Biological SERS-active sensor platform based on flexible silk fibroin film and gold nanoislands.

In contrast to conventional surface-enhanced Raman scattering (SERS) platforms implemented on non-biological substrates, silk fibroin has the unique advantages of long-term biosafety and controllable biodegradability for in vitro and in vivo biomedical applications, as well as flexibility and process-compatibility. In this study, a silk fibroin film was developed to fabricate a flexible SERS sensor template with nanogap-rich gold nanoislands. The proposed biological SERS platform presents fairly good enhancements in detection performance such as detection limit, sensitivity, and signal-to-noise ratio. In particular, the sensitivity improvement was by more than 10 times compared to that of the counterpart sample, and an excellent spatial reproducibility of 2.8% was achieved. In addition, the near-field calculation results were consistent with the experimental results, and the effect of surface roughness of the silk substrate was investigated in a quantitative way. It is believed that biological SERS-active sensors could provide the potential for highly sensitive, cost-effective, and easily customizable nanophotonic platforms that include new capabilities for future healthcare devices.

Highly reliable SERS substrate based on plasmonic hybrid coupling between gold nanoislands and periodic nanopillar arrays.

To improve both sensitivity and reliability, a hybrid SERS substrate of combining gold nanoislands (GNI) with periodic MgF2 nanopillar arrays was successfully developed. SERS detection performance of the proposed substrates was evaluated in terms of enhancement effect, signal-to-noise ratio (SNR), linearity, reproducibility and repeatability, and compared with the performance of a conventional SERS substrate based on GNI. Experimental and simulation results presented that significant improvement of SERS intensity and SNR by more than 3 times and a notable reduction in relative standard deviation were obtained. We hope that the suggested SERS platform with unique advantages in sensitivity and reliability could be extended to point-of-care detection of a variety of biomolecular reactions.

Effects of temperature-dependent optical properties on the fluence rate and temperature of biological tissue during low-level laser therapy.

The effects of temperature-dependent optical properties on the change of fluence rate and temperature distribution within biological tissues during low-level laser therapy (LLLT) were investigated by experimental and numerical methods. The fluence rate and temperature within a porcine skin were measured in vitro using an optical fiber sensor and a thermocouple, respectively, while irradiating the sample with a continuous wave laser (IPG Laser GmbH, Burbach, Germany, 1,064 nm, 3.14 W/cm(2)). The absorption and reduced scattering coefficients of porcine skin were estimated using an inverse adding-doubling algorithm from the total reflectance and transmittance measured with a double-integrating sphere. It was shown that the reduced scattering coefficient of porcine skin decreased significantly as the skin temperature increased within the range of 26-40 °C. To incorporate the temperature dependency of tissue optical properties in the simulation, a mathematical model that adopted coupled equations for fluence rate and bioheat transfer was developed. It was shown that the predicted fluence rate and temperature by the proposed mathematical model agreed closely with the measured values of porcine skin. The calculation of human skin temperature using the developed model revealed that the skin temperature could be significantly underestimated if the temperature dependency of optical properties of human skin were ignored during LLLT simulation.

Blood levels of cadmium and lead in residents near abandoned metal mine areas in Korea.

We analyzed national data on blood lead levels (BLL) and blood cadmium levels (BCL) in residents living near 38 abandoned metal mining areas (n = 5,682, 18-96 years old) in Korea that were collected by the first Health Effect Surveillance for Residents in Abandoned Metal mines (HESRAM) from 2008 to 2011. The geometric mean BCL and BLL were 1.60 µg/L (95 % CI = 1.57-1.62 µg/L) and 2.87 µg/dL (95 % CI = 2.84-2.90 µg/dL), respectively, notably higher than levels in the general population in Korea and other countries. We found significantly higher BLL and BCL levels in people living within 2 km of an abandoned metal mine (n = 3,165, BCL = 1.87 µg/L, BLL = 2.91 µg/dL) compared to people living more than 2 km away (n = 2,517, BCL = 1.31 µg/L, BLL = 2.82 µg/dL; P < 0.0001) and to the general population values reported in the literature.

Early on-site detection of strawberry anthracnose using portable Raman spectroscopy.

We developed a method for the early on-site detection of strawberry anthracnose using a portable Raman system with multivariate statistical analysis algorithms. By using molecular markers based on Raman spectra, the proposed method can detect anthracnose in strawberry stems 3 days after exposure to Colletotrichum gloeosporioides. A fiber-optic probe was applied for the portable Raman system, and the acquisition time was 10 s. We found that the molecular markers were closely related to the following subjects: i) an increase in amide III and fatty acids of C. gloeosporioides invading strawberry stems (Raman bands at 1180-1310 cm-1) and ii) a decrease in metabolites in strawberry plants, such as phenolic compounds and terpenoids (Raman bands at 760, 800, and 1523 cm-1). We also found that the increased fluorescence background caused by various chromophores within the invading C. gloeosporioides could serve as a marker. A two-dimensional cluster plot obtained by principal component analysis (PCA) showed that the three groups (control, fungal infection, and pathogen) were distinguishable. The linear discriminant analysis (LDA)-based prediction algorithm could identify C. gloeosporioides infection with a posterior probability of over 40%, even when no symptoms were visible on the inoculated strawberry plants.

A cohort study of hyperuricemia in middle-aged South Korean men.

Few prospective studies have assessed the incidence and determinants of asymptomatic hyperuricemia in free-living populations. The authors' goals in this study were to estimate the incidence of hyperuricemia and quantify the dose-response relations of specific risk factors with hyperuricemia in middle-aged South Korean male workers. The authors followed a cohort of 10,802 hyperuricemia-free men aged 30-59 years, examining them annually or biennially at a university hospital in Seoul, South Korea, from 2002 to 2009. A parametric Cox model and a pooled logistic regression model were used to estimate adjusted hazard ratios for incident hyperuricemia (defined as serum uric acid level ≥7.0 mg/dL) according to prespecified risk factors. During 51,210.6 person-years of follow-up, 2,496 men developed hyperuricemia (incidence rate = 48.7 per 1,000 person-years, 95% confidence interval: 46.8, 50.7). The incidence of hyperuricema increased across baseline categories of age, body mass index, alcohol intake, blood pressure, metabolic syndrome, high-sensitivity C-reactive protein, triglycerides, gamma-glutamyltransferase, and fatty liver, whereas fasting glucose, estimated glomerular filtration rate, and high density lipoprotein cholesterol levels were inversely associated with incident hyperuricemia. Development of hyperuricemia, a very common outcome among apparently healthy South Korean men, was predicted by a variety of cardiovascular and metabolic risk factors, suggesting that lifestyle modification may help reduce the incidence of hyperuricemia.

Adiponectin-targeted SERS immunoassay biosensing platform for early detection of gestational diabetes mellitus.

The anisotropic gold nanotriangles (AuNTs) were synthesized by a fast seedless growth process. The high-yield monodispersed AuNT colloids were obtained through a purification process based on depletion-induced interactions. AuNTs were modulated with a localized surface plasmon resonance (LSPR) peak of 638 nm wavelength coherent with the Raman excitation light. However, from finite element computation results, the AuNT clusters showed better performance for the 785 nm laser source due to a red shift in their LSPR properties, hence it was selected for the surface-enhanced Raman scattering (SERS) immunoassay. A self-assembly strategy using a thiol group and ON-OFF strategy in the heat map was performed to ensure the stability of SERS immunoassay platform. The sandwich SERS immunoassay biosensor platform for adiponectin detection demonstrated a wide assay range (10-15-10-6 g/mL), good reliability (R2 = 0.994, clinically relevant range), femto-scale limit of detection (3.0 × 10-16 g/mL), and excellent selectivity without interference from other biomarkers. This showed the possibility of effectively detecting adiponectin levels in the biofluids of pregnant women. Therefore, our technology is the first to quantitatively detect adiponectin based on SERS technology for early detection of gestational diabetes mellitus and has the potential to be used as a clinical biosensor capable of diagnosing various obstetric diseases during early pregnancy.

Effect of Dentin Desensitizer Containing Novel Bioactive Glass on the Permeability of Dentin.

The objective of this study was to evaluate the effect of novel bioactive glass (BAG)-containing desensitizers on the permeability of dentin. Experimental dentin desensitizers containing 3 wt% BAG with or without acidic functional monomers (10-MDP or 4-META) were prepared. A commercial desensitizer, Seal & Protect (SNP), was used as a control. To evaluate the permeability of dentin, real-time dentinal fluid flow (DFF) rates were measured at four different time points (demineralized, immediately after desensitizer application, after two weeks in simulated body fluid (SBF), and post-ultrasonication). The DFF reduction rate (ΔDFF) was also calculated. The surface changes were analyzed using field emission scanning electron microscopy (FE-SEM). Raman spectroscopy was performed to analyze chemical changes on the dentin surface. The ΔDFF of the desensitizers containing BAG, BAG with 10-MDP, and BAG with 4-META significantly increased after two weeks of SBF storage and post-ultrasonication compared to the SNP at each time point (p < 0.05). Multiple precipitates were observed on the surfaces of the three BAG-containing desensitizers. Raman spectroscopy revealed hydroxyapatite (HAp) peaks on the dentin surfaces treated with the three BAG-containing desensitizers. Novel BAG-containing dentin desensitizers can reduce the DFF rate about 70.84 to 77.09% in the aspect of reduction of DFF through the HAp precipitations after two weeks of SBF storage.

An excitation wavelength-optimized, stable SERS biosensing nanoplatform for analyzing adenoviral and AstraZeneca COVID-19 vaccination efficacy status using tear samples of vaccinated individuals.

We introduce a label-free surface-enhanced Raman scattering (SERS) biosensing platform equipped with metallic nanostructures that can identify the efficacy of Oxford-AstraZeneca (AZD1222) vaccine in vaccinated individuals using non-invasive tear samples. We confirmed the hypothesis that the tears of people who receive the AZD1222 vaccine may be similar to those of adenovirus epidemic keratoconjunctivitis patients since the Oxford-AstraZeneca vaccine is derived from a replication-deficient ChAdOx1 vector of chimpanzee adenovirus. Additionally, we confirmed the potential of the three markers for estimating the vaccination status via analyzing the signals emanating from antibodies or immunoglobulin G by-product using our label-free, SERS biosensing technique with a high reproducibility (<3% relative standard deviation), femtomole-scale limit of detection (1 × 10-14 M), and high SERS response of >108. Therefore, our label-free SERS biosensing nanoplatforms with long-term storage and robust stability will enable rapid and robust monitoring of the vaccine presence in vaccinated individuals.

Relationship between chronic kidney disease and risk of coronary heart disease in Korean men.

There have been many epidemiological researches of chronic kidney disease (CKD), accompanied by an increase in the incidence of coronary heart disease (CHD). However, as far as we know, little research has been done to examine the extent of the relationship between CKD and CHD as estimated by Framingham risk score (FRS) in Korean men. CKD was defined as either proteinuria or an eGFR of < 60 mL/min per 1.73 m(2). The FRS has been used to predict the 10-yr risk of coronary events and usually divided into three levels of risk < 10% (low), 10%-19% (intermediate) and ≥ 20% (high). We defined FRS ≥ 10% as more-than-a-moderate CHD risk group and FRS ≥ 20% as a high CHD risk group, respectively. After adjusting for covariates, multivariable-adjusted logistic regression analyses showed a strong statistical significant relationship between CKD and high risk of CHD (adjusted OR, 1.95 [95% CI, 1.32-2.87]). Dipstick urinalysis and eGFR can be readily measured in most clinical settings. The measurement of kidney function may represent a relatively inexpensive and efficient way to identify individuals at higher risk for CHD.

Apolipoprotein B is highly associated with the risk of coronary heart disease as estimated by the Framingham risk score in healthy Korean men.

The aim of this study was to examine the association between serum apolipoprotein B (apoB) and the risk of coronary heart disease (CHD) using Framingham risk score (FRS) in healthy Korean men. A total of 13,523 men without medication history of diabetes and hypertension were enrolled in this study. The FRS is based on six coronary risk factors. FRS ≥ 10% was defined as more-than-a-moderate risk group and FRS ≥ 20% as high risk group, respectively. The logistic regression analyses were conducted. When quartile 1 (Q1) set as a reference, in unadjusted analyses, the Q2, Q3, Q4 of apoB level had increased odds ratio (OR) for the risk of CHD in both more-than-a-moderate risk and high risk group, respectively. After adjusting for confounding variables, multivariable-adjusted logistic regression analyses showed a strong relationship between the quartiles of apoB level and more-than-a-moderate risk and high risk group, respectively. These associations were attenuated, but still remained statistically significant. ApoB is found to be independently related to the risk of CHD using FRS in healthy Korean men, and the link between apoB and the risk of CHD is dose-dependent.

Label-free breast cancer detection using fiber probe-based Raman spectrochemical biomarker-dominated profiles extracted from a mixture analysis algorithm.

We report the development of a label-free, simple, and high efficiency breast cancer detection platform with multimodal biomarker analytic algorithms on a portable 785 nm Raman setup with an endoscopic Raman-lensed fiber optic probe. We propose a multimodal biomarker extraction algorithm (PCMA) implemented by combining a multivariate statistics principal component analysis (PCA) algorithm and a multivariate curve resolution-alternating least squares (MCR-ALS) computational model for extraction of the biomarker information hidden in Raman spectrochemical data. We show that the six Raman spectrochemical peaks at 1009, 1270, 1305/1443, 1658, and 1750 cm-1 assigned to phenylalanine, amide III in proteins, CH2 deformation in lipids, amide I in proteins, and carbonyl, respectively, can be used as a biomarker for breast cancer diagnosis using the biomarker-dominated PCMA spectrochemical spectra of breast tissues. From 20 human breast tissues, the PCMA-linear discriminant analysis (PCMA-LDA) identification method achieved high classification performance with a sensitivity and specificity >99% along with an improvement of approximately 4.5% compared to the performance without the PCMA mixture analysis algorithm. Our label-free breast cancer detection method has the potential for clinical application to diagnose breast cancer in real-time during surgery.

Wavelength-dependent label-free identification of isolated nontuberculous mycobacteria using surface-enhanced Raman spectroscopy.

We investigated the effect of Raman excitation wavelengths on the surface-enhanced Raman spectroscopy (SERS)-based identification of isolated nontuberculous mycobacteria (NTM). The SERS spectra with 3 commonly used excitation wavelengths, 532, 638, and 785 nm, were compared across 6 representative NTM species that primarily cause human NTM infections in Korea and the United States; these species were identified. The statistical differences among NTM SERS spectra at each Raman excitation wavelength were verified using 1-way analysis of variance, and the 6 NTM species were identified using principal components-linear discriminant analysis with leave-one-out cross validation. The identification accuracies with aromatic amino acid biomarkers were 99.3%, 91.3%, and 90.7% for 532, 638, and 785 nm, respectively. We believe that the proposed SERS protocol with aromatic amino acid biomarkers at the 532-nm Raman excitation wavelength will enable fast and accurate identification of NTM compared to previous identification methods.

Effect of Novel Bioactive Glass-Containing Dentin Adhesive on the Permeability of Demineralized Dentin.

This study aimed to evaluate the effect of a novel bioactive glass (BAG)-containing dentin adhesive on the permeability of demineralized dentin. Bioactive glass (85% SiO2, 15% CaO) was fabricated using the sol-gel process, and two experimental dentin adhesives were prepared with 3 wt% silica (silica-containing dentin adhesive; SCA) or BAG (BAG-containing dentin adhesive; BCA). Micro-tensile bond strength (µTBS) test, fracture mode analysis, field-emission scanning electron microscopy (FE-SEM) analysis of adhesive and demineralized dentin, real-time dentinal fluid flow (DFF) rate measurement, and Raman confocal microscopy were performed to compare SCA and BCA. There was no difference in µTBS between the SCA and BCA (p > 0.05). Multiple precipitates were evident on the surface of the BCA, and partial occlusion of dentinal tubules was observed in FE-SEM of BCA-approximated dentin. The DFF rate was reduced by 50.10% after BCA approximation and increased by 6.54% after SCA approximation. Raman confocal spectroscopy revealed an increased intensity of the hydroxyapatite (HA) peak on the dentin surface after BCA application. The novel BAG-containing dentin adhesive showed the potential of both reducing dentin permeability and dentin remineralization.

Label-Free Surface-Enhanced Raman Spectroscopy Biosensor for On-Site Breast Cancer Detection Using Human Tears.

Surface-enhanced Raman scattering (SERS) is an ultrasensitive molecular screening technique with greatly enhanced Raman scattering signals from trace amounts of analytes near plasmonic nanostructures. However, research on the development of a sensor that balances signal enhancement, reproducibility, and uniformity has not yet been proposed for practical applications. In this study, we demonstrate the potential of the practical application for detecting or predicting asymptomatic breast cancer from human tears using a portable Raman spectrometer with an identification algorithm based on multivariate statistics. This potentiality was realized through the fabrication of a plasmonic SERS substrate equipped with a well-aligned, gold-decorated, hexagonal-close-packed polystyrene (Au/HCP-PS) nanosphere monolayer that provided femtomole-scale detection, giga-scale enhancement, and <5% relative standard deviation for reliability and reproducibility, regardless of the measuring site. Our results can provide a first step toward developing a noninvasive, real-time screening technology for detecting asymptomatic tumors and preventing tumor recurrence.

Time-dependent association between metabolic syndrome and risk of CKD in Korean men without hypertension or diabetes.

BACKGROUND: The time-dependent association between metabolic syndrome and risk of chronic kidney disease (CKD) is not clear. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: The study cohort was composed of 10,685 healthy men without CKD, hypertension, or diabetes who participated in a health-checkup program at a large work site. PREDICTOR: Metabolic syndrome. OUTCOMES & MEASUREMENTS: CKD was defined as an estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m(2). A standard Cox proportional hazards model and a time-dependent Cox model were used to calculate adjusted hazard ratios (HRs) in the CKD model. RESULTS: During 40,616.8 person-years of follow-up, 291 incident cases of CKD developed; 787 patients (7.4%) had metabolic syndrome at baseline and 1,444 (14.4%) developed incident metabolic syndrome during follow-up. After adjustment for age, baseline GFR, gamma-glutamyltransferase level, and uric acid level, metabolic syndrome at baseline was associated with a significantly increased risk of CKD (HR, 1.99; 95% confidence interval, 1.46 to 2.73). Metabolic syndrome over time as a time-dependent variable also predicted the development of CKD (HR, 1.83; [corrected] 95% confidence interval, 1.34 to 2.49) [corrected] The relationship between metabolic syndrome and incident CKD remained significant, even after further adjustment for the homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein level, current smoking, alcohol consumption, or regular exercise. In addition, there were graded relationships between number of metabolic syndrome traits or quintile of homeostasis model assessment of insulin resistance over time as a time-dependent variable and risk of CKD. Both increased triglyceride and low high-density lipoprotein cholesterol levels among metabolic syndrome traits were associated with significantly increased risk of CKD. These results were effectively unchanged, even after additional adjustment for incident hypertension and incident diabetes. LIMITATIONS: Estimated GFR was used instead of a directly measured GFR to define CKD. CONCLUSION: Metabolic syndrome is an independent risk factor for the development of CKD in Korean men without hypertension or diabetes, even with changes in status of metabolic syndrome over time.

Changes in body weight predict CKD in healthy men.

Several recent prospective studies have reported that obesity is associated with an increased risk for chronic kidney disease (CKD), but it is unknown whether weight gain increases the risk for CKD if one remains within the "normal" category of body mass index (BMI). We prospectively followed a cohort of 8792 healthy men who had no known risk factors for CKD and participated in a comprehensive health evaluation program at a large worksite. During 35,927 person-years of follow-up, 427 new incident cases of CKD (estimated GFR <64 ml/min per 1.73 m(2)) developed. Cox proportional hazards modeling revealed that in both the normal-weight and overweight groups, a U-shaped association between weight change categories and development of CKD was observed after adjustment for age, baseline GFR, baseline BMI, HDL, fasting blood glucose, uric acid, and exercise habits. The lowest risk for CKD was observed among those whose weight changed -0.25 to <0.25 kg/yr (P < 0.001 for quadratic term). Weight change as a time-dependent variable was significantly related to CKD incidence. These relationships remained significant even after further adjustment for Homeostasis Model Assessment of Insulin Resistance, high-sensitivity C-reactive protein, systolic BP, diastolic BP, metabolic syndrome, incident hypertension, or incident diabetes. In summary, increases in body weight are independently associated with an increased risk for CKD, even when the BMI remains within the normal range.

Risk factors for bone mineral density at the calcaneus in 40-59 year-old male workers: a cross-sectional study in Korea.

BACKGROUND: Few epidemiologic studies have attempted to investigate the prevalence and risk factors for osteopenia and osteoporosis in middle-aged Asian men. We performed this study to determine the prevalence and risk factors of osteopenia and osteoporosis in this population. METHODS: This cross-sectional study was conducted from March to July, 2004. The subjects were 2,073 males aged from 40 to 59 years in the KHNP (Korea Hydro & Nuclear Power) workplace-based cohort. Bone mineral density (BMD) was measured by peripheral, dual-energy, X-ray absorptiometry (DXA) at the calcaneus. Anthropometric and lifestyle factors were investigated using a standard, self-reported questionnaire. RESULTS: BMD was 0.60 +/- 0.09 g/cm2 (mean +/- standard deviation) and was negatively correlated with age (r = -0.18, P < 0.001), but positively correlated with waist-to-hip ratio (WHR; r = 0.15, P < 0.001), body fat (r = 0.10, P < 0.001), BMI (r = 0.35, P < 0.001), height (r = 0.26, P < 0.001), and weight (r = 0.43, P < 0.001). In multiple linear regression analysis, the independent determinants associated with BMD were increasing age (coefficient = -0.002, P < 0.001), physical activity (< or = 2/week vs. > or = 3/week; coefficient = 0.017, P < 0.001), WHR (coefficient = -0.796, P < 0.001), body mass index (BMI; coefficient = 0.023, P < 0.001) and smoking status (never vs. ever; coefficient = -0.018, P < 0.001). CONCLUSION: We suggest that BMD of the calcaneus is correlated negatively with exposure to smoke and increased WHR, but positively with regular exercise and increased BMI.

Radiation-related occupational cancer and its recognition criteria in South Korea.

Ionizing radiation is a well-known carcinogen, and is listed as one carcinogenic agent of occupational cancer. Given the increase in the number of workers exposed to radiation, as well as the increase in concern regarding occupational cancer, the number of radiation-related occupational cancer claims is expected to increase. Unlike exposure assessment of other carcinogenic agents in the workplace, such as asbestos and benzene, radiation exposure is usually assessed on an individual basis with personal dosimeters, which makes it feasible to assess whether a worker's cancer occurrence is associated with their individual exposure. However, given the absence of a threshold dose for cancer initiation, it remains difficult to identify radiation exposure as the root cause of occupational cancer. Moreover, the association between cancer and radiation exposure in the workplace has not been clearly established due to a lack of scientific evidence. Therefore, criteria for the recognition of radiation-related occupational cancer should be carefully reviewed and updated with new scientific evidence and social consensus. The current criteria in Korea are valid in terms of eligible radiogenic cancer sites, adequate latent period, assessment of radiation exposure, and probability of causation. However, reducing uncertainty with respect to the determination of causation between exposure and cancer and developing more specific criteria that considers mixed exposure to radiation and other carcinogenic agents remains an important open question.