of optimism in a longitudinal perspective and (b) optimism's protective effects on specific symptom clusters within the posttraumatic stress symptomatology.

Method: This study used prospective survey data from ministerial employees (n = 256) collected approximately 1, 2, and 3 years after the 2011 Oslo bombing. To examine relationships between optimism and development of posttraumatic stress, we applied a series of latent growth curve analyses of both overall posttraumatic stress and the 5 clusters within the posttraumatic stress symptomatology (intrusions, avoidance, numbing, dysphoric arousal, and anxious arousal) with predictors and interaction terms.

Results: The results showed that levels of exposure and optimism had main effects on starting levels of all clusters of posttraumatic stress. In addition, optimism had a protective-stabilizing effect on starting levels of avoidance, numbing, and dysphoric arousal. No associations between optimism and rate of change in symptoms clusters were found.

Conclusion: These results suggest that optimism may help to neutralize the effects of high exposure on levels of symptoms of avoidance, numbing, and dysphoric arousal but not on the symptoms of intrusions and anxious arousal. Thus, individuals high in optimism still experience intrusions and anxious arousal after trauma, but may be better equipped to cope with these so they do not develop into avoidance, numbing and dyshorical arousal. (PsycINFO Database Record
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http://dx.doi.org/10.1037/tra0000188DOI Listing
March 2017

Brain Activity in Response to Trauma-specific, Negative, and Neutral Stimuli. A fMRI Study of Recent Road Traffic Accident Survivors.

Front Psychol 2016 5;7:1173. Epub 2016 Aug 5.

Norwegian Centre for Violence and Traumatic Stress StudiesOslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of OsloOslo, Norway.

Most studies of neuro-functional patterns in trauma-exposed individuals have been conducted considerable time after the traumatic event. Hence little is known about neuro-functional processing shortly after trauma-exposure. We investigated brain activity patterns in response to trauma reminders as well as neutral and negative stimuli in individuals who had recently (within 3 weeks) been involved in a road traffic accident (RTA). Twenty-three RTA survivors and 17 non-trauma-exposed healthy controls (HCs) underwent functional MRI while viewing Trauma-specific, Negative, and Neutral pictures. Data were analyzed from four a priori regions of interest, including bilateral amygdala, subcallosal cortex, and medial prefrontal cortex. In addition, we performed a whole brain analysis and functional connectivity analysis during stimulus presentation. For both groups, Negative stimuli elicited more activity in the amygdala bilaterally than did Neutral and Trauma-specific stimuli. The whole brain analysis revealed higher activation in sensory processing related areas (bilateral occipital and temporal cortices and thalamus) as well as frontal and superior parietal areas, for the RTA group compared to HC, for Trauma-specific stimuli contrasted with Neutral stimuli. We also observed higher functional connectivity for Trauma-specific stimuli, between bilateral amygdala and somatosensory areas, for the RTA group compared to controls, when contrasted with Neutral stimuli. We argue that these results might indicate an attentional sensory processing bias toward Trauma-specific stimuli for trauma exposed individuals, a result in line with findings from the post-traumatic stress disorder literature.
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http://dx.doi.org/10.3389/fpsyg.2016.01173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974943PMC
August 2016

Thinking that one's life was in danger: perceived life threat in individuals directly or indirectly exposed to terror.

Br J Psychiatry 2016 10 7;209(4):306-310. Epub 2016 Apr 7.

Trond Heir, PhD, Norwegian Centre for Violence and Traumatic Stress Studies, Oslo, and Institute of Clinical Medicine, University of Oslo; Ines Blix, PhD, Charlotte K. Knatten, PhD, Norwegian Centre for Violence and Traumatic Stress Studies, Olso, Norway.

Background: Perceived life threat is associated with post-traumatic stress disorder (PTSD). Still, it is not known whether perceived threat may be important for PTSD in people indirectly exposed to trauma.

Aims: To examine the prevalence of perceived life threat and the association with PTSD in individuals directly or indirectly exposed to terror.

Method: Data are cross-sectional from a survey 10 months after the 2011 Oslo bombing. Perceived life threat was measured by the question: 'How great do you think the danger was that you would die?' scored on a five-point scale. PTSD was measured with the PTSD Checklist (PCL).

Results: The retrospective belief that one's life was in great or overwhelming danger was reported by 65% and 22% of employees who had been present or not present, respectively, at the site of the bomb explosion (n = 1923). A high perceived life threat was associated with PTSD among those present (odds ratio (OR) = 5.7, 95% CI 1.9-16.9) and not present (OR = 5.2. 95% CI 3.0-9.0), even after adjusting for objective exposure, demographics and neuroticism.

Conclusions: Perceived life threat may play a central role in the development and maintenance of PTSD in people directly as well as indirectly exposed to terror. Moderating perceptions of having been in serious danger may be an appropriate approach to the prevention and treatment of PTSD.
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http://dx.doi.org/10.1192/bjp.bp.115.170167DOI Listing
October 2016

Lysophosphatidic acid regulates adhesion molecules and enhances migration of human oral keratinocytes.

Eur J Oral Sci 2016 Apr 23;124(2):164-71. Epub 2016 Feb 23.

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

Oral keratinocytes are connected via cell-to-cell adhesions to protect underlying tissues from physical and bacterial damage. Lysophosphatidic acids (LPAs) are a family of phospholipid mediators that have the ability to regulate gene expression, cytoskeletal rearrangement, and cytokine/chemokine secretion, which mediate proliferation, migration, and differentiation. Several forms of LPA are found in saliva and gingival crevicular fluid, but it is unknown how they affect human oral keratinocytes (HOK). The aim of the present study was therefore to examine how different LPA forms affect the expression of adhesion molecules and the migration and proliferation of HOK. Keratinocytes were isolated from gingival biopsies obtained from healthy donors and challenged with different forms of LPA. Quantitative real-time RT-PCR, immunocytochemistry, and flow cytometry were used to analyze the expression of adhesion molecules. Migration and proliferation assays were performed. Lysophosphatidic acids strongly promoted expression of E-cadherin and occludin mRNAs and translocation of E-cadherin protein from the cytoplasm to the membrane. Occludin and claudin-1 proteins were up-regulated by LPA. Migration of HOK in culture was increased, but proliferation was reduced, by the addition of LPA. This indicates that LPA can have a role in the regulation of the oral epithelial barrier by increasing the expression of adhesion molecules of HOK, by promotion of migration and by inhibition of proliferation.
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http://dx.doi.org/10.1111/eos.12255DOI Listing
April 2016

The aftermath of terrorism: posttraumatic stress and functional impairment after the 2011 Oslo bombing.

Front Psychol 2015 7;6:1156. Epub 2015 Aug 7.

Norwegian Centre for Violence and Traumatic Stress Studies Oslo, Norway ; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo Norway.

Objective: In the present study we wanted to investigate the link between exposure, posttraumatic stress symptomatology, and functional impairment in the aftermath of terrorism.

Method: Posttraumatic stress symptomatology and functional impairment related to the Oslo bombing 22nd of July, 2011, in directly and indirectly exposed individuals (N = 1927) were assessed together with demographics, exposure, peri-traumatic reactions, and event centrality approximately 1 year after the attack.

Results: Directly and indirectly exposed individuals qualifying for posttraumatic stress disorder (PTSD) reported similar peri-traumatic reactions, event centrality, and functional impairment. However, clusters within the PTSD symptomatology were differentially associated with impairment as a function of their exposure. In the directly exposed group, all clusters within the PTSD symptomatology were associated with impairment in function, while only emotional numbing was associated with impairment within the indirectly exposed group.

Conclusion: Considering that terror attacks frequently involve directly exposed individuals and a larger population of indirectly exposed individuals, this finding is of importance, especially in the design of intervention programs and the development of treatment policies.
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http://dx.doi.org/10.3389/fpsyg.2015.01156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528096PMC
August 2015

Posttraumatic growth and centrality of event: A longitudinal study in the aftermath of the 2011 Oslo bombing.

Psychol Trauma 2015 Jan 18;7(1):18-23. Epub 2014 Aug 18.

Norwegian Centre for Violence and Traumatic Stress Studies.

Previous studies have reported that construing a traumatic event as central to one's life story and identity are associated with posttraumatic growth (PTG). Due to cross-sectional designs, these studies provide only weak evidence of a causal relationship between event centrality and PTG. The main aim in the present study is to examine the longitudinal associations and directionality between centrality of event and PTG in ministerial employees who were present at work during the 2011 Oslo bombing attack (N = 229). By applying a cross-lagged autoregressive model, the present study investigates both stability across time, possible time-lagged effects, and the relationship between centrality of event and PTG at 1 and 2 years after the bombing. The results showed that levels of centrality of event and PTG were stable across time. There was a significant association between centrality of event and PTG both 1 and 2 years after the bombing; however, this relationship attenuated over time. No time-lagged effects in either direction were found. The present findings are in line with previous findings indicating that centrality of a traumatic event is related to PTG. However, the present longitudinal data do not support a hypothesis about a long-term causal effect of event centrality on PTG. Rather, the relationship between centrality of event and PTG are concurrent, and attenuates with time.
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http://dx.doi.org/10.1037/tra0000006DOI Listing
January 2015

Latent classes of posttraumatic stress and growth.

Anxiety Stress Coping 2015 17;28(3):272-86. Epub 2014 Sep 17.

a Norwegian Centre for Violence and Traumatic Stress Studies , 181 Nydalen, 0409 Oslo , Norway.

Background And Objectives: Potentially traumatic events may lead to different patterns of posttraumatic stress symptoms and posttraumatic growth. The objective of the present study was to identify subgroups with different patterns of posttraumatic reactions, and to determine whether these subgroups differed in terms of personal and social resources and indicators of adjustment.

Design: This study used survey data collected 10 months after the 2011 Oslo bombing attack to investigate patterns of reactions among ministerial employees (N=1970).

Methods: We applied latent class analyses with covariates to extract subgroups of individuals.

Results: Three classes of individual reactions were extracted, and these were similar among those who were and those who were not physically proximate to the bombing attack: "High stress/high growth" (27% and 11%, respectively), "Low stress/high growth" (74% and 42%, respectively), and "Low stress/low growth" (only among the not physically proximate: 47%). The classes differed in terms of gender, neuroticism, and social support as well as life satisfaction and daily functioning.

Conclusions: Heterogeneous patterns of posttraumatic reactions were found. Physical proximity is not necessary to experience posttraumatic stress or growth after political violence. Among individuals with low stress, posttraumatic growth may not encompass higher life satisfaction or functioning.
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http://dx.doi.org/10.1080/10615806.2014.956097DOI Listing
October 2015

The oral commensal Streptococcus mitis shows a mixed memory Th cell signature that is similar to and cross-reactive with Streptococcus pneumoniae.

PLoS One 2014 13;9(8):e104306. Epub 2014 Aug 13.

Department of Oral Biology, University of Oslo, Oslo, Norway.

Background: Carriage of and infection with Streptococcus pneumoniae is known to predominantly induce T helper 17 (Th17) responses in humans, but the types of Th cells showing reactivity towards commensal streptococci with low pathogenic potential, such as the oral commensals S. mitis and S. salivarius, remain uncharacterized.

Methods: Memory CD4(+) T helper (Th) cell subsets were isolated from healthy human blood donors according to differential expression of chemokine receptors, expanded in vitro using polyclonal stimuli and characterized for reactivity against different streptococcal strains.

Results: Th cells responding to S. mitis, S. salivarius and S. pneumoniae were predominantly in a CCR6(+)CXCR3(+) subset and produced IFN-γ, and in a CCR6(+)CCR4(+) subset and produced IL-17 and IL-22. Frequencies of S. pneumoniae-reactive Th cells were higher than frequencies of S. mitis- and S. salivarius-specific Th cells. S. mitis and S. pneumoniae isogenic capsule knock-out mutants and a S. mitis mutant expressing the serotype 4 capsule of S. pneumoniae showed no different Th cell responses as compared to wild type strains. S. mitis-specific Th17 cells showed cross-reactivity with S. pneumoniae.

Conclusions: As Th17 cells partly control clearance of S. pneumoniae, cross-reactive Th17 cells that may be induced by commensal bacterial species may influence the immune response, independent of capsule expression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104306PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131883PMC
May 2015

The short form of TSLP is constitutively translated in human keratinocytes and has characteristics of an antimicrobial peptide.

Mucosal Immunol 2015 Jan 21;8(1):49-56. Epub 2014 May 21.

Department of Oral Biology, Dental Faculty, University of Oslo, Oslo, Norway.

Thymic stromal lymphopoietin (TSLP) has multifaceted immunological functions ranging from maintenance of tolerance to induction of disease. Two human transcript variants of TSLP are described: a long form (variant 1; lfTSLP) consisting of four exons and an alternative, short form (variant 2; sfTSLP) that lacks two exons compared with variant 1. SfTSLP has not been described at the protein level or functionally studied. Here, we demonstrate that the human sfTSLP is the predominant form of TSLP, constitutively expressed at the mRNA and protein level in keratinocytes of oral mucosa and skin and in salivary glands, is released in saliva, and is not regulated in the same manner as the long form. Compared with lfTSLP, sfTSLP exhibits a markedly stronger antibacterial activity. Synthetic sfTSLP did not activate signal transducer and activator of transcription 5 (STAT5) signaling in CD1c(+) dendritic cells nor interfered with STAT5 activation by lfTSLP. SfTSLP may, therefore, act as an antimicrobial peptide in the oral cavity and on the skin to create a defense barrier that aids in the control of both commensal and pathogenic microbes. The results show that the two translational products of the TSLP gene have a different expression and different biological properties, and emphasize the importance of analyzing the two TSLP isoforms separately.
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http://dx.doi.org/10.1038/mi.2014.41DOI Listing
January 2015

Posttraumatic growth, posttraumatic stress and psychological adjustment in the aftermath of the 2011 Oslo bombing attack.

Health Qual Life Outcomes 2013 Oct 2;11:160. Epub 2013 Oct 2.

Norwegian Centre for Violence and Traumatic Stress Studies, NKVTS, Pb 181 Nydalen, 0409 Oslo, Norway.

Background: Experiencing potentially traumatic events is associated with psychological distress. However, some survivors also experience positive personal and psychological changes in the aftermath of trauma.

Methods: The present study investigated perceived posttraumatic growth in 197 ministerial employees who were present at work during the 2011 Oslo bombing attack. The relationships between trauma-exposure, peritraumatic reactions and posttraumatic growth were studied. Moreover, the adaptive significance of posttraumatic growth was addressed.

Results: The results showed that higher levels of trauma-exposure and immediate reactions were significantly related to perceived posttraumatic growth. No support for an adaptive significance of posttraumatic growth was found. On the contrary, posttraumatic growth was associated with higher symptom levels of posttraumatic stress. After adjusting for posttraumatic stress symptoms no association was found between perceived growth and work and social adjustment. However, perceived growth was associated with higher levels of life satisfaction.

Conclusion: The present results are in line with previous findings indicating that perceived growth may be unrelated to psychological adjustment, and suggest that the concept and significance of posttraumatic growth should be interpreted with caution.
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http://dx.doi.org/10.1186/1477-7525-11-160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3850660PMC
October 2013

Distribution of carcinoembryonic antigen-related cellular adhesion molecules in human gingiva.

Eur J Oral Sci 2012 Oct;120(5):395-401

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

Carcinoembryonic antigen-related cellular adhesion molecules (CEACAMs) are glycoproteins produced in epithelial, endothelial, lymphoid, and myeloid cells. Carcinoembryonic antigen-related cellular adhesion molecules mediate cell-cell contact and host-pathogen interactions. The aims of this study were to map the distribution and examine the regulation of CEACAMs in human gingival sites. Quantitative real-time PCR performed on human gingival biopsies from periodontitis sites revealed mRNA coding for CEACAM1, -5, -6, and -7. Immunohistochemistry showed that CEACAMs were not found in oral gingival epithelium, except for CEACAM5 in periodontitis. Carcinoembryonic antigen-related cellular adhesion molecules 1, 5, and 6 were present in the oral sulcular epithelium of periodontitis but not in that of healthy gingiva. In junctional epithelium, all three molecules were present in healthy gingiva, but in periodontitis only CEACAM1 and -6 were detected. Staining for CEACAM1 and -6 was also seen in the inflammatory cell infiltrate in periodontitis. No staining for CEACAM7 was found. Proinflammatory mediators, including lipopolysaccharide (LPS), tumour necrosis factor-α (TNF-α)/interleukin-1β (IL-1β), and interferon-γ (IFN-γ), increased the expression of CEACAM1 and CEACAM6 mRNAs in cultured human oral keratinocytes. CEACAM1 and CEACAM6 mRNAs were also strongly up-regulated upon stimulation with lysophosphatidic acid. In conclusion, the distribution of different CEACAMs was related to specific sites in the gingiva. This might reflect different functional roles in this tissue.
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http://dx.doi.org/10.1111/j.1600-0722.2012.00981.xDOI Listing
October 2012

Mental time travel after trauma: the specificity and temporal distribution of autobiographical memories and future-directed thoughts.

Memory 2011 Nov 4;19(8):956-67. Epub 2011 Nov 4.

Department of Psychology, University of Oslo, Oslo, Norway.

The present study investigated the relationship between trauma exposure and specificity and temporal distribution of autobiographical memories and future-directed thoughts. A group of sexual assault victims were compared with women without previous trauma exposure in relation to specificity of autobiographical memories, as measured by the Autobiographical Memory Task (AMT) and specificity of future-directed thoughts as measured by the Future Cueing Task (FCT). The temporal distribution of future-directed thoughts and autobiographical memories was studied by asking the participants to estimate when each memory reported on the AMT had occurred and when each future event reported on the FCT would occur. The results showed no difference between the trauma group and the controls on specificity of autobiographical memories and future-directed thoughts. In line with a review of Moore and Zoellner (2007), PTSD symptoms as measured by the Impact of Event Scale (IES) correlated negatively with specificity. Furthermore, we observed no difference in temporal distribution of future-directed thoughts or autobiographical memories between trauma exposed participants and controls.
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http://dx.doi.org/10.1080/09658211.2011.618500DOI Listing
November 2011

Intentional forgetting of emotional words after trauma: a study with victims of sexual assault.

Front Psychol 2011 29;2:235. Epub 2011 Sep 29.

Department of Psychology, Center for the Study of Human Cognition, University of Oslo Oslo, Norway.

Following exposure to a trauma, people tend to experience intrusive thoughts and memories about the event. In order to investigate whether intrusive memories in the aftermath of trauma might be accounted for by an impaired ability to intentionally forget disturbing material, the present study used a modified Directed Forgetting task to examine intentional forgetting and intrusive recall of words in sexual assault victims and controls. By including words related to the trauma in addition to neutral, positive, and threat-related stimuli it was possible to test for trauma-specific effects. No difference between the Trauma and the Control group was found for correct recall of to-be-forgotten (F) words or to-be-remembered (R) words. However, when recalling words from R-list, the Trauma group mistakenly recalled significantly more trauma-specific words from F-list. "Intrusive" recall of F-trauma words when asked to recall R-words was related to symptoms of post-traumatic stress disorder reported on the Impact of Event Scale and the Post-traumatic Diagnostic Scale. The results are discussed in term of a source-monitoring account.
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http://dx.doi.org/10.3389/fpsyg.2011.00235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182753PMC
November 2011

What causes treatment failure - the patient, primary care, secondary care or inadequate interaction in the health services?

BMC Health Serv Res 2011 May 20;11:111. Epub 2011 May 20.

Dept, of Research, Innlandet Hospital Trust, Gjøvik, Norway.

Background: Optimal treatment gives complete relief of symptoms of many disorders. But even if such treatment is available, some patients have persisting complaints. One disorder, from which the patients should achieve complete relief of symptoms with medical or surgical treatment, is gastroesophageal reflux disease (GERD). Despite the fact that such treatment is cheap, safe and easily available; some patients have persistent complaints after contact with the health services. This study evaluates the causes of treatment failure.

Methods: Twelve patients with GERD and persistent complaints had a semi-structured interview which focused on the patients' evaluation of treatment failure. The interviews were taped, transcribed and evaluated by 18 physicians, (six general practitioners, six gastroenterologists and six gastrointestinal surgeons) who completed a questionnaire for each patient. The questionnaires were scored, and the relative responsibility for the failure was attributed to the patient, primary care, secondary care and interaction in the health services.

Results: Failing interaction in the health services was the most important cause of treatment failure, followed by failure in primary care, secondary care and the patient himself; the relative responsibilities were 35%, 28%, 27% and 10% respectively. There was satisfactory agreement about the causes between doctors with different specialities, but significant inter-individual differences between the doctors. The causes of the failures differed between the patients.

Conclusions: Treatment failure is a complex problem. Inadequate interaction in the health services seems to be important. Improved communication between parts of the health services and with the patients are areas of improvement.
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http://dx.doi.org/10.1186/1472-6963-11-111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126699PMC
May 2011

Retrieval-induced forgetting after trauma: a study with victims of sexual assault.

Cogn Emot 2012 23;26(2):321-31. Epub 2011 May 23.

Center for the Study of Human Cognition, Department of Psychology,University of Oslo, Oslo, Norway.

The Retrieval-Induced Forgetting (RIF) paradigm is used to study how the repeated retrieval practice of particular memories impairs the retrieval of related memory traces. A study is reported where this automatic form of forgetting was investigated in a group of sexual-assault victims and a control group. Using a recognition-cued RIF task, the present study examined RIF with neutral, positive, negative and trauma-specific stimuli. Response time data showed that irrespective of previous trauma exposure, a RIF effect was observed for neutral material, but not for emotional material. No differences in RIF between the trauma group and the control group were found. Inconsistencies with previous literature and the implications for emotional memory are discussed.
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http://dx.doi.org/10.1080/02699931.2011.570312DOI Listing
June 2012

Trauma exposure in childhood impairs the ability to recall specific autobiographical memories in late adolescence.

J Trauma Stress 2010 Apr;23(2):240-7

Center for the Study of Human Cognition, Department of Psychology, University of Oslo, Norway.

J. M. G. Williams (1996) predicted that exposure to potentially traumatizing events at an early age would give rise to overgeneral recall from autobiographical memory, i.e., recall of general rather than specific events, and that in adolescence this tendency would be uncorrelated with psychopathological symptoms, e.g., depression. This was supported by two studies where war-exposed Bosnian adolescents produced significantly fewer specific autobiographical memories than a Norwegian control group, as did bombing-exposed Serbian adolescents compared to nontrauma-exposed Serbians. No significant correlations were found between autobiographical memory specificity and measures of depression, anxiety, dissociation or impact of trauma, which is consistent with Williams' idea that an overgeneral memory retrieval strategy is at first protective, and a risk factor for depression only upon reaching adulthood.
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http://dx.doi.org/10.1002/jts.20513DOI Listing
April 2010

LPS from Actinobacillus actinomycetemcomitans and the expression of beta2 integrins and L-selectin in an ex vivo human whole blood system.

Eur J Oral Sci 1999 Feb;107(1):14-20

Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway.

Actinobacillus actinomycetemcomitans is assumed to be an important etiological agent in localized juvenile periodontitis (LJP) and to have the ability to invade periodontal tissues. This bacterium has also been noted for its potential to cause serious extraoral infections. In this study, the effect of lipopolysaccharides (LPS) extracted from A. actinomycetemcomitans on the expression of the leukocyte adhesion molecules CD11a/CD18, CD11b/CD18, CD11c/CD18 and L-selectin (CD 62L) were measured in an ex vivo whole blood system by use of fluorescent antibodies followed by flow cytometry. LPS from Escherichia coli, which is known to elicit a strong inflammatory response was used as a reference. The expression of the beta2 integrins CD11a/CD18, CD11b/CD18, and CD11c/CD18 were significantly upregulated in granulocytes and monocytes. This expression was dose-dependent. The baseline levels of L-selectin was high on all three types of leukocytes, but on granulocytes and monocytes it decreased dramatically after stimulation with LPS. The LPS from A. actinomycetemcomitans was equally potent as LPS from E. coli in its ability to affect the expression of the leukocyte integrins and L-selectin.
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http://dx.doi.org/10.1046/j.0909-8836.1999.eos107104.xDOI Listing
February 1999