Assessing Uveitis Risk following Pediatric Down Syndrome Diagnosis: A TriNetX Database Study.

Background and Objectives: The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a diagnosis of DS. Materials and Methods: This multi-institutional retrospective cohort study utilized the TriNetX database to identify individuals aged 18 years and younger with and without a diagnosis of DS between 1 January 2000 and 31 December 2023. The non-DS cohort consisted of randomly selected control patients matched by selected variables. This included gender, age, ethnicity, and certain comorbidities. The main outcome is the incidence of new-onset uveitis. Statistical analysis of the uveitis risk was reported using hazard ratios (HRs) and 95% confidence intervals (CIs). Separate analyses of the uveitis risk among DS patients based on age groups and gender were also performed. Results: A total of 53,993 individuals with DS (46.83% female, 58.26% white, mean age at index 5.21 ± 5.76 years) and 53,993 non-DS individuals (45.56% female, 58.28% white, mean age at index 5.21 ± 5.76 years) were recruited from the TriNetX database. Our analysis also showed no overall increased risk of uveitis among DS patients (HR: 1.33 [CI: 0.89-1.99]) compared to the non-DS cohort across the 23-year study period. Subgroup analyses based on different age groups showed that those aged 0-1 year (HR: 1.36 [CI: 0.68-2.72]), 0-5 years (HR: 1.34 [CI: 0.75-2.39]), and 6-18 years (HR: 1.15 [CI: 0.67-1.96]) were found to have no association with uveitis risk compared to their respective non-DS comparators. There was also no increased risk of uveitis among females (HR: 1.49 [CI: 0.87-2.56]) or males (HR: 0.82 [CI: 0.48-1.41]) with DS compared to their respective non-DS comparators. Conclusions: Our study found no overall increased risk of uveitis following a diagnosis of DS compared to a matched control population.

The impact of digital educational games on student's motivation for learning: The mediating effect of learning engagement and the moderating effect of the digital environment.

The utilization of digital educational infrastructure in schools has propelled digital educational games to the forefront of educational innovation. Despite an abundance of empirical studies on the relationship between digital educational games and student's motivation for learning, a consensus has yet to be reached. This study aims to bridge existing research gaps by adopting a mixed-methods approach grounded in behaviorist learning theory and contextual cognitive theory. A detailed questionnaire was disseminated to students from three distinct university in Thailand. After the exclusion of invalid responses, a robust sample of 434 valid responses was curated and utilized for analysis. Utilizing SPSS and MPLUS software, empirical analyses were conducted to explore the impact of digital educational games on student's motivation for learning. Research results indicate that: First, digital educational games positively influence student's motivation for learning; Second, learning engagement serves as a mediator between digital educational games and student's motivation for learning; Third, the digital environment moderates the relationship between digital educational games and student's learning engagement. Notably, the positive impact of digital educational games on student learning engagement is amplified in a more immersive digital environment. This study contributes to behaviorist theory and social cognition theory by elucidating how digital educational games affect student's motivation for learning through their engagement and by highlighting the moderating role of the digital environment. Practically, these findings underscore the significance of digital educational games and the digital environments in schools to enhance student's motivation for learning.

Emodin is a Potential Drug Targeting CD44-positive Hepatocellular Cancer.

BACKGROUND: Liver cancer is one of the most prevalent forms of cancer of the digestive system in our country. The most common subtype of this disease is hepatocellular carcinoma (HCC). Currently, treatment options for HCC patients include surgical resection, liver transplantation, radiofrequency ablation, chemoembolization, and biologic-targeted therapy. However, the efficacy of these treatments is suboptimal, as they are prone to drug resistance, metastasis, spread, and recurrence. These attributes are closely related to cancer stem cells (CSCs). Therefore, the utilization of drugs targeting CSCs may effectively inhibit the development and recurrence of HCC. METHODS: HepG2 and Huh7 cells were used to analyze the antitumor activity of emodin by quantifying cell growth and metastasis, as well as to study its effect on stemness. RESULTS: Emodin effectively suppressed the growth and movement of HCC cells. Emodin also significantly inhibited the proliferation of CD44-positive hepatoma cells. CONCLUSION: Emodin shows promise as a potential therapeutic agent for HCC by targeting CD44-- positive hepatoma cells.

The risk of ischemic stroke significantly increases in individuals with blepharitis: A population-based study involving 424,161 patients.

INTRODUCTION: To investigate the association of blepharitis and ischemic stroke. METHODS: This nationwide retrospective cohort study used population-based data in Taiwan. Individuals aged 20 and above with diagnosis of blepharitis was included based on electrical medical records. After exclusion of ineligible cases, 424,161 patients were identified between 2008 and 2018. The blepharitis and non-blepharitis cohorts were matched based on sex, age, and comorbidities. Multivariable-adjusted Cox proportional hazards model was adopted to calculate the hazard ratio and 95% confidence interval (CI) between blepharitis and non-blepharitis cohorts. The incidence of ischemic stroke was estimated by Kaplan-Meier analysis. RESULTS: 424,161 pairs of blepharitis cohort and non-blepharitis cohort were 1:1 propensity score matched for statistical analysis. Patients with blepharitis had significantly increased risk of ischemic stroke compared with the individuals without blepharitis (adjusted hazard ratio 1.32, 95% CI 1.29-1.34, P < 0.001). A significantly higher risk of ischemic stroke was observed in blepharitis cohort with a previous diagnosis of cancer than in those without cancer (P for interaction < 0.0001). Kaplan-Meier survival analysis revealed the cumulative incidence of ischemic stroke increased in the blepharitis cohort compared with that in the non-blepharitis cohort in 10 years (log-rank P < 0.001). The follow-up period analysis further indicated 1.41-fold adjusted hazard (95% CI 1.35-1.46, P < 0.001) of ischemic stroke within a year after blepharitis diagnosis. CONCLUSIONS: Patients with blepharitis had an elevated risk of developing ischemic stroke. Early treatment and active surveillance are suggested for patients with chronic blepharitis. Further research is required to determine the casual relationship between blepharitis and ischemic stroke, as well as the underlying mechanism.

Corneal Complications after COVID-19 Vaccination: A Systemic Review.

Multiple vaccines are now being used across the world, and several studies have described cases of corneal graft rejection following the administration of the COVID-19 vaccine. The purpose of this article is to review the corneal adverse event that occurred following COVID-19 vaccine administration. The literature search was conducted in March 2022 using MEDLINE, PubMed, and the Cochrane Database of Systematic Reviews. A total of 27 articles, including 37 cases, have documented corneal adverse events that occurred following COVID-19 vaccination. The mean age was 60 ± 14.9 years (range, 27-83 years). The most common events were acute corneal graft rejection (n = 21, 56.8%), followed by herpes zoster ophthalmicus (n = 11, 29.7%) and herpes simplex keratitis (n = 2, 5.4%). The mean time from vaccination to the event was 10 ± 8.5 days (range, 1-42 days) after the first or second dose of vaccine. All patients with corneal graft rejection, immune-mediated keratolysis, and peripheral ulcerative keratitis (PUK) (n = 24, 64.9%) were managed topically with or without oral corticosteroids. Patients with herpes zoster ophthalmicus and herpes simplex keratitis were managed with oral antiviral agents. Two patients received penetrating keratoplasty due to keratolysis after invalid topical treatment. Disease resolution was noted in 29 patients (78.3%), whereas 3 (8.1%) had persistent corneal edema after graft rejection, 1 (2.7%) had corneal infiltration after HZO, and 4 (10.8%) were not mentioned in the articles. Corneal adverse events could occur after COVID-19 vaccination. After timely treatment with steroids or antiviral agents, most of the events were mild and had a good visual outcome. Administrating or increasing steroids before vaccination may be useful for the prevention of corneal graft rejection. However, the prophylactic use of antiviral treatments in patients with a herpes viral infection history is not recommend.

Lifitegrast Ophthalmic Solution 5% Is a Safe and Efficient Eyedrop for Dry Eye Disease: A Systematic Review and Meta-Analysis.

Dry eye disease (DED) is a multifactorial disease that causes ocular discomfort and visual impairment on a damaged ocular surface. Lifitegrast, a novel T-cell integrin antagonist, was approved in the United States in July 2016 as a 5% (50 mg/mL) ophthalmic solution for DED management. Currently, no meta-analysis and systemic review based on relevant studies have been conducted. This study aimed to evaluate the efficacy and safety of lifitegrast in patients with DED. We systematically searched Embase, Medline, PubMed, and Web of Science for randomized controlled trials (RCTs) and nonrandomized studies evaluating lifitegrast effects on symptomatic DED. Then, inferior corneal staining score, total corneal staining score (TCSS), nasal lissamine staining score (NLSS), total lissamine staining score, ocular discomfort score (ODS), eye discomfort score (visual analog scale (VAS) score), eye dryness score (EDS), ocular surface disease index score (OSDI-S), and tear break-up time (TBUT) were assessed. Clinical global impression and safety profiles were also evaluated. The studies were pooled in a random-effects model. We included five RCTs, one case-control study, and four longitudinal or retrospective studies, comprising 3197 participants. In the meta-analysis, lifitegrast was superior to the placebo because it improved TCSS, NLSS, TBUT, ODS, eye discomfort score, EDS, and OSDI-Sin DED. However, lifitegrast showed higher risks for ocular and non-ocular treatment-emergent adverse events (TEAEs) overall or at a mild or moderate level. Nonetheless, its incidence of adverse events slightly differed from that in the placebo, especially instillation site discomforts and dysgeusia, thereby considered safe and tolerable. Claims of withdrawal during follow-up caused by TEAEs were extremely rare. Lifitegrast improves DED, although dysgeusia, installation site pain, and irritation may be a concern for some. Overall, most of the adverse events are tolerable. Lifitegrast can alleviate refractory DED and improves patients' quality of life.

MultiColor imaging in urticarial vasculitis with recurrent branch retinal artery occlusion in a case with positive toxoplasma IgG and interferon-gamma release assay - Case report.

INTRODUCTION: We report a male who presented with acute visual defect and was diagnosed with urticarial vasculitis with recurrent branch retinal artery occlusion (BRAO) after systemic disease survey, fluorescein angiography (FA), and MultiColor imaging (MCI). CASE REPORT: A 47-year-old male with a history of urticarial vasculitis presented with visual defect OD. Fundus examination showed two foci of ischemic retinal whitening beneath the inferior arcade and above the superior arcade. MCI demonstrated a greenish tinge in the corresponding area. FA revealed segmental arteriolar staining and arterial occlusive changes. BRAO with retinal arteritis was diagnosed. Toxoplasma IgG was positive. Sulfamethoxazole 400mg plus trimethoprim 80mg was given. His vision worsened after 1-week of treatment. The established lesions improved, but new lesions occurred. Interferon-gamma release assay was positive but tuberculosis DNA qualitative amplification test of sputum was negative. Sputum acid-fast stain was positive and culture revealed nontuberculous mycobacteria. Left facial itching and reactive lymphadenopathy developed. Prednisolone and cyclophosphamide were started. The initial retinal artery lesions regained perfusion. CONCLUSIONS: Urticarial vasculitis with recurrent BRAO is an immune complex-mediated disease. Greenish-tinged occlusive lesions were noted from MCI with high resolution and contrast. MCI could be a valuable method for retinal vessel occlusive disease detection before FA and follow up.

Analysis of wet deposition characteristics in the city of Guilin, China.

In this study, the rainfall, pH, conductivity, and ionic component data for Guilin from 2015 to 2017 were analyzed. Specifically, the relationship between the pH value of the rainfall, the change of each ion in the rainfall, and the primary ion sources was examined. The main results obtained were as follows. During the 3-year study period, the average annual pH value of Guilin was 5.45 and exhibited a downward trend. The seasonal variation of rainfall acidity was pronounced, with high pH values and low frequencies of acid rain in summer, and low pH values and high frequencies of acid rain in winter. From 2015 to 2017, the relative order of the average concentrations of the ionic components in the rainfall was SO42- > NO3- > Ca2+ > Cl- > NH4+ > Na+ > K+ > Mg2+ > F-, the annual average concentration of each ionic component displayed a downward trend, and seasonal changes were obvious. Only NH4+ showed an upward trend in rainfall. The (SO42-)/(NO3-) ratio was basically < 3 and manifested a downward trend; (Ca2+)/(NH4+) rose sharply in August and September each year. Using correlation analysis and enrichment factor analysis, it was concluded that the rainfall in Guilin is mainly affected by SO2, NOx, and NH3, with the geological conditions in the karst area also contributing a certain amount to the rainfall acidity. Calculating the enrichment factor revealed that most of the Ca2+ came from a crustal source; half the Mg2+ came from the ocean and half came from the crust; and most of K+ and Cl- originated from the ocean. Human activities contributed most of the SO42- and NO3- in the rainfall.

Mycobacterium vaccae Nebulization in the Treatment of COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Severe acute respiratory syndrome coronavirus 2 infection is associated with strong infectiousness and has no effective therapy. We aimed to explore the efficacy and safety of Mycobacterium vaccae nebulization in the treatment of Coronavirus Disease 2019 (COVID-19). Methods: In this randomized, double-blind, placebo-controlled clinical trial, we included 31 adult patients with moderate COVID-19 who were admitted to the Fourth People's Hospital of Nanning (Nanning, China) between January 22, 2020 and February 17, 2020. Patients were randomly divided into two groups: group A (standard care group) and group B (M. vaccae in combination with standard care group). The primary outcome was the time interval from admission to viral RNA negative conversion (oropharyngeal swabs were used in this study). Secondary outcomes included chest computed tomography (CT), mortality, length of hospital stay, complications during treatment, and so on. Patients were followed up to 4 weeks after discharge (reexamination of viral RNA, chest CT, etc.). Results: Nucleic acid test negative conversion time in group B was shorter than that in group A (2.9 days [2.7-8.7] vs. 6.8 days [3.3-13.8]; p = 0.045). No death and no conversion to severe or critical cases were observed in both groups. Two weeks after discharge, neither "relapse" nor "return to positive" cases were found. Four weeks after discharge, it was found that there was no case of " relapse " or "return to positive" in group B, and 1 patient in group A showed "return to positive", but there was no clinical manifestation and imaging progression. No adverse reactions related to M. vaccae were found during observation period. Conclusion:M. vaccae treatment might shorten the time interval from admission to viral RNA negative conversion, which might be beneficial to the prevention and treatment of COVID-19. Clinical Trial Registration: ChiCTR2000030016.

CX3CR1 might be a promising predictor of systemic lupus erythematosus patients with pulmonary fibrosis.

The inflammatory process in systemic lupus erythematosus (SLE) affects many organs including the lungs. Chemokines are suggested to play important roles in the pathogenesis of SLE with pulmonary fibrosis (PF). In the present study, our objective is to evaluate the correlation between chemokines and PF in SLE patients. Transcriptome sequencing analysis was used to find the different expressed genes between SLE patients with PF and without PF. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum levels of chemokines in SLE patients and healthy controls. Expression of CX3CR1 was measured by real-time polymerase chain reaction (PCR) and flow cytometer. Sixteen differentially chemokine genes were found to be associated to SLE with PF. Meanwhile, the upregulation of C-X3-C motif chemokine receptor 1 (CX3CR1) and its ligand, CX3C chemokine ligand 1 (CX3CL1) were observed in SLE patients with PF than that of SLE patients without PF and healthy control. Phenotypic analysis also showed that the surface expression of CX3CR1 increased in PBMCs from SLE patients with PF. Our observations indicated that CX3CL1/CX3CR1 axis is associated with PF in SLE. CX3CR1 might be a promising predictor of SLE with PF and the interactions between CX3CL1 and CX3CR1 might provide potential candidate target for the treatment of SLE with PF.

The prostaglandin E2 increases the production of IL-17 and the expression of costimulatory molecules on γδ T cells in rheumatoid arthritis.

γδ T cells play important roles in the development of rheumatoid arthritis (RA) through their antigen-presenting capacity, release of pro-inflammatory cytokines, immunomodulatory properties, interaction with CD4+ CD25+ Tregs and promotion of antibody production by helping B cells. Although prostaglandin E2 (PGE2) was proved to have the ability to enhance the antigen-presenting function of dendritic cells and IL-17 production of CD4+ αß T cells in RA, the role of PGE2 in γδ T cells from RA disease has not yet been clarified. The goal of this study was to determine the role of PGE2 in γδ T cells in RA. We first demonstrated that the population of γδT17 cells increased in patients with RA compared to healthy controls. Then, IL-17A level in patients with RA was shown to increase compared to healthy controls. After adding PGE2 to γδ T cells from patients with RA, the IL-17A level increased accordingly, and the expression of the costimulatory molecules, CD80 and CD86, on these cells also increased. These results suggest that PEG2 can increase the production of IL-17A and the expression of CD80 and CD86 on γδ T cells in patients with RA. These findings will benefit to explore new therapeutic targets for RA disease.

Ultra-widefield angiography in the diagnosis and management of uveitis.

PURPOSE: The aim of this study is to evaluate the clinical use of ultra-widefield angiography (UWFA) in uveitis. MATERIALS AND METHODS: We showed the UWFA and traditional 55° fluorescein angiography (FA) of four cases with Eales' disease, idiopathic retinal vasculitis, aneurysms, and neuroretinitis syndrome, Behçet's disease, and idiopathic panuveitis in a tertiary medical center. Comparison of UWFA with traditional 55°FA in the diagnosis and management of uveitis and review of the literature is also presented. RESULTS: Ultra-widefield FA revealed far-peripheral vascular imaging. This information would not have been easily obtained from traditional FA. With more information of the peripheral retina, it may facilitate appropriate diagnosis and monitoring, and the management may be revised. CONCLUSION: University of Western Australia played an important role to confirm the diagnosis of uveitis and to determine the corresponding treatment.

Choroid vascular occlusion and ischemic optic neuropathy after facial calcium hydroxyapatite injection- a case report.

BACKGROUND: We reported a case of sudden monocular vision loss after calcium hydroxyapatite (CaHA) injection into the nasal tip and dorsum with detailed retina images. CASE PRESENTATION: A healthy, 35-year-old woman received CaHA filler injection for nose augmentation. Ten minutes after the procedure, she developed nausea, vomiting, headache, ptosis, and left periorbital pain. After 30 minutes, she complained of progressively blurring vision in the left eye. The best-corrected visual acuity (BCVA) in her left eye was 30 cm ahead of hand motion. Left exotropia was noted in primary gaze. Limitations in adduction, supraduction, and infraduction of the left eye were also observed. Slit lamp examination of the left eye revealed a pink conjunctiva, a clear cornea, a mild anterior chamber reaction, a sluggish papillary light reflex, and a semi-dilated pupil. A positive relative afferent pupillary defect was observed in the left eye. Fundus examination revealed optic disc edema and some linear whitish opacity over the superior and temporal sites in the left eye, suggesting multiple CaHA emboli in the choroid vessels. CONCLUSIONS: Although the majority of adverse reactions are mild and transient, surgeons should be alert about extremely rare serious adverse events such as visual loss.