Importance of remission and residual somatic symptoms in health-related quality of life among outpatients with major depressive disorder: a cross-sectional study

Background: Major depressive disorder (MDD) is strongly associated with an impaired quality of life (QoL), which is itself affected by various factors. Symptom-oriented ratings poorly reflect the impact of disease on the QoL and level of functioning of the mental health of subjects. The purpose of this study was to assess health-related QoL (HRQoL) using preference-based measures in outpatients with MDD with regard to their remission achievement and clinical factors affecting the HRQoL. Methods: This was a cross-sectional observational study. We recruited 811 patients with MDD from 14 psychiatric outpatient clinics in Korea. They were divided into three groups as follows: a new visit group (n = 287), a remitted group (n = 235), and a non-remitted group (n = 289). The 17-item Hamilton Depression Rating Scale was used to assign patients to the remitted or non-remitted group. The general HRQoL was assessed with the EuroQol 5D (EQ-5D), using both the EQ-5D index score and the EuroQol Visual Analog Scale (EQ-VAS). The disease-specific HRQoL was assessed with the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Results: The non-remitted group showed a significant impairment of HRQoL in view of the subscales of EQ-5D index scores, EQ-VAS, and Q-LES-Q-SF. The EQ-5D index score in the remitted group was 0.77 ± 0.10, while it was 0.57 ± 0.23 in the non-remitted group and 0.58 ± 0.24 in the new visit group (p < 0.0001). The EQ-VAS scores for the remitted and non-remitted groups were 72.5 ± 16.6 and 50.9 ± 20.3, respectively (p < 0.0001). Likewise, patients with remission had the Q-LES-Q-SF total score of 46.5 ± 8.8, whereas those with non-remission reported 36.7 ± 7.7 (p < 0.0001). The symptom severity measured by the Depression and Somatic Symptoms Scale was significantly correlated with the HRQoL. Furthermore, patients with severe somatic symptoms showed a significantly lower EQ-5D index score (0.54 ± 0.24) than those with mild/moderate somatic symptoms (0.75 ± 0.12; p = 0.002). Conclusion: Non-remitted MDD patients, especially those with more severe somatic symptoms, show a distinct impairment of HRQoL and more clinical symptoms, suggesting the importance of achieving remission in the treatment of MDD

Serum immunoglobulin fused interferon-α inhibited tumor growth in athymic mice bearing colon 26 adenocarcinoma cells

Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 × : 30 µg/kg and 50 × : 150 µg/kg). A slight anti-tumoral effect was observed in all 10 × groups compared to the control. In the 50 × groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-β. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition

Enhanced Water Splitting by Fe 2

The effect of TiO2 layer applied to the conventional Fe2O3/FTO photoanode to improve the photoelectrochemical performance was assessed from the viewpoint of the microstructure and energy band structure. Regardless of the location of the TiO2 layer in the photoanodes, that is, Fe2O3/TiO2/FTO or TiO2/Fe2O3/FTO, high performance was obtained when α-Fe2O3 and H-TiNT/anatase-TiO2 phases existed in the constituent Fe2O3 and TiO2 layers after optimized heat treatments. The presence of the Fe2O3 nanoparticles with high uniformity in the each layer of the Fe2O3/TiO2/FTO photoanode achieved by a simple dipping process seemed to positively affect the performance improvement by modifying the energy band structure to a more favorable one for efficient electrons transfer. Our current study suggests that the application of the TiO2 interlayer, together with α-Fe2O3 nanoparticles present in the each constituent layers, could significantly contribute to the performance improvement of the conventional Fe2O3 photoanode

Anisakis simplex Larvae: Infection Status in Marine Fish and Cephalopods Purchased from the Cooperative Fish Market in Busan, Korea

The infection status of marine fish and cephalopods with Anisakis simplex third stage larva (L3) was studied over a period of 1 year. A total of 2,537 specimens, which consisted of 40 species of fish and 3 species of cephalopods, were purchased from the Cooperative Fish Market in Busan, Korea, from August 2006 to July 2007. They were examined for A. simplex L3 from the whole body cavity, viscera, and muscles. A. simplex L3 were confirmed by light microscopy. The overall infection rate reached 34.3%, and average 17.1 larvae were parasitized per infected fish. Fish that recorded the highest infection rate was Lophiomus setigerus (100%), followed by Liparis tessellates (90%), Pleurogrammus azonus (90%), and Scomber japonicus (88.7%). The intensity of infection was the highest in Gadus macrocephalus (117.7 larvae per fish), followed by S. japonicus (103.9 larvae) and L. setigerus (54.2 larvae). Although abundance of A. simplex L3 was not seasonal in most of the fish species, 10 of the 16 selected species showed the highest abundance in February and April. A positive correlation between the intensity of L3 infection and the fish length was obvious in S. japonicus and G. macrocephalus. It was likely that A. simplex L3 are more frequently infected during the spring season in some species of fish. Our study revealed that eating raw or undercooked fish or cephalopods could still be a source of human infection with A. simplex L3 in Korea

Sonographically Guided Core Biopsy of the Breast: Comparison of 14-Gauge Automated Gun and 11-Gauge Directional Vacuum-Assisted Biopsy Methods

OBJECTIVE: To compare the outcomes of 14-gauge automated biopsy and 11-gauge vacuum-assisted biopsy for the sonographically guided core biopsies of breast lesions. MATERIALS AND METHODS: We retrospectively reviewed all sonographically guided core biopsies performed from January 2002 to February 2004. The sonographically guided core biopsies were performed with using a 14-gauge automated gun on 562 breast lesions or with using an 11-gauge vacuum-assisted device on 417 lesions. The histologic findings were compared with the surgical, imaging and follow-up findings. The histologic underestimation rate, the repeat biopsy rate and the false negative rates were compared between the two groups. RESULTS: A repeat biopsy was performed on 49 benign lesions because of the core biopsy results of the high-risk lesions (n = 24), the imaging-histologic discordance (n = 5), and the imaging findings showing disease progression (n = 20). The total underestimation rates, according to the biopsy device, were 55% (12/22) for the 14-gauge automated gun biopsies and 36% (8/22) for the 11-gauge vacuum-assisted device (p = 0.226). The atypical ductal hyperplasia (ADH) underestimation (i.e., atypical ductal hyperplasia at core biopsy and carcinoma at surgery) was 58% (7/12) for the 14-gauge automated gun biopsies and 20% (1/5) for the 11-gauge vacuum-assisted biopsies. The ductal carcinoma in situ (DCIS) underestimation rate (i.e., ductal carcinoma in situ upon core biopsy and invasive carcinoma found at surgery) was 50% (5/10) for the 14-gauge automated gun biopsies and 41% (7/17) for the 11-gauge vacuum-assisted biopsies. The repeat biopsy rates were 6% (33/562) for the 14-gauge automated gun biopsies and 3.5% (16/417) for the 11-gauge vacuum-assisted biopsies. Only 5 (0.5%) of the 979 core biopsies were believed to have missed the malignant lesions. The false-negative rate was 3% (4 of 128 cancers) for the 14-gauge automated gun biopsies and 1% (1 of 69 cancers) for the 11-gauge vacuum-assisted biopsies. CONCLUSION: The outcomes of the sonographically guided core biopsies performed with the 11-gauge vacuum-assisted device were better than those outcomes of the biopsies performed with the 14-gauge automated gun in terms of underestimation, rebiopsy and the false negative rate, although these differences were not statistically significant.This study is supported by KISTEP and the Ministry of Science and Technology, Korea

Enhancement of paclitaxel-induced breast cancer cell death via the glycogen synthase kinase-3 beta-mediated B-cell lymphoma 2 regulation

Glycogen synthase kinase-3 beta (GSK-3 beta) is a serine/threonine protein kinase that is known to mediate cancer cell death. Here, we show that B-cell lymphoma 2 (Bcl-2), an anti-apoptotic protein, is regulated by GSK-3 beta and that GSK-3 beta-mediated regulation of Bcl-2 is crucial for mitochondrial-dependent cell death in paclitaxel-stimulated cells. We demonstrate that MCF7 GSK3 beta siRNA cells are more sensitive to cell death than MCF7 GFP control cells and that in the absence of GSK-3 beta, Bcl-2 levels are reduced, a result enhanced by paclitaxel. Paclitaxel-induced JNK (c-Jun N-terminal kinase) activation is critical for Bcl-2 modulation. In the absence of GSK-3 beta, Bcl-2 was unstable in an ubiquitination-dependent manner in both basal-and paclitaxel-treated cells. Furthermore, we demonstrate that GSK-3 beta-mediated regulation of Bcl-2 influences cytochrome C release and mitochondrial membrane potential. Taken together, our data suggest that GSK-3 beta-dependent regulation of Bcl-2 is crucial for mitochondria-dependent cell death in paclitaxel-mediated breast cancer therapy.clos

The paradoxical effect of aldosterone on cardiovascular outcome in maintenance hemodialysis patients

Background Patients with end-stage kidney disease face increased risk of cardiovascular events, and left ventricular diastolic dysfunction (LVDD) contributes to the high occurrence of cardiovascular mortality (CM). Although a high serum aldosterone (sALD) level is involved in the development of cardiovascular complications in the general population, this association is unclear in patients undergoing hemodialysis. We aimed to determine the impact of sALD on LVDD and CM among hemodialysis patients (HDPs). Methods We performed a prospective cohort study of maintenance HDPs without cardiovascular disease. The patients were divided into two groups according to the median level of sALD. All patients underwent baseline echocardiography to evaluate diastolic dysfunction (E/e' ratio > 15). The LVDD and CM rates were compared between the high and low aldosterone groups. Results We enrolled a total of 60 adult patients (mean age, 57.9 ± 12.1 years; males, 30.0%). The low aldosterone group had an increased left ventricular diastolic dimension compared with the high aldosterone group (52.2 ± 8.4 mm vs. 50.3 ± 5.2 mm, respectively; p = 0.03). Low log-aldosterone (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.19–0.86) and large left atrial dimension (OR, 1.31; 95% CI, 1.11–1.54) were independent risk factors for LVDD at baseline. In addition, Cox regression analysis demonstrated that low sALD was an independent predictor of CM in HDPs (hazard ratio, 0.46; 95% CI, 0.25–0.85; p = 0.01) during follow-up. Conclusion Low sALD was not only associated with LVDD but was also an independent predictor of CM among HDPs regardless of their interdialytic weight gain

Identification of a novel antiapoptotic protein that antagonizes ASK1 and CAD activities

Diverse stimuli initiate the activation of apoptotic signaling pathways that often causes nuclear DNA fragmentation. Here, we report a new antiapoptotic protein, a caspase-activated DNase (CAD) inhibitor that interacts with ASK1 (CIIA). CIIA, by binding to apoptosis signal-regulating kinase 1 (ASK1), inhibits oligomerization-induced ASK1 activation. CIIA also associates with CAD and inhibits the nuclease activity of CAD without affecting caspase-3–mediated ICAD cleavage. Overexpressed CIIA reduces H2O2- and tumor necrosis factor-α–induced apoptosis. CIIA antisense oligonucleotides, which abolish expression of endogenous CIIA in murine L929 cells, block the inhibitory effect of CIIA on ASK1 activation, deoxyribonucleic acid fragmentation, and apoptosis. These findings suggest that CIIA is an endogenous antagonist of both ASK1- and CAD-mediated signaling

Synergistic effect of ERK inhibition on tetrandrine-induced apoptosis in A549 human lung carcinoma cells

Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to have anti-tumor activity in various malignant neoplasms. However, the precise mechanism by which TET inhibits tumor cell growth remains to be elucidated. The present studies were performed to characterize the potential effects of TET on phosphoinositide 3-kinase/Akt and extracellular signal-regulated kinase (ERK) pathways since these signaling pathways are known to be responsible for cell growth and survival. TET suppressed cell proliferation and induced apoptosis in A549 human lung carcinoma cells. TET treatment resulted in a down-regulation of Akt and ERK phosphorylation in both time-/concentration-dependent manners. The inhibition of ERK using PD98059 synergistically enhanced the TET-induced apoptosis of A549 cells whereas the inhibition of Akt using LY294002 had a less significant effect. Taken together, our results suggest that TET: i) selectively inhibits the proliferation of lung cancer cells by blocking Akt activation and ii) increases apoptosis by inhibiting ERK. The treatment of lung cancers with TET may enhance the efficacy of chemotherapy and radiotherapy and increase the apoptotic potential of lung cancer cells

Clinically Conserved Genomic Subtypes of Gastric Adenocarcinoma

Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions