Estimating retrospective exposure of household humidifier disinfectants.

UNLABELLED: We conducted a comprehensive humidifier disinfectant exposure characterization for 374 subjects with lung disease who presumed their disease was related to humidifier disinfectant use (patient group) and for 303 of their family members (family group) for an ongoing epidemiological study. We visited the homes of the registered patients to investigate disinfectant use characteristics. Probability of exposure to disinfectants was determined from the questionnaire and supporting evidence from photographs demonstrating the use of humidifier disinfectant, disinfectant purchase receipts, any residual disinfectant, and the consistency of their statements. Exposure duration was estimated as cumulative disinfectant use hours from the questionnaire. Airborne disinfectant exposure intensity (µg/m(3)) was estimated based on the disinfectant volume (ml) and frequency added to the humidifier per day, disinfectant bulk level (µg/ml), the volume of the room (m(3)) with humidifier disinfectant, and the degree of ventilation. Overall, the distribution patterns of the intensity, duration, and cumulative exposure to humidifier disinfectants for the patient group were higher than those of the family group, especially for pregnant women and patients ≤6 years old. Further study is underway to evaluate the association between the disinfectant exposures estimated here with clinically diagnosed lung disease. PRACTICAL IMPLICATIONS: Retrospective exposure to household humidifier disinfectant as estimated here can be used to evaluate associations with clinically diagnosed lung disease due to the use of humidifier disinfectant in Korea. The framework, with modifications to account for dispersion and use patterns, can also be potentially adapted to assessment of other household chemical exposures.

Air pollution interacts with past episodes of bronchiolitis in the development of asthma.

BACKGROUND: Exposure to ambient air pollution and bronchiolitis are risk factors for asthma. The aim of this study was to investigate the effect of air pollution on the development of asthma in children with past episodes of bronchiolitis. METHODS: A prospective 2-year follow-up survey consisting of parental responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and allergy evaluations were conducted in 1743 children with a mean age of 6.8 years. Recent 5-year exposure to air pollution was estimated using a geographic information system. RESULTS: Higher exposure to ozone was associated with airway hyper-responsiveness (PC20  ≤ 16 mg/ml) at enrollment (odds ratio [OR] = 1.60, 95% CI [confidence interval] = 1.13-2.27) and with new episodes of wheezing during the 2-year period (OR = 1.92, 95% CI = 0.96-3.83). Past episodes of bronchiolitis were associated with both current wheezing and physician-diagnosed asthma. When the two factors were combined, the prevalence of bronchial hyper-reactivity (OR = 2.96, 95% CI = 1.41-6.24) and new wheezing (OR = 4.17, 95% CI = 0.89-19.66) as well as current wheezing and physician-diagnosed asthma was even greater (P for trend <0.05 for all). In children with both risk factors, lung function was significantly decreased, with atopic children being particularly vulnerable. CONCLUSION: In children, the interaction between air pollution and past episodes of bronchiolitis resulted in a greater prevalence of asthma and pointed to an association with bronchial hyper-reactivity and decreased lung function. These results suggest mechanisms underlying the development of asthma.

Assessment of the fatty liver index as an indicator of hepatic steatosis for predicting incident diabetes independently of insulin resistance in a Korean population.

AIMS: Fatty liver disease, especially non-alcoholic fatty liver disease, is considered to be the hepatic manifestation of the metabolic syndrome, both closely associated with insulin resistance. Furthermore, fatty liver disease assessed by ultrasonography is known to be a predictor of the development of Type 2 diabetes mellitus. However, it remains unclear whether fatty liver disease plays a role in the pathogenesis of Type 2 diabetes independently of insulin resistance. In this study, we investigated whether fatty liver disease assessed by the fatty liver index can predict the development of Type 2 diabetes independently of systemic insulin resistance. METHODS: We examined the clinical and laboratory data of 7860 subjects without diabetes who underwent general routine health evaluations at the Asan Medical Center in 2007 and had returned for follow-up examinations in 2011. Fatty liver index was calculated using an equation that considers serum triglyceride levels, γ-glutamyltransferase, waist circumference and BMI. RESULTS: During a 4-year period, 457 incident diabetes cases (5.8%) were identified. The odds ratios for the development of Type 2 diabetes were significantly higher in the group with a fatty liver index ≥ 60 (fatty liver index-positive) than in the group with a fatty liver index < 20 (fatty liver index-negative) after adjusting for various confounding variables including homeostasis model assessment of insulin resistance. Odds ratios were significant regardless of the insulin resistance status at baseline. CONCLUSIONS: Our results suggest that fatty liver index as a simple surrogate indicator of hepatic steatosis is valuable in identifying subjects at high risk for Type 2 diabetes. In addition, fatty liver disease itself contributes to the development of Type 2 diabetes independently of systemic insulin resistance.

Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression.

Presenilin 1 (PS1), a polytopic membrane protein, has a critical role in the trafficking and proteolysis of a selected set of transmembrane proteins. The vast majority of individuals affected with early onset familial Alzheimer's disease (FAD) carry missense mutations in PS1. Two studies have suggested that loss of PS1 function, or expression of FAD-linked PS1 variants, compromises the mammalian unfolded-protein response (UPR), and we sought to evaluate the potential role of PS1 in the mammalian UPR. Here we show that that neither the endoplasmic reticulum (ER) stress-induced accumulation of BiP and CHOP messenger RNA, nor the activation of ER stress kinases IRE1alpha and PERK, is compromised in cells lacking both PS1 and PS2 or in cells expressing FAD-linked PS1 variants. We also show that the levels of BiP are not significantly different in the brains of individuals with sporadic Alzheimer's disease or PS1-mediated FAD to levels in control brains. Our findings provide evidence that neither loss of PS1 and PS2 function, nor expression of PS1 variants, has a discernable impact on ER stress-mediated induction of the several established 'readouts' of the UPR pathway.

Post-growth annealing effects of Mg doped GaAs epitaxial layers on microstructural and optical properties.

The post-growth thermal annealing effects of Mg doped GaAs epitaxial layers on the microstructural and optical properties grown by molecular beam epitaxy (MBE) have been investigated. The properties of Mg doped GaAs are estimated after the process of rapid thermal annealing (RTA) in the temperature range of 600 approximately 750 degrees C. The photoluminescence (PL) peak position of as-grown sample blueshifted from 1.473 to 1.485 eV as well as the pronounced enhancement in PL intensity by annealing at 600 degrees C. In the sample grown at the temperature of T(s) = 475 degrees C, the full-width at half maximum (FWHM) of double crystal X-ray diffraction (DCXRD) decreased form 27 to 8 arcsec with increasing of annealing temperature (600 approximately 700 degrees C). The crystalline quality variation of Mg doped GaAs layers by RTA is greatly dependent upon the doping level.

Prognostic factors for neurologic outcome after endovascular revascularization of acute symptomatic occlusion of the internal carotid artery.

BACKGROUND AND PURPOSE: Management of acute symptomatic internal carotid artery (ICA) occlusion remains controversial. We evaluated outcome predictors of a good recovery in patients with acute symptomatic ICA occlusion. MATERIALS AND METHODS: We retrospectively evaluated 33 consecutive patients (men/women, 23/10; mean age, 66 years) with: 1) acute symptomatic ICA occlusion within 6 hours of symptom onset or with mismatch of symptoms and an early infarct area, 2) National Institutes of Health Stroke Scale (NIHSS) score of 6 or more, and 3) attempted endovascular revascularization of the occluded ICA. Various single and multiple variable analyses were conducted to assess the association of 14 predictors with short-term (1-month NIHSS) and long-term (1-year modified Rankin Scale [mRS]) outcomes. RESULTS: Successful recanalization (at or more than grade 2 distal residual occlusion) was obtained in 14 (42%) of 33 and good recovery (mRS

Design of a collective scattering system for small scale turbulence study in Korea Superconducting Tokamak Advanced Research.

The design characteristics of a multi-channel collective (or coherent) scattering system for small scale turbulence study in Korea Superconducting Tokamak Advanced Research (KSTAR), which is planned to be installed in 2017, are given in this paper. A few critical issues are discussed in depth such as the Faraday and Cotton-Mouton effects on the beam polarization, radial spatial resolution, probe beam frequency, polarization, and power. A proper and feasible optics with the 300 GHz probe beam, which was designed based on these issues, provides a simultaneous measurement of electron density fluctuations at four discrete poloidal wavenumbers up to 24 cm(-1). The upper limit corresponds to the normalized wavenumber kθρe of ∼0.15 in nominal KSTAR plasmas. To detect the scattered beam power and extract phase information, a quadrature detection system consisting of four-channel antenna/detector array and electronics will be employed.

Ion gyroscale fluctuation measurement with microwave imaging reflectometer on KSTAR.

Ion gyroscale turbulent fluctuations with the poloidal wavenumber kθ ∼ 3 cm-1 have been measured in the core region of the neutral beam (NB) injected low confinement (L-mode) plasmas on Korea superconducting tokamak advanced research. The turbulence poloidal wavenumbers are deduced from the frequencies and poloidal rotation velocities in the laboratory frame, measured by the multichannel microwave imaging reflectometer. Linear and nonlinear gyrokinetic simulations also predict the unstable modes with the normalized wavenumber kθρs ∼ 0.4, consistent with the measurement. Comparison of the measured frequencies with the intrinsic mode frequencies from the linear simulations indicates that the measured ones are primarily due to the E × B flow velocity in the NB-injected fast rotating plasmas.

Mechanical and heat sensitization of cutaneous nociceptors in rats with experimental peripheral neuropathy.

This study examined whether or not the properties of cutaneous nociceptive fibers are altered in the neuropathic state by comparing lumbars 5 and 6 spinal nerve ligation (SNL) rats with sham-operated controls. The rats with the unilateral SNL developed mechanical allodynia in the ipsilateral hind limb, whereas the sham group did not. Two to 5 weeks after the neuropathic or sham surgery, rats were subjected to single fiber-recording experiments to examine the properties of afferent fibers in the sural and plantar nerves. A total of 224 afferents in the C- and Adelta-ranges were characterized in the neuropathic and sham groups. Spontaneous activity was observed in 16 of 155 fibers in the neuropathic group and one of 69 fibers in the sham group. The response threshold of both the C- and Adelta-fibers to mechanical stimuli was lower in the neuropathic group than the sham group. The afferent fibers responsive to heat stimuli were all C-fibers, and none were Adelta-fibers. The response threshold of the C-fibers to the heat stimuli was lower in the neuropathic group than the sham group. The magnitude of the responses of both C- and Adelta-fibers to the suprathreshold intensity of the mechanical stimulus was greater in the neuropathic group than the sham group. However, the magnitude of the responses of C-fibers to the suprathreshold intensity of the heat stimulus in the neuropathic group was not different from that in the sham group. These results suggest that after a partial peripheral nerve injury, the nociceptors on the skin supplied by an uninjured nerve become sensitized to both mechanical and heat stimuli. This nociceptor sensitization can contribute to neuropathic pain.

Isolation of p-hydroxycinnamaldehyde as an antibacterial substance from the saw fly, Acantholyda parki S.

We purified an antibacterial substance from larvae of the saw fly, Acantholyda parki S., and identified its molecular structure as p-hydroxycinnamaldehyde. We then synthesized it by reduction of p-hydroxycinnamic acid. The antibacterial activity of the synthetic p-hydroxycinnamaldehyde was equal to that of the authentic substance. This molecule was found to have a broad antibacterial spectrum against not only Gram-negative, but also Gram-positive bacteria. Furthermore, it showed antifungal activity against Candida albicans. We suggest that this substance may play a role in the defense system of this insect. This is the first report of p-hydroxycinnamaldehyde of animal origin.

Fiber counts at multiple sites along the rat ventral root after neonatal peripheral neurectomy or dorsal rhizotomy.

We hypothesized that the afferent fibers in the ventral root of the rat are the third branches of dorsal root ganglion cells; these afferent processes in the ventral root are of varying length and end bluntly along the length of the root. In the case of an injury at either the central or the peripheral processes of the dorsal root ganglion cells in the neonatal stage, these fibers sprout at the blunt endings along the length of the ventral root. We cut either the sciatic nerve or the dorsal root on one side in neonatal rats. After the rats were fully grown, the number of both myelinated and unmyelinated fibers was counted in electron photomicrographs at multiple sites along the length of the ventral root. We observed a greatly increased number of unmyelinated fibers in the ventral root after the sciatic nerve had been cut at the neonatal stage. The magnitude of increase was more at the distal than at the proximal portion of the ventral root, suggesting that added fibers originated from the distal side. Neonatal dorsal rhizotomy, however, did not produce the same result. These results are consistent with our hypothesis that peripheral nerve injury at the neonatal stage triggers sprouting of the third branches of the dorsal root ganglion cells which end bluntly along the length of the ventral root in the normal animal.

Peripheral glutamate receptors contribute to mechanical hyperalgesia in a neuropathic pain model of the rat.

We hypothesized that glutamate (Glu) released from the peripheral terminals of primary afferents contributes to the generation of mechanical hyperalgesia following peripheral nerve injury. Nerve injury was performed on rats with a lumbar 5 spinal nerve lesion (L5 SNL), which was preceded by L5 dorsal rhizotomy (L5 DR) to avoid the potential central effects induced by L5 SNL through the L5 dorsal root. Mechanical hyperalgesia, as evidenced by a reduction in paw withdrawal threshold (PWT), was short-lasting (<6 days) after L5 DR, but persistent (>42 days) after L5 SNL preceded by L5 DR. When an intraplantar injection into the affected hind paw was given immediately before L5 SNL, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (20 nmol), group-I metabotropic Glu (mGlu) receptor antagonist DL-amino-3-phosphonopropionic acid (DL-AP3; 70 nmol), and selective group-II mGlu receptor agonist 4-aminopyrrolidine-2,4-dicarboxylate (APDC; 20 nmol) delayed the onset of PWT reduction for 1-4 days. However, this onset was not affected by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4,-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX; 100 nmol). When the same injection was given after L5 SNL-induced mechanical hyperalgesia had been established, MK-801 reversed the PWT reduction for 30-75 min, whereas NBQX, DL-AP3, or APDC had no effect. These results suggest that the manipulation of the peripheral Glu receptors reduces neuropathic pain, by blocking NMDA and group-I mGlu receptors and by stimulating group-II mGlu receptor during the induction phase of neuropathic pain, but only by blocking the NMDA receptor during its maintenance phase.

PM(10) exposure, gaseous pollutants, and daily mortality in Inchon, South Korea.

To evaluate the relative importance of various measures of particulate and gaseous air pollution as predictors of daily mortality in Inchon, South Korea, the association between total daily mortality and air pollution was investigated for a 20-month period (January 1995 through August 1996). Poisson regression was used to regress daily death counts on each air pollutant, controlling for time trends, season, and meteorologic influences such as temperature and relative humidity. Regression coefficients of a 5-day moving average of particulate matter less than or = to 10 microm in aerodynamic diameter (PM(10)) on total mortality were positively significant when considered separately and simultaneously with other pollutants in the model. PM(10) remained significant when the models were confined to cardiovascular or respiratory mortality. Sulfur dioxide (SO(2)) and carbon monoxide (CO) were significantly related to respiratory mortality in the single-pollutant model. Ozone exposure was not statistically significant with regard to mortality in the above models, and graphic analysis showed that the relationship was nonlinear. A combined index of PM(10), nitrogen dioxide, SO(2), and CO seemed to better explain the exposure-response relationship with total mortality than an individual air pollutant. Pollutants should be considered together in the risk assessment of air pollution, as opposed to measuring the risk of individual pollutants.

Activity-dependent conduction latency changes in A beta fibers of neuropathic rats.

Activity-dependent changes of the conduction latency of single A beta fibers of primary afferent neurons were characterized in both neuropathic (L4 and L6 ligated) and normal rats. Activity-dependent increases in conduction latency of dorsal root fibers in neuropathic rats were significantly stronger than those in normal rats. Different profiles of activity dependence were also observed between injured and adjacent intact dorsal root fibers of neuropathic rats. However, activity-dependent latency changes in sciatic nerves distal to the dorsal root ganglion were not different between neuropathic and normal rats. These results suggest that partial nerve injury induces activity-dependent excitability changes in the dorsal root fibers of neuropathic rat and that these changes may be responsible for the altered sensory processing such as those seen in allodynia.

Activity-dependent conduction velocity changes of A(delta) fibers in a rat model of neuropathy.

Activity-dependent changes of conduction velocity (CV) and conduction block in single A(delta) fibers of primary afferent neurons were characterized in a rat model of neuropathy (NP). Injured dorsal root (DR) fiber in NP rats exhibited profoundly greater decreases of CV following impulse activity than did DR fiber in normal rats. Activity-dependent conduction block was absent up to 100 Hz of activity rate in DR fiber of NP rats, but was present above 25 Hz in normal rats. Profiles of activity dependence in sciatic fibers were similar in both NP and normal rats. These results suggest that nerve injury may alter activity-dependent hypoexcitability of A(delta) DR fibers. Furthermore, this excitability change may be responsible for the elevated pain perception in neuropathy.

Somatic afferent fibers which continuously discharge after being isolated from their receptors.

A previous study in our laboratory has shown that some afferent axons produce prolonged discharges after the axons have been completely isolated. We have attempted to identify the type of afferent fibers displaying such activity. Single unit activity was recorded from a filament dissected from the distal stump of the cut sural or plantar nerve of an anesthetized rat. After thorough identification of the receptor type, the nerve was cut at a site between the recording electrode and the receptive field, completely isolating the fiber being recorded. Unit activity was recorded up to 1 h after sectioning the nerve. Upon sectioning the nerve, most units showed brief injury discharges lasting only a few seconds. However, 21 of 70 units exhibited prolonged discharges lasting at least 30 min after having been isolated from their receptors. These 21 units included 8 slowly adapting type II cutaneous mechanoreceptors, 3 Pacinian corpuscles and 10 muscle spindle afferent units. These results suggest that prolonged injury discharges can be produced in the axons of the slowly adapting type II cutaneous mechanoreceptors, Pacinian corpuscles, and muscle spindle afferents. This phenomenon may have important clinical and experimental consequences.

Electrophysiological evidence for the antinociceptive effect of transcutaneous electrical stimulation on mechanically evoked responsiveness of dorsal horn neurons in neuropathic rats.

Using a rat model of peripheral neuropathy induced by a tight ligation of L5-6 spinal nerves, the effects of transcutaneous electrical stimulation on the mechanical responses of wide dynamic range (WDR) dorsal horn neurons were investigated. The responses of the WDR neurons to both the brush and pinch stimuli were found to be enhanced in the neuropathic rats compared to those in the normal rats. These enhanced responses were depressed by low-frequency and high-intensity transcutaneous electrical stimulation (2 Hz, 4-5 mA) applied to the somatic receptive field. The durations of the depressive effects on the brush responses ranged between 30 and 45 min and those on the pinch responses were 60-90 min. These results imply that the transcutaneous electrical stimulation used here produces an antinociceptive effect via a depressive action on the enhanced mechanical responsiveness of the spinal neurons in this rat model of peripheral neuropathy.

Involvement of alpha2-adrenoceptors in mediating sympathetic excitation of injured dorsal root ganglion neurons in rats with spinal nerve ligation.

The present study examined the effects of sympathetic stimulation on the activity of primary afferent neurons that had peripheral axons being injured previously by a spinal nerve ligation. About 22% of afferents with injured fibers that showed spontaneous discharge were excited by sympathetic stimulation or systemic injection of adrenaline. Most sympathetically-excited afferent neurons had axons that conducted in the A-fiber range. This sympathetically-evoked afferent excitation was not affected by cutting the spinal nerve at a place close to the dorsal root ganglion (DRG). Yohimbine, alpha2-antagonist, suppressed sympathetically-evoked afferent excitation which was not affected by alpha1-antagonist prazosin. Clonidine, alpha2-agonist, exerted an excitatory effect, whereas alpha1-agonist phenylephrine had no effect on the activity of afferents with injured fibers. No afferent fibers in control preparations responded to sympathetic stimulation. The results suggest that after a spinal nerve ligation, injured DRG neurons with fast-conducting fibers become sensitive to sympathetic activity via activation of alpha2-adrenoceptors.

N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor antagonists differentially suppress dorsal horn neuron responses to mechanical stimuli in rats with peripheral nerve injury.

The effects of iontophoretically ejected glutamate receptor antagonists on mechanically evoked responsiveness were examined on wide dynamic range (WDR) dorsal horn neurons in anesthetized rats that received a unilateral ligation of the L5 and L6 spinal nerves 10-15 days previously. Both brush- and pinch-evoked responses of dorsal horn neurons on the nerve-injured side were enhanced. N-Methyl-D-aspartate (NMDA) receptor antagonist, 2-amino-5-phosphonopentanoic acid (AP5), preferentially suppressed the enhanced pinch-evoked response, whereas (RS)-a-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptor selective antagonist, 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (NBQX), preferentially attenuated the enhanced brush-evoked response. The results indicate that the enhanced responses to noxious and non-noxious peripheral inputs induced in WDR dorsal horn neurons following the nerve injury are mediated by activation of NMDA and AMPA receptors, respectively.