Publications by authors named "Wesley Chan"

45 Publications

Acute Central Retinal Artery Occlusion Seen within 24 Hours at a Tertiary Institution.

J Stroke Cerebrovasc Dis 2021 Jul 13;30(9):105988. Epub 2021 Jul 13.

Department of Ophthalmology, Emory University School of Medicine, 1365-B Clifton Road NE, Suite B4500, Atlanta, GA 30322, United States; Department of Neurology, Emory University School of Medicine, Atlanta, GA 30322, United States. Electronic address:

Objective: Acute central retinal artery occlusion (CRAO) is an emergency with poor visual outcome. Intravenous thrombolysis within 4.5 h of vision loss is safe and may improve vision, but is rarely administered because of frequent delays in presentation. We describe a subgroup of CRAO patients presenting within 24 h of vision loss to a tertiary care center affiliated with a comprehensive stroke center.

Materials And Methods: Retrospective review of 181 consecutive CRAO patients seen at our institution from 2010 to 2020.

Results: Out of 181 CRAO patients, 62 (34%) presented within 24 h of vision loss and tended to live closer to the hospital. These patients were more likely to be admitted to the hospital and receive comprehensive stroke work-up compared to patients who presented after 24 h of vision loss. Patients presenting after 24 h did not necessarily receive prior appropriate work-up at outside institutions. Conservative treatments for CRAO were administered to 20/181 patients, and only 3 patients received intravenous thrombolysis.

Conclusions: Patients with CRAO do not present to the emergency department fast enough and diagnosis of CRAO is often delayed. Despite having a protocol in place, only 3/181 patients received IV thrombolysis, emphasizing the difficulty in administering very acute treatments for CRAO. Public education regarding CRAO is necessary to improve presentation times, management, and visual outcomes. Hospitals need to develop accelerated diagnostic pathway protocols for patients with acute vision loss so that CRAO patients may be diagnosed and be considered for potential acute treatments as quickly as possible.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.105988DOI Listing
July 2021

Design of Functional Chiral Cyclen-Based Radiometal Chelators for Theranostics.

Inorg Chem 2021 May 9;60(10):7082-7088. Epub 2021 Mar 9.

Department of Applied Biology and Chemical Technology, State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom 999077, Hong Kong SAR.

A series of water-soluble chiral cyclen-based chelators with chemical handles for selective targeting have been synthesized (cyclen = 1,4,7,10-Tetraazacyclododecane). Optical studies, relaxivity measurements, and competitive titrations were performed to show the versatility of these chiral chelators. The complexations of L3, L4, and L5 with Lu, Y, Sc and Cu were successfully demonstrated in around 90% to 100% yields. Efficient and rapid radiolabeling of L5 with Lu was achieved under mild conditions with 96% yield. The chelators exhibit near quantitative labeling efficiencies with a wide range of radiometal ions, which are promising for the development of targeting specific radiopharmaceutical and molecular magnetic resonance imaging contrast agents.
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http://dx.doi.org/10.1021/acs.inorgchem.0c03734DOI Listing
May 2021

DCP and AFP-L3 Are Complementary to AFP in Predicting High-Risk Explant Features: Results of a Prospective Study.

Clin Gastroenterol Hepatol 2021 Jan 29. Epub 2021 Jan 29.

Division of Gastroenterology and Hepatology, Department of Medicine, University of California San Francisco, San Francisco, California. Electronic address:

Among patients with hepatocellular carcinoma (HCC), elevated α-fetoprotein (AFP) has been shown to predict waitlist dropout, high-risk histopathologic features, and inferior post-liver transplant (LT) outcome. Nevertheless, many patients with HCC have a normal AFP and yet still experience waitlist dropout or post-LT recurrence. Because of the degree of imprecision associated with AFP, there is a quest for other biomarkers that may be complementary to or better than AFP in predicting prognosis in LT. Lectin-reactive AFP (AFP-L3) and des-gamma-carboxyprothrombin (DCP) are biomarkers that have been used in conjunction with AFP as HCC surveillance or diagnostic tools. However, the utility of these biomarkers in LT for HCC is not established.
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http://dx.doi.org/10.1016/j.cgh.2021.01.043DOI Listing
January 2021

Unusual Magnetic Field Responsive Circularly Polarized Luminescence Probes with Highly Emissive Chiral Europium(III) Complexes.

Angew Chem Int Ed Engl 2021 01 3;60(2):1004-1010. Epub 2020 Nov 3.

Department of Applied Biology and Chemical Technology, State Key Laboratory of Chemical Biology and Drug Discovery, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.

Chirality is ubiquitous within biological systems where many of the roles and functions are still undetermined. Given this, there is a clear need to design and develop sensitive chiral optical probes that can function within a biological setting. Here we report the design and synthesis of magnetically responsive Circularly Polarized Luminescence (CPL) complexes displaying exceptional photophysical properties (quantum yield up to 31 % and |g | up to 0.240) by introducing chiral substituents onto the macrocyclic scaffolds. Magnetic CPL responses are observed in these chiral Eu complexes, promoting an exciting development to the field of magneto-optics. The |g | of the D → F transition increases by 20 % from 0.222 (0 T) to 0.266 (1.4 T) displaying a linear relationship between the Δg and the magnetic field strength. These Eu complexes with magnetic CPL responses, provides potential development to be used in CPL imaging applications due to improved sensitivity and resolution.
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http://dx.doi.org/10.1002/anie.202012133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821146PMC
January 2021

Copper-catalyzed (4+1) and (3+2) cyclizations of iodonium ylides with alkynes.

Chem Commun (Camb) 2020 Sep;56(77):11429-11432

School of Chemistry, The Key Laboratory of Low-Carbon Chemistry & Energy Conservation of Guangdong Province, Sun Yat-Sen University, Guangzhou 510275, People's Republic of China.

The copper(ii)-catalyzed (4+1) cyclizations and copper(i)-catalyzed (3+2) cycloadditions of iodonium ylides and alkynes were successfully developed by employing efficient and safe iodonium ylides instead of traditional diazo compounds. Highly functionalized dimethyl (E)-3-benzylideneindoline-2,2-dicarboxylates and methyl 5-(2-hydroxyphenyl)-2-methoxy-4-phenylfuran-3-carboxylates were conveniently prepared in moderate to excellent yields. The possible reaction mechanisms were also discussed.
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http://dx.doi.org/10.1039/d0cc04373gDOI Listing
September 2020

Non-Compaction Cardiomyopathy Presented with Atrial Fibrillation: A Case Report and Literature Review.

Am J Med Case Rep 2020 29;8(9):281-283. Epub 2020 May 29.

Department of Medicine, State University of New York Downstate Health Science University, Brooklyn, NY 11203 USA.

Background: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare congenital cardiomyopathy characterized by increased trabeculation in one or more segments of the ventricle. LVNC presented with non-specific symptoms and highly variable clinical presentation ranging from asymptomatic to progressive heart failure and recurrent or life-threatening arrhythmias.

Case Presentation: 54-year-old Black man with a history of hypertension, diabetes and end-stage renal disease presented with one day palpitations and lightheadedness following a dialysis session. He denied any dyspnea or syncope. On examination, blood pressure was 175/91 mmHg with irregular pulse. No murmur, rubs or gallops were appreciated. Laboratory were unremarkable except increased creatinine and mild anemia with normal thyroid function test. Electrocardiogram (ECG) revealed atrial fibrillation with normal ventricular rate. Transthoracic echocardiogram revealed mildly increased left ventricular (LV) wall thickness with prominent trabeculation and ejection fraction of 55-60 percent, a pseudo-normal LV filling pattern, with concomitant abnormal relaxation and increased filling pressure, suggestive of LVNC. The patient was switched to apixaban. Genetic testing was recommended for family members.

Conclusions: LVNC is rare congenital cardiomyopathy with non-specific symptoms and should be considered among the possible diagnosis in patients presenting with arrythmia patients. Echocardiographic and cardiac magnetic resonance imaging can be utilized to establish diagnosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413176PMC
May 2020

Transverse venous sinus stenosis in idiopathic intracranial hypertension: a prospective pilot study.

Can J Ophthalmol 2020 10 23;55(5):401-405. Epub 2020 Jun 23.

Dalhousie University, Halifax, N.S.; Division of Neuroradiology, Department of Diagnostic Imaging, Nova Scotia Health Authority, Halifax, N.S.; Department of Radiology, University of Manitoba, Winnipeg, MB.. Electronic address:

Objective: Whether transverse venous sinus stenosis (TVSS) causes idiopathic intracranial hypertension (IIH) or is an effect of the increased intracranial pressures is controversial. The purpose of this study was to assess the feasibility of serial imaging in patients with IIH on medical management.

Design And Participants: Patients found to have IIH and TVSS on contrast-enhanced magnetic resonance venography (CEMRV) were recruited in a prospective cohort study. Patients were medically managed and followed with a CEMRV immediately after lumbar puncture, 3-6 months after diagnosis with resolution of IIH symptoms, and 1 year after diagnosis. Ophthalmological data were collected at the time of diagnosis, 3-6 months after diagnosis, and 1 year after diagnosis. Feasibility data, including patient recruitment rate, barriers, and logistical issues, were recorded.

Results: Twenty patients with suspected IIH were screened, and 5 of 7 (71.4%; 95% confidence interval: 36.21-100) eligible patients were enrolled in 1 year, at completion. All recruited patients had clinical resolution of their IIH on medical therapy, and none of them had any obvious change in their TVSS.

Conclusions: Prospective examination of TVSS with serial magnetic resonance imaging in patients with IIH is feasible. TVSS in patients with IIH did not show any change, despite clinical improvement on medical management in all participants.
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http://dx.doi.org/10.1016/j.jcjo.2020.05.008DOI Listing
October 2020

Transmembrane emp24 domain proteins in development and disease.

Genet Res (Camb) 2019 12 27;101:e14. Epub 2019 Dec 27.

Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

Regulated transport through the secretory pathway is essential for embryonic development and homeostasis. Disruptions in this process impact cell fate, differentiation and survival, often resulting in abnormalities in morphogenesis and in disease. Several congenital malformations are caused by mutations in genes coding for proteins that regulate cargo protein transport in the secretory pathway. The severity of mutant phenotypes and the unclear aetiology of transport protein-associated pathologies have motivated research on the regulation and mechanisms through which these proteins contribute to morphogenesis. This review focuses on the role of the p24/transmembrane emp24 domain (TMED) family of cargo receptors in development and disease.
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http://dx.doi.org/10.1017/S0016672319000090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045115PMC
December 2019

Complications of ocular tattooing: a Canadian case series.

Can J Ophthalmol 2019 12 31;54(6):e273-e277. Epub 2019 May 31.

Dalhousie University, Halifax, N.S.

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http://dx.doi.org/10.1016/j.jcjo.2019.03.013DOI Listing
December 2019

Polycystic ovary syndrome (PCOS) is associated with NASH severity and advanced fibrosis.

Liver Int 2020 02 12;40(2):355-359. Epub 2019 Nov 12.

Department of Pathology, UCSF, San Francisco, CA, USA.

Background: Polycystic ovary syndrome (PCOS) affects 10% of reproductive-aged women, and is marked by irregular menses and high androgens. PCOS is a known risk factor for imaging-confirmed steatosis, and we now aim to evaluate whether PCOS influences histologic severity of non-alcoholic fatty liver disease (NAFLD).

Methods: Retrospective study of women ages 18-45 years with biopsy-confirmed NAFLD between 2008 and 2019. Metabolic comorbidities were captured within 6 months of biopsy. Histologic features of non-alcoholic steatohepatitis (NASH) were independently evaluated by two pathologists blinded to PCOS status.

Results: Among 102 women meeting study criteria, 36% (n = 37) had PCOS; median age was 35 years; 27% were white, 6% black, 19% Asian and 47% reported Hispanic ethnicity. Women with PCOS had higher LDL (122 vs 102 mg/dL, P = .05) and body mass index(BMI) (38 vs 33 kg/cm , P < .01). NASH was present in 76% of women with PCOS vs 66% without PCOS (P = .3), and a higher proportion with PCOS had severe ballooning (32% vs 13%, P = .02), presence of any fibrosis (84% vs 66%, P = .06) and advanced fibrosis (16% vs 6%, P = .10). Adjusted for age and BMI, PCOS remained associated with severe hepatocyte ballooning (OR 3.4, 95% CI 1.1-10.6, P = .03) and advanced fibrosis (OR 7.1, 95% CI 1.3-39, P = .02). Among women with advanced fibrosis, median age was 5 years younger in those with as compared to those without PCOS (40 vs 45 years, P = .02).

Conclusion: Polycystic ovary syndrome is independently associated with more severe NASH, including advanced fibrosis. Hepatologists should routinely inquire about PCOS in reproductive-aged women with NAFLD, and evaluate for more severe liver disease in this population.
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http://dx.doi.org/10.1111/liv.14279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6980925PMC
February 2020

Reproducibility of CRISPR-Cas9 methods for generation of conditional mouse alleles: a multi-center evaluation.

Genome Biol 2019 08 26;20(1):171. Epub 2019 Aug 26.

Department of Basic Medicine, Division of Basic Medical Science and Molecular Medicine, School of Medicine, Tokai University, 143, Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.

Background: CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides as donors (referred herein as "two-donor floxing" method).

Results: We re-evaluate the two-donor method from a consortium of 20 laboratories across the world. The dataset constitutes 56 genetic loci, 17,887 zygotes, and 1718 live-born mice, of which only 15 (0.87%) mice contain cKO alleles. We subject the dataset to statistical analyses and a machine learning algorithm, which reveals that none of the factors analyzed was predictive for the success of this method. We test some of the newer methods that use one-donor DNA on 18 loci for which the two-donor approach failed to produce cKO alleles. We find that the one-donor methods are 10- to 20-fold more efficient than the two-donor approach.

Conclusion: We propose that the two-donor method lacks efficiency because it relies on two simultaneous recombination events in cis, an outcome that is dwarfed by pervasive accompanying undesired editing events. The methods that use one-donor DNA are fairly efficient as they rely on only one recombination event, and the probability of correct insertion of the donor cassette without unanticipated mutational events is much higher. Therefore, one-donor methods offer higher efficiencies for the routine generation of cKO animal models.
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http://dx.doi.org/10.1186/s13059-019-1776-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709553PMC
August 2019

Catalytic asymmetric oxo-Diels-Alder reactions with chiral atropisomeric biphenyl diols.

Beilstein J Org Chem 2019 18;15:955-962. Epub 2019 Apr 18.

The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, PR China.

New chiral atropisomeric biphenyl diols , and containing additional peripheral chiral centers with different steric bulkiness and/or electronic properties were synthesized. The X-ray crystal structure of shows the formation of a supramolecular structure whereas that of , containing additional CF substituents, shows the formation of a monomeric structure. Diols - were found to be active organocatalysts in oxo-Diels-Alder reactions in which recorded a 72% ee with trimethylacetaldehyde as a substrate.
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http://dx.doi.org/10.3762/bjoc.15.92DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541354PMC
April 2019

Irreversibility of transverse venous sinus stenosis and optic nerve edema post-lumbar puncture in idiopathic intracranial hypertension.

Can J Ophthalmol 2019 04 25;54(2):e57-e59. Epub 2018 Aug 25.

Department of Diagnostic Radiology, Dalhousie University, Halifax, N.S., Canada.

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http://dx.doi.org/10.1016/j.jcjo.2018.06.023DOI Listing
April 2019

Triboluminescence of Centrosymmetric Lanthanide β-Diketonate Complexes with Aggregation-Induced Emission.

Molecules 2019 Feb 13;24(4). Epub 2019 Feb 13.

Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hung Hom, Kowloon 999077, Hong Kong, China.

Triboluminescence (TL) is a form of light emission induced upon mechanical forces on the material. However, our understanding of this phenomenon is still unclear and more examples are therefore needed in order to elucidate its mechanism. In this work, two types of TL complexes, [Eu(-dbm-Cl₂)₃phen] and [Eu(-dbm-Cl₂)₃phen], which also displays aggregation-induced emission (AIE) were synthesized and investigated for its photo-physical and crystal structural properties. These complexes were crystallized in a centro-symmetric space group 2₁/, and remarkably, displayed TL upon grinding that may be due to the presence of extensive π···π, C-H···π and C-H···Cl-C interactions in the close molecular packing of its structure. This rare example deviates from the widely accepted mechanism of TL, hence widening the scope of our understanding in the area.
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http://dx.doi.org/10.3390/molecules24040662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412301PMC
February 2019

Synthesis of a Conformationally Stable Atropisomeric Pair of Biphenyl Scaffold Containing Additional Stereogenic Centers.

Molecules 2019 Feb 12;24(3). Epub 2019 Feb 12.

The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, PR China.

The synthesis of a new CF₃-containing stereogenic atropisomeric pair of ortho-disubstituted biphenyl scaffold is presented. The atropisomers are surprisingly conformationally stable for isolation. X-ray structures show that their stability comes from an intramolecular hydrogen bond formation from their two hydroxyl groups and renders the spatial arrangement of their peripheral CF₃ and CH₃ groups very different. The synthesized stereogenic scaffold proved to be effective in catalyzing the asymmetric -nitroso aldol reaction of enamine and nitrosobenzene. Compared to similar scaffolds without CF₃ groups, one of our atropisomer exhibits an increase in enantioselectivity in this reaction.
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http://dx.doi.org/10.3390/molecules24030643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385101PMC
February 2019

An Integrative Systems Biology and Experimental Approach Identifies Convergence of Epithelial Plasticity, Metabolism, and Autophagy to Promote Chemoresistance.

J Clin Med 2019 Feb 7;8(2). Epub 2019 Feb 7.

Duke Cancer Institute and the Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.

The evolution of therapeutic resistance is a major cause of death for cancer patients. The development of therapy resistance is shaped by the ecological dynamics within the tumor microenvironment and the selective pressure of the host immune system. These selective forces often lead to evolutionary convergence on pathways or hallmarks that drive progression. Thus, a deeper understanding of the evolutionary convergences that occur could reveal vulnerabilities to treat therapy-resistant cancer. To this end, we combined phylogenetic clustering, systems biology analyses, and molecular experimentation to identify convergences in gene expression data onto common signaling pathways. We applied these methods to derive new insights about the networks at play during transforming growth factor-β (TGF-β)-mediated epithelial⁻mesenchymal transition in lung cancer. Phylogenetic analyses of gene expression data from TGF-β-treated cells revealed convergence of cells toward amine metabolic pathways and autophagy during TGF-β treatment. Knockdown of the autophagy regulatory, ATG16L1, re-sensitized lung cancer cells to cancer therapies following TGF-β-induced resistance, implicating autophagy as a TGF-β-mediated chemoresistance mechanism. In addition, high ATG16L expression was found to be a poor prognostic marker in multiple cancer types. These analyses reveal the usefulness of combining evolutionary and systems biology methods with experimental validation to illuminate new therapeutic vulnerabilities for cancer.
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http://dx.doi.org/10.3390/jcm8020205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406733PMC
February 2019

Achieving NIR Emission for Donor-Acceptor Type Platinum(II) Complexes by Adjusting Coordination Position with Isomeric Ligands.

Inorg Chem 2018 Nov 2;57(22):14208-14217. Epub 2018 Nov 2.

Institute of Molecular Functional Materials and Department of Applied Biology and Chemical Technology , The Hong Kong Polytechnic University , Hung Hom, Hong Kong , P. R. China.

Four platinum(II) complexes Pt-1, Pt-2, Pt-3, and Pt-4 with the isomeric donor-acceptor (D-A) conjugated ligand framework are designed and prepared, and their thermal, photophysical, and electrochemical characteristics investigated. Crystal structures for Pt-1 and Pt-4 are determined with single-crystal X-ray diffraction analysis, showing distorted and nonplanar geometry. Complex Pt-4 exhibits much greater distortion, attributed to the steric interactions between benzothiadiazole and naphthalene. Remarkably different photophysical, electrochemical, and electroluminescent properties are found for these platinum(II) complexes. Photoluminescence wavelengths of these complexes range from 590 to 800 nm with bandgaps of 1.7-2.0 eV. Coordination with [1,2,5]thiadiazolo[3,4- c]pyridine and triphenylamine can enhance D-A interactions, reducing the bandgap and producing near-infrared emission for Pt-3. Organic light-emitting devices (OLEDs) display electroluminescence with emission peaks at 626, 645, 826, and 571 nm, with maximum external quantum efficiencies of 0.13%, 0.04%, 0.49%, and 0.22% for Pt-1, Pt-2, Pt-3, and Pt-4 doped OLEDs, respectively. Thus, adjusting the coordination position with the isomeric conjugation framework ligand is an appropriate strategy to tune the light-emitting properties of platinum complexes in OLEDs.
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http://dx.doi.org/10.1021/acs.inorgchem.8b02220DOI Listing
November 2018

Transient myopic shift due to ciliary body detachment as the sole ocular manifestation of hypertensive emergency - A case report.

Am J Ophthalmol Case Rep 2018 Sep 20;11:84-86. Epub 2018 Jun 20.

Department of Ophthalmology and Visual Sciences, Dalhousie University, QEII Health Sciences Centre, 2035-2 West Victoria Building, 1276 South Park Street, Halifax, Nova Scotia, Canada, B3H 2Y9.

Purpose: Hypertensive emergency usually presents to ophthalmologists in the form of hypertensive retinopathy. We present a case of hypertensive emergency that presented as bilateral transient myopic shift due to ciliary body detachment in the absence of any retinal pathology. The purpose of this paper is to showcase another ocular manifestation of hypertensive emergency.

Observations: A 35 year-old female with a blood pressure of 192/114 mmHg presented to the emergency department with headache and acute onset blurry vision. Computed Tomography (CT) of the head, and lumbar puncture were within normal limits. Visual acuity was counting fingers in the right eye and 6/90 in the left eye, both of which improved to 6/9 with -5.00 diopters spherical correction in the right eye, and -4.75 diopters correction in the left eye. Intraocular pressures were normal. Anterior chambers were shallow, and there were no retinal changes on dilated fundus examination. Enhanced-depth optical coherence tomography (EDI-OCT) showed bilateral increased choroidal thickness and ultrasound biomicroscopy (UBM) showed 360° ciliary body detachment with angle closure. With improved blood pressure control, her ciliary body detachment resolved and her refractive error returned to baseline.

Conclusions: & Importance: Hypertensive emergency may present with choroidal thickening with anterior ciliary body rotation and detachment. A review of medications is important, as this presentation has also been reported as a rare side effect of sulphonamide drugs. In the absence of retinopathy, UBM and EDI-OCT imaging should be considered in the acutely hypertensive patient presenting with myopic shift.
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http://dx.doi.org/10.1016/j.ajoc.2018.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019763PMC
September 2018

Assembly of Lanthanide(III) Cubanes and Dimers with Single-Molecule Magnetism and Photoluminescence.

Inorg Chem 2018 Jun 29;57(12):6893-6902. Epub 2018 May 29.

Department of Applied Biology and Chemical Technology , The Hong Kong Polytechnic University , Hung Hom , Kowloon 999077 , Hong Kong.

Discrete lanthanide(III) tetranuclear cubane-like clusters seldom occur throughout the Ln series and behave as single-molecule magnets (SMMs). Herein, a series of cubanes, [Ln(μ-OH)(μ-tfa)(hfa)(phen)] (1-9, Ln = La-Dy (except Pm), tfa = trifluoroacetate, hfa = hexafluoroacetylacetonate, phen = 1,10-phenanthroline), and dinuclear clusters, [Ln(μ-OH)(hfa)(phen)] (10-16, Ln = Tb-Lu), were synthesized and characterized. Two types of clusters were formed due to the change of preferred coordination geometry for lighter and heavier Ln ions which favor nine-coordinated cubanes and eight-coordinated dimers, respectively. A magnetic study shows that 8-Tb and 9-Dy are ferromagnetically coupled and SMM in nature because of the larger Ln···Ln distance compared to other discrete cubanes. The anisotropic barriers, U, of 9-Dy are determined to be 67.0 K. In addition, the photophysical properties of 6-Eu, 8-Tb, and 10-Tb owing to tfa, hfa, and phen sensitization and O-H quenching are discussed.
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http://dx.doi.org/10.1021/acs.inorgchem.8b00505DOI Listing
June 2018

NUT carcinoma of the sinonasal tract infiltrating the orbit in a man with birdshot chorioretinitis.

Saudi J Ophthalmol 2018 Jan-Mar;32(1):62-65. Epub 2018 Mar 9.

Department of Ophthalmology & Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.

A 48-year-old man with a history of birdshot chorioretinitis presented with blurry vision, retro-bulbar pain and sinusitis. Though visual acuity was unaffected, he had left optic disc oedema and mild restriction of left eye abduction. His symptoms progressed quickly, with diplopia in primary gaze, epistaxis from his left nostril, and a left relative afferent pupillary defect (RAPD). On computed tomography, there was a mass in the nasal cavity that extended through the left cribriform plate and lamina papyracea and posteriorly into the optic canal. Pathological examination of biopsy specimens revealed sheets of undifferentiated cells with extensive areas of necrosis and islands of squamous differentiation. The tumour cells expressed monokeratin, p63, CD34, and p16. Molecular testing indicated rearrangement of the (15q14) locus and fusion of the and (19p13.12) loci, confirming the diagnosis of NUT carcinoma of the sinonasal tract. This is the first reported case of NUT carcinoma in a patient with birdshot chorioretinitis. The onset of chorioretinitis may have been the earliest sign of the effects of the BRD4-NUTM1 fusion protein, resulting in expression of HLA-A29. There is evidence that bromodomain and extra terminal (BET) family proteins play a role in inflammatory marker expression.
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http://dx.doi.org/10.1016/j.sjopt.2018.02.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943985PMC
March 2018

Chiral DOTA chelators as an improved platform for biomedical imaging and therapy applications.

Nat Commun 2018 02 27;9(1):857. Epub 2018 Feb 27.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, China.

Despite established clinical utilisation, there is an increasing need for safer, more inert gadolinium-based contrast agents, and for chelators that react rapidly with radiometals. Here we report the syntheses of a series of chiral DOTA chelators and their corresponding metal complexes and reveal properties that transcend the parent DOTA compound. We incorporated symmetrical chiral substituents around the tetraaza ring, imparting enhanced rigidity to the DOTA cavity, enabling control over the range of stereoisomers of the lanthanide complexes. The Gd chiral DOTA complexes are shown to be orders of magnitude more inert to Gd release than [GdDOTA]. These compounds also exhibit very-fast water exchange rates in an optimal range for high field imaging. Radiolabeling studies with (Cu-64/Lu-177) also demonstrate faster labelling properties. These chiral DOTA chelators are alternative general platforms for the development of stable, high relaxivity contrast agents, and for radiometal complexes used for imaging and/or therapy.
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http://dx.doi.org/10.1038/s41467-018-03315-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829242PMC
February 2018

Cobalamin-Associated Superoxide Scavenging in Neuronal Cells Is a Potential Mechanism for Vitamin B-Deprivation Optic Neuropathy.

Am J Pathol 2018 01 14;188(1):160-172. Epub 2017 Oct 14.

Maisonneuve-Rosemont Hospital Research Center and Department of Ophthalmology, University of Montreal, Montreal, Quebec, Canada; Department of Ophthalmology, McGill University, Montreal, Quebec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada; Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Electronic address:

Chronic deficiency of vitamin B is the only nutritional deficiency definitively proved to cause optic neuropathy and loss of vision. The mechanism by which this occurs is unknown. Optic neuropathies are associated with death of retinal ganglion cells (RGCs), neurons that project their axons along the optic nerve to the brain. Injury to RGC axons causes a burst of intracellular superoxide, which then signals RGC apoptosis. Vitamin B (cobalamin) was recently shown to be a superoxide scavenger, with a rate constant similar to superoxide dismutase. Given that vitamin B deficiency causes an optic neuropathy through unknown mechanisms and that it is a potent superoxide scavenger, we tested whether cobalamin, a vitamin B vitamer, would be neuroprotective in vitro and in vivo. We found that cobalamin scavenged superoxide in neuronal cells in vitro treated with the reduction-oxidation cycling agent menadione. In vivo confocal scanning laser ophthalmoscopy demonstrated that optic nerve transection in Long-Evans rats increased superoxide levels in RGCs. The RGC superoxide burst was significantly reduced by intravitreal cobalamin and resulted in increased RGC survival. These data demonstrate that cobalamin may function as an endogenous neuroprotectant for RGCs through a superoxide-associated mechanism.
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http://dx.doi.org/10.1016/j.ajpath.2017.08.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5745528PMC
January 2018

Gynecologic cancer in HIV-infected women: treatment and outcomes in a multi-institutional cohort.

AIDS 2018 Jan;32(2):171-177

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health.

Objective: To evaluate gynecologic cancer treatments in HIV-infected women for adherence to National Comprehensive Cancer Network (NCCN) guidelines and to describe survival by adherence to guidelines.

Design: Beyond cervical cancer, there are little data on treatment and outcomes for these women. This is a retrospective cohort study of HIV-infected women with gynecologic cancers.

Methods: HIV-infected women with gynecologic cancers from 2000 to 2015 were identified at two urban, comprehensive cancer centers. Chart reviews extracted demographic, HIV, and cancer-related variables. Cancer treatment was evaluated for adherence to NCCN guidelines. Overall survival was compared between those who received NCCN adherent and nonadherent cancer care.

Results: Fifty-seven women were identified; 15 vulvar (26%), 26 cervical (46%), nine ovarian (16%), and seven endometrial (12%) cancers. Median time from HIV to cancer diagnosis was 8.5 years, and 88% of women were black. Thirty patients (53%) had stage I, and 27 (47%) had stage II-IV disease. Overall, 28 women (49%) received NCCN-adherent care; 22 of 30 stage I (73%) and six of 27 stage II-IV patients (22%). Among 29 women not receiving NCCN-adherent care, 69% were due to patient-related factors or toxicity. Among women with II-IV cancers, 48-month survival was higher in women who received NCCN-adherent care than those who did not (60 versus 28%).

Conclusion: Most HIV-infected women with advanced gynecologic cancers did not receive NCCN-adherent care and had worse survival compared to those who did. Focus on treatment-related toxicities and patient-related barriers to cancer care are necessary in this population.
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http://dx.doi.org/10.1097/QAD.0000000000001664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5921933PMC
January 2018

Cascade Amination and Acetone Monoarylation with Aryl Iodides by Palladium/Norbornene Cooperative Catalysis.

Org Lett 2017 08 31;19(16):4335-4338. Epub 2017 Jul 31.

Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University , Hung Hom, Kowloon, Hong Kong.

A palladium/norbornene cocatalyzed three-component reaction of aryl iodides, O-benzoylhydroxylamines, and acetone is reported. o'-Aminoaryl acetones or o,o'-diaminoaryl acetones are efficiently prepared via tandem ortho-C-H amination/ipso-C-I α-arylation sequence, and the regiospecificity has been confirmed by X-ray analysis. The proposed method addresses the condensation/amination of free-N-H-bearing substrates in acetone monoarylations and the synthesis of extremely congested 2,6-disubstituted aryl acetones.
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http://dx.doi.org/10.1021/acs.orglett.7b02023DOI Listing
August 2017

Regioselective Synthesis of Polycyclic and Heptagon-embedded Aromatic Compounds through a Versatile π-Extension of Aryl Halides.

Angew Chem Int Ed Engl 2017 06 16;56(25):7166-7170. Epub 2017 May 16.

Department of Applied Biology and Chemical Technology & SKLC, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, Hong Kong.

A versatile π-extension reaction was developed based on the three-component cross-coupling of aryl halides, 2-haloarylcarboxylic acids, and norbornadiene. The transformation is driven by the direction and subsequent decarboxylation of the carboxyl group, while norbornadiene serves as an ortho-C-H activator and ethylene synthon via a retro-Diels-Alder reaction. Comprehensive DFT calculations were performed to account for the catalytic intermediates.
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http://dx.doi.org/10.1002/anie.201703551DOI Listing
June 2017

Mechanistic Investigation of Inducing Triboluminescence in Lanthanide(III) β-Diketonate Complexes.

Inorg Chem 2017 May 7;56(9):5135-5140. Epub 2017 Apr 7.

Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University , Hung Hom, Hong Kong.

In this work, we synthesized a series of lanthanide(III) β-diketonate complexes to investigate the induction of triboluminescence. Triboluminescence (TL) spectra, solid-state emission spectra, and luminescence lifetimes of the complexes were obtained to prove consistent emitting species for steady-state and triboluminescence measurements. Detailed analyses of the crystal lattice packing were conducted in an attempt to correlate crystal symmetry, gas discharge, and structural arrangements with "triboexcitation", and it is found that either noncentrosymmetric or centrosymmetic compounds can be TL-active. Furthermore, an intensely TL compound, Eu(dbm)TMP, was achieved, and its light emission can be seen under daylight upon mechanical stress.
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http://dx.doi.org/10.1021/acs.inorgchem.7b00273DOI Listing
May 2017

Deep vein thrombosis in a transgender woman.

CMAJ 2017 04;189(13):E502-E504

Department of Opthalmology and Visual Sciences (Chan), Queen Elizabeth II Health Sciences Centre, Halifax, NS; Stettler Medical Clinic (Drummond), Stettler, Alta.; Department of Family Medicine (Kelly); University of Calgary Cumming School of Medicine, Calgary, Alta.

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http://dx.doi.org/10.1503/cmaj.160408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378510PMC
April 2017

Retinal thickness measured with optical coherence tomography and risk of disability worsening in multiple sclerosis: a cohort study.

Lancet Neurol 2016 May 18;15(6):574-84. Epub 2016 Mar 18.

University of Calgary, Calgary, AB, Canada.

Background: Most patients with multiple sclerosis without previous optic neuritis have thinner retinal layers than healthy controls. We assessed the role of peripapillary retinal nerve fibre layer (pRNFL) thickness and macular volume in eyes with no history of optic neuritis as a biomarker of disability worsening in a cohort of patients with multiple sclerosis who had at least one eye without optic neuritis available.

Methods: In this multicentre, cohort study, we collected data about patients (age ≥16 years old) with clinically isolated syndrome, relapsing-remitting multiple sclerosis, and progressive multiple sclerosis. Patients were recruited from centres in Spain, Italy, France, Germany, Czech Republic, Netherlands, Canada, and the USA, with the first cohort starting in 2008 and the latest cohort starting in 2013. We assessed disability worsening using the Expanded Disability Status Scale (EDSS). The pRNFL thickness and macular volume were assessed once at study entry (baseline) by optical coherence tomography (OCT) and was calculated as the mean value of both eyes without optic neuritis for patients without a history of optic neuritis or the value of the non-optic neuritis eye for patients with previous unilateral optic neuritis. Researchers who did the OCT at baseline were masked to EDSS results and the researchers assessing disability with EDSS were masked to OCT results. We estimated the association of pRNFL thickness or macular volume at baseline in eyes without optic neuritis with the risk of subsequent disability worsening by use of proportional hazards models that included OCT metrics and age, disease duration, disability, presence of previous unilateral optic neuritis, and use of disease-modifying therapies as covariates.

Findings: 879 patients with clinically isolated syndrome (n=74), relapsing-remitting multiple sclerosis (n=664), or progressive multiple sclerosis (n=141) were included in the primary analyses. Disability worsening occurred in 252 (29%) of 879 patients with multiple sclerosis after a median follow-up of 2·0 years (range 0·5-5 years). Patients with a pRNFL of less than or equal to 87 μm or less than or equal to 88 μm (measured with Spectralis or Cirrus OCT devices) had double the risk of disability worsening at any time after the first and up to the third years of follow-up (hazard ratio 2·06, 95% CI 1·36-3·11; p=0·001), and the risk was increased by nearly four times after the third and up to the fifth years of follow-up (3·81, 1·63-8·91; p=0·002). We did not identify meaningful associations for macular volume.

Interpretation: Our results provide evidence of the usefulness of monitoring pRNFL thickness by OCT for prediction of the risk of disability worsening with time in patients with multiple sclerosis.

Funding: Instituto de Salud Carlos III.
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http://dx.doi.org/10.1016/S1474-4422(16)00068-5DOI Listing
May 2016
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