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Articles 61 - 90 of 116
Full-Text Articles in Eye Diseases
Immunologic Basis For Development Of Keratoconjunctivitis Sicca In Systemic Autoimmune Diseases: Role Of Innate Immune Sensors, Michael E Stern, Argyrios N Theofilopoulos, Philipp Steven, Jerry Y Niederkorn, Robert Fox, Margarita Calonge, Christof Scheid, Stephen C Pflugfelder
Immunologic Basis For Development Of Keratoconjunctivitis Sicca In Systemic Autoimmune Diseases: Role Of Innate Immune Sensors, Michael E Stern, Argyrios N Theofilopoulos, Philipp Steven, Jerry Y Niederkorn, Robert Fox, Margarita Calonge, Christof Scheid, Stephen C Pflugfelder
Faculty, Staff and Students Publications
The literature is filled with citations reporting an increased incidence of chronic dry eye disease, also known as keratoconjunctivitis sicca, in patients with systemic autoimmune diseases such as rheumatoid arthritis, Sjögren's Syndrome, systemic sclerosis and lupus. As the most environmentally exposed mucosal surface of the body, the conjunctiva constantly responds to environmental challenges which are typically self limited, but when persistent and unresolved may provoke pathogenic innate and adaptive immune reactions. Our understanding of the pathophysiological mechanisms by which systemic autoimmune diseases cause dry eye inducing ocular surface inflammation continues to evolve. Conjunctival immune tone responds to self or foreign …
A Double-Blind, Randomized Controlled Study Of The Effects Of Celecoxib On Clinical Symptoms And Cognitive Impairment In Patients With Drug-Naïve First Episode Schizophrenia: Pharmacogenetic Impact Of Cyclooxygenase-2 Functional Polymorphisms, Dong-Mei Wang, Da-Chun Chen, Mei-Hong Xiu, Li Wang, Thomas R Kosten, Xiang-Yang Zhang
A Double-Blind, Randomized Controlled Study Of The Effects Of Celecoxib On Clinical Symptoms And Cognitive Impairment In Patients With Drug-Naïve First Episode Schizophrenia: Pharmacogenetic Impact Of Cyclooxygenase-2 Functional Polymorphisms, Dong-Mei Wang, Da-Chun Chen, Mei-Hong Xiu, Li Wang, Thomas R Kosten, Xiang-Yang Zhang
Faculty, Staff and Students Publications
Chronic low-grade peripheral and central nervous system inflammation may have a role in the pathogenesis of schizophrenia (SCZ). Inhibition of cyclooxygenase-2 (COX2), the arachidonic acid pathway, may inhibit cytokine responses and minimize inflammation. In this study, we added the COX2 inhibitor celecoxib to risperidone monotherapy to examine its efficacy on clinical symptoms and cognitive deficits in drug-naïve first episode (DNFE) SCZ patients. First, we genotyped two polymorphisms (rs5275 and rs689466) in the COX-2 gene in a case-control study of 353 SCZ patients and 422 healthy controls. Ninety patients participated in a 12-week, double-blind, randomized, placebo-controlled trial of celecoxib 400 mg/day. …
Functional Vision In Patients With Biallelic Ush2a Variants, Elise Heon, Michele Melia, Laura E Bocchino, Lassana Samarakoon, Jacque L Duncan, Allison R Ayala, Isabelle Audo, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Carel B Hoyng, Nieraj Jain, Kanishka T Jayasundera, Mark E Pennesi, Christina Y Weng, Foundation Fighting Blindness Consortium Investigator Group
Functional Vision In Patients With Biallelic Ush2a Variants, Elise Heon, Michele Melia, Laura E Bocchino, Lassana Samarakoon, Jacque L Duncan, Allison R Ayala, Isabelle Audo, Chris Bradley, Janet K Cheetham, Gislin Dagnelie, Todd A Durham, Carel B Hoyng, Nieraj Jain, Kanishka T Jayasundera, Mark E Pennesi, Christina Y Weng, Foundation Fighting Blindness Consortium Investigator Group
Faculty, Staff and Students Publications
Purpose: To describe functional vision (FV) and investigate the relationship between FV, visual acuity (VA), and hill of vision (VTOT) at baseline in patients with biallelic USH2A variants.
Design: Multicenter, international, cross-sectional study.
Methods: In individuals with biallelic disease-causing variants in USH2A, clinical diagnosis of Usher syndrome type 2 (USH2) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP) was based on history of hearing loss and audiology examinations. The VALVVFQ-48 was administered verbally to participants ≥18 years old. VA was measured in both eyes; VTOT was determined from static perimetry in the study eye (better VA). FV scores were calculated using …
Reply: Efficacy Of Segmented Axial Length And Artificial Intelligence Approaches To Intraocular Lens Power Calculation In Short Eyes, Karim Kozhaya, Peter I Kenny, Li Wang, Mitchell P Weikert, Douglas D Koch
Reply: Efficacy Of Segmented Axial Length And Artificial Intelligence Approaches To Intraocular Lens Power Calculation In Short Eyes, Karim Kozhaya, Peter I Kenny, Li Wang, Mitchell P Weikert, Douglas D Koch
Faculty, Staff and Students Publications
No abstract provided.
Smaller Total And Subregional Cerebellar Volumes In Posttraumatic Stress Disorder: A Mega-Analysis By The Enigma-Pgc Ptsd Workgroup, Ashley A Huggins, C Lexi Baird, Melvin Briggs, Sarah Laskowitz, Ahmed Hussain, Samar Fouda, Courtney Haswell, Delin Sun, Lauren E Salminen, Neda Jahanshad, Sophia I Thomopoulos, Dick J Veltman, Jessie L Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawjin, Li Wang, Ye Zhu, Gen Li, Dan J Stein, Jonathan Ipser, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Benjamin Suarez-Jimenez, Xi Zhu, Yoojean Kim, Xiaofu He, Sigal Zilcha-Mano, Amit Lazarov, Yuval Neria, Jennifer S Stevens, Kerry J Ressler, Tanja Jovanovic, Sanne J H Van Rooij, Negar Fani, Anna R Hudson, Sven C Mueller, Anika Sierk, Antje Manthey, Henrik Walter, Judith K Daniels, Christian Schmahl, Julia I Herzog, Pavel Říha, Ivan Rektor, Lauren A M Lebois, Milissa L Kaufman, Elizabeth A Olson, Justin T Baker, Isabelle M Rosso, Anthony P King, Isreal Liberzon, Mike Angstadt, Nicholas D Davenport, Scott R Sponheim, Seth G Disner, Thomas Straube, David Hofmann, Rongfeng Qi, Guang Ming Lu, Lee A Baugh, Gina L Forster, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Adi Maron-Katz, Amit Etkin, Andrew S Cotton, Erin N O'Leary, Hong Xie, Xin Wang, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven Bruce, Josh Cisler, Marisa Ross, Ryan J Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, William S Kremen, Michael J Lyons, Carol E Franz, Evan M Gordon, Geoffrey May, Steven M Nelson, Chadi G Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H Krystal, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elizabeth A Wilde, Ian H Harding, Rebecca Kerestes, Paul M Thompson, Rajendra Morey
Smaller Total And Subregional Cerebellar Volumes In Posttraumatic Stress Disorder: A Mega-Analysis By The Enigma-Pgc Ptsd Workgroup, Ashley A Huggins, C Lexi Baird, Melvin Briggs, Sarah Laskowitz, Ahmed Hussain, Samar Fouda, Courtney Haswell, Delin Sun, Lauren E Salminen, Neda Jahanshad, Sophia I Thomopoulos, Dick J Veltman, Jessie L Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawjin, Li Wang, Ye Zhu, Gen Li, Dan J Stein, Jonathan Ipser, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Benjamin Suarez-Jimenez, Xi Zhu, Yoojean Kim, Xiaofu He, Sigal Zilcha-Mano, Amit Lazarov, Yuval Neria, Jennifer S Stevens, Kerry J Ressler, Tanja Jovanovic, Sanne J H Van Rooij, Negar Fani, Anna R Hudson, Sven C Mueller, Anika Sierk, Antje Manthey, Henrik Walter, Judith K Daniels, Christian Schmahl, Julia I Herzog, Pavel Říha, Ivan Rektor, Lauren A M Lebois, Milissa L Kaufman, Elizabeth A Olson, Justin T Baker, Isabelle M Rosso, Anthony P King, Isreal Liberzon, Mike Angstadt, Nicholas D Davenport, Scott R Sponheim, Seth G Disner, Thomas Straube, David Hofmann, Rongfeng Qi, Guang Ming Lu, Lee A Baugh, Gina L Forster, Raluca M Simons, Jeffrey S Simons, Vincent A Magnotta, Kelene A Fercho, Adi Maron-Katz, Amit Etkin, Andrew S Cotton, Erin N O'Leary, Hong Xie, Xin Wang, Yann Quidé, Wissam El-Hage, Shmuel Lissek, Hannah Berg, Steven Bruce, Josh Cisler, Marisa Ross, Ryan J Herringa, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Carissa W Tomas, Jacklynn M Fitzgerald, Jennifer Urbano Blackford, Bunmi O Olatunji, William S Kremen, Michael J Lyons, Carol E Franz, Evan M Gordon, Geoffrey May, Steven M Nelson, Chadi G Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H Krystal, Emily L Dennis, David F Tate, David X Cifu, William C Walker, Elizabeth A Wilde, Ian H Harding, Rebecca Kerestes, Paul M Thompson, Rajendra Morey
Faculty, Staff and Students Publications
Although the cerebellum contributes to higher-order cognitive and emotional functions relevant to posttraumatic stress disorder (PTSD), prior research on cerebellar volume in PTSD is scant, particularly when considering subregions that differentially map on to motor, cognitive, and affective functions. In a sample of 4215 adults (PTSD n = 1642; Control n = 2573) across 40 sites from the ENIGMA-PGC PTSD working group, we employed a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation to obtain volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to …
Centriole And Transition Zone Structures In Photoreceptor Cilia Revealed By Cryo-Electron Tomography, Zhixian Zhang, Abigail R Moye, Feng He, Muyuan Chen, Melina A Agosto, Theodore G Wensel
Centriole And Transition Zone Structures In Photoreceptor Cilia Revealed By Cryo-Electron Tomography, Zhixian Zhang, Abigail R Moye, Feng He, Muyuan Chen, Melina A Agosto, Theodore G Wensel
Faculty, Staff and Students Publications
Primary cilia mediate sensory signaling in multiple organisms and cell types but have structures adapted for specific roles. Structural defects in them lead to devastating diseases known as ciliopathies in humans. Key to their functions are structures at their base: the basal body, the transition zone, the "Y-shaped links," and the "ciliary necklace." We have used cryo-electron tomography with subtomogram averaging and conventional transmission electron microscopy to elucidate the structures associated with the basal region of the "connecting cilia" of rod outer segments in mouse retina. The longitudinal variations in microtubule (MT) structures and the lumenal scaffold complexes connecting them …
Ectoine, From A Natural Bacteria Protectant To A New Treatment Of Dry Eye Disease, Xin Chen, Na Lin, Jin-Miao Li, Haixia Liu, Anmar Abu-Romman, Ebru Yaman, Fang Bian, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li
Ectoine, From A Natural Bacteria Protectant To A New Treatment Of Dry Eye Disease, Xin Chen, Na Lin, Jin-Miao Li, Haixia Liu, Anmar Abu-Romman, Ebru Yaman, Fang Bian, Cintia S De Paiva, Stephen C Pflugfelder, De-Quan Li
Faculty, Staff and Students Publications
Ectoine, a novel natural osmoprotectant, protects bacteria living in extreme environments. This study aimed to explore the therapeutic effect of ectoine for dry eye disease. An experimental dry eye model was created in C57BL/6 mice exposed to desiccating stress (DS) with untreated mice as controls (UT). DS mice were dosed topically with 0.5-2.0% of ectoine or a vehicle control. Corneal epithelial defects were detected via corneal smoothness and Oregon Green dextran (OGD) fluorescent staining. Pro-inflammatory cytokines and chemokines were evaluated using RT-qPCR and immunofluorescent staining. Compared with UT mice, corneal epithelial defects were observed as corneal smoothness irregularities and strong …
Examining The Association Between Posttraumatic Stress Disorder And Disruptions In Cortical Networks Identified Using Data-Driven Methods, Jin Yang, Ashley A Huggins, Delin Sun, C Lexi Baird, Courtney C Haswell, Jessie L Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Dick J Veltman, Benjamin Suarez-Jimenez, Xi Zhu, Yuval Neria, Anna R Hudson, Sven C Mueller, Justin T Baker, Lauren A M Lebois, Milissa L Kaufman, Rongfeng Qi, Guang Ming Lu, Pavel Říha, Ivan Rektor, Emily L Dennis, Christopher R K Ching, Sophia I Thomopoulos, Lauren E Salminen, Neda Jahanshad, Paul M Thompson, Dan J Stein, Sheri M Koopowitz, Jonathan C Ipser, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Li Wang, Ye Zhu, Gen Li, Anika Sierk, Antje Manthey, Henrik Walter, Judith K Daniels, Christian Schmahl, Julia I Herzog, Israel Liberzon, Anthony King, Mike Angstadt, Nicholas D Davenport, Scott R Sponheim, Seth G Disner, Thomas Straube, David Hofmann, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Jennifer U Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Chadi G Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H Krystal, Rajendra A Morey, Aristeidis Sotiras
Examining The Association Between Posttraumatic Stress Disorder And Disruptions In Cortical Networks Identified Using Data-Driven Methods, Jin Yang, Ashley A Huggins, Delin Sun, C Lexi Baird, Courtney C Haswell, Jessie L Frijling, Miranda Olff, Mirjam Van Zuiden, Saskia B J Koch, Laura Nawijn, Dick J Veltman, Benjamin Suarez-Jimenez, Xi Zhu, Yuval Neria, Anna R Hudson, Sven C Mueller, Justin T Baker, Lauren A M Lebois, Milissa L Kaufman, Rongfeng Qi, Guang Ming Lu, Pavel Říha, Ivan Rektor, Emily L Dennis, Christopher R K Ching, Sophia I Thomopoulos, Lauren E Salminen, Neda Jahanshad, Paul M Thompson, Dan J Stein, Sheri M Koopowitz, Jonathan C Ipser, Soraya Seedat, Stefan Du Plessis, Leigh L Van Den Heuvel, Li Wang, Ye Zhu, Gen Li, Anika Sierk, Antje Manthey, Henrik Walter, Judith K Daniels, Christian Schmahl, Julia I Herzog, Israel Liberzon, Anthony King, Mike Angstadt, Nicholas D Davenport, Scott R Sponheim, Seth G Disner, Thomas Straube, David Hofmann, Daniel W Grupe, Jack B Nitschke, Richard J Davidson, Christine L Larson, Terri A Deroon-Cassini, Jennifer U Blackford, Bunmi O Olatunji, Evan M Gordon, Geoffrey May, Steven M Nelson, Chadi G Abdallah, Ifat Levy, Ilan Harpaz-Rotem, John H Krystal, Rajendra A Morey, Aristeidis Sotiras
Faculty, Staff and Students Publications
Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD …
Biallelic Variants In Rbm42 Cause A Multisystem Disorder With Neurological, Facial, Cardiac, And Musculoskeletal Involvement, Yiyao Chen, Bingxin Yang, Xiaoyu Merlin Zhang, Songchang Chen, Minhui Wang, Liya Hu, Nina Pan, Shuyuan Li, Weihui Shi, Zhenhua Yang, Li Wang, Yajing Tan, Jian Wang, Yanlin Wang, Qinghe Xing, Zhonghua Ma, Jinsong Li, He-Feng Huang, Jinglan Zhang, Chenming Xu
Biallelic Variants In Rbm42 Cause A Multisystem Disorder With Neurological, Facial, Cardiac, And Musculoskeletal Involvement, Yiyao Chen, Bingxin Yang, Xiaoyu Merlin Zhang, Songchang Chen, Minhui Wang, Liya Hu, Nina Pan, Shuyuan Li, Weihui Shi, Zhenhua Yang, Li Wang, Yajing Tan, Jian Wang, Yanlin Wang, Qinghe Xing, Zhonghua Ma, Jinsong Li, He-Feng Huang, Jinglan Zhang, Chenming Xu
Faculty, Staff and Students Publications
Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of …
Editorial: Managing Cancer Metastasis By Tackling Anticancer Drug Resistance, Erxi Wu, Zhongzhi Wu, Chao-Yie Yang, Dan Qi, Xiaoxiao Hu, Wei Li
Editorial: Managing Cancer Metastasis By Tackling Anticancer Drug Resistance, Erxi Wu, Zhongzhi Wu, Chao-Yie Yang, Dan Qi, Xiaoxiao Hu, Wei Li
Faculty, Staff and Students Publications
No abstract provided.
Ginkgo Biloba For Tardive Dyskinesia And Plasma Mnsod Activity: Association With Mnsod Ala-9val Variant: A Randomized, Double-Blind Trial, Dongmei Wang, Yang Tian, Jiajing Chen, Rongrong Zhu, Jiaxin Li, Huixia Zhou, Dachun Chen, Li Wang, Thomas R Kosten, Xiang-Yang Zhang
Ginkgo Biloba For Tardive Dyskinesia And Plasma Mnsod Activity: Association With Mnsod Ala-9val Variant: A Randomized, Double-Blind Trial, Dongmei Wang, Yang Tian, Jiajing Chen, Rongrong Zhu, Jiaxin Li, Huixia Zhou, Dachun Chen, Li Wang, Thomas R Kosten, Xiang-Yang Zhang
Faculty, Staff and Students Publications
Background: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype.
Methods: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded …
Optical Coherence Elastography Measures The Biomechanical Properties Of The Ex Vivo Porcine Cornea After Lasik, Achuth Nair, Fernando Zvietcovich, Manmohan Singh, Mitchell P Weikert, Salavat R Aglyamov, Kirill V Larin
Optical Coherence Elastography Measures The Biomechanical Properties Of The Ex Vivo Porcine Cornea After Lasik, Achuth Nair, Fernando Zvietcovich, Manmohan Singh, Mitchell P Weikert, Salavat R Aglyamov, Kirill V Larin
Faculty, Staff and Students Publications
SIGNIFICANCE: The biomechanical impact of refractive surgery has long been an area of investigation. Changes to the cornea structure cause alterations to its mechanical integrity, but few studies have examined its specific mechanical impact.
AIM To quantify how the biomechanical properties of the cornea are altered by laser assisted in situ keratomileusis (LASIK) using optical coherence elastography (OCE) in ex vivo porcine corneas.
APPROACH: Three OCE techniques, wave-based air-coupled ultrasound (ACUS) OCE, heartbeat (Hb) OCE, and compression OCE were used to measure the mechanical properties of paired porcine corneas, where one eye of the pair was left untreated, and the …
Neuroimaging-Based Classification Of Ptsd Using Data-Driven Computational Approaches: A Multisite Big Data Study From The Enigma-Pgc Ptsd Consortium, Xi Zhu, Yoojean Kim, Orren Ravid, Xiaofu He, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Seonjoo Lee, Chadi G Abdallah, Michael Angstadt, Christopher L Averill, C Lexi Baird, Lee A Baugh, Jennifer U Blackford, Jessica Bomyea, Steven E Bruce, Richard A Bryant, Zhihong Cao, Kyle Choi, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Michael D Debellis, Emily L Dennis, Maria Densmore, Terri Deroon-Cassini, Seth G Disner, Wissam El Hage, Amit Etkin, Negar Fani, Kelene A Fercho, Jacklynn Fitzgerald, Gina L Forster, Jessie L Frijling, Elbert Geuze, Atilla Gonenc, Evan M Gordon, Staci Gruber, Daniel W Grupe, Jeffrey P Guenette, Courtney C Haswell, Ryan J Herringa, Julia Herzog, David Bernd Hofmann, Bobak Hosseini, Anna R Hudson, Ashley A Huggins, Jonathan C Ipser, Neda Jahanshad, Meilin Jia-Richards, Tanja Jovanovic, Milissa L Kaufman, Mitzy Kennis, Anthony King, Philipp Kinzel, Saskia B J Koch, Inga K Koerte, Sheri M Koopowitz, Mayuresh S Korgaonkar, John H Krystal, Ruth Lanius, Christine L Larson, Lauren A M Lebois, Gen Li, Israel Liberzon, Guang Ming Lu, Yifeng Luo, Vincent A Magnotta, Antje Manthey, Adi Maron-Katz, Geoffery May, Katie Mclaughlin, Sven C Mueller, Laura Nawijn, Steven M Nelson, Richard W J Neufeld, Jack B Nitschke, Erin M O'Leary, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, K Luan Phan, Rongfeng Qi, Yann Quidé, Ivan Rektor, Kerry Ressler, Pavel Riha, Marisa Ross, Isabelle M Rosso, Lauren E Salminen, Kelly Sambrook, Christian Schmahl, Martha E Shenton, Margaret Sheridan, Chiahao Shih, Maurizio Sicorello, Anika Sierk, Alan N Simmons, Raluca M Simons, Jeffrey S Simons, Scott R Sponheim, Murray B Stein, Dan J Stein, Jennifer S Stevens, Thomas Straube, Delin Sun, Jean Théberge, Paul M Thompson, Sophia I Thomopoulos, Nic J A Van Der Wee, Steven J A Van Der Werff, Theo G M Van Erp, Sanne J H Van Rooij, Mirjam Van Zuiden, Tim Varkevisser, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Li Wang, Xin Wang, Carissa Weis, Sherry Winternitz, Hong Xie, Ye Zhu, Melanie Wall, Yuval Neria, Rajendra A Morey
Neuroimaging-Based Classification Of Ptsd Using Data-Driven Computational Approaches: A Multisite Big Data Study From The Enigma-Pgc Ptsd Consortium, Xi Zhu, Yoojean Kim, Orren Ravid, Xiaofu He, Benjamin Suarez-Jimenez, Sigal Zilcha-Mano, Amit Lazarov, Seonjoo Lee, Chadi G Abdallah, Michael Angstadt, Christopher L Averill, C Lexi Baird, Lee A Baugh, Jennifer U Blackford, Jessica Bomyea, Steven E Bruce, Richard A Bryant, Zhihong Cao, Kyle Choi, Josh Cisler, Andrew S Cotton, Judith K Daniels, Nicholas D Davenport, Richard J Davidson, Michael D Debellis, Emily L Dennis, Maria Densmore, Terri Deroon-Cassini, Seth G Disner, Wissam El Hage, Amit Etkin, Negar Fani, Kelene A Fercho, Jacklynn Fitzgerald, Gina L Forster, Jessie L Frijling, Elbert Geuze, Atilla Gonenc, Evan M Gordon, Staci Gruber, Daniel W Grupe, Jeffrey P Guenette, Courtney C Haswell, Ryan J Herringa, Julia Herzog, David Bernd Hofmann, Bobak Hosseini, Anna R Hudson, Ashley A Huggins, Jonathan C Ipser, Neda Jahanshad, Meilin Jia-Richards, Tanja Jovanovic, Milissa L Kaufman, Mitzy Kennis, Anthony King, Philipp Kinzel, Saskia B J Koch, Inga K Koerte, Sheri M Koopowitz, Mayuresh S Korgaonkar, John H Krystal, Ruth Lanius, Christine L Larson, Lauren A M Lebois, Gen Li, Israel Liberzon, Guang Ming Lu, Yifeng Luo, Vincent A Magnotta, Antje Manthey, Adi Maron-Katz, Geoffery May, Katie Mclaughlin, Sven C Mueller, Laura Nawijn, Steven M Nelson, Richard W J Neufeld, Jack B Nitschke, Erin M O'Leary, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, K Luan Phan, Rongfeng Qi, Yann Quidé, Ivan Rektor, Kerry Ressler, Pavel Riha, Marisa Ross, Isabelle M Rosso, Lauren E Salminen, Kelly Sambrook, Christian Schmahl, Martha E Shenton, Margaret Sheridan, Chiahao Shih, Maurizio Sicorello, Anika Sierk, Alan N Simmons, Raluca M Simons, Jeffrey S Simons, Scott R Sponheim, Murray B Stein, Dan J Stein, Jennifer S Stevens, Thomas Straube, Delin Sun, Jean Théberge, Paul M Thompson, Sophia I Thomopoulos, Nic J A Van Der Wee, Steven J A Van Der Werff, Theo G M Van Erp, Sanne J H Van Rooij, Mirjam Van Zuiden, Tim Varkevisser, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Li Wang, Xin Wang, Carissa Weis, Sherry Winternitz, Hong Xie, Ye Zhu, Melanie Wall, Yuval Neria, Rajendra A Morey
Faculty, Staff and Students Publications
Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group.
Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls …
Clinical Diagnosis And Management Of Demodex Blepharitis: The Demodex Expert Panel On Treatment And Eyelid Health (Depth), Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu
Clinical Diagnosis And Management Of Demodex Blepharitis: The Demodex Expert Panel On Treatment And Eyelid Health (Depth), Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu
Faculty, Staff and Students Publications
Background: Twelve ocular surface disease experts convened to achieve consensus about Demodex blepharitis (DB) using a modified Delphi panel process.
Methods: Online surveys were administered using scaled, open-ended, true/false, and multiple-choice questions. Consensus for questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panellists agreed. Questions were randomized, and results of each survey informed the following survey.
Results: Twelve practitioners comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). Following 3 surveys, experts agreed that DB is chronic (n …
Clinical Trials Submissions To The Ocular Surface, Gary D Novack, Cintia S De Paiva
Clinical Trials Submissions To The Ocular Surface, Gary D Novack, Cintia S De Paiva
Faculty, Staff and Students Publications
No abstract provided.
Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu
Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Brandon D Ayres, Eric Donnenfeld, Marjan Farid, Ian Benjamin Gaddie, Preeya K Gupta, Edward Holland, Paul M Karpecki, Richard Lindstrom, Kelly K Nichols, Stephen C Pflugfelder, Christopher E Starr, Elizabeth Yeu
Faculty, Staff and Students Publications
BACKGROUND: Twelve ocular surface disease experts convened to achieve consensus about Demodex blepharitis (DB) using a modified Delphi panel process.
METHODS: Online surveys were administered using scaled, open-ended, true/false, and multiple-choice questions. Consensus for questions using a 1 to 9 Likert scale was predefined as median scores of 7-9 and 1-3. For other question types, consensus was achieved when 8 of 12 panellists agreed. Questions were randomized, and results of each survey informed the following survey.
RESULTS: Twelve practitioners comprised the Demodex Expert Panel on Treatment and Eyelid Health (DEPTH). Following 3 surveys, experts agreed that DB is chronic (n …
Tnf Is A Critical Cytokine In Age-Related Dry Eye Disease, Yashaswini Kelagere, Kaitlin K Scholand, Erica N Dejong, Andrea I Boyd, Zhiyuan Yu, Roger A Astley, Michelle C Callegan, Dawn Me Bowdish, Helen P Makarenkova, Cintia S De Paiva
Tnf Is A Critical Cytokine In Age-Related Dry Eye Disease, Yashaswini Kelagere, Kaitlin K Scholand, Erica N Dejong, Andrea I Boyd, Zhiyuan Yu, Roger A Astley, Michelle C Callegan, Dawn Me Bowdish, Helen P Makarenkova, Cintia S De Paiva
Faculty, Staff and Students Publications
Aging is a complex biological process that is characterized by low-grade inflammation, called inflammaging. Aging affects multiple organs including eye and lacrimal gland. Tumor necrosis factor (TNF) is a pleiotropic cytokine that participates in inflammation, activation of proteases such as cathepsin S, and formation of ectopic lymphoid organs. Using genetic and pharmacological approaches, we investigated the role of TNF in age-related dry eye disease, emphasizing the ocular surface and lacrimal gland inflammation. Our results show the increased protein and mRNA levels of TNF in aged lacrimal glands, accompanied by increased TNF, IL1β, IL-18, CCL5, CXCL1, IL-2, IL-2 receptor alpha (CD25), …
Conditional Deletion Of Cd25 In The Corneal Epithelium Reveals Sex Differences In Barrier Disruption, Anmar Abu-Romman, Kaitlin K Scholand, Sonali Pal-Ghosh, Zhiyuan Yu, Yashaswini Kelagere, Ghasem Yazdanpanah, Winston W-Y Kao, Vivien J Coulson-Thomas, Mary Ann Stepp, Cintia S De Paiva
Conditional Deletion Of Cd25 In The Corneal Epithelium Reveals Sex Differences In Barrier Disruption, Anmar Abu-Romman, Kaitlin K Scholand, Sonali Pal-Ghosh, Zhiyuan Yu, Yashaswini Kelagere, Ghasem Yazdanpanah, Winston W-Y Kao, Vivien J Coulson-Thomas, Mary Ann Stepp, Cintia S De Paiva
Faculty, Staff and Students Publications
PURPOSE: IL-2 promotes activation, clonal expansion, and deletion of T cells. IL-2 signals through its heterotrimeric receptor (IL-2R) consisting of the CD25, CD122 and CD132 chains. CD25 knockout (KO) mice develop Sjögren Syndrome-like disease. This study investigates whether corneal CD25/IL-2 signaling is critical for ocular health.
METHODS: Eyes from C57BL/6 mice were collected and prepared for immunostaining or in-situ hybridization. Bulk RNA sequencing was performed on the corneal epithelium from wild-type and CD25KO mice. We generated a conditional corneal-specific deletion of CD25 in the corneal epithelium (CD25
RESULTS: In C57BL/6 mice, CD25 mRNA was expressed in ocular tissues. Protein expression …
Our Search Of Immune Invaders In The Aged Lacrimal Gland, Claudia M Trujillo-Vargas, Cintia S De Paiva
Our Search Of Immune Invaders In The Aged Lacrimal Gland, Claudia M Trujillo-Vargas, Cintia S De Paiva
Faculty, Staff and Students Publications
No abstract provided.
Cognitive Ergonomics: A Review Of Interventions For Outpatient Practice, Jennifer Li-Wang, Alexandra Townsley, Rajani Katta
Cognitive Ergonomics: A Review Of Interventions For Outpatient Practice, Jennifer Li-Wang, Alexandra Townsley, Rajani Katta
Faculty, Staff and Students Publications
Doctoring is difficult mental work, involving many cognitively demanding processes such as diagnosing, decision-making, parallel processing, communicating, and managing the emotions of others. According to cognitive load theory (CLT), working memory is a limited cognitive resource that can support a finite amount of cognitive load. While the intrinsic cognitive load is the innate load associated with a task, the extraneous load is generated by inefficiency or suboptimal work conditions. Causes of extraneous cognitive load in healthcare include inefficiency, distractions, interruptions, multitasking, stress, poor communication, conflict, and incivility. High levels of cognitive load are associated with impaired function and an increased …
Effects Of Cathepsin S Inhibition In The Age-Related Dry Eye Phenotype, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Zhiyuan Yu, Cintia S De Paiva
Effects Of Cathepsin S Inhibition In The Age-Related Dry Eye Phenotype, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Wolfgang Haap, Tiago Santos-Ferreira, Christoph Ullmer, Zhiyuan Yu, Cintia S De Paiva
Faculty, Staff and Students Publications
PURPOSE: Aged C57BL/6J (B6) mice have increased levels of cathepsin S, and aged cathepsin S (Ctss-/-) knockout mice are resistant to age-related dry eye. This study investigated the effects of cathepsin S inhibition on age-related dry eye disease.
METHODS: Female B6 mice aged 15.5 to 17 months were randomized to receive a medicated diet formulated by mixing the RO5461111 cathepsin S inhibitor or a standard diet for at least 12 weeks. Cornea mechanosensitivity was measured with a Cochet-Bonnet esthesiometer. Ocular draining lymph nodes and lacrimal glands (LGs) were excised and prepared for histology or assayed by flow cytometry to quantify …
Accuracy Of Artificial Intelligence In Estimating Best-Corrected Visual Acuity From Fundus Photographs In Eyes With Diabetic Macular Edema, William Paul, Philippe Burlina, Rohita Mocharla, Neil Joshi, Zhuolin Li, Sophie Gu, Onnisa Nanegrungsunk, Kira Lin, Susan B Bressler, Cindy X Cai, Jun Kong, T Y Alvin Liu, Hadi Moini, Weiming Du, Fouad Amer, Karen Chu, Robert Vitti, Farshid Sepehrband, Neil M Bressler
Accuracy Of Artificial Intelligence In Estimating Best-Corrected Visual Acuity From Fundus Photographs In Eyes With Diabetic Macular Edema, William Paul, Philippe Burlina, Rohita Mocharla, Neil Joshi, Zhuolin Li, Sophie Gu, Onnisa Nanegrungsunk, Kira Lin, Susan B Bressler, Cindy X Cai, Jun Kong, T Y Alvin Liu, Hadi Moini, Weiming Du, Fouad Amer, Karen Chu, Robert Vitti, Farshid Sepehrband, Neil M Bressler
Faculty, Staff and Students Publications
IMPORTANCE: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely.
OBJECTIVE: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information.
DESIGN, SETTING, AND PARTICIPANTS: Deidentified color fundus …
Differentially Expressed Tear Proteins In Sjögren's Syndrome Keratoconjunctivitis Sicca, Stephen P Yoon, Zhiyuan Yu, Stephen C Pflugfelder, Cintia S De Paiva
Differentially Expressed Tear Proteins In Sjögren's Syndrome Keratoconjunctivitis Sicca, Stephen P Yoon, Zhiyuan Yu, Stephen C Pflugfelder, Cintia S De Paiva
Faculty, Staff and Students Publications
Purpose: The purpose of this study was to determine if there are significant differences in the concentrations of tear proteins in Sjögren's syndrome keratoconjunctivitis sicca (SS KCS) compared to healthy controls.
Methods: Tear samples were collected with unmarked Schirmer strips from 15 patients with SS KCS and 21 healthy controls. Tear protein was eluted and the concentration measured. Inflammatory mediators were assayed with a Raybiotech L-507 glass slide array and normalized by strip wetting length. All patients underwent an ocular surface exam to evaluate tear break-up time (TBUT), corneal fluorescein (CF) staining, and conjunctival (CJ) staining. The symptom assessment questionnaire …
When Patient Rudeness Impacts Care: A Review Of Incivility In Healthcare, Alexandra Townsley, Jennifer Li-Wang, Rajani Katta
When Patient Rudeness Impacts Care: A Review Of Incivility In Healthcare, Alexandra Townsley, Jennifer Li-Wang, Rajani Katta
Faculty, Staff and Students Publications
Healthcare workers increasingly face incivility and rude behaviors from patients, families, and visitors. Although these are less severe than other types of mistreatment, studies have documented that they may still impact healthcare worker well-being and patient care. Defining and measuring incivility can be challenging because current research relies on the perceptions of the targets. Furthermore, there is often overlap among different types of mistreatment, and much of it goes unreported by those who experience it. Nevertheless, multiple studies have documented that incivility is common in healthcare and has been associated with burnout and intent to leave. In clinical settings, multiple …
An Ocular Th1 Immune Response Promotes Corneal Nerve Damage Independently Of The Development Of Corneal Epitheliopathy, Alexia Vereertbrugghen, Manuela Pizzano, Florencia Sabbione, Irene Angelica Keitelman, Carolina Maiumi Shiromizu, Douglas Vera Aguilar, Federico Fuentes, Cintia S De Paiva, Mirta Giordano, Analía Trevani, Jeremías G Galletti
An Ocular Th1 Immune Response Promotes Corneal Nerve Damage Independently Of The Development Of Corneal Epitheliopathy, Alexia Vereertbrugghen, Manuela Pizzano, Florencia Sabbione, Irene Angelica Keitelman, Carolina Maiumi Shiromizu, Douglas Vera Aguilar, Federico Fuentes, Cintia S De Paiva, Mirta Giordano, Analía Trevani, Jeremías G Galletti
Faculty, Staff and Students Publications
Proper sight is not possible without a smooth, transparent cornea, which is highly exposed to environmental threats. The abundant corneal nerves are interspersed with epithelial cells in the anterior corneal surface and are instrumental to corneal integrity and immunoregulation. Conversely, corneal neuropathy is commonly observed in some immune-mediated corneal disorders but not in others, and its pathogenesis is poorly understood. Here we hypothesized that the type of adaptive immune response may influence the development of corneal neuropathy. To test this, we first immunized OT-II mice with different adjuvants that favor T helper (Th)1 or Th2 responses. Both Th1-skewed mice (measured …
Imi-Management And Investigation Of High Myopia In Infants And Young Children, Ian Flitcroft, John Ainsworth, Audrey Chia, Susan Cotter, Elise Harb, Zi-Bing Jin, Caroline C W Klaver, Anthony T Moore, Ken K Nischal, Kyoko Ohno-Matsui, Evelyn A Paysse, Michael X Repka, Irina Y Smirnova, Martin Snead, Virginie J M Verhoeven, Pavan K Verkicharla
Imi-Management And Investigation Of High Myopia In Infants And Young Children, Ian Flitcroft, John Ainsworth, Audrey Chia, Susan Cotter, Elise Harb, Zi-Bing Jin, Caroline C W Klaver, Anthony T Moore, Ken K Nischal, Kyoko Ohno-Matsui, Evelyn A Paysse, Michael X Repka, Irina Y Smirnova, Martin Snead, Virginie J M Verhoeven, Pavan K Verkicharla
Faculty, Staff and Students Publications
Purpose: The purpose of this study was to evaluate the epidemiology, etiology, clinical assessment, investigation, management, and visual consequences of high myopia (≤-6 diopters [D]) in infants and young children.
Findings: High myopia is rare in pre-school children with a prevalence less than 1%. The etiology of myopia in such children is different than in older children, with a high rate of secondary myopia associated with prematurity or genetic causes. The priority following the diagnosis of high myopia in childhood is to determine whether there is an associated medical diagnosis that may be of greater overall importance to the health …
Practice Efficiency In Dermatology: Enhancing Quality Of Care And Physician Well-Being, Rajani Katta, Emily Strouphauer, Marina K Ibraheim, Jennifer Li-Wang, Harry Dao
Practice Efficiency In Dermatology: Enhancing Quality Of Care And Physician Well-Being, Rajani Katta, Emily Strouphauer, Marina K Ibraheim, Jennifer Li-Wang, Harry Dao
Faculty, Staff and Students Publications
A focus on improved efficiency can impact both patient care and physician well-being. Efficiency is one of the six domains of healthcare quality. It is also recognized as one of the three main pillars of professional fulfillment. Quality improvement measures in the area of efficiency are focused on reducing waste, specifically related to physicians' time, energy, and cognitive demands. Interventions and practices reported in the literature or communicated by dermatologists have documented efforts centered on patient care workflows, documentation, communication, and other areas. Team-based care models maximize the skill sets of other trained providers, while workflow changes encompassing process standardization, …
Evaluation Of Retinal Nerve Fibre Layer Thickness As A Possible Measure Of Diabetic Retinal Neurodegeneration In The Epic-Norfolk Eye Study, Sidra Zafar, Kristen A Staggers, Jie Gao, Yao Liu, Praveen J Patel, Paul J Foster, Benjamin J Frankfort, Michael Abramoff, Charles G Minard, Alasdair Warwick, Anthony P Khawaja, Roomasa Channa
Evaluation Of Retinal Nerve Fibre Layer Thickness As A Possible Measure Of Diabetic Retinal Neurodegeneration In The Epic-Norfolk Eye Study, Sidra Zafar, Kristen A Staggers, Jie Gao, Yao Liu, Praveen J Patel, Paul J Foster, Benjamin J Frankfort, Michael Abramoff, Charles G Minard, Alasdair Warwick, Anthony P Khawaja, Roomasa Channa
Faculty, Staff and Students Publications
BACKGROUND/AIMS: Markers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness.
METHODS: Leveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also …
Ectopic Lymphoid Structures In The Aged Lacrimal Glands, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Zhiyuan Yu, Olivier Mauduit, Vanessa Delcroix, Helen P Makarenkova, Cintia S De Paiva
Ectopic Lymphoid Structures In The Aged Lacrimal Glands, Jeremias G Galletti, Kaitlin K Scholand, Claudia M Trujillo-Vargas, Zhiyuan Yu, Olivier Mauduit, Vanessa Delcroix, Helen P Makarenkova, Cintia S De Paiva
Faculty, Staff and Students Publications
Aging is a complex biological process in which many organs are pathologically affected. We previously reported that aged C57BL/6J had increased lacrimal gland (LG) lymphoid infiltrates that suggest ectopic lymphoid structures. However, these ectopic lymphoid structures have not been fully investigated. Using C57BL/6J mice of different ages, we analyzed the transcriptome of aged murine LGs and characterized the B and T cell populations. Age-related changes in the LG include increased differentially expressed genes associated with B and T cell activation, germinal center formation, and infiltration by marginal zone-like B cells. We also identified an age-related increase in B1
Lacrimal Gland Epithelial Cells Shape Immune Responses Through The Modulation Of Inflammasomes And Lipid Metabolism, Vanessa Delcroix, Olivier Mauduit, Menglu Yang, Amrita Srivastava, Takeshi Umazume, Cintia S De Paiva, Valery I Shestopalov, Darlene A Dartt, Helen P Makarenkova
Lacrimal Gland Epithelial Cells Shape Immune Responses Through The Modulation Of Inflammasomes And Lipid Metabolism, Vanessa Delcroix, Olivier Mauduit, Menglu Yang, Amrita Srivastava, Takeshi Umazume, Cintia S De Paiva, Valery I Shestopalov, Darlene A Dartt, Helen P Makarenkova
Faculty, Staff and Students Publications
Lacrimal gland inflammation triggers dry eye disease through impaired tear secretion by the epithelium. As aberrant inflammasome activation occurs in autoimmune disorders including Sjögren's syndrome, we analyzed the inflammasome pathway during acute and chronic inflammation and investigated its potential regulators. Bacterial infection was mimicked by the intraglandular injection of lipopolysaccharide (LPS) and nigericin, known to activate the NLRP3 inflammasome. Acute injury of the lacrimal gland was induced by interleukin (IL)-1α injection. Chronic inflammation was studied using two Sjögren's syndrome models: diseased