Diagnosis and classification of kidney transplant rejection using machine learning-assisted surface-enhanced Raman spectroscopy using a single drop of serum.

The quest to reduce kidney transplant rejection has emphasized the urgent requirement for the development of non-invasive, precise diagnostic technologies. These technologies aim to detect antibody-mediated rejection (ABMR) and T-cell-mediated rejection (TCMR), which are asymptomatic and pose a risk of potential kidney damage. The protocols for managing rejection caused by ABMR and TCMR differ, and diagnosis has traditionally relied on invasive biopsy procedures. Therefore, a convergence system using a nano-sensing chip, Raman spectroscopy, and AI technology was introduced to facilitate diagnosis using serum samples obtained from patients with no major abnormality, ABMR, and TCMR after kidney transplantation. Tissue biopsy and Banff score analysis were performed across the groups for validation, and 5 µL of serum obtained at the same time was added onto the Au-ZnO nanorod-based Surface-Enhanced Raman Scattering sensing chip to obtain Raman spectroscopy signals. The accuracy of machine learning algorithms for principal component-linear discriminant analysis and principal component-partial least squares discriminant analysis was 93.53% and 98.82%, respectively. The collagen (an indicative of kidney injury), creatinine, and amino acid-derived signals (markers of kidney function) contributed to this accuracy; however, the high accuracy was primarily due to the ability of the system to analyze a broad spectrum of various biomarkers.

Early-stage diagnosis of bladder cancer using surface-enhanced Raman spectroscopy combined with machine learning algorithms in a rat model.

Early diagnosis and accurate assessment of tumor development facilitate early bladder cancer resection and initiation of drug therapy. This study enabled an early, accurate, label-free, noninvasive diagnosis of bladder tumors by analyzing nano-biomarkers in a single drop of urine through surface-enhanced Raman spectroscopy (SERS). In a standard N-butyl-N-4-hydroxybutyl nitrosamine-induced rat model of bladder cancer, cancer stage and polyp tumor development were monitored using a small endoscope with a diameter of 1.2 mm in a minimally invasive manner without the need to kill the rats. Samples were divided into cancer-free, early-stage, and polyp-form cancer. Training data were classified according to micro-cystoscopic 5-aminolevulinic acid fluorescence diagnosis, and specimens were postmortem verified through histopathological analysis. A drop of urine from each sample group was placed on an Au-coated zinc oxide nanoporous chip to filter nano-biomaterials and selectively enhance the Raman signals of nanoscale analytes via SERS. Principal component analysis was used to reduce the dimensionality of the collected Raman spectra, and partial least squares discriminant analysis was used to find diagnostic clusters based on the labeled samples. The combination of SERS and machine learning achieved an accuracy ≥99.6% in diagnosing both early- and polyp-stage bladder tumors. With an area under the receiver operating characteristic curve greater than 0.996, the accuracy of the diagnosis in the rat model suggests that SERS-based diagnostic methods are promising when coupled with machine learning. Low-cost, label-free, and noninvasive surface-enhanced Raman spectra are ideal for developing clinically relevant point-of-care diagnostic techniques.

Smartphone-Based Rigid Endoscopy Device with Hemodynamic Response Imaging and Laser Speckle Contrast Imaging.

Modern smartphones have been employed as key elements in point-of-care (POC) devices due to remarkable advances in their form factor, computing, and display performances. Recently, we reported a combination of the smartphone with a handheld endoscope using laser speckle contrast imaging (LSCI), suggesting potential for functional POC endoscopy. Here, we extended our work to develop a smartphone-combined multifunctional handheld endoscope using dual-wavelength LSCI. Dual-wavelength LSCI is used to monitor the changes in dynamic blood flow as well as changes in the concentration of oxygenated (HbO2), deoxygenated (Hbr), and total hemoglobin (HbT). The smartphone in the device performs fast acquisition and computation of the raw LSCI data to map the blood perfusion parameters. The flow imaging performance of the proposed device was tested with a tissue-like flow phantom, exhibiting a speckle flow index map representing the blood perfusion. Furthermore, the device was employed to assess the blood perfusion status from an exteriorized intestine model of rat in vivo during and after local ischemia, showing that blood flow and HbO2 gradually decreased in the ischemic region whereas hyperemia and excess increases in HbO2 were observed in the same region right after reperfusion. The results indicate that the combination of LSCI with smartphone endoscopy delivers a valuable platform for better understanding of the functional hemodynamic changes in the vasculatures of the internal organs, which may benefit POC testing for diagnosis and treatment of vascular diseases.

Label-free atherosclerosis diagnosis through a blood drop of apolipoprotein E knockout mouse model using surface-enhanced Raman spectroscopy validated by machine learning algorithm.

The direct preventative detection of flow-induced atherosclerosis remains a significant challenge, impeding the development of early treatments and prevention measures. This study proposes a method for diagnosing atherosclerosis in the carotid artery using nanometer biomarker measurements through surface-enhanced Raman spectroscopy (SERS) from single-drop blood samples. Atherosclerotic acceleration is induced in apolipoprotein E knockout mice which underwent a partial carotid ligation and were fed a high-fat diet to rapidly induce disturbed flow-induced atherosclerosis in the left common carotid artery while using the unligated, contralateral right carotid artery as control. The progressive atherosclerosis development of the left carotid artery was verified by micro-magnetic resonance imaging (micro-MRI) and histology in comparison to the right carotid artery. Single-drop blood samples are deposited on chips of gold-coated ZnO nanorods grown on silicon wafers that filter the nanometer markers and provide strong SERS signals. A diagnostic classifier was established based on principal component analysis (PCA), which separates the resultant spectra into the atherosclerotic and control groups. Scoring based on the principal components enabled the classification of samples into control, mild, and severe atherosclerotic disease. The PCA-based analysis was validated against an independent test sample and compared against the PCA-PLS-DA machine learning algorithm which is known for applicability to Raman diagnosis. The accuracy of the PCA modification-based diagnostic criteria was 94.5%, and that of the machine learning algorithm 97.5%. Using a mouse model, this study demonstrates that diagnosing and classifying the severity of atherosclerosis is possible using a single blood drop, SERS technology, and machine learning algorithm, indicating the detectability of biomarkers and vascular factors in the blood which correlate with the early stages of atherosclerosis development.

Diagnosis of Ischemic Renal Failure Using Surface-Enhanced Raman Spectroscopy and a Machine Learning Algorithm.

To diagnose renal function using a biochip capable of detecting SERS and to assess Raman measurements taken from a bilateral renal ischemia model and the feasibility of early diagnosis was done. After generating a bilateral renal ischemia rat model, blood and urine were collected. After confirming the presence of renal injury and function, liquid drops were placed onto a Raman chip whose surface had been enhanced with Au-ZnO nanorods. SERS biomarkers that diffused into the nanogaps were selectively amplified. Raman signals varied based on the severity of the renal function, and these differences were confirmed statistically. These results confirm that renal ischemia leads to renal dysfunction and that surface-enhanced Raman spectroscopy and a machine learning algorithm can be used to track signals in the urine from the release of SERS biomarkers.

Spectral Multiplexing of Fluorescent Endoscopy for Simultaneous Imaging with Multiple Fluorophores and Multiple Fields of View.

Complex clinical procedures and small-animal research procedures can benefit from dual-site imaging provided by multiple endoscopic devices. Here, an endoscopic system is proposed which enables multiple fluorescence microendoscopes to be spectrally multiplexed on a single microscope base, enabling light sources and optical relays to be shared between endoscopes. The presented system is characterized for resolution using USAF-1951 resolution test charts and for modulation transfer function using the slanted edge method. Imaging is demonstrated both directly and with microendoscopes attached. Imaging of phantoms was demonstrated by targeting USAF charts and fiber tissues dyed for FITC and Texas Red fluorescence. Afterwards, simultaneous liver and kidney imaging was demonstrated in mice expressing mitochondrial Dendra2 and injected with Texas Red-dextran. The results indicate that the system achieves high channel isolation and submicron and subcellular resolution, with resolution limited by the endoscopic probe and by physiological movement during endoscopic imaging. Multi-channel microendoscopy provides a potentially low-cost means of simultaneous multiple endoscopic imaging during biological experiments, resulting in reduced animal harm and potentially increasing insight into temporal connections between connected biological systems.

A Wi-Fi-Based Mask-Type Laryngoscope for Telediagnosis During the COVID-19 Pandemic: Instrument Validation Study.

BACKGROUND: Owing to the COVID-19 pandemic, social distancing has become mandatory. Wireless endoscopy in contactless examinations promises to protect health care workers and reduce viral spread. OBJECTIVE: This study aimed to introduce a contactless endoscopic diagnosis system using a wireless endoscope resembling a mask. METHODS: The Wi-Fi-based contactless mask endoscopy system comprises a disposable endoscope and a controller. First, the effective force applied by the tip during insertion was evaluated in a simple transoral model consisting of a force sensor on a simulated oropharynx wall. Second, the delay in video streaming was evaluated by comparing the frame rate and delays between a movement and its image over direct and Wi-Fi connections. Third, the system was applied to a detailed laryngopharyngeal tract phantom. RESULTS: The smartphone-controlled wireless endoscopy system was successfully evaluated. The mean, maximum, and minimum collision forces against the wall of the transoral model were 296 mN (30 gf), 363 mN (37 gf), and 235 mN (24 gf), respectively. The delay resulting from the wireless connection was 0.72 seconds. Using the phantom, an inexperienced user took around 1 minute to orient the endoscope to a desired area via the app. CONCLUSIONS: Device articulation does not pose a significant risk of laryngopharyngeal wall penetration, and latency does not significantly impede its use. Contactless wireless video streaming was successful within the access point range regardless of the presence of walls. The mask endoscope can be controlled and articulated wirelessly, minimizing contact between patients and device operators. By minimizing contact, the device can protect health care workers from infectious viruses like the coronavirus.

SERS Effect on Spin-Coated Seeding of Tilted Au-ZnO Nanorods for Low-Cost Diagnosis.

Uniformly parallel Au-coated ZnO nanorods have previously been shown to amplify local Raman signals, providing increased sensitivity to disease markers in the detection of inflammation and cancer. However, practical and cost-effective fabrication methods of substrates for surface-enhanced Raman spectroscopy (SERS) fail to produce highly uniform surfaces. Here, the feasibility of Raman enhancement on less-uniform substrates is assessed. ZnO nanorod structures were fabricated by hydrothermal synthesis, starting from spin-coated seed substrates. Following analysis, the nanostructures were coated with Au to create stochastically variant substrates. The non-uniformity of the fabricated Au-coated ZnO nanorod structures is confirmed morphologically by FE-SEM and structurally by X-ray diffraction, and characterized by the angular distributions of the nanorods. Monte Carlo finite element method simulations matching the measured angular distributions and separations predicted only moderate increases in the overall Raman enhancement with increasing uniformity. Highly variant substrates exhibited approximately 76% of the Raman enhancement of more uniform substrates in simulations and experiments. The findings suggest that, although highly inhomogeneous Au-coated ZnO nanorod substrates may not attain the same Raman enhancement as more uniform substrates, the relaxation of fabrication tolerances may be economically viable.

Modeling of long range transport pathways for radionuclides to Korea during the Fukushima Dai-ichi nuclear accident and their association with meteorological circulations.

The Lagrangian FLEXible PARTicle (FLEXPART) dispersion model and National Centers for Environmental Prediction/Global Forecast System (NCEP/GFS) meteorological data were used to simulate the long range transport pathways of three artificial radionuclides: (131)I, (137)Cs, and (133)Xe, coming into Korean Peninsula during the Fukushima Dai-ichi nuclear accident. Using emission rates of these radionuclides estimated from previous studies, three distinctive transport routes of these radionuclides toward the Korean Peninsula for a period from 10 March to 20 April 2011 were exploited by three spatial scales: 1) intercontinental scale - plume released since mid-March 2011 and transported to the North to arrive Korea on 23 March 2011, 2) global (hemispherical) scale - plume traveling over the whole northern hemisphere passing through the Pacific Ocean/Europe to reach the Korean Peninsula with relatively low concentrations in late March 2011 and, 3) regional scale - plume released on early April 2011 arrived at the Korean Peninsula via southwest sea of Japan influenced directly by veering mesoscale wind circulations. Our identification of these transport routes at three different scales of meteorological circulations suggests the feasibility of a multi-scale approach for more accurate prediction of radionuclide transport in the study area. In light of the fact that the observed arrival/duration time of peaks were explained well by the FLEXPART model coupled with NCEP/GFS input data, our approach can be used meaningfully as a decision support model for radiation emergency situations.

BMP2 shows neurotrophic effects including neuroprotection against neurodegeneration.

In this study, we found that BMP2 exerts neurotrophic effects, including a neuroprotective effect against nocodazole-induced neuritic degeneration, on neuronal cells. We also found that BMP2-induced neurotrophic effects are directly involved in Smad-dependent signaling as well as PI3K/PTEN-Akt-mTOR signaling. Moreover, BMP2-induced neurotrophic effects occur by stabilization of neuronal microtubules. Thus, these findings suggest that BMP2 can be a potential therapeutic target for nerve injury treatment.

Lactococcus lactis BFE920 activates the innate immune system of olive flounder (Paralichthys olivaceus), resulting in protection against Streptococcus iniae infection and enhancing feed efficiency and weight gain in large-scale field studies.

The protective effect of a food-grade lactic acid bacterium Lactococcus lactis BFE920 against disease of olive flounder (Paralichthys olivaceus) cultivated on a large scale was studied. Initially, antimicrobial activity of L. lactis against several fish pathogens was evaluated in vitro; the probiotic showed strong antibacterial activity against Streptococcus iniae, Streptococcus parauberis and Enterococcus viikkiensis, and moderate activity against Lactococcus garviae. When olive flounders were fed for two weeks with experimental diets containing varying concentrations of L. lactis (1 × 10(6), 5 × 10(6), 2.5 × 10(7) and 1.25 × 10(8) CFU/g feed), all the experimental feed groups showed 68-77% survival upon challenge with S. iniae. A field-scale feeding trial with L. lactis dietary supplement was conducted in a local fish farm (n = 12,000) for three months, and disease resistance, innate immune parameters and growth performance were evaluated. The average weight gain and feed efficiency were increased up to 6.8% and 8.5%, respectively. At the end of the feeding trial, the olive flounders were challenged with S. iniae. The L. lactis-fed group was protected from S. iniae challenge with a 66% survival rate. This disease protection is due to the flounder's innate immunity activated by the L. lactis administration: increased lysosomal activities and production of IL-12 and IFN-γ. These data clearly indicated that L. lactis BFE920 may be developed as a functional feed additive for protection against diseases, and for enhancement of feed efficiency and weight gain in olive flounder farming.

Memristor-based programmable logic array (PLA) and analysis as Memristive networks.

A Memristor theorized by Chua in 1971 has the potential to dramatically influence the way electronic circuits are designed. It is a two terminal device whose resistance state is based on the history of charge flow brought about as the result of the voltage being applied across its terminals and hence can be thought of as a special case of a reconfigurable resistor. Nanoscale devices using dense and regular fabrics such as Memristor cross-bar is promising new architecture for System-on-Chip (SoC) implementations in terms of not only the integration density that the technology can offer but also both improved performance and reduced power dissipation. Memristor has the capacity to switch between high and low resistance states in a cross-bar circuit configuration. The cross-bars are formed from an array of vertical conductive nano-wires cross a second array of horizontal conductive wires. Memristors are realized at the intersection of the two wires in the array through appropriate processing technology such that any particular wire in the vertical array can be connected to a wire in the horizontal array by switching the resistance of a particular intersection to a low state while other cross-points remain in a high resistance state. However the approach introduces a number of challenges. The lack of voltage gain prevents logic being cascaded and voltage level degradation affects robustness of the operation. Moreover the cross-bars introduce sneak current paths when two or more cross points are connected through the switched Memristor. In this paper, we propose Memristor-based programmable logic array (PLA) architecture and develop an analytical model to analyze the logic level on the memristive networks. The proposed PLA architecture has 12 inputs maximum and can be cascaded for more input variables with R(off)/R(on) ratio in the range from 55 to 160 of Memristors.

Changes in oxidative stress biomarker and gene expression levels in workers exposed to volatile organic compounds.

Exposure to volatile organic compounds (VOCs) was known to result in immunologic, respiratory, carcinogenic, reproductive, neurologic, and cardiovascular effects. However, the mechanisms by which VOCs induce these adverse health effects are not well understood. To evaluate the change of oxidative stress biomarker and gene expression levels in workers exposed to VOCs, we obtained urine and blood samples from 21 subjects before and after occupational exposure to VOCs. We measured levels of muconic acid (MuA), hippuric acid (HA), mandelic acid (MaA), and methyl hippuric acid (MHA) as urinary exposure biomarkers for benzene, toluene, ethylbenzene, and xylene (collectively BTEX), and malondialdehyde (MDA) and 8-hydroxydeoxyguanine (8-OHdG) as oxidative stress biomarkers in all subjects. We also evaluated BTEX-mediated RNA expression using cDNA microarray in 14 subjects. HA and MHA levels were higher following occupational exposure to VOCs (p < 0.01). In the linear regression analysis, HA ratios of after- and before-exposure were found to be significantly associated with increase of MDA ratios of after- and before-exposure after controlling for age, body mass index, and smoking (ß = 0.06, p = 0.031). Evaluation of the gene expressions by HA showed that 23 gene expressions were found to be significantly associated with HA levels after adjusting for age, body mass index, and smoking (p < 0.001). In particular, expressions of ENO3 and CDNA FLJ39461 fis among the 23 genes were significantly associated with the change in MDA level (p < 0.05). Our study results suggest that exposure to VOCs, specifically toluene, induces oxidative stress and various gene expression change of which some may be responsible for oxidative stress.

TLR4-mediated activation of mouse macrophages by Korean mistletoe lectin-C (KML-C).

Korean mistletoe lectin (KML-C) is an adjuvant that activates systemic and mucosal immune cells to release cytokines including TNF-alpha, which induces immunity against viruses and cancer cells. Although the immunomodulatory activity of KML-C has been well established, the underlying mechanism of action of KML-C has yet to be explored. When mouse peritoneal macrophages were treated with KML-C, both transcription and translation of TLR4 were upregulated. KML-C-induced TLR4 downstream events were similar to those activated by LPS: the upregulation of interleukin-1 receptor-associated kinase-1 (IRAK1); resulting in macrophage activation and TNF-alpha production. When TLR4 was blocked using a TLR4-specific neutralizing antibody, TNF-alpha production from the macrophages was significantly inhibited. Moreover, TLR4-deficient mouse macrophages treated with KML-C also secreted greatly reduced level of TNF-alpha secretion. Finally, TLR4 molecules were co-precipitated with KML-C, to which agarose beads were conjugated, indicating that those molecules are associated. These data indicate that KML-C activates mouse macrophages to secrete TNF-alpha by interacting with the TLR4 molecule and activating its signaling pathways.

Differential oxidative stress response in young children and the elderly following exposure to PM(2.5).

OBJECTIVES: The mechanism of the adverse health effects of ambient particulate matter on humans has not been well-investigated despite many epidemiologic association studies. Measurement of personal exposure to particulate pollutants and relevant biological effect markers are necessary in order to investigate the mechanism of adverse health effects, particularly in fragile populations considered to be more susceptible to the effects of pollutants. METHODS: We measured personal exposure to PM(2.5) and examined oxidative stress using urinary malondialdehyde three times in 51 preschoolers and 38 elderly subjects. A linear mixed-effects model was used to estimate PM(2.5) effects on urinary MDA levels. RESULTS: Average personal exposure of the children and elderly to PM(2.5) was 80.5 +/- 29.9 and 20.7 +/- 12.7 mug/m(3), respectively. Mean urinary MDA level in the children and the elderly was 3.6 +/- 1.9 and 4.0 +/- 1.6 mumol/g creatinine. For elderly subjects the PM(2.5) level was significantly associated with urinary MDA after adjusting for age, sex, BMI, passive smoking, day-care facility site, alcohol consumption, cigarette smoking, and medical history (heart disease, hypertension and bronchial asthma). However, there was no significant relationship for children. CONCLUSIONS: The elderly were more susceptible than young children to oxidative stress as a result of ambient exposure to PM(2.5). Identification of oxidative stress induced by PM(2.5) explains the mechanism of adverse health effects such as cardiovascular or respiratory diseases, particularly in the elderly.

Community level exposure to chemicals and oxidative stress in adult population.

Little information is available on the role of environmental chemical exposure in oxidative stress. This study was designed to investigate whether exposure to environmental chemicals, such as polycyclic aromatic hydrocarbons, volatile organic compounds, bisphenol A or phthalates, induces oxidative stress in urban adult populations. A total of 960 adults dwelling in urban areas were evaluated between April and December 2005. To assess environmental chemical exposure, we measured urinary levels of 1-hydroxypyrene, 2-naphthol, hippuric acid, methyl hippuric acid, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, and mono-butyl phthalate and bisphenol A. Urinary malondialdehyde and 8-hydroxydeoxyguanosine were also measured to evaluate oxidative stress. Significant dose-responsive relationship was found between urinary concentrations of the chemical exposure biomarkers and oxidative stress levels in simple regression analyses (P<0.05). Regression coefficients of these exposure biomarkers except bisphenol A remained significantly in the multiple regression models after controlling for age, sex, weight, smoking, and exercise for at least one of the two oxidative stress biomarkers (P<0.05). The oxidative stress biomarkers significantly affected the indicators of insulin resistance, particularly glucose level. This study indicates that environmental chemical exposure is associated with oxidative stress in urban adult populations and suggests that exposure to certain environmental chemicals might contribute to insulin resistance.

Maternal exposure to environmental tobacco smoke, GSTM1/T1 polymorphisms and oxidative stress.

Environmental tobacco smoking (ETS) is known to be associated with adverse pregnancy outcomes. The purpose of this study was to investigate the relationship between maternal exposure to ETS and oxidative stress for neonates, as well as the effect of maternal genetic polymorphisms, glutathione-S-transferase M1 (GSTM1) and GSTT1, on this relationship. We used the radioimmunoassay to measure the urinary concentration of cotinine in 266 pregnant women who denied smoking cigarettes during pregnancy and in their singleton babies. In addition, the urinary concentration of malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were assessed using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. We also extracted DNA from whole blood obtained from the mothers and then conducted polymerase chain reaction on the samples to determine the GSTM1 and GSTT1 genotypes. The maternal cotinine concentration was found to be significantly associated with the fetal cotinine concentration, particularly for mothers whose urine cotinine concentrations were above 120 microg/gcr (p<0.01). The fetal urine cotinine concentration was also found to be significantly associated with the fetal urine MDA concentration (p<0.01). When the null type maternal GSTM1 or the wild type GSTT1 was present, the maternal oxidative stress level increased significantly as the maternal continine concentration increased (MDA: p<0.01; 8-OH-dG: p<0.01). No significant relationships were found between maternal cotinine and fetal oxidative stress markers, however, the fetal MDA levels increased significantly as fetal cotinine levels increased. These results suggest that the maternal exposure to ETS affects the fetal urine cotinine concentration and induces production of maternal oxidative stress. In addition, maternal genetic polymorphisms of GSTM1 and GSTT1 may modify the oxidative stress by maternal exposure to ETS.

Maternal and fetal exposure to bisphenol A in Korea.

Bisphenol A (BPA) is a well-known endocrine disrupter used widely. Despite the potential risk of human exposure to BPA, little information exists concerning maternal and fetal exposure to BPA during pregnancy in Korea. This study purposed to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels to BPA in Korean pregnant women and their fetuses. Maternal blood and umbilical cord blood were collected from 300 subjects, and total BPA levels were measured. Blood BPA concentrations ranged from non-detectable to 66.48 microg/L in pregnant women and from non-detectable to 8.86 microg/L in umbilical cords. Serum BPA levels in most pregnant women were higher than in corresponding fetal umbilical cords and a positive correlation was found between in maternal and fetal BPA concentrations (p<0.05).

Metals in particulate pollutants affect peak expiratory flow of schoolchildren.

BACKGROUND: The contribution of the metal components of particulate pollutants to acute respiratory effects has not been adequately evaluated. Moreover, little is known about the effects of genetic polymorphisms of xenobiotic metabolism on pulmonary function. OBJECTIVES: This study was conducted to assess lung function decrement associated with metal components in particulate pollutants and genetic polymorphisms of glutathione S-transferase M1 and T1. METHODS: We studied 43 schoolchildren who were in the 3rd to 6th grades. Each student measured peak expiratory flow rate three times a day for 42 days. Particulate air concentrations were monitored every day, and the concentrations of iron, manganese, lead, zinc, and aluminum in the particles were measured. Glutathione S-transferase M1 and T1 genetic polymorphisms were determined using DNA extracted from participant buccal washings. We used a mixed linear regression model to estimate the association between peak expiratory flow rate and particulate air pollutants. RESULTS: We found significant reduction in the peak expiratory flow rate after the children's exposure to particulate pollutants. The effect was shown most significantly 1 day after exposure to the ambient particles. Manganese and lead in the particles also reduced the peak expiratory flow rate. Genetic polymorphisms of glutathione S-transferase M1 and T1 did not significantly affect peak expiratory flow rate. CONCLUSIONS: This study demonstrated that particulate pollutants and metals such as manganese and lead in the particles are associated with a decrement of peak expiratory flow rate. These effects were robust even with consideration of genetic polymorphisms of glutathione S-transferase.

Seasonal variation of effect of air pollution on blood pressure.

BACKGROUND: Many studies have shown a consistent association between ambient air pollution and an increase in death due to cardiovascular causes. An increase in blood pressure is a common risk factor for a variety of cardiovascular diseases. However, the association between air pollution and blood pressure has not been evaluated extensively. METHODS: In this cross-sectional study, we measured blood pressure in 10,459 subjects who had a health examination from 2001 to 2003, and calculated individual's exposure to ambient levels of air pollutants. To evaluate the relationship between exposure to air pollutants and blood pressure with respect to season, we performed a multiple regression analysis, separately, according to season, controlling for individual characteristics and meteorological variables. RESULTS: In the warm-weather season (July-September), particulate air pollutant of <10 microm (PM(10)) and nitrogen dioxide (NO(2)) concentrations were significantly associated with measures of blood pressure. During cold weather (October-December), blood pressure was significantly associated with sulphur dioxide (SO(2)) and ozone (O(3)) concentrations. The significant association between PM(10) or NO(2) and blood pressure disappeared during the cold-weather season. CONCLUSION: We found a seasonal variation for the association between ambient air-pollutant concentrations and blood pressure.