Estimates of particulate matter inhalation doses during three-dimensional printing: How many particles can penetrate into our body?

Harmful emissions including particulates, volatile organic compounds, and aldehydes are generated during three-dimensional (3D) printing. Ultrafine particles are particularly important due to their ability to penetrate deep into the lung. We modeled inhalation exposure by particle size during 3D printing. A total of six thermoplastic filaments were used for printing under manufacturer's recommended conditions, and particle emissions in the size range between 10 nm and 10 µm were measured. The inhalation exposure dose including inhaled and deposited doses was estimated using a mathematical model. For all materials, the number of particles between 10 nm and 1 µm accounted for a large proportion among the released particles, with nano-sized particles being the dominant size. More than 1.3 × 109 nano-sized particles/kgbw/g (95.3 ± 104.0 ng/kgbw/g) could be inhaled, and a considerable amount was deposited in respiratory regions. The total deposited dose in terms of particle number was 3.1 × 108 particles/kgbw/g (63.6% of the total inhaled dose), and most (41.3%) were deposited in the alveolar region. The total mass of particles deposited was 19.8 ± 16.6 ng/kgbw/g, with 10.1% of the total mass deposited in the alveolar region. Given our findings, the inhalation exposure level is mainly determined by printing conditions, particularly the filament type and manufacturer-recommended extruder temperature.

Resistance-Breaking Tomato Spotted Wilt Virus Variant that Recently Occurred in Pepper in South Korea is a Genetic Reassortant.

Tomato spotted wilt virus (TSWV) is a destructive viral pathogen in various crops, including pepper. Although the single dominant gene Tsw has been utilized in pepper breeding to confer resistance to TSWV, the occurrence of TSWV variants that overcome Tsw-mediated resistance has been reported in various countries after several years of growing resistant cultivars. In this study, we determined the complete genome sequence of a resistance-breaking TSWV variant (TSWV-YI) that recently emerged in pepper in South Korea. TSWV-YI infected all of the resistant pepper cultivars tested. The phylogenetic and recombination analyses of the complete TSWV-YI genome sequence showed that it is a reassortant that acquired its L and M RNA segments from the existing South Korean TSWV population and its S RNA in an isolate from another country. Given that TSWV-YI is a resistance-breaking variant, it appears that reassortment of the S RNA led to the emergence of this variant that breaks the Tsw gene in pepper grown in South Korea. Our results suggest that resistance-breaking TSWV variants are a potential threat to pepper production in South Korea and that strategies to manage these variants should be developed to ensure sustainable pepper production.

Interpreting complex geochemistry of groundwater in a coastal paddy field near a mine using isotopic signatures of sulfate and water.

In the area around the abandoned Seoseong mine, South Korea, coastal paddy fields undergo seawater intrusion and possible sulfate reduction. Here, channel water is used for irrigation, fertilizers are applied, and some paddy fields are contaminated by mining activities, which subsequently contaminate a groundwater well with arsenic. In this complex environment, the isotopic signatures of sulfate and water in water samples were assessed to reveal sources of sulfate, water and processes in the groundwater system. Sulfur and oxygen isotopes of sulfate indicated three major sources of sulfate-namely the mine including tailings, intruded seawater, and fertilizer-and an additional process of sulfate reduction. The sulfate sources and sulfate reduction could be distinguished more clearly after the variable of sulfate contribution from seawater was introduced. According to the analysis results of hydrogen and oxygen isotopes of water, areas affected by irrigation from a reservoir and its downstream channel were distinguished, possibly because the reservoir underwent evaporation effect. A schematic diagram was proposed to explain complex sources and processes in the studied area. Especially, a suggested plot of δ34SSO4 against the sulfate contribution from seawater [f(SO42-seawater)] could efficiently differentiate various contamination sources (e.g., mining activity and fertilizer) and processes (e.g., seawater intrusion and sulfate reduction) in coastal aquifer.

Determination of soil contamination sources in mining area using Zn/Cd ratios with mobile Cd.

Paddy fields near metalliferous mining area are sometimes contaminated by tailings or mine water. In the contaminated paddy fields around the abandoned Seoseong mine, South Korea, groundwater, surface water, and soil samples were assessed to infer sources (tailings and/or mine water) of soil contamination. Major contaminants in the soil included As and Pb which were not detected in the adit water. Moreover, δ34SSO4 values of groundwater at contaminated downstream paddy fields were higher than those of ground and surface water in the mining area, which indicated water-derived contamination is not evident. The Zn/Cd ratios of soil were assessed to verify the source (tailings) of soil contamination. Plots of the Zn/Cd ratio against Zn and As contents showed that soil samples contaminated from tailings had Zn/Cd ratios (108-247) which were similar with the Zn/Cd range of the tailings. In contrast, the ratios of the soil samples were different from the Zn/Cd range of contaminated water samples. The Zn/Cd ratios were determined using 0.1 M HCl-extractable Cd, and the fraction of 0.1 M HCl-extractable Cd in aqua regia-digestible Cd increased with increasing aqua regia-digestible Cd content. These observations suggest that Zn/Cd ratios in contaminated soil are primarily controlled by 0.1 M HCl-extractable Cd, possibly due to the greater exchangeability of 0.1 M HCl-extractable Cd than that of total Cd. This suggests that Zn/Cd ratios determined using 0.1 M HCl-extractable Cd can be especially sensitive and useful for determining sources of soil contamination in mining areas such as tailings or contaminated water.

White matter alterations in narcolepsy patients with cataplexy: tract-based spatial statistics.

Functional imaging studies and voxel-based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus-thalamus-orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake-sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug-naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug-naïve narcolepsy patients with cataplexy (n = 22) and healthy age- and gender-matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole-brain diffusion tensor imaging, and tract-based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto-orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto-orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract-based spatial statistics study demonstrated that drug-naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy.

Determination of lamotrigine in human serum by high-performance liquid chromatography­tandem mass spectrometry.

A rapid and sensitive liquid chromatography­tandem mass spectrometry method was developed and validated for quantification of lamotrigine in human serum. After a simple protein precipitation using acetonitrile, the analytes were separated on a Shideido 150 mm × 2.0 mm, 5 µm Capcell Pak C18 MG column using 70% acetonitrileas mobile phase at a flow rate of 200 µl/min. Lamotrigine was eluted at 1.98 min, ionized using electrospray ionization source, and then detected by multiple reaction monitoring mode. The precursor to product ion transitions of m/z 256.1­109.0 was used to quantify. The analytical measurement range is from 0.1 to 20 µg/ml and the upper clinical reportable range is chosen to be 100 µg/ml. The method was successfully employed in a clinical application.

Comparison of the validity of three biomarkers for gastric cancer screening: carcinoembryonic antigen, pepsinogens, and high sensitive C-reactive protein.

PURPOSE: To identify a desirable serum marker for screening tools for gastric cancer, we evaluated the validity of 3 biomarkers, namely, carcinoembryonic antigen (CEA), pepsinogens (PGs), and high sensitive C-reactive protein (hsCRP). METHODS: We estimated the mean serum levels of CEA, PGs, and hsCRP and compared the sensitivity and specificity of these 3 biomarkers in 378 subjects who were classified into 7 groups: normal, chronic atrophic gastritis, intestinal metaplasia, adenoma, early gastric cancer (EGC), advanced gastric cancer (AGC) without metastasis, and AGC with metastasis (M1). RESULTS: There were no significant differences among the normal, high-risk (chronic atrophic gastritis, intestinal metaplasia, and adenoma), and EGC groups for CEA and hsCRP. However, the levels of CEA were relatively higher in the AGC group with intestinal-type cancer (P<0.01). Likewise, hsCRP was relatively higher in the AGC group with diffuse-type cancer (P<0.01). For the PG I/II ratio, there was no significant difference among the normal, high-risk, and cancer groups, including EGC (P<0.01). In addition, there was a negative correlation with grades (gammas=-0.480, P<0.01). However, the PG I/II ratio was relatively less effective in diffuse-type cancer compared with intestinal-type cancer. The combination of serum hsCRP and the PG I/II ratio had a higher sensitivity (77%) than did the PG I/II ratio alone (61%) in diffuse-type cancers. CONCLUSIONS: The combination of serum hsCRP and PG I/II ratio would be helpful as a screening tool for gastric cancer in high incidence populations and may help to select high-risk subjects in need of further specific invasive screening tools such as endoscopy.

Identification of HLA-A33-restricted CMV pp65 epitopes as common targets for CD8(+) CMV-specific cytotoxic T lymphocytes.

OBJECTIVE: To identify an immunodominant HLA-A33-restricted epitope within the CMV matrix phosphoprotein 65 (pp65) that could be used to elicit CMV-specific CTLs. METHODS: A computer algorithm was used to identify pp65 peptides that were expected to bind to HLA-A33. The peptides were screened for their ability to reactivate memory T lymphocytes from CMV-seropositive HLA-A33 donors by using quantitative real-time RT-PCR. The most promising peptides were then tested for their ability to expand a CD8(+) population of HLA-A33 CTLs that produced interferon-gamma (IFN-gamma) and were cytotoxic to either peptide-loaded or CMV-infected target cells. RESULTS: Sixteen out of 250 peptides were selected using a computer algorithm and peptide stimulation by 8 out of the 16 induced a significant quantity of IFN-gamma mRNA transcript from CMV-seropositive HLA-A33 peripheral blood mononuclear cells. All the eight peptides induced consistent T-cell reactivation. One specifically, the peptide pp65(91-100) (SVNVHNPTGR), proved to be more active. T cells in vitro sensitized for 2 or 3 weeks with pp65(91-100) were cytotoxic to both HLA-A33 peptide-loaded and CMV-infected target cells. CONCLUSIONS: CMV pp65(91-100) is a new HLA-A33-restricted peptide that broadens the list of antigenic determinants that can be used for CMV adoptive immunotherapy.

Adsorption of As(III), As(V) and Cu(II) on zirconium oxide immobilized alginate beads in aqueous phase.

A composite adsorbent to remove arsenite [As(III)], arsenate [As(V)], and copper [Cu(II)] from aqueous phase was synthesized by immobilizing zirconium oxide on alginate beads (ZOAB). The composition (wt%) of ZOAB (Zr-34.0; O-32.7; C-21.3; Ca-1.0) was confirmed by energy dispersive X-ray (EDX) analysis. Sorption studies were conducted on single and binary sorbate systems, and the effects of contact time, initial adsorbate concentration, and pH on the adsorption performance of ZOAB (pHPZC = 4.3) were monitored. The sorption process for As(III)/As(V) and Cu(II) reached an equilibrium state within 240 h and 24 h, respectively, with maximum sorption capacities of 32.3, 28.5, and 69.9 mg g(-1), respectively. The addition of Cu(II) was favorable for As(V) sorption in contrast to As(III). In the presence of 48.6 mg L(-1) Cu(II), the sorption capacity of As(V) increased from 1.5 to 3.8 mg g(-1) after 240 h. The sorption data for As(III)/As(V) and Cu(II) conformed the Freundlich and Langmuir isotherm models, respectively. The adsorption of As(III), As(V), and Cu(II) followed pseudo second order kinetics. The effect of arsenic species on Cu(II) sorption was insignificant. The results of present study demonstrated that the synthesized sorbent could be useful for the simultaneous removal of both anionic and cationic contaminants from wastewaters.

The neural correlates of motor intentional disorders in patients with subcortical vascular cognitive impairment.

Subcortical vascular cognitive impairment (SVCI) refers to cognitive impairment associated with small vessel disease. Motor intentional disorders (MID) have been reported in patients with SVCI. However, there are no studies exploring the neuroanatomical regions related to MID in SVCI patients. The aim of this study, therefore, was to investigate the neural correlates of MID in SVCI patients. Thirty-one patients with SVCI as well as 10 healthy match control participants were included. A "Pinch-Grip" apparatus was used to quantify the force control capabilities of the index finger in four different movement phases including initiation, development, maintenance, and termination. All participants underwent magnetic resonance imaging (MRI). Topographical cortical areas and white matter tracts correlated with the performances of the four different movement phases were assessed by the surface-based morphometry and tract-based spatial statistics analyses. Poorer performance in the maintenance task was related to cortical thinning in bilateral dorsolateral prefrontal, orbitofrontal and parietal cortices, while poorer performance in the termination task was associated with the disruption of fronto-parietal cortical areas as well as the white matter tracts including splenium and association fibers such as superior longitudinal fasciculus. Our study demonstrates that cortical areas and underlying white matter tracts associated with fronto-parietal attentional system play an important role in motor impersistence and perseveration in SVCI patients.

Evaluation of the extraction method for the cytotoxicity testing of latex gloves.

In this study, the cytotoxicity of medical latex gloves to cultured L-929 cells was determined using various extraction conditions. According to the extraction time and temperature, three types of extraction conditions were used: 1) 24 h at 37 degrees C; 2) 72 h at 37 degrees C; 3) 72 h at 50 degrees C. Also, four different extraction vehicles were used, namely, distilled water (DW), 9 g/l sodium chloride (saline) in DW, and culture media with or without serum. Under the above-mentioned conditions, the samples were extracted and then 2-fold serially diluted in the concentration range 3.13 - 50%. When extracted with either DW or saline for 24 h or 72 h at 37 degrees C, only 50% diluted samples showed distinct cytotoxicity to L-929 cells. Moreover, no cytotoxic potentials were observed when gloves were extracted with DW or saline at 50 degrees C for 72 h. Cytotoxicity was markedly greater when gloves were extracted with culture medium, irrespective of the presence of serum in the medium. These results suggest that optimal extraction conditions should be established for the cytotoxicity evaluations of biomaterials and medical devices.

A framework to analyze cerebral mean diffusivity using surface guided diffusion mapping in diffusion tensor imaging.

The mean diffusivity (MD) value has been used to describe microstructural properties in Diffusion Tensor Imaging (DTI) in cortical gray matter (GM). Recently, researchers have applied a cortical surface generated from the T1-weighted volume. When the DTI data are analyzed using the cortical surface, it is important to assign an accurate MD value from the volume space to the vertex of the cortical surface, considering the anatomical correspondence between the DTI and the T1-weighted image. Previous studies usually sampled the MD value using the nearest-neighbor (NN) method or Linear method, even though there are geometric distortions in diffusion-weighted volumes. Here we introduce a Surface Guided Diffusion Mapping (SGDM) method to compensate for such geometric distortions. We compared our SGDM method with results using NN and Linear methods by investigating differences in the sampled MD value. We also projected the tissue classification results of non-diffusion-weighted volumes to the cortical midsurface. The CSF probability values provided by the SGDM method were lower than those produced by the NN and Linear methods. The MD values provided by the NN and Linear methods were significantly greater than those of the SGDM method in regions suffering from geometric distortion. These results indicate that the NN and Linear methods assigned the MD value in the CSF region to the cortical midsurface (GM region). Our results suggest that the SGDM method is an effective way to correct such mapping errors.

Extrafrontal structural changes in juvenile myoclonic epilepsy: a topographic analysis of combined structural and microstructural brain imaging.

PURPOSE: An increasing amount of evidence has demonstrated that juvenile myoclonic epilepsy (JME) is associated with structural abnormalities in not only the thalamofrontal system but its adjacent regions such as temporal or parieto-occipital areas. The goal of this study was to systematically characterize morphological changes and the subsequent pathophysiological implications in JME patients using the combined structural and diffusion tensor MRI analysis. METHODS: Comparisons of white matter (WM) water diffusivity and gray matter (GM) cortical thickness were analyzed with tract-based spatial statistics (TBSS) and a Constrained Laplacian-based Anatomic Segmentation with Proximity (CLASP) algorithm, respectively. Additionally, volumes of the bilateral thalami and hippocampi were obtained using manual volumetry (MV). RESULTS: Compared with 22 normal controls, 18 patients with JME exhibited WM alterations in the antero-superior corona radiata, corpus callosum, both centro-parietal regions, and the left temporal lobe. JME patients also had reduced GM thickness (right paracentral lobule, precuneus, dorsolateral parietal and inferior temporal cortex; left dorsolateral frontal and anterior temporal areas). Furthermore, MV analyses revealed a significant volume reduction in the bilateral thalami and hippocampi. CONCLUSIONS: In addition to structural changes in the thalamofrontal system, there was a conspicuous alteration of WM diffusivity in widespread extra-frontal areas and an associated decreased GM thickness in temporoparietal regions, including a significant reduction of hippocampal volume. These findings suggest that the pathophysiology of JME may be not confined to the thalamofrontal circuit but may also involve extensive areas of the extra-frontal network which encompasses temporo-parietal regions.

Changes in background electroencephalography and regional cerebral glucose metabolism in focal epilepsy patients after 1-month administration of levetiracetam.

The antiseizure efficacy and safety of levetiracetam (LEV) is well documented; however, few clinical studies have investigated the predictability of patient responsiveness to LEV, especially when the drug is first administered. The aim of this study was to ascertain the utility of clinical, electrophysiological, and neuroimaging parameters for assessing the early response to LEV treatment in focal epilepsy patients. Twelve confirmed focal epilepsy patients were included who had never taken LEV before. At baseline and 1 month after LEV administration, all subjects underwent 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and electroencephalography (EEG), and completed the Quality of Life in Epilepsy questionnaire (QOLIE-31). Participants were divided by drug response: good versus poor. The good response group (seven subjects) was defined by a >50% decrease in seizure frequency compared to baseline (3 months before LEV intake). The other five participants with a <50% decrease in seizure frequency were placed into the poor response group. We compared the differential changes in brain glucose metabolism on FDG-PET, power spectrum on the EEG, and QOLIE-31 results between the two groups after a 1-month LEV trial. In the good response group, it was possible to identify brain regions with increased glucose metabolism, including the bilateral caudate nuclei and both frontal and left parietal regions (uncorrected P<0.005). In the poor response group, FDG-PET did not reveal any areas with significantly increased glucose metabolism. In the good response group, spectral EEG analysis revealed decreased delta power (1-3 Hz, P<0.05) in the parietal region and increased beta1 power (13-19 Hz, P<0.05) in the frontal region, whereas no significant changes were observed in the poor response group. There were no significant changes on the QOLIE-31 in either group after a 1-month LEV trial. Our results suggest that LEV-induced glucose metabolism and EEG spectral changes may be indicative of initial drug responsiveness as early as 1 month following treatment initiation. These parameters may be useful prognostic markers of antiseizure effects caused by LEV medication or may indicate an epiphenomenon of LEV-induced changes in glucose metabolism and EEG frequency. Further studies with larger sample sizes are warranted.

Evaluation of the cytotoxicity of polyetherurethane (PU) film containing zinc diethyldithiocarbamate (ZDEC) on various cell lines.

A polyetherurethane (PU) film containing 0.1% zinc diethyldithiocarbamate (ZDEC) is the international standard reference material for testing the in vitro cytotoxicity of polymer based biomaterials. Nowadays, culturing L929 or BALB/3T3 cells in direct contact or in an extract dilution condition is the most frequently using method for evaluating the cytotoxicity from biomaterials and medical devices. However, the results often vary, because it is directly related to the cellular functions and the mechanism of the toxicity of the contacting cells. In this study, 13 cell lines originating from various tissues were used to detect the cytotoxic activities of a PU film containing 0.1% ZDEC (PU-ZDEC). The correlation between the reactivity zone size and the relative cytotoxicity by quantifying the released total protein from each cell in the direct contact testing method was investigated. Hepa-1c1c7 cells demonstrated the highest sensitivity in the reactivity zone size, while CHO/dhFr(-) cells were the most sensitive in terms of the relative cytotoxicity. A correlation between the two processes in each cell line was not found (r=-0.478). In the extract dilution method, which involved cultivating the cells in the medium with various ZDEC concentrations prepared by diluting the PU incubation, the cytotoxicity increased with increasing ZDEC concentration in all cell lines. The BALB/ 3T3 cells demonstrated the highest sensitivity in the extract dilution method. No correlation in a comparison of the relative cytotoxicity from the direct contact method with the extract dilution method in each cell line, was found (r=-0.445). In this experiment, Hepa-1c1c7, BALB/3T3, CHO/dhFr(-) and L-929 cells among the 13 types of cell lines were the sensitive cell lines according to the two methods. The preliminary results suggest that a comparison of at least one or more cytotoxicity testing methods and many cell lines is necessary for an in vitro cytotoxicity test of biomaterials.

Adoptive immunotherapy for cytomegalovirus (CMV) disease in immunocompromised patients.

Cytomegalovirus (CMV) reactivation in immune compromised patients such as those undergoing hematopoietic progenitor cell transplantation (HPCT) and those with HIV infections can cause severe morbidity and mortality despite treatment with appropriate antiviral agents. The recovery of Cytomegalovirus (CMV) specific cytotoxic T lymphocytes (CTL) plays an important role in the reconstitution of CMV specific immunity in immunocompromised patients. Recent studies have reported that CMV reactivation can be successfully treated by adoptive transfer of CMV-specific T cell clones from CMV seropositive donors expanded in vitro with CMV infected fibroblasts or lysates of CMV infected cells. Other studies have used immune dominant CMV proteins or peptides to expand CMV-specific cytotoxic T lymphocytes. This review describes the clinical manifestations of CMV disease in immunocompromised patients, recent advances of antiviral therapy for CMV disease, the principals of the induction of cellular immune response to CMV, and the clinical application of CMV immunotherapy.

Education and certification of laboratory medicine.

Not only are there differences in the definition of a specialist, but there are also different education systems for residents and certifications of specialists of laboratory medicine from country to country. The resident education program, the certification system of specialists of laboratory medicine, requirements for specialist examination, requirements for training hospitals, and the quota system for resident distribution in Korea are reported here for comparison with other countries' systems. Also, the function of a specialist society for laboratory medicine is described, to demonstrate its profound involvement in the education and certification of laboratory medicine.

Association of urinary sodium/creatinine ratio and urinary sodium/specific gravity unit ratio with blood pressure and hypertension: KNHANES 2009-2010.

BACKGROUND: We investigated the association between urinary sodium/creatinine ratio (U[Na(+)]/Cr) or urinary sodium/specific gravity unit ratio (U[Na(+)]/SGU), estimated from spot urine, and blood pressure (BP) and hypertension. METHODS: The study population consisted of a total of 9674 adults (4478 men, 5196 women) who participated in the Korea National Health and Nutrition Examination Surveys conducted in 2009 and 2010. Urine levels of sodium and creatinine, urine specific gravity (SG), and BP were measured along with other risk factors of hypertension. SGU is the calculated parameter of (SG-1)×100. RESULTS: There were significant trends of increasing mean systolic and diastolic BPs and prevalence of hypertension with increasing quartile of U[Na(+)]/Cr and U[Na(+)]/SGU. After adjusting for age, total cholesterol, alcohol drinking, obesity, current smoking, mild renal dysfunction, and diabetes mellitus, the odds ratios (ORs) for hypertension in the top quartile of U[Na(+)]/Cr compared with the bottom quartile were 1.40 in men and 2.68 in women. Similarly, the ORs for hypertension in the top quartile of U[Na(+)]/SGU were 1.29 in men and 3.02 in women after adjustment. CONCLUSIONS: U[Na(+)]/Cr and U[Na(+)]/SGU are associated with BP and hypertension, supporting the possible clinical value of U[Na(+)]/Cr and U[Na(+)]/SGU in general medical facilities.