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Purpose: To assess retinopathy of prematurity (ROP) practice patterns during the coronavirus (COVID-19) pandemic., Methods: A survey on ROP practice patterns during the COVID-19 pandemic was sent to the American Academy of Ophthalmic Executives, the International Pediatric Ophthalmology and Strabismus Council members, and to various national societies on May 19, 2020. The survey closed on the 31st of June 2020., Results: Two hundred ninety-two ophthalmologists from 41 countries responded to the survey. Most replies originated in Asia (48%) and North America (38%). During the COVID-19 pandemic compared to the pre-COVID-19 period, respondents reported a reduction of 15% in the number of NICU inpatients and 19.8% of the ROP outpatients' follow-up visits. The number of ROP outpatients' follow-up visits and inpatients' exams was significantly greater in North America than in Asia (72.0% versus 37.2% and 87.8% versus 49.6%, respectively, P < 0.001). Only 14% of the ophthalmologists adopted new screening guidelines, and 7.2% reported changing their preferred treatment. In 50% of responders, laser photocoagulation was the preferred treatment. A significantly higher percentage of ophthalmologists reported using telemedicine during the pandemic, 29.8% (n = 85/285), and 15.6% (44/282) prior to the pandemic (χ2 = 15.51, p < 0.001)., Conclusions: During the COVID-19 pandemic, fewer ROP screening and follow-up visits were conducted on premature infants; these findings were especially prominent among physicians in Asia. Telemedicine usage increased during the pandemic. This study highlights the need to maintain screening protocols for ROP during pandemics. The utility of technological measures could enable this, along with adequate prevention of physical contact., (© 2024. The Author(s).)

Purpose: To determine the role of diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) in differentiating the inflammatory process and malignant lymphoma of the lacrimal gland., Methods: A retrospective analysis of all subjects who underwent lacrimal gland biopsy and magnetic resonance (MR) imaging with DWI sequences during a 10-year period at the Sheba Medical Center, Israel. The lacrimal glands' ADC values were documented bilaterally by blinded observers and correlated with the final histology verified diagnoses., Results: Twenty-eight patients were included, with 19 females (68%) with a mean ± SD age of 48.1 ± 25.7 years. The right orbit was involved in 14 cases (50%) and the left in 13 (46%); one patient (4%) had bilateral involvement. Seventeen cases (61%) had a final diagnosis of idiopathic inflammation or dacryoadenitis, and six cases (21%) were diagnosed with lymphoma. Additional diagnoses included pleomorphic adenoma in 3 (11%), adenoid cystic carcinoma, and solitary fibrous tumor. Lower mean ADC values were observed in the lymphoma versus inflammatory group (1.03 × 10-3 Vs. 1.45 × 10-3, P = 0.02)., Conclusion: Restricted diffusion on MR imaging can serve as a diagnostic tool in the differentiation between inflammatory processes of the lacrimal gland and lymphoma., (Copyright © 2024 Copyright: © 2024 Indian Journal of Ophthalmology.)

This study presents a comparative analysis of the publications of students participating in the Arrow Research Program in comparison to those of attending physicians and researchers at the same tertiary medical center in order to assess the impact of the Arrow Research Program on the students' scientific achievements. The study encompassed 90 Arrow Research Program students that were involved in the program at the Sheba Medical Center between 2019 and 2021. As a comparison group, 2082 attending physicians and researchers affiliated with the same center during the same period of time were considered. Publications were collected from the Web of Science Database, and the publication data parameters of each group were compared to assess scientific outcomes. The Arrow Research Program students collectively published 67 articles, and the 2082 physicians and researchers in the comparison group produced 4283 papers during the study timeframe. Similarly, the average impact factor of the journals in which the Arrow Research Program papers were published was 4.16 ± 2.68, similar to the average impact factor of 4.74 ± 6.26 in the comparison group (p = 0.388). Likewise, the average quartile of the journals in which the Arrow Research Program articles were published was 1.39 ± 0.59, which is similar to the comparison group's average quartile of 1.39 ± 0.63 (p = 0.997). In conclusion, the Arrow Research Program demonstrates its effectiveness in empowering young students to execute successful research projects. This study may help develop educational programs worldwide.

Purpose: To evaluate high-risk histopathological features (HRHF) following primary enucleation of eyes with retinoblastoma (RB) and assess the patient outcomes across continents., Methods: Retrospective study of 1426 primarily enucleated RB eyes from five continents., Results: Of all, 923 (65%) were from Asia (AS), 27 (2%) from Australia (AUS), 120 (8%) from Europe (EUR), 162 (11%) from North America (NA), and 194 (14%) from South America (SA). Based on the continent (AS vs. AUS vs. EUR vs. NA vs. SA), the histopathology features included massive choroidal invasion (31% vs. 7% vs. 13% vs. 19% vs. 27%, p=0.001), post-laminar optic nerve invasion (27% vs. 0% vs. 16% vs. 21% vs. 19%, p=0.0006), scleral infiltration (5% vs. 0% vs. 4% vs. 2% vs. 7%, p=0.13), and microscopic extrascleral infiltration (4% vs. 0% vs. <1% vs. <1% vs. 4%, p=0.68). Adjuvant chemotherapy with/without orbital radiotherapy was given in 761 (53%) patients. Based on Kaplan-Meier estimates in different continents (AS vs. AUS vs. EUR vs. NA vs. SA), the 6-year risk of orbital tumor recurrence was 5% vs. 2% vs. 0% vs. 0% vs. 12% (p<0.001), systemic metastasis was reported in 8% vs. 5% vs. 2% vs. 0% vs. 13% (p=0.001), and death in 10% vs. 3% vs. 2% vs. 0% vs. 11% (p<0.001) patients., Conclusion: There is a wide variation in the infiltrative histopathology features of RB across continents, resulting in variable outcomes. SA and AS had a higher risk of orbital tumor recurrence, systemic metastasis, and death compared to AUS, EUR, and NA., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Efforts to tap into the broad antimicrobial, insecticidal, and antioxidant activities of essential oils (EOs) are limited due to their strong odor and susceptibility to light and oxidation. Encapsulation of EOs and subsequent drying overcome these limitations and extend their applications. This study characterized freeze-dried (lyophilized) emulsions of eugenol (EU) and thymol (TY) EOs, encapsulated by chemically unmodified cellulose, a sustainable and low-cost resource. High-resolution scanning electron microscopy showed successful lyophilization. While the observed "flake-like" structure of the powders differed significantly from that of the emulsified microcapsules, useful properties were retained. Fourier transform infrared spectroscopy confirmed the presence of EOs in their corresponding powders and thermo-gravimetric analysis demonstrated high encapsulation efficiency (87-88%), improved thermal stability and resistance to evaporation, and slow EO release rates in comparison to their free forms. The lightweight and low-cost cellulose encapsulation, together with the results showing retained properties of the dried powder, enable the use of EOs in applications requiring high temperatures, such as EO incorporation into polymer films, that can be used to protect agricultural crops from microbial infections.

Idiopathic intracranial hypertension (IIH) may result in optic nerve fiber loss and even atrophy. The timing of the optical coherence tomography (OCT) indices reaching the lowest point (nadir) and the factors that predict the patient's anatomical outcome are not known. We aimed to determine the timing and the factors that affect nadir retinal nerve fiber layer (RNFL) thickness. The medical records of 99 IIH patients who were treated from December 2009 to January 2020 were retrospectively reviewed. The mean RNFL thickness at presentation was 263.5 ± 106.4 µm. The mean time to nadir was 7.9 ± 6.3 months. The average RNFL and ganglion cell complex (GCC) thickness at the nadir were 92.6 ± 14.5 µm (47% showed thinning) and 77.9 ± 27.8 µm (70% showed thinning), respectively. The Frisén disc edema stage and average RNFL thickness at baseline correlated with a longer time to nadir, (r = 0.28 P = 0.003 and r = 0.24, P = 0.012, respectively). The nadir average RNFL thickness and the nadir average GCC thickness (r = 0.32, P = 0.001, r = 0.29, P = 0.002, respectively) correlated with the baseline visual field mean deviation. The final anatomical outcome of IIH episodes in this study resulted in RNFL and GCC thinning. The time to RNFL nadir and its values correlated with IIH severity at presentation., (© 2024. The Author(s).)

Objective: To determine the effect of perinatal and neonatal risk factors on retinopathy of prematurity (ROP) and to examine the association of fertility treatments on the risk for ROP in very low birth weight (VLBW) preterm twins., Methods: The population-based observational study consisted of VLBW twins born at 24-29 weeks gestational age (GA). Data from the Israel national database (1995-2020) were applied. Univariate and multivariable logistic regression using the General Estimating Equation were used for assessment of risk factors., Results: The study population comprised 4092 infants of whom 2374 (58%) were conceived following fertility treatments. ROP was diagnosed in 851 (20.8%) infants. The odds for ROP approximately doubled with each week decrease in GA: at 24 weeks, Odds Ratio (OR) 58.00 (95% confidence interval (CI) 31.83-105.68); 25 weeks, OR 25.88 (95% CI 16.76-39.96); 26 weeks, OR 12.69 (95% CI 8.84-18.22) compared to 29 weeks GA. Each decrease in one birthweight z-score was associated with 1.82-fold increased risk for ROP (OR, 1.82, 95% CI 1.59-2.08). Infertility treatments were not associated with ROP. Neonatal morbidities significantly associated with ROP were surgical necrotizing enterocolitis (NEC) (OR, 2.04, 95% CI 1.31-3.19); surgically treated patent ductus arteriosus (PDA) (OR, 1.63, 95% CI 1.12-2.37); sepsis (OR, 1.43, 95% CI 1.20-1.71) and bronchopulmonary dysplasia (OR, 1.52, 95% CI 1.22-1.90)., Conclusion: Among preterm VLBW twins, poor intrauterine growth and surgical interventions for NEC and PDA were associated with high odds for ROP. This study does not support an association of fertility treatments with increased risk for ROP., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To investigate the effects of pseudophakic cystoid macular edema (PCME) on retinal nerve fiber layer (RNFL) thickness before and after treatment using optical coherence tomography (OCT)., Methods: A retrospective, observational study of consecutive patients diagnosed with PCME after cataract surgery. Patients underwent macular and RNFL OCT imaging at time of diagnosis and during follow up. OCT was performed for both the study eye and the contralateral healthy eye which served as control. All patients were followed for a period of at least 6 months., Results: Overall, 40 eyes of 40 patients with a mean age of 71.1 ± 8.1 years of which 45% (n = 18) were of male gender were included in this study. At presentation, the central thickness in the PCME eye was significantly higher than in the contralateral eye (515.7 ± 127.9μm versus 238.1 ± 41.8μm, p < 0.001). Similarly, all macular measurements were significantly higher in the PCME eye compared to the contralateral eye (p < 0.001 for all). In terms of RNFL measurements, the PCME eyes had greater global (p < 0.001), superonasal (p = 0.001) and superotemporal (p = 0.005) thickness values. PCME eyes demonstrated a significant decrease in thickness for all macular and RNFL parameters following resolution of CME (p < 0.05 for all)., Conclusions: PCME patients presents with greater global, superotemporal and superonasal RNFL thickness in comparison to the other healthy eye. After resolution of PCME, there is significant thinning of RNFL. Peripapillary RNFL thickness may serve as an additional parameter for diagnosis and follow-up of PCME., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Mast cells (MCs) are immune cells that play roles in both normal and abnormal processes. They have been linked to tumor progression in several types of cancer, including non-small cell lung cancer (NSCLC). However, the exact role of MCs in NSCLC is still unclear. Some studies have shown that the presence of a large number of MCs is associated with poor prognosis, while others have suggested that MCs have protective effects. To better understand the role of MCs in NSCLC, we aimed to identify the initial mechanisms underlying the communication between MCs and lung cancer cells. Here, we recapitulated cell-to-cell contact by exposing MCs to membranes derived from lung cancer cells and confirming their activation, as evidenced by increased phosphorylation of the ERK and AKT kinases. Profiling of the microRNAs that were selectively enriched in the extracellular vesicles (EVs) released by the lung cancer-activated MCs revealed that they contained significantly increased amounts of miR-100-5p and miR-125b, two protumorigenic miRNAs. We explored the pathways regulated by these miRNAs via enrichment analysis using the KEGG database, demonstrating that these two miRNAs regulate p53 signaling, cancer pathways, and pathways associated with apoptosis and the cell cycle., (© 2023. The Author(s).)

Purpose: To provide real-life data on azole treatment outcomes and the role of surgery in the current management of invasive fungal rhinosinusitis complicated by orbitocranial fungal infection (OCFI)., Methods: Data was collected retrospectively from a chart review from four participating centers and a systematic literature review. The study group included patients with OCFI treated with azole antifungals. The control cases were treated with other antifungal agents. The cranial and orbital involvement degree was staged based on the imaging. The extent of the surgical resection was also classified to allow for inter-group comparison., Results: There were 125 patients in the azole-treated group and 153 in the control group. Among the patients with OCFI cranial extension, 23% were operated on in the azole-treated group and 18% in the control group. However, meninges and brain resection were performed only in the controls (11% of patients) and never in the azole antifungals group. Orbital involvement required surgery in 26% of azole-treated cases and 39% of controls. Despite a more aggressive cranial involvement, azole-treated patients' mortality was significantly lower than in controls, with an OCFI-specific mortality rate of 21% vs. 52%. A similar, though not statistically significant, trend was found for the extent of the orbital disease and surgery., Conclusion: Despite less aggressive surgical intervention for cranial involvement, OCFI patients treated with azoles had a higher survival rate. This finding suggests we may improve morbidity with a more conservative surgical approach in conjunction with azole treatment. The same trend is emerging for orbital involvement.

Purpose: To compare the anatomical and functional outcomes of fovea-on, fovea-off, and fovea-split rhegmatogenous retinal detachment (RRD)., Methods: Retrospective case series of consecutive patients diagnosed with RRD and treated with only pars plana vitrectomy (PPV). Preoperative and postoperative optical coherence tomography (OCT) and functional outcomes were obtained prior to and 6 months after surgery. RRD extending to the edge of the fovea on OCT was termed fovea-split RRD., Results: A total of 152 eyes were included, out of which 89 eyes presented with a fovea-off, 36 with a fovea-on, and 27 with a fovea-split RRD. The mean visual acuity (VA) preoperatively was 1.32 ± 0.58 logMAR (20/400 equivalent on Snellen chart), 0.19 ± 0.20 (20/30), and 0.71 ± 0.56 (20/100) for the fovea-off, fovea-on, and fovea-split groups, respectively (p < 0.001). The mean VA at 6 months of follow-up significantly improved for the fovea-split and fovea-off groups to 0.54 ± 0.79 (20/70) (p < 0.001) and 0.45 ± 0.29 (20/50) (p = 0.01), respectively, and remained stable for the fovea-on group 0.24 ± 0.20 (20/30) (p = 0.25). Differences in alterations of the outer retinal layers (p < 0.001) and in the in-segment/outer-segment ratio (p < 0.001) were found between the groups., Conclusion: Eyes with fovea-split RRD had both a preoperative and a final postoperative VA between those of fovea-on and fovea-off eyes and different anatomical changes on OCT. This new entity warrants different patient expectations for postoperative outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: The authors declare that they have no conflicts of interest to disclose.

Purpose: The purpose of this study was to investigate the visual results and patient satisfaction after implantation of an extended depth-of-focus (EDOF) intraocular lens (IOL) in the second eye of patients implanted previously with a monofocal IOL in the first eye., Methods: The medical records and self-reported questionnaires from patients who were implanted with monofocal IOLs in the first eye and EDOF IOLs in the second eye (group A) and from patients implanted bilaterally with EDOF IOLs (group B) were compared for visual acuity (VA), spectacle independence, patient satisfaction, and photic phenomena., Results: Group A (23 eyes of 23 patients) had similar distance uncorrected VA and intermediate uncorrected VA compared with group B (72 eyes of 36 patients) (0.03±0.05 vs. 0.04±0.16; P =0.136 and 0.660, respectively). There was a tendency toward a better near uncorrected VA in group A compared with group B (0.15±0.14 vs. 0.23±0.17; P =0.074). Patients' perception of their VA was similar between groups. Spectacle independence for distance vision was reported by 16/17 (94.1%) and 35/36 (97.2%) patients ( P =0.543), 13/17 (76.5%) and 32/36 (88.9%) patients ( P =0.252) for intermediate vision, and 4/17 (23.6%) and 22/36 (61.1%) patients for near vision ( P =0.011), in groups A and B, respectively. There was no difference in complaints of photic phenomena between groups., Conclusions: Patients previously implanted with a monofocal IOL in 1 eye who are interested in improving their spectacle independence can be considered for an EDOF IOL implantation in the second eye and may have similar results to those implanted bilaterally with EDOF IOLs., Competing Interests: E.I.A.: Hanita Lenses—Consultant. Biotechnology General (Israel) Ltd—Consultant. Vision Care Technologies—Research fee, options holder. APX Ophthalmology—Founder, CMO. IOPtima—Share holder. VisiDome—Founder, CMO. CorNeat—Share holder. G.K.: Hanita Lenses—Consultant. CorNeat—Consultant. Johnson and Johnson—Consultant. The remaining authors have no funding or conflicts of interest to declare., (Copyright © 2023 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Purpose: The main objective of the study is to investigate the prevalence of anxiety in patients with neovascular age-related macular degeneration (nAMD)., Methods: A retrospective cross-sectional study of 3 304 nAMD patients and 16 515 age- and gender-matched controls. The proportions of patients with anxiety were compared between the groups using univariate analyses and a multivariate logistic regression model. Proportion of anxiety in patients with nAMD was compared with the proportion of anxiety in controls, matched for age and gender. Data was obtained from the largest health maintenance organization in Israel (Clalit Health Services) with 4 200 000 members., Results: The mean age of patients was 79.7 years; 54.8% were females; Anxiety was more common in patients with nAMD (13.2%) compared to the control group (10.2%) (OR 1.3; 95%CI 1.2-1.5). Multivariate logistic regression analysis revealed a significant association between anxiety and nAMD (OR 1.3; 95% CI: 1.2-1.5), adjusted for age, gender, and socio-economic status., Conclusion: Our study demonstrated that anxiety is more common in patients with nAMD compared to a control group. Physicians treating patients with nAMD should be aware of this association, in order to provide appropriate care for the anxiety associated with nAMD.

Purpose: To provide a bibliographical-historical perspective and main interest in the field of myopia., Methods: In this bibliographic study, the Web of Science Database was searched from 1999 to 2018. Recorded parameters included journal name, impact factor, year and language, number of authors, type and origin, methodology, number of subjects, funding, and topics., Results: Epidemiological assessments were the leading type of article (28%), and half of the papers were prospective studies. The number of citations for multicenter studies was significantly higher ( P = 0.034). The articles were published in 27 journals, with the majority in Investigative Ophthalmology, Vision Sciences (28%), and Ophthalmology (26%). Etiology, signs and symptoms, and treatment equally encompassed the topics. Papers addressing etiology, specifically genetic and environmental factors ( P = 0.029), signs and symptoms ( P = 0.001), and prevention, specifically public awareness (47%, P = 0.005), received significantly more citations. Treatment to decrease myopia progression was a much more common topic (68%) than refractive surgery (32%). Optical treatment was the most popular modality (39%). Half of the publications came from 3 countries: the United States (US), Australia, and Singapore. The highest ranked and cited papers came from the US ( P = 0.028) and Singapore ( P = 0.028)., Conclusions: To our knowledge, this is the first report of the top-cited articles on myopia. There is a predominance of epidemiological assessments and multicenter studies originating from the US, Australia, and Singapore, assessing etiology, signs and symptoms, and prevention. These are more frequently cited, emphasizing the great interest in mapping the increase in the incidence of myopia in different countries, public health awareness, and myopia control., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Rachel Shemesh et al.)

Objective: To review the academic benchmark of highly influential ophthalmologists listed in the ophthalmology '2020 Power List'., Methods: In this cross-sectional study, the academic profiles, achievements, and bibliometric profiles of all ophthalmologists listed in the 'Power List of 2020', regarded as the most influential figures in ophthalmology today, were analysed., Results: Ninety-five ophthalmologists were studied, after excluding 10 non-ophthalmologist figures that are also listed. Their mean age is 63 ± 11.7 years, with a strong male predominance (84.2%, n = 80 males, P < 0.001). All have a medical doctorate degree, and 31% (n = 29) have a Philosophy Doctor (PhD) degree. Fifty-three percent (n = 51) are graduates of medical schools in the United States (US). However, non-US ophthalmologists have a higher percentage of PhD degrees (41%, 18/44) vs. US ophthalmologists (22%, 11/51, P = 0.069), and also a longer duration of post-residency training (5.8 ± 3.1 vs. 1.8 ± 0.9 years, P < 0.001). The most common subspecialty was cataract and anterior segment surgery (42%, n = 40). The mean and standard deviation of the total number of papers published by ophthalmologists were 307.4 ± 226.3, with a mean citation record of 11,835.7 ± 13,330.5, and a mean h-index of 46.9 ± 27.9., Conclusions: The ophthalmologists listed on the 'Power List of 2020' are leaders with high accomplishments and an established interest in research evidenced by a high record of publications and an exceptional bibliometric profile. The list contains more US figures with a gender disparity, demonstrating a greater difficulty for international ophthalmologists, especially women, in achieving this high level of recognition., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To summarize the characteristics and trends of interest in retinoblastoma (Rb) in the last 50 years., Methods: The Web of Science Database was used to find all studies focused on Rb published from 1970 to 2018. The term "retinoblastoma" was used to search for the 100 most cited records., Results: The mean number of citations was 153.55 ± 88.9. The majority were from the United States (US) ( n = 68). Drs. Shields authored 38% of the papers. The number of citations per year was positively correlated with the number of authors, r = 0.26 ( p = 0.008). The number of patients was significantly associated with the number of citations per year ( p = 0.012). Although papers on radiotherapy were the most common, publications about intra-arterial chemotherapy (IAC) were associated with 88.3% more citations per year ( p = 0.031) and papers on intravenous chemotherapy (IVC) were associated with 40.3% more citations per year ( p = 0.04). Review and meta-analysis studies had a higher median of citations (10.5) than interventional (6.4) or observational (5.2) studies., Conclusions: This study compiles a comprehensive analysis of the most-cited articles on Rb. Studies with a higher number of citations per year were associated with IAC, which emphasizes the significance of the advances in Rb treatments that allow for the saving of eyes and vision as well as lives. Review studies had more citations than observational or interventional studies. More citations were associated with a larger number of authors or more reported patients per paper. These findings highlight the importance of collaborations to achieve relevant, high-quality research of Rb.

Objective: The transnasal endoscopic approach may provide better visualisation and a safer approach to the orbital apex. This study presents a case series of orbital apex lesions managed by this approach., Method: This study was an eight-year retrospective analysis of seven patients who were operated on for orbital apex lesions in two tertiary medical centres., Results: Complete tumour removal was performed in three patients and partial removal was performed in four patients. Visual acuity improved in three patients, remained stable in one patient and decreased in the other two patients. The visual field improved in four patients and did not change in two patients. Complications included worse vision and visual fields in 28.6 per cent of patients and late enophthalmos (of -1.25 ± 4.6 mm) in 2 patients., Conclusion: The transnasal approach to orbital apex lesions in selected cases may provide a rational alternative to transorbital surgery. Complete tumour removal should be weighed against the risk of damage to the optic nerve.

Background: The prevalence of myopia keeps increasing during the COVID-19 pandemic. We aimed to map the worldwide treatment preferences of ophthalmologists managing myopia control during the first wave of the pandemic., Methods: An online questionnaire inquiring about pharmacological and optical treatment patterns during the first half of 2020 was sent to pediatric ophthalmology as well as general ophthalmology memberships worldwide. The results among pediatric ophthalmologists were compared to a previous study we performed before the pandemic., Results: A total of 2269 respondents from 94 countries were included. Most respondents were pediatric ophthalmologists (64.6%), followed by ophthalmologists from other subspecialties (32.3%). The preferred modality for all geographical regions was a combination therapy of pharmacological and optical treatments. When evaluated independently, the pharmacological treatment was more popular than the optical treatment in most regions other than East Asia (P < 0.001). Compared to a pre-pandemic questionnaire, the participation of pediatric ophthalmologists affiliated with non-university hospitals increased. Additionally, the prevalence of respondents utilizing either any type of pharmacological treatment and those that using only evidence-based treatments increased globally. Although a decline in the use of optical treatment was evident worldwide, the use of evidence-based optical treatments increased., Conclusion: Ophthalmologists around the world preferred a combination therapy of pharmacological and optical treatments. More pediatric ophthalmologists treated myopia progression and preferred a better evidence-based approach to control myopia. These trends reflect a positive response and more awareness of the rising prevalence of myopia due to the increased burden of myopia imposed by the COVID-19 pandemic., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Essential oils (EOs) are volatile natural organic compounds, which possess pesticidal properties. However, they are vulnerable to heat and light, limiting their range of applications. Encapsulation of EOs is a useful approach to overcome some of these limitations. In this study, a novel emulsification technique is utilized for encapsulation of thymol (TY) and eugenol (EU) (EOs) within microcapsules with an unmodified cellulose shell. Use of low cost materials and processes can be beneficial in agricultural applications. In the encapsulation process, unmodified cellulose was dissolved in 7% aqueous NaOH at low temperature, regenerated to form a dispersion of cellulose hydrogels, which was rigorously mixed with the EOs by mechanical mixing followed by high-pressure homogenization (HPH). Cellulose:EO ratios of 1:1 and 1:8 utilizing homogenization pressures of 5000, 10,000 and 20,000 psi applied in a microfluidizer were studied. Light microscopy, high-resolution cryogenic scanning electron microscopy (cryo-SEM) and Fourier transform infrared spectroscopy (FTIR) revealed successful fabrication of EO-loaded capsules in size range of 1 to ~8 µm. Stability analyses showed highly stabilized oil in water (O/W) emulsions with instability index close to 0. The emulsions exhibited anti-mold activity in post-harvest alfalfa plants, with potency affected by the cellulose:EO ratio as well as the EO type; TY showed the highest anti-mold activity. Taken together, this study showed potential for anti-fungal activity of cellulose-encapsulated EOs in post-harvest hay.

This paper presents compression molding of peptide assemblies with low-density polyethylene (LDPE) for the robust production of antimicrobial polymeric films. These films show a significant reduction of colony-forming units and plaque-forming units. Moreover, they significantly inhibited the growth of three different fungi. These innovative active polymeric films can potentially be applied for medical device wrapping, food packaging, and agriculture applications.

Purpose: To characterize ocular surface temperature (OST) in healthy eyes and its association with systemic risk factors of cardiovascular and ischemic heart disease., Methods: This prospective cross-sectional study included consenting subjects who were examined at the Institute for Medical Screening in Sheba Medical Center. A Therm-App™ thermal imaging camera (Opgal LTD, Israel) was used for OST acquisition, and the mean OST of the medial canthal, lateral canthal, and central cornea regions were measured. Room and body temperatures were also recorded. Past medical and ocular history as well as data from various clinical examinations performed at the same visit were obtained., Results: Thermographic images were obtained from 186 subjects, 150 of which were included in the final analysis. OST was significantly higher in the medial canthal, central cornea, and lateral canthal regions in people with a history of ischemic heart disease ( p = 0.02, p = 0.02, and p = 0.03, respectively). There were no significant OST differences (ANOVA test) associated with the presence of hypertension, diabetes mellitus, or active smoking status., Conclusions: OST correlated positively with the presence of ischemic heart disease. This correlation, its pathophysiological base, and its clinical application warrants further investigation.

Objective: The role of bilateral bone conduction amplification in patients with bilateral conductive hearing loss is unclear because cranial attenuation is usually considered negligible, and both cochleae can be stimulated with similar efficacy by each device. The aim of the study was to determine if bilateral bone-conduction hearing aids can improve hearing in noise in a homogeneous group of normal-hearing subjects with bilateral pseudo-conductive hearing loss., Study Design: Prospective, comparative., Setting: Department of Communication Sciences and Disorders in University of Haifa, Israel., Subjects: Department of Communication Sciences and Disorders in University of Haifa, Israel., Interventions: Induction of bilateral pseudo-conductive hearing loss of more than 35 dB using earplugs and earmuffs., Main Outcome Measures: Hearing quality on blinded comparison of unilateral versus bilateral amplification with bone-conduction hearing aids under different locations of noise., Results: Unilateral and bilateral amplification had similar efficacy when both signal and noise were presented from the front. However, bilateral amplification was significantly better when signals were presented from the front and noise was presented from both sides (SNR -10: 92% vs. 84%, p = 0.001; SNR -15: 84% vs. 78%, p = 0.005). Analysis of subject responses on blinded questionnaires revealed that 81% found hearing easier with bilateral amplification. Noise was reported to be more disturbing with unilateral amplification by 55% of the subjects and with bilateral amplification, by 9%., Conclusions: Bilateral amplification with bone conduction devices can improve understanding in noise in the binaural squelch setting. Subjective improvements with bilateral bone-conduction aids included better sound quality and reduced noise disturbance. These findings are consistent with the binaural mechanism of spectral release from masking.

Purpose: Delayed sinonasal complications of radiation therapy include choanal stenosis, osteoradionecrosis, chronic sinusitis, and intranasal synechiae. Only sporadic cases on their surgical treatment have been reported, with equivocal results., Methods and Materials: We performed a prospective case series of all patients who had been surgically treated for delayed sinonasal complications of radiation therapy in our institution during the past 10 years. The inclusion criteria required ≥6 months of follow-up after surgery. The included patients were asked to complete a Sino-Nasal Outcome Test 16-item questionnaire preoperatively and 6 months after surgery., Results: Nine patients with history of radiation therapy for nasopharyngeal carcinoma were included in our series. In all cases, partial or complete subjective improvement occurred., Conclusions: In select cases, endoscopic sinus surgery could be of benefit in the treatment of delayed sinonasal complications of radiation therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Significant research has been directed toward the incorporation of bioactive plant extracts or essential oils (EOs) into polymers to endow the latter with antimicrobial functionality. EOs offer a unique combination of having broad antimicrobial activity from a natural source, generally recognized as safe (GRAS) recognition in the US, and a volatile nature. However, their volatility also presents a major challenge in their incorporation into polymers by conventional high-temperature-processing techniques. Herein, antimicrobial polypropylene (PP) cast films were produced by incorporating carvacrol (a model EO) or carvacrol, loaded into halloysite nanotubes (HNTs), via melt compounding. We studied the composition-structure-property relationships in these systems, focusing on the effect of carvacrol on the composition of the films, the PP crystalline phase and its morphology and the films' mechanical and antimicrobial properties. For the first time, molecular dynamics simulations were applied to reveal the complex interactions between the components of these carvacrol-containing systems. We show that strong molecular interactions between PP and carvacrol minimize the loss of this highly-volatile EO during high-temperature polymer processing, enabling semi-industrial scale production. The resulting films exhibit outstanding antimicrobial properties against model microorganisms ( Escherichia coli and Alternaria alternata ). The PP/(HNTs-carvacrol) nanocomposite films, containing the carvacrol-loaded HNTs, display a higher level of crystalline order, superior mechanical properties and prolonged release of carvacrol, in comparison to PP/carvacrol blends. These properties are ascribed to the role of HNTs in these nanocomposites and their effect on the PP matrix and retained carvacrol content., Competing Interests: The authors declare no conflict of interest.

Introduction: We recently showed that the psycho-stimulant norepinephrine-dopamine reuptake inhibitor methylphenidate (MP) prolonged cold pain threshold and tolerance in adults with attention-deficit hyperactivity disorder (ADHD)., Objectives: The objectives of the present study were to: (1) examine whether MP has antinociceptive properties in healthy men; (2) test MP's effects on responses to aversive auditory stimuli. The underlying aim was to determine whether MP exerts antinociceptive properties or more generalized, nonspecific attenuating effects on different aversive sensory modalities., Methods: This double-blind, crossover, randomized placebo-controlled study consisted of 2 sessions one week apart from each other. In each session, pain threshold (seconds) and tolerance (seconds) in response to painful cold stimulation were measured. Additionally, threshold (dB) and tolerance (seconds) to loud aversive auditory stimuli (500 Hz, 2000 Hz and white noise) were also tested prior to and 2 hours following the administration of a single dose of either 20 mg MP or an identical looking placebo., Results: Forty men, 26.1 ± 4.0 (mean ± SD) years were enrolled in the study. Wilcoxon signed-rank test analyses showed that MP, but not the placebo, produced a significant increase in cold pain threshold (from 4.1 ± 2.6 to 5.4 ± 3.1 seconds, P = 0.001 and from 4.5 ± 2.6 to 4.3 ± 2.7 seconds, P = 0.2, respectively) and tolerance (from 57.8 ± 54.0 to 73.8 ± 61.8 seconds, P = 0.001 and from 52.5 ± 53.7 sec to 57.0 ± 52.9 seconds, P = 0.1, respectively). No significant changes were found in any of the auditory parameters., Conclusion: These results suggest that MP has an effect on nociceptive pathways rather than a nonspecific, generalized attenuating effect on aversive sensory stimuli., Competing Interests: Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Objectives: Noise-induced hearing loss (NIHL) may result from occupational noise exposures and is considered as an 'Occupational Disease'; therefore, it is compensable. To verify the existence and severity of the work-related hearing loss, there is a need of an objective, reliable auditory measure in cases of arbitration of financial disputes to resolve any medicolegal aspects. The objective of the study was to compare between the ABR and ASSR for predicting the behavioural threshold in subjects with normal hearing or NIHL., Design: The study included 82 subjects regularly exposed to high levels of occupational noise, with normal hearing and NIHL. ABR to clicks and to tone bursts were recorded followed by multiple-frequency ASSR. Physiological and behavioural thresholds were compared for specific frequencies (1000, 2000 Hz) and average of high-frequency range (2000 and 4000 Hz). In addition, Pearson correlations and the specificity and sensitivity of each measure were also calculated using receiver operating characteristic (ROC) curves., Results: In the NIHL group, there was a significantly smaller difference between the behavioural threshold and click-ABR than the ASSR in high-frequency range. Pearson correlations were significantly higher for click-ABR. Analysis of specific frequencies yielded a smaller difference between behavioural and ASSR than tone-burst-ABR thresholds, with a slightly better correlation for ASSR than tone-burst-ABR. Higher sensitivity but lower specificity was suggested for ASSR than ABR., Conclusions: ASSR is associated with high-frequency specificity, shorter test sessions and good correlations with behavioural thresholds, making it a potentially better measure than ABR for predicting audiograms in subjects with NIHL. These findings have diagnostic implications, especially in cases of workers' compensation when subjects may be uncooperative., (© 2015 John Wiley & Sons Ltd.)

Background: Severe gram-negative bacterial infections and sepsis are major causes of morbidity and mortality. Dysregulated, excessive proinflammatory cytokine expression contributes to the pathogenesis of sepsis. A CD28 mimetic peptide (AB103; previously known as p2TA) that attenuates CD28 signaling and T-helper type 1 cytokine responses was tested for its ability to increase survival in models of polymicrobial infection and gram-negative sepsis., Methods: Mice received AB103, followed by an injection of Escherichia coli 0111:B4 lipopolysaccharide (LPS); underwent induction E. coli 018:K1 peritonitis induction, followed by treatment with AB103; or underwent cecal ligation and puncture (CLP), followed by treatment with AB103. The effects of AB103 on factors associated with and the lethality of challenge infections were analyzed., Results: AB103 strongly attenuated induction of tumor necrosis factor α and interleukin 6 (IL-6) by LPS in human peripheral blood mononuclear cells. Receipt of AB103 following intraperitoneal injection of LPS resulted in survival among 73% of CD1 mice (11 of 15), compared with 20% of controls (3 of 15). Suboptimal doses of antibiotic alone protected 20% of mice (1 of 5) from E. coli peritonitis, whereas 100% (15 of 15) survived when AB103 was added 4 hours following infection. Survival among mice treated with AB103 12 hours after CLP was 100% (8 of 8), compared with 17% among untreated mice (1 of 6). In addition, receipt of AB103 12 hours after CLP attenuated inflammatory cytokine responses and neutrophil influx into tissues and promoted bacterial clearance. Receipt of AB103 24 hours after CLP still protected 63% of mice (5 of 8)., Conclusions: Single-dose AB103 reduces mortality in experimental models of polymicrobial and gram-negative bacterial infection and sepsis, warranting further studies of this agent in clinical trials., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the role of otoacoustic emissions (OAEs) in the prediction of idiopathic sudden sensorineural hearing loss (ISSNHL) outcome., Study Design: Open-label prospective study., Setting: Tertiary referral medical center., Patients: Fifteen ISSNHL patients (age: 57.6 ± 16.2 years) were prospectively followed 7 days, 14 days, and 3 months post-presentation and the commencement of treatment., Intervention: Pure-tone audiometry, TEOAEs (Transient Evoked OAEs), and DPOAEs (Distortion Product OAEs) testing., Main Outcome Measures: The pure-tone threshold averages of the three most affected frequencies, detectability, and the signal-to-noise ratios (SNRs) values of the TEOAEs and DPOAEs were calculated. The main outcome measures were pure-tone hearing improvement, sensitivity, and specificity of the OAEs measures towards ISSNHL outcome., Results: Patients having detectable TEOAEs on the first follow-up evaluation had average hearing improvement of 62 ± 41% whereas those with no response improved only by 11 ± 15% (P < 0.001). For the DPOAEs hearing improvement, results were 71 ± 37% and 10 ± 14%, respectively (P < 0.001). The sensitivity of recordable TEOAEs on the seventh day of follow-up towards the prediction of significant hearing improvement reached 71% and the specificity 100%. For the DPOAEs, the corresponding values were 83% and 100%. Univariate analysis showed significant contribution for the variance in hearing improvement by both TEOAEs and DPOAEs and their interaction (P values of 0.043, 0.005, and 0.009, respectively)., Conclusion: The results suggest potential role of TEOAEs and DPOAEs evaluation in the early stage of treatment in the prediction of ISSNHL outcome.

Objectives: Currently available behavioral tools for the assessment of noise-induced hearing loss (NIHL) depend on the reliable cooperation of the subject. Furthermore, in workers' compensation cases, there is considerable financial gain to be had from exaggerating symptoms, such that accurate assessment of true hearing threshold levels is essential. An alternative objective physiologic tool for assessing NIHL is the auditory steady state response (ASSR) test, which combines frequency specificity with a high level of auditory stimulation, making it applicable for the evaluation of subjects with a moderate to severe deficit. The primary aim of the study was to assess the value of the multifrequency ASSR test in predicting the behavioral warble-tone audiogram in a large sample of young subjects with NIHL of varying severity or with normal hearing. The secondary goal was to assess suprathreshold ASSR growth functions in these two groups., Design: The study group included 157 subjects regularly exposed to high levels of occupational noise, who attended a university-associated audiological clinic for evaluation of NIHL from 2009 through 2011. All underwent a behavioral audiogram, and on the basis of the findings, were divided into those with NIHL (108 subjects, 216 ears) or normal hearing (49 subjects, 98 ears). The accuracy of the ASSR threshold estimations for frequencies of 500, 1000, 2000, and 4000 Hz was compared between groups, and the specificity and sensitivity of the ASSR test in differentiating ears with or without NIHL was calculated using receiver operating characteristic analysis. Linear regression analysis was used to formulate an equation to predict the behavioral warble-tone audiogram at each test frequency using ASSR thresholds. Multifrequency ASSR amplitude growth as a function of stimulus intensity was compared between the NIHL and normal-hearing groups for 1000 Hz and 4000 Hz carrier frequencies., Results: In the subjects with NIHL, ASSR thresholds to various frequencies were significantly and highly correlated with the behavioral warble-tone thresholds; Pearson correlation coefficients ranged from 0.6 to 0.8 over the four frequencies tested. Differences between thresholds ranged from 10 to 13 dB. The configuration of the ASSR waveforms closely approximated the behavioral audiogram. The sensitivity for screening hearing thresholds was 92%; by frequency, sensitivity ranged between 92.7 and 98.4%, but specificity was lower, especially at the low frequencies. ASSR accurately predicted moderate and severe NIHL. The mean ASSR growth amplitude to increasing stimulus level for 1000 and 4000 Hz was significantly steeper in the NIHL than in the normal-hearing group, with no significant difference between frequencies., Conclusions: The ASSR test has a high sensitivity to detect moderate to severe hearing loss in subjects with NIHL. Its use can facilitate the early identification of noise-exposed workers with NIHL. It may also serve an important medico-legal function in cases of workers' compensation. The ASSR test is not, by itself, an appropriate tool for hearing screening in the general population.

Staphylococcus aureus and group A Streptococcus pyogenes (GAS) express superantigen (SAg) exotoxin proteins capable of inducing lethal shock. To induce toxicity, SAgs must bind not only to the major histocompatibility complex II molecule of antigen-presenting cells and the variable β chain of the T-cell receptor but also to the dimer interface of the T-cell costimulatory receptor CD28. Here, we show that the CD28-mimetic peptide AB103 (originally designated "p2TA") protects mice from lethal challenge with streptococcal exotoxin A, as well as from lethal GAS bacterial infection in a murine model of necrotizing soft-tissue infection. Administration of a single dose of AB103 increased survival when given up to 5 hours after infection, reduced inflammatory cytokine expression and bacterial burden at the site of infection, and improved muscle inflammation in a dose-dependent manner, without compromising cellular and humoral immunity. Thus, AB103 merits further investigation as a potential therapeutic in SAg-mediated necrotizing soft-tissue infection.

Hypothesis: In the absence of patent cochlear windows, cochlear fluid inertia depends on the presence of a "third window" as a major component of the bone-conduction response., Background: Studies have shown conflicting results regarding changes in air and bone conduction whenever, the round window, oval window, or both windows were occluded., Method: The study was performed in a tertiary university-affiliated medical center. Auditory brain responses to clicks and 1-kHz tone bursts delivered by air and bone conduction were tested in 5 adult-size fat sand rats. The round window membrane (total, 7 ears) was sealed with Super Glue, and auditory brain response testing was repeated. Thereafter, the stapes footplate was firmly fixated, and auditory brain responses were recorded for a third time., Results: Round-window fixation induced a significant increase in air-conduction thresholds to clicks from 36.4 ± 0.9 to 69.3 ± 4.1 dB SPL, with no significant change in bone-conduction thresholds. When the stapes footplate was immobilized as well, air conduction increased by another 20 dB, on average, with no change in bone conduction. A similar deterioration was seen in response to 1 kHz stimulus., Conclusion: These findings support and complement earlier studies in the same animal model, suggesting that when the pressure outlet through the cochlear windows are abolished, still bone conduction displaces the cochlear partition probably because of a functioning "third window."

Objective: To assess sound field auditory thresholds of hearing-impaired adults by using auditory steady-state evoked responses (ASSRs)., Design: ASSRs were recorded to carrier frequencies of 500, 1000, 2000, and 4000 Hz, each uniquely modulated at a single frequency of 80-100 Hz. ASSR thresholds were compared to behavioral auditory thresholds., Study Sample: Twenty adults (11 male, age 35.6 years) with moderate-severe sensorineural hearing loss who had used hearing aids, and 10 normal-hearing subjects (mean age 22.4 years)., Results: For most frequencies, behavioral sound-field thresholds were slightly lower than ASSR thresholds in both aided and unaided conditions, with a significant correlation between them. Differences between ASSR and behavioral thresholds ranged between 516 dB in the unaided and between 5-16 dB in the aided condition. The ASSR amplitude growth function to 2000 Hz was steeper in both the aided and unaided conditions than in the normal-hearing group., Conclusions: Sound-field ASSRs can predict behavioral auditory thresholds in both the unaided and aided condition, as well as behavioral functional gains. The ASSR growth function for 2000 Hz is suggested to reflect an underlying mechanism of intensity encoding common to abnormal loudness perception frequently reported in cases of cochlear hearing loss.

Background: Experimental studies have shown that creating a window in the bony cover of the cochlea and vestibular parts of the inner ear, with preservation of membranous and middle-ear functions, induces an air-bone gap (ABG). This study sought to determine if a similar mechanism explains the ABG frequently observed in audiograms of cochlear implant candidates., Method: The study group included 47 candidates for a cochlear implant (94 ears) attending a university-affiliated tertiary medical center who had an ABG component in the audiogram in the absence of external or middle-ear abnormalities. Air- and bone-conduction thresholds on pure-tone audiometry were analyzed for 250 to 8,000 Hz and 250 to 4,000 Hz, respectively. In the 25 patients operated on during the study period, differences in the ABG and in cerebrospinal fluid (CSF) leak were compared between those with and without anomalies on computed tomography., Results: Imaging revealed an abnormal inner-ear structure in 46% of cases, mostly a large vestibular aqueduct, alone or combined with other cochlear or vestibular malformations. ABG was evident over high and low frequencies and was significantly larger at low frequencies and in ears with structural anomalies. A high rate of CSF leak was observed in patients with an ABG and structural anomalies imaging as well as in those with an ABG and normal imaging findings., Conclusion: In cochlear implant candidates, the presence of a third window could cause an ABG because of stapes motion-induced shunting of acoustic energy outside the cochlear duct in response to air-conducted stimuli while bone conduction is preserved.

Objective: Superior semicircular dehiscence syndrome is associated with vestibular symptoms and an air-bone gap component in the audiogram, apparently caused by the creation of a pathological bony "third window" in the superior semicircular canal. The aim of this study was to evaluate changes in auditory air- and bone-conduction thresholds to low- and high-frequency stimuli in an animal model of a bony fenestration facing the aerated mastoid cavity., Study Design: Anatomic, audiological., Setting: Tertiary university-affiliated medical center., Animals: A small hole was drilled in the bony apical portion of the superior semicircular canal facing the mastoid bulla/cavity, with preservation of the membranous labyrinth, in 5 adult-size fat sand rats., Main Outcome Measures: Auditory brain stem responses to clicks and 1-kHz tone bursts delivered by air and bone conduction before surgery, after opening the bulla, and after fenestration., Results: After fenestration, a significant air-bone gap was measured in response to clicks (mean ± standard deviation, 37 ± 5.8 dB) and bursts (mean ± standard deviation, 34 ± 14.5 dB). The gap was attributable solely to the significant deterioration in air-conduction thresholds, in the absence of a significant change in bone conduction thresholds. The pattern of auditory brain response changes closely resembled that reported for middle ear dysfunction, namely, an increase in absolute latency of waves I, III, and V without significant alterations in interpeak latency differences., Conclusions: Bony fenestration of the superior semicircular canal toward an aerated cavity in a rodent model mimics the auditory loss pattern of patients with superior semicircular dehiscence syndrome. The dehiscent membrane accounts for the auditory changes.

Pulmonary fibrosis is a progressive and lethal lung disease characterized by accumulation of extracellular matrix and loss of pulmonary function. No cure exists for this pathologic condition, and current treatments often fail to slow its progression or relieve its symptoms. Relaxin was previously shown to induce a matrix-degrading phenotype in human lung fibroblasts in vitro and to inhibit pulmonary fibrosis in vivo. A novel peptide that targets the relaxin RXFP1/LGR7 receptor was recently identified using our computational platform designed to predict novel G protein-coupled receptor peptide agonists. In this study, we examined the antifibrotic properties of this novel peptide, designated CGEN25009, in human cell-based assays and in a murine model of bleomycin-induced pulmonary fibrosis. Similar to relaxin, CGEN25009 was found to have an inhibitory effect on transforming growth factor-β1-induced collagen deposition in human dermal fibroblasts and to enhance MMP-2 expression. The peptide's biological activity was also similar to relaxin in generating cellular stimulation of cAMP, cGMP, and NO in the THP-1 human cell line. In vivo, 2-week administration of CGEN25009 in a preventive or therapeutic mode (i.e., concurrently with or 7 days after bleomycin treatment, respectively) caused a significant reduction in lung inflammation and injury and ameliorated adverse airway remodeling and peribronchial fibrosis. The results of this study indicate that CGEN25009 displays antifibrotic and anti-inflammatory properties and may offer a new therapeutic option for the treatment of pulmonary fibrosis.

It is well established that the vast majority of proteins of all taxonomical groups and species are initiated by an AUG codon, translated into the amino acid methionine (Met). Many attempts were made to evaluate the importance of the sequences surrounding the initiation codon, mostly focusing on the RNA sequence. However, the role and importance of the amino acids following the initiating Met residue were rarely investigated, mostly in bacteria and fungi. Herein, we computationally examined the protein sequences of all major taxonomical groups represented in the Swiss-Prot database, and evaluated the preference of each group to specific amino acids at the positions directly following the initial Met. The results indicate that there is a species-specific preference for the second amino acid of the majority of protein sequences. Interestingly, the preference for a certain amino acid at the second position changes throughout evolution from lysine in prokaryotes, through serine in lower eukaryotes, to alanine in higher plants and animals., (Copyright © 2010 Beijing Genomics Institute. Published by Elsevier Ltd. All rights reserved.)