Coping with test anxiety using imagery rescripting: A two-session randomized controlled trial.

BACKGROUND: Up to 55 % of students experience test anxiety (TA), which is characterized by intense physiological and psychological symptoms before or during exams, such as anxiety, fear of failure, sweating, or increased heart rate. Furthermore, TA increases graduation times and can result in discontinuance of the graduate program all together. Previous research demonstrated the beneficial effects of combining cognitive behavioral therapy with imagery rescripting, however, treatment programs are comparably long. Hence, they do not account for the students´ time-sensitive schedules. Therefore, the present study investigates a two-session short-intervention using imagery rescripting to treat TA. METHODS: 44 students and pupils were randomly assigned to either the two-session imagery rescripting intervention (22 participants) or the waitlist-control condition (22 participants). One week before the intervention clinical interviews were conducted and self-report questionnaires on TA, self-efficacy, symptoms of depression, and intrusive prospective images were completed (T1). The same questionnaires were completed one week (T2) and six months after the intervention (T3). RESULTS: Test anxiety significantly decreased from T1 to T2, as well as from T1 to T3 within the intervention group. Furthermore, there were medium to large within and between group effects for situational test anxiety, self-efficacy, symptoms of depression, as well as prospective intrusive images, showing significant improvements for the intervention group at six months follow-up. LIMITATIONS: The study is limited to the comparably small sample size, as well as the sole usage of self-report measurements. CONCLUSIONS: The presented short-intervention provides a feasible treatment technique, which can be easily applied within school and university counseling centers.

The Association Between Test Anxiety, Self-Efficacy, and Mental Images Among University Students: Results From an Online Survey.

Background and Objectives: A substantial portion of students report test anxiety, and those reporting low levels of self-efficacy seem to be especially affected. Previous research has indicated the relevance of mental images in the maintenance of anxiety disorders, however, no data are available with respect to test anxiety. In order to close this gap, the present study investigates the association between test anxiety, self-efficacy and mental images. Method: One hundred sixty-three university students completed an online survey. Test anxiety (PAF), general self-efficacy (WIRKALL-r), study-related self-efficacy (WIRK_STUD), intrusiveness of mental images (IFES), spontaneous use of imagery (SUIS) and vividness of imagery (VVIQ) were examined. Results: Test-related mental images were frequently reported among the surveyed students. Test anxiety showed a positive correlation with IFES and a negative correlation with self-efficacy. Mediation analyses showed that about one fifth of the influence of self-efficacy on test anxiety is mediated by IFES. Discussion: The present study gives first indication about an association between test anxiety, self-efficacy and mental images, even though the results are limited with respect to generalizability. Further investigations with respect to the impact of test-related mental images on the self-efficacy/test-anxiety linkage are needed.

Epigenetic impacts of ascorbate on human metastatic melanoma cells.

In recent years, increasing evidence has emerged demonstrating that high-dose ascorbate bears cytotoxic effects on cancer cells in vitro and in vivo, making ascorbate a pro-oxidative drug that catalyzes hydrogen peroxide production in tissues instead of acting as a radical scavenger. This anticancer effect of ascorbate is hypoxia-inducible factor-1α- and O2-dependent. However, whether the intracellular mechanisms governing this effect are modulated by epigenetic phenomena remains unknown. We treated human melanoma cells with physiological (200 µM) or pharmacological (8 mM) ascorbate for 1 h to record the impact on DNA methyltransferase (DNMT)-activity, histone deacetylases (HDACs), and microRNA (miRNA) expression after 12 h. The results were analyzed with the MIRUMIR online tool that estimates the power of miRNA to serve as potential biomarkers to predict survival of cancer patients. FACS cell-cycle analyses showed that 8 mM ascorbate shifted BLM melanoma cells toward the sub-G1 fraction starting at 12 h after an initial primary G2/M arrest, indicative for secondary apoptosis induction. In pharmacological doses, ascorbate inhibited the DNMT activity in nuclear extracts of MeWo and BLM melanoma cells, but did not inhibit human HDAC enzymes of classes I, II, and IV. The expression of 151 miRNAs was altered 12 h after ascorbate treatment of BLM cells in physiological or pharmacological doses. Pharmacological doses up-regulated 32 miRNAs (≥4-fold) mainly involved in tumor suppression and drug resistance in our preliminary miRNA screening array. The most prominently up-regulated miRNAs correlated with a significantly increased overall survival of breast cancer or nasopharyngeal carcinoma patients of the MIRUMIR database with high expression of the respective miRNA. Our results suggest a possible epigenetic signature of pharmacological doses of ascorbate in human melanoma cells and support further pre-clinical and possibly even clinical evaluation of ascorbate for melanoma therapy.

The ROS-induced cytotoxicity of ascorbate is attenuated by hypoxia and HIF-1alpha in the NCI60 cancer cell lines.

Intravenous application of high-dose ascorbate is used in complementary palliative medicine to treat cancer patients. Pharmacological doses of ascorbate in the mM range induce cytotoxicity in cancer cells mediated by reactive oxygen species (ROS), namely hydrogen peroxide and ascorbyl radicals. However, little is known about intrinsic or extrinsic factors modulating this ascorbate-mediated cytotoxicity. Under normoxia and hypoxia, ascorbate IC50 values were determined on the NCI60 cancer cells. The cell cycle, the influence of cobalt chloride-induced hypoxia-inducible factor-1α (HIF-1α) and the glucose transporter 1 (GLUT-1) expression (a pro-survival HIF-1α-downstream-target) were analysed after ascorbate exposure under normoxic and hypoxic conditions. The amount of ascorbyl radicals increased with rising serum concentrations. Hypoxia (0.1% O2 ) globally increased the IC50 of ascorbate in the 60 cancer cell lines from 4.5 ± 3.6 mM to 10.1 ± 5.9 mM (2.2-fold increase, P < 0.001, Mann-Whitney t-test), thus inducing cellular resistance towards ascorbate. This ascorbate resistance depended on HIF-1α-signalling, but did not correlate with cell line-specific expression of the ascorbate transporter GLUT-1. However, under normoxic and hypoxic conditions, ascorbate treatment at the individual IC50 reduced the expression of GLUT-1 in the cancer cells. Our data show a ROS-induced, HIF-1α- and O2 -dependent cytotoxicity of ascorbate on 60 different cancer cells. This suggests that for clinical application, cancer patients should additionally be oxygenized to increase the cytotoxic efficacy of ascorbate.

Dual antitumour effect of 5-azacytidine by inducing a breakdown of resistance-mediating factors and epigenetic modulation.

BACKGROUND: The cytokine tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown promising anticancer activity in early clinical settings by selectively inducing apoptosis in different tumour types. However, some tumour entities such as hepatocellular carcinoma (HCC) display an inherent resistance to TRAIL. A huge effort has been made to unravel strategies for a clinically applicable sensitisation of resistant cancer cells to TRAIL. Reversible epigenetic alterations such as DNA methylation play a major role in development, maintenance and resistance phenomena of tumour cells. Currently, several clinical trials are exploiting the potential of epigenetic drugs, such as 5-azacytidine (5-aza-CR) or 5-aza-2'-deoxycytidine (5-aza-dC) to break primary or secondary resistance phenomena of cancer cells. Therefore, 5-aza-CR and 5-aza-dC were investigated in the context of TRAIL resistance. METHODS: Alterations in proliferation, apoptosis, regulatory proteins and toxicity were investigated in TRAIL-resistant hepatoma, and also in renal, colon and pancreatic cancer cells as well as non-transformed human-derived primary hepatocytes, tissue slices isolated from human liver and non-malignant colon cells, all of which had been exposed to demethylating drugs and/or TRAIL. RESULTS: Within hours, 5-aza-CR but not 5-aza-dC sensitised in vitro cultured tumour cells to TRAIL, first by activating caspases, followed by a subsequent induction of apoptosis. This surprisingly rapid sensitisation was confirmed in vivo employing a chorioallantoic membrane assay. As a major mechanism, a 5-aza-CR-induced inhibition of cellular protein synthesis was found which led to a breakdown of tumour-protecting factors such as the antiapoptotic factor FLICE inhibitory protein (FLIP). Importantly, TRAIL and 5-aza-CR did not induce relevant toxicity or apoptosis in primary hepatocytes, liver slices from different human donors and in normal colon cells. CONCLUSIONS: Molecular evidence is provided for a novel 5-aza-CR-based translational approach enabling a twofold treatment of apoptosis-resistant tumour entities, not only by an epigenetic reversion of the malignancy-associated phenotype but also by an efficient resensitization to apoptosis-inducing substances such as TRAIL.