53 research outputs found
Depletion of stromal cells expressing fibroblast activation protein-α from skeletal muscle and bone marrow results in cachexia and anemia.
Fibroblast activation protein-α (FAP) identifies stromal cells of mesenchymal origin in human cancers and chronic inflammatory lesions. In mouse models of cancer, they have been shown to be immune suppressive, but studies of their occurrence and function in normal tissues have been limited. With a transgenic mouse line permitting the bioluminescent imaging of FAP(+) cells, we find that they reside in most tissues of the adult mouse. FAP(+) cells from three sites, skeletal muscle, adipose tissue, and pancreas, have highly similar transcriptomes, suggesting a shared lineage. FAP(+) cells of skeletal muscle are the major local source of follistatin, and in bone marrow they express Cxcl12 and KitL. Experimental ablation of these cells causes loss of muscle mass and a reduction of B-lymphopoiesis and erythropoiesis, revealing their essential functions in maintaining normal muscle mass and hematopoiesis, respectively. Remarkably, these cells are altered at these sites in transplantable and spontaneous mouse models of cancer-induced cachexia and anemia. Thus, the FAP(+) stromal cell may have roles in two adverse consequences of cancer: their acquisition by tumors may cause failure of immunosurveillance, and their alteration in normal tissues contributes to the paraneoplastic syndromes of cachexia and anemia
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Neural connectivity during affect labeling predicts treatment response to psychological therapies for social anxiety disorder
BackgroundAlthough psychological treatments for social anxiety disorder (SAD) can be highly effective, many individuals do not respond to treatment. Identifying factors associated with improved outcomes can facilitate individualized treatment choices. We investigated whether patterns of neural connectivity predicted treatment responses and whether treatment type, cognitive behavioral therapy (CBT) or acceptance and commitment therapy (ACT), moderated this effect.MethodsParticipants with SAD (n = 34) underwent fMRI prior to treatment and completed implicit and explicit emotion regulation tasks. Neural connectivity measures were estimates of amygdala-prefrontal cortex connectivity. Treatment responder status was defined using the 'clinically significant change index' (Loerinc et al., 2015).ResultsRight amygdala-right ventrolateral prefrontal cortex connectivity during implicit emotion regulation was a significant predictor of treatment response (OR = 9.01, 95% CI = 1.77, 46.0, p = .008). Stronger inverse connectivity was associated with greater likelihood of treatment response. There were no significant neural moderators of treatment response to CBT versus ACT.LimitationsThe primary limitation of this work was the small sample size which restricted the power to detect significant moderation effects, and results should be interpreted as preliminary.ConclusionsAmygdala-vlPFC connectivity during affect labeling predicted treatment responder status following CBT or ACT for social anxiety disorder. This suggests that the functioning of neural circuitry supporting emotion regulation capacities may be a 'gateway' to receiving benefit from psychological treatments. Future work should aim to replicate this effect in a larger sample and consider methods for enhancing functional connectivity within this circuitry as a potential treatment adjunct
Public speaking avoidance as a treatment moderator for social anxiety disorder.
Background and objectivesCognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT) have both garnered empirical support for the effective treatment of social anxiety disorder. However, not every patient benefits equally from either treatment. Identifying moderators of treatment outcome can help to better understand which treatment is best suited for a particular patient.MethodsForty-nine individuals who met criteria for social anxiety disorder were assessed as part of a randomized controlled trial comparing 12 weeks of CBT and ACT. Pre-treatment avoidance of social situations (measured via a public speaking task and clinician rating) was investigated as a moderator of post-treatment, 6-month follow-up, and 12-month follow-up social anxiety symptoms, stress reactivity, and quality of life.ResultsPublic speaking avoidance was found to be a robust moderator of outcome measures, with more avoidant individuals generally benefitting more from CBT than ACT by 12-month follow-up. In contrast, clinician-rated social avoidance was not found to be a significant moderator of any outcome measure.LimitationsResults were found only at 12-month follow-up. More comprehensive measures of avoidance would be useful for the field moving forward.ConclusionsFindings inform personalized medicine, suggesting that social avoidance measured behaviorally via a public speaking task may be a more robust factor in treatment prescription compared to clinician-rated social avoidance
Studying Children’s Growth in Self-Regulation using Changing Measures to Account for Heterotypic Continuity: A Bayesian Approach to Developmental Scaling
Manuscript accepted for publication in Developmental Scienc
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