Effectiveness of home hospice care: a nationwide prospective observational study.

PURPOSE: Many assert the need for home hospice care. However, limited research has shown its effectiveness. The authors of this study thus evaluated the effectiveness of a home hospice care pilot project regarding (1) early enrollment in hospice care, (2) efficient use of inpatient hospice resources, and (3) enabling terminally ill patients to stay at their preferred place of care. METHODS: The authors conducted a nationwide prospective observational study. Patients were divided into home hospice care users (ever-users, n = 902) and inpatient-only hospice care users (never-users, n = 8210). Information about hospice service utilization was collected from a web-based registry system. Patients were registered if they started to receive the hospice service after providing written informed consent during the pilot project from March 2016-July 2017. RESULTS: Most ever-users preferred to stay at home (84.0%), while never-users preferred hospital admission (66.9%). Most ever-users were enrolled in hospice by home care (78.9%) and used both home and inpatient care (72.4%). The overall duration of hospice care was significantly longer among ever-users than never-users (median 39 vs. 15 days, respectively; mean ± SD 59.6 ± 62.8 vs. 24.8 ± 32.1, respectively; p < .001). Participation in the pilot program improved bed utilization (p = .025) and turnover rate (p < .001) of inpatient hospice service. CONCLUSIONS: Home hospice care enabled early enrollment in hospice services and provided a valid option to patients who wished to stay at home. Policy efforts to facilitate home hospice care are needed.

Decursinol Angelate Inhibits LPS-Induced Macrophage Polarization through Modulation of the NFκB and MAPK Signaling Pathways.

Inflammation is considered the root cause of various inflammatory diseases, including cancers. Decursinol angelate (DA), a pyranocoumarin compound obtained from the roots of Angelica gigas, has been reported to exhibit potent anti-inflammatory effects. In this study, the anti-inflammatory effects of DA on the MAP kinase and NFκB signaling pathways and the expression of pro-inflammatory cytokines were investigated in phorbol 12-myristate 13-acetate (PMA)-activated human promyelocytic leukemia (HL-60) and lipopolysaccharide (LPS)-stimulated macrophage (Raw 264.7) cell lines. PMA induced the activation of the MAP kinase-NFκB pathway and the production of pro-inflammatory cytokines in differentiated monocytes. Treatment with DA inhibited the activation of MAP kinases and the translocation of NFκB, and decreased the expression and exogenous secretion of IL-1ß and IL-6. Furthermore, LPS-stimulated Raw 264.7 cells were found to have increased expression of M1 macrophage-associated markers, such as NADPH oxidase (NOX) and inducible nitric oxide synthase (iNOS), and the M2 macrophage-associated marker CD11b. LPS also activated pro-inflammatory cytokines and Erk-NFκB. Treatment with DA suppressed LPS-induced macrophage polarization and the inflammatory response by blocking Raf-ERK and the translocation of NFκB in Raw 264.7 cells. Treatment with DA also inhibited the expression of pro-inflammatory cytokines, such as IL-1ß and IL-6, NOX, and iNOS in Raw 264.7 cells. These results suggest that DA has the potential to inhibit macrophage polarization and inflammation by blocking the activation of pro-inflammatory signals. These anti-inflammatory effects of DA may contribute to its potential use as a therapeutic strategy against various inflammation-induced cancers.

Awareness about past diagnosis and treatment history: nationwide survey of childhood cancer survivors and their parents.

OBJECTIVE: To assess the awareness of past medical history and long-term care issues of childhood cancer survivors (CCS) in Korea. METHODS: A nationwide survey was conducted on CCS and their parents in 10 regional cancer centers in Korea. Answers regarding cancer diagnosis and treatment history were compared with the treatment summary and categorized into three ('specific,' 'general,' and 'no') or two ('yes' and 'no') groups. RESULTS: Out of 343 contacts, 293 dyads completed the survey, and 281 dyads were analyzed. Awareness of cancer diagnosis was mostly specific for parents (76.5%) and CCS (35.2%). Awareness of anti-cancer treatment exposure was mostly general (84.6% for surgery, 67.9% for chemotherapy, and 53.9% for hematopoietic stem cell transplantation) rather than specific. In particular, more than half of the parents were not aware of the exposure to cardiotoxic agents (72.9%) or radiation therapy (56.3%). Providing information about long-term side effects and prevention of secondary cancer was significantly correlated only with more concern and more follow-up visits (P ≤ 0.001, respectively), without correlation with more specific awareness of exposure to cardiotoxic agents or radiation. CONCLUSION(S): Most of the parents of CCS were not aware of treatment-related risk factors necessary for long-term care. Providing information was significantly correlated with more concern and more follow-up visits, without improving corresponding knowledge about their past medical history. Effort aimed towards improving awareness about risk factors, the manner of providing information, and the patient referral system within which we use this information is warranted.

High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers.

UNLABELLED: Screening for hepatocellular carcinoma (HCC) is clinically important given that its early detection has remarkable survival benefits. We investigated the possible role of FIB-4, a recently developed noninvasive marker for liver fibrosis based on routine laboratory tests, as a clinical indicator for predicting future HCC among hepatitis B surface antigen (HBsAg) carriers. Our retrospective cohort study involved 986 Korean HBsAg carriers 40 years of age or older who visited Seoul National University Hospital for a health checkup. National medical service claims data were used to determine HCC incidence. Median follow-up time was 5.4 years (interquartile range: 4.4 years). Adjusted for age, sex, body mass index, smoking, alcohol, and antiviral medication for hepatitis B, compared to subjects with FIB-4 <1.25, subjects with 1.7≤ FIB-4 <2.4 showed an adjusted hazard ratio (aHR) of 4.57 (95% confidence interval [CI]: 1.50-13.92) and subjects with FIB-4 ≥2.4 showed an aHR of 21.34 (95% CI: 7.73-58.92) for HCC incidence. FIB-4 was shown to have incremental predictive value to ultrasonographic liver cirrhosis for HCC incidence (C-index: 0.701 vs. 0.831; P = 0.001). FIB-4 was also better predictive of HCC incidence, compared to that of ultrasonographic liver cirrhosis (C-index: 0.775 vs. 0.701; P = 0.040). CONCLUSION: High FIB-4 is a highly predictive risk factor for HCC incidence among Korean HBsAg carriers. FIB-4 is a promising, easily applicable, and cost-effective clinical tool in identifying a subpopulation of HBsAg carriers who are at heightened risk. Our study needs to be replicated in larger future studies on various ethnic groups; nonetheless, our study suggests that FIB-4 may play a valuable role in HCC screening among HBsAg carriers.

Prediction of future hepatocellular carcinoma incidence in moderate to heavy alcohol drinkers with the FIB-4 liver fibrosis index.

BACKGROUND: Although heavy alcoholics are at heightened risk for hepatocellular carcinoma (HCC), there are no guidelines that recommend HCC screening for heavy alcoholics. This study investigated FIB-4, a noninvasive and easily applicable liver fibrosis index, as a risk factor for HCC incidence among alcohol drinkers without viral hepatitis. METHODS: This retrospective cohort study included 6661 generally healthy adults who were 30 years old or older, did not have chronic viral hepatitis, and visited Seoul National University Hospital for a general, routine health evaluation. The future HCC incidence was determined from National Health Insurance medical service claims data (median follow-up, 6.2 years). RESULTS: With adjustments for age, sex, body mass index, smoking, and alcohol, compared with subjects with FIB-4 values less 1.00, subjects with FIB-4 values greater than or equal to 1.75 and less than 2.10 and subjects with FIB-4 values greater than or equal to 2.10 had adjusted hazard ratios (aHRs) of 5.18 (95% confidence interval [CI], 1.12-24.00) and 13.63 (95% CI, 3.77-49.33), respectively, for HCC incidence. This was heightened in subjects who drank more 30 g of alcohol per day: the aHRs were 8.39 (95% CI, 1.28-54.87) and 16.58 (95% CI, 3.87-71.04), respectively. FIB-4 was shown to have a higher predictive value for HCC incidence than ultrasonographically detected liver cirrhosis (C-index, 0.665 vs 0.527; P = .044). CONCLUSIONS: High FIB-4 is a risk factor with a high predictive value for HCC incidence, especially among moderate to heavy alcoholics (>30 g/d). FIB-4 is a readily available and probably cost-effective clinical tool with potential value for identifying subpopulations of alcoholics at particularly high risk who would benefit from regular HCC screening. Further investigations are warranted to validate our results; nonetheless, our study suggests that FIB-4 may be useful in HCC screening among alcoholics.

Discordance among patient preferences, caregiver preferences, and caregiver predictions of patient preferences regarding disclosure of terminal status and end-of-life choices.

BACKGROUND: The complexity of end-of-life (EOL) communication in cancer care is often increased by family caregivers, who frequently affect the information and decision-making process. We assessed cancer patient preferences (PP), family caregiver preferences (FCP), and family caregiver predictions of patient preferences (FCPPP) regarding the disclosure of terminal status, family involvement in the disclosure process, and EOL choices, and we evaluated the concordances among them. METHODS: A national, multicenter, cross-sectional survey of 990 patient-caregiver dyads (participation rate = 76.2%) was performed. A set of paired questionnaires was independently administered to patients and their caregivers. RESULTS: While patients and family caregivers had wide spectra of preferences, patients significantly preferred disclosure, direct disclosure by a physician, and palliative care options (all P < 0.001). Family caregiver predictions were similar to PP with regard to terminal disclosure (P = 0.35) but significantly different with regard to family involvement in the disclosure process and EOL choices (P < 0.001). The concordances of PP and FCP (κ = 0.08-0.13), and those of PP and FCPPP (κ = 0.09-0.17), were poor. The concordances of FCP and FCPPP were fair to moderate (κ = 0.35-0.67). Discrepancies between PP and FCP and between PP and FCPPP were associated with dysfunctional family communication. CONCLUSIONS: Family caregivers do not generally concur with patients in their preferences, nor do they reliably predict PP. Open dialogue between patient and family caregivers would reduce the discrepancy. More emphasis on incorporating family caregivers in EOL communication is needed from clinical, research, and training perspectives.

Treatment Gap in the National Health-screening Program in Korea: Claim-based Follow-up of Statin Use for Sustained Hypercholesterolemia.

Participation in a screening program by itself may not improve clinical outcomes. Treatment gaps in the program may limit its full benefit. We evaluated statin prescription rates for subjects with sustained hypercholesterolemia to assess the treatment gaps in the National Health Screening Program (NHSP) in Korea. A retrospective, random cohort was established among National Health Insurance Corporation (NHIC) members. Finally, we examined 465,499 individuals who attended the NHSP from 2003 to 2010 without any history of dyslipidemia, statin prescription, or hospitalization for cardiovascular events until the end of 2002. The subsequent statin prescription rates were identified from the NHIC medical service claim database from 2003 to 2011. Descriptive data and odds ratio from multivariate logistic analyses on statin prescription rates and the corresponding correlations were evaluated. The NHSP detected 114,085 (24.5%) cases of newly diagnosed hypercholesterolemia. However, only 8.6% of these received statin prescription within 6 months of diagnosis. For cases of sustained hypercholesterolemia determined in the next screening visit by the NHSP, the statin prescription rate increased, but only to 12.2%. Statin prescriptions were more common among females, older individuals, and hypertension or diabetes patients. Furthermore, the statin prescription rates had increased over the study period. The NHSP exhibited low statin prescription rate which has been improving. For the NHSP to be effective, it would be worthwhile to decrease the gap between the diagnosis of hypercholesterolemia and the following treatment.

Effect of the fragrance inhalation of essential oil from Asarum heterotropoides on depression-like behaviors in mice.

BACKGROUND: Psychological stressors may cause affective disorders, such as depression and anxiety, by altering expressions of corticotropin releasing factor (CRF), serotonin (5-HT), and tyrosine hydroxylase (TH) in the brain. This study investigated the effects of essential oil from Asarum heterotropoides (EOAH) on depression-like behaviors and brain expressions of CRF, 5-HT, and TH in mice challenged with stress. METHODS: Male ICR mice received fragrance inhalation of EOAH (0.25, 0.5, 1.0, and 2.0 g) for 3 h in the special cage capped with a filter paper before start of the forced swimming test (FST) and tail suspension test (TST). The duration of immobility was measured for the determination of depression-like behavior in the FST and TST. The selective serotonin reuptake inhibitor fluoxetine as positive control was administered at a dose of 15 mg/kg (i.p.) 30 min before start of behavioral testing. Immunoreactivities of CRF, 5-HT, and TH in the brain were also measured using separate groups of mice subjected to the FST. RESULTS: EOAH at higher doses (1.0 and 2.0 g) reduced immobility time in the FST and TST. In addition, EOAH at a dose of 1.0 g significantly reduced the expected increases in the expression of CRF positive neurons in the paraventricular nucleus and the expression of TH positive neurons in the locus coeruleus, and the expected decreases of the 5-HT positive neurons in the dorsal raphe nucleus. CONCLUSION: These results provide strong evidence that EOAH effectively inhibits depression-like behavioral responses, brain CRF and TH expression increases, and brain 5-HT expression decreases in mice challenged with stress.

Guilt, censure, and concealment of active smoking status among cancer patients and family members after diagnosis: a nationwide study.

OBJECTIVES: We aimed to identify the prevalence of feelings of guilt, censure, and concealment of smoking status among cancer patients and their family members who continued to smoke after the patient's diagnosis. METHODS: Among 990 patient-family member dyads, 45 patients and 173 family members who continued to smoke for at least 1 month after the patients' diagnoses were administered questions examining feelings of guilt, censure, and smoking concealment. RESULTS: Most patients who continued to smoke reported experiencing feelings of guilt toward their families (75.6%) and censure from their family members (77.8%), and many concealed their smoking from their family members (44.4%) or healthcare professionals (46.7%). Family members who continued to smoke also reported feelings of guilt with respect to the patient (63.6%) and that the patient was critical of them (68.9%), and many concealed their smoking from the patient (28.5%) or healthcare professionals (9.3%). Patients' feeling of guilt was associated with concealment of smoking from family members (55.9% vs. 10.0%) or health care professionals (55.9% vs. 20.0%). Family members who reported feeling guilty (36.5% vs. 16.3%) or censured (34.5% vs. 16.7%) were more likely to conceal smoking from patients. CONCLUSION: Many patients and family members continue to smoke following cancer diagnosis, and the majority of them experience feelings of guilt and censure, which can lead to the concealment of smoking status from families or health care professionals. Feelings of guilt, censure, and concealment of smoking should be considered in the development and implementation of smoking cessation programs for cancer patients and family members.

The impact of awareness of terminal illness on quality of death and care decision making: a prospective nationwide survey of bereaved family members of advanced cancer patients.

OBJECTS: We aimed to assess whether awareness of a terminal illness can affect care decision making processes and the achievement of a good death in advanced cancer patients receiving palliative care services. METHODS: Awareness of terminal illness at the time of palliative care service admission was assessed by the health care professionals during the routine initial comprehensive assessment process and was recorded in the national terminal cancer patient registry. A follow-up nationwide bereavement survey was conducted, which contained questions regarding decision making processes and the Korean version of the Good Death Inventory. RESULTS: Among the 345 patients included in the final analysis, the majority (68.4%) of the patients were aware of the terminal illness. Awareness of the terminal illness tended to reduce discordances in care decision making (adjusted odds ratio = 0.55; 95% CI: 0.29-1.07), and increased the patients' own decision making when there were discordances between patients and their families (adjusted odds ratio = 3.79; 95% CI: 1.31-10.94). The Good Death Inventory score was significantly higher among patients who were aware of their terminal illnesses compared with those who were not (5.04 vs. 4.80; p = 0.013) and especially in the domains of 'control over the future' (5.18 vs. 4.04; p < 0.001), 'maintaining hope and pleasure' (4.55 vs. 3.92; p = 0.002), and 'unawareness of death' (4.41 vs. 4.26; p = 0.024). CONCLUSION: Awareness of the terminal illness had beneficial effect on the harmonious decision making, patient autonomy, and patient's quality of death. Disclosure of terminal illness should be encouraged.

Angelica keiskei ameliorates scopolamine-induced memory impairments in mice.

Memory impairment is the most common symptom in patients with Alzheimer's disease (AD). Angelica keiskei (AK) has traditionally been used as a diuretic, laxative, analeptic and galactagogue. However, the anti-amnesic effects of AK and its molecular mechanisms have yet to be clearly elucidated. The aim of the present study is to evaluate the effects of AK on scopolamine-induced memory impairments in mice. The regulatory effect of AK on memory impairment was investigated using passive avoidance, Y-maze and the Morris water maze tasks. Acetylcholinesterase (AChE) activity assay was performed to investigate the cholinergic antagonistic effect of AK in the hippocampus. The effect of AK on phosphorylation of cAMP response element-binding protein (CREB) and expression of brain-derived neurotrophic factor (BDNF) were evaluated by Western blot assays and immunohistochemistry. The findings showed that AK significantly attenuated scopolamine-induced cognitive impairment in mice. Increase of AChE activity caused by scopolamine was significantly attenuated by AK. Additionally, AK significantly recovered the phosphorylation of CREB and expression of BDNF reduced by scopolamine in the hippocampus. Taken together, these results provide experimental evidence that AK might be a useful agent in preventing deficit of learning and memory caused by AD and aging.

The ameliorative effect of sophoricoside on mast cell-mediated allergic inflammation in vivo and in vitro.

Sophoricoside exhibits numerous pharmacological effects, including anti- inflammatory and anti-cancer actions, yet the exact mechanism that accounts for the anti-allergic effects of sophoricoside is not completely understood. The aim of the present study was to elucidate whether and how sophoricoside modulates the mast cell-mediated allergic inflammation in vitro and in vivo. We investigated the pharmacological effects of sophoricoside on both compound 48/80 or histamine-induced scratching behaviors and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis in mice. Additionally, to find a possible explanation for the anti-inflammatory effects of sophoricoside, we evaluated the effects of sophoricoside on the production of histamine and inflammatory cytokines and activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). The finding of this study demonstrated that sophoricoside reduced compound 48/80 or histamine-induced scratching behaviors and DNCB-induced atopic dermatitis in mice. Additionally, sophoricoside inhibited the production of inflammatory cytokines as well as the activation of NF-κB and caspase-1 in stimulated HMC-1. Collectively, the findings of this study provide us with novel insights into the pharmacological actions of sophoricoside as a potential molecule for use in the treatment of allergic inflammation diseases.

Clinical Implication of Glenohumeral and Subacromial Synovitis in Rotator Cuff Tears.

Background: Synovitis of the glenohumeral (GH) joint and the subacromial (SA) space is commonly observed during arthroscopic rotator cuff surgery. Purpose: To investigate the distribution, severity, and clinical implications of synovitis in the GH joint and SA space in patients with a full-thickness rotator cuff tear (RCT). Study Design: Case series; Level of evidence, 4. Methods: Data were retrospectively collected from 207 patients with a full-thickness RCT who underwent arthroscopic repair. Preoperative parameters used in the clinical assessment included pain, range of motion (ROM), muscle strength, and functional scores. Macroscopic assessment of synovitis was performed intraoperatively in the 3 regions of interest (ROIs) of the GH joint and 4 ROIS of the SA space using an evaluation system. The distribution and severity of synovitis and the association between synovitis and clinical assessment were evaluated. Results: Synovitis was more severe in the GH joint than in the SA space (P < .001). Synovitis in the posterior GH joint and the lateral SA space, where most of the rotator cuff was located, was the most severe area among the ROIs of the GH joint and the SA space, respectively (P < .05). All types of pain, except for pain at rest, were associated with synovitis in the posterior GH joint (P < .05). All ROM measures were associated with synovitis in the posterior and inferior GH joint (|r| > 0.20; P < .05 for both). The strength of the supraspinatus and the infraspinatus was associated with synovitis in the posterior GH joint (P < .05). Shoulder function was associated with synovitis in the posterior and inferior GH joint and more in the posterior GH joint (P < .05 for both). Synovitis in the SA space was not associated with any of the clinical parameters. Conclusion: Synovitis in the posterior GH joint was the most severe form of synovitis in the GH joint in patients with a full-thickness RCT. Synovitis in the posterior GH joint was closely associated with increased pain and decreased ROM, muscle strength, and functional score. Synovitis in the SA space was milder and not associated with any clinical parameters.

Non-cancer mortality among long-term survivors of adult cancer in Korea: national cancer registry study.

OBJECTIVES: To investigate the pattern of non-cancer deaths and to determine whether there is excess mortality from non-cancer causes among Korean long-term survivors of adult cancer. METHODS: We merged national cancer registry data and national death registration data to determine non-cancer death patterns of 243,713 people who were diagnosed with cancer from 1993 to 2000 and who survived > or =5 years. We calculated standardized mortality ratios (SMRs) by an indirect standardization method. RESULTS: Of the patient population, 26,498 (10.9%) had died as of December 2005; the cause of death for 6,364 (24.0%) of those was not cancer. The proportion of non-cancer mortality increased with age at diagnosis and correlated with the 5-year survival rate (r = 0.336 for women, 0.571 for men). Although the risk for non-cancer death was lower among long-term survivors in general (SMR, 0.78; 95% CI, 0.76-0.80), it was higher among younger survivors (SMR, 1.23-2.50, for those who died before 50) than the general population. Survivors had an elevated suicide rate (SMR, 1.28; 95% CI, 1.15-1.42), especially male (SMR, 1.35; 95% CI, 1.19-1.53) and stomach cancer survivors (SMR, 1.38; 95% CI, 1.14-1.66). CONCLUSIONS: Appropriate medical attention for long-term adult cancer survivors, especially younger survivors, is warranted to prevent premature deaths from non-cancer causes.

Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway.

Inhibition of angiogenesis is an attractive approach for the treatment of angiogenic diseases, such as cancer. Vascular endothelial growth factor (VEGF) is one of the most important activators of angiogenesis and interacts with the high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2. The pyranocoumarin compounds decursin and decursinol angelate isolated from the herb, Angelica gigas, are known to possess potent anti-inflammatory activities. However, little is known about their antiangiogenic activity or their underlying mechanisms. Here, we show the antiangiogenic effects of decursin and decursinol angelate using in vitro assays and in vivo animal experiments. Decursin and decursinol angelate inhibited VEGF-induced angiogenic processes in vitro, including proliferation, migration and tube formation of human umbilical vein endothelial cells. Decursin and decursinol angelate significantly suppressed neovessel formation in chick chorioallantoic membrane and tumor growth in a mouse model. The microvessel density in tumors treated with decursin for 14 days was significantly decreased compared with a vehicle control group. Decursin and decursinol angelate inhibited VEGF-induced phosphorylation of VEGFR-2, extracellular signal-regulated kinases and c-Jun N-terminal kinase mitogen-activated protein kinases. Taken together, these results demonstrate that decursin and decursinol angelate are novel candidates for inhibition of VEGF-induced angiogenesis.

Impact of breast cancer diagnosis and treatment on work-related life and factors affecting them.

We investigated the impacts of breast cancer diagnosis and treatment on employment status and the ability to perform occupational and housekeeping tasks. We performed a cross-sectional study to compare Korean breast cancer survivors (n = 1,594) who had been working before cancer diagnosis with a group of 20 to 60-year-old women from the general Korean population (n = 415). Employment decreased from 47.6% to 33.2% after cancer treatment. It was significantly smaller relative to the general population (52.1%) [adjusted odds ratio (aOR) = 1.68; 95% confidence interval (CI): 1.35-2.11). There was an inverse association between employment and low levels of education, low household income, multiple comorbidities, disease stage, and mastectomy. In addition, women who lived with a spouse were more likely to quit working after treatment compared to women who had no spouse. Fatigue and exhaustion were the most frequent difficulties encountered during occupational work (by 46.8% of cancer survivors) and housework (64.6%). Our findings suggest that breast cancer has a greater impact on employment among Korean women than among women in previously studied Western populations. Our data suggest that socio-cultural factors, as well as certain clinical characteristics, influence the decisions of Korean women to return or to not return to work after surviving breast cancer.

Decursin inhibits retinal neovascularization via suppression of VEGFR-2 activation.

PURPOSE: Pathologic angiogenesis in the retina leads to the catastrophic loss of vision. Retinopathy of prematurity (ROP), a vasoproliferative retinopathy, is a leading cause of blindness in children. We evaluated the inhibitory effect of decursin on retinal neovascularization. METHODS: Anti-angiogenic activity of decursin was evaluated by vascular endothelial growth factor (VEGF)-induced proliferation, migration, and in vitro tube formation assay of human retinal microvascular endothelial cells (HRMECs). We also used western blot analysis to assess inhibition of vascular endothelial growth factor receptor-2 (VEGFR-2) phosphorylation by decursin. After intravitreal injection of decursin in a mouse model of ROP, retinal neovascularization was examined by fluorescence angiography and vessel counting in cross-sections. The toxicity of decursin was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HRMECs as well as histologic and immunohistochemistry examination for glial fibrillary acidic protein in the retina. RESULTS: Decursin significantly inhibited VEGF-induced proliferation, migration, and the formation of capillary-like networks of retinal endothelial cells in a dose-dependent manner. Decursin inhibited VEGF-induced phosphorylation of VEGFR-2, blocking the VEGFR-2 signaling pathway. When intravitreously injected, decursin dramatically suppressed retinal neovascularization in a mouse model of ROP. Even in a high concentration, decursin never induced any structural or inflammatory changes to cells in retinal or vitreous layers. Moreover, the upregulation of glial fibrillary acidic protein expression was not detected in Mueller cells. CONCLUSIONS: Our data suggest that decursin may be a potent anti-angiogenic agent targeting the VEGFR-2 signaling pathway, which significantly inhibits retinal neovascularization without retinal toxicity and may be applicable in various other vasoproliferative retinopathies as well.

Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer quality of life questionnaire cervical cancer module.

OBJECTIVES: This study was conducted to evaluate the psychometric properties of the Korean version of the Quality of Life questionnaire cervical cancer module (QLQ-CX24), developed by the European Organization for Research and Treatment of Cancer (EORTC). METHODS: The EORTC QLQ-CX24 and the core questionnaire (the EORTC QLQ-C30) were administered to 860 Korean disease-free survivors of cervical cancer and 494 female control subjects from the general Korean population. The construct reliability and validity of the EORTC QLQ-CX24 questionnaire were assessed via factor analysis, multitrait scaling analyses and known group comparisons. RESULTS: Factor structure of the Korean version of the EORTC QLQ-CX24 questionnaire agreed with the originally hypothesized scale structure. Scale reliability was confirmed by Cronbach's alpha coefficients for internal consistency, which ranged from 0.78 to 0.87. Convergent and discriminant validity was confirmed by multitrait scaling analysis, which revealed scaling errors of 0.9. The clinical validity of the Korean version of the EORTC QLQ-CX24 was demonstrated by the ability to discriminate among controls and patient subgroups of different stages, treatments and overall health status. CONCLUSIONS: The Korean version of the EORTC QLQ-CX24 was found to be a reliable and a valid measure of quality of life among survivors of cervical cancer when administered in a large survey setting.

Regulation of type IV collagen alpha chains of glomerular epithelial cells in diabetic conditions.

An early feature of diabetic nephropathy is the alteration of the glomerular basement membrane (GBM), which may result in microalbuminuria, subsequent macroproteinuria, and eventual chronic renal failure. Although type IV collagen is the main component of thickened GBM in diabetic nephropathy, cellular metabolism of each alpha chains of type IV collagen has not been well studied. To investigate the regulation of alpha(IV) chains in diabetic conditions, we examined whether glucose and advanced glycosylation endproduct (AGE) regulate the metabolism of each alpha(IV) chains in the diabetic tissue and glomerular epithelial cells (GEpC). Glomerular collagen alpha3(IV) and alpha5(IV) chains protein were higher and more intense in immunofluorescence staining according to diabetic durations compared to controls. In vitro, mainly high glucose and partly AGE usually increased total collagen protein of GEpC by [(3)H]-proline incorporation assay and each alpha(IV) chain proteins including alpha1(IV), alpha3(IV), and alpha5(IV) in time-dependent and subchain-specific manners. However, the changes of each alpha(IV) chains mRNA expression was not well correlated to the those of each chain proteins. The present findings suggest that the metabolism of individual alpha(IV) chains of GBM is differentially regulated in diabetic conditions and those changes might be induced not only by transcriptional level but also by post-translational modifications.

The ameliorative effect of Protaetia brevitarsis Larvae in HFD-induced obese mice.

Protaetia brevitarsis Lewis (P. brevitarsis) larvae, edible insect, traditionally is consumed for various health benefits. However, little information is available with respect to its direct anti-obesity effects. Thus, the present study was designed to investigate the regulatory effect of P. brevitarsis against high-fat diet (HFD)-induced obese mice. HFD-fed mice showed an increase in the body weight and serum levels of total cholesterol as well as low-density lipoprotein-cholesterol, and triglycerides. The administration of P. brevitarsis to obese mice induced a reduction in their body weight, lipid accumulation in liver and serum lipid parameter compared with the HFD fed mice. P. brevitarsis also inhibited the expression of obesity-related genes such as CCAAT/enhancer-binding protein alpha and fatty acid synthesis in 3T3-L1 cells. Moreover, oleic acid was identified as predominant fatty acid of P. brevitarsis by gas chromatography analysis. Conclusively, these findings suggested that P. brevitarsis may help to prevent obesity and obesity-related metabolic diseases.