Integrating virtual realities and psychotherapy: SWOT analysis on VR and MR based treatments of anxiety and stress-related disorders.

The use of virtual reality (VR) and mixed reality (MR) technology in clinical psychology is growing. Efficacious VR-based treatments for a variety of disorders have been developed. However, the field of technology-assisted psychotherapy is constantly changing with the advancement in technology. Factors such as interdisciplinary collaboration, consumer familiarity and adoption of VR products, and progress in clinical science all need to be taken into consideration when integrating virtual technologies into psychotherapies. We aim to present an overview of current expert opinions on the use of virtual technologies in the treatment of anxiety and stress-related disorders. An anonymous survey was distributed to a select group of researchers and clinicians, using an analytic framework known as Strengths, Weaknesses, Opportunities, and Threats (SWOT). Overall, the respondents had an optimistic outlook regarding the current use as well as future development and implementation of technology-assisted interventions. VR and MR psychotherapies offer distinct advantages that can overcome shortcomings associated with traditional therapy. The respondents acknowledged and discussed current limitations of VR and MR psychotherapies. They recommended consolidation of existing knowledge and encouraged standardisation in both theory and practice. Continued research is needed to leverage the strengths of VR and MR to develop better treatments.Abbreviations: AR: Augmented Reality; MR: Mixed Reality; RCT: Randomised Controlled Trial; SWOT: Strengths, Weaknesses, Opportunities, and Threats; VR: Virtual Reality; VR-EBT: Virtual Reality Exposure-Based Therapy.

Seeking neutral: A VR-based person-identity-matching task for attentional bias modification - A randomised controlled experiment.

BACKGROUND: Attentional bias modification (ABM) aims to reduce anxiety by attenuating bias towards threatening information. The current study incorporated virtual reality (VR) technology and 3-dimensional stimuli with a person-identity-matching (PIM) task to evaluate the effects of a VR-based ABM training on attentional bias and anxiety symptoms. METHODS: One hundred participants with elevated social anxiety were randomised to four training groups. Attentional bias was assessed at pre- and post-training, and anxiety symptoms were assessed at pre-training, post-training, 1-week follow-up, and 3-month follow-up. RESULTS: Change in anxiety did not correlate with change in bias (r = -0.08). A repeated-measures ANOVA showed no significant difference in bias from pre- to post-ABM, or between groups. For anxiety symptoms, a linear mixed-effects model analysis revealed a significant effect of time. Participants showed reduction in anxiety score at each successive assessment (p < .001, Nagelkerke's pseudo r 2 = 0.65). However, no other significant main effect or interactions were found. A clinically significant change analysis revealed that 4% of participants were classified as 'recovered' at 3-month follow-up. CONCLUSIONS: A single session of VR-based PIM task did not change attentional bias. The significant reduction in anxiety was not specific to active training, and the majority of participants remained clinically unchanged.

Attentional Bias Modification in Virtual Reality - A VR-Based Dot-Probe Task With 2D and 3D Stimuli.

BACKGROUND: Attentional bias modification (ABM) aims to reduce anxiety by attenuating bias toward threatening information. The current study incorporated virtual reality (VR) technology and three-dimensional stimuli with a dot-probe task to evaluate the effects of a VR-based ABM training on attentional bias and anxiety symptoms. METHODS: A total of 100 participants were randomized to four training groups. Attentional bias was assessed at pre- and post-training, and anxiety symptoms were assessed at pre-training, post-training, 1-week follow-up, and 3-months follow-up. RESULTS: Change in anxiety did not correlate with change in bias (p = 0.24). A repeated-measures ANOVA showed no significant difference in bias from pre- to post-ABM (p = 0.144), or between groups (p = 0.976). For anxiety symptoms, a linear mixed-effects model analysis revealed a significant effect of time. Participants showed reduction in anxiety score at each successive assessment (p < 0.001). However, no other significant main effect or interactions were found. A clinically significant change analysis revealed that 9% of participants were classified as 'recovered' at 3-months follow-up. CONCLUSION: A single session of VR-based ABM did not change attentional bias. The significant reduction in anxiety was not specific to active training, and the majority of participants remained clinically unchanged.

Transcriptional repression of O6-methylguanine DNA methyltransferase gene rendering cells hypersensitive to N,N'-bis(2-chloroethyl)-N-nitrosurea in camptothecin-resistant cells.

O(6)-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl-adducts from the O(6)-guanine in DNA and is a crucial defense against O(6)-alkylating agent-induced cytotoxicity. We demonstrated here that two camptothecin (CPT)-resistant cell lines (CPT30 and KB100) were more sensitive to N,N'-bis(2-chloroethyl)-N-nitrosurea (BCNU) than their parental cells. Enhanced sensitivity to BCNU in these two CPT-resistant cells involved transcriptional repression of the MGMT gene. The mechanism of MGMT gene down-regulation in CPT-resistant cells was not through gene abnormality, mRNA stability, and CpG island hypermethylation. However, the high level of methyl-CpG-binding protein 2 (MeCP2) and dimethylation of H3K9 in the promoter region were found in CPT30 and KB100 cells. Furthermore, increased MeCP2 binding on MGMT promoter was also found to be correlated with MGMT gene-silencing in short-term CPT treatment; thus, enhanced BCNU sensitivity was found in CPT-treated cells. Taken together, we suggest that CPT is able to suppress the transcription of the MGMT gene through recruiting of MeCP2 and H3K9 dimethylation, thus causing a synergistic interaction with BCNU. These findings provide a possible explanation regarding why the combination of CPT and BCNU results in a better objective response than single-use alone. In addition, this study supports a new indication for treating patients who are receiving refractory CPT derivatives with BCNU.

Tamoxifen accelerates proteasomal degradation of O6-methylguanine DNA methyltransferase in human cancer cells.

Tamoxifen, a synthetic triphenyl-ethylene compound, is a member of a class of anticancer drugs known as selective estrogen receptor modulators. It may block tumor growth by mimicking estrogen and binding to the estrogen receptors, preventing cancerous growth. Clinical studies have demonstrated that a combination chemo/hormonal therapy regimen with tamoxifen and O(6)-alkylating drugs increased the tumor response rate in cancer patients. The mechanism of action of this combined regimen remains undefined. In this study, we demonstrated that treatment of human colorectal HT-29 carcinoma cells with tamoxifen decreased the repair activity and expression level of O(6)-methylguanine DNA methyltransferase (MGMT) protein in a concentration- and time-dependent manner. This inhibition was also shown in other malignant human cells, regardless of their estrogen receptor status. Furthermore, MGMT inactivation by tamoxifen was associated with a significantly increased susceptibility of cells to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). No alteration in MGMT mRNA levels was observed in tamoxifen-treated cells. The half-life of MGMT protein was markedly decreased in the presence of tamoxifen. Tamoxifen-induced MGMT degradation could be blocked by MG-132, a proteasome inhibitor. An increased level of ubiquitinated MGMT protein was found after tamoxifen treatment. We conclude that tamoxifen decreased the MGMT protein level by accelerating protein degradation through the ubiquitin-dependent proteasomal pathway. These findings provide a strong rationale for combined chemo/hormonal therapy with tamoxifen and BCNU in the treatment of human cancers.

Molecular cloning and kinetic characterization of an aldehyde dehydrogenase gene in Klebsiella pneumoniae.

BACKGROUND AND PURPOSE: Klebsiella pneumoniae liver abscess with metastatic complications is an emerging infectious disease in Taiwan. The present study aimed to identify virulence genes involved in the pathogenicity of K. pneumoniae. METHODS: The closely related Escherichia coli genome array was employed to study the expression of the putative genome of K. pneumoniae. Total mRNA expression levels of a K. pneumoniae strain (designated National Taiwan University Hospital [NTUH]-K2044), isolated from a patient with liver abscess, and another strain (designated NTUH-K9), from a patient with sepsis only, were compared on the E. coli array. RNA blot was used to reconfirm mRNA expression in NTUH-K9, K2044 and in 9 other sepsis strains and 9 other liver abscess strains. RESULTS: One of the genes which was found to be highly expressed in NTUH-K2044, designated aldA, was selected for further study. The aldA gene codes for the enzyme aldehyde dehydrogenase (aldehyde:NAD[P](+) oxidoreductase; ALDH). Kinetic properties of ALDH isolated from the 2 strains, designated K2044 ALDH and K9 ALDH respectively, were characterized. The isolated recombinant K2044 ALDH and K9 ALDH, both with subunit molecular weight 55 kDa, exhibited similar substrate specificity and coenzyme preference with glycolaldehyde (V(max)/K(m) = 27 and 17 U/mg/mM, respectively) and glyceraldehyde (maximum velocity [V(max)]/ Michaelis constant [K(m)] = 42 and 30 U/mg/mM, respectively) being the much better substrates and NAD(+) being the preferred coenzyme (K(m) = 0.28 and 0.23 mM, respectively). Unlike K9 ALDH, K2044 ALDH displayed inhibition at high concentrations of glycolaldehyde (substrate inhibition constant [K(i)] = 7.4 mM) and glyceraldehyde (K(i) = 2.6 mM). CONCLUSION: The expression of the aldA gene is higher in K. pneumoniae strains from patients with liver abscess. The aldA gene encodes functional ALDH and can use glycolaldehyde and glyceraldehydes as substrates.

Genomic heterogeneity in Klebsiella pneumoniae strains is associated with primary pyogenic liver abscess and metastatic infection.

BACKGROUND: Primary pyogenic liver abscess (PLA) with septic complication by Klebsiella pneumoniae is an emerging infectious disease. METHODS AND RESULTS: Using DNA microarray hybridization, we identified a 20-kb chromosomal region that contained 15 open-reading frames (ORFs), including an iron-uptake system (kfu), a phosphoenolpyruvate sugar phosphotransferase system (PTS), and 6 unknown ORFs. The region was more prevalent among tissue-invasive strains (35/46) than among noninvasive strains (19/98) (P<.0001, chi2 test). To test the role played by this region in pathogenesis, 3 different deletion mutants (NTUH-K2044 [Delta kfu], K2044 [Delta ORF7-9], and K2044 [Delta PTS]) were constructed. Only the Delta kfuABC mutants showed decreased virulence in mice, compared with the wild-type strain. An in vitro assay confirmed the involvement of kfu in iron acquisition. There was a high correlation rate (85%) between the kfu/PTS region and 2 tissue invasion-associated chromosomal regions (allS and magA). Moreover, all 3 regions were present in strains that caused PLA plus endophthalmitis or meningitis. CONCLUSION: Our results suggest that chromosomal heterogeneity is present in tissue-invasive K. pneumoniae strains. A genotype containing all 3 regions is strongly associated with PLA and metastatic infection. These regions may serve as convenient markers for the rapid diagnosis of emergent tissue-invasive strains.

Isolation of a chromosomal region of Klebsiella pneumoniae associated with allantoin metabolism and liver infection.

Klebsiella pneumoniae liver abscess with metastatic complications is an emerging infectious disease in Taiwan. To identify genes associated with liver infection, we used a DNA microarray to compare the transcriptional profiles of three strains causing liver abscess and three strains not associated with liver infection. There were 13 clones that showed higher RNA expression levels in the three liver infection strains, and 3 of these 13 clones contained a region that was absent in MGH 78578. Sequencing of the clones revealed the replacement of 149 bp of MGH 78578 with a 21,745-bp fragment in a liver infection strain, NTUH-K2044. This 21,745-bp fragment contained 19 open reading frames, 14 of which were proven to be associated with allantoin metabolism. The K2044 (DeltaallS) mutant showed a significant decrease of virulence in intragastric inoculation of BALB/c mice, and the prevalence of this chromosomal region was significantly higher in strains associated with liver abscess than in those that were not (19 or 32 versus 2 of 94; P = 0.0001 [chi(2) test]). Therefore, the 22-kb region may play a role in K. pneumoniae liver infection and serve as a marker for rapid identification.