Unraveling the Potential of Vinyl Ether as an Ethylene Surrogate in Heteroarene C─H Functionalization via the Spin-Center Shift.

Despite the simplicity and abundance of ethylene, its practical application presents significant hurdles due to its nature as a highly flammable gas. Herein, a strategic use of easily handled vinyl ether is reported as a latent ethylene surrogate achieved via a spin-center shift (SCS) pathway, enabling the successful three-component reaction that bridges heteroarenes and various coupling partners, including sulfinates, thiols, and phosphine oxides. Through a photoredox catalytic process, α-oxy radicals are generated by combining various radicals with phenyl vinyl ether, which are subsequently added to N-heteroarenes. Subsequently, the radical-mediated SCS pathway serves as the driving force for C─O bond cleavage, effectively engaging the phenoxy group as a leaving group. In addition, by broadening the utility of the method, a valuable synthon is provided for efficient C─H vinylation of N-heteroarenes following sulfonyl group elimination. This approach not only enriches the toolbox of synthetic methodology but also provides a more streamlined alternative, circumventing the challenges associated with direct ethylene gas usage. The versatility of the method, particularly evident in late-stage functionalizations of medicinally relevant molecules and peptides, underscores its capability to produce invaluable three-component compounds and vinylated N-heteroarene derivatives.

HIF-1α inhibition by MO-2097, a novel chiral-free benzofuran targeting hnRNPA2B1.

INTRODUCTION: Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator mediating adaptive responses to hypoxia. It is up-regulated in the tumor microenvironment and recognized as an effective anticancer drug target. Previously, we discovered that the natural compound moracin-O and its synthetic derivative MO-460 inhibited HIF-1α via hnRNPA2B1. OBJECTIVES: This study aimed to develop novel HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural products moracins-O and P. METHODS: In an ongoing search for novel HIF-1 inhibitors, a series of nature-inspired benzofurans with modifications on the chiral rings of moracins-O and P were synthesized. They showed improved chemical tractability and were evaluated for their inhibitory activity on HIF-1α accumulation under hypoxic conditions in HeLa CCL2 cells. The most potent derivative's chemical-based toxicities, binding affinities, and in vivo anti-tumorigenic effects were evaluated. Further, we examined whether our compound, MO-2097, exhibited anticancer effects in three-dimensional cultured organoids. RESULTS: Herein, we identified a novel synthetic chiral-free compound, MO-2097, with reduced structural complexity and increased efficiency. MO-2097 exhibited inhibitory effects on hypoxia-induced HIF-1α accumulation in HeLa CCL2 cells via inhibition of hnRNPA2B1 protein, whose binding affinities were confirmed by isothermal titration calorimetry analysis. In addition, MO-2097 demonstrated in vivo efficacy and biocompatibility in a BALB/c mice xenograft model. The immunohistochemistry staining of MO-2097-treated tissues showed decreased expression of HIF-1α and increased levels of apoptosis marker cleaved caspase 3, confirming in vivo efficacy. Furthermore, we confirmed that MO-2097 works effectively in cancer patient-based organoid models. CONCLUSION: MO-2097 represents a promising new generation of chemotherapeutic agents targeting HIF-1α inhibition via hnRNPA2B1, requiring further investigation.

Cancer risk in Vietnam war veterans from the Korean Vietnam war veterans' health study cohort.

Introduction: During the Vietnam War, several unknown chemicals, such as Agent Orange, were used in Vietnam by the military. Therefore, there have been continuous health concerns among the Vietnamese population and veterans exposed to these hazardous chemicals. This study aimed to investigate the risk of all cancers and also organ-specific cancers among Korean veterans of the Vietnam War. Methods: This study used a national representative cohort that included all Korean Vietnam War veterans as the interest group, with 1:4 age-sex-region-matched general Korean citizens as the reference group, from 2002 to 2018. Age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for all cancers and for 31 organ-specific cancer categories based on the medical facility visit data. Results: An increased SIR of 1.07 (95% CI, 1.06-1.08) was observed for all cancers among the veterans. There was a significantly increased risk of cancer among 22/31 organspecific cancers, with 18 cancer categories showing a significantly higher risk than all cancers. The highest risk was observed for "malignant neoplasms of other parts of the central nervous system" (SIR, 1.71; 95% CI, 1.51-1.92). Discussion: This study evaluated the risk of cancer among Korean Vietnam War veterans. Further studies are warranted to investigate various health determinants in the veterans as well as the Vietnamese population.

Standards for recognition and approval rate of occupational cerebro-cardiovascular diseases in Korea.

Background: Although working hours have decreased in Korea, they are still high compared to that of other countries. In Korea, cardiovascular and cerebrovascular diseases (CCVDs) related to overwork in Korea continually occur, and the social burden from overwork is estimated to be high. This study investigated the amendment of regulations affecting the approval rate of occupational CCVDs. Methods: The change in approval rate of occupational CCVDs and related regulations were investigated using the Act and public notice on the standards for recognition of occupational CCVDs and the yearbooks of the Ministry of Employment and Labor. The CCVD mortality was estimated using data on the number of deaths according to the cause of death, the number of employed people, and resident registration population aged 15-64 years. The cumulative mortality of CCVDs was estimated using the Kaplan-Meier method. Results: Since the establishment of the standards for recognition in Korea in 1982, the scope of occupational diseases has been expanded to include intracerebral hemorrhage, subarachnoid hemorrhage, cerebral infarction, myocardial infarction, and aortic dissection. In 2013, the concept of working hours was introduced in chronic overwork. The approval rate of occupational CCVDs was 44.7% in 2006, which decreased to 12.9% in 2011. After the improvement of related regulations, the approval rate increased to 41.3% in 2018. From 2000 to 2017, the CCVD mortality of both the unemployed and employed tended to decrease, and their cumulative CCVD mortalities were 549.3 and 319.7 per 100,000 people, respectively. Conclusions: CCVDs are recognized as occupational diseases in Korea. The amendments to the standards for recognition, the introduction of the Occupational Disease Adjudication Committee, the principle of presumption, and the reduction of working hours have changed the approval rate of occupational CCVDs. A strategic approach is needed to further reduce the incidence of CCVDs.

Concordance rate of radiologists and a commercialized deep-learning solution for chest X-ray: Real-world experience with a multicenter health screening cohort.

PURPOSE: Lunit INSIGHT CXR (Lunit) is a commercially available deep-learning algorithm-based decision support system for chest radiography (CXR). This retrospective study aimed to evaluate the concordance rate of radiologists and Lunit for thoracic abnormalities in a multicenter health screening cohort. METHODS AND MATERIALS: We retrospectively evaluated the radiology reports and Lunit results for CXR at several health screening centers in August 2020. Lunit was adopted as a clinical decision support system (CDSS) in routine clinical practice. Subsequently, radiologists completed their reports after reviewing the Lunit results. The DLA result was provided as a color map with an abnormality score (%) for thoracic lesions when the score was greater than the predefined cutoff value of 15%. Concordance was achieved when (a) the radiology reports were consistent with the DLA results ("accept"), (b) the radiology reports were partially consistent with the DLA results ("edit") or had additional lesions compared with the DLA results ("add"). There was discordance when the DLA results were rejected in the radiology report. In addition, we compared the reading times before and after Lunit was introduced. Finally, we evaluated systemic usability scale questionnaire for radiologists and physicians who had experienced Lunit. RESULTS: Among 3,113 participants (1,157 men; mean age, 49 years), thoracic abnormalities were found in 343 (11.0%) based on the CXR radiology reports and 621 (20.1%) based on the Lunit results. The concordance rate was 86.8% (accept: 85.3%, edit: 0.9%, and add: 0.6%), and the discordance rate was 13.2%. Except for 479 cases (7.5%) for whom reading time data were unavailable (n = 5) or unreliable (n = 474), the median reading time increased after the clinical integration of Lunit (median, 19s vs. 14s, P < 0.001). CONCLUSION: The real-world multicenter health screening cohort showed a high concordance of the chest X-ray report and the Lunit result under the clinical integration of the deep-learning solution. The reading time slight increased with the Lunit assistance.

Association between occupational or environmental noise exposure and renal function among middle-aged and older Korean adults: a cross-sectional study.

Exposure to occupational and environmental noise is closely linked to various auditory system diseases. Few studies have focused on the effect of noise exposure on the extra auditory system, especially the urinary system. We analyzed 17,154 participants aged 40-79 years from the Korea National Health and Nutrition Examination Survey between 2013 and 2018. A self-reported questionnaire was used to assess occupational or environmental noise exposure. Logistic regression was used to determine the differences in the prevalence of chronic kidney disease (CKD) based on noise exposure characteristics. For participants with noise exposure, linear regression was performed to determine relationship of the noise exposure period and estimated glomerular filtration rate (eGFR). In the noise exposure group, a higher CKD prevalence was associated with females who experienced long-term occupational noise (≥ 240 months) (adjusted OR 2.72, 95% CI 1.11-6.66). An increase of one month of occupational noise exposure was associated with a 0.0106 mL/min/1.73 m2 decrease in eGFR in females aged < 60 years. Overall, noise exposure may be a risk factor for reduced renal function, especially long-term occupational noise exposure. More precise studies should determine (1) the relationship between noise and renal function and (2) the underlying mechanisms.

Effect of changes in cerebral oximeter values during cardiac surgery on the incidence of postoperative neurocognitive deficits (POND): A retrospective study based on propensity score-matched analysis.

OBJECTIVES: The occurrence of postoperative neurocognitive deficits(POND)after major cardiac surgery is associated with an increase in perioperative mortality and morbidity. Oxidative stress caused by oxygen can affect neuronal damage, which can lead to POND. Whether the intraoperative rSO2 value reflects oxidative stress and the associated incidence of POND is unknown. METHODS: Among 3482 patients undergoing cardiac surgery, 976 patients were allocated for this retrospective study. Of these, 230 patients (32.5%) were observed to have postoperative neurologic symptoms. After propensity score 1:2 ratio matching, a total of 690 patients were included in the analysis. Recorded data on the occurrence of POND from the postoperative period to predischarge were collected from the electronic records. RESULTS: The mean baseline rSO2 value was higher in the POND (-) group than in the POND (+) group. The mean overall minimum rSO2 value was lower in the POND (+) group (52.2 ± 8.3 vs 48.3 ± 10.5, P < 0.001). The mean overall maximum rSO2 values were not significantly different between the two groups (72.7 ± 8.3 vs 73.2 ± 9.2, P = 0.526). However, there was a greater increase in the overall maximum rSO2 values as compared with baseline in the POND (+) group (10.9 ± 8.2 vs 17.9 ± 10.2, P < 0.001). The degree of increase in the maximum rSO2 value was a risk factor affecting the occurrence of POND (adjusted odds ratio, 1.08; 95% confidence interval [CI], 1.04-1.11; P < 0.001). The areas under the receiver-operating characteristic curve for delta values of minimal and maximal compared with baseline values were 0.60 and 0.71, respectively. CONCLUSIONS: Increased cerebral oximeter levels during cardiac surgery may also be a risk factor for POND. This is considered to reflect the possibility of oxidative neuronal damage, and further studies are needed in the future.

Identifying disease-gene associations using a convolutional neural network-based model by embedding a biological knowledge graph with entity descriptions.

Understanding the role of genes in human disease is of high importance. However, identifying genes associated with human diseases requires laborious experiments that involve considerable effort and time. Therefore, a computational approach to predict candidate genes related to complex diseases including cancer has been extensively studied. In this study, we propose a convolutional neural network-based knowledge graph-embedding model (KGED), which is based on a biological knowledge graph with entity descriptions to infer relationships between biological entities. As an application demonstration, we generated gene-interaction networks for each cancer type using gene-gene relationships inferred by KGED. We then analyzed the constructed gene networks using network centrality measures, including betweenness, closeness, degree, and eigenvector centrality metrics, to rank the central genes of the network and identify highly correlated cancer genes. Furthermore, we evaluated our proposed approach for prostate, breast, and lung cancers by comparing the performance with that of existing approaches. The KGED model showed improved performance in predicting cancer-related genes using the inferred gene-gene interactions. Thus, we conclude that gene-gene interactions inferred by KGED can be helpful for future research, such as that aimed at future research on pathogenic mechanisms of human diseases, and contribute to the field of disease treatment discovery.

Associations of Abnormal Sleep Duration with Occupational and Leisure-time Physical Activity in the Working Population: A Nation-wide Population-based Study.

BACKGROUND: The present study investigated the association between two domains of physical activity (occupational physical activity [OPA] and leisure-time physical activity [LTPA]) and sleep duration. METHODS: We investigated 3,421 paid workers from the Korea National Health and Nutrition Examination Survey, 2014-2015. Sleep duration was categorized into three categories (short for less than 5 h, optimal for 5-9 h, and long for more than 9 h). OPA and LTPA were defined in terms of answers to relevant questions. Odds ratios were calculated for sleep duration according to each physical activity domain using multinomial logistic regression models. RESULTS: There were 464 subjects (13.6%) who showed short sleep duration, and 169 subjects (4.9%) who showed long sleep duration. Prevalence of OPA and LTPA was higher in male workers than in female workers (for OPA: 3.67% and 1.76%, respectively, p = 0.0108; for LTPA: 16.14% and 6.07%, respectively, p < 0.0001). The odds ratio of OPA for long sleep duration in female workers was 3.35 (95% confidence interval, 1.37-8.21). Otherwise, LTPA was not associated with sleep duration in female paid workers, nor both physical activity domains in male paid workers. CONCLUSION: Female paid workers with work-related physical activity were at risk of oversleeping. These findings also suggested that physical activity has distinct associations with sleep duration according to the physical activity domains and sex.

Determinants of Resting Oxidative Stress in Middle-Aged and Elderly Men and Women: WASEDA'S Health Study.

Previous studies have not investigated the determinants of resting oxidative stress, including physical fitness, as it relates to redox regulation. The present study therefore was aimed at identifying lifestyle and biological factors that determine resting oxidative stress, including objectively measured physical fitness. In 873 middle-aged and elderly men and women, age and anthropometric parameters, lifestyle-related parameters, medication and supplementation status, physical fitness, biochemical parameters, and nutritional intake status, as well as three plasma oxidative stress markers: protein carbonyl (PC), F2-isoprostane (F2-IsoP), and thiobarbituric acid reactive substances (TBARS), were surveyed and measured. The determinants of PC, F2-IsoP, and TBARS in all participants were investigated using stepwise multiple regression analysis. In PC, age (ß = -0.11, P = 0.002), leg extension power (ß = -0.12, P = 0.008), BMI (ß = 0.12, P = 0.004), and HDL-C (ß = 0.08, P = 0.040) were included in the regression model (adjusted R 2 = 0.018). In the F2-IsoP, smoking status (ß = 0.07, P = 0.060), BMI (ß = 0.07, P = 0.054), and HbA1c (ß = -0.06, P = 0.089) were included in the regression model (adjusted R 2 = 0.006). In TBARS, glucose (ß = 0.18, P < 0.001), CRF (ß = 0.16, P < 0.001), age (ß = 0.15, P < 0.001), TG (ß = 0.11, P = 0.001), antioxidant supplementation (ß = 0.10, P = 0.002), and HbA1c (ß = -0.13, P = 0.004) were included in the regression model (adjusted R 2 = 0.071). In conclusion, the present study showed that age, anthropometric index, lifestyle-related parameters, medication and supplementation status, objectively measured physical fitness, biochemical parameters, and nutritional intake status explain less than 10% of oxidative stress at rest.

Relationship of Bone Mineral Density and Knee Osteoarthritis (Kellgren-Lawrence Grade): Fifth Korea National Health and Nutrition Examination Survey.

BACKGROUND: Osteoarthritis (OA) and osteoporosis (OP) are the 2 most common bone disorders associated with aging. We can simply assume that older patients have a higher incidence of OA and OP with more severity. Although several papers have conducted studies on the relationship between OA and OP, none of them has demonstrated a conclusive link. In this study, we used radiological knee OA and bone mineral density (BMD; T-score of the total hip and lumbar spine) to analyze the incidence of OA and OP in a large population. We aimed to determine the relationship between OA and OP and investigate the associated risk factors. METHODS: This cross-sectional study used data extracted from the 2010-2012 Korea National Health and Nutrition Examination Survey. We evaluated a total of 4,250 participants aged ≥ 50 years who underwent knee radiography and dual-energy X-ray absorptiometry and their laboratory results. The relationship between radiological knee OA and BMD was assessed. The generalized linear model was used to evaluate the relationship between BMD and Kellgren-Lawrence (KL) grade. RESULTS: The higher KL grade was associated with older age, higher body mass index (BMI), female sex, and lower hemoglobin level (p < 0.001). No significant association was found between OA and the following variables: white blood cell, platelet, total cholesterol, vitamin D, alkaline phosphatase, parathyroid hormone, hypertension, diabetes, asthma, dyslipidemia, smoking status, alcohol consumption, and regular exercise (p > 0.05). After adjusting for confounding factors (age, BMI, diabetes, hypertension, smoking, and alcohol consumption), the average T-scores of total hip and lumbar spine were the highest in the mild OA group with KL grade 2 (-0.22 ± 1.08 and -0.89 ± 1.46, respectively, p < 0.001). The average T-scores of the total hip and lumbar spine significantly decreased as OA progressed from moderate (KL grade 3; -0.49 ± 1.05 and -1.33 ± 1.38, respectively, p < 0.001) to severe (KL grade 4; -0.73 ± 1.13 and -1.74 ± 1.75, respectively, p < 0.001). T-scores of the moderate-to-severe OA group were significantly lower than those of the non-OA group (KL grades 0 and 1, p < 0.001). CONCLUSIONS: Compared with the non-OA group, BMD (T-scores of the total hip and lumbar spine) was higher in the mild OA group and lower in the moderate-to-severe OA group.

Stabilization of acid-rich bio-oil by catalytic mild hydrotreating.

Although liquid products derived from the pyrolysis of biomass are promising for the production of petroleum-like hydrocarbon fuels, the catalytic burden of hydrodeoxygenation must be reduced to achieve feasible upgrading processes. Herein, mild hydrotreating of an acid-rich biomass pyrolysis oil (bio-oil) with an unusually high total acid number (588 mg KOH/g bio-oil) was performed to stabilize the low-quality bio-oil. Ru-added TiO2-supported transition metal catalysts stabilized the bio-oil by reducing its acidity more compared to what could be achieved by Ru-free catalysts; this process also leads to lower loss of organic compounds compared to when using a Ru/TiO2 catalyst. Based on the performance of transition metal catalysts, including Ni, Co, and Cu, supported on TiO2, tungstate-zirconia, or SiO2, supported bimetallic catalysts were prepared by adding Ru to the TiO2-supported metal catalysts. The bimetallic catalysts Ru/Ni/TiO2 and Ru/Co/TiO2 exhibited good decarboxylation activity for the removal of carboxylic acids and a higher yield of organic compounds compared to that provided by Ru, which can be deemed appropriate for feedstocks when hydrodeoxygenation needs to suppress the loss of organic reactants. Using these catalysts, the carboxylic acid concentration was reduced to 319-323 mg KOH/g bio-oil with organic yields of 62-63 wt% at reaction temperatures 150-170 °C lower than the temperature required for direct conversion of carboxylic acids to alcohols or deoxygenates. The improved catalytic hydrotreating activity of Ru-added transition metals can be attributed to the high acid site densities of these catalysts along with their improved hydrogenation activities.

Changes in Urinary Biomarkers of Organ Damage, Inflammation, Oxidative Stress, and Bone Turnover Following a 3000-m Time Trial.

Strenuous exercise induces organ damage, inflammation, and oxidative stress. Currently, to monitor or investigate physiological conditions, blood biomarkers are frequently used. However, blood sampling is perceived to be an invasive method and may induce stress. Therefore, it is necessary to establish a non-invasive assessment method that reflects physiological conditions. In the present study, we aimed to search for useful biomarkers of organ damage, inflammation, oxidative stress, and bone turnover in urine following exercise. Ten male runners participated in this study and performed a 3000-m time trial. We measured biomarkers in urine collected before and immediately after exercise. Renal damage markers such as urea protein, albumin, N-acetyl-ß-D-glucosaminidase (NAG), and liver-fatty acid binding protein (L-FABP), and an intestinal damage marker, intestine-fatty acid binding protein (I-FABP), increased following exercise (p < 0.05). However, a muscle damage marker, titin N-terminal fragments, did not change (p > 0.05). Inflammation-related factors (IRFs), such as interleukin (IL)-1ß, IL-1 receptor antagonist (IL-1ra), IL-6, complement (C) 5a, myeloperoxidase (MPO), calprotectin, monocyte chemoattractant protein (MCP)-1, and macrophage colony-stimulating factor (M-CSF), increased whereas IRFs such as IL-4 and IL-10 decreased following exercise (p < 0.05). IRFs such as tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-12p40, and interferon (IFN)-γ did not change (p > 0.05). Oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and nitrotyrosine, did not change following exercise (p > 0.05) whereas 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased (p < 0.05). Bone resorption markers, such as cross-linked N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), did not change following exercise (p > 0.05). These results suggest that organ damage markers and IRFs in urine have the potential to act as non-invasive indicators to evaluate the effects of exercise on organ functions.

Preoperative Oral Carbohydrate Loading in Laparoscopic Gynecologic Surgery: A Randomized Controlled Trial.

STUDY OBJECTIVE: To determine whether carbohydrate loading improves the postoperative quality of recovery (QoR) better than the midnight fasting policy in laparoscopic gynecologic surgeries. DESIGN: Randomized, parallel-group trial. SETTING: Tertiary university hospital. PATIENTS: Female patients scheduled for laparoscopic gynecologic surgery for nonmalignant gynecologic diseases. INTERVENTIONS: Eighty-eight women were randomly assigned to the midnight fasting group (nil per os, NPO group) or the carbohydrate loading group (carbohydrate group). Patients in both groups adhered to the enhanced recovery after surgery protocol except for carbohydrate intake in the carbohydrate group. MEASUREMENTS AND MAIN RESULTS: The postoperative QoR was evaluated using the QoR 15-item questionnaire on postoperative day 2. The times to readiness for discharge of the groups were compared. The QoR 15-item questionnaire scores were 97.7 ± 23.0 in the NPO group and 99.6 ± 22.4 in the carbohydrate group; they were not statistically different (p = .702). The times to readiness for discharge of both groups were also not different: 36.8 ± 12.2 hours in the NPO group and 37.6 ± 11.8 hours in the carbohydrate group (p = .684). CONCLUSION: The benefit of carbohydrate beverage intake was not significant in laparoscopic gynecologic surgeries when following the enhanced recovery after surgery protocol.

Mediterranean Diet and Naltrexone/Bupropion Treatment for Weight Loss in Overweight and Obese Breast Cancer Survivors and Non-Cancer Participants: A Pilot Randomized Controlled Trial.

INTRODUCTION: The objective of this pilot randomized controlled trial was to investigate the combined effect of a Mediterranean diet and naltrexone/bupropion treatment on body weight, metabolic parameters, and quality of life in overweight or obese breast cancer survivors. METHODS: Forty-four breast cancer survivors were randomly assigned to receive the Mediterranean diet plus naltrexone/bupropion medication (breast cancer survivor MeDiet+NB group) or the Mediterranean diet alone (breast cancer survivor MeDiet-only group). Twenty-eight age-matched non-cancer patients were instructed to consume the Mediterranean diet plus naltrexone/bupropion medication (non-cancer MeDiet+NB group). After the 8-week intervention, changes in body weight, metabolic parameters, nutrient intake, and quality of life of the three groups were assessed. RESULTS: Significant weight loss of 2.8 kg was noted for the breast cancer survivor MeDiet+NB group, 1.8 kg for the breast cancer survivor MeDiet-only group, and 2.5 kg for the non-cancer MeDiet+NB group after 8 weeks (P < 0.05 versus baseline by Wilcoxon's signed-rank test). All three groups also exhibited significantly lower fasting glucose, insulin, and homeostasis model assessment of insulin resistance levels (P < 0.05). Quality of life as assessed by self-reported questionnaires showed improvement in all participants (P < 0.05). However, there were no significant differences of changes in body weights, metabolic parameters, and quality of life among the three groups or between the MeDiet+NB and MeDiet-only groups. CONCLUSION: We found that the Mediterranean diet, with or without naltrexone/bupropion treatment, facilitates weight loss, improves metabolic parameters, and increases quality of life. The combination of the Mediterranean diet with naltrexone/bupropion treatment did not produce superior changes when compared to the Mediterranean diet alone. TRIAL REGISTRATION: This trial was retrospectively registered on 10 July 2018 as NCT03581630 at ClinicalTrials.gov (https://clinicaltrials.gov/ct2/show/NCT03581630).

Chronic Cadmium Intoxication and Renal Injury Among Workers of a Small-scale Silver Soldering Company.

BACKGROUND: Cadmium exposure may induce chronic intoxication with renal damage. Silver soldering may be a source of cadmium exposure. METHODS: We analyzed working environment measurement data and periodic health screening data from a small-scale silver soldering company with ten workers. Concentrations of cadmium in air from working environment measurement data were obtained. Concentrations of blood and urinary cadmium, urine protein, and urine ß2-microglobulin (ß2M) were obtained. The generalized linear model was used to identify the association between blood and urine cadmium and urine ß2M concentrations. Clinical features of chronic cadmium intoxication focused with toxicological renal effects were described. RESULTS: The mean duration of work was 8.5 years (standard deviation [SD] = 6.9, range = 3-20 years). Cadmium concentrations in air were ranged from 0.006 to 0.015 mg/m3. Blood cadmium concentration was elevated in all ten workers, with a highest level of 34.6 µg/L (mean = 21.288 µg/L, SD = 11.304, range = 9.641-34.630 µg/L). Urinary cadmium concentration was elevated in nine workers, with a highest level of 62.9 µg/g Cr (mean = 22.151 µg/g creatinine, SD = 19.889, range = 3.228-62.971 µg/g creatinine). Urine ß2M concentration was elevated in three workers. Urinary cadmium concentration was positively associated with urine protein concentration (beta coefficient = 10.27, 95% confidence interval = [4.36, 16.18]). Other clinical parameters were compatible with renal tubular damage. CONCLUSION: Cadmium intoxication may occur at quite low air concentrations. Exposure limit may be needed to be lowered.

Adherence to general medical checkup and cancer screening guidelines according to self-reported smoking status: Korea National Health and Nutrition Examination Survey (KNHANES) 2010-2012.

OBJECTIVES: The National Lung Screening Trial (NLST) revealed that low-dose computed tomography (LDCT) screening could reduce lung cancer mortality in heavy smokers. Lung screening with LDCT was implemented in July 2019 as part of the National Cancer Screening Program in Korea for heavy smokers who meet NLST criteria [smokers aged 55-74 years with 30 pack-years (PY) or more, excluding former smokers with more than 15 years since smoking cessation]. This study evaluated NLST-eligible heavy smokers' adherence to general medical checkup and cancer screening guidelines. METHODS: Using the Korea National Health and Nutrition Examination Survey (KNHANES) from 2010 to 2012, we compared adherence of Korean adults (55-74 years, n = 5,480) to general medical checkup and cancer (gastric, colorectal, breast, and cervical) screening guidelines according to self-reported smoking status. Smoking and PY data were available, but no data indicating when former smokers ceased smoking were available. Accordingly, smoking status was only classified as NLST (smokers with a history ≥ 30 PY) and non-NLST. Individuals who met NLST criteria were subdivided into current (NLST-current) and former smokers (NLST-former). Multivariable logistic regression was used to evaluate adherence to screening recommendations as a function of the study group (NLST-current, NLST-former, non-NLST) using possible covariates (sociodemographic factors, health-related behaviors, comorbidities, and self-reported health status). RESULTS: Weighted prevalence of NLST-current was 9.7%, of NLST-former was 9.6%, and of non-NLST was 80.7%. Overall screening rates were 70.7% (medical checkup), 59.1% (stomach cancer), 58.1% (colorectal cancer), 59.1% (breast cancer), and 48.9% (cervical cancer). Adherence to colorectal cancer screening and medical checkup was lower in NLST-current than non-NLST (AOR 0.59; 95% CI 0.44-0.78 for colorectal cancer; AOR 0.70; 95% CI 0.52-0.95 for medical checkup). Screening practices for other cancers were not different. CONCLUSIONS: Current heavy smokers meeting NLST criteria were less likely to have colorectal cancer screening or general medical checkup. Understanding the screening practices of this target population might enable the development of more effective plans to implement lung screening and improve screening compliance for other cancers.

Plant-Derived Purification, Chemical Synthesis, and In Vitro/In Vivo Evaluation of a Resveratrol Dimer, Viniferin, as an HCV Replication Inhibitor.

Oligostilbenoid compounds, a group of resveratrol multimers, display several anti-microbial activities through the neutralization of cytotoxic oxidants, and by inhibiting essential host and viral enzymes. In our previous study, we identified a series of oligostilbenoid compounds as potent hepatitis C virus (HCV) replication inhibitors. In particular, vitisin B, a resveratrol tetramer, exhibited the most dramatic anti-HCV activity (EC50 = 6 nM and CC50 > 10 µM) via the disruption of the viral helicase NS3 (IC50 = 3 nM). However, its further development as an HCV drug candidate was halted due to its intrinsic drawbacks, such as poor stability, low water solubility, and restricted in vivo absorption. In order to overcome these limitations, we focused on (+)-ε-viniferin, a resveratrol dimer, as an alternative. We prepared three different versions of (+)-ε-viniferin, including one which was extracted from the grapevine root (EVF) and two which were chemically synthesized with either penta-acetylation (SVF-5Ac) or no acetylation (SVF) using a newly established synthesis method. We confirmed their anti-HCV replication activities and minimal cytotoxicity by using genotype 1b and 2a HCV replicon cells. Their anti-HCV replication action also translated into a significant reduction of viral protein expression. Anti-HCV NS3 helicase activity by EVF was also verified in vitro. Finally, we demonstrated that SVF has improved pharmacokinetic properties over vitisin B. Overall, the favorable antiviral and pharmacokinetic properties of these three versions of viniferin warrant their further study as members of a promising new class of anti-HCV therapeutics.

Radiation-induced cutaneous angiosarcoma of the abdomen in a patient with cervical cancer: A case report.

Cutaneous angiosarcoma (CA) is a rare and aggressive malignant tumor that develops from vascular endothelium. Secondary CAs are often caused by radiotherapy and chronic lymphedema. Most radiation-induced CAs are associated with breast or gynecologic cancer. The prognosis of CA is extremely poor, with a 5-year survival rate ranging from 12% to 34%. Therapeutic options are limited, and surgical excision with negative margins remains the mainstay of treatment. We report a case of a 63-year-old woman who developed secondary CA at an irradiated site 7 years after receiving radiotherapy for cervical cancer.

Dose-Dependent Toxic Effect of Cotinine-Verified Tobacco Smoking on Systemic Inflammation in Apparently Healthy Men and Women: A Nationwide Population-Based Study.

Chronic exposure to tobacco smoke leads to chronic low-grade systemic inflammation; however, little is known about the dose-dependent toxic effect of objective tobacco smoking on systemic inflammation. We examined the dose-dependent toxic effect of cotinine-verified tobacco smoking on leukocyte count in a representative sample of Korean adults, including 8655 men and 10,432 women aged 19⁻65 years from the Korean National Health and Nutrition Examination Survey. The participants were categorized into five groups by the level of urine cotinine (Ucot) as follows: A non-smoker group (<50.00 ng/mL) and four quartile groups for smokers for both men and women. The odds ratios (ORs) and 95% confidence intervals (CIs) for sex-specific high leukocyte count (≥75th percentile) were calculated across five groups of Ucot concentrations using multiple logistic regression analyses. The mean values of leukocyte count gradually increased according to the grade of Ucot concentration in both sexes. The ORs (95% CIs) for high leukocyte count in the 4th Ucot quartile concentrations versus the non-smokers were 4.09 (3.39⁻4.94) for men and 3.91 (2.82⁻5.41) for women after adjusting for confounding variables. The present study confirmed the dose-response toxic effect of tobacco smoking on chronic low-grade systemic inflammation.