Tuberculous pleural effusion-induced Arg-1+ macrophage polarization contributes to lung cancer progression via autophagy signaling.

BACKGROUND: The association between tuberculous fibrosis and lung cancer development has been reported by some epidemiological and experimental studies; however, its underlying mechanisms remain unclear, and the role of macrophage (MФ) polarization in cancer progression is unknown. The aim of the present study was to investigate the role of M2 Arg-1+ MФ in tuberculous pleurisy-assisted tumorigenicity in vitro and in vivo. METHODS: The interactions between tuberculous pleural effusion (TPE)-induced M2 Arg-1+ MФ and A549 lung cancer cells were evaluated. A murine model injected with cancer cells 2 weeks after Mycobacterium bovis bacillus Calmette-Guérin pleural infection was used to validate the involvement of tuberculous fibrosis to tumor invasion. RESULTS: Increased CXCL9 and CXCL10 levels of TPE induced M2 Arg-1+ MФ polarization of murine bone marrow-derived MФ. TPE-induced M2 Arg-1+ MФ polarization facilitated lung cancer proliferation via autophagy signaling and E-cadherin signaling in vitro. An inhibitor of arginase-1 targeting M2 Arg-1+ MФ both in vitro and in vivo significantly reduced tuberculous fibrosis-induced metastatic potential of lung cancer and decreased autophagy signaling and E-cadherin expression. CONCLUSION: Tuberculous pleural fibrosis induces M2 Arg-1+ polarization, and M2 Arg-1+ MФ contribute to lung cancer metastasis via autophagy and E-cadherin signaling. Therefore, M2 Arg-1+ tumor associated MФ may be a novel therapeutic target for tuberculous fibrosis-induced lung cancer progression.

Tuberculous Pleural Effusion-Derived Exosomal miR-130b-3p and miR-423-5p Promote the Proliferation of Lung Cancer Cells via Cyclin D1.

Epidemiologic studies have shown an association between tuberculosis and lung cancer. The altered tumor microenvironment after tuberculosis infection appears to contribute to cancer progression. Pleural effusions are enriched in exosomes, which act as mediators of intercellular communication. We hypothesized that tuberculous pleural effusion (TPE)-derived exosomes mediate intercellular communication. Then, we examined the interaction between TPE-derived exosomes and cancer cells. Exosomal miRNA profiling of TPE was performed using a microRNA array. An in vitro lung cancer cell experiment and an in vivo mouse xenograft tumor model were used to evaluate the effects of the selected exosomal microRNAs. TPE-derived exosome treatment enhanced the growth of A549 cells both in vitro and in a nude mouse xenograft model. Neighboring cancer cells were observed to take up TPE-derived exosomes, which promoted cancer cell invasion. Exosome-mediated transfer of the selected microRNAs, including miR-130b-3p and miR-423-5p, to A549 lung cancer cells activated cyclin D1 signaling and increased the expression of phosphorylated p65, a cyclin D1 transcription factor. Inhibitors of miR-130b and miR-423-5p suppressed the promotion of lung cancer by TPE-derived exosomes and reduced the expression of p65 and cyclin D1. These results suggest that TPE-derived exosomal miRNAs can serve as a novel therapeutic target in tuberculous fibrosis-induced lung cancer.

Uric acid induced the phenotype transition of vascular endothelial cells via induction of oxidative stress and glycocalyx shedding.

Recent data suggested a causative role of uric acid (UA) in the development of renal disease, in which endothelial dysfunction is regarded as the key mechanism. Endothelial-to-mesenchymal transition (EndoMT) and shedding of the glycocalyx are early changes of endothelial dysfunction. We investigated whether UA induced EndoMT in HUVECs and an animal model of hyperuricemia fed with 2% oxonic acid for 4 wk. UA induced EndoMT in HUVECs with a generation of reactive oxygen species via the activation of membranous NADPH oxidase (from 15 min) and mitochondria (from 6 h) along with glycocalyx shedding (from 6 h), which were blocked by probenecid. GM6001, an inhibitor of matrix metalloproteinase, alleviated UA-induced glycocalyx shedding and EndoMT. Antioxidants including N-acetyl cysteine, apocynin, and mitotempo ameliorated EndoMT; however, they did not change glycocalyx shedding in HUVECs. In the kidney of hyperuricemic rats, endothelial staining in peritubular capillaries (PTCs) was substantially decreased with a de novo expression of α-smooth muscle actin in PTCs. Plasma level of syndecan-1 was increased in hyperuricemic rats, which was ameliorated by allopurinol. UA caused a phenotypic transition of endothelial cells via induction of oxidative stress with glycocalyx shedding, which could be one of the mechanisms of UA-induced endothelial dysfunction and kidney disease.-Ko, J., Kang, H.-J., Kim, D.-A., Kim, M.-J., Ryu, E.-S., Lee, S., Ryu, J.-H., Roncal, C., Johnson, R. J., Kang, D.-H. Uric acid induced the phenotype transition of vascular endothelial cells via induction of oxidative stress and glycocalyx shedding.

Paricalcitol attenuates TGF-ß1-induced phenotype transition of human peritoneal mesothelial cells (HPMCs) via modulation of oxidative stress and NLRP3 inflammasome.

Phenotype transition of mesothelial cells, such as epithelial-to-mesenchymal transition (EMT), is one of the early mechanisms of peritoneal fibrosis, which is mediated by oxidative stress and inflammation. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a multiprotein oligomer that promotes the maturation of IL-1ß and IL-18. Paricalcitol is reported to exert an anti-inflammatory effect; however, there are no studies as to whether paricalcitol modulates the activation of NLRP3 inflammasome. We investigated the role of NLRP3 inflammasome in peritoneal EMT with an exploration of the effect of paricalcitol on oxidative stress, NLRP3 inflammasome, and EMT of mesothelial cells. TGF-ß1-induced EMT in human peritoneal mesothelial cells (HPMCs) was associated with an up-regulation of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and procaspase-1, with an increased production of IL-1ß and IL-18, which was ameliorated by small interfering (si)NLRP3, siASC, caspase inhibitors, or neutralizing antibodies for IL-1ß and IL-18. TGF-ß1 enhanced reactive oxygen species generation with an increase in NADPH oxidase (NOX) activity and mitochondrial NOX4 production. Paricalcitol alleviated TGF-ß1-induced EMT and the NLRP3 inflammasome, which was associated with a down-regulation of NOX activity by interfering with p47phox and p22phox interaction and mitochondrial NOX4 production in HPMCs. Taken together, paricalcitol ameliorated EMT of HPMCs via modulating an NOX-dependent increase in the activity of NLRP3 inflammasome. Paricalcitol could be a novel approach to protect the peritoneum from the development of EMT and peritoneal fibrosis.-Ko, J., Kang, H.-J., Kim, D.-A., Ryu, E.-S., Yu, M., Lee, H., Lee, H. K., Ryu, H.-M., Park, S.-H., Kim, Y.-L., Kang, D.-H. Paricalcitol attenuates TGF-ß1-induced phenotype transition of human peritoneal mesothelial cells (HPMCs) via modulation of oxidative stress and NLRP3 inflammasome.

Computer-aided Diagnosis-generated Kinetic Features of Breast Cancer at Preoperative MR Imaging: Association with Disease-free Survival of Patients with Primary Operable Invasive Breast Cancer.

Purpose To retrospectively investigate the relationship between the kinetic features of breast cancer assessed with computer-aided diagnosis (CAD) at preoperative magnetic resonance (MR) imaging and disease-free survival in patients with primary operable invasive breast cancer. Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. The authors identified 329 consecutive women (mean age, 52.9 years; age range, 32-88 years) with newly diagnosed invasive breast cancer who had undergone preoperative MR imaging and surgery between January 2012 and February 2013. All MR images were retrospectively reviewed by using a commercially available CAD system, and the following kinetic parameters were noted for each lesion: peak enhancement (highest pixel signal intensity in the first series obtained after administration of contrast material), angio-volume (total volume of the enhancing lesion), and delayed enhancement profiles (the proportions of washout, plateau, and persistently enhancing component within a tumor). Cox proportional hazards modeling was used to identify the relationship between CAD-generated kinetics and disease-free survival after adjusting for clinical-pathologic variables. Results A total of 36 recurrences developed at a median follow-up of 50 months (range, 15-55 months). CAD-measured peak enhancement at preoperative MR imaging enabled differentiation between patients with and patients without recurrence (area under the receiver operating characteristic curve = 0.728; 95% confidence interval [CI]: 0.676, 0.775; P < .001). Multivariate Cox analysis showed that a higher peak enhancement (hazard ratio [HR] = 1.001; 95% CI: 1.000, 1.002; P = .004), a higher washout component (HR = 1.029; 95% CI: 1.005, 1.054; P = .017), and lymphovascular invasion at histopathologic examination (HR = 3.011; 95% CI: 1.302, 6.962; P = .010) were associated with poorer disease-free survival. Conclusion Higher values of CAD-measured peak enhancement and washout component at preoperative MR imaging were significantly associated with poorer disease-free survival of patients with primary operable breast cancer. © RSNA, 2017.

Biologic Profiles of Invasive Breast Cancers Detected Only With Digital Breast Tomosynthesis.

OBJECTIVE: The purpose of this study was to analyze the clinicopathologic and immunohistochemical features of invasive breast cancers detected only with digital breast tomosynthesis (DBT), compared with those of cancers detected with both DBT and full-field digital mammography (FFDM). MATERIALS AND METHODS: The medical records of 261 women (108 without and 153 with symptoms) with invasive breast cancers who underwent FFDM and DBT between April 2015 and June 2016 were retrospectively reviewed. To assess detectability, all DBT and FFDM images were reviewed independently by three radiologists blinded to clinicopathologic information. The reference standard was established by an unblinded consensus review of all images. Clinicopathologic and immunohistochemical features were analyzed according to the detectability status. RESULTS: Of the 261 cancers, 223 (85.4%) were detected with both DBT and FFDM (both-detected group). Twenty-four cancers (9.2%) not detected with FFDM (DBT-only group) were classified by DBT as a mass (58.3%), architectural distortion (33.3%), or asymmetry (8.3%). The remaining 14 cancers (5.4%) were not detected with either DBT or FFDM (both-occult group). On multivariate analysis, a dense breast parenchyma (p = 0.007), small tumor size (≤ 2 cm; p = 0.027), and luminal A-like subtype (estrogen receptor positive or progesterone receptor positive or both, human epidermal growth factor receptor 2 negative, and Ki-67 expression < 14%; p = 0.008) were significantly associated with the DBT-only group. For 108 screening-detected cancers, a dense breast parenchyma (p = 0.007) and luminal A-like subtype (p = 0.008) also maintained significance. CONCLUSION: The addition of DBT to FFDM in screening would aid in the detection of less-aggressive subtypes of invasive breast cancers in women with dense breasts.

Apparent diffusion coefficient of breast cancer and normal fibroglandular tissue in diffusion-weighted imaging: the effects of menstrual cycle and menopausal status.

The purpose of this study was to investigate prospectively whether the apparent diffusion coefficients (ADCs) of both breast cancer and normal fibroglandular tissue vary with the menstrual cycle and menopausal status. Institutional review board approval was obtained, and informed consent was obtained from each participant. Fifty-seven women (29 premenopausal, 28 postmenopausal) with newly diagnosed breast cancer underwent diffusion-weighted imaging twice (interval 12-20 days) before surgery. Two radiologists independently measured ADC of breast cancer and normal contralateral breast tissue, and we quantified the differences according to the phases of menstrual cycle and menopausal status. With normal fibroglandular tissue, ADC was significantly lower in postmenopausal than in premenopausal women (P = 0.035). In premenopausal women, ADC did not differ significantly between proliferative and secretory phases in either breast cancer or normal fibroglandular tissue (P = 0.969 and P = 0.519, respectively). In postmenopausal women, no significant differences were found between ADCs measured at different time intervals in either breast cancer or normal fibroglandular tissue (P = 0.948 and P = 0.961, respectively). The within-subject variability of the ADC measurements was quantified using the coefficient of variation (CV) and was small: the mean CVs of tumor ADC were 2.90 % (premenopausal) and 3.43 % (postmenopausal), and those of fibroglandular tissue ADC were 4.37 % (premenopausal) and 2.55 % (postmenopausal). Both intra- and interobserver agreements were excellent for ADC measurements, with intraclass correlation coefficients in the range of 0.834-0.974. In conclusion, the measured ADCs of breast cancer and normal fibroglandular tissue were not affected significantly by menstrual cycle, and the measurements were highly reproducible both within and between observers.

Wnt/ß-catenin signalling maintains self-renewal and tumourigenicity of head and neck squamous cell carcinoma stem-like cells by activating Oct4.

Accumulating evidence suggests that a distinct subpopulation of cancer stem cells (CSCs) is responsible for tumour initiation and progression in head and neck squamous cell carcinoma (HNSCC). Wnt/ß-catenin signalling is essential for stem cell regulation and tumourigenesis, but its molecular mechanism in HNSCC CSCs remains unknown. We investigated whether Wnt/ß-catenin signalling regulates self-renewal and tumourigenicity of HNSCC stem-like cells in vitro and in vivo. Cytoplasmic/nuclear ß-catenin, a major effector of Wnt/ß-catenin signalling, was expressed in a subpopulation of tumour cells in primary HNSCC tissue but in none of normal head and neck tissues. Overexpression of ß-catenin increased proliferation of HNSCC cells and induced dedifferentiation of these cells to cells with stem-like features. Knockdown of ß-catenin in HNSCC stem-like cells blocked their self-renewal capacity, stemness-associated gene expression, chemoresistance, and in vivo tumourigenicity. Furthermore, ß-catenin directly regulates Oct4 transcription in HNSCC stem-like cells. In addition, the effect of shRNA-mediated repression of ß-catenin on CSC traits in HNSCC stem-like cells was reversed by overexpression of Oct4. In patients with HNSCC, higher levels of both cytoplasmic/nuclear ß-catenin and Oct4 correlated with the worst prognosis. These results suggest inhibition of Wnt/ß-catenin signalling as a novel therapeutic strategy for targeting HNSCC stem-like cells.

Comparison of the Microarray-Based Assay, the Real-Time PCR Assay, and the Bidirectional Sequencing Method for CYP2C19 Genotyping.

BACKGROUND: Cytochrome P450 2C19 (CYP2C19) is a clinically important enzyme that metabolizes a wide variety of drugs. Recently, some new genetic assays designed to identify the CYP2C19 genotype were introduced. METHODS: We compared the abilities of the microarray-based Verigene CYP2C19 Test (Nanosphere, USA) and the AccuPower Real-time PCR CYP (*2,*3,*17) assay (Bioneer, Korea) with the ability of the bidirectional sequencing method for the detection of CYP2C19 genotypes in 78 whole blood samples. RESULTS: Among 78 specimens, 28 were *1/*1, 1 was *1/*17, 27 were *1/*2, 10 were *1/*3, 8 were *2/*2, 1 was *3/*3, and 3 were *2/*3. In the initial test, five samples (6.4%) in the Verigene assay and two samples (2.4%) in the AccuPower assay failed to generate definite results. All retests with both assays generated definitive results. In both assays, the results of CYP2C19 genotyping showed 100% final concordance with those obtained by the direct sequencing method. CONCLUSIONS: These two assays could be useful for the identification of CYP2C19 genotypes in clinical laboratories.

Degradation of gas-phase organic contaminants via nitrogen-embedded one-dimensional rod-shaped titania in a plug-flow reactor.

In this study, one-dimensional rod-shaped titania (RST) and nitrogen-doped RST (N-RST) with different ratios of N to Ti were prepared using a hydrothermal method and their applications for purification of indoor toxic organic contaminants in a plug-flow reactor were examined under visible or ultraviolet (UV) irradiation. The surface characteristics of as-prepared photocatalysts were investigated by transmission electron microscopy (TEM), X-ray diffraction (XRD), and UV-visible spectroscopy. The TEM images revealed that both pure RSTs and N-RSTs displayed uniform and nanorod-shaped structures. XRD revealed that the photocatalysts had crystalline TiO2. The UV-visible spectra demonstrated that the N-RSTs could be activated in the visible region. In most cases, N-RSTs showed higher degradation efficiencies than pure RSTs under visible-light and UV irradiation. N-RSTs with a N-to-Ti ratio of 0.5 exhibited the highest degradation efficiencies of benzene, toluene, ethyl benzene, and o-xylene (BTEX), suggesting the presence of an optimal N-to-Ti ratio for preparation of N-RSTs. In addition, the average degradation efficiencies of BTEX determined for the N-RSTs with a N-to-Ti ratio of 0.5 under visible-light irradiation for the lowest initial concentration (IC, 0.1 ppm) were 19%, 53%, 85%, and 92%, respectively, while the degradation efficiencies for the highest IC (2.0 ppm) were 2%, 8%, 17%, and 33%. These values decreased as the stream flow rate increased. Overall, the as-prepared N-RSTs could be effectively applied for degradation of toxic gas-phase organic contaminants under visible-light as well as UV irradiation.

Relationship Between Electronic Health Literacy and Self-Management in People With Type 2 Diabetes Using a Structural Equation Modeling Approach.

BACKGROUND: Electronic health (eHealth) literacy is a relatively new concept used to determine health outcomes. However, it is not well known how eHealth literacy relates to health outcomes such as diabetes self-management. PURPOSE: This study was designed to examine the relationships among eHealth literacy, self-efficacy, social support, and self-management in people with Type 2 diabetes. METHODS: A cross-sectional design was used to examine secondary data from a field survey of people with Type 2 diabetes recruited from outpatient clinics from August to December 2021 ( N = 453). A structural equation model was used that first analyzed the measurement model using confirmatory factor analysis and then tested the hypothesized structural model to estimate the expected relationships among the study variables. The significance of the statistical estimates for the model was assessed based on the 95% bias-corrected bootstrap confidence interval from 5,000 bootstrap resamples. RESULTS: Significant, indirect relationships were found between eHealth literacy and self-management via self-efficacy (ß = 0.26, B = 0.17, 95% CI [0.10, 0.24]) and via social support and, in turn, self-efficacy (ß = 0.08, B = 0.05, 95% CI [0.04, 0.08]). eHealth literacy, social support, and self-efficacy together explained 58.1% of the variance in self-management. CONCLUSION/IMPLICATIONS FOR PRACTICE: This study provides new evidence regarding how eHealth literacy relates to self-management in people with Type 2 diabetes via two indirect pathways, including self-efficacy alone and social support and self-efficacy in series. An eHealth literacy program for self-management should be developed in clinical practice that includes strategies for inducing synergistic effects from self-efficacy and social support on self-management in people with Type 2 diabetes.

Mapping the spatial distribution of primary and secondary PM2.5 in a multi-industrial city by combining monitoring and modeling results.

Industrial cities are strongly influenced by primary emissions of PM2.5 from local industries. In addition, gaseous precursors, such as sulfur oxides (SOX), nitrogen oxides (NOX), and volatile organic compounds (VOCs), emitted from industrial sources, undergo conversion into secondary inorganic and organic aerosols (SIAs and SOAs). In this study, the spatial distributions of primary and secondary PM2.5 in Ulsan, the largest industrial city in South Korea, were visualized. PM2.5 components (ions, carbons, and metals) and PM2.5 precursors (SO2, NO2, NH3, and VOCs) were measured to estimate the concentrations of secondary inorganic ions (SO42-, NO3-, and NH4+) and secondary organic aerosol formation potential (SOAFP). The spatial distributions of SIAs and SOAs were then plotted by combining atmospheric dispersion modeling, receptor modeling, and monitoring data. Spatial distribution maps of primary and secondary PM2.5 provide fundamental insights for formulating management policies in different districts of Ulsan. For instance, among the five districts in Ulsan, Nam-gu exhibited the highest levels of primary PM2.5 and secondary nitrate. Consequently, controlling both PM2.5 and NO2 emissions becomes essential in this district. The methodology developed in this study successfully identified areas with dominant contributions from both primary emissions and secondary formation. This approach can be further applied to prioritize control measures during periods of elevated PM levels in other industrial cities.

Measurement invariance of the patient health questionnaire-9 depression scale in a nationally representative population-based sample.

The Patient Health Questionnaire-9 (PHQ-9) is widely used to measure the severity of depressive symptoms and to screen for depressive disorder, but its measurement invariance has received little research attention. The aim of this study was to assess the measurement invariance of the PHQ-9 across various sociodemographic and medical-condition groups. The structural validity and internal consistency of the PHQ-9 were also assessed as the prerequisite properties for measurement invariance. This study was conducted using data from the Korea National Health and Nutrition Examination Survey. The included participants comprised 5,347 people older than 19 years. Exploratory graph analysis (EGA) and confirmatory factor analysis (CFA) were performed to determine structural validity, and the omega coefficient (ω) was used to determine internal consistency. Measurement invariance (configural, metric, and scalar invariance) was evaluated using multigroup confirmatory factor analysis (MGCFA). The single structural model of the PHQ-9 that was validated by EGA was also satisfactory with fit indices of χ2 = 770.765 (p < 0.001), CFI = 0.944, SRMR = 0.040, and RMSEA = 0.076 (90% CI = 0.072-0.081). The ω of the PHQ-9 was 0.812, implying satisfactory internal consistency. The one-factor PHQ-9 had equivalent overall structure, factor loadings, and item intercepts across age groups, suggesting invariance across ages. Partial scalar invariance was demonstrated across sex and marital-status groups. Partial metric and scalar invariance were supported across education groups. Scalar invariance was supported among all of the medical-condition (hypertension, diabetes, cancer, arthritis, asthma, and heart disease) groups. Overall, the measurement invariance of the one-factor PHQ-9 was empirically supported across sociodemographic and medical-condition groups. The PHQ-9 can be reliably used to compare the severity of depressive symptoms across these groups in research and practice.

Relationship between Type D personality and adverse health outcomes in people with type 2 diabetes: The parallel mediating roles of diabetes distress and social isolation.

AIM: To investigate the relationship between Type D personality and adverse health outcomes [glycated haemoglobin (HbA1c) and health-related quality of life (HRQOL)] directly, and indirectly via diabetes distress and social isolation in people with type 2 diabetes. DESIGN: A secondary analysis of 524 participant's data derived from a cross-sectional, correlational study with people with type 2 diabetes. METHODS: Data were analysed using the PROCESS macro of SPSS. RESULTS: Type D personality was present in 31.3% of the participants, and exerted a direct effect on HRQOL but not on HbA1c. Type D personality indirectly affected both HbA1c and HRQOL via the mediators of diabetes distress and social isolation. Nurses need to monitor people with type 2 diabetes to determine whether Type D personality is present. Those with Type D personality should be provided with interventions to reduce diabetes distress and alleviate social isolation in order to improve HbA1c and HRQOL.

Association between breakfast frequency and metabolic syndrome among young adults in South Korea.

Skipping breakfast is highly prevalent but it is not clear whether breakfast frequency is associated with metabolic syndrome in young adults. We aimed to assess the association between breakfast frequency and metabolic syndrome in Korean young adults. This cross-sectional study was based on health check-up data of university students aged 18-39 years between 2016 and 2018. Participants were stratified into three groups by breakfast frequency (non-skipper, skipper 1-3 days/week, skipper 4-7 days/week). Multivariable-adjusted logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of metabolic syndrome. Out of 12,302 participants, 56.8% skipped breakfast at least 4 days/week. Metabolic syndrome prevalence was higher in those skipping breakfast for 4 or more days/week compared to non-skipper. (3.1% vs 1.7%) In the age- and sex-adjusted model, individuals skipping breakfast for 4-7 days per week had a higher OR of metabolic syndrome (OR 1.73, 95% CI 1.21-2.49) compared to non-skipper. Although this association became insignificant (OR 1.49, 95% CI 0.99-2.23) after a fully adjusted multivariable model, trends of positive association between frequency of breakfast skipping and metabolic syndrome was significant (P for trend = 0.038). Frequent breakfast skipping was associated with higher odds of metabolic syndrome in young adults. Further longitudinal studies in the long term are needed to understand the association of meal patterns with metabolic syndrome.

Psychometric properties of the revised Diabetes Knowledge Test using Rasch analysis.

OBJECTIVE: The revised Diabetes Knowledge Test (DKT2) is the instrument that is the most widely used for measuring diabetes knowledge; nevertheless, its structural validity has never been evaluated. This study aimed to determine the psychometric properties of the DKT2. METHODS: This study performed a secondary data analysis of people with diabetes recruited at university hospitals. Rasch analysis was used. RESULTS: One item in the 14-item DKT2 measuring general diabetes knowledge exhibited a poor-fit, and so it was eliminated. The person-item map showed that items of greater difficulty need to be added to the instrument. The principal-components analysis of residuals revealed a unidimensional structure. The person reliability was 0.50, with a person separation index of 1.01. Measurement invariance was not satisfied for items 11 and 2 according to gender and age. CONCLUSIONS: The unidimensional structure of the 13-item DKT2 demonstrated poor person reliability and a low person separation index. Females and elderly persons found it more difficult to respond to items 11 and 2, respectively. PRACTICE IMPLICATIONS: Careful consideration is necessary when using the 13-item DKT2 in practice and research. It is recommended for future studies to add items of greater difficulty to the instrument.

Angiopoietin-2 exocytosis is stimulated by sphingosine-1-phosphate in human blood and lymphatic endothelial cells.

OBJECTIVE: Although diverse functions of angiopoietin-2 (Ang2) have been revealed, little is known about upstream signaling molecules regulating Ang2 exocytosis. We therefore investigated the mechanism of Ang2 exocytosis in human blood and lymphatic endothelial cells (BECs and LECs) by stimulation with sphingosine-1-phosphate (S1P). METHODS AND RESULTS: By immunostaining and ELISA analyses using our newly developed human Ang2-specific antibodies, Ang2 exocytosis from human endothelial cells was examined. Both exogenous and endogenous S1P trigger rapid Ang2 exocytosis in time- and dose-dependent manners. Intriguingly, S1P-induced Ang2 exocytosis is higher in LECs than BECs. These effects of S1P are mainly mediated by the endothelial differentiation gene receptor 1, which subsequently activates its downstream phospholipase C and intracellular calcium mobilization to trigger Ang2 exocytosis. Consistently, S1P also dramatically stimulates Ang2 exocytosis from the ECs of ex vivo-incubated blood vessels. CONCLUSION: These results imply that the rapid secretion of Ang2 by exocytosis from endothelial cells is another possible mechanism underlying S1P-induced angiogenesis and inflammation.

[Relationship of Workplace Violence to Turnover Intention in Hospital Nurses: Resilience as a Mediator].

PURPOSE: This study aimed to identify the relationship between workplace violence and turnover intention, and the mediation effect of resilience on the relationship in hospital nurses. METHODS: This was a cross-sectional study. A total of 237 registered nurses were recruited from three hospitals in South Korea from April to May 2019. Participants were invited to complete self-reported questionnaires that measure workplace violence, turnover intention, resilience, and demographic information. The data obtained were analyzed using multiple regression and a simple mediation model applying the PROCESS macro with 95% bias-corrected bootstrap confidence interval (5,000 bootstrap resampling). RESULTS: After controlling demographic covariates, workplace violence significantly accounted for the variance of turnover intention. It was also demonstrated that resilience partially mediated the relationship between workplace violence and turnover intention in hospital nurses. A 73.8% of nurses had experienced workplace violence (such as attack on personality, attack on professional status, isolation from work, or direct attack). CONCLUSION: Workplace violence directly influences turnover intention of nurses and indirectly influences it through resilience. Therefore, hospital administrators need to develop and provide a workplace violence preventive program and resilience enhancement program to decrease nurses' turnover intention, and leaving.

Evaluation of Studies on the Measurement Properties of Self-Reported Instruments.

PURPOSE: The purpose of this study was to evaluate studies on the measurement properties of self-reported instruments. METHOD: This descriptive review included studies on measurement properties that were reported in Asian Nursing Research over a five-year period from 2016 to September 2020. Nine key measurement properties were reviewed for each study: content validity, structural validity, internal consistency, cross-cultural validity/measurement invariance, reliability, measurement error, criterion validity, hypotheses-testing construct validity, and responsiveness. RESULTS: The most commonly applied measurement properties were structural validity and internal consistency. However, structural validity using confirmatory factor analysis or item response theory/Rasch analysis needs to be rigorously analyzed and interpreted. None of the studies assessed measurement error and responsiveness. CONCLUSION: It is recommended for nursing researchers to assess measurement properties beyond structural validity and internal consistency using more rigorous methodologies.