The incidence and risk factors of retinopathy of prematurity in South Korea: A nationwide cohort study.

Retinopathy of prematurity (ROP) is a major treatable cause of childhood blindness. Thus, epidemiological investigations are necessary for detecting and preventing ROP. Determining risk factors for ROP are also essential to improve screening methods. Therefore, we aimed to investigate the incidence and risk factors of ROP in Korea. The National Health Insurance Service (NHIS) covers almost all Koreans. Furthermore, the National Health Screening Program for Infants and Children (NHSPIC) is a government-run, health-screening program for children aged < 6 years. We used the NHIS-Infants and Children's Health Screening cohort database to evaluate the incidence of preterm infants and ROP. The database contains data on 84,005 participants, drawn from 5% of the NHSPIC survey on participants born annually during 2008 to 2012. Sociodemographic factors and systemic diseases were assessed as potential risk factors for ROP. We identified 2615 premature infants (3.11%); 846 of them had ROP (cumulative incidence: 32.4%). Although preterm births increased annually in 2008 to 2012, the ROP incidence in preterm infants did not increase by the birth year. Twenty patients (2.4%) with ROP underwent laser photocoagulation or surgery. Extremely low birth weight was a high risk factor (odds ratio [OR] = 49.86, P < .001). Moreover, chorioamnionitis (OR = 2.77, P = .028), respiratory distress syndrome (OR = 4.09, P < .001), apnea (OR = 1.59, P = .008), anemia (OR = 2.41, P < .001), and intraventricular hemorrhage (OR = 2.34, P < .001) were found to be risk factors for ROP. In conclusion, the incidence of premature babies increased between 2008 and 2012. However, the overall incidence of ROP among premature infants remained unchanged by birth year. Our findings revealed the roles of birth weight, respiratory conditions, anemia, and intraventricular hemorrhage in ROP.

Intravascular papillary endothelial hyperplasia in the lungs of a wild Korean raccoon dog.

A male Korean raccoon dog of unknown age was rescued and placed at the Daejeon Wildlife Rescue Center, Korea. Physical examination revealed severe emaciation and dehydration, as well as thick crusts and alopecia over most of the body. During medical care, the animal died and was submitted for postmortem examination. Firm, brown-red lesions of various sizes were observed on the surface of the lungs. In cross-sections of the lungs, pulmonary vessels were thickened and dilated, with white irregular papillary luminal projections. Histologically, pulmonary blood vessels were severely hyperplastic, characterized by thickened dilated walls and fibrous papillary projections covered with a single layer of endothelial cells (ECs). Hyperplastic fibrous connective tissue was confirmed by Masson trichrome staining. The ECs expressed CD31. We diagnosed the lesion as intravascular papillary endothelial hyperplasia, a unique non-neoplastic reactive process that has not been reported previously in pulmonary vessels of canids, equids, or felids, to our knowledge.

Phenotypic characteristics of circulating tumor cells and predictive impact for efficacy of chemotherapy in patients with pancreatic cancer: a prospective study.

Objective: Early chemoresistance and tumor mass progression are associated with poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Circulating tumor cells (CTCs) have been studied as potential predictors of treatment response and prognosis in PDAC; however, this approach has yet to be applied in clinical practice. The aim of our study was to investigate the phenotypic characteristics of CTCs and determine their predictive value for PDAC progression. Methods: We prospectively enrolled 40 patients who were pathologically diagnosed with PDAC and collected blood samples at diagnosis, 2 months after diagnosis, and during disease progression or recurrence. We used a microfabricated filter-based enrichment system to retrieve and analyze CTCs, which were classified using immunofluorescence staining (CD45, EpCAM, and vimentin). Results: Our study included 20 women and 20 men (median age, 66 years). Overall, 45% of the patients (18/40) had disseminated disease, and 77.5% (31/40) received chemotherapy. Multivariate analysis revealed that the total CTC count and carbohydrate antigen 19-9 level at 2 months after diagnosis were associated with disease progression (P<0.05). Linear mixed model analysis revealed that the total CTC count and vimentin-positive CTCs were significantly correlated with treatment response during chemotherapy (P=0.024 and 0.017, respectively). Kaplan-Meier analysis showed that total CTC positivity at 2 months was significantly associated with poor progression-free survival (P=0.038). Conclusion: Our study's findings suggest that CTCs can serve as predictive biomarkers of clinical outcomes in patients with PDAC receiving palliative chemotherapy. In particular, the total CTC count and vimentin-positive CTCs showed changes associated with the chemotherapy response.

Coexistence of open-angle glaucoma and sarcoidosis-associated optic neuropathy.

BACKGROUND: In cases with advanced glaucomatous disc changes, further changes associated with other optic neuropathies cannot be easily identified. We present a case of preexisting open-angle glaucoma and concurrent involvement of sarcoidosis-associated optic neuropathy. CASE PRESENTATION: A 53-year-old man presented with gradual visual loss in his left eye, which began 1 year ago and accelerated 3 months ago. The best-corrected visual acuity in the right eye was 20/20 and counting fingers in the left. Intraocular pressures (IOP) were 12 mmHg in the right eye and 34 mmHg in the left. We diagnosed him with advanced open-angle glaucoma in the left eye based on the advanced glaucomatous cupping of the left optic disc. The IOP in the left eye dropped to 10 mmHg and was well controlled with antiglaucomatous medication; however, his left optic disc developed pallor 3 months after the treatment. The patient was revealed to be diagnosed with sarcoidosis a month ago and had been treated with systemic corticosteroids thereafter by a pulmonologist. Orbital magnetic resonance imaging revealed sarcoidosis-associated optic neuropathy in the left eye. Subsequently, optic neuropathy occurred in his right eye. CONCLUSIONS: In eyes with advanced glaucomatous disc change, detecting the coexistence of other optic neuropathies can be difficult. This report highlights the importance of careful ophthalmic examinations and investigation for etiologies of other optic neuropathies if non-glaucomatous changes are suspected even in eyes with advanced glaucoma.

Choroidal detachment and hypotony following selective laser trabeculoplasty: a case report.

BACKGROUND: Selective laser trabeculoplasty (SLT) is relatively safe and effective in lowering intraocular pressure (IOP). However, although rare, complications can occur after SLT. This report describes a patient with choroidal detachment due to hypotony following SLT without anterior chamber (AC) inflammation. CASE PRESENTATION: A 67-year-old man was referred for elevated IOP in his left eye with advanced glaucomatous visual field loss. He had previously been diagnosed with idiopathic uveitic glaucoma in the left eye, for which he underwent laser iridotomy, trabeculectomy, and cataract surgery. At the first visit, the IOP of his left eye measured by Goldmann tonometry was 28 mmHg despite maximally tolerated medical treatment. SLT was performed in his left eye, resulting in an IOP of 7 mmHg 7 days later. At 3 weeks post-procedure, the patient experienced ocular pain and decreased visual acuity in his left eye. Slit-lamp examination revealed deep anterior chamber depth and no inflammation reaction, but the IOP in his left eye was 4 mmHg, and both fundus and B-scan ultrasonography showed serous choroidal detachment. All anti-glaucoma agents were stopped, and the patient was started on treatment with oral prednisolone and cyclopentolate eye drops. Three weeks later, choroidal detachment had resolved and the IOP in his left eye had stabilized at 8 mmHg. Follow-up 3 months later showed that the IOP in his left eye remained stable. CONCLUSIONS: Choroidal detachment-related hypotony is a rare complication of SLT. This possible complication following SLT should be informed to the patients and considered when performing the procedure.

Efficacy of selenium supplementation for mild-to-moderate Graves' ophthalmopathy in a selenium-sufficient area (SeGOSS trial): study protocol for a phase III, multicenter, open-label, randomized, controlled intervention trial.

BACKGROUND: The therapeutic effect of selenium has been demonstrated in mild Graves' ophthalmopathy (GO) in a European region where selenium status is suboptimal. However, there is a lack of evidence to support selenium use in selenium-sufficient areas. The aim of this study is to evaluate the therapeutic effect of selenium in mild-to-moderate GO in selenium-sufficient South Korea. METHODS: The SeGOSS trial is a multicenter, prospective, randomized, open-label trial in South Korea. Eighty-four patients aged 19 years or older with mild-to-moderate GO will be randomized to receive either vitamin B complex alone or vitamin B complex with selenium for 6 months with three monthly follow-up visits. The primary outcome is comparison of the improvement in quality of life at 6 months from baseline between the control and selenium groups. The secondary outcomes are intergroup differences in changes in quality of life at 3 months, clinical activity of GO at 3 and 6 months, thyroid autoantibody titers at 3 and 6 months, and the response rate at 3 and 6 months from baseline. Quality of life will be measured by questionnaire for patients with GO, and the clinical activity of GO will be evaluated by the clinical activity score (CAS). A positive response is defined as either changes in the CAS < 0 or the changes in the GO-QOL score ≥ 6. DISCUSSION: The SeGOSS study will evaluate the therapeutic potential of selenium for mild-to-moderate GO in a selenium-sufficient area and provide support in tailoring better treatment for GO. TRIAL REGISTRATION: KCT0004040. Retrospectively registered on 5 June 2019. https://cris.nih.go.kr/cris/search/detailSearch.do/14160 .

Automatic measurement of mouse visual acuity based on optomotor response: SKY optomotry.

In the field of visual science study using rodents, several assessment methods have been developed for measuring visual function. However, methods such as electroretinograms tests, visual evoked potentials tests and maze tests have limitations in that they measure function of only a specific type of cells, are difficult to quantify or require sufficient training time. The method which uses an optokinetic reflex and optomotor response, a compensatory eye and head movement in response to changes in the visual scene, became the most widely used method. However, this method requires highly trained experimenters and is time consuming. We showed that measured visual acuity values are significantly different between beginner and expert. Here we suggest an automated optometry program, 'SKY optomotry', which automatically tracks rodents' optomotor response to overcome subjectivity and the lengthy scoring procedure of the existing method. To evaluate the performance of SKY optomotry using 8-12-week-old C57BL/6 mice we compared the binomial decision of SKY optomotry with a skilled expert, and the area under the curve of SKY optomotry was 0.845. Comparing the final visual acuity, the intraclass correlation coefficient value between SKY optomotry and an expert was 0.860 (95% confidence interval (CI) 0.709-0.928), whereas that between an expert and a beginner was 0.642 (95% CI 0.292-0.811). SKY optomotry showed an excellent level of performance with good inter-rater agreements based on the visual acuity measured by an expert. With the use of our application, researchers will be able to test an experimental animal's eyesight more accurately while saving time on specialized training.

The Incidence and Risk Factors of Medial and Inferior Orbital Wall Fractures in Korea: A Nationwide Cohort Study.

PURPOSE: We aimed to investigate orbital wall fracture incidence and risk factors in the general Korean population. METHOD: The Korea National Health Insurance Service-National Sample Cohort dataset was analyzed to find subjects with an orbital wall fracture between 2011 and 2015 (based on the diagnosis code) and to identify incident cases involving a preceding disease-free period of 8 years. The incidence of orbital wall fracture in the general population was estimated, and the type of orbital wall fracture was categorized. Sociodemographic risk factors were also examined using Cox regression analysis. RESULTS: Among 1,080,309 cohort subjects, 2415 individuals with newly diagnosed orbital wall fractures were identified. The overall incidence of orbital wall fractures was estimated as 46.19 (95% CI: 44.37-48.06) per 100,000 person-years. The incidence was high at 10-29 and 80+ years old and showed a male predominance with an average male-to-female ratio of 3.33. The most common type was isolated inferior orbital wall fracture (59.4%), followed by isolated medial orbital wall fracture (23.7%), combination fracture (15.0%), and naso-orbito-ethmoid fracture (1.5%). Of the fracture patients, 648 subjects (26.8%) underwent orbital wall fracture repair surgeries. Male sex, rural residence, and low income were associated with an increased risk of orbital wall fractures. CONCLUSIONS: The incidence of orbital wall fractures in Korea varied according to age groups and was positively associated with male sex, rural residency, and low economic income. The most common fracture type was an isolated inferior orbital wall fracture.

Change in the eye position under general anesthesia in children with intermittent exotropia.

PURPOSE: To evaluate the eye position in subjects with intermittent exotropia and normal subjects under general anesthesia (GA) using the strabismus photo analyzer. METHODS: This retrospective case-control study included 78 subjects with intermittent exotropia and 25 normal control subjects who underwent epiblepharon surgery. Eye position under GA was assessed using the strabismus photo analyzer, based on eye models generated from corneal lights and limbus in pre- and post-anesthesia images. Eye positions under GA in the control and intermittent exotropia groups were compared. Preoperative angle of deviation was also compared with amount of change in eye position under GA in the intermittent exotropia group. RESULTS: Eye position under GA was more divergent in subjects with intermittent exotropia than in controls (P = 0.008). The amount of change in eye position under GA was correlated with the preoperative angle of deviation (r2 = 0.47; P < 0.001). In small preoperative exodeviations, the change in eye position was primarily more divergent, whereas in large exodeviations, a convergent tendency-less exotropic compared with the preoperative angle of exodeviation-was observed. CONCLUSIONS: In subjects with small preoperative exodeviations, there was a tendency for eye position to become more divergent after GA; in those with large exodeviations, there was less exotropia after GA.

The incidence and presumed aetiologies of fourth cranial nerve palsy in Korea: a 10-year nationwide cohort study.

AIMS: To investigate the incidence and presumed aetiologies of fourth cranial nerve (CN4) palsy in Korea METHODS: Using the nationally representative dataset of the Korea National Health Insurance Service-National Sample Cohort from 2006 to 2015, newly developed CN4 palsy cases confirmed by a preceding disease-free period of ≥4 years were identified. The presumed aetiology of CN4 palsy was evaluated based on comorbidities around the CN4 palsy diagnosis. RESULTS: Among the 1,108,292 cohort subjects, CN4 palsy newly developed in 390 patients during 10-year follow-up, and the overall incidence of CN4 palsy was 3.74 per 100,000 person-years (95% confidence interval, 3.38-4.12). The incidence of CN4 palsy showed a male preponderance in nearly all age groups, and the overall male-to-female ratio was 2.30. A bimodality by age-group was observed, with two peaks at 0-4 years and at 75-79 years. The most common presumed aetiologies were vascular (51.3%), congenital (20.0%), and idiopathic (18.5%). The incidence rate of a first peak for 0-4 years of age was 6.17 per 100,000 person-years, and cases in this group were congenital. The second peak incidence rate for 75-79 years of age was 11.81 per 100,000 person-years, and the main cause was vascular disease. Strabismus surgery was performed in 48 (12.3%) patients, most of whom (72.9%) were younger than 20 years. CONCLUSION: The incidence of CN4 palsy has a male predominance in Koreans and shows bimodal peaks by age. The aetiology of CN4 palsy varies according to age-groups.

Postnatal ophthalmological characteristics in patients with congenital cataract diagnosed by fetal ultrasonography.

PURPOSE: To evaluate the findings of postnatal ophthalmological examinations in patients diagnosed with cataracts by prenatal fetal sonography. METHODS: We retrospectively identified patients diagnosed with fetal cataract without other ocular abnormalities using antenatal ultrasound. We analyzed data including the patients' family history, the presence of metabolic or systemic disease-associated cataracts, gestational age at diagnosis, fetal sonography reports, and the results of postnatal ophthalmological examinations. RESULTS: In total, eight patients were diagnosed with cataracts by prenatal fetal ultrasonography, and all these patients showed mild to severe degrees of cataract after birth. Patients showed hyperechoic opacity of the lens in the available images. The mean gestational age at diagnosis was 26 ± 3 weeks (range, 22-28 weeks), and three patients (37.5%) had a family history of congenital cataract. All patients, except one patient who had patent ductus arteriosus, showed no systemic abnormalities associated with cataracts on postnatal evaluation. Six (75.0%) were diagnosed with bilateral cataracts after birth, and of these, two patients had been diagnosed with unilateral left cataract prenatally. Postnatal ophthalmological examination revealed that all patients showed opacities involving the nucleus of the lens and three patients (37.5%) had associated abnormalities of microcornea or microphthalmia, which were not diagnosed antenatally. CONCLUSION: In all our subjects, the lens opacities on prenatal fetal sonography were diagnosed postnatally as cataracts involving the nucleus. A careful postnatal examination is essential to detect the presence of associated ocular abnormalities such as microcornea and/or microphthalmia and cataract in the contralateral eye in patients with congenital cataract.

Topographic Relationship with a Retinal Nerve Fiber Layer Defect Differs between ß-Zone and γ-Zone Parapapillary Atrophy.

INTRODUCTION: γ-Zone parapapillary atrophy (PPA), an associated feature in myopic tilted optic disc, is considered to be relevant with glaucomatous optic nerve damage in myopic eyes. This study determines the topographic relationship of γ-zone PPA with a retinal nerve fiber layer defect. PURPOSE: To determine the topographic relationship of γ-zone PPA with a RNFL defect and to compare it with that of ß-zone PPA. DESIGN: Cross-sectional, observational study. Participants. Eighty-nine eyes from 89 patients with primary open-angle glaucoma who had ß-zone PPA (n = 49) or γ-zone PPA (n = 40) and a single localized RNFL defect. METHODS: PPA was classified according to the presence or absence of Bruch's membrane on the PPA bed in spectral-domain optical coherence tomography. The angular location of the point of maximum radial extent of PPA (PMRE) and the RNFL defect was measured with the fovea-disc axis set at 0° in color and red-free fundus photographs. Main Outcome Measures. Angular distance between the RNFL defect and the PMRE. RESULTS: There was no significant intergroup difference in the extent of the RNFL defect (P=0.920). The angular distance between the RNFL defect and the PMRE was significantly greater in γ-zone than ß-zone PPA (26.49 ± 17.27° vs. 60.31 ± 17.12°, P < 0.001). The angular location of the PMRE was significantly correlated with the location of the RNFL defect in the ß-zone group (r = 0.822, P < 0.001) but not in the γ-zone group. The RNFL defect was mostly located near the edge of γ-zone PPA in the γ-zone group (10.56 ± 9.47°). CONCLUSIONS: An RNFL defect was observed near the edge of PPA in eyes with γ-zone PPA, in contrast to it being close to the PMRE in eyes with ß-zone PPA.

Glucosamine regulates hepatic lipid accumulation by sensing glucose levels or feeding states of normal and excess.

Dose-dependent lipid accumulation was induced by glucose in HepG2 cells. GlcN also exerted a promotory effect on lipid accumulation in HepG2 cells under normal glucose conditions (NG, 5 mM) and liver of normal fed zebrafish larvae. High glucose (HG, 25 mM)-induced lipid accumulation was suppressed by l-glutamine-d-fructose 6-phosphate amidotransferase inhibitors. ER stress inhibitors did not suppress HG or GlcN-mediated lipid accumulation. HG and GlcN stimulated protein expression, DNA binding and O-GlcNAcylation of carbohydrate-responsive element-binding protein (ChREBP). Furthermore, both HG and GlcN increased nuclear sterol regulatory element-binding protein-1 (SREBP-1) levels in HepG2 cells. In contrast to its stimulatory effect under NG, GlcN suppressed lipid accumulation in HepG2 cells under HG conditions. Similarly, GlcN suppressed lipid accumulation in livers of overfed zebrafish. In addition, GlcN activity on DNA binding and O-GlcNAcylation of ChREBP was stimulatory under NG and inhibitory under HG conditions. Moreover, GlcN enhanced ChREBP, SREBP-1c, ACC, FAS, L-PK and SCD-1 mRNA expression under NG but inhibited HG-induced upregulation in HepG2 cells. The O-GlcNAc transferase inhibitor, alloxan, reduced lipid accumulation by HG or GlcN while the O-GlcNAcase inhibitor, PUGNAc, enhanced lipid accumulation in HepG2 cells and liver of zebrafish larvae. GlcN-induced lipid accumulation was inhibited by the AMPK activator, AICAR. Phosphorylation of AMPK (p-AMPK) was suppressed by GlcN under NG while increased by GlcN under HG. PUGNAc downregulated p-AMPK while alloxan restored GlcN- or HG-induced p-AMPK inhibition. Our results collectively suggest that GlcN regulates lipogenesis by sensing the glucose or energy states of normal and excess fuel through AMPK modulation.

The Incidence and Etiologies of Third Cranial Nerve Palsy in Koreans: A 10-year Nationwide Cohort Study.

PURPOSE: This study aimed to determine the incidence, prevalence, and etiologies of third cranial nerve (CN3) palsy in Koreans. METHODS: Data were collected from the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database of South Korea and analyzed. Incident CN3 palsy subjects in the cohort population were defined as cases occurring after the initial 4-year or longer washout period. The incidence and prevalence were analyzed by sex, age group, and year. The etiologies of CN3 palsy were evaluated using comorbidities. RESULTS: Of 1,108,253 subjects, 387 patients were newly diagnosed with CN3 palsy between 2006 and 2015. The incidence of CN3 palsy was 3.71 per 100,000 person-years (95% confidence interval, 3.35-4.09). The incidence of CN3 palsy increased with age and accelerated after the age of 60 years. The mean male-to-female incidence ratio was 1.16. The main cause was presumed to be vascular disease (52.7%), followed by idiopathic causes (25.8%), intracranial neoplasm (7.8%), unruptured cerebral aneurysm (5.4%), and trauma (5.2%). CONCLUSIONS: The incidence of CN3 palsy in Koreans increased with age and peaked between 75 and 79 years. The main cause of CN3 palsy was vascular disease.

Effects of resveratrol, granulocyte-macrophage colony-stimulating factor or dichloroacetic acid in the culture media on embryonic development and pregnancy rates in aged mice.

The success rate of assisted reproductive technology is closely correlated with maternal age. Reproductive aging pathologies are frequently caused by impaired DNA repair, genomic instability, and mitochondrial dysfunction. Several reports have shown that resveratrol can prevent age-related diseases by improving mitochondrial function. Improved blastocyst development and mitochondrial output by dichloroacetic acid (DCA) supplementation were reported in aged mice. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has significant effects on implantation rates in women with previous miscarriages. Therefore, this study was conducted to observe how those compounds influence the developmental and the reproductive potential of aged oocytes. BDF1 female mice at 58-62 weeks old were used for this study. MII oocytes were fertilized and cultured in MRC media supplemented with or without resveratrol (0.5 µM), GM-CSF (2 ng/ml) or DCA (1.0 mM). The addition of resveratrol, GM-CSF or DCA tended to increase blastocyst development and pregnancy rates. Supplementation with resveratrol significantly increased the pregnancy and implantation rates (p < 0.05). Moreover, resveratrol decreased reactive oxygen species production and increased mitochondrial membrane potential. These results suggest that the addition of resveratrol can increase pregnancy outcomes in women of advanced maternal age.

The Long Way to Refugee Status Acquisition and Mental Health in Post-Migration: Based on Asylum Seekers and Refugees in South Korea.

Apart from North Korean defectors, South Korea is becoming a destination for Asylum seekers from all over the world. However, 1 out of 220 asylum applicants receives recognition through long and arduous administration and litigation process while being underrepresented in any kind of support services.This particular study comparatively tested the mental health status of recognized refugees(n = 45) and Asylum applicants (n = 55) to determine if the acquisition of refugee status could make a difference in their overall quality of life. We first employed the Depression, Anxiety and Stress Test and then applied an independent t-test using SPSS 22 software.As a result, there is a statistically significant difference in the mean scores of depression and anxiety. However, the stress scale did not show a statistical significance--indicating there are still lingering stressing factors even after the acquisition of refugee status. Ways and preconditions to improve the mental health service for asylum seekers and refugees are suggested at the end of the paper.

Lithium chloride promotes lipid accumulation through increased reactive oxygen species generation.

LiCl is widely prescribed for bipolar disorder but adversely associated with a higher incidence of increased body weight. Here, we investigated effects and underlying mechanisms of LiCl on lipid accumulation. LiCl induced dose-dependent lipid accumulation in HepG2 and RAW264.7 cells under normal as well as high glucose conditions. LiCl exposure additionally promoted lipid accumulation in livers of zebrafish. SB216763, a specific GSK-3ß inhibitor, did not affect lipid accumulation in HepG2 cells. Expression of key lipogenic enzymes, such as FAS and aP2, as well as SR-B1 were increased in RAW264.7 cells. LiCl enhanced FAS, ACC and SCD-1 mRNA levels while suppressing CPT-1 in HepG2 cells. LiCl stimulated DNA binding activities of SREBP-1c and ChREBP. LiCl activated AMPK phosphorylation but the AMPK inhibitor, AICAR, did not suppress LiCl-induced lipid accumulation in RAW264.7. LiCl, but not SB216763, induced a significant increase in ROS in RAW264.7 and HepG2 cells. NOX activity was dose-dependently enhanced by LiCl. Furthermore, NOX-1, NOX-2 and DUOX-1 mRNA levels were upregulated at an early stage of LiCl stimulation. LiCl-induced lipid accumulation was suppressed by the antioxidant, NAC, and inhibitors of NOX, DPI and APO. Phosphorylation and transcriptional activity of CREB were enhanced by LiCl. The cell-permeable cAMP analog, di-butyryl cAMP, not only promoted lipid accumulation itself but also LiCl-induced lipid accumulation in RAW264.7 cells. H-89, a PKA inhibitor, suppressed CREB activation, lipid accumulation and NOX activity in RAW264.7 cells. Our results indicate that LiCl stimulates lipid accumulation in hepatocyte and macrophage cells potentially through increased PKA-dependent ROS production.

Hemistepsin A alleviates liver fibrosis by inducing apoptosis of activated hepatic stellate cells via inhibition of nuclear factor-κB and Akt.

Hemistepsin A (HsA), isolated from Hemistepta lyrata (Bunge) Bunge, has the ability to ameliorate hepatitis in mice. However, the effects of H. lyrata and HsA on other types of liver disease have not been explored. In this report, we investigated the effects of H. lyrata and HsA on liver fibrosis and the underlying molecular mechanisms in activated hepatic stellate cells (HSCs). Based on cell viability-guided isolation, we found HsA was the major natural product responsible for H. lyrata-mediated cytotoxicity in LX-2 cells. HsA significantly decreased the viability of LX-2 cells and primary activated HSCs, increased the binding of Annexin V, and altered the expression of apoptosis-related proteins, suggesting that HsA induces apoptosis in activated HSCs. HsA reduced the phosphorylation of IKKε and the transactivation of nuclear factor-κB (NF-κB). Moreover, HsA decreased the phosphorylation of Akt and its downstream signaling molecules. Transfection experiments suggested that inhibition of NF-κB or Akt is essential for HsA-induced apoptosis of HSCs. In a CCl4-induced liver fibrosis model, HsA administration significantly decreased ALT and AST activities. Furthermore, HsA attenuated CCl4-mediated collagen deposits and profibrogenic genes expression in hepatic tissue. Thus, HsA may serve as a natural product for managing liver fibrosis through inhibition of NF-κB/Akt-dependent signaling.

Epidemiological Association Between Systemic Diseases and Keratoconus in a Korean Population: A 10-Year Nationwide Cohort Study.

PURPOSE: To investigate the association of systemic diseases with keratoconus in the general Korean population. METHODS: This is a nationwide population-based retrospective cohort study using the Korean National Health Insurance Service-National Sample Cohort database from 2002 to 2015, involving 1,108,369 individuals. Patients with keratoconus were identified using the Korean standard classification of diseases code H18.6. The prevalence and annual incidence rates were estimated. To examine the risk factors, 5 controls were matched per patient with keratoconus by propensity score matching using age and household income. Univariate and multivariate regression analyses were performed to assess the association between relevant factors and keratoconus. RESULTS: A total of 613 subjects were identified as patients with keratoconus from the cohort database. The prevalence rate was 55.31 cases per 100,000 people [95% confidence interval (CI): 51.01-59.86]. The annual incidence rate, calculated using a predate 1-year washout period, was 4.47 cases per 100,000 person-years (95% CI: 4.11-4.85). People with allergic conjunctivitis had a 37% increased odds of being diagnosed with keratoconus [odds ratio: 1.37 (95% CI: 1.12-1.67), P = 0.002] compared with those without allergic conjunctivitis. By contrast, people with allergic rhinitis had a 52% reduced odds of being diagnosed with keratoconus [odds ratio: 0.48 (95% CI: 0.38-0.59), P < 0.001]. Atopy and eczema, asthma, connective tissue disorders, diabetes mellitus, sleep apnea, and inflammatory bowel disease had no significant association with a positive keratoconus diagnosis. CONCLUSIONS: Allergic conjunctivitis may increase the risk of developing keratoconus in Koreans.

The incidence and etiology of sixth cranial nerve palsy in Koreans: A 10-year nationwide cohort study.

We aimed to investigate the incidence, prevalence, and etiology of sixth cranial nerve (CN6) palsy in the general Korean population. The nationally representative dataset of the Korea National Health Insurance Service-National Sample Cohort from 2006 through 2015 was analyzed. The incidence and prevalence of CN6 palsy were estimated in the cohort population, confirming that incident cases of CN6 palsy involved a preceding disease-free period of ≥4 years. The etiologies of CN6 palsy were presumed using comorbidity conditions. Among the 1,108,256 cohort subjects, CN6 palsy developed in 486 patients during the 10-year follow-up. The overall incidence of CN6 palsy was estimated to be 4.66 per 100,000 person-years (95% confidence interval [CI], 4.26-5.08) in the general population. This incidence increased with age, accelerating after 60 years of age and peaking at 70-74 years of age. The mean male-to-female incidence ratio was estimated as 1.41 in the whole population, and the incidence and prevalence of CN6 palsy showed an increasing trend over time in the study period. Surgical incidence for CN6 palsy was only 0.19 per 100,000 person-years (95% CI, 0.12-0.29). The etiologies were presumed to be vascular (56.6%), idiopathic (27.2%), neoplastic (5.6%), and traumatic (4.9%). In conclusion, the incidence of CN6 palsy increases with age, peaking at around 70 years, and shows a mild male predominance in Koreans.