Randomized clinical trial of cognitive behavioral therapy (CBT) versus acceptance and commitment therapy (ACT) for mixed anxiety disorders

Objective: Randomized comparisons of acceptance-based treatments with traditional cognitive behavioral therapy (CBT) for anxiety disorders are lacking. To address this gap, we compared acceptance and commitment therapy (ACT) to CBT for heterogeneous anxiety disorders. Method: One hundred twenty-eight individuals (52% female, mean age = 38, 33% minority) with 1 or more DSM-IV anxiety disorders began treatment following randomization to CBT or ACT; both treatments included behavioral exposure. Assessments at pre-treatment, post-treatment, and 6- and 12-month follow-up measured anxiety-specific (principal disorder Clinical Severity Ratings [CSRs], Anxiety Sensitivity Index, Penn State Worry Questionnaire, Fear Questionnaire avoidance) and non-anxiety-specific (Quality of Life Index [QOLI], Acceptance and Action Questionnaire-16 [AAQ]) outcomes. Treatment adherence, therapist competency ratings, treatment credibility, and co-occurring mood and anxiety disorders were investigated. Results: CBT and ACT improved similarly across all outcomes from pre- to post-treatment. During follow-up, ACT showed steeper linear CSR improvements than CBT (p < .05, d = 1.26), and at 12-month follow-up, ACT showed lower CSRs than CBT among completers (p < .05, d = 1.10). At 12-month follow-up, ACT reported higher AAQ than CBT (p = .08, d = 0.42; completers: p < .05, d = 0.56), whereas CBT reported higher QOLI than ACT (p < .05, d = 0.42). Attrition and comorbidity improvements were similar; ACT used more non-study psychotherapy at 6-month follow-up. Therapist adherence and competency were good; treatment credibility was higher in CBT. Conclusions: Overall improvement was similar between ACT and CBT, indicating that ACT is a highly viable treatment for anxiety disorders. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

Characterization of the antibody response against Plasmodium falciparum erythrocyte membrane protein 1 in human volunteers

The immune response against the Plasmodium falciparum variant surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against falciparum malaria. In this study, we used sera from human volunteers who had been infected with the P. falciparum 3D7 strain to investigate the development, specificity, and dynamics of anti-PfEMP1 antibodies measured against six different strain 3D7 Duffy binding-like domain 1α (DBL1α) fusion proteins. We observed that a parasitemia of 20 to 200 infected erythrocytes per μl was required to trigger an antibody response to DBL1α and that antibodies against one DBL1α variant cross-react with other DBL1α variants. Both serum and purified immunoglobulin Gs (IgGs) were able to agglutinate infected erythrocytes, and purified anti-DBL1α IgGs bound to the live infected red blood cell surface in a punctate surface pattern, confirming that the IgGs recognize native PfEMP1. Analysis of sera from tourists naturally infected with P. falciparum suggests that the anti-PfEMP1 antibodies often persisted for more than 100 days after a single infection. These results help to further our understanding of the development of acquired immunity to P. falciparum infections.     

Detection of histoplasma antigen by a quantitative enzyme immunoassay

The second-generation Histoplasma antigen immunoassay is semiquantitative, expressing results as a comparison to a negative control, which requires repeat testing of the prior specimen with the current specimen to accurately determine a change in antigen. Reporting results in this manner often is confusing to the ordering physician and laboratory. Development of a quantitative assay could improve accuracy, reduce interassay variability, and eliminate the need to test the prior sample with the current sample in the same assay. Calibrators with known concentrations of Histoplasma antigen were used to quantitate antigen in specimens from patients with histoplasmosis and from controls. Samples from cases of disseminated histoplasmosis or other mycoses and controls were tested to evaluate the performance characteristics of the quantitative assay. Paired specimens were evaluated to determine if quantitation eliminated the need to test the current and prior specimens in the same assay to assess a change in antigen. The sensitivity in samples from patients with AIDS and disseminated histoplasmosis was 100% in urine and 92.3% in serum. Cross-reactions occurred in 70% of other endemic mycoses, but not in aspergillosis. Specificity was 99% in controls with community-acquired pneumonia, medical conditions in which histoplasmosis was excluded, or healthy subjects. A change in antigen level categorized as an increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in nanograms/milliliter determined from testing current and prior specimens in different assays. Sensitivity, specificity, and interassay precision are excellent in the new third-generation quantitative Histoplasma antigen immunoassay.     

Cervicovaginal, oral, and serum IgG and IgA responses to human papillomavirus type 16 in women with cervical intraepithelial neoplasia

Oncogenic human papillomaviruses (HPVs) are obligate mucosal pathogens and typically cause localized infections. The mucosal surface of the genital tract also provides the first line of defense against genital HPV infection. Although local antibody production following HPV-infection has been demonstrated, their role in protection from cervical disease is unclear. This study evaluated oral and cervical HPV infection and the associated linkage between HPV-16 oral, cervical and serum antibody responses in 103 women with varying grades of cervical intraepithelial neoplasia (CIN). We found that HPV-16 was the most prevalent cervical HPV infection (30/103, 29.1%) but was only detected in 1.1% (1/91) of the oral samples. Both the frequency and magnitude of HPV-16-specific cervical IgA was significantly elevated in women with CIN 2/3 compared with women with CIN 1 (P = 0.0073 frequency; P = 0.0045 magnitude). Women with cervical HPV-16 infection had significantly higher magnitude and frequency of cervical HPV-16 IgA responses than women without cervical HPV-16 DNA (P = 0.0002 frequency; P = 0.0052 magnitude). Despite our contention that mucosal HPV-16 antibody responses within distinct mucosal compartments may be linked, the concordance analysis carried out within and between mucosal compartments and serum suggests that no such linkage exists and that these compartments may be functioning independently of one another. An HPV-16 specific antibody response in one mucosal compartment in women with CIN is therefore not predictive of a response at another.     

Assessing gene-environment interactions on anxiety symptom subtypes across childhood and adolescence

Consistent evidence shows both genetic and stress-related risks on child and adolescent anxiety, yet few studies have considered the degree to which genetic effects are moderated by stress (gene-environment interaction). We used longitudinal data from both a child and adolescent sample of twins to examine three novel issues on the presence of gene-environment interaction on anxiety symptoms. First, we assessed moderation of genetic risks on anxiety symptoms by negative life events in each age group. Second, by distinguishing between "stable" and "age-specific" genetic factors, we explored the continuity of gene-environment interaction across time and/or its emergence at specific ages. Third, we compared the presence of gene-environment interaction across different symptom types (general, panic, social, and separation). Genetic effects on separation anxiety symptoms in childhood (mean age = 8 years, 6 months) and panic anxiety symptoms in adolescence (mean age = 15 years) increased across independent negative life events. Shared environmental effects on separation anxiety symptoms and non shared environmental effects on general anxiety symptoms in adolescence were also moderated by negative life events. We interpret these preliminary findings tentatively in the context of gene-environment interaction on anxiety in general, and on early separation and later panic anxiety in particular.     

Occult bone marrow involvement in patients with diffuse large B-cell lymphoma: results of a pilot study

AIMS: It is known that advanced stage disease in diffuse large B-cell lymphoma (DLBCL) confers a poor prognosis, and staging investigations are routinely performed at diagnosis, including a bone marrow (BM) biopsy. However, examination of the BM is usually limited to routine light microscopy, with the role of ancillary investigations remaining unestablished. The aim of this pilot study was to estimate the incidence of occult marrow involvement using flow cytometry, immunohistochemistry and immunoglobulin heavy chain (IgH) gene rearrangements, and to determine the impact on survival. METHODS: Clinical and pathological data were obtained on 36 patients diagnosed with DLBCL. Immunohistochemistry using CD3, CD45RO, CD20 and CD79a, and polymerase chain reaction (PCR) to look for IgH gene rearrangements were performed on formalin fixed BM trephines. RESULTS: Nine patients had morphologically apparent BM involvement. Occult marrow involvement was found in seven of 36 (19.4%) patients using the additional diagnostic modalities. When these cases were included with morphologically apparent cases in a proposed new definition of marrow involvement, the median survival of patients with BM involvement was statistically worse (p=0.02) than those without involvement. CONCLUSIONS: The results indicate that use of additional tests on BM at diagnosis can upstage disease for a proportion of patients, which appears to correlate adversely with survival.     

Recruiting and retaining GPs and patients in intervention studies: the DEPS-GP project as a case study

Background  

Recruiting and retaining GPs for research can prove difficult, and may result in sub-optimal patient participation where GPs are required to recruit patients. Low participation rates may affect the validity of research.     

The role of macrophage migration inhibitory factor in the cascade of events leading to reperfusion-induced inflammatory injury and lethality

Ischemia and reperfusion (I/R) injury is associated with a systemic inflammatory response, characterized by intense tumor necrosis factor (TNF)-alpha production and TNF-alpha-dependent tissue injury. Macrophage migration inhibitory factor (MIF) is a potent proinflammatory cytokine that may induce TNF-alpha release and play an important role in innate immune and inflammatory responses. The aim of this work was to assess whether MIF was involved the inflammatory cascade and injury that follows intestinal I/R. To this end, wild-type (WT) and MIF-deficient (MIF(-/-)) mice underwent 60 minutes of ischemia followed by 60 minutes of reperfusion, after which they were culled for the assessment of inflammatory parameters. I/R was accompanied by an increase in circulating levels of MIF and an increase of vascular permeability, hemorrhage, and production of TNF-alpha in the intestine and lungs. The latter parameters were markedly suppressed in reperfused MIF(-/-) mice, and this was associated with decreased lethality (80% in WT versus 20% in MIF(-/-) mice). Interestingly, the reperfusion-associated neutrophil accumulation in the intestine and lungs was similar in WT and MIF(-/-) mice. Leukocytes isolated from lungs of MIF(-/-) mice were less activated, as assessed by their response to zymosan in a luminol-enhanced chemiluminescence assay. In conclusion, our results suggest that MIF plays an important role in the cascade of events leading to TNF-alpha production and reperfusion-induced tissue injury and lethality in mice.     

Putative tumor suppressor EDD interacts with and up-regulates APC

Adenomatous polyposis coli (APC), whose mutation causes colorectal cancers, is a key player in the Wnt signaling pathway. While the role of APC in inhibition of beta-catenin/LEF1-dependent activation of transformation-inducing genes has been intensively studied and well established, regulation of APC expression at the protein level is only partially understood. Here we report that APC is up-regulated by EDD, the mammalian orthologue of Drosophila melanogaster"hyperplastic discs" gene (hyd) that is considered to be a putative tumor suppressor. Screening of APC immunocomplexes by mass spectrometry identified EDD as a putative APC-interacting protein. Exogenously expressed and endogenous APC interacted with EDD in vivo. Indirect immunofluorescent analyses demonstrated that APC and EDD co-localized in the cytoplasm of the cell. Over-expression of EDD enhanced the protein expression level of APC and its binding partner Axin, resulting in inhibition of Wnt signaling downstream of beta-catenin. Conversely, siRNA knock-down of EDD down-regulated APC at the protein level without altering its mRNA level, causing enhanced protein expression of beta-catenin. Thus, through protein-protein interaction, EDD stabilizes APC and up-regulates APC's function to inhibit beta-catenin, suggesting that EDD could act as a colorectal tumor suppressor.