The Relationship Between Posttraumatic Embitterment Disorder and Stress, Depression, Self-Esteem, Impulsiveness, and Suicidal Ideation in Korea Soldiers in the Local Area.

BACKGROUND: The purpose of this study was to identify the prevalence of posttraumatic embitterment disorder (PTED) among soldiers, and examine its relation to stress, depression, self-esteem, impulsiveness, and suicidal ideation. METHODS: The subjects of this study were 200 soldiers and 197 control subjects, a total of 397 persons. Measurement tools used included the PTED self-rating scale, Stress Response Inventory, Beck Depression Inventory, Rosenberg Self-Esteem Inventory, Barratt Impulsiveness Scale, and Beck Scale of Suicide Ideation. RESULT: The major findings of the analysis are as follows: first, 11.5% of the soldiers were in the risk group for PTED, and 4% of them had PTED. Second, PTED in the soldiers was significantly associated with a number of variables such as their educational background, stress, depression, self-esteem, impulsiveness, and suicidal ideation, while it was not significantly associated with age. Third, through the hierarchical multiple regression analysis, it was found that academic background, stress, and depression had a statistically significant positive effect on the incidence of PTED in the soldiers. CONCLUSION: In order to prevent and effectively intervene in PTED in soldiers, there is a need for interventional efforts focused on depression and stress related to negative life events.

Modification of ASC1 by UFM1 is crucial for ERα transactivation and breast cancer development.

Biological roles for UFM1, a ubiquitin-like protein, are largely unknown, and therefore we screened for targets of ufmylation. Here we show that ufmylation of the nuclear receptor coactivator ASC1 is a key step for ERα transactivation in response to 17ß-estradiol (E2). In the absence of E2, the UFM1-specific protease UfSP2 was bound to ASC1, which maintains ASC1 in a nonufmylated state. In the presence of E2, ERα bound ASC1 and displaced UfSP2, leading to ASC1 ufmylation. Polyufmylation of ASC1 enhanced association of p300, SRC1, and ASC1 at promoters of ERα target genes. ASC1 overexpression or UfSP2 knockdown promoted ERα-mediated tumor formation in vivo, which could be abrogated by treatment with the anti-breast cancer drug tamoxifen. In contrast, expression of ufmylation-deficient ASC1 mutant or knockdown of the UFM1-activating E1 enzyme UBA5 prevented tumor growth. These findings establish a role for ASC1 ufmylation in breast cancer development by promoting ERα transactivation.

Seasonality in hip fracture among haemodialysis patients and kidney transplant recipients in South Korea.

AIM: The seasonality of hip fracture in haemodialysis (HD) patients and kidney transplant recipients (KTRs) have not been reported. We assessed seasonal variations in hip fractures among patients with end-stage kidney disease who undergo maintenance HD and KTRs. METHODS: Using the Korean National Health Insurance System database from January 2012 to December 2017, monthly counts of hip fracture were calculated among HD patients (n = 77 420) and KTRs (n = 8921). The 6-year normalized monthly fraction and seasonal fractions of hip fractures were calculated. A cosinor analysis was performed to determine the seasonality of the monthly incidence of hip fractures. RESULTS: The 6-year average monthly fraction of hip fractures was lowest in June and highest in October in HD patients, and lowest in February and highest in November in KTRs. The 6-year average seasonal fraction among HD patients was lowest in summer and highest in winter, and lowest in summer and highest in autumn among KTRs, but there was no significant difference. The incidence ratio of hip fractures was lowest in June and highest in January in HD patients, and lowest in August and highest in November in KTRs. On cosinor analysis, HD patients showed significant seasonality in hip fracture incidence, with a trough in summer and a peak in winter (p = .031), whereas KTRs did not exhibit a significant trend (p = .44). CONCLUSION: Hip fractures occurred more frequently in winter and less frequently in summer in patients undergoing HD, whereas KTRs did not show a seasonal trend.

Title: efficacy of intravitreal dexamethasone implant on hard exudate in diabetic macular edema.

BACKGROUND: To investigate the effect of intravitreal dexamethasone implant (DEX implant) on hard exudate (HE) accompanying diabetic macular edema (DME). METHODS: This study was a non-comparative non-randomized 1-year prospective interventional study. Patients with DME and HE were treated using DEX implant two or three times. Color fundus photography and optical coherence tomography (OCT) were performed at every visit. HE area was measured semi-automatically from the fundus photographs. RESULTS: Thirty-five patients completed the study. Eleven patients (31.4%) received two injections, while the remaining received three times. HE area (primary outcome) significantly decreased from 1.404±2.094 mm2 (baseline) to 0.212±0.592 mm2 (last visit), which was 24% of the baseline HE area (P<0.001). HE1500 (HE within 1500 µm from the fovea) area also decreased significantly from 0.382±0.467 mm2 to 0.066±0.126 mm2 (P<0.001). Furthermore, anaverage best corrected visual acuity (BCVA) improvement of 4.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters was observed (from 49.9±18.3 to 54.3±20.4 letters) (P= 0.008). Central macular thickness (CMT) decreased from 455.8±23.6 µm to 366.8±31.1 µm (P=0.009). Repetitive measurements for entire study duration was analyzed using generalized estimating equations (GEE), where BCVA was related to age, CMT, and HE1500 area in multivariate analyses. CONCLUSION: DEX implant could reduce and suppress HE in DME for one year with two or three injections. And centrally located HE area (HE1500 area) is related to vision. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02399657 , Registered 26 March 2015.

Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease.

This study explores the potential anticancer effects of lesbicoumestan from Lespedeza bicolor against human leukemia cancer cells. Flow cytometry and fluorescence microscopy were used to investigate antiproliferative effects. The degradation of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) was evaluated using immunoprecipitation, Western blotting, and confocal microscopy. Apoptosis was investigated using three-dimensional (3D) Jurkat cell resistance models. Lesbicoumestan induced potent mitochondrial depolarization on the Jurkat cells via upregulated expression levels of mitochondrial reactive oxygen species. Furthermore, the underlying apoptotic mechanisms of lesbicoumestan through the MALT1/NF-κB pathway were comprehensively elucidated. The analysis showed that lesbicoumestan significantly induced MALT1 degradation, which led to the inhibition of the NF-κB pathway. In addition, molecular docking results illustrate how lesbicoumestan could effectively bind with MALT1 protease at the latter's active pocket. Similar to traditional 2D cultures, apoptosis was markedly induced upon lesbicoumestan treatment in 3D Jurkat cell resistance models. Our data support the hypothesis that lesbicoumestan is a novel inhibitor of MALT1, as it exhibited potent antiapoptotic effects in Jurkat cells.

Anticancer Effects of Propionic Acid Inducing Cell Death in Cervical Cancer Cells.

Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.

Iroquois Homeobox Protein 2 Identified as a Potential Biomarker for Parkinson's Disease.

The diagnosis of Parkinson's disease (PD) is initiated after the occurrence of motor symptoms, such as resting tremors, rigidity, and bradykinesia. According to previous reports, non-motor symptoms, notably gastrointestinal dysfunction, could potentially be early biomarkers in PD patients as such symptoms occur earlier than motor symptoms. However, connecting PD to the intestine is methodologically challenging. Thus, we generated in vitro human intestinal organoids from PD patients and ex vivo mouse small intestinal organoids from aged transgenic mice. Both intestinal organoids (IOs) contained the human LRRK2 G2019S mutation, which is the most frequent genetic cause of familial and sporadic PD. By conducting comprehensive genomic comparisons with these two types of IOs, we determined that a particular gene, namely, Iroquois homeobox protein 2 (IRX2), showed PD-related expression patterns not only in human pluripotent stem cell (PSC)-derived neuroectodermal spheres but also in human PSC-derived neuronal cells containing dopaminergic neurons. We expected that our approach of using various cell types presented a novel technical method for studying the effects of multi-organs in PD pathophysiology as well as for the development of diagnostic markers for PD.

Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson's Disease.

Parkinson's disease (PD) is a well-known age-related neurodegenerative disease. Considering the vital importance of disease modeling based on reprogramming technology, we adopted direct reprogramming to human-induced neuronal progenitor cells (hiNPCs) for in vitro assessment of potential therapeutics. In this study, we investigated the neuroprotective effects of cryptotanshinone (CTN), which has been reported to have antioxidant properties, through PD patient-derived hiNPCs (PD-iNPCs) model with induced oxidative stress and cell death by the proteasome inhibitor MG132. A cytotoxicity assay showed that CTN possesses anti-apoptotic properties in PD-hiNPCs. CTN treatment significantly reduced cellular apoptosis through mitochondrial restoration, such as the reduction in mitochondrial reactive oxygen species and increments of mitochondrial membrane potential. These effects of CTN are mediated via the nuclear factor erythroid 2-related factor 2 (NRF2) pathway in PD-hiNPCs. Consequently, CTN could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD.

Antiproliferative Pterocarpans and Coumestans from Lespedeza bicolor.

Chromatographic purification of a methanol extract of the roots of Lespedeza bicolor led to the isolation of four new pterocarpans (1-4), two new coumestans (6 and 7), two new arylbenzofurans (8 and 9), and the known pterocarpan 1-methoxyerythrabyssin II (5). Their structures were identified using NMR spectroscopy, UV spectroscopy, and mass spectrometry. Cytotoxicity assays showed that compounds 1-9 exerted antiproliferative effects on blood cancer cells. Of these compounds, 1 and 6 induced mitochondrial depolarization and induced apoptosis in Jurkat cells. These compounds promoted cell death by inducing cell-cycle arrest at the G1 stage, reducing levels of BCL2, and increasing cleavage of PARP-1. These findings indicate that 1 and 6 are possible lead compounds for the treatment of human leukemia cells via intracellular signaling.

The economic burden of cancer attributable to obesity in Korea: A population-based cohort study.

OBJECTIVE: Cancer is a major cause of the burden of disease, and obesity is widely recognised one of the most important modifiable risk factor of cancer. Considering the economic impact of obesity and cancer, it is necessary to measure the economic burden of cancer attributable to excess body mass index (BMI). METHODS: This study used medical check-up sample cohort data of National Health Insurance Service (NHIS) claims and during 2002-2015. To estimate the costs (direct and indirect) according to obesity-related cancer sites, we performed a Cox proportional hazard model and cost of illness (COI) methods. RESULTS: Among male obesity-related cancer sites, the largest total costs caused by overweight or obesity were 5.5 trillion USD for liver cancer, 1.8 trillion USD for colorectal cancer and 1.6 trillion USD for kidney cancer. Among women, post-menopausal breast, liver and colorectal cancers had the largest total costs attributable to excess BMI (breast: 3.7 trillion USD, liver: 2.3 trillion USD, colorectal: 2.1 trillion USD). CONCLUSIONS: Approximately, 4.5% and 15.8% of total costs in obesity-related cancers can be reduced in men and women respectively. This study's findings highlight the importance of improved interventions, which can yield healthier lives and economic benefits beyond simply reducing cancer incidence and mortality.

Healthcare Utilization and Treatment Patterns in Diabetic Macular Edema in Korea: a Retrospective Chart Review.

BACKGROUND: Limited data exist on real-world treatment patterns for diabetic macular edema (DME) in Korea. In this study, we investigated DME treatment patterns from 2009 to 2014 and the impact of baseline treatment on healthcare resource utilization and visual acuity (VA) outcomes. METHODS: A retrospective cohort chart review of DME patients treated at 11 hospital ophthalmology clinics between January 1, 2012 and December 31, 2013 was conducted. We collected data on demographics, healthcare resource utilization (clinic visits, treatment visits, and visits for ocular investigations), distribution of DME treatments, and VA. RESULTS: Overall, 522 DME patients (men, 55.2%; mean age, 59 years; mean HbA1c [n = 209], 8.4%) with 842 DME eyes were evaluated. For all treatments, healthcare resource utilization was significantly higher during the first 6 months versus months 7-12, year 2, or year 3 (P ≤ 0.001), but was highest for patients whose first treatment was an anti-vascular endothelial growth factor (VEGF) treatment (visits/quarter; anti-VEGF, 1.9; corticosteroids, 1.7; laser, 1.4). Use of macular laser therapy decreased (44% to 8%), whereas use of anti-VEGF injections increased (44% to 69%) during the study period. However, VA improvement was not commensurate with healthcare resource utilization of anti-VEGF treatment (mean VA gain, 2.7 letters). CONCLUSION: A trend toward increasing use of intravitreal anti-VEGF injections for DME treatment was observed in Korea. However, the frequency of dosing and monitoring was lower in clinical practice versus major clinical trials, which may have led to the less-than-favorable improvements in visual outcomes.

Platyphylloside Isolated from Betula platyphylla is Antiproliferative and Induces Apoptosis in Colon Cancer and Leukemic Cells.

Betula platyphylla bark has been evaluated for the treatment of dermatitis, inflammatory conditions, and cancer. Diarylheptanoids are the major constituents of the B. platyphylla bark and possess various pharmacological effects. Our previous study confirmed the selective antiproliferative effect of platyphylloside (BPP) isolated from B. platyphylla on colon cancer and leukemic cells using 60 different cancer cell lines from thr National Cancer Institution (NCI). In line with previous reports, this study focuses on the apoptotic pathway of BPP, a phenolic glycoside composed of two aromatic rings joined by a seven-carbon chain. Cytotoxicity assays in solid tumor and blood cancer cell models demonstrated that BPP possesses potent antiproliferative activity. The level of apoptosis increased with BPP treatment, causing cell cycle arrest at the G1 phase along with the downregulation of IκBα phosphorylation and BCL-2, as well as upregulation of cleaved caspase 3 and BAX proteins. In addition, BPP displayed potent mitochondrial depolarization effects in Jurkat cells. The combined findings revealed that the cytotoxic effects of BPP were mediated by intracellular signaling, possibly through a mechanism involving the upregulation of mitochondrial reactive oxygen species (ROS). Thus, BPP could be a potential multitarget therapeutic agent in leukemia and colon cancer.

Factors Related to the Institutionalization of Older Aged Individuals Using Home- and Community-Based Care Services: Data From the South Korea Long-Term Care Insurance Program, 2008-2013.

South Korea introduced a public long-term care insurance (LTCI) program in response to its rapidly aging population. This study analyzed the association between living arrangement and caregiver type with institutionalization in LTCI grade 1 (very severe limitations), 2 (severe limitations), and 3 (moderate limitations) beneficiaries using data from the LTCI cohort, 2008 to 2013. The dependent variable was alteration status from home to institutional care within 1 year of receiving home service. Independent variables were living arrangement and primary caregiver type. The analysis was conducted using the generalized estimating equation model. Higher likelihoods of institutionalization were found in individuals living with a non-family member compared to individuals living with their spouses. Individuals without a caregiver or with a paid caregiver were also more likely to experience institutionalization than individuals with a spouse primary caregiver. Our findings underscore the importance of monitoring identified vulnerable groups of individuals to attain LTCI sustainability and enhance elderly quality of life.

The influence of family stress and conflict on depressive symptoms among working married women: A longitudinal study.

In the present study, researchers examined the association between depressive symptoms and family stress and conflict from multiple roles, along with the combined effect of family stress and family-work conflict. We used data from the 2008-2012 Korean Welfare Panel Study, consisting of 4,663 baseline participants. We measured depressive symptoms using the 11-item Center for Epidemiologic Studies Depression Scale. There was a significant relationship between depressive symptoms and family stress and conflict among working married women. With regard to the combined analysis, working married women who reported both family stress and family-work conflict exhibited the highest odds of depressive symptoms.

Efficacy of fixed-dosing aflibercept for treating polypoidal choroidal vasculopathy: 1-year results of the VAULT study.

PURPOSE: To investigate fixed-dosing aflibercept for treating polypoidal choroidal vasculopathy (PCV). METHODS: This phase IV, prospective, single-arm, interventional case series was conducted in eight centers. Forty treatment-naïve PCV patients were administered three monthly doses of intravitreal aflibercept (2.0 mg) and an injection every 2 months thereafter. Best-corrected visual acuity (BCVA) and central subfield macular thickness (CSMT) were measured at each visit. Fluorescein and indocyanine green angiography (ICGA) were performed at baseline, 3 and 12 months. The primary outcome measure was the proportion of patients who maintained BCVA (<15 letters loss) at 12 months. Changes in BCVA, macular appearance, and polypoidal lesion appearance were also examined. RESULTS: Thirty-five eyes (87.5 %) had maintained BCVA at 12 months. Average BCVA was significantly higher at 12 months (20/53, 64.2 letters) than at baseline (20/80, 55.1 letters, 9-letter gain; P < .001). Mean CSMT was significantly lower at 12 months (253.6 µm) than at baseline (365.2 µm, P < .001). The macula was dry in 32 (76.2 %), 27 (64.3 %), and 24 eyes (60.0 %) at 3, 6, and 12 months respectively. Fourteen eyes (33.3 %) had a fluid recurrence or increase at 6 months, and they had a significantly lower vision gain (P = .005) than other patients at 12 months. Complete polyp regression occurred in 26 eyes (66.7 %) at 12 months. CONCLUSIONS: Fixed-dosing aflibercept showed favorable outcomes in PCV patients at 12 months. However, some patients had worse outcomes because of fluid recurrence during maintenance dosing, and these patients would require additional treatments.

TOPOGRAPHIC CHANGES OF THE MACULA AFTER CLOSURE OF IDIOPATHIC MACULAR HOLE.

PURPOSE: To investigate retinal displacement in the macula after surgical closure of idiopathic macular hole and to identify factors correlated with displacement. METHODS: This retrospective multicenter study included 73 eyes of 73 patients having idiopathic macular hole. A custom program was developed to compare the position of the retinal vessels in the macula between preoperative and postoperative photographs. En face images of a 6 mm × 6 mm optical coherence tomography volume scans were registered to calculate the scale. A grid comprising 16 sectors in 2 rings (inner; 2-4 mm and outer; 4-6 mm) was superimposed. The displacement of the retinal vessels was measured as a vector value by comparing the location of the retinal vessels in each sector. The correlation between displacement and various clinical parameters was analyzed. RESULTS: The average displacement was 57.2 µm at an angle of -3.3° (nasal and slightly inferior). Displacement was larger in the inner ring (79.2 µm) than in the outer ring (35.3 µm, P < 0.001), and larger in the temporal sectors than in the corresponding nasal sectors (P ≤ 0.008). Inferior and superior displacement was noted in the superior and inferior sectors, respectively. Multiple regression analysis revealed that basal horizontal macular hole diameter and size of internal limiting membrane removal were independent factors of displacement. CONCLUSION: The macula was displaced centripetally, nasally, and slightly inferiorly after surgical closure of idiopathic macular hole. Hole closure, contraction of the nerve fiber layer, and gravity are the suggested mechanisms of macular displacement caused by internal limiting membrane peeling.

The association between number of doctors per bed and readmission of elderly patients with pneumonia in South Korea.

BACKGROUND: There is an urgent need to reduce readmission of patients with pneumonia and improve quality of care. To assess the association between hospital resources and quality of care, we examined the effect of number of doctors per bed on 30-day readmission and investigated the combined effect of number of doctors per bed and number of beds. METHODS: We used nationwide cohort sample data of health insurance claims by the National Health Insurance Service (NHIS) from 2002 to 2013. Pneumonia admissions to acute care hospitals among 7446 inpatients older than 65 were examined. We conducted a multivariate Cox proportional hazard model to analyze the association between the number of doctors per bed and 30-day readmission, as well as that of pneumonia-specific 30-day readmission with the combined effects of number of doctors per bed and number of beds. RESULTS: Overall, 1421 (19.1%) patients were readmitted within 30 days and 756 (11.2%) patients were readmitted for pneumonia within 30 days. Patients with pneumonia treated by very low or low number of doctors per bed showed higher readmission (pneumonia-specific readmission: hazard ratio [HR] = 1. 406, 95% confidence interval [CI] = 1.072-1.843 for low number of doctors per bed; all-cause readmissions: HR = 1.276, 95% CI = 1.026-1.587 for very low number of doctors per bed, and HR = 1.280, 95% CI = 1.064-1.540 for low number of doctors per bed). CONCLUSIONS: This empirical study showed that patients with pneumonia cared for in hospitals with more doctors were less likely to be readmitted. Pneumonia-specific 30-day readmission was also significantly associated with the combined effect of the number of doctors and the number of hospital beds.

Lack of Retirement Preparation is Associated with Increased Depressive Symptoms in the Elderly: Findings from the Korean Retirement and Income Panel Study.

The aim of this study was to investigate the relationship between retirement preparation and depressive symptoms among Koreans 50 years of age or older. We used data from the 2009 to 2013 Korean Retirement and Income Panel Study (KReIS), which included data from the 365 baseline participants of 50 years of age or older. Our sample included only newly retired participants who worked in 2009, but had retired in the 2011 and 2013. To monitor the change in depressive symptoms according to retirement preparation, we used repeated measurement data. We measured depressive symptoms using the Center for Epidemiological Studies Depression (CES-D) 20-item scale. In addition, we measured retirement preparation using a single self-report question asking whether the participant was financially ready for retirement. We evaluated relationship between retirement preparation and depressive symptoms after multivariable adjustment. Compared to subjects who had prepared for retirement (reference group), participants who had not prepared for retirement had increased depression scores (ß = 2.49, P < 0.001). In addition, individuals who had not prepared for retirement and who had low household income had the highest increase in depression scores (ß = 4.43, P < 0.001). Individuals, who had not prepared for retirement and without a national pension showed a considerable increase in depression scores (ß = 3.02, P < 0.001). It is suggested that guaranteed retirement preparation is especially important for mental health of retired elderly individuals with low economic strata.

Relationship between Mobile Phone Addiction and the Incidence of Poor and Short Sleep among Korean Adolescents: a Longitudinal Study of the Korean Children & Youth Panel Survey.

Three of ten teenagers in Korea are addicted to mobile phones. The aim of this study was to examine the relationship between mobile phone addiction and the incidence of poor sleep quality and short sleep duration in adolescents. We used longitudinal data from the Korean Children & Youth Panel Survey conducted by the National Youth Policy Institute in Korea (2011-2013). A total of 1,125 students at baseline were included in this study after excluding those who already had poor sleep quality or short sleep duration in the previous year. A generalized estimating equation was used to analyze the data. High mobile phone addiction (mobile phone addiction score > 20) increased the risk of poor sleep quality but not short sleep duration. We suggest that consistent monitoring and effective intervention programs are required to prevent mobile phone addiction and improve adolescents' sleep quality.

Effect of Changes in Sleep Quantity and Quality on Depressive Symptoms Among Korean Children.

This study aims to determine whether changes in sleep quantity and quality in childhood are associated with incidence of depressive symptoms. We used the three waves of the Korean Children & Youth Panel Survey (2011-2013). Statistical analysis using a generalized estimating equation model was performed. The 2,605 subjects analyzed included 1,453 students in 2012 and 1,152 students in 2013 without depressive symptoms in the prior year. We found that deteriorated or consistently poor sleep quality were important risk factors for depressive symptoms in children. We suggest that early detection and intervention of poor sleep quality in elementary school is required to reduce early onset depressive symptoms.