| 1. |
- Udayappan, S. D., et al.
(författare)
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Intestinal Ralstonia pickettii augments glucose intolerance in obesity
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:11
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Tidskriftsartikel (refereegranskat)abstract
- An altered intestinal microbiota composition has been implicated in the pathogenesis of metabolic disease including obesity and type 2 diabetes mellitus (T2DM). Low grade inflammation, potentially initiated by the intestinal microbiota, has been suggested to be a driving force in the development of insulin resistance in obesity. Here, we report that bacterial DNA is present in mesenteric adipose tissue of obese but otherwise healthy human subjects. Pyrosequencing of bacterial 16S rRNA genes revealed that DNA from the Gram-negative species Ralstonia was most prevalent. Interestingly, fecal abundance of Ralstonia pickettii was increased in obese subjects with pre-diabetes and T2DM. To assess if R. pickettii was causally involved in development of obesity and T2DM, we performed a proof-of-concept study in diet-induced obese (DIO) mice. Compared to vehicle-treated control mice, R. pickettii-treated DIO mice had reduced glucose tolerance. In addition, circulating levels of endotoxin were increased in R. pickettii-treated mice. In conclusion, this study suggests that intestinal Ralstonia is increased in obese human subjects with T2DM and reciprocally worsens glucose tolerance in DIO mice.
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| 2. |
- Koopen, A., et al.
(författare)
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Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study
- 2022
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 71:8, s. 1577-1587
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Tidskriftsartikel (refereegranskat)abstract
- Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.
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| 3. |
- Fjermestad, Krister W., et al.
(författare)
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Factor Structure and Validity of the Therapy Process Observational Coding System for Child Psychotherapy-Alliance Scale
- 2012
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Ingår i: Journal of clinical child and adolescent psychology (Print). - : Informa UK Limited. - 1537-4416 .- 1537-4424. ; 41:2, s. 246-254
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to examine the factor structure and psychometric properties of an observer-rated youth alliance measure, the Therapy Process Observational Coding System for Child Psychotherapy-Alliance scale (TPOCS-A). The sample was 52 youth diagnosed with anxiety disorders (M age = 12.43, SD = 2.23, range = 8-15; 56% boys; 98% Caucasian) drawn from a randomized controlled trial. Participants received a manualized individual cognitive behavioral treatment, the FRIENDS for life program, in public community clinics in Norway. Diagnostic status, treatment motivation, and perceived treatment credibility were assessed at pretreatment. Using the TPOCS-A, independent observers rated child-therapist alliance from the third therapy session. Child-and therapist-reported alliance measures were collected from the same session. An exploratory factor analysis supported a one-factor solution, which is consistent with previous studies of self-and observer-rated youth alliance scales. Psychometric analyses supported the interrater reliability, internal consistency, and convergent/divergent validity of the TPOCS-A. Accumulating psychometric evidence indicate that the TPOCS-A has the potential to fill a measurement gap in the youth psychotherapy field. In youth psychotherapy, alliance may be unidimensional, so establishing a strong bond and engaging the child in therapeutic activities may both be instrumental to establishing good alliance early in treatment. However, it is important to be cautious when interpreting the factor analytic findings, because the sample size may have been too small to identify additional factors. Future research can build upon these findings by examining the factor structure of youth alliance measures with larger, more diverse samples.
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| 4. |
- Fjermestad, K. W., et al.
(författare)
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Motivation and treatment credibility predict alliance in cognitive behavioral treatment for youth with anxiety disorders in community clinics
- 2018
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Ingår i: Journal of Clinical Psychology. - : Wiley. - 0021-9762 .- 1097-4679. ; 74:6, s. 793-805
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Tidskriftsartikel (refereegranskat)abstract
- Objective We examined whether motivation and treatment credibility predicted alliance in a 10-session cognitive behavioral treatment delivered in community clinics for youth anxiety disorders.Method Ninety-one clinic-referred youths (mean(age)=11.4 years, standard deviation=2.1, range 8-15 years, 49.5% boys) with anxiety disorders-rated treatment motivation at pretreatment and perceived treatment credibility after session 1. Youths and therapists (YT) rated alliance after session 3 (early) and session 7 (late). Hierarchical linear models were applied to examine whether motivation and treatment credibility predicted YT early alliance, YT alliance change, and YT alliance agreement.Results Motivation predicted high early YT alliance, but not YT alliance change or alliance agreement. Youth-rated treatment credibility predicted high early youth alliance and high YT positive alliance change, but not early therapist alliance or alliance agreement. Conclusion Efforts to enhance youth motivation and treatment credibility early in treatment could facilitate the formation of a strong YT alliance.
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| 5. |
- Fjermestad, Krister W., et al.
(författare)
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Therapist-youth agreement on alliance change predicts long-term outcome in CBT for anxiety disorders
- 2016
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Ingår i: Journal of Child Psychology and Psychiatry. - : Wiley. - 0021-9630 .- 1469-7610. ; 57:5, s. 625-632
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Tidskriftsartikel (refereegranskat)abstract
- Background: In individual cognitive behavioral therapy (ICBT) for youth anxiety disorders, it is unclear whether, and from whose perspective, the alliance predicts outcome. We examined whether youth- and therapist-rated alliance, including level of youth-therapist alliance agreement, predicted outcome in a randomized controlled trial.Methods: Youth (N = 91, M age = 11.4 years (SD = 2.1), 49.5% boys, 86.8% Caucasian) diagnosed with separation anxiety disorder, social phobia, or generalized anxiety disorder drawn from the ICBT condition of an effectiveness trial were treated with an ICBT program. Youth- and therapist-rated alliance ratings, assessed with the Therapeutic Alliance Scale for Children (TASC-C/T), were collected following session 3 (early) and 7 (late). Early alliance, change in alliance from early to late, and level of youth-therapist agreement on early alliance and alliance change were examined, in relation to outcomes collected at posttreatment and 1-year follow-up. Outcome was defined as primary diagnosis loss and reduction in clinicians' severity ratings (CSR; Anxiety Disorders Interview Schedule; ADIS-C/P) based on youth- and parent-report at posttreatment and follow-up, and youth treatment satisfaction collected at posttreatment (Client Satisfaction Scale; CSS).Results: Early TASC-C scores positively predicted treatment satisfaction at posttreatment. Higher levels of agreement on change in TASC-C and TASC-T scores early to late in treatment predicted diagnosis loss and CSR reduction at follow-up.Conclusions: Only the level of agreement in alliance change predicted follow-up outcomes in ICBT for youth anxiety disorders. The findings support further examination of the role that youth-therapist alliance discrepancies may play in promoting positive outcomes in ICBT for youth anxiety disorders. Clinical trial number NCT00586586, clinicaltrials.gov.
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| 6. |
- Kodal, Arne, et al.
(författare)
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Long-term effectiveness of cognitive behavioral therapy for youth with anxiety disorders
- 2018
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Ingår i: Journal of Anxiety Disorders. - : Elsevier BV. - 0887-6185 .- 1873-7897. ; 53, s. 58-67
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavioral therapy (CBT) has demonstrated favorable long-term outcomes in youth with anxiety disorders in efficacy trials. However, long-term outcomes of CBT delivered in a community setting are uncertain. This study examined the long-term outcomes of individual (ICBT) and group CBT (GCBT) in youth with anxiety disorders treated in community mental health clinics. A total of 139 youth (mean age at assessment 15.5 years, range 11-21 years) with a principal diagnosis of separation anxiety disorder (SAD), social anxiety disorder (SOP), and/or generalized anxiety disorder (GAD) were evaluated, on average, 3.9 years post-treatment (range 2.2-5.9 years). Outcomes included loss of all inclusion anxiety diagnoses, loss of the principal anxiety diagnosis and changes in youth- and parent-rated youth anxiety symptoms. At long-term follow-up, there was loss of all inclusion anxiety diagnoses in 53%, loss of the principal anxiety diagnosis in 63% of participants as well as significant reductions in all anxiety symptom measures. No statistical significant differences in outcome were obtained between ICBT and GCBT. Participants with a principal diagnosis of SOP had lower odds for recovery, compared to those with a principal diagnosis of SAD or GAD. In conclusion, outcomes of CBT for youth anxiety disorders delivered in community mental health clinics were improved at nearly 4 years post-treatment, and recovery rates at long-term follow-up were similar to efficacy trials.
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| 7. |
- Kodal, Arne, et al.
(författare)
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Predictors of long-term outcome of CBT for youth with anxiety disorders treated in community clinics
- 2018
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Ingår i: Journal of Anxiety Disorders. - : Elsevier BV. - 0887-6185 .- 1873-7897. ; 59, s. 53-63
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive behavioral therapy (CBT) has proven long-term effects in youth with anxiety disorders. However, only a few studies have examined predictors of long-term outcomes of CBT treatment. The present study investigated possible predictors of long-term treatment outcomes in youth with mixed anxiety disorders treated in community mental health clinics. A total of 139 youth (mean age at assessment 15.5 years, range 11–21 years) with a principal diagnosis of separation anxiety disorder, social anxiety disorder, and/or generalized anxiety disorder were evaluated a mean of 3.9 years post-treatment (range 2.2–5.9 years). Outcomes were loss of all inclusion anxiety diagnoses, loss of the principal inclusion anxiety diagnosis, and changes in youth- and parent-rated youth anxiety symptoms. Predictors encompassed youth, parent and demographic factors, and post-treatment recovery. The most consistent finding was that low family social class predicted poorer outcomes. Higher treatment motivation was associated with better outcome whereas a diagnosis of social anxiety was associated with poorer outcome. Identified predictors extend on previous findings from efficacy trials, and the results indicate a need for more specific treatment protocols.
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| 8. |
- Marx, P. F., et al.
(författare)
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The activation peptide of thrombin-activatable fibrinolysis inhibitor: a role in activity and stability of the enzyme?
- 2009
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 7:3, s. 445-452
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Tidskriftsartikel (refereegranskat)abstract
- Background: Thrombin-activatable fibrinolysis inhibitor (TAFI) is a 56-kDa procarboxypeptidase. Proteolytic enzymes activate TAFI into TAFIa, an inhibitor of fibrinolysis, by cleaving off the N-terminal activation peptide (amino acids 1-92), from the enzyme moiety. Activated TAFI is unstable, with a half-life of approximately 10 min at 37 degrees C. So far, it is unknown whether the activation peptide is released or remains attached to the catalytic domain, and whether it influences TAFIa's properties. The current study was performed to clarify these issues. Methods: TAFI was activated, and the activity and half-life of the enzyme were determined in the presence and absence of the activation peptide. Results: TAFIa was active both before and after removal of the activation peptide, and the half-life of TAFIa was identical in the two preparations. Furthermore, we observed that intrinsically inactivated TAFIa (TAFIai) aggregated into large, insoluble complexes that could be removed by centrifugation. Conclusions: The data presented in this article show that the activation peptide of TAFI is not required for TAFIa activity and that the activation peptide has no effect on the stability of the enzyme. These results are in favour of a model in which the activation peptide solely stabilizes the structure of the proenzyme. After activation of TAFI and subsequent breakage of interactions between the activation peptide and the catalytic domain, the activation peptide is no longer capable of performing this stabilizing task, and the integrity of the catalytic domain is lost rapidly. The resulting TAFIai is more prone to proteolysis and aggregation.
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