Potential role of Fibrosis-4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study.

AIM: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD. METHODS: Korean adults (n = 340 825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods. RESULTS: In 93 HCC cases, 71 were identified in G4, whereas 20 cases (21.5%) in G2 and G3 combined where ultrasound and Fibrosis-4 performed similarly to alpha-fetoprotein and ultrasound. In G2, Fibrosis-4 and ultrasound had the highest area under the receiver operating characteristic curve (0.93 [0.87-0.99]), whereas in G3, the combined screening methods had the highest area under the receiver operating characteristic curve (0.98 [0.95-1.00]). The positive predictive value was lower in G2 and G3 than in G4, but was >5% when restricted to a high Fibrosis-4 score. CONCLUSIONS: More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the Fibrosis-4 score in identifying individuals at high risk of HCC.

Association between body fat and bone mineral density in Korean adults: a cohort study.

Although obesity was once considered protective against osteoporosis, various factors influence the relationship between fat and bone mineral density (BMD). To establish the importance of healthy body composition in decelerating declines in BMD, we conducted a study to compare the association between body fat composition and BMD in Korean adults. Using data collected from the Kangbuk Samsung Health Study from 2012 to 2019, this cohort study compared the incidence of decreased BMD among the following four groups: normal BMI and normal adiposity (NBMI-NA), normal BMI and high adiposity (NBMI-HA), overweight, and obesity. Decreased BMD was defined as a Z-score ≤ - 2.0 in premenopausal women and men < 50 years of age or a T-score < - 1.0 in postmenopausal women and men ≥ 50 years of age. Individuals who were diagnosed with osteoporosis or compression fracture after their second visit were categorized as having decreased BMD. The incidence rate of decreased BMD in the NBMI-NA group was 3.37, and that in the NBMI-HA group was 4.81, which was the highest among all groups. After adjusting for confounding factors, NBMI-HA led to a significantly greater risk of decreased BMD compared to NBMI-NA (HR 1.47; 95% CI 1.09-1.99). Even with a normal BMI, a high BFP was associated with an increased risk of decreased BMD. Therefore, healthy body composition management, not simply BMI, is important in preventing decreased BMD.

Cardiac Manifestations after Ingestion of a Commercial Desiccant: A Case Report.

Background and Objectives: The rise in suicidal attempts has led to an increase in unusual intoxication cases. The ingestion of anhydrous calcium chloride (CaCl2) causes direct injury to the gastrointestinal wall via a thermal burn. Therefore, previous reports on CaCl2 ingestion primarily considered the gastrointestinal injury. Severe CaCl2 intoxication can induce a hypercalcemic crisis, presenting with arrhythmia, acute pancreatitis, and acute kidney injury. This case report details a patient with hematemesis and hypercalcemia following the ingestion of a commercial desiccant. We aimed to report the progression of the case, with a focus on the electrocardiographic manifestations. Case Presentation: A 39-year-old female presented at a regional emergency center with blood in her vomit after the ingestion of a commercial desiccant. Bloody emesis was the initial symptom, and various electrolyte imbalances developed during admission. Electrocardiogram (ECG) changes occurred early after hospitalization and disappeared before the electrolyte levels normalized. The patient was maintained in an NPO (Nil Per Os) state throughout her hospital stay. The bloody emesis and abdominal pain resolved quite early, despite her minimal mention of symptoms, possibly due to her suspected negative psychiatric symptoms. Conclusions: In this case, we observed dynamic and prolonged multiple electrolyte imbalances along with the early-phase ECG changes, all of which responded well to supportive care. This report adds to the understanding of the diverse manifestations and management of CaCl2 intoxication.

Acute esophageal obstruction after ingestion of psyllium seed husk powder: A case report.

BACKGROUND: Bezoar is a mass of hardened external material found in the gastrointestinal (GI) tract. It may form anywhere in the GI tract, but esophageal bezoar is rare because of the short esophageal transit time. Psyllium seed husk is an indigestible natural derivative that is widely used as an herbal laxative. Herein, we report a case of acute esophageal obstruction caused by a bezoar after ingestion of psyllium seed husk powder. CASE SUMMARY: A 76-year-old male with Parkinson's disease visited the emergency department with swallowing difficulty approximately 10 h after ingesting psyllium seed husk powder. Symptoms began a few hours after ingestion and progressed to severe dysphagia. There were no abnormal findings on simple radiography. However, a computed tomography scan revealed an approximately 2.0 cm × 2.5 cm mass located near the gastro-esophageal junction. After grinding, the mass was removed using an endoscopic capture net. Esophageal bezoars may cause life-threatening complications. Patients with Parkinson's disease may have esophageal motility dysfunction, which may increase esophageal transit time. Since our patient had Parkinson's disease, this effect may have contributed to the formation of the bezoar. CONCLUSION: Attention should be paid to using bulk-laxatives, and an appropriate specified regimen will be needed when marketed as a dietary supplement.

Status of dyslipidemia management and statin undertreatment in Korean cancer survivors: A Korean National Health and Nutrition Examination Survey study.

AIMS: Due to improving cancer treatment results, non-cancer mortality is an important issue for cancer survivors. Cardiovascular diseases are the leading causes of death in Korea and globally. In addition to lowering the risk of cardiovascular disease, the use of statins has led to an overall reduction in cancer mortality in recent observational studies. We investigated the status of current dyslipidemia management in cancer survivors with reference to 2018 guidelines. METHODS: The study is a cross-sectional analysis of 1460 cancer survivors aged from 40 to 75 years who participated in the Korean National Health and Nutrition Examination Survey from 2007 to 2016. Dyslipidemia management status among cancer survivors was assessed according to 2018 American College of Cardiology/American Heart Association guidelines and Korean Coronary Heart Disease Risk Score guidelines. RESULTS: The rate of treatment for dyslipidemia was 8.5% for males, 13.8% for females, and 11.9% overall. Among cancer survivors who were not receiving treatment for dyslipidemia, 59.6% of males, 34.2% of females and 43.9% of total cancer survivors would have been eligible for statin therapy under the 2018 American College of Cardiology/American Heart Association guidelines and Korean Coronary Heart Disease Risk Score guidelines. The rate of undertreatment of dyslipidemia increased with age and length of time since cancer diagnosis. CONCLUSION: Nearly 50% of cancer survivors remain untreated although they are eligible for statin therapy. This emphasizes the need for more attention to prevent atherosclerotic cardiovascular disease among cancer survivors.

Comparison of COVID-19 Pandemic-Related Stress among Frontline Medical Personnel in Daegu City, Korea.

Background and Objectives: Frontline medical staff usually experience high levels of stress, which could greatly impact their work output. We conducted a survey to investigate the level of stress and its association with job types, work departments, and medical centers among COVID-19 pandemic frontline medical personnel. Materials and Methods: We conducted a cross-sectional survey using a self-administered questionnaire among 307 frontline medical staff who cared for COVID-19 patients in Daegu city. We used a 33-item questionnaire to assess respondents' general characteristics, job stress, personal effects associated with the COVID-19 pandemic, and their stress level. A general health questionnaire-12 (GHQ-12) was included in our questionnaire. Results: Majority (74.3%) of the respondents were in the stress group. The mean GHQ-12 score was 14.31 ± 4.96. More females (67.4%, p < 0.05) and nurses (73.3%, p = 0.001) were in the stress group compared to males and doctors. Medical staff in the general ward considered the severity of the COVID-19 pandemic situation higher. Nurses perceived work changes (p < 0.05), work burden (p < 0.05), and personal impact (p < 0.05) more serious than doctors. Medical staff in Level 3 emergency department (ED) perceived a lack of real-time information (p = 0.012), a lack of resources, and negative personal impacts associated with the pandemic as more serious than staff in Level 1 and Level 2 EDs. Medical staff in the intensive care unit perceived work changes (p < 0.05), work burden (p < 0.05), and lack of personal protective equipment (p = 0.002) as more serious than staff in the ED and general ward. Conclusion: Providing real-time information and resources for reducing work burden and negative personal impact is central to maximizing the work output of the COVID-19 pandemic frontline medical staff. Supporting their mental health through regular programs and intervention is also imperative.

Cardiovascular risk and undertreatment of dyslipidemia in lung cancer survivors: A nationwide population-based study.

BACKGROUND: In lung cancer survivors, cardiovascular diseases (CVDs) are the leading cause of noncancer deaths. Nonetheless, there is lack of information on management of dyslipidemia, a major risk factor for future CVD events, in lung cancer survivors. This study aimed to assess dyslipidemia management and prevalence of statin eligibility in lung cancer survivors. METHODS: From the Korean National Health Insurance Service database, we selected 7349 lung cancer survivors who received surgery for lung cancer from 2007 to 2014. We used descriptive statistics for analyses of dyslipidemia management status on the basis of the National Cholesterol Education Program Adult Treatment Panel III guidelines. We also identified those who met the criteria for treatment on the basis of CVD risk according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) guidelines. RESULTS: The overall awareness and treatment rates for lung cancer survivors with dyslipidemia were 31.8% and 29.7%, respectively. The overall control rate for those receiving treatment was 88.7%, but was lowest in the highest risk group (78.1%). Furthermore, undertreatment of dyslipidemia was more prominent in young, male lung cancer survivors and those diagnosed with lung cancer within 3 years. Among those not receiving treatment for dyslipidemia, 61.7% were indicated for statin according to the ACC/AHA guidelines. CONCLUSION: Over half of lung cancer survivors were not receiving treatment, although they were eligible for statin under current guidelines. To reduce noncancer mortality, statin use and adequate management of CVD risk factors should be encouraged in lung cancer survivors.

Application of calcium nebulization for mass exposure to an accidental hydrofluoric acid spill.

PURPOSE: To determine the long-term prevalence and characteristics of acute hydrofluoric acid (HF) exposure in 2223 patients during the first 30 months after a mass-casualty exposure, and to confirm the antidotal effect of nebulized calcium on inhalation burns caused by HF. METHODS: This observational cohort study included patients after an HF spill in the Republic of Korea on September 27, 2012; registered patients were followed until April 2015. We assessed toxic effects, distance from spill, degree of acute poisoning, and the effect of nebulized calcium in HF-exposed individuals. RESULTS: Overall, 2223 patients received emergency management or antidote therapy for 20 days. Seventy-four of 134 patients with dermal toxicity received calcium-lidocaine gel, and 368 individuals with bronchial irritation signs received calcium gluconate via nebulizer nCG. A total 377 ampoules 786 g of calcium gluconate were used in the nCG formulation. Calcium administration did not cause adverse reactions during the observation period. Long-term cohort observation showed that 120 patients (120/2233, 5.4%) returned to medical facilities for management of HF-related symptoms within 1 month; 18 persons (18/1660, 1.1%) returned 1-3 months later with chronic cough and respiratory symptoms; and 3 patients (3/1660, 0.2%) underwent medical treatment due to upper-airway toxic symptoms more than 2 years after HF exposure. CONCLUSION: Respiratory toxicity after mass exposure to an HF spill was successfully treated by calcium nebulizer. Based on our experience, detoxification processes and the amounts of antidote stocked are important when planning for future chemical disasters at the community level.

Crowding and confinement effects on enzyme stability in mesoporous silicas.

To understand the protein functions within a cell, where proteins exist in an extremely crowded and confined state, various modeling and experimental methods have been proposed. Here, we propose a new experimental approach to modulate the macromolecular crowding and/or confinement effects by using mesoporous silicas with two different pore structures. SBA-15 and MSU-F with linear and mesocellular pore structures, respectively, were used to adsorb a model enzyme, glucose oxidase (GOx), in various concentrations ranging from 3 to 430 mg ml-1. The concentration of adsorbed GOx in the mesopores, representing the degree of crowding, showed a good correlation with thermal enzyme stability. Interestingly, the increase of thermal stability as a function of macromolecular crowding showed different correlations depending on the pore structure of mesoporous silicas. It represents that combination of crowding and confinement effects can promote different microenvironments for enzyme molecules, while mesoporous silicas can impose controlled crowding and confinement effects on enzymes due to their uniform and tunable pore structures. It is anticipated that this new and simple approach can provide a tool to elucidate crowding and confinement effects on the protein functions, including its stability in vivo, because the mesopore environments could mimic the real macromolecular cell system under crowding.

Educational Disparities in Risk for Metabolic Syndrome.

BACKGROUND: The objective of this study was to evaluate the relationship between educational level as a surrogate marker of socioeconomic status and the risk of developing metabolic syndrome (MetS). METHODS: Study subjects were 1915 Korean adults (1193 women and 722 men) who participated in a cohort study. Educational level was categorized into two groups: (1) high education (more than 12 years of education), and (2) low education (less than 12 years of education). MetS was defined according to diagnostic criteria of the National Cholesterol Education Program (NCEP-III) and the International Diabetes Federation (IDF). Multiple logistic regression analysis and Cox proportional hazard analysis were performed to evaluate cross-sectional and prospective association between MetS or MetS components and educational level after adjusting for covariates. RESULTS: The overall prevalence of MetS at baseline was 15.0% in women and 20.4% in men. Incidence of MetS over 4.52 years was 16.6 per 1000 person-year in women and 27.6 per 1000 person-year in men. The prevalence and incidence of MetS were higher in the low educational group than those in the high educational group in both sexes. At baseline, the risk of MetS (odds ratio [OR]: 1.63, 95% confidence interval [CI]: 1.05-2.53 for NCEP criteria; OR: 2.30, 95% CI: 1.41-3.76 for IDF criteria) and abdominal obesity (OR: 2.62, 95% CI: 1.75-3.93) were higher in less educated women compared with those in more educated women. In men, there was no association between Mets or MetS components and educational level. Over 4.6 years of follow-up, the risk of developing MetS in women in the low education group (hazard ratio [HR]: 1.95, 95% CI: 1.12-3.50 for NCEP criteria; HR: 2.36, 95% CI: 1.14-4.86 for IDF criteria) was significantly higher than that in the high education group. In men, low education significantly increased the risk of developing impaired fasting glucose (HR: 1.95, 95% CI: 1.12-3.40). CONCLUSION: An inverse association between educational level and MetS was found in Korean women, suggesting that socioeconomic disparities might increase the risk of MetS development, especially in women.

A tryptamine-paeonol hybridization compound inhibits LPS-mediated inflammation in BV2 cells.

In the present study, we synthesized and evaluated the anti-inflammatory effects of three tryptamine (Trm) hybrid compounds, HBU-375, HBU-376 and HBU-379. The Click reaction between the azido-Trm and 2- or 4-propazylated paeonol moiety resulted in HBU-376 and HBU-375, respectively. HBU-379 was generated by hybridizing Trm with propazylated acetyl-syringic acid. HBU-376 and HBU-375 dose-dependently inhibited LPS and caused nitric oxide (NO) generation in BV2 cells, whereas HBU-379 minimally inhibited NO generation, indicating that the paeonol unit plays an important role in the anti-inflammatory effect of Trm hybrid compounds. Although HBU-375 and HBU-376 demonstrated a similar inhibitory effect on LPS-induced NO generation, HBU-376 resulted in less cellular toxicity presumably due to the free phenolic hydroxyl group of paeonol. Therefore, HBU-376 may be a promising anti-inflammatory agent conferring minimal cytotoxicity. HBU-376 significantly and dose-dependently inhibited LPS-induced NO products, NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6, MCP-1 and interleukin-1ß mRNA expressions and iNOS and COX-2 protein expressions. However, at the same concentrations, Trm or paeonol individually did not inhibit LPS-mediated production of inflammatory molecules. HBU-376 inhibited both LPS-induced STAT-3 phosphorylation and nuclear factor-kappa B (NF-κB) activation. Furthermore, LPS-mediated DNA binding of c-Rel, p50 and p52 to the NF-κB binding site of the iNOS promoter was inhibited by HBU-376, whereas Trm and paeonol did not inhibit LPS-induced NF-κB activation and DNA binding of c-Rel, p50 and p52. Overall, our data suggest that the Trm-paeonol hybrid compound down-regulates inflammatory responses by inhibiting NF-κB and NF-κB-dependent gene expression. This suggests that it is a potential therapeutic agent for inflammatory diseases of the central nervous system.

Ultrasonic bonding method for heterogeneous microstructures using self-balancing jig.

Perfect sealing of heterogeneous microstructures in plastic-based microfluidic devices is a significant and urgent challenge to be able to apply them in various microfluidic-based applications, including biosensing, biofiltering, chemical reactors and lab-on-a-chip. In this study we report a simple but practical and effective method to bond a microstructure-incorporated microfluidic device using an ultrasonic bonding method. The specially designed hemisphere-shaped jig, which is called a self-balancing jig, provides a free motion in all x, y, and z directions. These unique properties of the jig allow us to precisely adjust and bond the heterogeneous microstructures in the device. A conventional jig shows in solution leakages around the heterogeneous microstructures while the self-balancing jig did not show any leakages in devices. Furthermore, the bonding performance was also confirmed by using a black ink and fluorescent dye solution. The micro-pillar arrays in the device also demonstrated its capability for selective filtering of microbeads. We believe that this technique would be a useful tool for producing microfluidic devices with heterogeneous microstructures.

Multifunctional polyurethane sponge for polymerase chain reaction enhancement.

Selective filtering of target biomaterials from impurities is an important task in DNA amplification through polymerase chain reaction (PCR) enhancement and gene identification to save endangered animals and marine species. Conventional gene extraction methods require complicated steps, skilled persons, and expensive chemicals and instruments to improve DNA amplification. Herein, we proposed an alternative method for overcoming such challenges by imparting secondary functionality using commercially available polyurethane (PU) sponges and cost-effective fabrication approaches through polydopamine and polysiloxane coatings. The porous, highly flexible, and chemically modified superhydrophilic and superhydrophobic PU sponges allow large surface areas and mechanically stable frames for effective extraction of genomic DNA through selective filtering of fish tissues and oils. Furthermore, these chemically modified PU sponges allow separation of genes and improvement of PCR for DNA amplification for the identification of fish species. The combination of a simple fabrication method and functionalized PU sponges could be a useful platform for PCR enhancement and gene-based identification of species for practical applications.

A one-step, electrochemical biosensing strategy that is based on transport of signaling CdS nanoparticles controlled by biomolecules.

A novel, one-step electrochemical biosensing technique has been developed by utilizing a strategy in which a biomolecule controls transport of CdS-signaling nanoparticles to the surface of an electrode. The viability of this approach was explored using DNA as a model target biomolecule. The capture and signaling probes both contain nucleic acid sequences that are complementary to the target DNA. The detection chamber consists of a gold matrix modified with the capture probe on the bottom, a glassy carbon (GC) working electrode on the top, and a buffered electrolyte containing the signaling probe conjugated with the CdS nanoparticle. When target DNA is not present in the chamber, the CdS-signaling probe is freely transported to the GC electrode where CdS accumulates during the preconcentration step and undergoes electrochemical anodic stripping voltammetry (ASV) that subsequently generates a current signal during the following oxidative stripping step. On the other hand, target DNA present in the sample undergoes simultaneous hybridization to both the capture and signaling probes in a sandwich-like manner. This phenomenon leads to fixation of the CdS nanoparticles on the bottom of the chamber, thus preventing their electrochemical reduction on the GC electrode. As a result, the electrochemical signal is reduced in the presence of target DNA. Based on the reduction of the current signal, target DNA from C. trachomatis was successfully detected without the need for any complicated secondary procedures. This electrochemical one-step detection method could serve as a conceptually new technology enabling highly convenient biosensing that is applicable to point-of-care testing (POCT).

A one-step electrochemical method for DNA detection that utilizes a peroxidase-mimicking DNAzyme amplified through PCR of target DNA.

A novel one-step electrochemical method for DNA detection is described. The procedure utilizes a reaction catalyzed by a peroxidase-mimicking DNAzyme to produce a product, which forms an insoluble precipitation layer on the surface of an electrode. A rationally designed forward primer, conjugated with a peroxidase DNAzyme complementary sequence at its 5'-end, is used for PCR amplification of target DNA. As a result, the DNAzyme sequence is produced by amplification only when the target DNA is present in the sample. The PCR product is then subjected to the precipitation reaction on the electrode surface using an electrolyte assay buffer containing 4-chloronaphthol, hydrogen peroxide, ferrocenemethanol, hemin, and 5'-lambdaexonuclease. Finally, analysis is carried out using Faradaic impedance spectroscopy. The impedance value was found to greatly increase when target DNA is present owing to the formation of a precipitation layer on the electrode surface caused by the catalytic action of the DNAzyme. In contrast, no impedance increase is observed when a control sample not containing target DNA is utilized. By employing this strategy, target DNA from Chlamydia trachomatis was reliably detected within a 10 min period following precipitation without the need for complicated secondary procedures. This effort has led to the development of a highly convenient electrochemical one-step method for DNA detection that utilizes a peroxidase-mimicking DNAzyme, which is specifically designed to undergo amplification during PCR of target DNA.

Electrochemical detection of DNA mutations on a PNA-modified electrode utilizing a single-stranded DNA specific endonuclease.

Utilizing a peptide nucleic acid (PNA)-modified electrode and a single-stranded DNA specific endonuclease, a novel electrochemical method to identify DNA mutations has been developed and represents a totally new strategy for the electrochemical diagnosis of human genetic mutations.

Investigation of the signaling mechanism and verification of the performance of an electrochemical real-time PCR system based on the interaction of methylene blue with DNA.

The operation of an electrochemical real-time PCR system, based on intercalative binding of methylene blue (MB) with dsDNA, has been demonstrated. PCR was performed on a fabricated electrode-patterned glass chip containing MB while recording the cathodic current peak by measuring the square wave voltammogram (SWV). The current peak signal was found to decrease with an increase in the PCR cycle number. This phenomenon was found to be mainly a consequence of the lower apparent diffusion rate of the MB-DNA complex (D(b) = 6.82 × 10(-6) cm(2) s(-1) with 612 bp dsDNA) as compared to that of free MB (D(f) = 5.06 × 10(-5) cm(2) s(-1)). Utilizing this signal changing mechanism, we successfully demonstrated the feasibility of an electrochemical real-time PCR system by accurately quantifying initial copy numbers of Chlamydia trachomatis DNA templates on a direct electrode chip. A standard calibration plot of the threshold cycle (C(t)) value versus the log of the input template quantity demonstrated reliable linearity and a good PCR efficiency (106%) that is comparable to that of a conventional TaqMan probe-based real time PCR. Finally, the system developed in this effort can be employed as a key technology for the achievement of point-of-care genetic diagnosis based on the electrochemical real-time PCR.

Mismatch DNA-specific enzymatic cleavage employed in a new method for the electrochemical detection of genetic mutations.

Utilizing enzymatic mismatched DNA-specific cleavage and electrocatalytic signaling, a new electrochemical method for the detection of DNA mutations was developed and successfully applied to detect various mutations in the BRCA1 gene.