Clinical Efficacy of 2% Rebamipide in Patients With Video Display Terminal-Associated Dry Eye Disease: A Prospective, Randomized, Double-Blinded Study.

PURPOSE: To compare the effects of 2% rebamipide clear solution and 0.1% sodium hyaluronate eye drops in patients with visual display terminal (VDT)-related dry eye disease (DED). DESIGN: Prospective, randomized, double-blinded Study. METHODS: This was a prospective, double-blind, and randomized controlled study. Patients with VDT-related DED were randomly allocated to a 2% rebamipide (REB) group or a 0.1% sodium hyaluronate (HYA) group (4 times/day for 4 weeks). The ocular surface disease index (OSDI), dry eye questionnaire-5 (DEQ-5), Placido disk-tear film analyzer, fluorescein-stained tear break-up time (FBUT), ocular surface staining score, and Schirmer 1 test were examined before and after the instillation of drug. RESULTS: A total of 56 eyes of 28 patients (28 eyes of 14 patients in each group) were included. There were no significant differences in the baseline data. The OSDI, DEQ-5, FBUT, and conjunctival erosion scores improved significantly in both groups after treatment. In the REB group, corneal staining and bulbar nasal redness scores also improved significantly after treatment (P<0.001 and 0.036, respectively), whereas no significant differences were found in these parameters in the HYA group (P=0.326 and 0.118, respectively). The REB group showed a significantly larger decrease in the corneal staining score than the HYA group (P=0.016). No adverse reactions were observed. CONCLUSIONS: A 2% rebamipide clear solution effectively improved the symptoms and signs in patients with VDT-related DED and was superior to 0.1% sodium hyaluronate ophthalmic solution in improving corneal epithelial damage, making it a safe and effective treatment option for VDT-related DED.

Effect of Corneal and Lens Eccentricity Difference on Rigid Corneal Lens Treatment in Patients With Keratoconus.

OBJECTIVE: To evaluate the effects of rigid corneal lenses (RCL) in patients with keratoconus, based on eccentricity. METHODS: Eighty-four eyes from 84 patients were included in this retrospective comparative study. Based on the median value of eccentricity difference between the cornea and back surface of the RCL, the patients were divided into groups 1 (<0.08) and 2 (≥0.08). Visual acuity, refractive index, and corneal topography indices were compared before and three months after lens use. RESULTS: Visual acuity, astigmatism, refractive error, corneal curvature, and corneal thickness improved significantly in both groups. Apical power and anterior elevation improved significantly in group 1, with small differences in eccentricity, but not in group 2. Changes in apical power before and after lens use were significantly different between the two groups. CONCLUSION: The RCL was effective for the cornea of keratoconus, especially when the prescription was made with a small difference in eccentricity.

Comprehensive LC-MS/MS method combined with tandem hybrid hydrolysis for multiple exposure assessment of multiclass environmental pollutants.

Environmental pollutants (EPOLs), such as phthalates, volatile organic compounds, phenols, parabens, polycyclic aromatic hydrocarbons, pyrethroids, and environmental tobacco smoke, are highly heterogeneous compounds. Recently, attention has been drawn to the assessment of the combinatory effects of multiple EPs. To correlate multiple exposures with potential health implications, advanced comprehensive analytical methods covering multiclass EPOLs are essential. However, because of several technical problems associated with enzyme hydrolysis, simultaneous extraction, and multiresidue liquid chromatography-tandem mass spectrometry analysis, it is difficult to establish a comprehensive method covering a number of EPOLs in a single sample preparation and analytical run. We developed tandem hybrid hydrolysis, modified direct injection, and a comprehensive mobile phase to overcome these technical problems and established a comprehensive analytical method for simultaneous biomonitoring of multiclass EPOLs. Tandem hybrid hydrolysis using ß-glucuronidase and consecutive acid hydrolysis allowed selective hydrolysis of glucuronide- and sulfate-conjugated metabolites without phthalate degradation. The comprehensive mobile phase composed of 0.01% acetic acid and acetonitrile enabled us to simultaneously analyze 86 EPOLs, with good chromatographic behavior and ionization efficiency. Modified direct injection allowed a small amount of sample and simultaneous urinary extraction. The method was validated and applied to 39 urine samples from 19 mother-newborn pairs for multiple exposure assessment. Results showed that BP-3, a general component in sunblock products, and monoethyl phthalate, a metabolite of diethyl phthalate, exhibit a clear positive correlation between mothers and newborns. Therefore, the developed method has potential as a novel analytical tool for long-term, large-scale, and data-rich human biomonitoring of EPOLs.

Genotypic Homogeneity in Distinctive Transforming Growth Factor-Beta Induced (TGFBI) Protein Phenotypes.

Background: To evaluate the distribution of the transforming growth factor-beta induced (TGFBI) corneal dystrophies in a multi-ethnic population in Singapore, and to present the different phenotypes with the same genotype. Methods: This study included 32 patients. Slit lamp biomicroscopy was performed for each patient to determine the disease phenotype. Genomic DNA was extracted from the blood samples and the 17 exons of the TGFBI gene were amplified by PCR and sequenced bi-directionally for genotype analysis. Results: Regarding phenotypes, the study patients comprised 11 (34.4%; 8 with R555W and 3 with R124H mutation) patients with granular corneal dystrophy type 1 (GCD1), 6 (18.8%; 5 with R124H and 1 with R124C mutation) patients with GCD2, 13 (40.6%; 7 with R124C, 2 with H626R, 2 with L550P, 1 with A620D and 1 with H572R) patients with lattice corneal dystrophy (LCD) and 2 (6.3%; 1 with R124L and 1 with R124C) patients with Reis-Bückler corneal dystrophy. Regarding genotype, R124H mutation was associated with GCD2 (5 cases; 62.5%) and GCD1 (3 cases; 37.5%). R124C mutation was associated with LCD (7 cases; 87.5%) and GCD2 (1 case; 12.5%). All the 8 cases (100%) of R555W mutation were associated with GCD1. Conclusions: Although the association between genotype and phenotype was good in most cases (65.7%; 21 of 32 patients), genotype/phenotype discrepancy was observed in a significant number.

Supersaturable self-microemulsifying drug delivery system enhances dissolution and bioavailability of telmisartan.

To enhance the dissolution and oral bioavailability of telmisartan (TMS), a poorly water-soluble anti-hypertensive drug, a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) was developed. Amorphous alkalinized TMS (AAT) was formulated into a SMEDDS, composed of Capmul® MCM (oil), Cremophor® RH40 (surfactant), and tetraglycol (co-surfactant). Although the SMEDDS was rapidly dissolved (>80% within 5 min) in a limited condition (500 mL, pH 6.8), drug precipitation was observed over time, resulting in a decrease in dissolution levels. The precipitation was due to drug recrystallization, as determined by differential scanning calorimetry and powder X-ray diffraction analyses. Several polymers, including Soluplus® (SOL), were screened as precipitation inhibitors; ultimately, SuSMEDDS-SOL was prepared by admixing SOL and the SMEDDS at a 5:100 (w/w) ratio. SuSMEDDS-SOL was superior in terms of dissolution efficiency (>90% over 2 h) and dissolution-retaining time (no precipitation over 2 h). An in vivo pharmacokinetic study in rats revealed that the oral bioavailability of SuSMEDDS-SOL was 4.8-, 1.3-, and 1.2-fold greater than those of the TMS suspension, AAT solution, and SMEDDS, respectively. Therefore, SuSMEDDS-SOL is a promising candidate to enhance the dissolution and oral bioavailability of TMS.

Efficacy of Modified Amnion-Assisted Conjunctival Epithelial Redirection (ACER) for Partial Limbal Stem Cell Deficiency.

Background and objectives: the aim of this study was to analyze the efficacy of a modified "amnion-assisted conjunctival epithelial redirection (ACER)" technique for the treatment of partial limbal stem cell deficiency (LSCD). Materials and methods: the medical records of three patients with partial LSCD who underwent corneal surface reconstruction with modified ACER following superficial keratectomy were retrospectively studied. Briefly, in this technique, an inner amniotic membrane (AM) layer was applied on the corneal surface to promote corneal re-epithelialization. The outer AM layer was applied as a barrier to prevent the invasion of conjunctival epithelial cells into the cornea before the corneal surface was completely covered by corneal epithelial cells derived from the remaining intact limbal stem cells. Results: in all three cases, the outer AM layer successfully kept the conjunctival epithelium away from the corneal surface and prevented an admixture of conjunctival epithelial cells with corneal epithelial cells. In all three patients, the cornea was completely re-epithelized with epithelial cells derived from the remaining healthy limbal stem cells, and a clear visual axis was maintained without recurrence for a mean follow-up period of 37.3 ± 8.6 months. Conclusions: the preliminary results suggest that modified ACER appears to be a viable option for patients with partial LSCD.

Emission characteristics of particulate matter, odors, and volatile organic compounds from the grilling of pork.

Meat-grilling restaurants are considered to be residential emission sources of air pollutants. To investigate the emission characteristics of particulate matter (PM), odors, and volatile organic compounds (VOCs) from the grilling of meat, a grilling apparatus equipped with butane gas burners was used to grill pork belly and marinated pork ribs in a laboratory setting. When grilling the pork belly, the emission factor for PM with a diameter of 2.5 µm or below (PM2.5) was 754 mg-PM·kg-meat-1, accounting for 99% of total suspended particles (TSPs), while that of the marinated pork ribs was 137 mg-PM·kg-meat-1 (96% of TSPs). Ammonia and acetaldehyde were the most common odors emitted during grilling at 43-88 mg·kg-meat-1 and 22-30 mg·kg-meat-1, respectively. Aldehydes were the most significant contributor to total odor intensity (36%-67%). Benzene, vinyl acetate, and hexene were the most abundant VOCs for the pork belly, while butane, vinyl acetate, and n-dodecane were the most abundant for the marinated ribs. Among the VOCs emitted from the pork grilling process, hexene, butane, and toluene were the dominant ozone precursors. The information obtained in this study is useful for furthering the understanding of the characteristics of air pollutants emitted from actual meat-grilling restaurants. Additionally, knowledge of the PM, odor, and VOC emission characteristics and their emission factors is useful for establishing management strategies for air pollutants from meat-grilling restaurants.

Efficacy of bevacizumab injection after pterygium excision and limbal conjunctival autograft with limbal fixation suture.

PURPOSE: To determine the efficacy of subconjunctival bevacizumab injection after pterygium excision with limbal conjunctival autograft and limbal fixation suture. METHODS: This retrospective study included a total of 150 eyes of 150 patients with primary pterygium who received three different procedures after pterygium excision, i.e., 49 eyes with limbal conjunctival graft (group A), 48 eyes with limbal conjunctival autograft with limbal fixation suture (group B), and 53 eyes with limbal conjunctival autograft with limbal fixation suture followed by bevacizumab injection (group C). Image analysis was performed using preoperative anterior segment photographs to measure parameters including relative length, relative width, relative area, and vascularity index of pterygium. Recurrence of pterygium was determined at 1 year after surgery, and outcomes were compared between the 3 groups. Risk factors related to recurrence were evaluated using univariate and multivariate analyses. RESULTS: Recurrence rates after 1 year were 18.4% (9/49), 8.3% (4/48), and 1.9% (1/53) in groups A, B, and C, respectively (P = 0.004). Multivariate analysis showed that patients in group C had significantly reduced risk of recurrence compared with those in group A (P = 0.009), whereas the risk of recurrence was not significantly different between groups A and B (P = 0.227) and groups B and C (P = 0.068), respectively. Among various parameters, higher vascularity index had significant correlation with increased risk of recurrence (P = 0.008). CONCLUSIONS: Bevacizumab injection after limbal conjunctival autograft and limbal fixation suture may effectively reduce recurrence after pterygium excision. The vascularity of pterygium was associated with a higher risk of recurrence.

Ocular coloboma combined with cleft lip and palate: a case report.

BACKGROUND: Ocular coloboma is an excavation of ocular structures that occurs due to abnormal fusion of the embryonic optic fissure. Further, cleft lip/palate (CL/P), a congenital midline abnormality, is caused by a defect in the fusion of the frontonasal, maxillary, and mandibular prominences. No study has reported the association between these two phenotypes in the absence of other systemic abnormalities. We present a case of ocular coloboma along with CL/P and without other neurological abnormalities. CASE PRESENTATION: A 5-year-old Asian boy presented with decreased visual acuity in his right eye. Physical examination revealed no abnormal findings except CL/P, which was surgically corrected at the age of 9 months. Best-corrected visual acuity was 20/60 in the right eye and 20/25 in the left eye. Anterior segment examination revealed iris coloboma in the inferior quadrant of his right eye as well as a large inferonasal optic disc and chorioretinal coloboma in the same eye. He was prescribed glasses based on his cycloplegic refractive errors and part-time occlusion of the left eye was recommended. After 3 months, best-corrected visual acuity improved to 20/30 in the right eye. CONCLUSION: The association of ocular coloboma should be kept in mind when encountering a patient with CL/P without other neurological or systemic abnormalities.

Antioxidant Activity of Hydrogen Water Mask Pack Composed of Gel-Type Emulsion and Hydrogen Generation Powder.

In this study, hydrogen generation powder samples were prepared using zinc carbonate as a precursor, at a temperature varying from 400 to 700 °C in H2 atmosphere, and were characterized in terms of antioxidant activity. The concentration of dissolved hydrogen obtained by the powder samples was measured using a dissolved hydrogen meter as a function of time. In addition, the antioxidant activity of the samples was evaluated based on the Oyaizu's method, removal rate of ·OH radicals, and ferric reducing antioxidant power. Finally, the hydrogen mask pack was fabricated using the hydrogen generation powder sample and gel-type emulsion. In the clinical test on the mask pack, the effect of the mask on skin aging was characterized and compared to that of a commercial sample. The skin densities of the participants in the experimental group and the control group increased by 18.41% and 9.93% after 4 weeks, respectively. The improved skin density of the participants who used the hydrogen mask pack in the experimental group, might be attributed to the recovery effect of the hydrogen molecule in the mask pack on the denatured thick skin layer.

Analysis of Nicotine Metabolites in Hair and Nails Using QuEChERS Method Followed by Liquid Chromatography-Tandem Mass Spectrometry.

Many studies have analyzed nicotine metabolites in blood and urine to determine the toxicity caused by smoking, and assess exposure to cigarettes. Recently, hair and nails have been used as alternative samples for the evaluation of smoking, as not only do they reflect long-term exposure but they are also stable and easy to collect. Liquid-liquid or solid-phase extraction has mainly been used to detect nicotine metabolites in biological samples; however, these have disadvantages, such as the use of toxic organic solvents and complex pretreatments. In this study, a modified QuEChERS method was proposed for the first time to prepare samples for the detection of nicotine metabolite cotinine (COT) and trans-3'-hydroxycotinine (3-HCOT) in hair and nails. High-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze traces of nicotine metabolites. The established method was validated for selectivity, linearity, lower limit of quantitation, accuracy, precision and recovery. In comparison with conventional liquid-liquid extraction (LLE), the proposed method was more robust, and resulted in higher recoveries with favorable analytical sensitivity. Using this method, clinical samples from 26 Korean infants were successfully analyzed. This method is expected to be applicable in the routine analysis of nicotine metabolites for environmental and biological exposure monitoring.

Screening of Phosphodiesterase-5 Inhibitors and Their Analogs in Dietary Supplements by Liquid Chromatography-Hybrid Ion Trap-Time of Flight Mass Spectrometry.

An accurate and reliable method based on ion trap-time of flight mass spectrometry (IT-TOF MS) was developed for screening phosphodiesterase-5 inhibitors, including sildenafil, vardenafil, and tadalafil, and their analogs in dietary supplements. Various parameters affecting liquid chromatographic separation and IT-TOF detection were investigated, and the optimal conditions were determined. The separation was achieved on a reversed-phase column under gradient elution using acetonitrile and water containing 0.2% acetic acid at a flow rate of 0.2 mL/min. The chromatographic eluents were directly ionized in the IT-TOF system equipped with an electrospray ion source operating in the positive ion mode. The proposed screening method was validated by assessing its linearity, precision, and accuracy. Sequential tandem MS was conducted to obtain structural information of the references, and the fragmentation mechanism of each reference was proposed for providing spectral insight for newly synthesized analogs. Structural information, including accurate masses of both parent and fragment ions, was incorporated into the MSn spectral library. The developed method was successfully applied for screening adulterated dietary supplement samples.

Dry Eye Symptoms May Have Association With Psychological Stress in Medical Students.

PURPOSE: To evaluate the prevalence and risk factors of symptomatic dry eye disease (DED) among medical students. METHODS: This cross-sectional study included 209 students at a medical school in Korea. Dry eye symptoms were assessed using a 9-item questionnaire, and DED was defined as having one or more dry eye symptoms often or all the time. The ocular surface disease index (OSDI) and visual analog scale (VAS) questionnaires were also administered to quantify the dry eye symptoms. A survey including demographic data, potential risk factors for DED, personal habits, and psychological stress was also performed. RESULTS: Of the 209 students, 188 (93 men and 95 women) completed the survey. The average age was 28.0±2.5 (mean±SD; range, 23-37) years. Prevalence of DED was 27.1% (51/188). Participants with DED had significantly higher VAS and OSDI than those without DED (P<0.001 for both). Univariate analysis revealed that female sex (P=0.001), contact lens (CL) wear (P=0.034), prolonged computer use (P=0.001), and higher psychological stress score (P<0.001) had significant association with DED. Multivariate analysis also showed the significant association between DED and female sex (P=0.026), CL wear (P=0.042), prolonged computer use (P=0.004), and higher stress score (P=0.014). CONCLUSIONS: Symptomatic DED was prevalent among medical students. Increased psychological stress was associated with higher risk of DED. Its risk also increased among women, CL wearers, and prolonged computer users.

Efficacy and Safety of Conjunctival Cystectomy Using High-Frequency Radiowave Electrosurgery: A Preliminary Report.

PURPOSE: To evaluate the efficacy and safety of conjunctival cystectomy using high-frequency radiowave electrosurgery. METHODS: This retrospective study included 11 patients who underwent conjunctival cystectomy using high-frequency radiowave electrosurgery and had a follow-up of at least 6 months. Briefly, conjunctival opening with a diameter of 1 mm was made with using high-frequency radiowave electrosurgery (Ellman Surgitron; Ellman International, Inc., Hewlett, NY) in cut mode. The cyst was then extracted using a nontoothed forceps through the opening without rupture. Medical record of the patients was reviewed. RESULTS: In all the 11 patients, conjunctival wound healed in 1 week without any complication. No recurrence was detected in any patients over the 6-month follow-up. CONCLUSIONS: Conjunctival cystectomy with the adjunctive use of high-frequency radiowave electrosurgery was shown to be effective and safe.

Ionization of Gas-Phase Polycyclic Aromatic Hydrocarbons in Electrospray Ionization Coupled with Gas Chromatography.

Herein, gas-phase polycyclic aromatic hydrocarbons (PAHs) as nonpolar compounds were ionized to protonated molecular ions [M + H]+ without radical cations and simultaneously analyzed using gas chromatography (GC)/electrospray ionization (ESI)-tandem mass spectrometry (MS/MS). The ionization profile, dissociation, and sensitivity were first investigated to understand the significant behavior of gas-phase PAHs under ESI. The formation of protonated molecular ions of PAHs was distinguished according to the analyte phase and ESI spray solvents. The protonated PAHs exhibited characteristic dissociations, such as H-loss, H2-loss, and acetylene-loss, via competition of internal energy. In addition, GC/ESI-MS/MS resulted in relatively lower concentration levels (better sensitivity) for the limits-of-detection (LODs) of PAHs than liquid chromatography (LC)/ESI-MS/MS, and it seems to result from the characteristic ionization mechanism of the gas-phase analyte under ESI. Furthermore, the LODs of gas-phase PAHs depended on molecular weight and proton affinity (PA). Consequently, we demonstrated the relationship among the analyte phases, sensitivities, and structural characteristics (molecular weight and PA) under ESI. The gas-phase PAHs provided enhanced protonation efficiency and sensitivity using GC/ESI-MS/MS, as their molecular weight and PA increased. Based on these results, we offered important information regarding the behavior of gas-phase analytes under ESI. Therefore, the present GC/ESI-MS/MS method has potential as an alternative method for simultaneous analysis of PAHs.

Case Report: Ocular Myasthenia Gravis Associated with In Vitro Fertilization Procedures.

SIGNIFICANCE: Ocular myasthenia gravis is a localized form of myasthenia gravis, which is a postsynaptic disorder of the neuromuscular junction that causes fluctuating weakness of extraocular muscles resulting from autoimmune mechanisms. In women with myasthenia, changes in sex hormone levels and administration of corticosteroids can trigger or worsen symptoms of myasthenia gravis. PURPOSE: To describe a case of seronegative ocular myasthenia gravis whose first symptom appeared a day after in vitro fertilization procedure. CASE REPORT: A 37-year-old woman suddenly developed mild ptosis and fluctuating diplopia that worsened in the evening. Before the development of symptoms, she had undergone in vitro fertilization procedure and had taken oral steroids. Ocular motility examination revealed an intermittent exotropia in primary gaze at both distance and near. The neostigmine test confirmed her diagnosis as ocular myasthenia gravis. CONCLUSIONS: When taking a history for young women with sudden onset of binocular diplopia, steroids and sex hormones should be taken into account, which may trigger or exacerbate symptoms of ocular myasthenia gravis.

Aquilanols A and B, Macrocyclic Humulene-Type Sesquiterpenoids from the Agarwood of Aquilaria malaccensis.

Four new and five known sesquiterpenoids were isolated from the agarwood of Aquilaria malaccensis. Aquilanols A and B (1 and 2) have an unprecedented macrocyclic humulene structure with a bicyclic 7/10 ring system. Compound 2 was obtained as a scalemic mixture that was resolved by HPLC analysis using a chiral column. Their structures were deduced based on spectroscopic data analysis, and the absolute configurations were unambiguously determined by X-ray crystallographic data and ECD spectroscopic analysis. A putative biosynthetic pathway of these sesquiterpenoids is proposed.

High-Performance Chemically Regenerative Redox Fuel Cells Using a NO3- /NO Regeneration Reaction.

In this study, we proposed high-performance chemically regenerative redox fuel cells (CRRFCs) using NO3- /NO with a nitrogen-doped carbon-felt electrode and a chemical regeneration reaction of NO to NO3- via O2 . The electrochemical cell using the nitrate reduction to NO at the cathode on the carbon felt and oxidation of H2 as a fuel at the anode showed a maximal power density of 730 mW cm-2 at 80 °C and twofold higher power density of 512 mW cm-2 at 0.8 V, than the target power density of 250 mW cm-2 at 0.8 V in the H2 /O2 proton exchange membrane fuel cells (PEMFCs). During the operation of the CRRFCs with the chemical regeneration reactor for 30 days, the CRRFCs maintained 60 % of the initial performance with a regeneration efficiency of about 92.9 % and immediately returned to the initial value when supplied with fresh HNO3 .

A comprehensive and sensitive method for hair analysis in drug-facilitated crimes and incorporation of zolazepam and tiletamine into hair after a single exposure.

Hair is a highly relevant specimen that is used to verify drug exposure in victims of drug-facilitated crime (DFC) cases. In the present study, a new analytical method involving ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed for determining the presence of model drugs, including zolazepam and tiletamine and their metabolites in hair specimens from DFCs. The incorporation of zolazepam and tiletamine into hair after a single exposure was investigated in Long-Evans rats with the ratio of the hair concentration to the area under the curve. For rapid and simple sample preparation, methanol extraction and protein precipitation were performed for hair and plasma, respectively. No interference was observed in drug-free hair or plasma, except for hair-derived diphenhydramine in blank hair. The coefficients of variance of the matrix effects were below 12%, and the recoveries of the analytes exceeded 70% in all of the matrices. The precision and accuracy results were satisfactory. The limits of quantification ranged from 20 to 50 pg in 10 mg of hair. The drug incorporation rates were 0.03 ± 0.01% for zolazepam and 2.09 ± 0.51% for tiletamine in pigmented hair. We applied the present method to real hair samples in order to determine the drug that was used in seven cases. These results suggest that this comprehensive and sensitive hair analysis method can successfully verify a drug after a single exposure in crimes and can be applied in forensic and clinical toxicology laboratories.