Illness behavior in patients on long-term sick leave due to chronic musculoskeletal pain

Background and purpose Methods for identification of patients with illness behavior in orthopedic settings are still being debated. The purpose of this study was to test the association between illness behavior, depressed mood, pain intensity, self-rated disability, and clinical status in patients with chronic musculoskeletal pain (CMP)

The Role of CD4+ T cells in the CD8+ T cell Response to Vaccinia Viral Infection

<p>The role of CD4 T cell help in primary and secondary CD8 T cell responses to infectious pathogens remains incompletely defined. The primary CD8 T response to infections was initially thought to be largely independent of CD4 T cells, but it is not clear why some primary, pathogen-specific CD8 T cell responses are CD4 T cell-dependent. Furthermore, although the generation of functional memory CD8 T cells is CD4 T cell help-dependent, it remains controversial when the "help" is needed. The goal of this thesis project is to determine requirement and mechanisms of CD4 help during the CD8 response to vaccinia viral (VV) infection.</p><p>The first aim of this project was to determine when CD4 T cell help is required during the CD8 response to VV infection. Using both CD4-deficient mice and mice with transient depletion of CD4 T cells, we demonstrated that CD4 T cell help was not needed for the activation and effector differentiation of CD8 T cells during the primary response to VV infection. However, the activated CD8 T cells showed poor survival without CD4 T cell help, leading to a reduction in clonal expansion and a diminished, but stable CD8 memory pool. In addition, we observed that CD4 T cell help provided during both the primary and secondary responses was required for the survival of memory CD8 T cells during recall expansion. Our study indicates that CD4 T cells play a crucial role in multiple stages of CD8 T cell response to VV infection and may help to design effective vaccine strategies. </p><p>Given that CD4 T cell help is critical for the survival of activated CD8 T cells during both the primary and memory recall responses, it is still unclear how CD4 T cell help promotes CD8 T cell survival. The second aim of this project was to determine the mechanism of CD4 help for the survival of activated CD8 cells. We first showed that CD4 help in vitro was mediated by IL-21, a cytokine produced predominantly by activated CD4 T cells. We then demonstrated direct action of IL-21 on CD8 T cells was critical for the VV-specific CD8 T cell response in vivo. This intrinsic IL-21 signaling was essential for the survival of activated CD8 T cells and the generation of long-lived memory cells. We further revealed that IL-21 promoted CD8 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 pathways and subsequent upregulation of the pro-survival molecules Bcl-2 and Bcl-xL. Collectively, these results identify a critical role for CD4-derived IL-21 signaling in CD8 T cell responses to acute VV infection in vivo and may help design effective vaccine strategies in situations where CD4 cells are not fully functional.</p>Dissertatio

Optimizing the timing of 4CMenB vaccination in adolescents and young adults based on immune persistence and booster response data

Introduction: Meningococcal disease has an incidence peak spread over several years during adolescence and young adulthood in the United States. Meningococcal serogroup B (MenB) vaccines have been introduced relatively recently and may help protect individuals in these age groups. Currently there is insufficient long-term experience to determine the duration of disease protection after any MenB vaccine. Understanding antibody persistence after primary vaccination and responses to booster can help inform MenB vaccination strategies and optimize disease prevention. Areas covered: Four studies in adolescents/young adults vaccinated with meningococcal B vaccine 4CMenB were reviewed with the aim to compare findings across studies and draw key learnings. The studies varied by geographic location, population characteristics, and timing of antibody measurement relative to primary vaccination. Expert opinion: Antibody persistence data for 4CMenB are substantial, extending 7.5 years post-primary vaccination. Vaccination at age 16–18 years may help protect adolescents throughout their highest age-based risk period. Similar robust responses to a single booster dose were observed 4 and 7.5 years after primary vaccination. In outbreak settings it is beneficial to have received prior vaccination; residual circulating antibodies may provide protection, and a single dose induces booster responses within 7 days, which is quicker than administration of a 2-dose series to vaccine-naïve individuals

Assessing older adults with generalized anxiety: A replication and extension

Anxiety is a major health problem for older adults. The cornerstone for further work in this area is research that establishes the psychometric utility of standardized measurement strategies to characterize anxiety in older adults. The goals of the current study were to replicate and extend prior research addressing the psychometric properties of five self-report measures of anxiety in a sample of 57 older adults with generalized anxiety disorder (GAD). Data addressed the descriptive characteristics, internal consistency, test-retest reliability, interrelation of subscales, and convergent and divergent validity of the Penn state worry questionnaire (PSWQ), worry scale (WS), Spielberger state-trait anxiety inventory - Form Y (STAI), and two versions of the fear questionnaire (FQ). Descriptive data generally replicated prior findings, with some increased state and trait anxiety in the current sample. Measures were internally consistent, with evidence that a revised version of the FQ that focuses on severity of fear irrespective of associated avoidance demonstrated greater internal consistency than the original version. Measures of content-specific fears and worries (WS, FQ) were stable over time and demonstrated convergent validity. Evidence of convergent validity also was evident for measures of worry and general anxiety (WS, PSWQ, STAI-Trait), but two of these measures (PSWQ, STAI) were not reliable over time. Only the PSWQ showed evidence of divergent validity with respect to self-report measures of depression. Copyright (C) 2001 Elsevier Science Ltd

Measures of depression in older adults with generalized anxiety disorder: A psychometric evaluation

Generalized anxiety disorder (GAD) is the most common of the pervasive anxiety disorders among older adults, with lifetime prevalence estimates of 6%. Because of this high prevalence rate, it is important to establish the utility of assessment tools with this population. Preliminary data exist with regard to the use of anxiety measures with older anxious adults; however, no similar information is available for self-report measures of depression in this population. This study examined the psychometric properties of the Beck Depression Inventory (BDI) and the Geriatric Depression Scale (GDS) with a sample of 54 older adults diagnosed with GAD, 22 of whom were diagnosed with a coexistent depressive disorder. Internal consistency, convergent and divergent validity, construct validity, and discriminative validity of the BDI and the GDS were examined. Overall, the results support the reliability and validity of these self-report measures of depressive symptoms in a sample of older anxious adults. (C) 2000 Wiley-Liss, Inc