Citral and triclosan synergistically silence quorum sensing and potentiate antivirulence response in Pseudomonas aeruginosa.

Among the ESKAPE pathogens, Pseudomonas aeruginosa is an extensively notorious superbug that causes difficult-to-treat infections. Since quorum sensing (QS) directly promotes pseudomonal virulence, targeting QS circuits is a promising approach for disarming phenotypic virulence. Hence, this study scrutinizes the anti-QS, antivirulence, and anti-biofilm potential of citral (CiT; phytochemical) and triclosan (TcN; disinfectant), alone and in combination, against P. aeruginosa PAO1/PA14. The findings confirmed synergism between CiT and TcN and revealed their quorum quenching (QQ) potential. At sub-inhibitory levels, CiT-TcN combination significantly impeded pyocyanin, total bacterial protease, hemolysin, and pyochelin production alongside inhibiting biofilm formation in P. aeruginosa. Moreover, the QQ and antivirulence potential of CiT and TcN was positively correlated by molecular docking studies that predicted strong associations of the drugs with QS receptors of P. aeruginosa. Collectively, the study identifies CiT-TcN as an effective drug combination that harbors QQ, antivirulence, and anti-biofilm prospects against P. aeruginosa.

Evaluating the knowledge, attitudes, and practices of healthcare workers regarding high-risk nosocomial infections: A global cross-sectional study.

Background: Healthcare workers (HCWs) play a vital role in delivering care and are frequently exposed to the risk of acquiring infections within the hospital setting. Around 15% of hospitalized patients suffer from these infections globally. However, the role and awareness of HCWs in the transmission of hospital-acquired infections (HAIs) or nosocomial infections is still unclear. This study aimed to evaluate the knowledge, attitude, and practices (KAP) toward high-risk microbial infections among HCWs on a global scale to identify measures to address this problem. Method: A cross-sectional descriptive study was conducted between 2022 and 2023, with HCWs selected as the study population. Data concerning KAP were collected through a self-administered online survey questionnaire, using a nonprobability convenience sampling method. Descriptive statistics and regression analysis were used to analyze the data. Results: A total of 743 HCWs from various countries participated in the study, with the majority of respondents being doctors (64.9%). Data were mainly obtained from Saudi Arabia (26.78%), Iraq (25.84%), India (15.7%), the United States of America (15.2%), and Africa (Sudan, Nigeria) (13.98%). The frequency of good KAP scores among physicians (KAP: 82.5, 80.66, and 70.5), nurses (KAP: 74.1, 73.07, and 88.7), medical practitioners (KAP: 87.2, 77.58, and 75.1), and technicians (KAP: 76.1, 74.38, and 89.6) were obtained as mentioned. With respect to experience, HCWs showed good KAP scores in 1-5 years (KAP: 82.4, 83.3, and 74.1), 5-10 years (KAP: 80.6, 74.54, 83), 10-20 years (KAP: 74.7, 79.1, and 82.7), and >20 years (KAP: 84.6, 78.8, and 82.8) categories. Conclusion: This study suggests that HCWs have good KAP regarding infection prevention, but there is still room for improvement. Educational seminars and awareness programs can provide better adherence to barrier protection measures such as hand washing, use of gloves, and hand disinfection.

Simultaneous Topography-Guided PRK/CXL Versus Topography-Assisted PTK/CXL: 1-Year Prospective Outcomes in Keratoconic Eyes.

PURPOSE: To compare 1-year visual and tomographic outcomes of topography-guided photorefractive keratectomy (TGPRK) and topography-assisted phototherapeutic keratectomy (TPTK) with corneal cross-linking (CXL). METHODS: TGPRK and TPTK were performed in 72 eyes (68 patients) and 74 eyes (71 patients), respectively. Based on the TGPRK ablation plan, the eyes underwent TPTK where the theoretical minimum corneal thickness (MCT) after surgery was less than 400 µm. In the TGPRK group, the theoretical maximum ablation depth was 50 µm after epithelium removal. In TPTK, a decentered single-step PTK was performed only in the steepest anterior curvature zone and the stromal ablation depth was limited to 25 µm. After ablation, accelerated CXL was performed in the central 8-mm zone (9 mW/cm2 for 10 minutes in "epithelium-off" mode) in both TGPRK and TPTK. The visual acuity and tomography were assessed. RESULTS: Improvement in uncorrected (P = .73) and corrected (P = .66) distance visual acuity was similar between the two groups. However, TGPRK eyes had a greater decrease in keratometry, anterior defocus, and spherical aberration (P < .001) at the cost of greater ablation of tissue (P < .001). The median MCT decreased by 27 and 52.5 µm in the TPTK and TGPRK eyes, respectively. Both groups had similar decreases in anterior root mean square of lower (P = .10) and higher (P = .12) order aberrations. CONCLUSIONS: Both TGPRK and TPTK improved visual acuity in the keratoconic eyes at 1 year of follow-up. However, TPTK removed less volume of tissue. Further, it could be an alternative to TGPRK if the theoretical stromal ablation exceeds 50 µm in thin keratoconic corneas. [J Refract Surg. 2021;37(8):562-569.].

Altered ocular surface immune cell profile in patients with dry eye disease.

PURPOSE: Aberrant inflammation and immune dysregulation are known pathogenic contributors in dry eye disease (DED). Aim of the study was to determine the proportions of immune cell subsets on the ocular surface (OS) of DED patients. METHODS: 15 healthy controls (22 eyes) and 48 DED subjects (36 eyes with evaporative DED - EDED; 60 eyes with aqueous deficient DED - ADED) were included in the study. Tear break up time (TBUT), Schirmer's test 1 (ST1), corneal staining (CS) and ocular surface disease index (OSDI) scoring were recorded. OS wash was used to collect immune cells on the OS of study subjects. The cells immunophenotyped using flow cytometry include leukocytes, neutrophils, macrophages, natural killer-NK cells and T cell subsets (CD4; CD8; double positive-DP; gamma delta-γδ and NK T cells). RESULTS: Significantly higher proportions of leukocytes, neutrophils, CD4 T cells, CD8 T cells, DP T cells and CD4/CD8 T cells ratio were observed in EDED and/or ADED patients. Significantly higher proportions of neutrophils and lower proportions of NK cells were observed in ADED subjects with corneal staining compared to those without and controls. Neutrophils/NK cells ratio was significantly higher in EDED and ADED subjects compared to controls. Correlation analysis revealed pathological relationships between proportions of leukocytes, neutrophils, CD4 T cells and Neutrophil/NK cells ratio with DED clinical parameters. CONCLUSION: OS immune cell subset proportion changes in DED patients were associated with DED types and severity. The data suggests the potential for a new generation of therapies targeting immune cells on the ocular surface.

Relevance of IgE, allergy and eye rubbing in the pathogenesis and management of Keratoconus.

Keratoconus (KC) is an ectatic disease of the cornea characterized by localized thinning and protrusion causing irregular astigmatism, which can lead to significant visual impairment. KC has often been associated with allergy and/or atopy, which are immune-mediated inflammatory reactions primarily driven by IgE. A higher proportion of KC patients were reported to have history or suffer from systemic and/or ocular allergy with elevated allergen-specific IgE and/or total serum IgE. Eye rubbing, one of the risk factors for worsening of the disease and developing related complications in KC, is associated with IgE driven conditions. The current review enumerates and contextualizes the evidence related to IgE in mediating KC pathogenesis, including aberrant extra-cellular matrix remodeling. This review also discusses clinical strategies directed at modulating IgE-mediated responses in the management of KC, and the emerging academic and plausible clinical relevance of assessing serum and tear IgE (allergen-specific and total) status in improving the understanding of disease pathobiology, treatment planning, and prognosis.

Accuracy of OCT Curvature and Aberrations of Bowman's Layer: A Prospective Comparison With Physical Removal of Epithelium.

PURPOSE: To compare optical coherence tomography (OCT) and Scheimpflug curvature and aberrations of the Bowman's layer before and after removal of the epithelium. METHODS: Bowman's layer was mapped with OCT (Optovue Inc., Irvine, CA) before and after removal of the epithelium in normal eyes undergoing photorefractive keratectomy (n = 14) and keratoconic eyes undergoing corneal cross-linking (n = 25). The anterior corneal surface before removal and the underlying Bowman's layer after removal of the epithelium were also mapped with Pentacam (Oculus Optikgeräte, Wetzlar, Germany), and the surface aberrations with ray tracing were computed. RESULTS: The agreement of OCT curvatures before and after removal of the epithelium was excellent (intraclass correlation coefficient [ICC] = 0.9). A similar trend was seen between OCT and Pentacam after removal of the epithelium. The agreement of surface wavefront aberrations of the Bowman's layer before and after removal of the epithelium was excellent (ICC = 0.9) between the devices for keratoconic eyes. However, this agreement was relatively inferior in normal eyes (ICC < 0.5). CONCLUSIONS: The virtual OCT curvature and aberrations of the Bowman's layer agreed well with its actual magnitudes on removal of the epithelium in the keratoconic eyes. In normal eyes, the agreement was inferior for aberrations but not for curvature. [J Refract Surg. 2020;36(3):193-198.].

Status of Residual Refractive Error, Ocular Aberrations, and Accommodation After Myopic LASIK, SMILE, and TransPRK.

PURPOSE: To analyze residual refractive error, ocular aberrations, and visual acuity (VA) during accommodation simultaneously with ocular aberrometry in eyes after laser-assisted in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), and transepithelial photorefractive keratectomy (TransPRK). METHODS: Ocular aberrometry (Tracey Technologies, Houston, TX) was performed 3 months after LASIK (n = 95), SMILE (n = 73), and TransPRK (n = 35). While measuring the aberrations, VA was measured at distance (20 ft), intermediate (60 cm), and near (40 cm) targets. The examinations were done monocularly. A parallel group of age-matched normal eyes (n = 50) with 20/20 Snellen distance VA also underwent aberrometry. RESULTS: Distribution of residual spherical error of LASIK eyes matched the normal eyes the best, followed by SMILE and TransPRK. However, the distribution of cylindrical error of the SMILE eyes was distinctly different from the rest (P < .05). The SMILE eyes tended to be undercorrected by approximately 0.25 diopters (D) on average at all reading targets compared to LASIK eyes (P < .05). The undercorrection was greater when the magnitude of the preoperative cylinder exceeded 0.75 D (P < .05). The VA of LASIK and SMILE eyes was similar to normal eyes at all targets, but the TransPRK eyes were marginally inferior (P < .05). Only the ocular defocus changed differentially between the study groups during accommodation and the magnitude of change was least for TransPRK eyes (P < .05). However, postoperative near and intermediate accommodation of LASIK eyes were similar to normal eyes, followed by SMILE eyes and then TransPRK eyes. CONCLUSIONS: The refractive and aberrometric status of the LASIK eyes was closest to the normal eyes. The SMILE procedure may benefit from slight overcorrection of the preoperative refractive cylinder. [J Refract Surg. 2019;35(10):624-631.].

Dysregulated Tear Fluid Nociception-Associated Factors, Corneal Dendritic Cell Density, and Vitamin D Levels in Evaporative Dry Eye.

Purpose: The purpose of this study was to study the status and association among tear-soluble factors, corneal dendritic cell density, vitamin D, and signs and symptoms in dry eye disease (DED). Methods: A total of 33 control subjects and 47 evaporative dry eye patients were included in the study. DED diagnosis and classification was based on the 2017 Report of the Tear Film & Ocular Surface Society International Dry Eye Workshop (TFOS DEWS II). DED workup, including tear film break-up time (TBUT), Schirmer's test I (STI), corneal and conjunctival staining, ocular surface disease index (OSDI) scoring, and in vivo confocal microscopy (to assess corneal dendritic cell density [cDCD] and subbasal nerve plexus [SBNP] features) was performed in the study subjects. Tear fluid using Schirmer's strip and serum were collected from the subjects. Multiplex ELISA or single analyte ELISA was performed to measure 34 tear-soluble factors levels including vitamin D. Results: Significantly higher OSDI discomfort score, lower TBUT, and lower STI were observed in DED patients. cDCD was significantly higher in DED patients. No significant difference was observed in SBNP features. Tear fluid IL-1ß, IL-17A, MMP9, MMP10, MMP9/TIMP ratio, and VEGF-B were significantly higher in DED patients. Significantly lower tear fluid IL-2, IP-10, NPY, VEGF-A, and vitamin D was observed in DED patients. These dysregulated tear factors showed significant associations with DED signs and symptoms. Conclusions: Altered tear fluid soluble factors with potential to modulate nociception exhibited a distinct association with ocular surface discomfort status, TBUT, STI, and cDCD. This implies a functional relationship between the various tear-soluble factors and dry eye pathogenesis, indicating new molecular targets for designing targeted therapies.