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Oliver Davidson,1,2 Anand E Rajesh,1,2 Marian Blazes,1,2 Ashley Batchelor,1,2 Aaron Y Lee,1,2 Cecilia S Lee,1,2,&ast; Laura C Huang1,3,&ast; On behalf of the IRIS® Registry Analytic Center Consortium1Department of Ophthalmology, University of Washington, Seattle, WA, USA; 2Roger and Angie Karalis Johnson Retina Center, Seattle, WA, USA; 3Division of Ophthalmology, Seattle Children’s Hospital, Seattle, WA, USA&ast;These authors contributed equally to this workCorrespondence: Laura C Huang, Department of Ophthalmology, Seattle Children’s Hospital and University of Washington, OA.9.220, 4800 Sand Point Way NE, Seattle, WA, USA, Tel +1 206-987-2177, Email lchuang1@uw.eduPurpose: Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice patterns.Patients and Methods: Retrospective cohort study on patients < 18 years old who were diagnosed with both juvenile idiopathic arthritis and uveitis based on International Classification of Diseases tenth edition codes in the Intelligent Research in Sight Registry through December 2020. Surgical history was extracted using current procedural terminology codes. The primary outcome was incidence of blindness (20/200 or worse) in at least one eye in association with sociodemographic factors. Secondary outcomes included cataract and glaucoma surgery following uveitis diagnosis. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards models.Results: Median age of juvenile idiopathic arthritis-associated uveitis diagnosis was 11 (Interquartile Range: 8 to 15). In the Cox models adjusting for sociodemographic and insurance factors, the hazard ratios of best corrected visual acuity 20/200 or worse were higher in males compared to females (HR 2.15; 95% CI: 1.45– 3.18), in Black or African American patients compared to White patients (2.54; 1.44– 4.48), and in Medicaid-insured patients compared to commercially-insured patients (2.23; 1.48– 3.37).Conclusion: Sociodemographic factors and insurance coverage were associated with varying levels of risk for poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis.Keywords: rheumatology, ophthalmology, uveitis, health inequity, social determinants of health

Madison Fraser,1 Nagashree Seetharamu,2 Matthew Diamond,2 Chung-Shien Lee2,3 1Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, USA; 2Division of Medical Oncology and Hematology, Northwell Health Cancer Institute, Lake Success, NY, USA; 3Department of Clinical Health Professions, St. John’s University, Queens, NY, USACorrespondence: Chung-Shien Lee, Email leec3@stjohns.eduAbstract: Aberrant c-MET (Mesenchymal–Epithelial Transition) signaling contributes to cancer cell development, proliferation, and metastases of non-small cell lung cancer (NSCLC). MET exon 14 (METex14) skipping mutation is noted in approximately 4% of NSCLC cases and is targetable with the recently approved tyrosine kinase inhibitors capmatinib and tepotinib. Capmatinib, the focus of this review article, is a highly selective MET inhibitor approved for use in patients with METex14 mutated NSCLC. In this review, we discuss cMET as a target, the pharmacology of capmatinib, key trials of capmatinib in MET-altered lung cancer, and toxicity profile. We highlight some ongoing capmatinib clinical trials that expand their role to other subsets of patients, especially those with EGFR mutations, who develop MET alterations as a resistance pathway. We further provide our perspective on the management of METex14 NSCLC, strategies for sequencing agents, and toxicity management.Keywords: non-small cell lung cancer, Mesenchymal–Epithelial Transition gene, MET exon 14 skipping mutation, tyrosine kinase inhibitor, capmatinib

Ting-Yu Lin,1,2 Chun-Yu Lo,1,2 Po-Jui Chang,1,2 Yu-Lun Lo,1,2 Chung-Shu Lee,1– 3 Chih-Hao Chang,1– 3 Chih-Teng Yu,1,2 Jonathan Huai Yao,1 Shu-Min Lin1,2 1Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Pulmonary and Critical Care Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, TaiwanCorrespondence: Shu-Min Lin, Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa N. Road, Taipei, Taiwan, Fax + 886 33272474, Email smlin100@gmail.comBackground: The immunological features of eosinophils in early-onset asthma (EOA) differ from those in late-onset asthma (LOA). Clinical trials of anti-interleukin-5 (IL-5) treatment for severe eosinophilic asthma showed a better response for LOA patients than EOA patients. We wonder if the transcriptional activity of activated eosinophils was different in EOA and LOA.Methods: Eosinophils obtained from well-controlled EOA and LOA patients and normal subjects were compared in terms of the mRNA expression of activation-related genes and specific markers related to cell functions in eosinophils activated by IL-5 or IL-17. The correlation between mRNA expression and clinical features and lung function was further analyzed.Results: The transcriptional expression of most genes was higher in activated eosinophils from LOA patients than in those from EOA patients and normal subjects. After IL-17 stimulation, the expression of certain genes was higher in atopic EOA patients than in non-atopic EOA patients. Similar observation was noted in obese EOA patients. After IL-5 stimulation, the transcriptional expression of most genes in eosinophils from LOA patients was negatively correlated with indicators of lung function. These correlations were less pronounced in EOA patients: After IL-17 stimulation, some genes in EOA patients were negatively correlated with post-bronchodilator changes in lung function.Conclusion: This study describes differences in the transcriptional active patterns of eosinophils and their correlation to atopy and obesity by age of onset. High transcriptional activity in activated eosinophils and a negative correlation to lung function indicate the importance of eosinophils in the pathogenesis of LOA.Graphical Abstract: Keywords: late-onset asthma, early-onset asthma, eosinophils, messenger RNA

Jeong Eun Lee,1 Jinyoung Oh,1 Jun Nyung Lee,2 Hyun-Su Ri,3 Chang Sub Lee,3 Jinseok Yeo1 1Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Kyungpook National University Chilgok Hospital, Daegu, Korea; 2Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Daegu, Korea; 3Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Kyungpook National University Hospital, Daegu, KoreaCorrespondence: Jinseok Yeo, Department of Anesthesiology and Pain Medicine Kyungpook National University School of medicine, Kyungpook National University Chilgok Hospital, Daegu, Korea, Tel +82-53-200-2644, Fax +82-53-200-2027, Email painfree@gmail.comBackground: Opioid use after surgery is a potential contributor to the opioid epidemic. An adequate pain control method after surgery while minimizing opioid exposure is needed. This study aimed to compare the effect of non-opioid multimodal analgesia (NOMA) protocol with opioid-based patient-controlled analgesia (PCA) for pain relief after robot-assisted radical prostatectomy (RARP).Methods: This prospective randomized, open, non-inferiority trial included 80 patients scheduled for RARP. The NOMA group received pregabalin, paracetamol, bilateral quadratus lumborum block, and pudendal nerve block. PCA group received PCA. Pain scores, postoperative nausea and vomiting, opioid requirements, and quality of recovery were recorded 48 hours after surgery.Results: We found no significant differences in pain scores. The mean difference in pain score during rest at 24 h was 0.5 (95% CI − 0.5 to 2.0). This result demonstrated the non-inferiority of NOMA protocol to PCA at our non-inferiority margin (− 1). In addition, 23 patients in the NOMA group did not receive any opioid agonist for 48 h after surgery. Recovery of bowel function was also faster in the NOMA group than in the PCA group (25.0 hours vs 33.4 hours, p = 0.01).Limitations: We did not evaluate whether our NOMA protocol could decrease the incidence of new continuous opioid use after surgery.Conclusion: NOMA protocol successfully controlled postoperative pain and was non-inferior to morphine-based PCA regarding patient-reported pain intensity. It also promoted recovery of bowel function and decreased postoperative nausea and vomiting.Keywords: multimodal analgesia, opioid sparing, postoperative pain, robot-assisted radical prostatectomy

Jeongsoo Kim,1 Ho-Jin Lee,1,2 Young-Ju Lee,3 Chang-Soon Lee,1,2,4 Yongjae Yoo,1,2,4 Jee Youn Moon1,2,4 1Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; 3Department of Anesthesiology and Pain Medicine, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; 4Integrated Cancer Management Center, Seoul National University Cancer Hospital, Seoul, Republic of KoreaCorrespondence: Jee Youn MoonDepartment of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of KoreaTel +82-2-2072-2462Fax +82-2-763-9390Email jymoon0901@gmail.comPurpose: Ultrasound-guided thoracic paravertebral block (US-TPVB) is considered a treatment option for the management of acute pain in various pain-related conditions. We conducted a prospective pilot study to evaluate the possibility of US-TPVB as a sympathetic blockade in patients with neuropathic pain disorders in the upper extremities.Patients and Methods: A total of 12 patients underwent US-TPVB between the T2 and T3 paravertebral space with 10 mL of 1% mepivacaine. The temperature change (°C) before and after the procedure was compared between the ipsilateral and contralateral hands. We counted the proportion of patients showing a temperature increase ≥ 1.5°C and compared a change in the pain intensity before and after the procedure.Results: The median increase in the temperature change between the ipsilateral and contralateral hands was 1.54°C (interquartile range, 1.28– 2.20). There were seven patients (58.3%) who showed a temperature difference ≥ 1.5°C between both hands after the US-TPVB. Eleven patients (91.7%) reported a reduction in pain according to the score on the 11-point numerical rating scale. No serious complications relevant to the procedure were reported.Conclusion: US-TPVB could be a useful technique for sympathetic blockade in patients with upper extremity pain.Keywords: neuropathic pain, upper extremity, paravertebral block, sympathetic block, ultrasound

Chung-Shien Lee,1,2 Sandhya Sharma,3 Emily Miao,4 Cheryl Mensah,5 Kevin Sullivan,2 Nagashree Seetharamu2 1Department of Clinical Health Professions, St. John’s University, College of Pharmacy and Health Sciences, Queens, NY 11439, USA; 2Division of Medical Oncology and Hematology, Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Lake Success, NY 11042, USA; 3Department of Hematology and Oncology, Denver Health, Denver, CO 80204, USA; 4Albert Einstein College of Medicine, Bronx, NY, USA; 5Weil Cornell School of Medicine, Department of Hematology and Oncology, Weill Cornell of Medicine, New York, NY, USACorrespondence: Nagashree SeetharamuDivision of Medical Oncology and Hematology, Northwell Health Cancer Institute, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, 450 Lakeville Road, Lake Success, NY 11042, USATel +1 516-734-8855Email nseetharamu@northwell.eduAbstract: Mutations in the epidermal growth factor receptor (EGFR) are common amongst those with non-small cell lung cancer and represent a major factor in treatment decisions, most notably in the advanced stages. Small molecule tyrosine kinase inhibitors (TKIs) that target the EGFR, such as erlotinib, gefitinib, icotinib, afatinib, dacomitinib and osimertinib, have all shown to be effective in this setting. Osimertinib, a third-generation EGFR TKI, is a favorable option, but almost all patients develop resistance at some time point. There are no effective treatment options for patients who progress on osimertinib, but ongoing trials will hopefully address this unmet need. The aim of this review is to provide a comprehensive review of the data with EGFR TKIs, management of the toxicities and the ongoing trials with this class of agents.Keywords: non-small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor

© 2014 American College of Radiology. Radiologists in the United States are required to complete the Practice Quality Improvement (PQI) program as part of their Maintenance of Certification by the ABR. The Institute for Healthcare Improvement's (IHI) Model for Improvement (MFI) offers an alternative to the 3-phase approach currently advocated by the ABR. The MFI implicitly assumes that many interventions will need to be tested and refined for any meaningful project, and provides a project management approach that enables rapid assessment and improvement of performance. By collecting data continuously, rather than simply before and after interventions, more interventions can be tested simultaneously and projects can progress more rapidly. In this article, we describe the ABR's 3-phase approach, and introduce the MFI and how it can be employed to affect positive changes. Using a radiology case study, we demonstrate how one can utilize the MFI to enable rapid quality improvement.

Grace L Su,1 Douglas M Baughman,2 Qinqin Zhang,3 Kasra Rezaei,2 Aaron Y Lee,2 Cecilia S Lee2 1Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 2Department of Ophthalmology, 3Department of Bioengineering, University of Washington, Seattle, WA, USA Purpose: The aim of this study was to compare physician preferences regarding the commercially available spectral-domain (SD) optical coherence tomography angiography (OCTA) and swept-source (SS) OCTA prototype device.Design: Comparative analysis of diagnostic instruments was performed.Patients and methods: Subjects at the University of Washington Eye Institute and Harborview Medical Center were prospectively recruited and imaged with the Zeiss SD OCTA (HD-5000, Angioplex) and Zeiss SS OCTA (Plex Elite, Everest) devices on the same day. The study included 10 eyes from 10 subjects diagnosed with a retinal/choroidal disease. Deidentified images were compiled into a survey and sent to retina specialists in various countries. The survey presented masked SD and SS images of each eye for each retinal sublayer side by side. Respondents were asked about their image preference and impact on clinical management. A priori and post hoc preferences for SD vs SS were collected.Results: Fifty-four retina specialists responded to the survey. Median years in practice was 3.00 (interquartile range [IQR] 1.50–17.00). At baseline, 23 (48%) physicians owned an OCTA machine. The majority of physician responses showed a preference for the SS over SD OCTA, independent of the retinal pathology shown (n=454 overall responses, 74%). Nevertheless, the majority indicated that both SD and SS would be equally valuable in informing clinical decisions (n=374 overall responses, 61%).Conclusion: These findings indicate that the majority of retina specialists surveyed prefer SS over SD OCTA based on image quality, regardless of the retinal pathology shown. Regarding the clinical utility of each modality, the majority of physicians perceive SD and SS as equally effective. Keywords: swept-source optical coherence tomography angiography, spectral-domain optical coherence tomography angiography, physician preference

Adozelesin is a synthetic analog of the antitumor antibiotic CC-1065, which alkylates the N3 of adenine in the minor groove in a sequence-selective manner. Since the cytotoxic potency of a DNA alkylating agent can be modulated by DNA excision repair system, we investigated whether nucleotide excision repair (NER) and base excision repair (BER) enzymes are able to excise the bulky DNA adduct induced by adozelesin. The UvrABC nuclease and 3-methyladenine-DNA glycosylase, that exhibit a broad spectrum of substrate specificity, were selected as typical NER and BER enzymes, respectively. The adozelesin-DNA adduct was first formed in the radiolabeled restriction DNA fragment and its excision by purified repair enzymes was monitored on a DNA sequencing gel. The treatment of the DNA adduct with a purified UvrABC nuclease and sequencing gel analysis of cleaved DNA showed that UvrABC nuclease was able to incise the adozelesin adduct. The incision site corresponded to the general nuclease incision site. Excision of this adduct by 3-methyladenine-DNA glycosylases was determined following the treatment of the DNA adduct with a homogeneous recombinant bacterial, rat and human 3-methyladenine-DNA glycosylases. Abasic sites generated by DNA glycosyalses were cleaved by the associated lyase activity of the E. coli formamidopyrimidine-DNA glycosylase (Fpg). Resolution of cleaved DNA on a sequencing gel showed that the DNA glycosylase from different sources could not release the N3-adenine adducts. A cytotoxicity assay using E. coli repair mutant strains showed that E. coli mutant strains defective in the uvrA gene were more sensitive to cell killing by adozelesin than E. coli mutant strain defective in the alkA gene or the wild type. These results suggest that the NER pathway seems to be the major excision repair system in protecting cells from the cytotoxicity of adozelesin.

A variety of alkylated base adducts are repaired by 3-methyladenine DNA glycosylases, one of the base excision repair enzymes. In this study, we examined the DNA adducts induced by hepsulfam and determined whether alkylated base adducts can be substrates for bacterial and mammalian 3-methyladenine DNA glycosylases by electrophoresis methods. Hepsulfam, a synthetic analogue of busulfan, is known to alkylate DNA and form interstrand cross-links. The extent of DNA interstrand cross-links induced by hepsulfam and busulfan was found to be similar but significantly lower than that induced by chlorambucil, as measured by an agarose gel assay. The major monofunctional alkylation site of hepsulfam was observed at the N7 position of guanine, and not at the N3 position of adenine. Both compounds did not exhibit any sequence selective DNA alkylation patterns. The excision of hepsulfam-induced DNA adducts has been determined by treatment with homogeneous recombinant bacterial, rat and human 3-methyladenine DNA glycosylases and successive treatments by formamidopyrimidine-DNA glycosylase. The Escherichia coli alkA protein was shown to completely excise N7 guanine adducts, whereas mammalian 3-methyladenine DNA glycosylase failed to excise them. In addition, the cytotoxicity assay showed that E. coli mutant strains defective in the alkA gene or the uvrA gene were more sensitive to killing by hepsulfam than the wild type.

The $^{174}$Yb($^{29}$Si,5n) reaction at 148 MeV with thin targets was usedto populate high-angular momentum states in $^{198}$Po. Resulting $\gamma$ rayswere observed with Gammasphere. A weakly-populated superdeformed band of 10$\gamma$-ray transitions was found and has been assigned to $^{198}$Po. This isthe first observation of a SD band in the $A \approx 190$ region in a nucleuswith $Z > 83$. The ${\cal J}^{(2)}$ of the new band is very similar to those ofthe yrast SD bands in $^{194}$Hg and $^{196}$Pb. The intensity profile suggeststhat this band is populated through states close to where the SD band crossesthe yrast line and the angular momentum at which the fission process dominates.

Hui Yi Tan,1 Aniruddha Agarwal,2 Cecilia S Lee,3 Jay Chhablani,4 Vishali Gupta,5 Manoj Khatri,6 Jayabalan Nirmal,7 Carlos Pavesio,8 Rupesh Agrawal1,7–9 1Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 2Department of Vitreoretina, Stanley M Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, 3Department of Ophthalmology, University of Washington, Seattle, WA, USA; 4Department of Vitreoretina, L V Prasad Eye Institute, Hyderabad, Telangana, 5Department of Retina and Uvea, Post Graduate Institute of Medical Education and Research, Chandigarh, 6Department of Retina, Rajan Eye Care Hospital, Chennai, Tamil Nadu, India; 7School of Material Science and Engineering, Nanyang Technological University, Singapore; 8Department of Medical Retina, Moorfields Eye Hospital, NHS Foundation Trust, London, UK; 9Department of Ophthalmology, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore Abstract: Uveitis is an important cause of vision loss worldwide due to its sight-threatening complications, especially cystoid macular edema, as well as choroidal neovascularization, macular ischemia, cataract, and glaucoma. Systemic corticosteroids are the mainstay of therapy for noninfectious posterior uveitis; however, various systemic side effects can occur. Intravitreal medication achieves a therapeutic level in the vitreous while minimizing systemic complications and is thus used as an exciting alternative. Corticosteroids, antivascular endothelial growth factors, immunomodulators such as methotrexate and sirolimus, and nonsteroidal anti-inflammatory drugs are currently available for intravitreal therapy. This article reviews the existing literature for efficacy and safety of these various options for intravitreal drug therapy for the management of noninfectious uveitis (mainly intermediate, posterior, and panuveitis). Keywords: intravitreal therapy, noninfectious uveitis, posterior uveitis, intravitreal steroids, intravitreal methotrexate

Sun-Hee Cho,1,* Ji Hyeon Hong,2,* Young-Woock Noh,1 Eunji Lee,2 Chang-Soo Lee,3 Yong Taik Lim1 1SKKU Advanced Institute of Nanotechnology, School of Chemical Engineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 2Graduate School of Analytical Science and Technology, Chungnam National University, 3Hazards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology, Yuseong-gu, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: In this research, we synthesized bioderived poly(amino acid) hydrogel particles that showed pH-dependent membrane-disrupting properties and controlled cytosolic delivery of antitumor drugs. Poly(γ-glutamic acid) (γ-PGA) that has been produced extensively using bacteria, especially those of Bacillus subtilis species, was modified with cholesterol (γ-PGA/Chol), and the γ-PGA/Chol conjugates were used to form polymeric nanoparticles the size of 21.0±1.1 nm in aqueous solution. When the polymeric nanoparticles were mixed with doxorubicin (Dox), raspberry-like hydrogel particles (RBHPs) were formed by the electrostatic interaction between the cationically charged Dox and the anionically charged nanoparticles. The average size and surface charge of the RBHPs in aqueous solution were 444.9±122.5 nm and -56.44 mV, respectively. The loaded amount of Dox was approximately 63.9 µg/mg of RBHPs. The RBHPs showed controlled drug release behavior in both in vitro and ex vivo cell-based experiments. Through fluorescence microscopy and fluorescence-activated cell sorting, the cellular uptake of RBHPs into human cervical cancer cells (HeLa) was analyzed. The cytotoxic effect, evaluated by the methyl tetrazolium salt assay, was dependent on both the concentration of RBHPs and the treatment time. The pH-dependent membrane-disrupting properties of the RBHPs and the subsequent cytosolic delivery of Dox were evaluated using a standard hemolysis assay. Upon an increase in hydrophobicity at the lysosomal acidic pH, RBHPs could easily interact, penetrate cell membranes, and destabilize them. Taken together, the data suggested that RBHPs could be used as drug delivery carriers after loading with other therapeutic drugs, such as proteins or small interfering RNA for cancer therapy. Keywords: hydrogel particles, controlled release, endosomal escape, antitumor

Taekyung Lee,1 Eshaan Mathew,2 Santhosh Rajaraman,2 Geetha Manivasagam,2 Ashok Kumar Singh,3 Chong Soo Lee4 1Department of Mechanical Engineering, Northwestern University, Evanston, IL, USA; 2Centre for Biomaterials Science and Technology, School for Mechanical and Building Sciences, Vellore Institute of Technology, Vellore, Tamil Nadu, India; 3Defense Metallurgical Research Laboratory, Hyderabad, India; 4Graduate Institute of Ferrous Technology (GIFT), Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea Abstract: Development of submicrocrystalline structure in biomedical alloy such as Ti-13Nb-13Zr (in wt%) through warm-rolling process has been found to enhance mechanical properties compared to conventional thermomechanical processing routes including hot-rolling process. The present study investigated the tribological and corrosion behaviors of warm-rolled (WR) and hot-rolled Ti-13Nb-13Zr alloys which have not been studied to date. Both tribological and corrosion experiments were carried out in simulated body fluid conditions (Hank’s solution at 37°C) based on the fact that the investigated alloys would be used in a human body as orthopedic implants. The WR Ti-13Nb-13Zr demonstrated a submicrocrystalline structure that provided a significant enhancement in hardness, strength, and corrosion resistance. Meanwhile, there was no notable difference in wear resistance between the WR and hot-rolled samples despite the different microstructure and hardness. The present study confirmed the enormous potential of WR Ti-13Nb-13Zr with not only great mechanical properties but also high corrosion resistance in the simulated body fluid. Keywords: titanium alloy, multi-pass caliber-rolling, grain refinement, tribology, corrosion

Asima Bajwa,1 Chang Sup Lee,1 Jim Patrie,2 Wenjun Xin,2 Ashvini K Reddy1 1Department of Ophthalmology, 2Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA Purpose: To report the clinical outcomes of uveitis patients at the University of Virginia. Methods: Retrospective, observational study of uveitis patients seen at the University of Virginia from 1984 to 2014. Parametric and nonparametric methods were used to analyze the change in best-corrected visual acuity (BCVA) in relation to demographics, diagnoses, management, and complications. Results: The study included 644 eyes of 491 patients. Patients with mild visual loss (logMAR 1.0) (P=0.002). Females were more likely to have mild visual loss as compared to males (P=0.025). Median overall BCVA was logMAR 0.18 at initial and final presentation (P=1.00). Vision loss at diagnosis was a predictor for moderate visual loss (MVL, logMAR 0.4 to

Cecilia S Lee,1 Aaron Y Lee,2 Farzin Forooghian,3 Chris S Bergstrom,1 Jiong Yan,1 Steven Yeh11Section of Vitreoretinal Disease and Surgery, Department of Ophthalmology, Emory Eye Center, Emory University, Atlanta, GA, USA; 2Department of Ophthalmology and Visual Sciences, Washington University in St Louis, St Louis, MO, USA; 3Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, CanadaPurpose: To describe the fundus autofluorescence (FAF) features of the inflammatory ­maculopathies and develop a quantification method for FAF analysis.Methods: This is a retrospective, consecutive case series of patients with inflammatory maculopathies from two tertiary centers. The clinical findings, demographics, and FAF imaging characteristics were reviewed. Foveal autofluorescence (AF) was analyzed. Median and standard deviation (SD) of foveal AF intensity were measured.Results: Thirty eyes of 15 patients were evaluated with both qualitative and quantitative FAF analysis. In acute macular neuroretinopathy, the active phase showed foveal hypoautofluorescence, which became hypoautofluorescent with resolution. In acute posterior multifocal placoid pigment epitheliopathy, multiple lesions with hypoautofluorescent centers with hyperautofluorescent borders were observed in active disease and became hypoautofluorescent with disease convalescence. In multifocal choroiditis and punctate inner choroiditis, the active hyperautofluorescent lesions progressed to inactive, hypoautofluorescent scars. Active serpiginous choroiditis showed hyperautofluorescent borders adjacent to a helicoid-shaped, hypoautofluorescent scar. Active unilateral acute idiopathic maculopathy (UAIM) showed a complex pattern of hypo- and hyperautoflourescence in the macula. The median foveal AF was the greatest in acute macular neuroretinopathy and UAIM among the maculopathies, while the greatest SD of foveal AF intensity was observed in UAIM.Conclusion: The active phase of the majority of inflammatory maculopathies was characterized by hyperautofluorescent lesions. Increased SD of foveal AF correlated with a mixture of hypo- and hyperautoflourescence. Median and SD may be useful metrics in foveal AF and quantifiable values that may be assessed over time as a disease process evolves. Improvements in quantification methods of FAF imaging may allow us to objectively evaluate posterior uveitis.Keywords: posterior uveitis, foveal autofluorescence, quantification, fundus autofluorescence imaging

Sunhyae Jang1,*, Ji Won Park2,*, Hye Rim Cha1, Sun Young Jung1, Jeong Eun Lee1, Sung Soo Jung1, Ju Ock Kim1, Sun Young Kim1, Choong Sik Lee3, Hee Sun Park1 1Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Medical School, Daejeon, 2Division of Pulmonology, Department of Internal Medicine, Daejeon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, 3Department of Pathology, Chungnam National University Medical School, Daejeon, South Korea*These authors contributed equally to this workAbstract: The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.Keywords: allergic airway disease, hypoxia inducible factor-1α, vascular endothelial growth factor

Myung Joo Kang1, Jae Yoon Eum1, Mi Sook Jeong2, Sang Han Park1, Ki Young Moon1, Mean Hyung Kang1, Min Soo Kim1, Sun Eun Choi1, Min Won Lee1, Do Ik Lee1, Hyoweon Bang2, Chung Soo Lee2, Seong Soo Joo3, Kapsok Li2, Mi-Kyung Lee2, Seong Jun Seo2, Young Wook Choi11College of Pharmacy, ChungAng University, Heuksuk-dong, Dongjak-gu, Seoul, 2College of Medicine, Chung-Ang University, Heuksukdong, Dongjak-gu, Seoul, 3Division of Marine Molecular Biotechnology, Gangneung-Wonju National University, Gangneung, South KoreaBackground: The aim of the present study was to enhance a topical delivery of hirsutenone (HST), a naturally occuring immunomodulator, employing Tat peptide-admixed elastic liposomes (EL/T).Methods: HST-loaded EL, consisting of phosphatidylcholine and Tween 80 (85:15 w/w%), were prepared using thin film hydration method. By adding Tat peptide to EL (0.16 w/w%), EL/T were formulated. The in vitro skin permeation of HST was examined using a Franz diffusion cell mounted with depilated mouse skin. Lesions for atopic dermatitis (AD) were induced by a topical application of diphenylcyclopropenone to NC/Nga mice. Therapeutic improvements of AD were evaluated by clinical skin severity scores. Immunological analyses on inducible nitric oxide synthase and cyclooxygenase-2 levels in the skin and interleukin (IL)-4, IL-13, immunoglobulin E, and eosinophil levels in the blood were also performed.Results: EL systems were superior to conventional cream, revealing greater flux values in a permeation study. The addition of Tat peptide further increased the skin permeation of HST. In an efficacy study with AD-induced NC/Nga mice, an HST-containing EL/T formulation brought a significant improvement in both skin severity score and immune-related responses for the levels of nitric oxide synthase, cyclooxygenase-2, IL-4, IL-13, immunoglobulin E, and eosinophils.Conclusion: A novel EL/T formulation was successfully developed for topical delivery of HST to treat AD.Keywords: hirsutenone, elastic liposomes, atopic dermatitis, NC/Nga mice, Tat peptide