Cognitive therapy for compulsive checking in obsessive-compulsive disorder: A pilot trial

We evaluated a novel, empirically-based cognitive therapy for compulsive checking – a common form of obsessive-compulsive disorder. Twelve adults completed 12 sessions of the therapy. Significant reductions in checking-related symptoms were found pre- to post-treatment, and pre-treatment to 6-month follow-up (moderate to large effect sizes). Participants reported high treatment acceptability after the third session, which was maintained at post-treatment. This pilot trial provides preliminary support for treating compulsive checking using this novel cognitive approach

Immunohistochemical analysis of oxidative stress and DNA repair proteins in normal mammary and breast cancer tissues

<p>Abstract</p> <p>Background</p> <p>During the course of normal cellular metabolism, oxygen is consumed and reactive oxygen species (ROS) are produced. If not effectively dissipated, ROS can accumulate and damage resident proteins, lipids, and DNA. Enzymes involved in redox regulation and DNA repair dissipate ROS and repair the resulting damage in order to preserve a functional cellular environment. Because increased ROS accumulation and/or unrepaired DNA damage can lead to initiation and progression of cancer and we had identified a number of oxidative stress and DNA repair proteins that influence estrogen responsiveness of MCF-7 breast cancer cells, it seemed possible that these proteins might be differentially expressed in normal mammary tissue, benign hyperplasia (BH), ductal carcinoma in situ (DCIS) and invasive breast cancer (IBC).</p> <p>Methods</p> <p>Immunohistochemistry was used to examine the expression of a number of oxidative stress proteins, DNA repair proteins, and damage markers in 60 human mammary tissues which were classified as BH, DCIS or IBC. The relative mean intensity was determined for each tissue section and ANOVA was used to detect statistical differences in the relative expression of BH, DCIS and IBC compared to normal mammary tissue.</p> <p>Results</p> <p>We found that a number of these proteins were overexpressed and that the cellular localization was altered in human breast cancer tissue.</p> <p>Conclusions</p> <p>Our studies suggest that oxidative stress and DNA repair proteins not only protect normal cells from the damaging effects of ROS, but may also promote survival of mammary tumor cells.</p

Zinc Coordination Is Required for and Regulates Transcription Activation by Epstein-Barr Nuclear Antigen 1

Epstein-Barr Nuclear Antigen 1 (EBNA1) is essential for Epstein-Barr virus to immortalize naïve B-cells. Upon binding a cluster of 20 cognate binding-sites termed the family of repeats, EBNA1 transactivates promoters for EBV genes that are required for immortalization. A small domain, termed UR1, that is 25 amino-acids in length, has been identified previously as essential for EBNA1 to activate transcription. In this study, we have elucidated how UR1 contributes to EBNA1's ability to transactivate. We show that zinc is necessary for EBNA1 to activate transcription, and that UR1 coordinates zinc through a pair of essential cysteines contained within it. UR1 dimerizes upon coordinating zinc, indicating that EBNA1 contains a second dimerization interface in its amino-terminus. There is a strong correlation between UR1-mediated dimerization and EBNA1's ability to transactivate cooperatively. Point mutants of EBNA1 that disrupt zinc coordination also prevent self-association, and do not activate transcription cooperatively. Further, we demonstrate that UR1 acts as a molecular sensor that regulates the ability of EBNA1 to activate transcription in response to changes in redox and oxygen partial pressure (pO2). Mild oxidative stress mimicking such environmental changes decreases EBNA1-dependent transcription in a lymphoblastoid cell-line. Coincident with a reduction in EBNA1-dependent transcription, reductions are observed in EBNA2 and LMP1 protein levels. Although these changes do not affect LCL survival, treated cells accumulate in G0/G1. These findings are discussed in the context of EBV latency in body compartments that differ strikingly in their pO2 and redox potential

When it's at: An examination of when cognitive change occurs during cognitive therapy for compulsive checking in obsessive-compulsive disorder

BACKGROUND AND OBJECTIVES: The cognitive theory of compulsive checking in OCD proposes that checking behaviour is maintained by maladaptive beliefs, including those related to inflated responsibility and those related to reduced memory confidence. This study examined whether and when specific interventions (as part of a new cognitive therapy for compulsive checking) addressing these cognitive targets changed feelings of responsibility and memory confidence. METHODS: Participants were nine adults with a primary or secondary diagnosis of OCD who reported significant checking symptoms (at least one hour per day) on the Yale-Brown Obsessive-Compulsive Scale. A single-case multiple baseline design was used, after which participants received 12 sessions of cognitive therapy. From the start of the baseline period through to the 1 month post-treatment follow-up assessment session, participants completed daily monitoring of feelings of responsibility, memory confidence, and their time spent engaging in compulsive checking. RESULTS: Results revealed that feelings of responsibility significantly reduced and memory confidence significantly increased from baseline to immediately post-treatment, with very high effect sizes. Multilevel modelling revealed significant linear changes in feelings of responsibility (i.e., reductions over time) and memory confidence (i.e., increases over time) occurred following the sessions when these were addressed. Finally, we found that improvements in these over the course of the treatment significantly predicted reduced time spent checking. LIMITATIONS: The small sample size limits our ability to generalize our results. CONCLUSIONS: Results are discussed in terms of a focus on the timing of change in cognitive therapy