Evaluation of inhalation risk during quarantine work with quaternary ammonium compounds-based disinfectant.

Quarantine work is widely recognized as an indispensable endeavor in curbing the propagation of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Furthermore, the heavy workload places workers at a heightened risk of chemical exposure and respiratory damage. Consequently, it is paramount to systematically perform health risk assessments and meticulously oversee the work by wearing personal protective equipment to minimize these risks. To assess the inhalation exposure, this study examined data on disinfectant exposure from quarantine professional users who utilized disinfectants containing quaternary ammonium compounds. Through a survey of 6,199 cases conducted by 300 quarantine professional users who actively engaged in quarantine work, we assembled a database of exposure factors derived from their utilization of spray-type disinfectants for quarantine purposes. Based on these data, we formulated an inhalation exposure algorithm, which considers the time-weighted average (TWA) air concentrations. The test results demonstrated that the industrial-grade respirator mask could prevent a minimum of 68.3 % of particles, reducing respiratory exposure. Consequently, the hazard quotient (HQ) due to disinfectant exposure also decreased. This research is essential in safeguarding the safety and health of professional users engaged in quarantine-related tasks. By implementing strict measures like health risk assessments and personal protective equipment, individuals with quarantine experience can safely carry out their quarantine work. The results of this study are expected to serve as a framework for improving policies and regulations concerning quarantine work and safeguarding the health of professional users.

The Microbiome Matters: Its Impact on Cancer Development and Therapeutic Responses.

In the evolving landscape of cancer research, the human microbiome emerges as a pivotal determinant reshaping our understanding of tumorigenesis and therapeutic responses. Advanced sequencing technologies have uncovered a vibrant microbial community not confined to the gut but thriving within tumor tissues. Comprising bacteria, viruses, and fungi, this diverse microbiota displays distinct signatures across various cancers, with most research primarily focusing on bacteria. The correlations between specific microbial taxa within different cancer types underscore their pivotal roles in driving tumorigenesis and influencing therapeutic responses, particularly in chemotherapy and immunotherapy. This review amalgamates recent discoveries, emphasizing the translocation of the oral microbiome to the gut as a potential marker for microbiome dysbiosis across diverse cancer types and delves into potential mechanisms contributing to cancer promotion. Furthermore, it highlights the adverse effects of the microbiome on cancer development while exploring its potential in fortifying strategies for cancer prevention and treatment.

Autolysis of Pseudomonas aeruginosa Quorum-Sensing Mutant Is Suppressed by Staphylococcus aureus through Iron-Dependent Metabolism.

Microorganisms usually coexist as a multifaceted polymicrobial community in the natural habitats and at mucosal sites of the human body. Two opportunistic human pathogens, Pseudomonas aeruginosa and Staphylococcus aureus commonly coexist in the bacterial infections for hospitalized and/or immunocompromised patients. Here, we observed that autolysis of the P. aeruginosa quorum-sensing (QS) mutant (lasRmvfR) was suppressed by the presence of the S. aureus cells in vitro. The QS mutant still displayed killing against S. aureus cells, suggesting the link between the S. aureus-killing activity and the autolysis suppression. Independent screens of the P. aeruginosa transposon mutants defective in the S. aureus-killing and the S. aureus transposon mutants devoid of the autolysis suppression revealed the genetic link between both phenotypes, suggesting that the iron-dependent metabolism involving S. aureus exoproteins might be central to both phenotypes. The autolysis was suppressed by iron treatment as well. These results suggest that the interaction between P. aeruginosa and S. aureus might be governed by mechanisms that necessitate the QS circuitry as well as the metabolism involving the extracellular iron resources during the polymicrobial infections in the human airway.

A TetR family regulator of an RND efflux system that directs artemisinin resistance in Vibrio cholerae.

Artemisinin (ARS) displayed bactericidal activity against Vibrio cholerae. To assess the mechanistic details of its antibacterial action, we have isolated V. cholerae mutants with enhanced ARS resistance and identified a gene (VCA0767) whose loss-of-function resulted in the ARS resistance phenotypes. This gene (atrR) encodes a TetR family transcriptional regulator, and its deletion mutant displayed the reduction in ARS-induced ROS formation and DNA damage. Transcriptomic analysis revealed that the genes encoding a resistance-nodulation-cell division (RND) efflux pump operon (vexRAB) and the outer membrane component (tolC) were highly upregulated in the artR mutant, suggesting that AtrR might act as a negative regulator of this operon and tolC. Gene deletion of vexR, vexB, or tolC abrogated the ARS resistance of the atrR mutant, and more importantly, the ectopic expression of VexAB-TolC was sufficient for the ARS resistance, indicating that the increased expression of the VexAB-TolC efflux system is necessary and sufficient for the ARS resistance of the atrR mutant. The cytoplasmic accumulation of ARS was compromised in the vexBtolC mutant, suggesting that the VexAB-TolC might be the primary efflux system exporting ARS to reduce its toxicity inside of the bacterial cells. The atrR mutant displayed resistance to erythromycin as well in a VexR-dependent manner. This result suggests that AtrR may act as a global regulator responsible for preventing intracellular accumulation of toxic chemicals by enhancing the RND efflux system.IMPORTANCEDrug efflux protein complexes or efflux pumps are considered as the major determinants of multiple antimicrobial resistance by exporting a wide range of structurally diverse antibiotics in bacterial pathogens. Despite the clinical significance of the increased expression of the efflux pumps, their substrate specificity and regulation mechanisms are poorly understood. Here, we demonstrated that VexAB-TolC, a resistance-nodulation-cell division (RND) efflux pump of V. cholerae, is responsible for the resistance to artemisinin (ARS), an antimalarial drug with bactericidal activity. Furthermore, we newly identified AtrR, a TetR family repressor, as a global regulator for VexRAB and the common outer membrane channel, TolC, where VexR functions as the pathway-specific regulator of the vexAB operon. Our findings will help improve our insight into a broad range of substrate specificity of the VexAB-TolC system and highlight the complex regulatory networks of the multiple RND efflux systems during V. cholerae pathogenesis.

Primary and additional treatment preference in aggressive retinopathy of prematurity and type 1 retinopathy of prematurity.

OBJECTIVE: This study aimed to evaluate the preference for antivascular endothelial growth factor (anti-VEGF) versus laser ablation therapy as primary and additional treatment in aggressive retinopathy of prematurity (ROP) and type 1 ROP. METHODS: This multicentre retrospective study was conducted at nine medical centres across South Korea. A total of 94 preterm infants with ROP who underwent primary treatment between January 2020 and December 2021 were enrolled. All eyes were classified as having type 1 ROP or aggressive ROP. Data on the zone, primary treatment chosen, injection dose, presence of reactivation and additional treatment were collected and analysed. RESULTS: Seventy infants (131 eyes) with type 1 ROP and 24 infants (45 eyes) with aggressive ROP were included. Anti-VEGF injection was selected as the primary treatment in 74.05% of the infants with type 1 ROP and 88.89% with aggressive ROP. Anti-VEGF injection was selected as the ROP was located in zone I or posterior zone II, and laser ablation was selected when it was located in zone II. The anti-VEGF injection doses varied and tended to be higher in the aggressive ROP group. Infants with aggressive ROP were 2.08 times more likely to require additional treatment than those with type 1 ROP. When ROP reactivation occurred, laser therapy was preferred as an additional treatment. CONCLUSION: In Korea, the preference for anti-VEGF therapy or laser therapy differed according to ROP subtype, zone and primary or secondary treatment. These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.

Interactive Direct Interhospital Transfer Network System for Acute Stroke in South Korea.

BACKGROUND AND PURPOSE: Interhospital transfer is an essential practical component of regional stroke care systems. To establish an effective stroke transfer network in South Korea, an interactive transfer system was constructed, and its workflow metrics were observed. METHODS: In March 2019, a direct transfer system between primary stroke hospitals (PSHs) and comprehensive regional stroke centers (CSCs) was established to standardize the clinical pathway of imaging, recanalization therapy, transfer decisions, and exclusive transfer linkage systems in the two types of centers. In an active case, the time metrics from arrival at PSH ("door") to imaging was measured, and intravenous thrombolysis (IVT) and endovascular treatment (EVT) were used to assess the differences in clinical situations. RESULTS: The direct transfer system was used by 27 patients. They stayed at the PSH for a median duration of 72 min (interquartile range [IQR], 38-114 min), with a median times of 15 and 58 min for imaging and subsequent processing, respectively. The door-to-needle median times of subjects treated with IVT at PSHs (n=5) and CSCs (n=2) were 21 min (IQR, 20.0-22.0 min) and 137.5 min (IQR, 125.3-149.8 min), respectively. EVT was performed on seven subjects (25.9%) at CSCs, which took a median duration of 175 min; 77 min at the PSH, 48 min for transportation, and 50 min at the CSC. Before EVT, bridging IVT at the PSH did not significantly affect the door-to-puncture time (127 min vs. 143.5 min, p=0.86). CONCLUSIONS: The direct and interactive transfer system is feasible in real-world practice in South Korea and presents merits in reducing the treatment delay by sharing information during transfer.

Bilateral posterior scleritis after sequential bilateral cataract surgery: a case report.

BACKGROUND: Posterior scleritis is a rare, inflammatory ophthalmic disease, leading to severe visual impairment if untreated. Posterior scleritis occurring after surgery, unrelated to systemic inflammatory diseases, is even rarer. This report discusses a case of bilateral posterior scleritis, after cataract surgery in both the eyes, treated with high-dose steroids. CASE PRESENTATION: A 55-year-old man, who had undergone bilateral sequential cataract surgery one week before, presented with sudden loss of vision and ocular pain in both eyes. The patient had no systemic diseases or neurological symptoms. Serous retinal detachment of the macula with optic disc swelling was observed on fundus examination in both the eyes, and bilateral thickening of choroid and sclera was seen in ultrasonography. Under diagnosis of bilateral posterior scleritis due to the increased signal of sclera in both the eyes on magnetic resonance imaging, high-dose steroid therapy was performed. After treatment, improvement in visual acuity and retinal detachment were observed, and thereafter, it has been maintained without relapse. CONCLUSIONS: With high-dose steroid therapy, we successfully treated a rare case of bilateral posterior scleritis following cataract surgery in both eyes. To our knowledge, this is the first report on posterior scleritis occurring after surgery, unrelated to systemic inflammatory diseases.

An iron-chelating sulfonamide identified from Drosophila-based screening for antipathogenic discovery.

We exploited bacterial infection assays using the fruit fly Drosophila melanogaster to identify anti-infective compounds that abrogate the pathological consequences in the infected hosts. Here, we demonstrated that a pyridine-3-N-sulfonylpiperidine derivative (4a) protects Drosophila from the acute infections caused by bacterial pathogens including Pseudomonas aeruginosa. 4a did not inhibit the growth of P. aeruginosa in vitro, but inhibited the production of secreted toxins such as pyocyanin and hydrogen cyanide, while enhancing the production of pyoverdine and pyochelin, indicative of iron deprivation. Based on its catechol moiety, 4a displayed iron-chelating activity in vitro toward both iron (II) and iron (III), more efficiently than the approved iron-chelating drugs such as deferoxamine and deferiprone, concomitant with more potent antibacterial efficacy in Drosophila infections and unique transcriptome profile. Taken together, these results delineate a Drosophila-based strategy to screen for antipathogenic compounds, which interfere with iron uptake crucial for bacterial virulence and survival in host tissues.

Artemisinin displays bactericidal activity via copper-mediated DNA damage.

Artemisinin (ARS) and its semi-synthetic derivatives are effective drugs to treat malaria and possess multiple therapeutic activities based on their endoperoxide bridge. Here, we showed that ARS displayed antibacterial efficacy in Drosophila systemic infections caused by bacterial pathogens but killed only Vibrio cholerae (VC) in vitro, involving reactive oxygen species (ROS) generation and/or DNA damage. This selective antibacterial activity of ARS was attributed to the higher intracellular copper levels in VC, in that the antibacterial activity was observed in vitro upon addition of cuprous ions even against other bacteria and was compromised by the copper-specific chelators neocuproine (NC) and triethylenetetramine (TETA) in vitro and in vivo. We suggest that copper can enhance or reinforce the therapeutic activities of ARS to be repurposed as an antibacterial drug for the treatment of bacterial infections.

Antimicrobial Activities of Propolis in Poloxamer Based Topical Gels.

Propolis contains a group of compounds with various activities. However, their low solubility is a drawback for the development of pharmaceutical formulations. In this study, poloxamers as a solubilizer and gelling agent were evaluated to develop a topical antimicrobial formulation of propolis. The effects of poloxamer type and concentration on the propolis solubility, release rate, and antimicrobial activities were investigated. Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans) were the representative bacteria and fungi, respectively. At 5%, poloxamer 407 (P407) and poloxamer 188 (P188) enhanced the propolis solubility by 2.86 and 2.06 folds, respectively; at 10%, they were 2.81 and 2.59 folds, respectively. The micelle size in the P188 formulation increased in the presence of propolis, whereas there was no change in the P407 formulation. Release rates of propolis decreased with the P188 concentration increase, which was attributed to viscosity increase. Both P188 and P407 formulations showed antimicrobial activity against S. aureus in a time-kill kinetics assay. However, only the P188 formulation reduced the cell's numbers significantly against C. albicans, compared to the control. We speculate that P188 mixed micelles were more effective in releasing free active compounds to exhibit anti-microbial activity compared to the P407 micelles encapsulating the hydrophobic compounds in their cores. Propolis in P188 formulation is proposed as a potential topical antimicrobial agent based on its activity against both S. aureus and C. albicans.

High Chloride Burden and Clinical Outcomes in Critically Ill Patients With Large Hemispheric Infarction.

Background: In general, disease severity has been found to be associated with abnormal chloride levels in critically ill patients, but hyperchloremia is associated with mixed results regarding patient-centered clinical outcomes. We aimed to investigate the impact of maximum serum chloride concentration on the clinical outcomes of critically ill patients with large hemispheric infarction (LHI). Methods: We conducted a retrospective observational cohort study using prospective institutional neurocritical care registry data from 2013 to 2018. Patients with LHIs involving over two-thirds of middle cerebral artery territory, with or without infarction of other vascular territories, and a baseline National Institutes of Health Stroke Scale score of ≥13 were assessed. Those with a baseline creatinine clearance of <15 mL/min and required neurocritical care for <72 h were excluded. Primary outcome was in-hospital mortality. Secondary outcomes included 3-month mortality and acute kidney injury (AKI) occurrence. Outcomes were compared to different maximum serum chloride levels (5 mmol/L increases) during the entire hospitalization period using multivariable logistic regression analyses. Results: Of 90 patients, 20 (22.2%) died in-hospital. Patients who died in-hospital had significantly higher maximum serum chloride levels than did those who survived up to hospital discharge (139.7 ± 8.1 vs. 119.1 ± 10.4 mmol/L; p < 0.001). After adjusting for age, sex, and Glasgow coma scale score, each 5-mmol/L increase in maximum serum chloride concentration was independently associated with an increased risk of in-hospital mortality (adjusted odds ratio (aOR), 4.34; 95% confidence interval [CI], 1.98-9.50; p < 0.001). Maximum serum chloride level was also an independent risk factor for 3-month mortality (aOR, 1.99 [per 5 mmol/L increase]; 95% CI, 1.42-2.79; p < 0.001) and AKI occurrence (aOR, 1.57 [per 5 mmol/L increase]; 95% CI, 1.18-2.08; p = 0.002). Conclusions: High maximum serum chloride concentrations were associated with poor clinical outcomes in critically ill patients with LHI. This study highlights the importance of monitoring serum chloride levels and avoiding hyperchloremia in this patient population.

A phage protein-derived antipathogenic peptide that targets type IV pilus assembly.

Phage-inspired antibacterial discovery is a new approach that recruits phages in search for antibacterials with new molecular targets, in that phages are the biological entities well adapted to hijack host bacterial physiology in favor of their own thrive. We previously observed that phage-mediated twitching motility inhibition was effective to control the acute infections caused by Pseudomonas aeruginosa and that the motility inhibition was attributed to the delocalization of PilB, the type IV pilus (TFP) assembly ATPase by binding of the 136-amino acid (aa) phage protein, Tip. Here, we created a series of truncated and point-mutant Tip proteins to identify the critical residues in the Tip bioactivity: N-terminal 80-aa residues were dispensable for the Tip activity; we identified that Asp82, Leu84, and Arg85 are crucial in the Tip function. Furthermore, a synthetic 15-aa peptide (P1) that corresponds to Leu73 to Ala87 is shown to suffice for PilB delocalization, twitching inhibition, and virulence attenuation upon exogenous administration. The transgenic flies expressing the 15-aa peptide were resistant to P. aeruginosa infections as well. Taken together, this proof-of-concept study reveals a new antipathogenic peptide hit targeting bacterial motility and provides an insight into antibacterial discovery targeting TFP assembly.

Clinical characteristics and prognostic factors in hypertensive anterior uveitis diagnosed with polymerase chain reaction.

Aim of the study is to report the clinical characteristics and prognostic factors in hypertensive anterior uveitis (AU) diagnosed with multiplex polymerase chain reaction (PCR). Eighty-eight eyes of 88 patients with hypertensive AU were enrolled from 2015 to 2019 in a tertiary center in South Korea. All patients underwent multiplex PCR that was performed using aqueous humor samples collected at first visit to detect the DNA of six herpesviruses. Twenty-eight (31.8%) eyes were PCR positive. Herpes simplex virus was found in 6 (6.8%) eyes, varicella-zoster virus in 7 (8.0%) eyes, cytomegalovirus in 14 (15.9%) eyes, and Epstein-Barr virus in 1 (1.1%) eye. On multivariate regression analysis, PCR positivity was significantly associated with coin-shaped keratic precipitates (odds ratio (OR) = 6.01, P = 0.044). Recurrence and final visual acuity were significantly associated with a presumed diagnosis of viral endotheliitis (OR = 21.69, P = 0.04 and OR = 6.3, P = 0.004, respectively). This study showed the importance of PCR positivity, suggesting that identification of the virus through active PCR testing could affect the course, treatment, and prognosis of hypertensive AU.

An antipathogenic compound that targets the OxyR peroxide sensor in Pseudomonas aeruginosa.

Introduction. Antipathogenic or antivirulence strategy is to target a virulence pathway that is dispensable for growth, in the hope to mitigate the selection for drug resistance.Hypothesis/Gap Statment. Peroxide stress responses are one of the conserved virulence pathways in bacterial pathogens and thus good targets for antipathogenic strategy.Aim. This study aims to identify a new chemical compound that targets OxyR, the peroxide sensor required for the full virulence of the opportunistic human pathogen, Pseudomonas aeruginosa.Methodology. Computer-based virtual screening under consideration of the 'eNTRy' rules and molecular docking were conducted on the reduced form of the OxyR regulatory domain (RD). Selected hits were validated by their ability to phenocopy the oxyR null mutant and modulate the redox cycle of OxyR.Results. We first isolated three robust chemical hits that inhibit OxyR without affecting prototrophic growth or viability. One (compound 1) of those affected the redox cycle of OxyR in response to H2O2 treatment, in a way to impair its function. Compound 1 displayed selective antibacterial efficacy against P. aeruginosa in Drosophila infection model, without antibacterial activity against Staphylococcus aureus.Conclusion. These results suggest that compound 1 could be an antipathogenic hit inhibiting the P. aeruginosa OxyR. More importantly, our study provides an insight into the computer-based discovery of new-paradigm selective antibacterials to treat Gram-negative bacterial infections presumably with few concerns of drug resistance.

Title: efficacy of intravitreal dexamethasone implant on hard exudate in diabetic macular edema.

BACKGROUND: To investigate the effect of intravitreal dexamethasone implant (DEX implant) on hard exudate (HE) accompanying diabetic macular edema (DME). METHODS: This study was a non-comparative non-randomized 1-year prospective interventional study. Patients with DME and HE were treated using DEX implant two or three times. Color fundus photography and optical coherence tomography (OCT) were performed at every visit. HE area was measured semi-automatically from the fundus photographs. RESULTS: Thirty-five patients completed the study. Eleven patients (31.4%) received two injections, while the remaining received three times. HE area (primary outcome) significantly decreased from 1.404±2.094 mm2 (baseline) to 0.212±0.592 mm2 (last visit), which was 24% of the baseline HE area (P<0.001). HE1500 (HE within 1500 µm from the fovea) area also decreased significantly from 0.382±0.467 mm2 to 0.066±0.126 mm2 (P<0.001). Furthermore, anaverage best corrected visual acuity (BCVA) improvement of 4.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters was observed (from 49.9±18.3 to 54.3±20.4 letters) (P= 0.008). Central macular thickness (CMT) decreased from 455.8±23.6 µm to 366.8±31.1 µm (P=0.009). Repetitive measurements for entire study duration was analyzed using generalized estimating equations (GEE), where BCVA was related to age, CMT, and HE1500 area in multivariate analyses. CONCLUSION: DEX implant could reduce and suppress HE in DME for one year with two or three injections. And centrally located HE area (HE1500 area) is related to vision. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02399657 , Registered 26 March 2015.

Nitrate Respiration Promotes Polymyxin B Resistance in Pseudomonas aeruginosa.

Aims: Polymyxin B (PMB) is known to require reactive oxygen species (ROS) for its bactericidal activity, but the mechanism of PMB resistance in various Pseudomonas aeruginosa strains has been poorly understood. This study examined the role of nitrate respiration (NR) of some P. aeruginosa strains in the PMB resistance. Results: We observed that the minimum inhibitory concentration (MIC) value of PMB against P. aeruginosa PA14 was eightfold reduced (from 2.0 to 0.25 µg/mL) by agitation, but not against P. aeruginosa PAO1 (from 2.0 to 1.0 µg/mL). Transcriptomic and phenotypic analyses using both strains and their NR mutants revealed that the higher NR in PAO1 than in PA14 accounted for the higher MIC value (i.e., PMB resistance) of PAO1, which was sufficient to compromise the antibacterial activity of PMB in Drosophila infections. We also confirmed the contribution of the NR to the PMB resistance is independent of the major catalase (KatA), suggesting that the NR might affect the ROS generation rather than the ROS disintegration. Furthermore, this PMB resistance was relatively common among clinical P. aeruginosa isolates and correlated with higher NR in those strains. Innovation and Conclusion: These results suggest P. aeruginosa strains could display intrinsic resistance to antibiotics in clinical settings and that NR is a crucial factor in the intrinsic antibiotic resistance, and also provide an insight into another key target for successful antibiotic treatment of P. aeruginosa infections. Antioxid. Redox Signal. 34, 442-451.

The usefulness of Time-of-Flight MR angiography in detection of intraplaque hemorrhage in patients with acute ischemic stroke with symptomatic carotid stenosis.

OBJECTIVE: Carotid intraplaque hemorrhage (IPH) is a well-known risk indicator of thromboembolism, but it is not easy to rapidly detect IPH in acute symptomatic carotid disease. The aim of this study was to assess the utility of time-of-flight (TOF) magnetic resonance angiography (MRA) in the detection of IPH and evaluate the degree of stenosis and stroke patterns in patients with acute symptomatic carotid disease. METHODS: We retrospectively identified consecutive patients with acute symptomatic carotid disease who were admitted within 12 h after stroke onset. Fifty-nine patients underwent TOF MRA at admission and were categorized according to the presence or absence of intraplaque high signal intensity (HSI). The severity of carotid stenosis and diffusion-weighted magnetic resonance imaging lesion patterns were evaluated. RESULTS: Intraplaque HSI was detected in 28.8% of the enrolled patients (17/59). Mild-to-moderate symptomatic carotid stenosis was more frequent in the intraplaque HSI-positive group (70.6%) than in the intraplaque HSI-negative group (42.8%) (p = 0.015). The patients with intraplaque HSI more frequently exhibited a disseminated small infarction pattern (76.5% in the intraplaque HSI-positive group, 47.6% in the -negative group), and did not exhibit a border-zone infarction pattern (0% in the positive group, 16.7% in the negative group). CONCLUSIONS: TOF MRA may be a useful noninvasive and rapid tool to detect IPH in patients with acute symptomatic carotid disease. IPH was common in those with a lower degree of carotid stenosis and manifested as a disseminated small infarction pattern. Intraplaque HSI on TOF MRA in acute symptomatic carotid disease may help to determine the mechanism of stroke and establish early treatment plans.

Repositioning of a mucolytic drug to a selective antibacterial against Vibrio cholerae.

Drug repositioning, the approach to explore existing drugs for use in new therapeutic indications, has emerged as an alternative drug development strategy. In this study, we found that a mucolytic drug, N-acetylcysteine (NAC) showed antibacterial activity against Vibrio cholerae. NAC can provide acid stress that selectively inhibited the growth of V. cholerae among other bacterial pathogens. To address the antibacterial mechanism of NAC against V. cholerae, six acr (acetylcys-teine-resistant) mutants were isolated from 3,118 random transposon insertion clones. The transposon insertion sites of the six mutants were mapped at the five genes. All these mutants did not display NAC resistance under acidic conditions, despite their resistance to NAC under alkaline conditions, indicating that the NAC resistance directed by the acr mutations was independent of the unusual pH-sensitivity of V. cholerae. Furthermore, all these mutants displayed attenuated virulence and reduced biofilm formation, suggesting that the acr genes are required for pathogenesis of V. cholerae. This study validates the relevance of drug repositioning for antibacterials with new modes of action and will provide an insight into a novel antibacterial therapy for V. cholerae infections to minimize side effects and resistance emergence.

Factors associated with myopia in Korean children: Korea National Health and nutrition examination survey 2016-2017 (KNHANES VII).

BACKGROUND: To evaluate the prevalence and risk factors associated with myopia and high myopia in children in South Korea. METHODS: A total of 983 children 5-18 years of age who participated in the Korean National Health and Nutrition Examination Survey 2016-2017 (KNHANES VII), a nationwide population-based cross-sectional study, were evaluated. Myopia and high myopia were defined as a spherical equivalent (SE) ≤ - 0.5 diopters (D) and SE ≤ --6.0 D. The association between refractive errors and potential risk factors for myopia was analyzed. RESULTS: The prevalence of myopia and high myopia was 65.4 and 6.9%, respectively. Older age and parental myopia were significantly associated with both myopia and high myopia, while higher body mass index (BMI) was associated with high myopia only. Although the proportion of subjects who spent more time on near work activities (≥4 h/day) was sequentially increased with increased refractive error, this tendency was not statistically significant by multivariable logistic regression. CONCLUSIONS: Korean children had a high prevalence of myopia and high myopia. In this age group, the risk of myopia increased with aging and parental myopia. Higher BMI may be associated with high myopia.