BACKGROUND/OBJECTIVES: The diet is an important route of exposure to endocrinedisrupting chemicals (EDCs). However, few studies have investigated the association between dietary intake and EDC exposure levels among Koreans. In an earlier study, we showed that the bioactivity of serum aryl hydrocarbon receptor ligands (AhRLs) could be a surrogate biomarker to indicate exposure to EDCs and that they inhibit mitochondrial function. We also found that the mitochondria-inhibiting substances (MIS) in serum ascertained by intracellular adenosine triphosphate (MIS-ATP) and reactive oxygen species (MIS-ROS) levels could be biomarkers of exposure to EDCs, as they showed a strong correlation with AhRL and the levels of EDCs in the blood. Here, we investigated the association between the consumption of specific foods and surrogate serum biomarkers for EDCs, namely AhRL, MIS-ATP, and MIS-ROS, among middle-aged Korean adults. SUBJECTS/METHODS: A total of 1,466 participants aged 45–76 yrs from the Ansung cohort of the Korean Genome and Epidemiology Study were included. Food consumption, including that of meat, fish, vegetables, and fruits, was measured using a semiquantitative food frequency questionnaire. RESULTS: Fish intake was positively associated with AhRL (β = 0.0035, P = 0.0166), whereas cruciferous vegetable intake was negatively associated with AhRL (β = −0.0007, P = 0.0488).Cruciferous vegetable intake was positively associated with the MIS-ATP levels (β = 0.0051, P = 0.0420). A higher intake of fish was significantly associated with an increased risk of high AhRL (tertile: odds ratio [OR], 1.49; 95% confidence intervals (CIs), 1.08–2.06; P for trend = 0.0305). In addition, the second-highest tertile of cruciferous vegetable intake had lower odds of high AhRL than the lowest tertile (OR, 0.73; 95% CIs, 0.54–0.97), although no significant linear trend was observed. CONCLUSION Consumption of different types of foods may be differentially associated with EDC exposure in middle-aged Korean adults.

Purpose: To compare tear film lipid layer thickness (LLT) and dry eye parameters between non-diabetic and diabetic patients after cataract surgery. Methods: We retrospectively studied patients who underwent cataract surgery. We enrolled 65 eyes of 36 patients with cataracts but not diabetes (group I) and 35 eyes of 23 patients with both cataracts and diabetes (group II). The LLT, partial blink rate, tear break-up time (TBUT), and strip meniscometry tests were performed preoperatively and 1 and 2 months after surgery. The ocular surface disease index (OSDI) questionnaire was completed before and 2 months after surgery by both groups. Results: In group I, the strip meniscometry test value was 3.2 ± 1.4 mm before surgery, 2.3 ± 1.0 mm at 1 month, and 2.5 ± 1.0 mm at 2 months, thus significantly less than before surgery (p < 0.05). The TBUT result was 3.4 ± 1.6 seconds before surgery, 3.0 ± 1.5 seconds at 1 month, and 2.9 ± 1.5 seconds at 2 months, thus significantly less than before surgery (p < 0.05). The OSDI score was 30.8 ± 21.3 before surgery and 20.0 ± 15.8 at 2 months, thus significantly lower than before surgery (p < 0.05). In group II, the TBUT decreased significantly from the preoperative value of 3.6 ± 1.3 seconds to 3.0 ± 1.0 seconds at 1 month and 3.1 ± 1.0 seconds at 2 months (p < 0.05). The OSDI score was 30.0 ± 20.6 before surgery and 19.0 ± 16.0 at 2 months, thus significantly lower than before surgery (p < 0.05). Neither group evidenced any significant difference in the LLT before and after surgery. Conclusions There was a difference in dry eye parameters in each group before and after cataract surgery, but there was no difference between the two groups.

Background: Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels. Methods: We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays. Results: During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function. Conclusion Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.

Purpose: To investigate the safety of laser epithelial keratomileusis (LASEK) by drawing a comparison between two groups divided according to age (18-19 vs. 20-21 years old). Methods: The study was conducted as a retrospective analysis including 339 patients (678 eyes) who underwent LASEK between January 2017 and April 2020. Patients were divided by age group, group I (18-19 years old) and group II (20-21 years old). The objectives of the study included determination of visual acuity and refractive errors before and at 1, 3, and 6 months after the procedure. Results: The preoperative mean spherical equivalents (SEs) were -4.73 ± 0.88 diopters (D) in group I and -4.58 ± 0.87 D in group II (p = 0.34). At 1 month postoperatively, mean SEs were 0.32 ± 0.46 D in group I and 0.26 ± 0.59 D in group II (p = 0.18). At 3 months postoperatively, the mean SEs were 0.30 ± 0.47 D in group I and 0.28 ± 0.50 D in group II (p = 0.67). At 6 months postoperatively, the mean SEs were 0.15 ± 0.47 D in group I and 0.14 ± 0.50 D in group II (p = 0.89). There were no significant differences in postoperative best corrected visual acuity between group I and group II at 1, 3, or 6 months (p = 0.20, p = 0.13, and p = 0.11, respectively). Conclusions There were no significant differences in postoperative mean SE or safety of LASEK between moderate myopia patients 18-19 years old and those 20-21 years old.

Purpose: To seek Pearson correlations of tear film osmolarity measured by the I-PEN® (I-MED Pharma Inc., Dollard-des-Ormeaux, Canada) with Schirmer test result, tear break-up time, and Ocular Surface Disease Index score in patients with mild dry eye syndrome. Methods: Patients with mild dry eye syndrome were divided into two groups according to Ocular Staining Score: group 1 (50 patients; 67 eyes) and group 2 (59 patients; 91 eyes), 90 patients and 158 eyes in total. The above mentioned correlations were derived. Results: No significant correlations were observed between tear film osmolarity and Schirmer test result (r < -0.01, p = 0.97), tear break-up time (r = 0.05, p = 0.54), or Ocular Surface Disease Index score (r = 0.03, p = 0.76). When the two groups were compared, the Ocular Surface Disease Index score significantly differed between groups (p < 0.01), whereas the Schirmer test result (p = 0.31), tear break-up time (p = 0.11), and tear film osmolarity (p = 0.12) did not. Conclusions No significant correlations were found between tear film osmolarity and other dry eye indicators in patients with mild dry eye syndrome. The diagnostic utility of tear film osmolarity in patients with moderate dry eye syndrome is should be evaluated.

Objective: To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma. Materials and Methods: One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.5 ± 13.5 years) with glioblastoma who underwent preoperative MRI were enrolled in the study. Six hundred and forty-two radiomic features were extracted from volume transfer constant (Ktrans), fractional volume of vascular plasma space (Vp), and fractional volume of extravascular extracellular space (Ve) maps of DCE MRI, wherein the regions of interest were based on both T1-weighted contrast-enhancing areas and non-enhancing T2 hyperintense areas. Using feature selection algorithms, salient radiomic features were selected from the 642 features. Next, a radiomics risk score was developed using a weighted combination of the selected features in the discovery set (n = 105); the risk score was validated in the validation set (n = 45) by investigating the difference in prognosis between the “radiomics risk score” groups. Finally, multivariable Cox regression analysis for progression-free survival was performed using the radiomics risk score and clinical variables as covariates. Results: 16 radiomic features obtained from non-enhancing T2 hyperintense areas were selected among the 642 features identified. The radiomics risk score was used to stratify high- and low-risk groups in both the discovery and validation sets (both p < 0.001 by the log-rank test). The radiomics risk score and presence of isocitrate dehydrogenase (IDH) mutation showed independent associations with progression-free survival in opposite directions (hazard ratio, 3.56; p = 0.004 and hazard ratio, 0.34; p = 0.022, respectively). Conclusion We developed and validated the “radiomics risk score” from the features of DCE MRI based on non-enhancing T2 hyperintense areas for risk stratification of patients with glioblastoma. It was associated with progression-free survival independently of IDH mutation status.

Background: High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time. Methods: Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up. Results: AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose. Conclusion These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

Purpose: To seek Pearson correlations of tear film osmolarity measured by the I-PEN® (I-MED Pharma Inc., Dollard-des-Ormeaux, Canada) with Schirmer test result, tear break-up time, and Ocular Surface Disease Index score in patients with mild dry eye syndrome. Methods: Patients with mild dry eye syndrome were divided into two groups according to Ocular Staining Score: group 1 (50 patients; 67 eyes) and group 2 (59 patients; 91 eyes), 90 patients and 158 eyes in total. The above mentioned correlations were derived. Results: No significant correlations were observed between tear film osmolarity and Schirmer test result (r < -0.01, p = 0.97), tear break-up time (r = 0.05, p = 0.54), or Ocular Surface Disease Index score (r = 0.03, p = 0.76). When the two groups were compared, the Ocular Surface Disease Index score significantly differed between groups (p < 0.01), whereas the Schirmer test result (p = 0.31), tear break-up time (p = 0.11), and tear film osmolarity (p = 0.12) did not. Conclusions No significant correlations were found between tear film osmolarity and other dry eye indicators in patients with mild dry eye syndrome. The diagnostic utility of tear film osmolarity in patients with moderate dry eye syndrome is should be evaluated.

Objective: To develop a radiomics risk score based on dynamic contrast-enhanced (DCE) MRI for prognosis prediction in patients with glioblastoma. Materials and Methods: One hundred and fifty patients (92 male [61.3%]; mean age ± standard deviation, 60.5 ± 13.5 years) with glioblastoma who underwent preoperative MRI were enrolled in the study. Six hundred and forty-two radiomic features were extracted from volume transfer constant (Ktrans), fractional volume of vascular plasma space (Vp), and fractional volume of extravascular extracellular space (Ve) maps of DCE MRI, wherein the regions of interest were based on both T1-weighted contrast-enhancing areas and non-enhancing T2 hyperintense areas. Using feature selection algorithms, salient radiomic features were selected from the 642 features. Next, a radiomics risk score was developed using a weighted combination of the selected features in the discovery set (n = 105); the risk score was validated in the validation set (n = 45) by investigating the difference in prognosis between the “radiomics risk score” groups. Finally, multivariable Cox regression analysis for progression-free survival was performed using the radiomics risk score and clinical variables as covariates. Results: 16 radiomic features obtained from non-enhancing T2 hyperintense areas were selected among the 642 features identified. The radiomics risk score was used to stratify high- and low-risk groups in both the discovery and validation sets (both p < 0.001 by the log-rank test). The radiomics risk score and presence of isocitrate dehydrogenase (IDH) mutation showed independent associations with progression-free survival in opposite directions (hazard ratio, 3.56; p = 0.004 and hazard ratio, 0.34; p = 0.022, respectively). Conclusion We developed and validated the “radiomics risk score” from the features of DCE MRI based on non-enhancing T2 hyperintense areas for risk stratification of patients with glioblastoma. It was associated with progression-free survival independently of IDH mutation status.

Background: High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time. Methods: Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up. Results: AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose. Conclusion These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.