Purpose

Patterns of syncope evaluation vary widely among physicians and hospitals. The aim of this study was to assess current diagnostic patterns and medical costs in the evaluation of patients presenting with syncope at the emergency department (ED) or the outpatient department (OPD) of a referral hospital.

Materials and Methods

This study included 171 consecutive patients with syncope, who visited the ED or OPD between January 2009 and July 2009.

Results

The ED group had fewer episodes of syncope [2 (1-2) vs. 2 (1-5), p=0.014] and fewer prodromal symptoms (81.5% vs. 93.3%, p=0.018) than the OPD group. Diagnostic tests were more frequently performed in the ED group than in the OPD group (6.2±1.7 vs. 5.3±2.0; p=0.012). In addition, tests with low diagnostic yields were more frequently used in the ED group than in the OPD group. The total cost of syncope evaluation per patient was higher in the ED group than in the OPD group [823000 (440000-1408000) won vs. 420000 (186000-766000) won, p<0.001].

Conclusion

There were some differences in the clinical characteristics of patients and diagnostic patterns in the evaluation of syncope between the ED and the OPD groups. Therefore, a selective diagnostic approach according to the presentation site is needed to improve diagnostic yields and to reduce the time and costs of evaluation of syncope.

Purpose

Mucopolysaccharidosis type II (MPS II or Hunter syndrome) is a rare lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) deficiency. MPS II causes a wide phenotypic spectrum of symptoms ranging from mild to severe. IDS activity, which is measured in leukocyte pellets or fibroblasts, was reported to be related to clinical phenotype by Sukegawa-Hayasaka et al. Measurement of residual plasma IDS activity using a fluorometric assay is simpler than conventional measurements using skin fibroblasts or peripheral blood mononuclear cells. This is the first study to describe the relationship between plasma IDS activity and clinical phenotype of MPS II.

Methods

We hypothesized that residual plasma IDS activity is related to clinical phenotype. We classified 43 Hunter syndrome patients as having attenuated or severe disease types based on clinical characteristics, especially intellectual and cognitive status. There were 27 patients with the severe type and 16 with the attenuated type. Plasma IDS activity was measured by a fluorometric enzyme assay using 4-methylumbelliferyl-α-iduronate 2-sulphate.

Results

Plasma IDS activity in patients with the severe type was significantly lower than that in patients with the attenuated type (P=0.006). The optimal cut-off value of plasma IDS activity for distinguishing the severe type from the attenuated type was 0.63 nmol·4 hr-1·mL-1. This value had 88.2% sensitivity, 65.4% specificity, and an area under receiver-operator characteristics (ROC) curve of 0.768 (ROC curve analysis; P=0.003).

Conclusion

These results show that the mild phenotype may be related to residual lysosomal enzyme activity.

Foreign body ingestion is not uncommon in clinical practice, and it may occasionally lead to penetration injuries. Emergency physicians and radiologists sometimes fail to obtain complete histories including ingestion and may overlook the possibility of foreign body-induced complications. Herein, we report a case of stomach antrum perforation due to foreign body migration. We were unaware of the patient's history of eating the Korean delicacy "Kanjang-gaejang," which is raw crab seasoned with soy sauce. Several imaging diagnostic modalities had suggested the possibility of a malignant mass in the gastrocolic ligament area. During the operation, a crab leg was discovered as the cause of an intra-abdominal abscess. The patient underwent an antrectomy, a vagotomay, and a transverse colon wedge resection. We present this unusual case of a pseudotumorous lesion caused by ingestion of Kanjang-gaejang.

In urban environments, green roofs provide a number of benefits, including decreased urban heat island effects and reduced energy costs for buildings. However, little research has been done on the non-plant biota associated with green roofs, which likely affect their functionality. For the current study, we evaluated whether or not green roofs planted with two native plant communities in New York City functioned as habitats for soil fungal communities, and compared fungal communities in green roof growing media to soil microbial composition in five city parks, including Central Park and the High Line. Ten replicate roofs were sampled one year after planting; three of these roofs were more intensively sampled and compared to nearby city parks. Using Illumina sequencing of the fungal ITS region we found that green roofs supported a diverse fungal community, with numerous taxa belonging to fungal groups capable of surviving in disturbed and polluted habitats. Across roofs, there was significant biogeographical clustering of fungal communities, indicating that community assembly of roof microbes across the greater New York City area is locally variable. Green roof fungal communities were compositionally distinct from city parks and only 54% of the green roof taxa were also found in the park soils. Phospholipid fatty acid analysis revealed that park soils had greater microbial biomass and higher bacterial to fungal ratios than green roof substrates. City park soils were also more enriched with heavy metals, had lower pH, and lower quantities of total bases (Ca, K, and Mg) compared to green roof substrates. While fungal communities were compositionally distinct across green roofs, they did not differentiate by plant community. Together, these results suggest that fungi living in the growing medium of green roofs may be an underestimated component of these biotic systems functioning to support some of the valued ecological services of green roofs.

Purpose

To investigate the type of nocturia and concomitant voiding dysfunction (VD) and the effect of desmopressin treatment on nocturia in women.

Materials and Methods

We reviewed 84 women who experienced more than 2 nocturia episodes as recorded on a pretreatment frequency volume chart and who were treated with desmopressin. All patients underwent history taking, physical examination, urinalysis, International Prostate Symptom Score assessment, completion of a urinary sensation scale, and completion of a 3 day frequency volume chart. Nocturia was divided into nocturnal polyuria (NP), reduced nocturnal bladder capacity (RNBC), and mixed type. After treatment with desmopressin, a reduction in nocturia of over 50% compared with baseline was regarded as effective.

Results

Among 84 women, the most common concomitant VD was overactive bladder (OAB, 60.7%). NP was observed in 70.2% (59/84) of the women, RNBC in 7.1% (6/84), and mixed type in 22.6% (19/84). After medication with desmopressin, 73 women (86.9%) showed a significantly reduced number of nocturia episodes (1.4±1.5) compared with baseline (3.7±1.3, p<0.05). Eleven women (13.1%) did not show improvement. Of the 73 women who showed improvement, 41 women showed a reduction of more than 50% over baseline, and these women had a lower baseline urgency grade.

Conclusions

In the majority of women, nocturia coexisted with other VD such as OAB. Treatment with desmopressin effectively reduced the nocturia. However, other lower urinary tract symptoms (LUTS) such as urgency may reduce the effect of desmopressin. Therefore, consideration of concomitant LUTS seems to be necessary to increase the treatment effect of desmopressin on nocturia in women.

Purpose

There are conflicting results surrounding the prognostic significance of epidermal growth factor receptor (EGFR) status in glioblastoma (GBM) patients. Accordingly, we attempted to assess the influence of EGFR expression on the survival of GBM patients receiving postoperative radiotherapy.

Materials and Methods

Thirty three GBM patients who had received surgery and postoperative radiotherapy at our institute, between March 1997 and February 2006, were included. The evaluation of EGFR expression with immunohistochemistry was available for 30 patients. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis.

Results

EGFR was expressed in 23 patients (76.7%), and not expressed in seven (23.3%). Survival in EGFR expressing GBM patients was significantly less than that in non-expressing patients (median survival: 12.5 versus 17.5 months, p=0.013). Patients who received more than 60 Gy showed improved survival over those who received up to 60 Gy (median survival: 17.0 versus 9.0 months, p=0.000). Negative EGFR expression and a higher radiation dose were significantly correlated with improved survival on multivariate analysis. Survival rates showed no differences according to age, sex, and surgical extent.

Conclusion

The expression of EGFR demonstrated a significantly deleterious effect on the survival of GBM patients. Therefore, approaches targeting EGFR should be considered in potential treatment methods for GBM patients, in addition to current management strategies.

Purpose

To assess the risk factors for developing urinary retention after removal of the urethral catheter on postoperative day 1 in benign prostatic hyperplasia patients who underwent Greenlight HPS laser photoselective vaporization prostatectomy (PVP).

Materials and Methods

The study included 427 men who underwent Greenlight HPS laser PVP between 2009 and 2012, excluding patients in whom a catheter was maintained for more than 1 day because of urethral procedures. In all patients, a voiding trial was performed on postoperative day 1; if patients were unable to urinate, the urethral catheter was replaced before hospital discharge. The patients were divided into two groups: early catheter removal (postoperative day 1) and late catheter removal (urethral catheter reinsertion). Preoperative and perioperative parameters were compared between the groups.

Results

Catheters were successfully removed in 378 (88.6%) patients on postoperative day 1. In 49 patients, the catheters were reinserted and removed a mean of 6.45±0.39 days after surgery. In a multivariate analysis, a history of diabetes was the most significant predictor (p=0.028) of failure of early catheter removal, followed by operative time (p=0.039). There were no significant differences in age, prostate volume, International Prostate Symptom Score, or urodynamic parameters between the two groups.

Conclusions

It is feasible, safe, and cost-effective to remove the urethral catheter on postoperative day 1 after Greenlight HPS laser PVP, but the procedure should be done carefully in patients who have history of diabetes or an extended operative time.

The lichen-associated bacterial strain Sphingomonas sp. PAMC 26621 was isolated from an Arctic lichen Cetraria sp. on Svalbard Islands. Here we report the draft genome sequence of this strain, which could provide novel insights into the molecular principles of lichen-microbe interactions.

Sphingomonas sp. strain PAMC 26617 has been isolated from an Arctic lichen Umbilicaria sp. on the Svalbard Islands. Here we present the draft genome sequence of this strain, which represents a valuable resource for understanding the symbiotic mechanisms between endosymbiotic bacteria and lichens surviving in extreme environments.

The draft genome of Salinibacterium sp. PAMC 21357, isolated from permafrost soil of Antarctica, was determined. Here we present a 3.1-Mb draft genome sequence of Salinibacterium sp. that could provide further insight into the genetic determination of its cold-adaptive properties.

Psychrobacter spp. have shown characteristics indicating remarkable capabilities at subzero temperatures that identify them as potential model organisms for the study of low-temperature adaptations. Here we present the draft genome sequence of Psychrobacter sp. PAMC 21119, which was isolated from permafrost soil of Antarctica; this information could provide insight into adaptation and evolution strategies under extreme environmental conditions.

Escherichia coli RNase E contains a site that selectively binds to RNAs containing 5′-monophosphate termini, increasing the efficiency of endonucleolytic cleavage of these RNAs. Random mutagenesis of N-Rne, the N-terminal catalytic region of RNase E, identified a hyperactive variant that remains preferentially responsive to phosphorylation at 5′ termini. Biochemical analyses showed that the mutation (Q36R), which replaces glutamine with arginine at a position distant from the catalytic site, increases formation of stable RNA-protein complexes without detectably affecting the enzyme's secondary or tertiary structure. Studies of cleavage of fluorogenic substrate and EMSA experiments indicated that the Q36R mutation increases catalytic activity and RNA binding. however, UV crosslinking and mass spectrometry studies suggested that the mutant enzyme lacks an RNA binding site present in its wild-type counterpart. Two substrate-bound tryptic peptides, 65HGFLPLK71—which includes amino acids previously implicated in substrate binding and catalysis—and 24LYDLDIESPGHEQK37—which includes the Q36 locus—were identified in wild-type enzyme complexes, whereas only the shorter peptide was observed for complexes containing Q36R. Our results identify a novel RNase E locus that disparately affects the number of substrate binding sites and catalytic activity of the enzyme. We propose a model that may account for these surprising effects.

Purpose

Mucopolysaccharidosis IVA (MPS IVA; Morquio A syndrome) is rare lysosomal storage disorder caused by N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. Only a few MPS IVA cases have been reported in the Korean literature; there is a paucity of research about clinical or radiologic findings for this disorder. Therefore, we studied clinical findings, radiological features, and genetic data of Korean MPS IVA patients for determining factors that may allow early diagnosis and that may thus improve the patients' quality of life.

Method

MPS IVA was confirmed via assay for enzymatic activity of leukocytes in 10 patients. The GALNS gene was analyzed. Patients' charts were retrospectively reviewed for obtaining clinical features and evaluated for radiological skeletal surveys, echocardiography, pulmonary function test, and ophthalmologic test results.

Result

Nine patients had severe clinical phenotype, and 1 had an intermediate phenotype, on the basis of clinical phenotype criteria. Radiologic findings indicated skeletal abnormalities in all patients, especially in the hips and extremities. Eight patients had an odontoid hypoplasia, and 1 showed mild atlantoaxial subluxation and cord myelopathy. Genetic analysis indicated 10 different GALNS mutations. Two mutations, c.451C>A and c.1000C>T, account for 37.5% (6/16) and 25% (4/16) of all mutations in this samples, respectively.

Conclusion

An understanding of the clinical and radiological features involved in MPS IVA may allow early diagnosis of MPS IVA. Adequate evaluations and therapy in the early stages may improve the quality of life of patients suffering from skeletal abnormalities and may reduce life-threatening effects of atlantoaxial subluxation.

Background

Recently, laparoscopic resection for relatively small sized gastric gastrointestinal stromal tumors (GISTs) has been widely accepted as minimally invasive surgery. However, no report on the long-term safety and efficacy of this surgery for large sized gastric GISTs has been published to date.

Methods

Between July 1998 and January 2011, 104 consecutive patients who underwent resection for gastric GISTs were enrolled in this retrospective study. We assessed the clinicopathological characteristics, postoperative outcomes, patient survival, and tumor recurrence.

Results

Of the 104 patients with gastric GISTs who were included in the study, there were 47 males and 57 females whose mean age was 59.8 years. Sixty-four patients (61.5%) had symptoms associated with tumor. Ten patients included in the group 1, 49 in the group 2, 15 in the group 3a, 9 in the group 5, 14 in the group 6a, and 7 in the group 6b. There was one minor complication and no mortalities. Recurrence was noted in 5 patients, with a median follow-up period of 49.3 months (range, 8.4 to 164.4). The 5-year overall and disease free survival rates of 104 patients were 98.6% and 94.8%, respectively. When comparing large tumor (5–10 cm) between laparoscopic and open surgery, there were statistically differences in age, tumor size, tumor location, and length of hospitalization. There were no statistical differences in the 5-year survival rate between laparoscopic and open surgery for large tumor (5-10cm).

Conclusion

Laparoscopic surgery is feasible and effective as an oncologic treatment of gastric GISTs. Moreover, laparoscopic surgery can be an acceptable alternative to open methods for gastric GISTs of size bigger than 5 cm.

Pseudomonas spp. have shown characteristics of efficiently metabolizing environmental pollutants and also producing exopolysaccharides known as biofilms. Here we present the draft genome sequence of Pseudomonas sp. strain PAMC 25886, which was isolated from glacier cryoconite in the Alps mountain permafrost region and which may provide further insight into biodegradative and/or biofilm-producing mechanisms in a cold environment.

Sphingomonas is a Gram-negative, yellow-pigmented, chemoheterotrophic, strictly aerobic bacterium. The bacterium is known to be metabolically versatile and can utilize a wide range of natural compounds as well as some types of environmental contaminants, such as creosote, polychlorinated biphenyls, etc. Here, we report the draft genome sequence of Sphingomonas echinoides ATCC 14820, which will provide additional information to enhance our understanding of metabolic versatility of Sphingomonas.

The draft genome of Janthinobacterium sp. strain PAMC 25724, which is a violacein-producing psychrotolerant bacterium, was determined. The strain was isolated from glacier cryoconite of the Alps mountain permafrost region. The sequence will allow identification and characterization of the genetic determination of its cold-adaptive properties.

Purpose

Single-nucleotide polymorphism (SNP) markers within LIN28B have been reported to be related to the timing of pubertal growth. However, no study has investigated the frequency of genetic markers in girls with precocious puberty (PP) or early puberty (EP). This study aimed to determine the frequency of putative genetic markers in girls with PP or EP.

Methods

Genomic DNAs were obtained from 77 and 109 girls that fulfilled the criteria for PP and EP, respectively. The controls in this study were 144 healthy volunteers between 20 and 30 years of age. The haplotypes were reconstructed using 11 SNPs of LIN28B, and haplotype association analysis was performed. The haplotype frequencies were compared. Differences in the clinical and laboratory parameters were analyzed according to the haplotype dosage.

Results

Eleven SNPs in LIN28B were all located in a block that was in linkage disequilibrium. The haplotype could be reconstructed using 2 representative SNPs, rs4946651 and rs369065. The AC haplotype was less frequently observed in the PP group than in the controls (0.069 vs. 0.144, P=0.010). The trend that girls with non-AC haplotypes tended to have earlier puberty onset (P=0.037) was illustrated even in the EP+PP patient group by Kaplan-Meier analysis.

Conclusion

The results of the present study showed that non-AC haplotypes of LIN28B had a significant association with PP in girls.

Purpose

To evaluate the combined role of mescenchymal stem cells (MSCs) infected with recombinant adenoviruses expressing human BDNF (rAd/hBDNF) on the erectile dysfunction in rat with cavernous nerve injury.

Materials and Methods

Rats divided into 4 groups: control group, bilateral cavernous nerve crushing group (BCNC group), BCNC with MSCs group and BCNC with MSCs infected with rAd/hBDNF group. After 4-week, functional assessment was done. PKH26 and BDNF staining of major pelvic ganglion and masson's trichrome staining of corpus cavernosum were performed. Western blot analysis of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) was done in corpus cavernosum.

Results

After 4 weeks, BCNC with MSCs and MSCs infected with rAd/hBDNF groups showed significantly well-preserved erectile function compared with BCNC group. Moreover, the erectile function of MSCs infected with rAd/hBDNF group was significantly well-preserved than BCNC with MSCs group. The smooth muscle of corpus cavernosum was significantly preserved in BCNC with MSCs and MSCs infected with rAd/hBDNF groups compared with BCNC group. More preservation of smooth muscle was observed in rats with MSCs infected with rAd/hBDNF than with MSCs alone. Significant increase expression of eNOS and nNOS was noted in rats with MSCs infected with rAd/hBDNF than with MSCs alone.

Conclusions

The erectile function was more preserved after injection with MSCs infected with rAd/hBDNF in rat with ED caused by cavernous nerve injury. Therefore, the use of MSC infected with rAd/hBDNF may have a better treatment effect on ED cause by cavernous nerve injury.

Excessive nitric oxide (NO) production is toxic to the cochlea and induces hearing loss. However, the mechanism through which NO induces ototoxicity has not been completely understood. The aim of this study was to gain further insight into the mechanism mediating NO-induced toxicity in auditory HEI-OC1 cells and in ex vivo analysis. We also elucidated whether and how epigallocatechin-3-gallate (EGCG), the main component of green tea polyphenols, regulates NO-induced auditory cell damage. To investigate NO-mediated ototoxicity, S-nitroso-N-acetylpenicillamine (SNAP) was used as an NO donor. SNAP was cytotoxic, generating reactive oxygen species, releasing cytochrome c, and activating caspase-3 in auditory cells. NO-induced ototoxicity also mediated the nuclear factor (NF)-κB/caspase-1 pathway. Furthermore, SNAP destroyed the orderly arrangement of the 3 outer rows of hair cells in the basal, middle, and apical turns of the organ of Corti from the cochlea of Sprague–Dawley rats at postnatal day 2. However, EGCG counteracted this ototoxicity by suppressing the activation of caspase-3/NF-κB and preventing the destruction of hair cell arrays in the organ of Corti. These findings may lead to the development of a model for pharmacological mechanism of EGCG and potential therapies against ototoxicity.

AIM: To assess the prognostic significance of nuclear factor-κB (NF-κB) and its target genes in gastric cancer.

METHODS: The tumor tissues of 115 patients with gastric cancer were immunohistochemically evaluated using monoclonal antibodies against NF-κB RelA. Preoperative serum levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6) were assessed via enzyme-linked immuno-sorbent assay. C-reactive protein (CRP) and serum amyloid A (SAA) were measured via immunotrubidimetry.

RESULTS: Positive rate of NF-κB RelA was 42.6%. NF-κB RelA expression in tumor tissues was also related to serum levels of IL-6 (P = 0.044) and CRP (P = 0.010). IL-6, SAA, CRP were related to depth of invasion, VEGF and SAA were correlated with lymph node metastasis. IL-6, VEGF, SAA and CRP were related to the stage. Univariate analysis demonstrated that immunostaining of NF-κB RelA, levels of IL-6, VEGF, SAA were significantly related with both disease free survival and overall survival (OS). Multivariate analysis verified that NF-κB RelA [hazard ratio (HR): 3.40, P = 0.024] and SAA (HR: 3.39, P = 0.045) were independently associated with OS.

CONCLUSION: Increased expression of NF-κB RelA and high levels of serum SAA were associated with poor OS in gastric cancer patients.

The endosymbiotic bacterium Sphingomonas sp. strain PAMC 26605 was isolated from Arctic lichens (Ochrolechia sp.) on the Svalbard Islands. Here we report the draft genome sequence of this strain, which could provide further insights into the symbiotic mechanism of lichens in extreme environments.

For the past 10 to 13 million years, Antarctic notothenioid fish have undergone extraordinary periods of evolution and have adapted to a cold and highly oxygenated Antarctic marine environment. While these species are considered an attractive model with which to study physiology and evolutionary adaptation, they are poorly characterized at the molecular level, and sequence information is lacking. The transcriptomes of the Antarctic fishes Notothenia coriiceps, Chaenocephalus aceratus, and Pleuragramma antarcticum were obtained by 454 FLX Titanium sequencing of a normalized cDNA library. More than 1,900,000 reads were assembled in a total of 71,539 contigs. Overall, 40% of the contigs were annotated based on similarity to known protein or nucleotide sequences, and more than 50% of the predicted transcripts were validated as full-length or putative full-length cDNAs. These three Antarctic fishes shared 663 genes expressed in the brain and 1,557 genes expressed in the liver. In addition, these cold-adapted fish expressed more Ub-conjugated proteins compared to temperate fish; Ub-conjugated proteins are involved in maintaining proteins in their native state in the cold and thermally stable Antarctic environments. Our transcriptome analysis of Antarctic notothenioid fish provides an archive for future studies in molecular mechanisms of fundamental genetic questions, and can be used in evolution studies comparing other fish.

Purpose

Continuous renal replacement therapy (CRRT) is becoming the treatment of choice for supporting critically ill pediatric patients. However, a few studies present have reported CRRT use and outcome in neonates weighing less than 3 kg. The aim of this study is to describe the clinical application, outcome, and complications of CRRT in small neonates.

Methods

A retrospective review was performed in 8 neonatal patients who underwent at least 24 hours of pumped venovenous CRRT at the Samsung Medical Center in Seoul, Korea, between March 2007 and July 2010. Data, including demographic characteristics, diagnosis, vital signs, medications, laboratory, and CRRT parameters were recorded.

Results

The data of 8 patients were analyzed. At the initiation of CRRT, the median age was 5 days (corrected age, 38+2 weeks to 23 days), and the median body weight was 2.73 kg (range, 2.60 to 2.98 kg). Sixty-two patient-days of therapy were reviewed; the median time for CRRT in each patient was 7.8 days (range, 1 to 37 days). Adverse events included electrolyte disturbances, catheter-related complications, and CRRT-related hypotension. The mean circuit functional survival was 13.9±8.6 hours. Overall, 4 patients (50%) survived; the other 4 patients, who developed multiorgan dysfunction syndrome, died.

Conclusion

The complications of CRRT in newborns are relatively high. However, the results of this study suggest that venovenous CRRT is feasible and effective in neonates weighing less than 3 kg under elaborate supportive care. Furthermore, for using potential benefit of CRRT in neonates, efforts are required for prolonging filter survival.

Our objective was to determine whether melatonin increases retinal ganglion cell (RGC) survival in ischemic mouse retina. Transient retinal ischemia was induced by an acute elevation of intraocular pressure in C57BL/6 mice. To evaluate the effect of melatonin on retinal ischemia, an equal amount of either melatonin or vehicle was intraperitoneally injected into the mice 1 hour before ischemia, at the time of ischemia, and 1 hour after ischemia. Hypoxia inducible factor 1α (HIF-1α) and glial fibrillary acidic protein (GFAP) expression were assessed 6, 12, and 24 hours after ischemia-reperfusion by Western blot. RGC survival was measured 2 weeks after ischemia-reperfusion. The expression of HIF-1α and GFAP peaked 24 hours after ischemia-reperfusion in ischemic retina. The treatment of ischemic retina with melatonin resulted in the inhibition of increased expression of HIF-1α and GFAP. RGC survival was greater in retinas treated with melatonin than in retinas treated with vehicle 2 weeks after ischemia-reperfusion. On the basis of our results, we suggest that melatonin treatment increased RGC survival in ischemic mouse retina. The neuroprotective effect of melatonin is mediated by the inhibition of HIF-1α stabilization and reduced activity of glial cells in ischemic mouse retina.