Induction of anti-tumor immunity by vaccination with dendritic cells pulsed with anti-CD44 IgG opsonized tumor cells

Due to the pivotal role that dendritic cells (DC) play in eliciting and maintaining functional anti-tumor T cell responses, these APC have been exploited against tumors. DC express several receptors for the Fc portion of IgG (Fcγ receptors) that mediate the internalization of antigen-IgG complexes and promote efficient MHC class I and II restricted antigen presentation. In this study, the efficacy of vaccination with DC pulsed with apoptotic B16 melanoma cells opsonized with an anti-CD44 IgG (B16-CD44) was explored. Immature bone marrow derived DC grown in vitro with IL-4 and GM-CSF were pulsed with B16-CD44. After 48 h of pulsing, maturation of DC was demonstrated by production of IL-12 and upregulation of CD80 and CD40 expression. To test the efficacy of vaccination with DC+B16-CD44, mice were vaccinated subcutaneously Lymphocytes from mice vaccinated with DC+B16-CD44 produced IFN-γ in response to B16 melanoma lysates as well as an MHC class I restricted B16 melanoma-associated peptide, indicating B16 specific CD8 T cell activation. Upon challenge with viable B16 cells, all mice vaccinated with DC alone developed tumor compared to 40% of mice vaccinated with DC+B16-CD44; 60% of the latter mice remained tumor free for at least 8 months. In addition, established lung tumors and distant metastases were significantly reduced in mice treated with DC+B16-CD44. Lastly, delayed growth of established subcutaneous tumors was induced by combination therapy with anti-CD44 antibodies followed by DC injection. This study demonstrates the efficacy of targeting tumor antigens to DC via Fcγ receptors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45862/1/262_2005_Article_104.pd

Difficulty concentrating in generalized anxiety disorder: An evaluation of incremental utility and relationship to worry

Difficulty concentrating is one of the most common diagnostic criteria across DSM-5 categories, especially within the emotional (mood- and anxiety-related) disorders. A substantial literature has characterized cognitive functioning in emotional disorders using objective (behavioral) computerized cognitive tasks. However, diagnoses are typically formed on the basis of subjective (self-reported; clinician-rated) assessments of symptoms, and little is known about difficulty concentrating as a symptom. These questions are particularly important for generalized anxiety disorder (GAD), which has long been the subject of nosological debates, and for which several theoretical models that suggest a central role for cognitive impairments (including difficulty concentrating) in the maintenance of psychopathology have been proposed. The present study evaluated the incremental utility of difficulty concentrating and its relationship to worry and other symptoms in 175 GAD-diagnosed adults. Clinician-assessed difficulty concentrating incrementally predicted clinician-rated GAD, anxiety, and depression severity even after other GAD symptoms were controlled. Consistent with theoretical models of GAD that propose a direct relationship between worry and cognitive impairment, difficulty concentrating mediated the relationship between trait worry and clinical severity. These findings suggest that difficulty concentrating has value as a diagnostic criterion and is a potential mechanism by which worry increases distress and impairment

Intolerance of uncertainty is associated with heightened arousal during extinction learning and retention: preliminary evidence from a clinical sample with anxiety and obsessive-compulsive disorders

Background: uncertainty-related distress is considered a hallmark of anxiety and obsessive compulsive disorders (OCD). Previous research in community samples has demonstrated that individuals with high Intolerance of Uncertainty (IU), the tendency to find uncertainty aversive, display altered threat extinction learning and retention.Methods: here, we conducted an exploratory secondary analysis of an existing dataset (Steinman et al., 2022) to examine the extent to which IU in a clinical sample with anxiety and OCD predicts threat extinction learning and retention. Participants with an anxiety disorder and/or OCD completed a differential threat learning task across two days (n = 27). Skin conductance response (SCR) was used as an index of conditioned responding.Results: no significant effects of self-reported IU were observed for differential SCR during any of the experimental phases. However, higher self-reported IU, while controlling for trait anxiety, was specifically associated with greater SCR overall during same-day extinction training, next-day extinction training, and next-day reinstatement test.Conclusions: such findings provide preliminary evidence that higher IU within clinical samples with anxiety and/or OCD may be associated with heightened arousal under uncertainty, and highlight IU as a promising treatment target for anxiety and OCD.</p

Three-year outcomes of adults with anxiety and related disorders following cognitive-behavioral therapy in a non-research clinical setting

Anxiety and related disorders are highly prevalent and costly to society. Fortunately, a large number of randomized controlled trials have demonstrated the efficacy of cognitive behavioral therapy (CBT) in the treatment of anxiety and related disorders. A smaller number of effectiveness studies have also demonstrated that similar outcomes to randomized controlled trials can be obtained in "real-world" settings. There is minimal research, however, into long-term outcomes in effectiveness research. This study describes the outcomes of 98 individuals with anxiety and related disorders treated in an outpatient, fee-for-service setting using a case formulation CBT approach. Participants were followed up each year after their discharge, for a period of 3 years. The results indicate that patients maintained their treatment gains, with large effect sizes obtained from pre-treatment to each follow-up time point (d = 1.11-1.60). The results provide preliminary evidence to suggest that individuals treated with CBT in "real-world" settings maintain their treatment gains in the long-term

Psychometric Properties of the Difficulties in Emotion Regulation Scale (DERS) and Its Short Forms in Adults With Emotional Disorders

Objective: The Difficulties in Emotion Regulation Scale (DERS) is a widely used self- report measure of subjective emotion ability, as defined by a prominent clinically derived model of emotion regulation (Gratz and Roemer, 2004). Although the DERS is often used in treatment and research settings for adults with emotional (i.e., anxiety, mood, obsessive-compulsive, or trauma-related) disorders, its psychometric properties are not well-characterized in this population. Method: We examined the psychometric properties of the DERS and three popular short forms (DERS-16; DERS-18; and DERS-SF) in a large (N = 427) sample of treatment-seeking adults with one or more DSM-5 emotional disorders. Results: For the original DERS, internal consistency was strong for all subscales except Awareness. A bifactor structure consisting of one general emotion dysregulation factor and five uncorrelated specific factors corresponding to the original DERS subscales (excluding Awareness) provided the best fit. A series of structural equation models (SEMs) demonstrated unique incremental contributions of the general factor and several specific factors to explaining concurrent clinical severity. The general factor and one specific factor (Goals) also prospectively predicted treatment outcome following a naturalistic course of outpatient cognitive-behavioral therapy (CBT) in a subset of participants (n = 202) for whom discharge data were available. Specifically, more severe emotion dysregulation at intake predicted better CBT response, while more severe impairment in goal-directed activity when distressed predicted worse CBT response. All three short forms showed a robust bifactor structure and good internal consistency and convergent validity vis-à-vis the original measure, albeit with a slight decrement in incremental utility (1–3% less variance explained in clinical severity). Conclusion: With the Awareness items excluded, the DERS showed good internal consistency and a robust bifactor latent structure. The general factor and several specific factors incrementally and prospectively predicted clinical severity and treatment outcome, which suggests that the DERS may have clinical and predictive utility in treatment-seeking adults with emotional disorders. Additional research is needed to establish convergent and discriminant validity in this population. The use of a short form in lieu of the full DERS may be sufficient for many general clinical and research purposes, particularly when participant burden is a concern

Psychometric Properties of the Difficulties in Emotion Regulation Scale (DERS) and Its Short Forms in Adults With Emotional Disorders

Objective: The Difficulties in Emotion Regulation Scale (DERS) is a widely used self-report measure of subjective emotion ability, as defined by a prominent clinically derived model of emotion regulation (Gratz and Roemer, 2004). Although the DERS is often used in treatment and research settings for adults with emotional (i.e., anxiety, mood, obsessive-compulsive, or trauma-related) disorders, its psychometric properties are not well-characterized in this population.Method: We examined the psychometric properties of the DERS and three popular short forms (DERS-16; DERS-18; and DERS-SF) in a large (N = 427) sample of treatment-seeking adults with one or more DSM-5 emotional disorders.Results: For the original DERS, internal consistency was strong for all subscales except Awareness. A bifactor structure consisting of one general emotion dysregulation factor and five uncorrelated specific factors corresponding to the original DERS subscales (excluding Awareness) provided the best fit. A series of structural equation models (SEMs) demonstrated unique incremental contributions of the general factor and several specific factors to explaining concurrent clinical severity. The general factor and one specific factor (Goals) also prospectively predicted treatment outcome following a naturalistic course of outpatient cognitive-behavioral therapy (CBT) in a subset of participants (n = 202) for whom discharge data were available. Specifically, more severe emotion dysregulation at intake predicted better CBT response, while more severe impairment in goal-directed activity when distressed predicted worse CBT response. All three short forms showed a robust bifactor structure and good internal consistency and convergent validity vis-à-vis the original measure, albeit with a slight decrement in incremental utility (1–3% less variance explained in clinical severity).Conclusion: With the Awareness items excluded, the DERS showed good internal consistency and a robust bifactor latent structure. The general factor and several specific factors incrementally and prospectively predicted clinical severity and treatment outcome, which suggests that the DERS may have clinical and predictive utility in treatment-seeking adults with emotional disorders. Additional research is needed to establish convergent and discriminant validity in this population. The use of a short form in lieu of the full DERS may be sufficient for many general clinical and research purposes, particularly when participant burden is a concern