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Rahul K Reddy,1 Maziar Lalezary,1 Stephen J Kim,1 Jeffrey A Kammer,1 Rachel W Kuchtey,1 Edward F Cherney,1 Franco M Recchia,2 Karen M Joos,1 Anita Agarwal,1 Janice C Law11Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, TN, USA; 2Tennessee Retina, PC, Nashville, TN, USABackground: The purpose of this paper is to report the 3-month findings of the Prospective Retinal and Optic Nerve Vitrectomy Evaluation (PROVE) study.Methods: Eighty eyes of 40 participants undergoing vitrectomy were enrolled. Participants underwent baseline evaluation of the study (surgical) and fellow (control) eye that included: intraocular pressure, central corneal thickness, gonioscopy, cup-to-disc ratio measurement, color fundus and optic disc photography, automated perimetry, and optical coherence tomography of the macula and optic nerve. Evaluation was repeated at 3 months. Main outcome measures were changes in macula and retinal nerve fiber layer (RNFL) thickness and intraocular pressure.Results: All participants completed follow-up. Mean cup-to-disc ratio of study and fellow eyes at baseline was 0.43 ± 0.2 and 0.46 ± 0.2, respectively, and 13% of participants had undiagnosed narrow angles. There was no significant change in intraocular pressure, cup-to-disc ratio, or pattern standard deviation in study eyes compared with baseline or fellow eyes at 3 months. Vision improved in all study eyes at 3 months compared with baseline (P = 0.013), but remained significantly worse than fellow eyes (P < 0.001). Central subfield and temporal peripapillary RNFL thickness were significantly greater in eyes with epiretinal membrane (P < 0.05), and resolution after surgery correlated with visual improvement (P < 0.05).Conclusion: The 3-month results do not indicate any increased risk for open-angle glaucoma but suggest that a relatively high percentage of eyes may be at risk of angle closure glaucoma. Temporal RNFL thickness and central subfield were increased in eyes with epiretinal membrane, and resolution correlated with degree of visual recovery.Keywords: vitrectomy, open-angle glaucoma, intraocular pressure, epiretinal membrane, macular hole

Quaternary ammonium compounds (QACs) are widely detected in the aquatic environment due to their extensive use in a wide array of antibacterial products during the pandemic. In the current study, UV/monochloramine (UV/NH 2 Cl) was used to degrade three typical QACs, namely benzalkonium compounds (BACs), dialkyl dimethyl ammonium compounds (DADMACs), and alkyl trimethyl ammonium compounds (ATMACs). This process achieved high efficiency in removing BACs from water samples. The transformation products of QACs treated with UV/NH 2 Cl were identified and characterized using a high-resolution mass spectrometer, and transformation pathways were proposed. The formation of N-nitroso-N-methyl-N-alkylamines (NMAs) and N-nitrosodimethylamine (NDMA) were observed during QAC degradation. The molar formation yield of NDMA from C 12 -BAC was 0.04 %, while yields of NMAs reached 1.05 %. The ecotoxicity of NMAs derived from QACs was predicted using ECOSAR software. The increased toxicity could be attributed to the formation of NMAs with longer alkyl chains; these NMAs, exhibited a one order of magnitude increase in toxicity compared to their parent QACs. This study provides evidence that QACs are the specific and significant precursors of NMAs. Greater attention should be given to NMA formation and its potential threat to the ecosystem, including humans., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Manganese oxide (MnO 2 ) is one of the most abundant metal oxides, and it is renowned for its ability to degrade various phenolic micropollutants. However, under MnO 2 -mediated transformation, BP-3 transforms into 12 different radical-coupled transformation products (TPs) out of 15 identified TPs. These radical-coupled TPs are reported with adverse environmental impacts. This study explored the effects of MnO 2 on organic UV filter mixtures and different water constituents (i.e., bicarbonate ion (HCO 3 - ), humic acid (HA) and halide ions) in terms of degradation efficiency and transformation chemistry. When a mixture of benzophenone-3 (BP-3) and avobenzone (AVO) underwent transformation by MnO 2 , hybrid radical-coupled TPs derived from both organic UV filters were generated. These hybrid radical-coupled TPs were evaluated by an in silico prediction tool and Vibrio fischeri bioluminescence inhibition assay (VFBIA). Results showed that these TPs were potentially toxic to aquatic organisms, even more so than their parent compounds. The higher the concentration of HCO 3 - , HA, chloride ion (Cl - ) and bromide ion (Br - ), the greater the reduction in the efficiencies of degrading BP-3 and AVO. Contrastingly, in the presence of iodide ion (I - ), degradation efficiencies of BP-3 and AVO were enhanced; however, iodinated TPs and iodinated radical-coupled TPs were formed, with questionable toxicity. This study has revealed the environmental risks of hybrid radical-coupled TPs, iodinated TPs and iodinated radical-coupled TPs when the organic UV filters BP-3 and AVO are transformed by MnO 2 ., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the demographic, educational, and scholarly characteristics of Association of University Professors of Ophthalmology-accredited vitreoretinal surgery fellowship program directors in the United States and Canada. Methods: Demographic, educational, and scholarly profiles of identified program directors were collated from online public resources. Characteristics were compared by sex, program size, ranking, and affiliation. Results: Eighty-one program directors (mean age [±SD] 54.7 ± 11.0 years) from 78 fellowship programs were identified. The minority were women (14.8%), who were on average 6 years younger than their male counterparts ( P  = .07). The majority of program directors had an academic affiliation (90.1%), most commonly professor (54.8%). The mean h-index, 5-year h-index, and m-quotient were 20.9 ± 14.9, 5.9 ± 4.4, and 0.82 ± 0.42, respectively. Compared with their counterparts, program directors of both "top 10" and large programs published more manuscripts ( P  < .05), accrued more citations ( P  < .05), and had a higher h-index ( P  < .05). Fellowship programs with female program directors had a significantly larger proportion of female retina faculty ( P  = .002). Conclusions: The backgrounds of vitreoretinal surgery program directors are diverse. However, women remain underrepresented in this position, highlighting an area with the potential for greater equity in ophthalmology., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Purpose: To investigate attitudes, priorities, and behaviors of ophthalmologists in salary negotiations., Design: Cross-sectional study., Methods: A Qualtrics survey was disseminated to U.S.-based practicing ophthalmologists between November 1, 2021 and March 31, 2022 and assessed attitudes, behaviors, and priorities surrounding salary negotiation during the respondents' first negotiation as a practicing physician and currently. Optional case-based scenarios were also included., Results: Of 424 respondents, 155 (36.5%) identified as male (M) and 269 (63.3%) identified as female (F). Men were more likely to negotiate salary for their first position as an independent ophthalmologist (M 78.3%, F 68.2%; P = .04). Respondents of both genders assessed their success similarly; 85.0% of men and 75.7% of women (P = .07) felt that their negotiation was very successful or somewhat successful. Women were more likely to select "flexibility in clinic/OR schedule for personal commitments" as a priority during salary negation for their first position (M 14.8%, F 23.1%; P = .04). Women ophthalmologists reported feeling more uncomfortable (M 36.1%, F 49.1%; P = .01), intimidated (M 20.0%, F 43.5%; P < .01), and were less likely to feel well-trained (M 24.5%, F 13.0%; P < .01). Most respondents never received formal training in negotiation., Conclusions: We found significant gender differences among ophthalmologists in attitudes, priorities and behaviors surrounding salary negotiation. There were low reported levels of formal negotiation training, which appears to disadvantage women more than men. These gender disparities suggest that incorporating education about negotiation skills and career development early in training may be impactful., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Children are highly vulnerable to environmental pollutants, especially endocrine-disrupting chemicals (EDCs). Previous research has linked both organic UV filters and phthalates exposure to adiposity and pubertal development in children. Nevertheless, the individual and collective effects of these chemicals on this population remain poorly understood. In this study, twelve organic UV filters and metabolites, six phthalate metabolites and two oxidative stress biomarkers were analyzed in a prospective follow-up study in Shanghai, China after a baseline study conducted 1.5 years earlier. Results revealed a positive association between exposure to individual organic UV filters or their mixture and levels of 8-OHdG (β ranging from 0.242 to 0.588, P < 0.05), a marker of oxidative DNA damage. BP-3 and OD-PABA made a greater contribution to oxidative DNA damage than other UV filters. Levels of 8-OHdG were also positively correlated with single phthalate metabolites and their mixture, with MnBP and MMP contributing the most. Stratified analysis found that these associations were mainly observed in girls. Our mixture analysis revealed cumulative risks of oxidative DNA damage when there was co-exposure to these two kinds of EDCs. These results underscore the importance of considering the risks associated with organic UV filters and the necessity of evaluating the effects of all these pollutants, both individually and in mixtures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Radical-coupled transformation products (TPs) have been identified as the byproducts of various transformation processes, including both natural attenuation and artificial treatments, of phenolic micropollutants. Benzophenone-3 (BP-3), an organic UV filter of emerging concern, has been previously reported with ubiquitous occurrence in the natural environment and water bodies. Current research has demonstrated how TPs are formed from BP-3 when it is treated with manganese oxide (MnO 2 ). The ecological and toxicological risks of these TPs have also been assessed. Polymerization of BP-3 through radical coupling was observed as the major pathway by which BP-3 is transformed when treated with MnO 2 . These radical-coupled TPs haven't shown further degradation after formation, suggesting their potential persistence once occurred in the environment. In silico experiments predict the radical-coupled TPs will increase in mobility, persistence and ecotoxicity. If true, they also represent an ever-increasing threat to the environment, ecosystems and, most immediately, aquatic living organisms. In addition, radical-coupled TPs produced by MnO 2 transformation of BP-3 have shown escalated estrogenic activity compared to the parent compound. This suggests that radical coupling amplifies the toxicological impacts of parent compound. These results provide strong evidence that radical-coupled TPs with larger molecular sizes are having potential adverse impacts on the ecosystem and biota., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

While it is widely accepted that 2-butene-1,4-dial (BDA) is a toxic metabolite with genotoxic and carcinogenic properties, little is known about BDA and its analogues (BDAs) formation during water disinfection. In this study, the effects of different chlorination conditions on the formation of BDAs from bisphenol and its analogues (BPs analogues) were evaluated. A transformation pathway for the formation of BDAs upon chlorination of BPs analogues is proposed. The time profile of the transformation of BPs analogues into BDAs reveals that the generation of dichlorohydroquinone, dichloro-hydroxybenzenesulfonic acid and 2,4,6-trichlorophenol, are significantly associated with the formation of BDAs in the disinfected water. Owing to the different bridging groups contributing to the electrophilicity of BPs analogues in varying degrees, the stronger the electrophilicity of BPs analogues the more BDAs are formed. In addition, the type of BDAs produced is also affected. Four types of BDAs were detected in this study, one of which was newly identified. This study confirms that BPs analogues are an important source of BDAs and provides more insights into the formation of BDAs during chlorination. Greater attention should be given to the formation of BDAs in chlorinated water and their potential threat to humans and the ecosystem., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Increasing rates of antibiotic resistance in endophthalmitis have been reported. This study examines outcomes of triple therapy with intravitreal vancomycin, ceftazidime, and moxifloxacin for endophthalmitis., Methods: Retrospective, consecutive series of all patients treated with abovementioned intravitreal antibiotics from January 2009 to June 2021. Percentages of eyes attaining greater than or equal to 20/200 and 20/50 Snellen visual acuities and adverse events were evaluated., Results: 112 eyes met inclusion criteria. 63 of 112 eyes (56%) achieved a visual acuity of 20/200 during follow-up, with 39 (35%) returning to at least 20/50. In subgroup analysis, 23 of 24 (96%) eyes with post-cataract endophthalmitis obtained ≥ 20/200 acuity and 21 of 24 (88%) obtained ≥ 20/50 acuity during follow-up. There were no cases of macular infarction., Conclusions: Intravitreal moxifloxacin (160 µg/0.1 mL) was well tolerated as an adjunct to vancomycin and ceftazidime for bacterial endophthalmitis. Use of this novel combination offers several theoretical advantages compared to standard therapy with two antibiotics, including expanded gram-negative coverage and potential synergy, and may be particularly valuable in geographies where the local antibiogram supports empiric use. Further study is merited to verify the safety and efficacy profile., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs., (Copyright © 2023 by The American Association of Immunologists, Inc.)

The appropriate immunosurveillance tools are foundational for the creation of therapeutics, vaccines, and containment strategies when faced with outbreaks of novel pathogens. During the COVID-19 pandemic, there was an urgent need to rapidly assess immune memory following infection or vaccination. Although there have been attempts to standardize cellular assays more broadly, methods for measuring cell-mediated immunity remain variable across studies. Commonly used methods include ELISPOT, intracellular cytokine staining, activation-induced markers, cytokine secretion assays, and peptide-MHC tetramer staining. Although each assay offers unique and complementary information on the T cell response, there are challenges associated with standardizing these assays. The choice of assay can be driven by sample size, the need for high throughput, and the information sought. A combination of approaches may be optimal. This review describes the benefits and limitations of commonly used methods for assessing T cell immunity across SARS-CoV-2 studies., (Copyright © 2023 by The American Association of Immunologists, Inc.)

Objective  In medical school and residency training, there is little emphasis on the administrative and business aspects of running a clinical practice as either an employee or a business owner. However, by the first day of practice, young ophthalmologists need to have a basic understanding of the business of medicine to be successful in clinical practice and to avoid common pitfalls. Areas such as risk management, negotiation, financial health, lawsuits, marketing, coding, and professionalism are particularly important for practicing ophthalmologists to grasp. We instituted a formal practice management course to increase the early exposure of our trainees to the business aspects of ophthalmology. Methods  Ophthalmology trainees engaged in 11, 1-hour sessions over 3 weeks during a practice management course covering 10 of the most relevant business topics for early career ophthalmologists. A precourse needs assessment, and a postcourse satisfaction and outcomes survey were administered. Results  Of the 24 trainees who completed the presurvey, 96% of respondents had no previous training in contract negotiation, 88% lacked training in lawsuits, and 88% had no training in liability insurance. 96% had no inpatient coding education, and 88% had no outpatient coding training. Seventeen trainees completed the postsurvey, and statistically significant improvements in confidence ratings were found in all domains including coding, malpractice claims, and building a practice. 88% of trainees reported that the course improved their ability to code, and 100% agreed that the course improved their understanding of lawsuits, ability to negotiate a contract, and their understanding of the business of ophthalmology. Conclusion  A formal, targeted business of ophthalmology course improved the knowledge of trainees on essential business concepts. This course can serve as a model for other programs looking to meet this educational need., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Numerous agrochemicals, including pesticides and herbicides, are applied in modern agriculture, resulting in concerns for the ecosystem and human safety as humans are easily exposed to these compounds. Many agrochemicals, and their transformation products or metabolites, have shown toxicity in in vitro and in vivo studies. However, given the rapid development of novel agrochemicals, for many there is no information about their effects nor about metabolic transformations when ingested by humans. Tracing biomarkers may be the best method for assessing the impacts of agrochemicals. A combination of in vitro metabolism study and suspect screening of human samples (e.g., urine, blood) can be utilized to efficiently find biomarkers for agrochemical exposure. In the work reported here, we determined the in vitro metabolic profiling of six prioritized pesticides and synergists, namely boscalid, carbendazim, piperonyl butoxide, spiroxamine, dimethomorph and fludioxonil, in human liver microsomes. 17 major metabolites were structurally elucidated by high resolution mass spectrometry (HRMS). Major metabolic transformation processes (e.g., hydroxylation, demethylation and oxidation) were proposed for each pesticide. Individual in silico toxicity assessments showed that some metabolites had the same or even enhanced toxicity compared to parent compounds. Information about these metabolites obtained from HRMS was used for suspect screening in human activities related samples. Carbendazim and a metabolite of fludioxonil were identified in wastewater and laboratory urine samples, respectively. Our findings provide concrete evidence for the use of in vitro metabolites as biomarkers in biomonitoring studies of potential exposure to toxic chemicals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

BACKGROUNDLimited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).METHODSThis observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Ab and T cell responses to SARS-CoV-2, including neutralization against SARS-CoV-2 variants, were determined before and after 1 and 2 vaccine doses.RESULTSWe prospectively followed 150 subjects, 26 healthy controls, 9 patients with IMID on no treatment, 44 on anti-TNF, 16 on anti-TNF with methotrexate/azathioprine (MTX/AZA), 10 on anti-IL-23, 28 on anti-IL-12/23, 9 on anti-IL-17, and 8 on MTX/AZA. Ab and T cell responses to SARS-CoV-2 were detected in all participants, increasing from dose 1 to dose 2 and declining 3 months later, with greater attrition in patients with IMID compared with healthy controls. Ab levels and neutralization efficacy against variants of concern were substantially lower in anti-TNF-treated patients than in healthy controls and were undetectable against Omicron by 3 months after dose 2.CONCLUSIONSOur findings support the need for a third dose of the mRNA vaccine and for continued monitoring of immunity in these patient groups.FUNDINGFunded by a donation from Juan and Stefania Speck and by Canadian Institutes of Health (CIHR)/COVID-Immunity Task Force (CITF) grants VR-1 172711 and VS1-175545 (to THW and ACG), CIHR FDN-143250 (to THW), GA2-177716 (to VC, ACG, and THW), and GA1-177703 (to ACG) and the CIHR rapid response network to SARS-CoV-2 variants, CoVaRR-Net (to ACG).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces T cell, B cell, and Ab responses that are detected for several months in recovered individuals. Whether this response resembles a typical respiratory viral infection is a matter of debate. In this study, we followed T cell and Ab responses in 24 mainly nonhospitalized human subjects who had recovered from PCR-confirmed SARS-CoV-2 infection at two time points (median of 45 and 145 d after symptom onset). Ab responses were detected in 95% of subjects, with a strong correlation between plasma and salivary anti-spike (anti-S) and anti-receptor binding domain IgG, as well as a correlation between circulating T follicular helper cells and the SARS-CoV-2-specific IgG response. T cell responses to SARS-CoV-2 peptides were determined using intracellular cytokine staining, activation markers, proliferation, and cytokine secretion. All study subjects had a T cell response to at least one SARS-CoV-2 Ag based on at least one T cell assay. CD4 + responses were largely of the Th1 phenotype, but with a lower ratio of IFN-γ- to IL-2-producing cells and a lower frequency of CD8 + :CD4 + T cells than in influenza A virus (IAV)-specific memory responses within the same subjects. Analysis of secreted molecules also revealed a lower ratio of IFN-γ to IL-2 and an altered cytotoxic profile for SARS-CoV-2 S- and nucleocapsid-specific responses compared with IAV-specific responses. These data suggest that the memory T cell phenotype after a single infection with SARS-CoV-2 persists over time, with an altered cytokine and cytotoxicity profile compared with long-term memory to whole IAV within the same subjects., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Background Medical students are applying to dramatically more ophthalmology residency programs than in the past, causing an increased administrative burden for programs and financial harm to students. This study considers the background of this situation and looks at how a lack of transparency surrounding potential residency match filters contributes. Furthermore, this study raises several potential solutions to this lack of transparency that may increase the functionality of the ophthalmology residency match. Objective The purpose of this study was to determine the availability and consistency of potential ophthalmology residency match filters through training program websites and the American Medical Association's (AMA) Residency & Fellowship Database (FREIDA). Methods This study was a cross-sectional observational study of ophthalmology residency program websites and AMA's FREIDA database entries. For 119 ophthalmology residency programs, five potential filters were evaluated for both availability and consistency on individual residency websites and FREIDA. These filters were: (1) whether a program required a minimum United States Medical Licensing Examination (USMLE) Step 1 score; (2) minimum number of letters of recommendation required; 3) whether a minimum USMLE Step 2 score was required; (4) if the program accepts the Comprehensive Osteopathic Medical Licensing Examination (COMLEX) sequence in lieu of the USMLE; and (5) ability of the residency to sponsor a visa (J-1, H-1B, or F-1). Each program's website and FREIDA entry were independently evaluated by two authors to increase validity, with a third author brought in to break the tie in case of a disagreement. Results Only two ophthalmology residency programs had information about all five filters both available and consistent on their website and FREIDA. Inter-reviewer reliability was 92.5%. Conclusions Information about potential filters used in the ophthalmology residency match is neither publicly available nor consistent. This lack of transparency may contribute to the phenomenon of medical students applying to dramatically more ophthalmology residency programs. A standardized database of these filters is needed to increase transparency to applicants, which may reduce the expenses of medical students and the workload of program directors., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Markle et al.)

Objective: The purpose of this study is to investigate the amount of oral flora dispersion towards the ocular surface in relation to various face mask scenarios., Methods and Analysis: Thirty participants were recruited for this prospective cross-sectional study. Each participant was seated and instructed to hold a blood agar plate perpendicular to the bridge of their nose and facing downward. Participants then partook in three unique face mask scenarios: no face mask, surgical face mask and surgical face mask with tape securing the superior edge. During each scenario, participants were instructed to forcefully exhale for 5 s three times. The primary outcome measure was the number of colony-forming units (CFUs) grown on each face mask scenario-specific plate., Results: Thirty participants were recruited for the study, and a total of 90 chocolate agar plates were successfully incubated. The proportion of detecting any CFU was 6.67% (95% CI: 0.818% to 22.1%) for no mask scenario, 0% (95% CI: 0% to 11.6%) for mask scenario and 3.33% (95% CI: 0.0844% to 17.2%) for mask-taped scenario. The mean differences in proportion of detecting any CFU were 3.33% (95% CI: 0% to 10%, p=0.309) for no mask versus mask taped, 3.35% (95% CI: 0% to 10%, p=0.307) for mask taped versus mask and 6.68% (95% CI: 0% to 16.7%, p=0.142) for no mask versus mask., Conclusion: This study showed no difference in bacterial dispersion towards the ocular surface when comparing no face mask, a surgical face mask without tape or a surgical face mask with tape., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Transformation products (TPs) of micropollutants contaminating our water resources have become an emerging issue due to the potential threats they pose to environmental and human health. This study investigated the transformation chemistry, toxicity, physicochemical properties and environmental behavior resulting from photocatalytic transformation of organic UV filters as model micropollutants. 3-Benzylidene camphor (3-BC), 4-hydroxybenzophenone (4-HB) and octocrylene (OC) were effectively degraded by UV-A/TiO 2 treatment, with TPs identified and characterized with high resolution mass spectrometry. Nitrated-TPs were observed to be formed in the presence of nitrite and nitrate for 3-BC and 4-HB, suggesting that the transformation process could be altered by components in the water matrix. Vibrio fischeri bioluminescence inhibition assay revealed an increase in toxicity of TPs derived from photocatalytic treatment, with quantitative structure-activity relationship model (ECOSAR) predicted an enhanced toxicity of individual TPs' after transformation. Assessment of physicochemical properties and environmental behavior suggested that TPs as compared to parent organic UV filters, may represent even greater hazards due to their increased water solubility, persistence and mobility - in addition to retaining the parent organic UV filter's toxicity. The results provide important information relevant to the potential risks for the selected organic UV filters, and their corresponding transformation products., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

TRAF1 is a pro-survival adaptor molecule in TNFR superfamily (TNFRSF) signaling. TRAF1 is overexpressed in many B cell cancers including refractory chronic lymphocytic leukemia (CLL). Little has been done to assess the role of TRAF1 in human cancer. Here we show that the protein kinase C related kinase Protein Kinase N1 (PKN1) is required to protect TRAF1 from cIAP-mediated degradation during constitutive CD40 signaling in lymphoma. We show that the active phospho-Thr774 form of PKN1 is constitutively expressed in CLL but minimally detected in unstimulated healthy donor B cells. Through a screen of 700 kinase inhibitors, we identified two inhibitors, OTSSP167, and XL-228, that inhibited PKN1 in the nanomolar range and induced dose-dependent loss of TRAF1 in RAJI cells. OTSSP167 or XL-228 treatment of primary patient CLL samples led to a reduction in TRAF1, pNF-κB p65, pS6, pERK, Mcl-1 and Bcl-2 proteins, and induction of activated caspase-3. OTSSP167 synergized with venetoclax in inducing CLL death, correlating with loss of TRAF1, Mcl-1, and Bcl-2. Although correlative, these findings suggest the PKN1-TRAF1 signaling axis as a potential new target for CLL. These findings also suggest the use of the orally available inhibitor OTSSP167 in combination treatment with venetoclax for TRAF1 overexpressing CLL., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.)

The artificial sweetener Acesulfame (ACE) has been frequently detected in wastewater treatment plants (WWTPs) and is regarded as an emerging pollutant due to its low biodegradability. However, recent observations of ACE biodegradation in WWTPs have stimulated interest in the ACE-degrading bacteria and mineralization pathways. In this study, next-generation sequencing methods, Illumina and Nanopore sequencing, were combined to explore the ACE-degrading communities enriched from the activated sludge of six municipal wastewater treatment plants. Metagenomic investigations indicated that all enrichments were similarly dominated by the phyla Proteobacteria and Planctomycetes. Notably, at the species level, four metagenome-assembled genomes (MAGs) were shared by six enriched communities with considerable abundances, indicating that they may be responsible for ACE biodegradation in the enrichments. Besides, two ACE-degrading pure strains, affiliated to the genus Chelatococcus, were isolated from the enrichment. The genomic analysis showed that these two isolates were the new species that were genetically distinct from their relatives. Two type strains, Chelatococcus asaccharovorans DSM 6462 and Chelatococcus composti DSM 101465, could not degrade ACE, implying that the ACE-degrading capability was not shared among the different species in the genus Chelatococcus. The results of the degradation experiment showed that the two isolates could use ACE as the sole carbon source and mineralize ~90% of the total organic carbon. Three biotransformation products (TP96, TP180B, and TP182B) were demonstrated by UPLC-QTOF-MS. The results of this study provide valuable insights into ACE biodegradation and its biotransformation products., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: This work assesses the safety of resident-performed intravitreal injections by comparing the incidence of postinjection endophthalmitis associated with residents vs surgical retina attendings., Methods: In this retrospective noninferiority cohort study, the Current Procedural Technology code for an intravitreal injection was used to identify patients from July 1, 2015, to October 31, 2018, at a single-center Veterans Affairs hospital where patients receive intravitreal injections from attending vitreoretinal surgeons and residents. The medical record for each injection was reviewed for the training level of the proceduralist, indication, medication, and laterality. The main outcome was the incidence of postinjection endophthalmitis occurring within 30 days of an intravitreal injection, which was confirmed by at least 2 medical-record reviewers., Results: In this cohort of 593 patients, most were male (97.0%), and the average age was 70.3 years (±10.8 years). Of the 6934 injections given, 3877 (55.9%) were performed by residents and 3057 (44.1%) by attendings. Of the 5 cases of endophthalmitis identified, 3 were associated with a resident-performed injection in his or her fourth year of postgraduate training. The difference (0.012%; 95% CI, -0.168% to 0.169%) in the incidence of postinjection endophthalmitis between residents (0.077%) and attendings (0.065%) did not cross the predetermined noninferiority limit (0.200%)., Conclusions: At our teaching clinic, resident-performed injections were not associated with an elevated risk of endophthalmitis when compared with attending-performed injections. Under varying levels of supervision, residents appeared to demonstrate appropriate sterile injection technique., Competing Interests: Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To identify the role of gender and other factors in influencing ophthalmologists' compensation., Design: Cross-sectional study., Participants: U.S. practicing ophthalmologists., Methods: Between January and March 2020, an anonymous survey was sent to U.S. residency program directors and practicing ophthalmologists who recently completed residency training. Respondents who completed residency ≤ 10 years ago and responded to questions about gender, fellowship training, state of practice, and salary were included. Propensity score match (PSM) analysis was performed with age, academic residency, top residency, fellowship, state median wage, practice type, ethnicity, and number of workdays. Multivariate linear regression (MLR) analysis controlled for additional factors along with the aforementioned variables., Main Outcome Measures: Base starting salary with bonus (SWB) received in the first year of clinical position was the main outcome measure. A multiplier of 1.2 (20%) was added to the base salary to account for bonus., Results: Of 684 respondents, 384 (56% were female, 44% were male) from 68 programs were included. Female ophthalmologists received a mean initial SWB that was $33 139.80 less than that of their male colleagues (12.5%, P = 0.00). The PSM analysis showed an SWB difference of -$27 273.89 (10.3% gap, P = 0.0015). Additionally, SWB differences were calculated with the number of workdays substituted by operating room (OR) days (-$27 793.67 [10.5% gap, P = 0.0013]) and clinic days (-$23 597.57 [8.90% gap, P = 0.0064]) in separate PSM analyses. The SWB differences between genders were significant using MLR analyses, which also controlled for work, clinic, and OR days separately (-$22 261.49, $-18 604.65, and $-16 191.26, respectively; P = 0.017, P = 0.015, P = 0.002, respectively). Gender independently predicted income in all 3 analyses (P < 0.05). Although an association between gender and the attempt to negotiate was not detected, a greater portion of men subjectively reported success in negotiation (P = 0.03)., Conclusions: Female ophthalmologists earn significantly less than their male colleagues in the first year of clinical practice. Salary differences persist after controlling for demographic, educational, and practice type variables with MLR and PSM analyses. These income differences may lead to a substantial loss of accumulated earnings over an individual's career., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance  There is a lack of peer-reviewed literature on leadership development programs (LDP) in ophthalmology. Research into LDP demographics, outcomes, and methodology is needed. Objective  The aim of the study is to evaluate the extent to which LDPs targeting ophthalmologists meet the needs of emerging leaders. Design  The design type of the study is cross-sectional analysis. Setting  This study involves international setting. Participants  The participants involved were ophthalmologists at any career level. Methods  Routine internet search was used to identify LDPs targeting ophthalmologists. LDPs identified were categorized by the outcome data available into four levels based on prior literature. Participants were assessed using previously validated software for gender (Gender-API, 2020) and race or ethnicity (NamSor, 2020) Results  Nine programs were identified which were classified into LDP generations. The first LDP in ophthalmology was the American Academy of Ophthalmology (AAO) LDP, which served as the nidus for the formation of four multinational LDPs, together forming the Global LDP. These LDPs were similar in size and scope; program size ranging from nine to 30 participants; a length of 1 to 2 years; with similar curricular offerings; with funding primarily derived from cost-sharing with a nominating society. The second generation of ophthalmology LDPs in the United States has targeted female scientists or faculty (Women's LDP by ARVO) and academic ophthalmology leaders (Academic LDP by Association of University Professors of Ophthalmology). The AAO's LDP appears increasingly diverse with approximately 13% women at inception, gradually increasing from 40 to 65% women in the last 5 years ( n  = 389). There has also been a notable increase in ethnic diversity. Conclusion and Relevance  AAO LDP is the preeminent leadership training program for ophthalmologists, and it has influenced the creation of a new generation of LDP offerings. There remains a paucity of LDP evaluation metrics and reported outcomes. Newer iterations are successfully targeting academic leadership and attempting to address known disparities in gender and race or ethnicity. Further expansion of LDPs and related research can ensure equity and diversity in the pipeline., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Organic UV filters are compounds that absorb UV irradiation by their highly conjugated structure. With the developing consciousness over the last century of the skin damage UV radiation can cause, the demand for organic UV filters has risen, for use not only in sunscreens, but also in other personal care products. The massive production and usage of these organic UV filters has resulted in extensive release into the aquatic environment, and thereby making an important group of emerging contaminants. Considering the widespread occurrence of organic UV filters in not only ambient water, but also sediment, soil and even indoor dust, their threats towards the health of living organisms have been a subject of active investigation. In this review article, we present an overall review of existing knowledge on the risks of organic UV filters from the aspects of both environmental and human health impacts. As for the environment, some organic UV filters are proven to bioaccumulate in various kinds of aquatic organisms, and further to have adverse effects on different kinds of animal models. Toxicological studies including in vivo and in vitro studies are important and effective means to ascertain the effects and mechanisms of organic UV filters on both the ecosystem and humans. Subsequent concerns arise that these compounds will affect human health in the long term. This review concludes by suggesting future lines of research based on the remaining knowledge gaps., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

UV/monochloramine (UV/NH 2 Cl) is an emerging advanced oxidation process that can generate various reactive species like reactive chlorine species (RCS) and hydroxyl radicals for micropollutant removal. This study investigated the potential toxicity of transformation products resulting from UV/NH 2 Cl treatment of acesulfame (ACE), as an example of micropollutant, found in worldwide aquatic environment. Compared with UV photolysis and chloramination, the UV/NH 2 Cl process more effectively degraded ACE. The transformation products of ACE treated with the UV/NH 2 Cl process were identified and characterized with high resolution mass spectrometry. The formation of chlorinated-TPs indicated the role of RCS in UV/NH 2 Cl transformation even though UV photolysis was predominantly responsible for the ACE degradation. The Vibrio fischeri bioluminescence inhibition assay revealed a higher toxicity of TPs derived from UV/NH 2 Cl than from UV photolysis. The increased toxicity could be attributed to most of the generated chlorinated-TPs (Cl-TPs), in particular those halo-alcohols. The ECOSAR program predicts that halo-alcohol TPs are more toxic than their non-chlorinated analogues and other Cl-TPs. This study provides insight into the important role of reactive species in the micropollutants' transformation of UV/NH 2 Cl process. It further provides information relevant to the potential risk when applying the process for micropollutant removal in water treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There is a pressing need for an in-depth understanding of immunity to SARS-CoV-2. In this study, we investigated human T cell recall responses to fully glycosylated spike trimer, recombinant N protein, as well as to S, N, M, and E peptide pools in the early convalescent phase and compared them with influenza-specific memory responses from the same donors. All subjects showed SARS-CoV-2-specific T cell responses to at least one Ag. Both SARS-CoV-2-specific and influenza-specific CD4 + T cell responses were predominantly of the central memory phenotype; however SARS-CoV-2-specific CD4 + T cells exhibited a lower IFN-γ to TNF ratio compared with influenza-specific memory responses from the same donors, independent of disease severity. SARS-CoV-2-specific T cells were less multifunctional than influenza-specific T cells, particularly in severe cases, potentially suggesting exhaustion. Most SARS-CoV-2-convalescent subjects also produced IFN-γ in response to seasonal OC43 S protein. We observed granzyme B + /IFN-γ + , CD4 + , and CD8 + proliferative responses to peptide pools in most individuals, with CD4 + T cell responses predominating over CD8 + T cell responses. Peripheral T follicular helper (pTfh) responses to S or N strongly correlated with serum neutralization assays as well as receptor binding domain-specific IgA; however, the frequency of pTfh responses to SARS-CoV-2 was lower than the frequency of pTfh responses to influenza virus. Overall, T cell responses to SARS-CoV-2 are robust; however, CD4 + Th1 responses predominate over CD8 + T cell responses, have a more inflammatory profile, and have a weaker pTfh response than the response to influenza virus within the same donors, potentially contributing to COVID-19 disease., (Copyright © 2020 by The American Association of Immunologists, Inc.)

Recent studies have demonstrated that weathering modifies the physicochemical properties and sorption behavior of microplastics (MPs). However, little is known about the effects of such weathering on the simultaneous sorption by MPs of different organic pollutants in multi-solute systems. In this study, the role of cosolute properties in the formation of solute multilayers with a hydrophobic primary solute (4-MBC) on pristine and various weathered polystyrene MPs (PSMPs) was examined. Three weathered PSMPs were studied namely, UV-irradiated PS (UV-PS), microbially degraded PS (MD-NPS), and UV-irradiated PS with subsequent microbial degradation (MD-UV-PS). The weathered PSMPs generally exhibited higher degree of oxygenated functionalities with less surface hydrophobicity than pristine particles. Our findings showed that the formation of solute multilayers with hydrophobic cosolutes was drastically suppressed in UV-PS due to more severe competition at hydrophobic sorption sites. Nevertheless, hydrophilic cosolutes contributed to solute multilayer formation with 4-MBC on PSMPs after UV irradiation, probably due to the stronger sorption of hydrophilic compounds to the oxidized surfaces of these particles via enhanced H-bonding. Strikingly, the sorption of 4-MBC by MD-UV-PS was notably enhanced when hydrophobic cosolutes were present. The observed synergistic sorption indicates that adhered biofilms and/or organic matter on MD-UV-PS could sorb the hydrophobic cosolute molecules, and eventually promote sorption of 4-MBC. Our further toxicity tests revealed that such solute multilayers formed on PSMPs inhibited microalgal growth. These results suggest that the fate and biological effects of MP-mediated chemical exposure could be strongly affected by weathering processes and coexistence of multiple organic contaminants in natural environments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Human mononuclear phagocytes comprise specialized subsets of dendritic cells (DCs) and monocytes, but how these subsets individually regulate expression of the molecular signals involved in T cell costimulation is incompletely understood. Here, we used multiparameter flow cytometry and CITE-sequencing to investigate the cell type-specific responses of human peripheral blood DC and monocyte subsets to type I interferons (IFN-I), focusing on differential regulation of costimulatory molecules. We report that IFN-β drives the maturation of the recently identified human CD1c + CD5 - DC3 subset into cells with higher GITRL and lower CD86 expression compared with other conventional DC subsets. Transcriptomic analysis confirmed that DC3s have an intermediate phenotype between that of CD1c + CD5 + DC2s and CD14 + monocytes, characterized by high expression of MHCII, Fc receptors, and components of the phagocyte NADPH oxidase. IFN-β induced a shared core response in human DC and monocyte subsets as well as subset-specific responses, including differential expression of costimulatory molecules. Gene regulatory network analysis suggests that upon IFN-β stimulation NFKB1 drives DC3s to acquire a maturation program shared with DC2s. Accordingly, inhibition of NF-κB activation prevented the acquisition of a mature phenotype by DC3s upon IFN-β exposure. Collectively, this study provides insight into the cell type-specific response of human DC and monocyte subsets to IFN-I and highlights the distinct costimulatory potential of DC3s., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Background: UV filters, widely used in personal care and industrial products, are being found in the environment and, in humans where with limited understanding on their potential health effects, especially during puberty., Objectives: To examine the association between UV filter exposure and pubertal development in a prospective follow-up study., Methods: This study included 521 elementary and high school students from a suburban area of Shanghai. The initial study was done in October to November 2011; the follow-up study in April to May 2013. Twelve urinary organic UV filters were quantified, and the pubertal development was assessed at each study period by trained physicians using Tanner staging. We used (ordered) logistic regression model and multilevel mixed-effect (ordered) logistic regression model to assess cross-sectional and longitudinal effects between urinary concentration of five major UV filters and pubertal development of stages, onset and pace., Results: Ethylhexyl methoxycinnamate (EHMC) and its metabolite 4'-methoxyacetophenone (4'-MAP), two benzophenone derivatives (BP-2, BP-3) and Ethylhexyl dimethyl PABA (OD-PABA) were the most extensively detected UV filters in urine with geometric means (95% CI) in 2010 and 2012 as 1.77 (1.599, 1.956) and 2.28 (1.985, 2.622) ng/mL for EHMC; 4.55 (4.219, 4.907) and 5.26 (4.783, 5.775) ng/mL for 4'-MAP; 4.38 (4.011, 4.774) and 5.74 (5.023, 6.562) ng/mL for BP-2; 0.83 (0.760, 0.903) and 1.09 (0.967, 1.220) ng/mL for BP-3; 5.37 (4.949, 5.820) and 5.80 (5.193, 6.486) pg/mL for OD-PABA. Significant trend P-values (P < 0.05) include: EHMC and its metabolite were negatively correlated with stages of testicular volume and genital development; BP-3 was also negatively correlated with stages of testicular volume in boys, while OD-PABA positively correlated with stages of pubic hair and breast development in girls. Also, EHMC was associated with later pubertal onset of pubic hair and testicular volumes in boys, while OD-PABA correlated with earlier pubertal onset of breast development in girls. OD-PABA also significantly speeded up the progression of pubic hair and breast development in girls., Discussion: UV filters were extensively detected. Exposure to EHMC and BP-3 was significantly associated with later pubertal development in boys, and OD-PABA was associated with earlier pubertal development in girls. It demonstrates that the UV filters so widely used in personal care products and widely detected in environments are finding their way back into people where they are distorting endocrine function of adolescents., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Tissue resident memory T cells (Trm) are critical for local protection against reinfection. The accumulation of T cells in the tissues requires a post-priming signal from TNFR superfamily members, referred to as signal 4. Glucocorticoid-induced TNFR-related protein (GITR; TNFRSF18) signaling is important for this post-priming signal and for Trm formation during respiratory infection with influenza virus. As GITR signaling impacts both effector T cell accumulation and Trm formation, we asked if GITR differentially affects subsets of effector cells with different memory potential. Effector CD4 + T cells can be subdivided into 2 populations based on expression of lymphocyte antigen 6C (Ly6C), whereas effector CD8 + cells can be divided into 3 populations based on Ly6C and CX3CR1. The Ly6C hi and CX3CR1 hi T cell populations represent the most differentiated effector T cells. Upon transfer, the Ly6C lo CD4 + effector T cells preferentially enter the lung parenchyma, compared to the Ly6C hi CD4 + T cells. We show that GITR had a similar effect on the accumulation of both the Ly6C hi and Ly6C lo CD4 + T cell subsets. In contrast, whereas GITR increased the accumulation of all three CD8 + T cell subsets defined by CX3CR1 and Ly6C expression, it had a more substantial effect on the least differentiated Ly6C lo CX3CR1 lo subset. Moreover, GITR selectively up-regulated CXCR6 on the less differentiated CX3CR1 lo CD8 + T cell subsets and induced a small but significant increase in CD127 selectively on the Ly6C lo CD4 + T cell subset. Thus, GITR contributes to accumulation of both differentiated effector cells as well as memory precursors, but with some differences between subsets., (©2020 Society for Leukocyte Biology.)

Ethylhexyl methoxycinnamate (EHMC) is one of the most frequently used UV filters in sunscreens and other cosmetic products. Its ubiquitous presence in various environmental matrices and its endocrine disrupting properties have been widely reported. However, we know little about the effect of EHMC exposure on humans, mainly due to its fast metabolism. In this study, urine and plasma of EHMC-dosed rats were analysed to identify its major metabolites. Five metabolites were found, with four firstly reported. Two metabolites were putatively identified as 4-methoxycinnamic acid (4-MCA) and 4'-methoxyacetophenone (4'-MAP). Quantitative results revealed that their excretion concentrations were much higher than the parent compound. Because of these high concentrations, for the human biomonitoring study, EHMC and these two metabolites were detected simultaneously in urine samples from Chinese children and adolescents. The results indicated wide exposure to EHMC, 4-MCA and 4'-MAP. The correlation between urinary concentration of EHMC and 4-MCA as well as 4-MCA and 4'-MAP provided important clues as to the sources and metabolic pathways among these three compounds. Several demographic factors were also assessed with the exposure level. As the first human exposure study of EHMC in a Chinese population, this report would help to establish an exposure database facilitating health risk assessment of EHMC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To determine plasma metabolite and metabolic pathway differences between patients with type 2 diabetes with diabetic retinopathy (DR) and without retinopathy (diabetic controls), and between patients with proliferative DR (PDR) and nonproliferative DR (NPDR)., Methods: Using high-resolution mass spectrometry with liquid chromatography, untargeted metabolomics was performed on plasma samples from 83 DR patients and 90 diabetic controls. Discriminatory metabolic features were identified through partial least squares discriminant analysis, and linear regression was used to adjust for age, sex, diabetes duration, and hemoglobin A1c. Pathway analysis was performed using Mummichog 2.0., Results: In the adjusted analysis, 126 metabolic features differed significantly between DR patients and diabetic controls. Pathway analysis revealed alterations in the metabolism of amino acids, leukotrienes, niacin, pyrimidine, and purine. Arginine, citrulline, glutamic γ-semialdehyde, and dehydroxycarnitine were key contributors to these pathway differences. A total of 151 features distinguished PDR patients from NPDR patients, and pathway analysis revealed alterations in the β-oxidation of saturated fatty acids, fatty acid metabolism, and vitamin D3 metabolism. Carnitine was a major contributor to the pathway differences., Conclusions: This study demonstrates that arginine and citrulline-related pathways are dysregulated in DR, and fatty acid metabolism is altered in PDR patients compared with NPDR patients.

Widely recognized as a promising approach to degrading recalcitrant pollutants, Advanced Oxidation Processes (AOPs) have drawn much attention for their effectiveness and efficiency. Among all the AOPs, the Fenton system has been widely applied for oxidation and mineralization of micropollutants due to its ease of implementation and high catalytic efficiency. However, the necessity of preceding acidification, together with rapid consumption and slow regeneration of Fe(II) resulting in deterioration of reactivity, has reduced its competitiveness as a practical option for water treatment. Acknowledging the above drawbacks, this study investigates the potential viable option to enhance the Fenton system. Acesulfame was chosen as the model compound due to its ubiquitous occurrence and persistence in the environment. UV-assisted photo-Fenton treatment was found to remove the parent compound effectively; the transformation profile of acesulfame was identified and elucidated with the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Prolonged UV photo-Fenton treatment was effective for mineralization of the majority of the transformation products, without increasing the overall toxicity as indicated by Vibrio fischeri bioluminescence assay. The positive effects of the addition of redox mediators to Fenton systems at neutral pH were confirmed in this study. The results could be the basis for further development of homogeneous catalytic degradation techniques for the oxidation of environmental contaminants at circumneutral pHs to neutral pHs., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

CD8 + T cell exhaustion impedes control of chronic viral infection; yet how new T cell responses are mounted during chronic infection is unclear. Unlike T cells primed at the onset of infection that rapidly differentiate into effectors and exhaust, we demonstrate that virus-specific CD8 + T cells primed after establishment of chronic LCMV infection preferentially generate memory-like transcription factor TCF1 + cells that were transcriptionally and proteomically distinct, less exhausted, and more responsive to immunotherapy. Mechanistically, adaptations of antigen-presenting cells and diminished T cell signaling intensity promoted differentiation of the memory-like subset at the expense of rapid effector cell differentiation, which was now highly dependent on IL-21-mediated CD4 + T cell help for its functional generation. Chronic viral infection similarly redirected de novo differentiation of tumor-specific CD8 + T cells, ultimately preventing cancer control. Thus, targeting these T cell stimulatory pathways could enable strategies to control chronic infection, tumors, and enhance immunotherapeutic efficacy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The widespread use of UV filters has resulted in significant amounts of these chemicals appearing not only in the environment but also in organisms. This study first assessed the levels of nine UV filters in waters along the coast of Shenzhen, China, in tapwater, and in a nearby reservoir. UV filters were found to be high, in both winter and summer at most locations. Then, using zebrafish as a model, the influence of a UV filter mixture after dietary and aqueous exposure was assessed. After exposing artemia to three dominant UV filters at two levels and then feeding these artemia to zebrafish adults, concentrations in both were up to 4 times higher when exposed to the mixtures than when exposed to only a single UV filter. A short-term 25-day dietary exposure to the zebrafish adults did not appear to significantly influence early life stage development of the second generation; however, relatively long exposure over 47 days had significant adverse effects on embryo development. Aqueous exposure of fish embryos to mixtures of the three UV filters demonstrated a general trend of decreased heart/hatching rate as doses increased, coupled with significant changes in activities of catalase and malate dehydrogenase.

Purpose: To develop an internationally valid skill-based rubric that can be used as a global standardized platform for teaching, training, and evaluation of panretinal photocoagulation (PRP) in training programs., Design: A panel of educators and experts in retinal lasers was assembled to develop a standardized objective skill-based rubric., Participants: Sixteen international educators and retina specialists., Methods: The steps to performing slit-lamp delivery of PRP was described in detail. A group of 6 authors reviewed and agreed on the steps and assigned descriptors to expectation levels of novice, beginner, advanced beginner, and expert according to a modified Dreyfuss model. The tool then was vetted by an international panel of 10 retina specialists who are involved in training ophthalmologists in other countries., Main Outcome Measures: Final version of the tool agreed on by the international review panel., Results: The consecutive steps to performing PRP were outlined and broken down into preparation, procedure, and postoperative care. Descriptive words explaining what to expect from a novice, beginner, advanced beginner, and expert were listed for each step of PRP. Expert comments were incorporated, establishing face and content validity., Conclusions: This group of authors clearly defined expectations of a trainee at 4 levels of training according to the modified Dreyfus model, and an international panel of retina specialists agreed to its accuracy. This tool, the International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric for Panretinal Photocoagulation, has face and content validity. It can be used globally in training programs both to teach and assess this important comprehensive skill in ophthalmic training., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Ethyl-4-aminobenzoate (Et-PABA) is currently used as a substitute for 4-aminobenzoate (PABA) in sunscreens and anesthetic ointments. Despite its widespread use and hydrophilicity, Et-PABA has never been found in environmental waters. This study, probed the occurrence of Et-PABA in both seawater and drinking water sources in Hong Kong, and evaluated its transformation products (TPs) and environmental fate via cumulative potency and photocatalytic profile analyses. Another 11 UV filters used in skin-care products were also studied. Et-PABA was not detected in any water sample. Four other UV filters were dominant at ng/L level in both seawater and drinking water sources. UHPLC-QTOF-MS was used to elucidate the structure of TPs. With high resolution accurate mass data and fragment rationalization, 11 Et-PABA TPs were characterized, including seven intermediates firstly proposed as TPs; two compounds were reported for the first time. It is proposed that photocatalysis induces transformation pathways of (de)hydroxylation, demethylation and molecular rearrangement. Luminescent bacteria tests showed decreasing toxicity with increasing irradiation of Et-PABA, suggesting that irradiation TPs are less toxic than the parent compound. Transformation of Et-PABA appears to explain why Et-PABA has not been detected in the natural environment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Pseudallescheria boydii is a ubiquitous fungus that infects soft tissues and is known to cause ocular disease, including keratitis and endophthalmitis, in rare cases. In immunocompromised hosts, P. boydii can disseminate to or from the eye and other organs with lethal consequences. Postoperative P. boydii infections have, in rare cases, complicated several types of ocular surgeries in immunocompetent patients, but never for a scleral buckle. The authors present the first case of an infected scleral buckle from P. boydii. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:676-678.]., (Copyright 2017, SLACK Incorporated.)

Acesulfame (ACE) is one of the most commonly used artificial sweeteners. Because it is not metabolized in the human gut, it reaches the aquatic environment unchanged. In the present study, the reactivity of ACE in free chlorine-containing water was investigated for the first time. The degradation of ACE was found to follow pseudo-first-order kinetics. The first-order rate increased with decreasing pH from 9.4 to 4.8 with estimated half-lives from 693 min to 2 min. Structural elucidation of the detected transformation products (TPs) was performed by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Integration of MS/MS fragments, isotopic pattern and exact mass allowed the characterization of up to 5 different TPs in the ultrapure water extracts analyzed, including two proposed new chlorinated compounds reported for the first time. Unexpectedly, several known and regulated disinfection by-products (DBPs) were present in the ACE chlorinated solution. In addition, two of the six DBPs are proposed as N-DBPs. Time-course profiles of ACE and the identified by-products in tap water and wastewater samples were followed in order to simulate the actual disinfection process. Tap water did not significantly affect degradation, but wastewater did; it reacted with the ACE to produce several brominated-DBPs. A preliminary assessment of chlorinated mixtures by luminescence inhibition of Vibrio fischeri showed that these by-products were up to 1.8-fold more toxic than the parent compound. The generation of these DBPs, both regulated and not, representing enhanced toxicity, make chlorine disinfection a controversial treatment for ACE. Further efforts are urgently needed to both assess the consequences of current water treatment processes on ACE and to develop new processes that will safely treat ACE. Human health and the health of our aquatic ecosystems are at stake., (Copyright © 2017 Elsevier Ltd. All rights reserved.)