Effects of an Online Imagery-Based Treatment Program in Patients with Workplace-Related Posttraumatic Stress Disorder: A Pilot Study.

OBJECTIVE: We developed easily accessible imagery-based treatment program for patients with post-traumatic stress disorder (PTSD) related to workplace accidents and investigated the effects of the program on various PTSD related symptoms. METHODS: The program was based on an online platform and consisted of eight 15-min sessions that included script-guided imagery and supportive music. Thirty-five patients with workplace-related PTSD participated in this program 4 days per week for 4 weeks. Its effects were examined using self-report questionnaires before and after the take-home online treatment sessions. RESULTS: After completing the 4-week treatment program, patients showed significant improvements in depressed mood (t=3.642, p=0.001) based on the Patient Health Questionnaire-9 (PHQ-9), anxiety (t=3.198, p=0.003) based on the Generalized Anxiety Disorder seven-item (GAD-7) scale, and PTSD symptoms (t=5.363, p<0.001) based on the Posttraumatic Stress Disorder Check List (PCL). In particular, patients with adverse childhood experiences exhibited a greater degree of relief related to anxiety and PTSD symptoms than those without adverse childhood experiences. CONCLUSION: The present. RESULTS: demonstrated that the relatively short online imagery-based treatment program developed for this study had beneficial effects for patients with workplace-related PTSD.

Investigating effective treatment factors in brief cognitive behavioral therapy for panic disorder.

Numerous studies have provided evidence for the effectiveness of cognitive behavioral therapy (CBT) on panic disorders (PDs). There has also been growing attention on brief CBT with regard to delivering intensive treatment efficiently. This study investigated the essential parts of mindfulness-based brief CBT to optimize treatment benefits.A total of 37 patients were retrospectively enrolled in this study. They were recruited from the anxiety/panic/fear clinic of Seoul National University Hospital. The patients participated in group CBT once a week for a total of 4 sessions over a 4-week period, when they were assessed using the Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index-Revised (ASI-R), Albany Panic and Phobia Questionnaire (APPQ), State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and after brief CBT. Twenty-nine patients completed the 1-month follow-up.There were significant reductions in PDSS (P < .001), ASI-R-fear of respiratory symptoms (P = .006), ASI-R-fear of publicly observable anxiety reaction (P = .002), ASI-R-fear of cardiovascular symptoms (P < .001), ASI-R-fear of cognitive dyscontrol (P = .001), ASI-R-Total (P < .001), APPQ-Agoraphobia (P = .003), APPQ-Total (P = .028), STAI-State anxiety (P < .001), STAI-Trait anxiety (P = .002), BAI (P = .003), and BDI (P < .001) scores. We also found significant associations between ASI-R-fear of cardiovascular symptoms, ASI-R-Total, and changes in PDSS scores. A stepwise multiple linear regression analysis indicated that anxiety sensitivity for fear of cardiovascular symptoms predicted an improvement in panic severity (ß = 0.513, P = .004).Our findings suggested that behavioral aspects, especially physiological symptom control, needed to be considered in brief, intensive CBT for PD. The results also suggested that a mindfulness-based brief CBT approach might be particularly helpful for patients with PD who have severe cardiovascular symptoms.

Identification of active Plasmodium falciparum calpain to establish screening system for Pf-calpain-based drug development.

BACKGROUND: With the increasing resistance of malaria parasites to available drugs, there is an urgent demand to develop new anti-malarial drugs. Calpain inhibitor, ALLN, is proposed to inhibit parasite proliferation by suppressing haemoglobin degradation. This provides Plasmodium calpain as a potential target for drug development. Pf-calpain, a cysteine protease of Plasmodium falciparum, belongs to calpain-7 family, which is an atypical calpain not harboring Ca2+-binding regulatory motifs. In this present study, in order to establish the screening system for Pf-calpain specific inhibitors, the active form of Pf-calpain was first identified. METHODS: Recombinant Pf-calpain including catalytic subdomain IIa (rPfcal-IIa) was heterologously expressed and purified. Enzymatic activity was determined by both fluorogenic substrate assay and gelatin zymography. Molecular homology modeling was carried out to address the activation mode of Pf-calpain in the aspect of structural moiety. RESULTS: Based on the measurement of enzymatic activity and protease inhibitor assay, it was found that the active form of Pf-calpain only contains the catalytic subdomain IIa, suggesting that Pf-calpain may function as a monomeric form. The sequence prediction indicates that the catalytic subdomain IIa contains all amino acid residues necessary for catalytic triad (Cys-His-Asn) formation. Molecular modeling suggests that the Pf-calpain subdomain IIa makes an active site, holding the catalytic triad residues in their appropriate orientation for catalysis. The mutation analysis further supports that those amino acid residues are functional and have enzymatic activity. CONCLUSION: The identified active form of Pf-calpain could be utilized to establish high-throughput screening system for Pf-calpain inhibitors. Due to its unique monomeric structural property, Pf-calpain could be served as a novel anti-malarial drug target, which has a high specificity for malaria parasite. In addition, the monomeric form of enzyme may contribute to relatively simple synthesis of selective inhibitors.

Herbal compound farnesiferol C exerts antiangiogenic and antitumor activity and targets multiple aspects of VEGFR1 (Flt1) or VEGFR2 (Flk1) signaling cascades.

Farnesiferol C (FC) is one of the major compounds isolated from Ferula assafoetida, an Asian herbal spice used for cancer treatment as a folk remedy. Here, we examined the hypothesis that novel antiangiogenic activities of FC contribute to anticancer efficacy. In human umbilical vein endothelial cells (HUVEC), exposure to the 10 to 40 mumol/L concentration range of FC inhibited vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, invasion, tube formation, and the expression of matrix metalloproteinase-2. In addition, FC inhibited the angiogenic sprouting of VEGF-treated rat aorta in an ex vivo model. Furthermore, FC inhibited the in vivo growth of mouse Lewis lung cancer allograft model by 60% (P < 0.001) at a daily i.p. dosage of 1 mg/kg body weight without any negative effect on the weight of the host mice. Immunohistochemistry staining showed decreased microvessel density (CD34) and proliferative index (Ki-67) without affecting the apoptotic (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) index. Mechanistically, FC decreased the binding of VEGF to VEGFR1/Flt-1, but not to VEGFR2/KDR/Flk-1. In terms of early signaling, FC exerted a rapid inhibitory action (examined within 10 minutes) on VEGF-induced autophosphorylation of VEGFR1 without affecting that of VEGFR2. Nevertheless, FC decreased the phosphorylation of most of the kinases downstream of VEGFR2: focal adhesion kinase, Src, extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase, and c-jun-NH(2)-kinase without affecting AKT. Computer simulation suggests that FC may inhibit Src or focal adhesion kinase protein activities directly through its docking to their ATP-binding sites. Taken together, the multitargeting actions of FC, particularly VEGFR1 inhibition, may make it a novel drug candidate to complement current VEGF/VEGFR2-targeting antiangiogenic modalities for cancer.

Stereoselective synthesis and conformational study of novel 2',3'-Didehydro-2',3'-dideoxy-4'-selenonucleosides.

Stereoselective synthesis of novel 2',3'-didehydro-2',3'-dideoxy-4'-selenonucleosides (4'-seleno-d4Ns) 4a- c was accomplished via 4'-selenoribofuranosyl pyrimidines 11a- c, as key intermediates. 4'-Selenoribofuranosyl pyrimidines 11a- c were efficiently synthesized from d-ribose or d-gulonic gamma-lactone using a Pummerer-type condensation as a key step. Introduction of 2',3'-double bond was achieved by treating cyclic 2',3'-thiocarbonate with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine.