Development and Validation of the Mood Instability Questionnaire-Trait (MIQ-T).

Background and objectives: Mood instability (MI) is a stable trait associated with psychiatric disorders, yet there is a lack of tools to measure MI. The purpose of this study was to develop and validate the Mood Instability Questionnaire-Trait (MIQ-T) to evaluate MI in mood disorder patients. Material and methods: Items were taken from various established questionnaires to create an initial list of MIQ-T questions. Data from 309 psychiatric patients (n = 309; 62 major depressive disorder, 58 bipolar I disorder, and 189 bipolar II disorder) were gathered from their medical records and were utilized in an exploratory factor analysis to clarify the underlying components of MI. Then, anonymous survey data from 288 individuals from the general population were included in the analysis as a comparison group. Associations between MIQ-T and other previously validated clinical instruments for mood disorders were examined to test external validity. Results: The exploratory factor analysis demonstrated that the five-factor structure (Lability, Upward Tendency, Downward Tendency, Childhood Instability, and Seasonality) of 59 items was the most appropriate with clear, cohesive features. MIQ-T exhibited high internal consistency (α = 0.96) and moderate to strong correlations with other previously validated clinical instruments, which were consistent with theoretical predictions, providing evidence of criterion validity. Short forms were also created to address the high internal consistency value, which can indicate redundancy, and to increase the approachability of the measure. We found that the patients with bipolar II disorder had higher MIQ-T scores than the patients with bipolar I disorder or major depressive disorder and the comparison group. Conclusion: Together, these findings validate the newly developed MIQ-T as an instrument of mood instability. MIQ-T can be a potential research tool for mood disorder.

Rapid Symptom Improvement in Major Depressive Disorder Using Accelerated Repetitive Transcranial Magnetic Stimulation.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) has contributed to increase in the remission rate for patients with major depressive disorder (MDD). However, current rTMS treatment is practically inconvenient because it requires daily treatment sessions for several weeks. Accelerated rTMS treatment is as efficient and safe for MDD patients as conventional rTMS. METHODS: Fifty-one patients with MDD participated in this study; they were randomized into accelerated rTMS (n = 21), conventional rTMS (n = 22), and sham-treatment (n = 8) groups. The accelerated and conventional rTMS groups received 15 sessions for 3 days and 3 weeks, respectively. The sham-treatment group received 15 sham rTMS sessions for 3 days. Primary outcome was assessed using self-report and clinician-rated Korean Quick Inventory of Depressive Symptomatology (KQIDS-SR and KQIDS-C, respectively). Adverse effects were monitored using the Frequency, Intensity, and Burden of Side Effects Rating scale. Changes in depressive symptoms were compared among the three groups using mixed model analyses. RESULTS: For the KQIDS-SR score, there was a significant main effect of "time" (F3,47 = 11.05, p < 0.001), but no effect of "group" (F2,47 = 2.04, p = 0.142), and a trend-level interaction effect of "group × time" (F6,47 = 2.26, p = 0.053). Improvement in depressive symptoms, based on the KQIDS-SR score 3 weeks after treatment, was more prominent in the accelerated rTMS group than in the sham-treatment group (p = 0.011). Tolerability was comparable among the three groups. CONCLUSION: The accelerated rTMS treatment group showed rapid improvement of depressive symptoms compared with the sham-treatment and conventional rTMS treatment groups. Therefore, accelerated rTMS treatment could be a viable option for MDD, with improved accessibility.

Examination of the Ability of N-acetylcysteine Administration during Anesthesia to Prevent Perioperative Deterioration of Pulmonary Function in Patients Undergoing Nephrectomy.

BACKGROUND: Postoperative pulmonary complications are associated with significant morbidity and mortality in patients undergoing major surgeries. Acetylcysteine is a known antioxidant and is also used as a mucolytic agent to reduce hypersecretion and the viscosity of mucus secretions by the lung. Several studies have revealed that high doses of N-acetylcysteine can significantly prevent pulmonary complications. However, it has not yet been established whether low doses of N-acetylcysteine are also of clinical benefit. Here, we investigated the efficacy of a low dose of N-acetylcysteine, which was administered intravenously to patients under general anesthesia, in preventing perioperative deterioration of pulmonary function. METHODS: A total of 52 patients who were scheduled for nephrectomy were randomly assigned to receive either 600 mg of intravenous N-acetylcysteine or the same volume of normal saline. Patient hemodynamic and pulmonary parameters and the incidence of pulmonary complications were recorded and compared between the groups. RESULTS: No significant pulmonary complications occurred in either group. Moreover, no significant differences were observed regarding either patient characteristics or hemodynamic parameters between the two groups. Contrary to our expectations, the pulmonary parameters were also not significantly different between the two groups. CONCLUSION: A low dose of N-acetylcysteine appears to have only limited value in preventing perioperative pulmonary complications.

Overexpression of renal tumor antigen is associated with tumor invasion and poor prognosis of hepatocellular carcinoma.

PURPOSE: The aim of this study was to investigate the roles of renal tumor antigen (RAGE) in the progression and clinical outcome of hepatocellular carcinoma (HCC). METHODS: RAGE mRNA levels in 350 cases of HCC were investigated by quantitative real-time reverse transcription polymerase chain reaction. We analyzed the relationship of RAGE mRNA level with clinicopathologic parameters and clinical outcome. To identify the possible role of RAGE on cellular invasion, we performed in vitro analyses using small interfering RNAs (siRNAs). RESULTS: RAGE mRNA level was significantly higher in HCC than in noncancerous hepatic tissues (P < 0.001). Overexpression of RAGE was significantly correlated with the presence of multiple tumors (P = 0.021), high alfa-fetoprotein level (P = 0.042), and advanced tumor stage (P = 0.016). Higher levels of RAGE expression were associated with significantly shorter overall survival time (P = 0.029). Knockdown of RAGE expression by siRNAs suppressed the invasive ability of HCC cells and the expression and secretion of matrix metalloproteinase-9 (MMP-9). We found that RAGE and MMP-9 expressions were correlated in HCCs, and furthermore, the combination of RAGE and MMP-9 expression was associated with the survival of patients (P = 0.0066). CONCLUSIONS: Our results suggest that RAGE may be important in tumor invasion and could be a potential predictor for the prognosis of HCC patients.

Overexpression of high-mobility group box 2 is associated with tumor aggressiveness and prognosis of hepatocellular carcinoma.

PURPOSE: We investigated the expression of high-mobility group box 2 (HMGB2) in patients with hepatocellular carcinoma (HCC) and its clinical effects with underlying mechanisms. EXPERIMENTAL DESIGN: HMGB2 mRNA levels were measured in 334 HCC patients by real-time reverse transcription-PCR and HMGB2 protein levels in 173 HCC patients by immunohistochemical studies. The HMGB2 expression level was measured by Western blotting for three HCC cell lines. To clarify the precise role of HMGB2 on cell proliferation, we did in vitro analysis with expression vectors and small interfering RNAs. RESULTS: HMGB2 mRNA and protein expression were significantly higher in HCC than in noncancerous surrounding tissues (P < 0.0001) and showed a positive correlation (ρ = 0.35, P < 0.001). HMGB2 overexpression was significantly correlated with shorter overall survival time, both at mRNA (P = 0.0054) and protein level (P = 0.023). Moreover, HMGB2 mRNA level was an independent prognostic factor for overall survival in a multivariate analysis (P = 0.0037). HMGB2 knockdown by small interfering RNAs decreased cell proliferation, and overexpression of HMGB2 by expression vectors diminished cisplatin- and etoposide-induced cell death. CONCLUSIONS: Our clinical and in vitro data suggest that HMGB2 plays a significant role in tumor development and prognosis of HCC. These results can partly be explained by altered cell proliferations by HMGB2 associated with the antiapoptotic pathway.

Epithelial-mesenchymal transition gene signature to predict clinical outcome of hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most lethal cancers worldwide. More accurate stratification of patients at risk is necessary to improve its clinical management. As epithelial-mesenchymal transition is critical for the invasiveness and metastasis of human cancers, we investigated expression profiles of 12 genes related to epithelial-mesenchymal transition through a real-time polymerase chain reaction. From a univariate Cox analysis for a training cohort of 128 hepatocellular carcinoma patients, four candidate genes (E-cadherin [CDH1], inhibitor of DNA binding 2 [ID2], matrix metalloproteinase 9 [MMP9], and transcription factor 3 [TCF3]) with significant prognostic values were selected to develop a risk score of patient survival. Patients with high risk scores calculated from the four-gene signature showed significantly shorter overall survival times. Moreover, the multivariate Cox analysis revealed that four-gene signature (P = 0.0026) and tumor stage (P = 0.0023) were independent prognostic factors for overall survival. Subsequently, the four-gene signature was validated in an independent cohort of 231 patients from three institutions, in which high risk score was significantly correlated with shorter overall survival (P = 0.00011) and disease-free survival (P = 0.00038). When the risk score was entered in a multivariate Cox analysis with tumor stage only, both the risk score (P = 0.0046) and tumor stage (P = 2.6 x 10(-9)) emerged as independent prognostic factors. In conclusion, we suggest that the proposed gene signature may improve the prediction accuracy for survival of hepatocellular carcinoma patients, and complement prognostic assessment based on important clinicopathologic parameters such as tumor stage.

Expression of cystathionine beta-synthase is downregulated in hepatocellular carcinoma and associated with poor prognosis.

The cystathionine beta-synthase (CBS) gene encodes an enzyme that catalyzes the synthesis of cystathionine in the trans-sulfuration pathway and is subject to tight regulation because of its critical role in antioxidant and methylation metabolism. The expression level of CBS in 120 hepatocellular carcinoma (HCC) specimens evaluated by real-time reverse transcriptase PCR (RT-PCR) is markedly lower than in surrounding non-cancerous liver (P<0.0001). The correlation between CBS gene expression in HCC and clinicopathological parameters or survival of HCC patients was statistically analyzed in the present study. Our study demonstrated that reduced CBS expression is significantly correlated with high tumor stage (P=0.0019), high Edmondson grade (P=0.00084), and high AFP level (P=6.2x10(-5)). Interestingly, a survival analysis showed that a significantly shorter overall survival (OS) time is observed in patients with reduced CBS expression (P=0.0022), although CBS expression was determined not to be an independent prognostic factor for OS (P=0.071) after considering tumor stage, tumor size, and AFP level. However, for the 62 patients with low AFP levels (<100 ng/ml), reduced CBS expression was found to be an independent prognostic factor for OS (P=0.0042) after considering tumor stage and tumor size. Thus, the expression level of CBS mRNA could be useful to predict clinical outcome of HCC, especially for patients with low AFP levels.

Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common tumor in the adult liver, with high relapse and mortality rates despite diverse treatment modalities. In this study, nicotinamide N-methyltransferase (NNMT), a key enzyme in drug metabolism, was investigated as a potential prognostic factor. METHODS: Frozen tumors and non-cancerous surrounding tissues from 120 patients with primary HCC were studied. Expressions of NNMT and internal control genes were measured by real-time reverse-transcription PCR (RT-PCR). The relationship of NNMT mRNA level with clinicopathologic parameters and clinical outcome was evaluated. RESULTS: NNMT mRNA level is markedly reduced in HCCs compared to non-cancerous surrounding tissues (P < 0.0001), and NNMT expression in tumors was significantly correlated with tumor stage (P = 0.010). Moreover, stratification of patients based on tumor NNMT mRNA levels revealed that the patients who expressed higher NNMT mRNA levels tended to have a shorter overall survival (OS) time (P = 0.053) and a significantly shorter disease-free survival (DFS) time (P = 0.016). Both NNMT expression (P = 0.0096) and tumor stage (P = 0.0017) were found to be significant prognostic factors for DFS in a multivariate analysis. CONCLUSION: The results of this study indicated that NNMT gene expression is associated with tumor stage and DFS time in HCC cases. Because of the broad substrate specificity of NNMT, which could alter the efficacy and adverse effects of chemotherapy, NNMT merits further investigation regarding its role as a prognostic factor with a larger cohort of HCC patients.