Purpose: To identify clinical factors associated with the early reduction of corneal sensitivity (CS) in patients with herpes zoster ophthalmicus (HZO). Methods: Total 30 subjects were divided into two groups according to the occurrence of an early reduction of CS (group 1, normal CS; group 2, decreased CS). The demographics, ocular manifestations of HZO, and the ocular surface parameters were compared between two groups. Then, the relative risks of variables were analyzed to expect the early decrease of CS by HZO using logistic regression analysis. Results: Among total 30 subjects, the CS decreased in 10 subjects (3.2 ± 1.4 cm, group 2) and the other 20 subjects revealed normal CS (6.0 ± 0.0 cm, group 1). The age was higher in the group 2 (67.0 ± 16.6 years) than in group 1 (48.0 ± 17.6 years, p = 0.013), but sex and the comorbidity of diabetes mellitus was not difference between groups. The presence of corneal punctate epithelial erosions was a single factor among the ocular manifestations of HZO, which discriminated group 1 (5%) and group 2 (60%, p = 0.002). The ocular surface staining scores (i.e., National Eye Institute scores and Sjögren’s International Collaborative Clinical Alliance ocular surface score) were higher in group 2 (p = 0.001 and p = 0.021, respectively) than in group 1. The existence of corneal punctate epithelial erosions revealed as a sole risk factor for the early reduction of CS (odds ratio = 33.085; p = 0.016). Conclusions It is necessary to pay attention to the possible occurrence of neurotrophic keratopathy especially in older patients with HZO showing an initial presence of corneal punctate epithelial erosions.

Healthcare workers (HCWs) may be at high risk for exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their frequent contact with patients or the direct handling of respiratory samples. We investigated the seroprevalence of SARS-CoV-2 IgG in HCWs in Seoul compared to those in coronavirus disease (COVID-19) patients and community-based individuals to evaluate the antibody response. A total of 358 samples from 348 individuals (155 HCWs, 7 COVID-19 patients, and 186 community-based individuals) were collected from April to November 2020. SARS-CoV-2 IgG was detected in 1 of 155 HCWs (1 of 46 HCWs with direct contact), 7 of 7 COVID-19 patients, and none of the 186 communitybased individuals (95% CI: 0.6%, 0.1 - 3.6%; 100%, 64.5 - 100%; 0.0%, 0.0 - 2.0%, respectively).The single HCW with a positive result showed 2.32 signal-to-cutoff (S/C) and 2.31 S/C at a 3-week interval. Therefore, it was assumed to be a false positive due to autoantibody or medication. The positive samples from 7 patients had a median of 3.79 S/C (range 1.72 - 6.54). The seroprevalence of SARS-CoV-2 IgG in HCWs was very low. The current infection control standard seems to be effective in protecting HCWs from COVID-19.

Healthcare workers (HCWs) may be at high risk for exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their frequent contact with patients or the direct handling of respiratory samples. We investigated the seroprevalence of SARS-CoV-2 IgG in HCWs in Seoul compared to those in coronavirus disease (COVID-19) patients and community-based individuals to evaluate the antibody response. A total of 358 samples from 348 individuals (155 HCWs, 7 COVID-19 patients, and 186 community-based individuals) were collected from April to November 2020. SARS-CoV-2 IgG was detected in 1 of 155 HCWs (1 of 46 HCWs with direct contact), 7 of 7 COVID-19 patients, and none of the 186 communitybased individuals (95% CI: 0.6%, 0.1 - 3.6%; 100%, 64.5 - 100%; 0.0%, 0.0 - 2.0%, respectively).The single HCW with a positive result showed 2.32 signal-to-cutoff (S/C) and 2.31 S/C at a 3-week interval. Therefore, it was assumed to be a false positive due to autoantibody or medication. The positive samples from 7 patients had a median of 3.79 S/C (range 1.72 - 6.54). The seroprevalence of SARS-CoV-2 IgG in HCWs was very low. The current infection control standard seems to be effective in protecting HCWs from COVID-19.

Background: Several T-cell response assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are available; however, their comparability and correlations with antibody responses remain unclear. We compared four SARS-CoV-2 T-cell response assays and two anti-SARS-CoV-2 spike antibody assays. Methods: We enrolled 89 participants who had received a booster dose of the BNT162b2 vaccine after two doses of the ChAdOx1 or BNT162b2 vaccine. Fifty-six participants without breakthrough infection (BI) (ChAdOx1/BNT162b2 group: N=27; BNT162b2 group: N=29) and 33 with BI were included. We evaluated two whole-blood interferon-gamma release assays (IGRAs) (QuantiFERON and Euroimmun), T-SPOT.COVID, an in-house enzyme-linked immunospot (ELISPOT) assay (targeting the spike and nucleocapsid peptides of wild-type and Omicron SARS-CoV-2), Abbott IgG II Quant, and Elecsys Anti-S, using Mann–Whitney U, Wilcoxon signed-rank, and Spearman’s correlation tests. Results: The correlations between the IGRAs and between the ELISPOT assays (ρ=0.60–0.70) were stronger than those between the IGRAs and ELISPOT assays (ρ=0.33–0.57). T-SPOT.COVID showed a strong correlation with Omicron ELISPOT (ρ=0.70). The anti-spike antibody assays showed moderate correlations with T-SPOT.COVID, Euroimmun IGRA, and ELISPOT (ρ=0.43–0.62). Correlations tended to be higher in the BI than in the noninfected group, indicating that infection induces a stronger immune response. Conclusions T-cell response assays show moderate to strong correlations, particularly when using the same platform. T-SPOT.COVID exhibits potential for estimating immune responses to the Omicron variant. To accurately define SARS-CoV-2 immune status, both T-cell and B-cell response measurements are necessary.

Purpose: We report two cases of sudden intraocular pressure (IOP) elevation in children after steroid treatment.Case summary: (Case 1) An 8-year-old boy visited the hospital with vomiting and headache that had begun 3 days after application of dexamethasone eyedrops. IOPs were 55 and 62 mmHg in the right and left eyes, respectively; both anterior chambers were normal. The eyedrops were stopped and timolol/dorzolamide was applied twice daily. After intravenous mannitol injection, the IOPs of both eyes decreased to 18 mmHg within 24 hours. (Case 2) A 10-year-old boy diagnosed with coronavirus disease 2019 three days prior had been prescribed methylprednisolone 4 mg twice daily; he visited the hospital with headache, eye pain, and decreased vision that began 1 day after medication. IOPs were 41 and 54 mmHg in the right and left eyes, respectively; both anterior chambers were normal. After drug discontinuation, timolol/dorzolamide, brimonidine, and latanoprost eyedrops were applied. Subsequently, after intravenous mannitol injection, the IOPs decreased within 24 hours to 7 and 16 mmHg in the right and left eyes, respectively; they remained stable. However, thinning was observed in the retinal nerve fiber and ganglion cell-inner plexiform layer. Conclusions Children can develop rapid IOP elevation after even 1 day of steroid use; residual structural damage may be present, despite prompt treatment. Clinicians must closely monitor such patients for atypical IOP elevation.

Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix GeneChip® Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.
Acetaminophen ; Animals ; Drug-Induced Liver Injury ; Genetic Variation ; Incidence ; Lipoprotein Lipase* ; Lipoproteins* ; Liver ; Methods ; Mice ; Microarray Analysis ; Real-Time Polymerase Chain Reaction ; Receptors, GABA-A* ; Toxicogenetics ; Transcriptome

Increasing concern is being given to the association between risk of cancer and exposure to low-dose bisphenol A (BPA), especially in young-aged population. In this study, we investigated the effects of repeated oral treatment of low to high dose BPA in juvenile Sprague-Dawley rats. Exposing juvenile rats to BPA (0, 0.5, 5, 50, and 250 mg/kg oral gavage) from post-natal day 9 for 90 days resulted in higher food intakes and increased body weights in biphasic dose-effect relationship. Male mammary glands were atrophied at high dose, which coincided with sexual pre-maturation of females. Notably, proliferative changes with altered cell foci and focal inflammation were observed around bile ducts in the liver of all BPA-dosed groups in males, which achieved statistical significance from 0.5 mg/kg (ANOVA, Dunnett’s test, p<0.05). Toxicokinetic analysis revealed that systemic exposure to BPA was greater at early age (e.g., 210-fold in C(max), and 26-fold in AUC at 50 mg/kg in male on day 1 over day 90) and in females (e.g., 4-fold in C(max) and 1.6-fold in AUC at 50 mg/kg vs. male on day 1), which might have stemmed from either age- or gender-dependent differences in metabolic capacity. These results may serve as evidence for the association between risk of cancer and exposure to low-dose BPA, especially in young children, as well as for varying toxicity of xenobiotics in different age and gender groups.
Animals ; Area Under Curve ; Bile Ducts* ; Bile* ; Body Weight ; Child ; Female ; Humans ; Inflammation ; Liver Neoplasms* ; Liver* ; Male ; Mammary Glands, Human ; Rats* ; Rats, Sprague-Dawley ; Toxicokinetics ; Xenobiotics

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

While numerous studies have evaluated humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, data on the cellular responses to these vaccines remain sparse. We evaluated T cell responses to ChAdOx1-nCoV-19 and BNT162b2 vaccinations using an interferon gamma (IFN-γ) release assay (IGRA). ChAdOx1-nCoV-19- and BNT162b2-vaccinated participants initially showed stronger T cell responses than unvaccinated controls. The T cell response decreased over time and increased substantially after the administration of a BNT162b2 booster dose. Changes in the T cell response were less significant than those in the anti-receptor-binding domain IgG antibody titer. The study results can serve as baseline data for T cell responses after SARS-CoV-2 vaccination and suggest that the IGRA can be useful in monitoring immunogenicity.