3D Scaffold-Based Culture System Enhances Preclinical Evaluation of Natural Killer Cell Therapy in A549 Lung Cancer Cells.

Cell-based immunotherapies have emerged as promising cancer treatment modalities, demonstrating remarkable clinical efficacy. As interest in applying immune cell-based therapies to solid tumors has gained momentum, experimental models that enable long-term monitoring and mimic clinical administration are increasingly necessary. This study explores the potential of scaffold-based cell culture technologies, specifically three-dimensional (3D) extracellular matrix (ECM)-like frameworks, as promising solutions. These frameworks facilitate unhindered immune cell growth and enable continuous cancer cell culture. The three-dimensional (3D) cell culture model was developed using tailored scaffolds for natural killer (NK) cell culture. Within this framework, A549 lung cancer cells were cocultured with NK cells, allowing real-time monitoring for up to 28 days. The expression of critical markers associated with anticancer drug resistance and epithelial-mesenchymal transition (EMT) was evaluated in cancer cells within this 3D culture context. Compared to conventional 2D monolayer cultures, this 3D scaffold-based culture revealed that solid tumor cells, specifically A549 cells, exhibited heightened resistance to anticancer drugs. Additionally, the 3D culture environment upregulated the expression of EMT markers namely vimentin, N-cadherin, and fibronectin, while NK and zEGFR-CAR-NK cells displayed anticancer effects. In the two-dimensional (2D) coculture, only zEGFR-CAR-NK cells exhibited such effects in the 3D coculture system, highlighting an intriguing inconsistency with the 2D culture model, further confirmed by in vivo experiments. This in vitro 3D cell culture model reliably predicts outcomes in NK immunotherapy experiments. Thus, it represents a valuable tool for investigating drug resistance mechanisms and assessing the efficacy of immune cell-based therapies. By bridging the gap between in vitro and in vivo investigations, this model effectively translates potential treatments into animal models and facilitates rigorous preclinical evaluations.

STAT1 as a tool for non-invasive monitoring of NK cell activation in cancer.

Natural killer (NK) cells play a crucial role in immunotherapy for cancer due to their natural ability to target and destroy cancer cells. However, current methods to visualize NK cells' activity against tumors in live organisms are limited. We introduce an imaging method that non-invasively tracks NK cell activation by cancer cells through the STAT1 protein. To achieve this, we modified NK cells to include a specific genetic sequence that binds to STAT1 when activated. These engineered NK cells (GAS-NK) demonstrate their functionality through various biological tests and analysis. Observations of changes in cancer environments and patient-derived cancer organoid models further confirm the effectiveness of this approach. Our method provides a way to monitor NK cell activity, which could improve the prediction and effectiveness of NK cell-based cancer therapies, contributing to advances in cancer treatment.

Spatiotemporal variability of the association between greenspace exposure and depression in older adults in South Korea.

BACKGROUND: A number of studies based on young to middle aged adult and child samples have found that exposure to greenspace and bluespace can have a positive impact on mental health and well-being. However, there is limited research among older adults and the extant studies have provided mixed results. The present study was designed to examine how the association between these forms of exposure and depressive symptoms among older adults varies as a function of different spatially and temporally resolved exposure metrics. METHODS: The sample consisted of 617 individuals (46.19% female) aged ≥ 60 years of age. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies Depression Scale (CES-D). Individuals' greenspace exposure was quantified using spatially and temporally resolved metrics, including monthly and annual averaged satellite-derived normalized difference vegetation index (NDVI) across multiple buffer distances (250 m to 2,000 m) centered at participants' home address. We also quantified exposure to blue-greenspace from a highly detailed land use and land cover dataset. A multivariable logistic regression model assessed the association between greenspace and blue-greenspace exposure and depressive symptoms, adjusting for age, sex, income, education, marital status, current smoking, alcohol status, medical conditions, temperature, crime rate, population density, and per capita park area. RESULTS: We found a significant association between exposures to greenspace and blue-greenspace and depressive symptoms (CES-D cutoff ≥ 4) among older adults. After adjusting for confounding variables, the odds of depressive symptoms were significantly decreased by an IQR increment in residential exposure to greenspace [odds ratio (OR) = 0.67; 95% confidence interval (95% CI), 0.49 ~ 0.91] and blue-greenspace (OR = 0.59; 95% CI, 0.41 ~ 0.84) measured nearby their home address (i.e., as close as 250 m). When stratified by household income level, the association was only significant among low-income individuals. We also found temporal variation in the association between depressive symptoms and monthly NDVI-based greenspace exposure, in which the odds of depressive symptoms were the lowest for greenspace in cold months (i.e., January, February, and March). CONCLUSIONS: Our findings suggest that neighborhood greenspace may serve as a protective factor against depression among older adults, but the benefits may depend on the spatial and temporal context. More investigation is needed to replicate our findings on the spatial and temporal variations of greenspace exposure metrics and their effects on depressive symptoms.

Impact of Physical Activity on the Association Between Unhealthy Adolescent Behaviors and Anxiety Among Korean Adolescents: A Cross-sectional Study.

OBJECTIVES: Adolescents who engage in unhealthy behaviors are particularly vulnerable to anxiety. We hypothesized that participation in physical activity could influence the relationship between anxiety and unhealthy behaviors in adolescents. These behaviors include smoking, alcohol consumption, and unsafe sexual activity. METHODS: This study included 50 301 students from the first year of middle school to the third year of high school, all from Korea. The unhealthy adolescent behaviors examined included current alcohol consumption, current smoking, and unsafe sexual behavior. Anxiety levels were assessed using the Generalized Anxiety Disorder-7 questionnaire (GAD-7). RESULTS: The participants had a mean age of 15.19 years and an average GAD-7 score of 4.23. No significant differences were observed in GAD-7 score among exercising participants when categorized by smoking status (p=0.835) or unsafe sexual behavior (p=0.489). In contrast, participants in the non-exercise group who engaged in these behaviors demonstrated significantly higher GAD-7 scores (p<0.001 and 0.016, respectively). The only significant interaction was found between unsafe sexual behavior and exercise (p=0.009). Based on logistic regression analysis, within the non-exercise group, significant positive associations were observed between current smoking and anxiety (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.18 to 1.57), as well as between unsafe sexual behavior and anxiety (OR, 1.33; 95% CI, 1.02 to 1.73). However, within the exercise group, no significant association was found between anxiety and either smoking or unsafe sexual behavior. Furthermore, no significant interaction was observed between unhealthy behaviors and exercise. CONCLUSIONS: These findings are insufficient to conclude that physical activity influences the relationship between unhealthy behaviors and anxiety.

Excessive Postoperative Nasal Bleeding Following Septoplasty Caused by a Branch of the Middle Meningeal Artery.

Septoplasty is a widely performed procedure globally to correct a deviated nasal septum and improve nasal breathing. Life-threatening nasal bleeding as a complication of septoplasty has been reported in a few cases in the literature. In cases of massive postoperative nasal bleeding, transarterial embolization using angiography was performed for the treatment. This article documents 1 case of excessive postoperative nasal bleeding following an uneventful septoplasty, which was successfully treated with embolization of the frontal branch of the middle meningeal artery. This case represents an extremely rare occurrence, and we present it in conjunction with a literature review.

Healthcare utilization of lung cancer patients associated with exposure to fine particulate matter: A Korean cohort study.

BACKGROUND: Higher concentrations of particulate matter (PM) have been shown to cause deterioration of the symptoms of respiratory and cardiovascular disease in several regional studies. Here, we aimed to investigate the healthcare utilization of lung cancer patients associated with short-term exposure to PM at the national level in Korea. METHODS: We extracted the data of 210 558 subjects over a period of 3 years (2015-2017), who were diagnosed with lung cancer before 2015 and benefited from the National Health Insurance Sharing Service. We performed the interpolation method using the geographic information system to calculate the estimated mean PM2.5 and PM10 concentrations by regions and classified three groups as high (upper 10%), intermediate (10%-90%), and low (bottom 10%) based on the mean PM mass concentrations of the month. RESULTS: The monthly average number of outpatient visits was significantly increased in high PM2.5 urban areas (46.296 vs. 50.646, p = 0.015). In high PM2.5 nationwide regions, the monthly average number of emergency admission was significantly increased (0.528 vs. 0.785, p = 0.001). The outpatient visits tended to change with PM2.5 concentration and correlated with PM10 /PM2.5 concentrations in urban and nationwide areas. In high PM2.5 urban regions, there was a significant increase in bronchodilator prescriptions (3.102 vs. 3.758, p = 0.008). Concerning high PM2.5 nationwide regions, there were significantly increased prescriptions of antibiotics, steroids, bronchodilators, antihistamines, and mucolytics. CONCLUSIONS: This study suggests that exposure to PM2.5 is significantly associated with hospital utilization and drug prescription in lung cancer patients.

All-in-one glycol chitosan nanoparticles for co-delivery of doxorubicin and anti-PD-L1 peptide in cancer immunotherapy.

Synergistic immunotherapy of immune checkpoint blockade (ICB) and immunogenic cell death (ICD) has shown remarkable therapeutic efficacy in various cancers. However, patients show low response rates and undesirable outcomes to these combination therapies owing to the recycling mechanism of programmed death-ligand 1 (PD-L1) and the systemic toxicity of ICD-inducing chemotherapeutic drugs. Herein, we propose all-in-one glycol chitosan nanoparticles (CNPs) that can deliver anti-PD-L1 peptide (PP) and doxorubicin (DOX) to targeted tumor tissues for a safe and more effective synergistic immunotherapy. The PP-CNPs, which are prepared by conjugating ᴅ-form PP (NYSKPTDRQYHF) to CNPs, form stable nanoparticles that promote multivalent binding with PD-L1 proteins on the targeted tumor cell surface, resulting in effective lysosomal PD-L1 degradation in contrast with anti-PD-L1 antibody, which induces recycling of endocytosed PD-L1. Consequently, PP-CNPs prevent subcellular PD-L1 recycling and eventually destruct immune escape mechanism in CT26 colon tumor-bearing mice. Moreover, the ICD inducer, DOX is loaded into PP-CNPs (DOX-PP-CNPs) for synergistic ICD and ICB therapy, inducing a large number of damage-associated molecular patterns (DAMPs) in targeted tumor tissues with minimal toxicity in normal tissues. When the DOX-PP-CNPs are intravenously injected into CT26 colon tumor-bearing mice, PP and DOX are efficiently delivered to the tumor tissues via nanoparticle-derived passive and active targeting, which eventually induce both lysosomal PD-L1 degradation and substantial ICD, resulting in a high rate of complete tumor regression (CR: 60%) by a strong antitumor immune response. Collectively, this study demonstrates the superior efficacy of synergistic immunotherapy using all-in-one nanoparticles to deliver PP and DOX to targeted tumor tissues.

Stearoyl-CoA Desaturase 1 as a Therapeutic Biomarker: Focusing on Cancer Stem Cells.

The dysregulation of lipid metabolism and alterations in the ratio of monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) have been implicated in cancer progression and stemness. Stearoyl-CoA desaturase 1 (SCD1), an enzyme involved in lipid desaturation, is crucial in regulating this ratio and has been identified as an important regulator of cancer cell survival and progression. SCD1 converts SFAs into MUFAs and is important for maintaining membrane fluidity, cellular signaling, and gene expression. Many malignancies, including cancer stem cells, have been reported to exhibit high expression of SCD1. Therefore, targeting SCD1 may provide a novel therapeutic strategy for cancer treatment. In addition, the involvement of SCD1 in cancer stem cells has been observed in various types of cancer. Some natural products have the potential to inhibit SCD1 expression/activity, thereby suppressing cancer cell survival and self-renewal activity.

Inflammatory Endotypes of Chronic Rhinosinusitis in the Korean Population: Distinct Expression of Type 3 Inflammation.

PURPOSE: Cluster analyses on inflammatory markers of chronic rhinosinusitis (CRS) in Asians from multicenter data are lacking. This multicenter study aimed to identify the endotypes of CRS in Koreans and to evaluate the relationship between the endotypes and clinical parameters. METHODS: Nasal tissues were obtained from patients with CRS and controls who underwent surgery. The endotypes of CRS were investigated by measuring interleukin (IL)-5, interferon (IFN)-γ, IL-17A, IL-22, IL-1ß, IL-6, IL-8, matrix metalloproteinase-9, eotaxin-3, eosinophil cationic protein, myeloperoxidase (MPO), human neutrophil elastase (HNE), periostin, transforming growth factor-ß1, total immunoglobulin E (IgE), and staphylococcal enterotoxin (SE)-specific IgE. We performed hierarchical cluster analysis and evaluated the phenotype, comorbidities, and Lund-Mackay computed tomography (LM CT) score in each cluster. RESULTS: Five clusters and 3 endotypes were extracted from 244 CRS patients: cluster 1 had no upregulated mediators compared to the other clusters (mild mixed inflammatory CRS); clusters 2, 3, and 4 had higher concentrations of neutrophil-associated mediators including HNE, IL-8, IL-17A, and MPO (T3 CRS); and cluster 5 had higher levels of eosinophil-associated mediators (T2 CRS). SE-specific IgE was undetectable in T3 CRS and had low detectable levels (6.2%) even in T2 CRS. The CRS with nasal polyps (CRSwNP) phenotype and LM CT scores showed no significant differences between T2 and T3 CRS, while the incidence of comorbid asthma was higher in T2 CRS than T3 CRS. In T3 clusters, higher levels of neutrophilic markers were associated with disease severity and CRSwNP phenotype. CONCLUSIONS: In Koreans, there is a distinct T3 CRS endotype showing a high proportion of CRSwNP and severe disease extent, along with T2 CRS.

Association between serum klotho levels and cardiovascular disease risk factors in older adults.

BACKGROUND: Klotho deficiency is a significant predictor of cardiovascular disease (CVD)-related mortality and morbidity. However, research assessing the association between klotho and individual risk factors of CVD is limited. This study aimed to explore the association between circulating serum klotho levels and risk factors for CVD in adults. METHODS: We used the 2007-2016 National Health and Nutrition Examination Survey and included 13,154 participants for whom serum klotho levels were available. Body mass index (BMI), exercise, smoking status, alcohol consumption, hypertension, dyslipidemia, serum lipid parameters, and blood pressure were considered as CVD risk factors. RESULTS: Circulating klotho levels were negatively associated with being overweight (beta coefficient: - 22.609, p = 0.0025), obesity (beta coefficient: - 23.716, p = 0.0011), current smoking (beta coefficient: - 46.412, p < 0.0001), and alcohol consumption (beta coefficient: - 51.194, p < 0.0001). There was a positive association between serum klotho levels and no history of dyslipidemia (beta coefficient: 15.474, p = 0.0053). Serum klotho levels were significantly decreased by a unit increase in triglycerides (beta coefficient: - 0.117, p = 0.0006) and total cholesterol (beta coefficient: - 0.249, p = 0.0002). There was a significant non-linear relationship between serum klotho levels, triglycerides, and total cholesterol. CONCLUSIONS: Lower serum klotho levels are associated with certain CVD risk factors, including high BMI, smoking, alcohol consumption, and lipid parameters (triglycerides and total cholesterol). This study suggests that the soluble klotho level may be a potential marker for CVD risk.

Heterotypic cell-in-cell structures between cancer and NK cells are associated with enhanced anticancer drug resistance.

The heterotypic CIC structures formed of cancer and immune cells have been observed in tumor tissues. We aimed to assess the feasibility of using heterotypic CICs as a functional biomarker to predict NK susceptibility and drug resistance. The heterotypic CIC-forming cancer cells showed a lower response to NK cytotoxicity and higher proliferative ability than non-CIC cancer cells. After treatment with anticancer drugs, cancer cells that formed heterotypic CICs showed a higher resistance to anticancer drugs than non-CIC cancer cells. We also observed the formation of more CIC structures in cancer cells treated with anticancer drugs than in the non-treated group. Our results confirm the association between heterotypic CIC structures and anticancer drug resistance in CICs formed from NK and cancer cells. These results suggest a mechanism underlying immune evasion in heterotypic CIC cancer cells and provide insights into the anticancer drug resistance of cancer cells.

Upregulation of CYP1B1 by hypoxia is mediated by ERα activation in breast cancer cells.

Endocrine therapy for breast cancer often leads to drug resistance and tumor recurrence; tumor hypoxia is also associated with mortality and tumor relapse. Cytochrome P450 1B1 (CYP1B1) regulates estrogen metabolism in breast cells and is known to be overexpressed in breast cancer tissue. Although the individual association of hypoxia-induced hypoxia-inducible factor-1-alpha (HIF-1α) and CYP1B1 with tumorigenesis is well known, the association between HIF-1α and CYP1B1 leading to tumorigenesis has not been investigated. Here, we investigated the correlation between hypoxia and CYP1B1 expression in breast cancer cells for tumorigenesis-related mechanisms. Hypoxia was induced in the human breast cancer cell lines MCF-7 (Er-positive) and MDA-MB-231 (triple-negative) and the normal breast epithelial cell line MCF10A; these cell lines were then subjected to immunoblotting, transient transfection, luciferase assays, gene silencing using small interfering RNA, polymerase chain reaction analysis, chromatin immunoprecipitation, co-immunoprecipitation, and mammalian two-hybrid assays. Furthermore, immunofluorescence analysis of the tumor microarrays was performed, and the pub2015 and the Cancer Genome Atlas patient datasets were analyzed. HIF-1α expression in response to hypoxia occurred in both normal and breast cancer cells, whereas CYP1B1 was induced only in estrogen receptor α (ERα)-positive breast cancer cells under hypoxia. HIF-1α activated ERα through direct binding and in a ligand-independent manner to promote CYP1B1 expression. Therefore, we suggested the mechanism by which hypoxia and ER-positivity orchestrate breast cancer relapse.

Association of α-klotho and lead and cadmium: A cross-sectional study.

Epigenetic aging is associated with harmful health effects such as oxidative stress from heavy metal exposure. We considered the relationship between genes and heavy metals in association with oxidative stress and then investigated the association between serum α- klotho and lead and cadmium exposure among adults in the United States from 2007 to 2016 participating in the National Health and Nutrition Examination Survey (NHANES). Samples included 9800 adults aged 40 to 79 years with measurements of serum α-klotho, lead and cadmium, and complete covariate data. Lead and cadmium levels were measured by inductively coupled plasma mass spectrometry and serum α-klotho levels were measured using enzyme-linked immunosorbent assay (ELISA). Multivariate linear regression analysis was used to estimate the association between serum α-klotho and blood lead, blood cadmium, and urinary cadmium. A percent increase in blood lead, blood cadmium, and urinary cadmium was associated with a statistically significant 4.0 % (p < 0.001), 2.0 %, (p = 0.003) and 1.0 % (p = 0.020) decrease in serum klotho. After adjustment, a percent increase in blood lead was associated with a statistically significant 4.0 % (p < 0.001) decrease in serum klotho; blood and urinary cadmium did not show any statistically significant associations after adjustment (ß (95 % CI), p-value for blood cadmium: 0.00 (-0.02-0.01), p = 0.573; urinary cadmium: -0.01 (-0.03-0.01), p = 0.210). Mean serum klotho levels showed a statistically significant decreasing trend with increasing blood lead quartiles (unadjusted and all-adjusted geometric means and 95 % confidence intervals of serum klotho (in pg/mL) for Q1, Q2, Q3, and Q4: unadjusted: 827.49 (814.20-840.92), 811.92 (794.73-829.48), 791.48 (775.11-808.19), and 772.01 (754.23-790.29); adjusted: 830.64 (805.53-856.45), 816.07 (789.18-843.87), 800.71 (773.71-828.57), and 784.31 (757.94-811.59)). Blood lead and levels were negatively associated with serum α-klotho levels in a representative population of US adults. These results suggest that blood lead levels may be associated with the serum levels of a protein associated with cognition and aging. Further research is recommended to investigate the causality behind such relationship.

Retinoic acid promotes fibrinolysis and may regulate polyp formation.

BACKGROUND: Patients with aspirin-exacerbated respiratory disease (AERD) regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells. OBJECTIVES: This study sought to determine whether endogenous retinoids are involved in NP pathophysiology and disease severity in patients with CRSwNP and AERD. METHODS: NP tissue was collected from patients with AERD or CRSwNP, and concentrations of retinoids and fibrinolysis markers were measured using ELISA. Normal human bronchial epithelial cells were stimulated alone or in combination with RA and IL-13 for 24 hours. RESULTS: This study observed lower retinoid levels in nasal polyps of patients with AERD than those with CRSwNP or healthy controls (P < .01). Levels of the fibrin-breakdown product d-dimer were the lowest in AERD polyps (P < .01), which is consistent with lower tPA expression (P < .01). In vitro, all-trans RA upregulated tPA levels in normal human bronchial epithelial cells by 15-fold and reversed the IL-13-induced attenuation of tPA expression in cultured cells (P < .01). CONCLUSIONS: RA, a potent inducer of epithelial tPA in vitro, is reduced in tissue from patients with AERD, a finding that may potentially contribute to decreased levels of tPA and fibrinolysis in AERD. RA can induce tPA in epithelial cells and can reverse IL-13-induced tPA suppression in vitro, suggesting the potential utility of RA in treating patients with CRSwNP and/or AERD.

Cumulative exposure amount of PM2.5 in the ambient air is associated with coronary atherosclerosis - Serial coronary CT angiography study.

BACKGROUND: We investigated the change of coronary atherosclerosis with long-term exposure to fine particulate matter of aerodynamic diameter <2.5 â€‹µm (PM2.5) using coronary computed tomography angiography (CCTA). METHODS: Subjects undergoing serial CCTAs between January 2007 and December 2017 (n â€‹= â€‹3,127) were analyzed. Each individual's cumulative amount of PM2.5 exposure between the two CCTAs was evaluated by Kriging interpolation and zonal analysis, considering the time interval between the two CCTAs. The main outcome was progression of coronary artery calcium (CAC) with additional semiquantitative analysis on the changes in the severity and composition of atherosclerotic plaques. RESULTS: The CAC scores increased by 30.8 Agatston units per-year under a median PM2.5 concentration 24.9 â€‹µg/m3 and tended to increase with the cumulative amount of PM2.5 exposure (r â€‹= â€‹0.321, p â€‹<0.001). The CAC progressed in 1,361 (43.5%) subjects during a median 53 months follow-up. The cumulative amount of PM2.5 exposure was independently associated with CAC progression (adjusted OR 1.09, p â€‹<0.001). By random forest analysis, the relative impact of cumulative amount of PM2.5 exposure on CAC progression was higher than that of traditional cardiovascular risk factors and the average concentration of PM2.5. The extent of coronary atherosclerosis and newly developed calcified plaque on follow-up were also significantly associated with the cumulative amount of PM2.5 exposure. CONCLUSIONS: Cumulative exposure to air pollution is associated with the progression of diffuse coronary calcification, the importance of which may be more significant than other traditional cardiovascular risk factors. Further investigations into the causality between PM2.5 and coronary atherosclerosis are warranted to improve global cardiovascular health.

The versatile utility of cysteine as a target for cancer treatment.

Owing to its unique nucleophilicity, cysteine is an attractive sulfhydryl-containing proteinogenic amino acid. It is also utilized in various metabolic pathways and redox homeostasis, as it is used for the component of major endogenous antioxidant glutathione and the generation of sulfur-containing biomolecules. In addition, cysteine is the most nucleophilic amino acid of proteins and can react with endogenous or exogenous electrophiles which can result in the formation of covalent bonds, which can alter the cellular states and functions. Moreover, post-translational modifications of cysteines trigger redox signaling and affect the three-dimensional protein structure. Protein phosphorylation mediated by kinases and phosphatases play a key role in cellular signaling that regulates many physiological and pathological processes, and consequently, the modification of cysteine regulates its activities. The modification of cysteine residues in proteins is critically important for the design of novel types of pharmacological agents. Therefore, in cancer metabolism and cancer cell survival, cysteine plays an essential role in redox regulation of cellular status and protein function. This review summarizes the diverse regulatory mechanisms of cysteine bound to or free from proteins in cancer. Furthermore, it can enhance the comprehension of the role of cysteine in tumor biology which can help in the development of novel effective cancer therapies.

Relationship between chronic exposure to ambient air pollution and mental health in Korean adult cancer survivors and the general population.

BACKGROUND: Although a significant association between air pollution and mental health has been identified, few studies have addressed this relationship based on cancer diagnosis. This study investigated whether associations between long-term air pollution and mental health conditions differ based on whether the individual has been diagnosed with cancer. METHODS: Nationally representative data were used and a total of 38,101 adults were included in the analyses. We assessed mental health factors such as perceived stress, depressive symptoms, and suicidal ideation, and analyzed the associations between these factors and individuals' annual average exposure to air pollutants, including particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide, sulfur dioxide, and carbon monoxide. RESULTS: Compared with the general population, PM10 exposure in cancer survivors predicted a higher risk of depressive symptoms (odds ratio [OR] =1.34; 95% confidence interval [CI] = 1.06-1.69) and suicidal ideation (OR = 1.29; 95% CI = 1.01-1.64). Notably, the statistically significant relationship between PM10 exposure and suicidal ideation in cancer survivors disappeared after further adjustment for depressive symptoms (p = 0.3103). This pattern was also observed in the result of propensity score-matched analysis for comparison between cancer survivors and the general population. CONCLUSIONS: This study provides the first evidence that cancer survivors with depressive symptoms may be more susceptible to suicidal ideation in the context of persistent PM10 exposure.

Association Between Cadmium Exposure and Liver Function in Adults in the United States: A Cross-sectional Study.

OBJECTIVES: Cadmium is widely used, leading to extensive environmental and occupational exposure. Unlike other organs, for which the harmful and carcinogenic effects of cadmium have been established, the hepatotoxicity of cadmium remains unclear. Some studies detected correlations between cadmium exposure and hepatotoxicity, but others concluded that they were not associated. Thus, we investigated the relationship between cadmium and liver damage in the general population. METHODS: In total, 11 838 adult participants from National Health and Nutrition Examination Survey 1999-2015 were included. Urinary cadmium levels and the following liver function parameters were measured: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total bilirubin (TB), and alkaline phosphatase (ALP). Linear and logistic regression analyses were performed to assess the associations between urinary cadmium concentrations and each liver function parameter after adjusting for age, sex, race/ethnicity, annual family income, smoking status, alcohol consumption status, physical activity, and body mass index. RESULTS: The covariate-adjusted results of the linear regression analyses showed significant positive relationships between log-transformed urinary cadmium levels and each log-transformed liver function parameter, where beta±standard error of ALT, AST, GGT, TB, and ALP were 0.049±0.008 (p<0.001), 0.030±0.006 (p<0.001), 0.093±0.011 (p<0.001), 0.034±0.009 (p<0.001), and 0.040±0.005 (p<0.001), respectively. Logistic regression also revealed statistically significant results. The odds ratios (95% confidence intervals) of elevated ALT, AST, GGT, TB, and ALP per unit increase in log-transformed urinary cadmium concentration were 1.360 (1.210 to 1.528), 1.307 (1.149 to 1.486), 1.520 (1.357 to 1.704), 1.201 (1.003 to 1.438), and 1.568 (1.277 to 1.926), respectively. CONCLUSIONS: Chronic exposure to cadmium showed positive associations with liver damage.

Risk Model Establishment of Endoscopic Sinus Surgery for Patients with Chronic Rhinosinusitis: a Multicenter Study in Korea.

BACKGROUND: Endoscopic sinus surgery (ESS) is the mainstay treatment for refractory chronic rhinosinusitis (CRS). Since various factors may contribute to the surgical outcome, it is challenging for physicians to predict surgical outcomes. The aim of study was to analyze the prognostic factors of postoperative outcomes and to establish the prediction model with the risk factors that impact the postoperative outcomes. METHODS: Medical records of CRS patients who underwent ESS at 9 institutions in 2005, 2010, and 2016 were retrospectively reviewed. We classified the patients into 2 groups based on postoperative objective endoscopic outcomes. Demographics, nose-specific symptoms, olfactory function, eosinophil counts in blood (EoB) and nasal tissue (EoT), and Lund-Mackay CT score (LMS) were collected. Univariate and multivariate analyses were performed and established a prediction equation for postoperative endoscopic objective outcomes. RESULTS: In total (n = 1,249), 27.0% were not satisfied under postoperative endoscopic examination. Of 10 variables, LMS (> 5), sinus dominancy (maxillary sinus and ethmoid sinus), EoB (> 210), and EoT (> 100) were statistically significant in univariate analysis (P < 0.05, all). In multivariate analysis, EoT (> 100) and LMS (> 5) were significantly associated with poor postoperative outcome. Furthermore, 5 significant variables were employed to establish the risk model of postoperative outcomes and P (the value of prediction probability) = 1 / (1 + exp [-0.392 + 1.088 × EoT (> 100) + 0.123 × mean LMS (> 5) - 0.366 × sinus dominancy (maxillary) + 0.064 × sinus dominancy (similar) + 0.200 × EoB (4%) + 0.344 × EoB (> 210)] was developed. CONCLUSION: Tissue eosinophil count and radiographic severity predispose to a poorer outcome of ESS and the risk model established may be helpful to predict postoperative outcomes of ESS.

Strong association of type 2 diabetes with degenerative lumbar spine disorders.

Tantalizing connections between type 2 diabetes and degenerative lumbar spine disorders have become increasingly evident. However, the association of type 2 diabetes with degenerative lumbar spine disorders remains unclear. We sought to clarify the association between type 2 diabetes and lumbar spine disorders using nationwide data in Korea. Furthermore, we explored the association of diabetes with the prevalence of spinal procedures. The data in this study was obtained from Korean health claim database. Between 2016 and 2019, totals of 479,680 diabetes and 479,680 age- and sex-matched control subjects were enrolled. Patients with diabetes had more likely to have degenerative lumbar spine disorders and spinal procedures than controls. Using multivariate-adjusted analysis, patients with diabetes were at increased risk of being concomitantly affected by lumbar disc disorder [adjusted odds ratio 1.11 (95% confidence interval 1.10-1.12)], lumbar spondylotic radiculopathy [1.12 (1.11-1.13)], spondylolisthesis [1.05 (1.02-1.08)] and spinal stenosis [1.16 (1.15-1.18)], compared to controls. Furthermore, diabetic patients had an increased risk of undergoing lumbar spinal injection [1.13 (1.12-1.14)], laminectomy [1.19 (1.15-1.23)], and fusion surgery [1.35 (1.29-1.42)]. We demonstrated that type 2 diabetes was significantly associated with lumbar spine disorders and frequent spinal procedures. Our results suggest diabetes as a predisposing factor for lumbar spine disorders.