Search

Sexual dimorphism affects various biological functions, including immune responses. However, the mechanisms by which sex alters immunity remain largely unknown. Using Caenorhabditis elegans as a model species, we showed that males exhibit enhanced immunity against various pathogenic bacteria through the upregulation of HLH-30 (Helix Loop Helix 30/TFEB (transcription factor EB)), a transcription factor crucial for macroautophagy/autophagy. Compared with hermaphroditic C. elegans , males displayed increased activity of HLH-30/TFEB, which contributed to enhanced antibacterial immunity. atg-2 (AuTophaGy (yeast Atg homolog) 2) upregulated by HLH-30/TFEB mediated increased immunity in male C. elegans . Thus, the males appear to be equipped with enhanced HLH-30/TFEB-mediated autophagy, which increases pathogen resistance, and this may functionally prolong mate-searching ability with reduced risk of infection. Abbreviations: atg-2 : AuTophaGy (yeast Atg homolog) 2; FUDR: 5-fluoro-2'-deoxyuridine; GSEA: gene set enrichment analysis; HLH-30: Helix Loop Helix 30; LC3 : microtubule associated protein 1 light chain 3; NGM: nematode growth media; RNA-seq: RNA sequencing; SEM: standard error of the mean; TFEB: transcription factor EB; WT: wild-type.

In cases of recurrent exotropia, medial rectus resection after bilateral lateral rectus recession is often considered for reoperations. The surgical amount of medial rectus resection is typically determined according to the standard surgical dose table; however, postoperative variability has been noted in the surgical outcomes. In the current study, medial rectus tendon width (MRTW) was measured intraoperatively, and surgical dose-response was calculated as the ratio between amount of correction and resected medial rectus. The MRTW exhibited a positive correlation with age at time of surgery and surgical dose-response. MRTW could thus merit further study as a potential intraoperative predictor of surgical dose-response when considering medial rectus resection in patients with recurrent exotropia., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To observe postoperative histological changes in the anterior part of the posterior fixation suture after a Faden operation in an animal model., Methods: A posterior fixation suture was placed at two points 6 mm posterior to the insertion of the extraocular muscle on the superior rectus muscle of the right eye in eight rabbits. The superior rectus muscle of the left eye was used as a control. The eyes were enucleated and the anterior portion of the posterior fixation suture, including the myoscleral junction, was extracted 4 weeks after surgery. Postoperative adhesion was graded from 0 to 4 based on histologic findings (hematoxylin-eosin and Masson's trichrome staining)., Results: Histological evaluation revealed diffuse fibrosis at the myoscleral junction and the anterior part of the posterior fixation suture after the Faden operation. The graded scores for fibrosis, acute inflammation, chronic inflammation, and foreign body reactions in the Faden operation group were significantly higher than those in the control group ( P < .05). Postoperative diffuse fibrosis of the myoscleral junction and anterior-to-posterior fixation sutures were observed in an animal model., Conclusions: Histologic changes may affect ocular alignment and motility, making reoperation unpredictable after the Faden procedure. [ J Pediatr Ophthalmol Strabismus . 2024;61(5):371-375.] .

Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with daf-2/insulin/IGF-1 receptor mutant Caenorhabditis elegans. Our analysis unraveled multiple epistatic relationships at the transcriptomic level, in addition to verifying genetically established interactions. Our combinatorial analysis also revealed transcriptomic changes associated with longevity conferred by daf-2 mutations. In particular, we demonstrated that the extent of lifespan changes caused by various mutant alleles of the longevity transcription factor daf-16/FOXO matched their effects on transcriptomic changes in daf-2 mutants. We identified specific aging-regulating signaling pathways and subsets of structural and functional RNA elements altered by different genes in daf-2 mutants. Lastly, we elucidated the functional cooperation between several longevity regulators, based on the combination of transcriptomic and molecular genetic analysis. These data suggest that different biological processes coordinately exert their effects on longevity in biological networks. Together our work demonstrates the utility of transcriptomic dissection analysis for identifying important genetic interactions for physiological processes, including aging and longevity., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Purpose: To evaluate the effect of classroom illuminance on the development and progression of myopia in elementary school children., Methods: The daylight factor, a ratio of inside and outside illuminance, was obtained in 50 elementary schools. The firstgrade students in the school with the lowest daylight (LD) factor (LD school, 145 subjects; 0.51%) and with the highest daylight (HD) factor (HD school, 147 subjects; 13.35%) were selected. A survey was conducted to evaluate parental myopia, the amount of near-work and outdoor activities. The refractive error and axial length (AL) were measured at initial and after 6 months. The spherical equivalent, AL, and the survey results were compared between the two schools. The mean AL of the emmetropic children was obtained, and all subjects were divided into two groups, more and less than mean AL. Changes in refractive errors and AL were also compared according to AL., Results: The amount of change in spherical equivalent and AL after 6 months were not different between the two schools. Initial prevalence of myopia was high in the HD school. However, it became similar between the two schools after 6 months. The mean AL of 155 emmetropic children was 22.7 ± 0.63 mm. In the 185 children with AL ≥22.7 mm, there was no difference in the AL change between the two schools. However, the change in AL in 107 children with AL <22.7 mm was significantly larger in the LD school (0.19 mm) than that in the HD school (0.15 mm, p = 0.049). Parental myopia, near-work and outdoor activities were not different between the two schools., Conclusions: High classroom illuminance during the day reduced axial elongation in eyes of children with a shorter AL. Increase in classroom light level by permitting more sunlight can be a protective measure against the development of myopia.

Background: To investigate preoperative clinical features and postoperative results according to the correspondence between excyclotorsion and the paretic eye in patients with congenital unilateral superior oblique palsy (USOP)., Methods: A retrospective review of medical charts was performed. The patients were divided into the accordance (ocular excyclotorsion in the paretic eye) and disaccordance (ocular excyclotorsion in the non-paretic eye) groups. The degree of excyclotorsion (scale, 0-4) was measured. Age, sex, hypertropia at the primary position, fixation preference, inferior oblique overaction, and degree of excyclotorsion were measured., Results: Ninety-eight patients were included in this study. There were 70 (71.4%) and 28 patients (28.6%) in the accordance and disaccordance groups. Sixteen patients (22.9%) in the accordance group and 12 patients (42.9%) in the disaccordance group were aged under 2 years (p = 0.04). A fixation preference of the paretic eye was observed in 2 (2.9%) and 8 (28.6%) patients in the accordance and disaccordance groups (p < 0.01). The postoperative degree of excyclotorsion in the accordance group (0.14 ± 0.39) was lower than that in the disaccordance group (0.28 ± 0.71) (p = 0.01). The residual postoperative excyclotorsion (> 1) were observed in the disaccordance group (14 patients, 50%) and accordance group (16 patients, 22.9%) (p = 0.01)., Conclusion: Preoperative disaccordance between excyclotorsion and the paretic eye was observed in patients who were under 2 years of age and preferred fixation of the paretic eye. The postoperative degree of excyclotorsion was lower in the accordance group., (© 2022. The Author(s).)

Purpose. The aim of this article was to measure the safety perception level of workers on a South Korean construction site and investigate safety problems using the Nordic occupational safety climate questionnaire (NOSACQ-50). Methods. The survey was carried out via the NOSACQ-50 with 175 workers from five South Korean construction companies to evaluate their perception level. The results were then compared with the NOSACQ-50 criteria. Results. The safety perception of this South Korean construction site is high when compared with the NOSACQ-50 criteria. This high level was especially pronounced for the seventh dimension of the efficacy of the safety system, which showed the highest level among all dimensions. In addition, we suggested improvements and interventions to sustain a safety climate amongst workgroups. Conclusions. This study confirms that the seventh dimension showed the highest safety perception amongst all dimensions in South Korea. In the future, these findings can be utilized to develop an evaluation tool for the safety climate of the construction industry in South Korea.

We investigated the period of postoperative exodrift during follow-up and clinical factors that affect the rate of exodrift after surgery in the patients with intermittent exotropia (IXT). A retrospective review of medical records of patients with exodrift who underwent bilateral rectus recession for IXT was performed. Exodrift was defined as angle of deviation greater than 10 prism diopters (PD) at distance and near. The median survival period of postoperative exodrift was analyzed using Kaplan Meier survival analysis. The patients were divided into two groups according to the median period of postoperative exodrift (early and late group). The weighted Cox's proportional hazards regression analysis to investigate the risk factors that affect rate of postoperative exodrift was performed. A total of 108 patients was included. The preoperative angle of deviation at distance and near were 30.3 ± 7.2 PD and 29.5 ± 8.6 PD, respectively. The median survival period of postoperative exodrift was 24 months (range, 6-48 months).The angle of deviation at postoperative day 1 in early and late group were - 3.8 ± 5.5 PD (range, - 16-8 PD) and - 7.7 ± 4.6 PD (range, - 16-4 PD) (p < 0.01). Minus value means esodeviation. In regression analysis, the angle of deviation at postoperative day 1 was the significantly related with rate of exodrift (p < 0.01). The median period of exodrift after surgery was 24 months, angle of deviation at postoperative day 1 could affect the rate of exodrift in patients with IXT.

We evaluated the long-term surgical outcomes of medial rectus (MR) recession with the Faden operation in consecutive esotropia (CET). We retrospectively analyzed patients who underwent MR recession with the Faden operation for CET between 2013 and 2018, and compared surgical outcomes between patients who underwent MR recession with the Faden operation (Faden group) and MR recession only (control group). We followed up the patients at 24 months postoperatively. Postoperative success was defined as final deviation of less than distant 5 prism diopters (PD) of eso- or exodeviation at the final visit. We compared postoperative alignment and stereoacuity between the two groups. Stereoacuity was classified as good (60 or better seconds of arc), fair (80-3000 s of arc) or nil. The Faden and control group included 11 and 13 patients, respectively. All patients in the Faden group showed orthophoria and eight patients (72.7%) showed good stereoacuity at the final visit. One patient (9.1%) in the Faden group showed adduction limitation at the final visit. Eight patients (61.5%) in the control group had successful outcomes at the final visit. Six patients (46.2%) in the control group showed good stereoacuity at the final visit. One patient (7.7%) in the control group underwent reoperation for recurrent esotropia at 18 months postoperatively. The surgical outcomes after MR recession with the Faden operation for CET were excellent in long-term follow- up. The Faden operation could be a good surgical option for CET.

Purpose: To investigate the surgical outcome according to the initial postoperative angle of deviation in patients with thyroid eye disease., Methods: The medical records of patients who underwent strabismus surgery were retrospectively reviewed. The patients were divided into overcorrection (> 5 prism diopters [PD]), full correction, or undercorrection (> 5 PD) groups, according to the angle of deviation on postoperative day 1. The surgical outcome was considered successful when there was no diplopia vertically (< 5 PD) and horizontally (< 10 PD) at primary gaze. Surgical success rates were evaluated according to the initial postoperative angle of deviation at the final visit., Results: Seventy-eight patients were enrolled in this study. The mean age of the patients was 53.4 ± 9.5 years, and the mean follow-up duration was 17.4 ± 8.7 months. There were 51 patients with hypotropia and 27 patients with esotropia. Success rates for hypotropia were higher in the undercorrection (80.0%) and full correction (66.7%) groups than in the overcorrection (35.7%) group on postoperative day 1 (P = .02). Regarding esotropia, the success rates were higher in the undercorrection (84.6%) and full correction (83.3%) groups than in the overcorrection (37.5%) group on postoperative day 1 (P = .02). Reoperation for residual or overcorrected strabismus was performed in 15 patients (29.4%) with hypotropia and 7 patients (25.9%) with esotropia., Conclusions: Intended minimal undercorrection or full correction after hypotropia and esotropia surgery during early postoperative periods could improve surgical success rates in patients with thyroid eye disease. [J Pediatr Ophthalmol Strabismus. 2021;58(1):23-27.]., (Copyright 2021, SLACK Incorporated.)

Aim/Purpose: Exposure to various allergens has been shown to increase expression of ORMDL3 in the lung in models of allergic asthma. Studies using genetically modified (transgenic or knock out) mice have revealed some of the functions of ORMDL3 in asthma pathogenesis, although amid debate. The goal of this study was to use targeted post-transcriptional downregulation of ORMDL3 in allergen-challenged wild-type (WT) mice by RNA interference to further elucidate the functional role of ORMDL3 in asthma pathogenesis and evaluate a potential therapeutic option. Methods: Allergen (ovalbumin [OVA])-challenged WT mice were administered intranasally (i.n) with a single dose of five short hairpin RNA (shRNA) constructs with different target sequence for murine ORMDL3 cloned in a lentiviral vector or with the empty vector (control). Mice were evaluated for allergen-induced airway hyperresponsiveness (AHR) and various features of airway inflammation after 72 hours. Results: I.n administration of a single dose of ORMDL3 shRNAs to OVA-challenged mice resulted in reduction of ORMDL3 gene expression in the lungs associated with a significant reduction in AHR to inhaled methacholine and in the number of inflammatory cells recruited in the airways, specifically eosinophils, as well as in airway mucus secretion compared to OVA-challenged mice that received the empty vector. Administration of ORMDL3 shRNAs also significantly inhibited levels of IL-13, eotaxin-2 and sphingosine in the lungs. Additionally, ORMDL3 shRNAs significantly inhibited the allergen-mediated increase in monohexyl ceramides C22:0 and C24:0. Conclusions: Post-transcriptional down regulation of ORMDL3 in allergic lungs using i.n-delivered ORMDL3 shRNA (akin to inhaled therapy) attenuates development of key features of airway allergic disease, confirming the involvement of ORMDL3 in allergic asthma pathogenesis and serving as a model for a potential therapeutic strategy.

Purpose: To evaluate the clinical features and prognosis of a delayed-onset consecutive esotropia (ET) after surgical correction of intermittent exotropia., Methods: Thirty-four patients who developed consecutive ET after primary bilateral lateral rectus recession for the surgical correction of intermittent exotropia were evaluated retrospectively and were divided into two groups: delayed-onset consecutive ET group and the continuous consecutive ET group. Patients who developed esodeviation after once recovering to orthotropia within 1 month after the operation were included in the delayed-onset consecutive ET group, and patients with continuous esodeviation after the operation were included in the continuous consecutive ET group. We evaluated preoperative and postoperative angle of deviation, suppression, stereopsis, and follow up periods between the two groups and compared re-operation and success following non-surgical treatment between the continuous consecutive ET group and the delayed-onset consecutive ET group., Results: Among 34 patients with consecutive ET, 27 patients (79.4%) were included in the delayed-onset consecutive ET group, and seven patients (23.3%) were included in the continuous group. Success rate of non-surgical treatment was not statistically significant between two groups ( p = 0.55), but it was higher in the delayed-onset group with 37.5%, and 25% of patients in continuous group were successfully recovered to straight alignment. Duration of orthotropia in delayed-onset group was 7.4 ± 6.0 months (range, 2-29 months). Age, sex, preoperative refractive error, preoperative exodeviation, suppression, and near steroacuity were not statistically significant between two groups ( p > 0.05, all). In the delayed-onset group, three patients (11.1%) underwent re-operation, while three patients (42.9%) in continuous consecutive ET group underwent re-operation ( p = 0.048)., Conclusions: Re-operation rate of delayed-onset consecutive ET after surgical correction of intermittent exotropia was lower than that of continuous consecutive ET., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2020 The Korean Ophthalmological Society.)

Purpose: The purpose of this study was to investigate if the angle of deviation with Polarized glasses is effective for measuring maximal angles in patients with intermittent exotropia (IXT)., Design: Prospective cross-sectional study., Methods: This study was conducted on patients with >10 prism diopters (PD) of basic-type IXT at distance and near. Three consecutive, different methods for measurement of the angle of deviation were used: alternate prism cover test (ACT), ACT with Polarized glasses (Polaroid test), and ACT after 1 hour of monocular occlusion (occlusion test). Comparison of the 3 methods of measurement was conducted using the Friedman repeated ANOVA and Wilcoxon signed rank test., Results: A total of 60 patients were included in this study. Thirty (50%) patients were male. Mean age was 8.7 ± 5.1 years (range, 4-37 years) and measurements by ACT at distance and near were 25.2 ± 8.0 PD and 25.4 ± 8.2 PD, respectively. Angles of Polaroid and occlusion tests (29.0 ± 8.6 PD vs 30.6 ± 8.1 PD) were significantly increased compared to that of ACT at distance (P < .01), and there was no significant change between angles of Polaroid and occlusion tests at distance (P = .06). However, there was no significant change between angles of ACT and Polaroid tests (25.4 ± 8.2 PD vs 26.9 ± 8.1 PD) at near (P = .07)., Conclusion: The angle of deviation with Polarized glasses at distance increased and was comparable to that after the monocular occlusion test. The angle of exodeviation with Polarized glasses may be an easy, simple and effective alternative to measurement of maximum angle of deviation in IXT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate recovery from suppression when the target motor alignment is achieved following surgery for intermittent exotropia., Methods: The medical records of 237 patients who underwent surgery for exotropia were retrospectively reviewed. The age at surgery, sex, preoperative angle of deviation, suppression status, and near stereopsis were investigated. Suppression status was classified as no, alternate, or constant suppression. Target motor alignment was defined as 10 prism diopters (PD) or less of exodeviation or 2 PD of esodeviation at the final visit., Results: The mean age at surgery was 8.2 ± 3.2 years and 115 (48.5%) patients were male. The preoperative angle of deviation was 26.3 ± 5.9 PD and the follow-up postoperative period was 21.6 ± 7.6 months. The preoperative suppression status included 23 (9.7%), 55 (23.2%), and 159 (67.1%) patients who showed no, alternate, or constant suppression, respectively. Two hundred fifteen (90.7%) patients obtained the target motor alignment by the final visit. Of the 144 patients who demonstrated constant suppression preoperatively but achieved the target motor alignment postoperatively, 12 (8.3%) patients demonstrated residual suppression. All 12 of these patients had a preoperative angle of exotropia of greater than 20 PD., Conclusions: Most patients undergoing surgery for intermittent exotropia obtained both successful motor alignment and fusion postoperatively. However, successful motor alignment did not guarantee recovery of suppression when the preoperative angle of exotropia was greater than 20 PD. The preoperative factors and functional implications underlying this finding are unclear and merit further study. [J Pediatr Ophthalmol Strabismus. 2020;57(1):21-26.]., (Copyright 2020, SLACK Incorporated.)

Objective: To evaluate the surgical outcome of unilateral medial rectus resection with small advancement for recurrent exotropia, ≤30 prism diopters (PD), and verify new attachment site anatomically using anterior segment optical coherence tomography (ASOCT)., Method: This study is a retrospective chart review of patients who underwent 1.0 mm advancement of unilateral resected medial rectus from original medial rectus (OMR) insertion for recurrent exotropia since 2014. The age at operation, sex, preoperative angle of deviation, near stereopsis, and suppression were evaluated. Success was defined as ≤5 PD of esodeviation or ≤10 PD of exodeviation at the final visit. Preoperative scleral thickness was measured using ASOCT, 1.0 and 0.5 mm anterior to OMR insertion, and at the insertion., Results: A total of 76 patients, including 30 males (40.2%), were reviewed retrospectively. Continuous values were presented as mean ± standard deviation. Age at operation was 11.6 ± 6.6 years. The preoperative deviation was 20.9 ± 3.6 PD, and the amount of resected unilateral medial rectus was 4.5 ± 0.6 mm. The minimum required follow-up period after operation was 12 months after surgery. The postoperative follow-up period was 21.3 ± 8.0 months. A total of 65 patients (87.8%) showed successful outcome at the final visit. Preoperative scleral thickness at 1.0 and 0.5 mm anterior to OMR insertion site, and at OMR insertion site were 0.52 ± 0.05, 0.52 ± 0.06, and 0.43 ± 0.04 mm, respectively. Scleral thickness at OMR insertion site was significantly less compared with 1.0 and 0.5 mm from the OMR insertion site (p = 0.03)., Conclusion: The scleral thickness 1.0-0.5 mm anterior to OMR insertion site was thicker that than at the OMR insertion site. The new technique of medial rectus resection with small advancement may be safer and more effective than conventional technique., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To address the natural course of intermittent exotropia with small exodeviations (less than 20 prism diopters [PD]) according to the status of suppression, and to evaluate whether suppression testing at the initial visit can assist in predicting the progression of intermittent exotropia., Methods: Clinical records of patients at the Korea University Anam Hospital, Seoul, Korea diagnosed between January 2014 and December 2018 with basic-type intermittent exotropia and initial distance deviations of less than 20 PD, older than four years of age and a minimum of three follow-up visits within a 6-month span were retrospectively reviewed. The participants were divided into two groups, the suppression group and the non-suppression group, based on the Vectogram results at the initial visit. Clinical characteristics, rate of surgery, and rate of progression were compared between the two groups., Results: A total of 71 patients were included. Among them, 16 patients (22.5%) had visual suppression at the initial visit, while 55 patients (77.5%) had no suppression. At the initial visit, the mean distant angle of deviation was 13.7 ± 3.2 PD (range, 4 to 18 PD) in the suppression group and 12.7 ± 3.4 PD (range, 10 to 18 PD) in the non-suppression group. Ten patients (62.5%) underwent surgery in the suppression group and 12 patients (21.8%) underwent surgery in the non-suppression group ( p < 0.01). Eleven patients (68.8%) in the suppression group and 13 (23.6%) in the non-suppression group developed progression ( p < 0.01)., Conclusions: Suppression testing was important to predict the progression of intermittent exotropia, in patients with exodeviation angles less than 20 PD at the initial visit., Competing Interests: No potential conflict of interest relevant to this article was reported., (© 2019 The Korean Ophthalmological Society.)

Background: Early prediction of neurologic prognosis in children resuscitated from cardiac arrest is a major challenge. This study aimed to investigate the usefulness of a combined model based on brain computed tomography (CT) and initial blood gas analysis to predict neurologic prognoses in pediatric patients after cardiac arrest., Methods: We retrospectively analyzed the medical records of patients resuscitated after cardiac arrest from 2000 to 2018. Patients aged one month to 18 years were included. Gray to white matter ratio (GWR), ambient cistern effacement (ACE), and blood gas analysis were studied. The primary outcome was neurological prognosis, which was evaluated using the Pediatric Cerebral Performance Category (PCPC) scale at discharge., Results: Of 97 resuscitated patients, 64 brain CT images were available. Fourteen patients had a good neurologic outcome (PCPC 1-3) and 50 patients a poor neurologic outcome (PCPC 4-6). The multimodal model (AUC 0.897) containing GWR of basal ganglia (BG), ACE, and blood pH was found to be superior for predicting poor neurologic prognosis than single variable models (AUC of GWR-BG: 0.744, ACE: 0.804, pH: 0.747). Interestingly, we found the GWR-BG cutoff value for specificity 100% differed significantly between patients <4 years (cutoff value: 1.08, p = 0.04) and ≥4 years (cutoff value: 1.18, p = 0.004)., Conclusions: The combination of GWR-BG, ambient cistern effacement, and blood pH was found to usefully predict neurological outcome in children resuscitated from cardiac arrest. In addition, the cutoff value of GWR-BG for the prediction of neurologic outcome was found to increase with age., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Altered epithelial physical and functional barrier properties along with T H 1/T H 2 immune dysregulation are features of allergic asthma. Regulation of junction proteins to improve barrier function of airway epithelial cells has the potential for alleviation of allergic airway inflammation., Objective: We sought to determine the immunomodulatory effect of knob protein of the adenoviral capsid on allergic asthma and to investigate its mechanism of action on airway epithelial junction proteins and barrier function., Methods: Airway inflammation, including junction protein expression, was evaluated in allergen-challenged mice with and without treatment with knob. Human bronchial epithelial cells were exposed to knob, and its effects on expression of junction proteins and barrier integrity were determined., Results: Administration of knob to allergen-challenged mice suppressed airway inflammation (eosinophilia, airway hyperresponsiveness, and IL-5 levels) and prevented allergen-induced loss of airway epithelial occludin and E-cadherin expression. Additionally, knob decreased expression of T H 2-promoting inflammatory mediators, specifically IL-33, by murine lung epithelial cells. At a cellular level, treatment of human bronchial epithelial cells with knob activated c-Jun N-terminal kinase, increased expression of occludin and E-cadherin, and enhanced epithelial barrier integrity., Conclusion: Increased expression of junction proteins mediated by knob leading to enhanced epithelial barrier function might mitigate the allergen-induced airway inflammatory response, including asthma., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate clinical features for prescription of tapered hyperopia in patients with refractive accommodative esotropia (RAET)., Methods: The clinical features in patients with RAET who began tapering of hyperopia were analyzed. Within a range that can sustain corrected visual acuity and stereoacuity, patients were prescribed for tapered hyperopic correction by 0.25-diopters (D) interval, up to a maximum of 1.0 D. At every visit, visual acuity and esodeviation with and without correction, amount of tapered hyperopia, and near stereoacuity were measured., Results: One hundred and six patients were enrolled in this study. The follow-up period was 3.1 ± 0.2 years and frequency of visits was 6.3 ± 0.6. Tapering hyperopia was initiated at 6.1 ± 2.9 years, and baseline refraction was 7.6 ± 1.5 D. The esodeviation without correction was 24.3 ± 8.5 prism diopters (PD), and median near stereoacuity was 400 arc sec. The median amount of tapered hyperopia at visit was 0.5 D. At the final visit, there were no significant deteriorations in visual acuity, esodeviation with correction, or near stereoacuity (p > 0.05, all). The amount of tapered hyperopia was positively correlated with correction and the reduced esodeviation without correction (p = 0.03)., Conclusions: Esodeviation without correction should be considered for tapering hyperopia for patients with RAET. Esodeviation without correction can be easily measured, and its decline may be used as a clinical indicator for tapering hyperopia., (Copyright © 2018 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to compare the therapeutic efficacy of prolonged macrolide (PMC), corticosteroids (CST), doxycycline (DXC), and levofloxacin (LFX) against macrolide-unresponsive Mycoplasma pneumoniae (MP) pneumonia in children and to evaluate the safety of the secondary treatment agents., Methods: We retrospectively analyzed the data of patients with MP pneumonia hospitalized between January 2015 and April 2017. Macrolide-unresponsiveness was clinically defined with a persistent fever of ≥ 38.0°C at ≥ 72 hours after macrolide treatment. The cases were divided into four groups: PMC, CST, DXC, and LFX. We compared the time to defervescence (TTD) after secondary treatment and the TTD after initial macrolide treatment in each group with adjustment using propensity score-matching analysis., Results: Among 1,165 cases of MP pneumonia, 190 (16.3%) were unresponsive to macrolides. The proportion of patients who achieved defervescence within 48 hours in CST, DXC, and LFX groups were 96.9% (31/33), 85.7% (12/14), and 83.3% (5/6), respectively. The TTD after initial macrolide treatment did not differ between PMC and CST groups (5.1 vs. 4.2 days, P = 0.085), PMC and DXC groups (4.9 vs. 5.7 days, P = 0.453), and PMC and LFX groups (4.4 vs. 5.0 days, P = 0.283). No side effects were observed in the CST, DXC, and LFX groups., Conclusion: The change to secondary treatment did not show better efficacy compared to PMC in children with macrolide-unresponsive MP pneumonia. Further studies are needed to guide appropriate treatment in children with MP pneumonia., Competing Interests: Disclosure: The authors have no potential conflicts of interest to disclose.

Fatty acid binding protein 4 (FABP4), a member of a family of lipid-binding proteins, is known to play a role in inflammation by virtue of its ability to regulate intracellular events such as lipid fluxes and signaling. Studies have indicated a proinflammatory role for FABP4 in allergic asthma although its expression and function in eosinophils, the predominant inflammatory cells recruited to allergic airways, were not investigated. We examined expression of FABP4 in murine eosinophils and its role in regulating cell recruitment in vitro as well as in cockroach antigen (CRA)-induced allergic airway inflammation. CRA exposure led to airway recruitment of FABP4-expressing inflammatory cells, specifically eosinophils, in wild-type (WT) mice. FABP4 expression in eosinophils was induced by TNF-α as well as IL-4 and IL-13. FABP4-deficient eosinophils exhibited markedly decreased cell spreading/formation of leading edges on vascular cell adhesion molecule-1 and significantly decreased adhesion to intercellular adhesion molecule-1 associated with reduced β2-integrin expression relative to WT cells. Furthermore, FABP4-deficient eosinophils exhibited decreased migration, F-actin polymerization, calcium flux, and ERK(1/2) phosphorylation in response to eotaxin-1. In vivo, CRA-challenged FABP4-deficient mice exhibited attenuated eosinophilia and significantly reduced airway inflammation (improved airway reactivity, lower IL-5, IL-13, TNF-α, and cysteinyl leukotriene C4 levels, decreased airway structural changes) compared with WT mice. In conclusion, expression of FABP4 in eosinophils is induced during conditions of inflammation and plays a proinflammatory role in the development of allergic asthma by promoting eosinophil adhesion and migration and contributing to the development of various aspects of airway inflammation.

Background: To investigate surgical factors associated with the occurrence of oculocardiac reflex (OCR) and changes in heart rate (HR) during strabismus surgery., Methods: Patients who underwent strabismus surgery under general anesthesia were enrolled in this study. The HR during surgery was measured at baseline, and at the following points during surgery: traction of the muscle, maximal increase after traction (adrenergic phase), and the cutting of the muscle. OCR was defined as an HR reduction of more than 20% at traction of the muscle, when compared to baseline HR. The HR at each stage during the surgery was compared between patients with and without OCR., Results: A total of 162 operated muscles from 99 patients were enrolled. The incidence of OCR was 65% in patients. In patients with two muscle surgeries, there were significantly more OCRs in the first operated muscle than in the second operated muscle (p < 0.01). The difference in the decrease in HR in patients with OCR was significantly lower than that in patients without OCR at traction of the muscle, the adrenergic phase, and the cutting of the muscle (all, p < 0.01). The first operated muscle was a significant risk factor associated with the occurrence of OCR (OR = 3.95, p < 0.01)., Conclusion: The first operated muscle in patients with two muscle surgeries was a significant risk factor for OCR. Decreased HR at the traction of the muscle during surgery did not fully recover in patients with OCR.

Background: HSPGs are glycoproteins containing covalently attached heparan sulfate (HS) chains which bind to growth factors, chemokines, etc., and regulate various aspects of inflammation including cell recruitment. We previously showed that deletion of endothelial N-acetylglucosamine N-deacetylase-N-sulfotransferase-1 (Ndst1), an enzyme responsible for N-sulfation during HS biosynthesis, reduces allergic airway inflammation (AAI). Here, we investigated the importance of O-sulfation mediated by uronyl 2-O-sulfotransferase (Hs2st) in development of AAI relative to N-sulfation., Methods: Mice deficient in endothelial and leukocyte Hs2st (Hs2st f/f Tie2Cre + ) or Ndst1 (Ndst1 f/f Tie2Cre + ) and WT mice were challenged with Alternaria alternata and evaluated for airway inflammation. Trafficking of murine eosinophils on lung endothelial cells was examined in vitro under conditions of flow., Results: Exposure to Alternaria decreased expression level of Hs2st in WT mice while level of Ndst1 remained unchanged. Compared to WT mice, Alternaria-challenged Hs2st f/f Tie2Cre + mice exhibited significantly increased eosinophils in the bone marrow, bronchoalveolar lavage fluid [BALF] and lung tissue associated with persistent airway hyperresponsiveness, airway mucus hypersecretion and elevated Th2 cytokines. In contrast, Alternaria-challenged Ndst1 f/f Tie2Cre + mice exhibited a marked reduction in airway eosinophilia, mucus secretion and smooth muscle mass compared to WT counterparts. While BALF eotaxins were lower in Alternaria-challenged Hs2st f/f Tie2Cre + relative to WT mice, they were not reduced to background levels as in allergen-challenged Ndst1 f/f Tie2Cre + mice. Trafficking of murine eosinophils under conditions of flow in vitro was similar on Hs2st-deficient and WT endothelial cells. Expression of ZO-1 in Hs2st-deficient lung blood vessels in control and allergen-challenged mice was significantly lower than in WT counterparts., Conclusions: Our study demonstrates that allergen exposure reduces expression of Hs2st; loss of uronyl 2-O-sulfation in endothelial and leukocyte HSPG amplifies recruitment of eosinophils likely due to a compromised vascular endothelium resulting in persistent inflammation whereas loss of N-sulfation limits eosinophilia and attenuates inflammation underscoring the importance of site-specific sulfation in HSPG to their role in AAI.

Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzo[d]thiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown. In this study, we investigated whether MHY2013 alleviates hepatic lipid accumulation in aged Sprague-Dawley (SD) rats. We confirmed that MHY2013 increased the activities of three PPAR subtypes in HepG2 cells using luciferase assay. When administered orally in aged SD rats, MHY2013 markedly decreased the hepatic triglyceride levels without changes in body weight. Regarding underlying mechanisms, MHY2013 increased the mRNA levels of lipid oxidation-related genes, including carnitine palmitoyltransferase 1 (CPT1) and peroxisomal acyl-CoA oxidase 1 (ACOX1), without apparent change in the mRNA expression of lipogenesis-related genes. Furthermore, MHY2013 significantly increased systemic fibroblast growth factor 21 (FGF21) and adiponectin levels and suppressed inflammatory mRNA expression in the liver. In conclusion, MHY2013 alleviated age-related hepatic lipid accumulation, in part by upregulating β-oxidation signaling and suppressing inflammation in the liver. Therefore, MHY2013 is a potential pharmaceutical agent for treating age-related hepatic lipid accumulation.

Objective: To investigate the surgical outcome according to the angle of deviation at postoperative day 1 in patients with recurrent exotropia DESIGN: Retrospective case series METHODS: Surgical outcome in patients with recurrent exotropia for at least 1 year was analyzed retrospectively. Patients were divided into 3 subgroups according to the angle of deviation at postoperative day 1: overcorrection group (≥2 prism diopter [PD] of esodeviation), orthotropic group (orthotropia or <5 PD of exodeviation), and undercorrection group (≥5 PD of exodeviation). Success was defined as ≤5 PD of esodeviation or ≤10 PD of exodeviation at the final visit., Results: One hundred and six patients were included in this study. Age at surgery was 11.8 ± 6.9 years, and preoperative angle of deviation was 22.9 ± 6.3 PD at distant. Patients were followed-up for 24.4 ± 12.8 months. There were 20 (18.9%), 82 (77.4%), and 4 (3.8%) patients in overcorrection, orthotropic, and undercorrection groups at postoperative day 1 (p = 0.001). The surgical success rate at the final visit in the overcorrection group (95%) was higher than that in orthotropic and undercorrection groups (76.8% and 25%, respectively, p = 0.004). In univariate regression analysis, overcorrection at postoperative day 1 was the only reliable factor for long-term success (odds ratio [OR] = 24.101, p = 0.01)., Conclusion: Overcorrection at postoperative day 1 is a good surgical predictor of successful outcome in surgery for recurrent exotropia., (Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the clinical features and surgical outcome of A-pattern exotropia combined with dissociated vertical deviation and superior oblique overaction., Methods: The medical records of patients with A-pattern exotropia combined with dissociated vertical deviation and superior oblique overaction who underwent horizontal muscle surgery alone or in combination with superior oblique muscle weakening surgery were retrospectively reviewed. The patients were divided into two groups according to their surgery: the horizontal muscle surgery alone group and the horizontal muscle surgery with bilateral superior oblique weakening surgery (combined surgery) group. The preoperative clinical features and postoperative surgical outcomes at the patients' final follow-up visits were analyzed., Results: A total of 40 patients were included. The mean age at diagnosis was 5.5 ± 4.6 years. Amblyopia and latent nystagmus were observed in 18 (45%) and 10 (25%) patients, respectively. Six (15%) patients were associated with delayed development and hemiplegia. The mean angle of exodeviation was 27.7 ± 11.2 and 28.5 ± 10.9 prism diopters (PD) for distance and near, respectively. The mean degree of superior oblique overaction was 1.9 ± 1.1 and asymmetrical dissociated vertical deviation was observed in 24 (60%) patients. At the final follow-up visit, the horizontal angle of deviation was not significantly different between the groups. The success rates were 57.1% and 80% in the horizontal muscle surgery alone and combined surgery groups, respectively. These differences were statistically significant (P = .04)., Conclusion: Amblyopia was common and the prognosis of binocularity was poor in triad exotropia. Some patients had neurological deficits. The surgical success rate in this study was variable, ranging from 57.1% to 80%. [J Pediatr Ophthalmol Strabismus. 2017;54(6):363-368.]., (Copyright 2017, SLACK Incorporated.)

Central nervous system (CNS) involvement, including optic nerve involvement, in a patient with acute myeloid leukaemia (AML) is an extremely rare condition. We report a case of bilateral optic nerve involvement combined with unilateral facial palsy in a patient with AML who achieved complete remission following allogenic peripheral blood stem cell transplantation as a young patient. After further evaluation, the patient was diagnosed with a recurrence of AML with CNS involvement. The presentation of multiple types of CNS involvement in AML may be suspicious evidence of AML recurrence.

Objective: Odontoid fracture is common in cervical injury, representing about 20% of total cervical fractures. Classic odontoid fracture classification focused on anatomy of fracture site has no treatment recommendation and a modified treatment-oriented classification of odontoid fracture was suggested in 2005. We reviewed our odontoid fracture patients to assess the feasibility and efficacy of Grauer's classification., Methods: Between October 2000 and September 2015, we collected data from patients who came to our institute for odontoid fracture. Demographic data of patients was reviewed, and neck visual analog scale (VAS) score and fusion rate were assessed by reviewing electronic medical records retrospectively., Results: Sixty-nine patients out of a total of eighty two odontoid fracture patients were reviewed according to Grauer's classification. Neck VAS of all subtypes in odontoid fracture classification were decreased at last follow-up (p=0.001). Overall fusion rate was 88.4% at last follow-up. Concordance rate between Grauer's recommendation and our treatment was 69.9%, especially in type II with the concordance higher than 80%. Complication was minimal representing 7.2%, only in types I and III., Conclusion: In this study, there were statistically significant improvement in all subtypes in terms of neck VAS at the last follow up, especially in types II and III. Grauer's classification appears to be meaningful to decide treatment plan for odontoid fractures, especially type II odontoid fracture.

Purpose: To evaluate the effects of bilateral inferior oblique transposition (BIOT) on horizontal deviation from primary position among patients with bilateral dissociated vertical deviation (DVD) associated with inferior oblique overaction (IOOA) in infantile strabismus., Methods: Retrospective chart review was conducted among 19 patients with infantile strabismus. All patients had DVD and IOOA with consecutive or recurrent horizontal deviation and underwent modified BIOT surgery. Patients were divided into three subgroups: patients who underwent BIOT (BIOT group, n = 9) alone, BIOT with medial rectus recession or lateral rectus resection simultaneously (ET BIOT group, n = 6), or BIOT with lateral rectus recession or medial rectus resection simultaneously (XT BIOT group, n = 4). Postoperative angle of horizontal deviation (prism diopter, PD) and corrected magnitude of horizontal deviation (PD) at final visit after surgery were analyzed in each group., Results: The mean age was 55.11 ± 21.05 months (range, 32 to 115). The mean follow-up period was 8.68 ± 2.87 months (range, 6 to 18). Preoperative horizontal deviation was 4.23 ± 5.99 PD (range, 0 to 16) in BIOT, -17.33 ± 6.76 PD (range, -30 to -10) in ET BIOT, and 17.50 ± 2.52 PD (range, 14 to 20) in XT BIOT. Esodeviation is represented by negative values. DVD and IOOA were reduced less than +1 in all patients. The corrected amount of horizontal deviation was 3.56 ± 5.18 PD (range, 0 to 16) in BIOT surgery alone and larger in XT BIOT (18.50 ± 3.41 PD) than in ET BIOT (12.33 ± 5.57 PD, p = 0.004)., Conclusions: Minimal exodeviation was corrected by BIOT alone. In addition, secondary eso- or exodeviation at great magnitudes should be corrected with proper horizontal muscle surgery along with BIOT., Competing Interests: Conflict of Interest: No potential conflict of interest relevant to this article was reported.

Purpose: To investigate the efficacy of evaluating 3D asthenopia and 3D perception difficulty for screening of binocular vision abnormalities in children., Methods: Patients aged 6-12 years with abnormal binocularity, including strabismus, amblyopia, and anisometropia, were included. Age-matched normal subjects without any ophthalmologic abnormality other than a refractive error were also recruited. The best-corrected visual acuity, refractive error, angle of strabismus, and stereopsis were measured. Presenting visual acuity (PVA) was measured as the uncorrected visual acuity for subjects without glasses and spectacle-corrected visual acuity for those with glasses. After watching 3D TV for 30 min, a survey was administered to evaluate the 3D perception and 3D asthenopia. Receiver operation characteristic (ROC) curve analysis was conducted to evaluate the efficacy of the survey for detecting abnormal binocularity and poor PVA., Results: One hundred subjects were enrolled in this study. Among them, 59 had abnormal binocularity (strabismus, anisometropia, or amblyopia), and 41 were normal control. Among the entire subjects, the number of subjects with a PVA of 20/40 or worse in one or both eyes was 24 (7 from the normal control and 17 with abnormal binocularity). ROC curve analysis revealed that the survey did not effectively detect strabismus, anisometropia, or amblyopia. However, for detection of PVA 20/40 or worse in the subjects with abnormal binocularity, the total score of the survey yielded an area of 0.714 under the ROC curve (p = 0.010). The sensitivity was 88.2% and specificity was 61.9% with a cutoff at 0.50., Conclusion: The degree of 3D asthenopia and 3D perception while watching 3D TV were not effective for screening of abnormal binocularity. However, evaluation of the severity of 3D asthenopia and the quality of 3D perception can help screen of decrease in PVA that requires correction.

Purpose: To compare the amount of esotropia corrected by surgery under general anesthesia and in a conscious state in esotropia surgery., Methods: The charts of 42 patients who underwent surgery under general anesthesia for correction of esotropia were reviewed. Angle of deviation was measured by the alternate prism cover test in awakened state one day before and after surgery. Under general anesthesia, angle of deviation was measured by Hirschberg or Krimsky test in 5 prism diopters (PD) scale 30 minutes after induction and at the end of the surgery. The amount of the angle of esodeviation corrected by surgery measured in awakened state (A-correction) and under general anesthesia (G-correction) was compared and analyzed to identify significant differences., Results: The median age was 4.0 years and the median preoperative esodeviation angle was 30.0 PD. The median amount of G-correction of 30.0 PD was significantly different compared with that of A-correction at postoperative day one (p=0.003). However, differences between A-correction and G-correction were not evident at postoperative one week, one month, and final follow-up examination (p= 0.191, 0.215, and 0.396, respectively)., Conclusions: Esotropia in A-correction was comparable to that in G-correction only at postoperative day one. These results suggest that it is desirable to perform esotropia surgery according to the initial surgical plan of awakened state regardless of the divergence of eye position. When in doubt, it could be useful to confirm whether the actual amount of surgical correction under general anesthesia is consistent with the plan and modifying the surgical dose nomogram.

Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1-expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan- and dose-dependent. At concentrations ≤0.25 µM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1-induced migration. Exposure to concentrations ≥1 µM resulted in ERK(1/2)-dependent apoptosis and disruption of the F-actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1-deficient mice exhibited increased recruitment of eosinophils and CD3(+) T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis., Competing Interests: The authors declare no conflict of interest.

Purpose: To investigate the clinical effects of head-mounted display on the refractive error and oculomotor system in normal adolescents., Methods: Sixty volunteers (age: 13 to 18 years) watched a three-dimensional movie and virtual reality application of head-mounted display for 30 minutes. The refractive error (diopters [D]), angle of deviation (prism diopters [PD]) at distance (6 m) and near (33 cm), near point of accommodation, and stereoacuity were measured before, immediately after, and 10 minutes after watching the head-mounted display. The refractive error was presented as spherical equivalent (SE). Refractive error was measured repeatedly after every 10 minutes when a myopic shift greater than 0.15 D was observed after watching the head-mounted display., Results: The mean age of the participants was 14.7 ± 1.3 years and the mean SE before watching head-mounted display was -3.1 ± 2.6 D. One participant in the virtual reality application group was excluded due to motion sickness and nausea. After 30 minutes of watching the head-mounted display, the SE, near point of accommodation, and stereoacuity in both eyes did not change significantly (all P > .05). Immediately after watching the head-mounted display, esophoric shift was observed (0.6 ± 1.5 to 0.2 ± 1.5 PD), although it was not significant (P = .06). Transient myopic shifts of 17.2% to 30% were observed immediately after watching the head-mounted display in both groups, but recovered fully within 40 minutes after watching the head-mounted display., Conclusions: There were no significant clinical effects of watching head-mounted display for 30 minutes on the normal adolescent eye. Transient changes in refractive error and binocular alignment were noted, but were not significant. [J Pediatr Ophthalmol Strabismus. 2016;53(4):238-245.]., (Copyright 2016, SLACK Incorporated.)

Background: To investigate the accommodative loads change needed to maintain binocular fusion in patients with intermittent exotropia (IXT)., Methods: Seventeen consecutive patients with basic IXT and 15 normal controls were recruited. The WAM-5500 autorefractor (GrandSeiko, Fukuyama, Japan) was used to measure refractive error (D) under binocular and monocular viewing conditions at 6 m, 50 cm, 33 cm and 20 cm. The difference between binocular and monocular refractive error (D) at each distance defined the change in the accommodative load. The changes in accommodative load were compared between IXT patients and normal controls. We also investigated the change in accommodative loads according to the fixing preference in patients with IXT., Results: In IXT patients, the mean angles of deviation were 20.2 ± 7.19 and 21.0 ± 8.02 prism diopters at 6 m and 33 cm, respectively. Under binocular viewing, the changes in accommodative loads of each eye in IXT patients were significantly higher at 50, 33 and 20 cm than those of normal controls (p < 0.05, all). The changes in accommodative loads of fixating and deviating eyes at 6 m were not significantly different between IXT patients and normal controls (p = 0.193, 0.155, respectively). The changes in accommodative loads of the fixating eye at each distance were not significantly different from those of the deviating eye in IXT patients (p > 0.05)., Conclusion: The changes of accommodative loads at near fixation increased more in IXT patients than they did in normal controls while maintaining binocular fusion.

Purpose: To examine clinical preoperative and postoperative symptoms and changes in exotropia according to constancy and age., Methods: A survey was conducted of 50 patients on the day before and 1 month after exotropia surgery. Survey results were analyzed by type of exotropia at presentation and age. Changes in subjective symptoms from preoperatively to postoperatively were examined for stereopsis (5 items), asthenopia (5 items), and appearance (5 items). Each item was rated on a 5-point scale ranging from 0 to 4., Results: The mean age of the 50 patients was 10.6 ± 7.75 years, and there were 21 (41.2%) males and 29 (56.9%) females. Thirty-two patients with intermittent exotropia had no significant improvement in the stereopsis or asthenopia symptoms. However, they showed significant (P < .05) improvement in the appearance symptoms of squint and out of focus. Eighteen patients with constant exotropia showed significant improvements in the symptoms of tripping over objects or running into a wall in stereopsis and of squint and out of focus in appearance (P < .05). Postoperatively, all patients had significant improvement in appearance-related symptoms regardless of age (P < .05)., Conclusions: Patients with constant exotropia had improved symptoms in stereopsis, asthenopia, and appearance after surgery. Appearance was improved regardless of the type of exotropia or age., (Copyright 2016, SLACK Incorporated.)

Purpose: Cataracts are the leading cause of visual impairment and blindness, and therefore early identification and modification of the risk factors for cataracts are meaningful. This study aimed to investigate the relationship between socioeconomic status (SES) and lifestyle factors, and age-related cataracts in South Korea., Methods: This cross-sectional study was based on data collected in the 2008-2011 Korea National Health and Nutrition Examination Survey. A total of 15 866 subjects, aged ≥40 years, were included. SES was defined using household income and education level. Sociodemographic, lifestyle, and other associated factors were assessed by health interviews and examinations. Cataracts were diagnosed via slit-lamp examination using the Lens Opacities Classification System III., Results: The prevalence of any cataract was 38.9% in men and 42.3% in women (P<0.001). In women, the risk of cataracts increased with decreases in household income (P-value for trend=0.016 and 0.041 in any, and cortical cataract, respectively) and education level (P-value for trend=0.009, 0.027, and 0.016 in any, nuclear, and cortical cataract, respectively) after adjusting for confounding factors. Current smoking was correlated with nuclear cataracts in men (OR 1.21; 95% CI: 1.00, 1.46 in age-adjusted analysis) and cataract surgery in women (OR 2.25; 95% CI: 1.00, 5.04 in multivariate-adjusted analysis)., Conclusions: Socioeconomic disparities in cataract prevalence were observed in women; current smoking increased the risk of nuclear cataracts in men and surgery in women. Public health interventions focusing on gender differences are warranted to prevent and treat cataracts.

Purpose: To investigate patterns of functional magnetic resonance imaging (fMRI) activation during sentence reading before and after wearing color-tinted lenses., Methods: A total of 15 Meares-Irlen syndrome patients with a mean age of 23.4 years (range, 13 to 42 years) with no history of neurological or psychiatric disorders were scanned using a 3T MR scanner (Siemens, Tim-Trio, Germany). Each patient underwent two sessions of fMRI imaging (before and after MISViS color-tinted lens application). The fMRI paradigm included a block design of 20 seconds of rest (cross), 20 seconds of activation (sentence reading), and ten blocks (a total of 200 echo-planar image volumes) repeated for each session. Data preprocessing and analyses were performed using the SPM8 software package., Results: The reading speed of patients improved more than 20% while wearing the selected lenses. When compared to the before-lens session, the after-lens session identified significant regions of activation in the left middle and superior temporal gyri (paired t-test; maximal z score, 5.38; Montreal Neurological Institute coordinate, -60 / -39 / 0; threshold at p < 0.05; corrected for multiple comparisons using family-wise error). No region of activation at the same threshold was found in the before-lens session as compared to the after-lens session., Conclusions: In the current study, we confirmed activation in the left middle and superior temporal gyri during sentence reading after wearing color-tinted lenses. These results could explain the effectiveness of color-tinted lenses in patients with Meares-Irlen syndrome.

Efficient unconditionally stable FDTD method is developed for the electromagnetic analysis of dispersive media. Toward this purpose, a quadratic complex rational function (QCRF) dispersion model is applied to the alternating-direction-implicit finite-difference time-domain (ADI-FDTD) method. The 3-D update equations of QCRF-ADI-FDTD are derived using Maxwell's curl equations and the constitutive relation. The periodic boundary condition of QCRF-ADI-FDTD is discussed in detail. A 3-D numerical example shows that the time-step size can be increased by the proposed QCRF-ADI-FDTD beyond the Courant-Friedrich-Levy (CFL) number, without numerical instability. It is observed that, for refined computational cells, the computational time of QCRF-ADI-FDTD is reduced to 28.08 % of QCRF-FDTD, while the L 2 relative error norm of a field distribution is 6.92 %.

Purpose: To examine the associations of various parameters of obesity including adiposity with intraocular pressure (IOP) using nationally representative data of South Korean adults., Material and Methods: This cross-sectional study analyzed the data from the 2008-2010 Korea National Health and Nutrition Examination Survey. A total of 15,271 subjects (6600 men and 8671 women) participated. Body mass index (BMI), waist circumference (WC), total body fat mass, and total and regional body fat percentage were measured as parameters of obesity., Results: IOP showed positive linear associations with BMI, WC, total fat mass, and total and regional body fat percentages in men, and with BMI, WC, total fat mass, and trunk fat percentage in women after adjusting for confounding variables. Men with higher BMI, WC, total fat mass, and total and regional body fat percentages exhibited increasing trends in odd ratios for having IOP ≥ 18 mmHg after adjusting for all confounding factors (p for trend <0.001 for BMI and total fat mass; p for trend = 0.038 for WC; 0.003 for total body fat percentage; 0.002 for trunk fat percentage; 0.004 for leg fat percentage). However, only BMI showed a significantly increasing trend in the risk of IOP ≥18 mmHg in women., Conclusions: In addition to BMI, WC and total fat mass, total and regional body fat percentage in men and trunk fat percentage in women are positively associated with IOP. Increased BMI, WC, and total and regional body fat are positively associated with a risk of higher IOP (IOP ≥18 mmHg), especially in Korean men.

Heparan sulfate (HS) proteoglycans (HSPGs) participate in several aspects of inflammation because of their ability to bind to growth factors, chemokines, interleukins and extracellular matrix proteins as well as promote inflammatory cell trafficking and migration. We investigated whether HSPGs play a role in the development of airway remodeling during chronic allergic asthma using mice deficient in endothelial- and leukocyte-expressed N-deacetylase/N-sulfotransferase-1 (Ndst1), an enzyme involved in modification reactions during HS biosynthesis. Ndst1-deficient and wild-type (WT) mice exposed to repetitive allergen (ovalbumin [OVA]) challenge were evaluated for the development of airway remodeling. Chronic OVA-challenged WT mice exhibited increased HS expression in the lungs along with airway eosinophilia, mucus hypersecretion, peribronchial fibrosis, increased airway epithelial thickness and smooth muscle mass. In OVA-challenged Ndst1-deficient mice, lung eosinophil and macrophage infiltration as well as airway mucus accumulation, peribronchial fibrosis and airway epithelial thickness were significantly lower than in allergen-challenged WT mice along with a trend toward decreased airway smooth muscle mass. Leukocyte and endothelial Ndst 1 deficiency also resulted in significantly decreased expression of IL-13 as well as remodeling-associated mediators such as VEGF, FGF-2 and TGF-β1 in the lung tissue. At a cellular level, exposure to eotaxin-1 failed to induce TGF-β1 expression by Ndst1-deficient eosinophils relative to WT eosinophils. These studies suggest that leukocyte and endothelial Ndst1-modified HS contribute to the development of allergen-induced airway remodeling by promoting recruitment of inflammatory cells as well as regulating expression of pro-remodeling factors such as IL-13, VEGF, TGF-β1 and FGF-2 in the lung., (© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Preoperative identification of aggressiveness is important for the establishment of a treatment strategy in patients with soft-tissue sarcoma (STS). We compared the predictive values of various metabolic parameters derived from PET/CT with (18)F-FDG, including maximal standardized uptake value (SUVmax), total lesion glycolysis (TLG) and metabolic tumour volume (MTV)., Methods: A total of 66 patients with STS who had undergone FDG PET/CT before tumour resection were reviewed retrospectively. We determined SUVmax, TLG and MTV to compare their value in predicting disease progression, which was defined as local recurrence and metastases. Receiver operating characteristic curve (ROC) analysis was used to compare the accuracy. Univariate and multivariate analyses of conventional clinicopathological variables were used to compare the reliability of the metabolic parameters., Results: TLG exhibited greater accuracy than SUVmax or MTV in ROC analysis (area under curve, AUC, 0.802, 0.726 and 0.681, respectively). The cut-off values for disease progression derived from the AUC data were TLG 250; SUVmax 6.0, and MTV 40 cm(3). In univariate analysis, TLG (>250) was a more significant predictive factor than SUVmax and MTV (P < 0.001, P = 0.031 and P = 0.022, respectively). TLG was the only meaningful metabolic parameter in the multivariate analysis (P = 0.008) other than presence of metastasis at diagnosis (P = 0.003)., Conclusion: TLG is a more accurate predictor of disease progression than SUVmax or MTV. TLG enables accurate preoperative assessment of aggressiveness comparable with conventional clinicopathological parameters.

Obesity is an important risk factor for asthma but the mechanistic basis for this association is not well understood. In the current study, the impact of obesity on lung inflammatory responses after allergen exposure was investigated. C57BL/6 mice maintained on a high-fat diet (HFD) or a normal diet (ND) after weaning were sensitized and challenged with cockroach allergen (CRA). Airway inflammation was assessed based on inflammatory cell recruitment, measurement of lung Th1-Th2 cytokines, chemokines, eicosanoids, and other proinflammatory mediators as well as airway hyperresponsiveness (AHR). CRA-challenged mice fed a HFD exhibited significantly decreased allergen-induced airway eosinophilia along with reduced lung IL-5, IL-13, LTC4, CCL11, and CCL2 levels as well as reduced mucus secretion and smooth muscle mass compared to ND fed mice. However, allergen-challenged HFD fed mice demonstrated significantly increased PAI-1 and reduced PGE2 levels in the lung relative to corresponding ND fed mice. Interestingly, saline-exposed HFD fed mice demonstrated elevated baseline levels of TGF-β1, arginase-1, hypoxia-inducible factor-1α, and lung collagen expression associated with decreased lung function compared to corresponding ND fed mice. These studies indicate that a HFD inhibits airway eosinophilia while altering levels of PAI-1 and PGE2 in response to CRA in mice. Further, a HFD can lead to the development of lung fibrosis even in the absence of allergen exposure which could be due to innate elevated levels of specific profibrotic factors, potentially affecting lung function during asthma.

Galectin-3 (Gal-3), a β galactoside-binding lectin, is implicated in the pathogenesis of allergic airway inflammation and allergen-challenged mice deficient in Gal-3 (Gal-3(-/-)) exhibit decreased airway recruitment of eosinophils (Eos). Gal-3 is expressed and secreted by several cell types and can thus function extracellularly and intracellularly to regulate a variety of cellular responses. We sought to determine the role of Eos-expressed Gal-3 in promoting Eos trafficking and migration in the context of allergic airway inflammation using bone marrow (BM)-derived Eos from wild-type (WT) and Gal-3(-/-) mice. Airway recruitment of Eos in acute (4 weeks) and chronic (8-12 weeks) allergen-challenged WT mice correlated with Gal-3 expression in the lungs. BM-derived Eos were found to express Gal-3 on the cell surface and secrete soluble Gal-3 when exposed to eotaxin-1. Compared to WT Eos, Gal-3(-/-) Eos exhibited significantly reduced rolling on vascular cell adhesion molecule 1 (VCAM-1) and decreased stable adhesion on intercellular adhesion molecule 1 (ICAM-1) under conditions of flow in vitro. Evaluation of cytoskeletal rearrangement demonstrated that relatively fewer adherent Gal-3(-/-) Eos undergo cell spreading and formation of membrane protrusions. In addition, cell surface expression of integrin receptor αM (CD11b) was lower in Gal-3(-/-) Eos, which is likely to account for their altered adhesive interactions with VCAM-1 and ICAM-1. Gal-3(-/-) Eos also exhibited significantly decreased migration toward eotaxin-1 compared to WT Eos irrespective of similar levels of CCR3 expression. Further, eotaxin-induced migration of WT Eos remained unaffected in the presence of lactose, suggesting a role for intracellular Gal-3 in regulating Eos migration. Overall, our findings indicate that Gal-3 expression in the lungs correlates with Eos mobilization during allergic airway inflammation and signaling involving intracellular Gal-3 and/or secreted Gal-3 bound to the cell surface of Eos appears to be essential for Eos trafficking under flow as well as for migration.

Association of the neurotransmitter serotonin (5-HT) with the pathogenesis of allergic asthma is well recognized and its role as a chemoattractant for eosinophils (Eos) in vitro and in vivo has been previously demonstrated. Here we have examined the regulation of 5-HT-induced human and murine Eos trafficking and migration at a cellular and molecular level. Eos from allergic donors and bone marrow-derived murine Eos (BM-Eos) were found to predominantly express the 5-HT2A receptor. Exposure to 5-HT or 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-HT2A/C selective agonist, induced rolling of human Eos and AML14.3D10 human Eos-like cells on vascular cell adhesion molecule (VCAM)-1 under conditions of flow in vitro coupled with distinct cytoskeletal and cell shape changes as well as phosphorylation of MAPK. Blockade of 5-HT2A or of ROCK MAPK, PI3K, PKC and calmodulin, but not G(αi)-proteins, with specific inhibitors inhibited DOI-induced rolling, actin polymerization and changes in morphology of VCAM-1-adherent AML14.3D10 cells. More extensive studies with murine BM-Eos demonstrated the role of 5-HT in promoting rolling in vivo within inflamed post-capillary venules of the mouse cremaster microcirculation and confirmed that down-stream signaling of 5-HT2A activation involves ROCK, MAPK, PI3K, PKC and calmodulin similar to AML14.3D10 cells. DOI-induced migration of BM-Eos is also dependent on these signaling molecules and requires Ca(2+). Further, activation of 5-HT2A with DOI led to an increase in intracellular Ca(2+) levels in murine BM-Eos. Overall, these data demonstrate that 5-HT (or DOI)/5-HT2A interaction regulates Eos trafficking and migration by promoting actin polymerization associated with changes in cell shape/morphology that favor cellular trafficking and recruitment via activation of specific intracellular signaling molecules (ROCK, MAPK, PI3K and the PKC-calmodulin pathway).

ORM (yeast)-like protein isoform 3 (ORMDL3) has recently been identified as a candidate gene for susceptibility to asthma; however, the mechanisms by which it contributes to asthma pathogenesis are not well understood. Here we demonstrate a functional role for ORMDL3 in eosinophils in the context of allergic inflammation. Eosinophils recruited to the airways of allergen-challenged mice express ORMDL3. ORMDL3 expression in bone marrow eosinophils is localized in the endoplasmic reticulum and is induced by interleukin-3 and eotaxin-1. Overexpression of ORMDL3 in eosinophils causes increased rolling, distinct cytoskeletal rearrangement, extracellular signal-regulated kinase (1/2) phosphorylation and nuclear translocation of nuclear factor kappa B. Knockdown of ORMDL3 significantly inhibits activation-induced cell shape changes, adhesion and recruitment to sites of inflammation in vivo, combined with reduced expression of CD49d and CD18. In addition, ORMDL3 regulates interleukin-3-induced expression of CD48 and CD48-mediated eosinophil degranulation. These studies show that ORMDL3 regulates eosinophil trafficking, recruitment and degranulation, further elucidating a role for this molecule in allergic asthma and potentially other eosinophilic disorders.

Trafficking and recruitment of eosinophils during allergic airway inflammation is mediated by the phosphatidylinositol 3-kinase (PI3K) family of signaling molecules. The role played by the p110δ subunit of PI3K (PI3K p110δ) in regulating eosinophil trafficking and recruitment was investigated using a selective pharmacological inhibitor (IC87114). Treatment with the PI3K p110δ inhibitor significantly reduced murine bone marrow-derived eosinophil (BM-Eos) adhesion to VCAM-1 as well as ICAM-1 and inhibited activation-induced changes in cell morphology associated with reduced Mac-1 expression and aberrant cell surface localization/distribution of Mac-1 and α4. Infused BM-Eos demonstrated significantly decreased rolling and adhesion in inflamed cremaster muscle microvessels of mice treated with IC87114 compared with vehicle-treated mice. Furthermore, inhibition of PI3K p110δ significantly attenuated eotaxin-1-induced BM-Eos migration and prevented eotaxin-1-induced changes in the cytoskeleton and cell morphology. Knockdown of PI3K p110δ with siRNA in BM-Eos resulted in reduced rolling, adhesion, and migration, as well as inhibition of activation-induced changes in cell morphology, validating its role in regulating trafficking and migration. Finally, in a mouse model of cockroach antigen-induced allergic airway inflammation, oral administration of the PI3K p110δ inhibitor significantly inhibited airway eosinophil recruitment, resulting in attenuation of airway hyperresponsiveness in response to methacholine, reduced mucus secretion, and expression of proinflammatory molecules (found in inflammatory zone-1 and intelectin-1). Overall, these findings indicate the important role played by PI3K p110δ in mediating BM-Eos trafficking and migration by regulating adhesion molecule expression and localization/distribution as well as promoting changes in cell morphology that favor recruitment during inflammation.

Eosinophils are the predominant inflammatory cells recruited to allergic airways. In this article, we show that human and murine eosinophils express SWAP-70, an intracellular RAC-binding signaling protein, and examine its role in mediating eosinophil trafficking and pulmonary recruitment in a murine model of allergic airway inflammation. Compared with wild-type eosinophils, SWAP-70-deficient (Swap-70(-/-)) eosinophils revealed altered adhesive interactions within inflamed postcapillary venules under conditions of blood flow by intravital microscopy, exhibiting enhanced slow rolling but decreased firm adhesion. In static adhesion assays, Swap-70(-/-) eosinophils adhered poorly to VCAM-1 and ICAM-1 and exhibited inefficient leading edge and uropod formation. Adherent Swap-70(-/-) eosinophils failed to translocate RAC1 to leading edges and displayed aberrant cell surface localization/distribution of α4 and Mac-1. Chemokine-induced migration of Swap-70(-/-) eosinophils was significantly decreased, correlating with reduced intracellular calcium levels, defective actin polymerization/depolymerization, and altered cytoskeletal rearrangement. In vivo, recruitment of eosinophils to the lungs of allergen-challenged Swap-70(-/-) mice, compared with wild-type mice, was significantly reduced, along with considerable attenuation of airway inflammation, indicated by diminished IL-5, IL-13, and TNF-α levels; reduced mucus secretion; and improved airway function. These findings suggest that regulation of eosinophil trafficking and migration by SWAP-70 is important for the development of eosinophilic inflammation after allergen exposure.

Allergic airway inflammation, including asthma, is usually characterized by the predominant recruitment of eosinophils. However, neutrophilia is also prominent during severe exacerbations. Cell surface-expressed glycans play a role in leukocyte trafficking and recruitment during inflammation. Here, the involvement of UDP-N-acetylglucosamine:α-6-D-mannoside β1,6-N-acetylglucosaminyltransferase V (MGAT5)-modified N-glycans in eosinophil and neutrophil recruitment during allergic airway inflammation was investigated. Allergen-challenged Mgat5-deficient (Mgat5(-/-)) mice exhibited significantly attenuated airway eosinophilia and inflammation (decreased Th2 cytokines, mucus production) compared with WT counterparts, attributable to decreased rolling, adhesion, and survival of Mgat5(-/-) eosinophils. Interestingly, allergen-challenged Mgat5(-/-) mice developed airway neutrophilia and increased airway reactivity with persistent elevated levels of proinflammatory cytokines (IL-17A, TNFα, IFNγ)). This increased neutrophil recruitment was also observed in LPS- and thioglycollate (TG)-induced inflammation in Mgat5(-/-) mice. Furthermore, there was significantly increased recruitment of infused Mgat5(-/-) neutrophils compared with WT neutrophils in the peritoneal cavity of TG-exposed WT mice. Mgat5(-/-) neutrophils demonstrated enhanced adhesion to P-selectin as well as increased migration toward keratinocyte-derived chemokine compared with WT neutrophils in vitro along with increased calcium mobilization upon activation and expression of elevated levels of CXCR2, which may contribute to the increased neutrophil recruitment. These data indicate an important role for MGAT5-modified N-glycans in differential regulation of eosinophil and neutrophil recruitment during allergic airway inflammation.