Artificial Tear Instillation-Induced Changes in Corneal Topography.

This study aims to compare changes of corneal topography (Galilei G4) before and after the instillation of artificial tears in patients with dry eye disease (DED). Corneal topography was performed in patients 1 min before and after artificial tear instillation. Two types of artificial tears were used: 1% polysorbate 80 (PSB) and 0.5% carboxymethylcellulose (CMC). Of 135 patients, PSB and CMC were instilled in 101 and 34 eyes, respectively. The average value of Sim K increased significantly after instillation (44.07 ± 2.26 diopter (D)) compared to before (43.90 ± 2.02 D, p = 0.006) the instillation of artificial tears. Mean Sim K astigmatism was statistically increased after PSB instillation (1.48 ± 2.17 D) compared to before instillation (1.31 ± 2.10 D, p = 0.049). An axis change of astigmatism 10° or more after artificial tear instillation was found in 51.9% of patients, and 30° or more in 20.0% of patients. Increased Sim K value and significant changes in the astigmatic axis in the corneal topography were observed after instillation of artificial tears in DED patients. PSB instillation had a greater effect on corneal keratometry values than CMC instillation.

Clinical use of whole exome sequencing in children with developmental delay/intellectual disability.

BACKGROUND: Identifying the underlying etiology of developmental delay/intellectual disability (DD/ID) is challenging but important. The genetic diagnosis of unexplained DD/ID helps in the treatment and prognosis of the disability in patients. In this study, we reported our experience of using whole exome sequencing (WES) of children with unexplained DD/ID. METHODS: We conducted a retrospective analysis of WES results of children under 19 years of age with unexplained DD/ID between January 2020 and December 2021. The demographic data of all patients and variants identified through WES were evaluated. Furthermore, we evaluated the clinical characteristics that influenced the identification of genetic causes. RESULTS: Forty-one patients with DD/ID were included, of whom 21 (51.2 %) were male. The average age at symptom onset was 1.6 ± 1.3 years, and the duration from symptom onset to diagnosis was 3.1 ± 3.7 years. Hypotonia was the most common symptom (17 patients, 41.5 %), and epilepsy was confirmed in 10 patients (24.4 %). Twenty-two pathogenic/likely pathogenic variants were identified in 20 patients, and three variants of uncertain significance were identified in three patients. Family-based trio Sanger sequencing for candidate variants of 12 families was conducted; 10 variants were de novo, one variant paternally inherited, and two variants compound heterozygous. The diagnostic yield of WES for DD/ID was 48.8 % and was significantly high in patients with an early onset of DD/ID and facial dysmorphism. In contrast, patients with autism spectrum disorder (ASD) were more likely to have negative WES results compared with others without ASD. CONCLUSION: The diagnostic yield of WES was 48.8 %. We conclude that patients' characteristics, such as dysmorphic features and the age of symptom onset, can predict the likelihood that WES will identify a causal variant of a phenotype.

A Comprehensive Analysis of the Influence of Temperature and Humidity on Dry Eye Disease.

PURPOSE: To investigate the effects of humidity and temperature on dry eye disease (DED). METHODS: A retrospective, clinic-based study was conducted on DED patients undergoing dry eye treatment. Patients were followed up at least twice, and symptoms and signs were evaluated using the Symptoms Assessment Questionnaire in Dry Eye (SANDE) score, tear secretion, tear film breakup time (TBUT), ocular staining score, and tear osmolarity. Mean humidity and temperature values for 1 week before ocular examinations were used as the environmental exposure level. The relationship between humidity and temperature, with DED clinical parameters was analyzed in single- and multi-environmental factor models. RESULTS: The study included 33 patients with a mean age of 53.9 ± 12.2 years. The low humidity group showed significantly higher SANDE scores (p = 0.023) and tear osmolarity (p = 0.008), and the low temperature group had higher SANDE scores (p = 0.004), ocular staining scores (p = 0.036), and tear osmolarity (p < 0.001). In the linear mixed model, single factor analysis showed that an increase in humidity resulted in decreased SANDE scores (p = 0.043), and an increase in temperature led to a decrease in SANDE score (p = 0.007), ocular staining score (p = 0.007), and tear osmolarity (p = 0.012). In the multifactor analysis, changes in humidity had no significant effect on dry eye parameters, but an increase in temperature was significantly correlated with decreased SANDE score (p = 0.026), ocular staining score (p = 0.024), and tear osmolarity (p = 0.002). CONCLUSIONS: Lower temperature led to aggravated symptoms and signs of DED and the effect of temperature on DED was more pronounced than humidity. Tear osmolarity was the most sensitive clinical parameter to be affected by climate factors in DED patients.

Potent Antifungal Activity of Penta-O-galloyl-ß-d-Glucose against Drug-Resistant Candida albicans, Candida auris, and Other Non-albicans Candida Species.

Among fungal pathogens, infections by drug-resistant Candida species continue to pose a major challenge to healthcare. This study aimed to evaluate the activity of the bioactive natural product, penta-O-galloyl-ß-d-glucose (PGG) against multidrug-resistant (MDR) Candida albicans, MDR Candida auris, and other MDR non-albicans Candida species. Here, we show that PGG has a minimum inhibitory concentration (MIC) of 0.25-8 µg mL-1 (0.265-8.5 µM) against three clinical strains of C. auris and a MIC of 0.25-4 µg mL-1 (0.265-4.25 µM) against a panel of other MDR Candida species. Our cytotoxicity studies found that PGG was well tolerated by human kidney, liver, and epithelial cells with an IC50 > 256 µg mL-1 (>272 µM). We also show that PGG is a high-capacity iron chelator and that deletion of key iron homeostasis genes in C. albicans rendered strains hypersensitive to PGG. In conclusion, PGG displayed potent anti-Candida activity with minimal cytotoxicity for human cells. We also found that the antifungal activity of PGG is mediated through an iron-chelating mechanism, suggesting that the compound could prove useful as a topical treatment for superficial Candida infections.

Intraocular lens power calculation in eyes with a shallow anterior chamber depth and normal axial length.

We compared the accuracy of three intraocular lens (IOL) calculation formulas in eyes with a shallow anterior chamber depth (ACD) and normal axial length (AXL) and control eyes. We retrospectively reviewed eyes with a shallow ACD (<2.5 mm from the corneal epithelium) with normal AXL (22.5≤AXL<24.0 mm) and controls (3.0≤ACD<3.5 mm and normal AXL). Prediction error (PE) and median absolute error (MedAE) were evaluated with SRK/T, Barrett Universal II (BUII), and Kane formulas after adjusting the mean PE to zero for all patients. Percentages of eyes achieving a PE within 0.25 to 1.00 D, and correlations between ACD, lens thickness (LT), and PE were analyzed. Thirty-five shallow ACD and 63 control eyes were included. PE in the shallow ACD group showed more hyperopic results with BUII and Kane but not with SRK/T compared to controls. Within the shallow ACD group, PE showed more hyperopic results in BUII and Kane compared to SRK/T. However, the standard deviation (SD) of PE among formulas was not different. In the shallow ACD group, SRK/T showed a higher percentage of PE within 0.25 D than BUII and Kane, but the percentages within 0.50 to 1.00 D were similar. PE was negatively correlated with ACD in BUII and Kane, and positively correlated with LT in all formulas. BUII and Kane may induce slight hyperopic shift in eyes with a shallow ACD and normal AXL. However, the performance of the three formulas was comparable in the shallow ACD group in terms of MedAE, the SD of PE, and the percentage of eyes achieving PE within 0.50 D.

Functional genomic analysis of Candida albicans protein kinases reveals modulators of morphogenesis in diverse environments.

Candida albicans is a leading cause of mycotic infection. The ability to transition between yeast and filamentous forms is critical to C. albicans virulence and complex signaling pathways regulate this process. Here, we screened a C. albicans protein kinase mutant library in six environmental conditions to identify regulators of morphogenesis. We identified the uncharacterized gene orf19.3751 as a negative regulator of filamentation and follow-up investigations implicated a role for orf19.3751 in cell cycle regulation. We also uncovered a dual role for the kinases Ire1 and protein kinase A (Tpk1 and Tpk2) in C. albicans morphogenesis, specifically as negative regulators of wrinkly colony formation on solid medium but positive regulators of filamentation in liquid medium. Further analyses suggested Ire1 modulates morphogenesis in both media states in part through the transcription factor Hac1 and in part through independent mechanisms. Overall, this work provides insights into the signaling governing morphogenesis in C. albicans.

Endoplasmic reticulum stress in the intestinal epithelium initiates purine metabolite synthesis and promotes Th17 cell differentiation in the gut.

Intestinal IL-17-producing T helper (Th17) cells are dependent on adherent microbes in the gut for their development. However, how microbial adherence to intestinal epithelial cells (IECs) promotes Th17 cell differentiation remains enigmatic. Here, we found that Th17 cell-inducing gut bacteria generated an unfolded protein response (UPR) in IECs. Furthermore, subtilase cytotoxin expression or genetic removal of X-box binding protein 1 (Xbp1) in IECs caused a UPR and increased Th17 cells, even in antibiotic-treated or germ-free conditions. Mechanistically, UPR activation in IECs enhanced their production of both reactive oxygen species (ROS) and purine metabolites. Treating mice with N-acetyl-cysteine or allopurinol to reduce ROS production and xanthine, respectively, decreased Th17 cells that were associated with an elevated UPR. Th17-related genes also correlated with ER stress and the UPR in humans with inflammatory bowel disease. Overall, we identify a mechanism of intestinal Th17 cell differentiation that emerges from an IEC-associated UPR.

Molecular mechanisms governing antifungal drug resistance.

Fungal pathogens are a severe public health problem. The leading causative agents of systemic fungal infections include species from the Candida, Cryptococcus, and Aspergillus genera. As opportunistic pathogens, these fungi are generally harmless in healthy hosts; however, they can cause significant morbidity and mortality in immunocompromised patients. Despite the profound impact of pathogenic fungi on global human health, the current antifungal armamentarium is limited to only three major classes of drugs, all of which face complications, including host toxicity, unfavourable pharmacokinetics, or limited spectrum of activity. Further exacerbating this issue is the growing prevalence of antifungal-resistant infections and the emergence of multidrug-resistant pathogens. In this review, we discuss the diverse strategies employed by leading fungal pathogens to evolve antifungal resistance, including drug target alterations, enhanced drug efflux, and induction of cellular stress response pathways. Such mechanisms of resistance occur through diverse genetic alterations, including point mutations, aneuploidy formation, and epigenetic changes given the significant plasticity observed in many fungal genomes. Additionally, we highlight recent literature surrounding the mechanisms governing resistance in emerging multidrug-resistant pathogens including Candida auris and Candida glabrata. Advancing our knowledge of the molecular mechanisms by which fungi adapt to the challenge of antifungal exposure is imperative for designing therapeutic strategies to tackle the emerging threat of antifungal resistance.

Coffin-Siris Syndrome: Case Series of Three Patients and a Novel ARID2 Variant.

Coffin-Siris syndrome (CSS) is a rare congenital disorder characterized by coarse facial features, intellectual disability or developmental delay, and aplasia or hypoplasia of the tips of the fifth finger and/or toes. Mutations in genes affecting the switch/sucrose non-fermenting ATP-dependent chromatin remodeling complex are reported to cause CSS. Here, we describe three CSS patients. Two girls aged 3 and 2 years old presented with global developmental delay, poor growth, and a dysmorphic face. Whole-exome sequencing (WES) was performed and they were diagnosed with CSS due to heterozygous frameshift variants (c.3443_3444del, p.Lys1148ArgfsTer9 and c.2869_2890del, p.Pro957CysfsTer20) in ARID1B A 2-year-old girl presented with gross motor delay and dysmorphic face. She was diagnosed with CSS due to a novel heterozygous frameshift variant (c.4942_4943del: p.Gln1648GlyfsTer8) in ARID2.

Functional analysis of the Candida albicans kinome reveals Hrr25 as a regulator of antifungal susceptibility.

Candida albicans is a leading cause of death due to systemic fungal infections. Poor patient outcomes are attributable to the limited number of antifungal classes and the increasing prevalence of drug resistance. Protein kinases have emerged as rewarding targets in the development of drugs for diverse diseases, yet kinases remain untapped in the quest for new antifungals. Here, we performed a comprehensive analysis of the C. albicans kinome to identify genes for which loss-of-function confers hypersensitivity to the two most widely deployed antifungals, echinocandins and azoles. Through this analysis, we found a role for the casein kinase 1 (CK1) homologue Hrr25 in regulating tolerance to both antifungals as well as target-mediated echinocandin resistance. Follow-up investigations established that Hrr25 regulates these responses through its interaction with the SBF transcription factor. Thus, we provide insights into the circuitry governing cellular responses to antifungals and implicate Hrr25 as a key mediator of drug resistance.

Correlations between clinical parameters of dry eye disease and serologic profiles in Sjögren's syndrome.

PURPOSE: To investigate the difference in clinical parameters of dry eye disease (DED) according to the presence of serum anti-La antibodies and evaluate the correlations of autoantibody titers with DED parameters in patients with primary Sjögren's syndrome (pSS). METHODS: Sixty-two patients diagnosed with pSS according to the 2016 ACR-EULAR classification criteria were classified into two groups depending on the presence of anti-La antibodies: group 1 (anti-Ro positive alone, n = 31) and group 2 (both anti-Ro and anti-La positive, n = 31). DED parameters (conjunctival and corneal ocular staining score (OSS), tear film break-up time (TBUT), Schirmer I test, lipid layer thickness (LLT), meiboscore, and ocular surface disease index), serum autoantibodies (anti-Ro, anti-La, rheumatoid factor (RF), and antinuclear antibody) and focus score were assessed. RESULTS: The DED parameters were not significantly different between the two groups (P > 0.05). The anti-Ro titers, RF-positive rate, and the focus score were significantly higher in group 2 than in group 1 (P = 0.001, P = 0.049, P = 0.001, respectively). The anti-Ro titers had a significant positive correlation with conjunctival OSS (r = 0.273, P = 0.033) and the focus score had a positive correlation with LLT and meiboscore (r = - 0.358, P = 0.072; r = 0.379, P = 0.056). CONCLUSION: In this study, anti-Ro titers significantly correlated with conjunctival staining score, whereas anti-La did not statistically correlated with clinical DED parameters in SS. Meanwhile, anti-Ro titers and focus score were significantly higher in patients positive for both anti-Ro and anti-La, which suggests that examining anti-La with anti-Ro would be helpful in predicting clinical severities of SS patients.

Matrix metalloproteinase 9 is associated with conjunctival microbiota culture positivity in Korean patients with chronic Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) is an abnormal immune-response causing extensive exfoliation of the mucocutaneous tissue including conjunctiva. While several factors are associated with the alteration of conjunctival microbiota, the conjunctiva of SJS patients are found to harbor a different microbiota compared to healthy subjects. We investigated the conjunctival microbiota of Korean SJS patients, and identified factors associated with the conjunctival microbiota and its positive culture. METHODS: Medical records were retrospectively reviewed in 30 chronic SJS patients who had undergone conjunctival swab culture sampling. Demographic factors, chronic ocular surface complications score (COCS), tear break-up time (TBUT), tear secretion, tear matrix metalloproteinase 9 (MMP9), and results of conjunctival swab culture were assessed. RESULTS: Positive culture was seen in 58.1%. Gram positive bacteria was most commonly isolated, among which Coagulase-negative Staphylococci (45.5%) and Corynebacterium species (40.9%) were predominantly observed. Tear MMP9 positivity was observed significantly more in the positive culture group (100%) compared to the negative culture group (70%) (P = 0.041). Topical cyclosporine and corticosteroid were not associated with repetitive positive cultures. No significant differences in COCS, TBUT, and tear secretion were found between culture-positive and culture-negative groups. CONCLUSION: Our study suggests that tear MMP9 positivity may be related with the presence of an abnormal ocular surface microbiota in chronic SJS patients.

Trust your gut, lest thou be anxious.

Can gut-residing bacteria influence mood and anxiety? And can targeting bacteria-produced metabolites reduce anxiety? Based on two Nature and Nature Medicine papers, the answers to these questions are likely yes. Needham, Campbell, and colleagues identified bacteria that enhance anxiety-like behaviors in mice and ways to mitigate anxiety in autistic patients.

Recent trends of refractive surgery rate and detailed analysis of subjects with refractive surgery: The 2008-2015 Korean National Health and Nutrition Examination Survey.

The present study was conducted to investigate recent trends of refractive surgery rates and analyze subjects undergoing refractive surgery using large-scale population studies over the past 8 years. We used the dataset of the Korean National Health and Nutrition Examination Surveys, a nationwide population-based cross-sectional study which were performed from 2008 to 2015. Of the 21,415 participants aged 20 to 49 years, 1,621 had refractive surgeries. Seventy three percent of them were females and 81% of them were aged under 40 years old. Over the past 8 years, cumulative prevalence of refractive surgery rate increased more than 10%. Although young (< 40 years, odds ratio (OR) 0.31, P<0.001) women (OR 1.86, P<0.001) living in urban areas (OR 0.51, P<0.001) with high educational attainment (OR 2.67, P<0.001) and income levels (OR 3.16, P<0.001) accounted for a high proportion in refractive surgery group through all survey years, subgroup analyses revealed that gaps between genders (ORs 3.8 in 2008-2009, 2.1 in 2010-2012, and 1.5 in 2013-2015), educational level (ORs 3.0, 2.5, and 2.1, respectively), and highest/lowest quartiles of household income (ORs 5.2, 2.6, and 2.4, respectively) were decreasing over time. Overall, our study suggests that refractive surgery has reached an age where the majority accepts it, and indeed more and diverse people are undergoing refractive surgeries.

Chromosomal Microarray in Children With Developmental Delay: The Experience of a Tertiary Center in Korea.

Background and Objectives: Chromosomal microarray (CMA) is a first-tier genetic test for children with developmental delay (DD), intellectual disability (ID), autism spectrum disorders (ASDs), and multiple congenital anomalies (MCA). In this study, we report our experiences with the use of CMA in Korean children with unexplained DD/ID. Methods: We performed CMA in a cohort of 308 children with DD/ID between January 2010 and September 2020. We also retrospectively reviewed their medical records. The Affymetrix CytoScan 750 K array with an average resolution of 100 kb was used to perform CMA. Results: Comorbid neurodevelopmental disorders were ASD (37 patients; 12.0%), epilepsy (34 patients; 11.0%), and attention deficit hyperactivity disorders (12 patients; 3.9%). The diagnostic yield was 18.5%. Among the 221 copy number variants (CNVs) identified, 70 CNVs (57 patients; 18.5%) were pathogenic. Deletion CNVs were more common among pathogenic CNVs (PCNVs) than in non-PCNVs (P < 0.001). The size difference between PCNVs and non-PCNVs was not significant (P = 0.023). The number of included genes within CNV intervals was significantly higher in PCNVs (average 8.6; 0-347) than in non-PCNVs (average 47.5; 1-386) (P < 0.001). Short stature and hearing difficulty were also more common in the PCNV group than in the non-PCNV group (P = 0.010 and 0.070, respectively). Conclusion: This study provides additional evidence for the usefulness of CMA in genetic testing of children with DD/ID in Korea. The pathogenicity of CNVs correlated with the number of included genes within the CNV interval and deletion type of the CNVs, but not with CNV size.

A screen of kinase inhibitors reveals a potential role of Chk1 in regulating Hydra head regeneration and maintenance.

The cnidarian Hydra possesses remarkable regenerative capabilities which allow it to regrow lost or damaged body parts in a matter of days. Given that many key regulators of regeneration and development are evolutionarily conserved, Hydra is a valuable model system for studying the fundamental molecular mechanisms underlying these processes. In the past, kinase inhibitors have been useful tools for determining the role of conserved signaling pathways in Hydra regeneration and patterning. Here, we present a systematic screen of a commercially available panel of kinase inhibitors for their effects on Hydra regeneration. Isolated Hydra gastric segments were exposed to 5 µM of each kinase inhibitor and regeneration of the head and foot regions were scored over a period of 96 hours. Of the 80 kinase inhibitors tested, 28 compounds resulted in abnormal regeneration. We directed our focus to the checkpoint kinase 1 (Chk1) inhibitor, SB 218078, considering the role of Chk1 in G2 checkpoint regulation and the importance of G2-paused cells in Hydra regeneration. We found that Hydra exposed to SB 218078 were unable to regenerate the head and maintain head-specific structures. Furthermore, SB 218078-treated Hydra displayed a reduction in the relative proportion of epithelial cells; however, no differences were seen for interstitial stem cells or their derivatives. Lastly, exposure to SB 218078 appeared to have no impact on the level of mitosis or apoptosis. Overall, our study demonstrates the feasibility of kinase inhibitor screens for studying Hydra regeneration processes and highlights the possible role for Hydra Chk1 in head regeneration and maintenance.

Effect of Quinoa (Chenopodium quinoa Willd.) Starch and Seeds on the Physicochemical and Textural and Sensory Properties of Chicken Meatballs during Frozen Storage.

The effects of starch (corn and quinoa) and quinoa seeds on chicken meatballs' physicochemical, textural, and sensory properties were investigated during frozen storage. The chicken meatballs were prepared with corn starch (CS), quinoa starch (QS), quinoa seeds (Q), and combinations of corn starch and quinoa seeds (CS-Q), and quinoa starch and quinoa seeds (QS-Q), which were subjected to five freeze-thaw (F-T) cycles of temperature fluctuation conditions during frozen storage. Regardless of the type used (CS or QS), adding starch resulted in fewer cooking, drip, and reheating losses in chicken meatballs during frozen storage. The values of the hardness, gumminess, and chewiness of chicken meatballs with CS or QS were half those of chicken meatballs without starch, indicating that the addition of starch inhibited the change in the meatballs' texture. The total volatile basic nitrogen (TVB-N) and thiobarbituric acid reactive substance (TBARS) values were progressive but did not dynamically increase during five F-T cycles. Chicken meatballs containing CS-Q or QS-Q showed significantly lower TBARS values than those with CS, QS, or Q after five F-T cycles. Adding quinoa seeds significantly increased the antioxidant activity and the chewiness of meatballs (p < 0.05) compared with starch only. The addition of the combination of QS-Q to chicken meatballs increased the values of taste, texture, and overall acceptability, indicating that quinoa starch and seeds may be introduced as premium ingredients to frozen meat products.

Radiological manifestation of familial acute necrotizing encephalopathy with RANBP2 mutation in a Far-East Asian family: Case report.

RATIONALE: Acute necrotizing encephalopathy (ANE) is a specific type of encephalopathy usually followed by febrile infection. It has an aggressive clinical course; however, it usually does not recur after recovery in cases of spontaneous ANE. Nevertheless, there are several studies reporting recurrences in familial ANE with RAN-binding protein 2 (RANBP2) mutation. There are few cases of familial ANE with RANBP2 mutation in Asian populations. PATIENTS CONCERNS: A 21-month-old Korean boy who was previously healthy, presented with seizure following parainfluenza - a virus and bocavirus infection, followed by 2 recurrent seizure episodes and encephalitis after febrile respiratory illnesses. Meanwhile, his 3-year-old sister had focal brain lesions on neuroimaging studies when evaluated for head trauma. The siblings also had an older brother who presented status epilepticus after febrile respiratory illness at the age of 10 months old. DIAGNOSIS: Brain magnetic resonance imaging was performed to evaluate the seizure and neurologic symptoms. Imaging findings showed variable spectrum - from non-specific diffuse white matter injury pattern to typical "tricolor pattern" of the ANE on diffusion-weighted images. The other 2 siblings showed focal lesions in both external capsules and severe diffuse brain edema. Genetic tests identified a heterozygous missense mutation in the RANBP2 [c.1754C>T (p.Thr585Met)] in 2 siblings and their mother. INTERVENTIONS: Patients were treated conservatively with anticonvulsive agents, intravascular immunoglobulin, and steroids. OUTCOMES: Among the 3 siblings, 2 male siblings died from familial ANE, whereas the female sibling was asymptomatic. LESSONS: These cases highlight the radiological aspects of familial ANE with incomplete penetrance of the RANBP2 gene in 3 family members, showing variable involvements of the brain and natural history on magnetic resonance images. Radiologists should be aware of the typical and atypical imaging findings of familial ANE for prompt management of affected patients.

Characteristics of dry eye patients with thick tear film lipid layers evaluated by a LipiView II interferometer.

PURPOSE: To investigate the characteristics of eyes with dry eye disease (DED) whose lipid layer thickness (LLT) measured 100 nm on a LipiView II interferometer and compare the DED parameters of them to those with LLT below 100 nm. METHODS: A total of 201 eyes of 102 enrolled DED patients (mean age 56.4 ± 11.8 years) were classified into 3 groups according to their average LLT; < 60 nm as thin-LLT (n = 49), 60-99 nm as normal-LLT (n = 77), and 100 nm as thick-LLT (n = 75). LLT, meiboscore, Schirmer I test, tear film break-up time (TBUT), ocular surface staining (OSS), and ocular surface disease index (OSDI) were assessed. RESULTS: The OSS and TBUT were significantly worse in the thick-LLT group than in the normal-LLT group (p = 0.020, and p = 0.028, respectively). The OSDI was significantly higher in the thick-LLT group than in the thin-LLT group (p = 0.006). However, the meiboscore was not different among the three groups (p = 0.33). Age, OSS, and OSDI showed a positive correlation with LLT (r = 0.16, p = 0.023; r = 0.213, p = 0.003; and r = 0.338, p = 0.001, respectively). In sensitivity analyses, eyes with corneal erosions had a significantly higher average LLT (p = 0.015), higher OSDI (p = 0.009), shorter TBUT (p < 0.001), and shorter Schirmer I value (p = 0.024) than those with clear corneas. CONCLUSION: The average LLT of eyes with corneal erosions was thicker than those without erosions, suggesting that the LLT of 100 nm in the eyes with corneal erosions should not be regarded as a stable physiologic condition. Cautious interpretation of LLT along with other dry eye parameters is required.

Clinical utility of the FilmArray meningitis/encephalitis panel in children at a tertiary center in South Korea.

BACKGROUND: We retrospectively evaluated the pathogens in the cerebrospinal fluid (CSF) of pediatric meningitis/encephalitis (M/E) by FilmArray meningitis/encephalitis panel (FA-MEP), and the characteristics of children showing positive and negative FA-MEP results. METHOD: FA-MEP along with conventional tests (bacterial/viral cultures, and polymerase chain reaction tests) was performed in children who presented symptoms of M/E. Clinical and laboratory data were reviewed to evaluate the characteristics of children with pathogens detected by FA-MEP. RESULTS: The CSF specimens from 110 pediatric M/E patients were enrolled. Mean age of the patients was 5.9 ± 5.2 years. Overall positive rate of FA-MEP was 46.4% (51/110). The pathogens detected in the patients were enterovirus (23/51, 45.1%), parechovirus (10/51, 19.6%), S. pneumoniae (7/51, 13.7%), human herpesvirus type 6 (6/51, 11.8%), S. agalactiae (3/51, 5.9%), herpes simplex virus type 2 (1/51, 2.0%), and E. coli (1/51, 2.0%). Aseptic meningitis (OR, 3.24, 95% CI, 1.18-12.73) and a duration of <2 days from onset of symptoms to CSF test (OR, 3.56, 95% CI, 0.1-0.91) significantly contributed to detection of pathogens by the FA-MEP. Among the 14 children who were administered empiric antibiotics before the CSF test, the detection rate was significantly higher in the FA-MEP than in the conventional test (28.6 vs. 0.0%, p = 0.031). CONCLUSIONS: FA-MEP had a higher detection rate in children with M/E compared with conventional tests, particularly aseptic meningitis, and in case of shorter duration of time-to-test. This test was more effective than the conventional test in pediatric M/E patients that had been administered empiric antibiotics.